Received date: February 24, 2014; Accepted date: March 20, 2014; Published date: April 05, 2014
Citation: Cosse C, Sabbagh C, Rebibo L, Grelpois G, Galmiche A, et al. (2014) Kinetics of Procalcitonin in the Management of Small Bowel Obstruction: A Preliminary Report. Surgery Curr Res 4:184. doi: 10.4172/2161-1076.1000184
Copyright: © 2014 Cosse C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Procalcitonin; Kinetics; Small bowel obstruction
SBO: Small Bowel Obstruction; PCT: Procalcitonin, CM: Conservative Management; SM: Surgical Management; Se: Sensitivity; Sp: Specificity; PPV: Positive Predictive Value; NPV: Negative Predictive Value; AUC: Area Under The Curve; ROC: Receiver Operating Curve; SD: Standard Deviation
Small Bowel Obstruction (SBO) is a major health problematic that is responsible for between 1% and 3% of emergency department admissions [1-3] and 75% of all obstructions. The main aetiology for SBO is adhesions (65-75%)  acquired after abdominal surgery (in 67% to 93% of all cases, depending on the series) [4,5]. The treatment of SBO is based on two distinct approaches: conservative management with nasogastric tube suction or Surgical Management (SM) if there are clinical signs of intestinal ischemia  or if Conservative Management (CM) fails [7-8].
The main challenge in SBO management is to propose the more appropriate treatment for each patient. The difficulty for discriminate between the two options lies on the absence of accurate-enough clinico-biomarker. Our team previously proposed the use of serum Procalcitonin (PCT), precursor of calcitonin  first described in 1993 by Assicot et al. . In this series we showed that serum procalcitonin could discriminate on the one side between the conservative and the surgical management with a threshold of 0.17 ng/mL and on the other between patients surgically managed with or without peroperative bowel ischemia with a threshold of 0.57 ng/mL . However, no team reports the kinetics of PCT in SBO.
The objectives of the present study were i. to present the kinetics’ profiles of serum PCT in cases of CM success and Surgical Management (SM), ii. to identify the more predictive time points to discriminate between CM success and SM and iii. to validate the predictive value of PCT in case of preoperatively confirmed bowel ischemia.
From January to October 2013, 59 patients with adhesion-related SBO were included in a prospective, monocenter, non-randomized, clinical study (PCT kinetics’ study). The inclusion criteria were SBO diagnosed with CT scan and a clinical examination. The exclusion criteria were early postoperative obstruction, obstruction with neoplasia, obstruction with inflammatory bowel disease, colon obstruction, a history of abdominal radiotherapy, the presence of pneumoperitoneum, clinical signs of infection, age under 18, pregnancy, guardianship. Small bowel obstruction was diagnosed on the presence of standard clinical signs (abdominal pain, tenderness, nausea or vomiting, no passage of gas and/or stools) and radiological signs (presence of air fluid levels, dilated bowel loops) possibly secondary to an abdominal surgery.
The PCT kinetics’ study participants were divided into two groups: patients in whom the CM was successful (the CM group, n=47) and those in whom it had failed (the SM group, n=12).
Initially, each patient was managed conservatively with nasogastric tube suction. If renewed passage of gas and stools was observed, the nasogastric tube was clamped and removed; oral nutrition was resumed and the CM was considered to be a success. When faced with clinical signs (such as fever, abdominal pain) or biological signs (hyperleucocytosis i.e. leucocyte count ≥ 16×103/mL) and the absence of gas 48 hours after the initiation of CM, the conservative approach was considered to be a failure and the patient was scheduled for surgery.
The open surgical procedure consisted in gut viscerolysis and (in some cases in presence of ischemia) bowel resection. An anastomosis was created depending of local conditions. In each case, the presence or absence of intra-operative bowel ischemia or necrosis was noted. Any adherences were described by the surgeon and noted in the patient’s case report form.
The PCT kinetics’ study’s primary endpoint was to present the kinetics’ profiles of serum PCT in cases of CM success and SM. The secondary endpoints were the identification of the more predictive time points to discriminate between CM success and SM and the predictive value of PCT for bowel ischemia. The study’s patient disposition is shown in Figure 1.
The following items of patient data were collected: demographic information, laboratory blood test results (white blood cell count, platelet count, C reactive protein, urea, lactate, ions, ASAT, ALAT, and PCT), comorbidities (diabetes, hypertension, chronic kidney disease or angor), and the history of abdominal surgery. Data related to surgical management included surgical recommendations, intra-operative signs and the surgical technique.
The procalcitonin assay
For each included patient, PCT test had been done on serum samples and measured on arrival to the emergency department and in the digestive surgery department during 3 days maximum (or until the transit was restored), every six hours. The Kryptor® T.R.A.C.E® assay (B.R.A.H.M.S, Clichy, France), routine laboratory test, was used onsite in the Biochemical laboratory. The reference value for PCT is <0.5 ng/mL.
Data are expressed as mean ± Standard Deviation (SD) or median (minimum – maximum) or number (percentage of patients). Univariate analyses were performed with the chi-squared test or Fisher’s exact test for qualitative variables and the Student t test for quantitative variables.
The threshold for statistical significance was set to p ≤ 0.05. To identify the more predictive time points of PCT we generated Receiver Operating Characteristic (ROC) curves and calculated the area under the ROC curve (AUROCC). The predictive time points were presented with the sensitivity (Se), specificity (Sp), Positive Predictive Value (PPV), Negative Predictive Value (NPV) and the threshold. Statistical analysis was performed with SAS 9.2 (SAS Institute Inc., Cary, NC, USA) and PASW 18 (SPSS INC., Chicago, IL, USA).
Baseline characteristics of the population
The characteristics of the population are shown Table 1. There is an imbalance between the CM and SM groups in terms of PCT (p=0.002) and Chloride (p=0.003) i.e. patients in CM group presented at admission a lower PCT and a higher chloride than in the SM group.
|Variable||Conservative management (n = 47)||Surgical management (n = 12)||P value|
|Mean age, years (min – max)||65 (24 – 98)||76 (19 – 98)||0.15|
|Male sex, n (%)||20 (43)||4 (33)||0.56|
|Mean body mass index, Kg/m2 (min – max)||29 (20 – 62)||25 (21 – 33)||0.10|
|Diabetes, n (%)||3 (6)||1 (8)||0.81|
|Cancer, n (%)||13 (28)||3 (25)||0.85|
|Hypertension, n (%)||19 (40)||5 (42)||0.94|
|Dyslipidemia, n (%)||10 (21)||1 (8)||0.30|
|Peripheral vascular disease, n (%)||6 (13)||0 (0)||0.19|
|Cardiopathy, n (%)||9 (19)||2 (17)||0.84|
|Acute kidney disease, n (%)||3 (7)||1 (8)||0.81|
|Smoker, n (%)||8 (17)||1 (8)||0.46|
|Chronic obstructive pulmonary disease, n (%)||3 (7)||1 (8)||0.81|
|Appendectomy, n (%)||12 (26)||4 (33)||0.59|
|Cholecystectomy, n (%)||8 (17)||2 (17)||0.98|
|Peritonitis, n (%)||2 (4)||1 (8)||0.57|
|Previous history of SBO, n (%)||5 (11)||0 (0)||0.24|
|Hernia, n (%)||5 (11)||0 (0)||0.24|
|Haemoglobin, g/dL ± SD||14 ± 1.8||14 ± 2.7||0.96|
|Leukocytes, x 103/mm3 ± SD||12 ± 5.1||11 ± 6.9||0.81|
|Platelets, x103/mm3 ± SD||310 ± 100||299 ± 133||0.81|
|C reactive protein, mg/L ± SD||31 ± 40||54 ± 72||0.31|
|ALAT, UI/L ± SD||31 ± 22||48 ± 33||0.15|
|ASAT, UI/L ± SD||29 ± 19||34 ± 25||0.59|
|Urea, mmol/L ± SD||8 ± 6||14 ± 7||0.49|
|Lactates, mmol/L ± SD||2.1 ± 1||2.9 ± 1.6||0.26|
|Amylase, UI/L ± SD||73 ± 55||75 ± 33||0.91|
|Lipase, UI/L ± SD||48 ± 50||60 ± 28||0.39|
|Sodium, mmol/L ± SD||138 ± 3||134 ± 7||0.09|
|Potassium, mmol/L ± SD||4 ± 1||4 ± 1||0.28|
|Chloride, mmol/L ± SD||101 ± 5||95 ± 10||0.003|
|Calcium, mmol/L ± SD||2.21 ± 0.2||2.20 ± 0.2||0.84|
|Phosphorus, mmol/L ± SD||1.06 ± 0.3||1.19 ± 0.34||0.25|
|Procalcitonin, ng/mL ± SD||0.16 ± 0.14||1.23 ± 2.3||0.002|
Table 1: Baseline characteristics of the population.
Kinetics’ profiles of serum PCT
The kinetics’ profiles of serum PCT and the evolution of the ratio between PCT in the CM and SM are presented respectively in Figures 2 and 3. The PCT levels are always lower in the CM group than in the SM one. The ratio between PCT measured in the CM and SM groups is comprised between 2 and 4 during the first 36 hours after the admission, and is high as 20 at 48 hours. The rate of CM failure considering the PCT values is depicted in Figure 4. This rate is correlated (R2=0.989) with the serum PCT of which values correspond to the 2-folded; 3-folded and 4-folded predictive threshold at admission.
Predictive time points of PCT to discriminate between CM success and SM
At admission: Using a ROC curve, the AUROCC for PCT at admission and SM was 0.802 [95% CI, 0.65–0.954] (Figure 5). A PCT threshold >0.165 ng/mL for predicting SM yielded a sensitivity of 83.3%, a specificity of 61%, a PPV of 35.7% and an NPV of 93.3%.
18 hours after the admission: Using a ROC curve, the AUROCC for PCT 18 hours after the admission and SM was 0.89 [95% CI, 0.0 – 1] (Figure 6). A PCT threshold >0.275 ng/mL for predicting SM yielded a sensitivity of 100%, a specificity of 75%, a PPV of 30% and an NPV of 100%.
24 hours after the admission: Using a ROC curve, the AUROCC for PCT 24 hours after the admission and SM was 0.859 [95% CI, 0.692–1] (Figure 7). A PCT threshold >0.255 ng/mL for predicting SM yielded a sensitivity of 83.3%, a specificity of 73%, a PPV of 42% and an NPV of 95%.
Predictive time points of PCT to discriminate between SM without peroperative ischemia and SM with peroperative ischemia
Using a ROC curve, the AUROCC for PCT and SM with peroperative ischemia was 0.861 [95% CI, 0.641 – 1] (Figure 8). A PCT threshold >0.53 ng/mL for predicting SM yielded a sensitivity of 80%, a specificity of 84.8%, a PPV of 40% and an NPV of 90.7%.
Our study was designed to complete our previous data related on the management of SBO and the potential use of serum PCT as a biomarker. The interest of PCT kinetics’ study has been to validate our previous data in an independent cohort. Indeed, the present population is similar in terms of demographic data as those we previously analyzed . Even if the inclusion period and duration are not similar (34 months vs. 10 months) there is no imbalance between the patients’ characteristics (same age, same comorbidities). As we have already reported, at admission the threshold used to discriminate between conservative management’s success and failure is around 0.17 ng/mL meaning normal PCT levels. This concordance between the results of these two studies could be explained as follow: first the laboratory that made the assessment has already been involved in the previous study (same material, same technicians, and same techniques); secondly as Steinbach et al. have reported in their article  the intra-assay and inter-assay coefficients of variation for the Kryptor T.R.A.C.E ® method were below 5% and below 10%, respectively. The pertinence of this method (quick results, repeatable data) now used daily in the clinical practice and emergency situations, made it sure and reliable.
The complexity for the surgeon to operate the patient is laid on the difficulty to identify the good candidate but his decision should be quick to avoid to pejore the prognosis. To help the clinician some elements are available such as clinical - (abdominal distension, fever); biological - (leukocytes, lactates) and morphological signs (pneumoperitoneum). Nevertheless these signs are imperfect because in our study none of these signs was predictive of the surgery confirming the results of Evennett et al., Gearhart et al. and Delaney et al. [13-15] showing that these “old markers” are not accurate enough. At admission, with a PCT higher than 0.53 ng/mL the surgeon could decide to operate the patient whereas a PCT between 0.17 and 0.53 ng/mL involves an aggressive monitoring. Twenty four hours after the admission a PCT higher than 0.27 ng/mL impose a surgery.
The choice of serum PCT as a biomarker for SBO’s management lies on its half life time (24 hours) . As reported by numerous previous works [17-21], in case of inflammatory state (for example SBO), cytokines such as IL6, IL8 and TNFα are released inducing a secretion of PCT but in case of conservative management’s success (mainly during the first day after the nasogastric tube suction’s beginning) the inflammatory state decreases quickly so the PCT secretion does. Complementary to these works, the data from Nagata et al. ; Markogiannakis et al. ; Karabulut et al.  and Ayten et al.  had already presented PCT as a possible biomarker. The strong correlation between PCT and the conservative management failure rate accentuates this proposition.
The difference between the two groups in the study related on chloride has previously been reported . The ion seems be involved in the SBO’s management and the disease’s severity. Indeed, it is possible that patients requiring surgical management have presented SBO’s symptoms longer than the others patients (nausea and vomiting; pain more pronounced). In that case chloride’s osmolarity will be modified enhancing PCT’s secretion to regulate the calcium’s metabolism. The part of chloride in the PCT’s secretion is reflected by the ratio PCT SM/ PCT CM. It seems that that ion enhances the production by a factor 2 or 4 (if we consider that no other variable is involved). The increase in the ratio after 36 hours could be due to many factors: the inflammatory state due to the surgical procedure (because in our study the was mainly performed after the 36th hours) , the possible infectious phenomenon engendered by the surgery etc.
To validate the use of PCT in this situation, we enrolled patients with acute kidney disease to ensure that kidney disease don’t have an impact on this biomarker’s kinetics. In deed patients admitted with SBO are frequently aged and could present an altered renal function. Nevertheless, in our population this biological function does not have any effect on PCT’s levels. This observation confirms the data of Meisner et al.  who reported no difference of PCT in case of renal dysfunction.
This study validates the role of serum PCT as a biomarker of bowel ischemia. Indeed, in our previous study, we showed that PCT was a marker of ischemia with a threshold of 0.57 ng/mL. The confirmation of these data in an independent cohort let us think that PCT could be proposed as a systemic marker of bowel ischemia reflecting the inflammatory state engendering by the obstruction.
Our work confirms the previous data on the use of PCT as a biomarker in SBO’s management. The more predictive time points are at admission, 12 hours and 18 hours after admission to identify patients requiring surgery.
This article has been presented as a poster at the UEG Week 2013 in Berlin