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“APPLICATION OF SNAP II (SCORE FOR NEONATAL ACUTE PHYSIOLOGY II) IN NEONATAL SEPSIS TO PREDICT MORTALITY AND ORGAN DYSFUNCTION” Authors: Dr. Kulkarni Anagha , Dr. Verma A., Dr. Chandanwale A., Dr. Rajput U, Dr. Kulkarni R, Dr. Valvi C., Dr. Khadse S., Dr. Kinikar A Dept. of Paediatrics BJGMC and SGH, Pune

INTRODUCTION • The case fatality rate of sepsis among neonates ranges between 25% to 65% in India (1)(2) . • SNAP II (Score for Neonatal Acute Physiology II) is a system of assessment for the most important physiological variables affecting mortality. • SNAP II includes mean arterial pressure, urine output, blood pH, hypothermia, hypoxia and multiple seizures and helps predicting outcomes.

• Predicting the outcome of neonates is an important step in reducing the morbidity and mortality by initiating appropriate steps earlier. • Hence this study was undertaken to study the correlation of ‘Score for Neonatal Acute Physiology II’ (SNAP II) with outcome.

AIMS & OBJECTIVES • Primary: To study the correlation of ‘Score for Neonatal Acute Physiology II’ (SNAP II) applied within 12 hours from the onset of neonatal sepsis, with outcome, in the form of survival, mortality and organ dysfunction. • Secondary: To study the sensitivity, specificity, positive predictive value, negative predictive value of SNAP II in relation to mortality and organ dysfunction.

MATERIALS AND METHODS • Study design : Hospital based Observational study • Study type : Prospective study • Study setting : New born care unit, tertiary care centre • Duration : September 2014 to June 2016 • Sample size : 157

• Study Population: All inborn and outborn babies admitted to NICU and fulfilling the inclusion criteria. • Selection of Cases (Inclusion & Exclusion Criteria) Inclusion : Neonates diagnosed to have sepsis and not received antibiotics at all, or, if referred from outside hospital, then not received antibiotics for more that 2 days. Exclusion : 1. Neonates with major congenital malformations, severe asphyxia, prior blood products and post-operative surgical cases were excluded. 2. Outborn babies who have received antibiotics for more than 2 days

METHODOLOGY • Informed consent and assent was taken as necessary. • Ethical approval of the study protocol was obtained from the Institutional Ethics Committee (IEC). • All parents or caretakers were Counselled as per the standard hospital protocol and individual queries were answered separately.

• They were provided with the detailed information regarding neonatal sepsis and need for enrollment in this study and also they were provided information about the laboratory methods and study protocol that was to be employed for Septic screening. • Sepsis was diagnosed according to standard clinical and laboratory criteria. • Neonates were enrolled according to inclusion criteria and SNAPII was calculated within 12 hours after enrollment.

• All demographic details were recorded according to a pre- designed proforma. • All neonates were followed up until remission of organ dysfunction or death, whichever was earlier, up to a maximum of 14 days • Outcome was found as correlation of SNAP II score with death and morbidity in the form of organ dysfunction

• Positive predictive value, negative predictive value, sensitivity and specificity of each was found out by appropriate statistical tests and area under the curve. • Data analysis was done by using SPSS version 20:0 • P-value was calculated using chi-square test on numerical data.

SNAP II score

RESULTS • Out of 157 neonates, 90(57.3%) survived, 25(15.9%) had organ dysfunction and 42(26.8%) died. Outcome 27% Survived Organ Dysfunction 57% Death 16%

• In our study we found that 95(60.5%) of neonates had mild score, 44(28%) had moderate score and 18(11.5%) had severe SNAPII score. SNAP II severity 11% Mild Moderate 28% 61% Severe

Table no 1: Comparison of outcome and severity of SNAP II SNAP II Death Organ Alive(n), ( Total P-value score (n), (%) dysfunctio %) number, category n (n)(%) (%) Mild (1-20) 09(21.4%) 16 (64.0%) 70 (77.8%) 95 (60.5%) Moderate 15(35.7%) 09 (36.0%) 20 (22.2%) 44 (28.0%) **<0.001 (21-40) Severe 18(42.9%) 0 0 18 (11.5%) (>40) Total 42 26.8%) 25 (15.9%) 90 (57.3%) 157 (100.0%)

• Neonates with SNAPII mild (1-20) survived while severe (>40) died. • The sensitivity, specificity, PPV, NPV of SNAP II was 42.8%, 100%, 100% and 82.3% respectively with mortality. • From the ROC curve for SNAPII score and organ dysfunction it was found that area under the ROC curve= 0.553 ( 95% Confidence interval (CI) = 0.457 to 0.645),with sensitivity of 28% (95%CI 12.1- 49.4),and specificity of 85.6% (95%CI 76.6- 92.1) • From the ROC curve for SNAPII score and death it was found that area under the ROC curve = 0.726 (95% Confidence interval = 0.641 to 0.800) with sensitivity of 78.6 (CI 95%63.2- 89.7) With specificity of 56.7 (CI 95%45.8- 67.1)

Table No 2: Comparison of different parameters of SNAP II with outcome Parameters Survival Death Organ dysfunction(n=25) P-value (n=90) (n=42) MAP ≤ 29 mmHg 03 29 08 **<0.001 Lowest blood pH (<7.20) 25 28 013 0.0002 PaO2/FiO2 ratio (<2.50) 22 20 04 0.0188 Urine output (<1 04 15 03 **<0.001 mL/kg/hr) Lowest 05 10 04 0.0244 temperature(35.6ºC) Multiple seizures 25 12 08 0.9821

• In the above table we found that five the parameters related to circulatory failure had attained statistical significance p<0.05 and majority of neonates were associated with death as the outcome. • However, multiple seizures were found in 25 neonates who survived, 8 neonates who had organ dysfunction and 12 neonates who died, but still the multiple seizures parameter did not have statistical significance

DISCUSSION • A total of 157 patients were enrolled out of 1984 total admissions in NICU between September 2014 and June 2016 who met inclusion criteria for sepsis. • Out of 157 neonates 60.5% had mild illness [SNAPII=1-20], moderate illness in 28% [SNAP II=21-40] and severe illness in 11.5% [SNAP II>40]. • Similar observations were present In the study by Helal et al ., 57.7% neonates had mild illness [SNAPII=1-20],27.5% had moderate illness [SNAP II=21-40] and 14.8% had severe illness [SNAP II>40]. (3)

• In this study, SNAPII of the neonates who survived was less than the neonates who expired. • The mean SNAP II score of neonates who survived was 10.71 ± 9.417 and that of neonates who expired was 21.93 ± 15.422 , mean SNAPII score for organ dysfunction was 13.20 ± 11.698, • A study done by Maiya et al., on SNAP score to predict mortality reported the mean SNAP in neonates who survived versus who died as 4.88 vs 17.38 ( P <0.001). (4)

• In the present study, the median value for survival was 5(IQR 5- 19), median value for organ dysfunction was 10(IQR 5-23) and median value for death was 20(IQR9-20.75). The median value of death was more when compared to survival and organ dysfunction (20 IQR 9-20.5 vs 5 IQR5-19) with p value <0.001. Similarly, in a study done by Helal et al ., (3) the median score for • death was higher than survival. [median (IQR) 43 (36-53.5) vs . 18 (16-37),respectively; p <0.001]. In the study done by Helal et al ., (3) the area under the (ROC) • curve for SNAP II and death was 0.699 (95% CI 0.58- 0.818),had sensitivity for death was 29.6%( CI 95%11.2- 48.0),specificity was 92.5% (95%CI 85.1-99.8), which is similar to our study.

CONCLUSION • SNAP II ≥ 40 can predict organ dysfunction and death when applied on admission to neonates with sepsis. • Higher the SNAPII score, higher are the chances of death and organ dysfunction. • However the ROC curve for SNAPII score and death is more predictive in correlation to ROC curve for SNAPII score and organ dysfunction. • Mean arterial pressure, acidosis, decreased urine output, low PaO 2 /FiO 2 , Hypothermia were significantly associated with death as well as organ dysfunction.

REFERENCES 1. Bangi VB, Devi Ss. Neonatal sepsis: A risk approach. J Dr NTR Univ Heal Sci. 2014; 2. R. K, Manjunath S, Doddabasappa P, J. M. Evaluation of screening of neonatal sepsis. Int J Contemp Pediatr. 2018; 3. Helal NF. Can the Score for Neonatal Acute Physiology II (SNAPII) Predict Morbidity and Mortality in Neonates with Sepsis? J Neonatal Biol. 2013; 4. Maiya PP, Nagashree S, Shaik MS. Role of score for neonatal acute physiology (SNAP) in predicting neonatal mortality. Indian J Pediatr. 2001; 5. Sundaram V, Dutta S, Ahluwalia J, Narang A. Score for neonatal acute physiology II predicts mortality and persistent organ dysfunction in neonates with severe septicemia. Indian Pediatr. 2009;

ACKNOWLEDGEMENTS • Dr. Ajay Chandanwale, Dean, B.J. Medical College and Sassoon General Hospital,Pune. • Dr. Aarti Kinikar, Head of Department of Paediatrics, BJGMC, Pune