High risk of necrotising enterocolitis in term-born neonates with CHD delivered by caesarean section: a case-control study.

OBJECTIVE: Necrotising enterocolitis is linked with altered intestinal microbiota, and caesarean birth is associated with imbalance of newborn intestinal microbiome. We aimed to investigate the role of delivery mode (vaginal or caesarean) and gestational age in the development of necrotising enterocolitis among term-born neonates (≥ 37 weeks) with CHD. METHODS: Case-control study. We studied all newborns with CHD who underwent cardiac surgery during the neonatal (≤ 28 days of age) period, between 2007 and 2017. Totally, 60 cases of necrotising enterocolitis were matched (by year of birth and type of congenital heart lesion) with 180 controls (1:3 ratio). Multivariable conditional logistic regression was used to assess the study question. RESULTS: The overall prevalence of necrotising enterocolitis was 6.3% in term-born newborns with CHD. Neonates with a left-ventricular outflow tract lesion or single ventricle lesion accounted for 55% (n = 33) of cases. 62% (n = 37) cases were in the modified Bell's stage 2 or more for necrotising enterocolitis classification. In multivariable modelling, gestational age at birth was not associated with the development of necrotising enterocolitis [adjusted odds ratio per week increase, 95% confidence interval: 1.20 (0.90-1.60)]. Birth by caesarean delivery (compared to vaginal) was strongly associated with development of necrotising enterocolitis [adjusted odds ratio (95% confidence interval): 2.64 (1.31-5.29)]. We failed to identify an association between preoperative enteral nutrition and necrotising enterocolitis. CONCLUSION: This study showed a high risk of necrotising enterocolitis in newborns with critical CHD born via caesarean. This information is important given the high prevalence of planned birth by caesarean in newborns with CHD.

Trends in Childhood Oncology Admissions to ICUs in Australia and New Zealand.

OBJECTIVES: There are few robust, national-level reports of contemporary trends in pediatric oncology admissions, resource use, and mortality. We aimed to describe national-level data on trends in intensive care admissions, interventions, and survival for children with cancer. DESIGN: Cohort study using a binational pediatric intensive care registry. SETTING: Australia and New Zealand. PATIENTS: Patients younger than 16 years, admitted to an ICU in Australia or New Zealand with an oncology diagnosis between January 1, 2003, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined trends in oncology admissions, ICU interventions, and both crude and risk-adjusted patient-level mortality. Eight thousand four hundred ninety admissions were identified for 5,747 patients, accounting for 5.8% of PICU admissions. Absolute and population-indexed oncology admissions increased from 2003 to 2018, and median length of stay increased from 23.2 hours (interquartile range [IQR], 16.8-62 hr) to 38.8 hours (IQR, 20.9-81.1 hr) ( p < 0.001). Three hundred fifty-seven of 5,747 patients died (6.2%). There was a 45% reduction in risk-adjusted ICU mortality, which reduced from 3.3% (95% CI, 2.1-4.4) in 2003-2004 to 1.8% (95% CI, 1.1-2.5%) in 2017-2018 ( p trend = 0.02). The greatest reduction in mortality seen in hematological cancers and in nonelective admissions. Mechanical ventilation rates were unchanged from 2003 to 2018, while the use of high-flow nasal prong oxygen increased (incidence rate ratio, 2.43; 95% CI, 1.61-3.67 per 2 yr). CONCLUSIONS: In Australian and New Zealand PICUs, pediatric oncology admissions are increasing steadily and such admissions are staying longer, representing a considerable proportion of ICU activity. The mortality of children with cancer who are admitted to ICU is low and falling.

Opinion: on the importance of maintaining the functional form of explanatory variables.

In medical research, continuous variables are often categorised into two or more groups before being included in the analysis; this practice often comes with a cost, such as loss of power in analysis, less reliable estimates, and can often leave residual confounding in the results. In this research report, we show this by way of estimates from a regression analysis looking at the association between acute kidney injury and post-operative mortality in a sample of 194 neonates who underwent the Norwood operation. Two models were developed, one using a continuous measure of renal function as the main explanatory variable and second using a categorised version of the same variable. A continuous measure of renal function is more likely to yield reliable estimates and also maintains more statistical power in the analysis to detect a relation between the exposure and outcome. It also reveals the true biological relationship between the exposure and outcome. Categorising a continuous variable may not only miss an important message, it can also get it wrong. Additionally, given a non-linear relationship is commonly encountered between the exposure and outcome variable, investigators are advised to retain a predictor with a linear term only when supported by data. All of this is particularly important in small data sets which account for the majority of clinical research studies.

Early Peritoneal Dialysis and Postoperative Outcomes in Infants After Pediatric Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: Peritoneal dialysis (PD) is used in several cardiac surgical units after cardiac surgery, and early initiation of PD after surgery may have the potential to influence postoperative outcomes. This systematic review and meta-analysis aims to summarize the evidence for the association between early PD after cardiac surgery and postoperative outcomes. DATA SOURCES: MEDLINE, Embase, and PubMed from 1981 to November 1, 2021. STUDY SELECTION: Observational studies and randomized trials reporting on early PD after pediatric cardiac surgery. DATA EXTRACTION: Random-effects meta-analysis was used to estimate the pooled odds ratios (ORs) and their 95% CIs for postoperative mortality and pooled mean difference (MD) (95% CI) for duration of mechanical ventilation and ICU length of stay. DATA SYNTHESIS: We identified nine studies from the systematic review, and five were considered suitable for meta-analysis. Early initiation of PD after cardiac surgery was associated with a reduction in postoperative mortality (OR, 0.43 (95% CI, 0.23-0.80); number of estimates = 4). Early commencement of PD shortened duration of mechanical ventilation (MD [95% CI], -1.09 d [-1.86 to -0.33 d]; I2 = 56.1%; p = 0.06) and intensive care length of stay (MD [95% CI], -2.46 d [-3.57 to -1.35 d]; I2 = 18.7%; p = 0.30], respectively. All three estimates had broad 95% prediction intervals (crossing null) denoting major heterogeneity between studies and wide range of possible study estimates in similar future studies. Overall, studies reporting on the effects of early PD included only a subset of infants undergoing cardiac surgery (typically high-risk infants), so selection bias may be a major issue in published studies. CONCLUSIONS: This review suggests that early initiation of PD may be associated with beneficial postoperative outcomes in infants after cardiac surgery. However, these results were based on studies of varying qualities and risk of bias. Early identification of high-risk infants after cardiac surgery is important so that prevention or early mitigation strategies can be applied to this cohort. Future prospective studies in high-risk populations are needed to study the role of early PD in influencing postoperative outcomes.

Temperature Management and Health-Related Quality of Life in Children 3 Years After Cardiac Arrest.

OBJECTIVES: Therapeutic hypothermia minimizes neuronal injury in animal models of hypoxic-ischemic encephalopathy with greater effect when used sooner after the insult. Clinical trials generally showed limited benefit but are difficult to perform in a timely manner. In this clinical study, we evaluated the association between the use of hypothermia (or not) and health-related quality of life among survivors of pediatric cardiac arrest as well as overall mortality. DESIGN: Single-center, retrospectively identified cohort with prospective assessment of health-related quality of life. SETTING: PICU of a pediatric hospital. PATIENTS: Children with either out-of-hospital or in-hospital cardiac arrest from January 2012 to December 2017. INTERVENTIONS: Patients were assigned into two groups: those who received therapeutic hypothermia at less than or equal to 35°C and those who did not receive therapeutic hypothermia but who had normothermia targeted (36-36.5°C). The primary outcome was health-related quality of life assessment and the secondary outcome was PICU mortality. MEASUREMENTS AND MAIN RESULTS: We studied 239 children, 112 (47%) in the therapeutic hypothermia group. The median (interquartile range) of lowest temperature reached in the 48 hours post cardiac arrest in the therapeutic hypothermia group was 33°C (32.6-33.6°C) compared with 35.4°C (34.7-36.2°C) in the no therapeutic hypothermia group (p < 0.001). At follow-up, 152 (64%) were alive and health-related quality of life assessments were completed in 128. Use of therapeutic hypothermia was associated with higher lactate and lower pH at baseline. After regression adjustment, therapeutic hypothermia (as opposed to no therapeutic hypothermia) was associated with higher physical (mean difference, 15.8; 95% CI, 3.5-27.9) and psychosocial scores (13.6 [5.8-21.5]). These observations remained even when patients with a temperature greater than 37.5°C were excluded. We failed to find an association between therapeutic hypothermia and lower mortality. CONCLUSIONS: Out-of-hospital or in-hospital cardiac arrest treated with therapeutic hypothermia was associated with higher health-related quality of life scores despite having association with higher lactate and lower pH after resuscitation. We failed to identify an association between use of therapeutic hypothermia and lower mortality.

Recurrent Extubation Failure Following Neonatal Cardiac Surgery Is Associated with Increased Mortality.

Extubation failure (EF) following neonatal cardiac surgery is associated with increased mortality. Neonates who experienced EF twice or more (recurrent EF) may have worse outcomes than those who have a single EF or no-EF. The aims of this study are to investigate the in hospital mortality for neonates with recurrent EF compared to those with single or no-EF, and determine factors associated with recurrent EF. Neonates' ≤ 28 days who underwent cardiac surgery from January 2008 to December 2019 were included. EF was defined as unplanned reintubation within 72 h after a planned extubation. 1187 (18 recurrent EF, 84 single EF and 1085 no-EF) neonates were included. Recurrent EF occurred in 18 (17.6%) of 102 neonates undergoing a second extubation. The median time (IQR) to reintubation after the first and second extubations were similar, being 20.9 (3.3-45.2) versus 19.4 (5.5-47) h. The reason for a second-time EF was respiratory in 39% and cardiovascular in 33%. Recurrent EF and single EF was associated with increased mortality (odds ratio, 95% confidence interval (CI) 23.5, 6.9-79.9) and (odds ratio, 95% CI 5.2, 2.3-12.0) compared to no-EF. Based on the final model with risk adjustment, predicted mortality was 29.0% in recurrent EF, 6.5% in single EF, and 1.2% in no-EF. First-time EF due to cardiovascular compromise was associated with recurrent EF (odds ratio, 95% CI 3.1, 1.0-9.7). This study confirmed that patients with recurrent EF have a high morality. Neonates with a cardiovascular reason for first-time EF are more likely to have a recurrent EF than those with other causes.

Gestational Age and Risk of Mortality in Term-Born Critically Ill Neonates Admitted to PICUs in Australia and New Zealand.

OBJECTIVES: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (≥ 37 wk') admitted to PICUs in Australia and New Zealand. DESIGN: Observational multicenter cohort study. SETTING: PICUs in Australia and New Zealand. PATIENTS: Term-born neonates (≥ 37 wk) admitted to PICUs. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS:: We studied 5,073 infants born with a gestational age greater than or equal to 37 weeks and were less than 28 days old when admitted to a PICU in Australia or New Zealand between 2007 and 2016. The association between gestational age and mortality was estimated using a multivariable logistic regression model, adjusting for age, sex, indigenous status, Pediatric Index of Mortality version 2, and site. The median gestational age was 39.1 weeks (interquartile range, 38.2-40 wk) and mortality in hospital was 6.6%. Risk of mortality declined log-linearly with gestational age. The adjusted analysis showed a 20% (95% CI, 11-28%) relative reduction in mortality for each extra week of gestation beyond 37 weeks. The effect of gestation was stronger among those who received extracorporeal life support: each extra week of gestation was associated with a 44% (95% CI, 25-57%) relative reduction in mortality. Longer gestation was also associated with reduced length of stay in hospital: each week increase in gestation, the average length of stay decreased by 4% (95% CI, 2-6%). CONCLUSIONS: Among neonates born at "term" who are admitted to a PICU, increasing gestational age at birth is associated with a substantial reduction in the risk of dying in hospital. The maturational influence on outcome was more strongly noted in the sickest neonates, such as those requiring extracorporeal life support. This information is important in view of the increasing proportion of planned births in both high- and low-/middle-income countries.

Extubation Failure and Major Adverse Events Secondary to Extubation Failure Following Neonatal Cardiac Surgery.

OBJECTIVES: To describe the prevalence and consequences of major adverse events secondary to extubation failure after neonatal cardiac surgery. DESIGN: A single-center cohort study. SETTING: A medical-surgical, 30-bed PICU in Victoria, Australia. PATIENTS: One thousand one hundred eighty-eight neonates less than or equal to 28 days old who underwent cardiac surgery from January 2007 to December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Extubation failure was defined as unplanned reintubation within 72 hours after a planned extubation. Major adverse event was defined as one or more of cardiac arrest, emergency chest reopening, extracorporeal membrane oxygenation, or death within 72 hours after extubation. One hundred fifteen of 1,188 (9.7%) neonates had extubation failure. Hospital mortality was 17.4% and 2.0% in neonates with and without extubation failure. Major adverse event occurred in 12 of 115 reintubated neonates (10.4%). major adverse event included cardiac arrest (n = 10), chest reopening (n = 8), extracorporeal membrane oxygenation (n = 5), and death (n = 0). Cardiovascular compromise accounted for major adverse event in eight: ventricular dysfunction (n = 3), pulmonary overcirculation (n = 2), coronary ischemia (n = 2), cardiac tamponade (n = 1). In a multivariable logistic regression, factors associated with major adverse event were high complexity in cardiac surgery (odds ratio 5.9; 95% CI: 1.1-32.2) and airway anomaly (odds ratio 6.0; 95% CI: 1.1-32.6). Hospital morality was 25% and 17% in reintubated neonates with and without major adverse event. CONCLUSIONS: Around 10% of reintubated neonates suffered major adverse event within 72 hours of extubation. Neonates suffering major adverse event had high mortality. Major adverse event should be monitored and reported in future studies of extubation failure. Along with tracking of extubation failure rates, major adverse event secondary to extubation failure may also serve as a key performance indicator for ICUs and registries.

Early Peritoneal Dialysis and Major Adverse Events After Pediatric Cardiac Surgery: A Propensity Score Analysis.

OBJECTIVES: Early peritoneal dialysis may have a role in modulating the inflammatory response after cardiopulmonary bypass. This study sought to test the effect of early peritoneal dialysis on major adverse events after pediatric cardiac surgery involving cardiopulmonary bypass. DESIGN: In this observational study, the outcomes in infants post cardiac surgery who received early peritoneal dialysis (within 6 hr of completing cardiopulmonary bypass) were compared with those who received late peritoneal dialysis. The primary outcome was a composite of one or more of cardiac arrest, emergency chest reopening, requirement for extracorporeal membrane oxygenation, or death. Secondary outcomes included duration of mechanical ventilation, length of intensive care, and hospital stay. A propensity score methodology utilizing inverse probability of treatment weighting was used to minimize selection bias due to timing of peritoneal dialysis. SETTING: Cardiac ICU, The Royal Children's Hospital, Melbourne, VIC, Australia. PATIENTS: From 2012 to 2015, infants who were commenced on peritoneal dialysis after cardiac surgery were included. MEASUREMENTS AND MAIN RESULTS: Among 239 eligible infants, 56 (23%) were commenced on early peritoneal dialysis and 183 (77%) on late peritoneal dialysis. At 90 days, early peritoneal dialysis as compared with late peritoneal dialysis was associated with a decreased risk of primary outcome (relative risk, 0.16; 95% CI, 0.05-0.47; p < 0.001 and absolute risk difference, -18.1%; 95% CI, -25.1 to -11.1; p < 0.001). Early peritoneal dialysis was also associated with a decrease in duration of mechanical ventilation and intensive care stay. Among infants with a cardiopulmonary bypass greater than 150 minutes, early peritoneal dialysis was also associated with a survival advantage (relative risk, 0.14; 95% CI, 0.03-0.84; p = 0.03 and absolute risk difference, -7.8; 95% CI, -13.6 to -2; p = 0.008). CONCLUSIONS: Early peritoneal dialysis in infants post cardiac surgery is associated with a decrease in the rate of major adverse events. The role of early peritoneal dialysis warrants the conduct of randomized trials both in high and low-to-middle income countries; any beneficial effects if confirmed have the potential to strongly influence outcomes for children born with congenital heart disease.

Changing Risk of In-Hospital Cardiac Arrest in Children Following Cardiac Surgery in Victoria, Australia, 2007-2016.

BACKGROUND: Reported incidence of in hospital cardiac arrest (IHCA) after paediatric cardiac surgery varies between 3-4% in high income countries and this risk may have changed over time. We sought to examine this trend in detail. METHODS: A retrospective observational study of 3,781 children who underwent 4,938 cardiac surgeries between 1 January 2007 and 31 December 2016 in a tertiary children's hospital. IHCA was defined as cessation of cardiac mechanical activity requiring cardiac massage for ≥1minute. Surgical complexity was categorised using risk adjusted congenital heart surgery (RACHS-1) category. Poisson regression was used to analyse trends for every two-year period. RESULTS: There were a total of 211 (4.3%) IHCA events after surgery. These patients were younger, more likely to have had a premature birth, have a chromosomal or genetic syndrome association and have a high surgical complexity. Overall, there was a 52% reduction in IHCA rate over 10 years: reducing from 5.4 /100 surgeries in 2007-08 to 2.6/100 surgeries in 2015-16 (p-trend=<0.001). The reduction was mainly seen in low-to-moderate risk categories (RACHS-1 categories 1-4) and not in high risk categories (RACHS-1 category 5-6). Children in high risk categories were 13.6 times more likely to experience an IHCA (compared to low risk categories). Overall hospital mortality for children suffering IHCA decreased from 42.5/100 patients in 2007-08 to 11.1/100 patients in 2015-16 (p-trend=0.037). CONCLUSIONS: The IHCA rate following cardiac surgery has more than halved over the last decade; children who experience IHCA also have lower mortality than in previous years. High risk procedures still have a substantial rate of IHCA and efforts are needed to minimise the burden further in this population.

Major Adverse Events Following Over-Shunting Are Associated With Worse Outcomes Than Major Adverse Events After a Blocked Systemic-to-Pulmonary Artery Shunt Procedure.

OBJECTIVES: Causes of major adverse event after systemic-to-pulmonary shunt procedure are usually shunt occlusion or over-shunting. Outcomes categorized on the basis of these causes will be helpful both for quality improvement and prognostication. DESIGN: Retrospective cohort analysis of children who underwent a systemic-to-pulmonary shunt after excluding those who had it for Norwood or Damus-Kaye-Stansel procedure. SETTING: The Royal Children's Hospital, Melbourne, VIC, Australia. PATIENTS: From 2008 to 2015, 201 children who had a systemic-to-pulmonary shunt were included. INTERVENTIONS: Major adverse event is defined as one or more of cardiac arrest, chest reopening, or requirement for extracorporeal membrane oxygenation. Study outcome is a "composite poor outcome," defined as one or more of acute kidney injury, necrotizing enterocolitis, brain injury, or in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: Median (interquartile range) age was 12 days (6-38 d) and median (interquartile range) time to major adverse event was 5.5 hours (2-17 hr) after admission. Overall, 36 (18%) experienced a major adverse event, and reasons were over-shunting (n = 17), blocked shunt (n = 13), or other (n = 6). Fifteen (88%) in over-shunting group suffered a cardiac arrest compared with two (15%) in the blocked shunt group (p < 0.001). The composite poor outcome was seen in 15 (88%) in over-shunting group, four (31%) in the blocked shunt group, and 56 (34%) in those who did not experience a major adverse event (p < 0.001). By multivariable analysis, predictors for composite poor outcome were major adverse event due to over-shunting (no major adverse event-reference; over-shunting odds ratio, 18.60; 95% CI, 3.87-89.4 and shunt-block odds ratio, 1.57; 95% CI, 0.46-5.35), single ventricle physiology (odds ratio, 4.70; 95% CI, 2.34-9.45), and gestation (odds ratio, 0.84/wk increase; 95% CI, 0.74-0.96). CONCLUSIONS: Infants who suffer major adverse event due to over-shunting experience considerably poorer outcomes than those who experience events due to shunt block. A mainly hypoxic event with maintenance of systemic perfusion (as often seen in a blocked shunt) is less likely to result in poorer outcomes than those after a hypoxic-ischemic event (commonly seen in over-shunting).

Rhabdomyolysis in a Tertiary PICU: A 10-Year Study.

OBJECTIVES: Rhabdomyolysis is a disorder of muscle breakdown. The aim of this study was to describe the epidemiology of rhabdomyolysis in children admitted to a PICU and to assess the relationship between peak creatinine kinase and mortality. DESIGN: Retrospective cohort study in children admitted to the PICU with rhabdomyolysis between January 1, 2005, and December 31, 2014. Demographic, clinical, and outcome data were recorded. Outcomes were analyzed by level of peak creatinine kinase value (0-10,000, 10,001-50,000, > 50,000IU/L). Long-term renal outcomes were reported for PICU survivors. SETTING: A single-centre academic tertiary PICU. PATIENTS: Children admitted to the PICU with serum creatinine kinase level greater than 1,000 IU/L. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 182 children with rhabdomyolysis. The median peak creatinine kinase value was 3,583 IU/L (1,554-9,608). The primary diagnostic categories included sepsis, trauma, and cardiac arrest. Mortality for peak creatinine kinase values 0-10,000, 10,001-50,000, and > 50,000 IU/L were 24/138 (17%), 6/28 (21%), and 3/16 (19%), respectively (p = 0.87). Children with a peak creatinine kinase greater than 10,000 IU/L had a longer duration of mechanical ventilation and ICU length of stay than children with peak creatinine kinase less than 10,000. Renal replacement therapy was administered in 29/182 (16%). There was longer duration of mechanical ventilation (273 [141-548] vs. 73 [17-206] hr [p < 0.001]) and ICU length of stay (334 [147-618] vs. 100 [37-232] hr (p < 0.001)] in children receiving renal replacement therapy. Continuous veno-venous hemofiltration was the most common modality 23/29 (79%). Only one child required renal replacement therapy postintensive care stay, and adverse long-term renal outcomes were uncommon. CONCLUSIONS: In children with rhabdomyolysis requiring intensive care, peak creatinine kinase was not associated with mortality but is associated with greater use of intensive care resources. Chronic kidney disease is an uncommon sequelae of rhabdomyolysis in children requiring intensive care.

Extubation Failure Is Associated With Increased Mortality Following First Stage Single Ventricle Reconstruction Operation.

OBJECTIVES: To identify the prevalence, causes, risk factors, and outcomes associated with extubation failure following first stage single ventricle reconstruction surgery. DESIGN: Retrospective cohort analysis of neonates who underwent a first stage single ventricle reconstruction operation. Extubation failure was defined as endotracheal reintubation within 48 hours of first extubation attempt. SETTING: The Royal Children's Hospital, Melbourne. PATIENTS: Data were collected for all infants who underwent a Norwood or Damus-Kaye-Stansel procedure between 2005 and 2014 at our institution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Extubation failure occurred in 23 of 137 neonates (16.8%; 95% CI, 11.0-24.1%) who underwent a trial of extubation. Overall, 42 patients (30.7%) were extubated to room air, 88 (64.2%) to nasal continuous positive airway pressure, and seven (5.1%) to high-flow nasal cannulae, though there was no major difference in extubation failure rates between these three groups (p = 0.37). The median time to reintubation was 16.7 hours (interquartile range, 3.2-35.2), and male infants failed extubation more frequently (63.2% vs 87.0%; p = 0.02), although age, gestation, weight, cardiac diagnosis (hypoplastic left heart syndrome vs other single ventricle conditions), shunt type (modified Blalock-Taussig vs right ventricle-pulmonary artery shunt), intraoperative perfusion times, preextubation mechanical ventilation duration, preextubation acid-base status, and postoperative fluid balance were not related to extubation outcome. Infants who failed extubation had a higher intensive care mortality (19.4% vs 3.5%; p = 0.03) and in-hospital mortality (30.4% vs 6.1%; p < 0.001). CONCLUSIONS: There is a high prevalence of extubation failure following first stage single ventricle reconstruction, and this is associated with considerably worse patient outcomes. The high prevalence and also the wide variation in rates of extubation failure in reported literature provide with an opportunity for implementation of quality assurance activities to minimize this complication and improve outcomes.

A Case-Control Analysis of Postoperative Fluid Balance and Mortality After Pediatric Cardiac Surgery.

OBJECTIVES: A positive fluid balance after cardiac surgery may be associated with poor outcomes; however, previous studies looking at this association have been limited by the number of deaths in the study population. Our primary aim was to determine the relationship between postoperative cumulative fluid balance and mortality in cardiac surgical patients. Secondary aims were to study the association between fluid balance and duration of mechanical ventilation, intensive care and hospital length of stay. DESIGN: Case-control study. SETTING: A 30-bed multidisciplinary PICU. PATIENTS: All patients admitted to the PICU following cardiac surgery from 2010 to 2014. INTERVENTIONS: Deaths during PICU admission following cardiac surgery (cases) were matched 1:3 with children who survived to PICU discharge (controls) using the following criteria: age at surgery (within a 20% age range), Risk Adjusted Congenital Heart Surgery (RACHS-1) category, and year of admission. MEASUREMENTS AND MAIN RESULTS: Of 1,996 eligible children, 46 died (2.3%) of whom 45 (98%) were successfully matched. Cumulative fluid balance on days 2 and 7 was not associated with PICU mortality. On multivariable analysis, factors associated with mortality were cardiopulmonary bypass time (per 10-min increase, odds ratio [95% CI], 1.06 [1.00-1.12]; p = 0.03), extracorporeal membrane oxygenation requirement within 3 days (46.6 [9.47-230.11]; p < 0.001), peak serum chloride (mmol/L) in the first 48 hours (1.12 [1.01-1.23]), and time to start peritoneal dialysis after surgery (in comparison to no peritoneal dialysis, odds ratio [95% CI] in those started on early peritoneal dialysis was 1.07 [0.33-3.41]; p = 0.90 and in late peritoneal dialysis 3.65 [1.21-10.99]; p = 0.02). Children with cumulative fluid balance greater than or equal to 5% by day 2 spent longer on mechanical ventilation (median [interquartile range], 211 hr [97-539] vs 93 hr [34-225]; p <0.001), in PICU (11 d [8-26] vs 6 [3-13]; p < 0.001) and in hospital (22 d [13-39] vs 14 d [8-30]; p = 0.001). CONCLUSIONS: Early fluid overload is not associated with mortality. However, it is associated with increased duration of mechanical ventilation and PICU length of stay. Early peritoneal dialysis commencement (compared with late peritoneal dialysis) after surgery was associated with decreased mortality.

Late-Term Gestation Is Associated With Improved Survival in Neonates With Congenital Heart Disease Following Postoperative Extracorporeal Life Support.

OBJECTIVE: Several population-based studies have shown that gestational age 39-40 weeks at birth is associated with superior outcomes in various pediatric settings. A high proportion of births for neonates with congenital heart disease occur before 39 weeks. We aimed to assess the influence of late-term gestation (39-40 wk) on survival in neonates requiring extracorporeal life support following surgery for congenital heart disease. DESIGN: Retrospective cohort study. SETTING: The Royal Children's Hospital, Melbourne, Australia. PATIENTS: Neonates requiring extracorporeal life support after cardiac surgery for congenital heart disease. MEASUREMENTS AND MAIN RESULTS: From 2005 to 2014, 110 neonates (10.5% of neonates undergoing cardiac surgery) required extracorporeal life support after cardiac surgery. Indications were failure to separate from cardiopulmonary bypass in 40 (36%), extracorporeal cardiopulmonary resuscitation in 48 (44%), progressive low cardiac output in 15 (14%), and other reasons in seven (6%). Extracorporeal life support duration was 94 hours (interquartile range, 53-135), and 54 (49%) underwent single ventricle repair. Gestation at birth (n [%]) was as follows: less than 37 weeks, 19 (17%); 37-38 weeks, 38 (35%); 39-40 weeks, 50 (45%); 41 weeks or more, 3 (3%). By multivariable analysis (controlling for age, era of extracorporeal life support 2005-2009 vs 2010-2014, single ventricle status and acute renal failure), gestational age of 39-40 weeks was associated with the lowest odds for intensive care mortality: using less than 37 weeks as referent, the adjusted odds ratio (95% CI) for 37-38 weeks was 0.41 (0.12-1.33); for 39-40 weeks, 0.27 (0.08-0.84); and for 41 weeks or more, 1.06 (0.07-14.7). Similar association was also seen in a subcohort of study neonates (n = 66) who were commenced on extracorporeal life support after admission to intensive care: using less than 37 weeks as referent, the adjusted odds ratio (95% CI) for 37-38 weeks was 0.52 (0.10-2.80) and for 39-40 weeks, 0.15 (0.03-0.81). CONCLUSIONS: In this cohort of neonates requiring extracorporeal life support following cardiac surgery, 39-40 weeks of gestation at birth is associated with the best survival. The additional maturity gained by reaching a gestation of at least 39 weeks is likely to confer a survival advantage in this high-risk cohort.

Five-Year Survival of Children With Chronic Critical Illness in Australia and New Zealand.

OBJECTIVE: Outcomes for children with chronic critical illness are not defined. We examined the long-term survival of these children in Australia and New Zealand. DESIGN: All cases of PICU chronic critical illness with length of stay more than 28 days and age 16 years old or younger in Australia and New Zealand from 2000 to 2011 were studied. Five-year survival was analyzed using Kaplan-Meir estimates, and risk factors for mortality evaluated using Cox regression. SETTING: All PICUs in Australia and New Zealand. PATIENTS: Nine hundred twenty-four children with chronic critical illness. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Nine hundred twenty-four children were admitted to PICU for longer than 28 days on 1,056 occasions, accounting for 1.3% of total admissions and 23.5% of bed days. Survival was known for 883 of 924 patients (95.5%), with a median follow-up of 3.4 years. The proportion with primary cardiac diagnosis increased from 27% in 2000-2001 to 41% in 2010-2011. Survival was 81.4% (95% CI, 78.6-83.9) to PICU discharge, 70% (95% CI, 66.7-72.8) at 1 year, and 65.5% (95% CI, 62.1-68.6) at 5 years. Five-year survival was 64% (95% CI, 58.7-68.6) for children admitted in 2000-2005 and 66% (95% CI, 61.7-70) if admitted in 2006-2011 (log-rank test, p = 0.37). After adjusting for admission severity of illness using the Paediatric Index of Mortality 2 score, predictors for 5-year mortality included bone marrow transplant (hazard ratio, 3.66; 95% CI, 2.26-5.92) and single-ventricle physiology (hazard ratio, 1.98; 95% CI, 1.37-2.87). Five-year survival for single-ventricle physiology was 47.2% (95% CI, 34.3-59.1) and for bone marrow transplantation 22.8% (95% CI, 8.7-40.8). CONCLUSIONS: Two thirds of children with chronic critical illness survive for at-least 5 years, but there was no improvement between 2000 and 2011. Cardiac disease constitutes an increasing proportion of pediatric chronic critical illness. Bone marrow transplant recipients and single-ventricle physiology have the poorest outcomes.

Clinical Effects of Nitric Oxide Added to the Oxygenator of Children on Extracorporeal Membrane Oxygenation: Pre-Post Cohort Study.

Nitric oxide (NO) can be safely delivered through the sweep gas to the oxygenator of an extracorporeal membrane oxygenation (ECMO) circuit. It has theoretical benefits such as preventing platelet adhesion to surfaces, mitigating inflammatory response and protection against ischemia-reperfusion injury. In this uncontrolled before-after study of children on ECMO, the outcomes of those who received NO were compared with those who did not. Among 393 ECMO runs (from 337 patients), 192 of 393 (49%) received NO and 201 of 393 (51%) did not. The use of NO was associated with a 37% reduction in circuit change (adjusted risk ratio [aRR]: 0.63, 95% confidence interval [CI]: 0.42-0.93). The aRR (95% CI) for risk of neurologic injury was 0.72 (0.47-1.11). We observed potential heterogeneity of treatment effect for the risk of neurologic injury in children who had cardiac surgery: the risk with NO was lower in those who had cardiac surgery (aRR: 0.50, 95% CI: 0.26-0.96). There was no difference in survival between the study groups. In children managed with NO delivered through the ECMO circuit, we report a reduction in observed rate of circuit change and lower risk of neurologic injury in children who underwent cardiac surgery. Nitric oxide therapy on ECMO warrants prospective evaluation in children.

Potential benefits of prenatal diagnosis of TGA in Australia may be outweighed by the adverse effects of earlier delivery: likely causation and potential solutions.

OBJECTIVE: Prenatal diagnosis of transposition of great arteries (TGA) is expected to improve postoperative outcomes after neonatal arterial switch operation (ASO); however, published reports give conflicting results. We aimed to determine the association between prenatal diagnosis and early postoperative outcomes after neonatal ASO. METHODS: Cohort study involving 243 newborns who underwent ASO (70% prenatally diagnosed) between 2010 and 2019. Multivariable regression was used to determine the association between prenatal diagnosis and (a) birth characteristics and (b) postoperative outcomes. RESULTS: Gestational age and birthweight centile were lower and small-for-gestational-age more common (11.8% vs 1.4%) in those diagnosed prenatally. Among births which followed labour induction or prelabour caesarean, prenatal diagnosis was associated with earlier gestation at birth (mean (SD), 38.5 (1.6) vs 39.2 (1.4), p=0.01). Among births which followed spontaneous labour, prenatal diagnosis was associated with earlier gestation at labour onset (38.2 (1.8) vs 39.2 (1.4), p=0.01). Prenatal diagnosis was associated with longer postoperative mechanical ventilation (incidence rate ratio 1.74, 95% CI 1.37 to 2.21), intensive care (1.70, 1.31 to 2.21) and hospital length of stay (1.37, 1.14 to 1.66) after ASO. Gestational age mediated up to 60% of the effect of prenatal diagnosis on postoperative outcomes. CONCLUSION: Among newborns undergoing ASO for TGA, prenatal diagnosis is associated with poorer early postoperative outcomes. In addition to minimising iatrogenic factors (such as planned births) resulting in earlier births, evaluation of other dynamics following a prenatal diagnosis which may result in poor fetal growth and earlier onset of spontaneous labour is important.

Study protocol and statistical analysis plan for the Early Peritoneal Dialysis in Infants after Cardiac Surgery (EPICS) trial.

Background: Peritoneal dialysis (PD) is a commonly used therapy after infant cardiac surgery. It is unclear whether early PD commenced soon after admission to an intensive care unit (ICU) after cardiac surgery results in better outcomes. Objective: To describe the study protocol and statistical analysis plan for the Early Peritoneal Dialysis in Infants after Cardiac Surgery (EPICS) trial. Design, setting, participants and intervention: The EPICS trial is an open, randomised, two-group, single-centre clinical study of infants ≤ 180 days of age who had cardiac surgery (in Risk-Adjusted Classification for Congenital Heart Surgery version 1 categories 3-6) with cardiopulmonary bypass. Participants will be randomly assigned 1:1 to early PD (treatment group) or no early PD (control group). Those assigned to the treatment group will begin receiving PD soon after ICU admission and continue receiving it for 24 hours. Those in the control group will not receive PD during the first 24 hours. Main outcome measures: The primary outcome is a composite measure consisting of one or more of death, cardiac arrest, emergency chest reopening, and requirement for extracorporeal membrane oxygenation (ECMO) within 90 days. The main secondary outcomes are duration of mechanical ventilation, ICU length of stay, hospital length of stay, vasoactive-inotropic score at 24 hours, and cumulative per cent fluid balance by end of Day 2. At Day 90, events such as mortality, requirement for ECMO, cardiac arrest, chest reopening, volume of packed red blood cell transfusion, postoperative infection, readmission to ICU, renal injury and brain injury will be assessed. Conclusions: The EPICS trial aims to evaluate the role of early PD after infant cardiac surgery in lowering the rate of a composite major outcome. In addition, it will test the effect of early PD on duration of mechanical ventilation, and on ICU and hospital length of stay. Trial registration: ACTRN12617001614381.