The risk of adverse reactions in anaesthesia.
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Anesthesia↗
Biomedical subjects
W S Nimmo
Publications and source records attributed to W S Nimmo.
Pharmacokinetics of propofol (diprivan) in elderly patients.
The pharmacokinetics of propofol (2,6 diisopropylphenol) were compared in 12 patients aged 65-80 yr and 12 patients aged 18-35 yr. After premedication with papaveretum i.m., anaesthesia was induced with propofol 2.0 mg kg-1 in the elderly and 2.5 mg kg-1 in the younger patients. Alcuronium 12-20 mg was then given and the patient's lungs ventilated with halothane and nitrous oxide in oxygen. Blood was taken after various time intervals up to 24 h for the measurement of propofol concentrations by HPLC and for the estimation of propofol protein binding. The mean blood propofol concentration was generally higher in the elderly group, but this difference was only significant at 2 min after induction. The clearance of propofol was significantly lower in the elderly (1.44 +/- 0.10 (SE) litre min-1) than in the younger patients (1.79 +/- 0.12 litre min-1). The volume of the central compartment in the elderly patients was significantly smaller (19.6 +/- 5.2 litre) than that in the young (26.3 +/- 2.9 litre). There was no difference in the volume of distribution at equilibrium (1608 +/- 246 litre in the elderly and 1757 +/- 360 litre in the young), in the volume of distribution at steady state (691 +/- 139 litre in the elderly and 771 +/- 236 litre in the young) or in the half-lives of distribution and elimination. The plasma protein binding of propofol was similar in both groups and showed no trend with time after dose.
Adult↗
New non-invasive methods for measuring gastric emptying.
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Gastric Emptying↗
Plasma fentanyl concentrations during transdermal delivery of fentanyl to surgical patients.
Plasma fentanyl concentrations were measured during and after transdermal fentanyl delivery in groups of patients undergoing general surgery. At 8 and 12 h, concentrations did not differ from those observed in a matched group of patients receiving fentanyl by i.v. infusion. At 24 h, concentrations were significantly lower in one of the transdermal groups. Plasma fentanyl clearance did not differ significantly between the groups. Plasma fentanyl concentrations decreased slowly after removal of the transdermal system.
Abdomen↗
Changes in pupil diameter after oral administration of codeine.
Pupillary constriction occurs following administration of opioids and may be used as a marker of opioid activity. We have measured plasma concentrations and pupil diameters in 16 healthy volunteers after the oral administration of placebo or codeine. Pupil size decreased significantly after codeine compared with placebo. Pupil size was related to the plasma concentrations of codeine (P less than 0.05).
Administration, Oral↗
Effect of anaesthesia and surgery on pharmacokinetics and pharmacodynamics.
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Anesthesia↗
Reporting adverse reactions to anaesthetic drugs: a new way forward.
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Anesthetics↗
Plasma morphine concentrations after intramuscular injection into the deltoid or gluteal muscles.
The absorption of morphine 10 mg after intramuscular injection into the gluteal and deltoid muscles was investigated. Ten patients received the injection into the deltoid and 10 were given the injection into the upper outer quadrant of the buttock. Blood was taken at frequent intervals up to 2 hours after the injection for plasma morphine analysis by high performance liquid chromatography. Morphine concentrations were generally higher in the gluteal group although the mean peak concentrations (62.8 ng/ml in the gluteal group and 52.3 ng/ml in the deltoid group) were similar. Peak morphine concentrations varied from 22.5-99.3 ng/ml in the gluteal group and 26.5-84.5 ng/ml in the deltoid group. The area under the concentration-time curve was significantly greater in the gluteal group than in the deltoid group but this difference disappeared when allowance was made for differences in body weight of the two groups. We conclude that the absorption of morphine from the deltoid and gluteal sites is similar.
Adult↗
Comparison of the effect of cisapride and metoclopramide on morphine-induced delay in gastric emptying.
1. The effects of metoclopramide or cisapride on morphine-induced delay in gastric emptying in patients before surgery were compared. 2. Forty patients were allocated randomly to receive one of four premedications i.m.: placebo only, morphine 10 mg alone, morphine 10 mg with metoclopramide 10 mg and morphine 10 mg with cisapride 10 mg. Gastric emptying after each premedication was assessed indirectly from the rate of absorption of oral paracetamol. 3. Cisapride 10 mg reversed the delay in gastric emptying due to morphine. Its effects were significantly greater than those of metoclopramide 10 mg.
Acetaminophen↗
Measurement of FEV1 and FVC. Comparison of a pocket spirometer with the Vitalograph.
The performance of a pocket spirometer was compared with that of the Vitalograph to assess the extent of agreement between the instruments and the repeatability of measurements with each instrument. Both instruments showed a similar level of accuracy when measurements were repeated and in the estimation of forced vital capacity, but there was a mean difference of 201 ml in measurements of forced expiratory volume in one second, for which the Vitalograph gave the larger reading.
Adolescent↗
Adverse effects of opioid analgesic drugs.
Opioids were available in clinical practice since before the birth of modern anaesthesia--Setürner isolated morphine in 1806. They have a record of safety which is reflected in their high therapeutic ratios, especially the synthetic opioids introduced recently (table III). The most serious immediate adverse effect, respiratory depression, is a predictable effect related closely to analgesia. It is fortunate for anaesthetists who use opioids regularly, that recognition and treatment of respiratory problems are an integral part of their craft and that opioid antagonists are effective in reversing respiratory depression.
Analgesics, Opioid↗
Effect of cisapride on morphine-induced delay in gastric emptying.
Forty patients were allocated randomly to receive one of four premedications i.m.: placebo only, morphine 10 mg plus placebo, morphine 10 mg plus cisapride 10 mg and morphine 10 mg plus cisapride 4 mg. Gastric emptying after each premedication was assessed using the oral paracetamol absorption model. The morphine only group and the morphine and cisapride 4 mg group showed delayed gastric emptying when compared with the placebo group. Delay in gastric emptying in the morphine and cisapride 10 mg group was not demonstrated. It is concluded that cisapride 10 mg prevents the delay in gastric emptying associated with the administration of morphine.
Acetaminophen↗
Concurrent drug therapy in patients undergoing surgery.
In a retrospective study of 57,176 patients and a prospective study of 216 patients undergoing surgery, 24-32% of patients were receiving some concurrent medication. Between 10 and 16% were taking drugs for cardiovascular disease. Of these, only 71% had their normal medication prescribed before surgery and only 41% received their drugs on the day of surgery.
Drug Therapy↗
Analgesia from morphine and ketamine. A comparison of infusions of morphine and ketamine for postoperative analgesia.
Ketamine 4 micrograms/kg/minute produced pain relief similar to that from morphine 33 micrograms/minute in a double-blind study that compared analgesia from constant-rate intravenous infusions of the two drugs in 60 patients. The analgesic efficacy of the infusions, as assessed by pain scores and the requirement for supplementary self-administered morphine, was poor. Ventilatory depression, the most significant side effect, occurred only in patients who received morphine infusion. The low dose ketamine infusion did not provide clinically useful analgesia even though adequate plasma concentrations were achieved.
Clinical Trials as Topic↗
Pain relief after surgery.
Relief of pain after surgery remains poor for the majority of patients. The pain is unpleasant, and is associated with arterial hypoxaemia, venous thrombosis, myocardial ischaemia and a more florid hormonal response to surgery. Regional analgesia, systemic, subarachnoid or extradural opioids and antiprostaglandin drugs are all used to treat pain after surgery. Systemic opioids are used usually, because regional and axial techniques are labour intensive and antiprostaglandin drugs ineffective. Opioids given orally undergo extensive first pass metabolism and intramuscular doses are absorbed unpredictably. Intravenous administration avoids both problems and excellent results have been obtained using Patient Controlled Analgesia devices, but these machines are expensive. A simple regimen suitable for application to large numbers of surgical patients is required. Continuous infusion of fentanyl 100 micrograms h-1 IV begun two hours before surgery and supplemented by a single bolus dose of fentanyl 100 micrograms IV provided an effective background of analgesia.
Analgesics, Opioid↗
New intravenous anaesthetics and neuromuscular blocking drugs. A review of their properties and clinical use.
The newer neuromuscular blocking drugs include vecuronium and atracurium. Vecuronium is a competitive neuromuscular blocking drug with a steroid nucleus. A dose of 0.1 mg/kg has an onset time of 2 minutes and provides surgical paralysis for 20 minutes. Recovery to 90% twitch height occurs in 40 to 50 minutes. Vecuronium has few adverse effects and its use is associated with cardiovascular stability. Atracurium is a competitive neuromuscular blocking drug which undergoes Hofmann degradation and ester hydrolysis in plasma. A dose of 0.6 mg/kg has an onset time of around 2 minutes and provides surgical paralysis for 20 to 30 minutes. Recovery to 90% twitch height occurs in 60 to 80 minutes. Histamine release, usually only localised, has been reported in association with the use of atracurium. The organ-independent metabolism of atracurium allows its use in standard dosage in patients with renal or hepatic disease. Edrophonium, although not a new drug, has recently been re-evaluated for reversal of neuromuscular blockade. In a dose of 0.5 mg/kg it has been shown to be as effective as neostigmine at reversing neuromuscular blockade after recovery has started (greater than 25% twitch height recovery). However, if blockade is profound (less than 10% recovery), edrophonium is less effective. Among the newer intravenous anaesthetics are propofol (disoprofol) and midazolam. In a dose of 1.5 to 2.5 mg/kg, propofol produces sleep rapidly with a prompt recovery in 4 to 6 minutes. Induction of anaesthesia may be associated with a transient apnoea and a fall in systolic pressure. The rapid recovery has led to its use for maintenance of anaesthesia. Midazolam is a water-soluble benzodiazepine which has been used as an anaesthetic agent. The dose needed to induce sleep varies widely (0.15 to 0.5 mg/kg); onset is slow (1.5 to 5 minutes), and recovery may be prolonged. Midazolam is also used in lower doses as a sedative. Ketamine, an intravenous induction agent, has recently been used intrathecally and extradurally to provide analgesia.
Anesthesia, Intravenous↗
A haemorheological study of lignocaine.
Eight volunteers received lignocaine 75 mg i.m. Peak plasma lignocaine concentrations (mean 0.80 microgram ml-1; range 0.31-1.86 micrograms ml-1) were attained at 30 min. Haematocrit and red cell deformability remained unchanged. Lignocaine caused small but significant decreases in plasma viscosity and whole blood viscosity at both high and low shear rates (94 and 0.94 s-1). The small reductions in plasma viscosity and high shear blood viscosity observed ex vivo may be the result of alterations in plasma proteins. The reductions in low shear blood viscosity are considered to result from decreased red cell aggregation.
Adult↗
Pharmacokinetics of fentanyl during constant rate i.v. infusion for the relief of pain after surgery.
Forty-five patients in four groups undergoing orthopaedic, upper abdominal, prolonged or cardiac surgery received a constant rate i.v. infusion of fentanyl 100 micrograms h-1, for 24 h starting 2 h before surgery. A single bolus dose was given i.v. at the induction of anaesthesia. Plasma fentanyl concentrations, measured by radioimmunoassay were between 1 and 3 ng ml-1 until the infusions were discontinued. Clearance of fentanyl was decreased in the cardiac surgery group only. The elimination half-life was 7.3-9.7 h. This simple regimen produced effective analgesia.
Adult↗