The study flow is depicted in figure I. The mean maternal age was 25.5 ± 4.9 years. 34 (47.2%) of the mothers were primigravida. Pregnancy induced hypertension (PIH) and eclampsia were seen in 14 (19.4%) and eight (11.1%) mothers, respectively. Premature rupture of membranes was present in 29 (40.2%) cases. Mode of delivery was caesarean section in 42 (58.3%) patients.
Seven (9.7%) babies were more than 37 weeks of gestation, 34 (47.2%) babies between 32 to 36 weeks of gestation and 31 (43%) babies were less than 32 weeks of gestation. Of the 93 events of sepsis, seven were recorded in term neonates and 86 were recorded in preterm neonates. Mean PI at enrollment was 0.92 and 0.96 in term and preterm neonates, respectively. (Table I)
According to NeoKISS criteria, clinical sepsis was present in 77 (82.7%), non-coagulase negative Staphylococcus (CONS) sepsis in 12 (12.9%) and CONS sepsis in 4 (4.3%) of the events. In the no CONS group, blood culture showed Acinetobacter in 4 events, Klebsiella in 3 events, E. coli and methicillin-resistant Staphylococcus aureus (MRSA) in 1 event each and culture positive meningitis in 4 events (Enterococcus in 3 events and E. coli in 1 event).
Among the clinical parameters, new or more frequent apnea was most frequently encountered, that is, in 38(41%) events. This was followed by prolonged capillary filling time in 31(33.3%) events, heart rate variability in 26 (28%) events, temperature instability in 21 (22.6%) events, unexplained metabolic acidosis in 5(5.4%) events and new onset hyperglycemia in 4 (4.3%) events. Other signs of blood stream infection were seen in 65 (70%) of events.
Sepsis screen positivity, as defined by CRP of > 10 mg/dl, TLC of less than 5000/mm3 or ANC abnormal as per Manroe [20] and Mouzinho [21] charts, was seen in 70 (75.2%) of clinical events with median value of CRP being 27 mg/L (IQR 12–73), TLC being 11450/µL (IQR 5900–18250) and ANC being 5541/µL (IQR 2370–9708). Meningitis was present in 13 (13.9%) events. 4 events were associated with culture positive meningitis. Taking 0.88 cut off for preterm babies and 1.24 for term babies, in 67 (72%) events perfusion index was below the cut-offs prior to clinical detection of sepsis. The median time difference between detection of sepsis with fall in perfusion index as compared to clinical sepsis was 268 minutes (IQR 120–459) or 4.5 hours (IQR 0.25–22.4). (Table II)
Of the sixty-seven cases with low PI, 11 (12.3%) had negative sepsis screen while 56 (62.9%) cases had sepsis screen positive. Of the twenty-two cases where PI did not fall below the cut off, 15 (16.8 %) had positive sepsis screen while 7 (7.8%) had negative sepsis screen. Four cases, which were being treated for PDA at the time of detection of sepsis, were not included in analysis due to the possibility of PI being falsely high secondary to PDA.
The median PI in term babies at the time of sepsis came to be 1.5 which was same as median PI at admission, hence deferring its utility in diagnosing hospital acquired sepsis in term neonates. For detection of hospital acquired sepsis in preterm babies, PI showed a sensitivity of 89.47% (95% CI 78.48–96.04%), specificity of 56% (95% CI 34.93–75.60%), positive predictive value of 82.26% (95% CI 74.70–87.92%), and negative predictive value of 70% (95% CI 50.36–84.29%) in detection of sepsis in preterm neonates. The positive likelihood ratio of the test is 2.03 (95% CI 1.30 to 3.19) while the negative likelihood ratio is 0.19 (95% CI 0.08 to 0.43). The diagnostic accuracy of PI for diagnosis of sepsis is 79.27% (95% CI 68.89–87.43%). (Table III)
When the events associated with fall in PI and those in which PI did not fall before sepsis were compared, heart rate, respiratory rate and SNAPPE II scores at admission showed no significant difference in both the groups, however, the low PI group showed significantly lower values of temperature (p value = 0.0441) and PI (p value = 0.0048) at the time of admission to NICU. However, the median age at sepsis was 7 days or 268 hours and the median age at NICU admission was 8 hours, this seems to be a chance occurrence. (Table IV)
A one-way ANOVA was conducted to determine if there was any significant difference in the values of perfusion index 24 hours before sepsis, during sepsis and 24 hours after starting antibiotics. In both term and preterm neonates there was significant difference between the perfusion indices among three time periods (p < 0.001). The values of PI were significantly lower values in the sepsis period as compared to pre-sepsis period in both term (p < 0.05) and preterm (p < 0.05) neonates. In addition, preterm neonates showed significantly higher values of PI in the period 24 hours after starting antibiotics indicating positive response to starting treatment. The median value of PI during clinical sepsis in term and preterm neonates came out to be 1.5 (IQR 1.09–2.21) and 0.9 (IQR 0.58–1.5), respectively.
Amongst 72 neonates, 56 (77.7%) were discharged from the hospital, 7 (9.7%) took leave against medical advice, 1 (1.3%) was referred to higher center for surgical intervention and in 8 (11%) cases the outcome was death. The mean length of NICU stay was 24 (16.8) days and that of hospital stay was 41 (22.5) days.
The median enrolment PI of the babies who died was 0.65 (IQR 0.6–0.76, 95% CI 0.58–0.87) and those who survived was 0.8 (IQR 0.69–1.1, 95% CI 0.77–0.84) (p value = 0.0161) hence indicating that the babies with lower PI at the time of enrolment are predisposed to a poor outcome.
A positive association was seen between SNAPPE II score and duration of NICU stay, that is, higher SNAPPE II scores were associated with prolonged duration of NICU stay. (Correlation coefficient, r = 0.3774, p value = 0.0002)