Acute Abdomen in Crohn’s disease patients: short- and long-term outcomes

doi:10.21203/rs.3.rs-3417081/v1

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Acute Abdomen in Crohn’s disease patients: short- and long-term outcomes

https://doi.org/10.21203/rs.3.rs-3417081/v1

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Background. To determine long-term outcome in Crohn’s disease patients hospitalized for acute abdominal pain.

Methods. Retrospective chart review of consecutive Crohn’s disease patients hospitalized for acute abdominal pain at the tertiary referral centre in Eastern Europe.

Results. Between 2015 and 2020, 65 patients with Crohn’s disease were admitted at least once to hospitals’ emergency room because of acute abdominal pain. 13 patients were admitted twice, 8 three times, 3 patients four times and 3 patients five times. Also, the intake of immunosuppressive medication was apparently rare, thus, most patients have been treated by 5-ASA medication only. Most patients had ileal involvement. Two patients presented with an intraabdominal abscess. 53 of 65 patients underwent abdominal imaging during the hospitalization. After hospital admission, 45 patients were treated with antibiotics (65%),17 with steroids (17%), 8 patients received a nasogastric tube and 3 were put on parenteral nutrition. Six patients underwent an intestinal resection during the initial hospitalization (9%). The length of the hospitalization was median 8 days (range, 1 to 115) and it was significantly longer in those, who underwent surgery (mean 28 days vs. 9 days, p = 0.003). Follow-up information was obtained for all patients, and the median follow-up time was 42.8 months. During the follow-up period, 26 patients (40%) readmitted for abdominal emergencies. 14 patients underwent surgery – either at the initial or later hospitalization (21%). Thirteen out of 14 surgeries were emergencies, three were concluded by ostomy formation (21%). One patient developed postoperative intraabdominal complication, however, two patients died postoperatively (14%).

By multivariate analysis, complicated disease (stricturing or penetrating) was associated with hospital readmission (Hazard ratio, 5.8, 95% CI: 1.4–23.3; p = 0.013). An elevated C-reactive protein level was associated with a decreased risk of hospital readmission (Hazard ratio,0.08, 95% CI: 0.01–0.55; p = 0.010). Also, complicated disease (stricturing or penetrating) was associated with enhanced probability to undergo intestinal surgery (Hazard ratio, 10.3, 95% CI: 2.4–44.1; p = 0.002)

Conclusion. Ileocolic disease is the main cause of hospitalization for acute abdominal pain. Complicated (structuring or penetrating) disease should be diagnosed early and surveilled closely.

Crohn’s disease

acute abdomen

Emergency

repeat hospitalization

intestinal surgery

stricturing

penetrating

abdominal pains

perforation

IBD

Acute abdomen is a disorder that must be treated immediately. An infection, inflammation, vascular occlusion and intestinal obstruction are all potential causes of acute abdomen. Usually, the patient will experience an abrupt onset of stomach pain along with accompanying nausea or vomiting. In the emergency department (ED), acute abdominal pain is a common presenting symptom, comprising 5–10% of all ED visits [1–2].

There are no specific data on how many patients are hospitalized exactly due to Chron’s disease and acute abdomen, however, since the natural history of disease which is characterized by intraabdominal inflammation and intestinal obstruction is expected to lead to exceeding incidence of abdominal emergencies.

The population-based cohort of South-Limburg (The Netherlands) showed that the hospitalization rate due to Chron's disease decreased from 65.9–44.2% and the surgery rate from 42.9 to 17.4% at 5 years, respectively (both P < 0.01) [3]. Global Hospitalization Trends for Crohn’s Disease and Ulcerative Colitis in the 21st Century, showed that the hospitalization rate due to CD depends on the stage of industrialization of the country, varies from 3.62 to 10.94% [4]. Toxic colitis with or without megacolon, massive hemorrhage, free perforation, acute abscess (either intra-abdominal or perianal) with sepsis, and intestinal obstruction are examples of acute surgical emergencies [5]. The data did not differentiate between acute abdomen and other reasons for hospital admissions. Nevertheless, one might expect that acute abdominal pain was a reason for hospitalization in a significant proportion of cases.

WSES (World Society of Emergency Surgery) guidelines tells that CD can present with acute complications requiring emergency surgery in approximately 6 to 16% of hospitalized cases [6]. Acute surgical emergencies in patients with Crohn’s disease can have a high morbidity, thus knowledge of prognosis and natural history of those emergencies are from paramount importance.

According to the existing literature, the risk of surgery at 1, 5, and 10 years after CD diagnosis is 16.3%, 33.3% and 46.6%, respectively [7]. About 10–13% of intestinal resections are performed as emergency surgeries [Iesalnieks 2008], although the incidence is probably decreasing.

Patients who require emergency surgery are generally in critical condition and have intraabdominal sepsis or intestinal obstruction. Compromised immunity and malnutrition expose them to even a higher risk of complications and mortality. [8].

In this retrospective analysis, our objective was to discuss not only acute complications of CD and their treatment, but more importantly, what happened with patients after an episode of acute abdomen, how often patients are readmitted, and is it possible to decrease the rate of repeated hospitalizations by elective surgery.

A retrospective study was conducted in consecutive patients with Crohn’s disease who were admitted emergently to an academical referral center because of acute abdominal pain between 2015 and 2020. Demographic data, symptoms at presentation, current medication, results of abdominal imaging techniques, laboratory values, history of the disease were obtained by retrospective chart review. The disease phenotype was classified in each case according to the Montreal Classification of Crohn’s disease [9] based on abdominal imaging. If no abdominal imaging had been performed at the first hospitalization, clinical behaviour was obtained by intraoperative finding or data of diagnostic studies performed during the follow-up period. The main variables of the Montreal classification are disease localization (L1 – disease of terminal ileum, L2 – colonic disease, L3 – disease of both ileum and colon, L4 – disease of gastrointestinal tract proximally to terminal ileum. L4 is a modifier that can be added to L1–L3 when concomitant upper gastrointestinal disease is present) and the clinical behaviour (B1 – not stricturing/not penetrating disease, B2 – stricturing disease, B3 – penetrating disease). Penetrating disease (B3) is defined as presence of intraabdominal fistula, abscess, and/or an inflammatory mass. The mere presence of perianal fistulae is not considered as “penetrating disease”. B2 and B3 are exclusive: the clinical behaviour is classified as B3 in patients with intraabdominal fistula, abscess, or inflammatory mass even if a concomitant stricture is present. Severe anemia was defined as haemoglobin level of less than 10 g/dl.

Telephone interviews with patients and primary care physicians were conducted in order to obtain follow up data. Also, data from hospital records were used in case of repeat hospitalizations at Riga East Clinical University Hospital.

The primary endpoint of the study was the determination of risk factors for hospital readmission because of the Crohn’s disease. The secondary endpoint of the study was risk for the bowel resection for Crohn’s disease.

Statistics

Mann-Whitney test was applied in the case of non-normal distribution for continuous variables. Comparisons between patient groups were made using Fisher’s exact test for categorical variables. Variables associated to hospital readmission and risk of surgery at univariate analysis with a P < 0.2 were included in a multivariate analysis using a stepwise logistic regression model with backward elimination. P < 0.05 was considered to indicate statistical significance (two-tailed test). Statistical Package for the Social Sciences version 20 (IBM, Chicago, IL, United States) was used. The study was accepted by the local ethic committee of the University of Latvia.

Between 2015 and 2020, 65 patients with Crohn’s disease were admitted at least once to hospitals’ emergency room because of acute abdominal pain. Thirteen patients were admitted twice, 8 three times, 3 patients four times and 3 patients five times. Table 1 demonstrates patients’ and disease characteristics of the study population. There were a very high proportion of smokers. Also, the intake of immunosuppressive medication was apparently rare, thus, most patients have been treated by 5-ASA medication only. Most patients had ileal involvement. Two patients presented with an intraabdominal abscess. 53 of 65 patients underwent abdominal imaging during the hospitalization.

Table 1

Patients with Crohn’s disease attending emergency department for acute abdominal pain – demographics and disease characteristics.
Variable	Number
Female sex	35 (54%)
Age, years (mean, range)	42.6 (18–89)
Smokers	35 (58%)
Previous intestinal surgeries	9 (14%)
Medication at the time of hospital admission - Systemic Steroids - Azathioprine - Budesonide - Biologicals - No medication other the 5-ASA	8 (12%) 6 (9%) 4 (6%) 1 (1.5%) 50 (77%)
Vomiting at the initial presentation	23 (35%)
Diarrhea at the initial presentation	34 (52%)
Laboratory values - Elevated C-reactive level > 5mg/d - Elevated leucocyte count > 10/nl - Severe Anemia	53 (83%) 34 (52%) 12 (18%)
Disease localization - L1 – Ileitis - L2 – colitis - L3 - ileocolitis	28 (42%) 11 (17%) 26 (41%)
Clinical behavior - B1 – non-stricturing/non-penetrating - B2 – stricturing - B3 -penetrating	34 (61%) 6 (11%) 16 (29%)
Total	65 (100%)

After hospital admission, 45 patients were treated with antibiotics (65%),17 with steroids (17%), 8 patients received a nasogastric tube and 3 were put on parenteral nutrition. Six patients underwent an intestinal resection during the initial hospitalization (9%). The length of the hospitalization was median 8 days (range, 1 to 115) and it was significantly longer in those, who underwent surgery (mean 28 days vs. 9 days, p = 0.003).

Follow-up information was obtained for all patients, and the median follow-up time was 42.8 months. During the follow-up period, 26 patients (40%) readmitted for abdominal emergencies. Fourteen patients underwent surgery – either at the initial or later hospitalization (21%). Thirteen out of 14 surgeries were emergencies, three were concluded by ostomy formation (21%). One patient developed postoperative intraabdominal complication, however, two patients died postoperatively (14%).

Tables 2 and 3 depict the results of univariate analysis of factors associated with the risk of repeat hospitalizations and surgery. By multivariate analysis, complicated disease (stricturing or penetrating) was associated with hospital readmission (Hazard ratio, 5.8, 95% CI: 1.4–23.3; p = 0.013). An elevated C-reactive protein level was associated with a decreased risk of hospital readmission (Hazard ratio,0.08, 95% CI: 0.01–0.55; p = 0.010). Also, complicated disease (stricturing or penetrating) was associated with enhanced probability to undergo intestinal surgery (Hazard ratio, 10.3, 95% CI: 2.4–44.1; p = 0.002)

Table 2

Risk of hospital readmission after hospitalization for acute abdominal pain in Crohn’s disease patients
Variable	Number (%)	p
Age - < 40 years - ≥ 40 years	16 of 36 (44%) 10 of 29 (34%)	0.45
Sex - Female - Male	11 of 30 (37%) 15 of 35 (43%)	0.8
BMI at the time of hospitalization - < 20 kg/mg² - ≥ 20 kg/mg²	10 of 19 (53%) 14 of 44 (32%)	0.16
Smokers - Yes - No	15 of 38 (39%) 11 of 27 (41%)	1.0
C-reactive protein level at hospitalization - < 5mg/L - > 5 mg/L	8 of 11 (73%) 17 of 53 (32%)	0.018
Severe anemia - Yes - No	6 of 12 (50%) 20 of 53 (38%)	0.52
Clinical behavior - Non-stricturing/non-penetrating - Penetrating or stricturing	10 of 34 (29%) 13 of 22 (59%)	0.05
Ileal involvement - Yes - No	23 of 54 (43%) 3 of 11 (27%)	0.5
Previous intestinal surgeries - Yes - No	6 of 9 (66%) 20 of 56 (36%)	0.14

Table 3

Risk of to undergo surgery after hospitalization for acute abdominal pain in Crohn’s disease patients.
Variable	Number (%)	p
Age - < 40 years - ≥ 40 years	7 of 36 (19%) 7 of 29 (24%)	0.76
Sex - Female - Male	5 of 30 (17%) 9 of 35 (26%)	0.54
BMI at the time of hospitalization - < 20 kg/mg² - ≥ 20 kg/mg²	5 of 19 (26%) 7 of 44 (16%)	0.48
Smokers - Yes - No	9 of 38 (24%) 5 of 27 (18%)	0.76
C-reactive protein level at hospitalization - < 5mg/L - > 5 mg/L	2 of 11 (18%) 12 of 53 (23%)	1.0
Severe anemia - Yes - No	3 of 12 (25%) 11 of 53 (21%)	0.71
Clinical behavior - Non-stricturing/non-penetrating - Penetrating or stricturing	3 of 34 (9%) 11 of 22 (50%)	0.001
Ileal involvement - Yes - No	14 of 54 (26%) 0 of 11 (0%)	0.10
Previous intestinal surgeries - Yes - No	2 of 9 (22%) 12 of 56 (21%)	1.0

The present study demonstrated a high risk of hospital readmission (40%) and surgery (21%) during the first 4–5 years after in-hospital treatment of acute abdominal pain for Crohn’s disease. There was a significant risk of emergent surgery, ostomy formation at surgery and mortality, if immediate emergent surgery could not be avoided or at least postponed to be performed electively. Complicated disease (structuring or penetrating) was significantly associated with hospital readmission (59%) and risk of surgery (59%).

Despite the lack of studies specifically looking to patients with Crohn’s disease attending the emergency department because of acute abdominal pain, there are some data supporting our findings [10]. Sarikaya et al. [11] examined the outcomes of early surgery in 497 patients with Crohn's disease. The study found that surgery performed during an acute flare-up of Crohn's disease was associated with a higher risk of complications, reoperation, and anastomotic leaks, compared to surgery performed during a period of remission. However, the study also found that surgery performed during an acute flare-up was not associated with a higher risk of mortality. Another study by Kimura et al [12] published in 2020 evaluated the outcomes of emergency surgery in patients with Crohn's disease. The study found that emergency surgery was associated with a higher risk of complications, including wound infections and bowel obstructions, compared to elective surgery. The study also found that patients who underwent emergency surgery had a higher risk of reoperation and a longer hospital stay.

However, in some cases, emergent surgery may be necessary to manage acute symptoms and prevent complications. In fact, 13 out of 14 patients in our study underwent emergent surgery, however, 8 of those operations were performed during one of the next hospital admissions for acute abdominal pain. It underscores the importance to choose the right patient for elective surgery after successful medical treatment of acute abdominal symptoms. The presence of a stricture or a penetrating disease which are seen in distal ileum much more frequently than in the colon, should be a strong factor to plan the surgery in order to avoid further hospitalizations and emergent surgeries.

The optimal timing for surgery hospitalization due to Crohn's disease with an acute abdominal pain depends on several factors, including the patient's clinical condition, the severity and location of the disease, and the presence of complications. In some cases, emergency surgery may be necessary, such as when there is bowel perforation, or complete bowel obstruction. In these situations, surgery must be performed as soon as possible to prevent life-threatening complications. Unfortunately, there is a lack of studies determining the risk of emergent surgery in Crohn’s disease patients. In our study, 6 out of 65 patients underwent emergent surgery at the initial hospitalization for a risk of emergent surgery of 9%.

Since emergent surgery is associated with an increased morbidity – as clearly demonstrated by the present and abovementioned studies – patients’ management in the emergency room should be aimed to recognize the patients who need immediate surgery and those who will probably recover after medical treatment to postpone the decision whether to operate at all. There are no internationally established guidelines for abdominal emergencies in Crohn’s disease, thus, only some thoughts could be discussed. Steroids are frequently given in patients with acute abdominal pain due to Crohn’s disease. In our study, 17% of patients received steroids as an initial treatment. Steroids might reduce the swelling in the strictured intestinal segment relieving the signs of obstruction. However, surgery will be performed under high steroid dosage in case the steroids failed. In patients with penetrating disease, initial steroids should not be given in order to avoid the risk of septic derangement. Instead, antibiotics and fluid resuscitation might be the best primary choice. Abdominal cross-sectional imaging should be performed at the acute presentation to differentiate between complicated and uncomplicated disease and between stricturing and penetrating disease. Abscesses should be drained percutaneously. An abscess drainage – when technically feasible – might be one of the best tools to avoid emergent surgery, however, there were only 2 patients presenting with acute abdomen having an intraabdominal abscess in our study and many abscesses are to small or not accessible for percutaneous drainage [Müller-Wille, Iesalnieks 2013].

If the decision for elective surgery has been done some type of preoperative optimization strategies will be probably the right choice since impairment of the general health and particularly the nutritional status might be expected in many patients going through acute abdominal pain necessitating in-hospital treatment.

The low number of patients and lack of abdominal imaging in 12 patients during the initial hospitalization are limitations of our study. Also, we were no able to analyze te value of particular treatment strategies. The results might be different in other hospitals or countries. There was a very high number of smokers in our study. Also, there was an obviously low usage of immunosuppressive treatment in the current population as most patients were treated by 5-ASA medications only. Since the present study is of a retrospective manner, the proportion of patients with successful initial medical treatment might have been higher if avoiding of the emergent surgery was the primary goal of treatment. Physicians with less experience in Crohn’s disease might have more difficulties to predict the natural history of abdominal emergency in this particular population.

In conclusion, complicated Crohn's disease should be recognized early already in the emergency department in order to discuss the indications of operative therapy following recovery after successful emergent medical treatment.

Data availability statements

Data available on requests from the authors. The data that support the finding of this study are available from the corresponding author [J.O.] upon reasonable request.

Conflict of Interest:

None

Authors contribution

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Janis Opincans, Agris Rudzats and Zurabs Kecbaja, Aleksejs Kaminskis and Igors Ivanovs. The first draft of the manuscript was written by Janis Opincans and Igors Iesalnieks and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

No Funding was obtained for this study.

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No competing interests reported.

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Acute Abdomen in Crohn’s disease patients: short- and long-term outcomes

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Discussion

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