Barbiturate Levels

Barbiturates are sedatives/hypnotics used mainly for anesthesia and epilepsy treatment. They affect the gamma-aminobutyric acid (GABA) system and cause a CNS suppressive effect, which ranges from anxiolysis, sedation, and coma to fatal cardiovascular and respiratory arrest upon overdose. ^{[1, 2]} They are classified as short-acting, intermediate-acting, and long-acting. See Table 1 for classification and properties.

Table 1. Classification and Properties of Barbiturates (Open Table in a new window)

Minimally toxic levels of barbiturates (see Table 1) are considered toxic since even a slightly elevated level is sufficient to produce toxicity. When the barbiturate level is measured, the patient’s body weight, renal function, liver function, age, and the specific barbiturate used should all be considered, since all of these variables alter the clinical correlation.

For example, a phenobarbital level of 31 mg/L in an older patient with renal and/or liver dysfunction is more critical than a thialbarbital level of 10 mg/L in a younger healthy patient.

Container: Red-top tube

Collection method: Routine venipuncture

Specimen: Blood serum

Specimen volume: 1 mL (minimum, 0.4 mL)

Analysis method: Immunoassay and gas chromatography-mass spectrometry

Overview

Barbiturates work primarily on GABA-A receptors, which are the main neurosuppressant receptors in the brain cortex. Stimulation of GABA-A receptors results in increasing seizure threshold by decreasing postsynaptic excitation. However, this mechanism also produces the well-known side effects of barbiturates, such as drowsiness, sedation, and coma. Activation of the GABA system in the cerebellum causes ataxia.

The metabolic/excretory characteristics of barbiturates are as follows:

• Absorption: Fast absorption in the stomach when given orally

• Half-life: Varies by category

• Metabolism: CYP450 system and mainly by 2C9 substrate

• Excretion: 25%-50% of the long-acting barbiturates are excreted unchanged in urine (the remainder is excreted via hepatic oxidation); the vast majority of short-acting barbiturates are metabolized and excreted through the liver

Indications/Applications

Currently, barbiturates are used to induce anesthesia and to treat seizures (especially generalized seizures) and intracranial pressure in pediatric patients. ^[3]

Historically, barbiturates have been used to treat insomnia and anxiety, which is now treated instead with benzodiazepines because of their lower association with lethal overdoses.

Barbiturates were first used in 1903 as anticonvulsants, anxiolytics, sedatives, and anesthetics; currently, their clinical utility is limited to epilepsy and anesthesia because of various side effects and difficulty in monitoring. Barbiturate use may lead to tolerance, dependence, and addiction; in 1970, several barbiturates were designated as controlled substances in the United States.

Considerations

Potential adverse effects of barbiturates include the following:

• Neurologic: Confusion, hallucinations, coma

• Cardiopulmonary: Hypoventilation, apnea, syncope

• Hematologic (rare): Agranulocytosis, megaloblastic anemia

• Hepatic (rare): Liver injury

• Dermatologic (rare): Stevens-Johnson syndrome, erythroderma

Since barbiturates have a very narrow therapeutic index, patients can easily develop side effects and toxicity. Patients should be extremely careful when another medication is given along with barbiturates, such as opioids, benzodiazepines, or antidepressants, since these combinations could be fatal. In addition, over-the-counter medications that include antihistamines are also CNS depressants; when taken with barbiturates, the combination can lead to fatal respiratory failure.

A study by Adams et al indicated that in individuals who undergo anticonvulsant monotherapy with phenobarbital during pregnancy, offspring are more likely to display reduced verbal and full-scale IQ in comparison with unexposed children and those who had been exposed to monotherapy with phenytoin. ^[4]

Table 2. Chemical, Trade, and Street Names for Some Barbiturates (Open Table in a new window)