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Emergency Surgery 2 Perforated Peptic Ulcer Series Emergency surgery 2 Perforated peptic ulcer Kjetil Søreide, Kenneth Thorsen, Ewen M Harrison, Juliane Bingener, Morten H Møller, Michael Ohene-Yeboah, Jon Arne Søreide Lancet 2015; 386: 1288–98 Perforated peptic ulcer is a common emergency condition worldwide, with associated mortality rates of up to 30%. See Editorial page 1212 A scarcity of high-quality studies about the condition limits the knowledge base for clinical decision making, but a few This is the second in a Series of published randomised trials are available. Although Helicobacter pylori and use of non-steroidal anti-infl ammatory three papers about emergency drugs are common causes, demographic diff erences in age, sex, perforation location, and underlying causes exist surgery between countries, and mortality rates also vary. Clinical prediction rules are used, but accuracy varies with study Department of population. Early surgery, either by laparoscopic or open repair, and proper sepsis management are essential for good Gastrointestinal Surgery, Stavanger University Hospital, outcome. Selected patients can be managed non-operatively or with novel endoscopic approaches, but validation of Stavanger, Norway such methods in trials is needed. Quality of care, sepsis care bundles, and postoperative monitoring need further (Prof K Søreide MD, assessment. Adequate trials with low risk of bias are urgently needed to provide better evidence. We summarise the K Thorsen MD, evidence for perforated peptic ulcer management and identify directions for future clinical research. Prof J A Søreide MD); Department of Clinical Medicine, University of Introduction important role in diagnosis, as does early resuscitation, Bergen, Bergen, Norway Perforated peptic ulcer is a surgical emergency and is including administration of antibiotics. Appropriate risk (Prof K Søreide, associated with short-term mortality in up to 30% of assessment and selection of therapeutic alternatives ; MRC Centre Prof J A Søreide) 1 for Infl ammation Research, patients and morbidity in up to 50%. Worldwide becomes important to address the risk for morbidity and University of Edinburgh, Royal variations in demography, socioeconomic status, mortality. In this review, we present an update on the Infi rmary of Edinburgh, Helicobacter pylori prevalence, and prescription drugs present understanding and management of perforated Edinburgh, UK make investigation into risk factors for perforated peptic peptic ulcer. (E M Harrison MBChB); Department of Surgery, Mayo ulcer diffi cult. Perforated peptic ulcer presents as an acute Clinic, Rochester, MN 55905, abdominal condition, with localised or generalised Epidemiology of peptic ulcer disease and its USA (Prof J Bingener MD); peritonitis and a high risk for development of sepsis and complications Department of Intensive Care death. Early diagnosis is essential, but clinical signs can Complications to peptic ulcer disease include perforation, 4131, Copenhagen University 2,3 Hospital Rigshospitalet, be obscured in elderly people or immunocompromised bleeding, and obstruction. Although perforations are Copenhagen, Denmark patients, thus delaying diagnosis. Imaging has an second to bleeding in frequency (about 1:6 ratio), they represent the most common indication for emergency surgery for peptic ulcer disease.4–6 Overall progress in Key messages medical management has made obstruction from • Perforated peptic ulcer is associated with short-term mortality of up to 30% and is recurrent ulcer scarring a rare event, and the addition of regarded as one of the most lethal surgical emergencies worldwide • Incidence rates of perforated peptic ulcers have remained steady in developed Search strategy and selection criteria countries in recent decades, but with substantial geographical diff erences in other regions such as Africa and Asia We searched MEDLINE via PubMed and Embase for articles • Helicobacter pylori, non-steroidal anti-infl ammatory drugs, and smoking are confi rmed risk published between Jan 1, 2000, and Feb 28, 2015, and the factors for ulcers, but the pathogenesis that leads to perforation is not well understood Cochrane Library (issue 12, December, 2014), using the search • Clinical prediction rules can identify patients at high risk of death, but with variable terms “perforated peptic ulcer” and “gastric” or “duodenal” or accuracy “gastroduodenal ulcer” and “perforated” or “perforation”. • Elderly patients with sepsis, presenting with delay to surgery have the highest Articles published in all languages were considered for mortality rates inclusion. We also searched ClinicalTrials.gov, the ISRCTN • Surgical repair should not be delayed in patients with general peritonitis because every Registry, PROSPERO, and the WHO International Clinical Trials hour of delay increases the mortality risk Registry Platform databases for prospective trials for any • Laparoscopic surgical repair has similar morbidity and mortality rates as open surgery recruiting or closed studies (as yet unpublished) on • Patients with clinical signs of spontaneous resolution can be considered for perforated peptic ulcer. We focused on recently published non-operative management in selected cases research (within the past 5 years) where possible, and • Novel techniques, including endoscopy, might in the future reduce the surgical insult favoured studies or trials with a low risk of bias (systematic and improve outcomes reviews, randomised controlled trials, clinical trials, and • Future improvements should be achieved through enhanced patient selection for well-conducted population-based observational studies), but surgery or alternative strategies and improved perioperative management of sepsis did not exclude relevant commonly cited and highly regarded • Long-term follow-up studies are needed, since mortality risk remains increased for older publications. We also searched the reference lists of several years after surgery articles identifi ed by our search. 1288 www.thelancet.com Vol 386 September 26, 2015 Series endoscopic techniques and transarterial embolisation Pathogenesis, causes, and risk factors for (M H Møller MD); and has reduced the need for emergency surgery for bleeding perforation Department of Surgery, ulcers.3 In 2006, more than 150 000 patients were Although an overall imbalance between the protective Kwame Nkrumah University of Science and Technology, admitted to hospital for complicated peptic ulcer disease and the ulcerogenic factors is obvious in ulcer formation, Kumasi, Ghana in the USA alone. Although the overall share of the reasons why some patients’ ulcers perforate and (Prof M Ohene-Yeboah MBChB) complications caused by perforations (n=14 500 [9%]) others do not remain unclear. The ulcerogenesis involves Correspondence to: was seven-times lower than that attributable to bleeding, infection (H pylori), mucosal barrier injury (eg, use of Prof Kjetil Søreide, Department perforated peptic ulcers caused 37% of all ulcer-related drugs), and increased hydrochloric acid production of Gastrointestinal Surgery, Stavanger University Hospital, 4 4 deaths. According to US data, more than one in every (panel; fi gure 2). However, the precise risk estimates and PO Box 8100, ten hospital admissions for perforated peptic ulcer leads contribution of each factor are still poorly understood.26 N-4068 Stavanger, Norway to death. Indeed, perforated peptic ulcer had a fi vefold Only about a third of patients with perforated peptic ulcer [email protected] higher mortality rate than bleeding ulcers, and was the have a previous history of or current known peptic ulcer single most important contributor to inpatient mortality at the time of diagnosis. Furthermore, some patients in the USA between 1993 and 2006, with an odds ratio develop very small (<5 mm) perforations without large (OR) of 12·1 (95% CI 9·8–14·9).4 mucosal defects, which suggests that ulcer size is Many studies report a steady incidence of perforated unrelated to perforation risk, whereas others might peptic ulcer during the 1980s–90s, but studies from develop large mucosal defects with perforation several Sweden, Spain, and the USA in the 1990s and early centimetres in size. 2000s noted a fall in the incidence of both bleeding and The putative pathogenesis and role of Helicobacter perforations.7–9 Mortality rates for perforated peptic virulence factors is reviewed extensively elsewhere.27,28 For the Global Burden of ulcer in Europe have been quite stable during the past About 50% of the global population is colonised by Disease Study 2010 see http:// ghdx.healthdata.org/record/ 10 three to four decades, despite progress in perioperative H pylori in the gastric mucosa, yet it causes disease in global-burden-disease-study- care, imaging techniques, and surgical management.11 only 10–20% of people. H pylori shows a variable 2010-gbd-2010-results-cause- The epidemiology of peptic ulcer disease overall has prevalence (0–90%) in perforated ulcers, and ulcers can 1990-2010-country-level changed in the past 50 years, initially following changes also develop in the absence of H pylori infection and For the United Nations in socioeconomic development in high-income countries, non-steroidal anti-infl ammatory drug use.2 Notably, Development Programme Human Development Index see then with the identifi cation and medical treatment of co-factors such as smoking and alcohol are recorded http://hdr.undp.org/en/content/ 18,29 H pylori as a causative agent, and fi nally with the across studies from diff erent regions (fi gure 2). human-development-index-hdi
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