DESCRIPTION
- Class of sedative–hypnotic agents
- Derivatives of barbituric acid
- Mechanism:
- Enhances activity of γ-aminobutyric acid (GABA)
- At high levels, directly opens GABA-A associated chloride channel
- Leads to inhibition of vascular smooth muscle tone
- May lead to direct myocardial depression
ETIOLOGY
Overdose of barbiturates:
- Intentional or nonintentional
DIAGNOSIS
SIGNS AND SYMPTOMS
- CNS:
- Lethargy
- Slurred speech
- Incoordination
- Ataxia
- Coma (can mimic brain death)
- Loss of reflexes
- Cardiovascular:
- Ophthalmologic:
- Miosis (generally associated with deep coma)
- Nystagmus
- Dysconjugate gaze
- Other:
- Respiratory depression
- Hypothermia
- Bullae or “barb blisters”
History
- Determine if there was an intentional overdose:
- Pill bottles at the scene
- History of depression or suicidal ideation
- Determine if there was a medication error:
- What other medications was the patient taking?
- Were there any recent changes in dose?
- Estimate how long the patient may have been unresponsive.
Physical-Exam
- CNS abnormalities:
- Respiratory depression
- Cardiovascular:
- Bradycardia and hypotension
- Ophthalmologic:
- Miosis
- Nystagmus
- Dysconjugate gaze
- Hypothermia
- Bullae or “barb blisters”
ESSENTIAL WORKUP
- Fingerstick glucose
- Oxygen saturation monitor
- Monitor BP
ALERT
Barbiturate poisoning can mimic brain death:
- Cannot pronounce a patient brain dead until barbiturate poisoning has been ruled out
DIAGNOSIS TESTS & NTERPRETATION
Lab
- Electrolytes, BUN/creatinine, glucose:
- Calculate anion gap
- Assess for renal failure
- Urinalysis:
- For myoglobin
- For crystalluria (Primidone)
- Creatine phosphokinase for evidence of rhabdomyolysis
- Urine toxicology screen
- Obtain serum phenobarbital level (if suspected)
- Acetaminophen and salicylate levels if suspected suicide attempt
- Thyroid function tests
Imaging
- CT scan of head for altered mental status
- CXR for evidence of aspiration
Diagnostic Procedures/Surgery
- Noncontrast head CT
- Lumbar puncture
DIFFERENTIAL DIAGNOSIS
- Sedative–hypnotic poisoning (including γ-hydroxybutyrate [GHB] and its precursors)
- Carbon monoxide poisoning
- CNS infections
- Space-occupying lesions of the head
- Hypoglycemia
- Uremia
- Electrolyte imbalance (i.e., hypermagnesemia)
- Postictal state following seizure
- Hypothyroidism
- Liver failure
- Psychiatric illness
TREATMENT
PRE HOSPITAL
- Moderate to severe poisonings require paramedic transport.
- Intubation is often necessary because of respiratory depression or loss of gag reflex.
- IV access and supplemental oxygen:
- IV fluid bolus for hypotension
INITIAL STABILIZATION/THERAPY
- ABCs:
- Administer supplemental oxygen.
- Severe poisonings usually require endotracheal intubation.
- 0.9% NS:
- Hypotensive patients require at least 1–2 L IV fluid resuscitation.
- Pressor support may be necessary for refractory hypotension.
- Activated charcoal effectively binds barbiturates and may decrease systemic absorption.
ED TREATMENT/PROCEDURES
- Administer 1 dose of activated charcoal:
- Utility greatest if given within 1 hr of ingestion
- Ensure patient is awake and alert (or airway protected) prior to administration.
- Consider “gut dialysis” with repeated dose activated charcoal (without sorbitol) given q2–4h (as long as bowel sounds are present).
- Rewarm patient if hypothermic (see “Hypothermia” chapter).
- Treat hypotension resistant to IV fluid bolus with vasopressors (dopamine, norepinephrine, epinephrine).
- Treat hyperkalemia (from muscle breakdown) with calcium, sodium bicarbonate, insulin and glucose, and/or potassium-binding agents.
- Repeat phenobarbital level in 2–4 hr to determine whether level is increasing.
- Consider hemodialysis if patient has
- decreased or no renal function
- prolonged coma
- serum phenobarbital level >100 mg/dL
- refractory hypotension
- There is no role for urinary alkalinization
MEDICATION
First Line
- Activated charcoal: 1 g/kg PO
- Dopamine: 5–10 μg/kg/min titrating to desired effect (to max. of 20 μg/kg/min)
- Norepinephrine: 2–4 μg/min titrating to desired effect (to max. of 10 μg/min)
Second Line
Epinephrine: 0.1 μg/kg/min titrating to desired effect (to max. of 1 μg/kg/min)
FOLLOW-UP
DISPOSITION
Admission Criteria
ICU admission for:
- Coma
- Respiratory depression
- Hypotension
- Hypothermia
- Rhabdomyolysis
Discharge Criteria
Asymptomatic after a minimum of 6 hr of observation with 2 consecutive subtoxic phenobarbital levels before discharge
Issues for Referral
- If intentional overdose, will require psychiatric evaluation
- For nonintentional overdose, referral for adjustment in medications
FOLLOW-UP RECOMMENDATIONS
For nonintentional overdose, may need referral for adjustment in medications or change of medications to agents with a greater therapeutic window.
PEARLS AND PITFALLS
- Hypothermia may be pronounced:
- Ensure accurate core temperature is measured.
- Check for rhabdomyolysis, since the patient may have been down for a while.
- Barbiturate poisoning can cause prolonged coma:
- Ensure medication effects have resolved prior to making diagnosis of brain death.
ADDITIONAL READING
- Lee DC, Ferguson KL. Sedative-hypnotic agents. In: Nelson LS, Lewin NA, Howland MA, et al., eds.
Goldfrank’s Toxicologic Emergencies
. 9th ed. New York, NY: McGraw-Hill; 2010.
- Pond SM, Olson KR, Osterloh JD, et al. Randomized study of the treatment of phenobarbital overdose with repeated doses of activated charcoal.
JAMA
. 1984;251:3104–3108.
- Roberts DM, Buckley NA. Enhanced elimination in acute barbiturate poisoning—a systematic review.
Clin Toxicol (Phila).
2011;49:2–12.
See Also (Topic, Algorithm, Electronic Media Element)
- Benzodiazepine, Poisoning
- Coma
- Hypothermia
- Rhabdomyolysis
CODES
ICD9
967.0 Poisoning by barbiturates
ICD10
- T42.3X1A Poisoning by barbiturates, accidental (unintentional), init
- T42.3X2A Poisoning by barbiturates, intentional self-harm, init
- T42.3X4A Poisoning by barbiturates, undetermined, initial encounter