In Reply Dr Ward and colleagues note concerns about the potential adverse effects of anesthesia in adults. We are aware of the postoperative cognitive dysfunction syndrome in adults, but not of compelling evidence that the syndrome is primarily a drug safety issue for multiple agents in adults.
Nearly all studies of anesthetic agents in humans—adults or children—are at risk for confounding by the condition that prompts the surgery and by the procedure itself. On the other hand, in the studies of young animals summarized in our Viewpoint, anesthetic agents were unconfounded by surgery or predisposing conditions; and in longitudinal analyses, multiple anesthetic agents in a dose-dependent fashion influenced not only histopathology but also behavioral and cognitive outcomes during specific stages of neurodevelopment.