Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium.
BACKGROUND
The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of action.


METHODS
Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35.0 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, and > or = 37.0 degrees C. With temperature stabilized, vecuronium was infused at 5 microg x kg(-1) x min(-1) until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 microg x kg(-1) x min(-1), was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics and pharmacodynamics.


RESULTS
Decreasing core temperature over 38.0-34.0 degrees C decreases the plasma clearance of vecuronium (11.3% per degrees C), decreases the rate constant for drug equilibration between plasma and effect site (0.023 min(-1) per degrees C), and increases the slope of the concentration-response relationship (0.43 per degrees C).


CONCLUSIONS
Our results show that reduced clearance and rate of effect site equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influenced by core temperature.
Caldwell
J E
JE
Department of Anesthesia and Perioperative Care, University of California-San Francisco, 94143-0648, USA. caldwell@anesthesia.ucsf.edu
Heier
T
T
Wright
P M
PM
Lin
S
S
McCarthy
G
G
Szenohradszky
J
J
Sharma
M L
ML
Hing
J P
JP
Schroeder
M
M
Sessler
D I
DI
D000328:Adult; D015760:Alfentanil; D000769:Anesthesia, Inhalation; D018686:Anesthetics, Intravenous; D001831:Body Temperature; D005260:Female; D006801:Humans; D007035:Hypothermia / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015742:Propofol; D012737:Sex Factors; D014673:Vecuronium Bromide / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D003473:Neuromuscular Nondepolarizing Agents; D015760:Alfentanil; D014673:Vecuronium Bromide; D015742:Propofol