Effect of Standing Intravenous Acetaminophen on Postoperative Opioid Exposure in a Pediatric Cardiac Intensive Care Unit.

This study assessed the association between standing intravenous acetaminophen and opioid exposure after cardiac surgery. Before vs after implementation of a standardized pain pathway, we report decreased opioid exposure, 0.38 milligram per kilogram of morphine equivalents [IQR 0.10-0.81] vs 0.26 milligram per kilogram of morphine equivalents [0.09-0.56] (P = .01) and increased acetaminophen exposure, 3 [2-4] vs 4 [4-5] doses (P < .001).

Long-Term Increases in Mental Disorder Diagnoses After Invasive Mechanical Ventilation for Severe Childhood Respiratory Disease: A Propensity Matched Observational Cohort Study.

OBJECTIVES: To evaluate neurodevelopmental and mental disorders after PICU hospitalization in children requiring invasive mechanical ventilation for severe respiratory illness. DESIGN: Retrospective longitudinal observational cohort. SETTING: Texas Medicaid Analytic eXtract data from 1999 to 2012. PATIENTS: Texas Medicaid-enrolled children greater than or equal to 28 days old to less than 18 years old hospitalized for a primary respiratory illness, without major chronic conditions predictive of abnormal neurodevelopment. INTERVENTIONS: We examined rates of International Classification of Diseases, 9th revision-coded mental disorder diagnoses and psychotropic medication use following discharge among children requiring invasive mechanical ventilation for severe respiratory illness, compared with general hospital patients propensity score matched on sociodemographic and clinical characteristics prior to admission. Children admitted to the PICU for respiratory illness not necessitating invasive mechanical ventilation were also compared with matched general hospital patients as a negative control exposure. MEASUREMENTS AND MAIN RESULTS: Of 115,335 eligible children, 1,351 required invasive mechanical ventilation and were matched to 6,755 general hospital patients. Compared with general hospital patients, children requiring invasive mechanical ventilation had increased mental disorder diagnoses (hazard ratio, 1.43 [95% CI, 1.26-1.64]; p < 0.0001) and psychotropic medication use (hazard ratio, 1.67 [1.34-2.08]; p < 0.0001) following discharge. Seven-thousand seven-hundred eighty children admitted to the PICU without invasive mechanical ventilation were matched to 38,900 general hospital patients and had increased mental disorder diagnoses (hazard ratio, 1.08 [1.02-1.15]; p = 0.01) and psychotropic medication use (hazard ratio, 1.11 [1.00-1.22]; p = 0.049). CONCLUSIONS: Children without major comorbidity requiring invasive mechanical ventilation for severe respiratory illness had a 43% higher incidence of subsequent mental disorder diagnoses and a 67% higher incidence of psychotropic medication use. Both increases were substantially higher than in PICU patients with respiratory illness not necessitating invasive mechanical ventilation. Invasive mechanical ventilation is a life-saving therapy, and its application is interwoven with underlying health, illness severity, and PICU management decisions. Further research is required to determine which factors related to invasive mechanical ventilation and severe respiratory illness are associated with abnormal neurodevelopment. Given the increased risk in these children, identification of strategies for prevention, neurodevelopmental surveillance, and intervention after discharge may be warranted.

Multicenter Analysis of Truncal Valve Management and Outcomes in Children with Truncus Arteriosus.

Truncal valve management in patients with truncus arteriosus is a clinical challenge, and indications for truncal valve intervention have not been defined. We sought to evaluate truncal valve dysfunction and primary valve intervention in patients with truncus arteriosus and determine risk factors for later truncal valve intervention. We conducted a retrospective cohort study of children who underwent truncus arteriosus repair at 15 centers between 2009 and 2016. Multivariable competing risk analysis was performed to determine risk factors for later truncal valve intervention. We reviewed 252 patients. Forty-two patients (17%) underwent truncal valve intervention during their initial surgery. Postoperative extracorporeal support, CPR, and operative mortality for patients who underwent truncal valve interventions were statistically similar to the rest of the cohort. Truncal valve interventions were performed in 5 of 64 patients with mild insufficiency; 5 of 16 patients with mild-to-moderate insufficiency; 17 of 35 patients with moderate insufficiency; 5 of 9 patients with moderate-to-severe insufficiency; and all 10 patients with severe insufficiency. Twenty patients (8%) underwent later truncal valve intervention, five of whom had no truncal valve intervention during initial surgical repair. Multivariable analysis revealed truncal valve intervention during initial repair (HR 11.5; 95% CI 2.5, 53.2) and moderate or greater truncal insufficiency prior to initial repair (HR 4.0; 95% CI 1.1, 14.5) to be independently associated with later truncal valve intervention. In conclusion, in a multicenter cohort of children with truncus arteriosus, 17% had truncal valve intervention during initial surgical repair. For patients in whom variable truncal valve insufficiency is present and primary intervention was not performed, late interventions were uncommon. Conservative surgical approach to truncal valve management may be justifiable.

Nitric oxide-associated pulmonary edema in children with pulmonary venous hypertension.

Nitric oxide (NO)-associated pulmonary edema is rarely reported in children; in adults, it is often associated with left-sided heart failure. We report a case series of children with NO-associated pulmonary edema, which was defined as new multilobar alveolar infiltrates and worsening hypoxemia within 24 h of initiation or escalation of NO and radiologic or clinical improvement after NO discontinuation. We identified six patients (0.4-4 years old) with ten episodes of NO-associated pulmonary edema. Diagnoses included atrioventricular canal defect with mitral valve disease (n = 2), pulmonary atresia and major aorta-pulmonary collateral arteries (n = 2), total anomalous pulmonary venous return (n = 1), and pulmonary veno-occlusive disease (n = 1). All patients had evidence of pulmonary venous hypertension, and two had mitral valve disease resulting in clinical evidence of left-sided heart failure. Pulmonary edema improved or resolved within 24 h of discontinuing NO. At cardiac catheterization, mean left atrial pressure was <15 mmHg in three of three patients (none with mitral valve disease), whereas pulmonary artery occlusion pressure was >15 mmHg in two of five patients. In conclusion, we describe six young children with NO-associated pulmonary edema and pulmonary venous hypertension. Only two of these children had left-sided heart failure: Left atrial pressure as well as pulmonary artery occlusion pressure may not be helpful in identifying children at risk for NO-associated pulmonary edema.

Contemporary Multicenter Outcomes for Truncus Arteriosus With Interrupted Aortic Arch.

BACKGROUND: Truncus arteriosus with interrupted aortic arch (TA-IAA) is a rare congenital heart defect with historically poor outcomes. Contemporary multicenter data are limited. METHODS: A retrospective cohort study of children who underwent repair of TA-IAA between 2009 and 2016 at 12 tertiary care referral centers within the United States was performed. Major adverse cardiac events (MACE) were defined as postoperative extracorporeal membrane oxygenation, cardiopulmonary resuscitation, or operative mortality. TA-IAA patients were compared with TA patients who underwent repair during the study period from the same institutions. RESULTS: We reviewed 35 patients with TA-IAA. MACE occurred in 12 patients (34%). Improvement over time was observed during the study period with 11 events (92%) occurring in the first half of the study period (P = .03). Factors associated with MACE included moderate or severe truncal valve insufficiency (P < .01), concomitant truncal valve repair (P = .04), and longer cardiopulmonary bypass duration (P = .02). In comparison with 216 patients who underwent TA repair, patients with TA-IAA had a higher rate of MACE, but this finding was not statistically significant (34% vs 20%, respectively; P = .07). Additionally no differences between TA-IAA and TA groups were observed for unplanned reoperations (14% vs 22%, respectively; P = .3), hospital length of stay (24 vs 23 days, P = .65), or late deaths (7% vs 7%, P = 1.00). CONCLUSIONS: In this contemporary, multicenter cohort the rate of MACE after repair of TA-IAA was high but improved during the study period. Early childhood outcomes of patients with TA-IAA were similar to those with TA.

Early Thromboprophylaxis Initiation is Associated With Reduced Fontan Thromboses in the Early Postoperative Period.

Fontan circuit thrombosis is a significant cause of early postoperative morbidity and mortality. Thrombosis incidence and relationship to thromboprophylaxis choice and timing of initiation are not well established. We sought to evaluate the incidence of Fontan circuit thrombosis in the first 30 postoperative days and its relationship to thromboprophylaxis choice and timing. Patients undergoing Fontan surgery, 2006-2016, were reviewed. Fontan circuit thrombosis was defined by sonographic detection of intracardiac or deep venous thrombi. Logistic regression was used to assess relationships between thromboprophylaxis characteristics and thrombosis. One hundred ninety-two patients underwent Fontan. Fontan thrombosis occurred in 19 (10%) patients. 54% were started on aspirin, 27% coumadin, 4% heparin, and 7% none. There was no relationship between thrombosis and baseline anatomy, Fontan type or fenestration. Median time to thromboprophylaxis initiation was 4 days (interquartile range 2-6). Patients not started on thromboprophylaxis had 44.8 times the odds of thrombosis as those on thromboprophylaxis (confidence interval 6.4-311.7, P < 0.01); no children starting thromboprophylaxis before postoperative day 2 developed thromboses. For every day that thromboprophylaxis was delayed, odds of thrombosis increased by 30% (odds ratio 1.3; CI 1.1-1.6, P < 0.01). There was no difference in the odds of thrombosis between children taking aspirin vs other thromboprophylaxis types. Odds of early postoperative Fontan circuit thrombosis are increased in patients in whom thromboprophylaxis is delayed beyond the second postoperative day, with no difference in the odds of thrombosis between patients initiated on aspirin vs other thromboprophylaxis. Early aspirin institution post Fontan is recommended to reduce morbidity. Ultra-mini-Abstract: Odds of early postoperative Fontan circuit thrombosis are increased in patients in whom thromboprophylaxis is delayed beyond the second postoperative day, with no difference in the odds of thrombosis between patients initiated on aspirin vs other thromboprophylaxis. Early aspirin institution post Fontan is recommended to reduce morbidity and resource utilization.

Multicenter Analysis of Early Childhood Outcomes After Repair of Truncus Arteriosus.

BACKGROUND: Literature describing morbidity and mortality after truncus arteriosus repair is predominated by single-center reports. We created and analyzed a multicenter dataset to identify risk factors for late mortality and right ventricle-to-pulmonary artery (RV-PA) conduit reintervention for this patient population. METHODS: We retrospectively collected data on children who underwent repair of truncus arteriosus without concomitant arch obstruction at 15 centers between 2009 and 2016. Cox regression survival analysis was conducted to determine risk factors for late mortality, defined as death occurring after hospital discharge and greater than 30 days after operation. Probability of any RV-PA conduit reintervention was analyzed over time using Fine-Gray modeling. RESULTS: We reviewed 216 patients with median follow-up of 2.9 years (range, 0.1 to 8.8). Operative mortality occurred in 15 patients (7%). Of the 201 survivors there were 14 (7%) late deaths. DiGeorge syndrome (hazard ratio [HR], 5.4; 95% confidence interval [CI], 1.6 to 17.8) and need for postoperative tracheostomy (HR, 5.9; 95% CI, 1.8 to 19.4) were identified as independent risk factors for late mortality. At least one RV-PA conduit catheterization or surgical reintervention was performed in 109 patients (median time to reintervention, 23 months; range, 0.3 to 93). Risk factors for reintervention included use of pulmonary or aortic homografts versus Contegra (Medtronic, Inc, Minneapolis, MN) bovine jugular vein conduits (HR, 1.9; 95% CI, 1.2 to 3.1) and smaller conduit size (HR per mm/m2, 1.05; 95% CI, 1.03 to 1.08). CONCLUSIONS: In a multicenter dataset DiGeorge syndrome and need for tracheostomy postoperatively were found to be independent risk factors for late mortality after repair of truncus arteriosus, whereas risk of conduit reintervention was independently influenced by both initial conduit type and size.

Characteristics and operative outcomes for children undergoing repair of truncus arteriosus: A contemporary multicenter analysis.

OBJECTIVE: We sought to describe characteristics and operative outcomes of children who underwent repair of truncus arteriosus and identify risk factors for the occurrence of major adverse cardiac events (MACE) in the immediate postoperative period in a contemporary multicenter cohort. METHODS: We conducted a retrospective review of children who underwent repair of truncus arteriosus between 2009 and 2016 at 15 centers within the United States. Patients with associated interrupted or obstructed aortic arch were excluded. MACE was defined as the need for postoperative extracorporeal membrane oxygenation, cardiopulmonary resuscitation, or operative mortality. Risk factors for MACE were identified using multivariable logistic regression analysis and reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We reviewed 216 patients. MACE occurred in 44 patients (20%) and did not vary significantly over time. Twenty-two patients (10%) received postoperative extracorporeal membrane oxygenation, 26 (12%) received cardiopulmonary resuscitation, and 15 (7%) suffered operative mortality. With multivariable logistic regression analysis (which included adjustment for center effect), factors independently associated with MACE were failure to diagnose truncus arteriosus before discharge from the nursery (OR, 3.1; 95% CI, 1.3-7.4), cardiopulmonary bypass duration >150 minutes (OR, 3.5; 95% CI, 1.5-8.5), and right ventricle-to-pulmonary artery conduit diameter >50 mm/m2 (OR, 4.7; 95% CI, 2.0-11.1). CONCLUSIONS: In a contemporary multicenter analysis, 20% of children who underwent repair of truncus arteriosus experienced MACE. Early diagnosis, shorter duration of cardiopulmonary bypass, and use of smaller diameter right ventricle-to-pulmonary artery conduits represent potentially modifiable factors that could decrease morbidity and mortality in this fragile patient population.

Utilization of inhaled nitric oxide after surgical repair of truncus arteriosus: A multicenter analysis.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is common following repair of truncus arteriosus. Inhaled nitric oxide (iNO) is an effective yet costly therapy that is frequently implemented postoperatively to manage elevated PVR. OBJECTIVES: We aimed to describe practice patterns of iNO use in a multicenter cohort of patients who underwent repair of truncus arteriosus, a lesion in which recovery is often complicated by elevated PVR. We also sought to identify patient and center factors that were more commonly associated with the use of iNO in the postoperative period. DESIGN: Retrospective cohort study. SETTING: 15 tertiary care pediatric referral centers. PATIENTS: All infants who underwent definitive repair of truncus arteriosus without aortic arch obstruction between 2009 and 2016. INTERVENTIONS: Descriptive statistics were used to demonstrate practice patterns of iNO use. Bivariate comparisons of characteristics of patients who did and did not receive iNO were performed, followed by multivariable mixed logistic regression analysis using backward elimination to identify independent predictors of iNO use. MAIN RESULTS: We reviewed 216 patients who met inclusion criteria, of which 102 (46%) received iNO in the postoperative period: 69 (68%) had iNO started in the operating room and 33 (32%) had iNO initiated in the ICU. Median duration of iNO use was 4 days (range: 1-21 days). In multivariable mixed logistic regression analysis, use of deep hypothermic circulatory arrest (odds ratio: 3.2; 95% confidence interval: 1.2, 8.4) and center (analyzed as a random effect, p = .02) were independently associated with iNO use. CONCLUSIONS: In this contemporary multicenter study, nearly half of patients who underwent repair of truncus arteriosus received iNO postoperatively. Use of iNO was more dependent on individual center practice rather than patient characteristics. The study suggests a need for collaborative quality initiatives to determine optimal criteria for utilization of this important but expensive therapy.

Pentobarbital withdrawal and treatment in an infant in the pediatric cardiac intensive care unit.

Withdrawal syndromes following administration of sedative and analgesic infusions represent a significant morbidity that is described increasingly in the pediatric critical care literature. However, there are few descriptions of pentobarbital withdrawal symptoms and their treatment in the pediatric population. We describe an infant receiving multiple sedative and analgesic medications, including pentobarbital, who was resistant to our institution's standard weaning protocol, but whose severe withdrawal symptoms responded dramatically to phenobarbital loading and maintenance.

Heart transplantation in children with markedly elevated pulmonary vascular resistance: impact of right ventricular failure on outcome.

BACKGROUND: Pulmonary hypertension causes increased morbidity and mortality in adults after heart transplantation. The effect of markedly elevated pulmonary vascular resistance (PVR) on post-transplant outcomes in children has not been well described. METHODS: Outcomes were compared in a retrospective study between 58 children with an elevated PVR index (PVRI) ≥ 6 U/m(2) and 205 children with a PVRI < 6 U/m(2). Patients who did and did not respond to acute vasodilator testing and patients who underwent transplant before (pre-1995) and after (post-1995) the availability of inhaled nitric oxide (iNO) were compared. RESULTS: The pre-transplant diagnoses, and cardiopulmonary bypass and donor ischemic times were similar between the high and low PVRI groups. High PVRI patients were older at transplant (12 ± 6.2 vs 8 ± 7.1 years, p = 0.002). The post-transplant inotrope score was higher in the high PVRI group (12 ± 12 vs 2 ± 2, p = 0.0001) and 1-year survival was worse (76% vs 81%, p = 0.03). The PVRI fell to < 6 U/m(2) with acute vasodilator testing in 21 of 49 (42%) high PVRI patients. RV failure occurred in 4 (19%) of the responders and in 14 (50%) of the non-responders (p = 0.037). One responder (5%) and 4 non-responders (14%) died of RV failure. In the period after 1995, the year iNO became clinically available, the select group of high PVRI patients who received iNO preemptively had a lower incidence of post-transplant RV failure than the group that did not receive preemptive iNO (13% vs 54%, p = 0.04). CONCLUSIONS: Pre-transplant vasodilator testing identified patients at higher risk for RV failure. Patients who did not respond to vasodilator testing had an increased incidence of RV failure and death from RV failure. Preemptive use of iNO was associated with a decreased incidence of RV failure.