Original Article

Perforated Peptic Ulcer: Different Ethnic, Climatic and Fasting Risk Factors for Morbidity in Al-Ain Medical District, United Arab Emirates

Fawaz Chikh Torab, Mohamed Amer, Fikri M. Abu-Zidan and Frank James Branicki, Department of Surgery, Faculty of Medicine & Health Sciences, UAE University, UAE.

AIM: To evaluate risk factors, morbidity and mortality rates of perforated peptic ulcer (PPU) and to inves- tigate factors affecting postoperative complications of PPU. BACKGROUND: The incidence of PPU has remained constant, simple closure with omental patch repair being the mainstay of treatment. PATIENTS AND METHODS: One hundred and nineteen patients admitted to Al-Ain Hospital with PPU between January 2000 and March 2004 was studied retrospectively; two with deficient data were excluded from the analysis. Logistic regression was used to define factors affecting postoperative complications. RESULTS: The mean age of patients was 35.3 years (range, 20–65). 45.7% of patients were Bangladeshi, and 85.3% originated from the Indian subcontinent. One patient, subsequently found to have a perfo- rated gastric cancer, died. In 116 patients, 26 complications were recorded in 20 patients (17.2%). Common risk factors for perforation were smoking, history of (PUD) and use of non-steroidal anti-inflammatory drugs (NSAIDs). A significantly increased risk of perforation was evident during the daytime fasting month of Ramadan. An increase in the acute physiology and chronic health evaluation (APACHE) II score (p = 0.047) and a reduced white blood cell count (0.04) were highly significant for the prediction of postoperative complications. CONCLUSION: Patients with dyspeptic symptoms and a history of previous PUD should be considered for prophylactic treatment to prevent ulcer recurrence during prolonged daytime fasting in Ramadan, especially during the winter time. [Asian J Surg 2009;32(2):95–101]

Key Words: peptic ulcer, perforation

Introduction e.g. smoking,3 NSAID use, a previous history of PUD, infection4 and alcohol intake have dif- Although morbidity from peptic ulcer disease (PUD) ferent prevalence rates in differing communities and is decreasing in the west, the incidence of perforated affect the incidence of perforation in various ways with ulcer remains relatively constant.1,2 Perforated ulcers are additive effects of multiple factors.5–7 We observed in our decreasing in incidence in younger age patients and practice different epidemiological characteristics of pep- are increasingly being observed in the elderly and in tic ulcer perforation other than those evident in western women.1,2 Different risk factors for PUD and perforation societies.

Address correspondence and reprint requests to Professor Frank James Branicki, Department of Surgery, Faculty of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al-Ain, United Arab Emirates. E-mail: [email protected] ● Date of acceptance: 5 December 2008

© 2009 Elsevier. All rights reserved.

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Following developments in the medical treatment of postoperative death, thus the mortality rate was 1/117 PUD in the last two decades, surgical intervention is cur- (0.9%). This patient had a diagnosis of perforated gastric rently confined to the treatment of complicated disease, cancer and was excluded from the statistics of the study as namely, ulcer haemorrhage, perforation and obstruction.8 the disease had different etiology and morbidity. Of the Simple closure or omental patch repair is the mainstay of other 116 patients, 114 were male (98.3%). The mean age of treatment of perforated peptic ulcer (PPU),9–11 definitive patients was 35.3 years (range, 20–65). No patient had surgery being rarely practised12 with dependence now chronic cardiac, pulmonary or hepatic dysfunction. Renal on medical therapy to complete the healing process and dysfunction was evident in two patients (1.7%), hypertension prevent recurrence of the disease.10,13–15 occurred in three (2.6%), and four had diabetes mellitus In this retrospective study we reviewed our PPU admis- (3.4%). None had significant organ dysfunction or failure. sions during a 4-year period to identify risk factors in this particular community, determine our morbidity and mor- Management tality rates and study factors affecting postoperative com- All patients were treated, first by resuscitation, then plications of PPU including Boey16 and APACHE II scores.17 open laparotomy, peritoneal toilet and closure of the per- foration employing an omental patch. Postoperatively, Patients and methods intravenous antibiotics were used for 3–5 days. One hundred and thirteen patients (97.4%) received postop- This is a retrospective study of the medical records of all erative oral eradication therapy with Amoxicillin 1 g twice adult patients admitted to the Department of Surgery at daily, Clarithromycin 500 mg twice daily for 1–2 weeks Al-Ain Hospital with the diagnosis of a perforated peptic plus Omeprazole (Losec) 20 mg twice daily for 10 days. ulcer which was confirmed intraoperatively during the period from 1 January 2000 to 31 March 2004. After Intraoperative findings defining our objectives and reviewing the literature, we Ulceration in the duodenal bulb was found in 107 of 116 designed a documentation sheet to collect data necessary patients (92.2%) there being only one ulcer in the second to complete the study. We obtained the approval of the part of the duodenum, six prepyloric ulcers and two gas- Research Ethics Committee and the Head of the tric ulcers. The patient who died had a perforation in an Department of Surgery and the Medical Records section adenocarcinoma; the only case of malignant ulceration in to undertake the study. The data were collected from the study and this patient was excluded from our analy- patients’ charts anonymously and documented. sis. Ulcer size was only documented in 109 patients; in seven patients it was not recorded. The mean diameter Inclusion criteria was 5.2 mm (range, 1–20). All patients > 18 years of age admitted during the period of the study with operatively confirmed PPU. Postoperative course The range of postoperative hospital stay was 3–26 days, Exclusion criteria the mean ± SD being 7.6 ± 3 days. The patient who stayed Patients with (a) association of bleeding and perforation, 26 days developed postoperative pleural effusion, pneu- (b) immunodeficiency arising from any cause apart from monia, liver abscess, and . He was treated by percu- diabetes mellitus, (c) vital data missing from the medical taneous drainage of the effusion and the abscess in records or (d) pregnancy. addition to antibiotic therapy. The patient who stayed only 3 days left at his own request and against advice as Patients he planned to travel to his home country. Demographic data One hundred and nineteen patients had been treated, two Postoperative morbidity of whom were excluded; in one case a lost medical record Postoperative complications including organ dysfunction could not be retrieved despite every effort being made and or failure were defined according to the published in the other, operative notes were missing from the definitions of Deithch et al.18 Twenty patients (17.2%) patient’s file. In the remaining 117 patients there was one developed postoperative complications. The most

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common were respiratory complications, which occurred regression model was used to define factors related to in 12 patients (10.3%). Cardiac complications occurred in postoperative complications.19,20 The outcome variable of two patients (1.7%), intra-abdominal infection including the logistic model was whether the patient had postoper- pelvic and right iliac fossa collections, and liver abscess ative complications or not and the factors which were occurred in three patients (2.5%). Wound infection was entered into the logistic model as covariates were factors diagnosed in two patients (1.7%). Seven patients (6%) that had a p value of less than 0.05 in the univariate analy- experienced other complications. Morbidity encountered sis. Different direct logistic models have been tried and in these patients included paralytic ileus (two), uremia explored until the best model was found and presented. with convulsions (one), confusion with hallucination (one), Data were analyzed using the Statistical Package for the diarrhea (one), and a hypotensive episode with dehydration Social Sciences (version 15, SPSS Inc., Chicago, IL, USA). (one). One patient had a postoperative “acute abdomen” For all analyses, a p value < 0.05 was considered significant. and was found to have gangrenous small bowel possibly due to hypotension with non occlusion of mesenteric ves- Results sels on Angio computed tomography (CT). He underwent small bowel resection and right hemicolectomy. Fifteen Risk factors related to the incidence of the disease patients each had a single complication, four patients Seasonal distribution of admissions each had two complications and one patient had three The number of patients with PPU admitted during the complications. winter months of November to February was four cases per month. This was higher than the rate of 1.34 cases per Follow up endoscopy month in non winter months (Table 1). The number of The plan of the study, and according to the policy of the patients admitted during the fasting month of Ramadan hospital, was to follow up all patients with PPU with (27 patients) (Table 2) was significantly higher than the endoscopy, to exclude a persistent peptic ulcers. Patient demographics are explained by the fact that most of our Table 1. Frequency of admissions per month patients are heavy manual workers on camp sites or con- Month of Total number Rate of admission struction sites based out of town, who may leave the coun- admission of admissions per month try after having an operation. Only 25 patients came for follow up endoscopy (21.6%). The remaining patients January* 16 3.2 failed to attend (78.4%). Of the 25 patients who underwent February* 16 3.2 March 5 1.25 upper gastrointestinal (GIT) endoscopy, five had persistent April 8 2 ulcers, and one had a deformed duodenal bulb. We cannot May 7 1.75 assume that most patients, who did not come for endos- June 5 1.25 copy, had no residual ulcer disease symptoms. July 3 0.75 August 5 1.25 Statistical analysis September 4 1 Univariate analysis to compare patients with and without October 6 1.5 postoperative complications was performed using the November* 17 4.25 Mann-Whitney test for continuous or ordinal data and December* 24 6 Fisher’s exact test for categorical data. A multiple logistic *November to February are considered to be winter months.

Table 2. Individual Arabic (Ramadan) months of admissions

Ramadan month Gregorian equivalent No. of admissions

Ramadan 1,421 h 27/11/2000–25/12/2000 9 Ramadan 1,422 h 16/11/2001–14/12/2001 3 Ramadan 1,423 h 05/11/2002–03/12/2002 9 Ramadan 1,424 h 26/10/2003–24/11/2003 6

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expected number to be admitted in that month (10 usage was less common, 13 patients (11.2%). Alcohol patients) (p < 0.004, Fisher’s exact test; 27/116 compared intake was documented in three patients (2.6%). with 10/116). The highest admission rate occurred when there was a coincidence of winter month and fasting days Risk factors related to postoperative morbidity (26 patients within 110 days, 7.1 cases/month) which was Univariate analysis has shown four factors to be signifi- higher compared with winter months alone (47 cases cantly different between the group with postoperative within 431 days, 3.3 cases/month) or in non winter complications and the group without (Table 3). These months with non-fasting days (42 cases within 1,001 days, were age (p = 0.02), white blood cell count (p = 0.03), Boey 3 cases/month). Total Score (0.046), and APACHE II Score (p = 0.01). Those who had complications had significantly longer Nationality distribution postoperative hospital stay (p < 0.0001, median range, The highest frequency rates were observed in Bangladeshi 10 (5–26) days compared with 6 (3–12) days. nationals (45.7%), Pakistani patients (24.1%) and Indian The multiple logistic model was highly significant nationals (15.3%). Most patients (85.3%) emanated from (p = 0.003). The results of this model are shown in Table 4. the Indian subcontinent. Although 12.1% were of Arab An increase in the APACHE II Score (p = 0.047) and a origin, UAE nationals comprised only 1.7%. reduced white blood cell count (0.04) were highly signifi- cant to predict postoperative complications. Risk factors for perforation The Receiver Operator Curve (ROC) of the white Smoking and history of PUD were the most common fac- blood cell count has shown that a white blood cell count tors, 42 patients in each category (36.2%), while NSAID of less than 4,000 × 109/L was the best cut off point for

Table 3. Univariate analysis comparing patients without postoperative complications and those with complications

No postoperative Postoperative p value complications (n = 96) complications (n = 20)

Age 33 (20–65) 39 (24–55) 0.02 Gender (male:female) 94:2 20:0 0.68 Indian subcontinent nationality 83 16 0.49 Presence of risk factors 63 12 0.61 Fasting month 22 5 0.52 Temperature (°C) 37 (36–38.5) 37 (36–39) 0.68 Systolic blood pressure (mmHg) 120 (90–160) 125 (86–204) 0.28 Heart rate (bpm) 82 (56–120) 82.5 (54–160) 0.77 Haematocrit (%) 44.4 (29–61.8) 44.2 (35–56) 0.39 White blood cell count (109/L) 14.26 (3.39–32.7) 11.48 (2.94–25.1) 0.03 Ulcer size (mm) 5 (1–20) 5 (2–10) 0.79 Delay of treatment (h) 10 (4–62) 10 (6–72) 0.45 APACHE II Score 2 (0–15) 5 (0–12) 0.01 Boey Total Score 0 (0–2) 0 (0–2) 0.046 p = Mann-Whitney test or Fisher’s exact test as appropriate. Data are presented as numbers or median (range) as appropriate.

Table 4. Direct logistic regression model defining the factors affecting postoperative complications

Variable Estimate Standard error Wald test p value Odds ratio

Age 0.035 0.03 1.16 0.28 1.04 White blood cell count −0.1 0.05 4.3 0.038 0.9 Total APACHE Score 0.18 0.09 3.95 0.047 1.2

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23 1.0 4,000 × 109/L been observed by other authors from the region. The increased incidence in the Bangladeshi population may serve to highlight some racial and dietary features which 0.8 merit further investigation. The percentage of Bangladeshi patients who had PPU [53/116 (45.7%)] was significantly 0.6 higher than their percentage in our Trauma Registry at Al-Ain Hospital [296/2,573 (11.5%)], which was similar to their distribution in the real population (p < 0.00001, Sensitivity 0.4 Fisher’s exact test). This could be also related to different risk factors for H. pylori infection in different ethnic groups.3 It was shown that these risk factors have no 0.2 direct relationship to the likelihood of postoperative complications. As most of our patients were young and 0 fit, chronic illness was very infrequent compared with the 0 0.2 0.4 0.6 0.8 1.0 literature.11,24 1 – specificity Two scoring systems; Boey Scores16 and APACHE II Figure. Receiver Operator Curve of white blood cell count as Scores17 were examined for usefulness in predicting post- a predictor of postoperative complications. A white blood cell operative morbidity. Our logistic regression analysis has count less than 4,000 × 109/L was the best cut off point for predicting morbidity. shown that a reduced white blood cell count in the blood and APACHE II scores significantly correlated with the predicting morbidity. The ROC for APACHE II was not occurrence of complications. This is keeping with other useful in predicting morbidity as it was almost linear studies showing the usefulness of APACHE II Scores in without a plateau (Figure). selecting patients for laparoscopic repair of PPU.25 Others have reported coexisting medical illnesses, delayed treat- Discussion ment,21 and low albumin concentration to be independent risk factors for mortality.24 Age, pulse rate at admission, The stimulus to this study was the hypothesis that creatinine levels, delayed surgery, presence of shock, ASA Ramadan daylight fasting is associated with a higher inci- risk and definitive surgery were considered to be inde- dence of ulcer perforation than is seen in other non-fasting pendent factors associated with prognosis in PPU.23,26 months of the year. Table 1 shows that the incidence of One study showed that having an age more than 65 years, PPU is lowest in non-winter days with no fasting and is a haemoglobin level less than 10 g/dL, and hypotension increased with a relative risk of 2.62 for winter days with on admission were associated with poor outcome after no fasting, and this is even higher (5.67) in fasting days emergency gastrectomy irrespective of underlying gastric during the winter. pathology.27 The risk of developing a postoperative com- The higher incidence in younger age groups and in plication was found to be significantly influenced by males in the UAE, is most probably attributable to a greater the presence of concomitant medical illness, abdominal number of younger age patients in the UAE and the fact distension and a history suggestive of shock at the time that most manual workers, the social group mainly at risk, of admission.28 are male expatriates residing in the UAE without their All of these perforations were treated in the same way families. This observation was reported recently by a study regardless of the ulcer location. Although no imaging undertaken in a similar population.21 study was done to detect any leakage after repair, we did The most common risk factors for perforation in our not encounter any overt clinical leak, which might require study were smoking and a history of PUD, in addition to re-operation. Gastric ulcers were always biopsied, and we male gender and Bangladeshi nationality. Smoking more had only one malignant gastric ulcer perforation (0.9%). than 15 cigarettes a day compared with “never smoking” No test for H. pylori was routinely performed preoper- increased the risk of a perforated ulcer more than three- atively. The policy of the hospital is to give empiric eradi- fold.22 A high incidence in the male gender (88.8%) has cation for H. pylori to all patients with PPU. This policy

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arose from a previous study conducted in the same hos- 3. Pillay KV, Htun M, Naing NN, et al. Helicobacter pylori infection pital which had shown that more than 90% of patients in peptic ulcer disease: the importance of smoking and ethnic- with perforated ulcer were found to be H. pylori positive.29 ity. Southeast Asian J Trop Med Public Health 2007;38:1102–10. 4. Andreson H, Sillakivi T, Peetsalu M, et al. Persistence of In our study all five patients who had postoperative recur- Helicobacter pylori infection in patients with peptic ulcer perfora- rent ulcers had received postoperative oral eradication tion. Scand J Gastroenterol 2007;42:324–9. therapy; one was not compliant with treatment whilst 5. Andersen IB, Jorgensen T, Bonnevie O, et al. Smoking and alcohol the remaining four had received a full eradication regi- intake as risk factors for bleeding and perforated peptic ulcers: a men. Three of these had a history of PUD and one was population-based cohort study. Epidemiology 2000;11:434–9. 6. El Serag HB, Graham DY, Richardson P, et al. Prevention of a smoker and drank alcohol. It is known that there is complicated ulcer disease among chronic users of nonsteroidal increased risk of recurrent ulceration in patients with anti-inflammatory drugs: the use of a nomogram in cost- PUD who have a low eradication rate of H. pylori infection effectiveness analysis. Arch Intern Med 2002;162:2105–10. after surgical and antimicrobial treatment.30 This fre- 7. Hernandez-Diaz S, Rodriguez LA. Association between non- quent manifestation of infection is mostly caused by per- steroidal anti-inflammatory drugs and upper gastrointestinal sisting virulent strains of H. pylori.4 The importance of tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med 2000;160:2093–9. smoking in association with H. pylori infection was 8. Jamieson GG. Current status of indications for surgery in pep- 3 previously reported. tic ulcer disease. World J Surg 2000;24:256–8. Our zero mortality rate is much lower than that 9. Michelet I, Agresta F. Perforated peptic ulcer: laparoscopic reported in other studies from the region (3.9%),21 8.6%23 approach. Eur J Surg 2000;166:405–8. and 13.6%.26 This was also lower than rates reported 10. Millat B, Fingerhut A, Borie F. Surgical treatment of complicated worldwide (9–30%).24 This may be attributed to an older duodenal ulcers: controlled trials. World J Surg 2000;24:299–306. 11. Siu WT, Leong HT, Law BK, et al. Laparoscopic repair for perfo- mean age and higher comorbidity in other reports.31,32 rated peptic ulcer: a randomized controlled trial. Ann Surg 2002;235:313–9. Conclusion 12. Chang TM, Chan DC, Liu YC, et al. Long-term results of duo- denectomy with highly selective in the treatment of Patients with dyspeptic symptoms and/or a history of complicated duodenal ulcers. 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