Children with sedative hypnotic or anticonvulsant ingestions are relatively common emergency department presentations. For sedative hypnotics, the chief concern is respiratory insufficiency due to central nervous system (CNS) depression. While morbidity may be significant, the provision of meticulous respiratory supportive care results in minimal mortality. Specific interventions such as antidotes and extracorporeal removal are rarely indicated. Indeed, supportive care as the mainstay for poison treatment was first promoted for sedative hypnotic poisoning more than a half of a century ago as the “Scandinavian Method.”¹

Anticonvulsant poisoning has a greater morbidity and mortality because of cardiovascular toxicity. Extracorporeal removal techniques may be indicated for severe poisonings.

This chapter focuses upon benzodiazepines, phenobarbital, phenytoin, carbamazepine, and valproic acid.

Benzodiazepines are a large class of drugs with wide variation in potency and duration of action. They are used most commonly as anxiolytics, muscle relaxants, antiepileptic medications, and as treatment of withdrawal states. They have an extremely wide margin of safety, with respiratory failure being virtually unheard of in the absence of coingestants.²

PATHOPHYSIOLOGY

Benzodiazepines enhance the action of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS resulting in CNS depression after overdose.

CLINICAL PRESENTATION

CNS depression is the most common finding after overdose. Coma and respiratory depression are typically due to the combined effects of the benzodiazepine and a coingestant. Respiratory depression or arrest may occur following rapid IV infusion of short-acting benzodiazepines. These patients may manifest coma, respiratory depression, hypotension, hypothermia, and rhabdomyolysis.

LABORATORY STUDIES

Urine drug tests do not detect all benzodiazepines, including midazolam, so a negative screen does not rule out benzodiazepine ingestion.

TREATMENT

Supportive care with attention to the airway, breathing, and circulation is the mainstay of treatment. Overdose of a benzodiazepine as a single agent may cause a depressed level of consciousness but generally does not cause loss of airway reflexes. Even with large overdoses, hemodynamic instability is unlikely. However, when benzodiazepines are combined with other sedating agents, airway protection and hemodynamic support may be necessary.

Although benzodiazepines are adsorbed by activated charcoal, its use is not recommended because of the low morbidity of this poisoning. Flumazenil is a benzodiazepine receptor antagonist that can rapidly reverse the benzodiazepine effect, and is a potential antidote. However, its use is not recommended for the benzodiazepine-poisoned patient because of the risk of seizures and resedation.³

DISPOSITION

Patients with symptoms of altered mental status, respiratory depression, or hypotension should be admitted to the hospital. Those who are asymptomatic at 4 hours after ingestion can be discharged from the emergency department. Purposeful ingestions require a mental health evaluation.

Phenobarbital is a barbiturate drug used for the treatment of seizure disorders.

PATHOPHYSIOLOGY

Barbiturates cause depression of neuronal activity by increasing the duration of opening of GABA-mediated chlorine channels. In overdose, phenobarbital causes CNS depression due to enhanced GABA activity and hypotension secondary to direct myocardial depression.

CLINICAL PRESENTATION

With overdose, somnolence, confusion, nystagmus, slurred speech, and ataxia may occur. Severe effects include coma, hypotension, hypothermia, respiratory failure, and cardiovascular collapse. Pupils may be small or mid-position. Bullae on the skin may form secondary to prolonged immobilization from coma.

LABORATORY STUDIES

Measure the serum phenobarbital concentration. In nontolerant individuals, concentrations of greater than 60 to 80 mg/L are associated with coma and concentrations of greater than 150 to 200 mg/L are associated with hypotension. Obtain an ECG in patients with moderate-to-severe toxicity.

TREATMENT

Provide meticulous supportive care with attention to the airway, breathing, and circulation, including rewarming to correct hypothermia and vasopressors as needed. Clinical manifestations may be prolonged due to the long half-life of phenobarbital.

Consider activated charcoal in patients who have ingested a potentially toxic dose and have presented within 1 hour of ingestion.⁴ Urinary alkalinization can enhance the elimination of phenobarbital.⁵ Add 3 ampules of sodium bicarbonate to 1 L of D5W and run at 1.5 to 2 times maintenance fluid rates. Goal urine pH is 7.5 to 8. Follow urine pH, serum pH, and serum potassium, and add potassium chloride to IV bicarbonate if the serum potassium is low.