Hemodynamics During Induction of General Anesthesia With High and Low Propofol Dose. (PH)

Haemodynamic Stability During Induction of General Anesthesia With Propofol and Remifentanil: A Randomized, Controlled, Double-blind Study Comparing Low vs High Propofol Doses.

The study objective is to examine if a high propofol dose is non-inferior to a low dose in respect to hemodynamic stability in healthy patients during induction of general anesthesia with propofol and remifentanil.

Study Overview

• Status: Completed
• Conditions: Anesthesia, General; Anesthesia, Intravenous; Hemodynamics Instability
• Intervention / Treatment: Drug: Propofol; Drug: Propofol

Detailed Description

Typically, one or more adjuvant medications are administered to supplement induction of general anesthesia. When combining anesthetic drugs, 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.

Claeys (1988) and Fairfield (1991) examined the cardiovascular effects of propofol 2-2.5 mg/kg induction dose and found significant reductions i SBP and SVR and small changes in CO, SV and HR. De Wit (2016) examined hemodynamic changes in different steady state propofol serum concentrations, and found a dose dependent SBP reduction, reduction in resistance of arterial and systemic circulation and a reduction in mean systemic filling pressures (MSFP) indicative of a reduction in "stressed volumes". The effective dose (ED) 95% for loss of consciousness for propofol was determined to 1.75 mg/kg when used alone, and 1.38 mg/kg when used together with remifentanil 0.25 microg/kg/min (total induction dose 1.75 microg/kg remifentanil) in a study by Koh et al. We want to examine the hemodynamic effects of giving a low (1.4 mg/kg) vs a high (2.4 mg/kg) propofol dose combined with a moderate remifentanil dose (about 1.5 microg/kg).

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Rogaland
    • Haugesund, Rogaland, Norway, 5504
      • Kirurgisk Klinikk-Anestesi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: High Propofol; High Propofol induction dose	Drug: Propofol; 2,4 mg/kg; Other Names: Propolipid; Drug: Propofol; 1,4 mg/kg; Other Names: Propolipid
ACTIVE_COMPARATOR: Low Propofol; Low Propofol induction dose	Drug: Propofol; 2,4 mg/kg; Other Names: Propolipid; Drug: Propofol; 1,4 mg/kg; Other Names: Propolipid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure (SBP)	Relative change of SBP (mmHg)	The first 7.5 minutes during induction of general anesthesia
Heart rate (HR)	Relative change of HR (beats)	The first 7.5 minutes during induction of general anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke Volume (SV)	Relative change of SV (ml/beat)	The first 7.5 minutes during induction of general anesthesia
Cardiac Output (CO)	Relative change of CO (litre/min)	The first 7.5 minutes during induction of general anesthesia
Systemic Vascular Resistance (SVR)	Relative change of SVR (dynes-sec/cm5/m2)	The first 7.5 minutes during induction of general anesthesia

Collaborators and Investigators

• Sponsor: Helse Fonna
• Investigators: Principal Investigator: Gunnar H Sjøen, MD, Helse Fonna

Publications and helpful links

General Publications

• Koh JC, Park J, Kim NY, You AH, Ko SH, Han DW. Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial. Medicine (Baltimore). 2017 Dec;96(49):e9164. doi: 10.1097/MD.0000000000009164.
• Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth. 1988 Jan;60(1):3-9. doi: 10.1093/bja/60.1.3.
• 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.
• de Wit F, van Vliet AL, de Wilde RB, Jansen JR, Vuyk J, Aarts LP, de Jonge E, Veelo DP, Geerts BF. The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances. Br J Anaesth. 2016 Jun;116(6):784-9. doi: 10.1093/bja/aew126.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 3, 2019
• Primary Completion (ACTUAL): May 19, 2020
• Study Completion (ACTUAL): May 31, 2020

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (ACTUAL): March 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 17, 2020
• Last Update Submitted That Met QC Criteria: June 16, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Propofol; Stroke Volume (SV); Heart Rate (HR); Systolic Blood Pressure (SBP); Cardiac Output (CO); Systemic Vascular Resistance (SVR); Lithium Dilutional Cardiac Output (LiDCO); Minimal Invasive Hemodynamic Monitor; Propolipid
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: 2019/375; 2019-000958-56 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: LiDCO-csv raw data and processed data will be made public at the publishers site, and the supporting information by request to the Principal Investigator. Statistical Data Plan is included in Study Protocol.
• IPD Sharing Time Frame: The data will be stored for 15 years after end of study, and may be shared during this time frame.
• IPD Sharing Access Criteria: The data may be shared by contacting the Principal Investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No