Hemodynamics During Induction of General Anesthesia After Prophylactic Ephedrine, Phenylephrine or Norepinephrine.

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 when giving equipotent prophylactic injections of ephedrine 0,1 mg/kg, phenylephrine 1 microg/kg, norepinephrine 0,1 microg/kg or sodium chloride (NaCl) 9 mg/ml during induction of general anesthesia with propofol and remifentanil.

Detailed Description
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The LiDCOplus monitoring system (Lithium Dilutional Cardiac Output (LiDCO) Ltd., Cambridge, United Kingdom) is a minimally invasive monitor for measuring stroke volume (SV) using two different algorithms. The PulseCO (PulseCO ™, Cambridge, United Kingdom) is based on analyses of the the arterial pressure wave giving nominal values. The LiDCO uses lithium-dilution for calibration to give absolute values. In this trial, the investigators will use the PulseCO looking at relative changes in uncalibrated hemodynamic variables. Continual changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) will be measured. Earlier studies have shown that propofol 2.5 mg/kg induction without opioid reduces CO (-15%), SV (-5 %), MAP (-33%) and SVR (-11%) and a slight reduction i HR. High-dose remifentanil anesthesia (2 microg/kg/min), in coronary patients reduced cardiac index (-25%), SV (-14%) and MAP (-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. Several procedures have been proposed to minimize the negative hemodynamic changes during induction. Administration of a crystalloid or a colloid did not prevent the decrease in MAP after induction of general anesthesia with propofol and fentanyl. The hemodynamic effects in propofol-fentanyl anesthesia of preoperative ephedrine 0.07-0.15 mg/kg vs phenylephrine 1.5 microg/kg in valve surgery and concludes that ephedrine 0.07-0.1 mg/kg is safe and effective in counteracting hypotension. A dose of 0.15 mg/kg ephedrine is suggested for preventing hypotension during anesthesia induction with propofol 2.5 mg/kg and remifentanil 3 microg/kg.

Official Title
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Haemodynamic Stability During Induction of General Anesthesia With Propofol and Remifentanil: A Randomized, Controlled, Double-blind Study Comparing Equipotent Prophylactic Doses of Ephedrine, Phenylephrine, Norepinephrine vs Placebo.

Conditions
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Hemodynamic Instability, Anesthesia, General, Anesthesia, Intravenous

Intervention / Treatment
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* Drug: Ephedrine
* Drug: Phenylephrine
* Drug: Norepinephrine
* Drug: Sodium chloride
* Drug: Propofol
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy women Age 18-50 years Gynecological procedures General anesthesia Exclusion Criteria: Pre-existing hypertension Diabetes for several years Ischemic heart disease Cerebrovascular disease Heart valve disease Verified cardiac arrhythmia Anaemia Kidney or hepatic disease Hypersensitivity for soya, eggs or peanuts Pregnancy Poor health state Illicit substance use BMI <20 or >35 kg/m2 SBP >150 mmHg HR >100 beats/min

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: Ephedrine Propofol Remifentanil<br>Prophylactic Ephedrine | Drug: Ephedrine<br>* 0,1 mg/kg<br>* Other names: Ephedrine Sulphate Injection;Drug: Propofol<br>* 2 mg/kg<br>* Other names: Propolipid;Drug: Remifentanil<br>* 1,7 microg/kg<br>* Other names: Ultiva;|
| Active Comparator: Phenylephrine Propofol Remifentanil<br>Prophylactic Phenylephrine | Drug: Phenylephrine<br>* 1 microg/kg<br>* Other names: Phenylephrine Hydrocloride Injection;Drug: Propofol<br>* 2 mg/kg<br>* Other names: Propolipid;Drug: Remifentanil<br>* 1,7 microg/kg<br>* Other names: Ultiva;|
| Active Comparator: Norepinephrine Propofol Remifentanil<br>Prophylactic Norepinephrine | Drug: Norepinephrine<br>* 0,1 microg/kg<br>* Other names: Noradrenalin;Drug: Propofol<br>* 2 mg/kg<br>* Other names: Propolipid;Drug: Remifentanil<br>* 1,7 microg/kg<br>* Other names: Ultiva;|
| Sham Comparator: Sodium chloride Propofol Remifentanil<br>NaCl Placebo | Drug: Sodium chloride<br>* 0,1 ml/kg<br>* Other names: Sodium Chloride 0,9% injection;Drug: Propofol<br>* 2 mg/kg<br>* Other names: Propolipid;Drug: Remifentanil<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 SBP during induction as measured by the LiDCOplus monitoring system | First 7,5 minutes from start of induction | 
| Heart Rate (HR) | Change in HR during induction as measured by the LiDCOplus monitoring system | First 7,5 minutes from start of induction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke Volume (SV) | Change in SV during induction as measured by the LiDCOplus monitoring system | First 7,5 minutes from start of induction | 
| Cardiac Output (CO) | Change in CO during induction as measured by the LiDCOplus monitoring system | First 7,5 minutes from a start of induction | 
| Systemic Vascular Resistance (SVR) | Change in SVR during induction as measured by the LiDCOplus monitoring system | 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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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, Propofol, Remifentanil, Ephedrine, Phenylephrine, Norepinephrine