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This study examined the pharmacokinetics of propofol by infusion in ponies using an analyser for the rapid measurement of propofol concentrations. The analyser (Pelorus 1000; Sphere Medical Ltd., Cambridge, UK) has a measurement cycle of approximately five minutes. Ten Welsh-cross ponies (weighing 135-300 kg) undergoing minor procedures were studied after premedication with acepromazine 0.03 mg/kg and detomidine 0.015 mg/kg. Anaesthesia was induced with ketamine 2 mg/kg and diazepam 0.03 mg/kg, and maintained with an infusion of propofol at an initial rate of 0.16 mg/kg/min for the first thirty minutes, after a bolus of 0.3 mg/kg; and ketamine by infusion (20-40 μg/kg/min). Blood samples (

Summary Three possible factors predisposing to Althesin hypersensitivity, namely total dose, method of administration, either by bolus dose or infusion, and pregnancy have been studied in patients receiving the drug for the first time. Of 137 patients given Althesin, four exhibited clinical signs of mild hypersensitivity, while C3 conversion alone, indicative of a subclinical reaction, was seen in a further six patients. No reactions were observed in two control groups in whom anaesthesia was induced with thiopentone. Neither the total dose nor method of administration appeared consistently to influence the incidence of reactions, but eight of the ten patients producing an altered response to Althesin were pregnant.

Background The relative potency of the steroid anaesthetic agent eltanolone has been compared with respect to induction of anaesthesia in ASA I and II young (1840: years) and elderly (>65 years) patients. Results: Anaesthesia was adequately induced in 12/40 elderly and 7/40 young patients. The lowest effective induction dose was 0.2 mg/kg in elderly and 0.3 mg/kg in young patients. This gave a relative potency of 0.28 (95% CI 0.12–52; P=0.0039). The cardiovascular effects associated with induction were small; other side-effects included involuntary movement and hypertonus, and respiratory upsets (apnoea, hiccups and coughing). Conclusion: The effective induction dose of eltanolone was significantly lower in the elderly patients; but the drug safety profile was similar in both age groups of patients. Method:113 temazepam premedicated patients (60 elderly) were evaluated in an open randomised study. They were allocated to receive doses between 0.05 and 0.75 mg/kg given i.v. over 30 s. The first 33 patients formed a pilot phase; the formal study comprised 80 patients. The primary efficacy variable was loss of verbal contact within 120 s and an effect lasting more than 4 min. All patients breathed 100% oxygen throughout the study period. Safety data (heart rate, blood pressure, respiratory apnoea, involuntary movements, hypertonus and other adverse effects) were noted.

We have studied the effects of ketorolac, bupivacaine and low-dose heparin on three thrombelastographic (TEG) variables (r, alpha, MA) in vitro. Blood samples were obtained from 12 healthy volunteers and 88 ASA I-II elective surgical patients. Clinically relevant concentrations of ketorolac (4.1 micrograms ml-1) and bupivacaine (2.7 micrograms ml-1) had little or no effect on the TEG variables. However, low concentrations of heparin (0.07-0.28 u. ml-1) had marked effects on all three TEG variables. Thus the interpretation of TEG abnormalities during anaesthesia and surgery may be confounded by the presence of heparin, but not by clinical concentrations of ketorolac or bupivacaine.

Anaesthetists often provide anaesthesia by continuous infusion of intravenous drugs, using open-loop control systems. Such systems include syringe pumps and volumetric pumps.

Thoracic bio-impedance cardiography was used to study the haemodynamic changes in 28 patients undergoing transurethral prostatectomy (TURP) under either general or spinal anaesthesia. Cardiac output and mean arterial pressure fell with induction of general anaesthesia, whilst mean arterial pressure and systemic vascular resistance fell with induction of spinal anaesthesia. The transthoracic fluid index fell during resection under general anaesthesia, but no significant haemodynamic changes were seen during resection under either anaesthetic. This study suggests that resection has no specific adverse haemodynamic consequences. Spinal anaesthesia may produce less haemodynamic disturbance than general anaesthesia in patients undergoing TURP and formal comparison of the 2 techniques seems necessary.

General anaesthesia is the reversible depression of central nervous system function. There is still no agreement over what constitutes depth of anaesthesia, and the clinical anaesthetist must thus titrate drug input according to clinical signs (heart rate, blood pressure, somatic movement, autonomic responses). The potency of inhalational agents may be expressed in terms of the MAC (minimum alveolar concentration); comparable end-points (including blood concentrations) have been proposed for the intravenous agents. Kinetic infusion regimens can be constructed for the intravenous agents to achieve the ED95 concentrations required to provide clinically adequate anaesthesia. However, because of individual differences in drug kinetics and: dynamics, as well as the influences of disease states and intercurrent therapy, the clinician will titrate the dose according to response. Administration of volatile or intravenous anaesthetics by fixed regimens may result in either overdosage or the risk of patient awareness. The choice of anaesthetic drug is usually based on the nonhypnotic side effects of the different agents — including their central and regional cardiovascular effects, the speed and completeness of recovery, and the need to provide intraoperative analgesia. In addition, special techniques and drugs are often needed for neurosurgical, cardiothoracic and obstetric anaesthesia. All anaesthetic agents (inhalation and intravenous) have other side effects (such as cardio-respiratory depression and organ toxicity related to the liver or kidney). Both halothane and enflurane may be responsible for postoperative hepatic dysfunction, while the metabolism of enflurane can also result in nephrotoxicity in patients with pre-existing renal dysfunction. Isoflurane has been reported to cause ‘coronary steal’ in patients with ischaemic heart disease through its coronary vasodilator properties. Of the intravenous agents available for maintenance anaesthesia, large doses of thiopental result in prolonged recovery time, while ketamine may cause hallucinations. Benzodiazepines obtund these effects of ketamine, but are also accompanied by delayed recovery. At present, the combination of propofol and alfentanil offers the best pharmacological properties for maintenance of anaesthesia; however, caution is needed in the patient with ischaemic heart disease, hypertension or hypovolaemia.

The disposition of alfentanil has been investigated in 10 anaesthetized patients with chronic renal failure undergoing kidney transplantation and compared with eight age matched anaesthetized patients with normal renal function. Plasma samples were collected to 660 min following intravenous administration of alfentanil 3–5 mg (50 μg kg−1). Drug concentrations were measured by RIA; and alfentanil binding to plasma proteins by equilibrium dialysis against 0·1 M phosphate buffer, pH 7·4. Alfentanil binding to plasma proteins was 87·6% (s.d. 2·0) in the patients with chronic renal failure, and 89·7% (1·2) in patients with normal renal function (P = 0·025). There was no correlation between alfentanil binding and plasma albumin, total plasma proteins, plasma urea or plasma creatinine concentrations. In both groups, the drug concentration-time profile decayed in a curvilinear manner; in the chronic renal failure patients, restoration of function did not influence the decay profile. Elimination half life, mean residence time and apparent volume of distribution at steady state were not different in the two groups of patients (mean values: 142·4 and 120·2 min; 128·5 and 136·0 min; and 40·5 and 27·6 L, respectively in chronic renal failure patients and patients with normal renal function). Total drug clearance and Vd area were significantly increased in the chronic renal failure patients: 341·9 vs 211·8 mL min−1; and 69·3 and 35·5 L. There were no differences in intrinsic clearance or apparent volume of distribution at steady state for unbound drug between the two patient groups.

Summary A variety of methods are currently available for the management of the diabetic patient in the peri-operative period. A questionnaire about current clinical practice was sent to all anaesthetists in the Oxford region. The majority reported that minor surgery in both insulin treated and noninsulin treated diabetic patients warranted no intervention other than avoidance of meals and medication before surgery, and that, for major surgery, a glucose-insulin-potassium infusion should be used. Fifty one out of 71 respondents in the junior staff grades preferred this latter approach for intermediate surgical procedures in insulin treated patients compared with 27 out of 69 of the consultant staff. Most anaesthetists aimed for blood glucose levels of 7–13 mmolilitre in the peri-operative period. The literature is also reviewed.

A technique is described for the determination of equipotent rates of infusion of intravenous hypnotic agents. Two end points have been defined; the rates needed to suppress the initial response to the surgical incision in 50% (ED50) and 95% (ED95) of patients receiving continuous infusion anaesthesia to supplement 67% nitrous oxide in oxygen. For patients aged 20-60 years, and premedicated with morphine 0.15 mg/kg intramuscularly, the ED50 values for Althesin (as alphaxalone) and methohexitone by infusion were 13.7 and 48.8 micrograms/kg/minute respectively. The ED95 values were 18.1 and 75.9 micrograms/kg/minute. For patients of a similar age premedicated with diazepam 10 mg orally, the ED50 values for Althesin and methohexitone were 18.5 and 66.0 micrograms/kg/minute respectively; while the ED95 values were 24.2 and 80.8 micrograms/kg/minute.

In order to avoid Cremophor-related reactions and reduce the incidence of pain on injection, diisopropylphenol (ICI 35,868; propofol) has been reformulated as an emulsion. One hundred and fifteen patients received an induction dose of propofol in the new formulation. The dose required to induce anaesthesia in 95% of healthy, unpremedicated patients was 2.5 mg/kg. Induction was associated with a degree of cardiovascular and respiratory depression. There were no adverse reactions although there were a number of minor side-effects. The incidence of pain on injection was low (3%) and the overall quality of induction was assessed as good or adequate in 92% of patients.

Eighty women (40 for elective Caesarean section and 40 for elective gynaecological surgery) were randomly assigned to one of five treatment groups and received pre-operatively either no medication; magnesium trisilicate mixture (BP) 30 ml; metoclopramide 10 mg intramuscularly; ranitidine 150 mg orally on the night prior to, and the morning of, surgery; or metoclopramide 10 mg intramuscularly in combination with oral ranitidine 150 mg (the latter again given on the night prior, and the morning, of surgery). The effect of these medications on intragastric pH, volume and serum gastrin-17 was measured. No patient receiving ranitidine had a pH of less than 4. Magnesium trisilicate mixture resulted in the largest intragastric pH change although one woman in this group had a pH of 1.7. The largest intragastric volumes were seen in the patients who had received magnesium trisilicate mixture, whilst the patients who had received metoclopramide in combination with ranitidine had the smallest intragastric volumes. Magnesium trisilicate mixture and metoclopramide resulted in no change in serum gastrin levels. However, in the subjects who had received ranitidine on the night prior to surgery, the fasting serum gastrin was significantly higher (p less than 0.01) than the values in the remaining subjects, the mean (SEM) values being 60.3 (6.3) pg/ml in those not receiving ranitidine and 111.3 (19.5) pg/ml in those who had been given ranitidine.

A case of tracheal stenosis following a short period of intubation with a low pressure cuffed portex tube is described. The possible factors responsible for the tracheal damage are discussed.

The steroid anaesthetics, Althesin or minaxolone (a new water soluble steroid), or ICI 35 868 (di-isopropylphenol) have been administered as continuous i.v. infusions to supplement nitrous oxide 67% in oxygen anaesthesia. We have defined the minimum infusion rate (MIR) for i.v. agents as that infusion rate which suppressed movement of the patient in response to the initial and to subsequent sustained surgical stimulation. Following premedication with morphine 0.15 mg kg−1 and atropine 0.6 mg, MIR for 11 patients receiving Althesin was 18.0 ± 0.9 (SEM) μg min−1 kg−1 as total steroid, equivalent to 13.5 ± 0.7 μg min−1 kg−1 as alphaxalone. For nine patients receiving minaxolone MIR was 11.0 ± 0.5 μg min−1 kg−1, and for eight patients receiving ICI 35 868 51.3 ± 3.8 μg min−1 kg−1. There was no evidence of accumulation of any of the three drugs as the plasma concentrations remained steady between 30 min after starting the infusion, and the end of the infusion (range 55–245 min after the start). At the minimum infusion rates quoted above the plasma concentrations of the three i.v. agents were alphaxalone 1.9 ± 0.1 μg ml−1; minaxolone 0.6 ± 0.05 μg ml−1; ICI 35 868 1.54 ± 0.22 μg ml−1.

Hepatitis related to halothane has been found to follow about 1 in 35000 halothane anaesthesia [1]. One of the most important factors in unexplained hepatitis following halothane (UHFH) is repeated exposure to halothane within a short period, and the results of the investigation of a prospective series of patients undergoing radium implantation in Oxford in 1973–1974 appeared to confirm the association [2]. Subsequently, there has been extreme reluctance to repeat the use of halothane for anaesthesia within a few weeks (especially in middle-aged, obese women being treated for carcinoma of the cervix), despite other reports which show lack of adverse hepatic effects [3, 4].

The intravenous anaesthetic Althesin may be administered by continuous intravenous infusion for maintenance of general anaesthesia, sedation in patients in intensive care units or during investigational procedures. Published reports of experience with this technique are reviewed, with particular attention to the rates of administration employed and the influence of other anaesthetics and analgesic agents used concurrently.