Comparison of Pediatric Sequential Organ Failure Assessment and Pediatric Risk of Mortality III Score as Mortality Prediction in Pediatric Intensive Care Unit

Objective: To assess and compare the diagnostic accuracy of the Pediatric Risk of Mortality (PRISM) III score and Pediatric Sequential Organ Failure Assessment (p-SOFA) for the prediction of mortality in critically ill children. Methodology: This was a cross-validation study conducted at the Pediatric Intensive Care Unit (PICU) of the National Institute of Child Health Karachi from February 2021 to July 2021. Two hundred eighty-six critically ill children of age one month to 15 years of either gender staying in PICU for more than 24 hours were included. Within 24 hours of admission, the p-SOFA and PRISM III 24 scores were calculated for all eligible children. The outcome of the study was mortality within 30 days of PICU admitted children. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 23. Results: The median age was 24 months (range: 1-144 months). The 30-day mortality was estimated as 57%. The p-SOFA and PRISM scores were significantly greater in children who did not survive than survivors. The maximum p-SOFA score (area under the curve (AUC)=0.81, 95% CI=0.76-0.86, p=0.001) and PRISM III 24 score (AUC=0.75, 95% CI=0.69-0.81, p=0.001) had good discrimination for 30-day mortality. For the prediction of 30-day mortality at the cut-off value of p-SOFA>2, the sensitivity was 93.87%, specificity was 38.21%, and accuracy was 69.93%. Whereas at the cut-off value of PRISM III 24 score>8, the sensitivity was 55.83%, specificity was 77.24%, and accuracy was 65.03%. Conclusion: The p-SOFA score is a good predictor for 30-day mortality in critically ill children and had better accuracy than the PRISM III 24 score.


Introduction
The pediatric intensive care unit (PICU) plays an important role in delivering demanding and required care to seriously ill children. In both developing and developed countries, PICU children have a considerably higher risk of morbidity and death [1,2]. Quality and quantities of PICUs are improving in developing countries like Pakistan, but it is an uphill process, as the units need modern, expensive equipment and a large highly trained staff. So there is a need for time to employ methods, techniques, and scoring systems that are predictive of mortality and morbidity risk in these patients, thus allowing these systems to assist in timely and focused decisions regarding the deployment of different expertise and resources, to produce highly productive results [3,4].
Several prognostic scoring systems like Pediatric Index of Mortality (PIM and PIM2), Pediatric Risk of Mortality (PRISM, PRISM III), Sequential Organ Failure Assessment (SOFA), Pediatric Sequential Organ Failure Assessment Score (p-SOFA), and the Paediatric Logistic Organ Dysfunction (PELOD) score have been developed to predict PICU children's morbidity and death, which can be extremely helpful in treatment planning [1,2,[5][6][7][8][9]. The PRISM III 24 score is a commonly used system that is used to evaluate various scoring systems. PRISM III 24 score helps us in predicting institutional performance [10,11]. Models like the PRISM III 24 score provide one of the best ways to organize an intensive care unit. PRISM III 24 score takes 24 hours to complete and cannot be used in regulating admissions to the PICU but only to assess illness severity and length of stay [3,12]. The p-SOFA has been developed recently and so far only validated retrospectively in critically ill children [13,14]. Whereas only a few studies have been conducted for validation of p-SOFA and PRISM III in developing countries like Pakistan. An ideal scoring system would be accurate, easy to use, and simple, as well as minimally intrusive and low-cost. However, no scoring system is flawless, and each one has its own set of limitations, which is why studies are being conducted to enhance accuracy, verify existing ones, and develop new ones [15,16]. Therefore, the aim of our study was to assess and compare the diagnostic accuracy of the PRISM III and the p-SOFA for the prediction of mortality in critically ill children.

Materials And Methods
From February to July 2021, cross-validation research was done in the PICU of the National Institute of Child Health (NICH) in Karachi. This study was carried out with the approval of NICH Karachi's Institutional Ethical Review Board, approval number 42/2020, and with the signed informed consent of the children's parents. The sample size was calculated using the diagnostic accuracy sample size calculator by Dr. Lin Naing, with PRISM sensitivity of 70.6%, specificity of 82.3%, a margin of error of 5.2%, 30-day mortality prevalence of 28.1%, and a confidence level of 95%. The sample size was calculated to be 286 [2]. A nonprobability consecutive sampling approach was used to include critically ill children aged one month to 15 years of either gender who had been in the PICU for more than 24 hours. Patients with an underlying congenital deformity who were hospitalized for routine treatment before planned procedures such as intravenous immunoglobulin (IVIG) and hemodialysis, cardiopulmonary resuscitation (CPR) before admission, and children who died within 12 hours of admission were excluded from the research. Within 24 hours of admission, the p-SOFA score was calculated for all eligible children. p-SOFA score of higher than 2 is considered as a predictor of mortality. We calculated PRISM III score within 24 hours after admission, in addition to p-SOFA. A score of higher than 8 on the PRISM III 24 was deemed a predictor of mortality. On a pre-designed proforma, demographic data such as age, weight, type of admission (clinical or medical cases and surgical (post-surgical recovery cases)), length of stay in PICU, need for ventilator support, and inotropic support was also noted by the researcher himself. All of the children were followed up from admission till discharged from the PICU. Mortality within 30 days was the outcome of the study.
After collecting data the analyses were conducted by using Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, USA). We presented our numeric data with median and range as they were non-normally distributed. We presented our categorical variables with frequencies and percentages. We compared numeric data with the Mann-Whitney U test and categorical data with the chi-square test to assess the association with mortality. PRISM III 24 and p-SOFA scores were categorized according to the 25th, 50th, and 75th percentiles of these scores. Comparison between categories of PRISM III 24 score and p-SOFA with 30-day mortality were done using Pearson's chi-square test. Two by two tables were used to calculate the specificity (Sp), sensitivity (Sn), negative predictive value (NPV), positive predictive value (PPV), and accuracy of PRISM III 24 and p-SOFA scores by taking 30-day mortality as the gold standard. Spearmen's correlation was applied to assess the relationship between the duration of PICU stay and both scores (PRISM III 24 score and p-SOFA score). A p-value of ≤0.05 was taken as statistically significant.

Results
We included 286 children in the study. The median age was 24 months (range: 1-144 months). The 30-day mortality was estimated as 57%. The median age of 163 non-survivors was 24 months (range: 2-144 months).   Table 1). We next divided the children into three groups based on the p-SOFA score's 25th, 50th, and 75th percentiles, and found that the frequency of death increased substantially with the p-SOFA score (p=0.001) ( Figure 1). We found that PRISM III 24 score was significantly greater in children who did not survive than survivors (10 [range: 0-29] vs 3 [range: 0-20]; p=0.0001; Table 1). We further grouped children based on the 25th, 50th, and 75th percentiles of the PRISM III 24 score, we observed that frequency of mortality increased significantly with the PRISM III 24 score (p=0.001) (Figure 2).    We observed that the p-SOFA score was positively associated with the PRISM III 24 score (r=0.712, p=0.001).
No statistically significant correlation was found between PRISM III 24 score and duration of stay as well as between p-SOFA score and duration of hospital stay ( Table 3).

Discussion
In the PICU, scoring systems help healthcare managers determine a patient's prognosis and improve the decision-making process as well as the patient's outcome [9,17]. In a country like Pakistan, where tertiary care institutions are few, the outcome of PICU estimates the most effective use of limited resources and helps guide policy formation [3]. The use of scoring systems to predict PICU outcomes can also aid in prompt intervention [18]. However, developing the optimal scoring method for critically ill children admitted to the PICU remains a challenging task [19]. Although these scoring systems are effective in ICUs all over the world, it is important to evaluate them before using them in healthcare settings that are very different from where they were established [3,20,21]. Until now, the validation of the p-SOFA and PRISM III 24 scoring systems in Pakistani PICUs has not been extensively examined. Therefore, in this study, we evaluated the validity of the PRISM III 24 score and the p-SOFA score for predicting 30-day death in 286 critically ill children admitted to the PICU at a tertiary care hospital in Karachi. The 30-day death rate was predicted to be 57% in the current study, with the median age of non-survivors being 24 months. The higher number of clinical cases (92%) admitted to PICU might be the reason for the higher mortality rate. Similarly, in a Pakistani study, Quershi et al. [4] discovered that the median age of PICU children was 18 months and that the death rate was 28.7%, which was also higher than mortality rates documented by other validation studies. In addition, they also had a larger percentage of non-surgical patients (86%) in their research. Similarly, in an Indian study of 75 PICU children, Kumbar et al. discovered that 37.3% of the children died. They also discovered that older children (aged >15 years) had a greater death rate, whereas younger children had a higher survival rate. They did not, however, find a statistically significant association between age and death (p=0.513) [18].
In the current study, p-SOFA and PRISM III 24 scores at the time of admission to the PICU were found to be good predictors of death within 30 days. The probability of mortality increased in a stepwise way from smaller to larger p-SOFA and PRISM III 24 scores across patient sub-categories, with survivors having a significantly lower median p-SOFA and PRISM III 24 scores than non-survivors. Furthermore, the AUC value of 0.81 for the prediction of 30-day mortality was good for the p-SOFA score. This finding is comparable to that of El-Mashad et al., who reported a good AUC of 0.89 for the prediction of 30-day death in PICU children using the p-SOFA score [2]. Similarly, Matics et al. discovered a good AUC of 0.88 for the prediction of 30-day death in PICU infants using SOFA score in their investigation [14]. The PRISM III 24 score, on the other hand, had a lower AUC value of 0.75 for predicting 30-day mortality than the p-SOFA AUC value in the current investigation, according to ROC curve analysis [14]. Similarly, El-Mashad et al. also found that the SOFA score had a higher AUC than the PRISM score for the prediction of 30-day mortality (0.89 vs 0.84) in PICU children [2]. Another study by Zhou et al. also found that p-SOFA had higher predictive accuracy for the prognosis of PICU children with severe illness than PRISM III [22]. Lalitha et al. also found that p-SOFA had good accuracy (AUC=0.84) as compared to PRISM III (AUC=0.70) for the prediction of mortality [23]. In this study, we used >8 and >2 as the optimum PRISM III 24 and p-SOFA cut-off values for the prediction of 30day mortality. We found that p-SOFA (>2) had a greater sensitivity than PRISM III 24 (>8) (94% vs. 56%), while p-SOFA (>2) had a lower specificity than PRISM III 24 (>8) (38.2% vs 77.2%). Furthermore, p-SOFA (>2) had somewhat better accuracy than PRISM III 24 (>8) (70% vs 65%). El-Mashad et al. also discovered that the SOFA is more accurate than the PRISM score in predicting death in PICU children. They discovered that a SOFA score of more than 2 predicted death in 40% of PICU patients with 100% sensitivity and 5.2% specificity. At higher cut-off values of scoring systems for the prediction of 30-day mortality, they found p-SOFA score (cut-off >6.5) had sensitivity as 80.9% and specificity as 81.8%, whereas PRISM score (cut-off >17.2) had sensitivity as 70.6% and specificity as 82.3% [2]. We also found a positive correlation between the p-SOFA and PRISM III 24 score in PICU admitted children (r=0.712). El-Mashad et al. also revealed that the p-SOFA score was positively correlated with the PRISM score (r=0.59) [2].
Apart from the fact that p-SOFA was a better predictor of 30-day death among critically ill children than PRISM III in our study, the p-SOFA score offers other advantages over PRISM III. p-SOFA is free of cost and does not require the use of a calculator. p-SOFA has fewer calculation parameters than the PRISM III 24 score. p-SOFA is computed every day, providing a dynamic assessment of the progression of the disease, whereas PRISM is performed only at the time of admission. Because it is tailored to oxygen saturation (SPO2) values rather than partial pressure of oxygen (PaO2) readings, the p-SOFA does not need arterial blood gas analysis, which can be difficult to acquire in children [6,[23][24][25]. With limited resources, there are just a few tertiary care referral institutions for pediatric admission in Pakistan. In such circumstances, p-SOFA can be used to determine which patients require critical care and can also aid in predicting the patients' prognosis. There are several limitations to our research study. All the data was collected from a single PICU, in comparison to other validation studies, the present study's sample size was relatively small. More studies with a larger sample size are required in the future to improve the accuracy of results.

Conclusions
Mortality among the children admitted to critical care units is high despite the use of advanced equipment and sophisticated techniques. p-SOFA and PRISM III 24 both have proven to be valuable in objective prediction in these patients. In this study, we compared the diagnostic accuracy of the Pediatric Risk of Mortality (PRISM) III score and Pediatric Sequential Organ Failure Assessment (p-SOFA) for the prediction of mortality in critically ill children and showed that the p-SOFA score is a good predictor for 30-day mortality in critically ill children with better accuracy than the PRISM III 24 score.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethical Review Board National Institute of Child Health Karachi-75510 issued approval 42/2020. This is to inform you that the Ethical Review Committee of NICH has approved the study and permission is granted. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.