Hemodynamics During Induction of General Anesthesia With Medium or Low Remifentanil Doses.

Study Overview
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Brief Summary
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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
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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.

Official Title
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Hemodynamic Stability During Induction of General Anesthesia With Propofol and Remifentanil: A Randomized, Controlled, Double-blind Study Comparing Medium and Low Remifentanil Doses.

Conditions
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Hemodynamic Instability, Anesthesia, General, Anesthesia, Intravenous

Intervention / Treatment
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* Drug: Remifentanil R2
* Drug: Remifentanil R4
* Drug: Remifentanil R8


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled, double blind.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Remifentanil R2<br>Low dose Remifentanil induction dose (R2) | Drug: Remifentanil R2<br>* 0,7 microg/kg<br>* Other names: Ultiva;|
| Active Comparator: Remifentanil R4<br>Medium dose Remifentanil induction dose (R4) | Drug: Remifentanil R4<br>* 1,1 microg/kg<br>* Other names: Ultiva;|
| Active Comparator: Remifentanil R8<br>Medium dose Remifentanil induction dose (R8) | Drug: Remifentanil R8<br>* 1,7 microg/kg<br>* Other names: Ultiva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure (SBP) | Change in systolic blood pressure during induction | First 7,5 minutes from start of induction | 
| Heart Rate (HR) | Change in heart rate during induction | First 7,5 minutes from start of induction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke Volume (SV) | Change in stroke volume during induction | First 7,5 minutes from start of induction | 
| Cardiac Output (CO) | Change in cardiac output during induction | First 7,5 minutes from a start of induction | 
| Systemic Vascular Resistance (SVR) | Change in systemic vascular resistance during induction | First 7,5 minutes from start of induction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lithium Dilutional Cardiac Output (LiDCO), Minimal Invasive Hemodynamic Monitor, Remifentanil, Cardiac Output (CO), Systolic Blood Pressure (SBP), Systemic Vascular Resistance (SVR), Heart Rate (HR), Stroke Volume (SV)