The brain is unique in that it uses almost exclusively aerobic metabolism of glucose. The continuous availability of oxygen is secured by the cerebral vasculature’s autoregulatory mechanism [1], which controls the rate of blood flow over a wide range of blood pressures. If blood pressure drops too low for autoregulatory mechanisms to operate, oxygen extraction from the blood increases. Failure of this compensatory mechanism results in a changeover from aerobic to anaerobic metabolism.

In cardiac arrest, depletion of brain oxygen reserves occurs within 10 seconds, thereby eliminating the major source of neuronal energy from ATP (adenosine triphosphate) and phosphokinase. Excessive glutamate release and reduced reuptake lead to activation of the NMDA (N-methyl-D-aspartate) receptors and consequent ischemic cascade. The resulting intracellular (cytotoxic) edema leads to increased intracranial pressure.
The changeover to anaerobic metabolism results in neuronal catabolism. In cardiovascular collapse, loss of venous outflow leads to the accumulation of lactic acid and pyruvate, the end products of anaerobic metabolism. Buildup of these catabolites potentiates the cellular damage.

The first question to address when evaluating a comatose or obtunded patient with a possible hypoxic insult is whether the impaired consciousness is the result of a metabolic insult or a structural brain lesion. Coma caused by a mass lesion is usually associated with focal neurologic signs. Computed axial tomography (CT) or magnetic resonance imaging (MRI) scans usually reveal focal lesions in this setting. Metabolic causes, including anoxic encephalopathy, should be suspected when patients with impaired consciousness present with a non-focal examination.

The diagnosis is often suggested by the clinical setting (e.g., cardiac arrest in patients with arrhythmias or myocardial infarctions, or severe episodes of intraoperative hypotension). Arterial blood gas determination, if obtained during the causal event, can confirm the diagnosis. A partial pressure of oxygen of less than 40 mm Hg causes confusion and less than 30 mm Hg results in coma [2]. Associated abnormalities that potentiate anoxic damage include anemia, acidosis, hypercapnia, hyperthermia, and hypotension.

The internist or neurologist is often consulted to evaluate the patient who has impaired consciousness after well-documented cerebral hypoperfusion that has occurred during surgical operations requiring the use of extracorporeal circulation. The neurological examination is nonfocal. Because surgical patients with such a history often have preexisting illnesses (vascular disease, borderline renal function, hepatic impairment, diabetes), it is the obligation of the intensive care physician to determine new deficits due to anoxic encephalopathy, or other treatable conditions secondary to metabolic, infectious, and iatrogenic factors such as sedating medications. Intracerebral hemorrhage and subdural hematomas should also be sought, because they can occur spontaneously in the perioperative period, especially in anticoagulated patients.

The clinical outcome of patients with anoxic injuries depends on the degree and duration of oxygen deprivation to the brain as well as the maintenance of blood flow. With complete cessation of blood flow to the brain, consciousness is lost after several seconds. If anoxia is moderately prolonged, the patient awakens but may have residual deficits, such as cognitive impairment, or later sequelae, including extrapyramidal movement disorders or seizures, which may not develop for days to weeks.

A delayed postanoxic syndrome may occur rarely in patients with anoxic insults after the initial coma. Three to 30 days following the initial anoxic insult, after the patient has regained consciousness and cognitive function, there is a secondary decline characterized by irritability, confusion, lethargy, clumsiness, and increased muscle tone; patients may become comatose again and die. This uncommon condition occurs most often in cases of carbon monoxide poisoning. Pathologically, widespread demyelination is seen without gray matter changes. The cause is unknown, but it may be due to alteration of enzymatic processes, edema, or damage to small blood vessels [2,3].

The overall prognosis for a meaningful recovery in patients with nontraumatic coma is guarded; the longer patients are in coma, the worse the outcome [4,5,6]. Most improvement occurs within the first 30 days. Non-anoxic metabolic coma carries the best prognosis, while anoxic coma has a better prognosis than coma resulting from structural lesions. A good outcome is seen in 50% of patients who awaken within 24 hours. Although infrequent seizures or myoclonus do not affect prognosis, myoclonic or nonconvulsive status epilepticus is a grave prognostic sign and is associated with poor recovery [4,7].

If consciousness is maintained during a hypoxic event, there is rarely permanent brain damage. Irreversible damage is rarely seen in healthy individuals if the duration of anoxia is less than 4 minutes, although it may be incurred in individuals with preexisting cerebrovascular disease in shorter periods.

In cases of nontraumatic coma, the most valuable prognostic information is obtained from the physical examination. Favorable prognostic indicators include

Poor prognostic indicators in persistent coma include