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Biomedical subjects

J W Dundee

Publications and source records attributed to J W Dundee.

At least 91 records · Page 5Linked to original sources

Age and nature of operation influence the pharmacokinetics of midazolam.

The pharmacokinetics of midazolam were studied in surgical patients given 0.3 mg kg-1 i.v. for either the induction of anaesthesia, or postoperative sedation following cardiopulmonary bypass. The short elimination half-life of midazolam (2.4 h in patients less than 50 yr undergoing minor surgery) was significantly, although not markedly, prolonged with age (4.1 h in patients greater than 50 yr undergoing minor procedures) and by the nature of the operation (3.8 h after major operative procedures). These changes were the result of alterations in clearance and volume of distribution with age, and in volume of distribution with nature of operation.

Adult↗

Pharmacokinetics of diazepam and midazolam when used for sedation following cardiopulmonary bypass.

The water-soluble benzodiazepine, midazolam, was compared with diazepam for postoperative sedation in patients following cardiopulmonary bypass. Midazolam in repeated doses produced a stable plasma concentration within 4 h, showed no tendency to cumulation and was cleared rapidly following discontinuation. Similar doses of diazepam given with the same frequency produced plasma concentrations which were still increasing at the time of discontinuation and which were still greater than their baseline values 24 h later.

Anesthesia, General↗

Failure of two benzodiazepines to prevent suxamethonium-induced muscle pain.

In a randomised double-blind trial carried out on fit, unpremedicated patients undergoing standard minor operations with early postoperative mobility, using a standard form of anaesthesia, pretreatment with diazepam 0.15 mg/kg or midazolam 0.1 mg/kg failed to reduce significantly the incidence of postoperative muscle pains following suxamethonium 1 mg/kg. By contrast, tubocurarine 0.05 mg/kg proved to be effective as a pretreatment. Neither benzodiazepine influenced the incidence or severity of fasciculations seen with suxamethonium or the duration of neuromuscular block. Tubocurarine virtually abolished visible fasciculation and, in the dose used, reduced the intensity and duration of the neuromuscular block. There were no clinically significant changes in serum potassium, creatinine phosphokinase or aldolase after suxamethonium, although 5 out of 47 showed an atypical rise in creatinine phosphokinase.

Adolescent↗

The influence of age on the onset of anaesthesia with midazolam.

There was a considerable individual variation in response to a standard induction dose of 0.3 mg/kg midazolam in unpremedicated patients. This is shown by variations in time to onset of sleep and the fact that about one quarter of subjects did not lose consciousness in 3 minutes. In 166 fit patients a good negative correlation was demonstrated between the age of the patients and time to loss of consciousness. Patients over 50 years differed from younger patients in a greater reliability of effect and significantly shorter induction time. In elderly patients midazolam is a more reliable induction agent than in the young.

Adolescent↗

Failure of magnesium sulphate to prevent suxamethonium induced muscle pains.

In fit unpremedicated patients undergoing minor operations and who were ambulant on the afternoon of the operations, pretreatment with magnesium sulphate given intravenously did not reduce the incidence of suxamethonium induced myalgia below that in a similar series who received no prophylactic therapy. The injection of magnesium in conscious patients is followed by unpleasant side effects.

Early Ambulation↗

Influence of plasma proteins on the onset of hypnotic action of intravenous midazolam.

The action of midazolam is influenced by serum protein binding as seen in the relationship between the time of onset of action of a fixed dose of the drug and the plasma albumin. Pretreatment with intravenous aspirin produces a decrease in the in vitro binding of midazolam. In vivo this is manifest as an increase in the rapidity of action of the benzodiazepines. Probenecid pretreatment will also cause a decrease in the onset time of midazolam. However, this is not due to altered plasma protein binding of the sedative.

Adolescent↗

Haemodynamic changes during induction of anaesthesia with midazolam and diazepam (Valium) in patients undergoing coronary artery bypass surgery.

Midazolam 0.3 mg/kg and diazepam 0.5 mg/kg were used for induction of anaesthesia in two groups of 10 patients each undergoing coronary artery bypass surgery. Haemodynamic variables were measured during induction of anaesthesia, after pancuronium and following tracheal intubation. Haemodynamic indices were derived from these measurements using standard formulae. The induction of anaesthesia with midazolam produced a slight but significant increase in heart rate. There was a significant fall in systemic arterial pressure and pulmonary artery pressure following both drugs. Despite the fall in systemic arterial pressure, the cardiac index was maintained in patients who received midazolam. The cardio-stimulatory effect of laryngoscopy and tracheal intubation was not prevented by either of the benzodiazepines and morphine in the dosage used. Midazolam is a suitable alternative to diazepam as part of an intravenous induction regimen in patients with ischaemic heart disease.

Anesthesia, Intravenous↗

Cimetidine in labour: absence of adverse effect on the high-risk fetus.

In a prospective randomized trial, 36 women received cimetidine and 32 magnesium trisilicate mixture BP as antacid therapy every 2 h in labour. The women belonged to a high-risk category and the infants born were less than 36 weeks gestation, or less than 2000 g birthweight or otherwise in jeopardy because of severe maternal pre-eclampsia or diabetes. Measurements of a wide range of haematological and biochemical variables revealed no differences between the two groups of babies. The frequency of complications found in the infants was similar, although infants born to the women who received magnesium trisilicate required oxygen therapy for a longer period. Cimetidine did not appear to affect the development of gastric acidity, or to increase bacterial colonization of the gastrointestinal tract in the infant.

Adult↗

Age affects the induction dose of propofol ('Diprivan').

A standard method (fixed initial dose of 1.25 mg/kg followed by 10 mg every 15 s) for studying the induction dose of propofol showed a marked falling off in requirements in fit unpremedicated patients aged 60 y and over. With this slow technique of administration, side effects were rare, even in the elderly.

Adolescent↗

Intravenous anaesthesia and the need for new agents.

Ideally one would like a water-soluble, non-irritant, rapidly-acting, smooth induction agent, with no antanalgesic action. Cardiovascular and respiratory depression should be minimal with normal dosage. Since these are unlikely to be achieved with a single drug, the combination of opioid and induction agent offers possibilities that should be explored. A slight delay in onset would not be a major obstacle, provided this is predictable, but the prime need is for a rapidly acting less toxic alternative to thiopentone.

Anesthesia, Intravenous↗