Delayed emergence and emergence delirium in adults

INTRODUCTION — Failure to return to normal consciousness in a timely fashion following administration of general anesthesia may manifest as delayed emergence or emergence delirium. In most cases, these conditions are temporary and gradually resolve as anesthetic agents are metabolized and eliminated. Rarely, the cause is a serious medical or neurologic condition that requires urgent intervention.

This topic will review the causes and management of delayed emergence and emergence delirium after general anesthesia. Management of persistent postoperative delirium is addressed separately. (See "Delirium and acute confusional states: Prevention, treatment, and prognosis", section on 'Management'.)

Other problems that occur in the post-anesthesia care unit (PACU) are discussed separately. (See "Overview of post-anesthetic care for adult patients".)

NORMAL EMERGENCE — Emergence is 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 [1]. After emergence in the operating room, transport to the post-anesthesia care unit (PACU) is typically accomplished when the patient has been extubated and is breathing spontaneously with adequate oxygenation and ventilation, is hemodynamically stable, and can be aroused to follow simple verbal commands (eg, eye opening or hand squeezing).

Most patients become more fully conscious (ie, awake and aware of surroundings and identity) within approximately 15 minutes of extubation, and all patients should be responsive within 60 minutes after the last administration of any sedative, opioid, or anesthetic agent [2-4]. However, the time required for return of consciousness varies depending on the specific anesthetic and analgesic agents employed (including their dosing, duration, and time since last administration) (see 'Risk factors for prolonged drug effects' below); the type and duration of the surgical procedure; and the patient's preoperative physical and mental status. Evidence also suggests that recovery of consciousness and loss of consciousness are different processes with specific mechanisms in the brain, and that return of consciousness is partly dependent on external and internal stimuli [5-7].

DELAYED EMERGENCE

Initial management — After extubation, patients with excessive somnolence are frequently stimulated to assess level of sedation, encourage adequate ventilation, and reestablish orientation. Typically, these measures result in a gradual return to full consciousness. (See "Maintenance of general anesthesia: Overview", section on 'Transition to the emergence phase'.)

If the patient remains unresponsive or heavily sedated 30 to 60 minutes after last administration of any anesthetic or adjuvant agent, further evaluation and treatment target the most common as well as the most serious conditions (table 1). All possibilities should be considered quickly and simultaneously to eliminate those causes which might require urgent attention (eg, stroke) (table 2).

Consider prolonged drug effects — Residual effect of one or more anesthetic or adjuvant agents is the most common cause of delayed emergence. Residual effect of a neuromuscular blocking agent (NMBA) should also be considered; muscle weakness may result in hypoventilation, causing hypoxemia and/or hypercapnia, which may further exacerbate sedation.

An assessment should be made of the total and most recent doses of each anesthetic and adjuvant agent. Occasionally, a dosing error or accidental administration of an unintended anesthetic or adjuvant drug (eg, a syringe swap) may contribute to delayed emergence.

Risk factors for prolonged drug effects — The following drug-drug interactions may exacerbate residual drug effects and delay emergence:

●Combinations of anesthetic and adjuvant agents – When anesthetic drugs from different classes are combined, the central nervous system (CNS) effects are often synergistic. Synergy is particularly common when drugs acting primarily on GABA_A receptors (eg, midazolam, propofol, etomidate) are combined with drugs acting on other receptor types [8]. (See "General anesthesia: Intravenous induction agents".)

●Preoperative prescription and other drugs – Potentiation of CNS effects may also occur due to interactions of anesthetic agents with preoperative prescription drugs, supplements, recreational drugs, or alcohol (table 3).

Several conditions may alter drug metabolism, elimination, or sensitivity and contribute to delayed emergence:

●Hepatic or renal insufficiency – In patients with renal or hepatic insufficiency, decreased drug metabolism and clearance result in an increased duration of action for most intravenous (IV) anesthetic and adjuvant agents [9,10].

●Age and weight – Age-related changes in pharmacodynamics and pharmacokinetics intensify and prolong CNS effects of anesthetic and adjuvant agents in older adults. (See "Anesthesia for the older adult".)

Standard drug dosing in patients with very low body weight may result in absolute overdose, while relative overdose is common in patients with obesity who receive weight-based dosing of anesthetic agents. (See "Anesthesia for the patient with obesity", section on 'Dosing anesthetic drugs'.)

●Hypothermia – Hypothermia slows metabolism and elimination of most anesthetic and adjuvant agents. (See 'Consider temperature and metabolic derangements' below.)

●Hypothyroidism – Severely hypothyroid patients have impaired ventilatory drive and respiratory muscle weakness, which renders them more sensitive to the effects of sedatives, opioids, and neuromuscular blocking agents [11-15]. (See "Respiratory function in thyroid disease", section on 'Hypothyroidism' and "Anesthesia for patients with thyroid disease and for patients who undergo thyroid or parathyroid surgery", section on 'Hypothyroidism'.)

Opioids — Opioids may contribute to delayed emergence because opioid sedative effects are synergistic with all other anesthetic and adjuvant agents. In addition, hypercapnia due to opioid-induced hypoventilation may further exacerbate sedation. A finding of miosis and bradypnea along with sedation suggests that opioids may be contributing to delayed emergence, particularly if high doses or a very potent opioid was administered.

If opioid overdose is the most likely cause of heavy sedation, then a small dose of IV naloxone 40 to 80 mcg may be administered. Administration of naloxone may avoid reintubation, and also rules out opioid-induced alteration in mental status to allow evaluation of other possible causes. Repeat 40 mcg doses of naloxone may be administered at two- to five-minute intervals until the patient is responsive, without evidence of respiratory depression. The half-life of naloxone is 1 to 1.5 hours, which may be shorter than the half-life of the opioid being reversed. In rare cases, a continuous infusion of naloxone is necessary to treat recurrent respiratory depression, with close observation and titration of the infusion rate according to patient response (table 4). The effective dose varies, depending on the amount of opioid the patient has received, the patient's weight, and the degree of opioid penetrance into the CNS [16]. Naloxone is always carefully titrated to effect. Potential adverse effects include acute severe pain due to sudden reversal of analgesic effects of the opioid [17], as well as uncommon severe adverse cardiopulmonary effects (eg, arrhythmias [18-21], severe hypertension [18,22-25], flash pulmonary edema [18,26-32]). Massive release of catecholamines is the likely cause [17,33]. (See "Respiratory problems in the post-anesthesia care unit (PACU)".)

Benzodiazepines — Sedative and respiratory-depressant effects of benzodiazepines are synergistic with other anesthetic and adjuvant agents, particularly when midazolam is combined with fentanyl [8]. Benzodiazepines are also associated with adverse effects such as amnesia, drowsiness, and cognitive dysfunction, as well as an unpredictable and relatively high risk of paradoxical reactions, such as irritability and aggressiveness during emergence [34,35]. (See 'Risk factors for prolonged drug effects' above.)

In rare cases, flumazenil is administered if a high dose of midazolam or longer-acting benzodiazepine (eg, lorazepam) is the most likely cause of excessive sedation and severe respiratory depression (table 4) [34]. The initial adult dose of flumazenil is 0.2 mg IV over 30 seconds. Repeated doses of 0.2 mg may be given until the desired effect is achieved, up to a maximum dose of 1 mg. Since flumazenil may be shorter acting than the benzodiazepine being reversed, the patient is closely monitored for recurrence of sedation and/or hypoventilation. Flumazenil dosing may be repeated, but no more than 3 mg may be administered within a given hour. (See "Benzodiazepine poisoning", section on 'Role of antidote (flumazenil)'.)

Sedative-hypnotic agents — Although termination of sedation is typically rapid after discontinuation of IV sedative-hypnotic agents, their effects are synergistic with opioids and other anesthetic agents. (See 'Risk factors for prolonged drug effects' above.)

Recovery from an IV sedative-hypnotic infusion depends on the agent's context-sensitive half time (the time required for plasma concentrations to decline by 50 percent following discontinuation of a steady-state infusion), as well as the duration of infusion. For example, recovery time and awakening typically occur <25 minutes after discontinuation of a propofol infusion administered at maintenance doses for three hours [36]. (See "Maintenance of general anesthesia: Overview", section on 'Sedative-hypnotic agent: Propofol'.)

Dexmedetomidine is a highly selective alpha₂ agonist acting on receptors in the brain and spinal cord that may be administered by infusion in the perioperative period to take advantage of its analgesic, sedative, anxiolytic, and sympatholytic properties. Resolution occurs gradually after discontinuation of dexmedetomidine, such that residual sedation, as well as hemodynamic depression of heart rate and blood pressure, may persist in the early postoperative period [37]. (See "Maintenance of general anesthesia: Overview", section on 'Dexmedetomidine'.)

There are no reversal agents for any IV sedative-hypnotic. Somnolent patients are frequently stimulated to encourage ventilation and prevent exacerbation of sedation due to hypercapnia.

Volatile inhalation anesthetics — Although termination of sedation is typically rapid after discontinuation of an inhalation anesthetic, elimination may be prolonged with longer duration of administration [38], low minute ventilation, and/or low cardiac output. Isoflurane is eliminated more slowly than sevoflurane or desflurane. However, in one study of nearly 1500 patients, isoflurane prolonged emergence by only two minutes, and did not prolong length of stay in the PACU [39]. (See "Maintenance of general anesthesia: Overview", section on 'Transition to the emergence phase'.)

Although inhalation agents are unlikely to be a factor for excessive somnolence for more than a few minutes after initial emergence from general anesthesia, their effects are synergistic with opioids and other anesthetic agents (see 'Risk factors for prolonged drug effects' above). Thus, patients are stimulated frequently to encourage adequate ventilation during transport from the operating room and the first several minutes in the PACU, thereby avoiding hypoventilation and elimination of any residual inhalation anesthetic agent.

Anticholinergic agents — An overdose of scopolamine, atropine, or a combination of agents with anticholinergic activity rarely produces coma (table 5). Delirium and other features of anticholinergic intoxication such as mydriasis, hyperthermia, redness, or anhidrosis are more likely manifestations of anticholinergic overdose, especially in older adult patients [40,41]. (See 'Emergence delirium' below and "Anticholinergic poisoning", section on 'Clinical features of overdose'.)

Physostigmine 0.5 to 2 mg IV (or 25 to 50 mcg/kg) may be administered by slow IV push if anticholinergic overdose is strongly suspected, with continuous electrocardiographic monitoring to detect severe bradycardia, as well as close observation for seizures or bronchospasm (table 4). (See "Anticholinergic poisoning", section on 'Antidotal therapy with physostigmine for severe toxicity'.)

Neuromuscular blocking agents — Residual effect of NMBAs due to incomplete reversal is common in the PACU [42-45]. Consequent muscle weakness and hypoventilation may result in hypercapnia that exacerbates sedation, and also interfere with elimination of residual inhalation anesthetics.

A pharmacologic reversal agent (eg, neostigmine [up to 5 mg] given with glycopyrrolate [up to 1 mg], or sugammadex 2 mg/kg) is administered if residual blockade is suspected or confirmed with a peripheral nerve stimulator. If muscle weakness persists after administration of maximum doses of NMBA reversal agents, temporary controlled mechanical ventilation may be necessary. (See "Overview of the management of postoperative pulmonary complications".)

Consider hypoxemia and/or hypercapnia — Arterial blood gases are measured in patients with delayed emergence, and hypoxemia and/or hypercapnia are promptly treated. Hypoxemia is detected with pulse oximetry, but this is an insensitive monitor of hypoventilation and hypercapnia because supplemental oxygen is administered to most patients. Although hypercapnia is detected with continuous monitoring of end-tidal carbon dioxide (ETCO₂) while the patient is in the operating room, capnography may not be available in the PACU. Treatment of respiratory problems that cause hypoxemia and/or hypercapnia is discussed separately. (See "Respiratory problems in the post-anesthesia care unit (PACU)".)

Consider temperature and metabolic derangements — Temperature is measured, and standard point-of-care laboratory tests for glucose and electrolytes are obtained. Hypothermia, hyperthermia, or metabolic derangements may cause somnolence.

Temperature derangements are promptly treated.

●Hypothermia – Even mild hypothermia <35°C may impair consciousness and potentiate CNS-depressant effects of anesthetic agents. Warming in the PACU is typically achieved using forced-air warming devices. If temperature is <33°C, a period of controlled mechanical ventilation is typically necessary while the patient is rewarmed. (See "Perioperative temperature management", section on 'Hypothermia'.)

The most common cause of hypothermia is environmental exposure that occurred in the operating room, but certain medical conditions may exacerbate it (eg, hypoglycemia, adrenal insufficiency, sepsis, hypothyroidism). (See "Perioperative temperature management", section on 'Intraoperative hypothermia'.)

●Hyperthermia – Elevated temperature >38°C may cause mental status changes. The most common causes of hyperthermia are accidental overwarming and postoperative fever. Blankets are removed, evaporative cooling measures may be employed, and acetaminophen 650 mg is administered if fever is the cause. (See "Perioperative temperature management", section on 'Fever or hyperthermia'.)

Malignant hyperthermia should also be considered, particularly if sinus tachycardia and/or masseter or generalized muscle rigidity are present, or if laboratory studies reveal hypercarbia, metabolic acidosis, and/or hyperkalemia. (See "Malignant hyperthermia: Diagnosis and management of acute crisis".)

Other details regarding evaluation and management of postoperative fever are discussed separately. (See "Fever in the surgical patient".)

Glucose and electrolyte levels are checked and abnormalities are promptly treated.

●Glucose – Either hypoglycemia or hyperglycemia may cause sedation requiring prompt treatment.

Acute severe hypoglycemia (<50 mg/dL) is treated with an IV bolus of 25 to 50 g of dextrose, followed by a continuous dextrose infusion, with measurement of blood glucose concentrations every 30 to 60 minutes. Reversal of CNS symptoms may lag behind normalization of glucose levels.

Treatment of severe hyperglycemia is discussed separately. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment".)

●Sodium – Treatment of hyponatremia and hypernatremia are discussed separately. (See "Overview of the treatment of hyponatremia in adults" and "Treatment of hypernatremia in adults".)

Perioperative hyponatremia may occur in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) [46] (see "Causes of hypotonic hyponatremia in adults"). Hyponatremia may also be caused by a nonconductive (ie, nonelectrolyte) irrigation solution used during hysteroscopy or transurethral resection of the prostate (TURP) or bladder (TURB). (See "Hyponatremia following transurethral resection, hysteroscopy, or other procedures involving electrolyte-free irrigation".)

Perioperative hypernatremia may occur due to infusion of large volumes of saline or bicarbonate, intraoperative insensible water losses, or diabetes. (See "Etiology and evaluation of hypernatremia in adults".)

●Hypermagnesemia – Hypermagnesemia (>4 mEq/L) typically resolves with cessation of magnesium therapy (eg, IV magnesium infusion for treatment of eclampsia or preeclampsia). In the setting of renal insufficiency, patients with hypermagnesemia are treated with isotonic IV fluids plus a loop diuretic (eg, furosemide) in addition to discontinuing any magnesium therapy; dialysis may be required. (See "Hypermagnesemia: Causes, symptoms, and treatment".)

●Hypercalcemia – Postoperative hypercalcemia may occur in patients who had surgery for hyperparathyroidism or malignancy; treatment is discussed separately. (See "Treatment of hypercalcemia".)

Consider neurologic disorders — A basic neurologic examination is performed as soon as feasible when emergence is delayed (table 2) [47,48]. For patients with reduced level of consciousness, the neurologic examination assesses spontaneous behavior and responses to stimuli, as well as motor responses and cranial nerve function (eg, pupillary reactivity, eye movements) (figure 1). For unresponsive or poorly responsive patients, the Glasgow coma scale (GCS) may be used to gauge the severity of stupor or coma (table 6). (See "Stupor and coma in adults", section on 'Neurologic examination'.)

Neurologic causes of delayed emergence are more common in patients undergoing specific types of surgery, as noted below, particularly after craniotomy for neurosurgical procedures (eg, intracranial vascular procedures, tumor resection, evacuation of hematoma, trauma). In such cases, evaluation should include the surgeon to rule out possible surgical complications. (See "Anesthesia for craniotomy in adults", section on 'Delayed emergence'.)

Depending on the results of the initial examination and after assessment of possible causes as noted above, an urgent neurologic consultation and neuroimaging study may be requested to evaluate the possibility of an acute intracranial event such as:

●Acute stroke – Acute perioperative stroke may be caused by cerebral ischemia or intracranial hemorrhage. Although perioperative stroke is uncommon in patients undergoing noncardiac surgery, those undergoing carotid endarterectomy, aortic or peripheral vascular surgery, or resection of head and neck tumors are at higher risk than other surgical patients [49-52]. In some cases, the event may not be apparent in the PACU, but occurs a few hours or days later. The evaluation and management of acute stroke is discussed separately. (See "Perioperative stroke following noncardiac, noncarotid, and nonneurologic surgery" and "Initial assessment and management of acute stroke".)

●Seizures – A postictal state or nonconvulsive seizures are unusual causes of obtundation in the PACU.

Perioperative seizures occasionally occur due to epilepsy, acute stroke, surgery for traumatic brain injury, intracranial tumor, cerebral aneurysm or arteriovenous malformation, local anesthetic or other drug toxicity, or alcohol withdrawal (table 7). Treatment of convulsive seizures is discussed separately. (See "Convulsive status epilepticus in adults: Management", section on 'Emergency antiseizure treatment'.)

Evaluation and management of nonconvulsive seizures are discussed separately. (See "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis".)

●Hypoxic-ischemic encephalopathy – Hypoxic-ischemic encephalopathy may follow a precipitating perioperative event such as cardiac arrest or profound hypotension. Evaluation and treatment are discussed separately. (See "Hypoxic-ischemic brain injury in adults: Evaluation and prognosis".)

●Elevated intracranial pressure – Acute elevation of intracranial pressure may occur after surgery for intracranial hematoma or tumor, or because of cerebral edema (eg, severe traumatic brain injury, large cerebral infarction, acute hypoxic ischemic encephalopathy), malfunctioning ventriculoperitoneal (VP) shunt, or obstruction of cerebral venous outflow (eg, venous sinus thrombosis, jugular vein compression, neck surgery). Evaluation and treatment are discussed separately. (See "Evaluation and management of elevated intracranial pressure in adults".)

●Prior neurologic deficits – Transient focal neurologic deficits may occur after sedation or general anesthesia in patients with a prior history of neurologic insult from stroke or other cause; this phenomenon is known as differential awakening. Such deficits typically improve over 30 minutes to several hours, but multidisciplinary evaluation is required. (See "Anesthesia for craniotomy in adults", section on 'Differential emergence or awakening'.)

●Hyperperfusion syndrome – Cerebral hyperperfusion syndrome is a rare sequela of carotid endarterectomy. (See "Complications of carotid endarterectomy", section on 'Hyperperfusion syndrome'.)

●Air embolism or fat embolism syndrome – Focal neurologic deficits or mental status changes may occur shortly after surgery due to arterial air embolism [53] or fat embolism syndrome [54]. (See "Air embolism", section on 'Surgery and trauma' and "Fat embolism syndrome".)

EMERGENCE DELIRIUM

Clinical features — A brief period of agitation is common during emergence from general anesthesia. As patients transition through a stage of delirium during initial emergence, they may exhibit agitation, hyperexcitability, disinhibition, crying, restlessness, and mental confusion [55-58]. Terms to describe this phase include emergence excitement, emergence agitation, and emergence delirium. This intraoperative stage of emergence is usually very brief (a few minutes), and often resolves quickly following removal of a noxious stimulus, such as the endotracheal tube. A brief period of emergence delirium is particularly common in children. (See "Emergence from general anesthesia", section on 'Severe agitation' and "Emergence delirium and agitation in children".)

In one prospective observational study that employed the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) criteria in 400 adult patients, intraoperative agitation during emergence occurred in 19 percent [56]. A prospective observational study that employed a different method of assessment, the Richmond Agitation-Sedation Scale (RASS) in 1970 adult patients, 3.7 percent had evidence of emergence delirium in the operating room immediately after extubation, while only 1.3 percent remained delirious shortly after admission to the post-anesthesia care unit (PACU) [58]. Another observational study used the Nursing Delirium Screening Scale in 1000 patients undergoing orthopedic or abdominal surgery, noting "inadequate emergence," (defined as a score ≥2) in 10 percent upon arrival in the PACU, although 2 percent had a score ≥2 before the surgical procedure [38]. In this study, patients with positive scores for delirium had a longer duration of anesthesia.

In some patients, postoperative delirium persists or reoccurs after initial emergence from anesthesia, or only becomes evident in the PACU [38,59,60]. A lucid period usually is evident after initial emergence from general anesthesia, but not always. Postoperative delirium may manifest as agitation (hyperactive subtype) or as somnolence with altered mental status (hypoactive subtype) occurring in the postoperative period after initial emergence from general anesthesia [56,61]. Hyperactive delirium is more easily detected due to overt agitation, hyperexcitability, disinhibition, crying, restlessness, and mental confusion; some patients fluctuate between the hyper- and hypoactive subtypes [62]. In a study that employed the CAM-ICU criteria, 31 percent of 400 adult patients were delirious upon admission to the PACU after general anesthesia [56]. Approximately one-half of these patients exhibited hyperactive delirium, while one-half had the hypoactive subtype. The incidence of delirium decreased to 15 percent after 30 minutes, 8 percent after 60 minutes, and only 4 percent at the time of PACU discharge. Most of those with persistent delirium throughout their PACU stay had the hypoactive subtype (92 percent), and all met other criteria for discharge from the PACU [56]. Pediatric patients have a higher incidence of delirium during and shortly after emergence from general anesthesia compared with adults. (See "Emergence delirium and agitation in children".)

Evaluation and treatment — Hypoactive emergence delirium shares similar causes with delayed emergence; thus, evaluation and treatment of these entities are similar in the PACU setting (table 1 and table 2). (See 'Delayed emergence' above.)

In patients with hyperactive emergence delirium, other causes include acute pain due to surgery or other discomfort (eg, bladder distention) or panic due to dyspnea and respiratory distress caused by residual neuromuscular blockade. (See 'Neuromuscular blocking agents' above.)

Initial management of emergence delirium and/or agitation includes:

●Reassurance and reorientation.

●Treatment of acute pain. However, the clinical effect of each opioid dose is closely monitored because opioids may precipitate delirium [56,63]. Nonopioid agents and techniques are preferred, if effective. (See "Delirium and acute confusional states: Prevention, treatment, and prognosis", section on 'Prevention' and "Delirium and acute confusional states: Prevention, treatment, and prognosis", section on 'Management'.)

●Treatment of other discomfort (bladder distention, hypothermia). (See "Overview of post-anesthetic care for adult patients".)

●Laboratory testing to determine if hypoxemia, hypercarbia, hypoglycemia, or electrolyte imbalances are present.

●Consideration of effects of certain residual anesthetic agents (eg, benzodiazepines, opioids, scopolamine, diphenhydramine).

•Dexmedetomidine – Some studies suggest that intraoperative administration of dexmedetomidine ameliorates or reduces the incidence of hyperactive delirium [64-68] (see "Perioperative neurocognitive disorders in adults: Risk factors and mitigation strategies", section on 'Intravenous agents associated with lower risk'). A 2022 meta-analysis of randomized trials in patients undergoing noncardiac nonneurologic surgery (2676 patients; 33 studies) noted that intraoperative dexmedetomidine administration was associated with reduced incidence of emergence agitation (risk ratio [RR] 0.38, 95% CI 0.29-0.52) compared with placebo [68]. Also, a lower incidence of clinically significant pain (RR 0.50, 95% CI 0.32-0.80), nausea and vomiting (RR 0.54, 95% Ci 0.0.33-0.86), shivering (RR 0.24, 95% CI 0.12-0.49), and coughing (RR 0.69, 95% CI 0.61-0.79) was noted in patients receiving dexmedetomidine. However, hypotension in the PACU was more likely in those receiving dexmedetomidine (RR 5.39, 95% CI 1.12-5.89) [68]. Also, time to extubation was slightly longer in patients receiving dexmedetomidine (mean difference one minute, 95% CI 0.32-1.68 minutes), although the time to PACU discharge was not prolonged. We do not routinely use dexmedetomidine to minimize emergence agitation due to increased risk for hypotension and slight prolongation of time to emergence, but we may select this agent for airway or other procedures to minimize postoperative coughing.

•Ketamine – Although the psychotomimetic side effects of ketamine may present as emergence delirium (eg, hallucinations, nightmares, vivid dreams), this is not a consistent phenomenon [69-73]. We avoid routine co-administration of preoperative benzodiazepine since this is a predictor of emergence delirium in the recovery room [74]. (See 'Consider prolonged drug effects' above.)

●Consideration of preoperative substance abuse (eg, alcohol, amphetamines, cocaine, cannabinoids). If suspected, a toxicology screen may provide useful information. (See "Testing for drugs of abuse (DOAs)".)

●Consideration of other drug toxicity, including agents that may cause serotonin syndrome (table 8 and table 9). (See "Diagnosis of delirium and confusional states" and "Serotonin syndrome (serotonin toxicity)".)

In a severely agitated PACU patient, after treatment of reversible causes of delirium, and if redirection and reorientation have failed, administration of a small dose of haloperidol (eg, 0.5 to 2 mg) is reasonable, and this dose may be repeated (up to approximately 5 mg total dose). Because haloperidol does not worsen the overall course of delirium, we prefer it rather than a benzodiazepine to sedate a patient with severe agitation who is a danger to himself or others. (See "Sedative-analgesia in ventilated adults: Medication properties, dose regimens, and adverse effects".)

However, prophylactic haloperidol to prevent delirium is not recommended. Antipsychotics are on the Beers criteria list as drugs to avoid in older adults (see "Drug prescribing for older adults", section on 'Beers criteria'). In one multicenter study, medical and surgical patients older than 70 years were randomized to receive haloperidol or placebo on top of nonpharmacologic strategies to prevent delirium [75]. There were no differences in delirium incidence, duration, or severity. Similarly, other antipsychotics (either typical or atypical) have not altered delirium incidence, duration, or severity in either general medical or postoperative critically ill patients, and may confer harm [76-78].

A neurology consult is obtained if delirium is severe and persistent, although an acute intracranial event such as stroke is a rare cause. Delirium lasting hours or days is associated with older age, preoperative cognitive impairment, alcohol use, severe medical illness, and specific laboratory abnormalities (eg, sodium or glucose levels) [79-84]. Delirium at the time of PACU discharge is predictive of persistent delirium later in the postoperative course, with outcomes that are worse than patients without this complication (eg, mortality, prolonged length-of-stay in the hospital, institutionalization at discharge) [57,79,85-88]. (See "Delirium and acute confusional states: Prevention, treatment, and prognosis".)

Mitigation strategies and management of persistent postoperative delirium are discussed separately. (See "Perioperative neurocognitive disorders in adults: Risk factors and mitigation strategies" and "Delirium and acute confusional states: Prevention, treatment, and prognosis", section on 'Management'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Delirium and confusional states in older adults".)

SUMMARY AND RECOMMENDATIONS

●Delayed emergence

•Definition – Delayed emergence after general anesthesia is defined as a failure to return to a conscious state with intact protective reflexes within 60 minutes after last administration of any opioid, sedative-hypnotic, or other anesthetic agent. (See 'Normal emergence' above.)

•Initial management – Patients with excessive somnolence are frequently stimulated to assess level of sedation, produce arousal, encourage adequate ventilation, and reestablish orientation. Further evaluation and treatment target the most common and serious conditions (table 2). (See 'Initial management' above.)

•Management of residual effects of anesthetic agents – Delayed emergence or delirium is usually caused by residual effects of one or more anesthetic or adjuvant agents. (See 'Consider prolonged drug effects' above.)

-Sedative-hypnotic agents – There are no reversal agents for sedative-hypnotic agents or volatile anesthetic agents. (See 'Sedative-hypnotic agents' above and 'Volatile inhalation anesthetics' above.)

-Opioids – If opioid overdose is the most likely cause of heavy sedation and persistent bradypnea, we administer naloxone 40 to 80 mcg, with titration of additional 40 mcg doses at two- to five-minute intervals until the patient is responsive without evidence of respiratory depression (table 4). Administration of naloxone may avoid reintubation and rules out opioid-induced sedation, allowing assessment for other possible causes of alteration in mental status. (See 'Opioids' above.)

-Benzodiazepines – In rare cases, overdose of a benzodiazepine necessitates reversal with flumazenil, or overdose of anticholinergic agent(s) necessitates reversal with physostigmine (table 4). (See 'Benzodiazepines' above and 'Anticholinergic agents' above.)

-Neuromuscular blocking agents – Weakness due to residual effects of a neuromuscular blocking agent (NMBA) may contribute to delayed emergence by causing hypoventilation with hypercapnia, which exacerbates sedation and interferes with elimination of residual inhalation anesthetics. Reversal agents (eg, neostigmine given with glycopyrrolate, or sugammadex) are administered if NMBA effect is suspected or confirmed with a peripheral nerve stimulator. (See 'Neuromuscular blocking agents' above.)

•Management of other causes – Hypoxemia and/or hypercapnia, hypothermia or hyperthermia, hypoglycemia or hyperglycemia, and electrolyte imbalances are evaluated and promptly treated as possible causes of delayed emergence or delirium (table 2). (See 'Consider hypoxemia and/or hypercapnia' above and 'Consider temperature and metabolic derangements' above.)

•Treatment

-Nonpharmacologic treatment – Management of emergence or delirium agitation includes reassurance and reorientation, as well as treatment of acute pain and other discomfort (eg, bladder distention, hypothermia, weakness due to residual NMBA) and metabolic abnormalities. Other possible causes include preoperative substance abuse or other drug toxicity. (See 'Emergence delirium' above.)

-Pharmacologic treatment – Administration of a small dose of haloperidol (eg, 0.5 to 2 mg) is reasonable in a severely agitated patient in the post-anesthesia care unit (PACU) after treatment of reversible causes of delirium, and this dose may be repeated (up to approximately 5 mg total dose) (Grade 2C). Because haloperidol does not worsen the overall course of delirium, we prefer it rather than a benzodiazepine to sedate a patient with severe agitation who is a danger to himself or others. However, prophylactic haloperidol to prevent delirium is not recommended (Grade 2C).

●Management of persistent delay in emergence or delirium – A basic neurologic examination is performed if delayed emergence or delirium persists after assessment for other causes (table 2 and figure 1 and table 6). Urgent neurologic consultation and neuroimaging study are occasionally necessary to evaluate an acute intracranial event. (See 'Consider neurologic disorders' above.)

Causes and management of persistent delirium are discussed separately. (See "Perioperative neurocognitive disorders in adults: Risk factors and mitigation strategies" and "Delirium and acute confusional states: Prevention, treatment, and prognosis", section on 'Management'.)