Stupor and coma in children

INTRODUCTION — Coma is an alteration of consciousness in which a person appears to be asleep, cannot be aroused, and shows no awareness of the environment [1]. Coma is therefore the most profound degree to which the two components of consciousness, arousal and awareness, can be diminished. Less profound states of impaired consciousness (stupor, lethargy, obtundation) preserve one or more of these components to some degree.

Coma represents an acute, life-threatening emergency, requiring prompt intervention for preservation of life and brain function. Although discussed separately in this topic, the assessment and management are performed jointly in practice (table 1).

This topic will discuss the evaluation and management of children presenting in stupor or coma.

ANATOMIC BASIS OF CONSCIOUSNESS — Arousal depends on intact communication between the ascending reticular activating system (ARAS) and its targets in the hypothalamus, thalamus, and cerebral cortex. The ARAS is a loosely organized network of neurons within the brainstem whose major function is to modulate arousal in response to signals from the environment [2]. Awareness is based on an even more widely distributed network of connections between cortical and subcortical structures [3].

Consciousness can be diminished or abolished by dysfunction within the brainstem, impairment of both cerebral hemispheres, or insults that globally depress neuronal activity. Global insults include metabolic disturbances and disorders that deplete substrates for cerebral metabolism, alter neuronal cell homeostasis, or interfere with neuronal excitability. Unilateral cerebral lesions may cause coma if they compress or injure contralateral or brainstem structures.

DEFINITIONS — There is a spectrum of impaired consciousness between full arousal and complete unresponsiveness.

●Coma – Coma, a state of "unarousable unresponsiveness," is the most profound degree to which arousal and consciousness are impaired [1].

●Lethargy – Lethargy, obtundation, and stupor refer to states in which arousal is partially impaired. Patients in these states have some difficulty maintaining attention during an examination, tend to fall asleep when not stimulated, and respond poorly (if at all) to questions and commands. As these terms are imprecise, it is more useful to describe how a patient responds to stimulation.

●Delirium – Delirium is a disturbance of consciousness with reduced ability to focus, sustain, or shift attention. Patients with hyperactive delirium show both hyperactivity and diminished sleep. Confusion, excitement, hallucinations, and irritability are common. Patients with hypoactive delirium have little interaction with their environment and often appear somnolent. Delirium is caused by a subset of conditions that can lead to coma, including medical conditions, substance intoxications, and medication side effects (table 2). (See "Diagnosis of delirium and confusional states".)

Coma is a transient state. Comatose patients either recover, die, or evolve into a more permanent state of impaired consciousness:

●Persistent vegetative state – Persistent vegetative state (PVS), also referred to as "unresponsive wakefulness syndrome," describes patients who are completely unconscious but have spontaneous eye opening during cyclical periods of arousal. Such patients often have reflexive vocalizations (sounds but not words), facial expressions, and movements that can be misinterpreted by hopeful observers as reflecting awareness of their internal or external environment. Required features of PVS are [4]:

•No evidence of awareness of self or environment and no ability to interact with others.

•No evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli.

•No evidence of language comprehension or expression.

•Sleep-wake cycles manifested by the presence of intermittent periods of spontaneous eye opening.

•Sufficiently preserved hypothalamic and brainstem autonomic function to permit survival with medical and nursing care.

•Bowel and bladder incontinence.

•Some degree of preserved cranial nerve reflexes and spinal reflexes.

●Minimally conscious state – The minimally conscious state (MCS) describes patients with severe alteration in consciousness who nonetheless can be shown to have some degree of preserved awareness of the external world [5]. They can at least occasionally demonstrate purposeful movements or responses. These can include following simple commands, making gestural or verbal responses to questions, making intelligible verbalizations, smiling or crying in response to evocative sounds or images, reaching accurately toward the location of an object, or fixating on and pursuing visual stimuli [6]. Functional neuroimaging studies suggest that these patients have a different, less severe neuroanatomic substrate than do patients in PVS [7].

●Brain death or death by neurologic criteria – A diagnosis of death by neurologic criteria requires that a patient has suffered a catastrophic brain injury that results in a permanent loss of consciousness and of all brainstem reflexes. This diagnosis has a legal standing equivalent to death by cardiovascular criteria in most countries, with age-specific guidelines regarding diagnostic testing. (See "Diagnosis of brain death", section on 'Brain death in children'.)

ETIOLOGIES — A comprehensive list of potential etiologies of coma is presented in the table (table 3). Causes can be categorized as traumatic (including abusive head trauma) and nontraumatic. Common nontraumatic causes of coma include [2,3,8-11]:

●Infections (eg, meningitis, encephalitis, sepsis) (see "Bacterial meningitis in children older than one month: Clinical features and diagnosis" and "Acute viral encephalitis in children: Clinical manifestations and diagnosis" and "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis")

●Accidental and intentional poisonings and overdoses (see "Approach to the child with occult toxic exposure", section on 'Diagnosis of poisoning')

●Metabolic disorders (eg, hypoglycemia, diabetic ketoacidosis, inborn errors of metabolism) (see "Acute toxic-metabolic encephalopathy in children" and "Approach to hypoglycemia in infants and children" and "Diabetic ketoacidosis in children: Clinical features and diagnosis" and "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management" and "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management", section on 'Lethargy and coma')

●Seizures (see "Seizures and epilepsy in children: Classification, etiology, and clinical features")

●Drowning (see "Drowning (submersion injuries)")

●Intracranial hemorrhage (eg, due to vascular malformation) or mass lesion (eg, tumor) (see "Hemorrhagic stroke in children", section on 'Vascular malformations' and "Clinical manifestations and diagnosis of central nervous system tumors in children")

●Hypoxic-ischemic injury, which can result from any of the above mechanisms or from cardiopulmonary arrest (eg, arrhythmia, underlying congenital heart disease, foreign body aspiration, acute respiratory failure) (see "Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in children")

Traumatic and nontraumatic causes of coma have roughly equal annual incidences of approximately 30 per 100,000 children each [10]. With the exception of abusive head trauma, nontraumatic causes are more frequent in infancy and early childhood. The relative frequency of causes of nontraumatic coma varies according to the geographic location and demographic makeup of the population. In most series, infection is the leading cause, composing 30 to 60 percent of cases [8-11].

EVALUATION — Coma is a medical emergency whose evaluation requires a rapid, comprehensive, and systematic approach. Early identification of the underlying cause of coma can be crucial for patient management and prognosis. Although discussed separately in this topic, the assessment and management are performed jointly in practice (table 1).

History — The etiology may be apparent from the history, such as when coma results from the expected progression or complication of a known illness or injury [5]. Examples include a child who presents after a drowning injury or a child with diabetes presenting with hypoglycemic coma or with cerebral edema from diabetic ketoacidosis.

The history of symptoms leading up to coma may also provide clues. Coma of abrupt and unexplained onset suggests intracranial hemorrhage, seizure, trauma, or intoxication. A gradual deterioration of mental status suggests an infectious process, metabolic abnormality, or slowly expanding intracranial mass lesion. A history of preceding headache, double vision, or nausea suggests increased intracranial pressure (ICP). Inborn errors of metabolism may also present with slowly evolving coma or recurrent episodic coma [12]. A history from the caregiver that is vague or inconsistent with the examination may engender suspicion for nonaccidental trauma [13]. (See "Child abuse: Epidemiology, mechanisms, and types of abusive head trauma in infants and children".)

Toxic ingestions in young children are often unwitnessed, and parents and caregivers should be questioned regarding the possibility of available substances. (See "Approach to the child with occult toxic exposure", section on 'History'.)

General examination — Assessing vital signs and the ABCs (airway patency, breathing [ventilation and oxygenation], and circulation) are crucial for initial stabilization but may also provide clues about the underlying etiology:

●Temperature – Fever suggests infection but is also seen with inflammatory disorders, environmental or exertional heat stroke, neuroleptic malignant syndrome, status epilepticus, hyperthyroidism, and anticholinergic poisoning. When infection is suspected, possible complications such as intracranial seeding, septic shock, seizures, and exacerbation of an underlying metabolic disorder should also be considered.

Hypothermia can occur with infection in infants but is more often due to drug intoxication, environmental exposure, or hypothyroidism. Hypothermia itself blunts cognitive function and arousal, presumably by decreasing cerebral blood flow.

●Heart rate – Tachycardia can occur with fever, pain, hypovolemia, cardiomyopathy, tachyarrhythmia, and status epilepticus. Bradycardia occurs with hypoxemia and hypothermia, and with increased ICP as part of the Cushing triad (bradycardia, hypertension, irregular respirations). (See "Approach to the child with tachycardia" and "Bradycardia in children".)

●Respirations – Tachypnea can be seen with pain, hypoxia, metabolic acidosis, and pontine injury. Slow, irregular, or periodic respirations occur with metabolic alkalosis, diabetic ketoacidosis, sedative intoxication, and injury to extrapontine portions of the brainstem. (See 'Coma syndromes' below.)

●Blood pressure – Hypotension suggests hypovolemic, septic, or cardiogenic shock, intoxication, or adrenal insufficiency. Impaired consciousness may be an early indicator of poor end-organ perfusion in a patient with shock. (See "Initial evaluation of shock in children".)

Hypertension may be due to:

•Pain or agitation

•Certain toxidromes (eg, sympathomimetics, stimulants) (table 4)

•Increased ICP; hypertension associated with bradycardia and irregular respirations is referred to as the "Cushing triad" in this setting

●Skin – The skin appearance provides useful information (table 5):

•Mottling and delayed capillary refill suggest a shock state (see "Initial evaluation of shock in children")

•Bruising suggests traumatic injury (including abusive head trauma) (see "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children")

•Petechial and purpuric rashes (picture 1 and picture 2) may be suggestive of meningococcal infection (see "Clinical manifestations of meningococcal infection")

•Jaundice may suggest hepatic encephalopathy (see "Acute liver failure in children: Management, complications, and outcomes", section on 'Hepatic encephalopathy')

•A cherry-red appearance is suggestive of carbon monoxide poisoning (see "Carbon monoxide poisoning")

●Funduscopy – Papilledema suggests increased ICP of more than several hours duration [14]. Retinal hemorrhages are most commonly associated with abusive head trauma in infants. (See "Child abuse: Eye findings in children with abusive head trauma (AHT)" and "Child abuse: Epidemiology, mechanisms, and types of abusive head trauma in infants and children".)

●Meningismus – Meningeal irritation or inflammation suggesting meningitis is demonstrated by passive resistance to neck flexion (nuchal rigidity), involuntary knee flexion with forced hip flexion (Kernig sign), or involuntary hip and knee flexion with forced neck flexion (Brudzinski sign). These signs are often absent in infants and young children [15]. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Clinical findings'.)

Neurologic examination — The neurologic examination in this situation is necessarily brief and is directed at determining whether the pathology is structural or due to a systemic metabolic derangement (including drug toxicity or infection). The examiner assesses:

●Level of consciousness (see 'Glasgow Coma Scale' below)

●Pupil responsivity (see 'Pupils' below)

●Brainstem reflexes: pupillary responses to light, extraocular movements, and corneal reflexes (see 'Eye movements' below and 'Other brainstem reflexes' below)

●Motor responses (see 'Motor responses' below)

Important findings are abnormal reflexes that indicate dysfunction in specific regions of the brainstem and/or impending transtentorial herniation, or a consistent asymmetry between right- and left-sided responses. (See "Detailed neurologic assessment of infants and children", section on 'Neurologic examination'.)

Glasgow Coma Scale — The Glasgow Coma Scale (GCS) and its pediatric modification both grade coma severity according to three categories of responsiveness: eye opening, motor, and verbal responses (table 6) [3,16-18]. These have descriptive value for depth of coma but omit aspects of the neurologic examination important for diagnosis and management. An expanded scale, the Full Outline of UnResponsiveness (FOUR) score, was developed and validated for adults but is not widely used [19,20]. While not useful for diagnosis, the GCS has been linked to prognosis for a number of conditions.

Pupils — The pupillary examination is often abnormal in children who present with stupor and coma. Important findings include:

●Anisocoria suggests a brainstem insult or a supratentorial lesion that is causing compression of the oculomotor nerve or nucleus within the brainstem.

●Small, reactive pupils can be seen with metabolic disorders and certain intoxications (table 4). (See "Acute toxic-metabolic encephalopathy in children", section on 'Pupillary response'.)

●Bilaterally fixed pupils that are either midposition or dilated can be seen with severe afferent defects but are most often seen with brainstem insults that disrupt both the sympathetic and parasympathetic control of the eyes. Sympathomimetic and anticholinergic drugs also cause dilated pupils (table 4).

Eye movements — Persistent conjugate eye deviation to one side may suggest injury to the ipsilateral cerebral hemisphere or ongoing seizure activity arising from the contralateral hemisphere. Accompanying nystagmus also suggests seizure.

The presence of bilateral conjugate roving eye movements that appear full indicate an intact brainstem, and further reflex testing is not required. Otherwise, eye movements can be tested in comatose patients using reflex maneuvers:

●In the oculocephalic (doll's eye) reflex, the head is rotated to one side. With an intact brainstem, the eyes do not turn with the head but move in the opposite direction, thus appearing to maintain visual fixation (figure 1). When comatose patients have possible cervical spine injury, this reflex should not be tested. An abnormal response suggests a lesion within the brainstem or cranial nerves. Profound metabolic coma or drug intoxication can also impair this reflex.

●The oculovestibular (caloric) reflex test assesses the same pathways. Otoscopy should first confirm that the external ear canals are patent and the tympanic membranes are intact. With the head at 30 degrees elevation from horizontal, irrigation of the external ear canal with ice-cold water (10 to 30 mL) induces slow deviation of the eyes toward the irrigated side (figure 1). Five minutes should intervene before the other side is tested. Failure of the eyes to move conjugately as expected suggests a lesion of one or more cranial nerves or their nuclei within the brainstem. Conscious patients also have saccadic eye movements back toward midline that attempt to maintain visual fixation. When this occurs in an unresponsive patient, a psychogenic origin is suspected.

Other brainstem reflexes — The corneal reflex tests the sensory function of the trigeminal nerve and the motor function of the facial nerve. The patient's cornea is lightly touched with a fine wisp of cotton or a drop of sterile water; an intact reflex produces a bilateral (direct and consensual) eye blink. Bilaterally absent corneal reflexes can be seen with extensive structural lesions within the pons but also occur with metabolic disorders, intoxication, sedation, and paralysis.

The gag reflex requires intact function of the glossopharyngeal and vagal nerves (cranial nerves IX and X) and produces palate elevation with stimulation of each side of the posterior wall of the oropharynx. When a patient is intubated, endotracheal tube manipulation or suctioning to elicit a cough is often used as an alternative. However, cervical spinal cord reflexes can also mediate this response.

Motor responses — The motor examination in the comatose child should assess muscle tone, observe spontaneous and stimulus-elicited movements, and test deep tendon reflexes. Painful stimuli (eg, pressure applied to nail bed or supraorbital ridge) are often used to elicit motor responses in an unconscious child. Asymmetries may suggest involvement of the corticospinal tracts in the cerebral hemisphere or brainstem. The presence of spontaneous or purposeful limb movements (eg, withdrawing from or pushing away a painful stimulus) suggests a lighter depth of coma.

Abnormal flexion or extension of the arms and legs may occur spontaneously or in response to stimulation. Decerebrate posturing includes extension and internal rotation of the arms and legs; decorticate posturing produces adduction and flexion at the elbows, wrists, and fingers, with leg extension and rotation (figure 2). Classically, decerebrate posturing implies brainstem involvement from a compressive or destructive process, while decorticate posturing implies a more rostral and potentially less dire insult.

COMA SYNDROMES — Certain coma syndromes are important to recognize, as they may guide diagnostic evaluation and initial management.

Transtentorial herniation — Large and rapidly expanding mass lesions within the cranium induce dramatic increases in intracranial pressure (ICP) and may lead to transtentorial herniation, which can be fatal. Early recognition of the clinical signs of transtentorial herniation (decerebrate or decorticate posturing, periodic respirations, uni- or bilateral pupillary abnormalities, and/or hypertension with bradycardia) in a comatose patient is important, as these indicate the need for emergency measures to treat increased ICP. (See "Elevated intracranial pressure (ICP) in children: Management".)

Transtentorial herniation is manifest by progressive appearance of respiratory, motor, and pupillary signs in a comatose patient (figure 3). Relatively early signs of Cheyne-Stokes respiration, decorticate posturing, and small reactive pupils progress to ataxic, irregular respiration; decerebrate posturing; and pupils that are midposition and fixed. Generally, survival does not occur once herniation progresses beyond this point (ie, the lower pontine level) [14].

In uncal herniation, laterally directed compression leads to asymmetric signs, including the early appearance of third cranial nerve palsy with a unilateral, fixed, dilated pupil, often deviated downward and laterally. Hemiplegia due to compression of the corticospinal tract in the midbrain often follows soon after. The syndrome then follows the sequence of central herniation (figure 3).

Other signs of increased ICP, papilledema, and the Cushing triad (hypertension, bradycardia, and irregular respirations) may be observed in this setting.

Some metabolic derangements, intoxications, and seizure states may mimic the early signs of central herniation. Treating all children with these signs as if further herniation is imminent avoids missing an opportunity for preventing irreversible brainstem injury and death [14].

Metabolic encephalopathy — Metabolic coma usually occurs as a progression from delirium to stupor to coma, but more fulminant cases may present in coma.

A fluctuating examination is common; deficits can include abnormal brainstem reflexes, hypotonia, and even posturing in severe cases. Asymmetries in the examination and pupillary involvement are uncommon in metabolic coma. Multifocal myoclonus is very suggestive of a metabolic etiology. (See "Acute toxic-metabolic encephalopathy in children".)

Toxidromes — Some toxic ingestions are recognized by specific clinical syndromes or toxidromes (table 4). However, children often present with atypical clinical features [21]. (See "Approach to the child with occult toxic exposure".)

CONDITIONS MISTAKEN FOR COMA — Some conditions can be mistaken for coma because the child is unable to respond voluntarily, despite maintaining some degree of arousal and awareness. These include:

●Complete paralysis. Patients with acute lesions of the brainstem, particularly the pons, may be unable to move or speak while retaining awareness. Voluntary vertical eye movements and blinking may be retained. This condition is often called the "locked-in" state. Other causes of severe motor paralysis (eg, Guillain-Barré syndrome, botulism) may also cause a similar condition.

●Akinetic mutism or abulia may be produced by lesions in the portions of the frontal lobes responsible for initiating movement. The patient retains awareness and often tracks movements with the eyes but rarely initiates other movements or obeys commands. Tone, reflexes, and postural reflexes usually remain intact.

●Psychiatric unresponsiveness and catatonia are unusual in very young patients but may occur in adolescents. These patients often resist passive eye opening, move to avoid noxious stimuli, turn the eyes towards the floor regardless of which side they are lying on, or have episodes of nonepileptic seizure-like events. Catatonia is distinguished from coma by the preserved ability to maintain trunk and limb postures, even the ability to sit or stand.

A careful neurologic examination can usually distinguish these entities from coma, but occasionally a diagnostic test such as electroencephalography (EEG), brain magnetic resonance imaging (MRI), or electromyography/nerve conduction velocity (EMG/NCV) study is helpful in making the correct diagnosis. Locked-in states should be considered in any patient who presents with unexplained unresponsiveness.

DIAGNOSTIC STUDIES

Protocol for urgent evaluation and management — Although discussed separately in this topic, the assessment and management of children in coma are performed jointly in practice. These should proceed simultaneously and with urgency [22]. A protocol is outlined in the table (table 1).

Studies can be guided by history and physical examination findings, but most patients presenting with coma of unknown etiology require laboratory testing and a neuroimaging study as outlined below [23].

Laboratory testing — All patients presenting with altered consciousness should undergo a rapid bedside test for blood glucose and basic laboratory testing, including:

●Serum electrolytes, calcium, magnesium, glucose

●Arterial or venous blood gas

●Liver function tests, ammonia

●Complete blood count with differential

●Blood urea nitrogen, creatinine

●Urine and serum toxicology screening (see "Approach to the child with occult toxic exposure", section on 'Toxicology screens')

●Blood and urine cultures

Other tests of potential utility in specific situations include thyroid function tests, cortisol levels, carboxyhemoglobin levels for possible carbon monoxide poisoning, and coagulation studies.

Additional metabolic testing may be warranted if an inborn error of metabolism is suspected (eg, on the basis of severe metabolic derangements, hyperammonemia, or recurrent episodes of coma). The approach is discussed separately. (See "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management", section on 'Evaluation of specific critical presentations'.)

Neuroimaging — Computed tomography (CT) is the best initial neuroimaging test for evaluating a child in unexplained coma. CT quickly detects pathology in need of immediate surgical intervention, including hydrocephalus, herniation, and mass lesions due to infection, neoplasia, hemorrhage, and edema.

CT should be performed immediately when the examination suggests increased intracranial pressure (ICP; papilledema, bulging fontanelle in infants, or bradycardia with hypertension) or a transtentorial herniation syndrome (see 'Transtentorial herniation' above). When lumbar puncture (LP) is indicated, a CT is required in the comatose patient to rule out a mass lesion that might elevate the risk of transtentorial herniation being caused by the procedure.

MRI provides greater structural detail and is more sensitive for early evidence of encephalitis, infarction, diffuse axonal injury from head injury, petechial hemorrhages, cerebral venous thrombosis, and demyelination [24-27]. When initial testing (CT, laboratory studies) does not provide a definitive diagnosis, MRI can be helpful. Additional neuroimaging studies may be suggested by the history or initial CT or MRI, such as magnetic resonance, CT, or conventional angiography for cases of suspected vascular malformation, vasculitis, or venous thrombosis [28]. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

MRI may also offer information regarding prognosis in patients with anoxic or traumatic coma.

Repeat scanning, usually with CT, is often done emergently in patients with clinical deterioration to demonstrate or exclude worsening edema, hemorrhage, herniation, or hydrocephalus. However, patients without a surgically remediable lesion on initial, 24-, or 48-hour CT scans do not appear to benefit from continued routine imaging [29,30].

Lumbar puncture — Urgent evaluation of cerebrospinal fluid (CSF) is required when there is suspected infection of the central nervous system (CNS). In a patient with altered level of consciousness, neuroimaging to exclude an intracranial mass lesion is required prior to LP to avoid precipitating transtentorial herniation (table 1). Coagulation test results should also be obtained beforehand if coagulopathy is suspected. Opening pressure should be measured and recorded. (See "Lumbar puncture in children".)

CSF testing should include cell count and differential, glucose and protein, Gram stain and bacterial culture, and evaluation for viral infection and other causes of encephalitis, as clinically indicated. A serum glucose should be drawn as near in time as possible to the CSF to ensure that the CSF:serum glucose ratio can be calculated accurately. Additional microbiologic tests may be warranted in immunocompromised patients. Other tests that can be performed if the etiology remains uncertain include antibodies against neuronal antigens (eg, N-methyl-D-aspartate [NMDA] receptors) if autoimmune encephalitis is suspected and CSF lactate and pyruvate levels if a mitochondrial disease is suspected.

Empiric antimicrobial treatment is recommended when the diagnosis of bacterial meningitis or herpes encephalitis is strongly suspected, as early treatment improves prognosis of these conditions. Antimicrobial therapy should not be delayed by the need for cranial imaging or an LP. Antibiotics may reduce the diagnostic sensitivity of CSF cultures but should not affect other CSF tests (white blood cell [WBC], Gram stain, polymerase chain reaction [PCR]). Blood cultures should be obtained, prior to antibiotic intervention if possible, as they have at least a 50 percent yield in bacterial meningitis (table 7) [31]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy' and "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Evaluation'.)

Electroencephalogram — EEG should be performed in children with coma of unknown etiology (table 1). It is often the only means of recognizing nonconvulsive status epilepticus (NCSE), especially in patients who are paralyzed.

Periodic epileptiform discharges may occur in NCSE but also in underlying brain injury without seizures. Periodic lateralized epileptiform discharges (waveform 1) suggest herpes encephalitis or infarction. Multifocal or generalized periodic discharges (waveform 2) can also be seen with metabolic and infectious etiologies and are characteristic of subacute sclerosing panencephalitis.

Nonepileptiform features of the EEG, such as slowing or asymmetry, are largely nonspecific findings but can sometimes provide diagnostic or prognostic information. Continuous EEG can be used to assess and titrate the depth of sedation in patients placed under anesthesia for control of status epilepticus or increased ICP [32-36]. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Refractory intracranial hypertension'.)

MANAGEMENT — Early treatment of coma is generally supportive until a definitive diagnosis is made. An important goal of early treatment is to limit brain injury.

Although discussed separately in this topic, the assessment and management of children in coma are performed jointly in practice (table 1). The primacy of ABCs (airway, breathing, circulation) applies to coma as to other medical emergencies.

Initial stabilization

●Airway – Establishing a secure airway and providing adequate ventilation may be lifesaving and also may limit neurologic injury. Establishing a secure airway in a patient with coma may be attained by repositioning the child to open the airway but often requires intubation to ensure adequate ventilation and to prevent aspiration of secretions or gastric contents. (See "Technique of emergency endotracheal intubation in children".)

Patients with Glasgow Coma Scale (GCS) score ≤8 (table 6) are usually unable to adequately protect their airway and should be intubated [37]. If trauma is suspected, the cervical spine should be stabilized with a collar while securing the airway. Approaches to minimize the impact of intubation on potentially elevated intracranial pressure (ICP) should be considered. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis".)

●Breathing – Oxygen saturation should be continuously monitored and supplemental oxygen provided (see "Continuous oxygen delivery systems for the acute care of infants, children, and adults"). Adequacy of ventilation should be assessed by examination, end-tidal carbon dioxide monitoring, and/or blood gases.

For most patients, the goal of assisted ventilation is to maintain normal carbon dioxide levels (ie, P_aCO₂ 35 to 40 mmHg); hypo- and hyperventilation should be avoided since both can contribute to secondary brain injury. Hyperventilation is reserved only for patients with acute or impending herniation. In this setting, it is provided as a temporary measure while awaiting more definitive intervention. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Therapeutic hyperventilation'.)

●Circulation – Hypotension can contribute to secondary brain injury and should be treated aggressively [38-40]. Effective circulation, supported by intravenous (IV) isotonic fluid administration (normal saline or lactated Ringer) and vasoactive medications if necessary, is essential to adequate cerebral perfusion. (See "Shock in children in resource-abundant settings: Initial management", section on 'Fluid resuscitation' and "Shock in children in resource-abundant settings: Initial management", section on 'Vasoactive agents'.)

For patients with hypertensive encephalopathy, the blood pressure should be lowered slowly to avoid superimposing an ischemic insult. Short-acting IV medications are preferred to longer-acting agents for closer control of blood pressure. (See "Approach to hypertensive emergencies and urgencies in children", section on 'Treat hypertensive emergency or urgency'.)

Hypertensive encephalopathy has an excellent prognosis for recovery if ischemia can be avoided [41]. (See "Acute toxic-metabolic encephalopathy in children", section on 'Hypertensive encephalopathy and reversible posterior leukoencephalopathy'.)

Emergency management of causes and complications

●Glucose – Fingerstick blood sugar and a serum glucose should be checked immediately in the evaluation of a comatose child. Hypoglycemia may be a cause or complication of coma. In either case, hypoglycemia should be treated immediately with 2.5 mL/kg of 10 percent dextrose solution. Ongoing monitoring and treatment may be needed. (See "Approach to hypoglycemia in infants and children".)

●Intracranial pressure – When increased ICP is suspected based on CT findings, papilledema, split sutures, or a herniation syndrome, emergent treatment is recommended. Increased ICP is assumed when there is coma after head injury.

Early interventions to reduce ICP include treating fever, elevating the head of the bed to 30 degrees above horizontal, and administering hyperosmolar therapy (eg, mannitol or hypertonic saline). Neurosurgery should be consulted. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Ongoing Management' and "Elevated intracranial pressure (ICP) in children: Management", section on 'Treatment of elevated ICP'.)

●Seizures – Ongoing seizures (status epilepticus) are treated as an emergency; typically, lorazepam 0.1 mg/kg IV up to a maximum of 4 mg is administered as the initial treatment. (See "Management of convulsive status epilepticus in children", section on 'Emergency antiseizure treatment'.)

If seizures have occurred but are not ongoing, a loading dose of an antiseizure medication (eg, fosphenytoin, 20 mg/kg phenytoin equivalent IV or levetiracetam 60 mg/kg IV) should be administered to reduce the risk of recurrence. (See "Seizures and epilepsy in children: Initial treatment and monitoring".)

Recurrent seizures or status epilepticus may increase ICP and may be associated with secondary brain injury and worse neurologic outcome. Prolonged seizures have been associated with adverse outcomes in meningitis, encephalitis, and other central nervous system (CNS) infections [42-46]. (See "Management of convulsive status epilepticus in children".)

Nonconvulsive status epilepticus (NCSE) should be considered as a diagnosis even when there are no obvious seizure-like movements. Nonconvulsive seizures can cause coma and also complicate other etiologies of coma, including infection and metabolic disease. If nonconvulsive seizures are suspected and an EEG is not available, a therapeutic trial of lorazepam (ie, 0.1 mg/kg IV, up to a maximum 4 mg IV) is reasonable. (See "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis".)

●Infection – Empiric antibiotic and antiviral therapy is recommended if bacterial meningitis (eg, ceftriaxone 100 mg/kg per day in one or two divided doses, maximum dose 4 g per day, plus vancomycin 60 mg/kg per day in four divided doses) or viral encephalitis (acyclovir 30 to 60 mg/kg per day in three divided doses) are among the suspected entities [47,48]. Blood cultures should be obtained, prior to starting antibiotics if possible. Since lumbar puncture (LP) is generally deferred until neuroimaging is obtained, initiation of antimicrobials should not be delayed for LP. Antimicrobial therapy should be continued until infectious conditions have been excluded (table 7). (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy' and "Viral meningitis in children: Clinical features and diagnosis", section on 'Clinical features' and "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Clinical features'.)

●Temperature control – Fever should be treated aggressively with antipyretics and/or cooling blankets. Hyperthermia (>38.5°C) can contribute to brain damage in cases of ischemia. Fever also increases cerebral metabolism and blood flow [49]. This can cause worsening intracranial hypertension in patients with elevated ICP and further contribute to secondary brain injury following acute traumatic or anoxic brain injury. Shivering can also contribute to elevated ICP and may require management with antipyretics, skin counter-warming, sedation, or paralysis [50].

While induced hypothermia has been suggested as a second-tier therapy for refractory increased ICP in children with traumatic brain injury (TBI), it is currently not recommended for the treatment of severe TBI in children [37]. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Temperature control'.)

The use of targeted temperature management (ie, active control of temperature in a predefined range) for children after resuscitation after an out-of-hospital cardiac arrest is discussed separately. (See "Initial post-cardiac arrest care in children", section on 'Active temperature control'.)

●Acid-base and electrolyte imbalance – Electrolyte imbalance and acidosis may cause or be a complication of coma and may increase the risk of neurologic injury. Electrolyte abnormalities and acidosis should generally be corrected and monitored serially. (See "Acute toxic-metabolic encephalopathy in children", section on 'Electrolyte derangements' and "Approach to the child with metabolic acidosis".)

An exception to this is mild to moderate hypernatremia. Intervention is generally not necessary to correct mild to moderate hypernatremia in the management of children with severe traumatic or hypoxic-ischemic brain injury. Hypernatremia commonly occurs in patients treated with hypertonic saline for management of intracranial hypertension; moderate hypernatremia is a goal of therapy in this setting. (See "Elevated intracranial pressure (ICP) in children: Management", section on 'Hypertonic saline'.)

By contrast, hyponatremia can exacerbate cerebral edema and should be corrected while a search for the cause is underway. (See "Hyponatremia in children: Etiology and clinical manifestations".)

●Antidotes – Antidote use is recommended only in the setting of known or strongly suspected drug overdose [51]. Naloxone (neonates: 0.01 mg/kg IV, intramuscular [IM], or subcutaneous [SUBQ], repeated every two to three minutes; children: 0.01 mg/kg IV, IM, or SUBQ and then 0.1 mg/kg IV, IM, or SUBQ, up to a dose of 2 mg, if desired response is not obtained) is a relatively safe and effective treatment and should be considered when the history suggests possible opiate ingestion.

While flumazenil is an effective antidote for benzodiazepine overdose, such overdoses alone are rarely life-threatening and may be managed with supportive airway measures. However, if comprehensive management of the pediatric airway is not available, then reversal should be considered. Flumazenil will also render benzodiazepines ineffective in the event of a seizure, another reason to limit its use.

The management of toxic ingestions is discussed separately. (See "Approach to the child with occult toxic exposure" and "Opioid intoxication in children and adolescents".)

●Agitation – Sedative agents should be administered only when the benefits of relieving agitation outweigh the need for close neurologic monitoring by examination. Agitation may increase ICP, interfere with respiratory support, and increase the risk of injury. However, oversedation may obscure the neurologic examination and can contribute to hypotension and hypoventilation. During the acute postinjury period (ie, first 24 to 48 hours), short-acting sedative agents may be preferred to allow intermittent lifting of sedation for serial assessments of neurologic function.

PROGNOSIS — Coma is a transient state, usually lasting no more than two to four weeks [52]. Children either recover, die, or evolve into a persistent vegetative state (PVS) or minimally conscious state (MCS). The features of PVS and MCS are described separately. (See 'Definitions' above.)

The prognosis in coma is largely related to the etiology. For children presenting with stupor or coma due to poisoning or overdose (accidental or intentional) not complicated by secondary anoxic brain injury, the prognosis is generally good. With appropriate supportive care, most children make a full recovery. (See "Prevention of poisoning in children", section on 'Fatalities'.)

By contrast, for children with acute hypoxic-ischemic injury (eg, following cardiac arrest or drowning), outcomes are generally poor. (See "Initial post-cardiac arrest care in children".)

The prognoses of specific etiologies of coma are discussed separately:

●Bacterial meningitis (see "Bacterial meningitis in children: Neurologic complications")

●Encephalitis (see "Acute viral encephalitis in children: Treatment and prevention", section on 'Prognosis')

●Drowning (see "Drowning (submersion injuries)", section on 'Outcome')

●Brain tumors (see "Overview of the management of central nervous system tumors in children", section on 'Prognosis')

●Intracranial hemorrhage (see "Hemorrhagic stroke in children", section on 'Prognosis')

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Coma (The Basics)")

SUMMARY AND RECOMMENDATIONS — Stupor and coma are alterations in arousal; these are neurologic emergencies.

●Causes of coma – Etiologies of coma are diverse (table 3). Causes can be categorized as traumatic (including abusive head trauma) and nontraumatic, which have roughly equal frequencies in children.

Common nontraumatic causes of coma in children include infections (eg, meningitis, encephalitis, sepsis), intoxications, metabolic derangements (eg, hypoglycemia, diabetic ketoacidosis, inborn errors of metabolism), seizures, drowning, intracranial hemorrhage (eg, due to vascular malformation) or mass lesion (eg, tumor), and hypoxic-ischemic injury (which can result from any of the other mechanisms or from cardiopulmonary arrest). (See 'Etiologies' above.)

●Initial evaluation – A complete history and physical examination can provide valuable clues as to the underlying etiology. (See 'History' above and 'General examination' above.)

The neurologic examination in coma patients includes assessment of arousal, motor examination, and cranial nerve reflexes. Important findings are abnormal reflexes that indicate dysfunction in specific regions of the brainstem, or a consistent asymmetry between right- and left-sided responses, which indicates structural brain pathology as a cause. (See 'Neurologic examination' above.)

●Coma syndromes – Important syndromes to recognize include:

•Increased intracranial pressure (ICP) – Impending herniation manifests with decerebrate or decorticate posturing, periodic respirations, uni- or bilateral pupillary abnormalities, and/or hypertension with bradycardia in a comatose patient. (See 'Transtentorial herniation' above.)

•Toxic metabolic encephalopathy – In this setting, coma typically progresses from a prior state of confusion and/or stupor. A fluctuating examination is common; findings can include asterixis or myoclonus, abnormal brainstem reflexes, hypotonia, and even posturing in severe cases. Strictly lateralized deficits are uncommon. Some intoxications produce recognizable syndromes with typical vital signs and pupillary abnormalities (table 4). (See 'Metabolic encephalopathy' above.)

●Further evaluation and management – Diagnostic studies and early therapeutic interventions should proceed promptly, even simultaneously. A protocol for urgent evaluation and management is recommended (table 1).