Wuhan, China

Quantitative analysis of intestinal gas in patients with acute pancreatitis

Ying Liu and He-Sheng Luo

Wuhan, China

BACKGROUND: Disturbance of gastrointestinal function is a common complication in the early phase of acute pancreatitis (AP). Intestinal gas may reflect the function of the gut. Using plain abdominal radiographs, we investigated whether intestinal gas volume is related to AP.

METHODS: Plain abdominal radiographs of 68 patients with AP within 24 hours after admission and 21 normal controls were digitized and transmitted to a computer. The region of intestinal gas was identified by an image manipulation software and the gas volume score (GVS) was calculated. The relationships between the GVS values and various clinical factors of AP were analyzed.

RESULTS: The GVS in the AP group was 0.084±0.016, in the mild AP (MAP) group 0.070±0.005, and in the severe AP (SAP) group 0.094±0.013; all values were higher than that in the control group (P＜0.01). The GVS in the SAP group was higher than that in the MAP group. The GVSs were correlated to the Ranson's scores (r=0.762,P＜0.01) and the acute physiology and chronic health evaluation II (APACHE II) scores (r=0.801,P＜0.01). In addition, the GVS in patients with secondary pancreatic and/or peripancreatic infection was 0.107±0.014, higher than that in patients without secondary infection (P＜0.01). GVS was not related to gender, age, etiology or clinical outcome of AP.

CONCLUSIONS: Intestinal gas volume is significantly elevated in patients with AP. It is closely related to Ranson's and APACHE II score and secondary pancreatic and/or peripancreatic infection. GVS may be a new prognostic tool for assessing the severity of AP in the early course of the disease.

(Hepatobiliary Pancreat Dis Int 2012;11:314-318)

acute pancreatitis; gas volume score; intestinal gas; gut motility; bacterial overgrowth

Introduction

Disturbances of gastrointestinal function such as intestinal ileus, gut barrier dysfunction, bacterial overgrowth and bacterial translocation are common complications in the early phase of acute pancreatitis (AP)[1-3]and play critical roles in initiating the development of pancreatitis-associated sepsis and multiple organ dysfunction syndrome.[2-5]

Most intestinal gas is produced by the fermentation of unabsorbed carbohydrates by anaerobic organisms in the colon,[6-8]and the gases of bacterial origin include hydrogen, methane, hydrogen sulfide and mainly carbon dioxide.[7-9]Intestinal gas is easily visualized on plain abdominal radiographs. The quantity of intestinal gas, determined by the pixel value on images and standardized by physique, is defined as gas volume score (GVS).[10]The GVS is an objective estimate of intestinal gas volume and computed tomography is more accurate for volume estimation.[11]

The volume of intestinal gas depends on the rate of gas production and excretion. Conceivably, many pathological factors, such as disturbed gut motility and intestinal bacterial overgrowth, can increase the volume of gas retention. This suggests that intestinal gas itself may reflect bowel function to some extent and is potentially related to AP in the early course of this disease.

To clarify the association between intestinal gas volume and AP in the present study, we analyzed GVSs using plain abdominal radiographs and assessed the relationships between these findings and various clinical factors of AP.

Methods

Patients

Medical charts and computerized records for all patients with AP treated at Renmin Hospital of Wuhan University located in central China from January 2004 to January 2010 were retrospectively reviewed. The diagnosis and classification of AP were made accordingto the guide for diagnosis and treatment of AP (draft, 2004) formulated by the Pancreatology Unit, Division of Gastroenterology, Chinese Medical Association.

Eligible patients were at least 18 years of age, had undergone a supine abdominal radiographic examination within 24 hours after admission, and had received a diagnosis and classification of AP. Exclusion criteria were a history of inflammatory bowel disease, constipation, chronic diarrhea, diabetes, thyroid disease, previous abdominal surgery, and renal or hepatic disease. Patients were excluded if they had taken antibiotics, tegaserod, antispasmodics, or antidiarrheal agents in the previous 28 days. Patients who had a history of intestinal infection, colonoscopic examination, and large bowel enemas in the previous 28 days were also excluded.

Among the 68 patients finally enrolled in the study, 44 were male and 24 female. Their median age was 53 years (range 18-75). Twenty-seven of these patients were classified as having mild AP (MAP), and 41 as having severe AP (SAP). For the control group, 21 healthy subjects recruited from the medical and nursing staff of the center were enrolled.

Data extraction

The following data were extracted: demographic data, etiological factors, secondary pancreatic and/or peripancreatic infection, and clinical outcome. The Ranson's score and the acute physiology and chronic health evaluation II (APACHE II) score were calculated using data from the first 48 hours after admission.

Radiography

Taking into account that some patients were not orthostatic and the measurements should be unified, supine abdominal radiographs were chosen. Images that were stored as soft copies in a picture archival and communication system were converted to JPG format. The number of pixels in each area was determined by an image software (Adobe Photoshop version 7.0, Adobe Systems, Inc., San Jose, CA, USA). GVS was calculated as the number of pixels of gas-filled area divided by the number of pixels in a rectangle drawn by a horizontal line tangential to the superior margin of the pubic symphysis, a horizontal line tangential to the inferior margin of the tenth dorsal vertebra and vertical lines tangential to the left and right anterio-superior iliac crests.[10,11]

Statistical analysis

Statistical analysis was performed with SPSS version 13.0 (SPSS Inc., Chicago, IL., USA). Data are expressed as mean±SEM. Differences between or among the groups were compared by Student'sttest or one-way ANOVA. Correlations were assessed by Pearson's productmoment correlation coefficient test. APvalue ＜0.05 was considered statistically significant.

Results

GVS in patients with AP

The GVS in the AP group was 0.084±0.016, which was higher than that in the control group (0.057±0.006) (P＜0.01). The GVSs in the MAP (0.070±0.005) and SAP (0.094±0.013) groups were both higher than that in the control group (P＜0.01). The GVS in the SAP group was higher than that in the MAP group (P＜0.01) (Fig. 1).

Relationship between demographics and GVS

While the GVS in male patients (0.083±0.013;n=44) was lower than that in female patients (0.086±0.021;n=24), the difference was not significant (P=0.387).

The GVS of AP patients who were under 40 years of age was 0.084±0.021 (n=11), between 40 and 60 years was 0.083±0.013 (n=36), and over 60 years was 0.086± 0.019 (n=21). Hence the GVS was not correlated with age in AP patients (P=0.890).

Relationship between etiology and GVS

The GVSs in patients with AP caused by biliary (0.085±0.015;n=44), alcoholic (0.082±0.018;n=17), and other etiological factors (0.087±0.020;n=7) were not significantly different (P=0.771).

Correlations between Ranson's score, APACHE II score and GVS

The GVSs were correlated with the Ranson's scores (r=0.762,P＜0.01) and the APACHE II scores (r=0.801,P＜0.01) (Fig. 2). The coefficients of determination were 0.581 and 0.641, respectively.

Fig. 1. GVSs in patients with AP. *:P＜0.01, compared to the control group, #:P＜0.01, compared to the MAP group.

Fig. 2. Correlations of GVSs with Ranson's (A) and APACHE II (B) scores.

Relationship between secondary pancreatic and/or peripancreatic infection during hospitalization and GVS

Thirty patients developed secondary pancreatic and/ or peripancreatic infection during hospitalization. The GVS in these patients (0.107±0.014;n=30) was higher than that in patients without secondary infection (0.079± 0.011;n=38) (P＜0.01)

Relationship between clinical outcome and GVS

The GVS in non-survivors was 0.098±0.009 (n=4), which was higher than that in survivors (0.083±0.016;n=64), but the difference was not significant (P=0.082).

Discussion

In this study, the GVS in patients with AP was significantly elevated. The plain abdominal radiographs of these patients showed sentinel loops, colon cutoff sign, and bowel distention with multiple air-fluid levels.

The cause of the increased level of intestinal gas in patients with AP remains unexplained, but several mechanisms can account for it. First, soon after the onset of AP, various factors such as hormones, neurotransmitters, inflammatory mediators and endotoxin can alter gastrointestinal motility by a direct effect on smooth muscle cells or an indirect effect by influencing the neuronal circuits involved in peristalsis.[12,13]The reduced peristaltic activity may result in abnormal gas retention. Second, intestinal motility serves as a normal cleansing mechanism of the intestine.[14]Delayed motility with systemic and local immunosuppression from the early phase of AP can cause small intestinal bacterial overgrowth.[15-21]The contaminating flora in small intestinal bacterial overgrowth commonly feature colonic-type bacteria,[18]and gases of bacterial origin account for almost 3/4 of flatulence.[22,23]Therefore, bacterial overgrowth and intestinal content retention can create the potential for large quantities of gas within the intestinal lumen. GVS, reflecting gastrointestinal motility and intestinal bacterial overgrowth, appears to be a practical tool to assess gastrointestinal function. The significantly higher GVS in the SAP group demonstrates that these patients have greater gastrointestinal disturbance.

The Ranson's and APACHE II scores are the "traditional" multifactorial scoring systems in predicting the severity, pancreatic necrosis, and mortality of AP.[24]The data showed that the GVSs within 24 hours of admission were significantly correlated with these scores, suggesting that GVS may be a new and useful parameter for early prediction of the prognosis of AP. Intraabdominal hypertension and abdominal compartment syndrome due to the accumulation of gas within the intestinal lumen[25]may be some of the reasons for these strong correlations between GVS and these scores.

Secondary infection supervenes in 30%-70% of patients with pancreatic necrosis and is significantly associated with increased late death.[2,5,26]Enteric Gramnegative organisms account for most infections of pancreatic necrosis and subsequent sepsis,[27-29]suggesting the gut itself acts as a source of infection. The small bowel seems to be the major source of enteral bacteria in infected pancreatic necrosis.[30]In our study, the GVS in patients with secondary pancreatic and/or peripancreatic infection was significantly higher than that in patients without secondary infection. This implies that the increased level of intestinal gas may reflect the development of bacterial translocation. Although pathology of the intestine may be the initial cause of intra-abdominal hypertension, further intra-abdominal pressure can, in turn, result in intestinal mucosal ischemia and ischemia/reperfusion injury,[25]and then increase intestinal permeability to bacteria and endotoxin.[2]The development of abnormal bacterial overgrowth and an increase in intestinal permeability may partly explain why patients with secondary pancreatic and/or peripancreatic infection had higher GVSs.

Interestingly, the GVS in survivors was lower than that in non-survivors, but the difference was not significant. Perhaps the improvement of conservative management, surgical intervention and interventional intensive care account for this result.

AP is a dynamic and evolving process that involves the risk of multiple organ complications.[24]Many factors, such as extensive inflammatory processes in the retroperitoneum, visceral edema, increased capillary permeability, massive fluid resuscitation, electrolyte imbalance, formation of pancreatic ascites and pharmacological stimulation of intestinal propulsion appear to affect GVS. Whether GVS performs with high accuracy in the prediction of the severity and clinical outcome of AP over 24 hours after admission is still unknown. Moreover, the GVSs were not completely correlated with the Ranson's and APACHE II scores. For these reasons, additional structured analysis may be needed to determine the impact of multiple factors to accurately predict specific outcomes on a patient-bypatient basis.

In conclusion, intestinal gas volume is significantly elevated in patients with AP within 24 hours after admission and is closely related to Ranson's score, APACHE II score and secondary pancreatic and/or peripancreatic infection. GVS may be a new prognostic tool to assess the severity of AP in the early course of this disease. However, as GVS appears to be affected by many factors, other pathological indexes may be taken into account in the accurate prediction of the severity and outcome of AP.

Contributors: LY and LHS proposed the study. LY wrote the first draft. Both authors contributed to the design and interpretation of the study and to further drafts. LHS is the guarantor.

Funding: This work was supported by a grant from the National Natural Science Foundation of China (81070297).

Ethical approval: Not needed.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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June 17, 2011

Accepted after revision December 4, 2011

Correction

10.1016/S1499-3872(12)60167-2)

Author Affiliations: Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, China (Liu Y and Luo HS)

He-Sheng Luo, MD, Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, China (Tel: 86-27-88041911; Fax: 86-27-88042292; Email: luotang@public.wh.hb.cn)

? 2012, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(12)60166-0

The article entitled "Tumor ablation with nanosecond pulsed electric fields" by Chen et al (Hepatobiliary Pancreat Dis Int2012;11:122-124.) contains an error. The 3rd to last paragraph equates nanosecond pulsed electric fields with the Nanoknife. This is in error. Nanosecond pulsed electric fields (nsPEFs) use pulse durations in the nanosecond range while the Nanoknife uses microsecond pulses. Thus, really the term "Nanoknife" is an unfortunate, but established misnomer. The two technologies are distinctly different in the levels of pulse power applied and in cell and tissue responses to them. At least part of the death processes induced by nsPEFs is due to apoptosis. The Nanoknife induces necrosis, as best understood at this time. The full extent of cell response differences between nsPEFs and the Nanoknife remain to be determined.