Original Article
Acute Kidney Injury and Fluid Overload in Neonates Following Surgery for Congenital Heart Disease
World Journal for Pediatric and Congenital Heart Surgery 2015, Vol. 6(3) 401-406 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2150135115586814 pch.sagepub.com
Kurt D. Piggott, MD1, Meshal Soni, BS2, William M. Decampli, MD, PhD3, Jorge A. Ramirez, MD4, Dianna Holbein, ARNP5, Harun Fakioglu, MD1, Carlos J. Blanco, MD5, and Kamal K. Pourmoghadam, MD6
Abstract Background: Acute kidney injury (AKI) and fluid overload have been shown to increase morbidity and mortality. The reported incidence of AKI in pediatric patients following surgery for congenital heart disease is between 15% and 59%. Limited data exist looking at risk factors and outcomes of AKI or fluid overload in neonates undergoing surgery for congenital heart disease. Methods: Neonates aged 6 to 29 days who underwent surgery for congenital heart disease and who were without preoperative kidney disease were included in the study. The AKI was determined utilizing the Acute Kidney Injury Network criteria. Results: Ninety-five neonates were included in the study. The incidence of neonatal AKI was 45% (n ¼ 43), of which 86% had stage 1 AKI. Risk factors for AKI included cardiopulmonary bypass time, selective cerebral perfusion, preoperative aminoglycoside use, small kidneys by renal ultrasound, and risk adjustment for congenital heart surgery category. There were eight mortalities (five from stage 1 AKI group, three from stage 2, and zero from stage 3). Fluid overload and AKI both increased hospital length of stay and postoperative ventilator days. Conclusion: To avoid increased risk of morbidity and possibly mortality, every attempt should be made to identify and intervene on those risk factors, which may be modifiable or identifiable preoperatively, such as small kidneys by renal ultrasound. Keywords acute kidney injury, congenital heart disease, neonate, heart surgery, pediatric, fluid overload Submitted December 01, 2014; Accepted April 22, 2015.
Background Acute kidney injury (AKI) and fluid overload (FOL) in pediatric patients have been reported as risk factors for increased morbidity and mortality.1-6 Pediatric patients who undergo surgery for congenital heart disease are at risk for FOL and have been shown to be at increased risk for developing AKI, many of whom are neonates.1,3,4,6,7 The incidence of AKI in the latter cohort has been reported to be between 15% and 59%.1-10 Acute kidney injury is typically determined using either the pediatric Risk Injury Failure Loss End-stage (pRIFLE) criteria or the Acute Kidney Injury Network (AKIN) criteria. Promising data have been published, evaluating several serum and urinary biomarkers for early AKI, including cystin C, neutrophil gelatinaseassociated lipocalin (NGAL), interleukin 18, liver fatty acid–binding protein (L-FABP), and kidney injury molecule 1 (KIM-1).11-13 Nonetheless, creatinine still remains the most utilized marker for AKI.
1 Pediatric Cardiac Intensive Care, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, Orlando, FL, USA 2 University of Central Florida, Orlando, FL, USA 3 Pediatric Cardiothoracic Surgery, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, Orlando, FL, USA 4 Arnold Palmer Hospital for Children Hewell Kids Kidney Center, University of Central Florida College of Medicine, Orlando, FL, USA 5 Pediatric Cardiac Intensive Care, The Heart Center at Arnold Palmer Hospital for Children, Orlando, FL, USA 6 Pediatric Cardiothoracic Surgery, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, Orlando, FL, USA
Corresponding Author: Kurt D. Piggott, Pediatric Cardiac Intensive Care, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, 92 W. Miller St, MP307, Orlando, FL 32806, USA. Email: [email protected]
Downloaded from pch.sagepub.com at EMORY UNIV on August 24, 2015
402
World Journal for Pediatric and Congenital Heart Surgery 6(3) Table 1. Acute Kidney Injury Network Criteria.
Abbreviations and Acronyms AKI AKIN CPB FOL KIM-1 L-FABP NGAL PD
acute kidney injury acute kidney injury network cardiopulmonary bypass fluid overload kidney injury molecule 1 liver fatty acid–binding protein neutrophil gelatinase-associated lipocalin peritoneal dialysis
Although some data exists, evaluating the incidence and risk factors of AKI in neonates undergoing surgery for congenital heart disease, it is relatively limited. We sought to evaluate the incidence and risk factors for the development of AKI exclusively in neonates following surgery for congenital heart disease. Additionally, we wished to evaluate the percentage of FOL and AKI as they pertain to intensive care outcomes, including hospital length of stay, postoperative ventilator days, and mortality.
Materials and Methods Following approval by the institutional review board at the Arnold Palmer Medical Center, this retrospective cohort study was performed in the 20-bed cardiac intensive care unit at Arnold Palmer Hospital for Children in Orlando, Florida. We included all neonates who underwent cardiac surgery at our institution from May 2010 to December 2013, who were at least six days of age but less than 30 days of age on the day of surgery. Neonates with preexisting renal disease preoperatively, determined by creatinine clearance, were excluded from the study. In addition, if the last preoperative creatinine level was obtained prior to day 6, then the patient was excluded since this is likely a reflection of maternal creatinine. The primary variable for the study was the development of AKI as defined by the AKIN criteria (Table 1). We chose to use the AKIN criteria because while pRIFLE has been reported as the more sensitive criteria for diagnosing AKI, the majority of the patients are classified as having mild or ‘‘risk’’ category AKI and have only small changes in creatinine from the baseline. The AKIN criteria appear to identify higher risk patients, and we feel this is a better representation of clinically significant AKI.14,15 Acute kidney injury was determined by the change in creatinine during the 72 hours following cardiac surgery. Baseline serum creatinine was drawn within three days of surgery. If there was no creatinine obtained within three days of surgery, the patient was excluded from the study. Each patient’s daily morning creatinine value was recorded for postoperative days zero to four. The creatinine value obtained closest to hospital discharge was recorded as the discharge creatinine. The baseline and the discharge creatinine were entered into the updated Schwartz formula (0.413 body length [cm]/creatinine [mg/dL]) to calculate the estimated creatinine clearance and determine if renal dysfunction was present
Stage Serum Creatinine Criteria 1 2 3
Urine Output Criteria
Increase of 0.3 mg/dL or 150% to 6 h 200% of baseline (1.5- to 2.0-fold) Increase to >200% to 300% of 12 h baseline (>2- to 3-fold) 300% of baseline or anuria for 12 h (>3-fold) OR serum creatinine 4.0 mg/dL with an acute rise of at least 0.5 mg/dL
preoperatively and prior to discharge. Renal dysfunction was defined as 50% of normal creatinine clearance for age. Preoperative, intraoperative, and postoperative variables were collected and analyzed as the potential risk factors for AKI. We defined several variables as previously described by Taylor et al.7 Health care–associated infections as defined by the center for disease control. Prematurity was defined as an infant born earlier than 38 weeks’ gestation. Central nervous system injury was defined as clinical or electroencephalographic evidence of seizure or ischemia and/or hemorrhage by cranial ultrasound, magnetic resonance imaging, and/or computed tomography. Necrotizing enterocolitis was diagnosed clinically by the cardiac intensivist or surgical attending and/or by radiographic evidence of pneumatosis intestinalis. Diaphragm paresis or paralysis was diagnosed by fluoroscopy. Arrhythmia was defined as any abnormal rhythm requiring pacing and/or pharmacologic intervention. Mediastinal reexploration was defined as an unintended surgical exploration to control bleeding and/ or relieve tamponade. Reintervention was defined as the need for cardiac catheterization or reoperation within 72 hours of surgery. Peak lactate was the highest lactate recorded in the 24 hours following surgery. Each index surgery was assigned a risk adjustment for congenital heart surgery (RACHS-1) category. Decreased systolic function by echocardiogram was defined as any decrease in systolic function of the systemic ventricle as determined by postoperative transesophageal echocardiogram. Other variables included preoperative aminoglycoside exposure, which is defined as any neonate exposed to an aminoglycocide antibiotic prior to cardiac surgery. Vancomycin exposure is defined as any neonate exposed to vancomycin within 72 hours of cardiac surgery. Small kidneys by preoperative renal ultrasound is defined as decreased renal length measured by renal ultrasound when compared to established the standards in children.16 Mortality is defined as death within 30 days of cardiac surgery or prior to discharge. Percentage FOL was also recorded cumulatively at 24-, 48-, and 72-hour periods following surgery. Maximum FOL throughout the entire hospitalization was also calculated. Patients were divided into those less than or equal to 15% FOL and those greater than 15% FOL. Percentage FOL (%FOL) was calculated using the following formula17:
Downloaded from pch.sagepub.com at EMORY UNIV on August 24, 2015
Piggott et al
403
%FOL ¼ sum of daily ðfluid in fluid outÞ= CICU admission weight 100%: The goals for this article were to (1) determine the incidence of neonatal AKI using the AKIN criteria, (2) identify risk factors for the development of neonatal AKI, (3) determine if neonatal AKI and FOL affect hospital length of stay, postoperative mechanical ventilation days, and mortality, and (4) determine if neonates with AKI have renal dysfunction at the time of discharge.
Statistical Analysis IBM SPSS version 22.0.0 was used for statistical analysis. Data are reported as frequency with percentage or median value with interquartile range (25th-75th percentile). The Student t test was used to test the significance of continuous variables. The w2 test was used to test the statistical significance of categorical data, and Fisher exact test was used when more than 20% of the cells had expected counts of less than five. Multivariate logistic regression analysis was used to identify preoperative, intraoperative, and postoperative factors associated with AKI using covariates with a P value equal to or less than.1 by univariate analysis. A P value of less than or equal to .05 was considered to be statistically significant.
Results Of the 99 neonates initially enrolled in the study, 4 were excluded because they underwent cardiac surgery prior to six days of age. The remaining 95 neonates were included. The median age at the time of surgery was seven days (interquartile range, 6-29 days). Of these children, 33% (n ¼ 31) had singleventricle heart disease, and 17% (n ¼ 16) of neonates required preoperative mechanical ventilation. The breakdown of operations according the RACHS-1 criteria included 4% (n ¼ 4) category 1, 24% (n ¼ 23) category 2, 31% (n ¼ 29) category 3, 18% (n ¼ 17) category 4, 0% category 5, and 23% (n ¼ 22) category 6 (Table 1). Following surgery, 39% (n ¼ 37) of neonates met criteria for stage 1 (mild) AKI, 4% (n ¼ 4) for stage 2 (moderate), and 2% (n ¼ 2) for stage 3 (severe). This resulted in a cumulative AKI incidence of 45% (n ¼ 43). A total of three patients (3%) required peritoneal dialysis (PD) during their hospitalization, however, none were within the 72-hour period following cardiac surgery. Two of the three patients who required PD died prior to discharge. The one patient who survived to discharge had normal renal function at the time of discharge and the PD catheter was removed. In fact, all neonates who survived to discharge from both the AKI group and the no AKI group had normal renal function at the time of discharge. In univariate tests, factors associated with AKI are listed in Table 2. There was no difference in preoperative renal function between the group with AKI and the group without AKI. Multivariate logistic regression showed independent associations
with small kidneys by preoperative renal ultrasound, preoperative aminoglycoside exposure, selective cerebral perfusion, cardiopulmonary bypass (CPB) time, and RACHS-1 category (Table 3). A total of eight mortalities were identified. Of the eight mortalities, five had stage 1 (mild AKI) as determined by creatinine at the 72-hour period after cardiac surgery, while the remaining three mortalities had stage 2 (moderate) AKI at the time period 72 hours postsurgery. Sixty-nine neonates were less than or equal to 15% FOL in the first 72 hours following surgery. Twenty-six neonates were greater than 15% FOL. The group with >15% FOL had longer hospital length of stay (76 vs 39 days, P ¼ .03), ventilator days (25 vs 8 days, P ¼
Acute Kidney Injury and Fluid Overload in Neonates Following Surgery for Congenital Heart Disease
World Journal for Pediatric and Congenital Heart Surgery 2015, Vol. 6(3) 401-406 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2150135115586814 pch.sagepub.com
Kurt D. Piggott, MD1, Meshal Soni, BS2, William M. Decampli, MD, PhD3, Jorge A. Ramirez, MD4, Dianna Holbein, ARNP5, Harun Fakioglu, MD1, Carlos J. Blanco, MD5, and Kamal K. Pourmoghadam, MD6
Abstract Background: Acute kidney injury (AKI) and fluid overload have been shown to increase morbidity and mortality. The reported incidence of AKI in pediatric patients following surgery for congenital heart disease is between 15% and 59%. Limited data exist looking at risk factors and outcomes of AKI or fluid overload in neonates undergoing surgery for congenital heart disease. Methods: Neonates aged 6 to 29 days who underwent surgery for congenital heart disease and who were without preoperative kidney disease were included in the study. The AKI was determined utilizing the Acute Kidney Injury Network criteria. Results: Ninety-five neonates were included in the study. The incidence of neonatal AKI was 45% (n ¼ 43), of which 86% had stage 1 AKI. Risk factors for AKI included cardiopulmonary bypass time, selective cerebral perfusion, preoperative aminoglycoside use, small kidneys by renal ultrasound, and risk adjustment for congenital heart surgery category. There were eight mortalities (five from stage 1 AKI group, three from stage 2, and zero from stage 3). Fluid overload and AKI both increased hospital length of stay and postoperative ventilator days. Conclusion: To avoid increased risk of morbidity and possibly mortality, every attempt should be made to identify and intervene on those risk factors, which may be modifiable or identifiable preoperatively, such as small kidneys by renal ultrasound. Keywords acute kidney injury, congenital heart disease, neonate, heart surgery, pediatric, fluid overload Submitted December 01, 2014; Accepted April 22, 2015.
Background Acute kidney injury (AKI) and fluid overload (FOL) in pediatric patients have been reported as risk factors for increased morbidity and mortality.1-6 Pediatric patients who undergo surgery for congenital heart disease are at risk for FOL and have been shown to be at increased risk for developing AKI, many of whom are neonates.1,3,4,6,7 The incidence of AKI in the latter cohort has been reported to be between 15% and 59%.1-10 Acute kidney injury is typically determined using either the pediatric Risk Injury Failure Loss End-stage (pRIFLE) criteria or the Acute Kidney Injury Network (AKIN) criteria. Promising data have been published, evaluating several serum and urinary biomarkers for early AKI, including cystin C, neutrophil gelatinaseassociated lipocalin (NGAL), interleukin 18, liver fatty acid–binding protein (L-FABP), and kidney injury molecule 1 (KIM-1).11-13 Nonetheless, creatinine still remains the most utilized marker for AKI.
1 Pediatric Cardiac Intensive Care, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, Orlando, FL, USA 2 University of Central Florida, Orlando, FL, USA 3 Pediatric Cardiothoracic Surgery, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, Orlando, FL, USA 4 Arnold Palmer Hospital for Children Hewell Kids Kidney Center, University of Central Florida College of Medicine, Orlando, FL, USA 5 Pediatric Cardiac Intensive Care, The Heart Center at Arnold Palmer Hospital for Children, Orlando, FL, USA 6 Pediatric Cardiothoracic Surgery, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, Orlando, FL, USA
Corresponding Author: Kurt D. Piggott, Pediatric Cardiac Intensive Care, The Heart Center at Arnold Palmer Hospital for Children, University of Central Florida College of Medicine, 92 W. Miller St, MP307, Orlando, FL 32806, USA. Email: [email protected]
Downloaded from pch.sagepub.com at EMORY UNIV on August 24, 2015
402
World Journal for Pediatric and Congenital Heart Surgery 6(3) Table 1. Acute Kidney Injury Network Criteria.
Abbreviations and Acronyms AKI AKIN CPB FOL KIM-1 L-FABP NGAL PD
acute kidney injury acute kidney injury network cardiopulmonary bypass fluid overload kidney injury molecule 1 liver fatty acid–binding protein neutrophil gelatinase-associated lipocalin peritoneal dialysis
Although some data exists, evaluating the incidence and risk factors of AKI in neonates undergoing surgery for congenital heart disease, it is relatively limited. We sought to evaluate the incidence and risk factors for the development of AKI exclusively in neonates following surgery for congenital heart disease. Additionally, we wished to evaluate the percentage of FOL and AKI as they pertain to intensive care outcomes, including hospital length of stay, postoperative ventilator days, and mortality.
Materials and Methods Following approval by the institutional review board at the Arnold Palmer Medical Center, this retrospective cohort study was performed in the 20-bed cardiac intensive care unit at Arnold Palmer Hospital for Children in Orlando, Florida. We included all neonates who underwent cardiac surgery at our institution from May 2010 to December 2013, who were at least six days of age but less than 30 days of age on the day of surgery. Neonates with preexisting renal disease preoperatively, determined by creatinine clearance, were excluded from the study. In addition, if the last preoperative creatinine level was obtained prior to day 6, then the patient was excluded since this is likely a reflection of maternal creatinine. The primary variable for the study was the development of AKI as defined by the AKIN criteria (Table 1). We chose to use the AKIN criteria because while pRIFLE has been reported as the more sensitive criteria for diagnosing AKI, the majority of the patients are classified as having mild or ‘‘risk’’ category AKI and have only small changes in creatinine from the baseline. The AKIN criteria appear to identify higher risk patients, and we feel this is a better representation of clinically significant AKI.14,15 Acute kidney injury was determined by the change in creatinine during the 72 hours following cardiac surgery. Baseline serum creatinine was drawn within three days of surgery. If there was no creatinine obtained within three days of surgery, the patient was excluded from the study. Each patient’s daily morning creatinine value was recorded for postoperative days zero to four. The creatinine value obtained closest to hospital discharge was recorded as the discharge creatinine. The baseline and the discharge creatinine were entered into the updated Schwartz formula (0.413 body length [cm]/creatinine [mg/dL]) to calculate the estimated creatinine clearance and determine if renal dysfunction was present
Stage Serum Creatinine Criteria 1 2 3
Urine Output Criteria
Increase of 0.3 mg/dL or 150% to 6 h 200% of baseline (1.5- to 2.0-fold) Increase to >200% to 300% of 12 h baseline (>2- to 3-fold) 300% of baseline or anuria for 12 h (>3-fold) OR serum creatinine 4.0 mg/dL with an acute rise of at least 0.5 mg/dL
preoperatively and prior to discharge. Renal dysfunction was defined as 50% of normal creatinine clearance for age. Preoperative, intraoperative, and postoperative variables were collected and analyzed as the potential risk factors for AKI. We defined several variables as previously described by Taylor et al.7 Health care–associated infections as defined by the center for disease control. Prematurity was defined as an infant born earlier than 38 weeks’ gestation. Central nervous system injury was defined as clinical or electroencephalographic evidence of seizure or ischemia and/or hemorrhage by cranial ultrasound, magnetic resonance imaging, and/or computed tomography. Necrotizing enterocolitis was diagnosed clinically by the cardiac intensivist or surgical attending and/or by radiographic evidence of pneumatosis intestinalis. Diaphragm paresis or paralysis was diagnosed by fluoroscopy. Arrhythmia was defined as any abnormal rhythm requiring pacing and/or pharmacologic intervention. Mediastinal reexploration was defined as an unintended surgical exploration to control bleeding and/ or relieve tamponade. Reintervention was defined as the need for cardiac catheterization or reoperation within 72 hours of surgery. Peak lactate was the highest lactate recorded in the 24 hours following surgery. Each index surgery was assigned a risk adjustment for congenital heart surgery (RACHS-1) category. Decreased systolic function by echocardiogram was defined as any decrease in systolic function of the systemic ventricle as determined by postoperative transesophageal echocardiogram. Other variables included preoperative aminoglycoside exposure, which is defined as any neonate exposed to an aminoglycocide antibiotic prior to cardiac surgery. Vancomycin exposure is defined as any neonate exposed to vancomycin within 72 hours of cardiac surgery. Small kidneys by preoperative renal ultrasound is defined as decreased renal length measured by renal ultrasound when compared to established the standards in children.16 Mortality is defined as death within 30 days of cardiac surgery or prior to discharge. Percentage FOL was also recorded cumulatively at 24-, 48-, and 72-hour periods following surgery. Maximum FOL throughout the entire hospitalization was also calculated. Patients were divided into those less than or equal to 15% FOL and those greater than 15% FOL. Percentage FOL (%FOL) was calculated using the following formula17:
Downloaded from pch.sagepub.com at EMORY UNIV on August 24, 2015
Piggott et al
403
%FOL ¼ sum of daily ðfluid in fluid outÞ= CICU admission weight 100%: The goals for this article were to (1) determine the incidence of neonatal AKI using the AKIN criteria, (2) identify risk factors for the development of neonatal AKI, (3) determine if neonatal AKI and FOL affect hospital length of stay, postoperative mechanical ventilation days, and mortality, and (4) determine if neonates with AKI have renal dysfunction at the time of discharge.
Statistical Analysis IBM SPSS version 22.0.0 was used for statistical analysis. Data are reported as frequency with percentage or median value with interquartile range (25th-75th percentile). The Student t test was used to test the significance of continuous variables. The w2 test was used to test the statistical significance of categorical data, and Fisher exact test was used when more than 20% of the cells had expected counts of less than five. Multivariate logistic regression analysis was used to identify preoperative, intraoperative, and postoperative factors associated with AKI using covariates with a P value equal to or less than.1 by univariate analysis. A P value of less than or equal to .05 was considered to be statistically significant.
Results Of the 99 neonates initially enrolled in the study, 4 were excluded because they underwent cardiac surgery prior to six days of age. The remaining 95 neonates were included. The median age at the time of surgery was seven days (interquartile range, 6-29 days). Of these children, 33% (n ¼ 31) had singleventricle heart disease, and 17% (n ¼ 16) of neonates required preoperative mechanical ventilation. The breakdown of operations according the RACHS-1 criteria included 4% (n ¼ 4) category 1, 24% (n ¼ 23) category 2, 31% (n ¼ 29) category 3, 18% (n ¼ 17) category 4, 0% category 5, and 23% (n ¼ 22) category 6 (Table 1). Following surgery, 39% (n ¼ 37) of neonates met criteria for stage 1 (mild) AKI, 4% (n ¼ 4) for stage 2 (moderate), and 2% (n ¼ 2) for stage 3 (severe). This resulted in a cumulative AKI incidence of 45% (n ¼ 43). A total of three patients (3%) required peritoneal dialysis (PD) during their hospitalization, however, none were within the 72-hour period following cardiac surgery. Two of the three patients who required PD died prior to discharge. The one patient who survived to discharge had normal renal function at the time of discharge and the PD catheter was removed. In fact, all neonates who survived to discharge from both the AKI group and the no AKI group had normal renal function at the time of discharge. In univariate tests, factors associated with AKI are listed in Table 2. There was no difference in preoperative renal function between the group with AKI and the group without AKI. Multivariate logistic regression showed independent associations
with small kidneys by preoperative renal ultrasound, preoperative aminoglycoside exposure, selective cerebral perfusion, cardiopulmonary bypass (CPB) time, and RACHS-1 category (Table 3). A total of eight mortalities were identified. Of the eight mortalities, five had stage 1 (mild AKI) as determined by creatinine at the 72-hour period after cardiac surgery, while the remaining three mortalities had stage 2 (moderate) AKI at the time period 72 hours postsurgery. Sixty-nine neonates were less than or equal to 15% FOL in the first 72 hours following surgery. Twenty-six neonates were greater than 15% FOL. The group with >15% FOL had longer hospital length of stay (76 vs 39 days, P ¼ .03), ventilator days (25 vs 8 days, P ¼
