thiamylal and Seizures

Thiamylal, a chiral thiobarbiturate, is marketed as the racemate. The pharmacokinetic behavior of thiamylal enantiomers was studied in patients undergoing thiamylal treatment. The percentage of R(+)-thiamylal unbound to serum protein was 1.5 times greater than that of S(-)-enantiomer (17.5 +/- 2.6% and 11.7 +/- 2.0% mean +/- SD, p < 0.001, n = 7). The pharmacokinetic parameters of enantiomers were estimated in 6 patients. S(-)-thiamylal serum concentration was higher than R(+)-enantiomer in all patients at all time points examined. Total clearance of R(+)-thiamylal (0.27 +/- 0.23 1/hr/kg) was 1.8 times greater (p < 0.05) than that of S(-)-thiamylal (0.15 +/- 0.13). The volume of distribution at steady state of R(+)-thiamylal (3.66 +/- 1.99 l/kg) was 1.4 times higher (p < 0.05) than that of S(-)-enantiomer (2.60 +/- 1.35). The differences in these parameters may be due mainly to enantioselective binding to serum protein.

Topics: Adult; Aged; Blood Proteins; Chromatography, High Pressure Liquid; Female; Humans; Hypnotics and Sedatives; Infant; Injections, Intravenous; Male; Middle Aged; Protein Binding; Seizures; Stereoisomerism; Thiamylal

A 47-year-old female was scheduled for ulnar osteotomy under general anesthesia combined with brachial plexus block. She had a history of symptomatic epilepsy due to subarachnoid hemorrhage. Immediately after giving 100 mg bolus of propofol to the patient, she developed generalized convulsion similar to a grand mal. The seizure was suppressed by the administration of thiamylal. After that no further convulsive attack occurred. Although it has been known that propofol has anticonvulsive properties, there have been several reported cases of seizure following the administration of propofol. Further studies are needed to clarify the mechanism of seizure induced by propofol in the patients with epilepsy.

Topics: Anesthesia, General; Anesthetics, Intravenous; Brachial Plexus; Epilepsy; Female; Humans; Middle Aged; Nerve Block; Osteotomy; Propofol; Seizures; Subarachnoid Hemorrhage; Thiamylal

Two groups of six beagle dogs received rapid intravenous (IV) injections of ropivacaine or bupivacaine on two occasions in a blinded random fashion. Initially, a dose sufficient to cause convulsions (CD) was given followed by twice the CD (2 x CD), which was administered 48 h later. The CD of bupivacaine (4.3 mg/kg) and ropivacaine (4.9 mg/kg) caused significant (P less than 0.05) increases in heart rate and mean arterial blood pressure. There was no difference between drug groups. Seizures were abolished by 10 mg/kg of intravenous thiamylal. Endotracheal intubation and controlled respiration with O2-enriched air with no other treatment resulted in rapid and complete recovery in all dogs. All dogs receiving 2 x CD of bupivacaine (8.6 mg/kg) or ropivacaine (9.8 mg/kg) were initially treated with thiamylal and mechanical ventilation. Two dogs in the bupivacaine group developed hypotension, respiratory arrest, ventricular tachycardia, and ventricular fibrillation, which were resistant to closed chest cardiac massage, treatment with epinephrine, bretylium, and atropine, and direct current cardioversion. The four remaining dogs in the infusion group were successfully resuscitated. All of the animals in the ropivacaine-treated group survived the administration of the 2 x CD dose. Mild hypotension developed in one dog and was treated with intravenous epinephrine (0.75 mg). This resulted in nodal tachycardia, which was abolished after treatment with bretylium. Another dog had two 1-s bursts of premature ventricular contractions requiring no treatment. The rapid treatment of convulsions and cardiovascular toxicity resulted in a decreased number of deaths in both groups when compared with dogs from a previously published study in which no therapy was instituted. Thus, early aggressive treatment of central nervous system and cardiovascular system toxicity is capable of reducing the incidence of mortality associated with the rapid intravenous administration of excessive doses of local anesthetics.

Topics: Amides; Anesthetics, Local; Animals; Blood Pressure; Bupivacaine; Dogs; Epinephrine; Heart Rate; Hypotension; Injections, Intravenous; Lactates; Male; Norepinephrine; Random Allocation; Respiration, Artificial; Ropivacaine; Seizures; Thiamylal

New anesthetics have been introduced during the last 25 years which are not without inherent disadvantages. They are expensive, and some produce nephrotoxicity and possibly hepatotoxicity. Although the use of procaine intravenously as an anesthetic has been discarded, probably because of a convulsive effect, it is believed this disadvantage can be controlled by concomitant use of other drugs. Hence procaine, preceded by thiamylal, was administered to dogs to test its anesthetic capability, reversibility, and effects on the cardiovascular and central nervous systems. Blood levels of procaine were measured and correlated with these physiologic responses. Convulsive doses were ten times those producing anesthesia. There were no detrimental effects which would preclude a reevaluation in humans. Intravenous procaine produces definite general anesthesia, and it has the additional advantages of being rapidly hydrolyzed and providing antiarrhythmic effects. It may prove useful in modern anesthesia.

Topics: Anesthesia, General; Anesthesia, Intravenous; Animals; Dogs; Hemodynamics; Preanesthetic Medication; Procaine; Seizures; Thiamylal

Topics: Amnesia; Amygdala; Animals; Avoidance Learning; Body Temperature; Cold Temperature; Electroencephalography; Hippocampus; Humans; Hypothermia; Immersion; Memory; Pentobarbital; Phenytoin; Rats; Seizures; Sodium Chloride; Solutions; Thiamylal

Topics: Animals; Azides; Cerebellar Ataxia; Cerebellar Cortex; Cerebral Decortication; Disease Models, Animal; Dose-Response Relationship, Drug; Flurothyl; Haplorhini; Macaca; Respiration, Artificial; Seizures; Succinylcholine; Thiamylal

Topics: Anesthesia, General; Animals; Blood Pressure; Cardiovascular System; Catalepsy; Cats; Central Nervous System; Columbidae; Cyclohexanes; Dogs; Drug Synergism; Guinea Pigs; Haplorhini; Heart; Heart Rate; Humans; Hypertension; Mice; Motor Activity; Norepinephrine; Pentylenetetrazole; Phencyclidine; Phenethylamines; Rabbits; Rats; Seizures; Species Specificity; Tachycardia; Thiamylal

Topics: Barbiturates; Convulsive Therapy; Electroconvulsive Therapy; Seizures; Thiamylal