 The advances of modern medicine have made surgery more common than ever before. General anesthesia makes life-saving surgeries possible, but abnormal or slow recovery from general anesthesia can also have harmful effects. In a recent study, scientists at the University of Michigan found that the addition of a second anesthetic drug could paradoxically accelerate recovery while also deepening anesthesia. Recent attempts to get post-op patients back on their feet faster have focused on promoting the brain's own arousal systems. The neurotransmitter acetylcholine is a key component of the brain's main arousal system. In the cerebral cortex, acetylcholine levels are high during periods of conscious activity, such as wakefulness and dreaming. Ketamine activates the brain's arousal centers and increases cortical acetylcholine despite also acting as an anesthetic. Therefore, the researchers hypothesized that the drug could accelerate recovery from anesthesia. To test the idea, they implanted rats with electrodes so they could monitor brain activity and the level of anesthesia. They also implanted a probe to measure acetylcholine levels in the cortex. The researchers then anesthetized the rats with the inhaled anesthetic isofluorine, which is commonly used in the operating room, and injected them with either saline or a subanesthetic dose of ketamine. Ketamine did accelerate recovery. Rats that got ketamine woke up about 45% faster than those that received saline. But even though the ketamine dose was too low to induce unconsciousness on its own, the drug also deepened the isofluorine anesthesia. In particular, burst suppression, a sign of deep anesthesia, was more frequent and lasted longer in ketamine-treated animals. These paradoxical effects appear to stem from ketamine's ability to boost arousal and disrupt excitatory signaling. During isofluorine anesthesia, acetylcholine levels are low, and ketamine could not raise them as long as isofluorine was being given. But as soon as isofluorine was stopped, the break was removed, and acetylcholine levels shot up. This increase likely sped up recovery, while ketamine's additional effect on excitatory signaling could explain how it deepened the isofluorine anesthesia. The results suggest that in rats at least, ketamine can accelerate post-anesthetic recovery by enhancing the brain's natural arousal system. Future clinical studies may determine whether ketamine can also speed up recovery from anesthesia in patients.