Background:Prophylactic steroids are often used to reduce the systemic inflammatory response to cardiopulmonary bypass in infants undergoing heart surgery. The STRESS trial found that the likelihood of a worse outcome did not differ between infants randomized to methylprednisolone (n=599) versus placebo (n=601) in a risk-adjusted primary analysis (adjusted odds ratio [OR], 0.86; 95% CI, 0.71 to 1.05; P=0.14). However, secondary analyses showed possible benefits with methylprednisolone. To ensure that a potentially efficacious therapy is not unnecessarily avoided, we re-analyzed the STRESS trial using Bayesian analytics to assess the probability of benefit. Methods:Our Bayesian analysis used the original STRESS trial primary outcome measure, a hierarchically ranked composite of death, transplant, major complications and post-operative length of stay. We evaluated probability of benefit (OR<1) versus harm (OR>1) by comparing the posterior distribution of the OR assuming a neutral probability of benefit versus harm with weak prior belief strength (nearly non-informative prior distribution). Reference results were calculated under the vague prior distribution. To convey magnitude of effect we used model parameters to calculate a predicted risk of death, transplant or major complications for methylprednisolone and placebo. Analyses consisted of 10 Markov Chain Monte Carlo simulations, each consisting of 2000 iterations with a 1000 iteration burn-in to ensure proper posterior convergence. Sensitivity analyses evaluated pessimistic (5%-30% prior likelihood of benefit), neutral and optimistic (70%-95%) prior beliefs, and controlled strength of prior belief as weak (30% variance), moderate (15%) and strong (5%). Results:In primary analysis, the posterior probability of benefit from methylprednisolone was 91% and probability of harm was 9%. Composite death or major complication occurred in 18.8% of trial subjects with an absolute risk difference of -2% (95% CI -3%, +1%) associated with methylprednisolone. Each of 9 sensitivity analyses demonstrated greater probability of benefit than harm in the methylprednisolone group with 8 of 9 demonstrating >80% probability of benefit and ≥1% absolute difference in risk of death, transplant or major complications. Conclusion:Probability of benefit with prophylactic methylprednisolone is high and harm is unlikely. This more in-depth analysis of the data expands the initial clinical evaluation of methylprednisolone provided by the STRESS trial.

INTRODUCTION:Catheterisation is the gold standard used to evaluate pulmonary blood flow in patients with a Blalock-Thomas-Taussig shunt. It involves risk and cannot be performed frequently. This study aimed to evaluate if echocardiographic measurements obtained in a clinical setting correlate with catheterisation-derived pulmonary blood flow in patients with a Blalock-Thomas-Taussig shunt as the sole source of pulmonary blood flow.METHODS:Chart review was performed retrospectively on consecutive patients referred to the catheterisation lab with a Blalock-Thomas-Taussig shunt. Echocardiographic parameters included peak, mean, and diastolic gradients across the Blalock-Thomas-Taussig shunt and forward and reverse velocity time integral across the distal transverse aorta. In addition to direct correlations, we tested a previously published formula for pulmonary blood flow calculated as velocity time integral across the shunt × heart rate × Blalock-Thomas-Taussig shunt area. Catheterisation parameters included pulmonary and systemic blood flow as calculated by the Fick principle.RESULTS:18 patients were included. The echocardiography parameters and oxygen saturation did not correlate with catheterisation-derived pulmonary blood flow, systemic blood flow, or the ratio of pulmonary to systemic blood flow. As the ratio of reverse to forward velocity time integral across the transverse aorta increased, the probability of shunt stenosis decreased.CONCLUSION:Echocardiographic measurements obtained outside the catheterisation lab do not correlate with catheterisation-derived pulmonary blood flow. The ratio of reverse to forward velocity time integral across the transverse aortic arch may be predictive of Blalock-Thomas-Taussig shunt narrowing; this finding should be investigated further.

While hyperlactatemia in postoperative cardiac surgery patients was once believed to solely reflect hypoperfusion, either from the accumulated “oxygen debt” during bypass or ongoing inadequate perfusion, our understanding of lactate generation, clearance, and management has evolved. A contemporary understanding of lactate balance is critical to the management of the postoperative patient with hyperlactatemia. In this review, we summarize the current understanding of lactate metabolism in pediatric patients following cardiac surgery and highlight two types of hyperlactatemia: type A, which is secondary to inadequate oxygen delivery and tissue hypoxia, and type B, which in postoperative pediatric cardiac surgery patients largely reflects increased glycolysis driven by the stress response. Both types may coexist; thus, it is imperative that providers first assess the patient for evidence of hypoperfusion. In patients with evidence of adequate perfusion, a type B component is often associated with a concomitant balanced (normal anion gap) metabolic acidosis and hyperglycemia. These patients will benefit from a more nuanced approach to their type B hyperlactatemia, as many will have a benign course and may be managed expectantly.

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Wald, Eric1; Sanchez-Pinto, L. Nelson1; Smith, Craig1; Moran, Thomas1; Badke, Colleen1; Barhight, Matthew1; Malakooti, Marcelo1 Author Information

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.

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.

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.

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.

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.

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.

PURPOSE:Asymmetrical dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, is elevated in vascular pathologies such as hypertension and chronic kidney disease. Children undergoing cardiac surgery are at high risk of poor hemodynamic and renal outcomes secondary to cardiopulmonary bypass (CPB). This study tested the hypothesis that elevated preoperative ADMA levels are associated with overall worse clinical outcomes after pediatric CPB.METHODS:This was a prospective, observational study of 100 patients aged from 2 weeks to 18 years who underwent cardiac surgery involving CPB. Serum ADMA levels were obtained preoperatively and on postoperative days zero through four. Clinical outcomes measured included acute kidney injury (AKI) by pRIFLE criteria, low cardiac output syndrome (LCOS), length of mechanical ventilation, hospital and ICU length of stay, unplanned reoperation, and mortality.RESULTS:The 29 patients with an elevated preoperative ADMA were more likely to have prolonged mechanical ventilation, increased ICU and hospital length of stay, unplanned reoperation, and LCOS than those with a normal preoperative level. ADMA levels inversely correlated with estimated glomerular filtration rate (eGFR), but did not differ between patients with and without AKI after CPB. Preoperative ADMA levels correlated with hospital length of stay (r(s) = 0.289), ICU length of stay (r(s) = 0.308), and length of mechanical ventilation (r(s) = 0.402); [all p < 0.05]. ADMA levels before surgery had good predictive power for prolonged mechanical ventilation (AUC-ROC 0.809; 95 % CI 0.704, 0.914; p < 0.001).CONCLUSIONS:Patients with elevated ADMA before surgery were more likely to have prolonged mechanical ventilation, develop LCOS, require an extended length of stay, and require reoperation. ADMA levels inversely correlated with eGFR, but did not predict AKI. Preoperative serum ADMA appears to identify pediatric cardiac surgery patients at risk of poor postoperative outcomes following CPB.

This study aimed to compare the incidence of gastrointestinal complications among infants with single-ventricle heart defects after three first-stage palliation strategies: Norwood-modified Blalock-Taussig shunt (mBTS), Norwood right ventricle-to-pulmonary artery conduit (Sano), and hybrid procedures. A retrospective chart review was performed in a pediatric cardiac intensive care unit at a tertiary care medical center. The subjects were 32 neonates who had undergone single-ventricle palliation including 13 Norwood-mBTS, 11 Sano, and 8 hybrid procedures. The measurements included baseline as well as pre- and postoperative patient characteristics. The primary outcome was postoperative intraabdominal complications, and the secondary outcomes were feeding intolerance and necrotizing enterocolitis (NEC). Intraabdominal complications occurred for 34%, feeding intolerance for 13%, and NEC for 13% of the patients. The hybrid patients had a higher incidence of intraabdominal complications (75%) than the Norwood-mBTS (31%) or Sano (9%) patients (P = 0.01). The relative risk for intraabdominal complications in the hybrid group was 3.6 (95% confidence interval [CI], 1.5-8.7). In the multivariate analysis, the hybrid procedure remained an independent predictor of intraabdominal complications (hazard ratio, 8.4; 95% CI, 2.0-34.5). The hybrid, Norwood-mBTS, and Sano patients did not differ significantly in terms of feeding intolerance (25, 15, and 0%, respectively; P = 0.25) or NEC (25, 8, and 9%; P = 0.46). Gastrointestinal morbidity was common regardless of the palliative approach, although the hybrid patients had the highest incidence of intraabdominal complications. This supports the need for caution in using enteral nutrition with all single-ventricle patients, including the hybrid population. Patients undergoing the hybrid procedure may benefit from implementation of standardized feeding protocols.

CME EDUCATIONAL OBJECTIVES 1. Delineate the differential diagnosis of croup in children. 2. Review the clinical evidence supporting the use of nebulized epinephrine for croup in the emergency department, as well as the criteria for discharge home after treatment. 3. Discuss the clinical evidence supporting the use of systemic or nebulized steroids in the treatment of viral laryngotracheobronchitis.

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 children’s 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.

Objective: The pathophysiology of low-cardiac-output syndrome after cardiopulmonary bypass is incompletely understood, but adrenal insufficiency has been proposed as a contributing factor. Our objective was to examine the effect of cardiopulmonary bypass on the hypothalamic-pituitary-adrenal axis, specifically adrenal responsiveness, in patients with congenital heart disease undergoing surgery. We hoped to correlate bound and free cortisol values both postoperatively and after adrenocorticotropic hormone stimulation, in conjunction with corticosteroid-binding globulin levels, with clinical outcomes to determine whether these variables are sensitive indicators of adrenal axis function.Design: Prospective cohort study.Setting: A children's hospital.Patients: Fifty-two pediatric heart surgery patients undergoing cardiopulmonary bypass.Intervention: Total cortisol and corticosteroid-binding globulin levels were obtained pre- and postoperatively and after a postoperative cosyntropin stimulation test. Free cortisol was calculated by using Coolens' method.Measurements and Main Results: Nine of 51 (17.6%) patients had low (< 3 mu g/dL) baseline postoperative total cortisol, median 1.6 mu g/dL, yet all nine had normal (> 9 mu g/dL increase from postoperative baseline) stimulation tests. The corticosteroid-binding globulin levels declined from a mean of 29 mg/L preoperatively to 22 mg/L postoperatively (p < .001) and showed marked variability between patients. Patients with free cortisol delta > 6 mu g/dL (n = 18, 35%) had a longer length of stay (median 9 vs. 5 days; p = .002), higher inotrope scores (median 13.3 vs. 10.8; p = .05), greater fluid requirement (median 73.5 vs. 55.6 mL/kg; p = .007), and longer ventilator times (median 41.5 vs. 20 hrs; p = .013).Conclusions: Although hypothalamic-pituitary-adrenal axis dysfunction may play a role in low-cardiac-output syndrome among children undergoing congenital heart surgery, using total cortisol to investigate such dysfunction may be inadequate. Decreased corticosteroid-binding globulin levels and marked free cortisol increase after stimulation were associated with worse clinical outcomes. Further investigation into the cortisol-corticosteroid-binding globulin complex and its relationship to free cortisol is necessary to examine the problem of adrenal insufficiency from a more integrated perspective. (Pediatr Crit Care Med 2011; 12:190-196)