Gabapentin as a novel adjunct for postoperative irritability after superior cavopulmonary connection operation in children.

OBJECTIVES: Describing our institution's off-label use of gabapentin to treat irritability after superior cavopulmonary connection surgery and its impact on subsequent opiate and benzodiazepine requirements. METHODS: This is a single-center retrospective cohort study including infants who underwent superior cavopulmonary connection operation between 2011 and 2019. RESULTS: Gabapentin was administered in 74 subjects (74/323, 22.9%) during the observation period, with a median (IQR) starting dose of 5.7 (3.3, 15.0) mg/kg/day and a maximum dose of 10.7 (5.5, 23.4) mg/kg/day. Infants who underwent surgery in 2015-19 were more likely to receive gabapentin compared with those who underwent surgery in 2011-14 (p < 0.0001). Infants prescribed gabapentin were younger at surgery (137 versus 146 days, p = 0.007) and had longer chest tube durations (1.8 versus 0.9 days, p < 0.001), as well as longer postoperative intensive care (5.8 versus 3.1 days, p < 0.0001) and hospital (11.5 versus 7.0 days, p < 0.0001) lengths of stays. The year of surgery was the only predisposing factor associated with gabapentin administration in multivariate analysis. In adjusted linear regression, infants prescribed gabapentin on postoperative day 0-4 (n = 64) had reduced benzodiazepine exposure in the following 3 days (-0.29 mg/kg, 95% CI -0.52 - -0.06, p = 0.01) compared with those not prescribed gabapentin, while no difference was seen in opioid exposure (p = 0.59). CONCLUSIONS: Gabapentin was used with increasing frequency during the study period. There was a modest reduction in benzodiazepine requirements associated with gabapentin administration and no reduction in opioid requirements. A randomised controlled trial could better assess gabapentin's benefits postoperatively in children with congenital heart disease.

Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience.

OBJECTIVES: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.

Conjugated hyperbilirubinemia is associated with increased morbidity and mortality after neonatal heart surgery.

BACKGROUND: Cholestasis characterised by conjugated hyperbilirubinemia is a marker of hepatobiliary dysfunction following neonatal cardiac surgery. We aimed to characterise the incidence of conjugated hyperbilirubinemia following neonatal heart surgery and examine the effect of conjugated hyperbilirubinemia on post-operative morbidity and mortality. METHODS: This was a retrospective study of all neonates who underwent surgery for congenital heart disease (CHD) at our institution between 1/1/2010 and 12/31/2020. Patient- and surgery-specific data were abstracted from local registry data and review of the medical record. Conjugated hyperbilirubinemia was defined as perioperative maximum conjugated bilirubin level > 1 mg/dL. The primary outcome was in-hospital mortality. Survival analysis was conducted using the Kaplan-Meier survival function. RESULTS: Conjugated hyperbilirubinemia occurred in 8.5% of patients during the study period. Neonates with conjugated hyperbilirubinemia were more likely to be of younger gestational age, lower birth weight, and non-Caucasian race (all p < 0.001). Patients with conjugated hyperbilirubinemia were more likely to have chromosomal and non-cardiac anomalies and require ECMO pre-operatively. In-hospital mortality among patients with conjugated hyperbilirubinemia was increased compared to those without (odds ratio 5.4). Post-operative complications including mechanical circulatory support, reoperation, prolonged ventilator dependence, and multi-system organ failure were more common with conjugated hyperbilirubinemia (all p < 0.04). Patients with higher levels of conjugated bilirubin had worst intermediate-term survival, with patients in the highest conjugated bilirubin group (>10 mg/dL) having a 1-year survival of only 6%. CONCLUSIONS: Conjugated hyperbilirubinemia is associated with post-operative complications and worse survival following neonatal heart surgery. Cholestasis is more common in patients with chromosomal abnormalities and non-cardiac anomalies, but the underlying mechanisms have not been delineated.

Impact of Ventricular Dysfunction and Atrioventricular Valve Regurgitation on Pre-Fontan Attrition.

BACKGROUND: There is a significant incidence of pre-Fontan attrition-defined as failure to undergo Fontan completion-after superior cavopulmonary connection. This study investigated the impact of at least moderate ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) on pre-Fontan attrition. METHODS: This single-center retrospective cohort study included all infants who underwent Norwood palliation from 2008 to 2020 and subsequently underwent superior cavopulmonary connection. Pre-Fontan attrition was defined as death, listing for heart transplantation before Fontan completion, or unsuitability for Fontan completion. The study's secondary outcome was transplant-free survival. RESULTS: Pre-Fontan attrition occurred in 34 of 267 patients (12.7%). Isolated VD was not associated with attrition. However, patients with isolated AVVR had 5 times the odds of attrition (odds ratio, 5.4; 95% CI 1.8-16.2), and patients with both VD and AVVR had 20 times the odds of attrition (odds ratio, 20.1; 95% CI 7.7-52.8) compared with patients without VD or AVVR. Only patients with both VD and AVVR had significantly worse transplant-free survival compared with patients without VD or AVVR (hazard ratio, 7.7; 95% CI 2.8-21.6). CONCLUSIONS: The additive effect of VD and AVVR is a powerful contributor to pre-Fontan attrition. Future research investigating therapies that can mitigate the degree of AVVR may help improve Fontan completion rates and long-term outcomes.

Characterization of "ICU-30": A Binary Composite Outcome for Neonates With Critical Congenital Heart Disease.

Background Neonates with heart disease requiring cardiopulmonary bypass surgery are at high risk for mortality and morbidity. As it is rare, short-term mortality is difficult to use as a primary outcome for clinical studies. We proposed "ICU-30" as a binary composite "poor" outcome consisting of: (1) mortality within 30 days, (2) intensive care unit (ICU) admission ≥30 days, or (3) ICU readmission before day 30. To measure the utility of this composite, we assessed its prognostic properties for 6- and 12-month mortality. Methods and Results This was a retrospective single-center cohort study of neonates requiring cardiopulmonary bypass between 2013 and 2020. Mortality among patients with and without the ICU-30 outcome was compared using log-rank tests and Cox regression. Areas under the receiver operating characteristic curves assessed the ability of the composite to predict 12-month mortality. In 887 neonates, 232 (26.2%) experienced the ICU-30 outcome, with more prolonged ICU stays and readmissions (both ≥9%) than 30-day mortality (4.2%). ICU-30 was associated with higher rates of 6- and 12-month mortality (log-rank P<0.001) and predicted 12-month mortality with area under the receiver operating characteristic of 0.81 (95% CI, 0.77-0.85). In 30-day survivors, both prolonged ICU stay (hazard ratio, 12.3; 95% CI, 6.70-22.7; P<0.001) and ICU readmission (hazard ratio, 2.99; 95% CI, 1.17-7.63; P=0.02) were associated with 12-month mortality. Conclusions ICU-30, a composite outcome of mortality, ICU length of stay, or ICU readmission by 30 days was associated with 6- and 12-month mortality in neonates requiring cardiopulmonary bypass. ICU-30 is captured in routine data collection and appears to be a valid binary patient-centered outcome.

Association of a Home Monitoring Program With Interstage and Stage 2 Outcomes.

Background In shunt-dependent, single-ventricle patients, mortality remains high in the interstage period between discharge after neonatal surgery and stage 2 operation. We sought to evaluate the impact of our infant single-ventricle management and monitoring program ( ISVMP ) on interstage mortality and stage 2 outcomes. Methods and Results This retrospective single-center cohort study compared patients enrolled in ISVMP at hospital discharge with historical controls. The relationship of ISVMP to interstage mortality was determined with a bivariate probit model for the joint modeling of both groups, using an instrumental variables approach. We included 166 ISVMP participants (December 1, 2010, to June 30, 2015) and 168 controls (January 1, 2007, to November 30, 2010). The groups did not differ by anatomy, gender, race, or genetic syndrome. Mortality was lower in the ISVMP group (5.4%) versus controls (13%). An ISVMP infant compared with a historical control had an average 29% lower predicted probability of interstage death (adjusted probability: -0.29; 95% CI , -0.52 to -0.057; P=0.015). On stratified analysis, mortality was lower in the hypoplastic left heart syndrome subgroup undergoing Norwood operation (4/84 [4.8%] versus 12/90 [14%], P=0.03) but not in those with initial palliation of shunt only ( P=0.90). ISVMP participants were younger at the time of the stage 2 operation (138 versus 160 days, P<0.001), with no difference in postoperative mortality or length of stay. Conclusions In this single-center study, we report significantly lower interstage mortality for participants with hypoplastic left heart syndrome enrolled in ISVMP . Younger age at stage 2 operation was not associated with postoperative mortality or longer length of stay.