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The human brain, then, is the most complicated organization of matter that we know.

Isaac Asimov


The complexity of the brain renders its normal functioning—especially the production of consciousness—uniquely vulnerable to acute metabolic derangements and structural deformation. As a perpetual glucose and oxygen glutton, the brain is extremely intolerant of sudden changes in energy homeostasis, and in vivo neurons begin to die after only minutes of fuel deprivation. Likewise, the diffuse circuitry responsible for consciousness in the brain makes anatomic insults involving both cerebral hemispheres and the brainstem reticular activating system necessary and sufficient to perturb mental status. Regardless of etiology, altered mental status (AMS) or global cerebral dysfunction frequently prolongs hospital length of stay and worsens the prognosis of patients in the critical care setting. Rapid diagnosis is necessary to differentiate imminently life-threatening brain injury from more benign, reversible forms. As an amalgam of evidence-based practice and our clinical experience, this chapter will focus on the diagnostic and management challenges of AMS in the critically ill patient.


AMS is an impairment of consciousness, which is comprised of arousal and awareness.1 Arousal refers to general brain wakefulness, while awareness defines whether the individual has knowledge of his or her own existence and surroundings. Awareness demands a certain degree of arousal but it may be dissociated, as is best exemplified by the persistent vegetative state (PVS)—awake patients without clinically demonstrable self-awareness.2

Mental status forms the core of any neurologic examination. Providers should avoid labeling a patient “unresponsive” in favor of more descriptive categories based on the physical examination: lethargy, obtundation, stupor, and coma (Table 31-1).3,4 Lethargic patients manifest decreased alertness but retain awareness of their environment. Obtunded patients require a stimulus to rouse and follow simple commands but have lost awareness of their immediate surroundings. Stuporous patients do not follow commands and require a continuous painful stimulus to exhibit signs of arousal. Finally, comatose patients exhibit no awareness and no significant arousal response to even painful stimuli. Coma results from bilateral cerebral hemisphere impairment or dysfunction of the reticular activating system in the brainstem; unilateral hemispheric disease (such as a middle cerebral artery stroke) does not typically lead to coma unless there is associated midline shift and resultant contralateral hemispheric dysfunction. Although these categories are useful to help qualitatively describe the level of depressed consciousness in a patient, the lack of standardized definitions for these terms makes them prone to misuse and variable interpretation.

TABLE 31-1:Descriptive Categories of Altered Mental Status

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