Canadian Journal of Anesthesia, Vol 4, 295-337, Copyright © 1957 by Canadian Anesthesiologists' Society

The Physiological Effects of Intravenous Anaesthesia on Man

¹ Department of Anaesthesia, University of Saskatchewan College of Medicine and University Hospital, Saskatoon, Canada

The problems of comparing several anaesthetics are reviewed with particular reference to the effects of premedication, the intrinsic activity of drugs and their affinity for certain tissues and the effect of multiple drug interaction. The physiological and pathological states of those patients who are used as subjects of such studies are essential factors to be clearly determined. The effects of acute tolerance, cumulation and tachyphylaxis were also cited as factors to be considered.

A controlled study of respiratory and haemodynamic parameters was carried out on eight young healthy male subjects in order to determine the principal and statistically significant effects of thiopental, thiamylal, hexobarbital, buthalitone, methitural, Compound 25398 and Dolitrone.

Resting vital signs were initially obtained as well as other vital statistics. Basal metabolism and cardio-respiratory parameters were determined from nomograms related to the resting values. These data provided the base line for all control and experimental data. Plasma volume and red cell volume were initially determined simultaneously with radioactive iodinated human serum albumin (I¹³¹) and radioactive chromium⁵¹, employing the dilution principle. These were checked against venous haematocrit determinations.

Respiration data were obtained on a recording spirometer which also recorded oxygen consumption. Cardiovascular data (arterial and venous blood pressure) were recorded via intra-arterial and intravenous needles attached to Statham strain gauges, oscilloscopes and a photographic recorder. The pulse rate and electrocardiogram (lead 2) were also recorded on this system. The cardiac out-put was estimated by external body-counting of I¹³¹ following single injections of Rihsa, using a shielded scintillation detector directed over a fixed site on the chest where tissue circulation was minimal, in order to measure primarily the blood flow in the aortic arch. Mean circulation time and cardiac output were derived from measurements on the recordings, and stroke volume, total peripheral resistance, left ventricular work and intrathoracic blood volume were computed from the above data.

All data were analysed for mean alterations, and statistical significance was computed to determine the probability (P value) of random variation by the method of the Fisher t-test.

The accuracy of the technical procedures employed was reviewed, with particular reference to the newer methods for estimating blood volume, cardiac output and mean circulation time, and was found to compare reliably with that of tried and recognized methods. The limitations of clinical studies were also discussed, and data from animal studies were reviewed with a view to supplementing information on the toxicity and cumulative effects of these drugs.

A conservative evaluation of the results was essential in this study since it was assumed that deviations of values were normally distributed, and that the study dealt essentially with the healthiest type of subjects one ever encounters in clinical practice. The authors also felt, as noted by Johnson and Van Harreveld, that so many factors are involved in cardio-respiratory regulation, both before and during anaesthesia, that one must be extremely cautious in stating which factor is primarily involved in a change. One must therefore avoid conclusions from individual changes and base critical evaluation on consistent and statistically significant changes in a "homogenous" group, and then perhaps apply these data to an individual.

From the experiments, the seven intravenous anaesthetics studied could be divided into two main groups: those that produced a prolonged depression of respiration and circulation; and those that produced a brief depression of these parameters. Compound 25398, thiamylal and thiopental belong to the first group, while methitural, Dolitrone, hexobarbital and buthalitone belong to the second. All the drugs except hexobarbital depressed oxygen consumption. Tachycardia was a significant finding with all the drugs except methitural and acute hypotension (arterial and venous) was a consistent finding with all the drugs. Considering all the parameters, myocardial depression was induced by the first group, but this was not consistently manifested by a decrease in the cardiac output.

From this investigation, it is difficult to choose among the agents and state which disturbs human physiology to the least extent while providing clinically adequate hypnosis. It is only possible to state the advantage of a particular agent with reference to a specific patient, a specific type of operation and a specific clinical situation. On this basis, extensive clinical experience with one agent is probably the most reliable method of managing most situations, for then the problem comes down to a matter of dosage, concentration of the drug, and rate of its administration.