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 cohort's 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.

Republished: creating a safe, reliable hospital at night handover: a case study in implementation science.

BACKGROUND: We developed protocols to handover patients from day to hospital at night (H@N) teams. SETTING: NHS paediatric specialist hospital. METHOD: We observed four handover protocols (baseline, Phases 1, 2 and 3) over 2 years. A mixed-method study (observation, interviews, task analysis, prospective risk assessment, document and case note review) explored the impact of different protocols on performance. INTERVENTION: In Phase 1, a handover protocol was introduced to resolve problems with the baseline H@N handover. Following this intervention, two further revisions to the handover occurred, driven by staff feedback (Phases 2 and 3). RESULTS: Variations in performance between handover protocols on three process measures, start time efficiency, total length of handover, and number of distractions and interruptions, were identified. Univariate regression analysis showed statistically significant differences between handover protocols on two surrogate outcome measures: number of flagging omissions and the number of out of hours deteriorations (p=0.04 for Phase 3 vs Phase 1 for both measures (CI 1.04 to 4.08; CI 1.03 to 4.33), and for Phase 3 vs Phase 2 (p=0.006 and p=0.001 (CI 1.22 to 5.15; CI 1.62 to 9.0)), respectively). The Phase 1 and 2 handover protocols were effective at identifying patients whose clinical condition warranted review overnight. Performance on both surrogate outcome measures, length of handover and distractions, deteriorated in Phase 3. CONCLUSIONS: A carefully designed prioritisation process within the H@N handover can be effective at flagging acutely unwell patients. However, the protocol we introduced was unsustainable. In a complex healthcare system, sustainable implementation of new processes may be threatened by conflicting goals.

ECLS for children with late (post-discharge) rejection after heart transplantation.

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.

The impact of mechanical ventilation time before initiation of extracorporeal life support on survival in pediatric respiratory failure: a review of the Extracorporeal Life Support Registry.

OBJECTIVE: To evaluate the relationship between duration of mechanical ventilation before the initiation of extracorporeal life support and the survival rate in children with respiratory failure. Extracorporeal life support has been used as a rescue therapy for >30 yrs in children with severe respiratory failure. Previous studies suggest patients who received >7-10 days of mechanical ventilation were not acceptable extracorporeal life support candidates as a result of irreversible lung damage. DESIGN: A retrospective review encompassing the past 10 yrs of the International Extracorporeal Life Support Organization Registry (January 1, 1999, to December 31, 2008). SETTING: Extracorporeal Life Support Organization Registry database. PATIENTS: A total of 1325 children (≥ 30 days and ≤ 18 yrs) met inclusion criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The following pre-extracorporeal life support variables were identified as independently and significantly related to the chance of survival: 1) >14 days of ventilation vs. 0-7 days was adverse (odds ratio, 0.32; p < .001); 2) the presence of a cardiac arrest was adverse (odds ratio, 0.56; p = .001); 3) pH per 0.1-unit increase was protective (odds ratio, 1.15; p < .001); 4) oxygenation index, per 10-unit increase was adverse (odds ratio, 0.95; p = .002); and 5) any diagnosis other than sepsis was related to a more favorable outcome. Patients requiring >7-10 or >10-14 days of pre-extracorporeal life support ventilation did not have a statistically significant decrease in survival as compared with patients who received 0-7 days. CONCLUSIONS: There was a clear relationship between the number of mechanical ventilation days before the initiation of extracorporeal life support and survival. However; there was no statistically significant decrease in survival until >14 days of pre-extracorporeal life support ventilation was reached regardless of underlying diagnosis. We found no evidence to suggest that prolonged mechanical ventilation should be considered as a contraindication to extracorporeal life support in children with respiratory failure before 14 days.

Extracorporeal membrane oxygenation and term neonatal respiratory failure deaths in the United Kingdom compared with the United States: 1999 to 2005.

OBJECTIVE: To compare national neonatal extracorporeal membrane oxygenation data and deaths from primary respiratory disorders of term neonates between the United Kingdom and the United States from 1999 to 2005. DESIGN: Cross-sectional study. SETTING: National data sets from the United Kingdom and the United States. PATIENTS: Neonatal extracorporeal membrane oxygenation patients submitted to the Extracorporeal Life Support Organization Registry and national birth and death registrations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Meconium aspiration syndrome was the most common indication for extracorporeal membrane oxygenation in the United Kingdom: 50.6% vs. 25.8% in the United States (p < .001). Congenital diaphragmatic hernia was most common indication for extracorporeal membrane oxygenation in the United States: 30.7% vs. 15.4% in the United Kingdom (p < .001).Extracorporeal membrane oxygenation use was greater in the United States than the United Kingdom: rate ratio, 1.81 (95%, confidence interval, 1.64, 2.00). The extracorporeal membrane oxygenation rate decreased over time in the United States (p < .001) but was unchanged for all diagnoses in the United Kingdom (p = .49). The rates of extracorporeal membrane oxygenation use for meconium aspiration syndrome were equivalent in both countries: rate ratio, 0.92 (95% confidence interval, 0.80, 1.07) but greater in the United States for congenital diaphragmatic hernia: rate ratio, 3.60, (95% confidence interval, 2.82, 4.66) and persistent pulmonary hypertension newborn: rate ratio, 4.67 (95% confidence interval, 3.33, 6.74).National neonatal death rates included nonextracorporeal membrane oxygenation + extracorporeal membrane oxygenation death. Meconium aspiration syndrome deaths were equivalent overall between the two countries: rate ratio, 0.99 (95% confidence interval, 0.77, 1.29), but decreased in the United States (p < .001) although not in the United Kingdom (p = .17). Congenital diaphragmatic hernia deaths were more prevalent in the United Kingdom than in the United States: rate ratio, 1.57 (95% confidence interval, 1.34, 1.84). CONCLUSIONS: Extracorporeal membrane oxygenation is used more often in the United States: clinicians seem less willing to offer extracorporeal membrane oxygenation for persistent pulmonary hypertension of the newborn and congenital diaphragmatic hernia in the United Kingdom. In contrast to the United States, no reduction in either extracorporeal membrane oxygenation use or death due to meconium aspiration syndrome was observed in the United Kingdom. Early transfer to a tertiary center is recommended for term neonates with respiratory failure.

Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged

Parent stress levels during children's hospital recovery after congenital heart surgery.

The hospitalization of a child for cardiac surgery is known to be a stressful experience for parents. However, little is known about the time course or the relationships between parental stress and the child's actual or perceived recovery. This research aimed to investigate pre- and postoperative parental stress and to examine some of the influencing factors during the postoperative period for children undergoing elective cardiac surgery. Parents of 211 children completed questionnaires and structured interviews preoperatively and on postoperative days 3, 5, 8, and 15. The stress of the parents remained moderate to high throughout their children's hospitalization regardless of the severity of illness. Parents' perceptions of their children's level of illness correlated with an objective measure of postoperative morbidity. There were few differences between mothers' and fathers' stress or their perceptions of their children's illness. Parents in more deprived communities and mothers born outside the UK had higher stress levels. These findings indicate the negative impact of children's surgery and intensive care hospitalization on parents. Better identification of parents at risk for high stress and specific interventions to improve parental support and coping are needed.

Predictors of outcome for children requiring respiratory extra-corporeal life support: implications for inclusion and exclusion criteria.

OBJECTIVES: A range of children receive extra-corporeal life support (ECLS) for respiratory failure, but there is little published data on this group. Our aims were: (1) to analyse predictors of outcome and (2) comment on inclusion and exclusion criteria. DESIGN: Retrospective review. SETTING: Tertiary ECLS centre. PATIENTS: A total of 124 children categorised as 'paediatric respiratory ECLS' from July 1992 to December 2005. RESULTS: Fifty-three percent of children had one or more co-morbid conditions; the median age was 10.1 (IQR 3-34) months; the median ECLS duration was 9 (IQR 5-17) days; survival to discharge was 62% and at 1 year was 59%. Although survival varied according to primary reason for ECLS (range 36-100%), after adjustment for this, the presence of a co-morbid condition was unrelated to mortality (OR = 1.49, 95% CI 0.65, 3.42, P = 0.34) Predictors of mortality were increased pre-ECLS oxygenation index (OR = 1.09, 95% CI 1.00, 1.18, P = 0.05) and shock (OR 2.53, 95% CI 1.21, 5.28, P = 0.01). The relationship between mortality and end organ dysfunction (OR 2.12, 95% CI 0.89, 5.02, P = 0.09) and greater number of pre-ECLS ventilator days (OR 1.10, 95% CI 0.99, 1.22, P = 0.08) was less conclusive. CONCLUSIONS: Pre-existing co-morbid conditions may predispose children to develop severe respiratory failure but with careful case selection, do not appear to reduce the chance of survival. Severity of pulmonary dysfunction determined by OI and shock were key predictors of outcome and should remain important determinants of referral for ECLS.

Neonatal extra-corporeal life support: indications and limitations.

Cardiac extra-corporeal life support is used more frequently in the current era of complex, high-risk neonatal heart surgery. Although outcome for neonates with complex heart disease has improved in the last decade, thanks to advances in surgery and intensive care, survival in the subset that require extra-corporeal support remains unchanged at below 40%. Neonatal cardiac extra-corporeal support is a technically challenging therapy that is applied in a range of contexts including: post-operative low cardiac output syndrome, cardiac arrest, high-risk interventional catheterisation or as a bridge to recovery from dysrhythmia and myocarditis. Extra-corporeal life support has increased in particular for neonates with single ventricle disease in the last 5 years, mainly achieving similar results to biventricular patients. Further research is required in order to determine the optimal methods for patient selection and to establish important predictors of outcome including the longterm neurological development of survivors.

Healthcare-associated infection in pediatric patients on extracorporeal life support: The role of multidisciplinary surveillance.

OBJECTIVE: To describe the use of a multidisciplinary approach to sepsis surveillance and evaluate impact on outcome. DESIGN: Prospective clinical study or clinical audit cycle. SETTING: Tertiary pediatric extracorporeal membrane oxygenation (ECMO) center. PATIENTS: Patients were 215 children supported with ECMO January 1999 to December 2004. INTERVENTIONS: A multidisciplinary team met monthly to evaluate cases of bloodstream infection and mediastinitis, review trends, and update unit policies. Changes in practice were made at the end of 2001 in order to address a perceived high rate of sepsis: a) reeducation; b) introduction of electively preprimed ECMO circuits; and c) preference for neck rather than chest cannulation in cardiac patients. Prophylactic antibiotics were used from preprocedure for 24 hrs only throughout the study. MEASUREMENTS AND MAIN RESULTS: Over the entire study period, 39 children had 47 septic episodes, with a rate of 24.9 per 1000 ECMO days. Multiple logistic regression analyses indicated that infection was associated with duration of ECMO support (odds ratio 1.24; 95% confidence interval 1.15, 1.35 per day) and case type: Closed vs. open chest was protective in cardiac patients (odds ratio 0.08; 95% confidence interval 0.01, 0.50). Infection increased the odds of death by 2.01 (95% confidence interval 1.00, 4.05), but this effect was less important than case type and ECMO days. After policy changes were implemented, there was a reduction in sepsis from 29.3 to 20.1 episodes per 1000 ECMO days. There was reduced sepsis in respiratory patients: neonates from 28.0 to 6.6 and pediatric patients from 42.4 to 16.9 episodes per 1000 ECMO days. Despite policy changes, sepsis remained a problem in cardiac patients with open sternum: 65.1 per 1000 ECMO days. CONCLUSIONS: ECMO support is a high-risk setup for nosocomial infection, in particular for cardiac patients with open sternum for whom antibiotic prophylaxis is justified. Multidisciplinary surveillance offers an excellent approach for quality improvement in this challenging field.

The waiting game: bridging to paediatric heart transplantation.

BACKGROUND: Although mechanical circulatory support might not increase the number of adults surviving to transplantation, because of the shortage of donor organs, the situation might be different for children. Our aim was to assess the effect of mechanical assist devices to bridge children with end-stage cardiomyopathy to heart transplantation. METHODS: A 5-year retrospective review was undertaken with data from the UK paediatric transplant programme and from bridging to transplant done at two paediatric transplant centres in the UK. FINDINGS: Between Jan 1, 1998 and Dec 31, 2002, 22 children with end-stage cardiomyopathy, median age 5.7 years (range 1.2-17), were supported by a mechanical assist device as a bridge to first heart transplantation, with a 77% survival rate to hospital discharge. Nine were supported by a paracorporeal ventricular assist device, six received transplantation, five survived to discharge (55%), with one late death. 13 were supported by extra-corporeal membrane oxygenation, and 12 were transplanted and survived to discharge (92%) with one late death. With urgent listing, the median waiting time for a heart was 7.5 days (range 1.5-22 days). The correlation between the proportion of patients bridged to transplantation and the proportion of patients dying while on the transplant waiting list was r=-0.93, p=0.02. INTERPRETATION: Our findings lend support to the hypothesis that a national mechanical assist programme to bridge children to transplantation can minimise the number dying while on the heart transplant waiting list. In the context of urgent listing and a short waiting time, extra-corporeal membrane oxygenation seems to provide the safest form of support.

Recombinant factor VII for severe bleeding during extracorporeal membrane oxygenation following open heart surgery.

OBJECTIVES: Severe bleeding is a recognized complication during mechanical cardiopulmonary support with extracorporeal membrane oxygenation. We present the use of recombinant activated factor VII (rFVIIa) for severe, refractory bleeding during extracorporeal membrane oxygenation support after open-heart surgery for congenital heart disease. DESIGN: Retrospective review of all patients receiving rFVIIa on extracorporeal membrane oxygenation. SETTING: A pediatric extracorporeal membrane oxygenation center located within the cardiac intensive care unit of a tertiary care children's hospital. PATIENTS: Four patients treated with rFVIIa for refractory bleeding on extracorporeal membrane oxygenation. INTERVENTIONS: The patients received rFVIIa for severe, refractory blood loss despite applying clotting products and aprotinin infusion and excluding surgical reasons. MEASUREMENTS AND MAIN RESULTS: rFVIIa was given 4-7 hrs after commencing extracorporeal membrane oxygenation; a second identical dose was administered 4 hrs later. Bleeding decreased significantly in all patients within 30 mins after the first dose of rFVIIa; no side effects were observed. CONCLUSIONS: rFVIIa is effective to achieve control of refractory hemorrhage in patients on extracorporeal membrane oxygenation. Now a randomized controlled trial to evaluate risks and benefits of rFVIIa on patients undergoing extracorporeal membrane oxygenation is required.

Plasticizer di(2-ethylhexyl)phthalate (DEHP) release in wet-primed extracorporeal membrane oxygenation (ECMO) circuits.

A wet-primed ready-to-use extracorporeal membrane oxygenation (ECMO) circuit is used in some centres for rapid deployment of ECMO during cardiopulmonary resuscitation. Yet, the potential release of plasticizer di(2-ethylhexyl)phthalate (DEHP) from the polyvinyl chloride tubing in the circuit during storage is a concern. In this study, a high performance liquid chromatography method was used to determine the concentration of DEHP in the priming solution (Plasmalyte) from an ECMO circuit stored for up to 14 days at 8 degrees C. No accumulation of DEHP in the circulating fluid was detected. The results provide important information for centres where ECMO circuits are kept wet-primed prior to clinical use.

Sequential use of extracorporeal membrane oxygenation and the Berlin Heart Left Ventricular Assist Device for 106-day bridge to transplant in a two-year-old child.

We describe a 2 year-old girl with end-stage dilated cardiomyopathy in whom extracorporeal membrane oxygenation (ECMO) was used for mechanical cardiac assistance. After 4 weeks, ECMO-related complications necessitated change to a Berlin Heart Left Ventricular Assist Device (LVAD), and she received a successful cardiac transplant after a total of 106 days on mechanical cardiac support.

Surgical substrates of postoperative junctional ectopic tachycardia in congenital heart defects.

BACKGROUND: Junctional ectopic tachycardia is a major cause of postoperative morbidity after surgery for congenital cardiac disease. To elucidate the mechanism of junctional ectopic tachycardia, surgical correlations were studied in four types of congenital heart defects involving closure of a ventricular septal defect, relief of right ventricular outflow tract obstruction, or both. METHODS: Between 1997 and 1999, a total of 343 consecutive patients underwent repair of tetralogy of Fallot (n = 114), common truncus arteriosus (n = 10), ventricular septal defect (n = 161), and atrioventricular septal defect (n = 58). Variables studied included demographic and bypass data, surgical approaches toward ventricular septal defect closure and relief of right ventricular outflow tract obstruction, and resection as opposed to division of muscle bundles. RESULTS: Junctional ectopic tachycardia occurred most frequently after repair of tetralogy of Fallot (n = 25; 21.9%), with no cases occurring after repair of common trunk, 6 occurring after repair of ventricular septal defect (3.7%), and 6 occurring after repair of atrioventricular septal defect (10.3%). Stepwise logistic regression revealed that resection of muscle bundles (P <.0001), higher bypass temperatures (P <.03), and relief of right ventricular outflow tract obstruction through the right atrium (P <.05) significantly and independently predicted postoperative junctional ectopic tachycardia. CONCLUSIONS: Relief of right ventricular outflow tract obstruction appears to be more important in the causation of junctional ectopic tachycardia than does ventricular septal defect closure, which may explain the higher incidence of this complication after tetralogy of Fallot repair. Muscular resection seems to be more arrhythmogenic than is simple division. Increased traction through the right atrium for relief of right ventricular outflow tract obstruction would fit the hypothesis that enhanced automaticity of the His bundle, the morphologic substrate for junctional ectopic tachycardia, may result from direct trauma or infiltrative hemorrhage of the conduction system. When feasible, techniques avoiding both extensive muscle resection and excessive traction should be applied during resection of right ventricular outflow tract obstruction.

Improved early outcome for end-stage dilated cardiomyopathy in children.

OBJECTIVE: To review the impact of management changes on the early outcomes of end-stage dilated cardiomyopathy in children. METHODS: We conducted a retrospective study of all consecutive children with end-stage dilated cardiomyopathy who received hospital treatment since 1992. Over the past 3 years the following management changes were made: (1) more aggressive use of mechanical cardiac assistance; (2) high priority listing for transplantation; and (3) ABO incompatible transplants for infants. Outcomes for 46 patients admitted between 1992 and 1999 (group I) were compared with 53 patients between 2000 and March 2003 (group II). RESULTS: In group I, 12 (26%) patients received mechanical support with recovery in 3 and transplantation in 5 (1 died). In group II, 19 (36%) patients received extracorporeal membrane oxygenation, with recovery in 5 and transplantation in 12 (all survived). The use of mechanical assistance was associated with high morbidity related to bleeding, end-organ failure, and long-term mechanical ventilation. Five patients in group II received ABO incompatible transplants and all survived. There have been no episodes of rejection or need for increased immunosuppressive therapy. Hospital mortality has been significantly reduced (group I, 37% vs group II, 11%; P <.05). CONCLUSIONS: Recent refinements in the management of end-stage dilated cardiomyopathy in children have significantly reduced early mortality. Identification of markers of early myocardial recovery and development of mechanical devices for longer term and more physiologic support are essential to achieve further improvements in outcome.

Inhaled nitric oxide therapy in neonates and children: reaching a European consensus.

Inhaled nitric oxide (iNO) was first used in neonatal practice in 1992 and has subsequently been used extensively in the management of neonates and children with cardiorespiratory failure. This paper assesses evidence for the use of iNO in this population as presented to a consensus meeting jointly organised by the European Society of Paediatric and Neonatal Intensive Care, the European Society of Paediatric Research and the European Society of Neonatology. Consensus Guidelines on the Use of iNO in Neonates and Children were produced following discussion of the evidence at the consensus meeting.

Percutaneous left ventricular "vent" insertion for left heart decompression during extracorporeal membrane oxygenation.

OBJECTIVE: Description of a novel method of left ventricular decompression by a percutaneous technique under transthoracic echocardiographic guidance. DESIGN: Case report. SETTING: Supraregional cardiac referral center. PATIENT: PATIENT with end-stage cardiomyopathy. INTERVENTIONS: Percutaneous insertion of a modified Mullins transseptal sheath under transthoracic echocardiographic guidance. MEASUREMENTS AND MAIN RESULTS: Successful decompression of the left ventricle and subsequent orthotopic heart transplantation. CONCLUSIONS: In patients at high risk of bleeding, a percutaneous technique may be useful for left ventricular decompression.