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Biomedical subjects

M J Cousins

Publications and source records attributed to M J Cousins.

At least 19 recordsLinked to original sources
PubMed1992

The pharmacological relief of pain--contemporary issues.

OBJECTIVE: To provide a general description of the pharmacological principles of pain management particularly the management of severe pain with opioid analgetic agents. DATA SOURCES: Literature updating previous reviews by the authors in this Journal and the Proceedings of the VIth World Congress on Pain, Adelaide, 1-6 April 1990. STUDY SELECTION: Studies were selected under the subheadings: opioid receptors; endogenous opioids; development of new agents; recognition of the need to improve analgesia; pharmacokinetics and pharmacodynamics of opioids; and novel drug delivery methods. DATA EXTRACTION: The extracted information was more descriptive than quantitative. DATA SYNTHESIS: The pharmacological relief of pain involves treatment of patients with drugs characterised by extremely large interpatient variability in pharmacokinetics and pharmacodynamics by way of an extremely complex interaction with endogenous control mechanisms. It is not surprising that management of pain in many patients is less than adequate. CONCLUSIONS: Although much vigorous interdisciplinary research is being undertaken to develop a scientific basis for understanding pain and analgesia, improvements in the clinical management of pain can only occur if practitioners recognise the need for individualised methods of pain relief and treat their patients accordingly.

Acute Disease↗
PubMed1991

Assessment of antinociceptive drug effects in the presence of impaired motor performance.

The hot-plate (HP) and tail-flick (TF) tests are widely used to assess analgesic activity of drugs. These tests do not directly measure the intensity of the noxious stimulus perceived by the animal, but only the animal's response to it, and so may be affected by non-analgesic drugs. Sedatives and muscle relaxants, for example, may impair the ability to respond and hence be wrongly considered to have analgesic activity. We examined response of rats in the HP (55 degrees C, cutoff time 25 sec) and TF (cutoff time 5 sec) tests following administration of pentobarbitone, diazepam or pancuronium. These drugs all impaired motor performance as assessed by reduction in mean rotarod performance times to 6-32% of predrug values. However, HP and TF latencies were not appreciably prolonged. We also found that pancuronium did not alter effects of morphine on HP or TF latencies, despite reduction in rotarod performance to 38% of predrug values. Our results support the validity of HP and TF tests as analgesic assays even in the presence of substantial impairment of motor performance.

Analgesics↗
PubMed1991

Hepatic fibrosis and cirrhosis after chronic administration of alcohol and "low-dose" carbon tetrachloride vapor in the rat.

Rats were exposed to carbon tetrachloride vapor, 5 days/wk, 6 hr/day, for periods of 5 or 10 wk at a concentration that by itself caused only fatty change with minimal liver cell necrosis and no fibrosis. The same carbon tetrachloride exposure when given in association with chronic alcohol feeding resulted in extensive hepatic fibrosis at 5 wk and established micronodular cirrhosis at 10 wk. The periodicity of the exposure profile was chosen to simulate that of human exposure to environmental toxins, albeit at a higher dose than would be permitted in the workplace. The development of significant liver injury in this animal model raises the possibility that some chronic liver injury in humans may be due to alcohol potentiation of other hepatotoxins present in the environment at subtoxic levels.

Alanine Transaminase↗
PubMed1990

Contemporary pain management.

Pain management is a dynamic clinical area. Basic research is generating new drugs and new technologies for their delivery. Clinical research has demonstrated the important roles of psychological and environmental factors in the complaint of pain. Surgical strategies are improving. The recognition that the human brain plays a major role in pain perception and pain behaviours has led to the development of multidisciplinary teams that can bring a diversity of diagnostic and therapeutic skills to clinical medicine. The specialty of pain management is gaining momentum throughout the world. Australian health care delivery needs to respond to these developments to permit the citizens of this country to receive state-of-the-art care. Not only will this be more humane, but it will permit a reduction in the enormous financial costs of the poor management of both acute and chronic pain.

Acute Disease↗
PubMed1990

Leakage of fluid administered epidurally to rats into subcutaneous tissue.

Epidural catheters were implanted in rats under halothane/nitrous oxide anaesthesia. Contrast medium (Iopamidol) was injected via the catheter under fluoroscopic control 24-48 h after implantation. In 15 of 20 rats contrast could be seen leaking out of the epidural space, usually after only 25 microliters was administered. Leakage was associated with diminished antinociceptive response to morphine administered via the catheter. Both leakage and decreased response to morphine could be largely prevented by applying a drop of Supa-Glue over the site of entry of the catheter to the epidural space at the time of catheter implantation. Investigators using epidurally cannulated rats should document that leakage does not occur or discard results from rats showing evidence of leakage.

Analgesia, Epidural↗
PubMed1990

Influence of enzyme induction and exposure profile on liver injury due to chlorinated hydrocarbon inhalation.

Rats were exposed for four weeks either to air or to vapours of chloroform, carbon tetrachloride or 1,1-dichloroethylene given either as a constant concentration (continuous profile) or as repeated exposures for 6 hr per day, 5 days per week (fluctuating profile). Vapour concentrations were used such that the total exposure (concentration x time) was the same for the two profiles. Within each group, some animals received the enzyme-inducing agents, phenobarbitone or 1,3-butanediol, in their drinking water. Separate experiments were conducted to determine the influence of enzyme inducers and vapour concentration on chlorocarbon uptake and metabolism. In the case of chloroform, hepatic injury was more severe in animals exposed to constant vapour concentration, while dichloroethylene was more toxic when given as a fluctuating profile, especially in butanediol-treated rats. Carbon tetrachloride hepatotoxicity was similar in the two exposure profiles but was exacerbated by butanediol treatment. Butanediol-treated animals in the fluctuating profile group showed evidence of developing cirrhosis. These results could not be fully explained on the basis of the effect of enzyme inducers and exposure profile on amount of agent metabolized. Both the amount of toxic metabolites and the temporal pattern of their formation appear to be important determinants of liver injury.

Administration, Inhalation↗
PubMed1990

Halothane reductive metabolism in an adult surgical population.

The reductive metabolism of halothane was studied in 34 adult patients undergoing routine surgery. Reductive biotransformation of halothane was more extensive in females than males and was also enhanced in two patients treated preoperatively with phenytoin, an enzyme-inducing drug. Tobacco, ethanol and the patient's age, body weight and previous exposure to halothane did not influence reductive metabolism of halothane.

Adult↗
PubMed1990

Monitoring--the anaesthetist's view.

There is large variability in the pharmacokinetics and pharmacodynamics of sedative drugs in patients thus, a standard dose of sedative may produce undersedation in certain patients and substantial oversedation, resulting in anaesthesia, in others. Those who administer sedatives should, therefore, have the knowledge, skill, and equipment (including monitoring devices) to enable them to deal with an oversedated patient. Certain patients are at an increased risk of complications owing to sedative administration. Preoperative assessment of patients will enable the endoscopist to determine when and how to monitor the patient. If continuous monitoring is used, early detection of any potentially dangerous pathophysiology is more likely, and thus, the risk of cardiorespiratory arrest is minimized. Clinical observation is essential but can be supplemented by some extremely reliable and effective devices. Of these, the most important and relevant for monitoring during endoscopy is finger pulse oximetry. This technique is easy to use, does not interfere with the endoscopy procedure, enables continuous monitoring, and is extremely versatile. Pulse oximetry can also alert staff to cardiorespiratory problems.

Procedural Sedation↗
PubMed1989

Celiac plexus block following high-dose opiates for chronic noncancer pain in a four-year-old child.

This is the first case report documenting the use of a neurolytic celiac plexus block for relieving chronic noncancer pain in a pediatric patient. The child was a 4-yr-old male with an unknown form of inflammatory bowel disease since 1 yr of age. Chronic abdominal pain became a problem at 3 yr of age, following multiple bowel resections; continuous intravenous narcotic administration was implemented for pain control. The patient's pain became refractory to high-dose morphine administration (maximum dose, 267 mg/kg/day, iv), and, for that reason, a CT-guided neurolytic celiac plexus block was performed. This procedure resulted in improved pain control along with a major reduction in narcotic use to 7 mg/kg/day of morphine.

Celiac Plexus↗
PubMed1989

Influence of a high-fat meal on the absorption of morphine from oral solutions.

The influence of a high-fat meal on blood morphine concentrations after the administration of a morphine solution (50 mg dose) was studied in 12 patients with chronic pain. The oral morphine dose was administered in a total volume of 200 ml to patients either immediately after food intake or while in the fasting state. There was a 34% increase in the area under the curve (AUC) when morphine was administered immediately after food when compared with the fasting state (p less than 0.02). However, there was no significant difference between the maximum blood morphine concentration (Cmax) or the time to maximum concentration (tmax) between the two treatment regimens. The shape of the blood morphine concentration-time curve was consistently altered in the fed patients compared with patients who were in the fasting state, inasmuch as the blood morphine concentrations were maintained at a higher level from 240 to 600 minutes after the dose when the morphine was administered with food (p less than 0.02). It is suggested that morphine concentrations are maintained at higher levels, possibly resulting in more prolonged pain relief, when morphine is administered with food compared with the same dose administered to patients who are in the fasting state.

Administration, Oral↗
PubMed1989

Variables of patient-controlled analgesia. 1. Bolus size.

The efficacy of a range of demand doses of morphine for patient-controlled analgesia was studied. Patients who self-administered the smallest dose (0.5 mg) were frequently unable to achieve good pain control; patients who received the largest dose (2 mg) had a high incidence of ventilatory depression. A dose of 1 mg was the best increment under the conditions of this study but the relationship between increment and lockout interval requires consideration.

Abdomen↗
PubMed1989

Comparison of hyperbaric and plain bupivacaine with hyperbaric cinchocaine as spinal anaesthetic agents.

In a double-blind study, 90 patients (ASA 1 or 2) received spinal anaesthesia with 2 ml hyperbaric cinchocaine 0.5%, 4 ml hyperbaric bupivacaine 0.5% or 4 ml plain bupivacaine 0.5%. All injections were made in the left lateral position, and the patients turned supine immediately. Hyperbaric bupivacaine produced a significantly faster and a higher dermatomal level of bilateral complete sensory blockade than the other solutions (p less than 0.005 for each). The duration of sensory blockade was significantly longer with plain bupivacaine than with either hyperbaric solution (p less than 0.0005). The intensity of sensory blockade was significantly greater with both bupivacaine solutions than with hyperbaric cinchocaine (p less than 0.05). Onset and intensity of motor blockade were similar with all agents, but motor blockade was of significantly shorter duration with hyperbaric bupivacaine than the other agents (p less than 0.0005). Hyperbaric bupivacaine appears to be the best agent for rapid and intense sensory blockade of intermediate duration. Plain bupivacaine is more appropriate if a longer duration of action but a lower height of blockade are required, and has the advantage of less cardiovascular disturbance.

Aged↗
PubMed1989

Risk factors for halothane hepatitis.

Helothane hepatitis is a rare but sometimes fatal complication of halothane anaesthesia. Examination of case reports has pointed to a number of risk factors. Studies in animals and humans in the laboratory have provided evidence of a complex multifactorial basis for halothane hepatotoxicity, with the following factors playing a part: genetic predisposition; metabolism of halothane; repeated halothane anaesthetics; female sex; age of patient; intrahepatic hypoxia; and enzyme induction. Immunologic changes can be detected in a high percentage of cases of halothane hepatitis; however, studies establishing a cause-effect relationship are not available to determine if these changes cause, or result from, hepatic damage.

Anesthesia↗