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Paraldehyde therapy in childhood status epilepticus.

Intravenous (IV) diazepam or phenobarbital is generally accepted as the initial treatment of choice for status epilepticus in children. The risk of severe respiratory depression with either drug is a major problem, particularly in emergency centers that do not have appropriate equipment or personnel for rapid endotracheal intubation of infants. While some pediatric centers are not reluctant to recommend paraldehyde for secondary therapy in status epilepticus, most texts and publications recommend it only as a last resort because of reported complications. We investigated the benefits and complications from varied dosing regimens in 16 trials. The results indicated no significant complications in patients who did not receive an initial IV bolus. Even though treatment with phenobarbital or diazepam and phenytoin sodium had failed, 37% had a good therapeutic response.

Adolescent↗

The analysis of blood serum for paraldehyde by ultrafiltration and gas chromatography with a wide-bore capillary column.

The techniques of membrane ultrafiltration and capillary column gas chromatography were examined for their applicability to the quantification of paraldehyde in blood serum. Serum samples of standards, controls, and patients were treated with an aqueous solution of internal standard and then deproteinized by passage through a disposable ultrafiltration device. The ultrafiltrates were chromatographed on a wide-bore glass capillary column mounted in a packed column gas chromatograph. The method was shown to have adequate sensitivity, specificity, precision, accuracy, and linearity for therapeutic drug monitoring and toxicological purposes.

Chromatography, Gas↗

Pervasive seizures caused by hypoxic-ischemic encephalopathy: treatment with intravenous paraldehyde.

Seizures are commonly associated with hypoxic-ischemic encephalopathy. Although the majority of cases are controlled with first- or second-line therapy, others develop pervasive seizures, requiring multiple anticonvulsants. To provide data on the incidence of seizures and response to anticonvulsant therapies, a cohort of 90 term infants with hypoxic-ischemic encephalopathy treated at our institution between January 1, 1995, and July 1, 1999, was reviewed. Of the 60 infants who developed seizures, 59 received phenobarbital initially; in 29 cases, the seizures resolved. The remaining 30 infants received phenytoin as a second-line anticonvulsant, and seizures stopped in 10 cases. The 20 infants with ongoing pervasive seizures were treated with intravenous paraldehyde.

Anticonvulsants↗

Ketamine-paraldehyde anesthesia for rabbits.

Combination of ketamine hydrochloride (50 mg/kg) and paraldehyde (0.5 ml/kg), both administered intramuscularly, was found to be safe and effective for induction and maintenance of anesthesia for prolonged major surgical procedures in rabbits. Time of induction of deep surgical anesthesia was 20 to 30 minutes. Surgical procedures (creation of intestinal loops for perfusion studies) lasting 3 to 4 hours were performed, with an additional dose of ketamine (25 mg/kg) occasionally being given after 2 hours. At the end of the experiments, rabbits were killed. Another group of rabbits was maintained in a deep surgical plane of anesthesia for 5 hours without any surgical operation being done. Rabbits were then allowed to recover and, on the next day, were again anesthetized and allowed to recover without the performance of surgical operation. Finally, after a day's hiatus, the same rabbits were used in intestinal perfusion experiments. The use of 2 complementary anesthetics, each with a wide margin of safety for respiratory centers, provided safe anesthesia. The ability to administer a relatively fixed dose obviated the need for inordinate expertise to anesthetize rabbits for long periods.

Anesthesia↗

Metabolism of paraldehyde to acetaldehyde by rat liver microsomes.

Paraldehyde (PAL) was shown to be metabolized to acetaldehyde (AcH) by rat liver microsomes in vitro only when the cofactors for the cytochrome P-450 system were present. Microsomes from phenobarbital treated rats significantly increased the amount of AcH produced from PAL. Attempts to inhibit this reaction by addition of SKF-525A to the incubation medium resulted in augmentation of the AcH generated, very likely due to the metabolic deethylation of SKF-525A itself to AcH. Rats pretreated with D-penicillamine and then given PAL excreted 2,5,5-trimethylthiazolidine-4-carboxylic acid (TTCA)-a condensation product of AcH and D-penicillamine-in the urine. These results strongly suggest that PAL is metabolized in vivo by the hepatic microsomal system giving rise to AcH as a metabolite.

Acetaldehyde↗

A review of two safety factors in the use of paraldehyde.

Clinical observations and laboratory tests suggest that, contrary to normal practice, paraldehyde can be used with certain plastic syringes and has been safely used when well over six months old. This may make its use as an anticonvulsant in primary care more widely acceptable.

Child↗