Adnan T. Bhutta

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.

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)-1β 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.

Within a short time, Coronavirus disease 2019 (COVID-19) has evolved into a pandemic spreading at a speed and scale that has been able to overwhelm even the most advanced healthcare systems quickly. Multiple guidelines published by organizations such as the WHO and US’ CDC address the response to COVID-19 at the international, national, and local levels. Although these guidelines are meant to be globally accessible, implementing them is a challenge given the variability in the health care systems worldwide between low- and middle-income countries (LMIC) and high-income countries and even amongst different regions within each LMIC. We have chosen to evaluate the current guidelines focusing on LMIC and expand on the guidelines as necessary.

Background: The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally. Methods: We will conduct a prospective, observational, multicenter, multinational point prevalence study in sixty-one participating RLS hospitals from North, Central and South America, Africa, Middle East and South Asia with four sampling time points over a 12-month period. Children aged 29 days to 14 years evaluated for acute illness or injury in an emergency department) or directly admitted to an inpatient unit will be enrolled and followed for hospital outcomes and resource utilization for the first seven days of hospitalization. The primary outcome will be prevalence of acute critical illness, which Global PARITY has defined as death within 48 hours of presentation to the hospital, including ED mortality; or admission/transfer to an HDU or ICU; or transfer to another institution for a higher level-of-care; or receiving critical care-level interventions (vasopressor infusion, invasive mechanical ventilation, non-invasive mechanical ventilation) regardless of location in the hospital, among children presenting to the hospital. Secondary outcomes include etiology of critical illness, in-hospital mortality, cause of death, resource utilization, length of hospital stay, and change in neurocognitive status. Data will be managed via REDCap, aggregated, and analyzed across sites. Discussion: This study is expected to address the current gap in understanding of the burden, etiology, resource utilization and outcomes associated with pediatric acute and critical illness in RLS. These data are crucial to inform future research and clinical management decisions and to improve global pediatric hospital outcomes.

Care of children undergoing cardiac surgery occurs in dedicated cardiac intensive care units (CICU) or mixed intensive care units. In this article, we analyzed data from Virtual Pediatric Systems (VPS, LLC) database (2009-2014) for children <18 years of age undergoing cardiac surgery, classified according to Society of Thoracic Surgery-European Association of Cardiothoracic Surgery (STS-EACTS) risk category. We had 25,052 (52%) patients in 53 mixed units (mortality rate, 2.99%), and 22,762 (48%) patients in 19 dedicated CICUs (mortality rate, 2.62%). There was a direct relationship between STS-EACTS risk category and death rate in both units. By multivariable logistic and linear regression, there was no difference in mortality between mixed unit and CICU death rates within STS-EACTS risk categories. We found no difference in outcomes for children undergoing cardiac surgery based on the unit type (dedicated CICU or mixed unit).

Objectives: To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts. Methods: All children (1 month– 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31^st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C. Results: Thirty children with median age of 24 (interquartile range (IQR)1–192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis. Conclusions: Our MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes.

A survey-based pilot study was performed to examine the feasibility of videoconferencing to facilitate multidisciplinary rounds following the initiation of strict isolation and social distancing policies in a pediatric intensive care unit (PICU). The use of a mobile workstation was implemented as the central hub for rounding at the bedside by the attending physicians, while other members of the multidisciplinary and multispecialty team joined rounds from other locations with maintaining appropriate social distance. Fifty-eight staff members who participated in videoconferencing rounds completed the postimplementation survey. Eighty-eight per cent of staff agreed that the use of videoconferencing to facilitate rounds was an effective strategy to maintain social distancing between team members during the pandemic. Sixty-four percent of staff agreed that the use of videoconferencing improved participation of the PICU team and consultants by increasing access to rounds. Over 50% of staff agreed that the use of videoconferencing improved the efficiency of rounds and team productivity. Only 4% of staff responded that videoconferencing increased the duration of rounds and 37% responded that it decreased resident and team education. Fifty-five percent of staff agreed that videoconferencing was used to promote parental participation during this pandemic month. Videoconferencing was found to be a feasible solution to safely conduct multidisciplinary rounds while maintaining social distancing, and participants found it effective without interfering with normal workflow. Incorporating videoconferencing into traditional rounding practices may be advantageous following the pandemic to improve team and family access to rounds and workflow efficiency and rounding structure.

The study investigated the safety and efficacy of two antithrombin III (ATIII) products in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) by performing a retrospective analysis of patients who received either recombinant ATIII (rATIII) or human-derived ATIII (hATIII). Twenty-two patients were included in the study from January 2014 to September 2015 and all received unfractionated heparin (UFH) as anticoagulation during ECMO. In total, 86 doses of ATIII were included in the analysis in which 37 doses (43%) were rATIII and 49 doses (57%) were hATIII. Unfractionated heparin rates were also evaluated for all cases (n = 86) at 24 hours post-ATIII supplementation. The UFH rate decreased after the administration of both types of ATIII. However, neither the reduction in UFH rate between the two ATIII products (p = 0.52) nor the UFH rates pre- and post-ATIII supplementation at 24 hours (p = 0.08) reached statistical significance. There was a significant difference in cost favoring the rATIII product (p < 0.0001). An ad-hoc estimation of waste associated with ATIII supplementation showed >$100,000 in financial loss of unused drug. Future studies are warranted to evaluate the efficacy of ATIII supplementation in pediatric ECMO.

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.

Botulism in children can have severe complications necessitating intensive care. The current literature lacks data of children with botulism requiring critical care. We aim to describe the outcomes of pediatric botulism in the pediatric intensive care unit (PICU). Retrospective cohort data from Virtual Pediatric Systems (VPS, LLC, Los Angeles, California), from 2009 to 2016 including all PICU admissions among children with botulism, were analyzed. Characteristics and outcomes were compared with similar studies. A total of 380 children were identified over 8 years. Our cohort had the shortest length of stay (median 4.6 days), the smallest percent requiring mechanical ventilation (40%), and the highest median age (120 days) amongst comparable studies. Length of mechanical ventilation and PICU stay has decreased among children with botulism. Advances in PICU care may have contributed to these improved outcomes.