AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Barbiturates are a class of organic compounds that were developed in the late 19th century for the treatment of anxiety and insomnia. These agents were originally touted as safer alternatives to bromides, but soon after their introduction, their toxic effects and their low therapeutic index became clear, eventually leading to their replacement by the much safer benzodiazepines.

Barbiturates are used mainly as intravenous (IV) anesthetics, as anticonvulsants, and in the resuscitation of patients with cerebral injuries. Barbiturates are also used commonly in combination with other substances for the treatment of gastrointestinal illness and migraine. Their use as sedative-hypnotics is limited because of the availability of safer agents but may be encountered in the drug-using community, where barbiturates may be used to counteract the unpleasant effects of stimulants. Barbiturates traditionally have been classified into 4 categories according to their duration of action, as follows:

• Ultra–short-acting barbiturates (eg, thiopental, thiamylal, methohexital) are highly lipid soluble and penetrate the CNS within minutes of an IV injection. Their effects generally last less than 30 minutes; these agents are used mainly for the induction of anesthesia.
• Short-acting barbiturates (eg, secobarbital, pentobarbital) cross the blood-brain barrier and affect the CNS within 10-15 minutes of ingestion. Their effects generally last 3 hours. Traditionally, they have been prescribed as sedative-hypnotics, but their abuse potential precludes their use as first-line agents.
• Intermediate-acting barbiturates (eg, amobarbital, butalbital, butabarbital, aprobarbital) cross the blood-brain barrier and affect the CNS within 30-60 minutes of ingestion. Their effects generally last as long as 6 hours. These barbiturates traditionally were prescribed as sedative-hypnotics, but their abuse potential precludes their use as first-line agents. Butalbital is commonly used in combination with acetylsalicylic acid and acetaminophen for the treatment of migraine headaches.
• Long-acting barbiturates (eg, phenobarbital, mephobarbital) are much less lipid soluble, have virtually no acute mood-altering effects, and have the least potential for abuse. They are used mainly as anticonvulsants, and their effects last as long as 12 hours.

Pathophysiology

Barbiturates suppress the activity of all excitable tissue, including the CNS, the peripheral nervous system, and the cardiovascular system. They also depress gastrointestinal function and have a number of effects on hepatic function. Their effects on the respiratory system are mainly due to CNS inhibition.

Central nervous system effects

Although all excitable tissues are depressed, CNS depression is most important and is generally responsible for most of the observed effects of barbiturates. Virtually all levels of the neural axis, including the cerebral cortex, the cerebellum, the thalamus, the striated nucleus, and the spinal cord, are affected. Specifically, barbiturates facilitate the binding of gamma-aminobutyric acid (GABA) to its receptor in the postsynaptic membrane and inhibit the function of alpha-amino-3-hydroxy-5-methylisoxazole (AMPA) cationophores. Their effects on GABA result in prolongation of the duration of opening of GABA-gated chloride channels, leading to hyperpolarization of the membrane and suppression of neurotransmission.

At high concentrations, barbiturates may also stimulate the GABA receptor directly to open the chloride channels. Their effects on AMPA, a subunit of the excitatory glutamate receptor, result in the sequential reduction in conductance of sodium-gated channels and inhibition of the voltage-dependent potassium channels.

Additional mechanisms by which barbiturates cause CNS depression include enhancement of chloride conductance without GABA, inhibition of calcium-dependent release of neurotransmitters, and inhibition of calcium-dependent action potentials.

Clinically, CNS depression occurs in a graded fashion, progressing from sedation to hypnosis, anesthesia, coma, and death due to respiratory arrest. Respiratory depression also occurs in a graded, dose-dependent fashion, starting with mild inhibition of the neurogenic respiratory drive and progressing to loss of the hypoxic drive. The dose at which CNS depression occurs varies among individuals and depends on a number of factors, including the prior use of barbiturates, the concomitant use of other substances and drugs, and the presence of preexisting cardiovascular or hepatic disease, among others.

Peripheral nervous system effects

The effects of barbiturates on the peripheral nervous system include inhibition of nicotinic receptors of the autonomic ganglia, leading to hypotension and reduced cardiac function. At anesthetic doses, they also inhibit the nicotinic receptors of skeletal muscle, leading to impaired neuromuscular transmission.

Cardiovascular effects

Through their effects on the nicotinic receptors of autonomic ganglia, barbiturates may cause hypotension, which is generally mild, unless the patient has preexisting congestive heart failure, dehydration, and hypovolemia. Massive barbiturate overdose may result in shock, leading to renal failure and death. Other cardiovascular effects include decreased cardiac output, decreased cerebral blood flow, and direct impairment of myocardial contractility.

Hepatic effects

Long-term use of barbiturates induces the activity of the mixed-function oxidase-microsomal enzyme/cytochrome P-450 system, leading to a more rapid biotransformation of compounds using the same pathway for detoxification, which include the barbiturates themselves. This leads to reduced blood concentrations of the parent compounds and contributes to the development of tolerance. The experienced barbiturate user may require doses that might otherwise be toxic to achieve a specific therapeutic effect. Other enzymes induced by barbiturates include delta-aminolevulinic acid (ALA) synthetase and aldehyde dehydrogenase. Their effect on ALA synthetase leads to the accumulation of ALA, which can lead to exacerbations of acute intermittent porphyria and porphyria variegata.

Pharmacokinetics

Barbiturates are weak acids that are absorbed rapidly from the gastrointestinal tract and are distributed to all tissues and fluids.

Ultra–short-acting barbiturates have the highest lipid solubility. Once in the blood stream, they rapidly and freely diffuse into the brain, causing a rapid CNS depression followed by a fairly rapid redistribution out of the CNS and into all other tissues, leading to termination of their CNS effects. These barbiturates bind extensively to plasma proteins and are metabolized by the liver, where they are converted to water-soluble glucuronide products before excretion by the kidneys. Their onset of action is within minutes, and their duration of action is usually less than 30 minutes but may extend as long as 1 hour. They are commonly used in anesthesia as induction agents and for the rapid control of convulsive status epilepticus.

The short-acting and intermediate-acting barbiturates have an intermediate lipid solubility and protein binding and an intermediate duration of action. They are used as sedative-hypnotics and have the highest abuse potential of all barbiturates. They are generally well absorbed from the gastrointestinal tract and easily diffuse into the brain, causing CNS depression and sleep. Their onset of action varies from 10-60 minutes and may last as long as 3 hours (short-acting agents) and as long as 6 hours (intermediate-acting barbiturates). The presence of food in the stomach delays, but does not alter, their bioavailability.

Short-acting barbiturates are metabolized entirely by the liver into water-soluble glucuronide compounds, with only 3-6% remaining active before excretion by the kidneys. Before 1980, this group of barbiturates was responsible for a significant number of overdose fatalities. Similarly, more than 90% of intermediate-acting barbiturates undergo inactivation by the liver, with only 10-12% remaining active until excretion by the kidneys. In the case of aprobarbital, as much as 17.5% may be excreted unchanged.

Long-acting barbiturates have low lipid solubility, low plasma protein binding, low brain protein binding, a delayed onset of action, and a longer duration of action. They have virtually no abuse potential and are used mainly in the treatment of epilepsy. They penetrate the brain slowly and redistribute to the periphery slowly. Their effects usually last for 6-12 hours and are only partially inactivated by the liver. Most long-acting barbiturates have active metabolites that are excreted by the kidneys. Renal dysfunction results in prolonged effects and toxicity of these barbiturates.

Conditions that reduce the hepatic metabolism of barbiturates include old age, infancy, and pregnancy. The effect of hepatic disease on the metabolism of barbiturates varies. Drugs that potentiate the CNS depressant effects of barbiturates include other CNS depressants (eg, ethanol, benzodiazepines, antihistamines, tricyclic antidepressants, monoamine oxidase inhibitors). Methylphenidate and isoniazid may also potentiate the CNS depression.

Patients with impaired respiratory function, such as those with chronic obstructive pulmonary disease (COPD), those with cardiac and renal dysfunction, and those with myasthenia gravis and hypothyroidism, may be sensitive to the effects of barbiturates.

Frequency

United States

In the 1970s, barbiturates were commonly used in suicide attempts and were implicated in most lethal intentional overdoses in adults. As the use of barbiturates declined after the introduction of benzodiazepines, the incidence of deaths due to barbiturate poisoning also declined. The illicit use of short-acting barbiturates to antagonize the unpleasant effects of stimulants has recently increased in the drug community.

Mortality/Morbidity

Over the last several years, mortality rates from barbiturate poisoning declined markedly from 10% in the 1970s to 1% in the 1990s, largely because of improved supportive care. In 2004, 3149 barbiturate overdoses were reported to US poison control centers, with 11 deaths.¹ Most deaths (10 out of 11) were due to poisoning with long-acting agents.

Fatal poisonings have occurred with the ingestion of as little as 6 g of phenobarbital and 2-3 g of short-acting barbiturates. The presence of co-ingestants (eg, alcohol, tricyclic antidepressants) may increase the lethality of barbiturates.

The most common cause of death early in the course of barbiturate poisoning is respiratory failure. Cardiovascular collapse due to CNS depression may also contribute to death early in the course of barbiturate poisoning. Aspiration pneumonia, bronchopneumonia, pulmonary edema, renal failure, and cerebral edema are the most commonly cited fatal late complications of barbiturate poisoning.

Race

According to the Drug Abuse Warning Network (DAWN), whites are most likely to abuse barbiturates and are, therefore, at highest risk for barbiturate poisoning.

Sex

According to DAWN, males and females abuse barbiturates in equal numbers; therefore, they are poisoned with equal frequency. Pregnant women may be at higher risk of toxicity because pregnancy increases the protein binding of barbiturates, thereby increasing their half-life and increasing their toxicity. Barbiturates cross the placenta and are excreted in milk.

Age

According to DAWN, young adults aged 20-40 years are most likely to abuse barbiturates. Elderly patients and infants are at higher risk for barbiturate toxicity because they metabolize and eliminate barbiturates more slowly than young adults. On the other hand, children may eliminate phenobarbital twice as fast as young adults.

CLINICAL

Section 3 of 11  

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History

Patients with barbiturate toxicity or barbiturate poisoning present with coma accompanied by cardiorespiratory collapse and are unable to provide their history. Other substances are often used concomitantly. Every effort should be made to identify the ingested substance and the circumstances of ingestion. This may be accomplished by examining the patient's prior medical record and questioning prehospital personnel and family regarding the patient's psychiatric history, medical conditions, and the signs and symptoms immediately preceding presentation to the hospital. Additionally, patients receiving large doses of intravenous barbiturates for the treatment of status epilepticus and other neurologic conditions may be at risk for toxicity from the solvent used for injectable barbiturate solutions (propylene glycol).

The symptoms of short-acting barbiturate poisoning usually begin less than 1 hour after ingestion and peak 4-6 hours after ingestion. Symptoms of long-acting barbiturates usually begin within 2 hours after ingestion but may not peak until 12 hours after ingestion. In the absence of hypoxia, acute respiratory distress syndrome (ARDS), hypotension, and structural brain injury, CNS depression gradually improves over 2 days for short-acting barbiturates and over 4-7 days for long-acting agents.

Physical

• Temperature: Hypothermia with a temperature as low as 31°C often occurs and is due to depression of the thermoregulation center and reduced muscle activity. Exposure to a cold environment may worsen the extent of the hypothermia.
• Respiration: Barbiturates depress the medullary respiratory center. With moderate intoxications, the PaCO₂-dependent ventilatory drive is depressed, and, at high doses, the hypoxic drive is eliminated, resulting in bradypnea and apnea. In the presence of hypoxia and acidosis, respirations may become rapid and shallow, or they may follow a Cheyne-Stokes pattern. The pulmonary examination may reveal evidence of bronchopneumonia, atelectasis, or pulmonary edema.
• Cardiovascular system: Barbiturates depress the vasomotor centers of the medulla, resulting in arteriolar and venous dilatation and hypotension, progressing to shock. Barbiturates also depress the sympathetic ganglia, cardiac contractility, and smooth muscle and vascular tone, resulting in bradycardia, pulmonary edema, cardiovascular collapse, and shock. Tachycardia may be observed in patients with hypoxia and in patients with co-ingestions. The presence of hypotension indicates a significant ingestion. Hypotension due to significant ingestion is most pronounced in patients with congestive heart failure and in those with hypovolemia because barbiturates partially inhibit ganglionic transmission and suppress cardiovascular reflexes. Hypoxia may compound these effects and may result in shock, which is manifested by hypotension with a rapid, weak, and thready pulse; cold and sweaty skin; and renal failure.
• Central nervous system: In the absence of co-ingestions and structural brain disease, barbiturates depress the CNS in a predictable manner, and the patient's clinical status may, therefore, be monitored clinically. Mild toxicity manifests as disorders of mentation, slurred speech, loss of coordination, and ataxia. Severe intoxication manifests as stupor and additional neurologic dysfunction. In massive overdoses, the patient becomes deeply comatose, hypotonic, and areflexic. The brainstem reflexes, including the corneal and oculovestibular reflexes, may be obliterated, and the electroencephalogram (EEG) may exhibit periods of electrical silence.
• Eyes: The ocular examination reveals nystagmus and a dysconjugate gaze. The pupils usually appear normal but may be small and reactive to light. In the presence of co-ingestants and anoxia, however, the pupils may be dilated and paralyzed.
• Gastrointestinal system: Barbiturates reduce gastrointestinal muscle tone and peristaltic function, resulting in gastric dilatation with delayed gastric emptying and ileus with bowel distention. Bowel distention may become so severe as to cause bowel necrosis. Physical examination findings include a succussion splash, decreased bowel sounds, and abdominal distention.
• Renal system: Barbiturate overdose may result in urinary retention. Poisoning with short-acting barbiturates may result in high output of dilute urine, much like that of diabetes insipidus. Additionally, hemodynamic instability and shock may lead to acute tubular necrosis, which is manifested by azotemia, volume overload, hyperkalemia, and acidosis.
• Skin: Approximately 6% of patients with barbiturate poisoning and 50% of patients with lethal poisoning develop tense, clear, bullous skin lesions of unclear etiology. These lesions commonly occur on the hands, knees, and buttocks within 24 hours of ingestion and heal very slowly. The lesions are not specific to barbiturates and occur with other CNS depressant overdoses and with carbon monoxide poisoning.

Causes

The most common scenario for a massive barbiturate poisoning is an intentional overdose of barbiturate-based anticonvulsants or barbiturate-containing combination medications (eg, Fioricet, Fiorinal, Donnatal).

DIFFERENTIALS

Section 4 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

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• Follow-up
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Lab Studies

• Barbiturate levels
• • In general, the management of barbiturate poisoning depends on the clinical condition and not on quantitative barbiturate levels. Management may also be affected by the presence of comorbidities and co-ingestions.
  • Blood levels may be obtained to confirm the diagnosis, but they are not reliable in predicting the severity of the overdose because they do not reflect brain concentrations accurately. This is due to a number of different factors, including protein binding, plasma pH, and liver function.
  • In general, a level of 90 mg/L of a long-acting barbiturate and 35 mg/L of a short-acting barbiturate carry a higher morbidity for a nontolerant patient.
• Arterial blood gas: Analysis of arterial blood gases determines the presence of acidosis, hypoxia, hypercarbia, and carboxyhemoglobin. The development of severe metabolic acidosis during induction of barbiturate coma should prompt the consideration of propylene glycol toxicity in the differential diagnosis.
• • The analysis of electrolytes and glucose determines the presence of disorders of glucose, sodium, and calcium, which may cause coma.
  • Additionally, the calculation of the anion gap may provide some information about the presence of other sedative-hypnotics (eg, bromides), which cause a negative anion gap. In this case, the presence of a negative anion gap is due to a falsely elevated chloride level because the analyzer cannot distinguish between bromide and chloride.
• Renal function tests
• • Blood urea nitrogen and creatinine may be used in the differential diagnosis of coma and in monitoring renal complications of barbiturate poisoning. They may also be used to guide therapy for certain renally excreted barbiturates.
  • Urinalysis and urine pH may be useful in determining the presence of myoglobin, renal failure, and the monitoring of forced alkaline diuresis.
  • Creatinine phosphokinase and myoglobin are useful in diagnosing rhabdomyolysis, a common complication of prolonged coma.
• Liver function tests
• • Elevated plasma ammonia levels may suggest the presence of hepatic encephalopathy.
  • Liver enzymes, prothrombin, and activated partial thromboplastin time aid in the diagnosis of liver disease, which may have significant impact on the metabolism of barbiturates.
• CBC count may reveal an infectious etiology for coma or an infectious complication of barbiturate overdose.
• Toxicology
• • Acetaminophen is present in some combination barbiturates and is commonly co-ingested in suicide attempts.
  • Aspirin is present in some combination barbiturates and may be co-ingested in suicide attempts.
  • Alcohol is a common co-ingestant in overdoses and may deepen the coma in barbiturate poisoning.
  • A urine toxicology screen may help diagnose other conditions and co-ingestions.
• Pregnancy test: Pregnancy alters the protein binding of barbiturates, thereby affecting their duration of action and toxicity.

Imaging Studies

• Chest radiography: Radiographic evaluation of the chest in comatose patients may be invaluable in the diagnosis of bronchopneumonia, aspiration pneumonia, atelectasis, and ARDS.
• A CT scan of the brain is indicated in all comatose patients with suspected trauma, stroke, hemorrhage, or mass lesion in the brain.

Other Tests

• The electrocardiogram may help to reveal the cause of shock, as in the presence of abnormalities of cardiac rhythm or myocardial infarction.
• Electroencephalogram
• • In massive barbiturate poisoning, the EEG may be isoelectric and unresponsive to all stimuli, simulating brain death. These abnormalities may last as long as 24-28 hours, and, in the absence of hypoxia, cortical necrosis and head injury are completely reversible.
  • Because barbiturates and other sedative-hypnotics have predictable effects on the EEG, the pattern of EEG waves may be used to evaluate the depth of coma and the progress of patients in the intensive care unit. Seven EEG grades have been identified in barbiturate toxicity.
• The grading of barbiturate poisoning may be based on Matthew EEG findings or Reed classification of coma.
• • The Matthew EEG grades are as follows:
  • • Grade I - Alpha rhythm with beta waves and a few theta waves
    • Grade II - Predominant theta waves with some alpha, beta, and delta waves
    • Grade III - Predominant delta waves mixed with some theta waves
    • Grade IV - Delta waves with occasional isoelectric intervals
    • Grade V - Suppression alternating with burst activity of several seconds
    • Grade VI - Suppression with occasional burst activity of one half second
    • Grade VII - Isoelectric
  • The Reed coma classification is as follows:
  • • Grade 0 - Sleeping but arousable to spoken command
    • Grade I - Asleep but arousable by painful stimuli; vital signs and deep tendon reflexes (DTRs) normal
    • Grade II - Asleep and unresponsive to painful stimuli; vital signs and DTRs normal
    • Grade III - Asleep and unresponsive to painful stimuli; vital signs normal; DTRs absent
    • Grade IV - Asleep and unresponsive to painful stimuli, with cardiovascular and respiratory collapse

Procedures

• Endotracheal intubation is indicated to protect the airway and to ventilate and oxygenate the patient.
• Lumbar puncture is indicated to rule out meningitis.
• Orogastric intubation and lavage may be necessary in the case of massive oral overdose with ileus.
• Pulmonary artery catheter insertion may be necessary to determine the cause of shock.
• Hemodialysis or hemoperfusion may be considered in the setting of long-acting barbiturate overdose with pulmonary edema, renal failure, and cardiovascular instability.

Histologic Findings

The only abnormal histologic finding relates to the skin blisters associated with barbiturate poisoning. Skin blisters are due to subepidermal bullous formation, with necrosis of sweat glands and the epidermis.

TREATMENT

Section 6 of 11  

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Medical Care

The management of barbiturate poisoning cases is supportive. Airway protection, cardiovascular support, and the immediate identification and treatment of correctable metabolic and structural abnormalities have a great impact on patient survival. Once the patient is stabilized, gut decontamination and elimination enhancement are performed.

• Airway support
• • Patients with barbiturate poisoning exhibit severe CNS depression with loss of airway protective reflexes and a 40% risk of aspiration pneumonitis. Assessment and stabilization of the airway must be performed early in the course of poisoning, and mechanical ventilation with oxygenation must be provided immediately.
  • Positive pressure ventilation should be used with caution and only when necessary to maintain adequate oxygenation because barbiturates impair reflex cardiovascular adjustments to inflation of the lungs.
• Cardiovascular support
• • Hypotension, which is due to vasodilation and direct myocardial depressant effects, responds to crystalloid bolus infusions and rarely requires vasopressors.
  • When 2 L of crystalloid solution have been infused and the patient remains hypotensive, vasopressors (eg, dopamine, norepinephrine) may be initiated, and a search for other causes of shock must be conducted.
  • Insertion of a pulmonary artery catheter and hemodynamic measurements may guide fluid and vasopressor therapy.
• Metabolic support: The infusion of 25-50 g of dextrose, 2 mg of naloxone, and 100 mg of thiamine may be appropriate steps in the initial evaluation of these patients.
• Decontamination and elimination
• • Once the patient is stabilized, drug removal is performed. Removal may be accomplished with several different methods such as orogastric lavage, activated charcoal, forced alkaline diuresis, dialysis, and, possibly, exchange transfusion.
  • Gastric decontamination: The value of gastric lavage is not clear and has been questioned in a number of recent publications, especially in cases of delayed presentations. Orogastric intubation and lavage may be indicated for life-threatening overdoses that present soon after ingestion and should be performed only in patients with protected airways.
  • Gastrointestinal elimination may also be achieved with activated charcoal, and, for substances with extensive enterohepatic recirculation (eg, phenobarbital), gastrointestinal elimination may be enhanced with multiple doses of activated charcoal (MDAC). MDAC is capable of reducing the elimination half-life of phenobarbital from 148 hours to 19 hours. Furthermore, in a 3-arm study in human volunteers comparing MDAC alone to MDAC-forced alkaline diuresis and forced alkaline diuresis alone, MDAC appeared more effective than forced alkaline diuresis in clearing phenobarbital.² With MDAC, the elimination half-life of phenobarbital may be reduced from 148 to 19 hours, whereas alkaline diuresis reduces the half-life to only 47 hours.
• Renal elimination enhancement
• • Forced alkaline diuresis
  • • Because of its weak acidity and poor lipid solubility, the urinary elimination of phenobarbital (pKa of 7.2) may be enhanced with alkalinization of the urine, which increases the ionization of the drug and traps it in the urine to prevent it from flowing back through the tubular membranes.
    • Forced alkaline diuresis may be achieved with the addition of 2-3 ampules of sodium bicarbonate (44.6 mEq per ampule) to 1 L of dextrose 5% in water solution (D5W). The rate of infusion, started at 200 mL/h, is guided by the urinary pH level, which should be maintained between 7.5 and 8. Potassium replacement becomes of utmost importance in this setting because hypokalemia promotes bicarbonate ion retention and prevents bicarbonate excretion, thus interfering with alkalinization of the urine.
  • Extracorporeal drug removal: Conventional hemodialysis, hemoperfusion, or both significantly lower blood phenobarbital levels and are indicated for phenobarbital poisoning in the presence of renal failure with anuria (precluding the use of forced diuresis) and shock with ileus (precluding the use of multidose activated charcoal). This method of elimination enhancement has no role in poisonings with short-acting barbiturates. In one case report, continuous venovenous hemodiafiltration (CVVHDF), a mode of renal replacement therapy that is commonly used in critically ill patients with hemodynamic instability, was found to be efficacious in clearing phenobarbital.³ 
• Other measures: Plasma exchange transfusion was successful in removing phenobarbital in a 14-day-old neonate.
• Complications of barbiturate poisoning and complications of therapy: These must be monitored continuously. Hypothermia may be treated with passive rewarming and continuous temperature monitoring. Rarely, patients may require active rewarming maneuvers.

Consultations

• Toxicology consultation or consultation with the regional poison control center may help to elucidate the diagnosis and may offer recommendations regarding therapy.
• Nephrology consultation is indicated when hemodialysis or hemoperfusion is contemplated in the detoxification of the poison.
• Psychiatry consultation is indicated for patients with suicidal ingestions or ideations.

Diet

Patients with delayed gastric emptying and ileus should receive nothing by mouth (NPO) until the gastrointestinal tract recovers.

Activity

Patients with barbiturate toxicity have reduced judgment, reduced coordination, and are ataxic; therefore, these patients should be monitored closely when out of bed.

MEDICATION

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The goals of pharmacotherapy are to reduce absorption of the dose, to prevent complications, and to reduce morbidity

Drug Category: GI decontaminants

These agents are empirically used to minimize systemic absorption of the toxin. May only be of benefit if administered within 1-2 h of ingestion.

Drug Category: Alkalinizing agents

Sodium bicarbonate is the primary agent used clinically to enhance elimination. The goal is to alkalinize the urine to promote renal excretion and to decrease elimination half-life of the barbiturate.

Drug Category: Vasopressors

These agents may be used as adjuncts in the treatment of shock that is unresponsive to crystalloid infusions. A search for the cause of shock must always be conducted.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Psychiatric admission may be necessary for patients with suicidal ingestions.
• Patients with barbiturate dependence are at risk for an abstinence syndrome, which is characterized by hyperactivity and autonomic instability that may progress to delirium, convulsions, and cardiovascular collapse. Patients with barbiturate withdrawal require continued intensive therapy, which may require the reinstitution of barbiturate therapy and the use of benzodiazepines.

Deterrence/Prevention

Education regarding the dangers of barbiturate overdose, as well as the dangers of simultaneous ingestion of other CNS depressants, such as alcohol, may act as a deterrent to accidental barbiturate overdose.

Complications

• Complications of barbiturate overdose
• • Respiratory - ARDS, pneumonia, aspiration pneumonitis, atelectasis
  • Neurologic - Anoxic encephalopathy and cerebral edema
  • Metabolic and renal - Rhabdomyolysis and renal failure (may contribute to one sixth of delayed deaths due to barbiturate poisoning)
• Complications of induction of barbiturate coma 
• • Barbiturate toxicity as noted above
  • Propylene glycol toxicity (manifested by worsening mental status, hypotension, acidosis)
• Complications of therapy for barbiturate poisoning
• • Pulmonary and cerebral edema
  • Fluid overload
  • Hypernatremia
  • Hypokalemia
  • Hypomagnesemia
  • Hypocalcemia

Prognosis

With good supportive care, in-hospital mortality is less than 2%.

Patient Education

• Educate patients about the hazards of frequent barbiturate use and the use of co-intoxicants.
• For excellent patient education resources, visit eMedicine's Poisoning - First Aid and Emergency Center, Mental Health and Behavior Center, and Substance Abuse Center. Also, see eMedicine's patient education articles Barbiturate Abuse, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 11  

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• Medication
• Follow-up
• Miscellaneous
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Medical/Legal Pitfalls

• Failure to consider barbiturate poisoning in the differential of coma simulating brain death
• Failure to consider co-ingestions (eg, acetaminophen, aspirin) in the evaluation and management of any overdose
• Failure to consider other diagnoses (eg, hypoglycemia, carbon monoxide poisoning) in the evaluation and treatment of presumed barbiturate overdoses
• Failure to consider concomitant trauma
• Failure to evaluate efficacy and complications of therapy
• Premature declaration of brain death in a patient with a massive barbiturate overdose

Special Concerns

• Barbiturates freely cross the placental barrier, resulting in fetal and neonatal addiction and withdrawal. Acute barbiturate poisoning of the mother may lead to the same condition in the fetus and the neonate.
• Barbiturates also are excreted in milk, raising the possibility of neonatal exposure and addiction.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Barbiturate coma–related skin pressure points.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
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1. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2005;23(5):589-666. [Medline].
2. Frenia ML, Schauben JL, Wears RL, et al. Multiple-dose activated charcoal compared to urinary alkalinization for the enhancement of phenobarbital elimination. J Toxicol Clin Toxicol. 1996;34(2):169-75. [Medline].
3. Lal R, Faiz S, Garg RK, et al. Use of continuous venovenous hemodiafiltration in a case of severe phenobarbital poisoning. Am J Kidney Dis. Aug 2006;48(2):e13-5. [Medline].
4. Amitai Y, Degani Y. Treatment of phenobarbital poisoning with multiple dose activated charcoal in an infant. J Emerg Med. Jul-Aug 1990;8(4):449-50. [Medline].
5. Bertino JS Jr, Reed MD. Barbiturate and nonbarbiturate sedative hypnotic intoxication in children. Pediatr Clin North Am. Jun 1986;33(3):703-22. [Medline].
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Article Last Updated: Aug 22, 2008