Reduction of isoflurane minimal alveolar concentration by remifentanil.
BACKGROUND
Remifentanil is a new micro-specific opioid receptor agonist currently under investigation. The interaction between opioids and volatile anesthetics is complex. Defining this interaction provides a basis for more rational dosing schemes when such combinations are used for anesthesia and allows the anesthetic potency of remifentanil relative to other opioids to be determined.


METHODS
Two centers enrolled a total of 220 patients. Patients were randomized to receive a target concentration of remifentanil via a computer-assisted continuous infusion device of either 0.0, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 16.0, and 32.0 ng/ml initiated before the administration of isoflurane. Patients were also stratified by groups 18-30, 31-55, and 56-65 yr. After induction of anesthesia with isoflurane the initial patient in each dose group was assigned an age-adjusted isoflurane concentration. The isoflurane concentration for each subsequent patient was adjusted according to the up/down technique until a minimum of 12 patients were enrolled in each group. Arterial blood samples for remifentanil whole blood concentrations were obtained. The patient was observed for purposeful movement for up to 1 min after skin incision. The minimum alveolar concentration (MAC) of isoflurane (0 ng/ml remifentanil group) and MAC reduction of isoflurane by remifentanil were determined.


RESULTS
The MAC of isoflurane alone was 1.3%. Remifentanil caused an exponential reduction in the MAC of isoflurane with 1.37 ng/ml remifentanil a 77% reduction and 32 ng/ml a 91% reduction of isoflurane MAC.


CONCLUSIONS
The MAC reduction of isoflurane by remifentanil is similar to that produced by other opioids. Although remifentanil was given at extremely high concentrations in the absence of isoflurane, it did not provide adequate anesthesia. A 50% isoflurane MAC reduction is produced by 1.37 ng/ml remifentanil whole blood concentration compared to previously published plasma concentrations of fentanyl of 1.67 ng/ml or sufentanil of 0.14 ng/ml.
Lang
E
E
Duke University Medical Center, Durham, North Carolina 27710, USA.
Kapila
A
A
Shlugman
D
D
Hoke
J F
JF
Sebel
P S
PS
Glass
P S
PS
D000293:Adolescent; D000328:Adult; D000368:Aged; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007530:Isoflurane / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D000077208:Remifentanil
D018685:Anesthetics, Inhalation; D010880:Piperidines; D007530:Isoflurane; D000077208:Remifentanil