Aparna Hoskote

Delayed diagnosis of congenital heart disease worsens preoperative condition and outcome of surgery in neonates

Objectives: To assess whether the route by which neonatal congenital heart disease (CHD) is first recognised influences outcome after surgery. Methods: Surgical neonates admitted to a tertiary cardiac unit between March 1999 and February 2002 were retrospectively reviewed with analysis of risk factors for outcome. Three routes to initial recognition of CHD were compared: antenatal diagnosis, detection on the postnatal ward, and presentation after discharge to home. Outcome measures were mortality and duration of perioperative ventilation. Results: 286 neonates had cardiac surgery with a median duration of ventilation of 101 h and in-hospital mortality of 12%. Recognition of CHD was antenatal in 20%, on the postnatal ward in 55% and after discharge to home in 25%. Multiple regression analyses, including the cardiac diagnosis, associated problems and other risk factors, indicated that severe cardiovascular compromise on admission to the cardiac unit was significantly related to mortality and prolonged ventilation. Considered in isolation, the route to recognition of heart disease did not influence mortality or ventilation time. Route to initial recognition did, however, influence the patient’s condition on admission to the cardiac unit. Cardiovascular compromise and end organ dysfunction were least likely when recognition was antenatal and most common when presentation followed discharge to home. Conclusion: The setting in which neonatal CHD is first recognised has an impact on preoperative condition, which in turn influences postoperative progress and survival after surgery. Optimal screening procedures and access to specialist care will improve outcome for neonates undergoing cardiac surgery.

Acute right ventricular failure after pediatric cardiac transplant: predictors and long-term outcome in current era of transplantation medicine.

OBJECTIVES To identify pretransplant factors associated with postprocedural right ventricular failure and the relationship between right ventricular failure and long-term survival in children. METHODS Records were reviewed for children having heart transplantation from 2000 to 2006. RESULTS Right ventricular failure was identified by clinical and echocardiographic parameters in 33/129 (25%) recipients: dilated cardiomyopathy in 14/90 (15%), congenital heart disease in 11/27 (41%), and restrictive cardiomyopathy in 8/12 (66%). In 9 of 12 (75%), known elevated (reactive) pulmonary vascular resistance progressed to right ventricular failure. In a further 23/117 (20%) recipients, pulmonary vascular resistance within predefined acceptable range progressed to right ventricular failure. Multiple logistic regression analyses indicated elevated pulmonary vascular resistance (odds ratio 12.30; 95% confidence interval 2.73, 55.32; P = .001) and primary diagnosis, restrictive cardiomyopathy (odds ratio 9.21; 95% confidence interval 2.07, 41.12; P = .004), and congenital heart disease (odds ratio 4.07; 95% confidence interval 1.36, 12.19; P = .012) were strongly associated with right ventricular failure, but duration of heart failure, pretransplant mechanical support, donor status, and ischemic times were not. Treatment included inhaled nitric oxide in 28 (84%), mechanical support in 10 (31%), hemofiltration in 13 (40%), and retransplantation in 2. A Cox multiple regression model including: primary diagnosis, right ventricular failure, and elevated pulmonary vascular resistance indicated that only the latter was independently linked with eventual mortality (hazards ratio 5.45; 95% confidence interval 1.36, 21.96; P = .017). CONCLUSIONS Primary diagnosis and pretransplant elevated reactive pulmonary vascular resistance are both linked to the evolution of right ventricular failure. Pulmonary vascular resistance assessment in end-stage heart failure is challenging; therefore, avoidance of right ventricular failure may not always be possible. Aggressive early treatment may mitigate the effects of right ventricular failure: pretransplant elevated pulmonary vascular resistance was independently associated with long-term survival, but right ventricular failure was not.

Neonatal Hypoxia, Hippocampal Atrophy, and Memory Impairment: Evidence of a Causal Sequence

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohorts HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.

Multichannel near infrared spectroscopy indicates regional variations in cerebral autoregulation in infants supported on extracorporeal membrane oxygenation.

Assessing noninvasively cerebral autoregulation, the protective mechanism of the brain to maintain constant cerebral blood flow despite changes in blood pressure, is challenging. Infants on life support system (ECMO) for cardiorespiratory failure are at risk of cerebral autoregulation impairment and consequent neurological problems. We measured oxyhaemoglobin concentration (HbO(2)) by multichannel (12 channels) near-infrared spectroscopy (NIRS) in six infants during sequential changes in ECMO flow. Wavelet cross-correlation (WCC) between mean arterial pressure (MAP) and HbO(2) was used to construct a time-frequency representation of the concordance between the two signals to assess the nonstationary aspect of cerebral autoregulation and investigate regional variations. Group data showed that WCC increases with decreasing ECMO flow indicating higher concordance between MAP and HbO(2) and demonstrating loss of cerebral autoregulation at low ECMO flows. Statistically significant differences in WCC were observed between channels placed on the right and left scalp with channels on the right exhibiting higher values of WCC suggesting that the right hemisphere was more susceptible to disruption of cerebral autoregulation. Multichannel NIRS in conjunction with wavelet analysis methods can be used to assess regional variations in dynamic cerebral autoregulation with important clinical application in the management of critically ill children on life support systems.

Mechanical bridging to orthotopic heart transplantation in children weighing less than 10 kg: feasibility and limitations

OBJECTIVE Infants and young children are considered the most difficult group to bridge to orthotopic heart transplantation (OHT) and data regarding outcomes are scarce. METHODS We reviewed our patients ≤ 10 kg with those who were bridged to OHT using ventricular assist device (VAD) Berlin Heart (BH) Excor ± extracorporeal membrane oxygenation (ECMO) between 2004 and 2009. RESULTS Eleven children ≤ 10 kg with end-stage heart failure (cardiomyopathy or myocarditis) were treated with VAD as bridge to OHT: the median weight was 8.0 (range 3.9-10.0 kg)kg and median age was 12.3 (range 1.2-33.9 months) months. Five (45%) required ECMO support pre-BH and six were on mechanical ventilation and inotropes. In 9/11 (82%), the support mode was left ventricular assist device (L-VAD) (all alive): one of two patients needing Bi-VAD support died. On BH, the median support time was 27 days and time to extubation was 8 days. Two out of 11 (18%) suffered strokes confirmed on brain imaging; both recovered and one underwent resection of infarcted small bowel. Ten out of 11 (91%) were transplanted, one remains in hospital and nine are at home in good health. When compared to patients >10 kg bridged with BH (n = 15), the mortality (p = 0.51) and rates of neurological complications (p = 0.54) were similar. Post-transplant recovery (ventilation times and time to home discharge) was similar between the bridged children ≤ 10 kg and non-bridged children ≤ 10 kg who underwent OHT. CONCLUSIONS Mechanical bridging to transplantation is clinically feasible in children ≤ 10 kg, achieving excellent outcomes. Judicious use of VADs in smaller children will optimise the use of donor organs; however, the effect on overall OHT waiting times, if mechanical bridging was extended to a large number of small children, is unknown.

Outcome in neonates with congenital heart disease referred for respiratory extracorporeal membrane oxygenation

Aim: To evaluate the proportion of neonates referred for extracorporeal membrane oxygenation (ECMO) support in the modern era of advanced conventional treatments for respiratory failure who actually had congenital heart disease (CHD), and to assess the impact of this diagnostic route on patient condition and outcome. Methods: A retrospective case‐note review of neonatal ECMO and cardiac admissions to a single, tertiary ECMO and cardiac intensive care unit (ICU) between March 1999 and February 2002. Results: 287 symptomatic neonates presented to the ICU with previously undiagnosed cardiac or respiratory disease. Eighty‐two with presumed respiratory failure were referred for ECMO, and 205 with suspected CHD were referred for cardiac evaluation. Eight (10%) ECMO referrals, all with presumed persistent pulmonary hypertension of the newborn (PPHN), were found to have CHD (transposition: 3; total anomalous pulmonary venous connection: 3; left heart obstructive lesions: 2). Mortality in this group was 50%, compared with 11% for correctly identified CHD patients (odds ratio 8.2, 95% CI 1.92, 35.4, p<0.01). For all neonates with CHD, the risk of death was increased by the presence of cardiovascular collapse and end‐organ dysfunction at presentation to the ICU (p<0.01 for both).

Role of immunoglobulin supplementation for secondary immunodeficiency associated with chylothorax after pediatric cardiothoracic surgery.

Objective: To evaluate whether intravenous immunoglobulin was linked to a reduction in sepsis in patients with prolonged chylothoraces postpediatric cardiothoracic surgery. Design: Retrospective observational cohort study. Setting: Tertiary pediatric cardiac surgical center. Patients: Children with chylothoraces postcardiothoracic surgery from 1998 to 2006 divided into two groups: with and without intravenous immunoglobulin supplementation. Intervention: Intravenous immunoglobulin supplementation. Measurements and Main Results: Thirty-seven with chylothoraces (median duration 14 days; interquartile range, 10–32 and median maximum chyle drainage 1.9 mL/kg/hr; interquartile range, 1–3) were included, and 16 (43%) received intravenous immunoglobulin. The degree of lymphopenia was worse with longer duration of chylothorax (p = .005). There was a trend toward immunoglobulin depletion—IgG (p = .07) and IgM (p = .07) with higher volume chyle loss. Twenty-two of 37 (59%) developed bloodstream infection and 24 of 37 (65%) developed sepsis related to other organ systems. The rate of bloodstream infection and of sepsis in other organ systems was high at 25 (95% confidence interval 17–39) and 23 (95% confidence interval 15–34) episodes per 1,000 intensive care unit days, respectively. Intravenous immunoglobulin was not related to the bloodstream infection rate: adjusted hazard ratio 0.88 (95% confidence interval 0.20–3.94; p = .87) or rate of sepsis in other organ systems: hazard ratio 2.31 (95% confidence interval 0.21–24.29; p = .49) or the proportion surviving to hospital discharge (p = .37). Conclusion: Patients with prolonged, large-volume chyle loss had greater secondary immunodeficiency. Although the sample size was small and therefore able to detect only a large treatment effect from intravenous immunoglobulin, infectious outcomes were equal between the two groups.

Total donor ischemic time: Relationship to early hemodynamics and intensive care morbidity in pediatric cardiac transplant recipients*

Objective: Single-center studies have failed to link modest increases in total donor ischemic time to mortality after pediatric orthotopic heart transplant. We aimed to investigate whether prolonged total donor ischemic time is linked to pediatric intensive care morbidity after orthotopic heart transplant. Design: Retrospective cohort review. Setting: Tertiary pediatric transplant center in the United Kingdom. Patients: Ninety-three pediatric orthotopic heart transplants between 2002 and 2006. Methods: Total donor ischemic time was investigated for association with early post-orthotopic heart transplant hemodynamics and intensive care unit morbidities. Results: Of 43 males and 50 females with median age 7.2 (interquartile range 2.2, 13.0) yrs, 62 (68%) had dilated cardiomyopathy, 20 (22%) had congenital heart disease, and nine (10%) had restrictive cardiomyopathy. The mean total donor ischemic time was 225.9 (sd 65.6) mins. In the first 24 hrs after orthotopic heart transplant, age-adjusted mean arterial blood pressure increased (p < .001), mean pulmonary arterial pressure fell (p = .012), but central venous pressure (p = .58) and left atrial pressure (p = .20) were unchanged. After adjustment for age, primary diagnosis, pre-orthotopic heart transplant mechanical support, and marginal donor factors, longer total donor ischemic time was significantly associated with lower mean arterial blood pressure (p < .001) in the first 24 hrs after orthotopic heart transplant, longer post-orthotopic heart transplant mechanical ventilation (p = .03), longer post-orthotopic heart transplant stay in the intensive care unit (p = .004), and longer post-orthotopic heart transplant stay in hospital (p = .02). Total donor ischemic time was not related to levels of mean pulmonary arterial pressure (p = .62), left atrial pressure (p = .38), or central venous pressure (p = .76) early after orthotopic heart transplant. Conclusions: Prolonged total donor ischemic time has an adverse effect on the donor organ, contributing to lower mean arterial blood pressure, as well as more prolonged ventilation and intensive care unit and hospital stays post-orthotopic heart transplant, reflecting increased morbidity.

Cerebral and Peripheral Tissue Oxygenation in Children Supported on ECMO for Cardio-Respiratory Failure

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with cardio-respiratory failure. Establishing, maintaining and weaning from ECMO may increase the risk for intracranial injury. We used a dual channel near infrared system to monitor cerebral and peripheral tissue oxygenation in 3 venoarterial (VA) and 1 venovenous (VV) ECMO patients undergoing manipulations in the ECMO circuit flows. Spectral analysis was performed on the oxyhaemoglobin data collected from these patients with the aim of comparing oscillations at range of frequencies appearing in the two measurement sites.

Airway Function in Infants Treated With Inhaled Nitric Oxide for Persistent Pulmonary Hypertension

Inhaled nitric oxide (iNO), used for treatment of persistent pulmonary hypertension of newborn (PPHN), is an oxygen free radical with potential for lung injury. Deferring ECMO with iNO in these neonates could potentially have long‐term detrimental effects on lung function. We studied respiratory morbidity (defined as occurrence of respiratory infections requiring treatment, episodes of wheezing, and/or need for ongoing medications following discharge) and airway function at 1 year postnatal age in term neonates treated with iNO but not ECMO for PPHN, and compared data from similar infants recruited to the UK ECMO Trial randomized to receive ECMO or conventional management (CM).