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Hypoxic brain injury (HBI) is a term used to describe a diffuse brain injury as a result of global, temporary loss of blood supply and oxygen.  Hypoxic ischemic brain injury (HIBI) is now used to refer to damage due to interruptions in perfusion to the brain, usually due to cardiac arrest or profound hypotension. Another related term is anoxic brain injury, referring to complete lack of brain tissue oxygenation, which is rare in its pure form. Another commonly used term is hypoxic ischemic encephalopathy (HIE).1


Hypoxic brain injury results from cerebral hypoperfusion which can be caused by cardiogenic shock in setting of cardiac arrhythmias or arrest, or by inadequate circulating blood volume as a result of massive blood loss.  Lack of oxygenation with preserved cerebral perfusion is typically caused by respiratory failure such as pulmonary disease, suffocation, complications of anesthesia or drug use, strangulation, or hanging. Nonfatal drug overdose can result in HBI either by leading to respiratory depression or cardiac arrest. Impaired oxygen delivery may occur as the result of carbon monoxide (CO) poisoning.2,3

Epidemiology including risk factors and primary prevention

Specific incidence or prevalence of HBI is unknown.  HBI is a secondary effect of many primary pathologies, including those listed above. Epidemiologic research is difficult due to heterogeneity of the primary etiology.

Cardiac arrest continues to be the leading cause of HBI. Based on American Heart Association (AHA) data, the incidence of Emergency Medical Service (EMS) treated out-of-hospital cardiac arrest (OHCA) in the United States was 88.8 individuals per 100,000 in 2020.4 Based on the AHA data, the rate of survival to hospital discharge was 9.0% and survival with good neurologic function, which was defined as the Cerebral Performance Category (CPC) of 1 to 2, was 7.0% for OCHA. 10-22% of survivors of sudden cardiac arrest were found to have persistent cognitive impairment 12 months after injury.

Carbon monoxide (CO) intoxication is the cause of over 50,000 emergency department visits per year in the United States.5 CO poisoning can lead to a myriad of neurological sequelae, although exact incidence is unknown. Risk factors include the use of generators, grills, camp stoves, propane, natural gas, charcoal burning used inside home, basement, and garage or even outside near window.6

Non-fatal drug overdose can result immediately in HBI or delayed post-hypoxic leukoencephalopathy. The rate of opioid overdose has increased drastically in recent years, with the Center for Disease Control (CDC) estimating over 100,000 overdose-related deaths in 2021.7 The exact number of non-fatal overdoses is unknown since a large percentage of overdoses are unwitnessed or treated by bystanders. Nonetheless, it is estimated that for every overdose death, 20-30 non-fatal overdoses occur.7 The incidence HBI following overdose is also difficulty to estimate, as patients who are brought to the emergency department following overdose often have unknown duration of inadequate respiration and toxicology is not always obtained. Additionally, the timing of onset of neurologic symptoms is variable. Therefore, attributing impairments to a specific hypoxic event vs chronic substance use is difficult.


Highly metabolic areas of the brain are particularly vulnerable to hypoxic injury. These areas include the hippocampus (CA1 pyramidal neurons), basal ganglia (particularly reticular neurons of the thalamus and the striatum), and cerebellum (Purkinje cells). Pyramidal neurons in layers 3, 5, and 6 of the cerebral cortex are also vulnerable. Nuclei in the brainstem tend to be more resilient to hypoxic injury than other areas.3

Ischemic injury, caused by loss of adequate cerebral blood flow, tends to affect vascular “watershed” areas of the brain due to distance from the main arterial supply. These include vulnerable areas between major arterial territories, including the border zones between the anterior cerebral artery (ACA) and middle cerebral artery (MCA) and between the MCA and posterior cerebral artery (PCA) as well as internal border zone between MCA superficial branches and the deep branches of MCA/ACA.3

When the brain is deprived of oxygen, anaerobic glycolysis is used to produce adenosine triphosphate (ATP); however, glycolysis is insufficient to sustain the energy requirement of the brain and ATP depletion occurs. Subsequently, ATP depletion leads to Na+/K+ ATPase pump failure, cell membrane depolarization, and intracellular sodium influx. Cell membrane depolarization leads to an array of downstream sequelae which contributes to cell damage and death:1

  • Intracellular calcium accumulation
  • Cytotoxic edema
  • Glutamate release (which leads to excitotoxicity, leading to activation of destructive lipases, proteases, and muscles and neuronal breakdown)
  • Activation of calcium-dependent enzymes, which remodel cytoskeletal structures and alter neurotransmitter release

With cardiac arrest, the extent of ischemic damage and thus neurologic injury depends on the duration of circulatory arrest. Up to 95% of brain tissue can be damaged after 15 minutes of global ischemia from cardiac arrest.3 Purely hypoxic injuries, in comparison to hypoxic-ischemic injuries seen with circulatory arrest, may have better chance for good neurologic recovery due to preserved systemic circulation and adequate cerebral nutrient/glucose delivery and toxin removal. Hypoxia decreases pH through elevation of partial pressure of carbon dioxide. This will result in cerebral autoregulation, including cerebrovascular dilatation and increase in the cerebral blood flow. The preserved blood flow supplies continuous nutrients and glucose to the brain allowing toxic metabolites to be washed out. Thus, pure hypoxia affects neuronal synapses without brain necrosis.3 With return of circulation, a short period of hyperemia is followed by a lengthier period of hypoperfusion lasting 6-24 hours. Reperfusion provokes further secondary injury through production of excess free radicals and increased release of excitotoxic neurotransmitters. Additionally, capillary endothelial damage and dysfunction caused by ischemic injury can impede blood flow after resumption of cerebral circulation, leading to edema and microhemorrhage.1 In CO poisoning, CO inhibits oxygen-hemoglobin binding and impairs oxygen delivery and also disrupts oxygen utilization. This hypoxic state triggers free radial formation and apoptotic cell death. White matter petechial hemorrhages followed by multifocal necrosis occurs, particularly in corpus callosum, basal ganglia, and hippocampus.3,6

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

A wide spectrum of clinical features and outcomes are possible following hypoxic brain injury, ranging from complete recovery to a disorder of consciousness to death. The natural history of recovery of HBI is highly variable, depending on severity and mechanism of injury.8

Severe hypoxic ischemic brain injury initially presents with impaired consciousness. If consciousness is regained, clinical impairments seen are heterogeneous and related to neuroanatomy of injury and cause, duration, and extent of global ischemia. Clinical variables have prognostic predictive value during the acute period, but clinical presentation can be confounded by intensive care treatments and medical interventions such as sedatives and neuromuscular blockade.9

Cognitive recovery is greatest within the first 3 months of injury and may stabilize at 12 months post-injury, though more modest improvement can continue over time.6 Current literature suggests the cognitive recovery curve is similar to that of traumatic brain injury (TBI), whereas physical recovery in HBI occurs at slower rate.10,11 About 50% of HBI survivors have full or near full cognitive recovery.12 Some studies suggest a bimodal pattern of cognitive recovery. For some, there can be limited residual cognitive deficits while others with cognitive deficits can have significant functional impairment and disability.8

Specific secondary or associated conditions and complications

Knowing the areas of the brain most affected by HBI helps anticipate expected clinical features. Memory deficits can be seen with hippocampal damage whereas gait disturbance and ataxia can be seen with cerebellar injuries. Movement disorders, including dystonia, tics, and chorea, can be seen with injuries to the basal ganglia. It is estimated that 30-60% of survivors will have residual cognitive, behavioral, or other neurological problems.12

  • Disorders of consciousness (DoC) and arousal impairments:
    • Duration of coma after HBI is variable. Injuries to arousal and awareness networks, including reticulothalamic, thalamocortical,and reticulocortical networks can results in DoC. Unresponsive wakefulness syndrome (UWS) or vegetative state (VS) after HBI is considered “chronic” after 3 months, where recovery of consciousness after this time frame is unlikely. A minority of individuals with non-traumatic cause of UWS such as HBI may experience late recovery after 3 months. Some studies suggest that as high as 20% of chronic UWS may experience late transition to minimally conscious state (MCS).13
  • Cognitive deficits: Patterns of cognitive deficits reflect damages to vulnerable areas affected most by hypoxia and ischemia: cortical layers 3, 4, and 5, hippocampus, white matters at watershed zones, subcortical areas supplied by distal arterial branches, and the cerebellum. Cognitive domains that can be affected include:
    • Memory: Among cognitive impairments, memory impairment is the most commonly reported.10 Memory can be divided into declarative, procedural, and working forms. Networks involved in declarative memory include parietal and frontal cortices and the medial temporal region (entorhinal-hippocampal complex). Recall is mediated by prefrontal and hippocampal networks. Disturbances of immediate recall and working memory are associated with attentional deficits. Impairments in new learning and recall of prior learning can be seen with damage to hippocampus and frontal structures (cortex layers 3, 5, and 6).12 Immediate recall and visual memory tend to be more affected than delayed recall and verbal memory.10 However, other studies have noted that patterns of memory loss demonstrate relative preservation of immediate and remote memory.9
    • Attention: Sustained attention (vigilance or concentration), selective attention, and divided attention (sustained processing of multiple stimuli simultaneously) are closely related to working memory. Attentional networks are large and widely distributed, including involvement of the sensory cortex, frontal cortex, frontal-subcortical circuits. Injuries to these areas can cause attentional impairments.12
    • Processing speed: The rate of information processing in the brain can be affected by damage to white matter bundles connecting cortical-cortical and cortical-subcortical areas.12
    • Executive function: Results from injuries to the white matter tracks involved in the dorsolateral prefrontal-subcortical circuit, the lateral orbitofrontal-subcortical circuit, and the anterior cingulate-subcortical network. Their connections to other frontal-subcortical circuits, the limbic system, and the cerebellum can also further impact executive function.12
    • Visuospatial function: Visuospatial function, including visual perception and process, can be affected by watershed areas at temporo-parieto-occipital zones.1
  • Movement disorders and motor function: A variety of motor manifestations after hypoxic brain injury can be seen secondary to basal ganglia and cerebellar injury. These can include dystonia, parkinsonism, chorea, tremor, and myoclonus. Quadriparesis is a common motor finding among patients with hypoxic-ischemic brain injury.1 These can manifest in a delayed fashion, month to years after injury. Movement disorders may also be progressive, possibly due to release phenomenon from removal of inhibitory input within the basal ganglia.9 Lesions in the globus pallidus and putamen are more often associated with dystonia while necrosis within the external globus pallidus is associated with parkinsonism.1
    • Lance-Adams syndrome: Clinically manifesting as action-based myoclonus, this is one of the most common movement disorders after hypoxic-ischemic brain injury.1,14 Positive myoclonic jerks can be triggered by volitional movement, especially if it requires coordination or dexterity, startle, strong emotion, or sensory stimulation. It is also associated with cerebellar ataxia, postural lapses, gait disturbance, and seizure. Conversely, negative myoclonus or brief loss of tone in agonist muscles followed by compensatory jerk of antagonist muscles, can result in postural lapse and contribute to falls. Lance-Adams syndrome typically responds to treatment and is compatible with a good long-term outcome.15
    • Akinetic-rigid syndrome can develop secondary to pallidal lesions and inappropriate disinhibition of thalamic input to the supplementary motor area.14 This syndrome may present with bradykinesia, micrographia, axial rigidity, rest or postural tremor, and postural instability.
    • Myoclonus: about 20 %1 of individuals may develop myoclonus after cardiac arrest due to cortical or subcortical lesions. In one study, cortical myoclonus was found to occur twice as often as subcortical myoclonus, with cortical myoclonus conferring a higher risk of electrographic seizures and more common in patients who completed Targeted Temperature Management, which is a marker of longer arrest in the cohort. Patients with cortical myoclonus were more likely to be discharged in a comatose state. Mortality rates at discharge did not differ between the cortical and subcortical groups.16
    • Dystonia: damage to the putamen after HBI can clinically manifest with dystonia. It may present asymmetrically and progress to more symmetric and generalized symptoms over time.9
  • Seizure: the estimated incidence of seizure following HBI ranges from 15-36%.9 Seizures typically begin in the first 24 hours after HBI.9 Either partial or myoclonic seizures are the most common. There is no evidence to support use of prophylactic antiepileptic agents.15 Estimated incidence of late-onset seizures (>1-week post-arrest) range from 11-27%.1
  • Autonomic dysregulation: often termed paroxysmal sympathetic hyperactivity (PSH), this may arise in the first week. Most cases persist for weeks or months. Of acquired brain injury subtypes, hypoxic-ischemic brain injury is thought to have the strongest association with autonomic dysfunction.1 While the greater community incidence of TBI lends itself to an overall higher prevalence of PSH after TBI, severe hypoxic brain injury is thought to be a significant contributor to PSH.17 Episodes of PSH tend to persist the longest in individuals with anoxic brain injury.18
  • Delayed post-hypoxic leukoencephalopathy is a rare condition that occurs after an episode of severe ischemia or hypoxia, most documented in the setting of carbon monoxide exposure. Patients appear to make good clinical recovery but then rapidly deteriorate due to delayed demyelination in subcortical and deep white matter areas with no significant vascular abnormality or cerebral edema after 1-4 weeks. This typically presents with cognitive deterioration, urinary incontinence, and gait disturbance.9 Individuals may also exhibit signs of frontal lobe dysfunction, including grasp reflex and glabellar sign.14 No agents have yet been identified to reliably prevent or treat this condition.9,19
  • Depression: It is estimated that more than a third of survivors of HBI can experience depression in the first 3 months following injury, and that more than 30% experience depression at 12 months post-injury.12

Watershed infarcts can lead to various clinical syndromes.

  • “Man in a barrel syndrome”: due to infarcts at watershed zone between ACA and MCA territories. It clinically manifests with proximal upper extremity weakness and spares lower extremity function.9
  • Cortical blindness: infarcts at the watershed zone between the MCA and PCA can manifest clinically with cortical blindness.9
  • Balint-Holmes syndrome: due to infarcts at posterior watershed zones. Symptom complex may include psychic gaze paralysis, simultagnosia (inability to recognize multiple visual inputs or a while picture), and optical ataxia.9

Essentials of Assessment


A complete history includes the following:

Premorbid characteristics:

  • Medical comorbidities
  • Premorbid functional status
  • Prior brain injury
  • Educational and vocational history
  • Social supports

Injury characteristics:

  • Mechanism of injury
  • Duration of hypoxia and/or ischemia (including duration of cardiopulmonary resuscitation)
  • Acute neurologic abnormalities on exam
  • Associated injuries

Course characteristics:

  • Duration of disorder of consciousness
  • Duration of post-hypoxic amnesia
  • ICU interventions (i.e., time to targeted temperature management, use of extracorporeal membrane oxygenation)
  • Complications to hospital course (i.e., seizures, myoclonus)

Physical examination

For evaluation of consciousness after brain injury, a validated scale such as JFK-Coma Recovery Scale -Revised (JFK CRS-R) should be used.13,20   JFK CRS-R is a scale assessing 23 items that quantitate brainstem, subcortical and cortical process to assist diagnosis, prognostic assessment, and treatment planning.21  Evaluation of preservation of brainstem reflexes should also be done, especially pupillary and corneal reflexes as absence of these reflexes after 72 hours has high specificity for poor outcome.1 Use of a pupillometer to measure pupillary reflexes can improve accuracy over qualitative assessment. Corneal reflex should be elicited by squirting water into the patient’s eye, or, for more accuracy, applying a cotton-tipped applicator as close to the iris as possible. Exam should ideally be performed free from sedation and anesthesia, which can confound exam findings. Range of motion and muscle tone should also be done to assess for contractures, spasticity, or heterotopic ossification.

In conscious patients, cognitive assessment includes evaluation of arousal/alertness, attention, processing speed, memory, judgment/reasoning, insight, planning/organization, and problem-solving. Affect/behavior examination assesses for agitation, emotional lability, abulia, depression, or anxiety. Cerebellar/fine motor testing evaluates for choreoathetosis, ataxia, tremor, and myoclonus. Visual testing assesses agnosia, visuospatial impairments, and visual field cuts. Focal motor and sensory deficits and their effect on function should be evaluated.

Assessment of cognitive impairment and emotional/behavioral disturbances should continue at outpatient follow-up after hospitalization using validated screening tools.22

Functional assessment

Cognitive impairments can be assessed as mentioned above with neuropsychological testing. Other screening tools such as Montreal Cognitive Assessment (MoCA) can be used as a cognitive function assessment.

Other functional assessments include Disability Rating Scale (DRS) and Glasgow Outcome Scale (GOS) and Extended Glasgow Outcome Scale (GOS-E). Other functional assessments such as 36-Item Short Form Health Survey (SF-36), Craig Handicap Assessment and Report Technique (CHART) can be used as functional assessments. Functional Independence Measure (FIM) scale which looked at 13 physical domains and 5 cognitive domains is used less often since it has been phased out by the Centers for Medicare and Medicaid Services (CMS). Continuity Assessment Record and Evaluation (CARE) which is a standardized tool that assesses medical, functional, cognitive, and social support status is now part of the Medicare Post-Acute Care Payment Reform Demonstration (PAC-PRD).

Glasgow Coma Scale and Coma Recovery Scale-Revised which assesses cognition, language, vision and perception, communication, and functional mobility, can be used for functional assessment for those in disorder of consciousness.

Laboratory studies

Evaluation for confounding metabolic abnormalities should be assessed when hypoxic ischemic brain injury is suspected. Laboratory test should include a comprehensive metabolic workup including basic metabolic panel, hepatic studies including ammonia, and blood gas analysis for acid-base disturbances.  Complete blood count should also be done to assess hemoglobin measurement to ensure adequate delivery capacity for oxygen. Other laboratory test should also include workup for infection, toxicology, and/or drug overdose.

In setting of cardiac arrest, cardiac biomarkers should be considered. For CO poisoning, fingertip pulse CO oximeter can be used and an elevated CO hemoglobin level of 2% for non-smokers and >9% COHb for smokers strongly supports a diagnosis of CO poisoning.

Biomarkers such as neuro-specific enolase (NSE), S100 calcium-binding protein β, glial fibrillary acidic protein, neurofilament light, tau, or ubiquitin carboxyl hydrolase L1 have been studied in patients with cardiac arrest. In a study that assessed serum tau at 24, 48, and 72 hours in 689 patients, increased tau was associated with poor outcome and may be better than serum NSE23. In a systematic review and meta-analysis, neurofilament light, which indicates axonal injury and white matter damage, demonstrated the highest accuracy with prognostication.24


Neuroimaing can identify structural injury in patients with HBI. Computerized tomography (CT) of head is used to identify hemorrhage. CT head is typically normal immediately after a HBI but should be considered to rule out hemorrhage. Repeat CT imaging by post-arrest day 3 may be more useful for prognostication especially if it demonstrates loss of gray-white matter differentiation and signs of brain swelling.25,26 Magnetic resonance imaging (MRI) is more sensitive than CT head, especially with diffusion-weighted imaging (DWI) sequence. Its use is most beneficial day 3-5 after cardiac arrest15. Used singly or in combination, functional MRI, positron emission topography, diffusion tensor imaging, and magnetic resonance spectroscopy have shown potential to provide further prognosticate following HBI.27

Supplemental assessment tools

Electrophysiologic studies, electroencephalography (EEG), and somatosensory evoked potentials (SSEP) may be helpful in acute settings but technically challenging due to electrical interference in intensive care. Early-latency evoked potentials (N20) has been studied for prognosis.

Early predictions of outcomes

Multiple factors including patient characteristics, event characteristics, and acute course, can help predict patient outcome after HBI. Duration of anoxia, length of CPR, etiology of arrest, and type of arrhythmia are associated with outcome.28 With HIBI, shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia) is associated with favorable neurological outcome.1 Good functional status prior to event, witnessed arrest, and absence of mechanical ventilation are also predictors of good neurologic outcome in survivors.

Early indicators of poor prognosis among those with coma after cardiopulmonary arrest include:12

  • Myoclonic status epilepticus within first 24 hours
  • Absence of pupillary responses at 1-3 days
  • Absent corneal reflexes at 1-3 days
  • Absent or extensor motor responses after 3 days
  • Absent cortical SSEPs at 3 days

Bilateral absence of pupillary response at 72 hours after arrest is specific for likely poor outcome, however, sensitivity is low.15 It is important to note that absent or extensor motor responses may be confounded by sedatives and neuromuscular blockade, and therefore may be less reliable indicators of poor outcome in patients undergoing targeted temperature management. Additionally, bilateral absence of cortical SSEPs with medial nerve stimulation (N20) is specific for poor outcome but sensitivity is low, estimated 43-49%.15 Historically, myoclonic status epilepticus has been thought to predict poor outcome, however, good functional recovery in multiple patients with early myoclonic status has been reported in the literature.1

Predictors of good prognosis:15,29

  • Localizing movements at 72-96 hours from return of spontaneous circulation (ROSC)
  • Early return of continuous, reactive, normal voltage baseline activity on EEG
  • Normal neuron-specific enolase (NSE) value at 24-72 hours after ROSC
  • Somatosensory-evoked potential (SSEP) N20 wave amplitude >4µV within 72 hours from ROSC
  • Absent diffusion restriction in the cortex or deep gray matter on diffusion weighted imaging (DWI) at 2-7 days after ROSC

Use of EEG for neuroprognostication:15

Standard EEG assessment plays an important role in prognostication. Malignant EEG patterns (suppressed, burst-suppressed, with or without superimposed epileptiform discharges) have high specificity.

Use of neuroimaging for neuroprognostication:15

Studies have shown marked heterogeneity on timing of neuroimaging after HBI. Generally, predictors of poor outcome include decreased gray-white matter ratio on CT and diffusion-weighted abnormalities on MRI. Given overall low quality of evidence for neuroimaging, recommendations suggest using imaging studies as a lower-tier prognostic factor.1,15 In one study, Apparent Diffusion Coefficient (ADC) values in patients post-cardiac arrest showed that may be a good predictor of good neurologic recovery. Multimodal assessment with corneal reflex, EEG, and average ADC value of the post-central cortex had the highest accuracy for predicting good neurologic recovery at 6 months.30

Use of biomarkers for neuroprognostication:15,23,24,28

The study of blood biomarkers for breakdown products from neurons and astrocytes is a rapidly developing field. Neuron-specific enolase (NSE) peaks in the serum at cerebrospinal fluid (CSF) around 72 hours post injury. Some studies suggest that level >33µg/L at days 1 and 3 predicts poor outcome. High serum NSE may have reasonable prognostic performance for poor outcome with estimated sensitivity 52-63% and high specificity 95-100%. Neurofilament light chain and tau are also promising serum biomarker.

Multimodal prognostication:

Several studies have suggested combination of multiple factors to increase reliability of prognostication. European Resuscitation Council and European Society of Intensive Care Medicine guidelines describe a multimodal approach to neuroprognostication.31 These guidelines suggest poor outcome is likely in a comatose patient with GCS motor score of <4 and who is 3 or more days after resuscitation when at least two of the following are present: absent pupillary and corneal responses at 72+ hours, bilaterally absent N20 SSEP at 24+ hours, highly malignant EEG at >1 day, NSE >60 ug/L at 2-3 days, status myoclonus at <72 hours, or “diffuse and extensive anoxic injury” on brain CT/MRI. Notably, a significant source of bias in neuroprognostication after cardiac arrest is self-fulling prophecy, in which the care team uses results of the prognostic test to influence decisions that affect patient outcome, including Withdrawal of Life-Sustaining Treatment (WLST).

Another study15 suggests a practical approach to prognostication with:

  • Daily neurological examination, including brainstem reflexes
  • Continuous or routine EEG in first 24 hours, and EEG at 48-72 hours if remaining unconscious
  • Daily serum NSE sampling for first 3 days
  • CT for patients still unconscious at 48-72 hours
  • SSEPs, as triaged by EEG results, and for patients unconscious at 48-72 hours
  • MRI at day 3-5 after arrest if initial CT unremarkable

In a post-mortem study of patients who underwent brain autopsy after cardiac arrest, histopathologic findings suggestive of severe HIBI were found in patients who had bilaterally absent cortical SSEPs, gray-white matter ratio <1.10, highly malignant EMG, and serum NSE >0.67 ug/L. Histopathologic severity of HIBI was found to increase with the number of poor prognostic findings present, appearing to support a multimodal approach to neuroprognostication. More than 60% neuronal death in the cortex and hippocampus was present in most patients with two or more strong predictors of poor outcome.32

Any tests used for prognostication should be viewed within the clinical context. More than one test should be utilized for prognostication especially since all studies to date have had biases and limitations.


Given heterogenic nature of hypoxic ischemic brain injury and recovery patterns, environmental needs vary. Potential challenges for patients include motor deficit, especially affected by balance and vestibular changes, visual disturbances, weakness, ataxia, and movement disorders. Additional symptoms to consider for environmental needs includes communication, fatigue, behavior, and cognitive deficits. Modifications include accessible environments, adaptive equipment, individualized educational programs, structured work environment with supervision and/or accommodation if needed, and structured daily routine to reduce memory demands. Every patient needs an individualized plan of care for safe and successful transition into the community.

Social role and social support system

The physical, cognitive, and emotional effects of HBI can be disturbing to family, friends, colleagues, and employers. Educating patients’ social support systems about HBI effects, prognosis, and techniques to facilitate successful community re-entry is essential.

Professional Issues

Care of patients with HBI who have severe impairments may include life-sustaining treatment, causing ethical dilemmas within the medical community. Ethics consultations help mediate personal, legal, and medical issues surrounding the life and death of this population.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Literature on rehabilitative management is sparse, but approach should be individualized based on mechanism of injury, neuropathology, prognosis, and residual impairments/disability. HBI treatment approaches for recovery are generally modeled after management of persons with TBI or stroke. Individuals with HBI benefit from rehabilitation33. Studies have demonstrated significant improvement in FIM scores from admission to discharge for patients with HBI.10 A retrospective study has found that persons who sustained severe HBI have similar outcome as those who sustained severe TBI though with less gain in FIM scores.34 Additional show that there is no significant difference between motor and total FIM scores at inpatient rehabilitation discharge between HBI and TBI patients.35 However, other studies have shown significantly less Functional Assessment Measurement (FAM) efficiency for patients with anoxic injury as compared to patients with TBI, although this finding was partially explained by increased impairment in the anoxic injury group at rehabilitation admission.10

Nonpharmacologic approach to cognitive rehabilitation includes environment modification, behavioral adaptation, and compensatory strategies. Pharmacologic approach includes use of catecholaminergics for arousal, impaired processing speed, attention and memory. Cholinergics are sometimes used for impaired memory. Literature supporting pharmacologic treatment approaches in HBI is limited.11

At different disease stages

Acute management includes reestablishing and maintaining cerebral oxygenation and circulation; monitoring of respiratory, cardiac, vascular, and metabolic issues; and addressing concomitant injuries or medical problems. Primary rehabilitation goals in acute care are early mobilization as able and prevention of complications related to bedrest/immobility with frequent turning, range of motion, proper positioning/transfers, and braces or special mattresses if needed. Physiatrists can help differentiate patients with disorders of consciousness and help guide treatment plan and prognosis. In cases with poor prognosis for recovery, palliative care referral and family care conferences are essential.

As the patient progress, subacute management includes initiation of interdisciplinary rehabilitation program to promote sensorimotor and cognitive recovery. During this stage, patients should be evaluated for associated symptoms and sequalae, including agitation, sleep disturbance, mood disorders, spasticity, headaches, and cognitive deficits. Treatment plan and assessment should also include bowel/bladder issues, and secondary conditions of HBI as mentioned above. For spasticity, consider medications such as baclofen, dantrolene, or tizanidine, and/or chemical neurolysis (botulinum toxin, phenol) or intrathecal baclofen in select patients. Post-hypoxic seizures and movement disorders may require pharmacologic intervention (dopaminergics, anticholinergics). Initiate adaptive strategies for visual agnosias (label objects, maintain object locations). Serial examinations are useful as clinical deterioration can indicate new pathology and improvements can help guide the rehabilitation program.

Chronic management guided by a physiatrist includes gradual reintegration into the community with ongoing education on recovery/adaptation, support/counseling, and appropriate referrals. For those who are able, driving evaluations and vocational rehabilitation referrals may be issued. Continue to monitor for development of secondary conditions associated with HBI and obtain neuropsychological follow-up as needed during cognitive recovery and during major transitions (community reentry, return to work, educational pursuits).

Coordination of care

Care coordination is important during patient care transition between acute care and acute/subacute inpatient rehabilitation teams and for successful community re-entry. Social workers can identify financial and social resources through these transitions.

Patient & family education

Multiple meetings are required to discuss expected short-term and long-term recovery. Successful communication includes full disclosure with compassion, appreciation of personal values, and respect for religious preferences. Advanced directives or previously voiced patient wishes need to be reviewed. Support groups or formal counseling referrals can be utilized as needed.36 Serial neuropsychologic testing can monitor outcomes and guide individualized cognitive programs.

Emerging/unique interventions

Emerging treatment has been ongoing for treatment for HIBI. One of these interventions includes concurrent delivery of transcranial magnetic stimulation with functional magnetic resonance imaging (TMS-fMRI) is under investigation for neurocircuit mapping and as treatment for cognitive deficits and emotional regulation.37

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Resources, such as the Brain Injury Association of America, can provide local support to mitigate caregiver fatigue.

Cutting Edge/ Emerging and Unique Concepts and Practice

Research into neonatal hypoxic ischemic brain injury has been ongoing with 2020 Cocharne systematic meta-analysis that included use of stem cell-based therapies for prevention of morbidities and mortalities.38

Additionally, there is ongoing research on biomarkers, including microRNAs, which are small RNAs that function as regulators of posttranscriptional gene expression. Currently, it’s being investigated for potential therapeutic targets in neonatal HIBI.39 These types of studies may guide future treatment for those who suffered HIBI. Mild therapeutic hypothermia after circulatory restoration is shown to improve survival outcomes after cardiac arrest.19,20

Gaps in the Evidence-Based Knowledge

More research and evidence are needed in areas of cognitive rehabilitation, nonpharmacologic/pharmacologic strategies, role of diagnostic testing including serum markers and functional imaging, and optimal methods/systems of care for evaluation and rehabilitation.


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Original Version of the Topic

Erica Wang, MD, Billie Schultz, MD. Hypoxic brain injury. 12/10/2012.

Previous Revision(s) of the Topic

Sarah Ann Korth, MD, Mi Ran Shin, MD. Hypoxic brain injury. 9/1/2017

Author Disclosures

Cherry Junn, MD
Nothing to Disclose

Kayli Gimarc, MD
Nothing to Disclose

Allison Wallingford, MD, MSE
Nothing to Disclose