Dialysis for paediatric acute kidney injury in Cape Town, South Africa.

BACKGROUND: Dialysis is lifesaving for acute kidney injury (AKI), but access is poor in less resourced settings. A "peritoneal dialysis (PD) first" policy for paediatric AKI is more feasible than haemodialysis in low-resource settings. METHODS: Retrospective review of modalities and outcomes of children dialysed acutely at Red Cross War Memorial Children's Hospital between 1998 and 2020. RESULTS: Of the 593 children with AKI who received dialysis, 463 (78.1%) received PD first. Median age was 9.0 (range 0.03-219.3; IQR 13.0-69.6) months; 57.6% were < 1 year old. Weights ranged from 0.9 to 2.0 kg (median 7.0 kg, IQR 3.0-16.0 kg); 38.6% were < 5 kg. PD was used more in younger children compared to extracorporeal dialysis (ECD), with median ages 6.4 (IQR 0.9-30.4) vs. 73.9 (IQR 17.5-113.9) months, respectively (p = 0.001). PD was performed with Seldinger soft catheters (n = 480/578, 83%), predominantly inserted by paediatricians at the bedside (n = 412/490, 84.1%). Complications occurred in 127/560 (22.7%) children receiving PD. Overall, 314/542 (57.8%) children survived. Survival was significantly lower in neonates (< 1 month old, 47.5%) and infants (1-12 months old, 49.2%) compared with older children (> 1 year old, 70.4%, p < 0.0001). Survival was superior in the ECD (75.4%) than in the PD group (55.6%, p = 0.002). CONCLUSIONS: "PD First for Paediatric AKI" is a valuable therapeutic approach for children with AKI. It is feasible in low-resourced settings where bedside PD catheter insertion can be safely taught and is an acceptable dialysis modality, especially in settings where children with AKI would otherwise not survive.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Clinical decision support tools for paediatric sepsis in resource-poor settings: an international qualitative study.

OBJECTIVE: New paediatric sepsis criteria are being developed by an international task force. However, it remains unknown what type of clinical decision support (CDS) tools will be most useful for dissemination of those criteria in resource-poor settings. We sought to design effective CDS tools by identifying the paediatric sepsis-related decisional needs of multidisciplinary clinicians and health system administrators in resource-poor settings. DESIGN: Semistructured qualitative focus groups and interviews with 35 clinicians (8 nurses, 27 physicians) and 5 administrators at health systems that regularly provide care for children with sepsis, April-May 2022. SETTING: Health systems in Africa, Asia and Latin America, where sepsis has a large impact on child health and healthcare resources may be limited. PARTICIPANTS: Participants had a mean age of 45 years, a mean of 15 years of experience, and were 45% female. RESULTS: Emergent themes were related to the decisional needs of clinicians caring for children with sepsis and to the needs of health system administrators as they make decisions about which CDS tools to implement. Themes included variation across regions and institutions in infectious aetiologies of sepsis and available clinical resources, the need for CDS tools to be flexible and customisable in order for implementation to be successful, and proposed features and format of an ideal paediatric sepsis CDS tool. CONCLUSION: Findings from this study will directly contribute to the design and implementation of CDS tools to increase the uptake and impact of the new paediatric sepsis criteria in resource-poor settings.

Pediatric Acute Respiratory Distress Syndrome in South African PICUs: A Multisite Point-Prevalence Study.

OBJECTIVES: To describe the prevalence of pediatric acute respiratory distress syndrome (pARDS) and the characteristics of children with pARDS in South African PICUs. DESIGN: Observational multicenter, cross-sectional point-prevalence study. SETTING: Eight PICUs in four South African provinces. PATIENTS: All children beyond the neonatal period and under 18 years of age admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and demographic data were prospectively collected on a single day of each month, from February to July 2022, using a centralized database. Cases with or at risk of pARDS were identified using the 2015 Pediatric Acute Lung Injury Consensus Conference criteria. Prevalence was calculated as the number of children meeting pARDS criteria/the total number of children admitted to PICU at the same time points. Three hundred ten patients were present in the PICU on study days: 166 (53.5%) male, median (interquartile range [IQR]) age 9.8 (3.1-32.9) months, and 195 (62.9%) invasively mechanically ventilated. Seventy-one (22.9%) patients were classified as being "at risk" of pARDS and 95 patients (prevalence 30.6%; 95% CI, 24.7-37.5%) fulfilled pARDS case criteria, with severity classified as mild (58.2%), moderate (25.3%), and severe (17.6%). Median (IQR) admission Pediatric Index of Mortality 3 risk of mortality in patients with and without pARDS was 5.6 (3.4-12.1) % versus 3.9 (1.0-8.2) % ( p = 0.002). Diagnostic categories differed between pARDS and non-pARDS groups ( p = 0.002), with no difference in age, sex, or presence of comorbidities. On multivariable logistic regression, increasing admission risk of mortality (adjusted odds ratio [aOR] 1.02; 95% CI, 1.00-1.04; p = 0.04) and being admitted with a respiratory condition (aOR 2.64; 95% CI, 1.27-5.48; p = 0.01) were independently associated with an increased likelihood of having pARDS. CONCLUSIONS: The 30.6% prevalence of pARDS in South Africa is substantially higher than reports from other sociogeographical regions, highlighting the need for further research in this setting.

Lessons learned from regional training of paediatric nephrology fellows in Africa.

BACKGROUND: Access to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical. METHODS: Retrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town. RESULTS: A regionally appropriate 1-2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin. Program funding included fellowships from the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN), International Society of Peritoneal Dialysis (ISPD), and the African Paediatric Fellowship Program (APFP). Fellows were trained on both in- and out-patient management of infants and children with kidney disorders. "Hands-on skills" training included examination, diagnosis and management skills, practical insertion of peritoneal dialysis catheters for management of acute kidney injury and kidney biopsies. Of 16 trainees who completed > 1 year of training, 14 (88%) successfully completed subspecialty exams and 9 (56%) completed a master's degree with a research component. PN fellows reported that their training was appropriate and enabled them to make a difference in their respective communities. CONCLUSIONS: This training program has successfully equipped African physicians with the requisite knowledge and skills to provide PN services in resource-constrained areas for children with kidney disease. The provision of funding from multiple organizations committed to paediatric kidney disease has contributed to the success of the program, along with the fellows' commitment to build PN healthcare capacity in Africa. A higher resolution version of the Graphical abstract is available as Supplementary information.

Operationalizing Appropriate Sepsis Definitions in Children Worldwide: Considerations for the Pediatric Sepsis Definition Taskforce.

Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a "Think globally, act locally" approach is required.

Prevalence and Incidence of Pediatric Acute Respiratory Distress Syndrome in a Tertiary Academic PICU in South Africa.

OBJECTIVES: To determine the prevalence and incidence of pediatric acute respiratory distress syndrome (pARDS) among infants and children admitted to the PICU. DESIGN: A single-center descriptive point prevalence study with twice weekly data collection over a 6 months (August 2020 to February 12, 2021). SETTING: Red Cross War Memorial Children's Hospital, Cape Town, South Africa. PATIENTS: All infants and children admitted to the PICU on study days were included. INTERVENTIONS: Data were captured electronically on a standardized case record form using a Research Electronic Data Capture electronic database. MEASUREMENTS AND MAIN RESULTS: The Pediatric Acute Lung Injury Consensus Conference criteria were used to define pARDS cases. Prevalence was calculated as the total number of pARDS cases/1,000 PICU bed days. The study included 354 patients (median [interquartile range]) 10.1 months old (1.5-61.3 mo old), with 204 males (57.6%), who occupied 879 bed days. Of these 879 bed days, 266 (30.3%; 95% CI, 27.2-33.3%) were occupied by pARDS cases, with a calculated prevalence and incidence of 302.6 of 1,000 bed days (30.3%) and 29.7% (95% CI, 26.7-32.7%), respectively. Three cases from the cohort were defined using the oxygen saturation index calculation. In cases receiving invasive ventilation ( n = 494; 56.2%), pARDS severity was classified as mild ( n = 143; 16.3%), moderate ( n = 44; 5.0%), and severe ( n = 29, 3.3%). A further 205 beds (23.3%) were occupied by patients classified as being at risk of pARDS. CONCLUSIONS: The prevalence and incidence of pARDS in a South African PICU appears substantially higher than findings described in international reports. Further investigation of risk factors and outcomes is warranted.

Factors to be Considered in Advancing Pediatric Critical Care Across the World.

This article reviews the many factors that have to be taken into account as we consider the advancement of pediatric critical care (PCC) in multiple settings across the world. The extent of PCC and the range of patients who are cared for in this environment are considered. Along with a review of the ongoing treatment and technology advances in the PCC setting, the structures and systems required to support these services are also considered. Finally the question of how PCC can be made sustainable in a volatile world with the impacts of global crises such as climate change is addressed.

Pharmacokinetics of Vancomycin in Critically Ill Children: A Systematic Review.

BACKGROUND AND OBJECTIVE: Vancomycin is often used in the ICU for the treatment of Gram-positive bacterial infection. In critically ill children, there are pathophysiologic changes that affect the pharmacokinetics of vancomycin. A systematic review of vancomycin pharmacokinetics and pharmacodynamics in critically ill children was performed. METHODS: Pharmacokinetic studies of vancomycin in critically ill children published up to May 2021 were included in the review provided they included children aged > 1 month. Studies including neonates were excluded. A search was performed using the PubMed, Scopus, and Google Scholar databases. The Risk of Bias Assessment Tool for Systematic Reviews (ROBIS) was used to check for quality and reduce bias. Data on study characteristics, patient demographics, clinical parameters, pharmacokinetic parameters, outcomes, and study limitations were collected. RESULTS: Thirteen studies were included in this review. A wide variety of dosing and sampling strategies were used in the studies. Methods for estimating vancomycin pharmacokinetics, especially the area under the curve over 24 h, varied. Vancomycin doses of 20-60 mg/kg were given daily. This resulted in high variability in pharmacokinetic parameters. Vancomycin trough level was less than 15 µg/mL in most of the studies. Vancomycin clearance ranged from 0.05 to 0.38 L/h/kg. Volume of distribution ranged from 0.1 to 1.16 L/kg. Half-life was between 2.4 and 23.6 h. Patients in the study receiving continuous vancomycin infusion had AUC24 < 400 µg·h/mL. CONCLUSION: There is large variability in the pharmacokinetics of vancomycin among critically ill patients. Studies to assess the factors responsible for this variability in vancomycin pharmacokinetics are needed.

Pediatric Index of Mortality 3-An Evaluation of Function Among ICUs In South Africa.

OBJECTIVES: To evaluate the performance of the Pediatric Index of Mortality 3 as mortality risk assessment model. DESIGN: This prospective study included all admissions 30 days to 18 years old for 12 months during 2016 and 2017. Data gathered included the following: age and gender, diagnosis and reason for PICU admission, data specific for the Pediatric Index of Mortality 3 calculation, PICU outcomes (death or survival), and length of PICU stay. SETTING: Nine units that care for children within tertiary or quaternary academic hospitals in South Africa. PATIENTS: All admissions 30 days to 18 years old, excluding premature infants, children who died within 2 hours of admission, or children transferred to other PICUs, and those older than 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 3,681 admissions of which 2,253 (61.3%) were male. The median age was 18 months (interquartile range, 6-59.5 mo). There were 354 deaths (9.6%). The Pediatric Index of Mortality 3 predicted 277.47 deaths (7.5%). The overall standardized mortality ratio was 1.28. The area under the receiver operating characteristic curve was 0.81 (95% CI 0.79-0.83). The Hosmer-Lemeshow goodness-of-fit test statistic was 174.4 (p < 0.001). Standardized mortality ratio for all age groups was greater than 1. Standardized mortality ratio for diagnostic subgroups was mostly greater than 1 except for those whose reason for PICU admission was classified as accident, toxin and envenomation, and metabolic which had an standardized mortality ratio less than 1. There were similar proportions of respiratory patients, but significantly greater proportions of neurologic and cardiac (including postoperative) patients in the Pediatric Index of Mortality 3 derivation cohort than the South African cohort. In contrast, the South African cohort contained a significantly greater proportion of miscellaneous (including injury/accident victims) and postoperative noncardiac patients. CONCLUSIONS: The Pediatric Index of Mortality 3 discrimination between death and survival among South African units was good. Case-mix differences between these units and the Pediatric Index of Mortality 3 derivation cohort may partly explain the poor calibration. We need to recalibrate Pediatric Index of Mortality 3 to the local setting.

Decreased Human Leukocyte Antigen DR on Circulating Monocytes Expression After Severe Pediatric Trauma: An Exploratory Report.

OBJECTIVES: Major trauma in adults induces immune dysfunction, with diminished expression of human leukocyte antigen-DR on circulating monocytes. No pediatric data are available. This study described the kinetics of human leukocyte antigen-DR on circulating monocytes following major pediatric trauma and relationships between human leukocyte antigen-DR on circulating monocytes and outcomes. DESIGN: Prospective observational study. SETTING: PICU and trauma unit at a tertiary-care university hospital in South Africa. PATIENTS: Children between 1 month and 13 years hospitalized for severe brain trauma or trauma with an Injury Severity Score greater than or equal to 16, from November 2016 to March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 36 children. Median (interquartile range) age and Injury Severity Score were 7 years (4.9-10.5 yr) and 25 years (22.7-30 yr), respectively. Blood samples (n = 83) for standardized human leukocyte antigen-DR on circulating monocytes measurement were collected at days 1-2, 3-4, and 8-9 after injury (D1, D3, and D8, respectively). On D1, median (interquartile range) human leukocyte antigen-DR on circulating monocytes was markedly reduced relative to normal values (7,031 [5,204-11,201] antibodies per cell). There was a significant increase in human leukocyte antigen-DR on circulating monocytes from D1 to D8. Although all patients with secondary infections (n = 8; 22%) had human leukocyte antigen-DR on circulating monocytes less than 15,000 antibodies per cell at D3, human leukocyte antigen-DR on circulating monocytes levels were not associated with the occurrence of secondary infections (p = 0.22). At D3, human leukocyte antigen-DR on circulating monocytes was significantly higher in patients discharged home (n = 21) by Day 30 after trauma compared with those who died or were still hospitalized (n = 14) (p = 0.02). CONCLUSIONS: Pediatric severe trauma induced an early and dramatic decrease in human leukocyte antigen-DR on circulating monocytes expression. This alteration of innate immunity was not associated with the occurrence of secondary infection, possibly due to a lack of statistical power. However, human leukocyte antigen-DR on circulating monocytes at Day 3 is a potential indicator of those at high risk of secondary infection and worse outcomes.

Use of locally prepared peritoneal dialysis (PD) fluid for acute PD in children and infants in Africa.

BACKGROUND: In less well-resourced countries, the high cost of commercially available peritoneal dialysis (PD) fluid limits its use. The major concerns regarding bedside-prepared PD fluid is peritonitis as well as electrolyte disorders. The aim of this study was to review our experience with the use of PD fluids prepared at the bedside using the intravenous infusion solution Balsol (Fresenius Kabi). METHODS: This was a retrospective review of all patients who received PD for acute kidney injury (AKI) using a bedside-prepared PD solution adapted from the intravenous solution Balsol in our intensive care unit. RESULTS: In total, 49 cases of acute PD were performed. Of the 49 children, 21 (43%) were male. The ages of the patients ranged from newborn to 10.2 years (median 0.33 years). The weight of children ranged from 1.3 kg to 50 kg (median 4.1 kg). The type of PD catheters used: Cook catheters, 41 patients; Kimal peel-away, 10 patients; and surgical inserted Tenckhoff type of catheter, 2 patients. The duration of PD was 1-17 days (median 3 days) Complications included peritonitis in 2 of 49 patients and blocked catheter in 6 of 49 patients. There were no electrolyte disturbances as a result of the PD. Overall survival was 43% of patients. CONCLUSIONS: Locally prepared PD solutions at the bedside adapted from intravenous solutions can be used safely and effectively. This has important relevance for centres in less well-resourced countries, where commercially produced PD fluid is not available for the management of AKI.

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.