Peritoneal Dialysis vs Furosemide for Acute Kidney Injury After Cardiopulmonary Bypass

Early Renal Replacement Therapy vs. Furosemide for Neonates With Oliguria After Cardiopulmonary Bypass

Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) in infants is common and associated with poor outcomes. Peritoneal dialysis (PD) and furosemide have been used to attain negative fluid balance due to AKI induced oliguria, but have not been compared prospectively. The investigators will prospectively compare outcomes of infants with oliguria after CPB randomized to PD vs. furosemide with the hypothesis that infants receiving PD have superior outcomes.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Furosemide; Procedure: Peritoneal Dialysis

Detailed Description

Background: Acute kidney injury (AKI) is a common postoperative complication after heart surgery with cardiopulmonary bypass (CPB). Multiple studies have demonstrated that patients with AKI have worse clinical outcomes, such as longer ventilation times and increased length of stay, which is thought to be secondary to associated oliguria and subsequent fluid overload. Studies suggest that early renal replacement therapy (RRT) via peritoneal dialysis (PD) may prevent fluid overload and therefore be a superior management to diuretic (i.e. furosemide) administration. However, there is no published evidence to suggest superiority or laboratory data available to guide decision making.

Objective: Our primary objective is to determine if early institution of PD improves clinical outcomes compared to administration of furosemide in post-operative cardiac infants with acute kidney injury. We hypothesize that early initiation of PD will improve clinical outcomes. We will determine if these clinical outcomes will be better among good responders of furosemide compared to poor responders. We will determine if postoperative NGAL concentrations are predictive of poor response to furosemide.

Design / Methods: The study will be a single-center randomized clinical trial among neonates undergoing cardiac surgery with CPB with planned placement of a PD catheter due to risk of AKI. If patients demonstrate oliguria within the first postoperative day, they will be randomized to early PD or trial of furosemide. Clinical and laboratory data will be collected and compared between groups.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45223
      • Cincinnati Childrens Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age less than 6 months of age;
• Undergoing cardiothoracic surgery with CPB;
• Planned placement of PD catheter per institutional standard of care criteria.

Exclusion Criteria:

• Pre-existing chronic kidney disease stage 3 or above (correlating with estimated GFR<60 ml/min/m2, which will be calculated using routine preoperative serum creatinine value using the modified Schwartz equation).
• Known history of allergy to furosemide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furosemide; Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output >1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.	Drug: Furosemide; Patients randomized to the furosemide arm will be given 1 mg/kg intravenously every 6 hours for 2 doses and then as directed by CICU attending to augment urine output. Patients within this arm who have urine output <1 ml/kg/hr over 16 hours after the first dose of Lasix will be considered poor responders. These patients may be started on PD if clinically indicated. Those who show good response (urine output >1 ml/kg/hr over subsequent 16 hours) will continue furosemide as needed to augment urine output. If they subsequently develop oliguria or fluid overload unresponsive to diuretic therapy, these patients may later be started on PD at discretion of CICU attending with consultation of nephrology service.; Other Names: Lasix
Experimental: Peritoneal dialysis; Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management will be directed by CICU attending and Nephrology service	Procedure: Peritoneal Dialysis; Patients within the PD arm will begin PD with a standardized dialysis plan of 10ml/kg of 1.5% Dianeal™ with 1 hours cycles (5 minute fill, 45 minute dwell and 10 minute drain). Further PD management and discontinuation will be directed by CICU attending and Nephrology service.; Other Names: PD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Negative Fluid Balance on Postop Day 1	Difference of inputs and outputs, including urine output and PD drainage.	Postop day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Support Administered	Duration of initial course of postoperative mechanical ventilation	Duration of postoperative intubation (average time approximately- 1 week)
NGAL Concentration		Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr)
Duration of Cardiac ICU Stay	Total days of initial postoperative stay in cardiac ICU	Average 2 weeks
Duration of Hospital Stay	Total days of initial postoperative stay in hospital	Average 4 weeks
All Cause Mortality	In-hospital mortality	duration of hospitalization (an average of 2 weeks)
Renal/Electrolyte Abnormalities	Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol	Postop morning 1-5
Doses of Potassium Chloride or Arginine Chloride Required	Total doses of potassium chloride or arginine chloride given during the first five postoperative days.	Postop day 0-5
B-Natriuretic Peptide	BNP measured at 24 and 48 hours postoperatively	At 24hours and 48 hours postoperative
Modified Oxygenation Index	Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen	at 24 and 48 hours postoperative

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: David M Kwiatkowski, MD, Cinncinnati Children's Hospital Medical Center; Study Director: Catherine D Krawczeski, MD, Cinncinnati Children's Hospital Medical Center; Study Director: Stuart L Goldstein, MD, Cinncinnati Children's Hospital Medical Center

Publications and helpful links

General Publications

• Kwiatkowski DM, Goldstein SL, Cooper DS, Nelson DP, Morales DL, Krawczeski CD. Peritoneal Dialysis vs Furosemide for Prevention of Fluid Overload in Infants After Cardiac Surgery: A Randomized Clinical Trial. JAMA Pediatr. 2017 Apr 1;171(4):357-364. doi: 10.1001/jamapediatrics.2016.4538.

Helpful Links

• Center for Acute Care Nephology at Cincinnati Childrens

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: September 20, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Actual): June 9, 2017
• Last Update Submitted That Met QC Criteria: May 4, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: cardiopulmonary bypass; Acute kidney injury; AKI
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 2011-1730

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified patient data would be available to other researchers after publication of data at the discretion of the research team after communication with the PI