The effects of i.v. infusions of althesin, ketamine and thiopentone were studied in instrumented rabbits, in doses that produced similar levels of light anesthesia. The main hemodynamic differences were in the rises in mean arterial pressure (MAP) and in total peripheral resistance (TPR) which were in the order of ketamine > thiopentone > althesin. These rises in MAP and TPR did not occur in sino-aortic denervated rabbits suggesting that in normal rabbits these depended on the integrity of the arterial baroreceptors and/or chemoreceptors. The heart rate increased with all anesthetics mainly owing to reduction in vagal efferent activity, except with althesin where cardiac sympathetic activity increased also. Baroreceptor—heart rate reflex properties were studied by deriving sogmoid curves relating MAP to heart period (HP, i.e. pulse interval). All drugs depressed the following curve parameters: (i) HP range, i.e. the difference in HP plateaux from maximal tachycardia to maximal bradycardia; and (ii) the reflex gain (sensitivity). The order of depression was ketamine > thiopentone > althesin, i.e. the same as the order in which they evoked pressor effects. The results suggest that the 3 anesthetics produce differing depression of afferent mechanisms related to baroreceptor reflexes and that this accounts for both the differences in pressor effects (through disinhibition of constrictor tone) and in depression of the vagal and sympathetic components of the baroreceptor—heart rate reflex.

Role of baroreceptor reflexes in the hemodynamic and heart rate responses to althesin, ketamine and thiopentone anesthesia

SUMMARY Althesin was compared with thiopentone in the induction of anaesthesia in 240 patients who received Althesin 30, 50 or 70 μ1/kg or thiopentone 3, 5 or 7 mg/kg. Half of the patients received pethidine and atropine for premedication and 120 promethazine in addition. According to the ED50 values for the loss of eyelid reflex Althesin 30 μ1/kg was roughly equipotent to thiopentone 3 mg/kg. The dose-response curve of thiopentone, however, seemed to be steeper than that of Althesin. The ratio ED50 apnoea/ED50 loss of eyelid reflex was higher for Althesin (0.86) than for thiopentone (0.69). The changes in blood pressure and heart rate both during induction and operation were similar but the incidence of per- and postoperative untoward effects was slightly though not significantly higher after Althesin.

A comparison of althesin and thiopentone in induction of anaesthesia

Cardiorespiratory effects of ketamine and Althesin were measured in two groups of premedicated patients with cardiac disease The drugs were given in clinically equivalent doses with a second dose administered about 10 min after induction The first dose of ketamine caused a marked increase in systemic and pulmonary arterial pressure, heart rate, and central venous and wedge pressures and cardiac index The first dose of Althesin caused a decrease in systemic arterial pressure, central venous pressure, cardiac index and heart work, but little change in heart rate The second dose of induction agent was administered before the cardiorespiratory effects of the initial dose had resolved The second dose of Althesin caused changes similar to thosefollowing the first dose, but less marked The changes following the second dose of ketamine were opposite to those following the first dose

A comparison of some cardiorespiratory effects of althesin and ketamine when used for induction of anaesthesia in patients with cardiac disease

SUMMARY Changes in cerebrospinal fluid pressure after induction of anaesthesia with Althesin were recorded in 21 volunteer patients who had no abnormality of the central nervous or cardiorespiratory systems. In patients who breathed spontaneously, cerebrospinal fluid pressure fell by 45% at 1 min after intravenous injection of Althesin 0.1 ml/kg. It returned almost to preinduction levels by 12 min During this time, there was a slight increase in Pa co 2 . When Pa co 2 was controlled by mechanical ventilation, the cerebrospinal fluid pressure fell slightly more; by 53% when Pa co 2 , was kept between 38–42 mm Hg and by 50% when Pa co 2 was maintained between 30–34 mm Hg. The significant fall of cerebrospinal fluid pressure produced by Althesin in conjunction with the rapid clear-headed recovery, may allow Althesin to be a valuable anaesthetic for neurosurgical procedures.

Effects of althesin on cerebrospinal fluid pressure

Ten male volunteers received a 1-min i.v. infusion of a new water soluble steroid anaesthetic agent, ORG 21465. Individuals received doses ranging from 0.8 to 1.8 mg kg-1. All subjects experienced venous pain at the site of injection; those receiving 1.0 mg kg-1 or more became anaesthetized. There was no evidence of histamine release and apnoea did not occur. Excitatory phenomena were observed in all subjects and were dose related; no spikes were seen on the EEG. Pharmacokinetic analysis supported a three-compartment (non-weight-related) model with compartmental volumes V1, V2 and V3 of 4.31, 14.2 and 89.4 litre, respectively. Clearance from the central compartment V1 was 1.55 litre min-1. Inter-compartmental clearances Q1 and Q2 were 2.54 and 1.79 litre min-1. We found that ORG 21465 was an effective anaesthetic in humans. The relationship between sedation, anaesthesia and excitation requires further exploration.

Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent.

SUMMARY The interaction of the steroid anaesthetic agent CT1341 with selected muscle relaxants and volatile agents has been investigated in man. In four patients the effect at the neuromuscular junction was examined. No effect was seen with CT1341 alone and there was no clinically significant interaction with tubocurarine, pancuronium or suxamethonium. A further forty patients in six groups were anaesthetized using CT1341 and either pancuronium or tubocurarine with controlled respiration. One of the volatile agents, halothane, trichloroethylene or methoxyflurane, was then administered and the resulting effect on electrocardiogram, systolic and diastolic blood pressure, pulse rate and nasopharyngeal temperature noted. Three patients given methoxyflurane developed a marked sinus tachycardia which could be evidence of drug interaction. No other effect was observed.

D. Campbell

Papers

Ct1341: interaction with some anaesthetic agents

Haemodynamic effects of Althesin in poor-risk patients.

Althesin: further studies of interaction with anaesthetic agents.