Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery

Study Overview
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Brief Summary
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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.

Official Title
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Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery

Conditions
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Cardiovascular Diseases, Valvular Heart Disease

Intervention / Treatment
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* Drug: Hypertonic saline
* Drug: 0.9% saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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 be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |