1. To examine the metabolic effects of increases in circulating endogenous plasma catecholamines, we measured plasma glucose, potassium and magnesium in 14 patients undergoing elective coronary artery bypass grafting. The patients were randomized into two groups and received either sodium nitroprusside (a direct-acting vasodilator) or trimetaphan camsylate (a ganglion-blocking agent) for routine control of blood pressure during the operation. 2. There were significant differences between the two groups in the levels of all three metabolic variables studied. Plasma glucose levels rose in both groups, but were significantly higher in the sodium nitroprusside group [peak levels 9.14 (SEM 0.72)mmol/l compared with 6.71 (0.88) mmol/l, P less than 0.001, analysis of variance]. The cardioplegia solution caused a large increase in plasma magnesium in both groups but in the sodium nitroprusside group the level rose higher [to 1.59 (0.12)mmol/l compared with 1.34 (0.06)mmol/l] and fell faster (P less than 0.05, analysis of variance). In the group receiving sodium nitroprusside, plasma potassium fell, by a mean of 0.34mmol/l, as plasma catecholamine levels rose; no such fall was seen in the group receiving trimetaphan camsylate (P less than 0.05, analysis of variance). 3. It is concluded that the sympathoadrenal system is important in causing metabolic changes during cardiopulmonary bypass and may be relevant in other conditions such as acute myocardial infarction.

Thirty-seven patients with a wide range of illnesses were studied during mechanical ventilation of the lungs in an intensive care unit. Fifteen were sedated with a continuous propofol infusion, with analgesia provided by bolus doses of papaveretum. Twelve received a continuous infusion of papaveretum, supplemented by bolus doses of midazolam. The level of sedation was assessed every four hours and measurements were made of haemodynamic and respiratory variables. Levels of sedation were generally satisfactory in both groups. Six patients who received propofol required the use of muscle relaxants, because of their strong respiratory drives, to achieve synchronisation with the ventilator. There was no significant difference in respiratory or haemodynamic variables between the groups, but several patients required inotropic support because of their disease. There was no evidence of inhibition of adrenal steroidogenesis in the propofol group. Propofol can be a useful sedative agent in the intensive care unit, but sedative regimens should be tailored to individual patient requirements.

The ventilatory effects of a propofol infusion were studied in 10 females premedicated with atropine and nine with papaveretum and atropine. The infusion, at a rate of 20 mg kg-1 h-1 for 5 min, reducing to 12 mg kg-1 h-1 for 10 min and then 6 mg kg-1 h-1 thereafter, was known to produce a steady-state plasma propofol concentration for 20-25 min after 25 min from commencement. Minute ventilation, tidal volume, frequency and response to breathing carbon dioxide were measured before the infusion and during the steady-state period. Propofol decreased minute ventilation to 56% and 46% (P less than 0.01) of their mean control values in the atropine and papaveretum groups, respectively. Mean tidal volume was decreased to 41-44% (P less than 0.02) by propofol, but a tachypnoea observed in the atropine group during the infusion was absent in the papaveretum group. Propofol alone had no effect on the slopes of the carbon dioxide response curves but did produce a shift to the right (P less than 0.05). Following papaveretum premedication the minute ventilation-carbon dioxide response curve slope, was decreased to 55% of its mean control volume value by the infusion, but this failed to reach statistical significance.

The haemodynamic response to tracheal intubation was compared in 303 patients in whom anaesthesia was induced with either thiopentone 4 mg/kg, etomidate 0.3 mg/kg or propofol 2.5 mg/kg, with and without fentanyl 2 micrograms/kg. There was after propofol alone a significant decrease in arterial blood pressure, which did not increase above control values after intubation. Significant increases in arterial pressure followed intubation in patients induced with thiopentone or etomidate alone. Increases in heart rate occurred with all agents after laryngoscopy. The use of fentanyl resulted in arterial pressures lower than those after the induction agent alone, and in an attenuation, but not abolition of the responses to laryngoscopy and intubation.

Propofol (2,6,di-isopropylphenol) was given by continuous intravenous infusion to provide sedation after cardiac surgery in 30 patients and its effects compared with those of midazolam given to a further 30 patients. Propofol infusion allowed rapid and accurate control of the level of sedation, which was satisfactory for longer than with midazolam. Patients given propofol recovered significantly more rapidly from their sedation once they had fulfilled the criteria for weaning from artificial ventilation and as a result spent a significantly shorter time attached to a ventilator. There were no serious complications in either group. Both medical and nursing staff considered the propofol infusion to be superior to midazolam in these patients. These findings suggest that propofol is a suitable replacement for etomidate and alphaxalone-alphadolone for sedating patients receiving intensive care.

We have compared the acute ventilatory changes during induction of anaesthesia with equipotent doses of thiopentone and propofol in 12 premedicated female patients. Using ventilatory inductance plethysmography we have shown that both agents depress respiration to a similar and significant degree (P less than 0.001). However, although the functional residual capacity was reduced in patients receiving propofol, it increased slightly after induction with thiopentone (P less than 0.05).

The ventilatory effects of induction of anaesthesia with either propofol 2.5 mg/kg or thiopentone 4.0 mg/kg have been observed in patients premedicated with either atropine alone or papaveretum and hyoscine. Induction of anaesthesia with propofol was accompanied by a greater degree of ventilatory depression which was of longer duration than following thiopentone. The effect was accentuated by the opioid premedication.

The relative potencies of the intravenous anaesthetics propofol and thiopentone have been investigated by finding the dose necessary to produce unconsciousness in approximately 30%, 50% and 80% of patients. The estimated potency of propofol to thiopentone was 1:1.604 as obtained by the probit method of analysis which estimates the logarithm of the relative potency.

Intravascular and airway pressures, cardiac output (CO) and blood gas tensions were measured in five adult patients after hepatobiliary surgery. They were ventilated at frequencies of 15, 100 and 200 breaths min-1 (bpm) with the respiratory fresh gas (RFG) supplied at the proximal and distal end of a Mallinckrodt Hi-Lo tracheal tube. The peak airway pressure (P AW) fell from 1.20 kPa at 15 bpm to 0.6 kPa at 100 bpm, rising again to 1.9 kPa at 200 bpm, and both changes were significant (P less than 0.05). The mean pulmonary artery pressure (PAMP) remained in the range 1.87-2.00 kPa (14-15 mmHg) at 15 and 100 bpm but rose to over 2.67 kPa (20 mmHg) at 200 bpm (P less than 0.05). Cardiac output, heart rate and systemic arterial pressure remained unchanged. A small but significant (P less than 0.05) reduction in PaCO2 occurred when the RFG was moved to the distal end of the tracheal tube. A theoretical analysis predicts that the minimal P AW to maintain CO2 hemostasis will occur between 30 to 100 bpm, which is reflected in the results of the present study.

General anaesthesia was induced with, and maintained by, an infusion of either propofol or methohexitone, in patients undergoing surgery with the aid of regional blockade. Both agents provided satisfactory and controllable anaesthesia. Complications were few with a similar incidence for the two drugs. Recovery from anaesthesia was significantly faster following propofol.

Four studies have been carried out on propofol in this department, one being part of a multicentre trial. The minimum induction dose in unpremedicated patients was found to be 2.5 mg/kg. Propofol has been shown to be an acceptable induction agent, although with an incidence of pain on injection which is much higher when small veins are used. When given by continuous infusion to supplement regional anaesthesia, recovery was much more rapid than with methohexitone. The potency of propofol to thiopentone has been shown to be 1:1.604. Slight falls in cardiac output occurred following propofol 2.5 mg/kg, with significant reductions in mean arterial blood pressure and systemic vascular resistance. These changes were greater than those following an equipotent dose of thiopentone 4 mg/kg.

The haemodynamic changes following induction of anaesthesia with equipotent doses of propofol and thiopentone have been compared. Propofol caused a significant fall in arterial blood pressure and total peripheral resistance, with a slight fall in cardiac output. There were no changes in heart rate. Apart from an initial, but statistically insignificant increase in heart rate, similar changes were produced by thiopentone, but to a lesser degree. It is concluded that induction of anaesthesia with propofol results in acceptable haemodynamic changes, but that the agent is more depressant to the cardiovascular system than thiopentone.