Observation of Propofol Titration at Different Speeds (OPTDS)

November 6, 2022 updated by: SanQing Jin

Effects of Propofol Titration at Different Speeds on Hemodynamics and Stress During General Anesthesia Induction

Propofol is one of the most widely used anesthetics for its fast onset and quick elimination. The conventional speed of its induction dose often causes severe hemodynamics fluctuations with hypotension and arrhythmia. The recommended dosage on the drug insert comes from group pharmacokinetic studies which does not apply to the specific situation of every patient, so the investigators emphasize individualized medication. The investigators have observed the titration of propofol in general anesthesia induction, and found that the dosage was less and the hemodynamics was becoming more stable. At the same time, the investigators found that the hemodynamics still has obvious fluctuations in the titration of the administration rate recommended in the instructions. The investigators intend to further compare the effects of propofol titration administration at different rates for hemodynamics and stress during the induction period of general anesthesia, and find a safer and more appropriate rate of administration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Based on the recommended dosing speed in the propofol instructions, this research protocol further reduces the dosing speed (40 mg administered every 10 seconds), and sets three different titration dosing speeds: group I 2 mg/kg/min; group II 1 mg /kg/min; group III 0.5 mg/kg/min. The program is calculated by statistics, and it will be planned to enroll 276 participants undergoing elective surgery under general anesthesia with oral endotracheal intubation, and randomly divided into 3 groups according to a random number table, with 92 cases in each group. When participants reach the titration endpoint (OAAS score 1 point) during the titration of propofol in the induction, the investigators stop the dosing and switch to a maintenance dose, and give rocuronium 0.15 mg/kg and remifentanil 2 ug/kg; 2 minutes later the chief anesthetist performs tracheal intubation. The investigators will observe hemodynamics changes and brain electrical activity throughout the process, and adjust the drugs according to the blood pressure to make the hemodynamics as stable as possible.

After confirming the successful tracheal intubation, the investigators will give participants machine-controlled ventilation, and the total intravenous anesthesia (TIVA) will be given with propofol, remifentanil, and cis-atracurium. During the operation, remifentanil will be injected with a constant rate of 0.2ug/kg/min, and propofol will be injected with a fluctuating rate of 2-8mg/kg/h (the pump injection rate will be adjusted according to blood pressure and BIS, and the rate of remifentanil can be adjusted if necessary) to maintain BIS between 40-60.Fluid therapy will be performed according to the participants' hemodynamics and intraoperative conditions. After extubation, participants will be sent to the postoperative recovery room; a follow-up visit will be performed the next day, and a telephone return visit will be performed on the 30th day.

The investigators record the visual analogue scale(VAS) score for preoperative anxiety of each participant, bispectral index (BIS) and hemodynamics of patients when participants reach different stages of sedation as determined by the Observer's Assessment of Alertness/Sedation Scale (OAAS) score, and the lowest value and specific time of mean blood pressure(MBP) and BIS during induction of anesthesia；the investigators record various parameters at the following time points(10 minutes after entering the operating room before propofol administration, every minute after administration until intubation, immediately after tracheal intubation, and 1, 2, 4, 6, 8, 10, 20 min after intubation), and parameters include: systolic blood pressure(SBP) , diastolic blood pressure(DBP), MBP, heart rate(HR), electrocardiogram ST-T changes (V1), BIS, cardiac function parameters (heart rate variability(HRV), stroke volume (SV), stroke index(SVI), cardiac output (CO), cardiac index(CI) ), oxygen delivery parameters (oxygen delivery (DO2), oxygen delivery index (DO2I)), peripheral vascular resistance parameters (systemic vascular resistance (SVR), systemic vascular resistance index (SVRI)), volume parameters (stroke volume variation(SVV), pulse pressure variation (PPV), increase in stroke volume(△SV)); the investigators record the time for each participant reach the titration endpoint and the amount of propofol used, the time from the start of induction to the completion of the tracheal intubation and the amount of propofol, and the total amount of propofol during the operation.

The investigators record invasive blood during the trial, and use cameras to video the entire process of anesthesia induction.

The 11-30th participants in each group will be given arterial blood samples at 1, 3, 5, and 7 minutes after the administration of propofol to measure the blood concentration of propofol; when rocuronium is given and 30 seconds after the completion of tracheal intubation, venous blood will be drawn to measure the catecholamine concentration; ten cases of propofol with high, medium and low sensitivity will be selected for transcriptome RNA sequencing; Single nucleotide polymorphism（SNP） analysis of propofol-related genes in special cases.

During the induction period, the investigators will monitor EEG of the left and right frontal, temporal and occipital lobes, and analyze the power spectrum of β, α, θ, and σ brain waves; observe the pupil reflex and auditory evoked potential(brain stem auditory evoked potentials(BAEP): the incubation period and amplitude of III, V ; middle latency auditory evoked potentials（MLAEP）: the incubation period and amplitude of Pa, Nb) before induction , when the titration endpoint reaches and after finishing intubation.

Blind design:

The observer performs pre-entry screening, and does not know the group of participants during the induction process. The anesthesia nurse receives the experiment envelope in advance, adjusts the infusion pump according to the group, and adjusts the pump to the position facing away from the observer and the chief anesthetist. The chief anesthetist communicates with patients and performs OAAS scores scoring. When the titration endpoint reaches, the anesthesia nurse will stop propofol administer and shift to the maintenance dose, following the observer's order to add vasoactive drugs or propofol during the induction process, and do not participate in the postoperative follow-up work. The chief anesthetist (working for more than 3 years) is responsible for assisted ventilation and tracheal intubation. The anesthesiologist in the resuscitation room, the patient, and the post-operative return visitor do not know the group of the participant.

Study Type

Interventional

Enrollment (Actual)

276

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • The Sixth Affiliated Hospital, Sun Yat-sen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18-60 Years old
  2. Elective surgery for general anesthesia through oral tracheal intubation and surgery is expected to last more than 2 hours
  3. The American Society of Anesthesiologists(ASA) grade is I or II, and the cardiac function is 1-2;
  4. Body mass index (BMI) 18-30 kg/m2;

Exclusion Criteria:

  1. Patients have severe heart, lung, liver, and kidney diseases (heart function grade>3 / respiratory failure / liver failure / renal failure)
  2. Patients with arrhythmia: sinus bradycardia (ventricular rate <60 beats/min), atrial fibrillation, atrial flutter, atrioventricular block, frequent ventricular premature, multi-source ventricular premature, ventricular premature R on T, Ventricular fibrillation and ventricular flutter.
  3. Patients who are expected to be difficult to intubate, hypoalbuminemia(albumin is less than 35g/L), hypertension and diabetes;
  4. Patients with a higher risk of reflux and aspiration, such as full stomach, gastrointestinal obstruction, gastroparesis, and pregnant women;
  5. Patients have schizophrenia, epilepsy, Parkinson's disease, intellectual disability, hearing impairment, abnormal EEG, etc.;
  6. Patients who take sedative and analgesic drugs for a long time;
  7. Patients who are allergic to propofol or its fat emulsion;
  8. Patients who are participating in other clinical trials, and who refuse to sign informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group Ⅰ
titration dosing speeds of propofol at 2mg/kg/min
Drug: 2mg/kg/min
titration dosing speeds of propofol at 2mg/kg/min
Other Names:
  • Remifentanil 2ug/kg
  • Rocuronium 1.5mg/kg
Active Comparator: Group Ⅱ
titration dosing speeds of propofol at 1mg/kg/min
Drug: 1mg/kg/min
titration dosing speeds of propofol at 1mg/kg/min
Other Names:
  • Remifentanil 2ug/kg
  • Rocuronium 1.5mg/kg
Active Comparator: Group III
titration dosing speeds of propofol at 0.5mg/kg/min
Drug: 0.5mg/kg/min
titration dosing speeds of propofol at 0.5mg/kg/min
Other Names:
  • Remifentanil 2ug/kg
  • Rocuronium 1.5mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean blood pressure(MBP)
Time Frame: During the procedure of anesthesia induction
Relative change of MBP(decreased more than 30%) in the three groups
During the procedure of anesthesia induction

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stroke Volume (SV)
Time Frame: During the procedure of anesthesia induction
Relative change of SV (ml/beat) in the three groups
During the procedure of anesthesia induction
Cardiac Output (CO)
Time Frame: During the procedure of anesthesia induction
Relative change of CO (litre/min) in the three groups
During the procedure of anesthesia induction
Systemic Vascular Resistance (SVR)
Time Frame: During the procedure of anesthesia induction
Relative change of SVR (dynes-sec/cm5/m2) in the three groups
During the procedure of anesthesia induction
Catecholamine
Time Frame: During the procedure of anesthesia induction
Concentration of catecholamines in venous blood before and after tracheal intubation in the three groups
During the procedure of anesthesia induction
Plasma concentration change curves
Time Frame: During the procedure of anesthesia induction
Plasma concentration change curves of propofol in the three groups
During the procedure of anesthesia induction
The relative level of mRNA in serum
Time Frame: Baseline
Expression differences of RNA sequences in groups of high, middle and low propofol sensitivity through bioinformatics analysis.
Baseline
Brain electrical activity
Time Frame: During the procedure of anesthesia induction
Differences of brain electrical activity (EEG, AEP)in the three groups
During the procedure of anesthesia induction
The dosage of propofol
Time Frame: Through anesthesia completion, an average of 3 hours.
The dosage of propofol (reach the end of the titration, complete the tracheal intubation ) and intraoperative maintenance dosage in the three groups
Through anesthesia completion, an average of 3 hours.
Induction time
Time Frame: Through anesthesia completion, an average of 3 hours.
Induction time in the three groups
Through anesthesia completion, an average of 3 hours.
Recovery time
Time Frame: Through anesthesia completion, an average of 3 hours.
Postoperative recovery time in the three groups
Through anesthesia completion, an average of 3 hours.
The occurrence of important cardiovascular events
Time Frame: One month after finish operation
The occurrence of important cardiovascular events during the perioperative period
One month after finish operation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SanQing Jin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2020

Primary Completion (Actual)

March 25, 2021

Study Completion (Actual)

April 25, 2021

Study Registration Dates

First Submitted

September 23, 2020

First Submitted That Met QC Criteria

October 14, 2020

First Posted (Actual)

October 20, 2020

Study Record Updates

Last Update Posted (Actual)

November 8, 2022

Last Update Submitted That Met QC Criteria

November 6, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020ZSLYEC-182

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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