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

NCT ID: NCT03864094

Last Updated: 2024-10-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-15

Study Completion Date

2023-12-14

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.

Conditions

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Hemodynamic Instability Anesthesia, General Anesthesia, Intravenous

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, controlled, double-blind.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Randomization made by a person not involved in trial in other ways. Allocation masked in sealed envelopes, stored in a locked cash box only opened by two drug preparing nurses not involved in patient care. Syringe labelled with patient identification (ID) (eg 04Vaso). Patient, Care Provider and Investigator blinded for actual concentration of drug. Allocation break after data data wash and processing.

Study Groups

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Ephedrine Propofol Remifentanil

Prophylactic Ephedrine

Group Type ACTIVE_COMPARATOR

Ephedrine

Intervention Type DRUG

0,1 mg/kg

Propofol

Intervention Type DRUG

2 mg/kg

Remifentanil

Intervention Type DRUG

1,7 microg/kg

Phenylephrine Propofol Remifentanil

Prophylactic Phenylephrine

Group Type ACTIVE_COMPARATOR

Phenylephrine

Intervention Type DRUG

1 microg/kg

Propofol

Intervention Type DRUG

2 mg/kg

Remifentanil

Intervention Type DRUG

1,7 microg/kg

Norepinephrine Propofol Remifentanil

Prophylactic Norepinephrine

Group Type ACTIVE_COMPARATOR

Norepinephrine

Intervention Type DRUG

0,1 microg/kg

Propofol

Intervention Type DRUG

2 mg/kg

Remifentanil

Intervention Type DRUG

1,7 microg/kg

Sodium chloride Propofol Remifentanil

NaCl Placebo

Group Type SHAM_COMPARATOR

Sodium chloride

Intervention Type DRUG

0,1 ml/kg

Propofol

Intervention Type DRUG

2 mg/kg

Remifentanil

Intervention Type DRUG

1,7 microg/kg

Interventions

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Ephedrine

0,1 mg/kg

Intervention Type DRUG

Phenylephrine

1 microg/kg

Intervention Type DRUG

Norepinephrine

0,1 microg/kg

Intervention Type DRUG

Sodium chloride

0,1 ml/kg

Intervention Type DRUG

Propofol

2 mg/kg

Intervention Type DRUG

Remifentanil

1,7 microg/kg

Intervention Type DRUG

Other Intervention Names

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Ephedrine Sulphate Injection Phenylephrine Hydrocloride Injection Noradrenalin Sodium Chloride 0,9% injection Propolipid Ultiva

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Helse Fonna

OTHER

Sponsor Role lead

Responsible Party

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Gunnar Helge Sjøen

Consultant in Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gunnar Sjøen, MD

Role: PRINCIPAL_INVESTIGATOR

Helse Fonna

Locations

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Helse Fonna, Haugesund Sykehus

Haugesund, , Norway

Site Status

Countries

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Norway

References

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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.

Reference Type BACKGROUND
PMID: 1751277 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10844832 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9771299 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15449752 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21196672 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24803761 (View on PubMed)

Sjoen GH, Hauge TH, Falk RS, Tonnessen TI, Langesaeter E. Haemodynamic Changes After Prophylactic Doses of Ephedrine, Phenylephrine, Norepinephrine Versus Placebo During Induction of General Anaesthesia: A Randomised Trial. Acta Anaesthesiol Scand. 2026 Jan;70(1):e70138. doi: 10.1111/aas.70138.

Reference Type DERIVED
PMID: 41144827 (View on PubMed)

Other Identifiers

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2019-000965-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2019/374

Identifier Type: -

Identifier Source: org_study_id

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