Interaction of Sevoflurane Propofol and Remifentanil in Anesthesia for Laparoscopic Surgery

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

172 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2023-10-23

Brief Summary

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Recently a new model for the interaction of sevoflurane propofol and remifentanil was developed. The potency of any combination of the three drugs is defined as probability that a subject tolerates laryngoscopy without movement response. The model allows to compare the potency of intravenous and inhalation anesthetics. If the model is valid also for other stimuli than laryngoscopy and for other responses (e.g. blood pressure or heart rate increase upon stimulation). If the model is valid equipotent concentrations of sevoflurane and propofol the same remifentanil concentration would be sufficient to suppress hemodynamic response to a given stimulus. This will be investigated it the study.

Detailed Description

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Background

In general anesthesia propofol or volatile anesthetic are usually combined with opioids and the synergy between hypnotics and opioids is used to reduce the dose of each component in order to minimize side effects and to allow a rapid recovery. Current pharmacodynamic interaction models allow to estimate the potency of combinations of propofol and opioids, volatile anesthetics and opioids or propofol and sevoflurane respectively. In these interaction models the potency of the drug combinations is expressed as probability that motor response to laryngoscopy is suppressed (= tolerance of laryngoscopy, PTOL). The potency of the hypnotic drugs is represented by the concentration preventing motor response to laryngoscopy in 50% of the population (Ce50 hypnotic). Conversely potency of the opioids is represented as concentration reducing the Ce50 of the hypnotics by 50%.

The data of the three previous studies on propofol-remifentanil, propofol-sevoflurane and sevoflurane-remifentanil interaction were pooled and reanalyzed. The result was a triple interaction model of sevoflurane, propofol and remifentanil where sevoflurane and propofol were additive and either propofol or sevoflurane were synergistic with remifentanil. In contrast to the previous studies the response surface of the propofol-remifentanil and sevoflurane-remifentanil derived from the pooled re-analysis had a similar shape, which is reflected by a common C50 remifentanil and a common slope parameter. This means that remifentanil is equally synergistic to propofol and sevoflurane. The next step is to validate this interaction model with other stimuli than laryngoscopy and with other responses to stimulation that movement.

In clinical practice not motor response but hemodynamic response (heart rate and arterial blood pressure increase) upon surgical stimulation is used to titrate anesthetics and opioids.

In laparoscopic surgery after a small skin incision, carbon dioxide is inflated into the abdominal cavity to maintain an intraabdominal pressure of 14 mmHg. Recently the sevoflurane concentration preventing a heart rate or blood pressure increase greater than 20% upon installation of pneumoperitoneum (MAC BAR pneumoperitoneum) has been determined: The MAC BAR pneumoperitoneum (95% CI) of sevoflurane was 4.6 (4.3-4.9) without opioids and 2.4 (2.2-2.6) and 1.7 (1.4-2.1) vol% with an effect site remifentanil concentration of 1 and 2 ng ml-1.These values all correspond to 90% probability to tolerate laryngoscopy (PTOL) according to our triple interaction model (Hannivoort, BJA 2016), which indirectly supports our model.

The main purpose of this randomized controlled study is to validate our sevoflurane-propofol-remifentanil interaction model using skin incision and carbon dioxide insufflation (pneumoperitoneum) as stimulus and blood pressure and heart rate response as endpoint.

Objective

To determine the C50 remifentanil preventing a 20% increase of heart rate or mean arterial pressure upon installation of pneumoperitoneum at equipotent concentrations of sevoflurane or propofol To determine the C50 of sevoflurane and propofol preventing a 20% increase of heart rate or mean arterial pressure upon installation of pneumoperitoneum at a standardized concentration of remifentanil

To determine the C50 of propofol or sevoflurane preventing a 20% increase of heart rate or mean arterial pressure upon installation of pneumoperitoneum at standardized concentrations of remifentanil plus sevoflurane or propofol respectively.

Methods

Patients will be randomly assigned to six groups with different propofol sevoflurane and remifentanil target concentrations for skin incision: Two groups with be given propofol-remifentanil, sevoflurane-remifentanil and sevoflurane-propofol-remifentanil respectively. The up-and-down method will be applied to determine the C50ies. During surgery primarily remifentanil and secondarily sevoflurane or propofol are titrated to maintain mean arterial pressure and bispectral index within predefined limits.

Conditions

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Drug Interactions Anesthesia, Conduction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Intervention Type DRUG

Triple combination with intermediate propofol and sevoflurane and intermediate remifentanil.

Changing Sevoflurane for skin incision.

Triple combination with intermediate propofol and sevoflurane and intermediate remifentanil.

Changing Sevoflurane for skin incision.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* ASA physical status 1 or 2
* Written informed consent

Exclusion Criteria

* Cardiovascular disease
* Pulmonary disease
* Liver disease
* CNS disease
* Alcohol or drug abuse
* Chronic intake of CNS active drugs
* Body mass index \> 35
* Diabetes mellitus
* Hypersensitivity or allergy to one of the study drugs

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin Luginbühl, PD Dr. med.

Role: STUDY_CHAIR

Spital Tiefenau, Inselgruppe, Abteilung für Anästhesie und Intensivmedizin

Locations

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Department of Anesthesiology and Pain Therapy, Bern University Hospital

Bern, , Switzerland

Site Status

Countries

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Switzerland

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157/15

Identifier Type: OTHER

Identifier Source: secondary_id

SPRV

Identifier Type: -

Identifier Source: org_study_id

Interaction of Sevoflurane Propofol and Remifentanil in Anesthesia for Laparoscopic Surgery

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Study Design

Study Groups

PR1

Propofol and Remifentanil

PR2

Propofol and Remifentanil

SR1

Sevoflurane and Remifentanil

SR2

Sevoflurane and Remifentanil

SPR1

SPR 1

SPR2

SPR2

Interventions

Propofol and Remifentanil

Propofol and Remifentanil

Sevoflurane and Remifentanil

Sevoflurane and Remifentanil

SPR 1

SPR2

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Insel Gruppe AG, University Hospital Bern

Responsible Party

Principal Investigators

Martin Luginbühl, PD Dr. med.

Locations

Department of Anesthesiology and Pain Therapy, Bern University Hospital

Countries

References

Schumacher PM, Dossche J, Mortier EP, Luginbuehl M, Bouillon TW, Struys MM. Response surface modeling of the interaction between propofol and sevoflurane. Anesthesiology. 2009 Oct;111(4):790-804. doi: 10.1097/ALN.0b013e3181b799ef.

Heyse B, Proost JH, Schumacher PM, Bouillon TW, Vereecke HE, Eleveld DJ, Luginbuhl M, Struys MM. Sevoflurane remifentanil interaction: comparison of different response surface models. Anesthesiology. 2012 Feb;116(2):311-23. doi: 10.1097/ALN.0b013e318242a2ec.

Luginbuhl M, Schumacher PM, Vuilleumier P, Vereecke H, Heyse B, Bouillon TW, Struys MM. Noxious stimulation response index: a novel anesthetic state index based on hypnotic-opioid interaction. Anesthesiology. 2010 Apr;112(4):872-80. doi: 10.1097/ALN.0b013e3181d40368.

Other Identifiers

157/15

SPRV