Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery (HERACLES)

Background: Volume replacement strategies and type of fluid used in patients undergoing cardiac surgery have changed during the last years. Currently used crystalloid solutes have a variable composition and a major impact on organ function and outcome. Additionally critically ill patients are prone to fluid overload, which is despite common perception, not a benign occurrence as it is associated with prolonged ICU- and hospital length of stay and increased mortality rates. Fluid resuscitation using bolus or continuous infusion of hypertonic saline was used for more than thirty years. Only a few studies have been conducted so far, but they showed that infusion of hypertonic saline results in less volume administered, increased renal function less weight gain in critically ill patients when compared to other crystalloids.

Aim: This preliminary randomized controlled double-blind study aims to identify whether fluid resuscitation using hypertonic saline (HS) when used in addition to lactated Ringers solution results in less total fluid amount administered in patients following cardiac surgery. Additionally we want to evaluate whether the use of hypertonic saline results less need for pharmacological cardiocirculatory support, increased renal function, less postoperative volume overload shortened post-cardiac bypass immune suppression and increased postoperative outcomes.

Study intervention: At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will thereafter be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Valvular Heart Disease
• Intervention / Treatment: Drug: Hypertonic saline; Drug: 0.9% saline

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Intensive Care, Bern University Hospital and University of Bern, Bern, Switzerland

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:

• Adult patients undergoing cardiac surgery for ischemic or valvular heart disease

Exclusion Criteria:

• Patients unable to give informed consent
• Patients with age <18 years
• Pregnancy or breastfeeding
• Left-ventricular ejection fraction (LVEF) < 30% preoperatively
• Preexisting renal insufficiency with an eGFR <30 ml/min/1.73m2
• Patients with postoperative circulatory support devices such as LVAD, IABP, Impella, ECMO
• Preexisting serum sodium of >145mmol/l or <135 mmol/L
• Preexisting serum chloremia >107mmol/l or < 98 mmol/L
• Systemic steroid therapy (at any dose at time of inclusion)
• Chronic liver disease (bilirubin >3 mg.dl)
• Any signs of infection or sepsis defined as clear clinical evidence for active infection or current antibiotic therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 7.3% NaCl (intervention); At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl NaCl by infusion pump over 60 minutes.	Drug: Hypertonic saline; At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl by infusion pump over 60 minutes.; Other Names: 7.9% NaCl
Active Comparator: 0.9% NaCl (comparator); At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes.	Drug: 0.9% saline; At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes.; Other Names: normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
total cumulative amount of fluids infused	daily until ICU discharge, max until postoperative day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative weight gain		until postoperative day 6
total postoperative cumulative urinary output		daily until ICU discharge, max until postoperative day 90
total cumulative dose of inopressors per kg bodyweight /hour	cumulation of norepinephrine and epinephrine	until ICU discharge, max until postoperative day 90
time on inopressors	norepinephrine and/or epinephrine	from ICU admission until stop of inopressors, max until postoperative day 90
variation in renal function markers	renal damage maker (TIMP2-IGFB, creatinine)	until postoperative day 6
variation in acid-base homeostasis	pH, base excess, lactate, bicarbonate, electrolytes	until postoperative day 6
variation in immune function	mHLA-DR	until postoperative day 6
time on the ventilator		from ICU admission until time of extubation, maximum 90 days
occurence of infection		occurence of infection during the index hospitalisation or subsequent admissions due to infection upto 90 postoperative days
length of stay	time to ICU/hospital-discharge	time to ICU/hospital-discharge however long this may take, maximum 90 days
readmissions to the ICU		readmissions to the ICU within postoperative 90 days
mortality		until postoperative day 90

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Study Director: Joerg C Schefold, MD, Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland

Publications and helpful links

General Publications

• Pfortmueller CA, Messmer AS, Hess B, Reineke D, Jakob L, Wenger S, Waskowski J, Zuercher P, Stoehr F, Erdoes G, Luedi MM, Jakob SM, Englberger L, Schefold JC. Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial. Trials. 2019 Jun 14;20(1):357. doi: 10.1186/s13063-019-3420-6.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Actual): May 27, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: August 23, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases
• Other Study ID Numbers: 201706011.1

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
• product manufactured in and exported from the U.S.: No