Introduction

Infectious diseases leading to septic shock remain a major cause of childhood mortality in all settings [1]. Recommendations in the Surviving Sepsis Campaign (SSC), guidelines for pediatric patients rely on evidence from resource-rich settings [2]. However, recommendations are context dependent, and published guidelines deriving evidence primarily from resource-rich settings may be less relevant in areas where resources are minimal and the epidemiology is very different [3]. Thus recommendations for the treatment of septic shock in children in intensive care units (ICUs) in resource-limited settings are sorely needed, where there is often lacking laboratory support, equipment, and trained staff, serving as a supplement to existing guidelines from the World Health Organization (WHO) that focus upon emergency triage and treatment in non-ICU contexts [4]. There is no standardized definition of ICU, but for the purposes of these recommendations, we are focusing on referral hospitals with the capability to continuously monitor critically ill children, ideally with the availability of some form of mechanical ventilation, acknowledging a lack of dedicated pediatric ICUs and that children are likely cared for by a variety of providers [5, 6]. A further discussion of defining resource-limited intensive care is forthcoming in this series.

The need for these recommendations is underlined by the surprising results from one large randomized controlled trial on fluid therapy in African children [7], suggesting that not all evidence for benefit in resource-rich settings guarantees benefit in resource-limited settings. Whether these different results are due to variability in the care provided, the patients’ physiology or comorbidities, or altered pathogens remains unknown and deserves further research. These recommendations are not intended to be incorporated as a bundle or as formal guidelines, given the variability in resources available to care for critically ill children, even within countries, and the overall quality of the evidence base.

An international team of physicians with extensive clinical experience in resource-rich and resource-limited ICUs and systematic review methodology was formed under the auspices of the European Society of Intensive Care Medicine’s Global Intensive Care Working Group and mandated with the task of evaluating the evidence for pediatric sepsis and septic shock in ICUs in resource-limited settings. The subgroup members formulated eight clearly defined questions following the principles of the GRADE process [2]. Quality of evidence was scored from high (grade A), moderate (B), low (C), or very low (D) and recommendations as strong (1) or weak (2). The factors influencing this classification are presented in the online supplement Table 1, with major attention given to several other contextual factors relevant to delivery of care in resource-limited settings, such as the availability, affordability, feasibility and safety of care interventions in resource-limited ICUs. A strong recommendation was worded as “we recommend” and a weak recommendation as “we suggest”. One recommendation remained “ungraded” (UG) as it was not conducive to the process described above. A full explanation of methodology, group composition and selection, and overview of findings is available in the online supplement, as well as a complete list of relevant articles.

Results and recommendations

Key recommendations are provided in Table 1 and more detailed scoring details are available in the online supplement. A major challenge is early identification of children who are critically ill. The most important interventions to reduce sepsis morbidity and mortality must be made generically, often before the definitive diagnosis. Rapidly identifying which children have evidence of organ dysfunction or impaired circulation due to infections is vital. We recommend that severely ill children in ICUs with signs of infection be identified through observing for a combination of danger signs of end-organ dysfunction or impaired circulation. More studies are required to determine better definitions and scoring systems for risk stratification in these settings.

Table 1 Recommendations and suggestions on pediatric sepsis or septic shock management in resource-limited settings (with grading)
Full size table

We recognize that rapid vascular access is critical and usually a rate-limiting step in the early resuscitation of children. We suggest that in children with septic shock in resource-limited settings, the placement of an intraosseous line can be considered for vascular access after a short period of time for intravenous access attempts. Further studies are required to document its role in resource-limited settings, including maintaining training of practitioners.

We recommend a very careful and individualized approach to fluid administration in children with sepsis in ICUs in resource-limited settings. For children with severe acute malnutrition without signs of severe shock, we do suggest against rapid intravenous fluid administration. Children with severe acute malnutrition and signs of septic shock have very high levels of baseline mortality, and we suggest careful administration of intravenous fluids at an initial rate of 10–15 ml/kg/h [4]. For well-nourished children who do not have evidence of severely impaired circulation (see online supplement), we recommend administration of maintenance fluids only. For well-nourished children who have evidence of severely impaired circulation, we suggest very careful administration of 10–15 ml/kg of crystalloids over 30–60 min. This may be repeated if the shock is persistent and there are no signs of fluid overload, with careful titration following repeated observations. We could not make a recommendation regarding incorporating early goal-directed therapy for children with septic shock in resource-limited settings. Further studies are urgently required to clarify the definitions of septic shock in children in resource-limited settings.

We recommend incorporation of quality assurance protocols for timely antibiotic administration, oxygen and respiratory support, and fluid management protocols into resource-limited settings for the management of pediatric sepsis. We also recommend transfusing children with severe anemia and malaria only if there are signs such as respiratory distress or shock. Children in resource-limited settings with severe respiratory distress and hypoxemia from sepsis could benefit from bubble continuous positive airway pressure (CPAP). Research is needed to clarify the upper age limit for effectiveness of bubble CPAP and to clarify the role of high-flow nasal cannula. Finally, we recommend using a tidal volume of 5–8 ml/kg predicted body weight in all mechanically ventilated children with sepsis-induced lung injury, but further research is urgently needed to better define the management of pediatrics ARDS in resource-limited settings.

Conclusion

Most of the available evidence is from resource-rich settings, suggesting an urgent need for further studies in resource-limited settings. We present a set of recommendations, based upon varying degrees of evidence, that can be adapted to specific circumstances and resources available and can form the basis of a research agenda in this rapidly changing field. These recommendations are in line with existing recommendations from the WHO and SSC, which are focused on different contexts.