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.

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.

A pilot outreach physiotherapy and dietetic quality improvement initiative reduces IV antibiotic requirements in children with moderate-severe cystic fibrosis.

BACKGROUND: At our hospital the current model of care for children with moderate-severe CF is focused on intensive inpatient intervention, regular outpatient clinic review and specialist outreach care as required. An alternative model providing more regular physiotherapy and dietetic outreach support, in addition to these specialist services, may be more effective. METHODS: 16 children (4 male; 12 female; mean age 10.9±2.93; range 4-15 years) who required >40days of IV antibiotics in the 12-months pre-intervention were enrolled. Physiotherapy included weekly-supervised exercise sessions, alongside regular review of home physiotherapy regimens. Dietetic management included 1-2 monthly monitoring of growth, appetite, intake and absorption, and nutrition education sessions. RESULTS: There was a 23% reduction in inpatient IV antibiotic requirement and 20% reduction in home IV antibiotic requirement during the intervention year. Cost-benefit analyses showed savings of £113,570. VO(2Peak) increased by 4.9 ml·kg·min(-1) (95%CI 1.01 to 8.71; p=0.02), and 10 m-MSWT distance and increment achieved increased by 229 m (95%CI 109 to 350; p<0.001) and 2 levels (95%CI 1 to 3; p<0.002) respectively. No significant differences in physiological and patient reported outcomes were demonstrated, although there was a possible trend towards improvement in outcomes when compared to the pre-intervention year. CONCLUSION: This pilot programme demonstrated a reduction in IV and admission requirements with a cost benefit in a small group of children with moderate-severe CF. A fully powered clinical trial is now warranted.

Evaluation of the GlideScope Direct: A New Video Laryngoscope for Teaching Direct Laryngoscopy.

Background. Teaching direct laryngoscopy is limited by the inability of the instructor to simultaneously view the airway with the laryngoscopist. Our primary aim is to report our initial use of the GlideScope Direct, a video-enabled, Macintosh laryngoscope intended primarily as a training tool in direct laryngoscopy. Methods. The GlideScope Direct was made available to anyone who planned on performing direct laryngoscopy as the primary technique for intubation. Novices were those who had performed <30 intubations. Results. The GlideScope Direct was used 123 times as primarily a direct laryngoscope while the instructor viewed the intubation on the monitor. It was highly successful as a direct laryngoscope (93% success). Salvage by indirect laryngoscopy occurred in 7/9 remaining patients without changing equipment. Novices performed 28 intubations (overall success rate of 79%). In 6 patients, the instructor took over and successfully intubated the patient. Instructors used the video images to guide the operator in 16 (57%) of those patients. Seven different instructors supervised the 28 novices, all of who subjectively felt advantaged by having the laryngoscopic view available. Conclusions. The GlideScope Direct functions similarly to a Macintosh laryngoscope and provides the instructor subjective reassurance, while providing the ability to guide the trainee laryngoscopist.

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.

Impact of rapid leukodepletion on the outcome of severe clinical pertussis in young infants.

OBJECTIVES: Bordetella pertussis is a common, underrecognized, and vaccine-preventable cause of critical illness with a high mortality in infants worldwide. Patients with severe cases present with extreme leukocytosis and develop refractory hypoxemia and pulmonary hypertension that is unresponsive to maximal intensive care. This may reflect a hyperviscosity syndrome from the raised white blood cell (WBC) count. Case reports suggest improved outcomes with exchange transfusion to reduce the WBC count. Our objective was to quantify possible benefits of aggressive leukodepletion. METHODS: We, as a regional PICU and extracorporeal membrane oxygenation referral center, adopted a strategy of aggressive leukodepletion in January 2005. The impact of this strategy on crude and case mix-adjusted survival of all infants who were critically ill with B pertussis were compared with control subjects from January 2001 to December 2004 and Extracorporeal Life Support Organisation registry data. RESULTS: Nineteen infants (7 [37%] boys) received intensive care for B pertussis from 2001 to 2009. Admission WBC counts were equivalent in 2 time periods: 2001-2004 (mean: 52,000/µL) and 2005-2009 (mean: 75,000/µL). In 2001-2004, 5 (55%) of 9 patients survived the ICU. Between 2005 and 2009, 9 (90%) of 10 patients survived. When case-mix adjustment for age, WBC count, and extracorporeal membrane oxygenation referral were considered, the 2001-2004 predicted survival (4.4 [49%] of 9.0) was equivalent to the observed mortality (4.0 [44%] of 9.0). Between 2005 and 2009, observed mortality (1.0 [10%] of 10.0) was significantly better than predicted (4.7 [47%] of 10.0). CONCLUSIONS: Leukodepletion should be considered in critically ill infants with B pertussis and leukocytosis.

Patient handovers within the hospital: translating knowledge from motor racing to healthcare.

INTRODUCTION: This paper expands the analogy between motor racing team pit stops and patient handovers. Previous studies demonstrated how the handover of patients following surgery could be improved by learning from a motor racing team. This has been extended to include contributions from several motor racing teams, and by examining transfers at several different interfaces at a non-specialist UK teaching hospital. METHODS: Letters of invitation were sent to the technical managers of nine Formula 1 motor racing teams. Semistructured interviews were carried out at a UK teaching hospital with 10 clinical staff involved in the handover of patients from surgery to recovery and intensive care. RESULTS: Three themes emerged from the motor racing responses; (1) proactive learning with briefings and checklists to prevent errors; (2) active management using technology to transfer information, and (3) post hoc learning from the storage and analysis of electronic data records. The eight healthcare themes were: historical working practice; problems during transfer; poor awareness of handover protocols; poor team coordination; time pressure; lack of consistency in handover practice; poor communication of important information; and awareness that handover was a potential threat to patient safety. CONCLUSIONS: The lessons from motor racing can be applied to healthcare for proactive planning, active management and post hoc learning. Other high-risk industries see standardisation of working practices, interpersonal communication, consistency and continuous development as fundamental for success. The application of these concepts would result in improvements in the quality and safety of the patient handover process.

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.

Diabetes is not an independent predictor of gastroparesis in symptomatic patients referred for gastric emptying studies.

BACKGROUND: It is commonly presumed that diabetics are more prone to gastroparesis when compared to non-diabetics. OBJECTIVE: To ascertain whether diabetes is an independent predictor of gastroparesis in symptomatic patients who are referred for gastric emptying studies. METHODS: This was a cross sectional observational study. The study cohort consisted of 172 consecutive patients who had been referred for gastric emptying studies. Seventy-four of the 172 patients had evidence of diabetes. RESULTS: Gastroparesis was diagnosed in 93 of the 172 patients (54%). Multiple logistic regression analysis did not reveal diabetes to be an independent risk factor (OR 0.77, CI 0.37-1.56, p=0.46). But age>50 years was a significant predictor (OR 3.43, CI 1.62-7.23, p=0.001). The sex of the patient was not a contributing variable (OR 1.47, CI 0.72-2.98, p=0.28). CONCLUSION: Diabetes is not an independent predictor of gastroparesis in patients with gastrointestinal symptoms referred for gastric emptying studies. Age over 50 years was a significant predictor.

Biventricular pacing as bridge to rapid recovery in infancy.

The authors present the unique case of an 8-month-old baby diagnosed with severe left ventricular failure of unknown etiology. Due to a lack of organ availability for this age, a mechanical assist device and assessment for cardiac transplantation were not offered. Subsequent comprehensive echocardiographic dyssynchrony assessment and the presence of left bundle branch block were suggestive of response to cardiac resynchronization therapy. Dual-chamber epicardial pacing was initiated, resulting in prompt marked clinical and echocardiographic improvement, which continued until complete normalization of cardiac function. The pacing system was safely turned off 6 months after its implantation. In conclusion, cardiac resynchronization therapy should be considered as a treatment option even in infancy, regardless of the etiology of disease and/or patient age.

Genetic polymorphisms in the endotoxin receptor may influence platelet count as part of the acute phase response in critically ill children.

PURPOSE: To determine if common polymorphisms in the endotoxin recognition complex influence the acute phase response as determined by the development of the systemic inflammatory response syndrome (SIRS) and platelet count on admission. METHODS: This was a prospective observational cohort study. Paediatric intensive care patients (n = 913) were genotyped for common functional polymorphisms in the endotoxin recognition complex, including Toll-like receptor 4 (TLR4). We also selected potentially confounding polymorphisms in other genes of the innate immune system. SIRS was defined by age-specific consensus criteria. Platelet counts were recorded on admission. RESULTS: The development of SIRS was primarily determined by the nature of the insult, but carriers of TLR4 variant alleles had lower platelet counts than children with wild-type genotype [mean +/- standard error of the mean (SEM) 143 +/- 7 vs. 175 +/- 4; p = 0.0001)--independent of other innate immune system polymorphisms. These findings were validated using a patient cohort of 1,170 adults with coronary artery disease. Carriers of TLR4 polymorphisms with a history of myocardial infarction (n = 573) had lower platelet counts than those with the wild-type genotype (217 +/- 7 vs. 237 +/- 2.8; p = 0.021). CONCLUSIONS: Our results show that TLR4 variant alleles are associated with lower platelet counts across a range of ages and precipitating insults but that they do not influence the incidence of SIRS. This result may reflect redundancy and 'robustness' in the pathways leading to SIRS or the lack of specificity of this endpoint. Platelet count may vary with TLR4 genotype because it may be sufficiently sensitive and more linearly related to inflammation than other markers or, alternatively, there may be a direct TLR4-mediated platelet effect.

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

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.

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.