Development of pk/pd Model of Propofol in Patients With Severe Burns

Terminated

• Conditions: Anesthesia; Burned; Operative Wound
• Interventions: Drug: Propofol; Device: BIS

• Registration Number: NCT03704285
• Lead Sponsor: Victor Contreras, MSN

Brief Summary

Burn injuries are a prevalent problem. Actually, in Chile the Ministry of Health has recorded 6435 hospital burns and has reported 569 deaths from this cause. The specific mortality rate for burning in Chile was 4.5 per 100,000 inhabitants per year. Survival in extensive burns has progressively improved, thanks to advances in understanding the pathophysiology of the burn and its more aggressive treatment. This requires effective prehospital treatment, transportation, resuscitation, support of vital functions and repair of the skin cover.

Much of the procedures performed in large burns require general anesthesia. Being Total Intravenous Anesthesia (TIVA) with propofol an alternative that would have advantages over inhalational anesthesia, as a decrease in postoperative nausea and vomiting and produce less environmental pollution 3 and the antihyperalgesic effect of propofol. Within TIVA - Target Control Infusion (TCI) - uses infusion systems that incorporate PK-PD models for predict the dose of drug required to reach a certain concentration in the target organ.

The formulation of a PK model that considers the variables of this group of patients, such as: degree of injury, inflammatory state and compromised body surface; associated with general variables such as: age, weight and nutrition, it would allow to reduce the predictive error in this population, thus improving the dosing of these patients when using TCI.

Given the lack evidence on the PK-PD of propofol is this group of patients burned, has led to raise the development of this study that seeks to develop a PK-PD model that fits them.

Detailed Description

Patients will be invited to participate before surgery, the inclusion criteria will be revised and the informed consent will be signed.

In the operating room will be recorded demographic data and relevant background such as: Age, Weight, Size, BMI, Lean Mass, Fat Mass and Total body water among others.

Afterwards, in the operating room, the patient will be monitored regularly: ECG (DII) if feasible and pulse oximetry. An arterial catheter will be installed for monitoring and taking blood samples during the intraoperative period.

In addition, the EEG will be monitored through a frontal electroencephalographic monitoring (BIS) system; that will be recorded throughout the surgery.

The anesthetic induction will be with propofol and remifentanil. The propofol will be administered using an initial bolus of 1-2 mg / kg according to the criteria of the anesthetist and then a continuous infusion of 10 mg / kg / hr that will be adjusted adjusted to maintain a BIS between 40 and 60.

Plasma samples of propofol: arterial samples of 3-4 ml will be taken at 2, 5, 10, 30, 60 and/or 120 min after beginning the administration of propofol. Subsequently samples will be taken at 0, 5, 15, 30, 60, 120, 240 min and at 6-12 hrs after stopping the infusion of propofol. The samples will be centrifuged and stored at -20 ° C until analysis by HPLC.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-09-29
• Study First Submitted: 2018-10-03
• Study First Submitted QC: 2018-10-09
• Study First Posted: 2018-10-12
• Primary Completion: 2021-12-30
• Study Completion: 2021-12-30
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-07
• Last Update Posted: 2022-03-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Severe burns with life risk that require treatment in Burn Units and / or Critical Patient Units.
• In spontaneous ventilation
• SAS 4

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Exclusion Criteria

• Electric burns
• ASA IV o V
• Inability to install BIS

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Propofol	BIS	Severe burn adult under general anesthesia with propofol + remifentanil evaluation of propofol effect using BIS
Propofol	Propofol	Severe burn adult under general anesthesia with propofol + remifentanil evaluation of propofol effect using BIS

Primary Outcome Measures

Name	Time	Method
Propofol plasmatic levels Measured by high pressure liquid chromatography	From start of propofol infusion to 12 hrs after stopped infusion of propofol.	Propofol total dose. 2, 5, 10, 30, 60 and 120 min after induction with propofol. Subsequently, samples will be taken at 0, 5, 15, 30, 60, 120, 240 min and at 6-12 hrs after stopping infusion of propofol.

Secondary Outcome Measures

Name	Time	Method
Hemodynamics	Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.	Arterial pressure (mmHg)
Heart Rate	Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.	Heart rate (bpm)
Pulse oximetry	Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.	% oximetry saturation
BIS	Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.	Depth of anesthesia will be recorded with BIS monitor. From 60 - 40

Trial Locations

Locations (1)

Victor Contreras; 🇨🇱 Santiago, Región Metropolitana, Chile