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

Helse Fonna

Status and phase: Completed; Phase 4

Conditions: Hemodynamic Instability; Anesthesia, General; Anesthesia, Intravenous

Treatments: Drug: Phenylephrine; Drug: Sodium chloride; Drug: Norepinephrine; Drug: Propofol; Drug: Remifentanil; Drug: Ephedrine

Study type: Interventional

Funder types: Other

Identifiers

NCT03864094

2019/374

2019-000965-19 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 128 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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128 participants in 4 patient groups

Ephedrine Propofol Remifentanil

Active Comparator group

Description:

Prophylactic Ephedrine

Treatment:

Drug: Ephedrine

Drug: Remifentanil

Drug: Propofol

Phenylephrine Propofol Remifentanil

Active Comparator group

Description:

Prophylactic Phenylephrine

Treatment:

Drug: Remifentanil

Drug: Propofol

Drug: Phenylephrine

Norepinephrine Propofol Remifentanil

Active Comparator group

Description:

Prophylactic Norepinephrine

Treatment:

Drug: Remifentanil

Drug: Propofol

Drug: Norepinephrine

Sodium chloride Propofol Remifentanil

Sham Comparator group

Description:

NaCl Placebo

Treatment:

Drug: Remifentanil

Drug: Propofol

Drug: Sodium chloride