Morten Hylander Møller

Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients

PurposeTo assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU).MethodsWe performed a systematic review using meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane Collaboration methodology was used. Risk ratios/relative risks (RR) with 95xa0% confidence intervals (CI) were estimated. The predefined outcome measures were all-cause mortality, GI bleeding, and hospital-acquired pneumonia.ResultsTwenty trials (nxa0=xa01,971) were included; all were judged as having a high risk of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95xa0% CI 0.84–1.20; Pxa0=xa00.87; I2xa0=xa00xa0%) or hospital-acquired pneumonia (random effects: RR 1.23, 95xa0% CI 0.86–1.78; Pxa0=xa00.28; I2xa0=xa019xa0%) between SUP patients and the no prophylaxis/placebo patients. These findings were confirmed in the TSA. With respect to GI bleeding, a statistically significant difference was found in the conventional meta-analysis (random effects: RR 0.44, 95xa0% CI 0.28–0.68; Pxa0=xa00.01; I2xa0=xa048xa0%); however, TSA (TSA adjusted 95xa0% CI 0.18–1.11) and subgroup analyses could not confirm this finding.ConclusionsThis systematic review using meta-analysis and TSA demonstrated that both the quality and the quantity of evidence supporting the use of SUP in adult ICU patients is low. Consequently, large randomised clinical trials are warranted.

Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients

PurposeTo describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients.MethodsWe included adults without GI bleeding who were acutely admitted to the intensive care unit (ICU) during a 7-day period. The primary outcome was clinically important GI bleeding in ICU, and the analyses included estimations of baseline risk factors and potential associations with 90-day mortality.ResultsA total of 1,034 patients in 97 ICUs in 11 countries were included. Clinically important GI bleeding occurred in 2.6xa0% (95xa0% confidence interval 1.6–3.6xa0%) of patients. The following variables at ICU admission were independently associated with clinically important GI bleeding: three or more co-existing diseases (odds ratio 8.9, 2.7–28.8), co-existing liver disease (7.6, 3.3–17.6), use of renal replacement therapy (6.9, 2.7–17.5), co-existing coagulopathy (5.2, 2.3–11.8), acute coagulopathy (4.2, 1.7–10.2), use of acid suppressants (3.6, 1.3–10.2) and higher organ failure score (1.4, 1.2–1.5). In ICU, 73xa0% (71–76xa0%) of patients received acid suppressants; most received proton pump inhibitors. In patients with clinically important GI bleeding, crude and adjusted odds for mortality were 3.7 (1.7–8.0) and 1.7 (0.7–4.3), respectively.ConclusionsIn ICU patients clinically important GI bleeding is rare, and acid suppressants are frequently used. Co-existing diseases, liver failure, coagulopathy and organ failures are the main risk factors for GI bleeding. Clinically important GI bleeding was not associated with increased adjusted 90-day mortality, which largely can be explained by severity of comorbidity, other organ failures and age.

Preoperative prognostic factors for mortality in peptic ulcer perforation: a systematic review

Abstract Objective. Mortality and morbidity following perforated peptic ulcer (PPU) is substantial and probably related to the development of sepsis. During the last three decades a large number of preoperative prognostic factors in patients with PPU have been examined. The aim of this systematic review was to summarize available evidence on these prognostic factors. Material and methods. MEDLINE (January 1966 to June 2009), EMBASE (January 1980 to June 2009), and the Cochrane Library (Issue 3, 2009) were screened for studies reporting preoperative prognostic factors for mortality in patients with PPU. The methodological quality of the included studies was assessed. Summary relative risks with 95% confidence intervals for the identified prognostic factors were calculated and presented as Forest plots. Results. Fifty prognostic studies with 37 prognostic factors comprising a total of 29,782 patients were included in the review. The overall methodological quality was acceptable, yet only two-thirds of the studies provided confounder adjusted estimates. The studies provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality. Shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high American Society of Anaesthesiologists score, and preoperative delay >24 h were associated with poor prognosis. Conclusions. In patients with PPU, a number of negative prognostic factors can be identified prior to surgery, and many of these seem to be related to presence of the sepsis syndrome.

Perforated peptic ulcer

Summary Perforated peptic ulcer (PPU) is a frequent emergency condition worldwide with associated mortality up to 30%. A paucity of studies on PPU limits the knowledge base for clinical decision-making, but a few randomised trials are available. While Helicobacter pylori and use of non-steroidal anti-inflammatory drugs are frequent causes of PPU, demographic differences in age, gender, perforation location and aetiology exist between countries, as do mortality rates. Clinical prediction rules are used, but accuracy varies with study population. Early surgery, either by laparoscopic or open repair, and proper sepsis management are essential for good outcome. Selected patients can perhaps be managed non-operatively or with novel endoscopic approaches, but validation in trials is needed. Quality of care, sepsis care-bundles and postoperative monitoring need further evaluation. Adequate trials with low risk of bias are urgently needed for better evidence. Here we summarize the evidence for PPU management and identify directions for future clinical research.

Surgical delay is a critical determinant of survival in perforated peptic ulcer

Morbidity and mortality following perforated peptic ulcer (PPU) remain substantial. Surgical delay is a well established negative prognostic factor, but evidence derives from studies with a high risk of bias. The aim of the present nationwide cohort study was to evaluate the adjusted effect of hourly surgical delay on survival after PPU.

Multicentre trial of a perioperative protocol to reduce mortality in patients with peptic ulcer perforation

Morbidity and mortality rates in patients with perforated peptic ulcer (PPU) remain substantial. The aim of the present study was to evaluate the effect of a multimodal and multidisciplinary perioperative care protocol on mortality in patients with PPU.

Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery.

OBJECTIVES:The treatment of peptic ulcer bleeding (PUB) is complex, and mortality remains high. We present results from a nationwide initiative to monitor and improve the quality of care (QOC) in PUB.METHODS:All Danish hospitals treating PUB patients between 2004 and 2011 prospectively registered demographic, clinical, and prognostic data. QOC was evaluated using eight process and outcome indicators, including time to initial endoscopy, hemostasis obtainment, proportion undergoing surgery, rebleeding risks, and 30-day mortality.RESULTS:A total of 13,498 PUB patients (median age 74 years) were included, of which one-quarter were in-hospital bleeders. Preadmission use of anticoagulants, multiple coexisting diseases, and the American Society of Anesthesiologists scores increased between 2004 and 2011. Considerable improvements were observed for most QOC indicators over time. Endoscopic treatment was successful with primary hemostasis achieved in more patients (94% in 2010–2011 vs. 89% in 2004–2006, relative risk (RR) 1.06 (95% confidence intervals 1.04–1.08)), endoscopy delay for hemodynamically unstable patients decreased during this period (43% vs. 34% had endoscopy within 6u2009h, RR 1.33 (1.10–1.61)), and fewer patients underwent open surgery (4% vs. 6%, RR 0.72 (0.59–0.87)). After controlling for time changes in prognostic factors, rebleeding rates improved (13% vs. 18%, adjusted RR 0.77 (0.66–0.91)). Crude 30-day mortality was unchanged (11% vs. 11%), whereas adjusted mortality decreased nonsignificantly over time (adjusted RR 0.89 (0.78–1.00)).CONCLUSIONS:QOC in PUB has improved substantially in Denmark, but the 30-day mortality remains high. Future initiatives to improve outcomes may include earlier endoscopy, having fully trained endoscopists on call, and increased focus on managing coexisting disease.

The Peptic Ulcer Perforation (PULP) score: a predictor of mortality following peptic ulcer perforation. A cohort study

Accurate and early identification of high‐risk surgical patients with perforated peptic ulcer (PPU) is important for triage and risk stratification. The objective of the present study was to develop a new and improved clinical rule to predict mortality in patients following surgical treatment for PPU.

Association between biomarkers of endothelial injury and hypocoagulability in patients with severe sepsis: a prospective study

IntroductionPatients with severe sepsis often present with concurrent coagulopathy, microcirculatory failure and evidence of vascular endothelial activation and damage. Given the critical role of the endothelium in balancing hemostasis, we investigated single-point associations between whole blood coagulopathy by thrombelastography (TEG) and plasma/serum markers of endothelial activation and damage in patients with severe sepsis.MethodsA post-hoc multicenter prospective observational study in a subgroup of 184 patients from the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial. Study patients were admitted to two Danish intensive care units. Inclusion criteria were severe sepsis, pre-intervention whole blood TEG measurement and a plasma/serum research sample available from baseline (pre-intervention) for analysis of endothelial-derived biomarkers. Endothelial-derived biomarkers were measured in plasma/serum by enzyme-linked immunosorbent assay (syndecan-1, thrombomodulin, protein C (PC), tissue-type plasminogen activator and plasminogen activator inhibitor-1). Pre-intervention TEG, functional fibrinogen (FF) and laboratory and clinical data, including mortality, were retrieved from the trial database.ResultsMost patients presented with septic shock (86%) and pulmonary (60%) or abdominal (30%) focus of infection. The median (IQR) age was 67 years (59 to 75), and 55% were males. The median SOFA and SAPS II scores were 8 (6 to 10) and 56 (41 to 68), respectively, with 7-, 28- and 90-day mortality rates being 21%, 39% and 53%, respectively. Pre-intervention (before treatment with different fluids), TEG reaction (R)-time, angle and maximum amplitude (MA) and FF MA all correlated with syndecan-1, thrombomodulin and PC levels. By multivariate linear regression analyses, higher syndecan-1 and lower PC were independently associated with TEG and FF hypocoagulability at the same time-point: 100 ng/ml higher syndecan-1 predicted 0.64 minutes higher R-time (SE 0.25), 1.78 mm lower TEG MA (SE 0.87) and 0.84 mm lower FF MA (SE 0.42; all P <0.05), and 10% lower protein C predicted 1.24 mm lower TEG MA (SE 0.31).ConclusionsIn our cohort of patients with severe sepsis, higher circulating levels of biomarkers of mainly endothelial damage were independently associated with hypocoagulability assessed by TEG and FF. Endothelial damage is intimately linked to coagulopathy in severe sepsis.Trial registrationClinicaltrials.gov number: NCT00962156. Registered 13 July 2009.

Stress ulcer prophylaxis in the intensive care unit: is it indicated? A topical systematic review

Stress ulcer prophylaxis (SUP) is regarded as standard of care in the intensive care unit (ICU). However, recent randomized, clinical trials (RCTs) and meta‐analyses have questioned the rationale and level of evidence for this recommendation. The aim of the present systematic review was to evaluate if SUP in the critically ill patients is indicated. Data sources:u2005MEDLINE including MeSH, EMBASE, and the Cochrane Library. Participants: patients in the ICU. Interventions: pharmacological and non‐pharmacological SUP. Study appraisal and synthesis methods: Risk of bias was assessed according to Grading of Recommendations Assessment, Development, and Evaluation, and risk of random errors in cumulative meta‐analyses was assessed with trial sequential analysis. A total of 57 studies were included in the review. The literature on SUP in the ICU includes limited trial data and methodological weak studies. The reported incidence of gastrointestinal (GI) bleeding varies considerably. Data on the incidence and severity of GI bleeding in general ICUs in the developed world as of today are lacking. The best intervention for SUP is yet to be settled by balancing efficacy and harm. In essence, it is unresolved if intensive care patients benefit overall from SUP. The following clinically research questions are unanswered: (1) What is the incidence of GI bleeding, and which interventions are used for SUP in general ICUs today?; (2) Which criteria are used to prescribe SUP?; (3) What is the best SUP intervention?; (4) Do intensive care patients benefit from SUP with proton pump inhibitors as compared with other SUP interventions? Systematic reviews of possible interventions and well‐powered observational studies and RCTs are needed.