Barbiturates

Observational studies

In a comparison of thiopental, buthalitone, hexobarbital, and thiamylal in anesthesia (15 181 administrations in all). Respiratory and circulatory complications with hexobarbital and buthalitone were of sufficient frequency and intensity as to make their continued use in anesthesia difficult to justify [ ]. Hexobarbital also caused an unacceptably high incidence of excitatory phenomena, with muscle movements and tremor, particularly in the absence of opiate premedication.

Cardiovascular

In 50 patients undergoing lumbar spine surgery who were given fentanyl 3 micrograms/kg and were randomized to thiamylal 5 mg/kg or propofol 1.5 mg/kg for induction, thiamylal prolonged the QT _c interval and propofol shortened it [ ].

In 15 patients buthalitone prolonged the QT _c interval from 397 to a maximum of 454 ms at 5 minutes after injection of 11 mg/kg; in 15 patients thiopental prolonged the QT _c interval from 389 to 442 ms at 30 seconds after an injection of 5.5 mg/kg [ ].

Respiratory

Pulmonary eosinophilia has been attributed to febarbamate [ ]. There was a peripheral eosinophilia, a rash, and bilateral pulmonary infiltrates; bronchoalveolar lavage showed an increased eosinophil count and transbronchial biopsy showed intra-alveolar and interstitial eosinophil infiltration. The reaction cleared on withdrawal and rechallenge resulted in a peripheral eosinophilia and a rash.

Nervous system

Intracarotid injection of sodium amobarbital has been used in exploring cerebral language dominance in a procedure known as the Wada test [ ]. It has also been used to lateralize abnormal foci in temporal lobe epilepsy [ ]. Secobarbital has also been used instead of amobarbital [ ].

Of 92 patients who were given intracarotid amobarbital, five developed severe changes in affect and behavior, ranging from prolonged coma to an extended confusional state [ ]. Severe behavioral disturbances were more likely to occur in those with left frontal structural lesions when amobarbital was injected into the right hemisphere and patients with structural lesions of the anterior regions of the right hemisphere had no evidence of similar behavioral complications.

Seizures have been described after intracarotid injection of barbiturates, including methohexital and amobarbital. A retrospective chart review of 760 intracarotid amobarbital and methohexital tests showed that 16 patients (2.1%) had seizures [ ]. In three the seizures occurred before the injection. Of the other 13, 4 of 538 patients (0.7%) followed injection of amobarbital and nine of 222 (4.1%) followed methohexital injection. The authors suggested that methohexital was more likely to cause seizures than amobarbital.

There is a small risk of carotid dissection after intracarotid amobarbital administration. A retrospective chart review of 435 consecutive procedures showed that three patients had had carotid dissections; their mean age (51 years) was higher than the average age of 432 patients without dissection (32 years) and all had face or neck pain [ ].

A patient with a right temporal tumor who was given intracarotid amobarbital developed transient global amnesia [ ].

Occasional deaths have been reported during intracarotid amobarbital testing [ ], including the case of a 38-year-old man who had a right middle cerebral artery stroke, not having been at risk by Centers for Medicare and Medicaid Services criteria or invasive procedures nor having risk factors for embolic stroke [ ].

In 56 patients who underwent intracarotid amobarbital infusion, there was reduced anesthetization in two and very rapid recovery in nine; 10 of the 11 were taking a medication with some carbonic anhydrase-inhibitory effects—topiramate (n = 7), zonisamide (n = 2), hydrochlorothiazide (n = 1), and furosemide (n = 1) [ ]. Of 40 who were not taking a carbonic anhydrase inhibitor only one recovered early and that patient had recently stopped taking topiramate. The authors suggested that failure of anesthetization during intracarotid amobarbital infusion is associated with a possible interaction of amobarbital and carbonic anhydrase. This has been confirmed in an archival review of 81 patients, of whom 69 had conclusive findings; all of the other 12 in whom anesthetization failed were taking carbonic anhydrase-inhibitors at the time of the procedure [ ]. The implication is that intracarotid amobarbital infusion should not be performed until at least 8 weeks after withdrawal of a carbonic anhydrase inhibitor [ ].

In 26 individuals who drove after taking butalbital, the presence of which in the blood was confirmed and quantified, in concentrations of 1.0–30 mg/l, neurological impairment included horizontal and vertical nystagmus, lack of convergence, poor motor coordination, and balance and speech problems, similar to the effects of alcohol [ ].

When 17 healthy adults took pentobarbital 100, six developed up-beat, gaze-evoked, vertical nystagmus 12 hours later, three had nystagmus 36 hours later, and none had it 60 hours later [ ]. Other barbiturates have occasionally been reported to cause different types of nystagmus [ ] and thiopental-induced nystagmus has been used to test brain function in patients with central dizziness [ ]. However, different types of vestibular nystagmus do not help in localizing pathological lesions [ ].

Hematologic

Barbiturates are occasionally associated with thrombocytopenia; most of the reports have involved proxibarbal [ ].

Liver

Atrium is a formulation containing phenobarbital, febarbamate, and difebarbamate, also known as tetrabamate, which has often been associated with liver damage [ ], although since the formulation is often used to treat alcohol withdrawal, confounding by indication must be possible.

In 11 cases of liver damage attributed to tetrabamate the duration of treatment was 33–206 days, and there was a diffuse rash in three cases [ ]. Histology showed a wide spectrum of lesions: massive hepatocellular necrosis (n = 1), centrilobular and non-confluent hepatocyte necrosis (n = 2), intracellular cholestasis (n = 3), and granulomatous hepatitis (n = 1). In seven patients, there was complete recovery 3 weeks to 3 months after drug withdrawal but two patients died from hepatic failure.

In a series of 327 cases of hepatotoxicity, seven (2%) were attributed to tetrabamate after treatment for 15–730 days. [ ]. In four cases the presenting symptom was tremor. Liver damage was mainly cytolytic without evidence of hypersensitivity. In all cases there was complete recovery by 60–120 days. The authors recommended that tetrabamate should not be used in the treatment of alcohol withdrawal.

Skin

Stevens–Johnson syndrome has been attributed to tetrabamate in a patient with HIV infection [ ].