Neurocritical Care

30. Pitfalls of Brain Death Determination

A 20-year-old graduate student, sideswiped while driving at an intersection, was found comatose by paramedics. He was emergently intubated and admitted to the surgical trauma unit. He had multiple frontal and temporal lobe contusions, a pelvic fracture, and pulmonary contusions. He had no motor response to pain, pupils were fixed and dilated, and he did not grimace to pain. He lost his pulse and required cardiopulmonary resuscitation for 30 minutes.

Neurosurgery placed an intracranial pressure monitor that showed initial normal (< 20 mm Hg) intracranial pressure (ICP) readings, but ICP later increased to 40–50 mmHg, not responding to osmotic diuretics. Blood pressures remained unstable, requiring vasopressors. The trauma surgeon believes the patient is brain dead, as the patient stopped triggering the ventilator. You are asked to do a formal brain death examination. Upon questioning, the intensive care nurse tells you that the patient is not on any sedative drugs and fentanyl infusion was discontinued 4 hours ago.

What do you do now?

Severe traumatic brain injury may result in admission to a neurosciences intensive care unit (NICU) or a surgical trauma intensive care unit when there are additional multiple injuries. In most parts of the world neurosurgeons and neurologists determine whether the patient meets the clinical criteria of brain death. These patients may be in a designated NICU, but they can also be in other ICUs. Not being the attending physician means you need more time to understand the time course of events and interventions that have taken place. Commonly the situation and request for the determination of brain death are not crystal clear.

Any physician making the clinical diagnosis of brain death should work through a predetermined set of criteria. It starts with the recognition of “red flags,” confounders which neurologists recognize as unacceptable and which generally, when present, should make everyone uncomfortable to even proceed to a more formal neurological examination (Table 30.1). More difficult is the opposite situation. There may be an unnecessary delay of brain death determination, if certain clinical findings are misinterpreted as not compatible with the diagnosis of brain death (Table 30.2).

The question that is most often asked is: How long should one wait until a patient can be declared brain dead? The answer—of course—is as long as it takes to determine a treatment is futile and to exclude possible confounders. Patients admitted to ICUs who have deteriorated from a major brain injury may “look” imminently agonal, but aggressive treatment—in some—could lead to substantial improvement. It is therefore premature to declare a patient’s brain death with an active CNS infection, untreated brain edema, undrained hydrocephalus, non-decompressed mass effect, any major uncorrected laboratory abnormality, or marked hypothermia. In these patients some previously absent brainstem reflexes and motor responses can return. However, when all brainstem reflexes are lost in a demonstrable apneic patient and there is no other explanation these findings are irreversible.

TABLE 30.1 Signs that the Patient May Not Be Brain-Dead

Insufficient time of observation (any transfer from an outside hospital is potentially suspect for presence of sedative or neuromuscular blocking drugs)

Cause of coma not established

Treatable cause of coma

Fever and shock

Hypothermia (< 32i C)

Unsupported blood pressures, no need for vasopressors

Evidence of substantial alcohol or drug intake

TABLE 30.2 Signs Compatible with Brain Death

Spinal cord reflexes (neck-arm flexion, arm lifting, head turning, triple flexion response)

Ventilator, not patient, auto-triggering (ventilator at fault and auto-triggering due to minor changes in pressure or volume in the circuit)

Intracranial blood flow preserved

Presence of some EEG activity

Excluding sedative drugs does require calculation of time to elimination (the sum of 5 half-lives is conservative). The most common drugs are fentanyl (t ½ = 6 hours), lorazepam (t ½ = 15 hours), midazolam (t ½ = 6 hours), phenobarbital (t ½ = 100 hours), and thiopental (t ½ = 20 hours). If patients have been treated with therapeutic hypothermia or if there has been ischemic liver injury after cardiopulmonary resuscitation, it will be very difficult—if not actually impossible—to exclude a lingering sedative effect. Most neuromuscular junction blockers are eliminated within several hours (the commonly used atracurium t ½ = 30 minutes), but the simplest proof of its lack of effect is the return of tendon reflexes. Bedside nerve stimulators can also be used. Other potentially complicating medical conditions are hypothermia (usually less than 32°C), severe hyponatremia (< 110 mmol/L), hypernatremia (> 160 mmol/L), hypoglycemia (< 40 mg/dL), or hypercalcemia (>3.4 mmol/L).

The actual neurologic evaluation of determining brain death consists of 25 tests and verifications. Brain death determination is complex (it is more than checking a few brainstem reflexes in an apneic patient), requires expertise (hopefully a neurologist or neurointensivist), and demands perfect diagnostic accuracy (no room for error). The overriding principle is simple: establish cause, determine futility, exclude confounders, examine brainstem reflexes, and test for apnea. Many physicians have difficulty with the apnea test, but the test—a CO2 challenge using oxygen-diffusion—is simple and safe when its steps are carefully followed (The procedure is described in Table 30.3).

One examination suffices in adults, but some U.S. states require 2 physicians to examine the patient. In infants and children (30 days to 18 years), repeat examinations are recommended: 2 examinations by 2 separate examiners, and 12 hours apart. In neonates (newborn with at least 37 gestational weeks to 30 days), 2 examinations by 2 separate examiners, but 24 hours apart are required (these new recommendations are based on a consensus report sponsored by the Society of Critical Care Medicine and American Academy of Pediatrics). The clinical examination always concludes with an apnea test, and the time of completion of this test is the time of death. A checklist is shown in Table 30.3.

Confirmatory tests (or better called ancillary tests) may have far less specificity than previously appreciated. These tests may not fit the clinical examination. In fact, retained blood flow is just a reflection of the intracranial pressure, which may not be high enough to stop blood entry through the dura into the skull (in other words, very high ICP: no flow; high but not very high ICP: retained flow). The same applies to electrodiagnostic tests; they are just a reflection of cortical function and not brainstem function. To use these tests to shorten observation time or to declare brain death—assuming no flow or no electrical brain activity—in patients with confounding drug effects or even intoxication will only lead to errors. No physician wants to declare a patient brain-dead using a confirmatory test to override a confounder and be told by the nursing staff that there has been return of motor movement or spontaneous breathing. Nonetheless, these ancillary tests are mandatory in some countries in Europe, Latin America, and Asia. Sometimes it seems that the focus in brain death determination has unfortunately shifted to finding an ideal technical test rather than improving clinical competence.

So what should you do? The patient likely suffered anoxic-ischemic injury in addition to traumatic diffuse axonal and contusional brain injury, and reversal of this condition is not likely. In this patient it is prudent to wait another day (5 half-lives of fentanyl is 30 hours – 4 hours of discontinuation = 26 hours). A drug screen should be obtained to exclude drugs the patient may have co-ingested (alcohol level, serum toxicological screen).

Table 30.3 Twenty-Five Assessments to Declare a Patient Brain-Dead



Adapted from Wijdicks et al., 2010.

ABG = arterial blood gas; BP = blood pressure; CPAP = continuous positive airway pressure; PEEP = positive end expiratory pressure; TMJ = temporomandibular joints

Brain death determination allows closure and options for organ donation. There is no medical rationale to continue care if there is no consent for organ donation. No intensive care unit has the obligation to care for a legally deceased person, and in the extreme it would be unethical if holding the bed can cause refusal of necessary transfers of other patients.


· Brain death determination is time-consuming and involves multiple tests.

· Most time should be spent in finding possible confounding factors.

· The diagnosis is based on a clinical neurologic examination and not on cerebral blood flow or an electrodiagnostic study.

· Two examinations by 2 separate physicians are needed in infants and children.

· In the U.S. one examination is sufficient in adults (> 18 years).

· Some U.S. states require 2 physicians to examine the patient usually at approximately the same time.

· Confirmatory tests are legally necessary in some countries

Further Reading

Jain S, DeGeorgia JS. Brain death–associated reflexes and automatisms. Neurocrit Care 2005; 3:122–126.

Lustbader D, O´Hara D, Wijdicks EF, MacLean L, Tajik W, Ying A, Berg E, Goldstein M. Second brain death examination may negatively affect organ donation. Neurology. 2011;76:119–124.

Nakagawa TA, Ashwal S, Mathur M, Mysore M, and the Committee for Determination of Brain Death in Infants and Children. Guidelines for the determination of brain death in infants and children: an update of the 1987 task force recommendations Crit Care Med 2011, in press.

Wijdicks EFM, Varelas PN, Gronseth GS, Greer DM et al. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010; 74:1911–1918.

Wijdicks EFM. The case against confirmatory tests for determining brain death in adults. Neurology 2010; 75:77–83.

Wijdicks EFM. There is no reversible braindeath. Crit Care Med 2011; 39:2204–2205.