AIM: To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city.

METHODS: One hundred and forty-nine consecutive patients (M:F ratio = 110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings.

RESULTS: The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (χ²) with increased mortality in patients undergoing surgery (0.0001 < P < 0.03).

CONCLUSION: Factors such as concomitant diseases, shock on admission, delayed surgery, and postoperative abdominal and wound infections are significantly associated with fatal outcomes and need careful evaluation within the general workup of patients admitted for perforated peptic ulcer.

There has been a marked decrease in elective surgery for peptic ulcer disease (PUD) following introduction of medical therapies including H₂-receptor antagonists, and more recently proton pump inhibitors with or without antibiotics for H pylori eradication. By contrast, the number of acute complications e.g. ulcer perforation and bleeding requiring emergency surgery, have remained quantitatively constant[1,2]. Peptic ulcer perforation is a serious complication which affects almost 10% of PUD patients. Overall, PUD accounts for more than 70% of mortality associated with the disease[3,4]. Several potential predicting factors for perforation have been evaluated in the literature, including use of ulcerogenic drugs (e.g. steroids, NSAIDs, immunosuppressive agents, etc.), and the development of an acute, rather than chronic peptic ulcer[5-8].

In this paper, we studied the main factors associated with mortality in a large number of patients undergoing surgery for perforated peptic ulcers (PPU) in a large referral academic hospital in southern Italy.

The time between perforation and surgery was delayed in 51 patients (34.2%), 79 patients (53.0%) had associated diseases which are listed in Table 1. Cardiovascular, chronic obstructive pulmonary diseases and diabetes mellitus were the most frequently (over 65%) associated conditions. A previous history of PUD was found in 53 (35.6%) patients and 9 (6.0%) were shocked on admission. Gastric and duodenal ulcers were perforated in 23 (15.4%) and 126 (84.6%) patients, respectively.

Types of postoperative complications are reported in Table 2. The most frequent events were due to general, rather than abdominal complications or wound infections.

The analysis of factors associated with mortality is depicted in Table 3. Of the 149 patients, 6 died yielding an overall mortality rate of 4.0%. The presence of one or more associated diseases, delay in surgical approach, shock on admission, postoperative abdominal complications (6 dehiscence/abscess, 2 bleedings, 2 stenosis) and the postoperative wound infections were all significantly (0.0001 < P < 0.04) associated with increased mortality in patients undergoing surgery for PPU. By contrast, age, sex, previous history and site of peptic ulcer, type of surgical treatment and the development of postoperative general complications were not associated with increased mortality.

Several factors might contribute to increased postoperative mortality in patients with PPU. Perforation has been found to be a major complication of PUD with a mortality rate ranging from 6% to 31%[6-8,11-20].

Age of patients with PPU has been gradually increasing over the last years[21-23]. In this series, an age > 65 years tended to be associated with increased mortality. This finding is in line with other studies in which older patients frequently had associated diseases, or they were more on NSAIDs treatment[8,16,22]. It should be also noted that the mean age of patients from this series was considerably lower than that from patients included in different studies. Thus, such differences might account for the markedly lower overall mortality rate (4.0%), as compared to other series[6-8,11-20].

In accord with others[19,23], we could not find that male sex was associated with a greater mortality rate. Also, there was no significant difference in mortality rate between gastric or duodenal ulcer and in patients with or without previous ulcer history. Apparently, these findings were at variance with those from two other studies[13,24] reporting a higher mortality rate in gastric peptic ulcer than in duodenal peptic ulcer and in acute peptic ulcer than in chronic peptic ulcer. Such apparent discrepancies might be explained by the characteristics of patients included in the study, and/or by different age or different surgical procedures[16,18].

This study confirmed the previous observations[5,8,15,25-28] that shock on admission and delayed operation were both associated with a greater mortality rate.

Despite the fact that surgery remains the choice of treatment for PPU, the type of procedure in emergency is still debated. In some series definitive surgery had lower rates of recurrence and mortality than non definitive surgery[16,18,19,29,30]. Otherwise, non-definitive surgery was more frequently performed in patients admitted with more risk factors than definitive surgery, and this might explain the higher mortality rate of such studies. Moreover, diffusion of the laparoscopic approach to PPU with less surgical trauma and less metabolic and physiological disturbances, has determined an increase of non definitive surgical procedures performed by simple closures[3,20,22,31]. In the present study, there was no difference in mortality rate between definitive (i.e. Billroth II resection) or non-definitive (i.e. ulcer excision and suture with or without pyloroplasty) surgical procedure.

It has been reported that mortality rate increased progressively with increasing numbers of risk factors[6,8]. Indeed, the mortality rate was 0% and 7.6% in the group of patients without and with associated diseases, respectively. In the present study cardiovascular, chronic obstructive pulmonary diseases and diabetes mellitus were the most frequent concomitant diseases. Besides, 6 patients developing a postoperative abscess had a previous history of chronic obstructive pulmonary disease. A possible explanation for such an outcome could be the reduced tissue oxygenation resulting in damage of post-surgical wound healing process. This possibility was supported by recent studies from our group at the intestinal level in both experimental and clinical conditions[32-36].

We also observed that in patients developing postoperative abdominal complications (i.e. 6 abscesses, 2 bleedings, and 2 stenosis) and wound infections, the mortality rate was significantly higher (P = 0.0001) than those without abdominal complications. We would like to explain that such a striking difference was due to the development of a generalized sepsis in the group of patients with intra-abdominal abscess. Indeed, 83.3% (i.e. 5/6) of patients with dehiscence and abdominal abscess, died in the postoperative period, otherwise, in this group with postoperative complications, the appearance of stenosis or bleeding was not associated with a higher mortality rate. In our experience the presence of wound infection appeared to be a predictive factor for mortality. A careful analysis of the 3 patients who died of wound infection, however, revealed that the cause of exitus was septicaemia complicating an abdominal abscess. By contrast, postoperative general complications did not influence the prognosis of patients with PPU.

In conclusion, concomitant diseases, shock on admission, delayed surgery, and postoperative abdominal and wound infections are factors significantly associated with fatal outcomes in patients undergoing emergency surgery for perforated peptic ulcer. Older age tends to fulfill a similar trend. Thus, such factors need to be carefully taken into account during the general workup of patients admitted for PPU.