Mild Hypothermia Alters Propofol Pharmacokinetics and Increases the Duration of Action of Atracurium

Abstract

Comment This is one of those studies that really has its act together! It was well thought out in advance, the methods are sound, the data are good, and in the Discussion the authors have critiqued their findings appropriately. The authors report the results of two separate studies of the effect of hypo-thermia on pharmacokinetics. The studies look at the effect of mild hypodiermia on the pharmacokinetics of propofol and atracurium in anesdietized volunteers. They conclude that propofol decreases hepatic blood flow and, thereby, reduces its own clearance and elevates propofol blood levels. The findings with atracurium were not so clear. The duration of action of atracurium was increased approximately 60% by 3®C core hypodiermia. Recovery of the first twitch of a train-of-four to 10% was delayed but the recovery from 25 to 75% was not. Of several possible mechanisms, the effect of hypodiermia on the unique metabolism of atracurium seems most plausible. There are two minor problems with this study that the reader should consider. First, understandably, the number of subjects was small, only six. Each subject was studied twice, at least 1 wk apart. However, this was a study of normal volunteers, and it required approximately 7 hr of general anesthesia to complete each study. It would be difficult to carry out this study on a large number of subjects. Second, the authors used clearance of indocyanine green to estimate total hepatic blood flow and assumed that the effects of their administrations would be the same on each of the elements of total hepatic blood flow and hepatic arterial and portal venous blood flow. Hursh and colleagues have shown that this may not be the case with isoflurane and halotiiane.1 Direct measurement of total hepatic blood flow requires cannulation of the portal vein, hepatic artery, and vena cava, which are highly invasive procedures. This.