Clinical trial NCT03864094: Hemodynamics During Induction of General Anesthesia After Prophylactic Ephedrine, Phenylephrine or Norepinephrine.
Official title: "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."
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
Propofol
Remifentanil
Ephedrine
Phenylephrine
Norepinephrine
Lead sponsor: Helse Fonna
Sponsor class: OTHER
First posted: 2019-03-06
Enrollment: 128
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 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: 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.

Eligibility criteria: 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

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: Helse Fonna, Haugesund Sykehus
Study officials:
affiliation: Helse Fonna
name: Gunnar Sjøen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: Turner RJ, Gatt SP, Kam PC, Ramzan I, Daley M. Administration of a crystalloid fluid preload does not prevent the decrease in arterial blood pressure after induction of anaesthesia with propofol and fentanyl. Br J Anaesth. 1998 Jun;80(6):737-41. doi: 10.1093/bja/80.6.737.
citation: Al-Ghamdi A. Hydroxyethylstarch 6% preload does not prevent the hypotension following induction with propofol and fentanyl. Middle East J Anaesthesiol. 2004 Jun;17(5):959-68.
citation: El-Tahan MR. Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: a dose dependent study. Ann Card Anaesth. 2011 Jan-Apr;14(1):30-40. doi: 10.4103/0971-9784.74397.
citation: Masjedi M, Zand F, Kazemi AP, Hoseinipour A. Prophylactic effect of ephedrine to reduce hemodynamic changes associated with anesthesia induction with propofol and remifentanil. J Anaesthesiol Clin Pharmacol. 2014 Apr;30(2):217-21. doi: 10.4103/0970-9185.130024.