Emergence from General Anesthesia

Phases of Emergence

• Emergence from anesthesia is the process of returning to wakefulness and consciousness following a medically induced state of anesthesia.
• Discontinuation of anesthetic agents initiates redistribution and elimination, which are essential for emergence.
• Key elements of emergence include return of spontaneous ventilation, protective airway reflexes, and regaining consciousness.
• Emergence from general anesthesia occurs in part through the process of elimination of the anesthetic agent from the brain and other vital tissues. Several key components are listed below:
  • Redistribution: After cessation of inhaled anesthetics, the agent concentration decreases rapidly in the brain and other vessel-rich tissues due to high blood flow, resulting in rapid equilibration. This process leads to the initial decline in anesthetic effect.
  • Elimination of anesthetics: Anesthetic agents are typically cleared relatively quickly from highly vascular tissues. However, anesthetics are often stored in tissues, such as muscle and adipose tissue, which requires a longer time for their release and elimination.
  • Pharmacokinetic factors: The rate of emergence depends on the anesthetic’s blood/gas solubility, duration of anesthesia exposure, and the patient factors such as cardiac output and tissue blood flow.
  • Consciousness and cognitive recovery: As the anesthetic dissipates, the patient regains the ability to respond appropriately to commands. Signs of further recovery, such as orientation and cognition, may take longer to recover.
• The time required for complete emergence varies based on many factors, including the pharmacokinetics of anesthetic agents, the duration of anesthesia, and patient factors such as age and gender.
• The duration of anesthesia affects time to emergence, as longer exposure to anesthetic agents leads to greater accumulation in muscle and fat, slowing redistribution and elimination, which may result in delayed recovery.
• Desflurane, which has a low blood/gas solubility, has relatively short decrement times. The result is generally a quicker emergence. In contrast, agents with a higher solubility coefficient exhibit greater tissue accumulation and slower washout, which typically prolongs the time to emergence.
• For further details, please see the OA summary “Delayed Emergence After Anesthesia.” Link

Reactivation of Neural Circuits

• In addition to the elimination and redistribution of anesthetic agents, emergence also relies on the reactivation of neural circuits responsible for arousal, cognition, and consciousness.
• Brain electrical activity patterns during different states of consciousness:¹
  • Wakefulness: Prominent alpha activity
  • Initiation of anesthesia: increase in beta activity (13-25Hz)
  • General Anesthesia: increased delta activity (0-4Hz) and alpha oscillations
  • Deep Anesthesia: Burst suppression (mostly flat periods interrupted by occasional alpha/beta activity)
• Emergence shows different patterns of EEG activity depending on the anesthetic agent and patient factors.
• These patterns are especially prominent with the use of inhalation anesthetics and propofol. The patterns tend to differ with anesthetic agents that possess different mechanisms of action, such as the NMDA receptor antagonist, ketamine.²
• Clinically, the entire emergence process is monitored via physiological signs and patient behaviors. However, modern thought holds that emergence from general anesthesia is not a passive process and that, in the future, clinicians may be able to use therapeutic agents that actively regulate emergence.
• There is currently no clinical reversal agent available for general anesthesia. Some reversal agents exist for other medications typically given in concert with general anesthesia (e.g. sugammadex for neuromuscular blocking agents and naloxone for opiates.
• The early stages of emergence need to be closely monitored by a trained professional, as this period can lead to hemodynamic instability and carry the potential for acute complications as the patient regains spontaneous respirations.
• These complications include coughing, which may induce an increase in intracranial and intraocular pressures, respiratory events (e.g., laryngospasm) resulting in oxygenation problems, hypertension, and tachycardia, as well as mental status changes such as emergence delirium and delayed recovery of consciousness (i.e., hypoactive emergence).
• Once in the postanesthesia care unit, the patient continues to emerge from anesthesia and is often monitored closely until ready for discharge. The Aldrete scoring system evaluates a patient’s recovery from the anesthetic and consists of respirations, color, activity, blood pressure, and consciousness.

Neurobiology of Emergence

• Understanding the complex neurobiological mechanisms underlying emergence from general anesthesia could help clinicians improve patients’ recovery quality following anesthesia.
• General anesthetics are thought to interfere with both cortical and subcortical signaling pathways, leading to altered functional connectivity across brain regions, particularly between frontal and parietal areas.
• The connectivity between the thalamus and the cerebral cortex is significantly altered during general anesthesia³ (Figure 1).

• The essential brain regions involved in emergence include both deep brain structures and cortical areas, which regulate arousal and consciousness. More specifically, the thalamus and brainstem nuclei appear to play critical roles in the transition from unconsciousness to wakefulness (Figure 2). ⁴

• Throughout emergence, the disrupted neural connections slowly restore, and communication between the thalamus and cortex begins to re-establish.
• Many neurotransmitters play an important role in emergence from general anesthesia: acetylcholine, serotonin, histamine, and dopamine.⁵
• In addition, activation of arousal circuits plays an independent role in reversing anesthetic-induced unconsciousness and speeding up emergence.
• One such system is the orexinergic system of arousal. Neurons in the hypothalamus produce neuropeptides called orexins. Emerging data from animal models show that orexins speed the transition from anesthesia to wakefulness.⁶
• Stimulation of the catecholaminergic system is also thought to evoke arousal and accelerate emergence from anesthesia. In the picture below, the neural circuits are illustrated from the brain stem to the cortex as activated during emergence in the murine model.

• Stimulation of the dopaminergic neurons in the ventral tegmental area (midbrain) can also promote wakefulness and accelerate emergence.⁷
• Adenosine receptor subtypes A1 and A2A are expressed throughout the cortex and midbrain and are thought to play a role in arousal and emergence from general anesthesia. Caffeine is an antagonist to these specific receptors and has been shown to accelerate emergence in animal models.⁸
• Levels of consciousness involve intricate modulation of specific brainstem and thalamic circuits, which are shared with sleep but also exhibit distinct features under anesthesia.