Filtering Down to Risks and Solutions: Risk Factors and Stratification After Pediatric Cardiac Surgery.

Acute kidney injury after cardiac surgery (CS-AKI) is common in neonatal and pediatric populations and is a risk factor for poor outcomes, such as mortality and increased hospital resource utilization. This review presents a summary of CS-AKI risk factors, integration of biomarkers, and the need to improve risk stratification for targeting future clinical trials. To date, studies examining CS-AKI risk factors cannot be generalized easily owing to variability in patient age, surgical complexity or population, AKI definition, and center-specific practices. However, certain risk associations, such as younger age at surgery, history of prematurity, cardiopulmonary bypass time, and surgical complexity, have been identified across multiple, but not all, studies. CS-AKI appears to have different severity and duration phenotypes, and serum creatinine is limited in its ability to identify CS-AKI early and predict CS-AKI course. Treatment strategies are largely supportive, and efforts are ongoing to use biomarkers and clinical features to risk-stratify patients, which in turn may facilitate differential CS-AKI phenotyping and management with supportive care bundles, clinical decision support techniques, and modulation of modifiable risk factors.

Decreases in Nephrotoxic Pain Medications Are Not Associated With Increased Opioid Utilization in Critically Ill Children.

OBJECTIVES: Quality improvement initiatives to decrease rates of nephrotoxic medication exposure have reduced rates of acute kidney injury (AKI) in noncritically ill children. The objective of our study was to analyze the implementation of a similar program in critically ill children and to measure important balancing measures including opioid and benzodiazepine exposure. DESIGN: Prospective quality improvement study. SETTING: PICU at Children's Hospital Colorado between 2018 and 2020. PATIENTS: All children admitted to PICU. INTERVENTIONS: Quality improvement initiative called Nephrotoxic Injury Negated by Just-In-Time Action (NINJA). MEASUREMENT AND MAIN RESULTS: Eight thousand eight hundred thirty-three PICU patient admissions were included. Mean rates of nephrotoxic medication exposure/1,000 PICU patient days decreased from 46 to 26, whereas rates of nephrotoxic AKI/1,000 PICU patient days did not change. Nonsteroidal anti-inflammatory drug dispenses per 1,000 patient days were reduced from 521 to 456. Similarly, opioid and benzodiazepine exposures per 1,000 patient days were reduced from 812 to 524 and 441 to 227, respectively, during the study observation period. CONCLUSIONS: The NINJA intervention was efficaciously implemented in our single-center PICU. Nephrotoxic exposure is a modifiable factor that did not inadvertently increase exposure to opioids and benzodiazepines.

Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia.

OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

Assessment of the Independent and Synergistic Effects of Fluid Overload and Acute Kidney Injury on Outcomes of Critically Ill Children.

OBJECTIVES: Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients. DESIGN: Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study. SETTING: Single-center quaternary level PICU. PATIENTS: One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload patients, regardless of acute kidney injury status. Fluid overload/acute kidney injury patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload/acute kidney injury patients compared with patients without both classifications (17.4; 95% CI, 11.0-23.7 vs 8.8; 95% CI, 7.3-10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality. CONCLUSIONS: The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.

Risk Factors for Recurrent Acute Kidney Injury in Children Who Undergo Multiple Cardiac Surgeries: A Retrospective Analysis.

OBJECTIVES: Determine the risk factors for repeated episodes of acute kidney injury in children who undergo multiple cardiac surgical procedures. DESIGN: Single-center retrospective chart review. SETTING: Cardiac ICU at a quaternary pediatric care center. PATIENTS: Birth to 18 years who underwent at least two cardiac surgical procedures with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred eighty patients underwent two cardiac surgical procedures and 89 underwent three. Acute kidney injury was defined by the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Acute kidney injury frequency was 26% (n = 46) after surgery 1, 20% (n = 36) after surgery 2, and 24% (n = 21) after surgery 3, with most acute kidney injury occurring on postoperative days 1 and 2. The proportion of patients with severe acute kidney injury increased from surgery 1 to surgery 3. Patients with acute kidney injury had a significantly longer duration of ventilation and length of stay after each surgery. The odds of acute kidney injury after surgery 3 was 2.40 times greater if acute kidney injury was present after surgery 1 or 2 (95% CI, 1.26-4.56; p = 0.008) after adjusting for confounders. The time between surgeries was not significantly associated with acute kidney injury (p = 0.85). CONCLUSIONS: In a heterogeneous population of pediatric patients with congenital heart disease undergoing multiple cardiopulmonary bypass surgeries, odds of acute kidney injury after a third surgery was increased by the presence of acute kidney injury after prior procedures. Time between surgery did not play a role in increasing odds of acute kidney injury. Further studies in a larger multicenter investigation are necessary to confirm these findings.