Aparna Hoskote - Academia.edu (original) (raw)

Papers by Aparna Hoskote

Hippocampus, 2017

Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. ... more Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2...

Cardiology in the young, Jan 29, 2016

Morbidity is defined as a state of being unhealthy or of experiencing an aspect of health that is... more Morbidity is defined as a state of being unhealthy or of experiencing an aspect of health that is "generally bad for you", and postoperative morbidity linked to paediatric cardiac surgery encompasses a range of conditions that may impact the patient and are potential targets for quality assurance. As part of a wider study, a multi-disciplinary group of professionals aimed to define a list of morbidities linked to paediatric cardiac surgery that was prioritised by a panel reflecting the views of both professionals from a range of disciplines and settings as well as parents and patients. We present a set of definitions of morbidity for use in routine audit after paediatric cardiac surgery. These morbidities are ranked in priority order as acute neurological event, unplanned re-operation, feeding problems, the need for renal support, major adverse cardiac events or never events, extracorporeal life support, necrotising enterocolitis, surgical site of blood stream infection, a...

Aim: To evaluate the proportion of neonates referred for extracorporeal membrane oxygenation (ECM... more 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, p50.01). 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 (p50.01 for both).

Advances in Experimental Medicine and Biology, 2012

Neonates supported on extracorporeal membrane oxygenation (ECMO) are at high risk of brain injury... more Neonates supported on extracorporeal membrane oxygenation (ECMO) are at high risk of brain injury due to haemodynamic instability. In order to monitor cerebral and peripheral (muscle) haemodynamic and oxygenation changes in this population we used a dual-channel near-infrared spectroscopy (NIRS) system. In addition, to assess interrelations between NIRS and systemic variables, collected simultaneously, canonical correlation analysis (CCA) was employed. CCA can quantify the relationship between a set of variables and assess levels of dependency. In four out of fi ve patients, systemic variables were found to be less inter-related with cerebral rather than peripheral NIRS measurements. Moreover, during ECMO fl ow manipulations, we found that the interrelation between the systemic and the NIRS cerebral/peripheral variables changed. The CCA method presented here can be used to assess differences between NIRS cerebral and NIRS peripheral responses due to systemic variations which may be indicative of physiological differences in the mechanisms that regulate oxygenation and/or haemodynamics of the brain and the muscle.

Advances in Experimental Medicine and Biology, 2012

Extracorporeal membrane oxygenation can potentially affect cerebral blood fl ow dynamics and cons... more Extracorporeal membrane oxygenation can potentially affect cerebral blood fl ow dynamics and consequently in fl uence cerebral autoregulation. We applied wavelet cross-correlation (WCC) between multichannel cerebral oxyhemoglobin concentration (HbO 2 ) and mean arterial pressure (MAP), to assess regional variations in cerebral autoregulation. Six infants on veno-arterial (VA) ECMO were studied during sequential changes in the ECMO fl ows. WCC between MAP and HbO 2 for each fl ow period and each channel was calculated within three different frequency (wavelet scale) bands centered around 0.1, 0.16, and 0.3 Hz chosen to represent low frequency oscillations, ventilation, and respiration rates, respectively. The group data showed a relationship between maximum WCC and ECMO fl ow. During changes in ECMO fl ow, statistically signi fi cant differences in maximum WCC were found between right and left hemispheres. WCC between HbO 2 and MAP provides a useful method to investigate the dynamics of cerebral autoregulation during ECMO. Manipulations of ECMO fl ows are associated with regional changes in cerebral autoregulation which may potentially have an important bearing on clinical outcome.

Advances in experimental medicine and biology, 2010

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with cardio-respirato... more 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.

Pediatric Transplantation, 2013

Rejection with acute hemodynamic compromise after OHT is rare in children, and is associated with... more Rejection with acute hemodynamic compromise after OHT is rare in children, and is associated with poor survival. We retrospectively reviewed the management, course and outcome of recipients with late (following initial hospital discharge) rejection with acute hemodynamic compromise who were supported on ECLS. Of 197 consecutive children undergoing OHT (84 male; mean [SD] age 8.3 [5.7] [range 0.1-18.8 yr]) between 2/2002 and 10/2012, 187 children survived and were discharged from hospital. Mean (SD) follow-up was 5.0 (3.1) (range 0.1-10.6) yr. During follow-up, seven presented with severe hemodynamic compromise after transplantation (of whom one patient had been transplanted elsewhere). All seven children, who presented in hemodynamic collapse with poor cardiac function refractory to inotropic support, were placed on ECLS-two following in-hospital cardiac arrest. The median duration of ECLS was 6 (range 5-15) days. All survived to decannulation, with one death from overwhelming sepsis 20 days after presentation. The median (range) duration (in days) of inotropic requirement post ECLS was 11 (5-27), the median ventilation time was 8 (7-30), median ICU length of stay was 14 (10-54), and median hospitalization was 24 (19-118). In all, ventricular function normalized (FS >28%) within 10 (7-22) days. There was significant short-term morbidity; however, over a median follow-up of 5.9 (range 0.7-9.2) yr, all survivors have good functional status with no significant apparent neurological sequelae. ECLS thus appears to be a good rescue therapy for children with severe acute rejection post OHT, refractory to conventional treatment, leading to good medium-term outcome.

Pediatric Pulmonology, 2008

Rationale. Inhaled nitric oxide (iNO), used for treatment of persistent pulmonary hypertension of... more Rationale. 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). Methods. Maximal expiratory flow at FRC ðV 0 maxFRC Þ was measured in infants treated with iNO for PPHN (oxygenation index !25) at birth. Results. V 0 maxFRC was measured in 23 infants and expressed as z-scores, to adjust for sex and body size and compared to data from 71 (46 ECMO, 25 CM) infants studied at a similar age in the ECMO Trial. Respiratory morbidity was low in iNO group. V 0 maxFRC z-score was lower than predicted in all groups (P < 0.001), with no significant difference between those treated with iNO [mean (SD) z-score: À1.65 (1.2)] and those treated with ECMO [À1.59 (1.2)] or CM [À2.1(1.0)]. Within iNO, ECMO and CM groups; 26%, 37% and 56%, respectively, had V 0 maxFRC z-scores below normal. Conclusions. Respiratory outcome at 1 year in iNO treated neonates with moderately severe PPHN is encouraging, with no apparent increase in respiratory morbidity when compared to the general population. Sub-clinical reductions in airway function are evident at 1 year, suggesting that continuing efforts to minimize lung injury in the neonatal period are warranted to maximize lung health in later life.

Pediatric Critical Care Medicine, 2012

To evaluate whether intravenous immunoglobulin was linked to a reduction in sepsis in patients wi... more To evaluate whether intravenous immunoglobulin was linked to a reduction in sepsis in patients with prolonged chylothoraces postpediatric cardiothoracic surgery. Retrospective observational cohort study. Tertiary pediatric cardiac surgical center. Children with chylothoraces postcardiothoracic surgery from 1998 to 2006 divided into two groups: with and without intravenous immunoglobulin supplementation. Intravenous immunoglobulin supplementation. 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). 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.

The Journal of Thoracic and Cardiovascular Surgery, 2005

Respiratory insufficiency in children after cardiothoracic surgery delays weaning from the ventil... more Respiratory insufficiency in children after cardiothoracic surgery delays weaning from the ventilator and prolongs intensive care unit stay. There is little consensus as to the indications for tracheostomy and its safety in this population. We reviewed our institutional experience in 37 consecutive infants and children (median age, 8.6 months; weight, 7.2 kg) requiring a tracheostomy after cardiothoracic surgery between January 1998 and December 2001, with follow-up to June 2003. Twenty-four children underwent tracheostomy after corrective (n = 15) or palliative (n = 9) surgery for congenital heart disease, 8 had undergone thoracic transplantation, and 5 had undergone thoracic surgery. Median duration of pretracheostomy ventilation was 30 days, and median total duration of ventilation was 73 days. Tracheostomy was performed earlier in patients undergoing transplantation (median of 20 days postoperatively), with a duration of ventilation of 34 days. No patient experienced mediastinitis, and a wound infection in 1 child was the only identified complication. Twenty-two children survived to hospital discharge, of whom 15 have since been decannulated; 6 still have a tracheostomy in situ and 1 has been lost to follow-up. A number of preoperative and postoperative factors were identified in this cohort. These were preoperative respiratory insufficiency, a history of neonatal ventilation, the need for cardiac reoperations, diaphragmatic paralysis, tracheobronchomalacia, neurological comorbidity, and associated chromosomal abnormalities. Tracheostomy can be performed safely and without increased risk of complications in infants and children early after cardiothoracic surgery. The presence of identifiable factors in patients in whom weaning has been unsuccessful should alert clinicians to early consideration of tracheostomy.

The Journal of Thoracic and Cardiovascular Surgery, 2010

Objectives: To identify pretransplant factors associated with postprocedural right ventricular fa... more Objectives: To identify pretransplant factors associated with postprocedural right ventricular failure and the relationship between right ventricular failure and long-term survival in children.

The Journal of Thoracic and Cardiovascular Surgery, 2006

We sought to review the outcome of infants with a functional single ventricle receiving postopera... more We sought to review the outcome of infants with a functional single ventricle receiving postoperative extracorporeal life support.

The Journal of Thoracic and Cardiovascular Surgery, 2011

In the current era of advanced cardiac surgery and extracorporeal membrane oxygenation (ECMO), th... more In the current era of advanced cardiac surgery and extracorporeal membrane oxygenation (ECMO), there are serious limitations with inadequate neuromonitoring, misleading neuromonitoring, or both, especially in the setting of hemodilution and nonpulsatile flow. 1 Multimodal neurological monitoring is available and advocated in certain centers. 2 However, the implications of neurological monitoring with relevance to neurodevelopmental outcome have not been clearly delineated. As a result, there is equipoise about routine neuromonitoring, particularly with near-infrared spectroscopy (NIRS) and the relevance of data. Single-or dual-channel NIRS has been used widely in cardiac theaters. 4 In a previous study we used dual-channel NIRS in patients undergoing ECMO to understand cerebral and peripheral tissue oxygenation. 5 Power spectral density analysis was performed to extract vasomotion and respiratory and cardiac oscillations. To date, most NIRS studies have used optodes placed on the forehead, which monitor only a small area of the anterior cerebrum. We have developed a novel multichannel NIRS protocol for providing regional measures of cerebral oxygenation and hemodynamics for use in cardiac theaters and intensive care units. Because ECMO in the cardiac intensive care unit could be a surrogate model similar to a patient undergoing cardiac surgery during cardiopulmonary bypass, we have carried out preliminary studies on patients undergoing ECMO during manipulations in the ECMO circuit blood flows. We present our preliminary results with our first patient undergoing ECMO in which we have identified differences in regional cerebral oxygenation with changes in ECMO flows.

Journal of the American College of Cardiology, 2004

We investigated the effects of different CO 2 tensions on oxygenation, pulmonary blood flow (Qp),... more We investigated the effects of different CO 2 tensions on oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA). BACKGROUND Hypoxemia refractory to management of a high pulmonary vascular resistance index (PVRI) may complicate recovery from the BCPA.

The Journal of Heart and Lung Transplantation, 2009

hospital discharge. Adverse events using standardized definitions were analyzed as reported to EL... more hospital discharge. Adverse events using standardized definitions were analyzed as reported to ELSO. Results: Of 334 children who met the study inclusion criteria, the median age was 2.3 years (IQR 0.5 to 9.7); 162 (48.8%) were female, 209 (62.6%) were white, 135 (40.4%) had cardiomyopathy (CMP), and 111 (33.2%) received CPR prior to ECMO support. Overall 108 (32.3%) died on ECMO; 175 (52.4%) survived to hospital discharge including 76/135 (56.3%) with CMP and 99/199 (49.7%) with CHD (Pϭ0.27). Overall, the median duration of support was 22 days (95% CI 19 to 25). The following serious adverse events were reported: CNS injury (16.7%), infection (21.4%) and renal failure (8.4%). Survival to ECMO decannulation (PϽ0.01) and survival to hospital discharge (PϽ0.01) decreased significantly after 14 days on ECMO. Conclusions: ECMO is effective for short-term circulatory support but is not reliable for long-term circulatory support which is often necessary for children awaiting heart transplant. Half of all subjects bridged with ECMO failed to survive to hospital discharge with in-hospital mortality increasing significantly after 14 days of ECMO support. CNS injury, infection and renal failure were reported in a minority of patients on ECMO.

The Journal of Heart and Lung Transplantation, 2008

Cardiac transplantation is a viable treatment option for patients with a failing Fontan circulati... more Cardiac transplantation is a viable treatment option for patients with a failing Fontan circulation. In a single centre, survival post transplantation has been similar to survival after transplantation for cardiomyopathy in the same age group.

The Journal of Heart and Lung Transplantation, 2011

Journal of Biomedical Optics, 2012

Assessing noninvasively cerebral autoregulation, the protective mechanism of the brain to maintai... more 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.

Heart, Lung and Circulation, 2003

Hippocampus, 2017

Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. ... more Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2...

Cardiology in the young, Jan 29, 2016

Morbidity is defined as a state of being unhealthy or of experiencing an aspect of health that is... more Morbidity is defined as a state of being unhealthy or of experiencing an aspect of health that is "generally bad for you", and postoperative morbidity linked to paediatric cardiac surgery encompasses a range of conditions that may impact the patient and are potential targets for quality assurance. As part of a wider study, a multi-disciplinary group of professionals aimed to define a list of morbidities linked to paediatric cardiac surgery that was prioritised by a panel reflecting the views of both professionals from a range of disciplines and settings as well as parents and patients. We present a set of definitions of morbidity for use in routine audit after paediatric cardiac surgery. These morbidities are ranked in priority order as acute neurological event, unplanned re-operation, feeding problems, the need for renal support, major adverse cardiac events or never events, extracorporeal life support, necrotising enterocolitis, surgical site of blood stream infection, a...

Aim: To evaluate the proportion of neonates referred for extracorporeal membrane oxygenation (ECM... more 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, p50.01). 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 (p50.01 for both).

Advances in Experimental Medicine and Biology, 2012

Neonates supported on extracorporeal membrane oxygenation (ECMO) are at high risk of brain injury... more Neonates supported on extracorporeal membrane oxygenation (ECMO) are at high risk of brain injury due to haemodynamic instability. In order to monitor cerebral and peripheral (muscle) haemodynamic and oxygenation changes in this population we used a dual-channel near-infrared spectroscopy (NIRS) system. In addition, to assess interrelations between NIRS and systemic variables, collected simultaneously, canonical correlation analysis (CCA) was employed. CCA can quantify the relationship between a set of variables and assess levels of dependency. In four out of fi ve patients, systemic variables were found to be less inter-related with cerebral rather than peripheral NIRS measurements. Moreover, during ECMO fl ow manipulations, we found that the interrelation between the systemic and the NIRS cerebral/peripheral variables changed. The CCA method presented here can be used to assess differences between NIRS cerebral and NIRS peripheral responses due to systemic variations which may be indicative of physiological differences in the mechanisms that regulate oxygenation and/or haemodynamics of the brain and the muscle.

Advances in Experimental Medicine and Biology, 2012

Extracorporeal membrane oxygenation can potentially affect cerebral blood fl ow dynamics and cons... more Extracorporeal membrane oxygenation can potentially affect cerebral blood fl ow dynamics and consequently in fl uence cerebral autoregulation. We applied wavelet cross-correlation (WCC) between multichannel cerebral oxyhemoglobin concentration (HbO 2 ) and mean arterial pressure (MAP), to assess regional variations in cerebral autoregulation. Six infants on veno-arterial (VA) ECMO were studied during sequential changes in the ECMO fl ows. WCC between MAP and HbO 2 for each fl ow period and each channel was calculated within three different frequency (wavelet scale) bands centered around 0.1, 0.16, and 0.3 Hz chosen to represent low frequency oscillations, ventilation, and respiration rates, respectively. The group data showed a relationship between maximum WCC and ECMO fl ow. During changes in ECMO fl ow, statistically signi fi cant differences in maximum WCC were found between right and left hemispheres. WCC between HbO 2 and MAP provides a useful method to investigate the dynamics of cerebral autoregulation during ECMO. Manipulations of ECMO fl ows are associated with regional changes in cerebral autoregulation which may potentially have an important bearing on clinical outcome.

Advances in experimental medicine and biology, 2010

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with cardio-respirato... more 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.

Pediatric Transplantation, 2013

Rejection with acute hemodynamic compromise after OHT is rare in children, and is associated with... more Rejection with acute hemodynamic compromise after OHT is rare in children, and is associated with poor survival. We retrospectively reviewed the management, course and outcome of recipients with late (following initial hospital discharge) rejection with acute hemodynamic compromise who were supported on ECLS. Of 197 consecutive children undergoing OHT (84 male; mean [SD] age 8.3 [5.7] [range 0.1-18.8 yr]) between 2/2002 and 10/2012, 187 children survived and were discharged from hospital. Mean (SD) follow-up was 5.0 (3.1) (range 0.1-10.6) yr. During follow-up, seven presented with severe hemodynamic compromise after transplantation (of whom one patient had been transplanted elsewhere). All seven children, who presented in hemodynamic collapse with poor cardiac function refractory to inotropic support, were placed on ECLS-two following in-hospital cardiac arrest. The median duration of ECLS was 6 (range 5-15) days. All survived to decannulation, with one death from overwhelming sepsis 20 days after presentation. The median (range) duration (in days) of inotropic requirement post ECLS was 11 (5-27), the median ventilation time was 8 (7-30), median ICU length of stay was 14 (10-54), and median hospitalization was 24 (19-118). In all, ventricular function normalized (FS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;28%) within 10 (7-22) days. There was significant short-term morbidity; however, over a median follow-up of 5.9 (range 0.7-9.2) yr, all survivors have good functional status with no significant apparent neurological sequelae. ECLS thus appears to be a good rescue therapy for children with severe acute rejection post OHT, refractory to conventional treatment, leading to good medium-term outcome.

Pediatric Pulmonology, 2008

Rationale. Inhaled nitric oxide (iNO), used for treatment of persistent pulmonary hypertension of... more Rationale. 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). Methods. Maximal expiratory flow at FRC ðV 0 maxFRC Þ was measured in infants treated with iNO for PPHN (oxygenation index !25) at birth. Results. V 0 maxFRC was measured in 23 infants and expressed as z-scores, to adjust for sex and body size and compared to data from 71 (46 ECMO, 25 CM) infants studied at a similar age in the ECMO Trial. Respiratory morbidity was low in iNO group. V 0 maxFRC z-score was lower than predicted in all groups (P < 0.001), with no significant difference between those treated with iNO [mean (SD) z-score: À1.65 (1.2)] and those treated with ECMO [À1.59 (1.2)] or CM [À2.1(1.0)]. Within iNO, ECMO and CM groups; 26%, 37% and 56%, respectively, had V 0 maxFRC z-scores below normal. Conclusions. Respiratory outcome at 1 year in iNO treated neonates with moderately severe PPHN is encouraging, with no apparent increase in respiratory morbidity when compared to the general population. Sub-clinical reductions in airway function are evident at 1 year, suggesting that continuing efforts to minimize lung injury in the neonatal period are warranted to maximize lung health in later life.

Pediatric Critical Care Medicine, 2012

To evaluate whether intravenous immunoglobulin was linked to a reduction in sepsis in patients wi... more To evaluate whether intravenous immunoglobulin was linked to a reduction in sepsis in patients with prolonged chylothoraces postpediatric cardiothoracic surgery. Retrospective observational cohort study. Tertiary pediatric cardiac surgical center. Children with chylothoraces postcardiothoracic surgery from 1998 to 2006 divided into two groups: with and without intravenous immunoglobulin supplementation. Intravenous immunoglobulin supplementation. 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). 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.

The Journal of Thoracic and Cardiovascular Surgery, 2005

Respiratory insufficiency in children after cardiothoracic surgery delays weaning from the ventil... more Respiratory insufficiency in children after cardiothoracic surgery delays weaning from the ventilator and prolongs intensive care unit stay. There is little consensus as to the indications for tracheostomy and its safety in this population. We reviewed our institutional experience in 37 consecutive infants and children (median age, 8.6 months; weight, 7.2 kg) requiring a tracheostomy after cardiothoracic surgery between January 1998 and December 2001, with follow-up to June 2003. Twenty-four children underwent tracheostomy after corrective (n = 15) or palliative (n = 9) surgery for congenital heart disease, 8 had undergone thoracic transplantation, and 5 had undergone thoracic surgery. Median duration of pretracheostomy ventilation was 30 days, and median total duration of ventilation was 73 days. Tracheostomy was performed earlier in patients undergoing transplantation (median of 20 days postoperatively), with a duration of ventilation of 34 days. No patient experienced mediastinitis, and a wound infection in 1 child was the only identified complication. Twenty-two children survived to hospital discharge, of whom 15 have since been decannulated; 6 still have a tracheostomy in situ and 1 has been lost to follow-up. A number of preoperative and postoperative factors were identified in this cohort. These were preoperative respiratory insufficiency, a history of neonatal ventilation, the need for cardiac reoperations, diaphragmatic paralysis, tracheobronchomalacia, neurological comorbidity, and associated chromosomal abnormalities. Tracheostomy can be performed safely and without increased risk of complications in infants and children early after cardiothoracic surgery. The presence of identifiable factors in patients in whom weaning has been unsuccessful should alert clinicians to early consideration of tracheostomy.

The Journal of Thoracic and Cardiovascular Surgery, 2010

Objectives: To identify pretransplant factors associated with postprocedural right ventricular fa... more Objectives: To identify pretransplant factors associated with postprocedural right ventricular failure and the relationship between right ventricular failure and long-term survival in children.

The Journal of Thoracic and Cardiovascular Surgery, 2006

We sought to review the outcome of infants with a functional single ventricle receiving postopera... more We sought to review the outcome of infants with a functional single ventricle receiving postoperative extracorporeal life support.

The Journal of Thoracic and Cardiovascular Surgery, 2011

In the current era of advanced cardiac surgery and extracorporeal membrane oxygenation (ECMO), th... more In the current era of advanced cardiac surgery and extracorporeal membrane oxygenation (ECMO), there are serious limitations with inadequate neuromonitoring, misleading neuromonitoring, or both, especially in the setting of hemodilution and nonpulsatile flow. 1 Multimodal neurological monitoring is available and advocated in certain centers. 2 However, the implications of neurological monitoring with relevance to neurodevelopmental outcome have not been clearly delineated. As a result, there is equipoise about routine neuromonitoring, particularly with near-infrared spectroscopy (NIRS) and the relevance of data. Single-or dual-channel NIRS has been used widely in cardiac theaters. 4 In a previous study we used dual-channel NIRS in patients undergoing ECMO to understand cerebral and peripheral tissue oxygenation. 5 Power spectral density analysis was performed to extract vasomotion and respiratory and cardiac oscillations. To date, most NIRS studies have used optodes placed on the forehead, which monitor only a small area of the anterior cerebrum. We have developed a novel multichannel NIRS protocol for providing regional measures of cerebral oxygenation and hemodynamics for use in cardiac theaters and intensive care units. Because ECMO in the cardiac intensive care unit could be a surrogate model similar to a patient undergoing cardiac surgery during cardiopulmonary bypass, we have carried out preliminary studies on patients undergoing ECMO during manipulations in the ECMO circuit blood flows. We present our preliminary results with our first patient undergoing ECMO in which we have identified differences in regional cerebral oxygenation with changes in ECMO flows.

Journal of the American College of Cardiology, 2004

We investigated the effects of different CO 2 tensions on oxygenation, pulmonary blood flow (Qp),... more We investigated the effects of different CO 2 tensions on oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA). BACKGROUND Hypoxemia refractory to management of a high pulmonary vascular resistance index (PVRI) may complicate recovery from the BCPA.

The Journal of Heart and Lung Transplantation, 2009

hospital discharge. Adverse events using standardized definitions were analyzed as reported to EL... more hospital discharge. Adverse events using standardized definitions were analyzed as reported to ELSO. Results: Of 334 children who met the study inclusion criteria, the median age was 2.3 years (IQR 0.5 to 9.7); 162 (48.8%) were female, 209 (62.6%) were white, 135 (40.4%) had cardiomyopathy (CMP), and 111 (33.2%) received CPR prior to ECMO support. Overall 108 (32.3%) died on ECMO; 175 (52.4%) survived to hospital discharge including 76/135 (56.3%) with CMP and 99/199 (49.7%) with CHD (Pϭ0.27). Overall, the median duration of support was 22 days (95% CI 19 to 25). The following serious adverse events were reported: CNS injury (16.7%), infection (21.4%) and renal failure (8.4%). Survival to ECMO decannulation (PϽ0.01) and survival to hospital discharge (PϽ0.01) decreased significantly after 14 days on ECMO. Conclusions: ECMO is effective for short-term circulatory support but is not reliable for long-term circulatory support which is often necessary for children awaiting heart transplant. Half of all subjects bridged with ECMO failed to survive to hospital discharge with in-hospital mortality increasing significantly after 14 days of ECMO support. CNS injury, infection and renal failure were reported in a minority of patients on ECMO.

The Journal of Heart and Lung Transplantation, 2008

Cardiac transplantation is a viable treatment option for patients with a failing Fontan circulati... more Cardiac transplantation is a viable treatment option for patients with a failing Fontan circulation. In a single centre, survival post transplantation has been similar to survival after transplantation for cardiomyopathy in the same age group.

The Journal of Heart and Lung Transplantation, 2011

Journal of Biomedical Optics, 2012

Assessing noninvasively cerebral autoregulation, the protective mechanism of the brain to maintai... more 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.

Heart, Lung and Circulation, 2003