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Biomedical subjects

G K Gourlay

Publications and source records attributed to G K Gourlay.

At least 37 records · Page 2Linked to original sources
PubMed1987

A randomized prospective controlled study of the metabolism and hepatotoxicity of halothane in humans.

In a randomized prospective controlled study in humans, the metabolism and hepatic effects of a single administration of halothane were compared with enflurane and meperidine. Pre- and postoperative antipyrine pharmacokinetics, intraoperative indocyanine green clearance, liver histology, and postoperative liver function tests were determined in 24 patients undergoing abdominal surgery who were randomly allocated to receive either halothane (0.5%, group I), enflurane (0.8%, group II), or meperidine (group III) as a supplement to a common basal anesthetic regimen consisting of thiopental, nitrous oxide/oxygen/muscle relaxant. In addition, end-tidal concentrations of the volatile reductive metabolites of halothane, chlorodifluoroethylene (CDF), and chlorotrifluoroethane (CTF) were determined in group I patients and serum and urinary inorganic fluoride were determined in both group I and II patients. Indocyanine green clearance was measured before anesthesia (stage I), during basal anesthesia (stage II), in the presence of surgical stimuli (stage III), and after introduction of the selected anesthetic agent (stage IV). CDF and CTF were detectable within 20 min of the start of halothane anesthesia in every patient receiving halothane. Peak serum fluoride concentrations occurred at 2 and 24 hr in the enflurane and halothane groups, respectively, whereas urinary fluoride excretion was elevated postanesthesia in the enflurane group only. There was no difference between the pre- and postoperative disposition of antipyrine in group II or III, but after anesthesia, antipyrine clearance was significantly decreased (P less than 0.02) and plasma half-life increased (P less than 0.05) in group I patients (halothane). Concentrations of serum alanine aminotransferase (ALT) and bilirubin were significantly elevated (P less than 0.5) postoperatively in groups I and II but unchanged from preoperative values in group III patients. Three of the 24 liver biopsies taken at the end of stage IV showed several foci of acute liver cell necrosis; of these, two patients were from group I and one from group II. There were no significant differences in liver cell morphology (P greater than 0.5) in biopsies taken at the end of stage IV compared with biopsies at the end of stage III, from groups I and II. The results of this study show that reductive metabolism of halothane occurs routinely in patients undergoing halothane anesthesia under conditions of normoxia. This may be the cause of the changes in antipyrine clearance after halothane anesthesia.

Antipyrine↗
PubMed1987

Halothane hepatitis in an animal model: time course of hepatic damage.

The present study extends previous reports of hepatic damage 24 h after halothane anaesthesia in the phenobarbitone pretreated hypoxic rat model by fully characterizing the lesion during the time course of its onset and recovery. Phenobarbitone treated animals exposed to halothane (1% for 2 h in 14% inspired oxygen) were killed 1, 2, 4, 6, 12 and 24 h and 2, 3, 5, 10, 15 and 30 days after commencement of the anaesthetic period. Blood was collected 1 day before the administration of halothane and at the time of killing for determination of serum alanine aminotransferase (ALT), a biochemical index of hepatic damage. Liver tissue was obtained immediately at post-mortem for histological examination. Serum ALT was increased at the end of the anaesthetic period, i.e. 2 h, with peak levels occurring at 12-24 h and remaining elevated for 3 days after exposure. Minor changes in liver histology were evident at 2 h in 50% of the animals and by 6 h all animals had mild hepatic injury. The extent of the necrosis was maximal at 24 h and this was sustained until 3 days. By 5 days after exposure minimal evidence of liver damage was observed and animals killed at 30 days had morphologically normal livers. Elevation of serum ALT or changes in liver histology were not observed in other treatment groups. The early onset of damage at 2-6 h is in keeping with direct hepatotoxicity associated with the biotransformation of halothane.

Alanine Transaminase↗
PubMed1986

Epidural mass associated with lack of efficacy of epidural morphine and undetectable CSF morphine concentrations.

A case is presented in which epidurally administered morphine failed to provide the expected extent and duration of pain relief. The patient had severe back pain in the upper lumbar and low thoracic regions and epigastric pain which was presumed to be caused by widespread metastatic deposits in the vertebral column from a prostatic carcinoma. The lack of clinical effect of epidural morphine was shown to be related to the unexpected presence of an epidural mass which was located below the dermatomal region for the patient's pain. Myelography and a CT scan indicated that the mass effectively compressed the subarachnoid space, thereby preventing the rostral spread of morphine in the cerebrospinal fluid (CSF) following lumbar epidural administration, resulting in inadequate pain relief.

Aged↗
PubMed1986

A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control.

This study reports the results of a double-blind, parallel-group comparison of intravenous methadone with morphine for the control of postoperative pain. Twenty patients (ASA Status 1 or 2) undergoing a surgical procedure involving an upper abdominal incision were randomly allocated to the methadone (n = 10) or morphine (n = 10) treatment groups. The patients were administered a 20-mg intraoperative opioid dose and 5-mg intravenous increments of opioid from precoded syringes in response to pain in the recovery and surgical wards. There was no significant difference between the mean +/- SD amount of supplementary methadone (8 +/- 6.3 mg) and morphine (9 +/- 9 mg) required in the recovery ward to provide initial pain control. The time from initial pain control to the first supplementary dose in the surgical ward was significantly different (P less than 0.01) in the methadone group (20.7 +/- 20.2 h) when compared to the morphine group (6.2 +/- 3.0 h). Further, patients required significantly less (P less than 0.001) methadone (11.5 +/- 8.5 mg) than morphine (41 +/- 14.1 mg) in the surgical ward to provide adequate pain relief throughout the duration of the study (i.e., 60 h). There was a significant difference in visual analogue pain scores between the methoadone and morphine groups on postoperative days 1 and 2, suggesting the quality of pain relief was similar for both treatment groups. Blood opioid-concentration monitoring indicated that there was a relationship between blood opioid concentration and pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1985

A rapid method for the determination of blood morphine concentration suitable for use in studies involving acute and chronic pain.

This communication provides an improved sample preparation method for blood morphine concentration determination prior to high-performance liquid chromatography analysis with electrochemical detection. The lower limit of sensitivity is 1 ng/ml of whole blood, and the standard curve is linear to an upper limit of 500 ng/ml. The coefficient of variation of replicate determinations of morphine at concentrations of 10 and 400 ng/ml were 4.7 and 2.5%, respectively. This assay procedure is rapid and accurate and allows the large number of samples (usually 30-40 samples) generated by pharmacokinetic studies in acute and chronic pain to be conveniently analyzed in one day.

Acute Disease↗
PubMed1985

A technique for the insertion of an implantable portal system for the long-term epidural administration of opioids in the treatment of cancer pain.

The feasibility of using a subcutaneously implanted portal system attached to a conventional 16-gauge epidural catheter has been evaluated in 50 patients with sever pain associated with cancer. This technique allowed for the percutaneous epidural administration of morphine at 8-12-hourly intervals for pain control. The mean duration of implantation was 12 weeks and the longest period a portal remained in situ was 36 weeks. Five portals had to be removed for various reasons. The injection system has blocked on eight occasions due to catheter blockage (six times) and portal blockage (two occasions). These patients have continued to obtain excellent analgesia when either catheter or portal were replaced. In a cadaver, 300 injections were simulated using either 22-gauge Huber point needles or disposable needles (25 gauge) and the injectate examined by both light and scanning electron microscopy. Both needle types resulted in particulate contamination which was greater with the recommended Huber point needles.

Analgesia↗
PubMed1984

Analgesics.

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Analgesics↗
PubMed1984

Postoperative pain control with methadone: influence of supplementary methadone doses and blood concentration--response relationships.

The aim of the study was to establish whether there exists a relationship between blood methadone concentration and analgesic response and the intrasubject and intersubject variability in this relationship. Sixteen general surgical (upper abdominal) and orthopedic (spinal fusion) patients were administered methadone (20 mg, iv) as part of the general anesthetic and supplementary methadone doses (usually 5 mg, iv) in the recovery ward until postoperative pain was controlled effectively. The criteria established for the administration of supplementary methadone doses were the co-existence of 1) spontaneous reporting of significant pain by the patient; 2) an unstimulated respiratory rate of greater than 10 breaths/min, and 3) no significant depression of the level of consciousness. A median of two supplementary iv methadone doses (range 1-3) were administered to the patient by a titration method in the recovery ward to obtain effective pain control. This was achieved by a median dose of 10 mg (range 5-20 mg) in addition to the 20 mg intraoperative dose. Serial blood samples were collected for the estimation of blood methadone concentration following all doses. The methadone concentration in the blood sample collected immediately prior to a supplementary dose was termed the minimum effective concentration (MEC [methadone]). The mean (+/- SD) coefficient of variation in MEC (methadone) for the 16 patients was 21 +/- 10% (range: 7-38%), while the mean MEC for methadone was 57.9 +/- 15.2 ng/ml (range: 34.5-80.3 ng/ml) in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

The role of naloxone infusions in the treatment of overdoses of long half-life narcotic agonists: application to nor-methadone.

This report describes the use of a naloxone infusion at a rate of 300 micrograms/h to provide constant antagonism of the respiratory depressant effects of a near fatal nor-methadone dose in a 2 year old boy. The terminal half-life for nor-methadone was calculated to be 13.5 h. The results indicate that a single dose of a narcotic antagonist with a short half-life (e.g. naloxone) will probably be inadequate to provide long lasting reversal of the effects of overdoses of long half-life narcotic agonists, and that continuous infusion may be the preferable to repeated bolus doses.

Apnea↗
PubMed1981

A rapid gas-liquid chromatographic determination of antipyrine clearance in the rat.

The assay procedure described in this paper allows the calculation of pharmacokinetic data of antipyrine disposition to be obtained from a single animal with minimal disturbance in hematocrit. A sample volume (100 microliters) allows the repeated use of the same rat for studies of hepatic drug metabolism. The lower limit of sensitivity is 5 micrograms/ml, with a range of linearity extending to 100 micrograms/ml. This allows for various dosing regimens. The GLC assay is rapid and accurate as shown by comparison with previously published values for the half-life of antipyrine in rats.

Animals↗
PubMed1981

Genetic differences in reductive metabolism and hepatotoxicity of halothane in three rat strains.

The relationship between the reductive metabolism of halothane and hepatotoxicity was examined in three rat strains (Fischer 344, Sprague-Dawley, and black hooded Wistar) to determine if there were genetic differences in 1) the reductive metabolism of halothane under identical exposure conditions, and 2) the susceptibility to the hepatotoxic effects of halothane. Halothane hepatotoxic was produced in all rat strains by exposing phenobarbital-pretreated rats to 1 per cent halothane under mild hypoxia (14 per cent oxygen, inspired) for 2 h. Generally the levels of both 2-chloro-1,1,1-trifluoroethane (CTF) and 2-chloro-1,1-difluoroethylene (CDF), two volatile metabolites of halothane, increased from the onset of anesthetic exposure and reached a plateau after approximately 60 min. The exception to this trend were phenobarbital-pretreated Wistar rats (exposed to 1 per cent halothane with 14 per cent oxygen) where the levels of either CDF or CTF were high initially (10-min sample) and decreased in subsequent samples to reach a plateau after 80 min. The plateau levels of both CDF (approximately 6 ppm) and CTF (approximately 20 ppm) were not significantly different among the three rat strains exposed to halothane (1 per cent) and hypoxia with prior enzyme induction. There were, however, significant differences in both biochemical and pathological changes among the three strains exposed under the above identical conditions when the rats were killed 24 h after anesthetic exposure. For example, serum alanine aminotransferase (ALT) was increased fourfold in the Fischer strain but only doubled for the other two strains. Moreover, while all three strains had various amounts of hepatocyte damage in the vicinity of the central veins when the rats were exposed to halothane, hypoxia, and enzyme induction, only the Fischer strain showed hepatocyte damage under the exposure conditions of halothane (1 per cent) and normoxia (21 per cent oxygen, inspired) with prior enzyme induction. The results support the role of reductive metabolism of halothane in the etiology of halothane hepatotoxicity. Furthermore, they suggest that genetic variations in the susceptibility of the liver to the reactive intermediates or metabolites formed during reductive metabolism of halothane may be a significant factor in halothane hepatotoxicity.

Alanine Transaminase↗