The evaluation and management of prolonged emergence from anesthesia

Published on 07/02/2015 by admin

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The evaluation and management of prolonged emergence from anesthesia

Mary M. Rajala, MS, MD

Recovery from anesthesia occurs on a continuum: the patient initially responds to noxious stimuli and then to oral command, though the patient remains amnestic; motor control returns gradually; finally, in 15 to 45 min, the patient is able to converse rationally. Wakefulness requires diffuse cortical activation (arousal) elicited by afferent stimuli from the reticular formation in the brainstem. Within 15 min of admission to the postanesthesia care unit, 90% of patients regain consciousness. Delayed awakening after general anesthesia (i.e., >45-60 min after admission to the postanesthesia care unit) is secondary to a diverse number of causes and can be broadly classified as pharmacologic, metabolic, or neurologic (Box 113-1).

Box 113-1 Causes of Delayed Postoperative Arousal

Pharmacologic causes

Residual drugs, overdose

Medications administered during the perioperative period by personnel other than anesthesia providers

Benzodiazepines

Anesthetic agents—induction, inhalation or intravenous

Neuromuscular blockade

Decreased metabolism, excretion, or protein binding of drugs

Pharmacokinetic factors

Drug interactions

Underlying renal, hepatic, CNS, or pulmonary disease

Biologic variability

Decreased cardiac output-hypoperfusion, hypovolemia

Metabolic causes

Adrenal insufficiency

Hyperosmolar hyperglycemic nonketotic coma

Hyponatremia, SIADH, TURP syndrome

Neurologic causes

Low cardiac output, occlusive cerebrovascular disease

Air-venous, paradoxical

Intraoperative retraction, resection

Thrombus-atrial fibrillation

Intracerebral hemorrhage

Elevated intracranial pressure

Subdural or epidural hematoma

Malfunctioning shunt

Psychogenic unconsciousness

CNS, Central nervous system; SIADH, syndrome of inappropriate secretion of antidiuretic hormone; TURP, transurethral resection of the prostate.

The anesthesia provider should systematically evaluate the patient with delayed emergence from anesthesia (Box 113-2) while simultaneously managing the patient’s preoperative comorbid conditions and medications. This includes taking into consideration the type of operation, the type and doses of anesthetic drugs, drugs administered by the surgical team, and the duration and complications of anesthesia. Importantly, delayed emergence may be associated with the patient’s inability to protect his or her airway, airway obstruction, and respiratory failure. Many of the causes of delayed emergence are overlapping and may coexist.

Box 113-2 Management of Delayed Emergence

I. Airway, breathing, circulation

a. Maintain and protect airway; reintubate if necessary

b. Ventilate to maintain normal arterial CO₂

c. Assess heart rate, blood pressure, perfusion, and urine output

a. Review all medication that the patient has received perioperatively

b. Persistent neuromuscular blockade

i. Assess train-of-four with a peripheral nerve stimulator

ii. Assess for phase II block in patients who received succinylcholine

i. Check for pinpoint pupils and slow respiratory rate

ii. Administer naloxone in 40-μg increments, titrating to effect

iii. Reexamine the patient on a regular basis; the duration of intravenously administered naloxone is approximately 17 min

d. Benzodiazepine

i. Provide supportive management

ii. Consider administering a benzodiazepine antagonist, flumazenil, in 0.1- to 0.2-mg increments (maximal dose, 1 mg); arrhythmias, hypertension, and convulsions are potential side effects

e. Provide active warming if necessary

III. Electrolytes

a. Check blood glucose concentration

b. Check serum sodium concentration

c. Check magnesium, calcium, and phosphate concentrations

IV. Failure to find cause of delayed emergence

a. Consider the potential for a neurologic event to have occurred

b. Order neurologic imaging studies

Pharmacologic causes of delayed emergence

Anesthetic agents

The rate of emergence from general anesthesia correlates with the timing, half-life, and total dose of anesthetic agents used, as well as an individual’s biovariability. Residual effects of drugs administered during the perioperative period are the most frequently cited cause for delayed awakening. The cumulative effects of multiple drugs, some of which may be synergistic, may result in a relative drug overdose. Nonanesthetic medications may potentiate anesthetic effects, such as in the case of a lidocaine infusion used to treat cardiac arrhythmia. Patients given scopolamine or atropine may develop central anticholinergic syndrome. The highly soluble inhalation agents may be implicated when high concentrations are delivered for long periods of time or when hypoventilation slows emergence, prolonging recovery.

Opioids decrease the response to hypercarbia, resulting in hypoventilation and subsequent decreased clearance of inhalation agents. Benzodiazepines, droperidol, scopolamine, and ketamine—when given as premedication or as part of the anesthetic—may potentiate other general anesthetic agents, delaying arousal. Awakening may be delayed because of the timing of drug administration (e.g., agents administered shortly before emergence) or the route of administration (e.g., oral, rectal, or intramuscular have delayed absorption). Large doses of barbiturates or benzodiazepines may overwhelm lean tissue distribution and subsequent liver metabolism, thereby prolonging drug effects. Monoamine oxidase inhibitors potentiate the effects of opioids, barbiturates, and benzodiazepines.

Neuromuscular blockade

Muscle weakness, whether from inadequately reversed neuromuscular blocking agents or pseudocholinesterase deficiency, may result in hypoventilation, hypercarbia, and incomplete washout of inhalation anesthetic agents. Acidosis, hypermagnesemia, or certain drugs (clindamycin, gentamicin, neomycin, furosemide) accentuate the effects of neuromuscular blocking agents and may interfere with reversal of these agents. Patients may be conscious but may be unable to mount a motor response to noxious stimuli when they have muscle weakness and, therefore, appear as though they are still anesthetized.

Pharmacokinetic and pharmacodynamic factors

Low cardiac output can reduce perfusion to the lungs, kidneys, and liver, thus reducing metabolism and excretion of anesthetic agents. Decreased protein binding of anesthetic agents from hypoproteinemia or competition of binding sites with other drugs (e.g., intravenously administered contrast dyes, sodium acetrizoate, sulfadimethoxine) results in higher blood levels of active drug.

Liver metabolism of anesthetic agents is decreased in malnourished patients, in patients at extremes of age (through immature or decreased enzyme activity), in the presence of hypothermia (below 33°C-34°C), or during simultaneous administration of drugs dependent on liver microsomal detoxification (e.g., ethanol or barbiturates). Ketamine administration in patients with liver dysfunction delays anesthetic emergence. Patients with liver disease and a history of hepatic coma develop central nervous system (CNS) depression following the administration of small amounts of opioids; cimetidine may also cause mental-status changes in such patients. Although increased sensitivity to barbiturates has been reported in animals with hepatectomy or liver damage, such sensitivity has not been demonstrated in humans with these same conditions.

Renal failure and azotemia are associated with altered acid-base status, decreased protein binding (more likely due to hypoproteinemia than to acidosis), delayed or reduced excretion of drugs or their metabolites, and electrolyte changes, all of which contribute to delayed emergence. It is hypothesized that changes in permeability of the blood-brain barrier may increase sensitivity to hypnotics in patients with renal failure or azotemia.

Hypothermia not only reduces the metabolism of drugs by the liver, but also directly depresses CNS activity (cold narcosis) and increases the solubility of inhalation anesthetic agents, which, in turn, slows their transfer from blood into alveoli. Central respiratory depression and increased sensitivity to anesthetic agents are diagnoses of exclusion. Any anesthetic agent may cause central respiratory depression. Biologic variability in sensitivity to anesthetic drugs follows a bell-shaped gaussian distribution; sensitivity in older adults, compared with younger adults, is not equally distributed on such a curve. Anesthetic requirements diminish with age and in patients who are hypothermic or hypothyroid.

Metabolic disturbances of delayed emergence

Acid-base disorders

Mental-status changes occur with a cerebrospinal fluid pH of less than 7.25. During acute hypercapnia, CNS activity is depressed because hydrogen ions cross the blood-brain barrier more quickly than do bicarbonate ions. Hypoxia and hypercapnia accentuate residual anesthetic effects and the effects of preexisting conditions (e.g., hepatic encephalopathy). Metabolic encephalopathies, per se, sensitize patients to the effects of CNS depressants.

Endocrine disorders

Certain endocrine disorders (e.g., hypothyroidism, adrenal insufficiency) are associated with prolonged anesthetic emergence. The stress of anesthesia and surgery generally increases blood glucose concentrations. Sepsis, SIRS (systemic inflammatory response syndrome), uremia, pancreatitis, pneumonia, burns, and administration of hypertonic solutions or mannitol can trigger hyperosmolar hyperglycemic nonketotic coma, which can cause delayed anesthetic emergence. Hypoglycemia can occur secondary to perioperative administration of antiglycemic drugs, following manipulation of insulin-producing tumors and retroperitoneal carcinomas, or in patients with severe liver disease who have decreased gluconeogenesis. Hypoglycemia is associated with several CNS side effects, ranging from irritability to seizures and coma.

Electrolyte abnormalities

Electrolyte disorders—such as hypo-osmolality and hyponatremia due to absorption of large volumes of hypotonic fluids (e.g., during transurethral resection of the prostate) or from the syndrome of inappropriate antidiuretic hormone secretion—may delay emergence. Other electrolyte abnormalities to consider when evaluating a patient with delayed emergence include hypercalcemia, hypocalcemia, hypermagnesemia, and hypomagnesemia.

Neurologic causes of delayed emergence

Delayed arousal after anesthesia may be due to global or regional ischemia from cerebral hypoperfusion or hyperperfusion, hypoxia, elevated intracranial pressure, cerebral hemorrhage, or traumatic brain injury. Certain neurosurgical procedures and cerebral hypoperfusion from reduced cardiac output, obstruction to flow, or decreased systemic vascular resistance (systemic shock) have the potential to delay emergence from anesthesia. Arterial compression from retraction or improper positioning of the head and neck are other causes of hypoperfusion.

Hypotension occurring perioperatively may result in cerebral ischemia and stroke and occurs most often in patients with preexisting cerebrovascular disease. Thromboembolic events may be observed in patients undergoing cardiac, vascular, and invasive neck procedures or in patients with atrial fibrillation or hypercoagulable states. Venous air embolism can occur in cases in which the surgical site is higher than the heart; if patients have a patent foramen ovale, they are at increased risk for developing a paradoxical venous air embolism from even small amounts of entrained air. Stage II hypertension or a cerebrovascular accident from hemorrhage or hematoma can precipitate cerebral hyperperfusion, which can delay emergence. Intracranial pressure may increase from hyperperfusion or from intracerebral or subdural hemorrhage or hematoma. Cerebral edema, pneumocephalus, or a malfunctioning shunt or drain are also causes. Delayed emergence due to regional ischemia is manifested by hemiplegia or other focal signs, also known as differential awakening. In theory, focal areas of underperfused or previously injured brain tissue may have trapping or increased sensitivity to anesthetic agents.

Psychogenic unconsciousness, a diagnosis of exclusion, is a dissociative psychiatric disorder with sustained amnesia and unexplainable delayed emergence from anesthesia.

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