International Perspective on a Revised Pediatric Sepsis Definition

Pediatric sepsis was most recently defined by the International Pediatric Sepsis Consensus Conference (IPSCC) in 2005 to standardize an operational definition of sepsis primarily to aid investigational and epidemiologic studies.¹ However, this definition was fraught with challenges from its inception, including being informed by an incomplete understanding of sepsis pathobiology and a lack of a gold standard for validation. Additionally, implementation of the IPSCC sepsis definition in resource-limited environments was not considered, leading to inconsistent application of the definition both clinically and epidemiologically.²

After the 2016 release of the adult Consensus Definitions for Sepsis and Septic Shock (Sepsis-3),³ the Society of Critical Care Medicine organized the Pediatric Sepsis Definition Taskforce to systematically evaluate deficiencies in the current pediatric sepsis definitions and develop a revised, data-driven definition.⁴ The Taskforce began with a systematic review and metanalysis to characterize demographic, clinical, laboratory, and illness severity associations with the IPSCC sepsis definition.⁵ Next, recognizing the impact of resource constraints on the implementation of a revised sepsis definition, the Taskforce performed an international survey to (1) characterize current diagnostic practices for sepsis in children across a wide range of national economies and health care settings and (2) poll which updated definition of sepsis would be most clinically useful moving forward. Results of both studies are anticipated to inform the development and deployment of a new, more specific pediatric sepsis definition accessible to the global pediatric health care community.

In this issue of Pediatrics, Morin et al⁶ report the results of the international survey by the Pediatric Sepsis Definition Taskforce. Of the 2835 respondents, most were physicians who care for children in emergency departments, hospital wards, or critical care settings. Over 60% of respondents were from Asia or South America, whereas only 2.8% were from Africa and 2.7% from Oceania. Despite this geographic representation, only 14.1% of respondents were from low- or low-middle-income countries.

Consistent with the IPSCC definition, over 80% of respondents said they recognize sepsis in children by vital sign derangements and laboratory evidence of systemic inflammation in the presence of a suspected or confirmed infection. ∼95% of respondents defined pediatric septic shock as infection-induced organ dysfunction or need for cardiovascular support, aligning with the IPSCC definitions for severe sepsis and septic shock, respectively. Morin et al⁶ also report that although the IPSCC definition was perceived as slightly more useful for the recognition of pediatric sepsis, the Sepsis-3 definition, which has not been validated for use in children, was perceived as more useful for research, benchmarking, and prognostication purposes.

The revised sepsis definition that received the highest level of agreement was sepsis as a life-threatening infection with dysfunction of organ(s) remote from the site of primary infection. Although speculative, this response was most likely informed by Sepsis-3. It is clear, although implicit, from the survey responses that although most pediatric clinicians diagnose sepsis using the IPSCC diagnostic criteria, in principle they consider sepsis to be an infectious-mediated, life-threatening alteration in a child’s physiology and not merely infection plus systemic inflammation. Discovery of organ injury remote from the site of primary infection is a novel descriptor not encountered in the Sepsis-3 definition and will be helpful in distinguishing infection-mediated primary organ injury from secondary organ dysfunction related to the “dysregulated host response to infection.”³

Most respondents agreed that organ injury remote from the primary infection site should be required to make the diagnosis of sepsis in children, suggesting that incorporation of this criterion into the next pediatric sepsis definition would be well-received globally. It also logically follows that organ dysfunction as a requisite criterion for the diagnosis of pediatric sepsis would make the IPSCC category of severe sepsis superfluous. Further, adoption of this sepsis definition would more closely align pediatric terminology with that used in adults, which has the benefit of harmonizing adult and pediatric nomenclature for future research and epidemiologic studies.

Adoption of a Sepsis-3-like definition for pediatric sepsis carries the risk of improving criteria specificity at the expense of sensitivity.² Although a more accurate sepsis definition could theoretically improve resource allocation to those children most likely to benefit from aggressive treatments, early markers may be overlooked and the opportunity to avert life-threatening organ dysfunction missed. To this point, Morin et al⁶ propose a “both/and” approach using a tiered strategy for sepsis recognition similar to Sepsis-3. They suggest that a more specific pediatric sepsis definition be derived and validated first. Then, a highly sensitive screening tool should be validated to facilitate early identification of children who should undergo more definitive testing and closer observation. In this way, overburdened medical systems may be able to more appropriately triage children and allocate their limited resources.

In truth, the pursuit of a singular, precise definition of pediatric sepsis may be unrealistic. Sepsis is a heterogeneous disease process with a spectrum of phenotypes and outcome profiles,^7,8 making it difficult to crystalize operational criteria that discriminates with high specificity. As Morin et al⁶ demonstrate, resource limitations in various health care settings add additional constraints to the implementation of a refined sepsis definition. However, the pediatric health care community should not let perfection be the enemy of the good. Even incremental improvements in pediatric sepsis criteria can lead to substantial progress in childhood research and health care delivery.

Glossary

IPSCC

International Pediatric Sepsis Consensus Conference