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H Wark

Publications and source records attributed to H Wark.

8 recordsLinked to original sources

Halothane in children with chronic liver disease.

Exacerbation of pre-existing liver disease after halothane anaesthesia has been reported in adult patients. A prospective study was performed in 38 children with biopsy-proven liver disease to assess the effect of surgery and halothane anaesthesia on liver function. Plasma liver enzyme levels were measured immediately preoperatively and again four to eight days after surgery and halothane anaesthesia. Minor elevations of both AST and ALT occurred in four patients but this was not associated with a clinical deterioration in the patients' postoperative recovery. In the children studied pre-existing liver disease did not predispose to a deterioration of liver function following surgery and halothane anaesthesia.

Adolescent

Biliary excretion of the halothane metabolite trifluoroacetic acid in infants.

In humans the biliary excretion of trifluoroacetic acid, the major halothane metabolite, has not been studied. We investigated the biliary excretion of trifluoroacetic acid in two infants aged five months and two months following halothane anaesthesia for the operation of choledocholithotomy. Bile, urine and faeces were collected continuously for five days after operation and trifluoroacetic acid excretion measured. Estimates of halothane uptake, daily bile flow and the proportion of daily bile flow collected via the T-tube drainage catheter were subject to percentage errors possibly as large as 50%. Of the total trifluoroacetic acid produced from halothane metabolism, it was estimated that 17% in the five-month-old infant and 20% in the two-month infant was excreted in bile. In the five-month-old infant where approximately 80% of the bile produced entered the duodenum in the normal way, no faecal trifluoroacetic acid was detected suggesting an enterohepatic circulation for this metabolite.

Anesthesia, Inhalation

N-Trifluoroacetyl-ethanolamine: a proposed urinary metabolite of halothane: validation and measurement in children.

It has been postulated that trifluoroacetyl chloride, a halothane metabolite, can bind covalently with the phosphatidylethanolamine component of the hepatic cell membrane and cause cell necrosis. Breakdown of the necrotic hepatocyte would release N-trifluoroacetyl-ethanolamine (TFAE) into the serum with subsequent urinary excretion. An original High Performance Liquid Chromatography (HPLC) method for the measurement of TFAE is described. In six children 1% halothane was administered for one hour and the halothane uptake measured. Urinary excretion of TFAE was measured for up to eight days and found to be 0.09 +/- 0.07% or less of the absorbed halothane. In children TFAE is not a major urinary metabolite of halothane.

Anesthesia, Inhalation

A urinary cysteine-halothane metabolite: validation and measurement in children.

An attempt was made in children to identify a urinary halothane-cysteine conjugate which had been described previously in adult patients following administration of halothane. If this conjugate was found it would indicate that a reductive metabolite of halothane binds covalently with the sulphydryl-containing amino acid, cysteine, a reaction which could lead to hepatic injury. The potential halothane-cysteine conjugate, N-acetyl-S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine (acetyl BCFEC), was prepared and the identity of the compound established using hydrogen-1 and carbon-13 NMR spectroscopy and methane chemical ionization mass spectrometry. A measurement technique for acetyl BCFEC was developed using HPLC with u.v. detection at 200 nm. In six children after halothane anaesthesia, one child being studied twice, urine was collected for up to 1 week and analysed for acetyl BCFEC. Little or no acetyl BCFEC was detected in any of the 43 urine samples tested, indicating that in children it is not a significant urinary metabolite of halothane.

Acetylcysteine

Halothane metabolism in children.

Halothane (1% v/v inspired) was administered for 60 min to six children of mean age 74 months (range 14-119 months). Uptake of halothane was measured from the difference in the concentration in inspired and expired gas and varied from 176 to 310 mg kg-1, depending on minute ventilation. After administration of halothane ceased, its elimination in expired gas was measured in four patients until the conclusion of anaesthesia; 32-37% of the absorbed halothane was expired 90 min after halothane administration ceased. Urinary excretion of trifluoroacetic acid, fluoride and bromide was measured for up to 1 week. Of the absorbed halothane, 11.4% (range 6.3-18.2%) was excreted in urine as trifluoroacetic acid and 0.37% (range 0.10-0.64%) as inorganic fluoride. The urinary half-life of trifluoracetic acid was 41.8 h (range 10.4-59.1 h). The quantitative and qualitative metabolism of halothane via the reductive and oxidative pathways in children are comparable to values found in adults. No differences in the metabolism of halothane by children were found which would explain the different incidence of halothane-associated hepatitis compared with adults.

Anesthesia, Inhalation

Halothane hepatitis.

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Anesthesia, Inhalation