Chapter 58 Coma and Depressed Sensorium

• A Glasgow Coma Scale score less than 15 in children should be taken seriously.

• The ABCs (airway, breathing, and circulation) should be the priority during management of a child with coma.

• A spinal tap should be deferred until the possibility of raised intracranial pressure has been ruled out.

• The patient’s blood glucose level should be checked with urgency during the initial presentation of coma.

• When in doubt, it is better to protect the airway and prevent hypoxemia and hypercarbia electively.

• Unequal size of the pupils can be a sign of uncal herniation.

• The goal of therapy should be the prevention of secondary brain injury.

Coma, a state of unresponsiveness and unconsciousness, presents in many disorders ranging from structural central nervous system (CNS) injuries to diffuse systemic abnormalities. As a medical emergency, coma presents a challenge to providers because optimal care requires timely intervention; however, information is frequently limited during the initial evaluation. Knowledge of CNS anatomy and structures responsible for consciousness provide helpful clues as one attempts to interpret physical findings and optimize patient care. A careful general physical examination with a focused neurologic examination can suggest the diagnosis, aid in the location of lesions, guide therapeutic intervention, and determine prognosis. Further adjunctive radiologic and laboratory evaluation will then confirm physical findings. This chapter therefore considers CNS anatomy, the pathophysiology of coma, historical and physical findings that aid in localization of lesions, the emergent management and evaluation of patients presenting with an altered level of consciousness, and the prognosis of patients who present with coma.

Pathophysiology

The brain tolerates only limited physical or metabolic injury. Coma implies advanced brain failure, and the longer the brain failure lasts, the greater the possibility that the injury will result in permanent neurologic impairment. Coma may be described simplistically as a lack of consciousness. Posner and colleagues ¹ describe coma as a “state of unresponsiveness in which the patient lies with eyes closed and cannot be aroused to respond appropriately to stimuli even with vigorous stimulation.” Comatose patients may grimace in response to pain and the extremities may move in stereotypical withdrawal patterns, but the patient cannot localize responses or make defensive movements. As a coma deepens, responsiveness even to painful stimuli may be lost. Because motor reflexes are preserved, the depth of a coma cannot be assessed based only on motor responses. In many comatose patients, reflex movements will develop in response to stimuli. The depth of coma is best assessed by the patient’s level of consciousness.

Consciousness is a set of neural processes that allows an individual to perceive, comprehend, and act on and in the internal and external environment.^1,² Two neurophysiologic functions, arousal and awareness, which have discreet neuroanatomic locations, are integrated in the conscious person.³ Arousal or wakefulness describes the degree to which an individual appears to be able to interact within the environment. Awareness reflects the depth and content of the arousal state. When one is aware, one is alert (or aroused) and cognizant of self and surroundings. The relationship between wakefulness and awareness is hierarchical: Awareness cannot occur without wakefulness, but wakefulness may be observed in the absence of awareness (e.g., sleep/wake cycles in a vegetative patient).

Sleeping and waking are common examples of different states of arousal. Although coma and sleep both abolish conscious interaction with the environment, they differ physiologically because sleep is an active physiologic process with several distinct stages, and mechanisms for arousal remain intact. Sleep is dominated by a cortically generated slow wave (electroencephalogram [EEG]) activity within networks of neurons and glia, modulated by extracellular ion currents. Wakefulness is produced through the activation of brainstem and basal forebrain structures that disrupt sleep oscillations and elicit a global change in extracellular ion flow that results in modifications of glial and cerebral blood flow. Coma, however, occurs as a result of an impairment of physiologic components responsible for arousal and an inability to consciously interact.⁴^–⁶

Anatomy of Arousal and Ascending Reticular Activating System

Arousal occurs by physiologic mechanisms that can be selectively impaired by toxins, anesthetics, or physical destruction of the brain stem. Neuroanatomically, the ascending reticular activating system (ARAS) and related structures responsible for arousal are primarily located in the brainstem in the paramedian tegmental grey matter immediately ventral to the pons. Three ARAS principle pathways have been identified (Figure 58-1). Communications have been identified between the ARAS and the cortex and the limbic system via the thalamic reticular nucleus, the cortex hypothalamus, the basal forebrain, and the brainstem median raphe (locus caeruleus).⁴ Because the ARAS receives collaterals from and is stimulated by every major somatic and sensory pathway directly or indirectly, it is best regarded as a physiological rather than an anatomic entity. This partly explains why patients with very large discreet lesions (brain tumors) may be entirely alert, whereas patients with anatomically undetectable but biochemically widespread lesions (e.g., hepatic encephalopathy) may be deeply comatose.

Figure 58–1 Reticular activating system.

(Modified from Hudson AJ: Consciousness: physiological dependence on rapid memory access, Frontiers Biosci 14:2779-2800, 2009.)

Primarily, two types of lesions depress the level of arousal: direct brainstem-diencephalic injury involving the reticular formation and nuclei, or bilateral cerebral dysfunction. Consequently, conscious behavior depends on the interplay between the cerebral cortex and ARAS because these neural components are required for arousal and to maintain awareness.^1,⁴ Because the brain maintains a rich network of connections between the cortex, the ARAS, and the brainstem, patients with large discreet lesions might be alert on presentation, although localized neurological deficits are noted on physical examination. On the other hand, patients with only minimal exposure to CNS depressants present with a depressed sensorium. Changes in a patient’s level of consciousness imply significant dysfunction and can occur with variable degrees of wakefulness.

States of Impaired Sensorium

Precise definitions and descriptions of the various levels of consciousness are helpful in establishing a baseline, communicating with other health care providers, and interpreting changes in a patient’s condition. Box 58-1 describes definitions for varying levels of consciousness; however, many terms used to describe alterations in sensorium lack precision and are better avoided. Colloquial use of the terms lethargy, obtundation, somnolence, and stupor have rendered them imprecise, and health care workers are best served to avoid them when describing patients with altered consciousness. Numerous scoring systems have been developed to assess acute neurologic conditions. By far the most common is the Glasgow Coma Scale (GCS). Developed to classify the depth of coma in adults who have sustained a head injury, the use of the GCS has been expanded to evaluate patients who have sustained a variety of neurologic injuries. A GCS score of eight or less has been used as an alternative definition of coma. Although other scales are used to assess the severity of illness in coma (e.g., Liege coma scale, Apache II scale, and Reye syndrome), the GCS has gained wider acceptance because of its ease and familiarity.⁷ A modified GCS has been devised that is more applicable to infants.

Several states of depressed consciousness are described and deserve mention. Consciousness disorders should be distinguished from brain death, an irreversible loss of all brain and brainstem function.⁸^–¹⁰ Coma is a state characterized by the absence of arousal and awareness. To differentiate coma from more transient causes of depressed sensorium (e.g., syncope and concussion), coma must last more than 1 hour. Comatose patients do not speak, open their eyes spontaneously, follow commands, move spontaneously, or respond meaningfully to painful stimuli. Spinally mediated stereotypical movements may be made in response to pain, but patients do not actively withdraw. Sleep-wake cycles are not preserved in patients who are in a coma. Patients in a coma are in a transitional state and can either deteriorate to a more permanent state of depressed sensorium, deteriorate to fulfill brain death criteria, or recover.

In a vegetative state, arousal mechanisms are preserved but patients completely lack an awareness of self or the environment.^8,⁹ Patients in a vegetative state demonstrate spontaneous eye opening without the ability to visually track or fixate. Although they may display “sleep-wake cycles,” they cannot follow commands or move in a purposeful manner. Patients in a minimally conscious state do not meet the criteria for coma or the vegetative state. They demonstrate wakefulness and sleep-wake cycles and intermittently demonstrate self or environmental awareness. These patients may intermittently follow commands, communicate, and display purposeful behavior. Although data are limited, the minimally conscious state may be associated with a greater possibility of recovery than the vegetative state. Lesions associated with this state involve the cerebral hemispheres, with possibly greater sparing of corticocortical and corticothalamic connective fibers.

Akinetic mutism is a state of wakefulness with limited evidence of awareness. Patients with akinetic mutism frequently have more diencephalic injury than injury to the motor tracts. Akinetic mutism ⁸^–¹⁰ has been associated with bilateral medial frontal lobe injury. The medial frontal lobe injury leads to a profound deficiency in motivation and an inability to plan and initiate activity. Akinetic patients generally are unable to move or speak and have sleep-wake cycles indicated by eye opening. Unlike patients in a minimally conscious state, akinetic patients have no motor responsiveness to verbal, tactile, or noxious stimuli. Further, spasticity or abnormal reflexes do not develop in these patients as a result of relative sparing of the corticospinal tract.

The locked-in syndrome is not a disorder of consciousness as much as it is an entity frequently confused with states of depressed sensorium due to the limited ability of these patients to communicate.^8,⁹ Locked-in patients are quadriplegic and anarthric, but awareness and arousal are preserved. The locked-in syndrome is associated with injury to the ventral pons below the level of the third nerve nuclei and sparing of the ascending reticular activating system. Vertical eye movements and blinking usually are spared. More rostral injury may result in a total locked-in syndrome with loss of eye and eyelid movement that eliminates the ability of the patient to interact or communicate.

Identification of Cause

Coma may present as part of the progression of a known neurologic illness or the unpredictable consequence or complication of a known systemic disease, or it may result from a totally unexpected event or illness.¹⁰ An accurate history of the events and circumstances before the onset of the symptoms and information concerning the patient’s medical history and use of medications may be invaluable in determining the cause of coma and quickly lead to the most appropriate diagnostic testing and treatment. As in most pediatric disease, the differential diagnosis of coma is age related as described in Table 58.1. Common etiologies of coma seen in the pediatric population are described in Box 58-2.

Table 58–1 Common Considerations of Altered Mental Status at Various Ages

Infant	Child	Adolescent
Infection Inborn error of metabolism Metabolic Abuse Trauma	Ingestion Infection Intussusception Seizure Abuse Trauma	Ingestion Intentional Trauma Drug/alcohol overdose

Box 58–2 Etiologies of Impaired Consciousness and Coma

Metabolic-Toxic

A. Hypoxia-ischemia

1. Shock

2. Cardiac or pulmonary failure

3. Near drowning

4. Carbon monoxide poisoning

5. Strangulation

C. Fluid and electrolyte imbalance, dehydration, hyponatremia, calcium and magnesium imbalance

D. Endocrine disorders: thyroid dysfunction, adrenal insufficiency, hypoparathyroidism

E. Hypertensive encephalopathy

F. Vitamin deficiency (e.g., thiamin, pyridoxine, niacin)

G. Mitochondrial disorders

H. Exogenous toxins and poisons

1. Narcotics, neuroleptics, antidepressants, antiepileptic drugs, stimulants

2. Over-the-counter drugs, acetaminophen, mushroom

3. Industrial toxins (e.g., heavy metals, organic phosphate, cyanide, volatile hydrocarbons)

4. Substance abuse (e.g., alcohol, cocaine, heroin, amphetamine)

I. Poisoning in cases of Munchausen by proxy

K. Paroxysmal disorders

1. Epilepsy

2. Migraine

Initial Assessment and Immediate Resuscitation

The initial assessment of the comatose patient should start with an evaluation of airway patency, the adequacy of ventilation, and the status of the patient’s perfusion. Appropriate life support intervention should occur whenever life-threatening illness evolves throughout the assessment. Measurement of core temperature is an important adjunct. Many practitioners assign an initial GCS score at this time.

It is important to observe the respiratory pattern. The rate and regularity of respiration depends on a complex interplay of chemical and neural control systems that operate automatically to reset the rate and depth of breathing as changes occur in gas tensions and pH. In the comatose patient, abnormality may occur in rate and in the pattern. A low respiratory rate is associated with CNS depressants, for example, alcohol, barbiturates, benzodiazepines, and narcotics, and leads to hypoventilation. It also can be associated with elevated intracranial pressure (ICP). Tachypnea is far more commonly due to a physiologic response to hypoxia, metabolic acidosis, or fever, but central hyperventilation can be a sign of brainstem herniation.

The hemodynamic disturbance and hypotension leading to shock that occurs coincident with coma is mainly seen in systemic diseases (e.g., sepsis, drug ingestions, myocardial injury, and adrenal insufficiency), but it is not uncommon to see neurogenic shock related to severe traumatic brain injury (TBI) and spinal trauma as well. Hypertension is suggestive of an intracranial structural lesion and raised ICP but may be due to primary hypertensive encephalopathy.

Once the patient’s airway, breathing, and hemodynamics are stabilized, a complete general examination and specific neurologic examination should be noted, along with any signs of trauma. Cervical immobilization should be maintained until trauma has been excluded or cervical spine has been cleared by radiographic and physical examinations. The patient should be completely exposed to allow a visual appraisal of swelling, lacerations, bruises, and other obvious signs of trauma. Blood or clear fluid noted in the nose or ears suggests a basilar skull fracture. Injuries with characteristic patterns (e.g., cigarette burns and glove and stocking burns), characteristic shapes, and characteristic locations (e.g., finger marks on the buttocks and bruises over ear lobes) suggest child abuse (see also Chapter 113).

Focused Neurologic Examination

A focused neurologic examination is key to documenting a baseline neurologic status and helps to locate lesions and determine prognosis in patients with diminished level of conscious (LOC).¹¹ Because a diminished LOC requires either reticular system or bilateral hemispheric dysfunction, testing the structures immediately adjacent to the reticular system provides clues to the etiology of coma and directs subsequent investigations.² A thorough physical examination must be systematic and is as valuable as radiographic and laboratory studies. The neurologic examination of a comatose patient differs from that of an awake, communicative subject and involves pupillary response, respiratory pattern, stimuli required to illicit a motor response, and the general character of the responses. History and presenting symptoms should be evaluated in the context of neurologic findings. Taken together, the history and presenting symptoms help determine the cause of diminished LOC. The level of neurologic dysfunction often is best defined by the respiratory pattern (Table 58-2), associated eye findings, and motor examination (Table 58-3).

Table 58–2 Respiratory Patterns in Patients with Altered Mental Consciousness

Pattern	Description	Localization
Posthyperventilation apnea	Apnea for >10 seconds after 5 deep breaths	Bilateral hemispheric dysfunction
Cheyne-Stokes respiration	Rhythmic waxing and waning of respiratory amplitude	Bilateral hemispheric dysfunction
Central reflex hyperpnea	Continuous deep breathing	Bilateral hemispheric (e.g., trauma), lower midbrain, upper pons
Apneustic respiration	Prolonged aspiratory time (“inspiratory cramp”)	Pons
Ataxic respiration	Infrequent irregular breaths	Lower pons or upper medulla
Ondine’s curse	Failure of involuntary respiration with retained voluntary respiration	Medulla
Apnea	No respiration	Medulla down to C4: peripheral nerves, neuromuscular junction

Table 58–3 Differentiating Characteristics of Structural and Metabolic Coma

Supratentorial Lesions	Infratentorial Lesions	Toxic, Metabolic, or Infectious Processes
Initial focal signs Retrocaudal progression Asymmetric examination often present early	Brainstem abnormalities often initial signs Sudden onset of coma Cranial nerve abnormality often seen Respiratory pattern often altered, such as central reflex hyperpnea	Confusion/stupor often precede signs Symmetric examination Pupillary reactions preserved Respiratory rate often altered, such as Cheyne-Stokes breathing