Metabolic encephalopathies are characterized by a period of intoxication, toxic delirium, or agitation, after which the patient gradually becomes drowsy and finally comatose. Headache is not an initial symptom of metabolic encephalopathy except in meningitis, or poisoning caused by organophosphate compounds or carbon monoxide. Neurological examination typically fails to reveal focal hemispheric lesions (hemiparesis, hemisensory loss, aphasia) before loss of consciousness. Neurological findings are usually symmetric except in patients with hepatic encephalopathy and hypoglycemic coma, which may be accompanied by focal signs that lateralize or alternate sides. Asterixis may be present. The hallmark of metabolic encephalopathy is reactive pupils (a midbrain function) in the presence of impaired function of the lower brain stem (hypoventilation, loss of extraocular movements), an anatomically inconsistent set of abnormalities.
Unlike other organs, the brain relies almost entirely on glucose to supply its energy requirements. Abrupt hypoglycemia interferes rapidly with brain metabolism and produces symptoms quickly. The occurrence of hypoglycemia is most common in neonates followed by toddlers and infants, and rarely older children. Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of hypoglycemia in neonates, and insulin treatment for type 1 diabetes is the most common cause of hypoglycemia in infants and children (see Chapter 42).
Symptoms of hypoglycemia are likely to occur in neonates when blood sugar is less than 40-45 mg/dL, and in older children when blood sugar is less than 60-65 mg/dL. Signs and symptoms include tachycardia, sweating, blurred vision, cyanosis, apnea, poor feeding, and anxiety. Symptoms may warn the patient of impending hypoglycemia, but may be absent in patients with diabetic autonomic neuropathy or (more commonly) go unreported in preverbal children. Common neurological abnormalities are delirium, seizures, focal signs that alternate sides, and coma. Hypoglycemic coma may be tolerated for 60-90 minutes, but when flaccidity with hyporeflexia has been reached, glucose administration within 15 minutes is essential to avoid irreversible damage.
If possible, confirm hypoglycemia by analysis of drawn blood before treatment with bolus of dextrose solution. IV dose is dependent on weight/age/condition (see Table 19–2). Give an additional dose of dextrose solution as needed or begin dextrose infusion for patients who do not respond to initial treatment or who respond and relapse. Other therapies such as glucagon or octreotide typically have little role in routine cases of hypoglycemia but may be considered in specific cases such as overdose.
Awake patients should be fed and then observed for 1-2 hours after glucose supplementation has been discontinued to ensure that hypoglycemia does not recur before they are discharged from the hospital. Refractory or recurrent hypoglycemia may require hospitalization, especially if hypoglycemia recurs despite aggressive treatment or in the event of long-acting insulin or oral hypoglycemic agent overdose.
Drug overdose is one of the most common causes of coma in patients presenting to the emergency department. Drugs may be implicated, including alcohol, opiates, sedative-hypnotics, antiepileptics, and cyclic antidepressants. Management of drug overdose is discussed in Chapter 46.
Alcohol poisoning in children can arise from ingestion of ethanol, isopropyl alcohol, or methanol. Common household products containing alcohol (mouthwash) can be a cause of intoxication in children presenting to the emergency department. Alcohol intoxication produces a metabolic encephalopathy similar to that produced by sedative-hypnotic drugs, although nystagmus during wakefulness and early impairment of lateral eye movements are not as common. Peripheral vasodilation is a prominent manifestation and produces tachycardia, hypotension, and hypothermia. Symptoms include nausea, vomiting, confusion, seizures, cyanotic or pale skin, slow breathing, and unconsciousness.
Signs of intoxication occur when blood alcohol levels reach 50-75 mg/dL with absolute ethanol (95-99%) in young children, and coma commonly occurs when levels reach 125-200 mg/dL. Because alcohol has significant osmotic pressure (100 mg/dL = 22.4 mOsm), alcohol intoxication is a cause of hyperosmolality.
Patients should be observed until improvement has occurred with normal orientation and judgment, and satisfactory coordination. Hospitalize patients who have abnormalities that require hospitalization (metabolic abnormalities or other underlying conditions) or in whom the exposure suggests neglect or an unsafe disposition. Management of alcohol intoxication is discussed in Chapter 46.
Hypoventilation and pinpoint pupils are the cardinal features present in narcotic overdose, as well as absent extraocular movements in response to the doll’s eye maneuver. Pinpoint pupils are associated with disorders that must be ruled out, such as use of miotic eye drops, pontine hemorrhage, Argyll-Robertson pupils from syphilis (congenital or acquired), and organophosphate insecticide poisoning.
Narcotic intoxication is confirmed by rapid pupillary dilation and awakening after administration of a narcotic antagonist such as naloxone (see Table 19–1). Patients who have overdosed on a specific narcotic (propoxyphene) may not respond to initial dosing and may require twice the recommended amount. The duration of action of naloxone varies with the dose and route of administration and repeat doses or a continuous infusion may be necessary following intoxication with a long-acting narcotic (methadone).
Opioids such as methadone, hydrocodone, and fentanyl patches have proven fatal in children from accidental exposure. Clinical presentation is variable depending on the amount of opioid ingested and time of exposure, but commonly includes decreased respiration and mentation. Fentanyl patches in particular may deliver very high doses to young children who chew on them. Of the 26 reported cases of fentanyl toxicity since 1997, most children were younger than 2 years. There were 10 deaths and 12 hospitalizations.
Hospitalization is indicated for patients who do not recover completely in the emergency department or who have taken long-acting narcotics. Treatment of drug overdose and poisoning is discussed in Chapter 46.
Gamma-hydroxybutyrate is a CNS depressant and can induce coma. Known as the “date rape drug,” it is frequently used at parties although in younger children exposure may be more difficult to determine. Detection of the drug is difficult, because most is eliminated through the lungs. Treatment is primarily supportive and may involve endotracheal intubation. Some patients require hospitalization for prolonged supportive care.
DRUGS THAT CAUSE STATUS EPILEPTICUS
Ingestion of drugs that can cause status epilepticus leading to coma should be considered. Theophylline, tricyclic antidepressants (TCAs), amphetamines, cocaine, phenylpropanolamine, ephedra, and heroin in high doses can cause seizure. Tricyclic antidepressants are a class of drugs used to treat depression, as prophylaxis for migraine, and some chronic pain disorders. Their narrow therapeutic index increases the probability of overdose. Although infrequently used in the pediatric patients, unintentional exposure to a family member’s medication is possible. Most pediatric patients receive a therapeutic dose between 5-10 mg/kg/day. Adverse effects usually occur greater than 20 mg/kg/day with altered mental status and cardiovascular toxicity commonly appearing in presentation. Airway control and cardiac monitoring should be considered early in management. Seizures or arrhythmias associated with TCA ingestion may be refractory to commonly used agents and treatment with sodium bicarbonate or hypertonic saline indicated (Chapter 46).
Hyponatremia may present with delirium, seizures, vomiting, bradycardia, circulatory collapse, and respiratory depression, or coma. Hyponatremia may cause neurological symptoms when serum sodium levels are less than 120 mEq/L, and symptoms are common with levels less than 110 mEq/L. When the serum sodium level falls rapidly, symptoms occur at higher serum sodium levels (Chapter 17).
Hypertonic saline solution is a common treatment for hyponatremia in the setting of refractory seizures or coma. Conventional therapies such as fluid restriction, demeclocycline, lithium carbonate, or urea for hyponatremia can be toxic and take a number of days to reach maximal effect. Recently AVP-receptor antagonists (conivaptan, lixivaptan, and tolvaptan) are proving beneficial in raising serum sodium levels. Hospitalization is mandatory in symptomatic patients or in newly diagnosed hyponatremia with serum sodium levels less than 125 mEq/L.
HYPOTHERMIA & HYPERTHERMIA
Hypothermia and hyperthermia are associated with symmetric neurological dysfunction that may progress to coma. Comatose patients must have rectal temperature taken with an extended range thermometer if the standard thermometer fails to register.
Internal body temperature less than 26oC (78.8oF) uniformly causes coma; hypothermia with core temperature greater than 32oC (89.6oF) does not typically cause coma. Body temperatures of 26oC-32oC (78.8oF-89.6oF) are associated with varying degrees of decreased consciousness. Pupillary reaction will be sluggish below 32oC (89.6oF) and lost below 26.5oC (80oF). Internal body temperatures above 41oC-42oC (105.8oF-107.6oF) are associated with coma and may also rapidly cause permanent brain damage. Seizures are common, especially in children.
Hospitalization is mandatory for patients with altered mental status or other neurological deficits. Diagnostic and treatment measures for hypothermia and hyperthermia are discussed in Chapter 45.
Classic triad of fever, neck stiffness, and altered mental status is poorly sensitive for bacterial meningitis. Clinicians should have a low threshold for performing lumbar puncture to confirm suspected cases of meningitis. Patients with bacterial meningitis typically have a CSF pleocytosis, and a CSF glucose level less than 40 mg/dL or less than 60% of serum glucose levels, which are consistent with bacterial infection. Patients with viral or other infectious causes may have a pleocytosis but typically have normal CSF glucose levels. However, a patient with altered mental status, seizure, focal neurological deficit, or evidence of increased ICP should undergo neuroimaging prior to lumbar puncture to minimize risk of herniation. See Chapter 41 for additional information about meningitis.
Intiate antibiotic therapy immediately based on clinical findings, prior to obtaining imaging. Do not delay administration of antibiotics to obtain imaging or CSF studies. Current recommendations for neonates are ampicillin plus gentamycin or cefotaxime. Recommendations for infants are vancomycin and ampicillin plus ceftriaxone. Children 3 months and older should be administered cefotaxime or ceftriaxone, plus vancomycin. Dexamethasone given with antibiotics may be considered in older children (see Table 19–8). Hospitalization is indicated for all patients with meningitis who present in coma or in whom bacterial meningitis cannot be excluded. Acyclovir should be administered to patients for whom there is a clinical suspicion of herpes simplex virus encephalitis. Pediatric patients of the postneonatal age should receive a dosage of 10 mg/kg at 3 times per day, for 21 days. Neonatal administration has not been correlated with favorable outcomes compared with untreated patients (67% vs. 69%).
Table 19–8.Treatment for meningitis. |Favorite Table|Download (.pdf) Table 19–8. Treatment for meningitis.
|Antibiotic ||Neonate (< 1 mo) ||Infants (1-3 mo) ||Children > 3 mo |
|Ampicillin ||50-100 mg/kg every 6 h ||50-100 mg/kg every 6 h || |
|Gentamycin ||2.5 mg/kg every 8 h || || |
|Cefotaxime ||50 mg/kg every 6-8 h || ||75 mg/kg every 6-8 h, up to 12 g daily max |
|Vancomycin || ||15 mg/kg every 6 h ||15 mg/kg every 6 h, up to 1 g max per dose |
|Ceftriaxone || ||50 mg/kg every 12 h ||50 mg/kg every 12 h, up to 4 g daily max |
|Rifampicin || || ||10 mg/kg every 12 h, up to 600 mg daily max |
INBORN ERRORS OF METABOLISM THAT CAUSE COMA
Inborn errors of metabolism (IEM) is a broad category of metabolic disorders with some leading to altered mental status in children that are undiagnosed at birth. Neonates receive a heel-stick for laboratory testing to identify and potentially decrease the progression of the conditions, although many clinically significant disorders are not diagnosed at the time of birth. Notable IEMs leading to coma include maple syrup urine disorder, fatty acid oxidation disorders, urea cycle disorders, and nonketotic hyperglycinemia.
Children with IEMs can have symptoms consistent with other causes of coma (nausea, vomiting, feeding difficulties), which are challenging to identify in the differential diagnosis. Distinguishing features for IEMs (urine with a maple syrup smell) and blood analysis become vital in initiating early treatment. Adequate history should be taken to give the clinician possible causes of coma, particularly information relevant to IEM.
Immediate management of ABC should be achieved. Hypoglycemia is a common complicating presentation of several IEMs and may result in worse outcomes and thus should be avoided. In children with known disorders, parents may be knowledgeable regarding their child’s condition or may be able to provide the contact information for the specialist who follows their child. Admission for further management and consultation with metabolic disorders specialists is indicated.
Reye syndrome is a rare, but potentially life-threatening condition that causes cerebral and hepatic edema. The syndrome has been strongly linked with the use of salicylates following a viral illness (chickenpox, influenza virus, herpes simplex virus). Children with fatty oxidation disorders are at an increased risk of developing Reye syndrome.
Patients usually have cerebral edema and fatty deposits in the liver that cause degeneration. Symptoms are progressive and typically begin 3-5 days after viral infection. Children younger than 2 years initially present with diarrhea and tachypnea. Older children initially exhibit continuous vomiting and unusual sleepiness. As the syndrome progresses, patients can show irritability, confusion, decerebrate posturing, paralysis (arms and legs), staring, seizures and convulsions, decreased consciousness, and coma. Laboratory evaluations can reveal decreased glucose, and increased acidity and ammonia levels. Testing for Reye syndrome is nonspecific, but typically includes CT, lumbar puncture, and liver biopsy to help determine diagnosis.
Diuretics should be considered to decrease ICP. Administration of IV glucose and antiepileptic medications are indicated. Platelets, plasma, and vitamin K should be given as well as medications to prevent bleeding resulting from liver pathology as indicated.
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