Surgical procedures typically require patients to be placed under general anesthesia, which is usually well-managed and very safe. Emergence from anesthesia can have clinical complications, however, including delayed emergence, intraoperative decreases in oxygenation and emergence delirium, which can be associated with cognitive dysfunction and morbidity. There are no approved strategies for reversing the effects of general anesthesia in order to prevent these outcomes. Ken Solt, assistant professor of anesthesia at Harvard Medical School and Massachusetts General Hospital (Boston, MA), explained in a press release, “Clinically, emergence from general anesthesia is still a passive process during which we just wait for the drugs to wear off and the patient to wake up, a process that can take from a few minutes to an hour or longer. Finding a way to safely arouse patients from anesthesia... may reduce problems such as postoperative delirium and cognitive dysfunction.”

Solt is leading an effort to find such a strategy. The neurological underpinnings of emergence from general anesthesia are not well understood, but results from recent studies have shown that certain drugs that activate arousal pathways in the brain can encourage emergence. For example, Solt's team previously reported that the stimulant methylphenidate, a drug used to treat attention deficit hyperactivity disorder, aroused rats from general anesthesia by activating dopamine pathways.

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In Solt's new study, rats received electrodes implanted in one of two brain areas that contain dopamine-releasing neurons: the ventral tegmental area (VTA) or the substantia nigra. Application of a mild electrical current to the electrode stimulated dopamine release in the surrounding area. After the rats were anesthetized with one of two general anesthetic agents (isoflurane or propofol), an electrical current was applied to the implanted electrodes. Stimulation of the VTA, but not the substantia nigra, aroused the rats from anesthesia: they moved, lifted their heads and righted themselves (Anesthesiol. 121, 311–319; 2014). Electrical stimulation of the VTA also shifted the rats' brain activity to patterns associated with arousal. The effects of electrical stimulation of the VTA in inducing arousal from anesthesia closely resembled the effects of pharmacological activation of dopamine receptors using methylphenidate. Overall, the results suggest that the arousal effect of methylphenidate is mediated by dopamine release specifically in the VTA. Activating the VTA at the end of a surgical procedure might therefore be used to induce emergence from anesthesia, stimulate consciousness and, according to Solt, “treat common postoperative emergence-related problems such as delirium and restore cognitive function.”