Emergence from general anesthesia

INTRODUCTION — Emergence is a passive process with the gradual return of consciousness after discontinuing administration of anesthetic and adjuvant agents at the end of the surgical procedure. Most patients transition smoothly from a surgical anesthetic state to an awake state with intact protective reflexes.

This topic will discuss preparations and techniques for emergence from general anesthesia, as well as problems that may occur during this period. Extubation of the trachea at the end of a surgical procedure is discussed separately. (See "Extubation following anesthesia".)

Induction and maintenance of general anesthesia are discussed in separate topics:

●(See "Induction of general anesthesia: Overview".)

●(See "General anesthesia: Intravenous induction agents".)

●(See "Maintenance of general anesthesia: Overview".)

PREPARATIONS FOR EMERGENCE — Preparations for emergence are initiated as the surgical procedure is ending.

Discontinue anesthetic agents — Optimal timing for discontinuation of inhalation and/or intravenous (IV) anesthetic agents depends on the specific agents and doses employed and the duration of their administration. To prevent emergence that is either too early or delayed, timing for discontinuation must be individually planned for each inhalation and/or IV agent as the surgical procedure nears completion.

Inhalation agents — Clearance of inhalation agents with termination of anesthetic effects and return to wakefulness depends on the presence of a concentration gradient favoring clearance from brain to blood, then from blood to alveoli (where the agent is exhaled from the body). Clearance by exhalation depends on the following factors:

●Partition coefficients of the selected inhalation agent – Speed of recovery from anesthesia is faster if the selected agent has a lower blood:gas partition coefficient (ie, the ratio of agent solubility in blood to its solubility in gas), brain:blood partition coefficient (ie, the ratio of agent solubility in brain to its solubility in blood), and tissue:blood partition coefficient (ie, the ratio of agent solubility in tissue to its solubility in blood) (table 1) [1]. These concepts are explained in detail in a separate topic. (See "Inhalation anesthetic agents: Properties and delivery", section on 'Partition coefficients and potency'.)

●Minute ventilation – Minute ventilation is the volume of gas exchanged in the patient's respiratory system per unit of time. A faster clearance of inhalation agents occurs with higher minute ventilation, which depends on the patient's tidal volume (TV) and respiratory rate (RR). (See "Inhalation anesthetic agents: Properties and delivery", section on 'Respiratory factors'.)

Near the end of surgical procedure, the RR is typically decreased, so the arterial partial pressure of carbon dioxide (PaCO₂) will increase to facilitate return of spontaneous breathing due to responses of the CNS chemoreceptors to hypercapnia and/or acidosis. However, this practice may reduce minute ventilation enough to delay removal of inhalation anesthetics; if so, emergence from general anesthesia may be delayed. For this reason, we decrease the patient's RR only after inhalation agents have been eliminated using a higher minute ventilation. Also, if the patient's end tidal carbon dioxide (ETCO₂) during surgery has been appropriately maintained at approximately 40 mmHg, then only minimal reduction in RR will be needed. (See "Mechanical ventilation during anesthesia in adults".)

●Cardiac output – Generally, increased cardiac output (CO) during emergence increases washout of inhalation agent from the brain and other tissue compartments, potentially speeding emergence. However, the effect of CO on speed of emergence is a complex interaction between tissue washout and pulmonary clearance. (See "Inhalation anesthetic agents: Properties and delivery", section on 'Cardiovascular factors'.)

●Technique-related factors – (See "Inhalation anesthetic agents: Properties and delivery", section on 'Technique-related considerations'.)

•Duration of administration – Prolonged administration of an agent with a higher tissue:blood partition coefficient and tissue solubility prolongs emergence, particularly when a more potent lipophilic agent (eg, isoflurane) is administered. (See "Inhalation anesthetic agents: Properties and delivery", section on 'Oil:gas partition coefficient/potency'.)

Phenomena related to partition coefficients, as noted above (see "Inhalation anesthetic agents: Properties and delivery", section on 'Partition coefficients and potency'), are further explained by context-sensitivity decrement times for each inhalation agent, which correlate the duration of agent administration with the time needed to decrease its tissue concentration. Prolonged duration of administration increases the degree to which agent accumulates in tissue depots and slows the decrease in agent concentration during emergence.

Also, higher agent solubility promotes a greater accumulation of agent in tissues and slows overall concentration equilibration time, with complex effects on speed of emergence [2]. For example, the time to decrease tissue concentration after discontinuing a potent volatile inhalation agent is relatively short and similar for isoflurane, sevoflurane, and desflurane if duration of administration was <60 minutes. However, if duration of anesthetic administration is >60 minutes for isoflurane or >120 minutes for sevoflurane, the time required to decrease tissue concentration of these agents is much longer than that for desflurane (figure 1). For sevoflurane, this disadvantage can be overcome if sevoflurane is weaned during the final 15 minutes of surgery, and return of airway reflexes is as rapid as it would be after discontinuation of desflurane [3].

•Inhaled concentration of anesthetic agent – If concentration of inhaled agent is reduced to zero (ie, discontinuation of agent administration), the resultant concentration gradient favors transfer of agent from blood to alveoli, with subsequent elimination via exhalation. (See "Inhalation anesthetic agents: Properties and delivery", section on 'Concentration effect'.)

•Fresh gas flow in the breathing circuit – High fresh gas flow prevents rebreathing of inhaled gas containing any anesthetic agent, thereby contributing to rapid washout.

•Elimination of coadministered of nitrous oxide (N₂O) – The low blood:gas partition coefficient of N₂O allows its rapid elimination via alveoli at the end of procedure (see "Inhalation anesthetic agents: Clinical effects and uses", section on 'Nitrous oxide'). Bulk transfer of N₂O gas out of the blood promotes accelerated reduction of the partial pressure of coadministered volatile inhaled anesthetic agents, facilitating faster emergence. This phenomenon is termed the "second gas" effect [4,5]. (See "Inhalation anesthetic agents: Properties and delivery", section on 'Second gas effect'.)

However, such bulk diffusion of N₂O gas into alveoli during emergence also decreases alveolar oxygen (O₂) concentration, which may cause diffusion hypoxia. This is prevented by delivery of high inspired O₂ concentration for several minutes before and after discontinuing N₂O. (See "Inhalation anesthetic agents: Clinical effects and uses", section on 'Disadvantages and adverse effects'.)

Intravenous agents — For IV agents, recovery time depends on the rate of decrease of the agent from the central compartment (brain), either by redistribution or elimination. The metabolism of each agent depends on adequacy of the patient's liver and/or kidney function, potency of each agent, multi-compartmental pharmacokinetics after bolus and/or continuous infusion doses of each agent, and whether any administered agent has active metabolites.

●Bolus doses

•Sedative-hypnotic agents – After a bolus injection, duration of action is short for most anesthetic agents. For example, the duration of action after a bolus dose of propofol (eg, for induction of anesthesia) is approximately 10 minutes. Termination of action is due to rapid redistribution of this lipophilic agent from brain into a very large volume of distribution that includes other fatty tissues. Metabolism and excretion play minor roles in termination of effects following a single bolus. (See "General anesthesia: Intravenous induction agents", section on 'Propofol' and "Maintenance of general anesthesia: Overview", section on 'Sedative-hypnotic agent: Propofol'.)

•Opioids – Similarly, duration of action is short for most opioids administered via bolus injection to provide the analgesic component of a total intravenous anesthesia (TIVA) technique or as adjuvant agents during an inhalation anesthetic technique. For example, the duration of action after a fentanyl bolus is relatively short, approximately 30 to 45 minutes, primarily due to redistribution and its high lipid solubility, while the duration of action of the highly lipophilic opioid remifentanil is extremely short due to extremely rapid distribution to highly perfused tissues (eg, brain, heart, kidney, and gastrointestinal tract) (figure 2 and table 2). (See "Perioperative uses of intravenous opioids in adults: General considerations".)

●Combinations of agents – Combinations of anesthetic, opioid, and adjuvant agents result in synergistic rather than merely additive effects, necessitating dose reductions for each agent during the maintenance phase of anesthesia [6-8]. Such combinations of agents also result in increased total recovery time due to both the direct synergistic effects that may prolong the duration of an anesthetized state, as well as indirect effects such as respiratory depression causing delay in elimination of inhalation anesthetics and/or sedation due to carbon dioxide (CO₂) narcosis. Specific examples of combinations of anesthetic and analgesic agents that may delay emergence include:

•Propofol – Synergy occurs when propofol, a sedative-hypnotic agent primarily acting on gamma-aminobutyric acid type A (GABA_A) receptors, is administered concomitantly with medications acting on other receptor types. (See "Maintenance of general anesthesia: Overview", section on 'Sedative-hypnotic agent: Propofol' and "Delayed emergence and emergence delirium in adults", section on 'Sedative-hypnotic agents'.)

•Opioids – Opioids are commonly used as part of many general anesthetic techniques due to their analgesia, anxiolysis, and stress-response blunting effects. Their sedative effects are synergistic with all other anesthetic and adjuvant agents. Since opioids may contribute to delayed emergence when combined with other anesthetics, the benefits of opioid administration must be weighed against the possibility of respiratory depression, CO₂ narcosis, and sedation in the selection and dosing of specific opioid agents before emergence. (See "Perioperative uses of intravenous opioids in adults: General considerations" and "Delayed emergence and emergence delirium in adults", section on 'Opioids'.)

•Dexmedetomidine – Dexmedetomidine, a highly selective alpha₂ agonist acting on receptors in the brain and spinal cord, may be administered in the perioperative period to take advantage of its analgesic, sedative, anxiolytic, and sympatholytic properties [9,10]. This adjuvant anesthetic agent has synergistic effects when combined with anesthetic and opioid agents that act on other receptors; thus, dexmedetomidine reduces intraoperative dose requirements for these other agents [11,12].

Dexmedetomidine has a variable context-sensitive half-time after continuous infusion depending on the duration of infusion (eg, four minutes after infusion for 10 minutes; 250 minutes after infusion for eight hours) [13]. Resolution occurs gradually after discontinuation of dexmedetomidine, such that residual sedation, reduced ventilatory responses to hypoxia and hypercapnia, as well as hemodynamic depression of heart rate (HR) and blood pressure (BP), may persist in the early postoperative period [12,14,15]. This leads to difficulty in decisions regarding optimal timing for discontinuation of dexmedetomidine infusion in preparation for emergence from general anesthesia. Since there are no reversal agents for alpha₂-adrenergic agonists, timely discontinuation of administration or reduction of infusion rate is particularly important in planning for emergence. (See "Maintenance of general anesthesia: Overview", section on 'Dexmedetomidine' and "Delayed emergence and emergence delirium in adults", section on 'Sedative-hypnotic agents'.)

•Ketamine – As a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that blocks glutamate, ketamine produces dissociative anesthesia with profound analgesia. Clinical signs of ketamine overdose during and immediately after emergence include emergence delirium, delayed emergence, and respiratory depression [16,17], and even a single subanesthetic dose of ketamine can cause hallucination and nightmares [18]. (See "Ketamine poisoning", section on 'Clinical presentation' and "Delayed emergence and emergence delirium in adults", section on 'Evaluation and treatment'.)

•Lidocaine – Lidocaine is occasionally employed as an adjuvant agent during general anesthesia, typically administered as a bolus dose followed by a continuous infusion [19]. It reduces total propofol dosage during a TIVA technique, and reduces minimum alveolar concentration (MAC) for volatile agents observed during an inhalation anesthetic technique [7,20,21]. During emergence, excessive lidocaine levels may cause CNS toxicity manifesting as delayed emergence due to sedation or emergence agitation. (See "Maintenance of general anesthesia: Overview", section on 'Lidocaine' and "Major side effects of class I antiarrhythmic drugs", section on 'Neurologic toxicity'.)

•Benzodiazepines – A benzodiazepine, typically midazolam, may have been administered for anxiolytic effect. Sedative and respiratory depressant effects of benzodiazepines are synergistic with other anesthetic and adjuvant agents, particularly when midazolam is combined with fentanyl [7]. Also, there are potential adverse effects such as amnesia, drowsiness, and cognitive dysfunction [22], as well as an unpredictable and relatively high risk of paradoxical reactions such as irritability and aggressiveness during emergence [23]. (See "Delayed emergence and emergence delirium in adults", section on 'Benzodiazepines'.)

•Other agents – Other agents with sedative effects may delay emergence if administered in the preoperative or intraoperative period. Examples include magnesium sulfate and gabapentinoids [24-27]. Potentiation of CNS effects of intravenous and inhalation anesthetic agents may also occur due to interactions with preoperative prescription drugs, supplements, recreational drugs, or alcohol (table 3). Ingestion of such other agents in the preoperative period may be known or unknown to the anesthesiologist.

●Use of continuous infusions – If continuous infusions of sedative-hypnotic agents or opioids have been administered, considerations for termination of effect include the context-sensitive half-time of each agent (ie, the time required for plasma concentration to decline by 50 percent following discontinuation of a steady state infusion), as well as the duration of each agent's infusion. For propofol (the most commonly selected sedative-hypnotic agent), the low, flat plot of context-sensitive half-time correlates with a relatively short recovery time despite the duration of maintenance infusion (figure 3) (see "Maintenance of general anesthesia: Overview", section on 'Sedative-hypnotic agent: Propofol'). For fentanyl, a commonly selected opioid, the context-sensitive half-time after infusion is considerably longer (typically >200 minutes after infusion at a maintenance dose for approximately three hours), while the context-sensitive half-time for the ultrashort-acting opioid remifentanil is only approximately four minutes, regardless of duration of administration (figure 4) (see "Maintenance of general anesthesia: Overview", section on 'Analgesic component: Opioid agents'). If other nonopioid adjuvant agents were also administered (eg, dexmedetomidine, ketamine, lidocaine, benzodiazepines), either as part of a TIVA technique or to decrease the MAC during an inhalation anesthetic technique or as an opioid-free anesthetic technique, their effects also influence recovery time. (See "Maintenance of general anesthesia: Overview", section on 'Adjuvant agents'.)

Assess and reverse effects of neuromuscular blocking agents

●Assess degree of muscle relaxation – If a nondepolarizing neuromuscular blocking agent (NMBA) was administered, the degree of residual neuromuscular blockade is determined using a peripheral nerve stimulator. Residual neuromuscular block is associated with weakness of upper airway muscles and increased risk of hypoventilation and hypoxemia, as well as risk for aspiration and postoperative pulmonary complications. Full recovery of neuromuscular function (ie, train-of-four [TOF] ratio of ≥0.9) must be achieved prior to extubation of the trachea. We avoid use of the peripheral nerve stimulator to induce a tetanic stimulus just before TOF stimulation, as this may lead to underestimation of the degree of residual neuromuscular blockade if the patient is extubated shortly after the augmented TOF assessment. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Avoidance of residual neuromuscular blockade'.)

●Administer reversal agents – Appropriate doses of reversal agents (ie, neostigmine or sugammadex) are based on the level of existing neuromuscular block at the time of administration (table 4). In some cases, reversal of neuromuscular blockade can occur by spontaneous recovery. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Reversal of neuromuscular block'.)

Observe electroencephalographic evidence of return of consciousness — Evaluation of raw electroencephalographic (EEG) waveform, if available, typically shows gradual loss of slow-delta and alpha oscillations, with return of higher-frequency beta and gamma oscillations as the patient regains consciousness [28-30]. However, the raw EEG waveform varies before full return of consciousness, depending on the anesthetic agents that were administered. Processed EEG may also be used to analyze raw EEG signal and monitor the depth of anesthesia. (See "Accidental awareness during general anesthesia", section on 'Brain monitoring'.)

Evaluate physiologic signs of return of consciousness — During emergence, the patient's state of consciousness can be tracked by observing changes in physiologic signs (figure 5) [30]. Patients typically regain the ability to breathe spontaneously and shortly after the reversal of muscle relaxation and accumulation of carbon dioxide in the cerebral circulation. Although the respiratory pattern is typically irregular and tidal volumes are initially small, progression in the ability to breathe without assistance usually occurs within minutes [30]. Persistent hypoventilation and hypercapnia may be due to opioid effects and/or incomplete reversal of neuromuscular blocking agents. (See "Delayed emergence and emergence delirium in adults", section on 'Opioids' and "Delayed emergence and emergence delirium in adults", section on 'Neuromuscular blocking agents'.)

Swallowing and gagging reflexes, salivation, tearing, and grimacing typically occur concurrently with return of spontaneous breathing or shortly thereafter, indicating return of specific brainstem centers [30]. After reversal of a NMBA, return of the patient's muscle tone indicates return of function in motor circuits. Return of the corneal reflex indicates recovery of sensory function. Voluntary control of ocular movements indicates recovery of function in the midbrain, pons, and certain cortical cerebellar and basal ganglia circuits (figure 5) [30]. Finally, volitional demonstrations of volitional movements and responses to verbal commands indicate conscious awareness.

Notably, spontaneous eye opening is often one of the last signs observed during emergence from general anesthesia, and may occur well after reliable responses to verbal commands [30].

Confirm antiemetic prophylaxis — Specific agents and doses and timing for antiemetic prophylaxis are discussed in detail separately. (See "Postoperative nausea and vomiting", section on 'Our strategy'.)

Evaluate adequacy of analgesia — During return of consciousness, increases in HR, BP, and RR suggest that analgesia may be inadequate. Regional analgesic techniques or IV analgesic agents may be used to provide supplemental analgesia, as appropriate. Similar to the immediate postoperative setting, the timing, dose, and choice of agent or technique used to supplement analgesia during emergence should be tailored to the medical condition of the patient, likelihood of pain immediately after the specific surgical procedure, and whether the patient has a history of opioid dependency or abuse. (See "Approach to the management of acute pain in adults".)

Pain relief during emergence may be accomplished by the administration of judicious doses of a longer-acting opioid such as morphine or hydromorphone. Multimodal opioid-sparing strategies may also be utilized to achieve perioperative pain control. When possible, techniques such as surgical placement of a local surgical site infiltration, administration of an epidural analgesic dose, or performance of a transverse abdominis plane (TAP) block after abdominal surgery are employed shortly before emergence to decrease the required dose of IV opioids and other analgesic agents. (See "Approach to the management of acute pain in adults", section on 'Creating a plan for analgesia'.)

EMERGENCE WITH AN ENDOTRACHEAL TUBE — In most cases, patients with an endotracheal tube are extubated at the end of the surgical or other intervention. This process may be associated with complications, including loss of the airway and the need to reintubate. Since extubation is an elective procedure, it should be planned in advance and executed when conditions are optimal [31]. (See "Extubation following anesthesia", section on 'Extubation risk stratification' and "Extubation following anesthesia", section on 'Management of extubation'.)

Techniques and pharmacologic agents to ameliorate physiologic responses to extubation (eg, sympathetic stimulation caused by stimulation of airway reflexes) are described separately. (See "Extubation following anesthesia", section on 'Minimizing physiologic response to extubation'.)

Remifentanil extubation technique — In selected cases, it is desirable to avoid all coughing or retching during extubation (eg, when there is patient risk with any increase in intracranial pressure or intraocular pressure). In such cases, an infusion of remifentanil (eg, approximately 0.1 mcg/kg per minute) may be briefly administered to allow tracheal extubation as soon as the patient can follow commands, which typically occurs before spontaneous respiratory efforts or recovery of airway reflexes. (See "Anesthesia for emergency eye surgery", section on 'Emergence from anesthesia' and "Anesthesia for craniotomy in adults", section on 'Emergence from anesthesia'.)

Postponed extubation — In patients with respiratory failure, hemodynamic instability, airway edema, clinically-significant neuromuscular weakness, or known impaired sensorium, it is usually desirable to postpone extubation.

Spontaneous ventilation — In some cases, the patient may be breathing spontaneously, but the endotracheal tube (ETT) is left in place temporarily, with planned extubation in the post-anesthesia recovery unit (PACU) or intensive care unit (ICU). Spontaneous breathing without any ventilator support (eg, through a T-piece (figure 6)) may be allowed if the patient's work of breathing is not excessive. However, some patients may require a low level of pressure support using a ventilator (eg, inspiratory pressure augmentation of 5 to 8 cm H₂O).

Transport of the patient from the operating room (OR) to another location is done cautiously if the patient is emerging from general anesthesia. Intratracheal movement of the in situ ETT may occur due to movement onto the bed or gurney in preparation for transport, and inadequate levels of anesthesia can cause bronchospasm, especially in patients with preexisting reactive airway disease. Intravenous (IV) medications administered to deepen anesthesia to avoid or treat bronchospasm may cause spontaneous breathing to cease, which necessitates initiation of ventilatory support.

When the patient successfully passes a number of pre-set physiologic criteria (eg, heart rate, respiratory rate, blood pressure, gas exchange) with no contraindications to extubation, the ETT can be removed. Patients should always be extubated at a location with all the necessary equipment (including airway devices) and personnel immediately available in case of loss of the airway after extubation. (See "Initial weaning strategy in mechanically ventilated adults", section on 'Choosing a weaning method' and "Initial weaning strategy in mechanically ventilated adults".)

Controlled ventilation — For patients requiring ongoing controlled ventilation, continued sedation/analgesia allows tolerance of the endotracheal tube. As surgery concludes, general anesthetic techniques used in the OR are converted to continuous sedation techniques (eg, propofol infusion with or without infusion of an opioid such as fentanyl) in preparation for transfer of the intubated patient to the ICU. (See "Sedative-analgesia in ventilated adults: Management strategies, agent selection, monitoring, and withdrawal" and "Sedative-analgesia in ventilated adults: Medication properties, dose regimens, and adverse effects".)

Continuous sedation and controlled ventilation are maintained during transport of the intubated patient and during the subsequent handoff in the ICU. (See "Handoffs of surgical patients".)

EMERGENCE WITH A SUPRAGLOTTIC AIRWAY — A supraglottic airway (SGA), such as a laryngeal mask airway, may be used as the planned airway management device (with either spontaneous or controlled ventilation). (See "Supraglottic devices (including laryngeal mask airways) for airway management for anesthesia in adults".)

For patients who had ventilation by SGA during surgery, spontaneous breathing without assistance is resumed near the end of the procedure in preparation for SGA removal. Similar to requirements for endotracheal extubation, adequate reversal of neuromuscular blockade must be ensured prior to emergence from anesthesia (see 'Assess and reverse effects of neuromuscular blocking agents' above). To ensure airway patency after removal of the SGA, the patient must typically demonstrate return of airway reflexes and responses to verbal commands prior to removal. However, similar to "deep" extubation of an endotracheal tube (ETT), the SGA may be removed while the patient is still under general anesthesia after resumption of spontaneous breathing in selected patients who require avoidance of stimulation of airway reflexes and resultant coughing, straining, and hemodynamic stress.

After the removal of the SGA, oxygen (O₂) is provided by face mask as the patient gradually emerges from anesthesia. Simple airway maneuvers may be necessary to maintain oxygenation and airway patency. Similar to emergence with an ETT, patients should always be extubated at a location with all the necessary equipment (including airway devices) and personnel immediately available in case of loss of the airway after extubation. (See "Supraglottic devices (including laryngeal mask airways) for airway management for anesthesia in adults", section on 'Supraglottic airway-related complications'.)

EMERGENCE AFTER MASK VENTILATION — Airway management with facemask alone is sometimes used for short cases when there is no surgical need for muscle relaxation, but only if the anesthesiologist will have full access to the patient's airway throughout the case. (See "Airway management for induction of general anesthesia", section on 'Airway device options' and "Basic airway management in adults", section on 'Bag-mask ventilation'.)

For patients who were ventilated by facemask during surgery, spontaneous breathing without assistance is resumed at the end of the procedure. Techniques such as jaw thrust and oral or nasal airway insertion to avoid upper airway obstruction may be necessary in some patients, as well as continued administration of oxygen (O₂) to avoid hypoxemia.

UNANTICIPATED NEED TO INTERRUPT THE EMERGENCE SEQUENCE — In some cases, additional surgical interventions are determined to be necessary, or an unanticipated surgical complication occurs as the patient is emerging from general anesthesia. Such situations necessitate temporary re-establishment of a deeper level of anesthesia (ie, surgical or Stage III anesthesia (table 5)).

Typically, this is accomplished by administration of an intravenous (IV) sedative-hypnotic agent such as propofol. A supplemental short-acting inhaled agent such as nitrous oxide can be added if necessary.

If a surgical or other problem cannot be resolved after re-establishing general anesthesia, the patient may remain sedated and intubated with controlled ventilation. (See 'Postponed extubation' above.)

PROBLEMS DURING AND AFTER EMERGENCE — Problems during or immediately after emergence that may require urgent treatment while the patient is still in the operating room (OR) include respiratory complications, hemodynamic instability, or severe emergence agitation. Transport from the OR to a post-anesthesia care unit (PACU) is delayed until the patient is able to maintain adequate oxygenation and ventilation during spontaneous ventilation, is hemodynamically stable, and can be aroused to follow verbal commands. (See "Handoffs of surgical patients".)

Airway or respiratory problems — Airway and respiratory problems requiring urgent treatment may occur during emergence from general anesthesia, typically before or immediately after removal of an artificial airway (eg, endotracheal tube [ETT] or supraglottic airway [SGA]):

●Prior to removal of an ETT or SGA, coughing and "bucking" on the artificial airway may be noted as the patient transitions through Stage II (table 5), and this may be accompanied by bronchospasm. These reflex airway reactions to the noxious stimulus of the ETT or SGA may be attenuated by allowing spontaneous ventilation and/or administering small doses of intravenous (IV) lidocaine or an opioid. (See "Extubation following anesthesia", section on 'Minimizing physiologic response to extubation'.)

In one randomized study, administration of dexmedetomidine 1 mcg/kg at the end of the surgical procedure reduced the incidence of moderate to severe coughing (from 56 to 10 percent) compared with placebo [32]. However, 13 percent of patients receiving dexmedetomidine at this dose developed hypotension with systolic blood pressure (BP) <90 mmHg, compared with none in the placebo group. (See 'Hemodynamic instability' below.)

●Residual effects of neuromuscular blocking agents (NMBAs) may cause weakness with inadequate spontaneous ventilation and/or respiratory distress may occur before or after extubation. This is typically due to inadequate reversal of the effects of NMBAs. Inadequate muscle strength is confirmed with a peripheral nerve stimulator, and additional reversal agent is administered if indicated. Furthermore, persistent impairment of the peripheral chemoreflex with blunting of ventilatory responses to hypoxia can occur despite complete reversal of rocuronium with neostigmine or sugammadex [33]. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Avoidance of residual neuromuscular blockade' and "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Reversal of neuromuscular block'.)

Such residual weakness or reduced ventilatory responses to hypoxia may increase the risk for serious adverse respiratory events shortly after emergence from general anesthesia and in the PACU [34,35]. (See "Respiratory problems in the post-anesthesia care unit (PACU)", section on 'Pharyngeal muscular weakness' and "Respiratory problems in the post-anesthesia care unit (PACU)", section on 'Neuromuscular blocking agents'.)

●Apnea may occur before or after removal of an artificial airway. This is treated by resuming positive pressure ventilation via a mask while the patient is evaluated for residual effects of opioids or other anesthetic agents, residual neuromuscular blockade, hypothermia, or a neurologic disorder. (See "Respiratory problems in the post-anesthesia care unit (PACU)", section on 'Central and peripheral nervous system abnormalities'.)

If indicated, additional reversal agent for a NMBA is administered. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Reversal of neuromuscular block' and "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Avoidance of residual neuromuscular blockade'.)

Naloxone may be considered for reversal of opioid effects but is not routinely administered because of its potential adverse side effects (eg, acute severe pain, tachycardia, severe hypertension, flash pulmonary edema) (table 6). (See "Cardiovascular problems in the post-anesthesia care unit (PACU)", section on 'Anesthetic agents'.)

In some cases, persistent apnea in the OR necessitates continued controlled ventilation while waiting for elimination of residual anesthetic agents or recovery of muscle strength. (See "Extubation following anesthesia", section on 'Inability to tolerate extubation'.)

●Laryngospasm may occur after removal of an ETT or SGA. This is treated by removing the noxious stimulus (eg, removal of blood or secretions by suctioning the airway) and employing positive pressure bag-mask ventilation concurrent with a jaw thrust maneuver. Also, applying pressure with fingertips to the "laryngospasm notch," which is the area between the mastoid process, the ramus of the mandible, and the base of the skull (also known as "Larson’s maneuver" (picture 1)), may rapidly reverse laryngospasm [36-38].

If desaturation develops, it may be necessary to administer a small dose of IV succinylcholine 0.1 mg/kg to relax the cords in order to achieve adequate ventilatory support and oxygenation. In some cases, emergency intubation or reintubation may be necessary. Thus, an anesthetic induction agent, full intubating dose of succinylcholine, assortment of ETTs, laryngoscope(s), and the anesthesia breathing circuit should remain immediately available while the patient is still in the OR.

Possible scenarios in this setting include the following:

•If it is necessary to re-establish neuromuscular blockade to treat laryngospasm, succinylcholine is typically selected. However, onset of muscle relaxation may be delayed due to presence of residual nondepolarizing NMBA, with occupation of a fraction of the post-junctional nicotinic receptors [39].

•If rocuronium is selected rather than succinylcholine, a dose of 1.2 mg/kg if rocuronium is suggested within 30 minutes of sugammadex administration, and the minimum waiting time for muscle relaxation is five minutes [40].

•If it is necessary to re-establish longer lasting neuromuscular blockade shortly after sugammadex has been administered, a nonsteroidal benzylisoquinolinium-based NMBA such as cisatracurium may be used (since sugammadex has no effect on neuromuscular blockade achieved with these agents) [41,42]. However, the onset of muscle relaxation may be delayed and the duration of blockade may be shortened [43].

●Noncardiogenic negative pressure pulmonary edema may develop as a sequelae of airway obstruction due to biting that clamps off an ETT that is still in place, or due to laryngospasm or pharyngeal obstruction in a patient without an artificial airway. The mechanism is forceful inspiratory efforts against a closed glottis creating large negative intrathoracic pressures, increased left ventricular preload and afterload, and pulmonary capillary failure resulting in interstitial and alveolar edema and hemorrhage [44]. Onset is typically rapid, with severe respiratory distress and copious pink frothy secretions from the mouth or endotracheal tube.

Treatment of noncardiogenic pulmonary edema is supportive. Supplemental oxygen (O₂) is administered, and some patients receive diuretics. Endotracheal intubation or reintubation may be necessary if oxygenation is severely impaired, but a trial of noninvasive continuous positive airway pressure is appropriate if there are no contraindications. (See "Respiratory problems in the post-anesthesia care unit (PACU)", section on 'Ventilatory support' and "Overview of the management of postoperative pulmonary complications", section on 'Pulmonary edema'.)

In some patients, respiratory problems may develop or recur later after emergence, typically during transfer to the PACU or in the immediate postoperative period. (See "Respiratory problems in the post-anesthesia care unit (PACU)".)

Hemodynamic instability — Emergence from general anesthesia is associated with increased sympathetic tone, hypertension, and tachycardia. Typically, this is due to discomfort due to the ETT or withdrawal of anesthetic and analgesic medications at the end of the surgical procedure, which may unmask pain. Increased sympathetic tone also occurs with agitation, coughing, or thrashing during emergence. Hypertension and tachycardia increase risk for cardiovascular complications in patients with cardiovascular disease (eg, coronary artery disease, congestive heart failure, chronic or poorly controlled hypertension), and increases in BP may cause bleeding complications at freshly sutured surgical sites. Although administration of dexmedetomidine 1 mcg/kg at the end of the surgical procedure may reduce the incidence of hypertension and tachycardia compared with placebo, patients may develop hypotension (with systolic BP <90 percent) [32]. A 2019 meta-analysis noted that hypotension and bradycardia frequently occurred after administration of dexmedetomidine, and sometimes persisted even after cessation of administration [15].

Pain is managed with IV administration of analgesic medications, such as an opioid or ketorolac, or administration of a dose of a regional or neuraxial anesthetic medication. If pain is not the underlying cause of hypertension and/or tachycardia, administration of an IV dose of a beta blocker (eg, esmolol, metoprolol, labetalol) or other antihypertensive (eg, nicardipine, hydralazine) may be necessary. (See "Hemodynamic management during anesthesia in adults", section on 'Hypertension: Prevention and treatment' and "Arrhythmias during anesthesia", section on 'Sinus tachycardia'.)

Delay or failure to emerge — Causes and management delayed emergence are discussed in detail in a separate topic. (See "Delayed emergence and emergence delirium in adults", section on 'Delayed emergence'.)

Severe agitation — Patients may become agitated during emergence as they transition through the delirium stage of general anesthesia (Stage II) (table 5) [45-48]. Such transient agitation occurs in up to 19 percent of adult patients during emergence in the OR, depending on assessment criteria [46,48]. Some patients are extremely agitated with violent thrashing movements [49]. Although this stage is usually very brief (a few minutes), a struggling combative patient may jeopardize fresh surgical suture lines, orthopedic fixations, vascular grafts, drains, or intravascular catheters, or the patient may suffer a contusion, sprain, or corneal abrasion. Also, sympathetic stimulation in an agitated patient may result in severe tachycardia and hypertension. (See 'Hemodynamic instability' above.)

Often, noxious stimulation caused by the ETT is the primary cause of emergence agitation, with resolution immediately after the trachea is extubated. Patients who remain agitated after extubation should be further evaluated and treated before leaving the OR. Common causes include:

●Anxiety and disinhibition caused by residual effects of anesthetics or adjuvant agents. (See "Delayed emergence and emergence delirium in adults", section on 'Consider prolonged drug effects'.)

●Inadequately treated pain due to surgery or other discomfort (eg, urinary retention, trapped bowel gas, tight dressings). (See 'Persistent pain' below.)

●Panic caused by dyspnea and respiratory distress. In particular, residual effects of NMBAs may cause muscle weakness with inadequate respiration and discoordinated flapping movements that may mimic agitation. (See 'Airway or respiratory problems' above and "Delayed emergence and emergence delirium in adults", section on 'Neuromuscular blocking agents'.)

●Hypoxemia or hypercarbia. (See "Respiratory problems in the post-anesthesia care unit (PACU)".)

All possibilities are considered since multiple factors may be causative (table 7). Although uncommon, a neurologic disorder, such as cerebral hypoperfusion or seizure activity, may manifest as agitation. (See "Delayed emergence and emergence delirium in adults", section on 'Consider neurologic disorders'.)

Management includes reassurance and reorientation while identifiable causes are being treated. Pharmacologic treatment of emergence agitation may be appropriate in selected patients before leaving the OR (eg, administration of small doses of opioid to treat pain, or a short-acting benzodiazepine or haloperidol to treat severe anxiety and agitation in a patient without pain) [50]. However, such analgesic, anxiolytic, or sedative agents should not be administered if hypoxemia, hypercapnia, hypoglycemia, or hypotension are a suspected cause of agitation.

In some cases, hyperactive delirium with agitation, hyperexcitability, disinhibition, crying, restlessness, and mental confusion may not become evident until later after emergence, or may persist or reappear during the early postoperative period after initial treatment. Management of this complication in the PACU setting is described separately. (See "Delayed emergence and emergence delirium in adults", section on 'Emergence delirium'.)

Persistent pain — Patients with evidence of pain immediately after emergence may require small doses of an opioid or other IV or regional analgesic agents to prepare for a smooth exit from the OR and transport to the PACU. Dosing of opioids must be judicious to avoid apnea during transport. Further management of acute pain in this setting is discussed separately. (See "Approach to the management of acute pain in adults".)

Persistent hypothermia — Since even mild untreated postoperative hypothermia may cause complications, warming is continued uninterrupted at the end of the surgical procedure for patients with temperature <36°C. A decrease in body temperature as little as 2°C slows metabolism of anesthetics and NMBAs. For this reason, if temperature is <33°C, extubation is typically delayed until the patient can be adequately rewarmed. (See "Perioperative temperature management", section on 'Prolongation of drug effects'.)

After extubation at a temperature of >35°C, active patient warming (eg, using a forced-air warming device) should be continued in the PACU until the temperature reaches 36°C. (See "Perioperative temperature management", section on 'Postoperative temperature derangements'.)

SUMMARY AND RECOMMENDATIONS

●Typical emergence – Emergence is a passive process with the gradual return of consciousness after discontinuing administration of anesthetic and adjuvant agents at the end of the surgical procedure. Most patients transition smoothly from a surgical anesthetic state to an awake state with intact protective reflexes. (See 'Introduction' above.)

●Preparations for emergence – Preparations for emergence are initiated as the surgical procedure is ending. These include:

•Discontinuation of anesthetic agents and adjuvants. (See 'Discontinue anesthetic agents' above.)

•Assessment and reversal of effects of neuromuscular blocking agents (NMBAs). (See 'Assess and reverse effects of neuromuscular blocking agents' above.)

•Administration of antiemetics. (See 'Confirm antiemetic prophylaxis' above.)

•Evaluation of adequacy of analgesia. (See 'Evaluate adequacy of analgesia' above.)

●Emergence with an endotracheal tube

•In most cases, patients with an endotracheal tube (ETT) are extubated at the end of the surgical or other intervention when conditions are optimal. (See 'Emergence with an endotracheal tube' above.)

•In selected cases when it is desirable to avoid all coughing or retching during extubation, an infusion of remifentanil (eg, approximately 0.1 mcg/kg per minute) may be briefly administered to allow tracheal extubation as soon as the patient can follow commands. (See 'Remifentanil extubation technique' above.)

•In patients with impaired sensorium, respiratory failure, airway edema, clinically significant neuromuscular weakness, or hemodynamic instability, it is usually desirable to postpone extubation. The ETT can remain in place, with either spontaneous ventilation or sedation with controlled ventilation. (See 'Postponed extubation' above.)

●Emergence with a supraglottic airway – A supraglottic airway (SGA), such as a laryngeal mask airway, is removed at the end of the surgical procedure after resumption of spontaneous breathing without assistance. Similar to requirements for endotracheal extubation, adequate reversal of NMBAs must be ensured. Other techniques to avoid airway complications during SGA removal are described above. (See 'Emergence with a supraglottic airway' above.)

●Emergence after mask ventilation – In patients who had mask ventilation during surgery, spontaneous breathing without assistance is resumed at the end of the procedure, and techniques to avoid upper airway obstruction or hypoxemia are used if necessary. (See 'Emergence after mask ventilation' above.)

●Interruption of emergence – In some cases, additional surgical interventions are deemed necessary, or an unanticipated surgical complication occurs as the patient is emerging from general anesthesia. Such situations necessitate temporary re-establishment of a deeper level of anesthesia (table 5). (See 'Unanticipated need to interrupt the emergence sequence' above.)

●Problems during emergence – Problems during emergence may require urgent treatment (eg, airway or respiratory problems, hemodynamic instability, excessive somnolence, emergence agitation, persistent pain). Transport to the post-anesthesia care unit (PACU) is delayed until the patient can maintain adequate oxygenation and ventilation during spontaneous ventilation, is hemodynamically stable, can be aroused to follow verbal commands, is not agitated, and does not have moderate or severe pain. (See 'Problems during and after emergence' above.)