David K. Bailly

Pediatric cardiac intensive care society 2014 consensus statement: Pharmacotherapies in cardiac critical care fluid management

Objective: In this Consensus Statement, we review the etiology and pathophysiology of fluid disturbances in critically ill children with cardiac disease. Clinical tools used to recognize pathologic fluid states are summarized, as are the mechanisms of action of many drugs aimed at optimal fluid management. Data Sources: The expertise of the authors and a review of the medical literature were used as data sources. Data Synthesis: The authors synthesized the data in the literature in order to present clinical tools used to recognize pathologic fluid states. For each drug, the physiologic rationale, mechanism of action, and pharmacokinetics are synthesized, and the evidence in the literature to support the therapy is discussed. Conclusions: Fluid management is challenging in critically ill pediatric cardiac patients. A myriad of causes may be contributory, including intrinsic myocardial dysfunction with its associated neuroendocrine response, renal dysfunction with oliguria, and systemic inflammation with resulting endothelial dysfunction. The development of fluid overload has been associated with adverse outcomes, including acute kidney injury, prolonged mechanical ventilation, increased vasoactive support, prolonged hospital length of stay, and mortality. An in-depth understanding of the many factors that influence volume status is necessary to guide optimal management.

Development and Validation of a Score to Predict Mortality in Children Undergoing Extracorporeal Membrane Oxygenation for Respiratory Failure: Pediatric Pulmonary Rescue With Extracorporeal Membrane Oxygenation Prediction Score*

Objective: Our objective was to develop and validate a prognostic score for predicting mortality at the time of extracorporeal membrane oxygenation initiation for children with respiratory failure. Preextracorporeal membrane oxygenation mortality prediction is important for determining center-specific risk-adjusted outcomes and counseling families. Design: Multivariable logistic regression of a large international cohort of pediatric extracorporeal membrane oxygenation patients. Setting: Multi-institutional data. Patients: Prognostic score development: A total of 4,352 children more than 7 days to less than 18 years old, with an initial extracorporeal membrane oxygenation run for respiratory failure reported to the Extracorporeal Life Support Organization’s data registry during 2001–2013 were used for derivation (70%) and validation (30%). Bidirectional stepwise logistic regression was used to identify factors associated with mortality. Retained variables were assigned a score based on the odds of mortality with higher scores indicating greater mortality. External validation was accomplished using 2,007 patients from the Pediatric Health Information System dataset. Interventions: None. Measurements and Main Results: The Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction score included mode of extracorporeal membrane oxygenation; preextracorporeal membrane oxygenation mechanical ventilation more than 14 days; preextracorporeal membrane oxygenation severity of hypoxia; primary pulmonary diagnostic categories including, asthma, aspiration, respiratory syncytial virus, sepsis-induced respiratory failure, pertussis, and “other”; and preextracorporeal membrane oxygenation comorbid conditions of cardiac arrest, cancer, renal and liver dysfunction. The area under the receiver operating characteristic curve for internal and external validation datasets were 0.69 (95% CI, 0.67–0.71) and 0.66 (95% CI, 0.63–0.69). Conclusions: Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction is a validated tool for predicting in-hospital mortality among children with respiratory failure receiving extracorporeal membrane oxygenation support.

Extracorporeal Membrane Oxygenation for Pediatric Respiratory Failure: Risk Factors Associated With Center Volume and Mortality.

Objectives: Recent analyses show higher mortality at low-volume centers providing extracorporeal membrane oxygenation. We sought to identify factors associated with center volume and mortality to explain survival differences and identify areas for improvement. Design: Retrospective cohort study. Setting: Patients admitted to children’s hospitals in the Pediatric Health Information System database and supported with extracorporeal membrane oxygenation for respiratory failure from 2003 to 2014. Patients: A total of 5,303 patients aged 0–18 years old met inclusion criteria: 3,349 neonates and 1,954 children. Interventions: None. Measurements and Main Results: Low center volume was defined as less than 20, medium 20–49, and large greater than or equal to 50 cases per year. Center volume was also assessed as a continuous integer. Among neonates, clinical factors including intraventricular hemorrhage (relative risk, 1.4; 95% CI, 1.24–1.56) and acute renal failure (relative risk, 1.38; 95% CI, 1.20–1.60) were more common at low-volume compared to larger centers and were associated with in-hospital death. After adjustment for differences in demographic factors and primary pulmonary conditions, mild prematurity, acute renal failure, intraventricular hemorrhage, and receipt of dialysis remained independently associated with mortality, as did center volume measured as a continuous number. Among children, the risk of acute renal failure was almost 20% greater (relative risk, 1.18; 95% CI, 1.02–1.38) in small compared to large centers, but dialysis and bronchoscopy were used significantly less but were associated with mortality. After adjustment for differences in demographic factors and primary pulmonary conditions, acute renal failure, acute liver necrosis, acute pancreatitis, and receipt of bronchoscopy remained independently associated with mortality. Center volume measurement was not associated with mortality given these factors. Conclusions: Among neonates, investigation for intraventricular hemorrhage prior to extracorporeal membrane oxygenation and preservation of renal function are important factors for improvement. Earlier initiation of extracorporeal membrane oxygenation and careful attention to preservation of organ function are important to improve survival for children.

Extracorporeal membrane oxygenation, dialysis, and mortality: let's agree to agree.

Advances in technology and procedures related to pediatric ECMO have not been met with a commensurate improvement in survival or reduction of complications (1). Similarly, improved survival of patients with sepsis and acute respiratory distress syndrome (ARDS) were also stymied until the adoption of consensus definitions and guidelines (2, 3). In this issue of Pediatric Critical Care Medicine Lou et al. investigates the complex interactions between fluid overload (FO), acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT). He reports that CRRT used primarily to treat FO was not significantly associated with in hospital death (44%) compared to those not treated with CRRT (35%) during ECMO (4). Subjects were children treated with ECMO for all major indications (eg. sepsis, ‘E-CPR’, cardiac and respiratory failure) using primarily venoarterial support (>80%). Propensity matching was used to select a similarly ill comparison group not treated with CRRT. Although mortality was similar, those treated with CRRT had longer length of stay and were treated with more blood products. The authors concluded that CRRT could be safely used to treat FO and inferred this intervention caused greater survival than historically predicted. Contradictory to Lou’s finding, the Extracorporeal Life Support Organization (ELSO) and others consistently report that patients with elevated creatinine (Cr) and those treated with renal support have greater mortality across all pediatric ECMO indications (1, 5–7) Lou reported AKI in only 33% of subjects, while other single centers report that AKI occurs in over 50% of all ECMO patients (6). Relevant to pediatrics, serum Cr based scoring systems fail to account for differences in muscle mass, and distribution of Cr into both the intracellular and extracellular fluid compartments. The ELSO registry includes two measures of elevated Cr (1.5–3.0 mg/dL, and > 3 mg/dL) regardless of patient age or size (1). Furthermore, patients with FO; the leading cause for initiation of CRRT during ECMO (8), may have a ‘diluted Cr’ leading to delayed diagnosis of AKI (9, 10). The ELSO registry cords renal support therapies as dialysis, hemofiltration (HF), and continuous arterial venous hemofiltration with a countercurrent dialysis [(CAVHD); which is rarely deployed in the current era]. Unfortunately, missing from the registry are indications for initiation of renal support, accurate classification of the renal replacement therapy and type of equipment and methods for integration with the ECMO circuit. Broad application of research results is hindered by the clinical environments that are not controlled for nuances such as thresholds and timing for initiating and stopping renal replacement therapies and diuretics, rate and volume of fluid removal, and choice of ECMO and dialysis equipment. AKI in patients on ECMO is heterogenous and multifactorial which limits extrapolation of data even when patients are matched for severity of illness. AKI is highly contextual and effected not only by the pre-ECMO status, but also by the sequela of diminished pulsatility (11), hemolysis from centrifugal pumps (12), and rapid volume shifts during fluid removal. Thus comparing renal support therapies in critical care exclusive of ECMO remains complex with key questions unanswered (13). It is unlikely that investigations using only the present ELSO registry data will provide sufficiently accurate information to assess optimal definitions and ideal adjunctive therapies. Furthermore, while CRRT may hasten removal of lung water, it is not expected to restore Na/K ATPase activity or lower inflammatory mediators that also favor alveolar fluid accumulation (14). Caution regarding complications or rapid fluid removal is prudent. Multi-disciplinary physician leadership and study collaboration are needed to define objective clinical and biochemical markers for pediatric AKI and FO during ECMO and then to systematically compare therapies with consistent assessment measures. Lou reports data from a single center using propensity matching to adjust for severity of illness. Of note, data regarding severity of FO during ECMO was not included as a matching variable but has been shown to be associated with mortality (5). Some of the statistical analysis also warrants exploration. The authors report mortality rates of 44% compared to 35%, an increase of almost 10% with exposure to CRRT. Using a power calculation based on this mortality difference; if alpha =0.05 and power = 0.8, the sample size needed to demonstrate this difference is 432 per treatment group which is about 10 fold larger than available for analysis. The 43 subjects per group, was sufficiently large to provide 95% confidence to find a significant difference if mortality in the CRRT group increased to 66% compared to 35% (15). Like many pediatric ECMO studies, the current study is hampered by insufficient power to draw firm conclusions. The report by Lou et al. is provocative and attempts to addresses a common problem among a high risk, high cost patient population in an era of limited resources. Ultimately, the question as to how, when, and who (if anyone) will benefit from CRRT during ECMO, appears to require the adoption of similar consensus definitions, standards, technologies, and systems based practices that effectively changed the course of ARDS (3) and sepsis (2) nearly 20 years ago.

Differences in clinical outcomes and cost between complex and simple arterial switches

BACKGROUND This study evaluates the morbidity, mortality, and cost differences between patients who underwent either a simple or a complex arterial switch operation. METHODS A retrospective study of patients undergoing an arterial switch operation at a single institution was performed. Simple cases were defined as patients with d-transposition of the great arteries with usual coronary anatomy or circumflex artery originating from the right with either intact ventricular septum or ventricular septal defect. Complex cases included all other forms of coronary anatomy, aortic coarctation or arch hypoplasia, and Taussig-Bing anomalies. Costs were acquired using an institutional activity-based accounting system. RESULTS A total of 98 patients were identified, 68 patients in the simple group and 30 in the complex group. The mortality rate was 2% for the simple and 7% for the complex group, p=0.23. Major morbidities including cardiac arrest, extracorporeal membrane oxygenation, a major coronary event, surgical or catheter-based re-intervention, stroke, or permanent pacemaker placement, non-cardiac surgical procedures, mediastinitis, and sepsis did not differ between the simple and complex groups (16 versus 27%, p=0.16). The complex group had increased bleeding requiring re-exploration (0 versus 10%, p=0.04). Hospital and ICU length of stay did not differ. Complex patients had higher overall hospital costs (simple

Resource Use and Morbidities in Pediatric Cardiac Surgery Patients with Genetic Conditions

80,749 versus complex

Use of Extracorporeal Membrane Oxygenation and Mortality in Pediatric Cardiac Surgery Patients With Genetic Conditions: A Multicenter Analysis*

97,387, p=0.01) and higher postoperative costs (simple

Characteristics, Risk Factors, and Outcomes of Extracorporeal Membrane Oxygenation Use in Pediatric Cardiac ICUs: A Report From the Pediatric Cardiac Critical Care Consortium Registry.

60,192 versus complex

MODIFIABLE FACTORS PREDICT MORTALITY AFTER PROLONGED CRITICAL ILLNESS FOLLOWING CONGENITAL HEART SURGERY

70,132, p=0.02). The operating room and supplies accounted for the majority of the cost difference. CONCLUSION Complex arterial switches can be safely performed with low rates of morbidity and mortality but at an increased cost.

A protocol to decrease postoperative chylous effusion duration in children

Objective To evaluate and describe resource use and perioperative morbidities among those patients with genetic conditions undergoing cardiac surgery. Study design Using the Pediatric Health Information System database, we identified patients ≤18 years old with cardiac surgery classified by Risk Adjustment for Congenital Heart Surgery (RACHS) during 2003‐2014. A total of 95 253 patients met study criteria and included no genetic conditions (84.6%), trisomy 21 (9.9%), trisomy 13 or 18 (0.2%), 22q11 deletion (0.8%), Turner syndrome (0.4%), and “other” genetic conditions (4.2%). We compared perioperative complications and procedures in each genetic condition with patients without genetic conditions using regression analysis. Results All groups with genetic conditions, excluding trisomy 21 RACHS 3‐5, experienced increased length of stay and cost among survivors. Complications varied by genetic condition, with patients with trisomy 21 having increased odds of pulmonary hypertension and nosocomial infections. Patients with 22q11 only had increased odds of infection. Patients with Turner syndrome had increased odds of acute renal failure (OR 2.35). Patients with trisomy 13 or 18 had increased odds of pulmonary hypertension (OR 3.13), acute renal failure (OR 2.93), cardiac arrest (OR 2.84), and nosocomial infections (OR 3.53), and those with “other” genetic conditions had increased odds of all complications. Conclusions Children with congenital heart disease and genetic conditions, except trisomy 21 RACHS 3‐5, had increased costs and length of stay. Perioperative morbidities were more common and differed across genetic condition subgroups. Patient‐specific risk factors are important for risk stratification, benchmarking, and counseling with families.