Clinical trial NCT03861377: Hemodynamics During Induction of General Anesthesia With Medium or Low Remifentanil Doses.
Official title: "Hemodynamic Stability During Induction of General Anesthesia With Propofol and Remifentanil: A Randomized, Controlled, Double-blind Study Comparing Medium and Low Remifentanil Doses."
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemodynamic Instability
Anesthesia, General
Anesthesia, Intravenous
Keywords: Cardiac Output (CO)
Systolic Blood Pressure (SBP)
Systemic Vascular Resistance (SVR)
Heart Rate (HR)
Stroke Volume (SV)
Lithium Dilutional Cardiac Output (LiDCO)
Minimal Invasive Hemodynamic Monitor
Remifentanil
Lead sponsor: Helse Fonna
Sponsor class: OTHER
First posted: 2019-03-04
Enrollment: 99
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, double blind.
Primary purpose: BASIC_SCIENCE

Brief summary: In this trial the investigators want to examine if there is any difference in hemodynamic stability during induction when comparing two low and a medium remifentanil dose and keeping propofol induction dose at about 2.0 mg/kg.

Detailed description: Typically, one or more adjuvant medications is administered during induction of general anesthesia. When anesthetic drugs are combined, the hypnotic effects are often synergistic. Propofol is associated with hypotension and bradycardia and used together with remifentanil or sedative agents it may give synergistic or additive sedative and hemodynamic effects.

Remifentanil is infused at 0.05-0.3 microg/kg/min during induction of anesthesia. Some use a loading dose of 0.5-1.0 microg/kg before starting the continuous infusion. The onset of action of remifentanil is within one to two minutes and it reaches rapidly a steady state effect site concentration after a bolus dose.

Kazmaier (2000) showed that a high-dose remifentanil anesthesia (2 microg/kg/min) reduced cardiac index (-25%), stroke volume (-14%) and mean arterial blood pressure (-39%) in a similar manner as propofol/remifentanil (propofol target 2 microg/ml and remifentanil 0.5 microg/kg/min), but systemic vascular resistance index decreased (-14%) in propofol/remifentanil combination. Fairfield et al have earlier (1991) showed that propofol 2.5 mg/kg induction without opioid reduces cardiac output (-15%) stroke volume (-5 %), mean arterial pressure (-33%) and systemic vascular resistance (-11%) and a slight reduction i heart rate. Guarracino (2003) suggests the reduction in cardiac index during induction with propofol/remifentanil with a low propofol target (1.2 microg/ml) may be due to decreased heart rate. Zaballos (2009) have shown that remifentanil depresses sinus node and atrioventricular (AV) -nodal function in comparison with propofol alone in a closed chest porcine model. Hayashi (2016) states that even in a low remifentanil effect site concentration (3.5 nanog/ml) it may reduce heart rate significantly when combined with propofol bolus 30-50 mg.

Eligibility criteria: Inclusion Criteria:

* Gynecological procedure
* Age 18-50 years
* General anesthesia planned
* Systolic blood pressure \< 150 mmHg, HR \< 100 beats/min

Exclusion Criteria:

* Pre-existing hypertension
* Diabetes
* Ischemic heart disease or cerebrovascular disease
* Heart valve disease
* Verified cardiac arrhythmia other than extrasystoles
* Verified anaemia with hemoglobin level below 9.0 gr/dl.
* Kidney or hepatic disease
* Hypersensitivity for propofol, soya, eggs or peanuts
* Pregnancy
* Poor health state
* Illicit substance use
* BMI \<20 or \>35 kg/m2

Primary outcomes:
measure: Systolic Blood Pressure (SBP)
timeFrame: First 7,5 minutes from start of induction
measure: Heart Rate (HR)
timeFrame: First 7,5 minutes from start of induction
Secondary outcomes:
measure: Stroke Volume (SV)
timeFrame: First 7,5 minutes from start of induction
measure: Cardiac Output (CO)
timeFrame: First 7,5 minutes from a start of induction
measure: Systemic Vascular Resistance (SVR)
timeFrame: First 7,5 minutes from start of induction
Other outcomes:
Locations:
city: Haugesund
country: Norway
facility: Kirurgisk Klinikk Anestesi
state: Rogaland
Study officials:
affiliation: Helse Fonna
name: Gunnar Sjøen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kazmaier S, Hanekop GG, Buhre W, Weyland A, Busch T, Radke OC, Zoelffel R, Sonntag H. Myocardial consequences of remifentanil in patients with coronary artery disease. Br J Anaesth. 2000 May;84(5):578-83. doi: 10.1093/bja/84.5.578.
citation: Fairfield JE, Dritsas A, Beale RJ. Haemodynamic effects of propofol: induction with 2.5 mg kg-1. Br J Anaesth. 1991 Nov;67(5):618-20. doi: 10.1093/bja/67.5.618.
citation: Guarracino F, Penzo D, De Cosmo D, Vardanega A, De Stefani R. Pharmacokinetic-based total intravenous anaesthesia using remifentanil and propofol for surgical myocardial revascularization. Eur J Anaesthesiol. 2003 May;20(5):385-90. doi: 10.1017/s0265021503000589.
citation: Zaballos M, Jimeno C, Almendral J, Atienza F, Patino D, Valdes E, Navia J, Anadon MJ. Cardiac electrophysiological effects of remifentanil: study in a closed-chest porcine model. Br J Anaesth. 2009 Aug;103(2):191-8. doi: 10.1093/bja/aep131. Epub 2009 May 20.
citation: Hayashi K, Tanaka A. Effect-site concentrations of remifentanil causing bradycardia in hypnotic and non-hypnotic patients. J Clin Monit Comput. 2016 Dec;30(6):919-924. doi: 10.1007/s10877-015-9794-4. Epub 2015 Oct 13.