Eric Wald

Early postoperative fluid overload precedes acute kidney injury and is associated with higher morbidity in pediatric cardiac surgery patients.

Objective: Fluid overload has been independently associated with increased morbidity and mortality in pediatric patients with renal failure, acute lung injury, and sepsis. Pediatric patients who undergo cardiopulmonary bypass are at risk for poor cardiac, pulmonary, and renal outcomes. They are also at risk of fluid overload from cardiopulmonary bypass, which stimulates inflammation, release of antidiuretic hormone, and capillary leak. This study tested the hypothesis that patients with fluid overload in the early postcardiopulmonary bypass period have worse outcomes than those without fluid overload. We also examined the timing of the association between postcardiopulmonary bypass acute kidney injury and fluid overload. Design, Setting, and Patients: Secondary analysis of a prospective observational study of 98 pediatric patients after cardiopulmonary bypass at a tertiary care, academic, PICU. Interventions: None. Measurements and Main Results: Early postoperative fluid overload, defined as a fluid balance 5% above body weight by the end of postoperative day 1, occurred in 30 patients (31%). Patients with early fluid overload spent 3.5 days longer in the hospital, spent 2 more days on inotropes, and were more likely to require prolonged mechanical ventilation than those without early fluid overload (all p < 0.001). Fluid overload was associated with the development of acute kidney injury and more often preceded it than followed it. Conversely, acute kidney injury was not associated with more fluid accumulation. Patients with fluid overload were administered higher fluid volume over the study period, 395.4 ± 150 mL/kg vs. 193.2 ± 109.1 mL/kg (p < 0.001), and had poor urinary response to diuretics. Cumulative fluid administered was an excellent predictor of pediatric-modified Risk, Injury, Failure, Loss, and End-stage “Failure” (area under the receiver-operating characteristic curve, 0.963; 95% CI, 0.916–1.000; p = 0.002). Conclusions: Early postoperative fluid overload is independently associated with worse outcomes in pediatric cardiac surgery patients who are 2 weeks to 18 years old. Patients with fluid overload have higher rates of postcardiopulmonary bypass acute kidney injury, and the occurrence of fluid overload precedes acute kidney injury. However, acute kidney injury is not consistently associated with fluid overload.

Predictive power of serum cystatin C to detect acute kidney injury and pediatric-modified RIFLE class in children undergoing cardiac surgery

Objective: Acute kidney injury is a frequent and serious complication of cardiopulmonary bypass. In current clinical practice, serum creatinine is used to detect acute kidney injury. Cystatin C is a novel biomarker for kidney function that has been shown to be superior to serum creatinine in predicting acute kidney injury in adults after cardiopulmonary bypass. The aim of this study was to determine whether early cystatin C levels predict acute kidney injury associated with cardiopulmonary bypass in pediatric patients undergoing cardiac surgery and if cystatin C could predict pediatric-modified RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) class and renal injury as determined by estimated glomerular filtration rate. We also investigated whether ultrafiltration during cardiopulmonary bypass affects cystatin C levels. Design: Prospective, observational cohort study. Setting: Cardiac intensive care unit in a tertiary, academic pediatric hospital. Patients: One hundred pediatric patients who underwent cardiac surgery involving cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Acute kidney injury was defined as a 50% increase in serum creatinine from a preoperative baseline anytime through postoperative day 4. Severity of acute kidney injury was determined by pediatric RIFLE class using estimated glomerular filtration rate criteria only. Renal injury was also determined by an absolute estimated glomerular filtration rate <80 mL/min/1.73 m2. Cystatin C levels were measured before and after ultrafiltration. Twenty-eight patients (28%) developed acute kidney injury. Cystatin C predicted acute kidney injury as early as 8 hrs after surgery. When applying pediatric RIFLE criteria to the entire study, 30 patients reached “risk” and five developed “injury.” Cystatin C was a good predictor of the development of “injury” (under the receiver operating characteristic curve, 0.834–0.875) and of renal injury by estimated glomerular filtration rate (under the receiver operating characteristic curve, 0.717–0.835) (all p < .05). Cystatin C levels decreased perioperatively and correlated with volume of fluid removed by ultrafiltration. Conclusions: Cystatin C is an early predictor of acute kidney injury in children after cardiopulmonary bypass. Cystatin C is a good predictor of pediatric RIFLE classification and of decreased estimated glomerular filtration rate after cardiopulmonary bypass. Serum cystatin C may be cleared by ultrafiltration.

Red Blood Cell Distribution Width as a Pragmatic Marker for Outcome in Pediatric Critical Illness

Background Red cell distribution width (RDW) is a routine laboratory measure associated with poor outcomes in adult critical illness. Objective We determined the utility of RDW as an early pragmatic biomarker for outcome in pediatric critical illness. Methods We used multivariable logistic regression to test the association of RDW on the first day of pediatric intensive care unit (PICU) admission with prolonged PICU length of stay (LOS) >48 hours and mortality. The area under the receiver operating characteristic curve (AUROC) for RDW was compared to the Pediatric Index of Mortality (PIM)-2 score. Results Over a 13-month period, 596 unique patients had RDW measured on the first day of PICU admission. Sepsis was an effect modifier for LOS >48 hours but not mortality. In sepsis, RDW was not associated with LOS >48 hours. For patients without sepsis, each 1% increase in RDW was associated with 1.17 (95% CI 1.06, 1.30) increased odds of LOS >48 hours. In all patients, RDW was independently associated with PICU mortality (OR 1.25, 95% CI 1.09, 1.43). The AUROC for RDW to predict LOS >48 hours and mortality was 0.61 (95% CI 0.56, 0.66) and 0.65 (95% CI 0.55, 0.75), respectively. Although the AUROC for mortality was comparable to PIM-2 (0.75, 95% CI 0.66, 0.83; p = 0.18), RDW did not increase the discriminative utility when added to PIM-2. Despite the moderate AUROC, RDW <13.4% (upper limit of lower quartile) had 53% risk of LOS >48 hours and 3.3% risk of mortality compared to patients with an RDW >15.7% (lower limit of upper quartile) who had 78% risk of LOS >48 hours and 12.9% risk of mortality (p<0.001 for both outcomes). Conclusions Elevated RDW was associated with outcome in pediatric critical illness and provided similar prognostic information as the more complex PIM-2 severity of illness score. Distinct RDW thresholds best discriminate low- versus high-risk patients.

Type B Lactic Acidosis Secondary to Thiamine Deficiency in a Child With Malignancy

Type B lactic acidosis is an underrecognized clinical entity that must be distinguished from type A (hypoxic) lactic acidosis. We present the case of a 4-year-old boy with medulloblastoma who presented with lactic acidosis in the setting of septic shock. His hyperlactatemia persisted to high levels even after his hemodynamic status improved. After administration of intravenous thiamine, his lactate level rapidly normalized and remained stable. It was determined that his total parenteral nutrition was deficient in vitamins due to a national shortage. Because thiamine is an important cofactor for pyruvate dehydrogenase, he was unable to use glucose through aerobic metabolism pathways. We briefly review type A versus type B lactic acidosis in this case report.

Eosinophilic esophagitis in children following cardiac transplantation: association with post-transplant lymphoproliferative disorder and other transplant outcomes.

Although cardiac transplantation is life‐saving, morbidities from immunosuppression are significant. EoE is a complication of calcineurin inhibitors following liver transplant causing feeding intolerance, weight loss, vomiting, and dysphagia. There are limited reports of EoE following heart transplantation. We performed a retrospective single‐center review of pediatric cardiac transplant patients from 2000 to 2010. A case–control analysis of patients with and without EoE was performed evaluating heart transplantation outcomes such as rates of rejection, CAV, PTLD, and graft loss. Eighty‐six transplants were performed in 84 patients; 34 (40%) underwent diagnostic endoscopy, and 10 (12%) had EoE. Median time to diagnosis of EoE was 3.7 yr (IQR: 2.0–5.2). There were no differences in demographics or use of induction medications between patients with or without EoE. Patients with EoE had fewer episodes of treated rejection (1.0 vs. 2.5; p = 0.04). Four of 10 (40%) EoE patients had PTLD compared with only 2/24 (8%) of those without EoE (p = 0.048; OR 7.33 [95% CI: 1.1–50.2]). There were no differences in CAV or graft loss between groups. EoE should be considered as a cause of GI symptoms in children after cardiac transplantation and may be associated with fewer rejection episodes and increased rates of PTLD, thus representing a marker of over‐immunosuppression.

Total and free cortisol responses and their relation to outcomes after cardiopulmonary bypass in infants.

Background: Hypothalamic‐pituitary‐adrenal (HPA) axis dysfunction may be partially responsible for the hemodynamic instability experienced by infants after cardiopulmonary bypass (CPB). We report the full spectrum of the HPA response surrounding CPB for infant congenital cardiac surgery. Methods: We enrolled 84 infants who received 1 mg/kg of dexamethasone before initiation of CPB. Total cortisol (TC), free cortisol (FC), adrenocorticotropic hormone (ACTH), and corticosteroid‐binding globulin (CBG) were measured at 3 time points: immediately before CPB (TP1), on intensive care unit arrival (TP2), and at 24 hours after surgery (TP3). A 1‐&mgr;g ACTH stimulation test was performed at each time point to evaluate adrenal responsiveness. Results: Sixty‐eight infants completed all study procedures. Levels of TC, FC, CBG, and ACTH decreased significantly between the preoperative and 24‐hour postoperative measurements. There were no significant associations between preoperative FC responses and clinical outcomes after adjusting for weight and Risk‐Adjusted Scores for Congenital Heart Surgery. Infants with subnormal TC responses to ACTH stimulation (<9 &mgr;g/dL) at TP2 had greater fluid requirements (P < .001) and greater chest tube output (P < .001) during the first 24 hours, as well as longer length of stay (LOS) (P = .007). Except for LOS, these differences persisted for infants with subnormal stimulation tests at TP3. Conclusions: We observed a significant decline in all aspects of the HPA axis throughout the first 24 hours after infant CPB. TC and FC levels were not associated with clinical outcomes. Subnormal (&Dgr; <9 &mgr;g/dL) TC response to cosyntropin stimulation during the postoperative period was associated with increased fluid resuscitation and greater LOS.

Metabolic Uncoupling Following Cardiopulmonary Bypass

OBJECTIVE The objective of this study was to characterize the natural history of metabolic uncoupling (type B hyperlactemia and hyperglycemia) following cardiopulmonary bypass (CPB), and to determine the impact of insulin therapy on time to lactate normalization in patients without low cardiac output. DESIGN The design used was a retrospective cohort study. SETTING The study was set in a pediatric cardiac intensive care unit in a tertiary-care urban childrens hospital. PATIENTS All patients were aged ≤21 years admitted between 2007 and 2013 following cardiac surgery involving CPB with empiric intraoperative corticosteroids. ELIGIBILITY CRITERIA simultaneous hyperlactemia (≥3.5 mEq/L) and hyperglycemia (≥200 mg/dL) within 48 hours after bypass. EXCLUSION CRITERIA Exclusion criteria were evidence of low cardiac output state, diabetes or postoperative steroid administration. INTERVENTIONS Characteristics were compared between those treated with insulin and those who were not (controls). OUTCOME MEASURES Outcome measures used were time from admission to onset of hyperglycemia and hyperlactemia and time to resolution. Clinical outcomes included duration of mechanical ventilation, length of stay, unplanned readmission/reoperation, hypoglycemia and death. RESULTS Of the 1345 patients receiving CPB, 132 (9.8%) met inclusion criteria. Seventy-eight (59%) were treated with insulin, leaving 54 controls. Patient characteristics, surgical complexity and time to onset of hyperglycemia and hyperlactemia were similar between groups. The insulin group had a shorter duration of hyperglycemia. There was no significant difference between groups in time to lactate normalization, ventilator days, length of stay, readmission and reoperation rates. Hypoglycemia (<60 mg/dL) occurred in three patients. CONCLUSIONS In children with metabolic uncoupling after CPB, insulin use did not shorten the time to lactate normalization or alter clinical outcomes. These findings suggest that type B hyperlactemia with hyperglycemia after CPB will resolve spontaneously and does not warrant specific treatment.

Long-duration (>4 weeks) continuous renal replacement therapy in critical illness

INTRODUCTION Decreased pediatric survival has been reported with long-duration (>4 weeks) continuous renal replacement therapy (CRRT), though the practice has not been well-described. METHODS Retrospective chart review in a childrens hospital of all patients treated with CRRT over 2 years (2003-4), including those who underwent long (group 1) and shorter duration (group 2) therapy. RESULTS We identified 39 patients: median age was 6 years (range: 0.3-23; 7 were infants), median PRISM III score was 16 (range: 4-35), and the most frequent primary diagnosis was a stem cell transplant (in 12 out of 39). At continuous renal replacement therapy initiation, almost all patients (38 out of 39) had multiorgan dysfunction syndrome, most (35 out of 39) were being treated with at least one inotrope or vasopressor, and median fluid overload was 18% (range: 1-43%). Survival was poor (38%). Groups 1 (n = 7) and 2 (n = 32) had similar age (p = 0.44), PRISM III score (p = 0.61), and stem cell transplant diagnosis (p = 0.65). At CRRT initiation, the incidence of multiorgan dysfunction syndrome (p=0.18), inotrope or vasopressor treatment (p = 0.56), and fluid overload severity (p = 0.71) were similar. Those in group 1 had a longer mean CRRT as well as persistent cardiovascular dysfunction limiting the utility of intermittent dialysis. Survival was similar between groups (p = 1). CONCLUSIONS Critically-ill patients treated with long and shorter duration CRRT had a similar survival rate.

Fluid Management: Pharmacologic and Renal Replacement Therapies.

Objectives: Focusing on critically ill children with cardiac disease, we will review common causes of fluid perturbations, clinical recognition, and strategies to minimize and treat fluid-related complications. Data Source: MEDLINE and PubMed. Conclusions: Meticulous fluid management is vital in critically ill children with cardiac disease. Fluid therapy is important to maintain adequate blood volume and perfusion pressure in order to support cardiac output, tissue perfusion, and oxygen delivery. However, fluid overload and acute kidney injury are common and are associated with increased morbidity and mortality. Understanding the etiologies for disturbances in volume status and the pathophysiology surrounding those conditions is crucial for providing optimal care.

Establishing Quality Review of Cardiac and Respiratory Arrest in a Pediatric Intensive Care Unit

Cardiac arrest in children is a rare event; however, the outcomes following resuscitation are universally disappointing. Despite widespread recognition of its importance, there is no standard approach to conducting reviews surrounding critical resuscitation events. A standardized approach to the review of respiratory and cardiac arrests occurring in the pediatric intensive care unit focusing on processes of care and team performance was undertaken at a single pediatric academic medical center. Data collection and quality improvement tools were created, and a formal code review was established. Improvement in code team performance was observed. Clinician documentation improved, and multiple system redesigns were implemented that ultimately resulted in fewer clinician concerns. The rate of successful resuscitation was consistent with current published benchmarks. The development of an interdisciplinary code review process focusing on the procedure of resuscitation can identify critical issues that may impede successful resuscitation.