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ORIGINAL ARTICLE
Year : 2022  |  Volume : 27  |  Issue : 6  |  Page : 677-683
 

Sepsis screening of neonatal abdominal surgery and its outcomes


1 Department of General Surgery, ANIIMS and G. B. Pant Hospital, Port Blair, Andaman and Nicobar Islands; Department of Paediatric Surgery, ABVIMS and Dr. RML Hospital, New Delhi, India
2 Department of Paediatric Surgery, ABVIMS and Dr. RML Hospital, New Delhi, India
3 Department of Anesthesiology, AIIMS, Deoghar, Jharkhand, India

Date of Submission21-Jan-2022
Date of Decision19-May-2022
Date of Acceptance18-Jun-2022
Date of Web Publication11-Nov-2022

Correspondence Address:
Ritesh Kumar
6/31, Type IV NG Quarters, Chakkargaon, Port Blair - 744 112, Andaman and Nicobar Islands
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaps.jiaps_16_22

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   Abstract 


Aim: The aim of this study was to evaluate the early indicators of sepsis (sepsis screening) and their statistical correlation with sepsis in neonatal abdominal surgery.
Materials and Methods: A prospective observational study was performed on thirty consecutive neonate cases aged between 0 and 28 days with surgical abdomen at the Paediatric Surgery Department, ABVIMS and Dr. Ram Manohar Lohia Hospital, New Delhi. The study duration was 18 months. Septic screening was done in all neonates on day 0, 1, 3, 7, and 14 days of surgery with serum procalcitonin, C-reactive protein, total leukocyte count, immature/total neutrophil ratio, and microerythrocyte sedimentation rate. A septic screening-positive patient (three or more positive parameters out of five) was correlated with sepsis and analysis was done.
Results: A total of 30 neonates of abdominal surgical cases were included consequently, out of which 56.7% (n = 17) were male and 43.3% (n = 13) were female. Maximum cases were of congenital diaphragmatic hernia 20% (n = 6) and then anorectal malformation 16.7% (n = 5). About 70% of neonates were sepsis screening positive. Fifty percentage of neonates were diagnosed to have sepsis on the clinical or laboratory findings, so sensitivity and specificity of sepsis screening were 93.33% and 40%, respectively. There was total 30% mortality in this study.
Conclusion: Sepsis screening is an early marker of sepsis, which can be used to help in early detection of neonatal surgical sepsis and timely intervention that can lead to decrease mortality and morbidity in neonatal surgery.


Keywords: C-reactive protein, neonatal sepsis, neonatal surgery, procalcitonin, sepsis screening


How to cite this article:
Kumar R, Addagatla R, Jaglan SK, Divya G, Jaju R, Debnath PR, Sen A, Shah S. Sepsis screening of neonatal abdominal surgery and its outcomes. J Indian Assoc Pediatr Surg 2022;27:677-83

How to cite this URL:
Kumar R, Addagatla R, Jaglan SK, Divya G, Jaju R, Debnath PR, Sen A, Shah S. Sepsis screening of neonatal abdominal surgery and its outcomes. J Indian Assoc Pediatr Surg [serial online] 2022 [cited 2022 Dec 7];27:677-83. Available from: https://www.jiaps.com/text.asp?2022/27/6/677/360949





   Introduction Top


Neonatal surgery, the epitome of pediatric surgery, is extremely challenging and has a negligible margin of error. There is a huge global disparity in the rates of neonatal surgical mortality (NSM) varying from 4% to 80%.[1]

Despite all-purpose improvement in an intensive care of severely ill newborns, sepsis is still among the leading causes of mortality in neonatal population worldwide.[2] On a whole, neonatal sepsis was likely to occur in 1/1000 live births;[3] however, the incidence as high as 3% to 20% was reported in the preterm population of newborns, because of the presence of multiple synchronized risk factors for nosocomial sepsis.[4] Mortality because of neonatal sepsis is dependent strictly on causative pathogen and on gestational age, with a mortality rate as high as 20% observed in very preterm newborns.[3],[4]

Based on the timing of infection, the neonatal sepsis has been divided into early-onset sepsis (EOS) and late-onset sepsis (LOS).[5] This categorization helps guide the antibiotic therapy as it implies differences in presumed mode of transmission and the predominant organisms. EOS is described as sepsis onset in the first 3 days and generally the result of the vertical transmission of bacteria is from the mothers to the infants during intrapartum period.[6] LOS is described as an infection occurring after 1 week of life and is attributed to horizontal transmission of the pathogens acquired postnatally and is often more subtle in onset.[5]

The surgical neonates are more prone to infection due to invasive procedures and contact to pathogenic bacteria in hospital environment. Availability of better antibiotics has reduced deaths due to infection, but sepsis is still the significant cause of death among newborn surgical patients. In general, sepsis is the last common pathway to death in a seriously ill neonatal patient who suffers from postoperative complication. The effect of sepsis on cardiac, respiratory, and renal function is obvious and related directly to premortality incidents. Surgical site infections, peritonitis, postoperative sepsis, urinary tract infections, pneumonia, sepsis with renal failure in the posterior urethral valve, and the other obstructive uropathies are few situations encountered among the surgical neonates.[7],[8]

A rapid presupposition of sepsis might be made at bedside using “sepsis screen” that might help guide the requirement of antibiotic therapy and surgical intervention in some cases. Commonly used parameters are immature to total neutrophil ratio (IT ratio), total leukocyte count (TLC), C-reactive protein (CRP), and microerythrocyte sedimentation rate (μESR).[9]

We hypothesized that early detection of neonatal surgical sepsis with sepsis screening and specific targeted antibiotic therapy has better outcome. Hence, the aim of our study was to evaluate the early indicators of sepsis (sepsis screening) and their statistical correlation with septicemia.


   Materials and Methods Top


A prospective observational study was carried on thirty consecutive neonate cases aged between 0 and 28 days with surgical abdomen at the Paediatric Surgery Department, ABVIMS and Dr. Ram Manohar Lohia Hospital, New Delhi. The study duration was 18 months (from February 2018 to August 2019); after clearance from the ethical committee of the institute, written consent was taken from all the guardians of the neonates for taking part in the study.

All the consecutive neonates from 1.5 kg to 3.5 kg and from 0 to 28 days of age and underwent fresh intra-abdominal surgical intervention were included in the study, and neonates with age >1 month and weight <1.5 kg and neonate with any prior neonatal surgery were excluded from the study.

Local and English language were preferred to ask about the neonate from their attendants or parents using a confidential questionnaire. The questionnaire included questions providing information on personal data, which were properly encoded. The clinical data given by neonate parents were then complemented with information on the diagnosis of the disease, the treatment administered, adverse effects reported, and laboratory findings.

Routine investigations such as complete blood counts, random blood sugar, liver function test, and kidney function test were done (blood samples were obtained under strict aseptic precautions from peripheral venepuncture in all neonates within 24 h of admission, before initiation of antibiotic therapy).

Sepsis screening

'As a part of sepsis screening, five parameters were taken: CRP, procalcitonin (PCT), total leukocyte count, immature/total neutrophil (I/T) ratio, and micro-ESR. Three or more than three positive parameters were considered positive sepsis screening.

Microbiology

CRP, PCT (2–3 ml blood samples obtained under strict aseptic precautions from peripheral venepuncture in all neonates within 24 h of admission, before initiation of antibiotic therapy and both test done by enzyme-linked immunosorbent assay method).

Hematology

I/T (immature to mature neutrophil ratio) ratio done with automated method as part of complete blood count. Micro-ESR-estimated with capillary blood obtained by heel prick, collected in a standard 75 mm microhematocrit tube with internal diameter of 1.1 mm. I/T ratio >0.2 and micro-ESR >15 mm in 1st h, TLC >5000/mm were considered significant.

Diagnosis of sepsis

Sepsis was diagnosed on the basis of laboratory parameters (blood C/S, pus C/S, and urine C/S) or clinical parameters (hypotension, poor perfusion, hypothermia, pneumonia, wound infection, and peritonitis) in the sepsis screening-positive patient.

Postscreening in sepsis positive and clinically suspicious surgical sepsis cases where culture and sensitivity of blood, urine, and pus samples were collected under all aseptic precaution in sterile container and sent to microbiology department. X-ray of the chest and abdomen, ultrasonography, and computed tomography scan of the abdomen were done in the indicated case.

Postoperative screening was performed on 1st, 3rd, 7th, and 14th day of surgery or till the patient clinically improved.

Excel sheet was used to create database and producing the graphs, while the data were examined using Statistical Package for the Social Sciences (SPSS) version 23 for Windows. Descriptive analysis was done to assess the frequencies of multiple risk factors. P < 0.05 was considered statistically significant for all the tests.

Observation/results

This study was a prospective observational study, which was carried out on 30 neonates with abdominal surgical condition which presented to our department. All patients were new cases and were ≤28 days. Neonates underwent thorough clinical examination, preoperative workup, and demographic, clinical, and laboratory investigations; operative and pathological data were entered according to the proforma approved by the institutional review board and ethics committee.

The majority of the studied neonates were male (56.7%) and females were 43.3% [Figure 1]. Sepsis screening was also done at the time of admission before surgery which was found to be positive in 20% of neonates and negative in of 80% of neonates; on day 1 of surgery, sepsis screening was positive in 30% of the cases and was negative in 70% of the cases; and on day 3 of surgery, sepsis screening was positive in 50% of cases and negative in 46.7% and one neonate had expired. On day 7 of surgery, sepsis screening was positive in 36.7% and negative in 56.7% of cases and 2 neonates had expired. On day 14 of surgery, sepsis screening was positive in 3.3% of neonates and negative in 33.3% of neonates, and in 63.3% of patients, it was not done because either the patient expired or discharged [Table 1].
Figure 1: Sex distribution of studied cases

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Table 1: Sepsis screening of studied cases in different time period

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Blood culture was also done as a part of sepsis workup. It was sterile in most of the cases (86.7%). Escherichia coli were positive in 6.7% of cases and Klebsiella was positive in 3.3% of cases. For urine culture, most of them were sterile (96.7%). Only one was positive for E. coli (3.3%). Four patients developed wound infection and wound swab was taken in those patients. Pus culture (c/s) in four patients was done, out of which 6.7% were E. coli positive and 6.7% were sterile [Table 2].
Table 2: Blood culture, pus culture and urine culture of studied cases

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Preterm babies were significantly more prone to sepsis than term babies (P = 0.031). PCT, CRP, and sepsis screening were associated significantly with sepsis, which shows that if the later parameters or markers are positive, the chances of getting sepsis also increased (P < 0.05) [Table 2].

The sensitivity and specificity were 86.7% and 93.3%, respectively, for PCT, whereas for CRP, sensitivity and specificity were 93.33% and 40%, respectively. Finally, septic screening correlated with sepsis and sensitivity and specificity of sepsis screening were 93.33% and 53.33%, respectively [Table 3] and [Table 4].
Table 3: Correlation between different parameters and sepsis in studied cases

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Table 4: Sensitivity, specificity, negative predictive value, and positive predictive value and accuracy of the markers

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Different types of surgery and their contamination level are tabulated in [Table 5]. Clean cases were 33.33% (n = 10), clean contaminated 53.33% (n = 16), and contaminated 13.33% (n = 4).
Table 5: Different types of cases and types of surgical contamination

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   Discussion Top


Neonatal sepsis is a clinical syndrome characterized by systemic signs of infection, accompanied by bacteremia within the first 4 weeks of life (28 days). Neonatal sepsis is the most common cause of morbidity and mortality in neonatal period. Every year, 135 million babies are born alive worldwide. Statistical data in 2011 estimated that 3 million of these died during the first 4 weeks of life.[10]

Sepsis is a global health-care problem, characterized by inflammation in response to microbial infection, leading to organ dysfunction. Sepsis is defined as systemic inflammatory response syndrome (SIRS) with an infectious process and associated with high morbidity and mortality rates if initial therapy is delayed. Numerous biomarkers (interleukin [IL]-2, IL-6, and tumor necrosis factor-α), leukotrienes, acute phase proteins (CRP), and adhesion molecules have been assessed with variable results, forecasting the severity of sepsis and guiding its management.[11] Recently, PCT has been recommended as a novel biomarker that is helpful in guiding the therapeutic decision making in management of sepsis. It is a biomarker with earlier rise in response to infection, frequently used to distinguish sepsis from the systemic inflammation that can be helpful to reduce the antibiotic exposure in pediatric patients.[12] In response to infection, PCT concentration rises within 2 h and peak values are reached after 12 h, even though the physiologic increase in PCT concentration to occur within first 24 h after birth.[13]

In this study, a total of 30 neonates were included consequently and septic screening was performed in each neonate and further investigations were done accordingly. Sepsis was confirmed by laboratory or clinical signs and symptoms. Sepsis screening was correlated and analyzed with confirmed cases of sepsis.

In our study, out of the total studied neonates, males (56.7%) were in majority, followed by female neonates (43.3%), indicating slight male predominance. Male predominance was also observed in similar studies conducted in Nepal during the period of 2 years from July 2007 to June 2009 by Khinchi et al.,[14] who found that among 175 neonatal sepsis cases, 65.1% were male infants and 34.9% were female infants, and Patil and Patil.,[15] who reported that a total of 64 patients with the diagnosis of sepsis were enrolled in their study, out of which 67.2% were male and 32.8% were female, with a male: female ratio being 2:1. According to Kumar et al.,[16] among the 155 babies, there were 88 56.8% of males and 43.2% of females. This male predominance may be due to X-linked immune regulatory gene factor contributing to host's susceptibility to infections in male neonates.

In the present study, the cases which were in majority were congenital diaphragmatic hernia (20%), followed by ARM 16.7%, gastrointestinal tract perforation 13.3%, and intestinal atresia and omphalocele each 3 cases (10%). A study done by Ikol et al.[17] found that gastroschisis is the most common condition (26.6%). Ekenze et al.[18] found that esophageal atresia was the most common condition (23.1% and anorectal malformation were 19.9%).

Sepsis screening was also done at the time of admission before surgery, which was found to be positive in 20% of neonates; on day 1 of surgery, sepsis screening was positive in 30% of the cases, and on day 3 of surgery, sepsis screening was positive in 50%. On day 7 of surgery, sepsis screening was positive in 36.7%, and on day 14 of surgery, sepsis screening was positive in 1 (3.3%) neonate only. Among the different parameters of sepsis screening, the sensitivity of PCT and CRP was 86.7% and 93.3%, respectively, and their specificity was 93.3% and 40%, respectively. Hence, it shows that CRP is more sensitive but less specific biomarker for sepsis. And similarly, PCT is less sensitive compared to CRP but more specific biomarker for sepsis which is similar to study done by Misra et al.[19] and Adib et al.[20] Furthermore, CRP sensitivity and specificity were 100% and 66% as studied by Kataria et al.,[21] which is slightly different from our study with sensitivity and specificity of 93.3% and 40%, respectively, but both studies showing the same result that CRP is more sensitive but less specific. Sepsis was diagnosed in 50% of the patients either on the basis of laboratory findings or clinical findings, which is similar to the study done by Lakhey and Shakya.,[22] who found 48% sepsis rate in surgical neonates.

A similar study by Sakha et al.[23] showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PCT were 66.7%, 50%, 28.6%, and 83.3%, which is lower than that of the current study. Chiesa et al.[24] studied the dependability of PCT concentration in 28 infants having severe early-onset of neonatal sepsis. They found that the sensitivity, specificity, NPV, and PPV were 92.6%, 97.5%, 96.8%, and 94.3%, respectively. In this study, the specificity was higher than that of the current study. Vazzalwar et al.[25] assessed PCT for diagnosis of sepsis in 67 neonates was found that sensitivity and specificity were of 97.0% and 80.0% respectively.

Thus, many studies in neonates reported a higher sensitivity and a lower specificity for PCT than for CRP. The considerable heterogeneity of the results among the studies evaluating different markers for detection of neonatal sepsis can be explained by the lack of universally acceptable definition of neonatal sepsis, different cutoff values incorporated in the studies, and physiologic alterations of some markers such as PCT that occur in healthy neonates.[26]

Similarly, Nargis et al.[27] quoted that serum PCT and CRP values in sepsis cases, severe sepsis, and septic shock were higher significantly (P < 0.01) and PCT superior to CRP in identification and to evaluate severity of sepsis. Sharma and Duggal[28] in their study depicted that PCT along with CRP is a better diagnostic tool for sepsis. Tian et al.[29] found that PCT levels were important in discriminating the sepsis from SIRS and verifying sepsis severity in significantly ill patients. CRP is the most commonly used marker in screening for sepsis in neonates, but a few studies had found that PCT can have better specificity and accuracy.[30],[31]

In our findings, blood C/S was positive in our study in only in 10% of the cases, 2 were positive for E. Coli and 1 was for Klebsiella, 1 was urine C/S positive and 2 were pus C/S positive so total 6 (20.0%) cases were culture positive. Similar positivity percentage of blood culture had been reported in the study by Sucilathangam et al.,[32] who revealed 28.0% of positive blood culture in 50 samples. Shrestha et al.[33] in Nepal reported similar range of results of 30.8% of blood culture-positive cases. Kumar et al.[16] in their study reported that of total 155 cases, 89.0% of cases had blood culture negative with and 17 cases were positive, of which 4.5% of cases had Klebsiella positive with, 2.6% cases had E. coli growth with 2.6% cases had Pseudomonas growth with and 1.3% case had Coagulase negative staphylococcus.

In the present study, patients were categorized in the term and preterm and correlated with sepsis in postoperative period and the result came out to be significant (P = 0.031) suggestive of preterm baby are more prone for sepsis. In a similar study done by Kayange et al.,[34] Misra et al.,[19] and Kar et al.[35] found that increased prevalence of neonatal sepsis among low birth weight neonates when compared with normal birth weight neonates.

In 40% of neonates, there was a need of ventilation use in postoperative period, which was similar to the study done by Mokaddas et al.,[36] who found 42.0% ventilator use. In this study, there was 30.0% mortality [Figure 2]. Reported NSM shows a geographical variation that is in Japan, 35.0%–45.0% in India, 52.7% in Uganda and 62.2% in Nigeria.[8],[37],[38]
Figure 2: Mortality

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Finally, sepsis screening correlated with sepsis and different parameters and it was found significant and sensitivity and specificity of septic screening was 93.3% and 53.3% respectively which is more or less similar to other study like done by Vinay et al.[39] (sensitivity-77.0% and specificity-41.0%) and Philip et al.[40] (sensitivity-93.0% and specificity-88.0%).

Early diagnosis of neonatal sepsis by sepsis screening evaluation helps prevent neonatal mortality and morbidity and avoid unnecessary use of empirical antibiotics, which in turn helps in preventing drug resistance. Furthermore, from the current study, it is obvious that sepsis screening is more sensitive but not very specific.

Limitations of the study:

  • Small sample size: A larger cohort of the patients is required to further confirm upon the results
  • Short follow-up of 1 month due to constraints of our study period: A longer follow-up will be required to analyze the outcome and prognosis.



   Conclusion Top


Early recognition and diagnosis of neonatal sepsis are difficult due to the variable and nonspecific clinical presentation. It is important to make an early diagnosis of sepsis, because prompt initiation of antimicrobial therapy and intervention improves outcomes. In this study, sepsis screening was highly sensitive (93.33%) in detecting sepsis, but its specificity (53.33%) was not very good. However, as it is highly sensitive in detecting neonatal sepsis, it can be used as an early marker of sepsis, so that early intervention can be taken and it will improve the prognosis in neonatal sepsis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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  2005 - Journal of Indian Association of Pediatric Surgeons | Published by Wolters Kluwer - Medknow 

Online since 1st May '05