Anoxic brain injury: Assessment and prognosis

Andrew Garrow, MD Gerald L Weinhouse, MD

Sep 15, 1999

As techniques in resuscitation and artificial life support have improved, health care providers care for an enlarging population of patients with anoxic brain injury. These patients most often have suffered insults such as cardiac arrest, respiratory insufficiency, vascular catastrophe, poisoning (such as carbon monoxide or drug overdose), or trauma. Therapy for anoxic encephalopathy is in its infancy, but considerable study has been devoted to the natural history of this disorder, allowing reasonable estimates of prognosis to be generated.

The evaluation and prognosis of patients with non-traumatic anoxic brain injury are reviewed here. The general prognoses of common critical illnesses are reviewed separately. (See "Prognosis of common medical conditions observed in the intensive care unit").

NOMENCLATURE — Coma is defined as a state of pathologic unconsciousness; patients are unaware of their environment and are unarousable. It is caused by either dysfunction of the reticular activating system above the level of the mid-pons or dysfunction of bilateral cerebral hemispheres. Physical examination permits localization of the level of central nervous system dysfunction [1].

Coma must be distinguished from the persistent vegetative state, which is also characterized by unawareness, but in which patients have normal sleep-wake cycles and are arousable. Patients in a coma may progress to a vegetative state, but this may not be associated with an improvement in their overall functional outcome. Both coma and persistent vegetative states must be distinguished from brain death, locked-in syndrome, akinetic mutism, and dementia (show table 1) [2].

A 1975 classification scheme proposed 5 outcome categories for patients who suffer an anoxic injury [3]:

  •  Death or persistent coma
  •  Persistent vegetative state, in which patients are conscious but are not aware of their surroundings
  •  Severe disability, in which patients are conscious but disabled and are dependent upon others for activities of daily living (ADL)
  •  Moderate disability, in which patients are disabled but able to perform ADL without assistance
  •  Good recovery, in which patients are able to resume normal life, possibly with minor neurological or psychological deficits

Many authors define a good clinical outcome as moderate disability or good recovery, grouping severe disability, persistent vegetative state, and death as poor clinical outcomes. In one review of 500 patients who suffered nontraumatic, anoxic brain injury (excluding drug-induced coma), 16 percent of patients had a good recovery or were left with a moderate disability, 11 percent of patients were left with severe disability, and the remaining 73 percent never improved beyond a vegetative state. Of the patients who remained in a coma at 1 week, 7 percent improved to a good recovery or moderate disability. None of the patients who were in a coma at 2 weeks improved beyond severe disability [4].

Brain death — Brain death (death by brain criteria) is defined as the cessation of cerebral and brain stem function. There is no respiratory drive, and thus there are no spontaneous breaths regardless of hypercarbia or hypoxemia. There are no central reflexes or responses to stimuli, although spinal reflexes may persist. Cardiovascular activity may persist as long as 2 weeks, although usually there is cardiovascular collapse within several days. One is legally dead in the United States when criteria for brain death have been demonstrated. An accepted definition of brain death is outlined in Table 2 (show table 2) [5].

Persistent vegetative state — Patients in a persistent vegetative state represent a subgroup of patients who suffer severe anoxic brain injury and progress to a state of wakefulness without awareness. Persistent vegetative state may represent a transition between coma and recovery or between coma and death. The term was first used in 1972 and is defined as [2,3,4,6,7]:

  •  No evidence of awareness of self or environment and an inability to interact with others
  •  No evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli
  •  No evidence of language comprehension or expression
  •  Intermittent wakefulness manifested by the presence of sleep-wake cycles
  •  Sufficiently preserved hypothalamic and brain stem autonomic function to permit survival with medical and nursing care
  •  Bowel and bladder incontinence
  •  Variably preserved cranial nerve reflexes and spinal reflexes

If a patient remains comatose, the usual outcome is to recovery, persistent vegetative state, or death within 2 weeks. On the basis of available data, persistent vegetative state is judged to be permanent after three months if induced nontraumatically. After 3 months, recovery is rare and is associated with moderate to severe disability at best. In patients who continue in a persistent vegetative state, life expectancy is approximately 2 to 5 years, and most patients die from infection of the lungs or urinary tract, generalized system failure, sudden death of unknown cause, respiratory failure, or underlying disease. It is estimated that there are 10,000 to 25,000 adult patients in a persistent vegetative state in the United States, generating an estimated annual cost of care of up to 7 billion dollars.

CLINICAL EVALUATION — A thorough history from the patient's family members or health care providers is essential to the assessment, although in some cases it may be impossible to obtain. The time and pace of onset, history of drug and medication use, prodromal symptoms, and the duration of resuscitation and presumed cerebral hypoxia assist in determining both the etiology and the prognosis of a given patient's condition.

As an example, the circumstances of cardiopulmonary resuscitation (CPR) can affect prognosis after a cardiac arrest in terms of both survival and quality of life. In one study of out of hospital cardiac arrest, 44 percent of patients receiving CPR survived initially, 30 percent were alive at 24 hours, 13 percent at one month, and only 6 percent were alive after 6 months. The duration of CPR significantly correlated with outcome; no patient who required more than 15 minutes of CPR survived more than 6 weeks [8]. In other studies, variables such as age >70, stroke or renal failure prior to admission, and recent congestive heart failure were associated with a worse prognosis, and factors such as a witnessed arrest and an initial rhythm of ventricular fibrillation or tachycardia have correlated with a better prognosis [9,10].

The physical examination is the single most useful test in elucidating the patient's degree of CNS function and in determining prognosis (show table 3, and show table 4) [8,11]. Physical assessment should include a detailed neurologic examination, including documentation of:

  •  Presence or absence of spontaneous movements
  •  Response to voice, light touch, and painful stimuli
  •  Pupillary size and response to light
  •  Cranial nerve function, including corneal reflexes
  •  Respiratory pattern (spontaneous, ataxic, etc)
  •  Oculocephalic and cold caloric responses

Teasdale and Jennett described the Glasgow Coma Scale (GCS) in the early 1970s, which has proved useful in standardizing the reporting of the physical examination (show table 5) [12]. GCS has been shown to correlate with outcomes when serially measured at various times after injury [13,14].

DIAGNOSTIC TESTING — Many tests have been studied in the period after anoxic injury, but their utility remains adjunctive to the physical examination.

Neuroimaging — CT and MRI contribute little to the assessment of the anoxic patient unless stroke, bleeding, or trauma is suspected. In infants suffering hypoxic ischemic encephalopathy, there is a strong correlation between MRI findings and long term outcome [15].

Electroencephalography — Electroencephalography (EEG) may be of some prognostic utility when performed between 6 and 72 hours after anoxic injury. As an example, one study of 40 patients with intact brain stem function found that none of 11 who demonstrated malignant EEG findings recovered [16]. These findings were confirmed in a second study of 34 patients which found that only 2 of 22 patients with malignant EEG findings recovered, even though 15 patients demonstrated intact brain stem reflexes [17]. Thus, some patients not identified as having a poor prognosis by physical findings at 72 hours may be identified by malignant findings on EEG.

Somatosensory evoked potentials — Somatosensory evoked potentials are similar to the EEG in that they are most useful for predicting a poor or fatal outcome. However, evoked potentials are a more specific marker than EEG, with very few falsely pessimistic studies [17]. The bilateral absence of evoked response one week after insult is a reliable predictor of failure to regain consciousness [17,18].

Lumbar puncture — The utility of cerebrospinal fluid (CSF) analysis following anoxic injury has been examined in several studies. Patients with anoxic brain injury have increased CSF concentrations of creatine kinase (CK), CK-BB, and lactate, which correlate with poor clinical outcomes and lower GCS scores [19,20,21]. As an example, one retrospective study of 351 patients who had suffered cardiac arrest found a significant inverse correlation between CSF CK-BB concentrations and the probability of neurologic recovery [21]. Only 9 patients who awakened had CSF CK-BB concentrations greater than 50 U/L, and none regained independence in ADL. Smaller studies have examined the utility of CSF adenylate kinase, lactate dehydrogenase, acid phosphatase, and glutathione concentrations in predicting neurologic outcome [22].

Although certain values for these parameters correlate with poor outcome, none has demonstrated superiority in predicting prognosis versus the use of clinical findings alone. Therefore, the routine use of CSF chemistries cannot be recommended at this time.

Serum chemistry values — Serum concentrations of lactate are specific for a poor clinical outcome only when extremely high (>16mmol/L) [23]. Serum concentrations of neuron-specific enolase and S-100 protein may be useful for predicting outcome following anoxic injury, but like CSF studies, cannot supplant clinical evaluation [24,25].

PROGNOSIS — Several models have been created to predict the probability of recovery following an anoxic insult based upon a patient's initial and subsequent examinations; poor prognostic signs are included in Table 3 (show table 3). Assessment of the probability of regaining independent function after a cardiac arrest has been studied, and findings are summarized in Table 4 (show table 4) [11] . A 1998 meta-analysis of 33 studies found that 4 clinical signs predicted a poor clinical outcome following anoxic brain injury with close to 100 percent specificity [26]:

  •  Absence of pupillary light reactions after 72 hours
  •  Absent motor responses to pain after 72 hours
  •  Bilateral absence of early cortical responses to median nerve somatosensory evoked potentials within the first week
  •  Burst suppression or isoelectric pattern on EEG within the first week

These types of predictions are based upon population studies and may be useful for counseling families and making triage decisions, but they are not completely accurate in predicting the course of individual patients. A given patient's prognosis following anoxic injury depends upon comorbidities as well as the duration of anoxia and can be best predicted by the neurologic examination immediately following the injury and at subsequent intervals. Decisions regarding withdrawal of care versus continued support must take into account the prior desires of the patient, sociocultural issues, and the overall goals of therapy. (See "Ethics in the intensive care unit: Informed consent; withholding and withdrawal of life support; and requests for futile therapies-I" and see "Ethical issues near the end of life").

TREATMENT — Supportive and preventive care remains the mainstay of therapy in all forms of anoxic brain injury [3,4]. Efforts should be focused upon providing adequate nutritional support, reducing the potential for nosocomial infection, and providing adequate prophylaxis against venous thromboembolism and gastric stress ulceration. (See "Assessment of nutrition in the critically ill", see "Prevention of venous thromboembolic disease", and see "Stress ulcer prophylaxis in the intensive care unit").

Many treatment modalities have been studied in the immediate post-insult period in the hope of reducing the duration and severity of neurologic injury. As examples, hypothermia has been employed to decrease cerebral metabolic demand, blood flow modulators have been administered to increase oxygen delivery, and calcium channal blockers have been used to decrease cell damage due to calcium influx. These interventions have been beneficial in some animal studies, but further study is required before they can be recommended for clinical use [27]. There have been numerous trials of chemical, electrical, and sensory stimulation in patients in persistent vegetative states, although no therapy has proven consistently effective in controlled trials [2,7].

Family members of patients with severe neurologic injuries should be kept well informed about prognosis. They should be informed that patients in a coma are thought to experience no pain because there is no sense of awareness of self or environment, despite what may appear as grimaces, crying, or other expressions of discomfort. The perception of pain and suffering are conscious experiences governed by the cerebral cortex, while the expression of pain may be elicited at any level of the nervous system and includes the motor/behavioral, endocrinologic, and autonomic responses which may occur as reflexes in the absence of consciousness.