Plasma catecholamine concentration during sedation in ventilated patients requiring intensive therapy.

The effects of isoflurane and midazolam sedation on the catecholamine responses of ventilated patients were studied over a 24-h period. Sixty ventilated patients admitted to our intensive therapy unit were allocated randomly to receive either isoflurane or midazolam sedation. Arterial blood samples for plasma catecholamine concentrations were taken at baseline, 6 h after starting sedation and at the end of the study period. Patients sedated with isoflurane showed a progressive reduction in both adrenaline and noradrenaline concentrations during the period of sedation which reached statistical significance for adrenaline at 6 h (p less than 0.02) and at the end of the study (p less than 0.001). Patients sedated with midazolam showed no significant changes of adrenaline or noradrenaline concentrations. Overall, a more satisfactory degree of sedation was achieved with isoflurane.

Medical problems of surgical patients. Hypertension and ischaemic heart disease.

Pre-existing disease in the form of hypertension or ischaemic heart disease may increase morbidity and mortality in patients presenting for anaesthesia and surgery. The interaction of these two cardiovascular conditions in relation to anaesthesia has been studied in a series of 115 patients. The results did not support the view that antihypertensive drugs and beta-receptor blocking agents should be withdrawn before anaesthesia and surgery. The main cause for concern in providing anaesthesia for these patients is that sympathetic nervous activation induced either by anaesthetic manoeuvres or by surgical stimulation may lead to reflex cardiovascular responses which, by increasing myocardial oxygen demand, lead to episodes of myocardial ischaemia. In this respect beta-receptor blocking drugs appear to have a protective effect on the ischaemic myocardium.

On using a self-tuning controller for blood pressure regulation during surgery in man.

The generalized minimum-variance self-tuning controller of Clarke and Gawthrop has been used to adjust the flow rate of a modified Vickers Treonic IP4 syringe pump delivering phenylephrine to 20 patients undergoing lower abdominal surgery during epidural analgesia. This proved to be a very effective method of restoring and maintaining normal arterial pressure. The method has also been used to produce controlled hypotension in 18 patients undergoing plastic or neurosurgical procedures via sodium nitroprusside infusions. Valuable insight into patient responses to surgical stimuli, blood loss, fluid loads, opioids, relaxants and other agents was provided.

The pharmacology of propofol.

A review of the pharmacology of propofol, a new IV anesthetic agent, is presented. Solubilized in a soybean emulsion, propofol is one of a series of sterically hindered phenols that exhibit anesthetic activity. Induction of anesthesia with propofol may be associated with pain on injection, apnea, and a reduction in arterial blood pressure (BP) and cardiac output. Caution should be ascribed to its use in patients with coronary artery disease, where these effects may have the potential for producing myocardial ischemia. The hemodynamic responses to laryngoscopy and intubation are attenuated. The pharmacokinetic profile suggests suitability as an infusion for either maintenance of anesthesia or sedation. Use of propofol as an infusion during surgery may result in a further reduction in cardiac output, particularly with the concomitant administration of adjuvant increments of fentanyl. The ventilatory response to CO2 is depressed during such an infusion. The high clearance of propofol suggests that even after a prolonged infusion, recovery should be rapid. This finding has been confirmed in a series of studies establishing propofol as an ideal agent for use in a total IV anesthetic technique. Both the quality and speed of recovery, together with the absence of emetic sequelae, support the use of propofol in an outpatient setting. Propofol appears to have no long-term effect on adrenocortical function and appears safe for use in patients with acute intermittent porphyria and susceptibility to malignant hyperpyrexia.

Practical and pharmacological implications of continuous intravenous anesthesia.

The concept of continuous intravenous anesthesia is reviewed and the need for an index comparable to MAC (minimum alveolar concentration) for volatile and gaseous anesthetics is stressed. The pharmacokinetic requirements for an intravenous anesthetic for continuous infusion are stated, and the place of existing intravenous anesthetics is discussed.

Cardiovascular studies during induction with minaxolone.

The cardiovascular effects of induction of anesthesia with minaxolone, a new water soluble steroid agent, have been studied in 12 normotensive patients and 5 patients with treated hypertension. The arterial pressure, heart rate and ECG were continuously recorded before and during induction of anesthesia with Minaxolone 0.5 mg kg-1. Cardiac output measurements were made in the awake patient, at 3 minutes after the induction of anesthesia and 2 minutes after an increment of the drug. In both groups of patients, induction of anesthesia led to a decrease in systolic arterial pressure and a smaller decrease in diastolic arterial pressures. This was coupled with an increase in the heart rate. The decrease in cardiac output was similar in both the normal and treated hypertensive patients. Administration of an increment of minaxolone (0.1 mg kg-1) did not produce further significant changes in the cardiovascular variables. The results of this study show that the changes in hemodynamic variables with minaxolone are comparable with those seen following induction of anesthesia with other intravenous agents, with the one difference in that there was only minimal change in the diastolic arterial pressure.

Studies on premedication and ventilatory responses to minaxolone.

The effect of three premedications on induction, maintenance and recovery characteristics of minaxolone as a supplement to nitrous oxide and oxygen anesthesia were studied in 70 patients. Morphine and atropine premedication provided superior operative conditions with fewer side-effects when compared with atropine alone or diazepam and atropine. Recovery was significantly longer after minaxolone compared with a similar group of patients given Althesin. The ventilatory responses to the induction of anesthesia with minaxolone were measured in 25 patients. All patients showed an increase in respiratory frequency and a decrease in tidal volume. This effect was most marked in the group premedicated with diazepam and atropine.

Isoflurane compared with midazolam for sedation in the intensive care unit.

OBJECTIVE: To compare isoflurane with midazolam for sedation of ventilated patients. DESIGN: Randomised control study. Setting--Intensive care unit in university teaching hospital. PATIENTS: Sixty patients aged 18-76 who required mechanical ventilation. INTERVENTIONS: Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). END POINT: Achievement of a predetermined level of sedation for as much of the time as possible. MAIN RESULTS: Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. CONCLUSION: Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit.

Anaesthesia and severe pulmonary disease.

The key to the management of anaesthesia in patients with severe pulmonary disease lies in predicting the requirement for support of ventilation and/or oxygenation in the postoperative period, and the provision of effective pain relief in such a way as to allow the patient to maintain adequate spontaneous ventilation. This in turn depends on understanding the influence of the relevant surgical intervention on the patient's ability to sustain his normal breathing requirements, to breathe deeply, and to cough.

Role of anaesthesiologists in undergraduate medical education.

Although anaesthesia and intensive care medicine are postgraduate subjects, few would deny the value of exposing medical undergraduates to clinical training in these areas. The present review addresses developments in medical undergraduate training curricula, and the specific benefits that can be provided for medical students, at all stages of training, by anaesthesiologists working in operating theatres, intensive care units and pain clinics.

Interactions of anaesthesia and high pre-operative doses of beta-receptor antagonists.

Haemodynamic responses to anaesthesia and surgery were observed in 13 patients with severe renovascular hypertension treated with high doses of beta-receptor antagonists (equivalent to 10-37 mg/kg/day of propranolol) and 24 patients receiving moderate doses of beta-receptor antagonists (equivalent to 120-480 mg propranolol per day). Chronotropic and inotropic responses to the noxious stimuli of laryngoscopy or surgical stimulation were effectively suppressed by beta-receptor blockade thus increasing arterial pressure due to these stimuli or aortic cross-clamping which indicated a purely resistive load for the left ventricle. In no patient was evidence found that myocardial performance, and its effect on left ventricular ejection, was seriously compromised.