Point-of-care procalcitonin may predict the need for surgical treatment in patients with small bowel obstruction

a b s t r a c t

Background: The early identification of patients with Small bowel obstruction who require surgical treatment could potentially lead to improved patient outcomes. We evaluated the efficacy of point-of-care procalcitonin for predicting surgical treatment among patients with small bowel obstruction.

Methods: This was a prospective observational study. We measured serum procalcitonin levels in patients who presented to the emergency department and were diagnosed with small bowel obstruction from April 1, 2018 through March 31, 2019. Patients were grouped into two groups: the elevated procalcitonin and normal procalcitonin groups. Our primary outcome was surgical treatment.

Results: A total of 53 patients with small bowel obstruction were included in the study, and 11 patients (20.8%) were treated operatively. Baseline characteristics were similar, except for age, between the elevated procalcitonin (>=0.12 ng/ml) and normal procalcitonin groups. The elevated procalcitonin level was significantly correlated with surgical treatment and hospital length of stay (p b 0.05). The sensitivity, specificity, and positive likelihood of procalcitonin for the former were 45.5%, 85.7%, and 5.0 respectively.

Conclusion: The patients with small bowel obstruction who had elevated procalcitonin levels on presentation showed significantly higher rate of surgical treatment than those who had normal procalcitonin levels. Point- of-care procalcitonin might predict the need for surgical treatment in patients with small bowel obstruction and could be used as an additional diagnostic test. Further studies with more patients are needed to investigate the predictive value of point-of-care procalcitonin for surgical treatment.

Background

Small bowel obstruction (SBO) is one of the most common emer- gency surgical conditions, and has a high global burden [1]. A total of 967,332 days of care were attributed to primary and secondary adhesiolysis, and the related inpatient expenditures were $2.3 billion in the United States in 2005 [2].

All patients with inconclusive radiographs for complete or high grade SBO are recommended to undergo computed tomography (CT) scan according to the AAST guideline [3]. Patients with signs of strangu- lation or peritonitis require emergency surgery, and a low threshold for operative intervention is recommended. By contrast, patients without findings that suggest strangulation on CT are considered reasonable

* Corresponding author.

E-mail addresses: [email protected] (M. Murasaki), [email protected] (S. Maeda).

candidates for conservative management. However, water-soluble study or surgery is recommended when symptoms do not improve within 2 to 5 days after initiation of conservative management. It is daunting to make timely decisions for surgical management and various factors, including the patient’s condition, comorbidities, and the possi- bility of intestinal ischemia must be considered. Elderly patients are par- ticularly vulnerable to postoperative complications, and emergency surgery is a significant predictor for mortality among these patients [4]. Thus, a biomarker that provides accurate and objective assessment for surgery is required in patients with SBO.

procalcitonin , a 116 amino acid protein and precursor of calci- tonin, is a well-known plasma marker for sepsis and inflammation [5]. Several previous studies indicated a correlation between PCT and Bowel ischemia. Ayten et al. first reported the efficacy of PCT in the diag- nosis of bowel strangulation among rabbits [6]. Further, Cosse et al. in- dicated a correlation between PCT and failure of conservative management and suggested a PCT-based algorithm for adhesive SBO

https://doi.org/10.1016/j.ajem.2020.02.022

980 M. Murasaki et al. / American Journal of Emergency Medicine 38 (2020) 979–982

[7,8]. Another study showed that PCT was an independent predictor of bowel ischemia [9]. According to these studies, PCT would be promising for the management of SBO. The average turn-around time of PCT anal- ysis is 1-2 h in an in-house laboratory. However, on-site PCT measure- ment may not be available at many acute care hospitals [10]. Therefore, the results of PCT analysis would not be available to clinicians until 2-7 days after sample collection, and a timely decision for surgery based on the PCT levels would be impossible in such hospitals.

Several point-of-care PCT tests are commercially available, with the ease of measurement immediately after blood collection in the emer- gency department (ED). Our study aimed to determine the efficacy of point-of-care PCT for predicting the need for surgical treatment among patients with SBO.

Methods

We performed a prospective, single-center observational study. Dur- ing the study period from April 1, 2018 to March 31, 2019, we measured serum PCT levels in patients who were diagnosed with SBO and hospi- talized via the ED. Institutional Review Board approval was obtained be- fore study initiation. Written informed consent was obtained from all participants or their guardians before enrollment in this study.

Population

Patients with SBO who were diagnosed with a CT scan and hospital- ized via the ED were included. The exclusion criteria were as follows:

(1) early postoperative obstruction, (2) obstruction with neoplasia,

(3) a history of abdominal radiotherapy, (4) presence of pneumoperito- neum, (5) clinical signs of infection, (6) age b18 years, and

(7) pregnancy.

Procalcitonin assay

Point-of-care PCT was measured in the ED when the diagnosis of SBO was made. The AQT90 FLEX(R) (Radiometer, Tokyo, Japan) was used, and the turn-around time was approximately 20 min. All reagents and equipment were provided by Radiometer. The reference level for PCT was b0.12 ng/ml. Patients were classified into elevated or normal PCT groups based on the PCT levels.

Outcome

Our primary outcome was surgical treatment, which consisted of emergency surgery (defined as occurring within 24 h of presentation to the ED) and Urgent surgery after failure of conservative management. A surgical team decided whether emergency surgery should be per- formed. If the team decided that conservative management was appro- priate, the patient was hospitalized without surgery. A transnasal ileus tube or nasogastric tube was used based on the preference of the surgi- cal team. During hospitalization, urgent surgery was performed after failure of conservative management. The decision or timing of urgent surgery depended on the surgical team. The surgical team was blinded to patient PCT levels during treatment.

Secondary outcomes were hospital length of stay and mortal- ity. Other outcomes included time from symptom onset to operation, CT findings of strangulation and operative findings.

Statistical analyses

Summary statistics were presented as means +- standard deviations (SD), medians and interquartile ranges (IQR) or percentages, as appro- priate. The unpaired t-test, Mann-Whitney U test, and Fisher’s exact test were used to compare backgrounds between the elevated and normal PCT groups. For all analyses, a 2-tailed p value b0.05 was considered to indicate statistical significance. All statistical analyses were

performed using the STATA, version 14 (StataCorp, College Station, Texas, USA).

Results

During the study period, 53 patients with SBO were included. A flowchart of patient inclusion is shown in Fig. 1. Baseline characteristics were similar between the elevated PCT and normal PCT groups, except for age (Table 1). Overall, 11 (20.8%) and 42 (79.2%) patients underwent surgical and conservative treatment respectively. Emergency surgery was performed in 8 patients, and the remaining 3 patients in the oper- ative group underwent urgent surgery due to failure of conservative management during hospitalization.

Elevated PCT levels (>=0.12 ng/ml) significantly correlated with surgi- cal treatment (p b 0.05) (Table 2). The sensitivity, specificity, and odds ratio (OR) of elevated PCT and surgical treatment were as follows: 45.5%, 85.7% and 5.0 (95% confidence interval: 1.15-21.7). Further, ele- vated PCT levels were also correlated with LOS (p b 0.05), although a significant correlation was not found between elevated PCT levels and the mortality. There were no significant differences in the other out- comes between the elevated PCT and normal PCT groups. The results are also summarized in Table 3, comparing surgically treated and con- servatively treated groups.

Discussion

In this prospective study, patients with elevated point-of-care PCT levels were significantly more likely to require surgical treatment than those with normal PCT levels. Our findings suggest that point-of-care PCT can predict the need for surgical treatment and serve as an addi- tional diagnostic test in patients with SBO.

To the best of our knowledge, this is the first prospective study to evaluate point-of-care PCT in patients with SBO. Our findings were con- sistent with previous studies that indicated the predictive value of PCT for intestinal ischemia and necrosis in patients with bowel obstruction [7-9]. We investigated the diagnostic utility of point-of-care PCT in pa- tients with SBO, and those with elevated PCT levels were more likely to require surgery because of suspected peritonitis/strangulation or fail- ure of conservative management. Thus, clinicians may need to consider surgical treatment when patients with SBO present with elevated PCT levels. Further, we investigated point-of-care PCT with single measure- ment in this study, which requires lesser time than that required when PCT is measured in the laboratory and would enable physicians to make timely decisions. We did not perform multivariable analysis because of the small sample size. However, point-of-care PCT might be a useful di- agnostic marker in patients with SBO, and further research with more patients is necessary to confirm these findings.

Our study included patients who required emergency surgery and those who required urgent surgery after failure of conservative manage- ment. The decision for emergency surgery in patients with SBO was based on physical examination and CT results. However, PCT might pro- vide useful information for determining the need for emergency surgery when physical findings are unreliable or CT results are equivocal. Three patients with normal PCT levels who were initially suspected to have small bowel strangulation based on CT examination refused surgery in our study. All were successfully treated with conservative management, which also supports the utility of PCT for diagnosing bowel ischemia. Another 3 patients initially received conservative management but were subsequently treated surgically because conservative manage- ment failed. PCT was elevated in two of them, making the value of PCT for predicting failure of conservative management unclear due to the small number of outcomes in this study.

Significant differences in LOS were seen between the elevated PCT and normal PCT groups. Five out of 11 patients had bowel operations in the elevated PCT group. Thus, a significant difference could be caused by the bowel operations. However, we did not perform multivariable

M. Murasaki et al. / American Journal of Emergency Medicine 38 (2020) 979–982 981

Initial conservative management n=45

Emergency surgery n=8

Included n=53

Suspected of SBO and confirmed with CT scan n=66

Conservative management n=42

Surgical management n=11

Failure of conservative management n=3

Excluded n=13 Not hospitalized: 4

Colon obstruction: 9

Fig. 1. Flowchart of patient inclusion in the study. SBO: small bowel obstruction, CT: computed tomography.

analysis, and furthermore, we did not investigate postoperative and in- hospital complications. Therefore, further research would be necessary to explore whether SBO patients with elevated PCT levels have longer LOS.

According to Tables 3, 9 patients (82%) showed intestinal strangula- tion on CT, and 8 patients (73%) showed intraoperative bowel ischemia in the surgically treated group. This indicates that surgical treatment was appropriately selected for the patients in our study.

While we excluded patients with large bowel obstructions, a previ- ous study revealed that PCT reflected bowel ischemia and the failure of conservative management in both small and large bowel obstructions [9]. However, patients with large bowel obstructions tend to show higher PCT levels, suggesting that the same cut-off point for both small and large bowel obstruction is inappropriate [9]. Several factors are known to elevate PCT levels, but age was not previously considered to elevate PCT [11]. The patients in the elevated PCT group in our study

Table 1

Baseline characteristics of the population

Table 2

Outcomes in the elevated PCT and normal PCT groups.

	PCT elevated	PCT normal	p		PCT elevated	PCT normal	p
	n = 11	n = 42			n = 11	n = 42
Age, mean +- SD	81 (12)	69.5 (15)	b0.01?	Surgery, n (%)	5 (45)	6 (14)	0.04?
Male, n (%)	5 (46)	18 (43)	0.89	LOS, day (IQR)	11 (36)	8 (3)	0.04?
Charleson index, median (IQR)	3 (2)	2 (2)	0.1	Mortality, n (%)	1 (9)	1 (2)	0.38
Cause of SBO				Time from onset to operation, hour (IQR)	17 (116)	13 (34)	0.31
Adhesion, n (%)	6 (55)	29 (69)	0.48	CT findings of strangulation, n (%)	4 (36)	8 (19)	0.24
Hernia, n (%)	5 (45)	8 (19)	0.11	Operative findings
Foreign body, n (%)	0 (0)	5 (12)	0.57	Reversible bowel discoloration, n (%)	2 (18)	4 (10)	0.57
Previous laparatory, n (%)	10 (91)	36 (86)	0.67	Bowel necrosis, n (%)	1 (9)	1 (2)	0.99

PCT: procalcitonin, SD: standard deviation, IQR: interquartile range, SBO: small bowel obstruction.

Statistically significant.

PCT: procalcitonin, LOS: length of stay, IQR: interquartile range, CT: computed tomography.

Statistically significant.

982 M. Murasaki et al. / American Journal of Emergency Medicine 38 (2020) 979–982

Table 3

Outcomes in the surgically and conservatively treated groups.

Author contributions

Surgical n = 11

Conservative p n = 42

M.M. designed this study and performed the data acquisition. M.M and T.N. analyzed and interpreted the data. All of the authors wrote,

PCT elevated, n (%) 5 (45) 6 (14) 0.04?

LOS, day (IQR) 15 (32) 8 (3) b0.001?

Mortality, n (%) 1 (9) 1 (2) 0.38

edited, amended, revised and approved the revised manuscript.

Tine from onset to operation, hour (IQR)

17 (68) NA

Declaration of competing interest

CT findings of strangulation, n (%) 9 (82) 3 (7) b0.001?

Operative findings

Reversible bowel discoloration, n (%) 6 (55) NA Bowel necrosis, n (%) 2 (18) NA

PCT: procalcitonin, LOS: length of stay, IQR: interquartile range, CT: computed tomography.

* Statistically significant.

were significantly older than those in the normal PCT group in our study. Some of the older patients might have also had occult infections, including Aspiration pneumonia, which contributed to the elevated PCT. However, we did not investigate infectious complications in this study, and further research is needed to explore this question. PCT is sensitive to infection, and cautious interpretation would be required when it is el- evated [11]. The elapsed time from onset is another influential factor for PCT levels, and should be considered during clinical decision-making because they can be elevated as soon as 2 h after the onset of intestinal ischemia [6].

There were several limitations in this study. This was a single-center study with only 53 patients with SBO. Our sample size was small, and multivariable analysis could not be performed. Thus, a multi-center study with more patients is warranted to validate our findings. Sec- ondly, this was an observational study, and the decision for emergency or urgent surgery depended on the surgical team. Further, no specific al- gorithm or strategy was used during the study period. A randomized controlled study would be ideal to evaluate the diagnostic value of PCT, but it is an ethical issue to randomize patients who are recom- mended for surgery into conservative treatment groups. Lastly, we mea- sured point-of-care PCT once in the ED in order to make the study protocol simple. However, serial measurements would improve resolu- tion because PCT elevation takes a few hours, and patient conditions may worsen after hospitalization.

In conclusion, patients with SBO who had elevated PCT levels on pre- sentation to the ED were significantly more likely to require surgical treatment than those with normal PCT levels. Point-of-care PCT could predict the need for surgical treatment in patients with SBO, and it could be used as an additional diagnostic test. Further studies with more SBO patients are needed to establish the predictive value of point-of-care PCT for surgical treatment.

The test tubes and reagents used in this study were provided by Ra- diometer. Besides it, the authors have no conflicts of interest to declare.

Acknowledgements

We would like to express our appreciation for the excellent cooper- ation of the Departments of Surgery and the Department of Gastroen- terology at Fukui Prefectural Hospital.

References

AJEM