[Pharmacodynamic interaction between propofol and remifentanil on the tolerance response to electrical tetanus stimuli].
OBJECTIVE
To describe the pharmacodynamic interaction between propofol and remifentanil in suppressing somatic and hemodynamic responses to electrical tetanus stimuli (ETS) during induction of intravenous anesthesia with response surface method.


METHODS
Seventy patients of ASA I or II, aged 18-65 years, scheduled for elective surgery were anesthetized by propofol and remifentanil. Propofol was administered with a target-controlled infusion (TCI) device at a target concentration that remained constant throughout the study, and remifentanil was administered with a TCI device at increasing staircase target concentrations. The somatic and hemodynamic responses to electrical tetanus stimuli were assessed multiple times after allowing for plasma effect site equilibration. The pharmacodynamic interaction between propofol and remifentanil was analyzed by response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM.


RESULTS
Response surface method characterized the pharmacodynamic interactions between propofol (0-9 mg/L) and remifentanil (0-10 μg/L) qualitatively and quantitatively. The three-dimensional response surfaces showed considerable synergy between propofol and remifentani for blunting somatic and hemodynamic responses to ETS. When the target concentration of remifentani was 1 μg/L, 2 μg/L and 3 μg/L, the C50 of propofol for blunting somatic responses to ETS decreased by 40.1%, 71.5% and 82.1% respectively; and the C50 of propofol for blunting hemodynamic responses to ETS decreased by 45.0%, 72.8% and 83.7% respectively. However, further increases in remifentanil only modestly reduced the C50 of propofol associated with loss of response to ETS. Ceiling effect was seen.


CONCLUSIONS
Response surface method can analyze the pharmacodynamic interactions qualitatively and quantitatively. The response surface models revealed the significant synergy between propofol (≤9 mg/L) and remifentanil (≤10 μg/L) for blunting somatic and hemodynamic responses to electrical tetanus stimuli. The ceiling effects of remifentanil were demonstrated in the reduction of propofol C50 regarding tolerance of responses to ETS.
Yang
Lu
L
Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
Wei
Bin
B
Zhang
Li-ping
LP
Bi
Shan-shan
SS
Lu
Wei
W
Guo
Xiang-yang
XY
D000293:Adolescent; D000368:Aged; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D017558:Elective Surgical Procedures; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D011446:Prospective Studies; D000077208:Remifentanil; D055815:Young Adult
D018686:Anesthetics, Intravenous; D010880:Piperidines; D000077208:Remifentanil; D015742:Propofol