Prolonged Comatose States and Brain Death

Vegetative State

The advent of intensive care units and mechanical ventilation has allowed patients with devastating brain injuries to survive. While deeply comatose during the acute phase, some of these patients transition to a different clinical state in which they regain awake and sleep cycles, but remain unaware of their surroundings. This clinical syndrome—named persistent vegetative state (PVS) in the early 1970s—described patients with no evidence of a functioning mind ( ). This state has also been referred to as “unresponsiveness wakefulness syndrome” because of the alleged negative connotation of the word “vegetative” ( ). After prolonged coma, patients begin to have periods of spontaneous eye-opening but do not visually fixate or track objects with their eyes. The key feature is that patients show “no evidence of sustained, reproducible, purposeful, or voluntary behavioral responses” to external stimuli ( ). A patient’s eyes may open wide, but consistently demonstrated visual pursuit and fixation are absent. A large mirror held in front of the patient—to track his or her own face—is a useful test and probably the best stimulus to assess whether visual fixation and pursuit occur. A startle response is often present and may manifest as myoclonus, head flexion, or a decorticate response ( ). Primitive reflexes such as snout, glabella, and palmomental reflexes may be easily elicited. Random movements of the limbs and trunk, occasional grunts, and even occasional tears or smiles are all signs consistent with PVS but may provoke uncertainty for family members or inexperienced clinicians. Autonomic and brainstem functions are preserved so that patients generally can maintain adequate circulation and breathe spontaneously without difficulty. The clinical picture fits with what is seen pathologically, with the majority of brains at autopsy showing extensive damage to the subcortical white matter or thalamus, with sparing of the brainstem ( ).

At what point can a vegetative state (VS) be considered permanent? When is there a high degree of clinical certainty that the clinical state is irreversible and the chance of regaining consciousness is exceedingly unlikely? The clinical course of PVS depends in large part on the underlying etiology and the duration of unconsciousness. The most common causes are traumatic brain injury (TBI) and hypoxic-ischemic brain injury. The traditional approach to prognostication has been that patients in posttraumatic VS are unlikely to regain consciousness after 12 months, whereas those with anoxic brain injury have even less potential for improvement and very rarely recover consciousness after 3 months ( ). Although this is true for the majority of patients, a minority of patients may recover from PVS beyond these cutoffs ( ). A small prospective study of patients with anoxic VS found that 7 of 43 patients (16%) recovered responsiveness and were living at 2 years, 12 (28%) remained vegetative, and 24 (56%) died ( ). All responsive survivors had preserved pupillary light reflexes and present cortical responses with somatosensory-evoked potentials during the acute phase of injury. Notably, those who do become aware again often find themselves severely disabled. Age also plays a key role, particularly in TBI, with younger patients showing better recovery rates. The American Academy of Neurology, in collaboration with the American Congress of Rehabilitation Medicine and the National Institute on Disability, Independent Living, and Rehabilitation Research, formed a committee to develop a guideline on prolonged disorders of consciousness (DOC) ( ). The committee advocated more caution in prognostication and warned against clear time cutoff points beyond where no recovery occurs. The guideline suggests late (after 1 year) improvements primarily occurring in younger patients and approximately 20% of patients initially meeting PVS criteria.

The clinical assessment of a patient who is unconscious can be very challenging ( Fig. 6.2 ). The examination may need to be repeated at different times of the day because of fluctuations in awareness and circadian oscillations affecting arousal. Some studies suggest a misdiagnosis in a substantial minority of patients in PVS and a reclassification of 13%–28% of supposedly vegetative patients using formal scales such as the Full Outline of UnReponsiveness (FOUR) score or the Coma Recovery Scale-Revised (CRS-R) ( ). Diagnostic error rates of 40% have been cited, but this frequency might be falsely high because the evidence is based on poor reporting standards and insufficient follow-up ( ).