Chapter 31. Coma

Coma is a common neurological emergency seen in critically ill children. Coma is not a disease per se but instead an acute state of disordered consciousness clinically manifested due to a wide variety of medical and surgical disease processes that affect the central nervous system (CNS). It is usually described as "a state of unarousable unresponsiveness in which the eyes remain continuously closed and there is no understandable response to environmental or intrinsic stimulation."1 In contrast to the sleep state, during coma a person cannot be aroused by appropriate intense stimuli, there is no evidence of sleep–wake cycles on the electroencephalogram (EEG), and the behavioral responses mostly consist of reflex activity.

There is a lack of comprehensive large studies evaluating the overall incidence of coma in children. Most studies have a small number of subjects, are affected by the segregation of studies into traumatic and nontraumatic causes, and use a variety of definitions to define coma. This is further complicated by the fact that coma is seen in an extremely wide range of disease processes.

A number of studies report different epidemiologic rate and outcomes for coma in children. For example, a prospective, population-based, epidemiologic study from the United Kingdom of nontraumatic coma in 278 children aged between 1 month and 16 years defined coma as a Glasgow Coma Scale (GCS) score below 12 for more than 6 hours. They reported an incidence of 30.8 per 100,000 children per year, and 6.0 per 100,000 per year in the general population. In this study, age-specific incidence was significantly higher in the first year of life (ie, 160 per 100,000 children per year). CNS specific presentations became more common with increasing age, but in infants nearly two-thirds of cases presented with nonspecific systemic signs. Infection was the most common overall etiology and the etiology remained unknown in 14% of cases despite extensive investigation and/or autopsy. Mortality was highly dependent on etiology; at approximately 12 months after coma onset, overall series mortality was 46%.2 Another prospective observational study from a tertiary care teaching/referral hospital in India followed 100 children with all causes of coma from 2 months to 12 years of age. Overall mortality was 35%; CNS infection was the most common etiology followed by toxic/metabolic causes of coma in this study population.3

A recent analysis of children from 0 to 14 years of age who suffered from traumatic brain injury (TBI) in 2003 estimated that 1,565,000 TBIs in the United States resulted in 1,224,000 emergency department visits, 290,000 hospitalizations, and 51,000 deaths.4 Although many of these children sustained severe TBI (defined as GCS ≤ 8), it is not clear how many of these children were actually in coma after the injury. A previous study reported the rate of coma from TBI was 140 per 100,000 children per year in the United States.5 Kraus and associates calculated an incidence of severe TBI in children up to 14 years of age of 27 per 10,000 children per year.6 A 9-year prospective study from a pediatric trauma center in France followed 585 children from 1 month to 15 years of age with a presenting GCS lower than 8. Mortality rate was 22%; Glasgow Outcome Scale (GOS) score was lesser than 3 in 53% of the cases at discharge and 60% at 6-month follow-up.7 Most of the studies in children with coma or TBI also suggest that younger children are at higher risk of developing nontraumatic coma, with the lowest risk between 5 and 8 years of age, while the risk of traumatic coma increases with mobility with the highest rates seen in older-age children.

To understand coma and other disorders of consciousness it is important to define consciousness. Currently, there is no universally acceptable, satisfactory definition of consciousness. For medical purposes, normal consciousness is thought to be a product of two basic neurophysiologic functions of the brain: arousal and awareness. Arousal or wakefulness is used to describe a behavior change that occurs during transition from the sleep state to wakeful state. This brain function is linked to the ascending reticular activating system (ARAS), which is a network of neural tissues originating in the tegmentum of the pons and midbrain and projecting to the hypothalamus, thalamus, and cerebral cortex.8,9Awareness of self and environment encompasses multiple brain functions including attention to environment and perception to various stimuli, memory, executive function, and motivation.10 In children, the concept of consciousness requires understanding the child's developmental level and age-appropriate response.

Impaired consciousness can result from derangement in arousal, awareness, or both in varying depths. In general, awareness cannot occur without arousal, but arousal can be seen without awareness, as seen in patients with vegetative states. A wide range of terms have been used to describe the altered consciousness spectrum from normal consciousness to coma and brain death. Terms such as somnolence, stupor, obtundation, and lethargy lack precision and their use should be discouraged. Since impaired consciousness may be brief, lasting only a few minutes, as with syncope, hypoglycemic episodes, and seizures, this should not be confused with coma. Hence, coma is characterized by a complete absence of both arousal and awareness for more than or equal to 1 hour duration.11

Coma is a manifestation of a wide variety of medical and surgical conditions in which CNS involvement may result from a direct insult to the CNS, or may result from secondary brain involvement due to systemic disease. These conditions can be broadly categorized into two groups: (1) those with structural causes or (2) those with metabolic/toxic causes (Table 31-1). Structural conditions affecting the CNS can be further subdivided based on the location into (1) supratentorial and (2) subtentorial. In general, the following rules apply for structural lesions of CNS to induce coma:

1. Cerebral cortex lesions have to involve both hemispheres.

2. Unilateral cortical lesion must be large enough to cause displacement of midline brain structures.1

3. Smaller brainstem and diencephalic lesions have to involve bilateral structures.

4. Compartment shifts needs to be of significant magnitude to cause compression or disruption of ARAS.12

Metabolic and Toxic causes usually result in secondary injury to the CNS related to the pathophysiology of the disease process itself and may include hypoxia, hypoglycemia, seizures, toxicity, change in brain volume due to altered electrolytes, and toxins as listed in Table 31-1. Two other causes of coma in children are worth mentioning here. Although not very common, in some clinical situations coma can be pharmacologically induced as a therapeutic maneuver, such as for the treatment of refractory status epilepticus or increased intracranial pressure. Finally, coma rarely can be imitated by some psychological disease processes, but this should be differentiated from actual coma and should be termed "psychogenic unresponsiveness."

Diseases that cause a reduced level of consciousness in children present with similar overlapping clinical signs and symptoms and are difficult to differentiate from one another. For CNS structural lesions, one important clinical pattern to recognize is termed the "herniation syndrome." This term describes signs and symptoms resulting from compression of brain tissue by the pressure forces generated by intracranial space-occupying lesions, whether blood, edema, or tumor. The total volume of the cranial cavity is limited; therefore any space-occupying lesions must initially shift cerebrospinal fluid and then brain tissue itself from one intracranial compartment to another or toward the foramen magnum. Coma can result when the pressure on the brainstem disrupts the reticular activating system (RAS). In general, there are slight differences in presentation among the broad categories of causes of coma that are summarized in the following section.

Patients with supratentorial lesions usually present with focal neurological signs like contralateral hemiparesis, aphasia, sensory deficit, behavioral changes related to frontal lobe dysfunction, headache, and/or focal seizures. Abnormal signs usually are confined to a single or adjacent anatomic level. Motor dysfunction tends to move from a rostral to caudal direction. Brainstem functions are usually spared until herniation develops and coma ensues.

Patients with subtentorial lesions usually present with brainstem localizing signs. These include pupillary size and response abnormalities, absent or disconjugate caloric eye response, ataxic breathing, bilateral motor deficits, or signs of cerebellar dysfunction. These signs may precede coma, but the onset of coma in these cases could be sudden.

In contrast, patients with metabolic/toxic causes commonly present with delirium preceding coma. Signs and symptoms of systemic disease process are present. Pupillary reaction is generally symmetrical and usually preserved except for specific cases of poisoning. Abnormal motor signs, if present, are symmetrical and sensation is usually intact. Hypothermia is common and other signs like tremors, myoclonus, or asterixis may be present. Often these patients will have brain dysfunction at multiple anatomic levels simultaneously.

Coma must be differentiated from other conditions that mimic the clinical picture of coma. These conditions include locked-in syndrome, akinetic mutism, minimally conscious state, vegetative state, brain death, psychogenic unresponsiveness, and pharmacologically induced coma. These conditions are briefly described here and summarized in Table 31-2.

Locked-in syndrome is a rare condition, especially in children, but can occur with brainstem injuries sparing the midbrain. Patients have mostly intact arousal and awareness but a severely limited ability to communicate their awareness due to paralysis of voluntary muscles and anarthria. This has been seen in patients with trauma,13 pontine glioma,14 basilar artery occlusion15 with profound neuromuscular dysfunction from Guillain-Barré syndrome,16 spinal muscular atrophy,17 botulism, and organophosphate toxicity.18 The diagnosis can be substantiated with the help of EEG or functional MRI imaging.19,20

Akinetic mutism is a state of profound apathy with intact awareness, revealed by attentive visual pursuit, but a paucity and slowness of voluntary movements without evidence of paralysis. These patients seem on the verge of initiating speech or motor activity but that never seems to happen. It is seen with bilateral injuries within the paramedian midbrain, basal diencephalon, or inferior frontal lobes, occurring with traumatic brain injury,21 hydrocephalus,22 central nervous system (CNS) infection,23 tumors, and tumor resection.24,25

Minimally conscious state is a relatively new term used to describe patients who have some intermittent evidence of reproducible and purposeful (even if severely limited) nonreflexive motor movements or affective behaviors, such as simple command following, gestural or verbal responses to questions, intelligible verbalizations, smiling or crying in response to the emotional content of stimuli, reaching accurately toward the location of an object, or visual pursuit or fixation in response to visual stimuli.26 This condition is most commonly confused with vegetative state.

Vegetative state is a state in which the patient demonstrates arousal but self- and environmental awareness is absent. These patients have intact hypothalamic and brainstem (vegetative) functions, which are sufficient to allow for prolonged survival with supportive care.11,27 They have preservation of both respiratory function and sleep–wake cycles including periods of spontaneous eye opening. These patients demonstrate some irreproducible reflex movements in response to external stimuli, which may be interpreted by some observers as being purposeful and voluntary. A vegetative state is considered permanent if it lasts longer than 12 months after traumatic brain injury or longer than 3 months after nontraumatic brain injury.11

Brain death is a complete and irreversible loss of brain and brainstem function characterized by loss of consciousness, cranial nerve functions, and motor functions, and loss of breathing activity.

Psychogenic unresponsiveness can on rare occasion mimic coma in psychological conditions like schizophrenia, catatonia, hysteria, and malingering. These patients otherwise usually have normal neurological examinations. This can often be identified by the resistance offered during the examination such as resisting eye opening for eye examination or presence of bizarre motor responses during motor reflex assessment. The EEG pattern is usually normal.

Diagnosis of coma is purely clinical. Current diagnostic criteria for diagnosis of coma are mostly based on absence rather than presence of certain neurobehavioral actions seen in normal consciousness. All of the following are required.

• No spontaneous or stimulus-induced eye-opening
• No age-appropriate command following
• No intelligible age-appropriate speech or verbal response
• No purposeful movement
• No discrete defensive movements or capacity to localize noxious stimuli
• Duration of more than 1 hour
• Duration lasting rarely for more than 2 to 4 weeks

Defining Depth of Coma

Objective scoring systems have been used to uniformly define level of consciousness, such as the widely accepted Glasgow Coma Scale (GCS) originally published by Jennette and Bond in the 1970s.28 Although originally designed to assess depth of coma after head injury in adults, the GCS has been applied widely in the assessment of pediatric neurological status. This scale was subsequently modified for use in children less than 5 years of age and includes age-appropriate verbal and motor responses, although overall scoring remains the same as shown in Table 31-3.29,30 Children with normal consciousness have a GCS of 15; a GCS of 12 to 14 is considered "mild," GCS of 9 to 11 is considered "moderate," and GCS lesser than 8 is considered "severe" alteration of consciousness. GCS has its limitations with issues related to interobserver reliability and assessment of depth of coma, but it is widely accepted and is commonly used by health care providers. Other scoring system have been suggested, but are not commonly applied.31

History and Physical Examination

Evaluation of coma requires a rapid assessment and simultaneous initiation of therapies to avoid delays in treatment for potentially reversible causes that may resolve without long-term disability. Coma may present as progression of a known illness or without any precedent illness. Acute onset of coma within a few minutes suggests cerebrovascular disease or cardiac arrhythmia, while a subacute course of minutes to a few hours suggests a postictal state after seizure, infection, or drug intoxication. History of recent head injury should raise suspicion of intracranial bleeding (eg, subdural or epidural hematoma). A slower onset over hours to days of deterioration of mental status suggests the possibility of CNS tumor or metabolic causes.

The general physical examination may also render clues toward the underlying cause of coma. This should include complete examination of the head, scalp, skin, and back of the patient as initial stabilization is being done. Some helpful diagnostic clues on physical examination are listed in Table 31-4. Disordered breathing patterns have been described in patients with altered consciousness either due to injury involving brainstem respiratory centers or interference with higher regulation centers.32,33 Although sometimes helpful diagnostically, altered breathing can be seen in a variety of other conditions like hemodynamic shock, metabolic disorders, after giving drugs used for sedation or analgesia, and mechanical ventilation, which may limit the usefulness of these patterns in most patients. Cheyne-Stokes respiration is a cyclical pattern of alternating hyperpnea and apnea seen in patients with a bilateral hemispheric or diencephalic injury, but may also be present in congestive heart failure and sleep apnea. Hyperventilation is seen in injuries to pontine or midbrain tegmentum; however, it is also widely seen in various conditions including respiratory failure, hemodynamic shock, fever, sepsis, metabolic disarray, and psychiatric disease. Apneustic breathing is characterized by a prolonged pause at the end of inspiration and indicates lesions at the mid- and caudal portions of the pons. Ataxic breathing is irregular in both rate and tidal volume and suggests damage to the medulla.

The neurological examination is focused on assessing the etiology of coma with the basic goal of determining if the coma is due to a bilateral cortical hemispheric issue or a RAS problem. Pupillary size and response to light should be examined with bright light and preferably in a dark room. The pupillary reflex requires intact parasympathetic and sympathetic systems to constrict or dilate, and most midbrain lesion not only affect the RAS but also the pupil reactivity while metabolic causes of coma may spare these reflexes. Some abnormal responses are noted in Table 31-4.

Eye gaze and movements are coordinated by the following cranial nerves: oculomotor nerve (III), trochlear nerve (IV), abducens nerve (VI) and nuclei in the midbrain and pons. Conjugate horizontal eye movements require connections between the ipsilateral abducens (lateral rectus muscle) and contralateral oculomotor (medial rectus muscle) nuclei along the medial longitudinal fasciculus. Rapid eye movements (saccades) initiate from the frontal eye fields, whereas the smooth pursuit of a moving stimulus arises from the occipitoparietal visual area. Eye movements are modulated by proprioceptive (spinocerebellar tract) and vestibular nerve (VIII) inputs from the medulla and coordinated by the cerebellum. All of these help to maintain visual fixation despite movement of the head, and create the oculocephalic or "doll's-eye" reflex. An oculocephalic reflex is abnormal in a comatose patient when one or both eyes do not move in the opposite direction of head rotation or vertical movement. If neck movement is contraindicated, as with the cervical spine injury, the caloric response (oculovestibular reflex) is used to test the same pathways. Irrigation of one external ear canal with warm or cold water induces convection currents in the endolymph of the semicircular canals. When higher-level brain function is impaired, warm water stimulation leads to slow horizontal deviation of the eyes away from the irrigated ear, whereas cold water will effect slow deviation toward the irrigated ear. In conscious patients, saccades back toward the initial point of fixation attempt to counter these slow deviations. This could be memorized by the familiar mnemonic COWS (Cold water Opposite, Warm water Same). No saccadic responses are seen in comatose patients.

Corneal reflexes test the sensory input pathway along the ophthalmic branch of the trigeminal nerve (V) to its nucleus in the medulla, which communicates with the facial nerve (VII) nuclei in the pons to effect direct and consensual eyelid closure. An asymmetric response is suggestive of a structural lesion interrupting the reflex arc. Bilateral absence of the corneal reflex can be seen with metabolic disorders, but can be altered by use of sedation and paralysis. Gag and cough reflexes can be elicited if there is intact functioning of the glossopharyngeal nerve (IX) and vagal nerve (X) afferents. Although commonly assessed by manipulation of the endotracheal tube, this can be a less specific way of testing because it stimulates additional spinal cord-mediated reflexes.

Motor and verbal responses are a crucial part of neurological assessment of comatose patients as reflected by their inclusion in the GCS (Table 31-3). The patient should be observed for spontaneous motor activity and if not present, response to various stimuli should be elicited. Comatose patients may show purposeful movements sometimes, such as reaching for the endotracheal tube or localizing to pain stimuli at the notch of the supraorbital nerve. An asymmetric motor pattern represents contralateral lesions of the cerebral cortex, while localization suggests intact sensory pathways. Decorticate "flexor" posturing consist of flexion of arms and extension of legs; in contrast, both arms and legs are extended in decerebrate "extensor" posturing. Although decerebrate posturing carries a worse prognosis than decorticate posturing, both can result from hemispheric and brainstem lesions.

Finally, extreme care in interpreting motor responses is needed to avoid confusing reflex activity with other responses that may look like spontaneous activity. For example, the triple flexion response, which is flexion of lower extremity to tactile or pain stimuli of the lower extremity, can be seen in deep coma or brain-dead patients.34 This reflex response is recognized by a very rapid and stereotyped response.

Diagnostic Tests

Coma may require immediate lifesaving treatment before a conclusive diagnosis of the underlying etiology can be made. There are no studies validating the utility of any specific laboratory study in children with decreased mental status. In general, diagnostic tests are ordered based on clinical suspicion of the specific etiology, but certain routine laboratory studies should be obtained in all cases upon presentation. These tests are summarized in Table 31-5. Some of these tests may provide diagnostic clues while tests like arterial blood gas analysis and urine and blood toxicology could possibly help with acute management of the patient, such as use of antidotes if appropriate. It is important to remember that children often present with unfamiliar or atypical clinical features of specific drugs or toxins.35,36

Neuroimaging by computed tomography (CT) is routinely recommended in children with coma since it is the quickest study with sufficient sensitivity for detecting structural pathology that needs immediate intervention, such as cerebral edema, tumor, hemorrhage, and herniation. A diagnostic study of CT scan detection of raised intracranial pressure (ICP) as measured by ICP monitoring found a sensitivity of 84% with specificity of 44%. Thus, CT scanning is helpful, but it is important to remember that CT findings may be absent even in the presence of raised ICP.37 Abnormal head CT scans are more common in patients who have focal neurological signs, unfortunately some times structural lesion in children may not produce focal signs. Patients without a surgically remediable lesion on initial CT scan should not undergo serial examinations at 24 and 48 hours unless there is a clear deterioration of the clinical course.38 Magnetic resonance imaging (MRI) can provide greater structural detail as well as better early evidence of infection, infarction, diffuse axonal injury, and demyelination.39,40 Therefore, an MRI should be obtained in comatose children when the child can safely withstand the longer acquisition times.

Lumbar puncture is an invasive test but considered as a gold standard for microbiologic cultures and polymerase chain reaction studies to confirm CNS infection.41,42 Performing lumbar puncture in patients with raised intracranial pressure carries a risk of worsening impending herniation, as reported in adult patients.43 No pediatric studies have evaluated the risk of performing a lumbar puncture during increased intracranial pressure, but if clinical suspicion of raised intracranial pressure is high, a CT scan should be obtained before the procedure. Antimicrobial therapy should not be delayed to obtain a CSF sample if the clinical suspicion of CNS infection is strong.

Electroencephalography (EEG) is frequently indicated in patients with known seizure disorder and prolonged coma after seizure activity to rule out nonconvulsive status epilepticus or in cases of unexplained coma. Although diagnostic yield and specificity are low during coma, some helpful features have been suggested. In patients with metabolic coma, a generic pattern of diffusely decreased frequency and increased amplitude has been described, often in association with "triphasic waves."44 Some comatose patients have an EEG that superficially resembles an awake (alpha) pattern. This is called "alpha-coma," and is most commonly seen in patients with extensive damage or dysfunction involving the brainstem or cerebral cortex and generally carries a poor prognosis.45 Herpesvirus encephalitis has been associated with changes such as periodic sharp waves or epileptiform discharges called "PLEDS" (periodic lateralized epileptiform discharges).46,47

Consultation or Referral

Coma in pediatrics is an emergency and often requires a multidisciplinary approach for optimal patient care. Appropriate consultation from different pediatric subspecialists should be emergently obtained and transfer to an appropriate facility should be done quickly after initial stabilization. There is some evidence that outcome of severely injured children is better at specialized centers.48 Some suggested reasons for seeking immediate subspecialty consults are listed in Table 31-6. In general, referral should be considered in the following situations:

1. There is uncertainty regarding the diagnosis or management.

2. The clinician does not have privileges to provide the type of care needed (eg, surgery).

3. The clinician is ethically opposed to providing care (eg, hospice care, or alternatively, definitive care at the patient's/family's request when it would be futile).

4. When there is a conflict (eg, personality conflict or the patient is a close friend or family member) and the clinician feels he or she cannot be objective.

5. Consultation as a second opinion may be wise when the diagnosis is unexpected (eg, a young person with severe injury) and the prognosis is grim or the patient is not getting better.

Coma in many cases is a symptom of a potentially life-threatening condition that requires swift and prompt assessment and intervention simultaneously. No single algorithm is currently available for clinician to follow because of the wide spectrum of conditions causing coma. A basic sequential approach is suggested, consisting of initial stabilization, emergent diagnostic evaluation and intervention if needed, and then focusing on detailed evaluation and etiology-specific management as summarized in Figure 31-1.

Initial Stabilization

Regardless of the etiology, any child presenting with decreased level of consciousness should receive Airway, Breathing, Circulation, Disability, and Exposure (ABCDE) evaluation. Intervention should be done as quickly as possible for initial stabilization. No studies have evaluated the risk of airway obstruction and decreased rate of breathing with decreased mental status in children. In a pediatric near-drowning case series, 50% of children were apneic when their GCS was 3 or 4.49 The airway should be opened for signs of obstruction and oxygen should be provided if oxygen saturation is less than 95%. Bag-mask ventilation should be done for persistent hypoxemia, decreasing breathing rate, ineffective breathing, or apnea. Cervical spine injury should be assumed, especially in trauma patients because neck pain and tenderness are difficult to assess in patients with decreased mental status. Immobilization of the cervical spine should be done until definitive diagnosis is established. Endotracheal (ET) intubation should be considered with apnea, oxygen saturation below 92% despite airway positioning and bag-mask ventilation, GCS lower than 8 and loss of airway protective (cough and gag) reflexes, signs of raised intracranial pressure, shock state, and need for ongoing resuscitation. ET intubation should be done by the most experienced person available, especially in cases of trauma with possible C-spine injury or raised intracranial pressure. Hypotension and signs of poor perfusion (eg, capillary refill > 2 s, mottled extremities, diminished peripheral pulses, and decreased urine output) should be promptly treated with rapid IV normal saline boluses or blood depending upon presentation; hypotonic IV fluids should be avoided.50 A majority of patients with traumatic brain injury with intracranial hemorrhage, brain edema, or raised intracranial pressure will have hypertension on presentation most likely due to a stress response to maintain cerebral perfusion pressure. In the setting of traumatic or nontraumatic brain injury, hypertension should not be treated emergently except in patients with hypertensive encephalopathy coma. Laboratory tests, including blood glucose and electrolytes mentioned in Table 31-5, should be quickly checked. Complete patient exposure should be done to evaluate for signs of injuries and the GCS should be assessed for changes every 15 minutes in the initial few hours.

Narcotic ingestion or overdose and hypoglycemia are common findings in children with coma of an unknown etiology, and their immediate reversal can improve consciousness quickly. If raised intracranial pressure is suspected, mannitol or 3% saline should be given during stabilization. Doses and indications of some helpful initial medications for coma patients are listed in Table 31-7.

Immediately after hemodynamic stabilization, a head CT scan should be obtained in all children with coma and suspicion of structural cause or in otherwise unclear cases. Subsequently, a detailed history and physical examination should be obtained, and etiology-specific workup, including but not limited to lumbar puncture, EEG, or MRI, should be done along with appropriate consultation and transfer arrangements.

Specific Etiology Management

It is impossible to discuss the management of all the specific etiologies of coma in this chapter. There are a few common and important situations that clinicians managing pediatric patients with coma need to know. These are briefly discussed here.

Patients with Increased ICP

If raised ICP is suspected with traumatic or nontraumatic cause, treatment should be started immediately, especially if signs of herniation are identified. Detailed guidelines for traumatic brain injury management have been published.51 General measures include ET intubation and mechanical ventilation and avoiding hypoxemia and hyperventilation, elevation of the head of the bed to 30 to 45°, maintaining neutral neck position, and aggressively reducing fever. In cases of impending herniation, hyperventilation can be used for short duration until other measures are taken to decrease intracranial pressure. Since hyperventilation raises intrathoracic pressure and may impair venous return, it is important to avoid hypotension, hence blood pressure should be frequently monitored. Bolus fluid administration will often restore venous return to maintain a cerebral perfusion pressure greater than 50 mm Hg.52 Hyperosmolar therapy with either mannitol or 3% saline53 should be started immediately and subsequently continued guided by cerebral perfusion pressure and ICP, if available. Immediate neuroimaging with CT scan and neurosurgical consult should be obtained for surgical lesions. Patients should be subsequently managed in pediatric intensive care units. ICP monitoring and management can improve outcome following TBI, but has not been effective in improving outcome in patients with brain edema and raised ICP due to hypoxic ischemic brain injury.54

Patients with Meningitis and/or Severe Sepsis

In patients with strong suspicion of CNS infection or severe systemic infection, in addition to the general measures discussed above, emergent broad-spectrum antimicrobial administration is crucial. Although lumbar puncture is considered the gold standard to confirm the diagnosis of meningitis, antibiotic therapy should never be delayed for obtaining a CSF sample. Clinical decision rules have been published to help clinicians manage children with meningeal signs.41 Patients with meningitis and low GCS, abnormal pupillary reflexes, focal neurological signs, or posturing should undergo a CT scan to rule out increased ICP before lumbar puncture. Steroid therapy with dexamethasone, 0.15 mg/kg, before or with the first dose of antibiotics decreases mortality and neurological sequelae in bacterial meningitis in adults but its utility in children is still debated.55

Patients with Convulsive or Nonconvulsive Status Epilepticus

Patients with convulsive status are easy to identify and require prompt management with anticonvulsants. In refractory cases, emergent neurologist consultation and an EEG should be obtained. Electrolytes like serum sodium, calcium, and magnesium should be checked, especially in infants, and corrected if abnormal. Often patients will remain unconscious due to a post-ictal state for up to 1 hour. In general, if consciousness is not recovered by 30 minutes after seizure activity ends without any apparent reason, nonconvulsive status should be ruled out by obtaining an urgent EEG along with other neuroimaging. Children with refractory status epilepticus should be admitted to the PICU for induction of general anesthesia and EEG burst suppression.

Patients with Coma Due to Toxins

Patients with suspicion of drug ingestion or intoxication and coma should be stabilized with general measures first. If signs and symptoms of narcotics, benzodiazepines, or anticholinergics are present, antidotes like naloxone, flumazenil, or physostigmine respectively, could be used to improve consciousness. Sodium bicarbonate is suggested in cases of tricyclic antidepressent toxicity. Activated charcoal should be given to decrease systemic absorption, although this should be done only after securing the airway in the comatose child. Doses of these medications are given in Table 31-7.

Patients with Coma Due to Metabolic Causes

Although the list of metabolic diseases resulting in coma is very long, some common ones are hypoglycemia, diabetic ketoacidosis, hyperammonemia (eg, from hepatic failure, organic acidurias, urea cycle defects, amino acid transport defects, or Reye syndrome), and nonhyperglycemic ketacidosis (eg, from organic acidopathies, amino acidopathies, fatty acid oxidation defects, and mitochondrial diseases). After initial patient stabilization with general measures, emergent consult with endocrine and metabolic disease experts should be obtained. Patients with severe hyperammonemia may require emergent dialysis for correction. Special laboratory test like plasma lactate levels, plasma amino acids profile, urinary amino acid, and organic acid profile should be sent to delineate the diagnosis.

Outcome of children in coma is highly dependent on the cause, location, severity, and extent of brain injury caused by the disease process. In general, studies suggest that children with traumatic brain injury do much better as a group compared to adults.56 Traumatic brain injury is one of the most common causes of neurological morbidity and mortality during childhood.57 A large population-based study of nontraumatic coma in children reported 46% mortality and 30% neurological morbidity.58 A significant number of coma survivors require extensive support and rehabilitation care, especially if the recovery from coma results in a vegetative state.59