Limiting IV Chloride to Reduce AKI After Cardiac Surgery (LICRA)

Does Varying the Chloride Content of Intravenous Fluid Alter the Risk of Acute Kidney Injury After Cardiac Surgery?

This primary aim of this study is to test the impact of a strategy of perioperative chloride-restriction through intravenous (IV) fluid therapy on the incidence of acute kidney injury after cardiac surgery.

A prospective, open-label, single-centre 4-period sequential study of varying strategies of perioperative IV fluid composition will test the hypothesis that a perioperative protocol for the administration of chloride-poor intravenous fluids compared to chloride-rich intravenous fluids will reduce the incidence of AKI after adult cardiothoracic surgery.

Study Overview

• Status: Completed
• Conditions: Patients Undergoing Cardiothoracic Surgery
• Intervention / Treatment: Other: High-chloride perioperative intravenous fluid strategy; Other: Low-chloride perioperative intravenous fluid strategy

Detailed Description

After an initial run-in period of approximately 1 month (using a chloride-rich fluid strategy), the first study period of 5 months will commence, also comprising a chloride-rich perioperative IV fluid therapy strategy (0.9% saline or 4% albumin). This will include intraoperative fluid and postoperative fluid for the duration of stay in the intensive care unit. This will then be followed by a 1-month transition period before a second period of 5 months will commence where perioperative intravenous fluid therapy will consist of chloride-poor fluids (Lactated Ringer's solution or concentrated 20% albumin). A subsequent 1-month transition period will then be followed by a third period of 5 months characterized by perioperative IV fluid therapy with an alternative combination of chloride-poor solutions (PlasmaLyte® 148 or concentrated 20% albumin). A final 1-month transition period will be followed by a fourth and final period of 5 months characterized by a return to perioperative IV fluid therapy with chloride-rich fluids (0.9% saline or 4% albumin). A final 1-month run-off period using a chloride-rich perioperative fluid strategy will follow prior to study completion.

• Study Type: Interventional
• Enrollment (Actual): 1298
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All adult patients undergoing surgery by Division of cardiothoracic surgery

Exclusion Criteria:

Nil

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Chloride-rich IV fluid; The chloride-rich strategy will include 0.9% saline as the perioperative crystalloid of choice with 4% albumin as the perioperative colloid of choice.	Other: High-chloride perioperative intravenous fluid strategy; Other Names: Chloride-rich IV fluid
ACTIVE_COMPARATOR: Chloride-poor IV fluid; A low-chloride strategy of perioperative IV fluid will include PlasmaLyte 148 or Hartmann's solution as the crystalloid of choice with 20% albumin as the colloid of choice.	Other: Low-chloride perioperative intravenous fluid strategy; The low-chloride perioperative IV fluid strategy will include the use of PlasmaLyte 148 or Hartmann's solution as the crystalloid of choice and 20% albumin as the colloid of choice.; Other Names: Chloride-poor IV fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak ∆ serum creatinine	Maximum change in serum creatinine from baseline	5 days postoperatively
AKI ≥stage2	AKI, ≥stage2, defined by creatinine-based KDIGO criteria	5 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual stages of AKI	Individual stages of AKI, defined by creatinine-based KDIGO criteria	7 days
Mortality	Mortality	On discharge from hospital (7-30 days)
Renal replacement therapy	Renal replacement therapy	On discharge from hospital (7-30 days)
ICU Length of stay	ICU Length of stay	On discharge from hospital (7-30 days)
Hospital Length of stay	Hospital Length of stay	On discharge from hospital (7-30 days)
Time to first extubation	Time to first extubation	On discharge from hospital (7-30 days)
Red cell transfusion requirement	Volume of packed red blood cells transfused	Intraoperative and postoperatively through completion of postoperative day 1 or ICU discharge, whichever occurred first
Fresh frozen plasma transfusion requirement	Volume of fresh frozen plasma transfused	Intraoperative and postoperatively through completion of postoperative day 1 or ICU discharge, whichever occurred first
Platelet transfusion requirement	Volume of platelets transfused	Intraoperative and postoperatively through completion of postoperative day 1 or ICU discharge, whichever occurred first
Cryoprecipitate transfusion requirement	Volume of cryoprecipitate transfused	Intraoperative and postoperatively through completion of postoperative day 1 or ICU discharge, whichever occurred first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted mean serum chloride concentration	A time-weighted calculation of mean serum chloride concentration	First 5 days and through ICU admission
Incidence of hypernatremia	Incidence of hypernatremia (SNa+ >150 mmol/L)	On discharge from hospital (7-30 days)
Incidence of hyponatremia	Incidence of hyponatremia (SNa+ <130 mmol/L)	On discharge from hospital (7-30 days)
Incidence of hyperchloremia	Incidence of hyperchloremia (SCl- >110 mmol/L)	On discharge from hospital (7-30 days)
Incidence of hypochloremia	Incidence of hypochloremia (SCl- <96 mmol/L)	On discharge from hospital (7-30 days)
Incidence of acidemia	Incidence of acidemia (pH <7.3)	On discharge from hospital (7-30 days)
Incidence of alkalemia	Incidence of alkalemia (pH >7.5)	On discharge from hospital (7-30 days)

Collaborators and Investigators

• Sponsor: Bayside Health
• Collaborators: Australian and New Zealand College of Anaesthetists
• Investigators: Principal Investigator: David R McIlroy, MBBS, MClinEpi, FANZCA, Alfred Hospital and Monash University

Publications and helpful links

General Publications

• McIlroy DR, Murphy D, Shotwell MS, Bhatia D. Peak Serum Chloride and Hyperchloremia in Patients Undergoing Cardiac Surgery Is Not Explained by Chloride-Rich Intravenous Fluid Alone: A Post-Hoc Analysis of the LICRA Trial. J Cardiothorac Vasc Anesth. 2021 May;35(5):1321-1331. doi: 10.1053/j.jvca.2020.07.085. Epub 2020 Aug 7.
• McIlroy D, Murphy D, Kasza J, Bhatia D, Wutzlhofer L, Marasco S. Effects of restricting perioperative use of intravenous chloride on kidney injury in patients undergoing cardiac surgery: the LICRA pragmatic controlled clinical trial. Intensive Care Med. 2017 Jun;43(6):795-806. doi: 10.1007/s00134-017-4772-6. Epub 2017 Mar 25.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 3, 2014
• Primary Completion (ACTUAL): December 9, 2015
• Study Completion (ACTUAL): February 12, 2016

Study Registration Dates

• First Submitted: December 19, 2013
• First Submitted That Met QC Criteria: December 19, 2013
• First Posted (ESTIMATE): December 25, 2013

Study Record Updates

• Last Update Posted (ACTUAL): April 22, 2020
• Last Update Submitted That Met QC Criteria: April 20, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: cardiac surgery; acute kidney injury; Thoracic surgery; hyperchloremia; intravenous fluid
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 382/13