Immediate interventions are indicated to improve hemodynamic parameters. In this case, the presence of a large hemorrhage and severe hypertension mandate BP control. At this point, no medical care should be withheld on the basis of the physical examination since the patient was recently exposed to neuromuscular blocking agents as well as sedatives. Coupled with cardiovascular interventions, “brain resuscitation” with hyperosmolar therapy is indicated since increased intracranial pressure (ICP) is likely and cannot be adequately assessed on clinical grounds. If other physiologic derangements are present such as coagulation abnormalities, these should be promptly corrected. Insertion of an external ventricular drain (EVD) by an appropriately credentialed physician such as a neurosurgeon or neurointensivist should be considered at this point. An EVD would allow the intensivist to diagnose increased ICP, trigger hyperosmolar therapy use, directly reduce ICP by removal of cerebrospinal fluid, and adequately titrate BP medications in order to ensure adequate brain perfusion.

Limiting clinical interventions early in this case may be premature since the neurologic examination is confounded by sedative medications and neuromuscular junction–blocking agents. In addition, the patient has no advanced directives guiding the physicians to limit care in a situation such as this one and her husband has asked you to continue to deliver full medical care. At this point, safe and expedited transfer to the NeuroICU is indicated.

The first part of the systemic coma examination begins with the careful assessment of coma and brainstem reflexes. This is accomplished by testing and documenting the presence and quality of motor responses to noxious or painful stimuli. Gentle stimulation of the nares and periorbital area with a cotton swab is frequently all that is necessary to elicit a motor response. When deeper coma states exist, it is best to use standardized maneuvers that elicit pain such as supraorbital nerve, temporomandibular joint, or nail bed pressure.¹ An aggressive sternal rub, especially if done forcefully enough to depress the entire rib cage, may lead to unwanted adverse events and therefore is not recommended. There are other noxious stimuli one may use to elicit responses, if any.

The next step in the assessment of the comatose patient involves direct testing of brainstem function. Optimal tests assess the pathways of all three of the main parts of the brainstem: the midbrain, pons, and medulla. The classically described rostral-to-caudal progression of brainstem dysfunction is frequently observed; however, other patterns are also observed. Frequently the medulla is the last part of the brainstem to cease to function, and in some cases respiratory drive, mediated by the medullary respiratory centers, persists for prolonged periods of time.² A less frequently performed medullary function test is monitoring of heart rate after the administration of atropine. Increased heart rate suggests persistent function of the medullary vagal centers.^3,4 This test is not routinely performed in many institutions but should be familiar to neurointensivists. Table 59-1 presents commonly tested brainstem reflexes. When testing for spontaneous breathing at the bedside, one of the common mistakes made is simply switching the ventilation mode from assist-control (“AC”) to spontaneous setting (“PSV”) and observing for a decrease in the patient’s respiratory rate. This is not a sensitive test, as the modern ventilators are extremely sensitive to minimal respiratory changes, and depending on the sensitivity setting on the pressure or flow trigger, brain-dead patients may or may not trigger the ventilator even on spontaneous mode. The best method is simply to disconnect the patient and carefully observe for any chest rise or listen to the chest for any breath sounds.

The motor examination is performed jointly with the sensory examination, since the stimuli used to elicit movement must be processed before a response occurs. Non-cortically–mediated movements such as extensor and flexor posturing and triple flexion are frequently observed. The differentiation of reflex stereotyped movements from complex cortically mediated movements can be complicated and requires repeated testing with different noxious stimuli. However, in brain death, there will be absence of all cortically and brain stem–mediated movements.

No. This patient was exposed to neuromuscular-blocking agents and sedatives, which may confound the neurologic examination. A commonly used way of testing for the presence of neuromuscular blockade is the train-of-four test. In this test, a series of four consecutive electrical stimuli are applied along the path of a peripheral nerve, and the resulting contraction of the innervated muscles is measured. Absence or diminished response to electrical stimulation suggests the presence of neuromuscular-blocking agents. This test should be performed before repeating the neurologic examination. It should be noted that until confounding metabolic or pharmacologic factors are ruled out, the documented neurologic examination should not be used in the determination of brain death. In this case, the elimination half-life of propofol is short, and any meaningful pharmacologic effect should disappear within minutes to hours. It should be noted that given propofol’s lipophilic nature, continued infusion may lead to deposition and accumulation in fatty tissue, and the pharmacologic effects can be longer lasting. The clinical examination can be performed once a drug level (eg, barbiturates used to treat high ICP) is below the therapeutic range.^5,6 When levels are unavailable, a waiting period of 4 to 5 half-lives of the agent is necessary. If high suspicion of confounding due to pharmacologic effects remains despite an appropriate waiting period, an ancillary test may be performed. Documentation of specific testing for confounding conditions is an important part of the brain-death evaluation. Table 59-2 lists common conditions that must be excluded before performing a brain-death examination.

Although both warm and cold caloric testing are possible, cold caloric testing is the most commonly performed test at the bedside. In this test the absence of provoked eye movements must be confirmed. The tympanum should be irrigated with ice water after the head has been tilted 30°. There should be no tonic gaze deviation of an individual eye toward the cold stimulus. The unfortunate mnemonic COWS (cold other warm same) has been used by medical students to memorize the response to caloric stimuli. The COWS mnemonic refers to the fast component of nystagmus in a patient who is conscious, not comatose. In a comatose patient, the expected normal response is tonic gaze deviation toward the side irrigated with cold water. Performing otoscopy prior to irrigation of the tympanum is an important step because a ruptured membrane should not be irrigated because of risk of infection. Otoscopy should rule out the presence of clotted blood or cerumen in the ear canals which may diminish the response in a person who is not brain dead. No deviation of the eyes to irrigation in each ear with 50 mL of cold water is considered a positive test. One minute of observation should be allowed after irrigation. The clinician should wait 5 minutes before testing the contralateral vestibular apparatus.

An apnea test can be performed. When this test is performed, hypoventilation is induced by discontinuing mechanical ventilation with the goal of increasing the amount of CO₂ in arterial blood. The test is considered positive when no respiratory movements are observed after an adequate increase in CO₂. As a matter of convention, the threshold of maximal stimulation for the medullary respiratory centers has been set at a partial pressure of carbon dioxide (Paco₂) of 60 mm Hg. In chronic carbon dioxide retainers, an increase of 20 mm Hg from baseline in the Paco₂ is considered an acceptable stimulus.⁷

Preoxygenation is mandatory to perform this test safely and also helps eliminate the stores of respiratory nitrogen. To achieve this, the fraction of inspired oxygen (Fio₂) is set at 100% on the ventilator for a few minutes prior to discontinuation of mechanical ventilation. After mechanical ventilation is discontinued, a catheter is introduced through the endotracheal tube to infuse oxygen. The infusion rate of oxygen should not be too high to avoid unintended ventilation of CO₂. The generally accepted rate is 6 L/min. The mechanical ventilator must be disconnected in order to obtain an appropriate assessment, since the ventilator’s sensors may be triggered inappropriately, providing false-negative results.⁸ An increase in CO₂ usually occurs at a predictable rate of 3 mm Hg/min. A baseline ABG is used to assess the increase in CO₂ and confirm adequate oxygenation. Repeat blood gases are obtained periodically during the test, which can last for several minutes as long as hemodynamic stability and adequate oxygenation determined by pulse oximetry are maintained. The test is considered positive and consistent with brain death when no respiratory movements are observed and an adequate rise in the Paco₂ is documented.^1,9,10 Figure 59-2 is a flow diagram of a commonly followed protocol for apnea testing. It should be noted that protocols may vary in different institutions and that close collaboration with respiratory therapists is essential. Apnea testing is an essential component of brain-death evaluation.

At this time brain death has not been diagnosed. The purpose of a family meeting at this point is not to focus on brain death. Sudden-onset neurologic conditions with devastating consequences such as the one illustrated in this case frequently leave family members stunned and unable to adequately understand the situation. Establishing an open line of communication with families early on in the course of illness is essential. Except for rare occasions, family meetings should include all available close members of the family. In this case, it would be helpful to ask the patient’s husband who he thinks should be present at a family meeting. It should be emphasized that the term family is used to denote anyone who is designated as such by a healthcare agent, in this case, the husband. When a family is composed of a large group of people, it is helpful to designate a spokesperson. Communications outside of the context of a family meeting can then be directed to the family spokesperson, and he or she can disseminate the information. This method can help avoid misunderstandings and most efficiently utilizes the clinician’s time. It is worth mentioning that on occasion a healthcare agent (in this case the patient’s husband) may designate someone else as the family spokesperson, such as a sibling or close family friend. These requests should be honored as much as permitted by hospital policy and the individual state’s laws.