A Response Surface Model Approach for Continuous Measures of Hypnotic and Analgesic Effect during Sevoflurane–Remifentanil Interaction

Heyse, Björn; Proost, Johannes H.; Hannivoort, Laura N.; Eleveld, Douglas J.; Luginbühl, Martin; Struys, Michel; Vereecke, Hugo

doi:10.1097/aln.0000000000000180

Cited by 24 publications

(15 citation statements)

References 13 publications

(16 reference statements)

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“…Several factors need to be taken into account. First, the residual and waning effects of the intravenous induction agents (propofol, opioids) need to be taken in consideration, as well as the drug interactions between all these drugs [12,13]. Second, the rate of rise has to be titrated not only towards the physiological reserve of the patient but also towards the anticipated time of incision.…”

Section: Discussionmentioning

confidence: 99%

Automated gas control with the Maquet FLOW-i

Carette

Wolf

Hendrickx

2015

J Clin Monit Comput

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The FLOW-i anesthesia machine (Maquet, Solna, Sweden) can be equipped with automated gas control (AGC), an automated low flow tool with target control of the inspired oxygen concentration (FIO2) and end-expired concentration (FA) of a potent inhaled anesthetic. We examined the performance and quantitative aspects of the AGC. After IRB approval and individual informed consent, anesthesia in 24 ASA I-II patients undergoing abdominal or gynecological surgery was maintained with sevoflurane in O2/air with a target FIO2 of 40 % and a target sevoflurane FA (FAsevo) of 2.0 %. The AGC tool also allows the user to select 1 out of 9 different speeds with which the target FAsevo can be reached (with 9 being the fastest speed). Eight patients each were randomly assigned to speed 2, 4, and 6 (= group 2, group 4, and group 6, respectively); these three speeds were chosen arbitrarily. AGC was activated immediately after securing the airway, which defined the start of the study, and the study ended 60 min later. The following parameters were compared among the three groups: age, height, weight, FIO2, FAsevo, BIS values, heart rate, mean arterial blood pressure, fresh gas flow, and sevoflurane usage. Agent usage as reported by the FLOW-i was compared among the three groups. Patient demographics and maintenance FGF did not differ among groups. A very short-lived very high FGF (≈20 L min(-1) for 8-12 s) ensured that the target FIO2 was attained within 1-2 min in all patients. FAsevo was 1.8 % after 15, 10, and 6 min, and 1.9 % after 30, 20 and 15 min in groups 2, 4, and 6, respectively. Blood pressure, heart rate, and BIS values did not differ among the three groups. BIS values remained acceptable in all patients, even with the slowest speed. Cumulative agent usage differed among all three groups between 2 and 30 min (lower with the lower speed), and between group 2 and 6 between 35 and 60 min. AGC combines an exponentially decreasing FGF pattern with a choice of ramp functions for the end-expired target concentration of the inhaled anesthetic. Consequently, both FGF and the choice of speed become factors that influence agent usage. After 15 min, a 300 mL min(-1) maintenance FGF reduces agent usage to near closed-circuit conditions. This new addition to our automated low flow armamentarium helps to reduce anesthetic waste, cost, and pollution, while minimizing the ergonomic burden of low flow anesthesia.

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Section: Discussionmentioning

confidence: 99%

Automated gas control with the Maquet FLOW-i

Carette

Wolf

Hendrickx

2015

J Clin Monit Comput

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“…Unlike studies that attempted to identify the effective dose of sevoflurane in combination with different bolus doses of remifentanil, [7,8] this study controlled the participants’ age and general condition within a very narrow range. Only ASA class I patients aged 19 to 28 years participated in this study.…”

Section: Discussionmentioning

confidence: 99%

“…The other studies that have described additive or synergistic effects of the remifentanil–sevoflurane combination support the results of this study. [7,8] …”

Section: Discussionmentioning

confidence: 99%

“…[8] However, to our knowledge, no studies have identified the effective dose of sevoflurane in combination with different clinically used bolus doses of remifentanil to obtain adequate endotracheal intubation conditions without neuromuscular blockade. The aim of this study was to investigate the optimal exhaled sevoflurane concentration that produces adequate conditions for endotracheal intubation without neuromuscular blockade when sevoflurane is combined with the different bolus doses of remifentanil commonly used in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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The optimal exhaled concentration of sevoflurane for intubation without neuromuscular blockade using clinical bolus doses of remifentanil

2017

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Background:The aim of this study was to investigate the optimal exhaled sevoflurane concentration that produces adequate endotracheal intubation conditions when sevoflurane is combined with the different bolus doses of remifentanil used in clinical practice.Methods:The patients were randomized to 3 groups (groups 1.0, 1.5, and 2.0), receiving remifentanil bolus doses of 1.0, 1.5, and 2.0 μg/kg, respectively. For each group, the concentration of sevoflurane used for each consecutive patient was increased or decreased using the “up-and-down” method based on the success or failure to achieve adequate conditions for intubation in the previous patient. The remifentanil bolus dose was administered 90 s before intubation and after the target sevoflurane concentration was achieved.Results:In groups 1.0, 1.5, and 2.0, the effective concentration in 50% (EC50) of the sevoflurane concentration required to perform successful intubation was 3.0, 2.0, and 1.29 vol% and the effective concentration in 95% was 3.45, 2.91, and 1.89 vol%, respectively. When sevoflurane was administered for the induction, the increase in heart rate (HR) of group 1.0 was the highest among the groups. The highest number of adverse events occurred in group 2.0, including vocal cord rigidity, hypotension, and bradycardia.Discussion:The EC50 of the sevoflurane concentration was 3.0, 2.0, and 1.29 vol% when it was combined with a bolus dose of remifentanil of 1.0, 1.5, and 2.0 μg/kg, respectively. Of the 3 different bolus doses of remifentanil, the dose of 1.5 μg/kg was least associated with changes in the HR/mean blood pressure during intubation without increasing adverse effects.

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“…assumed that the concentration‐response relationship for each of the interacting drugs could be described using a direct pharmacodynamic model . The pharmacodynamic interaction between the two drugs has been well described by the Minto model in several studies . The Minto model is subject to interactive effects between propofol and remifentanil on muscle rigidity.…”

Section: Discussionmentioning

confidence: 99%

Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia

Choe

Choi

Lee

et al. 2016

Clin Exp Pharma Physio

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This study describes the pharmacodynamic interaction between propofol and remifentanil. Sixty patients who were scheduled for elective surgery under general anaesthesia (30 males/30 females) were enrolled. Patients were randomly allocated to receive one of 15 combinations of drug levels. Baseline electroencephalograms (EEGs) were recorded for 5 minutes prior to administering the drugs. Patients received a target-controlled infusion at one of four predefined doses of propofol (high, 3 μg/mL; medium, 1.5 μg/mL; low, 0.5 μg/mL; or no drug) and of remifentanil (high, 6 or 8 ng/mL; medium, 4 ng/mL; low, 2 ng/mL; or no drug). The occurrence of muscle rigidity, apnoea, and loss of consciousness (LOC) was monitored, and EEGs were recorded during the drug administration phase. Electroencephalographic approximate entropy (ApEn) and temporal linear mode complexity (TLMC) parameters at baseline and under steady state conditions were calculated off-line. Response surfaces were developed to map the interaction between propofol and remifentanil to the probability of occurrence for quantal responses (muscle rigidity, apnoea, LOC) and ApEn and TLMC measurements. Model parameters were estimated using non-linear mixed effects modelling. The response surface revealed infra-additive and synergistic effects for muscle rigidity and apnoea, respectively. The effects of the combined drugs on LOC and EEG parameters (eg, ApEn and TLMC) were additive. The C estimates of remifentanil (ng/mL) and propofol (μg/mL) were 9.11 and 130 000 for muscle rigidity, 8.99 and 6.26 for apnoea, 13.9 and 3.04 for LOC, 23.4 and 10.4 for ApEn, and 14.8 and 6.51 for TLMC, respectively. The probability of occurrence for muscle rigidity declined when propofol was combined with remifentanil.

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A Response Surface Model Approach for Continuous Measures of Hypnotic and Analgesic Effect during Sevoflurane–Remifentanil Interaction

Cited by 24 publications

References 13 publications

Automated gas control with the Maquet FLOW-i

Automated gas control with the Maquet FLOW-i

The optimal exhaled concentration of sevoflurane for intubation without neuromuscular blockade using clinical bolus doses of remifentanil

Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia

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