A Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study)

Not Applicable

Completed

Conditions: Sepsis

Interventions: Other: Conservative Fluid Management Strategy

Registration Number: NCT02159079

Lead Sponsor: Vanderbilt University

Brief Summary: Sepsis is a common inflammatory response to infection characterized by hypovolemia and vasodilation for which early administration of intravenous fluids has been suggested to improve outcomes. The ideal fluid balance following initial resuscitation is unclear. Septic patients treated in the intensive care unit commonly receive significant volumes of intravenous fluids with resultant positive fluid balance for up to a week after their initial resuscitation. Observational studies have associated fluid receipt and positive fluid balance in patients with severe sepsis and septic shock with increased mortality but are inherently limited by indication bias. In order to determine the optimal approach to fluid management following resuscitation in patients with severe sepsis and septic shock, a randomized controlled trial is needed. The primary hypothesis of this study is that, compared to usual care, a conservative approach to fluid management after resuscitation in patients with sepsis and cardiopulmonary dysfunction will increase intensive care unit free days.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

ICU patients
Adults
Sepsis as defined by at least two systemic inflammatory response syndrome criteria and receipt of antimicrobial therapy
Cardiopulmonary dysfunction as defined shock or respiratory failure

Exclusion Criteria

Inability to obtain consent
Greater than 48 hours since inclusion criteria initially met
Allergy to furosemide AND bumetanide
Rhabdomyolysis with creatinine kinase > 5000 U/L
Hypercalcemia with calcium >11 mg/dL
Diabetic Ketoacidosis requiring continuous insulin infusion
Tumor Lysis Syndrome diagnosed clinically
Pancreatitis diagnosed clinically
Chronic Hypoxic Respiratory Failure with Home Oxygen Use of FiO2≥0.3
Chronic ventilator dependence
cervical spinal cord injury at level C5 or higher
amyotrophic lateral sclerosis
Guillain-Barré Syndrome
myasthenia gravis
Renal failure requiring renal replacement therapy
Burns >20% of body surface area
Pregnant
Preexisting pulmonary hypertension with PAPmean>40 on RHC
Severe chronic liver disease with Childs-Pugh Score >11
Moribund and not expected to survive an additional 24 hours
Actively withdrawing life support or transitioning to comfort measures only
Unwillingness of treating physician to employ conservative fluid strategy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conservative Fluid Management Strategy	Conservative Fluid Management Strategy	For patients in the conservative fluid management arm, beginning 12 hours after admission to study ICU and ending at the first of ICU discharge, death, return to home inspired oxygen, or study day 14, fluid management will be controlled by a study protocol. Patients in shock will receive fluid boluses only as specified by the protocol for oliguria and rapidly increasing vasopressor requirement. Patients not in shock will receive fluid boluses only as specified by the protocol for oliguria. Output will exceed input each day using a diuretic drip if required. Study protocol will be held only for pre-specified Safety Endpoints of persistent oliguria, decompensating shock, diuretic side effect, and intervening acute event.

Primary Outcome Measures

Name	Time	Method
ICU-free Days to 14 Days After Enrollment	14 days	The primary outcome will be the number of ICU-free days to day 14 (defined as the number days alive and outside of the intensive care unit in the first 14 days after enrollment).

Secondary Outcome Measures

Name	Time	Method
Renal Replacement Therapy-free Days to Day 14	14 days	Renal replacement therapy-free days to day 14 (defined as the number of days alive and free of renal replacement therapy from the last receipt of renal replacement therapy after enrollment to study day 14)
Highest Plasma Creatinine Between Enrollment and 28 Days After Enrollment	28 days	Highest plasma creatinine (mg/dL) between enrollment and 28 days after enrollment, censored at hospital discharge
In-hospital Mortality to Day 14	14 days	A secondary outcome will be in-hospital mortality to day 14 (defined as the incidence of mortality prior to hospital discharge within 14 days after enrollment).
Highest Stage of Acute Kidney Injury	28 days	Highest stage of acute kidney injury as defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria Stage 0 (no acute kidney injury) Stage 1 Serum creatinine 1.5-1.9 times baseline or ≥0.3 mg/dl (≥26.5 mmol/l) increase or Urine output \<0.5 ml/kg/h for 6-12 hours Stage 2 Serum creatinine 2.0-2.9 times baseline or \<0.5 ml/kg/h for ≥12 hours Stage 3 Serum creatinine 3.0 times baseline or Increase in serum creatinine to ≥4.0 mg/dl (≥353.6 mmol/l) or Initiation of renal replacement therapy or in patients \<18 years, decrease in eGFR to \<35 ml/min per 1.73 m² or Urine output \<0.3 ml/kg/h for ≥24 hours or anuria for ≥12 hours
Ventilator-free Days to Day 14	14 days	A secondary outcome will be the number of ventilator-free days (defined as the number of days alive and breathing unassisted after the final achievement of unassisted breathing before day 14)
Receipt of Renal Replacement Therapy	28 days	receipt of renal replacement therapy between enrollment and the first of 28 days or hospital discharge