Impact of Propofol Reduction in Anesthesia Induction

Impact of Propofol Dose Reduction in Relation to the Time Since Administration of Fentanyl During Anesthesia Induction

Objective: Determine if, by reducing the dose of propofol and increasing the time elapsed between fentanyl and propofol administration, hemodynamic response is improved.

Methods: Patients were randomized into time groups (2 and 1 minute) and each subdivided into dose groups (1, 1.5 and 2 mg kg-1) obtaining six time-dose groups. After receiving 2 μg kg-1 of fentanyl, propofol was administered after the predetermined time. Time to hypnosis (BIS<60) and hemodynamic parameters at pre-induction, pre-intubation and postintubation were registered.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Propofol Adverse Reaction
• Intervention / Treatment: Drug: Propofol Injection

Detailed Description

A minimum of 162 patients were required, considering an expected Mean Difference of 5 with expected Standard Deviation of 22, confidence level of 95% and power of 80%. Estimating a possible loss of 15%, it was raised to 192. Consecutive identification numbers were assigned and the sample was randomized in six groups of 32 patients according to time and dose of propofol.

Pre-oxygenation was performed until the expired oxygen fraction exceeded 80% and 2 µg/kg of intravenous fentanyl were administered. Depending on the study group, 1 or 2 minutes were allowed to pass and 1, 1.5 or 2 mg/kg of propofol were supplied (prior administration of intravenous lidocaine 0.5 mg/kg). The time in which the BIS dropped below 60 was recorded. If it did not reach that level after two minutes or when it exceeded it but then rose above 60 again, an extra dose of propofol of 0.5 mg/kg was administered. Muscle relaxation was performed with rocuronium 0.6 mg/kg. The patient was manually ventilated until endotracheal intubation was performed by the same experienced anaesthesiologist and connected to mechanical ventilation.

Data were collected manually. Statistical analysis was performed using SPSS ver. 22. Inferential statistics were performed using t-test for quantitative variables, chi-square for qualitative and ANOVA for qualitative and quantitative comparisons. Non-parametric statistical tests were used when necessary. Confidence intervals were estimated at a level of 95% and a P value of <.05 was considered statistically significant.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28047
    • Hospital Central de la Defensa Gómez Ulla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults who required general anesthesia
• General anesthesia with endotracheal intubation (no supraglottic devices)
• Signed informed consent
• Non-cardiac surgery
• Same anesthesiologist

Exclusion Criteria:

• Hemodynamic instability (systolic BP < 90 mmHg with clinical signs of low cardiac output: impaired consciousness, diuresis <0.5 ml/kg/h, central venous saturation <60% with normal arterial saturation or lactate >3 mmol/l)
• Increased risk of bronchoaspiration (absence of fasting, stomach retention, intestinal obstruction, pregnancy, etc.)
• Suspected difficult airway
• Known allergy to anesthetic drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2 minute - 2 mg/kg group; 2 mcg/kg of fentanyl administrated intravenously. wait for 2 minutes to inject 2 mg/kg of propofol	Drug: Propofol Injection; 1, 1.5 or 2 mg/kg of propofol according to the subgroup
Active Comparator: 2 minute - 1,5 mg/kg group; 2 mcg/kg of fentanyl administrated intravenously. wait for 2 minutes to inject 1,5 mg/kg of propofol	Drug: Propofol Injection; 1, 1.5 or 2 mg/kg of propofol according to the subgroup
Active Comparator: 2 minute - 1 mg/kg group; 2 mcg/kg of fentanyl administrated intravenously. wait for 2 minutes to inject 1 mg/kg of propofol	Drug: Propofol Injection; 1, 1.5 or 2 mg/kg of propofol according to the subgroup
Active Comparator: 1 minute - 2 mg/kg group; 2 mcg/kg of fentanyl administrated intravenously. wait for 1 minute to inject 2 mg/kg of propofol	Drug: Propofol Injection; 1, 1.5 or 2 mg/kg of propofol according to the subgroup
Active Comparator: 1 minute - 1,5 mg/kg group; 2 mcg/kg of fentanyl administrated intravenously. wait for 1 minute to inject 1,5 mg/kg of propofol	Drug: Propofol Injection; 1, 1.5 or 2 mg/kg of propofol according to the subgroup
Active Comparator: 1 minute - 1 mg/kg group; 2 mcg/kg of fentanyl administrated intravenously. wait for 1 minute to inject 1 mg/kg of propofol	Drug: Propofol Injection; 1, 1.5 or 2 mg/kg of propofol according to the subgroup

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure Variation	Non-invasive systolic blood pressure change (%) at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in SBP between the studied moments. Negative results mean percentage increase in SBP between the studied moments.	Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned
Heart Rate Variation	Heart rate change (%) registered at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in HR between the studied moments. Negative results mean percentage increase in HR between the studied moments.	Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned
Systolic Blood Pressure Variation in Elderly (>55y)	Non-invasive SBP change (%) in patients > 55 years at baseline, pre-intubation and postintubation. Positive results mean percentage reduction in SBP between the studied moments. Negative results mean percentage increase in SBP between the studied moments.	Baseline before fentanyl administration, pre-intubation after propofol and bispectral index<60 and postintubation 15 seconds after endotracheal tube positioned

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Hypnosis	Bispectral index (BIS)<60 meaning "general anesthesia", BIS>60 meaning mild/moderate sedation. We measure the time until patient reachs hypnosis	After administration of propofol, time is measured in seconds until BIS values are less than 60
Number of Patients Who Needed Vasoactive Drug	Patients who suffered SPB reduction > 30% or SPB < 90mmHg, receive vasoactive drugs	1 minute after intubation

Collaborators and Investigators

• Sponsor: Hospital Central de la Defensa Gómez Ulla
• Investigators: Principal Investigator: Paula A Vullo, MD

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): October 26, 2018
• Study Completion (Actual): October 26, 2018

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 9, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 11, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: fentanyl; anesthesia induction; propofol synergy
• 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: 09/17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No