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

NCT03704285 | Terminated DMC FDA Drug FDA Device

• 1 other identifier: 171215006
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Anesthesia; Burned; Operative Wound

Keywords

anesthesia; burned; TIVA; propofol

Outcome Measures

Primary Outcomes (1)

• Propofol plasmatic levels Measured by high pressure liquid chromatography

  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.

  From start of propofol infusion to 12 hrs after stopped infusion of propofol.

Secondary Outcomes (4)

• Hemodynamics

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.

• Heart Rate

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.

• Pulse oximetry

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.

• BIS

  Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.

Study Arms (1)

Propofol

Severe burn adult under general anesthesia with propofol + remifentanil evaluation of propofol effect using BIS

Drug: Propofol; Device: BIS

Interventions

Propofol DRUG

Patients undergoing general anesthesia using target controlled infusion of propofol. Initial bolus of 1-2 mg/kg and then a continuous infusion of 10 mg/kg/hr that will be adjusted adjusted to maintain a BIS between 40 and 60.

Also known as: Propofol Intravenous dose

Propofol

BIS DEVICE

GeneralAnesthesia maintenance with propofol+remifentanil guided by BIS monitoring.

Also known as: General anesthetic

Propofol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with Major burns

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Victor Contreras, MSN: lead
• Pontificia Universidad Catolica de Chile: collaborator

Study Sites (1)

Victor Contreras

Santiago, Santiago Metropolitan, 8420525, Chile

Location

Related Publications (5)

• Shin SW, Cho AR, Lee HJ, Kim HJ, Byeon GJ, Yoon JW, Kim KH, Kwon JY. Maintenance anaesthetics during remifentanil-based anaesthesia might affect postoperative pain control after breast cancer surgery. Br J Anaesth. 2010 Nov;105(5):661-7. doi: 10.1093/bja/aeq257. Epub 2010 Sep 28.

  PMID: 20876698 BACKGROUND

• Cortinez LI, De la Fuente N, Eleveld DJ, Oliveros A, Crovari F, Sepulveda P, Ibacache M, Solari S. Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis. Anesth Analg. 2014 Aug;119(2):302-310. doi: 10.1213/ANE.0000000000000317.

  PMID: 24977639 BACKGROUND

• Cortinez LI, Anderson BJ, Penna A, Olivares L, Munoz HR, Holford NH, Struys MM, Sepulveda P. Influence of obesity on propofol pharmacokinetics: derivation of a pharmacokinetic model. Br J Anaesth. 2010 Oct;105(4):448-56. doi: 10.1093/bja/aeq195. Epub 2010 Aug 14.

  PMID: 20710020 BACKGROUND

• Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959. doi: 10.1016/j.bja.2018.01.018. Epub 2018 Mar 12.

  PMID: 29661412 BACKGROUND

• Rolle A, Paredes S, Cortinez LI, Anderson BJ, Quezada N, Solari S, Allende F, Torres J, Cabrera D, Contreras V, Carmona J, Ramirez C, Oliveros AM, Ibacache M. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients. Br J Anaesth. 2018 May;120(5):969-977. doi: 10.1016/j.bja.2018.01.040. Epub 2018 Mar 28.

  PMID: 29661414 BACKGROUND

MeSH Terms

Conditions

Burns; Surgical Wound

Interventions

Propofol; Anesthesia, General

Condition Hierarchy (Ancestors)

Wounds and Injuries

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Anesthesia; Anesthesia and Analgesia

Study Officials

• Luis I Cortinez, MD

  Pontificia Universidad Catolica de Chile

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Co-Investigator. Project Manager of Department of Anesthesiology

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: October 12, 2018
• Study Start: September 29, 2018
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: March 8, 2022

Record last verified: 2022-03

Locations

CL (1)