Predictor Prognosis of Pediatric Septic Shock : Literature review

Introduction: The unpredictability of body response to organ dysfunction needs an effective tool to predict the prognosis of shock septic. Early recognition and treatment of septic shock improved prognosis and reduced mortality, especially in pediatrics. This review aimed to identify the predictor of mortality in pediatric septic shock. Methods: We performed a literature review of the predictor of mortality in pediatric septic shock conducted between 2015 and 2020 in ProQuest, Google Scholar, PubMed, and Science Direct. We used keywords (predictor or predictive) and (septic shock or septic), and (prognostic or prognosis) and (pediatric or children). The study selection was using the Preferred Reporting Items for Systematic Review and Meta-Analysis PRISMA framework. Results: 944 articles identified in ProQuest, 720 articles in Science Direct, 339 articles in Google Scholar, and 67 in Pubmed. Equally, the total articles were 2,070 articles, and there were 414 duplicates. After review of the complete texts was performed for 35 potential studies. In the full-text review, we excluded review articles (n = 3), different populations (n=8), and of poor quality (n = 20). Eventually, four papers were reviewed in this study. We found PELOD, PELOD-2, PIM, PIM 2, PIM 3, PMODS, PRISM, PRISM-III, PRISM-IV, and pSOFA as a predictor of sepsis in pediatrics. Conclusion: In conclusion, pSOFA is a more accurate screening result for estimating the risk of death by being 10 times more sensitive and specific. However, adding biomarkers to pSOFA will improve the accuracy of the predictor prognosis of pediatric sepsis.


INTRODUCTION
At the 2016 international meeting, the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) proposed a new definition of sepsis, with the term Sepsis-3 Singer et al., 2016). In the latest definition of sepsis, it is explained that sepsis is a lifethreatening organ dysfunction caused by dysregulation of the body's response to infection.
Sepsis is one of the most common causes of death in pediatric intensive care units (PICU), and its incidence has more than doubled over a decade (Kumar et al., 2011). Understanding the pathophysiology of sepsis has changed dramatically in recent decades with the development of new diagnostic predictions and strategies to treat this complex disease, but sepsis remains one of the leading causes of death in childhood (Dellinger et al., 2013;Levy et al., 2018).
Hospital mortality due to sepsis in children is 25% in both developed and developing countries. about 67% of patients develop multiorgan dysfunction when sepsis is recognized, with 30% progressing to progressive multiorgan dysfunction. Unfortunately, 17% had a moderate disability due to sepsis survivors (Weiss et al., 2015). Severe sepsis and septic shock are one of the main causes of morbidity and mortality (60%) of children admitted to the pediatric intensive care unit (IDAI, 2016). Sepsis is caused by death worldwide in the pediatric population that estimated 7.5 million deaths each year (Hartman et al., 2013;Mangia et al., 2009;Weiss et al., 2015).
The validity of sepsis criteria is still debated in the literature, it was caused by a lack of information on the validity and predictive accuracy of sepsis criteria for predicting mortality in critically children condition (Sun et al., 2022). Generally, the sepsis predictor was SOFA score .
However, SOFA score was not adapted for children (Nieves Ortega et al., 2019).

DISCUSSION
This review aimed to evaluate the predictive validity of the predictor mortality in children with sepsis.
Generally, the sepsis predictor was SOFA score . However, the SOFA score is not adapted for children (Nieves Ortega et al., 2019). showed the weakest predictor of death of all tested scores and was significantly weaker than PRISM III, PIM, PIM 2 and PELOD 2. In addition, the predictive ability of the scores PRISM IV and PELOD is as also poor, although with a slightly higher AUC. The most recent PRISM IV and PIM 3 scores did not show improvement in predicting mortality (Niederwanger et al., 2020).
Of the many tools for assessing sepsis severity, PIM 2 was assessed within 1 hour of admission, did not require extensive laboratory testing and is unaffected by subsequent intervention since it is scored within 1 hour of admission resulting in early Notes. AUROC Score ranges in value from 0 to 1. A model whose predictions are 100% wrong has an AUC of 0.0; one whose predictions are 100% correct has an AUC of 1.0.
identification of the severity of illness and stratification of children for necessary intervention, thereby helping in counseling caregivers of sick children (Martha et al., 2005;Qureshi et al., 2007). A modified PIM 2 Score was no arterial blood gas analysis in PICU during the study period. The revised PIM 2 score unit increase doubled the risk of death. It showed that the score was sensitive to moral perception. This rating system had been validated and applied in many intensive care units worldwide (Teshager et al., 2020).
A study comparing PELOD-2 score of ≥ 11 and score ≥ 8 based on the consensus guidelines on the Indonesian Pediatric Association for the diagnosis and management of sepsis in children (Hadinegoro et al., 2016). Found that PELOD-2 score ≥ 8 lower prognostic value compared to other mortality predictors. Although it was not the best predictor of mortality, PELOD-2 score ≥ 8 was better than severe sepsis criteria based on diagnostic parameters. Both PELOD-2 scores of ≥ 11 and pSOFA scores had advantages in several diagnostic parameters (Teshager et al., 2020). Another study showed that The results showed that pSOFA and PELOD-2 were better than severe sepsis criteria to predict mortality.
But, the best sensitivity and specificity for PELOD-2 was using a cutpoint score of ≥ 8. A sensitivity of 88.1% and a specificity of 55.7% (Schlapbach et al., 2018).

Pediatric Sequential Organ Failure Assessment
(pSOFA) score is a tool adapted from SOFA in adults.
Adaptation used from 2 approaches. First, the cardiovascular and renal variables starting at age from the baseline SOFA score were using a validated cut-off from the PELOD-2 score system (Lalitha et al., 2020a;Leteurtre et al., 2013). Second, the respiratory variable was expanded to include the SpO2 : FiO2 ratio as an alternative to lung injury (Matics & Sanchez-Pinto, 2017). Pediatric SOFA score was shown in (Appendix 3).

Cardiovascular Criteria
Age-adjusted MAP cut-offs for the first score of the PELOD-2 cardiovascular criteria were used to assign a score of 1 in the pSOFA. Scores 2 to 4 remain the same as to the original SOFA criteria (Shime et al., 2017). Renal criteria Age-adjusted serum creatinine level cut-offs for the first score of the PELOD-2 renal criteria were used to assign a score of 1 in the pSOFA renal criteria. Scores 2 to 4 were modified by increasing the cut-off values for each score by the same factor as the original SOFA criteria, similar to the approach suggested by other authors (Shime et al., 2017). For this neonatal age group, the cutoff value increase for each score performed as the infant group (1-12 months) given the similarity in the glomerular filtration rate in both age groups (Schwartz et al., 1987).

Respiratory Criteria
The original PaO2:FiO2 ratio cut-off were kept identical to the original score, but the SpO2:FiO2 ratio was used as an alternative surrogate of lung injury.
The adaptation proposed by Khemani and colleagues were used to define the SpO2:FiO2 ratio cut-off (Matics & Sanchez-Pinto, 2017).

Coagulation, Hepatic, and Neurologic Criteria
The baseline coagulation and liver criteria were platelet counts and bilirubin level. Glasgow Coma Scale (GCS) criteria for the neurologic outcomes were also kept identical to the original score, but the pediatric version of the scale was used (Reilly et al., 1988). pSOFA score was performed in a similar way to the original SOFA score. The worst variable in each 24-hour period was used to assign a subscore for each system (ranging from 0-4 points). were not able to know the patient's condition directly.
Third, the limitation of our study include the small sample size, although some of the findings of our study may be generalizable to center with low mortality.

CONCLUSION
In conclusion, pediatric SOFA ( Severe sepsis criteria, PELOD-2, and pSOFA as predictors of mortality in critically ill children with sepsis. Paediatrica Indonesiana, 59 (6) The patients were divided into survivor group and nonsurvivor group according to the clinical outcome of 28 days after admission. The variables of pSOFA score, PELOD-2 score and P-MODS were collected and scored. Receiver operating characteristic (ROC) curve was plotted; the efficiency of the pSOFA score for predicting death was evaluated by the area under ROC curve (AUC).