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Table of Contents   
ORIGINAL ARTICLE
Year : 2023  |  Volume : 28  |  Issue : 2  |  Page : 93-102
 

Role of procalcitonin as a biomarker in early identification of adverse events following esophageal atresia surgery


1 Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
2 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
3 Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India
4 Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India

Date of Submission13-Jul-2021
Date of Decision19-Oct-2022
Date of Acceptance10-Jan-2023
Date of Web Publication03-Mar-2023

Correspondence Address:
Prabudh Goel
Department of Paediatric Surgery, Room No. 4002, 4th Floor, Teaching Block, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaps.jiaps_156_21

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   Abstract 


Introduction: Surgical complication following esophageal atresia repair is one of the several factors known to influence the final outcomes. Early identification of such complications may help in timely institution of therapeutic measures and translate into improved prognosis.
Objective: The objective of this study was to evaluate the role of procalcitonin in early prediction of the adverse events after surgery in patients of esophageal atresia and the temporal relationship with clinical manifestations and other inflammatory biomarkers such as C-reactive protein (CRP).
Materials and Methods: This was a prospective study on consecutive patients of esophageal atresia (n = 23). Serum procalcitonin and CRP levels were assessed at baseline (prior to surgery) and on postoperative days (POD) 1, 3, 5, 7, and 14. The trends in the biomarker values and temporal relationships of deviation in trend with the clinical and conventional laboratory parameters and patient outcomes were analyzed.
Results: Baseline serum procalcitonin was elevated (n = 23; 1.7 ng/ml: min: 0.07 ng/ml–max: 24.36 ng/ml) in 18/23 (78.3%) patients. Procalcitonin nearly doubled on POD-1 (n = 22; 3.28 ng/ml: min: 0.64 ng/ml–max: 16.51 ng/ml) followed by a gradual decline. CRP was also elevated on POD-1 (three times the baseline) and depicted a delayed peak at POD-3. POD-1 procalcitonin and CRP levels correlated with survival. POD-1 procalcitonin cutoff at 3.28 ng/ml predicted mortality with a sensitivity and specificity of 100% and 57.9% (P = 0.05). Serum procalcitonin and CRP were higher for patients who sustained complications, so was the time required for hemodynamic stabilization. Procalcitonin (baseline and POD-5) and CRP (POD-3 and POD-5) values correlated with the clinical course after surgery. Baseline procalcitonin cutoff at 2.91 ng/ml predicted the possibility of a major complication with a sensitivity of 71.4% and a specificity of 93.3%. POD-5 procalcitonin cutoff at 1.38 ng/ml predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3%. Patients who sustained major complications depicted a change in serum procalcitonin trend 24–48 h ahead of clinical manifestation of an adverse event.
Conclusions: Procalcitonin is a good indicator to identify the adverse events in neonates after surgery for esophageal atresia. The procalcitonin levels in patients who sustained a major complication depicted a reversal in trend 24–48 h of clinical manifestation. POD-1 procalcitonin correlated with survival while the baseline and POD-5 serum procalcitonin predicted the clinical course.


Keywords: Adverse event, biomarker, C-reactive protein, esophageal atresia, procalcitonin, sepsis, surgical complication


How to cite this article:
Mahajan D, Goel P, Jain V, Dhua AK, Yadav DK, Verma A, Sharma A, Gupta S, Chaturvedi PK, Kalaivani M, Agarwala S, Bajpai M. Role of procalcitonin as a biomarker in early identification of adverse events following esophageal atresia surgery. J Indian Assoc Pediatr Surg 2023;28:93-102

How to cite this URL:
Mahajan D, Goel P, Jain V, Dhua AK, Yadav DK, Verma A, Sharma A, Gupta S, Chaturvedi PK, Kalaivani M, Agarwala S, Bajpai M. Role of procalcitonin as a biomarker in early identification of adverse events following esophageal atresia surgery. J Indian Assoc Pediatr Surg [serial online] 2023 [cited 2023 Mar 31];28:93-102. Available from: https://www.jiaps.com/text.asp?2023/28/2/93/371166





   Introduction Top


The transition from fetal to postnatal life encompasses significant physiological and maturational change.[1] Neonates are also susceptible to serious complications emanating from seemingly local infections due to the immaturity of the immune system, poor nascent gut flora, and limited reserves, all contributing to increased susceptibility and early irreversibility of the disease process. The vulnerability is exponentially magnified following trauma inflicted by surgery in neonates born with esophageal atresia.

Early identification of surgical complications such as anastomotic leak or the onset of sepsis is one of the several factors known to influence the final outcomes. The initial presenting signs in a neonate are nonspecific and subtle such as a decrease in activity, mild hypothermia, sclerema, or mottling and not specific to differentiate early sepsis from a surgical event. The time taken for evolution of such symptoms into gross clinical features is the time required for the pathological cellular-level mechanisms to become generalized. This time interval may be vital in preserving the final outcomes of surgery by instituting appropriate corrective interventions. A biological marker which may predict the onset of an underlying adverse event ahead of its overt clinical manifestation may aid in early initiation of appropriate management thereby improvising upon the final outcomes.

The study has been planned to evaluate the role of procalcitonin, a biological marker of sepsis in early prediction of the adverse events after surgery in patients of esophageal atresia, and the temporal relationship with conventional parameters including C-reactive protein (CRP).


   Materials and Methods Top


This prospective, single-center-based study on consecutive patients of esophageal atresia (n = 23) managed over a period of 18 months (July 2019–Jan 2021) was conducted after clearance from the Institute Ethics Committee.

Observation parameters included patient demographics, clinical, laboratory, and radiological parameters, and the surgical details including the surgical procedure(s), duration, blood loss, and complications (both intra-and postoperative prior to discharge from the hospital). Periodic assessments including hemodynamics, activity, cry, hypothermia, capillary filling time, sclerema, mottling, surgical site infection (after surgery), ventilatory parameters, chest tube output (volume and content), and feeding were conducted as per standard protocols and findings recorded in predesigned excel (Microsoft® Excel version 16.48; Microsoft 365 subscription) charts. Baseline serum procalcitonin and CRP levels were assessed prior to surgery. Follow-up procalcitonin and CRP were assessed at 24 h following surgery and on postoperative days (POD) 3, 5, 7, and 14 (at 6:00 AM on the respective day).

The treatment of patients in this series was not dictated by the serum procalcitonin or CRP levels. The residents and consultants in charge of managing the participants were blinded to the procalcitonin and CRP values.

The patients were substratified into three subgroups: Group A: uneventful recovery (no complications), Group B: mild complications such as mild-to-moderate sepsis (necessitating change of antibiotics but no need for ionotropic or ventilatory support), surgical-site infections (limited to the skin and subcutaneous tissue; no muscle dehiscence), contained leak from the anastomosis, chest infections not requiring ventilatory support, etc., and Group C: major complications such as chest infections requiring ventilatory support, fulminant sepsis, and major anastomotic leaks requiring redo surgery [Chart 1].



Statistical analysis was performed using SPSS (version 26.0 for Windows, Chicago, Illinois, United States). Data were expressed as median and range. For data analysis, Mann–Whitney U and Student's t-tests were applied. A probability of P < 0.05 was considered statistically significant. The trends in the biomarker values were studied, and the temporal relationships of any change in values of these biomarkers with the other observation parameters and patient outcomes were analyzed.


   Results Top


The study cohort comprised 23 neonates with a mean age of 2 days (range: 1–7 days), mean gestation of 37.6 weeks (33 weeks + 2 days–40 weeks + 1 day), and weight of 2.43 kg (range: 1.15–3.49 kg) at presentation. At least one antenatal scan was done in 15 of 23 (65.2%) patients, with polyhydramnios in 4 of 15 (26.6%) and small-for-gestation fetus in 1 of 15 (6.7%). None of the cases were diagnosed or suspected antenatally. Delivery was conducted in a health-care facility in 17 of 23 (73.9%) with a cesarean section in 9 (39.1%).

The cardiovascular system was most commonly involved (15 of 23; 65.2%), with atrial septal defect being the most common anomaly (13 of 23; 56.5%) followed by patent ductus arteriosus (7 of 23; 30.4%) and ventricular septal defect (4 of 23; 17.3%). Other anomalies included anorectal malformation (2 of 23; 8.6%), laryngotracheomalacia (1 of 23; 4.3%), laryngotracheal cleft (1 of 23; 4.3%), and glandular hypospadias (1 of 23; 4.3%). Respiratory tract involvement in the form of tachypnea, crepts, or rhonchi present in 15 of 23 (65.2%) was largely due to saliva aspiration. Postsuctioning, pneumonia was confirmed radiologically in 8 of 23 (34.7%) patients.

Gross type C esophageal atresia (22 of 23; 95.7%) was most common followed by type B atresia (1 of 23; 4.3%). Surgical procedures included (a) right posterolateral thoracotomy and primary repair (n = 15; 65.2%), (b) right posterolateral thoracotomy and fistula ligation (n = 2; 8.7%), (c) cervical and abdominal esophagostomy (n = 3; 13%), and (d) thoracoscopic fistula ligation with feeding jejunostomy (n = 3; 13%). The clinical course and substratification of the participants into Groups A–C are mapped in [Chart 1]. Group C patients were peculiar with fulminant sepsis (n = 4), severe chest infection (n = 2), and anastomotic leak (n = 2).

The baseline serum procalcitonin level (n = 23) was 1.7 ng/ml (min: 0.07 ng/ml, max: 24.36 ng/ml). As against the expected normal <0.5 ng/ml, a higher baseline procalcitonin was encountered in 18 of 23 (78.3%) patients.[2] Serum procalcitonin peaked on POD-1 (two times the baseline), 3.28 ng/ml (n = 22; min: 0.64 ng/ml, max: 16.51 ng/ml) [Figure 1]. Thereafter, the levels depicted a gradual decline with recorded serum procalcitonin levels on POD-3, POD-5, POD-7, and POD-14 being 1.9 ng/ml (n = 21; min: 0.21, max: 16.56), 0.9 ng/ml (n = 21; min: 0.1, max: 8.35), 0.41 ng/ml (n = 21; min: 0.07, max: 6.4), and 0.18 (n = 19; min: 0.07, max: 3.7) ng/ml reading, respectively. Procalcitonin levels on POD-3 were comparable to the respective baseline (preoperative levels) but higher than the normal values for age.
Figure 1: Trends of serum procalcitonin and C-reactive protein levels in the study cohort (box and whisker chart)

Click here to view


Baseline CRP levels were also elevated in the study cohort (n = 23; 10.1 mg/L; min: 0.1, max: 178.83). The postoperative values depicted a three-fold level on POD-1 (n = 22; 31.2 mg/L; min: 2.2 mg/L, max: 190.23 mg/L); the peak of CRP was observed on POD-3 (n = 21; 43.45 mg/L; min: 2.5 mg/L, max: 150.2 mg/L) followed by a subsequent decline [Figure 1].

Effect of gender on procalcitonin and C-reactive protein

Preoperative values of procalcitonin were higher in female participants (n = 12; 2.11 ng/ml; min: 0.07 ng/ml, max: 24.36 ng/ml) as compared to males (n = 11; 1.4 ng/ml; min: 0.19 ng/ml, max: 13.25 ng/ml). The postoperative values of PCT were comparable between the two genders. No gender-based differences were not observed in CRP levels.

Effect of postnatal age, gestational age, and birth weight on procalcitonin and C-reactive protein

Baseline procalcitonin levels were higher in neonates 5 days or older (n = 12; 2.16 ng/ml; min: 0.40, max: 24.36) vis-à-vis those younger than 5 days (n = 11; 1.4 ng/ml; min: 0.07, max: 7.53). Such differences were not observed in the CRP levels. Baseline procalcitonin and CRP were comparable between term and preterm neonates as well as in neonates with birth weight >2.5 kg and those born with a low birth weight.

The gestational age, age at presentation, gender, birth weight, and age at surgery were not different between the participants who developed some complications vis-à-vis those who demonstrated an uneventful recovery.

Mortality and clinical course

Mortality in series was 17.4% (4 of 23). The POD-1 procalcitonin levels were higher in patients who expired (n = 3, 15.76 ng/ml; min: 3.29 ng/ml, max: 16.51 ng/ml) as compared to those who survived (n = 19, 2.91 ng/ml; min: 0.64 ng/ml, max: 12.75 ng/ml) (P = 0.05). Baseline procalcitonin was also higher in the patients who expired (n = 4, 5.23 ng/ml; min: 0.46 ng/ml, max: 13.25 ng/ml versus n = 19, 1.4 ng/ml; min: 0.07 ng/ml; max: 24.36 ng/ml); however, the difference was not significant (P = 0.194). Serum procalcitonin (POD-1) cutoff at 14.26 ng/ml predicted mortality with a sensitivity and specificity of 66.7% and 100% (P = 0.05). However, if the cutoff of serum procalcitonin was lowered to 3.28 ng/ml, the sensitivity and specificity of predicting mortality were 100% and 57.9%, respectively [Figure 2].
Figure 2: (a) ROC curves depicting sensitivity and specificity of serum procalcitonin at baseline between Groups A and B vs. Group C, (b) ROC curves depicting sensitivity and specificity of serum procalcitonin on POD-5 between Groups A and B vs. Group C, (c) ROC curves depicting sensitivity and specificity of serum procalcitonin on POD-1 between outcomes (mortality vs. no mortality), (d) ROC curves depicting sensitivity and specificity of serum CRP on POD-3 between Groups A and B vs. Group C, (e) ROC curves depicting sensitivity and specificity of serum CRP on POD-5 between Groups A and B vs. Group C. (f) ROC curves depicting sensitivity and specificity of serum CRP on POD-1 between outcomes (mortality vs. no mortality). CRP: C-reactive protein, POD: Postoperative days, ROC: Receiver operating characteristic

Click here to view


The POD-1 CRP levels were higher in patients who expired (n = 3, 155.59 mg/L; min: 56.42 mg/L, max: 190.23 mg/L) as compared to those who survived (n = 19, 28.57 mg/L; min: 2.2 mg/L, max: 178.21 mg/L) (P = 0.025). Baseline CRP levels were also higher in patients who expired (n = 4, 63.00 mg/L; min: 4.89 mg/L, max: 178.83 mg/L versus n = 19, 8.54 mg/L; min: 0.10 mg/L; max: 56.36 mg/L); however, the difference was not significant (P = 0.156). CRP (POD-1) cutoff at 45.42 mg/L predicted mortality with a sensitivity and specificity of 100% and 78.9% (P = 0.025) [Figure 2].

The serum procalcitonin levels for patients in Group C were higher than those in Group B which were higher than those in Group A. The time duration for hemodynamic stabilization presurgery was higher for Group C (4.5 days + 2.98) as compared to Groups A and B (1.6 days + 1.24). The CRP levels were also higher for Group C as compared to Groups A and B [Figure 3]; the difference in levels on POD-1 between the groups was not significant.
Figure 3: Trends of serum procalcitonin and C-reactive protein among patients stratified into Groups A, B, and C

Click here to view


Baseline and POD-5 serum procalcitonin levels correlated with the clinical course of the patient (Group C vis-à-vis A and B). A baseline procalcitonin level of 2.91 ng/ml or higher predicted the possibility of a major complication with a sensitivity of 71.4% and a specificity of 93.3%. However, if the cutoff for baseline procalcitonin was taken at 5.72 ng/ml, the sensitivity and specificity for predicting a major complication were 42.9% and 100%, respectively. A procalcitonin level of 1.38 ng/ml or higher on POD-5 predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3% [Figure 2].

CRP levels on POD-3 and POD-5 also correlated with the clinical course of the patient. A CRP level of 62.19 mg/L or higher on POD-3 predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3%. On POD-5, CRP level of 32.28 mg/L or higher predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 80% [Figure 2].

Group C patients: Introspection of clinical course

Group C comprised eight patients, all with Type C esophageal atresia. Of these, six patients underwent thoracotomy and primary repair while two patients were operated with thoracotomy and fistula ligation. In this subgroup, two patients were operated under compelling circumstances (bile reflux through the wide trachea-esophageal fistula) and expired within 24–48 h of surgical intervention.

The procalcitonin levels in the remaining six patients depicted a reversal in the normal trend as an indicator of an adverse event ahead of its clinical manifestation. The notional time gain using procalcitonin varied from 24 to 48 h: 24 h in n = 4 of 6 patients and 48 h in n = 2 of 6 patients. The temporal relationship of clinical indicators of underlying adverse events with the leukocyte count, CRP, and procalcitonin has been studied qualitatively and depicted diagrammatically [Figure 4].
Figure 4: Diagrammatic depiction of the temporal relationship of clinical indicators of underlying adverse events with the leukocyte count, CRP, and procalcitonin in individual patients substratified into Group C. CRP: C-reactive protein

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   Discussion Top


Procalcitonin is widely used as an inflammatory biomarker to aid in early detection of sepsis and antibiotic stewardship.[2],[3],[4],[5] The inflammatory release of procalcitonin is independent of calcium-phosphorus regulation[6] and induced by lipopolysaccharide or other toxic microbe metabolites. Besides, inflammatory mediators such as interleukin-6 and tumor necrosis factor-α are also known to induce the secretion of procalcitonin.[7] Procalcitonin has also been rated superior to leukocyte count and CRP levels as a biomarker for sepsis.[8] Besides sepsis, the utility of procalcitonin in ventilator-associated pneumonia[8],[9] and early detection of postsurgical infections has also been demonstrated in several studies.[10],[11],[12],[13],[14] CRP is a nonspecific biochemical marker of infection, inflammation, and tissue damage.[15] The plasma half-life of CRP is relatively constant and unaffected by the disease process; the circulating levels of CRP are largely determined by the rate of hepatocyte production, which is under the transcriptional control of IL-6.[16] Liver failure is known to impair the production of CRP.[17]

Patients who have higher baseline levels of procalcitonin are more prone to postoperative complications.[8],[18] Higher levels of procalcitonin in patients undergoing cardiac surgery have been shown to indicate the development of nonocclusive mesenteric ischemia[19] and aid in the early identification of the complication. Procalcitonin is also useful in monitoring after colorectal surgery.[20] Higher procalcitonin levels on POD-1 are predictive of anastomotic leak; the magnitude of rise of procalcitonin above the baseline after surgery has also been correlated with a higher incidence of anastomotic leaks.[18] The close association of procalcitonin levels with postoperative complications has also been shown in aortic surgery in addition to colon surgery.[13]

In esophageal atresia, the clinical manifestations of surgical complications may be related to anatomical disruption (pneumothorax) or a consequence of inflammation (sclerema, mottling, or hypothermia) triggered by the complication directly or mediated by secondary infection. The anatomic disruption may become manifest early such as visibility of saliva in the intercostal tube drain followed by the inflammatory cascade due to intrathoracic salivary pooling. Alternatively, the inflammatory cascade may precede the clinical manifestations if the drain is blocked or the leak is subtle. Early identification of such complications, especially in patients with esophageal atresia or other congenital malformations necessitating surgery during the neonatal period, may help in improvising upon the final outcomes.

The current study has depicted a higher baseline procalcitonin and CRP in patients of esophageal atresia. This could be related to the varying degrees of chest involvement in these patients due to aspiration of saliva and chemical pneumonitis related to regurgitation of gastric secretions and bile through the fistulous tract.[21] The reasoning is further supported by the fact that a higher baseline value of procalcitonin or CRP was associated with a longer length of time required for stabilization and preoperative preparation of the patient.

A rise in procalcitonin and CRP above the baseline following surgery is supported by the results reported in the literature.[12],[20] This is related to the major surgical insult from the reconstructive procedures. Transient endotoxemia or bacteremia is also possible following surgery of the esophagus and associated procedures such as insertion of a red-rubber catheter in the upper pouch to help in intraoperative identification or passage of a transanastomotic feeding tube through the nasogastric route.[20]

The peak of procalcitonin was observed on POD-1 in our series followed by a return to the baseline on POD-3 which is congruent with the kinetics reported in the literature. The procalcitonin rises within 4 h of endotoxin injection into healthy volunteers with a peak at 6–24 h followed by a steady decline with a half-life of 24 h.[22],[23] Contrarily, the peak CRP levels were witnessed on POD-3.[24] The magnitude of rise in CRP was more than that of procalcitonin. CRP is known for a swift rise in serum concentration during the acute phase with a possible magnitude of up to 1000-fold within 24–48 h in an attempt to mediate the elimination of pathogens and damaged host cells by recruiting the complement system and the phagocytic cells.[25] The reported elimination half-life of CRP is 19 h[26] but may be affected by the cumulative effect of multiple medications including steroid administration.[27] It has also been highlighted in the literature that the rise in CRP is not always due to surgery alone; minimal rise in CRP was observed in patients with no evidence of inflammation before surgery and absence of foreign bodies placed at the time of surgery[27] as in patent ductus arteriosus ligation.

The baseline procalcitonin was higher in the female participants. Such gender differences observed in the procalcitonin and PCT values are not supported by the literature.[28] This could be related to multiple factors including individual differences in the degree of chest infections and small number of participants in the study cohort. Most of the females presented to us in a poorer general condition as compared to their male counterparts. Prominent observations also included general neglect, late presentation, and hypothermia in the female patients. The higher procalcitonin in the females also correlated with clinical markers of sepsis and leukocytosis. The postoperative rise in procalcitonin was higher in the males. Gender differences with respect to septic complications have, however, been reported in the literature;[29] female patients with sepsis are known to have better survival.[30]

Under normal circumstances, the procalcitonin levels are known to peak in a 1-day old neonate and decline thereafter.[31] However, in our study, higher levels of baseline serum procalcitonin were observed in neonates who were 5 days of age or older. Continued aspiration of saliva and pulmonary reflux of biliogastric contents through the trachea-esophageal fistula resulting in chemical pneumonitis may have prevented procalcitonin from leveling or provided a stimulus for sustained rise. However, similar differences were not reflected in the CRP values. Palanisamy et al. have shown that CRP is high up to 95 h postnatal age in uninfected healthy neonates.[32] The peak of CRP however, has been reported differently at 70 h, 48 h, and 36 h by Chiesa et al.,[33] Perrone et al.,[34] and Nishida and Nishida,[35] respectively.

Higher levels of CRP and procalcitonin on POD-1 were found to be associated with ultimate outcomes (survival or mortality). A similar but less-stronger association was also observed with baseline values. This fact may be best interpreted in context of the understanding that the baseline values of procalcitonin and CRP are not reflective of the surgical trauma and the cumulative effect of the different variables associated with surgery including surgical duration, tissue handling, blood loss, and complications of surgery including postoperative sepsis. This is in sharp contrast to patients being managed medically wherein the procalcitonin and CRP values at admission are associated with final outcomes.[36],[37] Procalcitonin (POD-1) cutoffs at 3.28 ng/ml and 14.26 ng/ml were observed to predict mortality with 100% sensitivity and 100% specificity, respectively. CRP (POD-1) cutoffs at 45.42 mg/L predicted mortality with a sensitivity and specificity of 100% and 78.9%.

Baseline and POD-5 serum procalcitonin levels have been identified to predict the possibility of a major complication in patients with esophageal atresia. Baseline procalcitonin largely reflects the sepsis component or general well-being of the patients. The effects of surgical insult are reflected in the POD-1 and POD-3 values while the POD-5 levels reflect the cumulative effect of sepsis and the complications of surgery. Serum procalcitonin cutoffs of 5.72 ng/ml and 1.38 ng/ml identify the possibility of complications with very high specificity (100% and 93.3%, respectively). CRP levels on POD-3 and POD-5, however, were associated with the possibility of a major complication (Group C). A CRP cutoff at 62.19 mg/L on POD-3 and 32.28 mg/L on POD-5 predicted the possibility of a major complication with a specificity of 93.5% and 80%, respectively.

A qualitative introspection into individual case details and a study of temporal relationship between the various events (clinical or investigational) registered for respective cases have pointed out that the rise in serum procalcitonin precedes the clinical manifestation of adverse events which are nonspecific and subtle in the initial few hours or days. A rise in serum procalcitonin reflects the changes happening at cellular and molecular levels which build up gradually to become manifest clinically over 24–48 h. The additional window afforded by procalcitonin-based monitoring of the patients of esophageal atresia following surgery may be translated into early recognition of complications and timely institution of interventions.

The use of procalcitonin like any other biomarker has its own limitations too. In a surgical neonate, the rise in procalcitonin and CRP is a combined effect of inflammatory response elicited by the surgical trauma and sepsis.[38] Unless we have means to differentiate between the two factors or to quantify the magnitude of each, it is important that the trend of procalcitonin or CRP be considered for making clinical decisions rather than the absolute values of these biomarkers. Furthermore, clinical decisions should be based on an overall assessment of the patient including the clinical, laboratory, and radiological parameters. An optimal balance between the conventional and novel biomarkers of sepsis and surgical complications is likely to yield positive results. Larger, well-formulated studies and multicentric trials are required to formulate clinical protocols for optimal utilization of procalcitonin in the management of patients with esophageal atresia and other surgical diseases of the neonates and infants. The other biomarkers under investigation such as IL-6, IL-8,[39] CD64,[40] and presepsin[41] may also be included in the cumulative assessment for prognostic monitoring based upon their respective biological properties.


   Conclusions Top


Procalcitonin is a good indicator to identify the adverse events in neonates after surgery for esophageal atresia. Baseline and POD-5 serum procalcitonin levels correlated with the clinical course. Baseline serum procalcitonin >5.72 ng/ml predicted a major complication with a specificity of 100%. Procalcitonin >1.38 ng/ml on POD-5 predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3%. The procalcitonin levels in patients who sustained a major complication depicted a reversal in trend 24–48 h ahead of clinical manifestation.

Larger, multicentric trials are required to formulate clinical protocols for optimal utilization of procalcitonin in the management of patients with esophageal atresia and other surgical diseases of the neonates and infants.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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