Fluid Resuscitation in Burn Patients (CARE)

Clearance of Acetate During Fluid Resuscitation of Critically Ill Burn Patients: The CARE Trial.

Balanced solutions with low chloride concentration could represent an alternative to high chloride concentration solutions. Such balanced solutions contain other acid as buffers (i.e. acetate and/or gluconate). However, acetate has been associated with alteration of cardiac function when used as buffer in dialysate when high acetate concentrations are used and could promote the development of metabolic acidosis if it accumulates. Therefore, the safety of such solutions remains poorly explored. Because critically ill patients receive large amount of fluid during the early phase of resuscitation, large amount of acetate are to be administrated if such solutions are used. While acetate-containing solutions have been suggested to be safe in this setting, studies are still lacking regarding clearance and accumulation in critically ill patients.

It is expected to include 28 patients, the objective to analyze the data of 20 patients.

Study Overview

• Status: Completed
• Conditions: Severe Burns; Fluid Resuscitation
• Intervention / Treatment: Drug: Plasmalyte; Drug: Ringer lactate

Detailed Description

The main objectives of the study is 1) to determine whether Plasmalyte® promote the development of metabolic acidosis in comparison with an acetate-free balanced solutions: Ringer lactate (chloride concentration of 111 mmol/L) and 2) to determine Acetate & gluconate clearance during fluid resuscitation of severely burn patients Plasmalyte® (chloride concentration of 98 mmol/L) . Severely burn patients will be randomized to receive Plasmalyte® or Ringer Lactate for initial fluid resuscitation during the first 5 days following admission.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Departement of Anesthesiology, Critical Care and Burn Unit; Saint-Louis hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over 18 years
• TBSA>30%
• Admission to an intensive care unit within 12 hours after burn injury
• Signed informed consent to Patient / Parent / ( Inclusion in Emergency and Consent is Collected)
• social Insurance cover

Exclusion Criteria:

• Decline to participate
• pregnancy
• Metabolic alkalosis (excess of base> 5mmol / L)
• legal obstacle to participate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plasmalyte®; Plasmalyte® is a balanced solution containing a low chloride concentration (i.e. 98 mmol/L), it also contains acetate (27 mmol/L) and gluconate (23 mmol/L) as buffer solutions.	Drug: Plasmalyte; Parenteral administration of Plasmalyte initiated immediately after inclusion at a dosage of 4 ml / kg per percentage area of skin burned for the first 24 hours after burn injury and adjusted based on hemodynamic monitoring. Each patient will receive this solution up to 5 days.; Other Names: PLASMALYTE VIAFLO
Experimental: Ringer Lactate®; Ringer Lactate® is a balanced solution containing a low chloride concentration (i.e. 111mmol/L), it also contains lactate (29 mmol/L) as buffer solutions.	Drug: Ringer lactate; Parenteral administration of Ringer lactate initiated immediately after inclusion at a dosage of 4 ml / kg per percentage area of skin burned for the first 24 hours after burn injury and adjusted based on hemodynamic monitoring. Each patient will receive this solution up to 5 days.; Other Names: RINGER LACTATE VIAFLO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main endpoint is to compare the base deficit in patients receiving Plasmalyte® or Ringer lactate after 24 hours of admission.	Arterial blood gas analysis	after 24 hours of admission.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acetate, gluconate and lactate clearance respectively in patients receiving Plasmalyte® or Ringer lactate.	Arterial blood gas analysis	Every 6 hours for 48 hours, then every 12 hours for acid-base status during 5 days.
acid-base status and strong ion difference after 24 hours of Plasmalyte® or Ringer lactate infusion	Arterial blood gas analysis	Every 6 hours for 48 hours, then every 12 hours for acid-base status during 5 days.
Occurrence of cardiac dysfunction, defined as altered left ventricular ejection fraction(<50%)	Trans-thoracic or trans-esophageal ultrasound	Every day during 5 days
Incidence of AKI (according to the KDIGO definition)	urine output and serum creatinine	Every day during 5 days
Sequential Organ Failure Assessment score	SOFA score calculation	During the first 5 days of intensive care unit stay
mortality at day 28	Mortality will be collected	At 28 day after admission

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Matthieu Legrand, MD, PhD, Departement of Anesthesiology, Critical Care and Burn Unit; Saint-Louis hospital, 1 Avenue Claude Vellefaux, 75010, Paris & University Paris Diderot

Publications and helpful links

General Publications

• Shaw AD, Bagshaw SM, Goldstein SL, Scherer LA, Duan M, Schermer CR, Kellum JA. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg. 2012 May;255(5):821-9. doi: 10.1097/SLA.0b013e31825074f5.
• Hahn RG. Should anaesthetists stop infusing isotonic saline? Br J Anaesth. 2014 Jan;112(1):4-6. doi: 10.1093/bja/aet292. No abstract available.
• Zhou F, Peng ZY, Bishop JV, Cove ME, Singbartl K, Kellum JA. Effects of fluid resuscitation with 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis*. Crit Care Med. 2014 Apr;42(4):e270-8. doi: 10.1097/CCM.0000000000000145.
• Davies PG, Venkatesh B, Morgan TJ, Presneill JJ, Kruger PS, Thomas BJ, Roberts MS, Mundy J. Plasma acetate, gluconate and interleukin-6 profiles during and after cardiopulmonary bypass: a comparison of Plasma-Lyte 148 with a bicarbonate-balanced solution. Crit Care. 2011;15(1):R21. doi: 10.1186/cc9966. Epub 2011 Jan 14.
• Morgan TJ, Power G, Venkatesh B, Jones MA. Acid-base effects of a bicarbonate-balanced priming fluid during cardiopulmonary bypass: comparison with Plasma-Lyte 148. A randomised single-blinded study. Anaesth Intensive Care. 2008 Nov;36(6):822-9. doi: 10.1177/0310057X0803600611. Erratum In: Anaesth Intensive Care. 2012 Jul;40(4):719.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2017
• Primary Completion (Actual): September 12, 2018
• Study Completion (Actual): December 2, 2019

Study Registration Dates

• First Submitted: April 13, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Burns; Critically ill; Acid-Base status
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: P160502

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