Janet E. Donohue

Fluid Overload in Infants Following Congenital Heart Surgery

Objective: To describe postoperative fluid overload patterns and correlate degree of fluid overload with intensive care morbidity and mortality in infants undergoing congenital heart surgery. Design: Prospective, observational study. Fluid overload (%) was calculated by two methods: 1) (Total fluid in – Total fluid out)/(Preoperative weight) × 100; and 2) (Current weight – Preoperative weight)/(Preoperative weight) × 100. Composite poor outcome included: need for renal replacement therapy, upper quartile time to extubation or intensive care length of stay (> 6.5 and 9.9 days, respectively), or death ⩽ 30 days after surgery. Setting: University hospital pediatric cardiac ICU. Patients: Forty-nine infants < 6 months of age undergoing congenital heart surgery with cardiopulmonary bypass during the period of July 2009 to July 2010. Interventions: None. Measurements and Main Results: Patients had a median age of 53 days (21 neonates) and mean weight of 4.5±1.3kg. Forty-two patients (86%) developed acute kidney injury by meeting at least Acute Kidney Injury Network and Kidney Disease Improving Global Outcomes stage 1 criteria (serum creatinine rise of 50% or ≥ 0.3mg/dL). The patients with adverse outcomes (n = 17, 35%) were younger (7 [5 – 10] vs. 98 [33 – 150] days, p = 0.001), had lower preoperative weight (3.7±0.7 vs. 4.9±1.4kg, p = 0.0002), higher postoperative mean peak serum creatinine (SCr) (0.9±0.3 vs. 0.6±0.3mg/dL, p = 0.005), and higher mean maximum fluid overload by both method 1 (12% ± 10% vs. 6% ± 4%, p = 0.03) and method 2 (24% ± 15% vs. 14% ± 8%, p = 0.02). Predictors of a poor outcome from multivariate analyses were cardiopulmonary bypass time, use of circulatory arrest, and increased vasoactive medication requirements postoperatively. Conclusions: Early postoperative fluid overload is associated with suboptimal outcomes in infants following cardiac surgery. Because the majority of patients developed kidney injury without needing renal replacement therapy, fluid overload may be an important risk factor for adverse outcomes with all degrees of acute kidney injury.

Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Recent advances in treatment have led to dramatically improved survival rates. Standard ALL treatment includes multiple administrations of the chemotherapeutic drug vincristine, which is a known neurotoxic agent. Although peripheral neuropathy is a well‐known toxicity among children receiving vincristine acutely, the long‐term effects on the peripheral nervous system in these children are not clear. The objective of this study was to determine the prevalence of neuropathy and its impact on motor function and quality of life (QOL) among children who survived ALL. Thirty‐seven survivors of childhood ALL aged 8–18 underwent evaluation for neuropathy through self‐reported symptoms, standardized examinations, and nerve conduction studies (NCS). Functional impact of neuropathy was assessed using the Bruininks‐Oseretsky test of Motor Proficiency (BOT‐2). QOL was assessed using the PedsQL. Nerve conduction study abnormalities were seen in 29.7% of children who were longer than 2 years off therapy for ALL. Most children with an abnormal examination or NCS did not have subjective symptoms. Although overall motor function was below population norms on the BOT‐2, presence of neuropathy did not significantly correlate with motor functional status or QOL.

Bone mineral density in young adult survivors of acute lymphoblastic leukemia

The purpose of the current study was to determine the prevalence of low bone mineral density (BMD) (ie, osteopenia) and identify factors associated with low BMD in young adult survivors of childhood acute lymphoblastic leukemia (ALL).

Social Media Methods for Studying Rare Diseases

For pediatric rare diseases, the number of patients available to support traditional research methods is often inadequate. However, patients who have similar diseases cluster “virtually” online via social media. This study aimed to (1) determine whether patients who have the rare diseases Fontan-associated protein losing enteropathy (PLE) and plastic bronchitis (PB) would participate in online research, and (2) explore response patterns to examine social media’s role in participation compared with other referral modalities. A novel, internet-based survey querying details of potential pathogenesis, course, and treatment of PLE and PB was created. The study was available online via web and Facebook portals for 1 year. Apart from 2 study-initiated posts on patient-run Facebook pages at the study initiation, all recruitment was driven by study respondents only. Response patterns and referral sources were tracked. A total of 671 respondents with a Fontan palliation completed a valid survey, including 76 who had PLE and 46 who had PB. Responses over time demonstrated periodic, marked increases as new online populations of Fontan patients were reached. Of the responses, 574 (86%) were from the United States and 97 (14%) were international. The leading referral sources were Facebook, internet forums, and traditional websites. Overall, social media outlets referred 84% of all responses, making it the dominant modality for recruiting the largest reported contemporary cohort of Fontan patients and patients who have PLE and PB. The methodology and response patterns from this study can be used to design research applications for other rare diseases.

The quest to optimize neurodevelopmental outcomes in neonatal arch reconstruction: The perfusion techniques we use and why we believe in them

Major advances in surgical techniques and medical care have brought exciting change to the outcomes of children treated for complex congenital heart disease. Hypoplastic left heart syndrome, for example, was uniformly fatal only 30 years ago, but now has a 5-year survival of approximately 70%. Although the survival for those with surgically repaired complex congenital heart defects has markedly improved, associated morbidities remain high. The neurodevelopmental outcomes of infants and children requiring multiple cardiac operations in childhood are among the major concerns of those who care for patients with congenital heart disease. Deep hypothermic circulatory arrest (DHCA), an adjunctive surgical technique that requires cooling the patient to 18 C and ceasing all blood flow to the entire body including the brain, has until recently been the standard intraoperative procedure used to perform aortic arch reconstruction in infants and young children. The development of DHCA in the early 1970s was a breakthrough that allowed for the operative treatment of many lesions previously not amenable to repair in neonates. Unfortunately, although still a mainstay in congenital heart surgery, DHCA is associated with the potential for poor neurodevelopmental outcomes.

Hemorrhagic complications in pediatric cardiac patients on extracorporeal membrane oxygenation: an analysis of the Extracorporeal Life Support Organization Registry.

Objectives: To determine the prevalence of and risk factors for hemorrhagic complications in children with cardiac disease requiring extracorporeal membrane oxygenation. Design: Retrospective review of the Extracorporeal Life Support Organization Registry (2002–2013). Setting: Participating Extracorporeal Life Support Organization centers. Patients: Patients less than 18 years old on extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Of 21,845 patients requiring extracorporeal membrane oxygenation during the study period, 8,905 (41%) had cardiac disease, and 79% of whom (6,995) had cardiac surgery. Hemorrhagic complications occurred in 8,480 patients (39% of overall cohort), with higher rates in cardiac versus noncardiac patients (49% vs 32%; p < 0.0001) related to cannulation and surgical site bleeding. Cardiac surgical patients had higher rates of hemorrhage compared with cardiac medical patients (57% vs 38%; p < 0.0001), and cardiac patients with hemorrhage had higher extracorporeal membrane oxygenation mortality compared with those without (42% vs 22% in medical patients and 34% vs 20% in surgical patients; both p < 0.0001). In multivariable analysis in both the cardiac medical and surgical groups, hemorrhage risk was higher in children greater than 1 year old and in patients with longer extracorporeal membrane oxygenation duration. Additional independent risk factors for hemorrhage in cardiac surgical patients included pre-extracorporeal membrane oxygenation mediastinal exploration (odds ratio, 3.6; 95% CI, 2.1–6.3), Society of Thoracic Surgeons morbidity category 4–5 (odds ratio, 1.2; 95% CI, 1.03–1.5), cannulation less than 24 hours after surgery (odds ratio, 1.6; 95% CI, 1.3–1.9), and longer cardiopulmonary bypass time (≥ 282 min [upper quartile]; odds ratio, 1.5; 95% CI, 1.3–1.9). Conclusions: In this large, multicenter analysis, hemorrhagic complications occurred in nearly half of children with heart disease on extracorporeal membrane oxygenation and were associated with a significant mortality risk. Several factors were associated with hemorrhagic complications in cardiac surgical patients including pre-extracorporeal membrane oxygenation mediastinal exploration, greater surgical complexity, early postoperative cannulation, and longer bypass times. Whether these risks can be mitigated by modifying or delaying systemic anticoagulation requires further investigation.

Collaborative quality improvement in the cardiac intensive care unit: development of the Paediatric Cardiac Critical Care Consortium (PC4)

Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.

Fontan-Associated Protein-Losing Enteropathy and Plastic Bronchitis

OBJECTIVE To characterize the medical history, disease progression, and treatment of current-era patients with the rare diseases Fontan-associated protein-losing enteropathy (PLE) and plastic bronchitis. STUDY DESIGN A novel survey that queried demographics, medical details, and treatment information was piloted and placed online via a Facebook portal, allowing social media to power the study. Participation regardless of PLE or plastic bronchitis diagnosis was allowed. Case control analyses compared patients with PLE and plastic bronchitis with uncomplicated control patients receiving the Fontan procedure. RESULTS The survey was completed by 671 subjects, including 76 with PLE, 46 with plastic bronchitis, and 7 with both. Median PLE diagnosis was 2.5 years post-Fontan. Hospitalization for PLE occurred in 71% with 41% hospitalized ≥ 3 times. Therapy varied significantly. Patients with PLE more commonly had hypoplastic left ventricle (62% vs 44% control; OR 2.81, 95% CI 1.43-5.53), chylothorax (66% vs 41%; OR 2.96, CI 1.65-5.31), and cardiothoracic surgery in addition to staged palliation (17% vs 5%; OR 4.27, CI 1.63-11.20). Median plastic bronchitis diagnosis was 2 years post-Fontan. Hospitalization for plastic bronchitis occurred in 91% with 61% hospitalized ≥ 3 times. Therapy was very diverse. Patients with plastic bronchitis more commonly had chylothorax at any surgery (72% vs 51%; OR 2.47, CI 1.20-5.08) and seasonal allergies (52% vs 36%; OR 1.98, CI 1.01-3.89). CONCLUSIONS Patient-specific factors are associated with diagnoses of PLE or plastic bronchitis. Treatment strategies are diverse without clear patterns. These results provide a foundation upon which to design future therapeutic studies and identify a clear need for forming consensus approaches to treatment.

Clinical Epidemiology of Extubation Failure in the Pediatric Cardiac ICU: A Report From the Pediatric Cardiac Critical Care Consortium

Objective: To describe the clinical epidemiology of extubation failure in a multicenter cohort of patients treated in pediatric cardiac ICUs. Design: Retrospective cohort study using prospectively collected clinical registry data. Setting: Pediatric Cardiac Critical Care Consortium registry. Patients: All patients admitted to the CICU at Pediatric Cardiac Critical Care Consortium hospitals. Interventions: None. Measurements and Main Results: Analysis of all mechanical ventilation episodes in the registry from October 1, 2013, to July 31, 2014. The primary outcome of extubation failure was reintubation less than 48 hours after planned extubation. Repeated-measures analysis using generalized estimating equations to account for within patient and center correlation was performed to identify risk factors for extubation failure. Adjusted extubation failure rates for each hospital were calculated using logistic regression controlling for patient factors. Of 1,734 mechanical ventilation episodes (1,478 patients at eight hospitals) ending in a planned extubation, there were 100 extubation failures (5.8%). In multivariable analysis, only longer duration of mechanical ventilation was significantly associated with extubation failure (p = 0.01); the failure rate was 4% when ventilated less than 24 hours, 9% after 24 hours, and 13% after 7 days. For 503 patients intubated and extubated in the cardiac operating room, 15 patients (3%) failed extubation within 48 hours (12 within 24 hr). Case-mix-adjusted extubation failure rates ranged from 1.1% to 9.8% across hospitals. Patients failing extubation had greater median cardiac ICU length of stay (15 vs 3 d; p < 0.001) and in-hospital mortality (7.9 vs 1.2%; p < 0.001). Conclusions: Though extubation failure is uncommon overall, there may be opportunities to improve extubation readiness assessment in patients ventilated more than 24 hours. These data suggest that extubation in the operating room after cardiac surgery can be done with a low failure rate. We observed variation in extubation failure rates across hospitals, and future investigation must elucidate the optimal strategies of high-performing centers to reduce ventilation time while limiting extubation failures.

Personnel and unit factors impacting outcome after cardiac arrest in a dedicated pediatric cardiac intensive care unit

Objective: To assess the impact of personnel and unit factors on outcome from cardiac arrest in a dedicated pediatric cardiac intensive care unit. Design: Retrospective medical record review. Setting: Dedicated cardiac intensive care unit at a quaternary academic children’s hospital. Patients: Children and young adults who had cardiac arrest while cared for in the pediatric cardiac intensive care unit from January 1, 2006, to December 31, 2008. Interventions: None. Measurements and Main Results: One hundred two index cardiac arrests over a 3-yr period in our pediatric cardiac intensive care unit were reviewed. We defined successful resuscitation as either return of spontaneous circulation or successful cannulation to extracorporeal membrane oxygenation. Differences in resuscitation rates were assessed across categorical systems variables using logistic regression. The rate of successful resuscitation was 84% (return of spontaneous circulation 74%, extracorporeal membrane oxygenation 10%). Survival to hospital discharge was 48% for patients who had a cardiac arrest. 11% of arrests during the week and 31% during weekends (odds ratio 3.8; 95% confidence interval 1.2–11.5) were not successfully resuscitated. Unsuccessful resuscitation was significantly more likely when the primary nurse had <1 yr of experience in the pediatric cardiac intensive care unit (50% <1 yr vs. 13% >1 yr; odds ratio 6.8; confidence interval 1.5–31.0). Cardiac arrest on a weekend day and <1-yr pediatric cardiac intensive care unit nursing experience were also associated with unsuccessful resuscitation in a multivariable model. Resuscitation outcomes were similar when senior intensive care unit attending physicians were on-call at the time of arrest compared with other intensive care unit staff (17% unsuccessful vs. 15%; odds ratio 1.2; confidence interval 0.4–3.7). Arrests where the attending physician was present at the onset resulted in unsuccessful resuscitation 18% of the time vs. 14% for events where the attending was not present (odds ratio 1.3; confidence interval 0.5–3.9). Conclusions: Our data suggest that personnel and unit factors may impact outcome after cardiac arrest in a pediatric cardiac intensive care unit. Weekend arrests and less experience of the primary nurse were risk factors for unsuccessful resuscitation. Neither presence at arrest onset nor experience of the attending cardiac intensivist was associated with outcome.