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

Anesthesia Clinical Trial

— HUAPQ  

Official title:

Development of Pharmacokinetic / Pharmacodynamic (pk/pd) Model of Propofol in Patients With Severe Burns

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03704285
• Other study ID #: 171215006
• Status: Terminated
• Start date: September 29, 2018
• Est. completion date: December 30, 2021

Study information

• Verified date: March 2022
• Source: Pontificia Universidad Catolica de Chile
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia
• Burned
• Operative Wound
• Surgical Wound

Intervention

Drug:
• Propofol
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.

Device:
• BIS
GeneralAnesthesia maintenance with propofol+remifentanil guided by BIS monitoring.

Locations

Country	Name	City	State
Chile	Victor Contreras	Santiago	Región Metropolitana

Sponsors (2)

Lead Sponsor	Collaborator
Victor Contreras, MSN	Pontificia Universidad Catolica de Chile

Country where clinical trial is conducted

Chile, 

References & Publications (5)

Cortínez LI, Anderson BJ, Penna A, Olivares L, Muñoz 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. — View Citation

Cortínez 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. — View 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. Erratum in: Br J Anaesth. 2018 Aug;121(2):519. — View Citation

Rolle A, Paredes S, Cortínez LI, Anderson BJ, Quezada N, Solari S, Allende F, Torres J, Cabrera D, Contreras V, Carmona J, Ramírez 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. — View 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. — View Citation

Outcome

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