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Applying Sepsis-3 Criteria for Septic Shock to Children-Not As Shocking As at First Sight?

In this issue of Pediatric Critical Care Medicine, Sankar et al (1) from the All India Institute of Medical Sciences in New Delhi, India, report on their findings when comparing the International Pediatric Sepsis Consensus Conference (IPSCC) criteria for septic shock (2) with the recent Sepsis-3 shock criteria (3). In their retrospective cohort of 216 children under 18 years old admitted to hospital and fulfilling IPSCC criteria, Sepsis-3 criteria for shock (triad of hypotension and vasopressors and lactate > 2 mmol/L) were met in only 48% of children. The in-hospital mortality of this cohort was 42%. Sepsis-3 shock criteria were designed to capture a phenotype of substantially higher severity and mortality resulting from profound disturbances in circulatory, cellular, and metabolic abnormalities (4). As expected, respiratory failure (hypoxemia and hypercarbia), and impaired oxygen delivery (low central venous oxygen saturations), were more common in the Sepsis-3 group. Similar to a previous ICU study from Australia and New Zealand (5), this translated to a trend toward higher mortality and higher severity including the proportion of children without shock reversal, development and extent of multiple organ failure, all of which were more common in the Sepsis-3 shock group. The authors highlight the risks of applying Sepsis-3 shock criteria to children, which would exclude a group of patients with a mortality of 40% in IPSCC “only” shock patients. The study by Sankar et al (1) carries a number of limitations related to the retrospective single-center design, small sample size, and a drop-out of 61 of 277 patients (22%) due to missing data. The proportion of microbiologically confirmed infections (3/216) is very low in comparison to cohorts from high-income countries (6), which may reflect the reality in some low-income settings where major comorbidities such as oncologic disease are less frequent and where access to microbiological diagnostics for bacterial and viral diseases is restricted. Two features pertinent to sepsis mortality are striking in this cohort: first, the Kaplan-Meier survival curves reveal that deaths after 30 days account for a third of mortality, although it is not clear how many patients were alive and if patients were followed-through post ICU and post hospital discharge. The high proportion of late death contrasts with the pattern of fulminant deaths reported in high-income settings (5, 7), and may be affected by the exclusion of deaths occurring within 6 hours of admission. Second, the authors report on a high proportion of deaths due to uncontrolled intracranial pressure, suggesting neurologic injury rather than shock represents the main cause of death, but do not provide details on the relationship between disease at presentation, cerebral pathology, and mode and type of death. Despite these issues, the study by Sankar et al (1) is extremely important as it brings data from a resourcelimited setting regarding the spectrum of children with septic shock seen in their practice (8), and provides information on features such as pathogens, clinical features at presentation and outcomes. The development of Sepsis-3 criteria in adults represented not only a paradigm change from defining clinical phenotypes by expert opinion to criteria derived from contemporary big data; but as well from emphasizing sensitive rapid clinician assessment toward more objective criteria characterizing patient groups at higher mortality with high specificity (9). The merits of this approach include objective measures of organ dysfunction facilitating operationalization, and standardization of data collections for the purposes of coding, research, and benchmarking. A number of recent studies applied age-specific modifications of sepsis-3 criteria for children, confirming the limitations of sepsis criteria based on systemic inflammatory response syndrome (10, 11). Yet, the distinct features characterizing septic shock in children have received less attention. Importantly, the work around development and validation of Sepsis-3 criteria was largely restricted to healthcare settings in high-income countries, which may not address the needs of lowand middle-income settings *See also p. e122.