Clinical trial NCT03704285: Development of pk/pd Model of Propofol in Patients With Severe Burns
Official title: Development of Pharmacokinetic / Pharmacodynamic (pk/pd) Model of Propofol in Patients With Severe Burns
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Anesthesia
Burned
Operative Wound
Keywords: anesthesia
burned
TIVA
propofol
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
Collaborators: name: Pontificia Universidad Catolica de Chile
First posted: 2018-10-12
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults with Major burns

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Propofol plasmatic levels Measured by high pressure liquid chromatography
timeFrame: From start of propofol infusion to 12 hrs after stopped infusion of propofol.
Secondary outcomes:
measure: Hemodynamics
timeFrame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
measure: Heart Rate
timeFrame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
measure: Pulse oximetry
timeFrame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
measure: BIS
timeFrame: Every 5 min. Since entering operating room up to end of anesthesia and leaving to recovery room. In average 2 hrs.
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Victor Contreras
state: Región Metropolitana
Study officials:
affiliation: Pontificia Universidad Catolica de Chile
name: Luis I Cortinez, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.