Acute Kidney Injury
Conditions
Keywords
Acute kidney injury, AKI, cardiopulmonary bypass
Brief summary
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.
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.
Interventions
DRUGFurosemide
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.
PROCEDUREPeritoneal 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.
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Negative Fluid Balance on Postop Day 1 | Postop day 1 | Difference of inputs and outputs, including urine output and PD drainage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cause Mortality | duration of hospitalization (an average of 2 weeks) | In-hospital mortality |
| Respiratory Support Administered | Duration of postoperative intubation (average time approximately- 1 week) | Duration of initial course of postoperative mechanical ventilation |
| NGAL Concentration | Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr) | — |
| Duration of Cardiac ICU Stay | Average 2 weeks | Total days of initial postoperative stay in cardiac ICU |
| Duration of Hospital Stay | Average 4 weeks | Total days of initial postoperative stay in hospital |
| Doses of Potassium Chloride or Arginine Chloride Required | Postop day 0-5 | Total doses of potassium chloride or arginine chloride given during the first five postoperative days. |
| B-Natriuretic Peptide | At 24hours and 48 hours postoperative | BNP measured at 24 and 48 hours postoperatively |
| Modified Oxygenation Index | at 24 and 48 hours postoperative | Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen |
| Renal/Electrolyte Abnormalities | Postop morning 1-5 | Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Furosemide Patients randomized to receive furosemide | 32 |
| Peritoneal Dialysis Patients randomized to receive peritoneal dialysis | 41 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Pleural Peritoneal communication | 0 | 9 |
Baseline characteristics
| Characteristic | Peritoneal Dialysis | Total | Furosemide |
|---|---|---|---|
| Age, Continuous | 8 days | 8 days | 9 days |
| Baseline Creatinine (mg/dL) | 0.4 mg/dl | 0.4 mg/dl | 0.4 mg/dl |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 71 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Length (cm) | 50 cm | 50 cm | 50 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 37 Participants | 66 Participants | 29 Participants |
| Region of Enrollment United States | 41 participants | 73 participants | 32 participants |
| Sex: Female, Male Female | 15 Participants | 26 Participants | 11 Participants |
| Sex: Female, Male Male | 26 Participants | 47 Participants | 21 Participants |
| Weight (kg) | 3.4 kg | 3.4 kg | 3.4 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 32 | 1 / 41 |
| other Total, other adverse events | 0 / 32 | 2 / 41 |
| serious Total, serious adverse events | 0 / 32 | 0 / 41 |
Outcome results
Primary
Number of Participants With Negative Fluid Balance on Postop Day 1
Difference of inputs and outputs, including urine output and PD drainage.
Time frame: Postop day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Furosemide | Number of Participants With Negative Fluid Balance on Postop Day 1 | 21 Participants |
| Peritoneal Dialysis | Number of Participants With Negative Fluid Balance on Postop Day 1 | 29 Participants |
Secondary
All Cause Mortality
In-hospital mortality
Time frame: duration of hospitalization (an average of 2 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Furosemide | All Cause Mortality | 3 Participants |
| Peritoneal Dialysis | All Cause Mortality | 1 Participants |
Secondary
B-Natriuretic Peptide
BNP measured at 24 and 48 hours postoperatively
Time frame: At 24hours and 48 hours postoperative
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Furosemide | B-Natriuretic Peptide | 24 hours | 1334 pg/ml |
| Furosemide | B-Natriuretic Peptide | 48 hours | 1110 pg/ml |
| Peritoneal Dialysis | B-Natriuretic Peptide | 24 hours | 1168 pg/ml |
| Peritoneal Dialysis | B-Natriuretic Peptide | 48 hours | 663 pg/ml |
Secondary
Doses of Potassium Chloride or Arginine Chloride Required
Total doses of potassium chloride or arginine chloride given during the first five postoperative days.
Time frame: Postop day 0-5
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Doses of Potassium Chloride or Arginine Chloride Required | 2 doses given |
| Peritoneal Dialysis | Doses of Potassium Chloride or Arginine Chloride Required | 1 doses given |
Secondary
Duration of Cardiac ICU Stay
Total days of initial postoperative stay in cardiac ICU
Time frame: Average 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Duration of Cardiac ICU Stay | 9 days |
| Peritoneal Dialysis | Duration of Cardiac ICU Stay | 7 days |
Secondary
Duration of Hospital Stay
Total days of initial postoperative stay in hospital
Time frame: Average 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Duration of Hospital Stay | 15 days |
| Peritoneal Dialysis | Duration of Hospital Stay | 14 days |
Secondary
Modified Oxygenation Index
Product of Mean airway pressure delivered by mechanical ventilation and FiO2 of administered oxygen
Time frame: at 24 and 48 hours postoperative
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Furosemide | Modified Oxygenation Index | 24 Hours | 4 Units |
| Furosemide | Modified Oxygenation Index | 48 Hours | 3.8 Units |
| Peritoneal Dialysis | Modified Oxygenation Index | 24 Hours | 4 Units |
| Peritoneal Dialysis | Modified Oxygenation Index | 48 Hours | 2.8 Units |
Secondary
NGAL Concentration
Time frame: Pre-op, and postop (2hr, 6hr, 12hr, 24hr, 48hr)
Population: Data were collected but not analyzed. Due to a high incidence of volatile and un-reportable NGAL levels, concerns were raised about the storage or processing of samples affecting data validity. Given the overwhelming concern of erroneous data, analysis was not performed as planned.
Secondary
Renal/Electrolyte Abnormalities
Total sum of renal and electrolyte abnormalities over the first 5 postoperative days as defined in the protocol
Time frame: Postop morning 1-5
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Renal/Electrolyte Abnormalities | 6 abnormalities |
| Peritoneal Dialysis | Renal/Electrolyte Abnormalities | 4 abnormalities |
Secondary
Respiratory Support Administered
Duration of initial course of postoperative mechanical ventilation
Time frame: Duration of postoperative intubation (average time approximately- 1 week)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Furosemide | Respiratory Support Administered | 4 days |
| Peritoneal Dialysis | Respiratory Support Administered | 3 days |