Propofol Reduces Perioperative Remifentanil Requirements in a Synergistic Manner

Leiden University, Leyden, South Holland, Netherlands
Anesthesiology (Impact Factor: 5.88). 09/2003; 99(2):347-59. DOI: 10.1097/00000542-200308000-00016
Source: PubMed


Remifentanil is often combined with propofol for induction and maintenance of total intravenous anesthesia. The authors studied the effect of propofol on remifentanil requirements for suppression of responses to clinically relevant stimuli and evaluated this in relation to previously published data on propofol and alfentanil.
With ethics committee approval and informed consent, 30 unpremedicated female patients with American Society of Anesthesiologists physical status class I or II, aged 18-65 yr, scheduled to undergo lower abdominal surgery, were randomly assigned to receive a target-controlled infusion of propofol with constant target concentrations of 2, 4, or 6 microg/ml. The target concentration of remifentanil was changed in response to signs of inadequate anesthesia. Arterial blood samples for the determination of remifentanil and propofol concentrations were collected after blood-effect site equilibration. The presence or absence of responses to various perioperative stimuli were related to the propofol and remifentanil concentrations by response surface modeling or logistic regression, followed by regression analysis. Both additive and nonadditive interaction models were explored.
With blood propofol concentrations increasing from 2 to 7.3 microg/ml, the C(50) of remifentanil decreased from 3.8 ng/ml to 0 ng/ml for laryngoscopy, from 4.4 ng/ml to 1.2 ng/ml for intubation, and from 6.3 ng/ml to 0.4 ng/ml for intraabdominal surgery. With blood remifentanil concentrations increasing from 0 to 7 ng/ml, the C(50) of propofol for the return to consciousness decreased from 3.5 microg/ml to 0.6 microg/ml.
Propofol reduces remifentanil requirements for suppression of responses to laryngoscopy, intubation, and intraabdominal surgical stimulation in a synergistic manner. In addition, remifentanil decreases propofol concentrations associated with the return of consciousness in a synergistic manner.

Download full-text


Available from: Jaap Vuyk,
90 Reads
    • "In this scenario we have documented that propofol, a drug that is usually associated with opioids in course of TCI–TIVA procedures in animals (Gozalo-Marcilla et al., 2015; Knobloch et al., 2006; Seddighi and Doherty, 2012), does not modify the bronchial responsiveness of equine isolated bronchi stimulated by EFS and that it is characterized by a good safety profile in a wide range of concentrations, included those used for inducing deep anaesthesia (Franci et al., 2012; Mertens et al., 2003b; Milne et al., 2003; Nolan and Hall, 1985). Our study provides an important piece of information concerning the role of propofol on the modulation of equine bronchial tone since we have demonstrated that the relaxant activity of this drug is mainly mediated by nitric oxide, as the selective iNOS inhibitor BYK191023 prevented the protective role of propofol against the BHR induced by remifentanil. "
    [Show abstract] [Hide abstract]
    ABSTRACT: General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contractile response of equine isolated bronchi to electrical field stimulation (EFS) was assessed. The role of capsaicin-sensitive sensory nerves, inducible nitric oxide synthase (iNOS) and neurokinin 2 (NK2) receptor was also assessed. The interaction analysis was performed by Bliss Independence theory. Experiments were repeated in desensitized and passively sensitized airways. Remifentanil induced BHR in both non-sensitized and passively sensitized bronchi, (+56.33±8.01% and +99.10±14.52%, respectively; P<0.01 vs. control) and propofol significantly prevented this effect (P>0.05 vs. remifentanil). The inactivation of capsaicin sensory nerves via desensitization and blocking NK2 receptor inhibited the BHR remifentanil induced (P>0.05 vs. controls). The inhibition of iNOS reverted the protective effect of propofol on the BHR induced by remifentanil (non-sensitized: +47.11±7.70%; passively sensitized: +70.51±11.39%; P<0.05 vs. control tissues). Propofol synergistically interacted (overall ≈40%) in preventing the remifentanil-induced BHR. Remifentanil induces BHR via stimulating sensitive sensory nerves that facilitate the cholinergic neurotransmission through the activation of NK2 receptor. The propofol/remifentanil combination may be safely administered in course of TCI-TIVA procedures also in heaves affected horses.
    European journal of pharmacology 09/2015; DOI:10.1016/j.ejphar.2015.09.007 · 2.53 Impact Factor
  • Source
    • "Propofol and remifentanil are commonly co-administered in intravenous anesthesia and have shown a synergistic effect [1,2]. However, reports on hypnotic interaction between propofol and remifentanil measured by bispectral index (BIS) have been a few and contradictory [3-7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Propofol and remifentanil are usually co-administered and have shown synergistic effect for anesthesia. However, the synergistic effect of the two drugs on hypnosis measured by bispectral index (BIS) was controversial in previous studies. The aim of this study was to identify the interaction of propofol and remifentanil on BIS and the optimal dose combinations for hypnosis under 66% N(2)O during surgery. Patients (age 55-75 and American Society of Anesthesiologists [ASA] 1-2) undergoing gastrectomy were enrolled in this study. Propofol and remifentanil were co-administered incrementally at 1 : 1 potent ratio (the P1R1 group), at 1 : 2 potent ratio (the P1R2 group), or at 2 : 1 potent ratio (the P2R1 group) using effect site target-controlled infusion and BIS was measured. 66% N(2)O was concomitantly administered to all groups. The dose-effect curves, the 90% effective dose (EC(90)) for adequate hypnosis (BIS 40), isobolograms and combination index were obtained by Calcusyn program (Biosoft) to reveal the interaction of propofol and remifentanil. The P2R1 group showed synergistic action on BIS. However, the other groups needed larger amount of each drug than the doses of additive action. The EC(90) of the P2R1 group was propofol, 3.34 µg/ml and remifentanil, 2.41 ng/ml under 66% of N(2)O. Propofol dominant co-administration is needed for dose reduction in BIS guided hypnosis.
    Korean journal of anesthesiology 12/2010; 59(6):371-6. DOI:10.4097/kjae.2010.59.6.371
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The optimal dose of propofol and remifentanil induction to minimize the cardiovascular response associ-ated with tracheal intubation may exist. We investigated the cardiovascular response associated with tracheal intubation when various continuous induction doses of remifentanil in combination with propofol were used. Methods: Seventy-five patients were randomly allocated into 1 of 3 groups: the R-0.4 P-1 group (remifentanil 0.4 μg/kg/min and propofol 1 mg/kg); the R-0.5 P-1 group (remifentanil 0.5 μg/kg/min and propofol 1 mg/kg); and the R-0.4 P-2 group (remifen-tanil 0.4 μg/kg/min and propofol 2 mg/kg). One minute after remifentanil infusion commenced, a bolus of propofol was injected. Rocuronium 1 mg/kg was administered 1 min after propofol injection following loss of consciousness. Con-trolled ventilation was then performed for 2 min, and the trachea was intubated 4 min after the start of the remifentanil infusion. The infusion rate of remifentanil was decreased to 0.1 μg/kg/min after intubation. Blood pressure (BP) and heart rate (HR) were measured during this period until 5 min after tracheal intubation. Results: The changes in BP re-sponse due to tracheal intubation in the R-0.4 P-1 group were greater than those in the other 2 groups, whereas the HR responses to tracheal intubation were similar among the 3 groups. Conclusion: The combination of remifentanil 0.4 μg/kg/min and propofol 1 mg/kg led to an exaggerated cardiovascular response to tracheal intubation compared with the other combination groups.
    Open Journal of Anesthesiology 01/2012; 02(04). DOI:10.4236/ojanes.2012.24035
Show more