Effects of hypothermic cardiopulmonary bypass on the pharmacodynamics and pharmacokinetics of rocuronium.
OBJECTIVE
To study the influence of hypothermic cardiopulmonary bypass (CPB) on the pharmacodynamics and pharmacokinetics of rocuronium.


METHODS
Prospective, descriptive study.


METHODS
Operating room at a university hospital.


METHODS
Ten ASA class III and IV patients, ranging in age from 35 to 75 years, scheduled for elective coronary artery bypass grafting.


METHODS
Neuromuscular transmission was monitored mechanomyographically. The time course of action of maintenance doses and plasma concentration-response relationships were determined before, during, and after CPB. The plasma concentration decay and renal elimination were studied simultaneously. Plasma and urine concentration of rocuronium were determined by high-performance liquid chromatography.


RESULTS
Hypothermic CPB prolonged the duration of action of maintenance doses and coincided with a lower plasma concentration at a twitch response of 5% of control. The duration of action of maintenance doses returned to prehypothermic CPB level after rewarming to a nasopharyngeal temperature of 37 degrees C. The plasma concentration-response relationship did not return to precooling control value, probably owing to persisting peripheral hypothermia. Both the renal elimination of rocuronium and the plasma concentration decay after the last maintenance dose under normothermic conditions resembled values obtained in patients not undergoing hypothermic CPB.


CONCLUSIONS
Hypothermic CPB prolongs the duration of action of maintenance doses and alters the plasma concentration-response relationship of rocuronium. These changes may be the result of, on the one hand, an increased sensitivity of the neuromuscular transmission and/or decreased muscle contractility and, on the other hand, the result of a reduced plasma clearance during hypothermia.
Smeulers
N J
NJ
Research Group for Experimental Anesthesiology and Clinical Pharmacology, University Hospital, Groningen, Netherlands.
Wierda
J M
JM
van den Broek
L
L
Gallandat Huet
R C
RC
Hennis
P J
PJ
D000328:Adult; D000368:Aged; D000732:Androstanols / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D002315:Cardiopulmonary Bypass; D002851:Chromatography, High Pressure Liquid; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D017558:Elective Surgical Procedures; D004576:Electromyography; D006801:Humans; D007036:Hypothermia, Induced; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D011446:Prospective Studies; D017694:Rewarming; D000077123:Rocuronium; D009435:Synaptic Transmission / Q000187:drug effects; D014459:Ulnar Nerve / Q000187:drug effects
D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium