Brendan Carvalho

All Publications

• Optimization of Maternal Magnesium Sulfate Administration for Fetal Neuroprotection: Application of a Prospectively Constructed Pharmacokinetic Model to the BEAM Cohort. Journal of clinical pharmacology Brookfield, K. F., Elkomy, M., Su, F., Drover, D. R., Carvalho, B. 2017

  Abstract

  The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population-based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy. Among 1905 women who met inclusion criteria, the incidence of cerebral palsy in the cohort was 3.6% for women who had received magnesium sulfate and 6.4% for controls. The simulated maternal serum concentration at delivery associated with the lowest probability of delivering an infant with cerebral palsy was 4.1 mg/dL (95%CI 3.7 to 4.4). Our population-based estimates of magnesium disposition suggest that to optimize fetal neuroprotection and prevent cerebral palsy, magnesium sulfate administration should target a maternal serum magnesium level between 3.7 and 4.4 mg/dL at delivery.

  View details for DOI 10.1002/jcph.941

  View details for PubMedID 28589614

• What's trending now? An analysis of trends in internet searches for labor epidurals INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Sutton, C. D., Carvalho, B. 2017; 30: 52-57

  Abstract

  The study aim was to investigate internet use for obtaining information about epidurals for labor and delivery.Google Trends for US data was queried from 2004 to 2015 to find the most common searches and determine temporal trends. The Google Trends query used the term [epidural] and evaluated changes in search trends over time. Search comparisons were made for each year from 2004 to 2015, and three equal time epochs during the study period (2004-07, 2008-11, 2012-15) were compared. We also compared searches for epidurals with commonly searched birth-related terms.Internet searches are increasing; there were 726000 searches for [epidural] in 2015. Search terms with the most significant growth in the past 4years (2012-15) were "birth with epidural," "pain after epidural," "labor without epidural," "epidural birth video," and "epidural vs natural". Searches for epidural side effects, risks, and pain on insertion were among the most common and were increasing most rapidly. Searches related to epidurals were more common than searches related to "natural births", "home births", and "labor pain", but were less common than searches for "midwives" or "doulas".The findings provide an insight into internet use by those seeking information about labor analgesic options. Identifying the most common and rapidly increasing online search queries may guide physician-parturient interactions and online content creation, to address labor analgesic topics that most interest users.

  View details for DOI 10.1016/j.ijoa.2017.02.004

  View details for Web of Science ID 000401676500009

  View details for PubMedID 28347574

• Patient choice compared with no choice of intrathecal morphine dose for caesarean analgesia: a randomized clinical trial. British journal of anaesthesia Carvalho, B., Mirza, F., Flood, P. 2017; 118 (5): 762-771

  Abstract

  The study aimed to determine whether a patient's choice for their intrathecal morphine (ITM) dose reflects their opioid requirements and pain after caesarean delivery and if giving women a choice of ITM dose would reduce opioid use and improve pain scores compared with women who did not have a choice.A total of 120 women undergoing caesarean delivery with spinal anaesthesia were enrolled in this randomized, double-blind study. Patients were randomly assigned to a choice of 100 or 200 μg ITM or no choice. The study involved deception, such that all participants were still randomly assigned 100 or 200 μg ITM regardless of choice. Rescue opioid use over the 48-h study period was the primary outcome measure. Pain at rest and movement and side effect (pruritus, nausea, and vomiting) data were collected 3, 6, 12, 24, 36 and 48 h postoperatively. Data are presented as median [95% confidence interval (CI)].Women who requested the larger ITM dose required more supplemental opioid [median 0.8 (95% CI 0.4-1.3)] mg morphine equivalents at each assessment interval; P  < 0.001] and reported more pain with movement [median 1.2 (95% CI 0.5-1.9)] verbal numerical rating score of 0-10 points] than patients who requested the smaller ITM dose ( P  = 0.0008), regardless of the ITM dose given. There was no difference in opioid use whether the patient was offered a perceived choice or not.Women who were given a choice and chose the larger ITM dose correctly anticipated a greater postoperative opioid requirement and more pain compared with women who chose the smaller dose. Simply being offered a choice did not impact opioid use or pain scores after caesarean delivery.ClinicalTrials.gov (NCT01425762).

  View details for DOI 10.1093/bja/aex039

  View details for PubMedID 28486595

• Programmed Intermittent Epidural Boluses (PIEB) for Maintenance of Labor Analgesia: A Superior Technique to Continuous Epidural Infusion? Turkish journal of anaesthesiology and reanimation Riley, E. T., Carvalho, B. 2017; 45 (2): 65-66

  View details for DOI 10.5152/TJAR.2017.09031

  View details for PubMedID 28439433

• Analysis of Physiological Respiratory Variable Alarm Alerts Among Laboring Women Receiving Remifentanil ANESTHESIA AND ANALGESIA Weiniger, C. F., Carvalho, B., Stocki, D., Einav, S. 2017; 124 (4): 1211-1218

  View details for DOI 10.1213/ANE.0000000000001644

  View details for Web of Science ID 000397354100027

• Programmed Intermittent Epidural Boluses (PIEB) for Maintenance of Labor Analgesia: An Incremental Step Before the Next Paradigm Shift? Turkish journal of anaesthesiology and reanimation Carvalho, B., Riley, E. T. 2017; 45 (2): 73-75

  View details for DOI 10.5152/TJAR.2017.09034

  View details for PubMedID 28439436

• Effect of a High-Rate Versus a Low-Rate Oxytocin Infusion for Maintaining Uterine Contractility During Elective Cesarean Delivery: A Prospective Randomized Clinical Trial. Anesthesia and analgesia Duffield, A., McKenzie, C., Carvalho, B., Ramachandran, B., Yin, V., El-Sayed, Y. Y., Riley, E. T., Butwick, A. J. 2017; 124 (3): 857-862

  Abstract

  Oxytocin is routinely used as prophylaxis against uterine atony. During elective cesarean delivery (CD), an oxytocin bolus is used to initiate adequate uterine tone, followed by an oxytocin infusion to maintain uterine contractility. However, it is unclear whether oxytocin maintenance infusion rate influences total estimated blood loss (EBL).We performed a prospective, randomized, double-blind trial in 51 women undergoing elective CD. Women were randomly assigned to receive an oxytocin maintenance infusion of 2.5 or 15 U/h. All women received an oxytocin 1 U bolus to initiate adequate uterine tone. The primary outcome was EBL. EBL values between groups were compared using a Mann-Whitney U test; P < .05 as statistically significant. The median EBL difference with 95% confidence intervals was also calculated. Secondary outcomes included adequacy of uterine tone, use of additional uterotonics, and oxytocin-related side effects, including hypotension.Of 51 women, 24 received a low-rate infusion and 27 received a high-rate infusion. Median (interquartile range) EBL values in the low-rate and high-rate groups were 634 (340-886) mL versus 512 (405-740) mL, respectively (P = .7). The median difference in EBL between groups was 22 mL; 95% confidence interval = -158 to 236 mL. The rate of postpartum hemorrhage did not differ between groups (low-rate group: 4/24 [16.7%] versus high-rate group: 4/26 [15.4%]). There were no between-group differences over time (first 20 minutes after commencing infusion) in the incidence of adequate uterine tone (P = .72) or hypotension (P = .32).Among women undergoing elective CD receiving an oxytocin maintenance infusion, EBL and uterine tone did not differ between women receiving 2.5 U/h oxytocin and those receiving 15 U/h oxytocin. Our findings suggest that efficacy can be obtained with a low oxytocin maintenance infusion rate; however, dose-finding studies are needed to determine the infusion rate that optimizes drug efficacy while minimizing side effects.

  View details for DOI 10.1213/ANE.0000000000001658

  View details for PubMedID 28212181

  View details for PubMedCentralID PMC5319709

• Optimal Pain Management After Cesarean Delivery. Anesthesiology clinics Sutton, C. D., Carvalho, B. 2017; 35 (1): 107-124

  Abstract

  Cesarean delivery rates are increasing worldwide, and effective postoperative pain management is a key priority of women undergoing cesarean delivery. Inadequate pain management in the acute postoperative period is associated with persistent pain, greater opioid use, delayed functional recovery, and increased postpartum depression. In addition to pain relief, optimal management of patients after cesarean delivery should address the goals of unrestricted maternal mobility, minimal maternal and neonatal side effects, rapid recovery to baseline functionality, and early discharge home. Multimodal analgesia should include neuraxial morphine in conjunction with nonopioid adjuncts, with additional oral or intravenous opioids reserved for severe breakthrough pain.

  View details for DOI 10.1016/j.anclin.2016.09.010

  View details for PubMedID 28131114

• Postpartum hemorrhage following vaginal delivery: risk factors and maternal outcomes. Journal of perinatology Miller, C. M., Cohn, S., Akdagli, S., Carvalho, B., Blumenfeld, Y. J., Butwick, A. J. 2017; 37 (3): 243-248

  Abstract

  Limited understanding of risk factors exists for postpartum hemorrhage (PPH) post-vaginal delivery. The aim of this study was to identify risk factors for PPH post-vaginal delivery within a contemporary obstetric cohort.Retrospective case-control study. PPH was classified by an estimated blood loss ⩾500 ml. Risk factors for PPH were identified using univariable and multivariable logistic regression. We secondarily investigated maternal outcomes and medical and surgical interventions for PPH management.The study cohort comprised 159 cases and 318 controls. Compared with a second-stage duration <2 h, a second stage⩾3 h was associated with PPH (adjusted odds ratio=2.3; 95% CI=1.2 to 4.6). No other clinical or obstetric variables were identified as independent risk factors for PPH. Among cases, 4% received red blood cells and 1% required intensive care admission.Although PPH-related morbidity may be uncommon after vaginal delivery, PPH should be anticipated for women after a second stage ⩾3 h.

  View details for DOI 10.1038/jp.2016.225

  View details for PubMedID 27977018

• Clinical and microbiological features of maternal sepsis: a retrospective study INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Abir, G., Akdagli, S., Butwick, A., Carvalho, B. 2017; 29: 26-33

  View details for DOI 10.1016/j.ijoa.2016.09.003

  View details for Web of Science ID 000394917700006

• The impact of postpartum hemoglobin levels on maternal quality of life after delivery: a prospective exploratory study. Annals of hematology Miller, C. M., Ramachandran, B., Akbar, K., Carvalho, B., Butwick, A. J. 2016; 95 (12): 2049-2055

  Abstract

  Postpartum anemia has been associated with postpartum morbidities, such as depression and poor cognition. However, it is unclear whether postpartum anemia is associated with reduced health-related quality of life. We performed a prospective study to examine the relations between postpartum Hb levels with postpartum health-related quality of life (HRQoL). We collected data from 60 women intending vaginal delivery and assessed HRQoL and maternal fatigue on admission and on the first postpartum day using the RAND 36-Item Short-Form Health Survey (SF-36) and the Multidimensional Fatigue Inventory (MFI), respectively. Maternal Hb levels were measured on admission and on the first postpartum day. We also assessed patients for postpartum depression using the Edinburgh Postpartum Depression Scale (EPDS). We performed unadjusted and multivariate linear regression (adjusting for maternal age, parity, mode of delivery, and race) to assess the associations between postdelivery Hb with each subscale of the SF-36 and MFI. The mean predelivery and postpartum Hb levels were 12.3 (1.2) and 10.8 (1.4) g/dl, respectively. In our unadjusted and adjusted regression analyses, we observed no statistically significant associations between postpartum Hb levels with any SF-36 or MFI subscale (P > 0.05). Based on the EPDS, only one patient was depressed; her postpartum Hb was 11.2 g/dl. Our findings suggest that postpartum Hb levels may not influence HRQoL or fatigue. However, our findings may only apply to women without predelivery anemia, severe blood loss or moderate-to-severe anemia after delivery. Future studies are needed to determine whether postpartum Hb influences HRQoL among women with moderate or severe postpartum anemia.

  View details for PubMedID 27623626

• Analysis of Physiological Respiratory Variable Alarm Alerts Among Laboring Women Receiving Remifentanil. Anesthesia and analgesia Weiniger, C. F., Carvalho, B., Stocki, D., Einav, S. 2016: -?

  Abstract

  Remifentanil may be used by laboring women for analgesia, despite controversy because of potential apneas. We evaluated candidate variables as early warning alerts for apnea, based on prevalence, positive predictive rate, sensitivity for apnea event detection, and early warning alert time intervals (lead time) for apnea.We performed a secondary analysis of respiratory physiological data that had been collected during a prospective IRB-approved study of laboring women receiving IV patient-controlled boluses of remifentanil 20 to 60 μg every 1 to 2 minutes. Analyzed data included the respiratory rate (RR), end-tidal CO2 (EtCO2), pulse oximetry (SpO2), heart rate (HR), and the Integrated Pulmonary Index (IPI; Capnostream 20; Medtronic, Boulder, CO) that had been recorded continuously throughout labor. We defined immediate early warning alerts as any drop in a variable value below a prespecified threshold for 15 seconds: RR < 8 breaths per minute (bpm), EtCO2 < 15 mm Hg, and SpO2 < 92%. We defined alerts as "sustained" when the value remained below the threshold for ≥ 10 further seconds. The IPI value (1 to 10; 10 = healthy patient, ≤4 = immediate attention required, 1 = dire condition) was generated from a proprietary algorithm using RR, EtCO2, SpO2, and HR parameters. Apnea was defined as maximal CO2 < 5 mm Hg for at least 30 consecutive seconds.We counted 62 apneas, among 10 of 19 (52.6%) women who received remifentanil (total dose 1725 ± 1392 μg, administered over 160 ± 132 minutes). We counted 331 immediate early warning alerts for the variables; 271 (82%) alerts were sustained for ≥10 seconds. The positive predictive value of alerts for apnea was 35.8% (99% confidence interval [CI]: 27.1-45.6), 28.9% (99% CI: 20.8-38.7), 4.3% (99% CI: 1.9-9.6), and 24.6% (99% CI: 18.3-32.2) for RR, EtCO2, SpO2, and IPI, respectively. The sensitivity for apnea event detection was 100% (99% CI: 90.3-100) for RR (<8 bpm) and IPI (≤4); 75.8% (99% CI: 59.8-86.9) for EtCO2 <15 mm Hg; and 14.5% (99% CI: 6.5-29.4) for SpO2 <92%. We found a statistically significant difference in the timing of RR, EtCO2, SpO2, and IPI alerts for apnea; Friedman's Q = 33.53; P < .0001. The EtCO2 had a median (interquartile range) lead time of -0.2 (-12.2 to 0.7) seconds, and SpO2 had a median (interquartile range) lead time of 40.0 (40.0 to 40.0) seconds.The majority of women receiving IV remifentanil for labor analgesia experienced apneas. Alerts for EtCO2 (<15 mm Hg), RR (<8 bpm), and IPI (≤4) detected most apneas, whereas SpO2 alerts missed the majority of apneas. All variables had a low positive predictive rate, demonstrating the limitations of the respiratory monitors utilized as early warning surveillance for apneas in this setting.

  View details for PubMedID 27870644

• Survey of external cephalic version for breech presentation and neuraxial blockade use. Journal of clinical anesthesia Weiniger, C. F., Sultan, P., Dunn, A., Carvalho, B. 2016; 34: 616-622

  Abstract

  Neuraxial blockade may increase external cephalic version (ECV) success rates. This survey aimed to assess the frequency and characteristics of neuraxial blockade used to facilitate ECV.We surveyed Society for Obstetric Anesthesia and Perinatology members regarding ECV practice using a 15-item survey developed by 3 obstetric anesthesiologists and tested for face validity. The survey was e-mailed in January 2015 and again in February 2015 to the 1056 Society of Obstetric Anesthesiology and Perinatology members. We present descriptive statistics of responses.Our survey response rate was 322 of 1056 (30.5%).Neuraxial blockade was used for ECV always by 18 (5.6%), often by 52 (16.1%), sometimes by 98 (30.4%), rarely by 78 (24.2%), and never by 46 (14.3%) of respondents. An anesthetic sensory block target was selected by 141 (43.8%) respondents, and analgesic by 102 (31.7%) respondents. Epidural drug doses ranged widely, including sufentanil 5-25 μg; lidocaine 1% or 2% 10-20 mL, bupivacaine 0.0625% to 0.5% 6-15 mL, and ropivacaine 0.2% 20 mL. Intrathecal bupivacaine was used by 182 (56.5%) respondents; the most frequent doses were 2.5 mg used by 24 (7.5%), 7.5 mg used by 35 (10.9%), and 12 mg used by 30 (9.3%).Neuraxial blockade is not universally offered to facilitate ECV, and there is wide variability in neuraxial blockade techniques, in drugs and doses administered, and in the sensory blockade (anesthetic or analgesic) targeted. Future studies need to evaluate and remove barriers to allow for more widespread use of neuraxial blockade for pain relief and to optimize ECV success rates.

  View details for DOI 10.1016/j.jclinane.2016.05.040

  View details for PubMedID 27687460

• Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy. Journal of immunology Fragiadakis, G. K., Baca, Q. J., Gherardini, P. F., Ganio, E. A., Gaudilliere, D. K., Tingle, M., Lancero, H. L., McNeil, L. S., Spitzer, M. H., Wong, R. J., Shaw, G. M., Darmstadt, G. L., Sylvester, K. G., Winn, V. D., Carvalho, B., Lewis, D. B., Stevenson, D. K., Nolan, G. P., Aghaeepour, N., Angst, M. S., Gaudilliere, B. L. 2016

  Abstract

  Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4(+) and CD8(+) T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet(+)CD4(+) T cells, CD8(+) T cells, B cells, and CD56(lo)CD16(+) NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes.

  View details for PubMedID 27793998

  View details for PubMedCentralID PMC5125527

• Implementation of Programmed Intermittent Epidural Bolus for the Maintenance of Labor Analgesia. Anesthesia and analgesia Carvalho, B., George, R. B., Cobb, B., McKenzie, C., Riley, E. T. 2016; 123 (4): 965-971

  Abstract

  Programmed intermittent epidural bolus (PIEB) is an exciting new technology that has the potential to improve the maintenance of epidural labor analgesia. PIEB compared with a continuous epidural infusion (CEI) has the potential advantage of greater spread within the epidural space and therefore better sensory blockade. Studies have demonstrated a local anesthetic-sparing effect, fewer instrumental vaginal deliveries, less motor blockade, and improvements in maternal satisfaction with PIEB compared with CEI. However, the optimal PIEB regimen and pump settings remain unknown, and there are a number of logistical issues and practical considerations that should be considered when implementing PIEB. The PIEB bolus size and interval, PIEB start time delay period, and patient-controlled epidural analgesia bolus size and lockout time can influence the efficacy of PIEB used for epidural labor analgesia. Educating all members of the health care team is critical to the success of the technique. This review summarizes the role of PIEB for the maintenance of labor analgesia, outlines implementation strategies, suggests optimal settings, and presents potential limitations of the technique.

  View details for DOI 10.1213/ANE.0000000000001407

  View details for PubMedID 27464978

• Clinical and microbiological features of maternal sepsis: a retrospective study. International journal of obstetric anesthesia Abir, G., Akdagli, S., Butwick, A., Carvalho, B. 2016

  Abstract

  Identifying pregnant women with sepsis is challenging because diagnostic clinical and laboratory criteria overlap with normal pregnant physiologic indices. Our primary study aim was to describe clinical and laboratory characteristics of women diagnosed with sepsis, severe sepsis and septic shock. Our secondary aim was to determine positive predictive values for International Classification of Disease (ICD)-9 billing codes for sepsis, severe sepsis, and septic shock.After gaining Institutional Review Board approval, we identified women with ICD-9 codes for sepsis, severe sepsis and septic shock who were admitted to a single tertiary obstetric center from 2007-2013. Diagnoses were confirmed using criteria from the International Sepsis Definitions Conference report. Demographic, obstetric, vital signs and laboratory data were abstracted by medical chart review.We identified 190 women with sepsis-related ICD-9 codes: of these, 35 (18%) women met the criteria for a clinical diagnosis of sepsis, severe sepsis or septic shock. Twenty (57%) women had a sepsis-related diagnosis after cesarean delivery. Twenty-one (60%) women had one or more pre-existing medical conditions and 19 (54%) women had one or more obstetric-related conditions. The genital tract was the most common site of infection. We observed considerable heterogeneity in maternal vital signs and laboratory indices for women with ICD-9 codes for sepsis, severe sepsis, and septic shock. The positive predictive value for each sepsis-related ICD-9 code was low: 16% (95% CI 10 to 24%) for sepsis, 10% (95% CI 3 to 25%) for severe sepsis and 24% (95% CI 10 to 46%) for septic shock.We identified marked heterogeneity in patient characteristics, clinical features, laboratory indices and microbiological findings among cohorts of women diagnosed with maternal sepsis, severe sepsis or septic shock. Based on our findings, the incidence of maternal sepsis using ICD-9 codes may be significantly overestimated.

  View details for DOI 10.1016/j.ijoa.2016.09.003

  View details for PubMedID 27793427

• Challenging the 4-to 5-minute rule: from perimortem cesarean to resuscitative hysterotomy AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Lipman, S. S., Cohen, S., Mhyre, J., Carvalho, B., Einav, S., Arafeh, J., Jeejeebhoy, F., Cobb, B., Druzin, M., Katz, V., Harney, K. 2016; 215 (1): 129-131

  View details for DOI 10.1016/j.ajog.2016.03.043

  View details for Web of Science ID 000378630000043

  View details for PubMedID 27040085

• The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis ANESTHESIA AND ANALGESIA Sultan, P., Halpern, S. H., Pushpanathan, E., Patel, S., Carvalho, B. 2016; 123 (1): 154-164

  Abstract

  The intrathecal morphine dose achieving optimal analgesia for cesarean delivery while minimizing side effects has not yet been deduced. In this meta-analysis, our objective was to determine whether low- or high-dose intrathecal morphine provides acceptable duration and intensity of analgesia with fewer side effects.A literature search (PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and CINAHL) was performed to identify randomized controlled trials involving patients undergoing elective cesarean delivery under spinal anesthesia comparing low-dose (LD; 50-100 μg) morphine with higher dose (HD; >100-250 μg). The primary outcome was the time for first request for supplemental analgesia. The secondary outcomes included pain scores, morphine use, maternal side effects (vomiting and pruritus), and Apgar scores. Mean differences (MDs) and odds ratios (ORs) were calculated using random effects modeling with 95% confidence intervals (CIs).Eleven articles met our inclusion criteria. Four hundred eighty patients were recruited in all study groups (233 patients in the HD and 247 in the LD groups). The mean time to first analgesic request was longer (MD, 4.49 hours [95% CI, 1.85-7.13]; P = 0.0008) in the HD group compared with the LD group. Pain scores (0-100 scale) at 12 hours (MD, 2.54 [95% CI, -2.55 to 7.63]; P = 0.33) as well as morphine consumption at 24 hours (MD, 1.31 mg [95% CI, -3.06 to 7.31]; P = 0.42) were not significantly different. The incidence of nausea or vomiting (OR, 0.44 [95% CI, 0.27-0.73]; P = 0.002) and pruritus (OR, 0.34 [95% CI, 0.20-0.59]; P = 0.0001) was lower in the LD group. The incidence of Apgar scores <7 at 1 minute was not different between groups (OR, 1.11 [95% CI, 0.06-20.49]; P = 0.94).This meta-analysis shows that HDs of intrathecal morphine prolong analgesia after cesarean delivery compared with lower doses. The MD of 4.5 hours (95% CI, 1.9-7.1 and 99% CI, 1.0-8.2 hours) of pain relief must be balanced against the increased risk of maternal pruritus and vomiting. Results from this study can be used by clinicians to weigh the benefits and potential side effects of using HDs of intrathecal morphine for cesarean delivery.

  View details for DOI 10.1213/ANE.0000000000001255

  View details for Web of Science ID 000378083300020

  View details for PubMedID 27089000

• Reply to Dr Kumar. Regional anesthesia and pain medicine McKenzie, C. P., Carvalho, B., Riley, E. T. 2016; 41 (4): 547-?

  View details for DOI 10.1097/AAP.0000000000000433

  View details for PubMedID 27315183

• Pharmacokinetics and placental transfer of magnesium sulfate in pregnant women AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Brookfield, K. F., Su, F., Elkomy, M. H., Drover, D. R., Lyell, D. J., Carvalho, B. 2016; 214 (6)

  Abstract

  Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite its widespread use, there are limited data about magnesium pharmacokinetics, and magnesium is prescribed empirically without dose adjustment for different indications.The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women and to determine key covariates that impact the pharmacokinetics.This is a prospective pharmacokinetic cohort study of pregnant women who were prescribed magnesium sulfate for preeclampsia, preterm labor, or extreme prematurity. Women received a 4-g loading dose and 2 g/h maintenance dose as clinically indicated. Maternal blood samples were obtained before and at multiple time points during and after magnesium administration. Cord blood also was sampled at delivery. A population pharmacokinetic approach that used a nonlinear mixed-effects modeling was used to characterize magnesium disposition.Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady-state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared with 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 ± 0.15.The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates.

  View details for DOI 10.1016/j.ajog.2015.12.060

  View details for Web of Science ID 000377222800023

  View details for PubMedID 26767791

• Amniotic fluid embolism: update and review CURRENT OPINION IN ANESTHESIOLOGY Sultan, P., Seligman, K., Carvalho, B. 2016; 29 (3): 288-296

  Abstract

  This article reviews our current understanding of amniotic fluid embolism (AFE), specifically the pathogenesis, treatment strategies, potential diagnostic tests and future therapeutic interventions for AFE.The incidence and case mortality of AFE varies widely because of heterogeneous diagnostic criteria and varying reporting mechanisms across the world. Amniotic fluid embolism is thought to be caused by abnormal activation of immunologic mechanisms following entry of fetal antigens into maternal circulation. Mast cell degranulation and complement activation may play a role in this anaphylactoid or systemic inflammatory response syndrome. Development of serum biomarkers and immune-histochemical staining techniques to aid diagnosis and develop treatments are under development and evaluation. Treatment of AFE is supportive and directed at treating cardiovascular, pulmonary, and coagulation derangements. Treatment for coagulopathy (fresh frozen plasma, cryoprecipitate/fibrinogen concentrate, and antifibrinolytics) should be initiated promptly. Recombinant factor VIIa may lead to increased mortality and should not routinely be used. C1 esterase inhibitors may be a potential therapeutic option.AFE is a devastating obstetric complication that requires early and aggressive intervention with optimal cardiopulmonary resuscitation, as well as hemorrhage and coagulopathy management. Biomarkers offer promise to aid the diagnosis of AFE, and immunomodulation may provide future therapeutic interventions to treat this lethal condition.

  View details for DOI 10.1097/ACO.0000000000000328

  View details for Web of Science ID 000375943300006

  View details for PubMedID 27153475

• Programmed intermittent epidural boluses for maintenance of labor analgesia: an impact study INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA McKenzie, C. P., Cobb, B., Riley, E. T., Carvalho, B. 2016; 26: 32-38

  Abstract

  The aim of this impact study was to compare the analgesic efficacy and side effect profile of programmed intermittent epidural boluses (PIEB)+patient-controlled epidural analgesia (PCEA) to continuous epidural infusion (CEI)+PCEA for maintenance labor analgesia after the introduction of PIEB at our institution.We conducted a retrospective analysis after replacing the background CEI with PIEB for our labor PCEA. Pre-change pump settings were CEI 12mL/h with PCEA (12mL bolus, lockout 15min); PIEB settings were a 9mL bolus every 45min with PCEA (10mL bolus, lockout 10min). We compared medical records of all women receiving epidural or combined spinal-epidural labor analgesia for vaginal delivery for two months before PIEB implementation to a two-month period of PIEB utilization following a five-month introductory familiarization period. The primary outcome was the proportion of women requiring rescue clinician boluses.Fewer patients in the PIEB group required rescue clinician boluses compared to the CEI group (12% vs. 19%, P=0.012). Time to first rescue bolus request and total bolus dose were not different. Peak (median [IQR]) pain scores were 2[0-5] with CEI and 0[0-4] with PIEB. There was no difference in instrumental delivery rates.Using PIEB compared to CEI as the background maintenance epidural analgesia method in conjunction with PCEA reduced the number of women requiring clinician rescue boluses while providing comparable labor analgesia. The findings of this clinical care impact study confirm the results of randomized controlled studies and suggest PIEB may be a preferable technique to CEI for the maintenance of labor analgesia.

  View details for DOI 10.1016/j.ijoa.2015.11.005

  View details for Web of Science ID 000376707400007

  View details for PubMedID 26775896

• Active Warming Utilizing Combined IV Fluid and Forced-Air Warming Decreases Hypothermia and Improves Maternal Comfort During Cesarean Delivery: A Randomized Control Trial ANESTHESIA AND ANALGESIA Cobb, B., Cho, Y., Hilton, G., Ting, V., Carvalho, B. 2016; 122 (5): 1490-1497

  Abstract

  The aim of this study was to apply both IV fluid and forced-air warming to decrease perioperative hypothermia in women undergoing cesarean delivery with spinal anesthesia. The authors hypothesize that combined-modality active warming (AW) would increase maternal temperature on arrival at the postanesthesia care unit (PACU) and decrease the incidence of maternal perioperative hypothermia (<36°C) compared with no AW.Forty-six healthy women (n = 23 per group) undergoing scheduled cesarean delivery with spinal anesthesia (10-12 mg bupivacaine + 10 μg fentanyl) were enrolled in this double-blinded, randomized controlled trial. Women were randomly assigned to receive either AW (warmed IV fluid and lower body forced-air warmer) or no warming (NW; blankets only). SpotOn Monitoring System was used to measure core temperature intraoperatively and for 1 hour postoperatively. The primary outcome measure was maternal temperature on arrival at the PACU. Secondary outcome measures included incidence of maternal perioperative hypothermia (<36°C), incidence of shivering, thermal comfort scores (0-100 scale), Apgar scores, and umbilical cord blood gas analysis.Demographic, obstetric, and surgical data were similar between study groups. The AW group (35.9°C ± 0.5°C) had a significantly higher temperature on arrival at the PACU compared with the NW group (35.5°C ± 0.5°C, P = 0.006; 95% confidence interval of mean difference, 0.1°C-0.7°C). Fourteen (64%) women in the AW group and 20 (91%) in the NW group were hypothermic during the study period (P = 0.031). Median (interquartile range) thermal comfort scores were 100 (95-100) in the AW group and 90 (70-100) in the NW group (P = 0.008). There were no significant differences in the incidence of intraoperative shivering (22% in the AW and 45% in the NW groups; P = 0.11), Apgar scores, or umbilical vein blood gas values between the study groups.Fluid combined with forced-air warming is effective in decreasing the incidence of perioperative hypothermia and improving maternal thermal comfort. However, despite multimodal AW, the majority of women became hypothermic, and shivering was not prevented. The findings suggest that combined AW for cesarean delivery with spinal anesthesia is difficult, and only modest benefit should be expected.

  View details for DOI 10.1213/ANE.0000000000001181

  View details for Web of Science ID 000374664400040

  View details for PubMedID 26895002

• The Wiley Spinal Catheter-Over-Needle System for Continuous Spinal Anesthesia A Case Series of 5 Cesarean Deliveries Complicated by Paresthesias and Headaches REGIONAL ANESTHESIA AND PAIN MEDICINE McKenzie, C. P., Carvalho, B., Riley, E. T. 2016; 41 (3): 405-410

  Abstract

  Intrathecal catheter devices using a catheter-over-needle design and softer flexible material have been introduced to clinical practice with the aim of reducing some of the complications such as postdural puncture headaches and paresthesias seen with previous versions of intrathecal catheters. We present a case series of 5 cesarean deliveries using the Wiley Spinal intrathecal system (Epimed, Johnstown, New York), which was recently approved by the US Food and Drug Administration. The intrathecal catheter system consists of a flexible 23-gauge intrathecal cannula over a 27-gauge pencil-point spinal needle. The placement of the intrathecal catheter was successful in all 5 cases; however, paresthesias in 3 cases and postdural puncture headaches in 2 cases complicated the placement and use of the device. Although the unique catheter-over-needle design facilitates the use of smaller-gauge spinal needles for dural puncture and larger-gauge catheters for medication administration, this case series using the Wiley Spinal suggests that paresthesias and postdural puncture headaches may still limit its widespread utilization. Future studies are needed to determine the true incidence of complications and to determine the role of continuous spinal anesthesia in the obstetric population.

  View details for DOI 10.1097/AAP.0000000000000367

  View details for Web of Science ID 000378154200017

  View details for PubMedID 26909488

• Pharmacokinetics and Pharmacodynamics of Drugs Commonly Used in Pregnancy and Parturition. Anesthesia and analgesia Ansari, J., Carvalho, B., Shafer, S. L., Flood, P. 2016; 122 (3): 786-804

  Abstract

  The majority of pregnant women will be treated with a medication other than a vitamin supplement during their pregnancy. Almost half of these medications will be category C or D according to the former US Food and Drug Administration classification system, indicating a lack of human studies with animal studies suggesting adverse fetal effects (category C) or evidence of risk in humans (category D). Changes in maternal physiology alter drug bioavailability, distribution, clearance, and thus the drug half-life in often unpredictable ways. For many drugs, good pharmacokinetic and pharmacodynamic data in pregnancy and parturition are lacking. For other drugs, recent studies demonstrate major pharmacokinetic or pharmacodynamic changes that require dose adjustment in pregnancy, but current dosing guidelines do not reflect these data. In this review, we address the principles that underlie changes in pharmacology and physiology in pregnancy and provide information on drugs that anesthesiologists commonly encounter in treating pregnant patients.

  View details for DOI 10.1213/ANE.0000000000001143

  View details for PubMedID 26891392

• A Longitudinal Study to Evaluate Pregnancy-Induced Endogenous Analgesia and Pain Modulation REGIONAL ANESTHESIA AND PAIN MEDICINE Carvalho, B., Granot, M., Sultan, P., Wilson, H., Landau, R. 2016; 41 (2): 175-180

  Abstract

  The phenomenon of pregnancy-induced analgesia has been demonstrated in animal models but less consistently in human studies. This study aimed to assess endogenous pain modulation, evaluating inhibitory and excitatory pain pathways, over the course of pregnancy and postpartum.Healthy pregnant women were approached for participation in this prospective multicenter cohort study. Conditioned pain modulation (CPM), mechanical temporal summation (mTS), and temperature that induced pain 6 out of 10 (pain-6) were assessed toward the end of each trimester of pregnancy (8-12, 18-22, and 36 weeks) and at 6 to 12 weeks postpartum. To assess how pregnancy affects CPM, mTS, and pain-6, a mixed-effects analysis of variance was performed.Thirty-three pregnant women were enrolled. Pregnancy did not significantly impact CPM (F3,39 = 0.30, P = 0.83, partial η = 0.02), and there was no significant difference between CPM scores in the third trimester compared with postpartum. The mTS scores and pain-6 ratings were also not significantly changed by pregnancy (F3,42 = 1.20, P = 0.32, partial η = 0.08; and F3,42 = 1.90, P = 0.14, partial η = 0.12, respectively).This is the first study to assess CPM and mTS changes in pregnancy and postpartum. Endogenous pain modulation evaluating both inhibitory and excitatory pain pathways did not significantly change during pregnancy or postpartum. Future studies are required to determine the magnitude and clinical significance of pregnancy-induced analgesia.

  View details for DOI 10.1097/AAP.0000000000000359

  View details for Web of Science ID 000378153300013

  View details for PubMedID 26866295

• Checklists and multidisciplinary team performance during simulated obstetric hemorrhage. International journal of obstetric anesthesia Hilton, G., Daniels, K., Goldhaber-Fiebert, S. N., Lipman, S., Carvalho, B., Butwick, A. 2016; 25: 9-16

  Abstract

  Checklists can optimize team performance during medical crises. However, there has been limited examination of checklist use during obstetric crises. In this simulation study we exposed multidisciplinary teams to checklist training to evaluate checklist use and team performance during a severe postpartum hemorrhage.Fourteen multidisciplinary teams participated in a postpartum hemorrhage simulation occurring after vaginal delivery. Before participating, each team received checklist training. The primary study outcome was whether each team used the checklist during the simulation. Secondary outcomes were the times taken to activate our institution-specific massive transfusion protocol and commence red blood cell transfusion, and whether a designated checklist reader was used.The majority of teams (12/14 (86%)) used the checklist. Red blood cell transfusion was administered by all teams. The median [IQR] times taken to activate the massive transfusion protocol and transfuse red blood cells were 5min 14s [3:23-6:43] and 14min 40s [12:56-17:28], respectively. A designated checklist reader was used by 7/12 (58%) teams that used the checklist. Among teams that used a checklist with versus without a designated reader, we observed no differences in the times to activate the massive transfusion protocol or to commence red blood cell transfusion (P>0.05).Although checklist training was effective in promoting checklist use, multidisciplinary teams varied in their scope of checklist use during a postpartum hemorrhage simulation. Future studies are required to determine whether structured checklist training can result in more standardized checklist use during a postpartum hemorrhage.

  View details for DOI 10.1016/j.ijoa.2015.08.011

  View details for PubMedID 26421705

• Remifentanil for labor analgesia: an evidence-based narrative review INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Van de Velde, M., Carvalho, B. 2016; 25: 66-74

  Abstract

  This manuscript reviews the available literature on remifentanil patient-controlled intravenous analgesia in labor focusing on efficacy and safety. Remifentanil compares favorably to other potent systemic opioids but with fewer opioid-related neonatal effects. However, remifentanil provides modest and short-lasting labor analgesia that is consistently inferior when compared to neuraxial analgesia. The initial analgesic effect provided with remifentanil also diminishes as labor progresses. In several studies, remifentanil induced significant respiratory depressant effects in laboring women with episodes of desaturation, hypoventilation and even apnea. Given the safety concerns, we recommend that remifentanil patient-controlled intravenous analgesia should not be a routine analgesia technique during labor. In cases where neuraxial analgesia is refused or contraindicated and the use of remifentanil justified, continuous and careful monitoring is required to detect respiratory depression to provide safe care of both the pregnant woman and unborn child.

  View details for DOI 10.1016/j.ijoa.2015.12.004

  View details for Web of Science ID 000370109900011

  View details for PubMedID 26777438

• Simulation Study Assessing Healthcare Provider's Knowledge of Pre-Eclampsia and Eclampsia in a Tertiary Referral Center. Simulation in healthcare Hilton, G., Daniels, K., Carvalho, B. 2016; 11 (1): 25-31

  Abstract

  The aim of the study was to assess knowledge of labor and delivery healthcare providers at a tertiary referral center in the management of pre-eclampsia and eclampsia.Thirteen multidisciplinary teams participated in this institutional review board-exempt study. Each group encountered the same scenario that involved a pre-eclamptic parturient who progressed to eclampsia. The participants were unaware of the scenario topic before the drill and that key interventions would be recorded and timed. Seven of 13 groups were randomized to have a cognitive aid available.Twelve of 13 groups attempted to lower the blood pressure; however, only 7 of 12 groups used the correct first-line antihypertensive medication as per the American College of Obstetricians and Gynecologists' guidelines. All groups requested and administered the correct bolus dose of magnesium (4-6 g intravenously). Only 2 of 13 groups took appropriate action to lower the blood pressure to a "safe range" before induction of general anesthesia, and 4 of the 13 anesthesiologists made drug modifications for induction of anesthesia. None of the 7 groups randomized to have a cognitive aid used it.Our results show widespread magnesium sulfate utilization; however, the use of antihypertensive medication is not universally administered in compliance with current guidelines. The importance of blood pressure management to reduce maternal morbidity and mortality in the setting of pre-eclampsia needs to be emphasized. Interestingly, availability of a cognitive aid did not ensure its utilization in this scenario. Findings suggest that for cognitive aids to be effectively used, it is essential that staff has been trained and become familiar with them before an emergent event.

  View details for DOI 10.1097/SIH.0000000000000125

  View details for PubMedID 26836465

• A Prospective Cohort Study Evaluating the Ability of Anticipated Pain, Perceived Analgesic Needs, and Psychological Traits to Predict Pain and Analgesic Usage following Cesarean Delivery. Anesthesiology research and practice Carvalho, B., Zheng, M., Harter, S., Sultan, P. 2016; 2016: 7948412-?

  Abstract

  Introduction. This study aimed to determine if preoperative psychological tests combined with simple pain prediction ratings could predict pain intensity and analgesic usage following cesarean delivery (CD). Methods. 50 healthy women undergoing scheduled CD with spinal anesthesia comprised the prospective study cohort. Preoperative predictors included 4 validated psychological questionnaires (Anxiety Sensitivity Index (ASI), Fear of Pain (FPQ), Pain Catastrophizing Scale, and Eysenck Personality Questionnaire) and 3 simple ratings: expected postoperative pain (0-10), anticipated analgesic threshold (0-10), and perceived analgesic needs (0-10). Postoperative outcome measures included post-CD pain (combined rest and movement) and opioid used for the 48-hour study period. Results. Bivariate correlations were significant with expected pain and opioid usage (r = 0.349), anticipated analgesic threshold and post-CD pain (r = -0.349), and perceived analgesic needs and post-CD pain (r = 0.313). Multiple linear regression analysis found that expected postoperative pain and anticipated analgesic needs contributed to post-CD pain prediction modeling (R (2) = 0.443, p < 0.0001); expected postoperative pain, ASI, and FPQ were associated with opioid usage (R (2) = 0.421, p < 0.0001). Conclusion. Preoperative psychological tests combined with simple pain prediction ratings accounted for 44% and 42% of pain and analgesic use variance, respectively. Preoperatively determined expected postoperative pain and perceived analgesic needs appear to be useful predictors for post-CD pain and analgesic requirements.

  View details for DOI 10.1155/2016/7948412

  View details for PubMedID 27143966

• Cardiac Arrest in Pregnancy: A Scientific Statement From the American Heart Association. Circulation Jeejeebhoy, F. M., Zelop, C. M., Lipman, S., Carvalho, B., Joglar, J., Mhyre, J. M., Katz, V. L., Lapinsky, S. E., Einav, S., Warnes, C. A., Page, R. L., Griffin, R. E., Jain, A., Dainty, K. N., Arafeh, J., Windrim, R., Koren, G., Callaway, C. W. 2015; 132 (18): 1747-1773

  Abstract

  This is the first scientific statement from the American Heart Association on maternal resuscitation. This document will provide readers with up-to-date and comprehensive information, guidelines, and recommendations for all aspects of maternal resuscitation. Maternal resuscitation is an acute event that involves many subspecialties and allied health providers; this document will be relevant to all healthcare providers who are involved in resuscitation and specifically maternal resuscitation.

  View details for DOI 10.1161/CIR.0000000000000300

  View details for PubMedID 26443610

• Utilization of spinal anesthesia for external cephalic version: a clinical practice cohort analysis INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Weiniger, C. F., Ezra, Y., Dunn, A. L., Carvalho, B. 2015; 24 (4): 389-390

  View details for DOI 10.1016/j.ijoa.2015.06.005

  View details for Web of Science ID 000364255300013

  View details for PubMedID 26303753

• The Effect of patient warming during Caesarean delivery on maternal and neonatal outcomes: a meta-analysis BRITISH JOURNAL OF ANAESTHESIA Sultan, P., Habib, A. S., Cho, Y., Carvalho, B. 2015; 115 (4): 500-510

  View details for DOI 10.1093/bja/aev325

  View details for Web of Science ID 000362305700007

  View details for PubMedID 26385660

• Scheduled acetaminophen with as-needed opioids compared to as-needed acetaminophen plus opioids for post-cesarean pain management. International journal of obstetric anesthesia Valentine, A. R., Carvalho, B., Lazo, T. A., Riley, E. T. 2015; 24 (3): 210-216

  Abstract

  Combination opioid-acetaminophen drugs are commonly used for pain management after cesarean delivery. The aim of this study was to determine if scheduled acetaminophen decreases opioid use compared to as-needed combination acetaminophen-opioid administration.We performed a retrospective chart review of women who underwent cesarean delivery before and after a clinical practice change. All patients received spinal anesthesia containing intrathecal morphine 200μg and scheduled non-steroidal anti-inflammatory drugs for 48h postoperatively. The first group (As-Needed Group, n=120) received combination oral opioid-acetaminophen analgesics as needed for breakthrough pain. The second group (Scheduled Group, n=120) received oral acetaminophen 650mg every 6h for 48h postoperatively with oral oxycodone administered as needed for breakthrough pain. The primary outcome was opioid use, measured in intravenous morphine mg equivalents, in the first 48h postoperatively.The Scheduled Group used 9.1±2.1mg (95% CI 5.0-13.2) fewer intravenous morphine equivalents than the As-Needed Group (P <0.0001) over the study period. Fewer patients in the Scheduled Group exceeded acetaminophen 3g daily compared to the As-Needed Group (P=0.008). Pain scores were similar between study groups.After cesarean delivery, scheduled acetaminophen results in decreased opioid use and more consistent acetaminophen intake compared to acetaminophen administered as needed via combination acetaminophen-opioid analgesics, without compromising analgesia.

  View details for DOI 10.1016/j.ijoa.2015.03.006

  View details for PubMedID 25936786

• Intact Survival After Obstetric Hemorrhage and 55 Minutes of Cardiopulmonary Resuscitation. A & A case reports Anast, N., Kwok, J., Carvalho, B., Lipman, S., Flood, P. 2015; 5 (1): 9-12

  Abstract

  Cardiac arrest occurs in approximately 1:12,000 parturients. Among nonpregnant patients who have in-hospital cardiac arrest, those whose spontaneous circulation does not return within 15 to 20 minutes have a high risk of death and disability, so life support efforts are generally stopped after this period. However, among parturients, witnessed in-hospital arrest is often reversible and has a better prognosis. We describe a successful clinical outcome after maternal cardiac arrest and 55 minutes of advanced cardiac life support. This case underscores the importance of high-quality cardiopulmonary resuscitation and raises questions about the appropriate duration of resuscitation efforts in otherwise healthy young mothers with a potentially reversible cause of arrest.

  View details for DOI 10.1213/XAA.0000000000000163

  View details for PubMedID 26125692

• Second-line uterotonics and the risk of hemorrhage-related morbidity. American journal of obstetrics and gynecology Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5): 642 e1-7

  Abstract

  Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD).We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells (RBC) transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders.The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 - 2.6).In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic.

  View details for DOI 10.1016/j.ajog.2015.01.008

  View details for PubMedID 25582104

• Second-line uterotonics and the risk of hemorrhage-related morbidity AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5)

  View details for DOI 10.1016/j.ajog.2015.01.008

  View details for Web of Science ID 000353598500025

  View details for PubMedID 25582104

• Magnesium sulfate exposure and neonatal intensive care unit admission at term. Journal of perinatology Girsen, A. I., Greenberg, M. B., El-Sayed, Y. Y., LEE, H., Carvalho, B., Lyell, D. J. 2015; 35 (3): 181-185

  Abstract

  Objective:The aim of this study was to investigate the effect of maternal magnesium sulfate (MgSO4) exposure for eclampsia prophylaxis on neonatal intensive care unit (NICU) admission rates for term newborns.Study Design:A secondary analysis of the Maternal-Fetal Medicine Unit Network Cesarean Registry, including primary and repeat cesarean deliveries, and failed and successful trials of labor after cesarean was conducted. Singleton pregnancies among women with preeclampsia and >37 weeks of gestation were included. Pregnancies with uterine rupture, chorioamnionitis and congenital malformations were excluded. Logistic regression analysis was used to determine associations between MgSO4 exposure and NICU admission. P<0.05 was considered statistically significant.Result:Two thousand one hundred and sixty-six term pregnancies of women with preeclampsia were included, of whom 1747 (81%) received MgSO4 for eclampsia prophylaxis and 419 (19%) did not. NICU admission rates were higher among newborns exposed to MgSO4 vs unexposed (22% vs 12%, P<0.001). After controlling for neonatal birth weight, gestational age and maternal demographic and obstetric factors, NICU admission remained significantly associated with antenatal MgSO4 exposure (adjusted odds ratio 1.9, 95% confidence interval 1.3 to 2.6, P<0.001). Newborns exposed to MgSO4 were more likely to have Apgar scores <7 at 1 and 5 min (15% vs 11% unexposed, P=0.01 and 3% vs 0.7% unexposed, P=0.008). There were no significant differences in NICU length of stay (median 5 (range 2 to 91) vs 6 (3 to 15), P=0.5).Conclusion:Antenatal maternal MgSO4 treatment was associated with increased NICU admission rates among exposed term newborns of mothers with preeclampsia. This study highlights the need for studies of maternal MgSO4 administration protocols that optimize maternal and fetal benefits and minimize risks.Journal of Perinatology advance online publication, 16 October 2014; doi:10.1038/jp.2014.184.

  View details for DOI 10.1038/jp.2014.184

  View details for PubMedID 25321647

• Perioperative considerations of the patient with malaria CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE Soltanifar, D., Carvalho, B., Sultan, P. 2015; 62 (3): 304-318

  Abstract

  Malaria is a life-threatening infectious disease caused by the Plasmodium parasite. Increased global travel has resulted in an escalation in the number of imported cases seen in developed countries. Patients with malaria may present for surgery in both endemic and non-endemic countries. This article reviews the perioperative considerations when managing patients with malaria.A literature review of anesthesia, perioperative care, and malaria-related articles was performed using the MEDLINE(®), EMBASE™, and Web of Science databases to identify relevant articles published in English during 1945-2014. Of the 303 articles matching the search criteria, 265 were excluded based on title and abstract. Eleven of the remaining 38 articles were relevant to anesthesia/perioperative care, and 27 articles were identified as having direct relevance to critical care medicine.The majority of imported malaria cases are caused by the falciparum species, which is associated with the greatest degree of morbidity and mortality. Various organ systems may be impacted as a consequence of changes in the structure and function of parasitized erythrocytes. Preoperative assessment should focus on establishing the species of malaria, the severity of disease, assessing the degree of end-organ impairment, and initiating treatment of malaria prior to surgery. Intravenous artesunate is the treatment of choice for severe falciparum malaria. Quinine is a second-line agent but has a narrow therapeutic index and particularly hazardous side effects. Intraoperatively, attention should focus on fluid management, dynamics of cerebral blood flow, and avoidance of hypoglycemia. Postoperative care of severe cases should ideally take place in a critical care unit as there may be ongoing requirements for multi-organ support, including renal replacement therapy, ventilation, and/or inotropic support. The safety of neuraxial anesthesia has not been well studied in the setting of malaria.Malaria remains one of the most devastating infectious diseases worldwide. Multiple organ systems can be impacted as a consequence of changes in structure and function of parasitized erythrocytes. Safe perioperative management requires a sound knowledge of all these potential system effects.

  View details for DOI 10.1007/s12630-014-0286-7

  View details for Web of Science ID 000349912900010

  View details for PubMedID 25471683

• Ondansetron pharmacokinetics in pregnant women and neonates: towards a new treatment for neonatal abstinence syndrome. Clinical pharmacology & therapeutics Elkomy, M., Sultan, P., Carvalho, B., Peltz, G., Wu, M., Clavijo, C., Galinkin, J., Drover, D. 2015; 97 (2): 167-176

  Abstract

  Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). The pharmacokinetics of ondansetron have not been characterized in pregnant women or in newborns. A nonlinear mixed-effects modeling approach was used to analyze plasma samples obtained from 20 nonpregnant and 40 pregnant women following a single administration of 4 or 8 mg ondansetron, from umbilical cord blood at delivery, and from neonates after birth. The analysis indicates that: ondansetron disposition is not affected by pregnancy (P > 0.05), but influenced by dose (P < 0.05), and is characterized by rapid transplacental transfer and longer elimination half-life in neonates compared to their mother. A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates.

  View details for DOI 10.1002/cpt.5

  View details for PubMedID 25670522

• The impact of breastfeeding on postpartum pain after vaginal and cesarean delivery. Journal of clinical anesthesia Wen, L., Hilton, G., Carvalho, B. 2015; 27 (1): 33-38

  Abstract

  Oxytocin may play a role in pain modulation. The analgesic effects of breastfeeding with its associated endogenous oxytocin release have not been well investigated. To determine the impact of breastfeeding on incisional, perineal, and cramping pain after cesarean and vaginal delivery.Institutional review board-approved prospective observational study.Labor and delivery and maternity wards.Healthy (American Society of Anesthesiology physical statuses 1 and 2) multiparous women who had cesarean (n = 40) and vaginal (n = 43) deliveries of singleton term infants and who were breastfeeding were enrolled.Women completed diaries to record incisional, perineal, or cramping pain scores 5 minutes before, during, and 5 minutes after breastfeeding.Demographic, obstetric, and neonatal variables, as well as analgesic use, were recorded.There was no difference in incisional pain before, during, and after breastfeeding in women post-cesarean delivery. Cramping pain was significantly increased during, as compared with before or after breastfeeding in both the vaginal (P < .001) and cesarean (P < .001) delivery cohorts.There was no analgesic effect on incisional pain during breastfeeding, indicating that endogenous oxytocin associated with breastfeeding may not play a significant role in postpartum cesarean wound pain modulation. Breastfeeding increased cramping pain after vaginal and cesarean delivery. The increase in cramping pain is most likely due to the breastfeeding-associated oxytocin surge increasing uterine tone.

  View details for DOI 10.1016/j.jclinane.2014.06.010

  View details for PubMedID 25468582

• Drug labeling in the practice of obstetric anesthesia AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Carvalho, B., Wong, C. A. 2015; 212 (1): 24-27

  Abstract

  This commentary outlines the current drug labeling practices that potentially compromise the clinical care of pregnant women and their children. We highlight the need for drug manufacturers and lawmakers to change the status quo and consider practices and regulations that will provide much-needed guidance to clinicians on the safe administration of drugs to certain populations such as pregnant and nursing women. Current practices have de facto contributed to a situation in which evidence is inadequate for individual physicians and patients to weigh the risks and benefits of drug administration and make informed decisions for drug use during pregnancy and lactation.

  View details for DOI 10.1016/j.ajog.2014.04.040

  View details for Web of Science ID 000346585700006

  View details for PubMedID 24799312

• Survey of Accepted Practice following Failed Intubation for Emergency Caesarean Delivery. Anesthesiology research and practice Soltanifar, D., Bogod, D., Harrison, S., Carvalho, B., Sultan, P. 2015; 2015: 192315-?

  Abstract

  Background. There is no consensus on the optimum management of failed tracheal intubation in emergency cesarean delivery performed for fetal compromise. The decision making process on whether to wake the patient or continue anesthesia with a supraglottic airway device is an underexplored area. This survey explores perceptions and experiences of obstetric anesthetists managing failed intubation. Methods. Anesthetists attending the Group of Obstetric Anaesthetists London (GOAL) Meeting in April 2014 were surveyed. Results. Ninety-three percent of anesthetists surveyed would not always wake the patient in the event of failed intubation for emergency cesarean delivery performed for fetal compromise. The median (interquartile range) of perceived acceptability of continuing anesthesia with a well-fitting supraglottic airway device, assessed using a visual analogue scale (0-100; 0 completely unacceptable; 100 completely acceptable), was 90 [22.5]. Preoperative patient consent regarding the use of a supraglottic airway device for surgery in the event of failed intubation would affect the decision making of 40% of anaesthetists surveyed. Conclusion. These results demonstrate that a significant body of anesthetists with a subspecialty interest in obstetric anesthesia in the UK would not always wake up the patient and would continue with anesthesia and surgery with a supraglottic airway device in this setting.

  View details for DOI 10.1155/2015/192315

  View details for PubMedID 25821464

• Elective ceasarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial reply BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY Cho, Y., Carvalho, B., Butwick, A., Blumenfeld, Y., Riley, E. 2014; 121 (13): 1748-1749

  View details for DOI 10.1111/1471-0528.13080

  View details for Web of Science ID 000345508600045

• Elective ceasarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial. BJOG : an international journal of obstetrics and gynaecology Cho, Y., Carvalho, B., Butwick, A., Blumenfeld, Y., Riley, E. 2014; 121 (13): 1748-?

  View details for DOI 10.1111/1471-0528.13079

  View details for PubMedID 25413764

• Evaluation of a prospectively administered written questionnaire to reduce the incidence of suspected latex anaphylaxis during elective cesarean delivery INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Peer, L., BREZIS, M. L., Shalit, M., Carvalho, B., Levin, P. D., Seri, O., Weiniger, C. F. 2014; 23 (4): 335-340

  Abstract

  Life-threatening anaphylaxis has been reported in women exposed to latex during surgery. We compared a written screening questionnaire to identify suspected latex sensitivity with a verbal inquiry used previously in a historical control group of women undergoing cesarean delivery to determine if the incidence of suspected latex anaphylaxis could be reduced.To identify suspected latex sensitivity among women undergoing elective cesarean delivery in a single-site tertiary unit, a nine-item written screening questionnaire was compared to historical use of a standard verbal inquiry "Are you allergic to medications or latex?". Women who had suspected latex sensitivity risk factors, or who had known latex allergy, underwent latex-free surgery. Women with suspected anaphylaxis during cesarean delivery were recommended to undergo allergen testing. The primary study outcome was suspected anaphylaxis incidence during the two periods: historical control January to December 2008, questionnaire March 2010 to April 2011.The questionnaire identified suspected latex sensitivity in 66 of 453 women (14.6%) who completed the questionnaire. The standard verbal inquiry group had identified 12 of 460 women (2.6%) with self-reported latex sensitivity. The incidence of suspected anaphylaxis during cesarean delivery was significantly lower during the questionnaire period when compared to historical controls (3/516, 0.6% vs. 11/460, 2.4%, P=0.015). For both groups, 13 of 14 women (92.9%) with suspected latex anaphylaxis were contactable; five of 13 (38.5%) had undergone allergen testing and all were positive for latex.Use of the written screening questionnaire was associated with fewer cases of suspected anaphylaxis during cesarean delivery compared with the historical control. Most women with suspected anaphylaxis did not perform allergy testing; however, all who did were positive for latex.

  View details for DOI 10.1016/j.ijoa.2014.05.009

  View details for Web of Science ID 000345203200007

  View details for PubMedID 25201315

• Risk factors for obstetric morbidity in patients with uterine atony undergoing Caesarean delivery BRITISH JOURNAL OF ANAESTHESIA Butwick, A. J., Carvalho, B., El-Sayed, Y. Y. 2014; 113 (4): 661-668

  View details for DOI 10.1093/bja/aeu150

  View details for Web of Science ID 000343087400019

• Risk factors for obstetric morbidity in patients with uterine atony undergoing caesarean delivery. British journal of anaesthesia Butwick, A. J., Carvalho, B., El-Sayed, Y. Y. 2014; 113 (4): 661-668

  Abstract

  Uterine atony (UA) is recognized as a leading cause of postpartum haemorrhage. However, knowledge of risk factors of haemorrhage-related morbidity among patients diagnosed with UA is uncertain. We investigated risk factors for haemorrhage-related morbidity among patients undergoing Caesarean delivery with UA.We conducted a secondary analysis of data sourced from a 4-yr observational study at 19 US academic centres. Patients with UA were identified based on receiving methylergonovine or carboprost. Our primary outcome (haemorrhage-related morbidity) included a composite of intra- or postpartum transfusion; Caesarean hysterectomy; uterine or hypogastric artery ligation; intensive care admission for: pulmonary oedema, coagulopathy, adult respiratory distress syndrome, postoperative ventilation, or invasive line monitoring.Among 57 182 patients who underwent Caesarean delivery, 2294 (4%) patients developed UA. Haemorrhage-related morbidity occurred in 450 (19.6%) patients with UA. The risk of haemorrhage-related morbidity was increased among African-Americans [adjusted odds ratio (aOR)=2.36; 95% confidence interval (CI)=1.73-3.23], Hispanics (aOR=1.4; 95% CI=1.04-1.9), women with multiple gestations (aOR=1.59; 95% CI=1.06-2.38), placenta praevia (aOR=4.89; 95% CI=3.04-7.87), patients with ASA class III (aOR=1.4; 95 CI=1.03-1.9), or ASA class IV (aOR=5.88; 95% CI=2.48-13.9), exposure to general anaesthesia (GA) (aOR=2.4; 95% CI=1.59-3.62) and combined general and regional anaesthesia (aOR=4.0; 95% CI=2.62-6.09), and ≥2 prior Caesarean deliveries (aOR=1.62; 95% CI=1.1-2.39).Among patients with UA undergoing Caesarean delivery, the risk of haemorrhage-related morbidity is increased in African-Americans, Hispanics, patients with multiple gestations, placenta praevia, ASA class III or IV, ≥2 prior Caesarean deliveries and those undergoing GA.

  View details for DOI 10.1093/bja/aeu150

  View details for PubMedID 24907281

• The dilemma of vaginal breech delivery worldwide. Lancet Weiniger, C. F., Carvalho, B. 2014; 384 (9949): 1183-?

  View details for DOI 10.1016/S0140-6736(14)61718-9

  View details for PubMedID 25263673

• A prospective observational study evaluating the ability of prelabor psychological tests to predict labor pain, epidural analgesic consumption, and maternal satisfaction. Anesthesia and analgesia Carvalho, B., Zheng, M., Aiono-Le Tagaloa, L. 2014; 119 (3): 632-640

  Abstract

  Psychological characteristics may affect interpretation and expression of pain. In this study, we sought to determine whether validated psychological tests predict the labor pain experience.Thirty-nine women with singleton term or post-term pregnancies undergoing induction of labor and successful vaginal delivery comprised the study population for this prospective observational study. Four validated psychological questionnaires (Anxiety Sensitivity Index [ASI], Fear of Pain [FPQIII], Pain Catastrophizing Scale [PCS]), and Eysenck Personality Questionnaire-Short Scale) and 3-scaled ratings of anxiety, confidence, and analgesic expectations were completed before onset of labor. Outcome measures included time to epidural analgesia request, pain at request for epidural analgesia, area under the pain × time curve (AUC), epidural local anesthetic use per hour, and maternal satisfaction with analgesia. The relationship between psychological predictors and clinical responses was assessed using bivariate correlations and regression modeling.Labor pain AUC (R = 0.45, P = 0.006), epidural local anesthetic use (R = 0.45, P = 0.019), and time to epidural analgesia request (R = 0.36, P = 0.015) were predicted with models incorporating some of the prelabor predictors. ASI, PCS, personality traits (lying, extroversion, psychoticism), and scaled ratings of anxiety, confidence, and analgesic expectations all contributed to the regression models of the outcomes. After proper model selection, neither FPQIII nor PCS was in the final multivariate linear regression model for labor pain AUC, although ASI was still included (P = 0.022). There was no significant correlation between ASI and self-reported anxiety (r = 0.03, P = 0.91).Personality traits (psychoticism, extroversion, and lying), as well as scaled ratings of anxiety, confidence, and analgesia expectations, show some potential to predict labor pain, epidural local anesthetic use, and time to epidural analgesia request. Although ASI was included in the final model for labor pain AUC, and FPQ and PCS were not, further study is required to determine whether ASI is a better predictor than FPQ or PCS.

  View details for DOI 10.1213/ANE.0000000000000357

  View details for PubMedID 25029661

• In reply. journal of hand surgery Carvalho, B., Ahsan, Z. S., Yao, J. 2014; 39 (9): 1888-1889

  View details for DOI 10.1016/j.jhsa.2014.06.124

  View details for PubMedID 25154582

• Prospective longitudinal cohort questionnaire assessment of labouring women's preference both pre- and post-delivery for either reduced pain intensity for a longer duration or greater pain intensity for a shorter duration. British journal of anaesthesia Carvalho, B., Hilton, G., Wen, L., Weiniger, C. F. 2014; 113 (3): 468-473

  Abstract

  Assessments of labour pain focus on pain intensity, not on duration. We aimed to assess the importance labouring women apply to pain intensity and duration before labour and post-delivery.Forty healthy women scheduled for labour induction were enrolled in this institutional review board-approved, prospective cohort study. Participants completed a pain preference questionnaire before active labour and within 24-h of delivery. The questionnaire consisted of seven stem questions that evaluated preference for pain intensity or duration. The pain preference ratio was determined by dividing the percentage of women who preferred reduced pain intensity for longer duration by that of those who preferred greater pain intensity for shorter duration (estimate of the odds). The overall hypothetical pain burden was determined by multiplying intensity by time. All questions presented the same overall hypothetical pain burden.Pain preference questionnaire scores demonstrated preference for low intensity pain for a longer duration rather than higher intensity for a shorter duration, both pre-labour (P<0.001) and post-delivery (P<0.001): the null median imputed as 3 of 6 (i.e. no preference for pain intensity over pain duration). This preference for pain duration over intensity was greater post-delivery compared with before labour (P=0.03). There was a significant correlation (r=0.83; P=0.04) between the pain preference ratio vs overall hypothetical pain burden before labour but not after delivery (r=0.28; P=0.59).In this preliminary labour assessment, women preferred lower pain intensity at the cost of longer pain duration. This suggests that pain intensity is the primary driver of hypothetical pain burden-a preference reinforced post-delivery.

  View details for DOI 10.1093/bja/aeu149

  View details for PubMedID 24907280

• Pharmacokinetics of prophylactic cefazolin in parturients undergoing cesarean delivery. Antimicrobial agents and chemotherapy Elkomy, M. H., Sultan, P., Drover, D. R., Epshtein, E., Galinkin, J. L., Carvalho, B. 2014; 58 (6): 3504-3513

  Abstract

  The objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.

  View details for DOI 10.1128/AAC.02613-13

  View details for PubMedID 24733461

• Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Elkomy, M. H., Sultan, P., Drover, D. R., Epshtein, E., Galinkin, J. L., Carvalho, B. 2014; 58 (6): 3504-3513

  View details for DOI 10.1128/AAC.02613-13

  View details for Web of Science ID 000338776900064

• Preferred spoken language mediates differences in neuraxial labor analgesia utilization among racial and ethnic groups. International journal of obstetric anesthesia Caballero, J. A., Butwick, A. J., Carvalho, B., Riley, E. T. 2014; 23 (2): 161-167

  Abstract

  The aims of this study were to assess racial/ethnic disparities for neuraxial labor analgesia utilization and to determine if preferred spoken language mediates the association between race/ethnicity and neuraxial labor analgesia utilization.We performed a retrospective cohort study of 3129 obstetric patients who underwent vaginal delivery at a tertiary care obstetric center. Bivariate analyses and multivariate logistic regression models were used to assess the relationships between race/ethnicity, preferred spoken language and neuraxial labor analgesia.Hispanic ethnicity (adjusted OR 0.77, 95% CI 0.61-0.98) and multiparity (adjusted OR 0.59, 95% CI 0.51-0.69) were independently associated with a reduced likelihood of neuraxial labor analgesia utilization. When preferred spoken language was controlled for, the effect of Hispanic ethnicity was no longer significant (adjusted OR 0.84, 95% CI 0.66-1.08) and only non-English preferred spoken language (adjusted OR 0.82, 95% CI 0.67-0.99) and multiparity (adjusted OR 0.59, 95% CI 0.51-0.69) were associated with a reduced likelihood of neuraxial labor analgesia utilization.This study provides evidence that preferred spoken language mediates the relationship between Hispanic ethnicity and neuraxial labor analgesia utilization.

  View details for DOI 10.1016/j.ijoa.2013.09.001

  View details for PubMedID 24703871

• Application of Echogenic Technology for Catheters Used in Ultrasound-Guided Continuous Peripheral Nerve Blocks JOURNAL OF ULTRASOUND IN MEDICINE Mariano, E. R., Yun, R. D., Kim, T. E., Carvalho, B. 2014; 33 (5): 905-911

  Abstract

  Limited data exist regarding the echogenicity of perineural catheters, but visualization is crucial to ensure accurate placement and efficacy of the subsequent local anesthetic infusion. The objective of this study was to determine the comparative echogenicity of various regional anesthesia catheters. In an in vitro porcine-bovine model, we compared the echogenic qualities of 3 commercially available regional anesthesia catheters and 1 catheter under development to optimize echogenicity. Outcomes included visual echogenicity ranking, image quality, and scanning time, as assessed by 2 blinded investigators. The experimental catheter was found to be more echogenic than 2 of the 3 comparators.

  View details for DOI 10.7863/ultra.33.5.905

  View details for Web of Science ID 000335620700018

  View details for PubMedID 24764346

• The society for obstetric anesthesia and perinatology consensus statement on the management of cardiac arrest in pregnancy. Anesthesia and analgesia Lipman, S., Cohen, S., Einav, S., Jeejeebhoy, F., Mhyre, J. M., Morrison, L. J., Katz, V., Tsen, L. C., Daniels, K., Halamek, L. P., Suresh, M. S., Arafeh, J., Gauthier, D., Carvalho, J. C., Druzin, M., Carvalho, B. 2014; 118 (5): 1003-1016

  Abstract

  This consensus statement was commissioned in 2012 by the Board of Directors of the Society for Obstetric Anesthesia and Perinatology to improve maternal resuscitation by providing health care providers critical information (including point-of-care checklists) and operational strategies relevant to maternal cardiac arrest. The recommendations in this statement were designed to address the challenges of an actual event by emphasizing health care provider education, behavioral/communication strategies, latent systems errors, and periodic testing of performance. This statement also expands on, interprets, and discusses controversial aspects of material covered in the American Heart Association 2010 guidelines.

  View details for DOI 10.1213/ANE.0000000000000171

  View details for PubMedID 24781570

• In response. Anesthesia and analgesia Macario, A., Carvalho, B., Tan, J. M., Sultan, P., El-Sayed, Y. Y. 2014; 118 (4): 884-885

  View details for DOI 10.1213/ANE.0000000000000114

  View details for PubMedID 24651247

• Analgesia following cesarean delivery: "Sometimes it takes a painful experience to make us change our ways" (proverbs 20:30). Israel Medical Association journal Weiniger, C. F., Carvalho, B. 2014; 16 (3): 171-172

  View details for PubMedID 24761706

• Incidence of Failure of Continuous Peripheral Nerve Catheters for Postoperative Analgesia in Upper Extremity Surgery. journal of hand surgery Ahsan, Z. S., Carvalho, B., Yao, J. 2014; 39 (2): 324-329

  Abstract

  To explore the incidence of failure of continuous peripheral nerve blockade (CPNB) after upper extremity operations.Patient data regarding postoperative CPNB were retrospectively obtained from our institution's regional anesthesia database. Documented information on the first postoperative day included pain assessment ratings (numerical verbal pain scale, patient-reported breakthrough pain upon perceived return of sensation, appearance of the catheter site, complications, time of return of sensation, day of return of sensation, residual blockade, patient satisfaction with the block, and whether patient would receive the block again).A total of 207 patients received CPNB for postoperative analgesia. The failure rate on the first postoperative day for infraclavicular (133 patients) and supraclavicular (58 patients) CPNB was 19% and 26%, respectively. Interscalene CPNB (16 patients) yielded 3 incidences of failure. No significant difference was found between supraclavicular and infraclavicular block techniques. In addition, no significant differences were found between the incidences of CPNB failures with potentially more painful surgeries involving bone compared with potentially less painful soft tissue procedures.The CPNB technique used for hand surgery postoperative analgesia was associated with nontrivial failure rates. The potential of CPNB failure and resulting breakthrough pain upon recovery from the primary nerve block is important to help establish patient expectations.Therapeutic IV.

  View details for DOI 10.1016/j.jhsa.2013.11.011

  View details for PubMedID 24480691

• Temporal stability of conditioned pain modulation in healthy women over four menstrual cycles at the follicular and luteal phases PAIN Wilson, H., Carvalho, B., Granot, M., Landau, R. 2013; 154 (12): 2633-2638

  Abstract

  Conditioned pain modulation (CPM) is a phenomenon that may be tested with a dynamic quantitative sensory test that assesses the inhibitory aspect of this pain modulatory network. Although CPM has been adopted as a clinical assessment tool in recent years, the stability of the measure has not been determined over long time intervals. The question of stability over time is crucial to our understanding of pain processing, and critical for the use of this tool as a clinical test. The primary objective of this study was to evaluate the stability of a CPM paradigm over time in healthy women. The secondary objective was to determine the potential influence of menstrual cycle phase on CPM. CPM was assessed 8 times in 22 healthy women during the follicular and luteal phases of 4 different cycles. The CPM effect was evidenced by a reduction in the pain rating of a test stimulus (6.3±0.2) with the introduction of a conditioning stimulus (5.0±0.3; P<0.001). The intraclass correlation coefficient for the CPM effect was modest (0.39; CI=0.23-0.59), suggesting that there is significant variation in CPM over long time intervals. CPM did not vary across phases in the menstrual cycle. Prior to the adoption of CPM as a clinical tool to predict individual risk and aid diagnosis, additional research is needed to establish the measurement properties of CPM paradigms and evaluate factors that influence CPM effects.

  View details for DOI 10.1016/j.pain.2013.06.038

  View details for Web of Science ID 000327596200011

  View details for PubMedID 23811040

• The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE Sultan, P., Murphy, C., Halpern, S., Carvalho, B. 2013; 60 (9): 840-854

  Abstract

  The influence that different concentrations of labour epidural local anesthetic have on assisted vaginal delivery (AVD) and many obstetric outcomes and side effects is uncertain. The purpose of this meta-analysis was to determine whether local anesthetics utilized at low concentrations (LCs) during labour are associated with a decreased incidence of AVD when compared with high concentrations (HCs).We searched PubMed, Ovid EMBASE, Ovid MEDLINE, CINAHL, Scopus, clinicaltrials.gov, and Cochrane databases for randomized controlled trials of labouring patients that compared LCs (defined as ≤ 0.1% epidural bupivacaine or ≤ 0.17% ropivacaine) of epidural local anesthetic with HCs for maintenance of analgesia. The primary outcome was AVD and secondary outcomes included Cesarean delivery, duration of labour, analgesia, side effects (nausea and vomiting, motor block, hypotension, pruritus, and urinary retention), and neonatal outcomes. The odds ratios (OR) or weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated using random effects modelling. An OR < 1 or a WMD < 0 favoured LCs.Eleven studies met our criteria (eight bupivacaine and three ropivacaine studies), providing 1,145 patients in the LCs group and 852 patients in the HCs group for analysis of the primary outcome. Low concentrations were associated with a reduction in the incidence of AVD (OR = 0.70; 95% CI 0.56 to 0.86; P < 0.001). There was no difference in the incidence of Cesarean delivery (OR 1.05; 95% CI 0.82 to 1.33; P = 0.7). The LCs group had less motor block (OR 3.9; 95% CI 1.59 to 9.55; P = 0.003), greater ambulation (OR 2.8; 95% CI 1.1 to 7.14; P = 0.03), less urinary retention (OR 0.42; 95% CI 0.23 to 0.73; P = 0.002), and a shorter second stage of labour (WMD -14.03; 95% CI -27.52 to -0.55; P = 0.04) compared with the HCs group. There were no differences between groups in pain scores, maternal nausea and vomiting, hypotension, fetal heart rate abnormalities, five-minute Apgar scores, and need for neonatal resuscitation. One-minute Apgar scores < 7 favoured the HCs group (OR 1.53; 95% CI 1.07 to 2.21; P = 0.02), and there was more pruritus in the LCs group (OR 3.36; 95% CI 1.00 to 11.31; P = 0.05).When compared with HCs of local anesthetics, the use of LCs for labour epidural analgesia reduces the incidence of AVD. This may be due to a reduction in the amount of local anesthetic used and the subsequent decrease in motor blockade. We therefore recommend the use of LCs of local anesthetics for epidural analgesia to optimize obstetric outcome.

  View details for DOI 10.1007/s12630-013-9981-z

  View details for Web of Science ID 000323340700002

  View details for PubMedID 23925722

• Brief report: a cost analysis of neuraxial anesthesia to facilitate external cephalic version for breech fetal presentation. Anesthesia and analgesia Carvalho, B., Tan, J. M., Macario, A., El-Sayed, Y. Y., Sultan, P. 2013; 117 (1): 155-159

  Abstract

  BACKGROUND:In this study, we sought to determine whether neuraxial anesthesia to facilitate external cephalic version (ECV) increased delivery costs for breech fetal presentation.METHODS:Using a computer cost model, which considers possible outcomes and probability uncertainties at the same time, we estimated total expected delivery costs for breech presentation managed by a trial of ECV with and without neuraxial anesthesia.RESULTS:From published studies, the average probability of successful ECV with neuraxial anesthesia was 60% (with individual studies ranging from 44% to 87%) compared with 38% (with individual studies ranging from 31% to 58%) without neuraxial anesthesia. The mean expected total delivery costs, including the cost of attempting/performing ECV with anesthesia, equaled $8931 (2.5th-97.5th percentile prediction interval $8541-$9252). The cost was $9207 (2.5th-97.5th percentile prediction interval $8896-$9419) if ECV was attempted/performed without anesthesia. The expected mean incremental difference between the total cost of delivery that includes ECV with anesthesia and ECV without anesthesia was $-276 (2.5th-97.5th percentile prediction interval $-720 to $112).CONCLUSION:The total cost of delivery in women with breech presentation may be decreased (up to $720) or increased (up to $112) if ECV is attempted/performed with neuraxial anesthesia compared with ECV without neuraxial anesthesia. Increased ECV success with neuraxial anesthesia and the subsequent reduction in breech cesarean delivery rate offset the costs of providing anesthesia to facilitate ECV.

  View details for DOI 10.1213/ANE.0b013e31828e5bc7

  View details for PubMedID 23592608

• A Cost Analysis of Neuraxial Anesthesia to Facilitate External Cephalic Version for Breech Fetal Presentation ANESTHESIA AND ANALGESIA Carvalho, B., Tan, J. M., Macario, A., El-Sayed, Y. Y., Sultan, P. 2013; 117 (1): 155-159

  View details for DOI 10.1213/ANE.0b013e31828e5bc7

  View details for Web of Science ID 000326512300025

• Response times for emergency cesarean delivery: use of simulation drills to assess and improve obstetric team performance JOURNAL OF PERINATOLOGY Lipman, S. S., Carvalho, B., Cohen, S. E., Druzin, M. L., Daniels, K. 2013; 33 (4): 259-263

  Abstract

  We documented time to key milestones and determined reasons for transport-related delays during simulated emergency cesarean.Prospective, observational investigation of delivery of care processes by multidisciplinary teams of obstetric providers on the labor and delivery unit at Lucile Packard Children's Hospital, Stanford, CA, USA, during 14 simulated uterine rupture scenarios. The primary outcome measure was the total time from recognition of the emergency (time zero) to that of surgical incision.The median (interquartile range) from time zero until incision was 9 min 27 s (8:55 to 10:27 min:s).In this series of emergency cesarean drills, our teams required approximately nine and a half minutes to move from the labor room to the nearby operating room (OR) and make the surgical incision. Multiple barriers to efficient transport were identified. This study demonstrates the utility of simulation to identify and correct institution-specific barriers that delay transport to the OR and initiation of emergency cesarean delivery.

  View details for DOI 10.1038/jp.2012.98

  View details for Web of Science ID 000316833300002

  View details for PubMedID 22858890

• Evaluation of experimental pain tests to predict labour pain and epidural analgesic consumption BRITISH JOURNAL OF ANAESTHESIA Carvalho, B., Zheng, M., Aiono-Le Tagaloa, L. 2013; 110 (4): 600-606

  Abstract

  The aim of this study was to determine whether experimental pain tests (EPTs) using heat, pressure, and i.v. cannulation before induction of labour reliably predict epidural analgesic use and pain intensity during labour.Fifty healthy women with singleton, term pregnancies admitted for scheduled induction of labour comprised the study population for this prospective case-controlled study. Heat and pressure threshold, tolerance, and suprathreshold VAS pain ratings were determined using a Medoc thermal sensory analyser and Somedic pressure algometer, respectively, after admission before induction of labour. Verbal pain scores (VPS 0-10) were determined during peripheral 18 G i.v. placement. Response outcomes included time to epidural request, pain at epidural, labour pain [area under the curve (AUC) and worse score], and epidural local anaesthetic use. Bivariate analysis followed by forward-backward multiple regression modelling was performed to determine relationships between EPTs and labour pain response measures.Heat tolerance was significantly correlated with worst labour pain (r=0.33, P=0.025) and pain with i.v. cannulation was correlated with time to epidural request (r=0.33, P=0.025). Multiple linear regression analysis found that labour pain AUC could be predicted with suprathreshold heat VAS, heat tolerance, and pressure tolerance (R(2)=0.26; P=0.007). There were strong correlations among the various pre-labour QSTs.Pre-labour EPTs were not very reliable at predicting the labour pain experience. Consistent with postoperative studies, suprathreshold and tolerance tests appear more useful than the threshold for predicting labour pain responses. Pain rating during i.v. cannulation (an easy, rapid, point-of-care test) showed some utility as an EPT.

  View details for DOI 10.1093/bja/aes423

  View details for Web of Science ID 000316700600015

  View details for PubMedID 23188095

• Transversus abdominis plane blocks for rescue analgesia following Cesarean delivery: a case series CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE Mirza, F., Carvalho, B. 2013; 60 (3): 299-303

  Abstract

  The role of routine transversus abdominis plane (TAP) blocks at the time of surgery for Cesarean delivery analgesia is uncertain. Previous studies have shown no additional analgesic benefit in patients receiving intrathecal morphine. We present a series of three cases where TAP blocks were used for rescue analgesia in patients who had severe post-Cesarean delivery pain after a standard spinal anesthetic containing bupivacaine 12 mg, fentanyl 10 μg, and morphine 200 μg.All three women experienced severe incisional pain in the postanesthetic care unit (PACU) after offset of spinal anesthesia. When the pain did not subside with intravenous opioids, the women were offered either additional intravenous opioids or a TAP block. They chose the latter. Bilateral TAP blocks were performed in a sterile posterior approach under ultrasound guidance with 0.375% ropivacaine 20 mL with epinephrine 1:400,000. All three patients experienced significant pain relief that lasted 10-19 hr and allowed for a timely discharge from the PACU.These cases show that TAP blocks may play a valuable role as a rescue analgesic technique rather than as a routine preemptive block for all Cesarean delivery patients. Use of TAP blocks reduced the need for escalating intravenous opioid doses and potential maternal opioid-related side effects. Rescue TAP blocks should be considered after Cesarean delivery when intrathecal morphine does not provide adequate pain relief or for early breakthrough pain after offset of spinal anesthesia.

  View details for DOI 10.1007/s12630-012-9866-6

  View details for Web of Science ID 000315578700011

  View details for PubMedID 23263981

• The Effect of OPRM1 and COMT Genotypes on the Analgesic Response to Intravenous Fentanyl Labor Analgesia ANESTHESIA AND ANALGESIA Landau, R., Liu, S., Blouin, J., Carvalho, B. 2013; 116 (2): 386-391

  Abstract

  IV fentanyl is used as a labor analgesic; however, few studies have reported the effects of IV fentanyl for early labor analgesia. We evaluated the analgesic response to IV fentanyl according to the combined effect of the single-nucleotide polymorphisms rs1799971 (c.118A/G, p. 40Asn/Asp) of the µ-opioid receptor gene (OPRM1) and rs4680 (c.472G/A, p.158Val/Met) of the catechol-O-methyltransferase (COMT) gene in women requesting labor analgesia.Labor analgesia was initiated with IV fentanyl 1.5 μg/kg. The primary outcome was analgesic success, defined as Numerical Verbal Pain Scale score≤10/100 15 minutes after the dose of fentanyl. Analgesic and side effect outcomes were compared according to OPRM1 and COMT genotypes.One hundred six women were enrolled and received IV fentanyl. IV analgesic success was 6% in women with the combination Asn/Asn-Met/Met (n=17) versus 20% in all other women combined (not Asn/Asn-Met/Met; P=0.30; difference=14%; 95% confidence interval [CI], -10% to 26%). IV analgesic success was 20% in women 118A/A (Asn/Asn) versus 21% for A/G and G/G of OPRM1 (P=0.82; difference=2%; 95% CI, -17% to 19%), and 10% in women 472A (Met/Met) versus 22% for A/G (Met/Val) and G/G (Val/Val) of COMT (P=0.24; difference=12%; 95% CI, -6% to 26%). Met/Met158 (n=31) versus Met/Val or Val/Val of COMT was associated with a smaller decrease in Numerical Verbal Pain Scale (24±18 vs 37±23; P=0.005; mean difference=-13; 99% CI, -25 to -1).This study was underpowered to draw firm conclusions on the influence of OPRM1 and COMT genotypes on labor analgesia with IV fentanyl. Further larger studies are needed to evaluate whether genotyping COMT alone or in combination with OPRM1 may have potentially useful clinical implications, such as not offering IV fentanyl in early labor to women who will most likely not benefit from it.

  View details for DOI 10.1213/ANE.0b013e318273f2c7

  View details for Web of Science ID 000314078300019

  View details for PubMedID 23302985

• Postoperative Subcutaneous Instillation of Low-Dose Ketorolac But Not Hydromorphone Reduces Wound Exudate Concentrations of Interleukin-6 and Interleukin-10 and Improves Analgesia Following Cesarean Delivery JOURNAL OF PAIN Carvalho, B., Lemmens, H. J., Ting, V., Angst, M. S. 2013; 14 (1): 48-56

  Abstract

  The objectives of this study were to test the effects of low-dose ketorolac and hydromorphone added to continuous local anesthetic wound instillation on surgical-site inflammatory mediators, postoperative pain, and opioid consumption. Sixty healthy women undergoing cesarean delivery were enrolled in this randomized, double-blinded study. Patients were randomized to receive a subcutaneous wound instillation of bupivacaine .5% at 10 mg/hour (active control), bupivacaine .5% with ketorolac .6 mg/hour, or bupivacaine .5% with hydromorphone .04 mg/hour for 48 hours postcesarean. Wound exudate was sampled at 4, 24, and 48 hours postcesarean and assayed for interleukins IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-12, tumor necrosis factor (TNF-α), interferon (INF-γ), and granulocyte-macrophage colony stimulating factor (GM-CSF). The addition of ketorolac to bupivacaine significantly decreased IL-6 (P = .012) and IL-10 (P = .005) compared to plain bupivacaine. Ketorolac, but not hydromorphone, was associated with a decrease in pain (P = .018) and analgesic use (P = .020) following cesarean delivery. Our results are compatible with the view that significant analgesics effects are mediated through local modulation of inflammatory events. Low-dose ketorolac administered into surgical wounds exert significant anti-inflammatory and analgesic effects and may be a valuable analgesic alternative to systemic nonsteroidal anti-inflammatories (NSAIDs) but with potentially fewer side effects.This article demonstrates that low-dose ketorolac administered into wounds modulates local inflammatory events, decreases postoperative pain, and reduces opioid consumption. These results suggest that administration of NSAIDs into surgical wounds may be an analgesic alternative to higher systemic dosing of NSAIDs.

  View details for DOI 10.1016/j.jpain.2012.10.002

  View details for Web of Science ID 000314081100006

  View details for PubMedID 23218935

• Transport Decreases the Quality of Cardiopulmonary Resuscitation During Simulated Maternal Cardiac Arrest ANESTHESIA AND ANALGESIA Lipman, S. S., Wong, J. Y., Arafeh, J., Cohen, S. E., Carvalho, B. 2013; 116 (1): 162-167

  Abstract

  The purpose of this study was to compare cardiopulmonary resuscitation (CPR) for simulated maternal cardiac arrest rendered during transport to the operating room with that rendered while stationary in the labor room. We hypothesized that the quality of CPR would deteriorate during transport.Twenty-six teams composed of 2 providers (obstetricians, nurses, or anesthesiologists) were randomized to perform CPR on the Laerdal Resusci Anne SkillReporter™ mannequin during transport or while stationary. The primary outcome measure was the percentage of correctly delivered compressions, defined as compression rate ≥100 beats per minute, correct sternal hand placement, compression depth ≥1.5 inches (3.8 cm), and proper release. Secondary outcomes included interruptions in compressions, position of providers relative to the mannequin during the transport phase, and ventilation tidal volume.The median (interquartile range) percentage of correctly rendered compressions during phase II was 32% (10%-63%) in the transport group and 93% (58%-100%) in the stationary group (P = 0.002, 95% confidence interval of mean difference = 22%-58%). The median (interquartile range) compression rates were 124 (110-140) beats per minute in the transport group and 123 (115-132) beats per minute in the stationary group (P = 0.531). Interruptions in CPR were observed in 92% of transport and 7% of stationary drills (P < 0.001, 95% confidence interval of difference = 61%-92%). During transport, 18 providers kneeled next to the mannequin, 2 straddled the mannequin, and 4 ran alongside the gurney. Median (interquartile range) tidal volume was 270 (166-430) mL in the transport group and 390 (232-513) mL in the stationary group (P = 0.03).Our data confirm our hypothesis and demonstrate that transport negatively affects the overall quality of resuscitation on a mannequin during simulated maternal arrest. These findings, together with previously published data on transport-related delays when moving from the labor room to the operating room further strengthen recommendations that perimortem cesarean delivery should be performed at the site of maternal cardiac arrest.

  View details for DOI 10.1213/ANE.0b013e31826dd889

  View details for Web of Science ID 000313145300020

  View details for PubMedID 23223106

• Measuring the labor pain experience: delivery still far off INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Cohen, S. E. 2013; 22 (1): 6-9

  View details for DOI 10.1016/j.ijoa.2012.10.002

  View details for Web of Science ID 000315829600002

  View details for PubMedID 23182607

• Intrathecal morphine 100 and 200 mu g for post-cesarean delivery analgesia: a trade-off between analgesic efficacy and side effects INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Wong, J. Y., Carvalho, B., Riley, E. T. 2013; 22 (1): 36-41

  Abstract

  Intrathecal morphine is highly effective for post-cesarean analgesia; however, the optimal dose is yet to be established. The aim of this study was to compare analgesia and side effects after a change in institutional practice to give 200 μg rather than 100 μg.We conducted a retrospective chart review of 241 patients who had an elective cesarean delivery and received either 100 or 200 μg of intrathecal morphine. The primary outcome variables were mean and peak verbal pain scores (0-10) and analgesic use (milligram-morphine equivalents). Postoperative administration of antiemetics, antipruritics and episodes of nausea or vomiting were recorded. Data are reported as mean±SD or percentages with P<0.05 considered statistically significant.Women receiving intrathecal morphine 200 μg had lower pain scores and opioid use compared with morphine 100 μg. Mean verbal pain scores were 1.6±1.1 versus 2.0±1.1 (P=0.01) and peak verbal pain scores were 4.9±2.0 versus 5.6±1.8, respectively (P=0.008). The group receiving 200 μg used less opioids in the first 24 h after surgery (44±35 versus 54±35 milligram-morphine equivalents, respectively, P=0.04) and received less intravenous opioids (18% versus 30%, P=0.02). However, women receiving intrathecal morphine 200 μg had more nausea (mean number of episodes of nausea 1.9±1.3 versus 1.6±1.3, P=0.037) and used more antiemetics (52% versus 24%, P<0.0001).Intrathecal morphine 200 μg provided better analgesia but with more nausea compared with morphine 100 μg. Our results can be used to help guide intrathecal morphine dosing in cesarean delivery based on patient preference for analgesia versus side effects.

  View details for DOI 10.1016/j.ijoa.2012.09.006

  View details for Web of Science ID 000315829600007

  View details for PubMedID 23159009

• Peripartum outcomes and anaesthetic management of parturients with moderate to complex congenital heart disease or pulmonary hypertension ANAESTHESIA Maxwell, B. G., El-Sayed, Y. Y., Riley, E. T., Carvalho, B. 2013; 68 (1): 52-59

  Abstract

  We performed a retrospective cohort analysis of pregnancies among women with moderate to complex congenital heart disease or pulmonary hypertension over a 12-year period, resulting in a cohort of 107 cases in 65 women. Neuraxial analgesia or anaesthesia was provided in 84%, 89% and 95% of spontaneous vaginal, operative vaginal and caesarean deliveries, respectively. The caesarean delivery rate was 43% compared to our institution average of 27% over the same period (p = 0.02), and 38% had operative vaginal deliveries compared to a 10.5% institution rate (p < 0.01). Invasive monitoring was used in 28% of all deliveries. There were one maternal and two neonatal deaths. This study provides detailed anaesthetic and peripartum management of women with congenital heart disease, a patient population in whom evidence-based practice and data are largely lacking. We observed a predominance of neuraxial anaesthetic techniques, increased caesarean and operative delivery rates, and favourable maternal and neonatal outcomes. Multicentre studies and registries to compare anaesthetic and obstetric management strategies further and delineate risk factors for adverse outcomes are required.

  View details for DOI 10.1111/anae.12058

  View details for Web of Science ID 000312304000012

  View details for PubMedID 23121251

• Collecting And Measuring Wound Exudate Biochemical Mediators In Surgical Wounds JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Carvalho, B., Clark, D. J., Yeomans, D., Angst, M. S. 2012

  View details for DOI 10.3791/50133

  View details for Web of Science ID 000209225700056

• Failed epidural top-up for cesarean delivery for failure to progress in labor: the case against single-shot spinal anesthesia INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B. 2012; 21 (4): 357-359

  View details for DOI 10.1016/j.ijoa.2011.06.012

  View details for Web of Science ID 000310409000010

  View details for PubMedID 22112917

• Does intrathecal analgesia reduce the subsequent minimum local analgesic concentration of epidural bupivacaine? ANAESTHESIA Carvalho, B., Landau, R. 2012; 67 (9): 1054-1055

  View details for DOI 10.1111/j.1365-2044.2012.07283.x

  View details for Web of Science ID 000307055100032

  View details for PubMedID 22861521

• Continuous spinal anesthesia for Cesarean hysterectomy and massive hemorrhage in a parturient with placenta increta CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE Sultan, P., Hilton, G., Butwick, A., Carvalho, B. 2012; 59 (5): 473-477

  Abstract

  We present anesthetic management using a continuous spinal anesthesia (CSA) technique in a patient with placenta increta who underwent elective Cesarean hysterectomy with massive postpartum hemorrhage.A 34-yr-old parturient (G3P2) was scheduled for Cesarean delivery and possible hysterectomy at 35(+3) weeks due to suspected placenta accreta. Her body mass index was 21 kg·m(-2) and she had a reassuring airway. Inadvertent dural puncture occurred during combined spinal-epidural (CSE) placement, and a decision was made to thread the epidural catheter and utilize a CSA technique. Following delivery of a healthy infant, morbid adherence of the placenta to the myometrium was confirmed, and a supracervical hysterectomy was performed. Eight litres of blood loss occurred postpartum requiring resuscitation with crystalloid 3,800 mL, colloid 1,500 mL, red blood cells 16 units, fresh frozen plasma 16 units, platelets 4 units, and cryoprecipitate 1 unit. The patient developed pulmonary edema requiring conversion to general anesthesia. The patient's cardiovascular status was stable throughout surgery, and her lungs were mechanically ventilated for 18 hr postoperatively in the intensive care unit. The intrathecal catheter was removed 24 hr after placement. She developed no adverse neurological sequelae and reported no postdural puncture headache. The pathology report confirmed placenta increta.A CSA technique may be a viable option in the event of inadvertent dural puncture during planned CSE or epidural placement in patients with a reassuring airway undergoing Cesarean delivery. Although a catheter-based neuraxial technique is appropriate for Cesarean hysterectomy for abnormal placentation, conversion to general anesthesia may be required in the event of massive perioperative hemorrhage and fluid resuscitation.

  View details for DOI 10.1007/s12630-012-9681-0

  View details for Web of Science ID 000302574200007

  View details for PubMedID 22395824

• The quality of CPR deteriorates during transport in simulated maternal arrests 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World Congress of Anaesthesiologists Wong, J., Lipman, S., Cohen, S., Arafeh, J., Carvalho, B. OXFORD UNIV PRESS. 2012: 201–202

  View details for Web of Science ID 000302299100334

• Non-invasive haemoglobin measurement in patients undergoing elective Caesarean section BRITISH JOURNAL OF ANAESTHESIA Butwick, A., Hilton, G., Carvalho, B. 2012; 108 (2): 271-277

  Abstract

  The ability to measure haemoglobin (Hb) real-time and non-invasively offers important clinical value in the assessment of acute changes in maternal Hb during the peripartum period. This study evaluates the Masimo Rainbow SET(®) Radical-7 Pulse CO-Oximeter in a pregnant population undergoing Caesarean section (CS).Fifty patients undergoing elective CS were enrolled in this prospective, controlled study and followed for 48 h after surgery. Non-invasive Masimo Hb (SpHb) values were compared with laboratory Hb values from venous blood samples drawn at baseline, immediately post-CS, and 24 h post-CS using the Bland-Altman plots. Longitudinal analysis of SpHb changes over time was performed using mixed-effects regression modelling.For the comparison between SpHb and laboratory Hb, SpHb displayed a significant positive bias at baseline {1.22 g dl(-1) [95% confidence interval (CI): 0.89-1.54]} and at 24 h post-CS [1.36 g dl(-1) (95% CI: 1.04-1.68)]. The bias immediately post-CS was 0.14 g dl(-1) (95% CI: -0.18 to 0.46). The limits of agreement at baseline, immediately post-CS, and at 24 h post-CS were: -0.9 and 3.33, -2.35 and 2.56, and -0.55 and 3.27 g dl(-1), respectively. The mean decrease in SpHb from baseline to 48 h post-CS was ∼1 g dl(-1).The variability in bias and limits of agreements of the Rainbow SET(®) Radical-7 Pulse CO-Oximeter SpHb may limit its clinical utility for assessing Hb concentration in patients undergoing elective CS. Modifications are needed in the calibration of the device to improve accuracy and precision in an obstetric setting. The study was registered at clinicaltrials.gov (NCT01108471) before participant enrolment: URL=http://clinicaltrials.gov/ct2/show/NCT01108471?term=butwick&rank=1.

  View details for DOI 10.1093/bja/aer373

  View details for Web of Science ID 000299414800015

  View details for PubMedID 22116296

• Spinal anaesthesia for caesarean delivery in a parturient with babesiosis and Lyme disease ANAESTHESIA Sultan, P., Green, C., Riley, E., Carvalho, B. 2012; 67 (2): 180-183

  Abstract

  We present a case of a parturient with babesiosis and Lyme disease who was scheduled for elective caesarean section. The caesarean section was performed under spinal anaesthesia, and the patient had a coronary artery dissection 4 days postoperatively. Neuraxial anaesthesia and possible mechanisms for the coronary artery dissection in a patient with babesiosis and Lyme disease are discussed.

  View details for DOI 10.1111/j.1365-2044.2011.06941.x

  View details for Web of Science ID 000299158200012

  View details for PubMedID 22251109

• Intrathecal fentanyl added to bupivacaine and morphine for cesarean delivery may induce a subtle acute opioid tolerance INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Drover, D. R., Ginosar, Y., Cohen, S. E., Riley, E. T. 2012; 21 (1): 29-34

  Abstract

  Previous studies have demonstrated that the addition of intrathecal fentanyl to a spinal anesthetic for cesarean delivery improves intraoperative analgesia. However, intrathecal fentanyl may induce acute tolerance to opioids. The objective of this study was to investigate whether the addition of intrathecal fentanyl to spinal anesthesia with intrathecal morphine increases postoperative analgesic requirements and pain scores.In this randomized, double-blinded study, 40 women having elective cesarean delivery were enrolled. Patients received spinal anesthesia with hyperbaric bupivacaine 12 mg, morphine 200 μg, and fentanyl 0, 5, 10 or 25 μg. Each patient received intravenous patient-controlled analgesia morphine for 24h postoperatively. Outcome measures included postoperative morphine usage and pain scores, as well as intraoperative pain, nausea, hypotension and vasopressor use.Total morphine use over the 24-h post-spinal study period was similar among the study groups (P=0.129). Postoperative pain scores were higher in patients receiving fentanyl 5, 10 and 25 μg compared to fentanyl 0 μg control group (P=0.003).The study results suggest that intrathecal fentanyl may induce acute tolerance to intrathecal morphine. However, because there was no difference in postoperative analgesia requirement and the difference in pain scores was small, the clinical significance of this finding is uncertain.

  View details for DOI 10.1016/j.ijoa.2011.09.002

  View details for Web of Science ID 000301325800006

  View details for PubMedID 22100823

• Ultrasound-guided popliteal nerve block in a patient with malignant degeneration of neurofibromatosis 1. Case reports in anesthesiology Desai, A., Carvalho, B., Hansen, J., Hill, J. 2012; 2012: 753769-?

  Abstract

  A 41-year-old female patient with neurofibromatosis 1 presented with new neurologic deficits secondary to malignant degeneration of a tibial lesion. Ultrasound mapping of the popliteal nerve revealed changes consistent with an intraneural neurofibroma. Successful popliteal nerve blockade was achieved under ultrasound guidance.

  View details for DOI 10.1155/2012/753769

  View details for PubMedID 22649742

• Collecting and measuring wound exudate biochemical mediators in surgical wounds. Journal of visualized experiments : JoVE Carvalho, B., Clark, D. J., Yeomans, D., Angst, M. S. 2012

  Abstract

  We describe a methodology by which we are able to collect and measure biochemical inflammatory and nociceptive mediators at the surgical wound site. Collecting site-specific biochemical markers is important to understand the relationship between levels in serum and surgical wound, determine any associations between mediator release, pain, analgesic use and other outcomes of interest, and evaluate the effect of systemic and peripheral drug administration on surgical wound biochemistry. This methodology has been applied to healthy women undergoing elective cesarean delivery with spinal anesthesia. We have measured wound exudate and serum mediators at the same time intervals as patient's pain scores and analgesics consumption for up to 48 hours post-cesarean delivery. Using this methodology we have been able to detect various biochemical mediators including nerve growth factor (NGF), prostaglandin E2 (PG-E2) substance P, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNFα, INFγ, G-CSF, GM-CSF, MCP-1 and MIP-1β. Studies applying this human surgical wound bioassay have found no correlations between wound and serum cytokine concentrations or their time-release profile (J Pain. 2008; 9(7):650-7).(1) We also documented the utility of the technique to identify drug-mediated changes in wound cytokine content.

  View details for DOI 10.3791/50133

  View details for PubMedID 23117346

• Epidural Catheter Removal in Patients on Warfarin Thromboprophylaxis A More Cautious Interpretation of Results Required? REGIONAL ANESTHESIA AND PAIN MEDICINE Carvalho, B., Mariano, E. R., Butwick, A. J. 2011; 36 (6): 632-632

  View details for DOI 10.1097/AAP.0b013e31822e0c7e

  View details for Web of Science ID 000296532100021

  View details for PubMedID 22024706

• Endotracheal tube cuff pressure monitoring: a review of the evidence. Journal of perioperative practice Sultan, P., Carvalho, B., Rose, B. O., Cregg, R. 2011; 21 (11): 379-386

  Abstract

  Tracheal intubation constitutes a routine part of anaesthetic practice both in the operating theatre as well as in the care of critically ill patients. The procedure is estimated to be performed 13-20 million times annually in the United States alone. There has been a recent renewal of interest in the morbidity associated with endotracheal tube cuff overinflation, particularly regarding the rationale and requirement for endotracheal tube cuff monitoring intra-operatively.

  View details for PubMedID 22165491

• Labor Room Setting Compared With the Operating Room for Simulated Perimortem Cesarean Delivery A Randomized Controlled Trial OBSTETRICS AND GYNECOLOGY Lipman, S., Daniels, K., Cohen, S. E., Carvalho, B. 2011; 118 (5): 1090-1094

  Abstract

  To compare the labor room and operating room for perimortem cesarean delivery during simulated maternal arrests occurring outside the operating room. We hypothesized transport to the operating room for perimortem cesarean delivery would delay incision and other important resuscitation milestones.We randomized 15 teams composed of obstetricians, nurses, anesthesiologists, and neonatal staff to perform perimortem cesarean delivery in the labor room or operating room. A manikin with an abdominal model overlay was used for simulated cesarean delivery. The scenario began in the labor room with maternal cardiopulmonary arrest and fetal bradycardia. The primary outcome was time to incision. Secondary outcomes included times to important milestones, percentage of tasks completed, and type of incision.The median (interquartile range) times from time zero to incision were 4:25 (3:59-4:50) and 7:53 (7:18-8:57) minutes in the labor room and operating room groups, respectively (P=.004). Fifty-seven percent of labor room teams and 14% of operating room teams achieved delivery within 5 minutes. Contacting the neonatal team, placing the defibrillator, resuming compressions after analysis, and endotracheal intubation all occurred more rapidly in the labor room group.Perimortem cesarean delivery performed in the labor room was significantly faster than perimortem cesarean delivery performed after moving to the operating room. Delivery within 5 minutes was challenging in either location despite optimal study conditions (eg, the manikin was light and easily moved; teams knew the scenario mandated perimortem cesarean delivery and were aware of being timed). Our findings imply that perimortem cesarean delivery during actual arrest would require more than 5 minutes and should be performed in the labor room rather than relocating to the operating room.

  View details for DOI 10.1097/AOG.0b013e3182319a08

  View details for Web of Science ID 000296292600017

  View details for PubMedID 22015877

• Neuraxial blockade for external cephalic version: a systematic review INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Sultan, P., Carvalho, B. 2011; 20 (4): 299-306

  Abstract

  The desire to decrease the number of cesarean deliveries has renewed interest in external cephalic version. The rationale for using neuraxial blockade to facilitate external cephalic version is to provide abdominal muscular relaxation and reduce patient discomfort during the procedure, so permitting successful repositioning of the fetus to a cephalic presentation. This review systematically examined the current evidence to determine the safety and efficacy of neuraxial anesthesia or analgesia when used for external cephalic version.A systematic literature review of studies that examined success rates of external cephalic version with neuraxial anesthesia was performed. Published articles written in English between 1945 and 2010 were identified using the Medline, Cochrane, EMBASE and Web of Sciences databases.Six, randomized controlled studies were identified. Neuraxial blockade significantly improved the success rate in four of these six studies. A further six non-randomized studies were identified, of which four studies with control groups found that neuraxial blockade increased the success rate of external cephalic version. Despite over 850 patients being included in the 12 studies reviewed, placental abruption was reported in only one patient with a neuraxial block, compared with two in the control groups. The incidence of non-reassuring fetal heart rate requiring cesarean delivery in the anesthesia groups was 0.44% (95% CI 0.15-1.32).Neuraxial blockade improved the likelihood of success during external cephalic version, although the dosing regimen that provides optimal conditions for successful version is unclear. Anesthetic rather than analgesic doses of local anesthetics may improve success. The findings suggest that neuraxial blockade does not compromise maternal or fetal safety during external cephalic version.

  View details for DOI 10.1016/j.ijoa.2011.07.001

  View details for Web of Science ID 000297087100006

  View details for PubMedID 21925869

• Prior epidural lidocaine alters the pharmacokinetics and drug effects of extended-release epidural morphine (DepoDur®) after cesarean delivery. Anesthesia and analgesia Atkinson Ralls, L., Drover, D. R., Clavijo, C. F., Carvalho, B. 2011; 113 (2): 251-258

  Abstract

  A potential physicochemical interaction between epidural local anesthetics and extended-release epidural morphine (EREM) could negate the sustained release. In this study, we sought to determine the pharmacokinetic and drug effects of prior epidural lidocaine administration on EREM.Thirty healthy women undergoing cesarean delivery were enrolled in this randomized study. Patients received 8 mg EREM 1 hour after either a combined spinal-epidural (intrathecal bupivacaine and fentanyl 20 μg with no epidural medication; group SE) or an epidural anesthetic (epidural 2% lidocaine with fentanyl 100 μg; group E). Maximal concentration (Cmax), time to Cmax (Tmax), and AUC(0-last) (area under the concentration-time curve until the last plasma concentration that was below the limit of quantitation) for morphine levels were determined from a plasma sample at 0, 5, 10, 15, and 30 minutes, and 1, 4, 8, 12, 24, 36, 48, and 72 hours. Drug effects including pain, analgesic use, and side effects were measured for 72 hours after cesarean delivery.Epidural lidocaine administration (20-35 mL) 1 hour before epidural EREM administration increased the Cmax in group E (11.1 ± 4.9) compared with group SE (8.3 ± 7.1 ng/mL) (P = 0.038). There were no significant effects on Tmax and AUC(0-last) of venous morphine between the groups (P > 0.05). There was an increased incidence in vomiting, oxygen use, and hypotension in group E (patients who received lidocaine before EREM).A large dose of epidural lidocaine 1 hour before EREM administration alters the pharmacokinetics and drug effects of EREM. Clinicians must apply caution when EREM is administered even 1 hour after an epidural lidocaine "top-up" for cesarean delivery.

  View details for DOI 10.1213/ANE.0b013e318222f59c

  View details for PubMedID 21642610

• Challenges in Interpreting Joined Allelic Combinations of OPRM1 and COMT Genes ANESTHESIA AND ANALGESIA Landau, R., Ortner, C., Carvalho, B. 2011; 113 (2): 432-432

  View details for DOI 10.1213/ANE.0b013e31821f154f

  View details for Web of Science ID 000293064500047

  View details for PubMedID 21788333

• Prior Epidural Lidocaine Alters the Pharmacokinetics and Drug Effects of Extended-Release Epidural Morphine (DepoDur (R)) After Cesarean Delivery ANESTHESIA AND ANALGESIA Ralls, L. A., Drover, D. R., Clavijo, C. F., Carvalho, B. 2011; 113 (2): 251-258

  View details for DOI 10.1213/ANE.0b013e318222f59c

  View details for Web of Science ID 000293064500009

• The Proseal laryngeal mask airway and elective caesarean section ANAESTHESIA AND INTENSIVE CARE Dyer, R. A., James, M. F., Butwick, A. J., Carvalho, B. 2011; 39 (4): 760-761

  View details for Web of Science ID 000293264000036

  View details for PubMedID 21823396

• Non-invasive measurement of hemoglobin during cesarean hysterectomy: a case series INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Butwick, A. J., Hilton, G., Riley, E. T., Carvalho, B. 2011; 20 (3): 240-245

  Abstract

  Obstetric patients diagnosed with abnormal placentation (placenta accreta, increta or percreta) are at increased risk of major postpartum hemorrhage and cesarean hysterectomy. Obstetric anesthesiologists are primarily involved in intraoperative transfusion management in these cases. Hemoglobin assessment is invaluable for assisting transfusion decision-making during the acute period of obstetric hemorrhage. However, laboratory and point-of-care tests of hemoglobin concentration are time-dependent and intermittent, and do not provide a real-time assessment of change during the acute phase of blood loss. A new non-invasive hemoglobin monitor has been introduced recently, which provides real-time measurement of hemoglobin values (SpHb) using multi-wavelength pulse co-oximetry. We present a review of five patients with suspected abnormal placentation who received SpHb monitoring during cesarean hysterectomy at our institution. We discuss the potential clinical utility of non-invasive hemoglobin monitoring for pregnant patients at high risk of obstetric hemorrhage, and the potential role of SpHb in guiding transfusion therapy.

  View details for DOI 10.1016/j.ijoa.2011.03.009

  View details for Web of Science ID 000293042800009

  View details for PubMedID 21640577

• Oxytocin for labour and caesarean delivery: implications for the anaesthesiologist CURRENT OPINION IN ANESTHESIOLOGY Dyer, R. A., Butwick, A. J., Carvalho, B. 2011; 24 (3): 255-261

  Abstract

  The implications of the obstetric use of oxytocin for obstetric anaesthesia practice are summarised. The review focuses on recent research on the uterotonic effects of oxytocin for prophylaxis and management of uterine atony during caesarean delivery.Oxytocin remains the first-line agent in the prevention and management of uterine atony. In-vitro and in-vivo studies show that prior exposure to oxytocin induces uterine muscle oxytocin receptor desensitization. This may influence oxytocin dosing for adequate uterine tone following delivery. Oxytocin has important cardiovascular side-effects (hypotension, tachycardia and myocardial ischaemia). Recent studies suggest that the effective dose of oxytocin for prophylaxis against uterine atony during caesarean delivery is significantly lower than the 5-10 IU historically used by anaesthesiologists. Slow administration of small bolus doses of oxytocin minimises maternal haemodynamic disturbance. Continuous oxytocin infusions are recommended for maintaining uterine tone after bolus administration, although ideal infusion rates are still to be established. The efficacy of the long-acting oxytocin analogue carbetocin requires further investigation. Recommendations are presented for oxytocin dosing during caesarean delivery.Oxytocin remains the first-line uterotonic after vaginal and caesarean delivery. Recent research elucidates the therapeutic range of oxytocin during caesarean delivery, as well as receptor desensitization. Evidenced-based protocols for the prevention and treatment of uterine atony during caesarean delivery are recommended.

  View details for DOI 10.1097/ACO.0b013e328345331c

  View details for Web of Science ID 000289974800004

  View details for PubMedID 21415725

• A sensitive assay for the quantification of morphine and its active metabolites in human plasma and dried blood spots using high-performance liquid chromatography-tandem mass spectrometry ANALYTICAL AND BIOANALYTICAL CHEMISTRY Clavijo, C. F., Hoffman, K. L., Thomas, J. J., Carvalho, B., Chu, L. F., Drover, D. R., Hammer, G. B., Christians, U., Galinkin, J. L. 2011; 400 (3): 715-728

  Abstract

  Opioids such as morphine are the cornerstone of pain treatment. The challenge of measuring the concentrations of morphine and its active metabolites in order to assess human pharmacokinetics and monitor therapeutic drugs in children requires assays with high sensitivity in small blood volumes. We developed and validated a semi-automated LC-MS/MS assay for the simultaneous quantification of morphine and its active metabolites morphine 3β-glucuronide (M3G) and morphine 6β-glucuronide (M6G) in human plasma and in dried blood spots (DBS). Reconstitution in water (DBS only) and addition of a protein precipitation solution containing the internal standards were the only manual steps. Morphine and its metabolites were separated on a Kinetex 2.6-μm PFP analytical column using an acetonitrile/0.1% formic acid gradient. The analytes were detected in the positive multiple reaction mode. In plasma, the assay had the following performance characteristics: range of reliable response of 0.25-1000 ng/mL (r(2) > 0.99) for morphine, 1-1,000 ng/mL (r(2) > 0.99) for M3G, and 2.5-1,000 ng/mL for M6G. In DBS, the assay had a range of reliable response of 1-1,000 ng/mL (r(2) > 0.99) for morphine and M3G, and of 2.5-1,000 ng/mL for M6G. For inter-day accuracy and precision for morphine, M3G and M6G were within 15% of the nominal values in both plasma and DBS. There was no carryover, ion suppression, or matrix interferences. The assay fulfilled all predefined acceptance criteria, and its sensitivity using DBS samples was adequate for the measurement of pediatric pharmacokinetic samples using a small blood of only 20-50 μL.

  View details for DOI 10.1007/s00216-011-4775-z

  View details for Web of Science ID 000289297000015

  View details for PubMedID 21400080

• Crossing the pond: applying to train in the USA. British journal of hospital medicine Qadan, M., Kastenberg, Z., Carvalho, B., Sultan, P. 2011; 72 (4): M50-2

  View details for PubMedID 21537230

• ED50 and ED95 of Intrathecal Bupivacaine in Morbidly Obese Patients Undergoing Cesarean Delivery ANESTHESIOLOGY Carvalho, B., Collins, J., Drover, D. R., Ralls, L. A., Riley, E. T. 2011; 114 (3): 529-535

  Abstract

  It has been suggested that morbidly obese parturients may require less local anesthetic for spinal anesthesia. The aim of this study was to determine the effective dose (ED(50)/ED(95)) of intrathecal bupivacaine for cesarean delivery in morbidly obese patients.Morbidly obese parturients (body mass index equal to or more than 40) undergoing elective cesarean delivery were enrolled in this double-blinded study. Forty-two patients were randomly assigned to receive intrathecal hyperbaric bupivacaine in doses of 5, 6, 7, 8, 9, 10, or 11 mg (n = 6 per group) coadministered with 200 μg morphine and 10 μg fentanyl. Success (induction) was defined as block height to pinprick equal to or more than T6 and success (operation) as success (induction) plus no requirement for epidural supplementation throughout surgery. The ED(50)/ED(95) values were determined using a logistic regression model.ED(50) and ED(95) (with 95% confidence intervals) for success (operation) were 9.8 (8.6-11.0) and 15.0 (10.0-20.0), respectively, and were similar to corresponding values of a nonobese population determined previously using similar methodology. We were unable to measure ED(50)/ED(95) values for success (induction) because so few blocks failed initially, even at the low-dose range. There were no differences with regard to secondary outcomes (i.e., hypotension, vasopressor use, nausea, and vomiting).Obese and nonobese patients undergoing cesarean delivery do not appear to respond differently to modest doses of intrathecal bupivacaine. This dose-response study suggests that doses of intrathecal bupivacaine less than 10 mg may not adequately ensure successful intraoperative anesthesia. Even when the initial block obtained with a low dose is satisfactory, it will not guarantee adequate anesthesia throughout surgery.

  View details for DOI 10.1097/ALN.0b013e318209a92d

  View details for Web of Science ID 000287660300012

  View details for PubMedID 21307769

• Anticoagulant and antithrombotic drugs in pregnancy: what are the anesthetic implications for labor and cesarean delivery? JOURNAL OF PERINATOLOGY Butwick, A. J., Carvalho, B. 2011; 31 (2): 73-84

  Abstract

  Neuraxial anesthetic techniques are commonly used during the peripartum period to provide effective pain relief for labor and anesthesia during cesarean delivery. Major neurologic complications are rare after neuraxial anesthesia; however, spinal hematoma is associated with catastrophic neurologic outcomes (including lower-limb paralysis). Anticoagulant and antithrombotic drugs can increase the risk of spinal hematoma after neuraxial anesthesia, and better understanding of the pharmacokinetics and pharmacodynamics of anticoagulants has led to greater appreciation for withholding anticoagulation before and after neuraxial anesthesia. A number of national anesthetic societies have produced guidelines for performing neuraxial anesthesia in patients receiving anticoagulation. However, there is limited information about anesthetic implications of anticoagulation during the peripartum period. This article will review the risks of spinal hematoma after neuraxial anesthesia in pregnant patients; current guidelines for neuraxial anesthesia for anticoagulated patients; and relevant pharmacological data of specific anticoagulant and antithrombotic drugs in pregnancy.

  View details for DOI 10.1038/jp.2010.64

  View details for Web of Science ID 000286808100001

  View details for PubMedID 20559281

• Neuraxial Morphine and Respiratory Depression Finding the Right Balance DRUGS Sultan, P., Gutierrez, M. C., Carvalho, B. 2011; 71 (14): 1807-1819

  Abstract

  Morphine is a drug commonly administered via the epidural or intrathecal route, and is regarded by many as the 'gold-standard' single-dose neuraxial opioid due to its postoperative analgesic efficacy and prolonged duration of action. However, respiratory depression is a recognized side effect of neuraxial morphine administered in the perioperative setting. We conducted an extensive review of articles published since 1945 that examine respiratory depression or failure associated with perioperative intrathecal or epidural morphine use. Respiratory depression was previously thought to result from the interaction of opioid in the cerebrospinal fluid with ventral medullary opioid receptors. More recently, the preBötzinger complex located in the medulla has been identified as the site responsible for the decrease in respiratory rate following systemic administration of opioids. Neurons in the preBötzinger complex expressing neurokinin-1 receptors are selectively inhibited by opioids, and therefore are the mediators of opioid-induced respiratory depression. Epidural, intrathecal and plasma pharmacokinetics of opioids are complex, vary between neuraxial compartments, and can even differ within the epidural space itself depending upon level of insertion. Caution should be exercised when prescribing systemic opioids (intravenous or oral) in addition to neuraxial morphine as this can compound the potential for early or delayed respiratory depression. There is a wide range of incidences for respiratory depression following neuraxial morphine in a perioperative setting. Disparity of definitions used for the diagnosis of respiratory depression in the literature precludes identification of the exact incidence of this rare event. The optimal neuraxial opioid dose is a balance between the conflicting demands of providing optimal analgesia while minimizing dose-related adverse effects. Dose-response studies show that neuraxial morphine appears to have an analgesic efficacy 'ceiling'. The optimal 'single-shot' intrathecal dose appears to be 0.075-0.15 mg and the ideal 'single-shot' epidural morphine dose is 2.5-3.75 mg. Analgesic efficacy studies have not been adequately powered to show differences in the incidence of clinically significant respiratory depression. Opioid antagonists such as naloxone to prevent or treat opioid-induced respiratory depression have a number of limitations. Researchers have recently focused on non-opioid drugs such as serotonin receptor agonists. Early evidence suggests that ampakine (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA]) receptor modulators may be effective at reducing opioid-induced respiratory depression while maintaining analgesia. Sodium/proton exchanger type 3 (NHE3) inhibitors, which act centrally on respiratory pathways, also warrant further study.

  View details for Web of Science ID 000296069300002

  View details for PubMedID 21942973

• The Role of Interleukin-1 in Wound Biology. Part I: Murine In Silico and In Vitro Experimental Analysis ANESTHESIA AND ANALGESIA Hu, Y., Liang, D., Li, X., Liu, H., Zhang, X., Zheng, M., Dill, D., Shi, X., Qiao, Y., Yeomans, D., Carvalho, B., Angst, M. S., Clark, J. D., Peltz, G. 2010; 111 (6): 1525-1533

  Abstract

  Wound healing is a multistep, complex process that involves the coordinated action of multiple cell types. Conflicting results have been obtained when conventional methods have been used to study wound biology. Therefore, we analyzed the wound response in a mouse genetic model.We analyzed inflammatory mediators produced within incisional wounds induced in 16 inbred mouse strains. Computational haplotype-based genetic analysis of inter-strain differences in the level of production of 2 chemokines in wounds was performed. An in vitro experimental analysis system was developed to investigate whether interleukin (IL)-1 could affect chemokine production by 2 different types of cells that are present within wounds.The level of 2 chemokines, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein 1α, exhibited very large (75- and 463-fold, respectively) interstrain differences within wound tissue across this inbred strain panel. Genetic variation within Nalp1, an inflammasome component that regulates IL-1 production, correlated with the interstrain differences in KC and macrophage inhibitory protein 1α production. Consistent with the genetic correlation, IL-1β was shown to stimulate KC production by murine keratinocyte and fibroblast cell lines in vitro.Genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production by altering the amount of IL-1 produced.

  View details for DOI 10.1213/ANE.0b013e3181f5ef5a

  View details for Web of Science ID 000284973300032

  View details for PubMedID 20889942

• Continuous Subcutaneous Instillation of Bupivacaine Compared to Saline Reduces Interleukin 10 and Increases Substance P in Surgical Wounds After Cesarean Delivery ANESTHESIA AND ANALGESIA Carvalho, B., Clark, D. J., Yeomans, D. C., Angst, M. S. 2010; 111 (6): 1452-1459

  Abstract

  Recent evidence suggests that locally delivered local anesthetics may exert tissue-damaging effects such as chondrolysis after intraarticular injection. Alteration of the inflammatory response is a potential mechanism for local anesthetic-induced tissue toxicity. In this study, we tested the effects of continuous local anesthetic infiltration on the release of inflammatory and nociceptive mediators in skin wounds after cesarean delivery.Thirty-eight healthy women undergoing cesarean delivery with spinal anesthesia were enrolled in this study, and were randomized to receive subcutaneous surgical wound infiltration with bupivacaine 5 mg/mL or saline at 2 mL/h for 24 hours after cesarean delivery. Wound exudate was sampled at 1, 3, 5, 7, and 24 hours after cesarean delivery using a subcutaneous wound drain technique. Cytokines, chemokines, substance P, prostaglandin E(2), and nerve growth factor were assayed using multiplex Bio-Plex® (Bio-Rad, Hercules, CA) and enzyme-linked immunosorbent assays.Bupivacaine wound infusion resulted in a significant decrease of interleukin 10 and increase of substance P in wounds compared with saline infusion (area under the 24-hour concentration-time curve; P < 0.001). No statistically significant differences were detected for other cytokines, nerve growth factor, and prostaglandin E(2).This study demonstrates that the continuous administration of clinically used doses of bupivacaine into wounds affects the local composition of wound mediators. Observed changes in interleukin 10 are compatible with a disruption of antiinflammatory mechanisms. Whether such modulation combined with the release of the proinflammatory mediator substance P results in an overall proinflammatory wound response will require future studies of wound healing.

  View details for DOI 10.1213/ANE.0b013e3181f579de

  View details for Web of Science ID 000284973300020

  View details for PubMedID 20861424

• The Role of Interleukin-1 in Wound Biology. Part II: In Vivo and Human Translational Studies ANESTHESIA AND ANALGESIA Hu, Y., Liang, D., Li, X., Liu, H., Zhang, X., Zheng, M., Dill, D., Shi, X., Qiao, Y., Yeomans, D., Carvalho, B., Angst, M. S., Clark, J. D., Peltz, G. 2010; 111 (6): 1534-1542

  Abstract

  In the accompanying paper, we demonstrate that genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production through altering the amount of interleukin (IL)-1 produced. We further investigate the role of IL-1 in incisional wound biology and its effect on wound chemokine production in vivo and whether this mechanism could be active in human subjects.A well-characterized murine model of incisional wounding was used to assess the in vivo role of IL-1 in wound biology. The amount of 7 different cytokines/chemokines produced within an experimentally induced skin incision on a mouse paw and the nociceptive response was analyzed in mice treated with an IL-1 inhibitor. We also investigated whether human IL-1β or IL-1α stimulated the production of chemokines by primary human keratinocytes in vitro, and whether there was a correlation between IL-1β and chemokine levels in 2 experimental human wound paradigms.Administration of an IL-1 receptor antagonist to mice decreased the nociceptive response to an incisional wound, and reduced the production of multiple inflammatory mediators, including keratinocyte-derived chemokine (KC) and macrophage inhibitory protein (MIP)-1α, within the wounds. IL-1α and IL-1β stimulated IL-8 and GRO-α (human homologues of murine keratinocyte-derived chemokine) production by primary human keratinocytes in vitro. IL-1β levels were highly correlated with IL-8 in human surgical wounds, and at cutaneous sites of human ultraviolet B-induced sunburn injury.IL-1 plays a major role in regulating inflammatory mediator production in wounds through a novel mechanism; by stimulating the production of multiple cytokines and chemokines, it impacts clinically important aspects of wound biology. These data suggest that administration of an IL-1 receptor antagonist within the perioperative period could decrease postsurgical wound pain.

  View details for DOI 10.1213/ANE.0b013e3181f691eb

  View details for Web of Science ID 000284973300033

  View details for PubMedID 20889944

• Effect of a Preemptive Femoral Nerve Block on Cytokine Release and Hyperalgesia in Experimentally Inflamed Skin of Human Volunteers REGIONAL ANESTHESIA AND PAIN MEDICINE Carvalho, B., Aleshi, P., Horstman, D. J., Angst, M. S. 2010; 35 (6): 514-519

  Abstract

  Tissue injury is associated with the local release of inflammatory and nociceptive mediators and the development of hyperalgesia. It is unclear whether interrupting neuronal signaling using regional anesthetic techniques at the time of the injury modifies local nociceptive and inflammatory processes. The aim of this study was to determine whether a peripheral nerve block at the time of tissue injury could modify the development of wound hyperalgesia and the local release of inflammatory and nociceptive mediators.Twelve healthy volunteers participated in this controlled, crossover, randomized study. A femoral nerve block or a sham block was established before inducing an experimental UVB burn on the thigh. Twenty-four hours later, the interstitial wound fluid was sampled, and mechanical and heat pain thresholds were assessed. Wound fluid concentrations of an array of cytokines, chemokines, nerve growth factor, prostaglandin E2, and substance P were determined.Skin inflammation was associated with the release of inflammatory and nociceptive mediators and resulted in significant tissue hyperalgesia (P < 0.001). However, the presence of a fully established peripheral nerve block at the time of tissue injury did not alter the development of hyperalgesia after regression of the block. Similarly, the presence of a peripheral nerve block did not modify the release of inflammatory or nociceptive mediators.These findings suggest that a preemptive, single-shot peripheral nerve block minimally affects wound hyperalgesia and inflammation. Continuous nerve block techniques may be better suited to alter nociceptive and inflammatory events in wounds beyond the duration of the block.

  View details for DOI 10.1097/AAP.0b013e3181faa107

  View details for Web of Science ID 000284301300008

  View details for PubMedID 20975465

• Retrospective analysis of anesthetic interventions for obese patients undergoing elective cesarean delivery JOURNAL OF CLINICAL ANESTHESIA Butwick, A., Carvalho, B., Danial, C., Riley, E. 2010; 22 (7): 519-526

  Abstract

  To examine the relationship between body mass index (BMI), perioperative times, and anesthetic interventions in patients undergoing elective cesarean delivery.Retrospective chart review.University-affiliated hospital.All patients were ranked according to BMI (kg/m(2)) at the time of delivery. The BMI groups were designated a priori: ≤ 29.9 kg/m(2) (Group C); 30-34.9 kg/m(2) (Group I); 35-39.9 kg/m(2) (Group II), and ≥ 40 kg/m(2) (Group III). One hundred patients (25 pts per group) underwent elective cesarean delivery. Data collected included anesthetic technique, perioperative times, anesthesia-related costs, and neonatal outcomes.A higher percentage of Group III patients (60%) received combined spinal-epidural (CSE) anesthesia than did Group C or Group I (18% and 16%, respectively; P < 0.05). The total intraoperative period was significantly longer in Group III (101 min) compared with Groups C, I, and II (81 min, 90 min, and 92 min, respectively; P < 0.05). Total intraoperative time increased significantly with BMI (R = 0.394 kg/m(2); P < 0.001). The highest anesthesia-related costs during the study were generated by patients with BMI ≥ 40 kg/m(2).Our single-center experience showed that choice of anesthetic technique (CSE vs. spinal anesthesia) varies according to obesity class. Longer intraoperative periods must be considered in deciding upon the mode of anesthesia for patients with BMI ≥ 40 kg/m(2) who undergo elective cesarean delivery.

  View details for DOI 10.1016/j.jclinane.2010.01.005

  View details for Web of Science ID 000284791000006

  View details for PubMedID 21056808

• A practical guide to undertaking out of programme experience in the United States of America. British journal of hospital medicine Sultan, P., Qadan, M., Pushpanathan, E., Carvalho, B. 2010; 71 (10): M158-9

  View details for PubMedID 20944517

• Deficits in the provision of cardiopulmonary resuscitation during simulated obstetric crises AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Lipman, S. S., Daniels, K. I., Carvalho, B., Arafeh, J., Harney, K., Puck, A., Cohen, S. E., Druzin, M. 2010; 203 (2)

  Abstract

  Previous work suggests the potential for suboptimal cardiopulmonary resuscitation (CPR) in the parturient but did not directly assess actual performance.We evaluated 18 videotaped simulations of maternal amniotic fluid embolus and resultant cardiac arrest. A checklist containing 10 current American Heart Association recommendations for advanced cardiac life support (ACLS) in obstetric patients was utilized. We evaluated which tasks were completed correctly and the time required to perform key actions.Proper compressions were delivered by our teams 56% of the time and ventilations 50% of the time. Critical interventions such as left uterine displacement and placing a firm back support prior to compressions were frequently neglected (in 44% and 22% of cases, respectively). The mean +/- SD overall composite score for the tasks was 45 +/- 12% (range, 20-60%). The neonatal team was called in a median (interquartile range) of 1:42 (0:44-2:18) minutes:seconds; 15 of 18 (83%) teams called only after the patient was completely unresponsive. Fifty percent of teams did not provide basic information to the neonatal teams as required by neonatal resuscitation provider guidelines.Multiple deficits were noted in the provision of CPR to parturients during simulated arrests, despite current ACLS certification for all participants. Current requirements for ACLS certification and training for obstetric staff may require revision.

  View details for DOI 10.1016/j.ajog.2010.02.022

  View details for Web of Science ID 000280234500037

  View details for PubMedID 20417476

• Minimum effective bolus dose of oxytocin during elective Caesarean delivery BRITISH JOURNAL OF ANAESTHESIA Woo, C., McGlennan, A. 2010; 105 (1): 91-92

  View details for Web of Science ID 000278969500016

  View details for PubMedID 20560157

• Minimum effective bolus dose of oxytocin during elective Caesarean delivery BRITISH JOURNAL OF ANAESTHESIA Breeze, E. 2010; 104 (6): 783-783

  View details for Web of Science ID 000277731100026

  View details for PubMedID 20460573

• Neuraxial anesthesia in obstetric patients receiving anticoagulant and antithrombotic drugs INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Butwick, A. J., Carvalho, B. 2010; 19 (2): 193-201

  View details for DOI 10.1016/j.ijoa.2009.06.008

  View details for Web of Science ID 000277553700012

  View details for PubMedID 20202816

• Minimum effective bolus dose of oxytocin during elective Caesarean delivery BRITISH JOURNAL OF ANAESTHESIA Butwick, A. J., Coleman, L., Cohen, S. E., Riley, E. T., Carvalho, B. 2010; 104 (3): 338-343

  Abstract

  The aim of this study was to determine the lowest effective bolus dose of oxytocin to produce adequate uterine tone (UT) during elective Caesarean delivery (CD).Seventy-five pregnant patients undergoing elective CD under spinal anaesthesia were randomized to receive oxytocin (0.5, 1, 3, 5 units) or placebo. UT was assessed by a blinded obstetrician as either adequate or inadequate, and using a verbal numerical scale score (0-10; 0, no UT; 10, optimal UT) at 2, 3, 6, and 9 min after oxytocin administration. Minimum effective doses of oxytocin were analysed (ED(50) and ED(95)) using logistic regression. Oxytocin-related side-effects (including hypotension) were recorded.There were no significant differences in the prevalence of adequate UT among the study groups at 2 min (73%, 100%, 93%, 100%, and 93% for 0, 0.5, 1, 3, and 5 units oxytocin, respectively). The high prevalence of adequate UT after placebo and low-dose oxytocin precluded determination of the ED(50) and ED(95). UT scores were significantly lower in patients receiving 0 unit oxytocin at 2 and 3 min compared with 3 and 5 units oxytocin (P<0.05, respectively). The prevalence of hypotension was significantly higher after 5 units oxytocin vs 0 unit at 1 min (47% vs 7%; P=0.04).The routine use of 5 units oxytocin during elective CD can no longer be recommended, as adequate UT can occur with lower doses of oxytocin (0.5-3 units).

  View details for DOI 10.1093/bja/aeq004

  View details for Web of Science ID 000274485900011

  View details for PubMedID 20150347

• Cost-effectiveness of external cephalic version for term breech presentation BMC PREGNANCY AND CHILDBIRTH Tan, J. M., Macario, A., Carvalho, B., Druzin, M. L., El-Sayed, Y. Y. 2010; 10

  Abstract

  External cephalic version (ECV) is recommended by the American College of Obstetricians and Gynecologists to convert a breech fetus to vertex position and reduce the need for cesarean delivery. The goal of this study was to determine the incremental cost-effectiveness ratio, from society's perspective, of ECV compared to scheduled cesarean for term breech presentation.A computer-based decision model (TreeAge Pro 2008, Tree Age Software, Inc.) was developed for a hypothetical base case parturient presenting with a term singleton breech fetus with no contraindications for vaginal delivery. The model incorporated actual hospital costs (e.g., $8,023 for cesarean and $5,581 for vaginal delivery), utilities to quantify health-related quality of life, and probabilities based on analysis of published literature of successful ECV trial, spontaneous reversion, mode of delivery, and need for unanticipated emergency cesarean delivery. The primary endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted year of life gained. A threshold of $50,000 per quality-adjusted life-years (QALY) was used to determine cost-effectiveness.The incremental cost-effectiveness of ECV, assuming a baseline 58% success rate, equaled $7,900/QALY. If the estimated probability of successful ECV is less than 32%, then ECV costs more to society and has poorer QALYs for the patient. However, as the probability of successful ECV was between 32% and 63%, ECV cost more than cesarean delivery but with greater associated QALY such that the cost-effectiveness ratio was less than $50,000/QALY. If the probability of successful ECV was greater than 63%, the computer modeling indicated that a trial of ECV is less costly and with better QALYs than a scheduled cesarean. The cost-effectiveness of a trial of ECV is most sensitive to its probability of success, and not to the probabilities of a cesarean after ECV, spontaneous reversion to breech, successful second ECV trial, or adverse outcome from emergency cesarean.From society's perspective, ECV trial is cost-effective when compared to a scheduled cesarean for breech presentation provided the probability of successful ECV is > 32%. Improved algorithms are needed to more precisely estimate the likelihood that a patient will have a successful ECV.

  View details for DOI 10.1186/1471-2393-10-3

  View details for Web of Science ID 000296428000001

  View details for PubMedID 20092630

• An experimental paradigm for the prediction of Post-Operative Pain (PPOP). Journal of visualized experiments : JoVE Landau, R., Kraft, J. C., Flint, L. Y., Carvalho, B., Richebé, P., Cardoso, M., Lavand'homme, P., Granot, M., Yarnitsky, D., Cahana, A. 2010

  Abstract

  Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative short-term and long-term effects on the mother. Prior to women undergoing surgery, can we predict who is at risk for developing significant postoperative pain and potentially prevent or minimize its negative consequences? These are the fundamental questions that a team from the University of Washington, Stanford University, the Catholic University in Brussels, Belgium, Santa Joana Women's Hospital in São Paulo, Brazil, and Rambam Medical Center in Israel is currently evaluating in an international research collaboration. The ultimate goal of this project is to provide optimal pain relief during and after cesarean section by offering individualized anesthetic care to women who appear to be more 'susceptible' to pain after surgery. A significant number of women experience moderate or severe acute post-partum pain after vaginal and cesarean deliveries. (1) Furthermore, 10-15% of women suffer chronic persistent pain after cesarean section. (2) With constant increase in cesarean rates in the US (3) and the already high rate in Brazil, this is bound to create a significant public health problem. When questioning women's fears and expectations from cesarean section, pain during and after it is their greatest concern. (4) Individual variability in severity of pain after vaginal or operative delivery is influenced by multiple factors including sensitivity to pain, psychological factors, age, and genetics. The unique birth experience leads to unpredictable requirements for analgesics, from 'none at all' to 'very high' doses of pain medication. Pain after cesarean section is an excellent model to study post-operative pain because it is performed on otherwise young and healthy women. Therefore, it is recommended to attenuate the pain during the acute phase because this may lead to chronic pain disorders. The impact of developing persistent pain is immense, since it may impair not only the ability of women to care for their child in the immediate postpartum period, but also their own well being for a long period of time. In a series of projects, an international research network is currently investigating the effect of pregnancy on pain modulation and ways to predict who will suffer acute severe pain and potentially chronic pain, by using simple pain tests and questionnaires in combination with genetic analysis. A relatively recent approach to investigate pain modulation is via the psychophysical measure of Diffuse Noxious Inhibitory Control (DNIC). This pain-modulating process is the neurophysiological basis for the well-known phenomenon of 'pain inhibits pain' from remote areas of the body. The DNIC paradigm has evolved recently into a clinical tool and simple test and has been shown to be a predictor of post-operative pain.(5) Since pregnancy is associated with decreased pain sensitivity and/or enhanced processes of pain modulation, using tests that investigate pain modulation should provide a better understanding of the pathways involved with pregnancy-induced analgesia and may help predict pain outcomes during labor and delivery. For those women delivering by cesarean section, a DNIC test performed prior to surgery along with psychosocial questionnaires and genetic tests should enable one to identify women prone to suffer severe post-cesarean pain and persistent pain. These clinical tests should allow anesthesiologists to offer not only personalized medicine to women with the promise to improve well-being and satisfaction, but also a reduction in the overall cost of perioperative and long term care due to pain and suffering. On a larger scale, these tests that explore pain modulation may become bedside screening tests to predict the development of pain disorders following surgery.

  View details for DOI 10.3791/1671

  View details for PubMedID 20107427

• Analgesic requirements and postoperative recovery after scheduled compared to unplanned cesarean delivery: a retrospective chart review INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Coleman, L., Saxena, A., Fuller, A. J., Riley, E. T. 2010; 19 (1): 10-15

  Abstract

  Studies examining the effects of various analgesics and anesthetics on postoperative pain following cesarean delivery conventionally use the scheduled cesarean population. This study compares postoperative analgesic requirements and recovery profiles in women undergoing scheduled cesarean compared to unplanned cesarean delivery following labor. We postulated that unplanned cesarean deliveries may increase postoperative analgesic requirements.We conducted a retrospective chart review of 200 cesarean deliveries at Lucile Packard Children's Hospital, California. We examined the records of 100 patients who underwent scheduled cesarean delivery under spinal anesthesia (hyperbaric bupivacaine 12 mg with intrathecal fentanyl 10 microg and morphine 200 microg) and 100 patients that following a trail of labor required unplanned cesarean under epidural anesthesia (10-25 mL 2% lidocaine top-up with epidural morphine 4 mg after clamping of the umbilical cord). We recorded pain scores, analgesic consumption, time to first analgesic request, side effects, and length of hospital stay.We found no differences in postoperative pain scores and analgesic consumption between scheduled and unplanned cesarean deliveries for up to five days postoperatively. There were no differences in treatment of side effects such as nausea, vomiting, or pruritus (P>0.05).The results indicate that women experience similar pain and analgesic requirements after scheduled compared to unplanned cesarean delivery. This suggests that the non-scheduled cesarean population may be a suitable pain model to study pain management strategies; and that alterations in pain management are not necessary for the unplanned cesarean delivery population.

  View details for DOI 10.1016/j.ijoa.2009.02.012

  View details for Web of Science ID 000273845400004

  View details for PubMedID 19954964

• Survey of the Factors Associated with a Woman's Choice to Have an Epidural for Labor Analgesia. Anesthesiology research and practice Harkins, J., Carvalho, B., Evers, A., Mehta, S., Riley, E. T. 2010; 2010

  Abstract

  Objectives. The purpose of this study was to determine the factors associated with whether a woman received an epidural in labor and to determine the main source used to obtain information about labor epidurals. Methods. Over a one-month period, we surveyed all patients who labored, the day after their delivery. We used multiple logistic regression to identify potential predictive factors after initial univariate analysis. Results. 320 women who met enrollment criteria delivered during the study period and 94% completed the study. Of the 302 patients surveyed, 80% received an epidural for labor. Univariate analysis showed the following variables were associated with whether women received an epidural (P < .01): partner preference, prior epidural, language, education, type of insurance, age, duration, and pitocin use. Using computed multiple logistic regression only partner preference and prior epidural were associated with whether women received an epidural. Conclusion. It was not surprising that a previous epidural was predictive of a patient receiving an epidural. The strong association with partner preference and epidural use suggests this is an important factor when counseling pregnant women with regard to their decision to have a labor epidural.

  View details for DOI 10.1155/2010/356789

  View details for PubMedID 20721286

• Elevation of Uterine Basal Tone and Fetal Heart Rate Abnormalities After Labor Analgesia: A Randomized Controlled Trial OBSTETRICS AND GYNECOLOGY Landau, R., Carvalho, B., Wong, C., Smiley, R., Tsen, L., Van de Velde, M. 2009; 113 (6): 1374-1374

  View details for Web of Science ID 000266392400037

  View details for PubMedID 19461449

• Hetastarch co-loading is as effective as pre-loading for the prevention of hypotension following spinal anesthesia for cesarean delivery INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Mercier, F. J., Riley, E. T., Brummel, C., Cohen, S. E. 2009; 18 (2): 150-155

  Abstract

  Pre-loading with hetastarch decreases the incidence and severity of hypotension after spinal anesthesia for cesarean delivery. However, pharmacokinetic studies with crystalloid predict that fluid loading should be more efficacious if rapidly administered immediately after induction of spinal anesthesia. The aim of this study was to compare pre- and co-loading of hetastarch for the prevention of hypotension following spinal anesthesia for cesarean delivery.Forty-six healthy term parturients scheduled for cesarean delivery were randomized to receive 500 mL of 6% hetastarch intravenously, either slowly before spinal anesthesia (pre-loading) or as quickly as possible immediately after spinal anesthesia (co-loading). Systolic blood pressure was maintained at or above 90% of baseline with intravenous vasopressor boluses (ephedrine 5mg/mL+phenylephrine 25 microg/mL). The primary outcome was the volume of vasopressor mix required. Secondary outcomes included blood pressure and heart rate changes, time to first vasopressor use, nausea or vomiting, and neonatal outcomes (umbilical artery and vein pH, Apgar scores).The pre-loading group used 3.5+/-2 mL (mean+/-SD) of vasopressor mixture compared with 3.2+/-3 mL in the co-loading group (P=0.6). There were no differences in any important maternal hemodynamic or neonatal outcome values between the two study groups.Hetastarch co-loading is as effective as pre-loading for the prevention of hypotension after spinal anesthesia for cesarean delivery. Surgery need not be delayed to allow a predetermined pre-load to be administered before induction of spinal anesthesia.

  View details for DOI 10.1016/j.ijoa.2008.12.006

  View details for Web of Science ID 000265542200009

  View details for PubMedID 19223168

• Patient-Controlled Epidural Analgesia for Labor ANESTHESIA AND ANALGESIA Halpern, S. H., Carvalho, B. 2009; 108 (3): 921-928

  Abstract

  Patient-controlled epidural analgesia (PCEA) for labor was introduced into clinical practice 20 yr ago. The PCEA technique has been shown to have significant benefits when compared with continuous epidural infusion. We conducted a systematic review using MEDLINE and EMBASE (1988-April 1, 2008) of all randomized, controlled trials in parturients who received PCEA in labor in which one of the following comparisons were made: background infusion versus none; ropivacaine versus bupivacaine; high versus low concentrations of local anesthetics; and new strategies versus standard strategies. The outcomes of interest were maternal analgesia, satisfaction, motor block, and the incidence of unscheduled clinician interventions. A continuous background infusion improved maternal analgesia and reduced unscheduled clinician interventions. Larger bolus doses (more than 5 mL) may provide better analgesia compared with small boluses. Low concentrations of bupivacaine or ropivacaine provide excellent analgesia without significant motor block. Many strategies with PCEA can provide effective labor analgesia. High volume, dilute local anesthetic solutions with a continuous background infusion appear to be the most successful strategy. Research into new delivery strategies, such as mandatory programmed intermittent boluses and computerized feedback dosing, is ongoing.

  View details for DOI 10.1213/ane.0b013e3181951a7f

  View details for Web of Science ID 000263537300041

  View details for PubMedID 19224805

• Determining heat and mechanical pain threshold in inflamed skin of human subjects. Journal of visualized experiments : JoVE Angst, M. S., Tingle, M., Phillips, N. G., Carvalho, B. 2009

  Abstract

  In a previous article in the Journal of Visualized Experiments we have demonstrated skin microdialysis techniques for the collection of tissue-specific nociceptive and inflammatory biochemicals in humans. In this article we will show pain-testing paradigms that are often used in tandem with microdialysis procedures. Combining pain tests with microdialysis provides the critical link between behavioral and biochemical data that allows identifying key biochemicals responsible for generating and propagating pain. Two models of evoking pain in inflamed skin of human study participants are shown. The first model evokes pain with aid of heat stimuli. Heat evoked pain as described here is predominantly mediated by small, non-myelinated peripheral nociceptive nerve fibers (C-fibers). The second model evokes pain via punctuated pressure stimuli. Punctuated pressure evoked pain is predominantly mediated by small, myelinated peripheral nociceptive nerve fibers (A-delta fibers). The two models are mechanistically distinct and independently examine nociceptive processing by the two major peripheral nerve fiber populations involved in pain signaling. Heat pain is evoked with aid of the TSA II, a commercially available thermo-sensory analyzer (Medoc Advanced Medical Systems, Durham, NC). Stimulus configuration and delivery is handled with aid of specific software. Thermodes vary in size and shape but in principle consist of a metal plate that can be heated or cooled at various rates and for different periods of time. Algorithms assessing heat-evoked pain are manifold. In the experiments shown here, study participants are asked to indicate at what point they start experiencing pain while the thermode in contact with skin is heated at a predetermined rate starting at a temperature that does not evoke pain. The thermode temperature at which a subject starts experiencing pain constitutes the heat pain threshold. Mechanical pain is evoked with punctuated probes. Such probes are commercially available from several manufacturers (von Frey hairs). However, the accuracy of von Frey hairs has been criticized and many investigators use custom made punctuated pressure probes. In the experiments shown here eight custom-made punctuated probes of different weights are applied in consecutive order, a procedure called up-down algorithm, to identify perceptional deflection points, i.e., a change from feeling no pain to feeling pain or vice versa. The average weight causing a perceptional deflection constitutes the mechanical pain threshold.

  View details for DOI 10.3791/1092

  View details for PubMedID 19229176

• A Randomized Trial of Maximum Cephalad Sensory Blockade with Single-Shot Spinal Compared with Combined Spinal-Epidural Techniques for Cesarean Delivery 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Horstman, D. J., Riley, E. T., Carvalho, B. LIPPINCOTT WILLIAMS & WILKINS. 2009: 240–45

  Abstract

  Previous studies have shown more extensive cephalad sensory blockade in women receiving combined spinal-epidural (CSE) anesthesia compared with single-shot spinal (SSS) anesthesia for elective cesarean delivery. It has been postulated that introduction of the epidural needle during CSE disturbs the negative pressure in the epidural space, resulting in relatively greater cerebrospinal fluid (CSF) pressure and increased spread of intrathecal local anesthetic. We tested the hypothesis that CSE results in more extensive cephalad sensory blockade than SSS anesthesia and that loss-of-resistance during initiation of CSE anesthesia increases CSF pressure compared with SSS.Thirty parturients scheduled for elective cesarean delivery were enrolled in this randomized, double-blind study. Patients received either SSS or CSE anesthesia with equal doses of intrathecal anesthetic (hyperbaric bupivacaine 12 mg, fentanyl 10 microg and morphine 200 microg). Before the intrathecal injection, the CSF pressure was measured with a fiberoptic pressure sensor. Maximum cephalad sensory blockade to pinprick, cold and touch was measured. The total dose of phenylephrine required to maintain baseline arterial blood pressure was also recorded.There were no significant differences in the median (interquartile range) pinprick sensory block height [T4 (T4-2) vs T3 (T4-1)] or CSF pressures [6 (4-12) vs 9 (8-12) mm Hg] between the SSS and CSE groups. There were no significant correlations between CSF pressure and block height or total dose of phenylephrine.The SSS and CSE techniques inserted in the lateral decubitus position resulted in similar extent of sensory blockade and CSF pressure. These findings suggest that altering the intrathecal dose is not necessary and that any difference in intrathecal pressure associated with initial placement of an epidural needle in the epidural space during CSE anesthesia is clinically inconsequential.

  View details for DOI 10.1213/ane.0b013e31818e0fa6

  View details for Web of Science ID 000261963000037

  View details for PubMedID 19095857

• Epidural labor analgesia in a patient receiving fondaparinux INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Tagaloa, L. A., Carvalho, B. 2009; 18 (1): 94-95

  View details for DOI 10.1016/j.ijoa.2008.07.007

  View details for Web of Science ID 000262736700026

  View details for PubMedID 19046870

• A survey of perioperative and postoperative anesthetic practices for cesarean delivery. Anesthesiology research and practice Aiono-Le Tagaloa, L., Butwick, A. J., Carvalho, B. 2009; 2009: 510642-?

  Abstract

  The aim of this survey was to review cesarean delivery anesthetic practices. An online survey was sent to members of the Society of Obstetric Anesthesia and Perinatology (SOAP). The mode of anesthesia, preferred neuraxial local anesthetic and opioid agents, postoperative analgesic regimens, and monitoring modalities were assessed. 384 responses from 1,081 online survey requests were received (response rate = 36%). Spinal anesthesia is most commonly used for elective cesarean delivery (85% respondents), with 90% of these respondents preferring hyperbaric bupivacaine 0.75%. 79% used intrathecal fentanyl and 77% used morphine (median [range] dose 200 mcg [50-400]). 91% use respiratory rate, 61% use sedation scores, and 30% use pulse oximetry to monitor for postoperative respiratory depression after administration of neuraxial opioids. Postoperative analgesic regimens include: nonsteroidal anti-inflammatory agents, acetaminophen, oxycodone, and hydrocodone by 81%, 45%, 25%, and 27% respondents respectively. The majority of respondents use spinal anesthesia and neuraxial opioids for cesarean delivery anesthesia. There is marked variability in practices for monitoring respiratory depression postdelivery and for providing postoperative analgesia. These results may not be indicative of overall practice in the United States due to the select group of anesthesiologists surveyed and the low response rate.

  View details for DOI 10.1155/2009/510642

  View details for PubMedID 21217809

• Accidental intrathecal sufentanil overdose during combined spinal-epidural analgesia for labor INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Coleman, L., Carvalho, B., Lipman, S., Schmiesing, C., Riley, E. 2009; 18 (1): 78-80

  Abstract

  A laboring woman was accidentally given 45 microg of sufentanil intrathecally in the course of combined spinal-epidural analgesia. She experienced intense pruritus and transient swallowing difficulty without respiratory depression, but still had incomplete pain relief, with delivery and episiotomy repair requiring additional analgesia. This case highlights the importance of adding local anesthetic to intrathecal opioids to facilitate effective analgesia during the second stage of labor. The contributory systems issues and multiple factors that allowed this error to occur are examined.

  View details for DOI 10.1016/j.ijoa.2008.10.001

  View details for Web of Science ID 000262736700017

  View details for PubMedID 19111229

• Cytokine profile in human skin in response to experimental inflammation, noxious stimulation, and administration of a COX-inhibitor: A microdialysis study PAIN Angst, M. S., Clark, J. D., Carvalho, B., Tingle, M., Schmelz, M., Yeomans, D. C. 2008; 139 (1): 15-27

  Abstract

  Animal studies have documented a critical role for cytokines in cell signaling events underlying inflammation and pain associated with tissue injury. While clinical reports indicate an important role of cytokines in inflammatory pain, methodological limitations have made systematic human studies difficult. This study examined the utility of a human in vivo bioassay combining microdialysis with multiplex immunoassay techniques for measuring cytokine arrays in tissue. The first experiment measured cytokines in interstitial fluid collected from non-inflamed and experimentally inflamed skin (UVB). The effects of noxious heat on cytokine release were also assessed. The second experiment examined whether anti-hyperalgesic effects of the COX-inhibitor ibuprofen were associated with decreased tissue levels of the pro-inflammatory cytokines IL-1 beta and IL-6. In the first experiment, inflammation significantly increased IL-1 beta, IL-6, IL-8, IL-10, G-CSF, and MIP-1 beta. Noxious heat but not experimental inflammation significantly increased IL-7 and IL-13. In the second experiment, an oral dose of 400 and 800 mg ibuprofen produced similar anti-hyperalgesic effects suggesting a ceiling effect. Tissue levels of IL-1 beta and IL-6 were not affected after the 400mg dose but decreased significantly (44+/-32% and 38+/-13%) after the 800 mg dose. These results support the utility of explored method for tracking cytokines in human tissue and suggest that anti-hyperalgesic and anti-inflammatory effects of ibuprofen are at least partially dissociated. The data further suggest that high clinical doses of ibuprofen exert anti-inflammatory effects by down-regulating tissue cytokine levels. Explored human bioassay is a promising tool for studying the pathology and pharmacology of inflammatory and chronic pain conditions.

  View details for DOI 10.1016/j.pain.2008.02.028

  View details for Web of Science ID 000260159200003

  View details for PubMedID 18396374

• Respiratory depression after neuraxial opioids in the obstetric setting ANESTHESIA AND ANALGESIA Carvalho, B. 2008; 107 (3): 956-961

  Abstract

  Neuraxial opioids have contributed significantly to improved labor and postcesarean delivery analgesia. In the obstetric population, epidural and intrathecal opioids are associated with a very low risk of clinically significant respiratory depression. Although rare, respiratory depression is a serious risk; patients may die or suffer permanent brain damage as a consequence. This review discusses the mechanism and incidence, as well as the prevention, detection, and management of respiratory depression with morphine, extended-release epidural morphine, and lipophilic opioids in the labor and cesarean delivery setting.

  View details for DOI 10.1213/ane.0b013e318168b443

  View details for Web of Science ID 000258702500041

  View details for PubMedID 18713913

• Vaginal twin delivery: a survey and review of location, anesthesia coverage and interventions 38th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Saxena, A., Butwick, A., Macario, A. CHURCHILL LIVINGSTONE. 2008: 212–16

  Abstract

  Twin pregnancies are associated with increased perinatal morbidity and mortality. No consensus exists whether vaginal twin delivery should take place in the labor room or operating room, or whether anesthesiologists should be present. We surveyed members of the California Society of Anesthesiologists (CSA) to review management of vaginal twin delivery, and examined anesthetic intervention retrospectively at our institution.230 CSA members were asked to complete an online survey on location of vaginal twin delivery in their institution and whether they were required to be present throughout. We then retrospectively reviewed charts of vaginal twin deliveries at our institution over a 36-month period to analyze frequency and type of anesthetic intervention.The online survey response rate was 58%; 64% of responders reported that vaginal twin deliveries were performed in the operating room and 55% that an anesthesiologist was present. There was a strong association between anesthesiologist's presence and delivery in the operating room (OR 7; 95% CI 3-20). We reviewed 81 charts of women who underwent vaginal twin delivery. The median (range) time that the anesthesiologist was present for each delivery was 60 (20-380) min. Of women undergoing vaginal twin delivery, 27% required anesthetic intervention during the second stage of labor with 6% having emergency cesarean delivery.There is a lack of consensus regarding the appropriate location for vaginal twin delivery and the role of anesthesiologists. A significant percentage of women undergoing vaginal twin delivery in our institution received anesthetic intervention in the immediate delivery period.

  View details for DOI 10.1016/j.ijoa.2007.04.004

  View details for Web of Science ID 000257844200003

  View details for PubMedID 17881218

• Labor and cesarean delivery patterns ANESTHESIOLOGY Carvalho, B. 2008; 109 (1): 161-162

  View details for Web of Science ID 000257135300035

  View details for PubMedID 18580198

• Strategies to comply with the five-minute rule after maternal arrest INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Mhyre, J. M. 2008; 17 (3): 284-285

  View details for DOI 10.1016/j.ijoa.2008.03.004

  View details for Web of Science ID 000257844200022

  View details for PubMedID 18511259

• Local and systemic release of cytokines, nerve growth factor, prostaglandin E2, and substance P in incisional wounds and serum following cesarean delivery JOURNAL OF PAIN Carvalho, B., Clark, D. J., Angst, M. S. 2008; 9 (7): 650-657

  Abstract

  The objectives of this study were to test the feasibility of measuring inflammatory and nociceptive biochemical mediators at the surgical site and to evaluate the relationship between wound and serum levels as well as determine any associations between mediator release, pain, and analgesic consumption after cesarean delivery. Twenty healthy women undergoing elective cesarean delivery with spinal anesthesia were enrolled. Wound exudate and serum mediators, pain scores, and analgesic consumption were measured at 1, 6, 24, and 48 hours after cesarean. In wound exudate, 19 of 20 mediators were reliably detected including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor-alpha, interferon-gamma, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1 (MIP-1beta), nerve growth factor (NGF), prostaglandin E2 (PG-E2), and substance P. Wound PG-E2 and various cytokines peaked early, whereas NGF showed a more delayed release. There were no correlations between the concentration versus time profile of wound and serum cytokines. Analgesic consumption during the first 24 hours after surgery was negatively correlated with IL-1beta, IL-6, and G-CSF in the wound exudate. This study demonstrates the feasibility of collecting and measuring nociceptive and inflammatory mediators in surgical wounds at specific time points. The lack of significant correlations between wound and serum levels emphasizes the importance of determining site-specific release if localized pathologies are to be studied.This study demonstrates the feasibility of measuring real-time nociceptive and inflammatory mediators in surgical wounds. Our findings confirm the lack of correlation between wound and serum levels of many pro-inflammatory and anti-inflammatory cytokines and nerve growth factor.

  View details for DOI 10.1016/j.jpain.2008.02.004

  View details for Web of Science ID 000257640100010

  View details for PubMedID 18394968

• Collecting and measuring nociceptive and inflammatory mediators in surgical wounds. Journal of visualized experiments : JoVE Carvalho, B., Clark, D. J., Yeomans, D., Angst, M. S. 2008

  Abstract

  We describe a methodology by which we are able to collect and measure inflammatory and nociceptive biochemical mediators at the surgical wound site. Collecting site-specific biochemical markers allows us to evaluate the relationship between surgical wound and serum levels;determine any associations between mediator release, pain and analgesic consumption; and evaluate the effect of systemic and peripheral drug administration on surgical wound biochemistry.This methodology has been applied to healthy women undergoing elective cesarean delivery with spinal anesthesia. Wound exudate and serum mediators, in conjunction with pain scores and analgesics consumption were measured at 1, 6, 24, and 48 hours post-cesarean delivery.Biochemical mediators that were detected included IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNFα, INFγ, G-CSF, GM-CSF,MCP-1 and MIP-1β, nerve growth factor (NGF), prostaglandin E2 (PG-E2) and substance P. We found no correlations between wound and serum cytokines concentrations or time-release profiles (J Pain. 2008 Jul 9(7):650-7). This article describes and demonstrates the feasibility of collecting and assaying nociceptive and inflammatory mediators in surgical wounds at specific time points. The lack of significant correlations between serum and wound levels shows the importance of determining site-specific release if surgical wounds and localized pathologies are to be studied [corrected].

  View details for DOI 10.3791/962

  View details for PubMedID 19078937

• Assessment of knowledge regarding cardiopulmonary resuscitation of pregnant women INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Cohen, S. E., Andes, L. C., Carvalho, B. 2008; 17 (1): 20-25

  Abstract

  The 2000-2002 triennial UK Report on Confidential Enquiries into Maternal Deaths concluded that over 50% of maternal deaths involved substandard care and that many could have been prevented. Catastrophic events leading to cardio-respiratory arrest may necessitate the resuscitation of pregnant women in various hospital locations. This study was designed to evaluate knowledge about resuscitation of parturients among anesthesiologists, obstetricians and emergency physicians.A 12-question survey was distributed anonymously to residents and faculty in the anesthesia (ANES), obstetrics (OB), and emergency medicine (EM) departments at Stanford University Medical Center/Lucile Packard Children's Hospital, Stanford, California. Questions were designed to elicit knowledge deficiencies in four critical areas: need for left uterine displacement (LUD), advanced cardiac life support algorithms (ACLS), physiologic changes of pregnancy (PHYS), and the recommendation to perform cesarean delivery in parturients (>20 weeks gestation) after 4-5 min of unsuccessful resuscitation for cardiac arrest (5CD).In total, 74/75 physicians (43% ANES, 37% OB, and 20% EM) completed the test. ANES scored highest in overall test scores, and in knowledge of PHYS (P<0.05). Scores for LUD and 5CD were similar among groups, but 25-40% of these questions were answered incorrectly. In the ACLS category, the EM group scored highest (93%).We conclude that knowledge of important basic concepts, including the need for LUD and the potential benefit of early cesarean delivery during cardiac arrest, is inadequate among all three specialties. All three departments should provide ACLS physician training with emphasis on the special considerations for parturients.

  View details for DOI 10.1016/j.ijoa.2007.10.002

  View details for Web of Science ID 000253167900005

  View details for PubMedID 18162200

• Human in-vivo bioassay for the tissue-specific measurement of nociceptive and inflammatory mediators. Journal of visualized experiments : JoVE Angst, M. S., Tingle, M., Schmelz, M., Carvalho, B., Yeomans, D. C. 2008

  Abstract

  This in-vivo human bioassay can be used to study human volunteers and patients. Samples are collected from pertinent tissue sites such as the skin via aseptically inserted microdialysis catheters (Dermal Dialysis, Erlangen, Germany). Illustrated in this example is the collection of interstitial fluid from experimentally inflamed skin in human volunteers. Sample collection can be combined with other experimental tests. For example, the simultaneous assessment of locally released biochemicals and subjective sensitivity to painful stimuli in experimentally inflamed skin provides the critical biochemical-behavioral link to identify biomarkers of pain and inflammation. Presented assay in the living human organism allows for mechanistic insight into tissue-specific processes underlying pain and/or inflammation. The method is also well suited to examine the effectiveness of existing or novel interventions--such as new drug candidates - targeting the treatment of painful and/or inflammatory conditions. This article will provide a detailed description on the use of microdialysis techniques for collecting interstitial fluid from experimentally inflamed skin lesion of human study subjects. Interstitial fluid samples are typically processed with aid of multiplex bead array immunoassays allowing assaying up to 100 analytes in samples as small in volume as 50 microliters.

  View details for DOI 10.3791/1074

  View details for PubMedID 19229167

• Extended release epidural morphine, far from ideal for postcesarean delivery pain control ANESTHESIA AND ANALGESIA Roboubi, B. 2007; 105 (6): 1864-1864

  View details for Web of Science ID 000251274400063

  View details for PubMedID 18042899

• Intraoperative forced air-warming during cesarean delivery under spinal anesthesia does not prevent maternal hypothermia ANESTHESIA AND ANALGESIA Butwick, A. J., Lipman, S. S., Carvalho, B. 2007; 105 (5): 1413-1419

  Abstract

  Prewarming and intraoperative warming with forced air-warming systems prevent perioperative hypothermia and shivering in patients undergoing elective cesarean delivery with epidural anesthesia. We tested the hypothesis that intraoperative lower body forced air-warming prevents hypothermia in patients undergoing elective cesarean delivery with spinal anesthesia.Thirty healthy patients undergoing cesarean delivery with spinal anesthesia were randomly assigned to forced air-warming or control groups (identical cover applied with forced air-warming unit switched off). A blinded investigator assessed oral temperature, shivering, and thermal comfort scores at 15-min intervals until discharge from the postanesthetic care unit. Umbilical cord blood gases and Apgar scores were also measured after delivery.The maximum core temperature changes were similar in the two groups (-1.3 degrees C +/- 0.4 degrees C vs -1.3 degrees C +/- 0.3 degrees C for the forced air-warming group and control group, respectively; P = 0.8). Core hypothermia (< or =35.5 degrees C) occurred in 8 of 15 patients receiving forced air-warming and in 10 of 15 unwarmed patients (P = 0.5). The incidence and severity of shivering did not significantly differ between groups. Umbilical cord blood gases and Apgar scores were similar in both groups (P = NS).We conclude that intraoperative lower body forced air-warming does not prevent intraoperative hypothermia or shivering in women undergoing elective cesarean delivery with spinal anesthesia.

  View details for DOI 10.1213/01.ane.0000286167.96410.27

  View details for Web of Science ID 000250317500039

  View details for PubMedID 17959975

• Can we improve maternal outcome for high-risk obstetric patients? INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B. 2007; 16 (4): 311-313

  View details for DOI 10.1016/j.ijoa.2007.04.005

  View details for Web of Science ID 000250284800003

  View details for PubMedID 17698338

• The Episure (TM) syringe: A novel loss of resistance syringe for locating the epidural space 37th Annual Meeting of the Society-of-Obstetric-Anesthesiology-and-Perinatology Riley, E. T., Carvalho, B. LIPPINCOTT WILLIAMS & WILKINS. 2007: 1164–66

  Abstract

  The Episure syringe is a unique spring-loaded loss-of-resistance (LOR) syringe with a coaxial compression spring within a Portex Pulsator LOR syringe. This syringe supplies a constant pressure while the operator is advancing the Tuohy needle.We evaluated the syringe using an artificial model of the ligamentum flavum, an anesthetized pig, and women who desired epidural analgesia for labor.The operator, using the spring-loaded syringe, was able to stop the forward movement of the needle, so that compared with a standard LOR syringe less of the needle protruded out the back of the laboratory model. Satisfactory labor analgesia in the human study and radiograph analyses in the porcine model confirmed epidural placement in all attempts.The spring-loaded syringe is a potentially useful LOR syringe that provides a reliable, objective end-point for identification of the epidural space.

  View details for DOI 10.1213/01.ane.0000281935.78144.82

  View details for Web of Science ID 000249678500043

  View details for PubMedID 17898406

• Plasma and wound exudate cytokine, prostaglandin E2, substance P and nerve growth factor release following Cesarean delivery Carvalho, B., Clark, D., Angst, M. MARY ANN LIEBERT INC. 2007: 1103–

  View details for Web of Science ID 000250506100024

• Fetal oxygen saturation after combined spinal-epidural Labor analgesia: a case series JOURNAL OF CLINICAL ANESTHESIA Carvalho, B., Fuller, A. I., Brummel, C., Durbin, M., Riley, E. T. 2007; 19 (6): 476-478

  Abstract

  Fetal oxygen saturation (FSpo(2)) is an emerging technology for intrapartum fetal monitoring. We monitored FSpo(2) before and after combined spinal-epidural analgesia in 8 laboring women requesting neuraxial analgesia. Fetal heart rate (FHR) and FSpo(2) (using the Nellcor N400/FS14 system [Nellcor, Pleasanton, CA]) were recorded at baseline and every minute for 45 minutes after analgesia. We observed no significant changes in FSpo(2) after analgesia (mean DeltaFSpo(2) 2 +/- 7 %, P = 0.46). Fetal oxygen saturation at baseline and after analgesia was 53% +/- 9% and 51% +/- 8%, respectively. We observed no significant FHR changes or any fetal bradycardia following combined spinal-epidural analgesia.

  View details for DOI 10.1016/j.jclinane.2007.01.009

  View details for Web of Science ID 000250817600017

  View details for PubMedID 17967682

• Single-dose, extended-release epidural morphine (DepoDur (TM)) compared to conventional epidural morphine for post-cesarean pain ANESTHESIA AND ANALGESIA Carvalho, B., Roland, L. M., Chu, L. F., Campitelli, V. A., Riley, E. T. 2007; 105 (1): 176-183

  Abstract

  A single-dose of neuraxial morphine sulfate provides good post-Cesarean analgesia; however, its efficacy is limited to the first postoperative day. In a recent phase III study, extended-release epidural morphine (EREM) formulation provided more effective, prolonged analgesia after Cesarean delivery, compared to conventional epidural morphine. However, the study protocol did not allow for the use of nonsteroidal antiinflammatory drugs, used various postoperative analgesics, and monitoring and treatment of respiratory depression were not standardized. Our aims in this study were to compare postoperative analgesic consumption, pain scores and side effects of EREM with conventional morphine for the management of post-Cesarean pain in a setting more reflective of current obstetric practice.Seventy healthy parturients undergoing elective Cesarean delivery were enrolled in this randomized, double-blind study. Using a combined spinal epidural technique, patients received an intrathecal injection of bupivacaine 12 mg and fentanyl 10 mcg. After closure of the fascia, a single-dose of either conventional morphine 4 mg or EREM 10 mg was administered epidurally. Postoperatively, all patients received ibuprofen 600 mg orally every 6 h. Oral oxycodone and IV morphine were available for breakthrough pain. All patients received pulse oximetry and respiratory monitoring for 48 h post-Cesarean delivery.Single-dose EREM significantly improved pain scores at rest and during activity. The median (interquartile range) of supplemental opioid medication usage for 48 h post-Cesarean (in milligram-morphine equivalents) decreased from 17 (22) to 10 (17) mg with EREM compared to conventional epidural morphine (P = 0.037). Both drugs were well tolerated with no significant difference in adverse event profiles.EREM provides superior and prolonged post-Cesarean analgesia compared to conventional epidural morphine with no significant increases in adverse events.

  View details for DOI 10.1213/01.ane.0000265533.13477.26

  View details for Web of Science ID 000247444800032

  View details for PubMedID 17578973

• Neuraxial anesthesia for cesarean delivery in a parturient with type 1 von Willebrand disease and scoliosis JOURNAL OF CLINICAL ANESTHESIA Butwick, A. J., Carvalho, B. 2007; 19 (3): 230-233

  Abstract

  We present the case of a parturient with von Willebrand disease and scoliosis who required cesarean delivery. Neuraxial anesthesia was used for the patient. The indications for neuraxial anesthesia with regard to type 1 von Willebrand disease are reviewed.

  View details for DOI 10.1016/j.jclinane.2006.08.013

  View details for Web of Science ID 000247128200014

  View details for PubMedID 17531735

• A cost-analysis of neuraxial analgesia to facilitate external cephalic version 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Tan, J. M., Macario, A., El-Sayed, Y., Carvalho, B. LIPPINCOTT WILLIAMS & WILKINS. 2007: B53–B53

  View details for Web of Science ID 000246032500129

• Is external cephalic version cost-effective? 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Tan, J. M., Macario, A., Carvalho, B., El-Sayed, Y. LIPPINCOTT WILLIAMS & WILKINS. 2007: B16–B16

  View details for Web of Science ID 000246032500055

• Incisional wound and systemic cytokines release following cesarean section 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Clark, D., Angst, M. LIPPINCOTT WILLIAMS & WILKINS. 2007: B43–B43

  View details for Web of Science ID 000246032500109

• Plasma and wound exudate prostaglandin E2 and substance P release following cesarean section 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Angst, M., Clark, D. LIPPINCOTT WILLIAMS & WILKINS. 2007: B19–B19

  View details for Web of Science ID 000246032500061

• Local infiltration of epinephrine-containing lidocaine with bicarbonate reduces superficial bleeding and pain during labor epidural catheter insertion: a randomized trial INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Fuller, A., Brummel, C., Cohen, S. E. 2007; 16 (2): 116-121

  Abstract

  Superficial bleeding after labor epidural catheter placement is a common phenomenon. In addition to delaying securing the epidural catheter, it may loosen the adhesive catheter dressing. The primary aim of this study was to determine whether skin infiltration with epinephrine-containing rather than plain lidocaine reduces superficial bleeding after catheter placement. Secondary objectives were to determine whether adding epinephrine and/or sodium bicarbonate affected infiltration pain.After institutional review board approval and informed consent, 80 healthy women receiving epidural analgesia during labor were randomly assigned in a double-blind manner to four local anesthetic mixtures (n=20 in each group): group L: lidocaine 1.5%, group LB: lidocaine 1.5% with 8.4% sodium bicarbonate, group LE: lidocaine 1.5% with epinephrine 1:200000, and group LEB: lidocaine 1.5% with epinephrine 1:200000 and 8.4% sodium bicarbonate. Clinical endpoints included the amount of superficial bleeding at the catheter site, pain during local anesthetic infiltration and epidural catheter movement during labor.Demographic data were similar among the groups. The addition of epinephrine to lidocaine significantly reduced superficial bleeding. Solutions containing epinephrine were well tolerated and caused no cardiovascular disturbances. The addition of epinephrine did not increase pain, while bicarbonate reduced it [verbal score (scale 0-10) 3.6+/-2.2 vs. 2.6+/-1.8; P=0.04]. There were no differences in epidural catheter movement among the groups; no catheters became displaced during labor.Local infiltration of epinephrine-containing lidocaine before epidural catheter insertion reduces superficial bleeding and the addition of bicarbonate decreases pain during skin infiltration.

  View details for DOI 10.1016/j.ijoa.2006.09.006

  View details for Web of Science ID 000245838800004

  View details for PubMedID 17276670

• The effect of colloid and crystalloid preloading on thromboelastography prior to Cesarean delivery Annual Meeting of the Obstetric-Anaesthetists-Association Butwick, A., Carvalho, B. SPRINGER. 2007: 190–95

  Abstract

  Fluid preloading with colloids reduces hypotension after spinal anesthesia for Cesarean delivery more effectively than crystalloids. However, the effects of fluid preloading regimens on coagulation in pregnant patients remain unresolved. The aim of this study was to compare the effects on coagulation of fluid preloading with 6% hydroxyethyl starch (HES) and lactated Ringer's (LR) solution using thromboelastography (TEG) with kaolin-activated whole blood in healthy pregnant patients prior to spinal anesthesia for Cesarean delivery.After obtaining Ethics committee approval, 30 parturients were prospectively randomized prior to spinal anesthesia for elective Cesarean delivery to receive fluid preloading with either 1500 mL LR or 500 mL 6% HES over 30 min. Thromboelastography was performed immediately prior to and after fluid preloading. Standard TEG parameters were analyzed in terms of r time (min), k time (min), alpha angle (degrees) and maximum amplitude (mm).Group HES had statistically significant longer reaction times (r) and clot formation times (k) after fluid loading compared to baseline values (P < 0.05 respectively), although these post-fluid loading TEG parameters remained within a normal reference range. No significant differences in TEG values were seen after preloading within the LR group.Fluid preloading with 500 mL 6% HES in healthy parturients produced mild coagulation effects, as measured with TEG, prior to spinal anesthesia for Cesarean delivery. No significant effects on coagulation with TEG were observed following preloading with 1500 mL LR.

  View details for Web of Science ID 000245113600005

  View details for PubMedID 17331930

• Experimental heat pain for detecting pregnancy-induced analgesia in humans ANESTHESIA AND ANALGESIA Carvalho, B., Angst, M. S., Fuller, A. J., Lin, E., Mathusamy, A. D., Riley, E. T. 2006; 103 (5): 1283-1287

  Abstract

  Animal studies suggest that increased circulating estrogen and progesterone, and activation of the endorphin system cause prenancy-induced antinociceptive effects. Human studies have provided inconsistent results and have often lacked a nonpregnant control group. In this study, we compared sensitivity to experimental heat and cold pain in pregnant and nonpregnant women. Nineteen healthy nonpregnant female volunteers and 20 pregnant women at term were enrolled. Pain threshold and tolerance were examined using experimental heat-induced pain and cold pressor pain models. Subjects were evaluated pre- and 1-2 days post-delivery (pregnant), or on consecutive days (nonpregnant). Heat pain tolerance was significantly increased in the pregnant women during pre and postdelivery when compared with nonpregnant controls (50.0 +/- 1.0 vs 49.0 +/- 1.2 and 50.1 +/- 0.7 vs 49.2 +/- 1.2 degrees C; mean +/- sd). However, pain induced by the cold pressor test was endured for a similar amount of time by both study groups. Pregnancy-induced analgesic effects at term can be detected in a model of experimental heat pain. These effects persist during the first 24-48 h after delivery. Experimental heat pain is a suitable modality for further characterizing the phenomenon of pregnancy-induced analgesia in humans.

  View details for DOI 10.1213/01.ane.0000239224.48719.28

  View details for Web of Science ID 000241570600038

  View details for PubMedID 17056970

• Anesthesia for interventional radiology in parturients at risk of major hemorrhage at cesarean section delivery ANESTHESIA AND ANALGESIA Harnett, M. J., Carabuena, J. M., Tsen, L. C., Kodali, B. S. 2006; 103 (5): 1329-1330

  View details for DOI 10.1213/01.ane.0000242324.31955.2b

  View details for Web of Science ID 000241570600051

  View details for PubMedID 17056980

• Valdecoxib for postoperative pain management after cesarean delivery: A randomized, double-blind, placebo-controlled study 37th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Chu, L., Fuller, A., Cohen, S. E., Riley, E. T. LIPPINCOTT WILLIAMS & WILKINS. 2006: 664–70

  Abstract

  Although nonsteroidal antiinflammatory drugs (NSAIDs) improve postoperative pain relief after cesarean delivery, they carry potential side effects (e.g., bleeding). Perioperative cyclooxygenase (COX)-2 inhibitors show similar analgesic efficacy to nonsteroidal antiinflammatory drugs in many surgical models but have not been studied after cesarean delivery. We designed this randomized double-blind study to determine the analgesic efficacy and opioid-sparing effects of valdecoxib after cesarean delivery. Healthy patients undergoing elective cesarean delivery under spinal anesthesia were randomized to receive oral valdecoxib 20 mg or placebo every 12 h for 72 h postoperatively. As a result of cyclooxygenase-2 inhibitors safety concerns that became apparent during this study, the study was terminated early after evaluating 48 patients. We found no differences in total analgesic consumption between the valdecoxib and placebo groups (121 +/- 70 versus 143 +/- 77 morphine mg-equivalents, respectively; P = 0.26). Pain at rest and during activity were similar between the groups despite adequate post hoc power to have detected a clinically significant difference. There were also no differences in IV morphine requirements, time to first analgesic request, patient satisfaction, side effects, breast-feeding success, or functional activity. Postoperative pain was generally well controlled. Adding valdecoxib after cesarean delivery under spinal anesthesia with intrathecal morphine is not supported at this time.

  View details for DOI 10.1213/01.ane.0000229702.42426.a6

  View details for Web of Science ID 000240049800025

  View details for PubMedID 16931678

• A survey of labor patient-controlled epidural anesthesia practice in California hospitals 37th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Wang, P., Cohen, S. E. ELSEVIER SCI LTD. 2006: 217–22

  Abstract

  Patient-controlled epidural analgesia (PCEA) offers many advantages over continuous epidural infusions for labor analgesia including fewer physician interventions, improved analgesia and satisfaction, and reduced local anesthetic doses. However, anesthesiologists have been slow to adopt this technique, first described in 1988. No previous studies have evaluated specific labor patient-controlled epidural analgesia practices in the United States. The aim of this study was to determine labor epidural and patient-controlled epidural analgesia practices among California hospitals.Following institutional review board exemption approval, an online survey was created using freeonlinesurveys.com. An anonymous survey was sent via e-mail to 230 California Society of Anesthesiologists' members chosen at random to represent their hospitals' labor analgesia practices.We received 133 replies from the 230 survey requests sent, a 58% response rate. The median labor epidural rate among the hospitals involved was 65% (range 0-95%). Overall, only 25% of California hospitals use patient-controlled epidural analgesia for analgesia in labor, with greater use among hospitals with dedicated obstetric anesthesia coverage and larger numbers of deliveries. Reasons given for not using patient-controlled epidural analgesia include cost, clinician preference, safety concerns and the inconvenience of change.Despite the potential advantages of patient-controlled epidural analgesia over continuous epidural infusions for labor analgesia, patient-controlled epidural analgesia has not been widely adopted in California hospitals. Education regarding this technique is needed to encourage its increased use.

  View details for DOI 10.1016/j.ijoa.2006.03.006

  View details for Web of Science ID 000239166100007

  View details for PubMedID 16798447

• Solutions for patient-controlled epidural analgesia INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Paech, M. 2006; 15 (3): 262-262

  View details for DOI 10.1016/j.ijoa.2006.03.002

  View details for Web of Science ID 000239166100027

  View details for PubMedID 16798466

• Epidural labor analgesia in a patient with pemphigoid gestationis 38th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Roland, L., Collins, J., Carvalho, B. LIPPINCOTT WILLIAMS & WILKINS. 2006: B53–B53

  View details for Web of Science ID 000236428600141

• Epidural anesthesia for elective cesarean delivery with intraoperative arterial occlusion balloon catheter placement 36th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Fuller, A. J., Carvalho, B., Brummel, C., Riley, E. T. LIPPINCOTT WILLIAMS & WILKINS. 2006: 585–87

  Abstract

  Obstetric hemorrhage is a leading cause of maternal mortality. We describe the anesthetic management of elective cesarean delivery in patients at high risk for hemorrhage. The utility and limitations of intraarterial balloon catheter placement and epidural anesthesia are described.

  View details for DOI 10.1213/01.ane.0000189551.61937.ea

  View details for Web of Science ID 000234912900049

  View details for PubMedID 16428566

• Remifentanil patient-controlled analgesia in labor ANESTHESIA AND ANALGESIA Butwick, A., Carvalho, B. 2006; 102 (1): 333-333

  View details for Web of Science ID 000234275700071

  View details for PubMedID 16368862

• Nonobstetric surgery during pregnancy 80th Clinical and Scientific Congress of the International-Anesthesia-Research-Society Carvalho, B. LIPPINCOTT WILLIAMS & WILKINS. 2006: 23–30

  View details for Web of Science ID 000235983800005

• Patient preferences for anesthesia outcomes associated with Cesarean delivery ANESTHESIA AND ANALGESIA Carvalho, B., Cohen, S. E., Lipman, S. S., Fuller, A., Mathusamy, A. D., Macario, A. 2005; 101 (4): 1182-1187

  Abstract

  When deciding on neuraxial medication (e.g., spinal opioids) for cesarean delivery (CS) under regional anesthesia, anesthesiologists make treatment decisions that "trade off" relieving pain with the potential for increased risk of side effects. No previous studies have examined obstetric patients' anesthesia preferences. Researchers administered 100 written surveys to pregnant women attending our institutions' expectant parent class. We determined patients' preferences for importance of specific intraoperative and postoperative anesthesia outcomes using priority ranking and relative value scales. We also explored patients' fears, concerns, and tolerance regarding CS and analgesics. Eighty-two of 100 surveys were returned and analyzed. Pain during and after CS was the greatest concern followed by vomiting, nausea, cramping, pruritus, and shivering. Ranking and relative value scores were closely correlated (R2 = 0.7). Patients would tolerate a visual analog pain score (0-100 mm) of 56 +/- 22 before exposing their baby to the potential effects of analgesics they receive. In contrast to previous general surgical population surveys that found nausea and vomiting as primary concerns, we found pain during and after CS as parturients' most important concern. Common side effects such as pruritus and shivering caused only moderate concern. This information should be used to guide anesthetic choices, e.g., inclusion of spinal opioids given in adequate doses.Medical care can be improved by incorporating patients' preferences into medical decision making. We surveyed obstetric patients to determine their preferences regarding potential cesarean delivery anesthesia outcomes. Unlike general surgical patients who rate nausea and vomiting highest, parturients considered pain during and after cesarean delivery the most important concern.

  View details for DOI 10.1213/01.ane.0000167774.36833.99

  View details for Web of Science ID 000232115400045

  View details for PubMedID 16192541

• The ED50 and ED95 of intrathecal isobaric bupivacaine with opioids for cesarean delivery ANESTHESIOLOGY Carvalho, B., Durbin, M., Drover, D. R., Cohen, S. E., Ginosar, Y., Riley, E. T. 2005; 103 (3): 606-612

  Abstract

  The ideal intrathecal isobaric bupivacaine dose for cesarean delivery anesthesia is uncertain. While small doses (5-9 mg) of bupivacaine may reduce side effects such as hypotension, they potentially increase spinal anesthetic failures. This study determined the ED50 and ED95 of intrathecal isobaric bupivacaine (with adjuvant opioids) for cesarean delivery.After institutional review board approval and written informed consent were obtained, 48 parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this double-blind, randomized, dose-ranging study. Patients received a 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-mg intrathecal isobaric bupivacaine dose with 10 microg fentanyl and 200 microg morphine. Overall anesthetic success was recorded when no intraoperative epidural supplement was required during the cesarean delivery. ED50 and ED95 values for overall anesthetic success were determined using a logistic regression model.ED50 and ED95 values for overall anesthetic success were 7.25 and 13.0 mg, respectively. No advantages for low doses could be demonstrated with regard to hypotension, nausea, vomiting, pruritus, or maternal satisfaction, although this study was underpowered to detect significant differences in secondary outcome variables.The ED50 and ED95 values (7.25 and 13.0 mg, respectively) for intrathecal isobaric bupivacaine in this circumstance are similar to values the authors determined recently for hyperbaric bupivacaine using similar methodology. These ED50 and ED95 values are significantly higher than those advocated in previous reports in which success was claimed using lower intrathecal bupivacaine doses. The current study used stricter criteria to define "successful" anesthesia and support the use of larger bupivacaine doses to ensure adequate patient comfort.

  View details for Web of Science ID 000231574300023

  View details for PubMedID 16129987

• "Ultra-light" patient-controlled epidural analgesia during labor: effects of varying regimens on analgesia and physician workload INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Cohen, S. E., Giarrusso, K., Durbin, M., Riley, E. T., Lipman, S. 2005; 14 (3): 223-229

  Abstract

  Patient-controlled epidural analgesia (PCEA) offers many advantages over continuous epidural infusions for maintenance of labor analgesia. Some of these benefits may depend on the PCEA settings. This study evaluated several regimens for "ultra-light" (0.125%) PCEA with basal continuous infusion (CI) in labor with goals of minimizing physician interventions while providing good analgesia.Two hundred and twenty ASA I-II women receiving epidural analgesia during active labor (cervical dilation <5 cm) were randomly assigned in a double-blind manner to four treatment groups (n=30 in each). Analgesia was maintained with a PCEA/CI pump using bupivacaine 0.0625% + sufentanil 0.35 microg/mL. PCEA settings were: group A: CI 10 mL/h, PCEA bolus 6 mL, 8-min lockout; group B: CI 10 mL/h, PCEA bolus 12 mL, 16-min lockout; group C: CI 15 mL/h, PCEA bolus 6 mL, 8-min lockout; group D: CI 15 mL/h, PCEA bolus 12 mL, 16-min lockout.In groups A, B, C and D, 76, 77, 75 and 85% of parturients respectively, required no physician rescue boluses. Pain scores were low and maternal satisfaction was high in all groups, with minimal differences among them. Spontaneous vaginal delivery occurred in 78% of patients overall, instrumental (forceps or vacuum) delivery in 10% and cesarean section in 12%.These ultra-light PCEA regimens provided excellent analgesia with minimal physician workload and a high spontaneous delivery rate. Use of moderate to high-volume, ultra-light PCEA/CI techniques should facilitate provision of labor analgesia in busy obstetric units.

  View details for DOI 10.1016/j.ijoa.2005.02.003

  View details for Web of Science ID 000230915700008

  View details for PubMedID 15935646

• A survey of labor patient-controlled epidural anesthesia practice in Californian hospitals 37th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Wang, P., Riley, E. T., Cohen, S. E. LIPPINCOTT WILLIAMS & WILKINS. 2005: A29–A29

  View details for Web of Science ID 000228673000082

• Valdecoxib for postoperative pain management after cesarean section: A randomized, double-blinded, placebo controlled study 37th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Fuller, A. J., Brummel, C., Saxena, A., Chu, L., Riley, E. T., Cohen, S. E., Carvalho, B. LIPPINCOTT WILLIAMS & WILKINS. 2005: A15–A15

  View details for Web of Science ID 000228673000053

• Nitroglycerin to facilitate insertion of a labor epidural ANESTHESIOLOGY Carvalho, B. 2005; 102 (4): 872-872

  View details for Web of Science ID 000227923900036

  View details for PubMedID 15791131

• Single-dose, sustained-release epidural morphine in the management of postoperative pain after elective Cesarean delivery: Results of a multicenter randomized controlled study ANESTHESIA AND ANALGESIA Carvalho, B., Riley, E., Cohen, S. E., Gambling, D., PALMER, C., Huffnagle, H. J., Polley, L., Muir, H., Segal, S., Lihou, C., Manvelian, G. 2005; 100 (4): 1150-1158

  Abstract

  In this multicenter, randomized, controlled study, we compared the analgesic efficacy and safety profile of a new single-dose extended-release epidural morphine (EREM) formulation (DepoDur) with that of epidural morphine sulfate for the management of postoperative pain for up to 48 h after elective cesarean delivery. ASA physical status I or II parturients (n = 75) were anesthetized with a combined spinal/epidural technique. Parturients received intrathecal bupivacaine 12-15 mg and fentanyl 10 mug for spinal anesthesia and a single epidural injection of either 5 mg of standard (conventional preservative-free) morphine or 5, 10, or 15 mg of extended-release morphine after cord clamping for postoperative pain control. Single-dose EREM 10 and 15 mg groups significantly decreased total supplemental opioid medication use and improved functional ability scores for 48 h after surgery compared with those receiving 5 mg of standard morphine. Visual analog scale pain scores at rest and with activity at 24 to 48 h after dosing were significantly better in the 10- and 15-mg single-dose EREM groups versus the standard morphine group. There were no significant differences between the two 5 mg (single-dose EREM and standard morphine) groups. Single-dose EREM was well tolerated, and most adverse events were mild to moderate in severity. Single-dose EREM is a potentially beneficial epidural analgesic for the management of post-cesarean delivery pain and has particular advantages over standard morphine for the period from 24 to 48 h after surgery.

  View details for DOI 10.1213/01.ANE.0000149544.58230.FF

  View details for Web of Science ID 000227792400040

  View details for PubMedID 15781537

• The demise of general anesthesia in obstetrics revisited: prescription for a cure INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Lipman, S., Carvalho, B., Brock-Utne, J. 2005; 14 (1): 2-4

  View details for DOI 10.1016/j.ijoa.2004.10.003

  View details for Web of Science ID 000226572000002

  View details for PubMedID 15627530

• Patient preferences regarding cesarean section anesthesia outcomes 36th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Macario, A., Lipman, S., Muthusamy, A. D., Fuller, A., Brummel, C., Cohen, S. E. LIPPINCOTT WILLIAMS & WILKINS. 2004: B37–B37

  View details for Web of Science ID 000221070400116

• Pain tolerance in pregnancy 36th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Fuller, A. J., Lin, E., Mathusamy, A., Carvalho, B., Angst, M., Golianu, B. Y., Riley, E. T. LIPPINCOTT WILLIAMS & WILKINS. 2004: B9–B9

  View details for Web of Science ID 000221070400061

• Obstetric anaesthesia workload and time of day INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Coghill, J. 2004; 13 (2): 126-128

  View details for DOI 10.1016/j.ijoa.2003.09.007

  View details for Web of Science ID 000220424500018

  View details for PubMedID 15321423

• Neonatal chest wall rigidity following the use of remifentanil for cesarean delivery in a patient with autoimmune hepatitis and thrombocytopenia INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Mirikitani, E. J., Lyell, D., Evans, D. A., Druzin, A., Riley, E. T. 2004; 13 (1): 53-56

  Abstract

  Remifentanil is a useful adjunct in general anesthesia for high-risk obstetric patients. It provides effective blunting of the rapid hemodynamic changes that may be associated with airway manipulation and surgical stimulation. There have been no previous reports of opioid-related rigidity in the neonate delivered by a parturient receiving intraoperative remifentanil. We present a case of short-lived neonatal rigidity and respiratory depression following remifentanil administration during cesarean section to a parturient with autoimmune hepatitis complicated by cirrhosis, esophageal varices and thrombocytopenia.

  View details for DOI 10.1016/j.ijoa.2003.09.001

  View details for Web of Science ID 000188228500013

  View details for PubMedID 15321443

• Myocardial ischaemia precipitated by acute normovolaemic haemodilution TRANSFUSION MEDICINE Carvalho, B., Ridler, B. M., Thompson, J. F., Telford, R. J. 2003; 13 (3): 165-168

  Abstract

  Acute normovolaemic haemodilution (ANH) is widely used as part of a blood conservation strategy to minimize the use of allogenic blood in the peri-operative period. Its role has not been proven in a prospective randomized trial. The potential benefits must not blind clinicians to the possible hazards. We report a life-threatening complication of ANH prior to induction of anaesthesia for aortic aneurysm repair.

  View details for Web of Science ID 000183073100008

  View details for PubMedID 12791085

• "Ultra-light" PCEA techniques in labor: Minimizing physician workload while optimizing outcome 35th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Carvalho, B., Giarrusso, K., Durbin, M., Lipman, S., Rohlf, S., Riley, E. T., Cohen, S. E. LIPPINCOTT WILLIAMS & WILKINS. 2003: 2–2

  View details for Web of Science ID 000181969900005

• Vaginal examination: a requirement before calling the anaesthetist? BRITISH JOURNAL OF ANAESTHESIA Carvalho, B., Coghill, J. 2003; 90 (3): 402-402

  View details for DOI 10.1093/bja/aeg529

  View details for Web of Science ID 000181410300039

  View details for PubMedID 12594165

• The output of two sevoflurane vaporizers in the presence of helium BRITISH JOURNAL OF ANAESTHESIA Carvalho, B., Sanders, D. 2002; 88 (5): 711-713

  Abstract

  Modern vaporizers are designed to deliver accurate and stable concentrations of volatile anaesthetic agents. Carrier gas composition may adversely affect the output from vaporizers. No previous study has tested helium in combination with sevoflurane vaporizers, a clinically useful combination especially in anaesthesia for upper airway obstruction.This study evaluated the effect of increasing helium concentrations, carrier gas flow rates and varying the vaporizer dial setting on the output from Blease Datum and Drager Vapor 19.3 sevoflurane vaporizers.The presence of helium in the carrier gas had negligible effects on the output from both of the sevoflurane vaporizers tested. Carrier gas flow rates had the greatest effect on output but changes were within +/- 10% of baseline.Helium/oxygen mixtures can be used with these vaporizers without adversely affecting their performance.

  View details for Web of Science ID 000175399300017

  View details for PubMedID 12067011

• Single-session hypnotherapy for smoking cessation A cost-effective alternative? European Journal of General Practice Feldman M, James U, Carvalho B, Underwood MR 2002; 8 (2): 73-74
• Longterm functional recovery following day-case laparoscopic sterilisation: inhalational versus TIVA maintenance Ambulatory Surgery Carvalho B, Benton JI, Vickery PJ, Sneyd JR, Davies PRF, Langton JA 2002; 10 (1): 45-51
• Viagra (R): are anaesthetists rising to the challenge? ANAESTHESIA Carvalho, B., Smith, M. 2001; 56 (1): 91-93

  View details for Web of Science ID 000166796200032

  View details for PubMedID 11167459

• Hidden hazards of scavenging BRITISH JOURNAL OF ANAESTHESIA Hwang, N. C. 2000; 84 (6): 827-827

  View details for Web of Science ID 000087400200042

  View details for PubMedID 10895775

• Hyperkalaemia associated with transfusion of plasma reduced blood ANAESTHESIA Horsey, P. J. 2000; 55 (3): 294-294

  View details for Web of Science ID 000085738400031

  View details for PubMedID 10744565

• 'Near-miss' hyperkalaemic cardiac arrest associated with rapid blood transfusion ANAESTHESIA Carvalho, B., Quiney, N. F. 1999; 54 (11): 1094-1096

  Abstract

  A case is presented in which a relatively modest blood transfusion resulted in acute hyperkalaemia with a 'near-miss' cardiac arrest. While transfusion-related hyperkalaemia usually occurs in association with massive transfusions, several factors may have increased the risk of such an acute reaction. A high index of suspicion is required, especially in patients with risk factors. Anaesthetists should not be lulled into a false sense of security simply because modest volumes of blood are being transfused.

  View details for Web of Science ID 000083558400012

  View details for PubMedID 10540099

• Hidden hazards of scavenging BRITISH JOURNAL OF ANAESTHESIA Carvalho, B. 1999; 83 (3): 532-533

  View details for Web of Science ID 000082618700067

  View details for PubMedID 10655938