Evaluation of the Resources and Inequities Among Pediatric Critical Care Facilities in Pakistan.

OBJECTIVES: To evaluate nationwide pediatric critical care facilities and resources in Pakistan. DESIGN: Cross-sectional observational study. SETTING: Accredited pediatric training facilities in Pakistan. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A survey was conducted using the Partners in Health 4S (space, staff, stuff, systems) framework, via email or telephone correspondence. We used a scoring system in which each item in our checklist was given a score of 1, if available. Total scores were added up for each component. Additionally, we stratified and analyzed the data between the public and private healthcare sectors. Out of 114 hospitals (accredited for pediatric training), 76 (67%) responded. Fifty-three (70%) of these hospitals had a PICU, with a total of 667 specialized beds and 217 mechanical ventilators. There were 38 (72%) public hospitals and 15 (28%) private hospitals. There were 20 trained intensivists in 16 of 53 PICUs (30%), while 25 of 53 PICUs (47%) had a nurse-patient ratio less than 1:3. Overall, private hospitals were better resourced in many domains of our four Partners in Health framework. The Stuff component scored more than the other three components using analysis of variance testing ( p = 0.003). On cluster analysis, private hospitals ranked higher in Space and Stuff, along with the overall scoring. CONCLUSIONS: There is a general lack of resources, seen disproportionately in the public sector. The scarcity of qualified intensivists and nursing staff poses a challenge to Pakistan's PICU infrastructure.

Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.

We report orthotopic (life-supporting) survival of genetically engineered porcine cardiac xenografts (with six gene modifications) for almost 9 months in baboon recipients. This work builds on our previously reported heterotopic cardiac xenograft (three gene modifications) survival up to 945 days with an anti-CD40 monoclonal antibody-based immunosuppression. In this current study, life-supporting xenografts containing multiple human complement regulatory, thromboregulatory, and anti-inflammatory proteins, in addition to growth hormone receptor knockout (KO) and carbohydrate antigen KOs, were transplanted in the baboons. Selective "multi-gene" xenografts demonstrate survival greater than 8 months without the requirement of adjunctive medications and without evidence of abnormal xenograft thickness or rejection. These data demonstrate that selective "multi-gene" modifications improve cardiac xenograft survival significantly and may be foundational for paving the way to bridge transplantation in humans.

Application of Nonhuman Primate Models in the Studies of Pediatric Anesthesia Neurotoxicity.

Numerous animal models have been used to study developmental neurotoxicity associated with short-term or prolonged exposure of common general anesthetics at clinically relevant concentrations. Pediatric anesthesia models using the nonhuman primate (NHP) may more accurately reflect the human condition because of their phylogenetic similarity to humans with regard to reproduction, development, neuroanatomy, and cognition. Although they are not as widely used as other animal models, the contribution of NHP models in the study of anesthetic-induced developmental neurotoxicity has been essential. In this review, we discuss how neonatal NHP animals have been used for modeling pediatric anesthetic exposure; how NHPs have addressed key data gaps and application of the NHP model for the studies of general anesthetic-induced developmental neurotoxicity. The appropriate application and evaluation of the NHP model in the study of general anesthetic-induced developmental neurotoxicity have played a key role in enhancing the understanding and awareness of the potential neurotoxicity associated with pediatric general anesthetics.

Post-operative course of pulmonary artery pressure after complete atrioventricular canal defect repair.

Complete atrioventricular canal defect is a CHD associated with intra-cardiac shunting of blood, which can lead to irreversible changes in pulmonary vascular resistance and pulmonary artery hypertension if unrepaired. Patients with Trisomy 21 are at risk for early development of pulmonary artery hypertension if left uncorrected.1,2. OBJECTIVES: The purpose of this study is to describe the evolution of pulmonary artery hypertension after repair of complete atrioventricular canal defect and to determine the time to normalisation of pulmonary artery pressure in both patients with and without Trisomy 21. METHODS: This is a single centre, retrospective analysis of patients with complete atrioventricular canal defect admitted for surgical repair at the University of Maryland Medical Center from 2005 to 2015. T-test or Mann-Whitney test and Chi-Square or Fisher's exact tests were used to compare the two groups (patients with Trisomy 21 and those without). Repeated measures of analysis of variance and serial measurement analysis were performed. RESULTS: Twenty-nine patients meeting the inclusion criteria underwent repair of complete atrioventricular defects during the study period. The right ventricular pressure estimate remained elevated over time and did not show a significant difference between the two groups. Right ventricular to systolic blood pressure ratios for all patients remained > 0.5 over the time periods assessed. CONCLUSIONS: Our study suggests that in patients with complete atrioventricular canal defects, the right ventricular pressure remains elevated and does not normalise on echocardiograms performed up to one year after surgery, suggesting a sustained elevation in pulmonary vascular resistance.

Outcomes of Children With Firearm Injuries Admitted to the PICU in the United States.

OBJECTIVES: Firearm-related injury is the second leading cause of injury and death for children 1-18 years old in United States. The objective of our study was to analyze the outcomes of children admitted to the PICU with firearm injuries. DESIGN: Retrospective study. SETTING: PICUs in United States contributing data to Virtual Pediatric Systems, LLC, from January 2009 to December 2017. PATIENTS: Children age 1 month to 18 years old admitted to the PICU with firearm injury, identified by external cause of injury E-codes and International Classification of Diseases, 9th Edition, and International Classification of Diseases, 10th Edition, codes were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1,447 cases identified of which 175 (12%) died in the PICU. Unintentional firearm injury (67.7%) and assault with a firearm injury (20%) comprised 90% of the cases. Males comprised 78% of the cohort (1,122) and race distribution included 45% Black (646), 27% White (390), and 12% Hispanic (178). Among the children who died in the PICU, 55% were 13-18 years old. Children attempting suicide with a firearm were more likely to die in the PICU as compared to the other causes of firearm injury. Based on their Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores at discharge, there is high morbidity in children with firearm injuries. CONCLUSIONS: Mortality rate of children with firearm injury admitted to the PICU is high. Children admitted to the PICU with suicide attempt with a firearm carried the highest mortality. Further studies may help further define the epidemiology of firearm injuries in children and plan interventions to minimize these unnecessary deaths.

Characteristics and outcomes of children with congenital heart disease needing diaphragm plication.

BACKGROUND: Diaphragm dysfunction following surgery for congenital heart disease is a known complication leading to delays in recovery and increased post-operative morbidity and mortality. We aimed to determine the incidence of and risk factors associated with diaphragm plication in children undergoing cardiac surgery and evaluate timing to repair and effects on hospital cost and length of stay. METHODS: We conducted a multi-institutional retrospective observational cohort study. Forty-three hospitals from the Pediatric Health Information System database were included, and a total of 112,110 patients admitted between January 2004 and December 2014 were analysed. RESULTS: Patients less than 18 years of age who underwent cardiac surgery were included. Risk Adjustment for Congenital Heart Surgery was utilized to determine procedure complexity. The overall incidence of diaphragm dysfunction was 2.2% (n = 2513 out of 112,110). Of these, 24.0% (603 patients) underwent diaphragm plication. Higher complexity cardiac surgery (Risk Adjustment for Congenital Heart Surgery 5-6) and age less than 4 weeks were associated with a higher likelihood of diaphragm plication (p-value < 0.01). Diaphragmatic plication was associated with increased hospital length of stay (p-value < 0.01) and increased medical cost. CONCLUSIONS: Diaphragm plication after surgery for congenital heart disease is associated with longer hospital length of stay and increased cost. There is a strong correlation of prolonged time to plication with increased length of stay and medical cost. The likelihood of plication increases with younger age and higher procedure complexity. Methods to improve early recognition and treatment of diaphragm dysfunction should be developed.

School-Age Test Proficiency and Special Education After Congenital Heart Disease Surgery in Infancy.

OBJECTIVE: To evaluate test proficiency and the receipt of special education services in school-age children who had undergone surgery for congenital heart disease (CHD) at age <1 year. STUDY DESIGN: Data from Arkansas-born children who underwent surgery for CHD at Arkansas Children's Hospital at age <1 year between 1996 and 2004 were linked to state birth certificates and the Arkansas Department of Education longitudinal database containing achievement test scores in literacy and mathematics for grades 3-4 and special education codes. The primary negative outcome was not achieving grade-level proficiency on achievement tests. Logistic regression accounting for repeated measures was used to evaluate for associations between achieving proficiency and demographic data, maternal education, and clinical factors. RESULTS: A total of 362 of 458 (79%) children who underwent surgery for CHD were matched to the Arkansas Department of Education database, 285 of whom had grade 3 and/or 4 achievement tests scores. Fewer students with CHD achieved proficiency in literacy and mathematics (P < .05) compared with grade-matched state students. Higher 5-minute Apgar score, shorter duration of hospitalization, and higher maternal education predicted proficiency in literacy (P < .05). White race, no cardiopulmonary bypass, and shorter hospitalization predicted proficiency in mathematics (P < .05). Sex, gestational age, age at surgery, CHD diagnosis, and type and number of surgeries did not predict test proficiency. Compared with all public school students, more children with CHD received special education services (26.9% vs 11.6%; P < .001). CONCLUSION: Children with CHD had poorer academic achievement and were more likely to receive special education services than all state students. Results from this study support the need for neurodevelopmental evaluations as standard practice in children with CHD.

Optimizing Team Dynamics: An Assessment of Physician Trainees and Advanced Practice Providers Collaborative Practice.

OBJECTIVES: The presence of advanced practice providers has become increasingly common in many ICUs. The ideal staffing model for units that contain both advanced practice providers and physician trainees has not been described. The objectives of this study were to evaluate ICU staffing models that include physician trainees and advanced practice providers and their effects on patient outcomes, resident and fellow education, and training experience. A second aim was to assess strategies to promote collaboration between team members. DATA SOURCES: PubMed, CINAHL, OVID MEDLINE, and Cochrane Review from 2002 to 2015. STUDY SELECTION: Experimental study designs conducted in an ICU setting. DATA EXTRACTION: Two reviewers screened articles for eligibility and independently abstracted data using the identified search terms. DATA SYNTHESIS: We found 21 articles describing ICU team structure and outcomes. Four articles were found describing the impact of advanced practice providers on resident or fellow education. Two articles were found discussing strategies to promote collaboration between advanced practice providers and critical care fellows or residents. CONCLUSIONS: Several articles were identified describing the utilization of advanced practice providers in the ICU and the impact of models of care on patient outcomes. Limited data exist describing the impact of advanced practice providers on resident and fellow education and training experience. In addition, there are minimal data describing methods to enhance collaboration between providers. Future research should focus on determining the optimal ICU team structure to improve patient outcomes, education of trainees, and job satisfaction of team members and methods to promote collaboration between advanced practice providers and physicians in training.

Academic proficiency in children after early congenital heart disease surgery.

Children with early surgery for congenital heart disease (CHD) are known to have impaired neurodevelopment; their performance on school-age achievement tests and their need for special education remains largely unexplored. The study aimed to determine predictors of academic achievement at school age and placement in special education services among early CHD surgery survivors. Children with CHD surgery at <1 year of age from January 1, 1998 to December 31, 2003, at the Arkansas Children's Hospital were identified. Out-of-state births and infants with known genetic and/or neurologic conditions were excluded. Infants were matched to an Arkansas Department of Education database containing standardized assessments at early school age and special-education codes. Predictors for achieving proficiency in literacy and mathematics and the receipt of special education were determined. Two hundred fifty-six children who attended Arkansas public schools and who had surgery as infants were included; 77.7 % had either school-age achievement-test scores or special-education codes of mental retardation or multiple disabilities. Scores on achievement tests for these children were 7-13 % lower than those of Arkansas students (p < 0.01). They had an eightfold increase in receipt of special education due to multiple disabilities [odds ratio (OR) 10.66, 95 % confidence interval (CI) 4.23-22.35] or mental retardation (OR 4.96, 95 % CI 2.6-8.64). Surgery after the neonatal period was associated with decreased literacy proficiency, and cardiopulmonary bypass during the first surgery was associated with decreased mathematics proficiency. Children who had early CHD surgery were less proficient on standardized school assessments, and many received special education. This is concerning because achievement-test scores at school age are "real-world" predictors of long-term outcomes.

Extubation failure in infants with shunt-dependent pulmonary blood flow and univentricular physiology.

OBJECTIVE: The objective of the study was to identify incidence, aetiology, and outcomes of extubation failure in infants with shunt-dependent pulmonary blood flow at a single tertiary care, academic children's hospital. The second objective of this study was to determine the haemodynamic effects of transition of positive pressure ventilation to spontaneous breathing in infants with extubation failure. PATIENTS AND METHODS: Extubation failure for our study was defined as the need for positive pressure ventilation within 96 hours after extubation. We collected demographics, pre-operative, intra-operative, post-operative, and peri-extubation data in a retrospective, observational format in patients who underwent a modified Blalock-Taussig shunt between January, 2005 and March, 2011. Infants undergoing Norwood operation or Damus-Kaye-Stansel with modified Blalock-Taussig shunt were excluded from the study. The cardiorespiratory variables collected before extubation and immediately after extubation included heart rate, respiratory rate, mean arterial blood pressure, central venous pressures, near infrared spectroscopy, oxygen saturations, and lactate levels. Clinical outcomes evaluated included the success or failure of extubation, cardiovascular intensive care unit length of stay, hospital length of stay, and mortality. Descriptive and univariate statistics were utilised to compare groups with extubation failure and extubation success. RESULTS: Of the 55 eligible patients during the study period, extubation failure occurred in 27% (15/55) of the patients. Of the 15 patients with extubation failure, 10 patients needed reintubation and five patients received continuous positive pressure ventilation without getting reintubated. There were three patients who had extubation failure in the first 2 hours after extubation, nine patients in the 2-24-hour period, and three patients in the 24-96-hour period. In all, eight patients were extubated in the second attempt after the first extubation failure, with a median duration of mechanical ventilation of 2 days (1 day, 6 days). The median age of patients at extubation was 19 days (12 days, 22 days) and median weight of patients was 3.6 kg (3.02 kg, 4.26 kg). In all, 38% (21/55) of the patients were intubated before surgery. The most common risk factors for failed extubation were lung disease in 46% (7/15), cardiac dysfunction in 26% (4/15), diaphragmatic paralysis in 13% (2/15), airway oedema in 6% (1/15), and vocal cord paralysis in 6% (1/15). The median duration of mechanical ventilation was 4 days (1 day, 10.5 days), median cardiovascular intensive care unit length of stay was 11 days (6.5 days, 23.5 days), and the median hospital length of stay was 30 days (14 days, 48 days). The overall mortality at the time of hospital discharge was 7%. CONCLUSIONS: Extubation failure in infants with shunt-dependent pulmonary blood flow and univentricular physiology is high and aetiology is diverse. Cardiopulmonary effects of removal of positive pressure ventilation are more pronounced in children with extubation failure and include escalation in the need for oxygen requirement and increase in mean arterial blood pressure. The majority of extubation failures in this select patient population occurs in the first 24 hours. Extubation failure in these patients is not associated with increased hospital length of stay or mortality.

Remote Didactic Education Effectively Increases Cardiac Critical Care Nursing Staff Knowledge in Low-Resource Settings.

Background: While progress has been made to decrease mortality in children under age five, there continues to be a need for improvement in the treatment of children with congenital heart disease. Many of these patients require surgical correction and live in areas without the expertise of surgical teams. Research has shown that appropriate training is critical to ensure the best clinical outcomes. The Ethiopian government has identified the need for increased training of health care professionals as a method to improve hospital outcomes. Methods: Twenty-five cardiac critical nurses participated in a remote didactic education curriculum over the course of multiple months. We used a pre- and post-test model to evaluate knowledge acquisition and retention after the curriculum. Nurses completed post-tests at 1-, 3-, 6-, and 12-month intervals to monitor knowledge retention over time. Results: We found a significant increase in nursing knowledge that was retained over the course of 12 months. Nursing knowledge on pre- and post-tests was impacted by experience level. However, after completion of the curriculum experience was not a significant factor. Conclusion: Virtual curriculum delivered via remote didactic education is an inexpensive and effective way to increase nursing knowledge in cardiac critical care. It encourages bidirectional learning and allows the sharing of expertise from individuals who may otherwise be limited by travel or finances. Our approach is generalizable and further research needs to be done to evaluate the effectiveness of this type of curriculum in other environments.

Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation.

A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus.

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.

Impact of 22q11.2 deletion on the postoperative course of children after cardiac surgery.

The primary objective of this study was to describe the impact of 22q11.2 deletion (del22q11) on the clinical characteristics, postoperative course, and short-term outcomes of children undergoing surgery for congenital heart disease. The charts of all children ages 1 day-18 years who received cardiac surgery for interrupted aortic arch (IAA), tetralogy of Fallot (TOF), or truncus arteriosus (TA) repair from 1 January 2001 to 31 December 2011 were retrospectively reviewed. The patients were divided into two groups: the 22q11 group including children with del22q11 undergoing surgery for TOF, IAA, or TA and the non-22q11 or control group including children with no chromosomal or genetic abnormality undergoing surgery for TOF, IAA, or TA. Demographic information, cardiac diagnoses, noncardiac abnormalities, preoperative factors, intraoperative details, surgical procedures performed, postoperative complications, and in-hospital deaths were collected. The outcome data collected included days of inotrope use, need for dialysis, length of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS, and mortality. The study enrolled 173 patients: 65 patients in the 22q11 group and 108 patients in the control group. Of the 65 patients in the 22q11 group, 36 (55 %) underwent repair for TOF, 13 (20 %) for IAA, and 16 (25 %) for TA. The two groups did not differ in terms of age or weight. The preexisting conditions were similar in the two groups. Unplanned noncardiac operations were more common in the children with del22q11, but delayed chest closure was similar in the two groups. The incidence of postoperative noncardiac complications such as reintubation, vocal cord paralysis, and diaphragmatic paralysis was similar in the two groups. However, increasing numbers of patients in del22q11 group needed dialysis in one form or the other during the immediate postoperative stay. The incidence of fungal infection and wound infection was higher in the del22q11 group than in the control group. Duration of mechanical ventilation, ICU LOS, and hospital LOS were similar in the two groups, except in certain subgroups. Mortality did not differ significantly between the two groups. In conclusion, children with del22q11 have a higher risk of postoperative complications after cardiac surgery, with no difference in length of mechanical ventilation, ICU LOS, hospital LOS, or mortality. However, short-term outcomes may differ in certain subgroups.

Multi-tiered analysis of brain injury in neonates with congenital heart disease.

Early brain injury occurs in newborns with congenital heart disease (CHD) placing them at risk for impaired neurodevelopmental outcomes. Predictors for preoperative brain injury have not been well described in CHD newborns. This study aimed to analyze, retrospectively, brain magnetic resonance imaging (MRI) in a heterogeneous group of newborns who had CHD surgery during the first month of life using a detailed qualitative CHD MRI Injury Score, quantitative imaging assessments (regional apparent diffusion coefficient [ADC] values and brain volumes), and clinical characteristics. Seventy-three newborns who had CHD surgery at 8 ± 5 (mean ± SD) days of life and preoperative brain MRI were included; 38 also had postoperative MRI. Thirty-four (34 of 73, 47 %) had at least one type of preoperative brain injury, and 28 of 38 (74 %) had postoperative brain injury. The 5-min APGAR score was negatively associated with preoperative injury, but there was no difference between CHD types. Infants with intraparenchymal hemorrhage, deep gray matter injury, and/or watershed infarcts had the highest CHD MRI Injury Scores. ADC values and brain volumes were not different in infants with different CHD types or in those with and without brain injury. In a mixed group of CHD newborns, brain injury was found preoperatively on MRI in almost 50 %, and there were no significant baseline characteristic differences to predict this early brain injury except 5-min APGAR score. We conclude that all infants, regardless of CHD type, who require early surgery should be evaluated with MRI because they are all at high risk for brain injury.

Development of a primate model to evaluate the effects of ketamine and surgical stress on the neonatal brain.

With advances in pediatric and obstetric surgery, pediatric patients are subject to complex procedures under general anesthesia. The effects of anesthetic exposure on the developing brain may be confounded by several factors including pre-existing disorders and surgery-induced stress. Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is routinely used as a pediatric general anesthetic. However, controversy remains about whether ketamine exposure may be neuroprotective or induce neuronal degeneration in the developing brain. Here, we report the effects of ketamine exposure on the neonatal nonhuman primate brain under surgical stress. Eight neonatal rhesus monkeys (postnatal days 5-7) were randomly assigned to each of two groups: Group A (n = 4) received 2 mg/kg ketamine via intravenous bolus prior to surgery and a 0.5 mg/kg/h ketamine infusion during surgery in the presence of a standardized pediatric anesthetic regimen; Group B (n = 4) received volumes of normal saline equivalent to those of ketamine given to Group A animals prior to and during surgery, also in the presence of a standardized pediatric anesthetic regimen. Under anesthesia, the surgery consisted of a thoracotomy followed by closing the pleural space and tissue in layers using standard surgical techniques. Vital signs were monitored to be within normal ranges throughout anesthesia. Elevated levels of cytokines interleukin (IL)-8, IL-15, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1ß at 6 and 24 h after surgery were detected in ketamine-exposed animals. Fluoro-Jade C staining revealed significantly higher neuronal degeneration in the frontal cortex of ketamine-exposed animals, compared with control animals. Intravenous ketamine administration prior to and throughout surgery in a clinically relevant neonatal primate model appears to elevate cytokine levels and increase neuronal degeneration. Consistent with previous data on the effects of ketamine on the developing brain, the results from the current randomized controlled study in neonatal monkeys undergoing simulated surgery show that ketamine does not provide neuroprotective or anti-inflammatory effects.

Capacity Building in Pediatric Critical Care-Global Health Research and Education: The Blantyre Experience.

Pediatric critical care medicine (PCCM), as it is practiced in high-income countries, is focused on specialized medical care for the most vulnerable pediatric patient populations. However, best practices for provision of that care globally are lacking. Thus, PCCM research and education programming can potentially fill significant knowledge gaps by facilitating the development of evidence-based clinical guidelines that reduce child mortality on a global scale. Malaria remains a leading cause of pediatric mortality worldwide. The Blantyre Malaria Project (BMP) is a research and clinical care collaborative that has focused on reducing the public health burden of pediatric cerebral malaria in Malawi since 1986. In 2017, the requirements of a new research study led to the creation of PCCM services in Blantyre, creating the opportunity to establish a PCCM-Global Health Research Fellowship by BMP in collaboration with the University of Maryland School of Medicine. In this perspective piece, we reflect on the evolution of the PCCM-Global Health research fellowship. Although the specifics of this fellowship are out of the scope of this perspective, we discuss the context allowing for the development of this program and explore some early lessons learned to consider for future capacity-building efforts in the future of PCCM-Global Health research.

Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda.

BACKGROUND: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies. METHODS: Secondary analysis of verbal autopsy data from children admitted to 6 hospitals across Uganda from July 2017 to March 2020. Structured verbal autopsy interviews were conducted for all deaths within 6 months after discharge. Two physicians independently classified a primary cause of death, up to 4 alternative causes, and up to 5 contributing conditions using the Start-Up Mortality List, with discordance resolved by consensus. RESULTS: Verbal autopsies were completed for 361 (98.6%) of the 366 (5.9%) children who died among 6191 discharges (median admission age: 5.4 months [interquartile range, 1.8-16.7]; median time to mortality: 28 days [interquartile range, 9-74]). Most deaths (62.3%) occurred in the community. Leading primary causes of death, assigned in 356 (98.6%) of cases, were pneumonia (26.2%), sepsis (22.1%), malaria (8.5%), and diarrhea (7.9%). Common contributors to death were malnutrition (50.5%) and anemia (25.7%). Reviewers were less confident in their causes of death for neonates than older children (P < .05). CONCLUSIONS: Postdischarge mortality frequently occurred in the community in children admitted for suspected sepsis in Uganda. Analyses of the probable causes for these deaths using verbal autopsies suggest potential areas for interventions, focused on early detection of infections, as well as prevention and treatment of underlying contributors such as malnutrition and anemia.

Outcomes after in-hospital cardiac arrest in children with cardiac disease: a report from Get With the Guidelines--Resuscitation.

BACKGROUND: Small studies suggest that children experiencing a cardiac arrest after undergoing cardiac surgery have better outcomes than other groups of patients, but the survival outcomes and periarrest variables of cardiac and noncardiac pediatric patients have not been compared. METHODS AND RESULTS: All cardiac arrests in patients <18 years of age were identified from Get With the Guidelines-Resuscitation from 2000 to 2008. Cardiac arrests occurring in the neonatal intensive care unit were excluded. Of 3323 index cardiac arrests, 19% occurred in surgical-cardiac, 17% in medical-cardiac, and 64% in noncardiac (trauma, surgical-noncardiac, and medical-noncardiac) patients. Survival to hospital discharge was significantly higher in the surgical-cardiac group (37%) compared with the medical-cardiac group (28%; adjusted odds ratio, 1.8; 95% confidence interval, 1.3-2.5) and the noncardiac group (23%; adjusted odds ratio, 1.8; 95% confidence interval, 1.4-2.4). Those in the cardiac groups were younger and less likely to have preexisting noncardiac organ dysfunction, but were more likely to have ventricular arrhythmias as their first pulseless rhythm, to be monitored and hospitalized in the intensive care unit at the time of cardiac arrest, and to have extracorporeal cardiopulmonary resuscitation compared with those in the noncardiac group. There was no survival advantage for patients in the medical-cardiac group compared with those in the noncardiac group when adjusted for periarrest variables. CONCLUSION: Children with surgical-cardiac disease have significantly better survival to hospital discharge after an in-hospital cardiac arrest compared with children with medical-cardiac disease and noncardiac disease.

Biomarkers for risk stratification of febrile neutropenia among children with malignancy: a pilot study.

BACKGROUND: Patients receiving myelosuppressive chemotherapy remain at increased risk for developing febrile neutropenia (FN). For this heterogeneous population, a biomarker based risk stratification of FN patients may be a useful clinical tool. We hypothesized that serum biomarkers during initial presentation of an FN event could be predictive of subsequent clinical outcome. PROCEDURE: Eighty-nine FN events from 36 non-consecutive subjects were analyzed. "High-risk" FN criteria included prolonged hospitalization (≥ 7 days), admission to pediatric intensive care unit (PICU) or a microbiology confirmed bacteremia. Patients with "low risk" FN had none of the above. Biomarkers measured during the first 2 days of FN hospitalization were analyzed and correlated with respective clinical outcome. RESULTS: Of the 89 FN events, 44 (49%) fulfilled pre-defined high-risk criteria and 45 (51%) were low-risk. Procalcitonin level (>0.11 ng/ml) was found to be associated with the high-risk FN outcome with sensitivity of 97%. With an increase in log scale by 1, the odds of being high-risk FN increased twofold. Hs-CRP >100 mg/L had sensitivity of 88% in predicting high-risk FN. The odds of a high-risk FN event increased by approximately 1.8-fold with an increase in the log scale of hs-CRP by 1 (10-fold). In univariate analysis, IL-6, IL-8, and IL-10 were statistically significant and associated with high-risk FN. However, no statistically significant difference was found for IL-1α, sIL-2Ra, IL-3, or TNF-α. CONCLUSIONS: Biomarkers with appropriate critical threshold values may be a useful clinical tool for appropriate risk stratification of children with FN.