Mette Krag

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: MEDLINE 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.

Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries.

Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries.

Stress ulcer prophylaxis in the intensive care unit.

Purpose of reviewStress ulcer prophylaxis (SUP) is considered standard of care in the majority of critically ill patients in the ICU. In this review, we will present the current evidence for the use of SUP in ICU patients, including data on the prevalence of gastrointestinal bleeding and the balance between benefits and harms of SUP. Recent findingsThe prevalence of overt gastrointestinal bleeding in critically ill patients is in the area of 5%. Consistent risk factors for gastrointestinal bleeding have been identified, but indications for SUP vary considerably. SUP is used in three out of four critically ill patients, most frequently in the form of proton pump inhibitors. A recent systematic review of SUP vs. placebo or no prophylaxis in critically ill patients highlights the lack of evidence supporting the use of SUP. Importantly, data suggest potential harm, including increased risk of nosocomial infections and cardiovascular events. SummaryThe prevalence of gastrointestinal bleeding in critically ill patients in the ICU is low, the prognostic importance is ambiguous, and SUP is widely used. The balance between benefits and harms of SUP is unknown, and clinical equipoise exists. High-quality randomized controlled trials and systematic reviews assessing benefits and harms of SUP in ICU patients are highly warranted.

Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis

BACKGROUND Atraumatic needles have been proposed to lower complication rates after lumbar puncture. However, several surveys indicate that clinical adoption of these needles remains poor. We did a systematic review and meta-analysis to compare patient outcomes after lumbar puncture with atraumatic needles and conventional needles. METHODS In this systematic review and meta-analysis, we independently searched 13 databases with no language restrictions from inception to Aug 15, 2017, for randomised controlled trials comparing the use of atraumatic needles and conventional needles for any lumbar puncture indication. Randomised trials comparing atraumatic and conventional needles in which no dural puncture was done (epidural injections) or without a conventional needle control group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of postdural-puncture headache incidence and additional safety and efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42016047546. FINDINGS We identified 20 241 reports; after exclusions, 110 trials done between 1989 and 2017 from 29 countries, including a total of 31 412 participants, were eligible for analysis. The incidence of postdural-puncture headache was significantly reduced from 11·0% (95% CI 9·1-13·3) in the conventional needle group to 4·2% (3·3-5·2) in the atraumatic group (relative risk 0·40, 95% CI 0·34-0·47, p<0·0001; I2=45·4%). Atraumatic needles were also associated with significant reductions in the need for intravenous fluid or controlled analgesia (0·44, 95% CI 0·29-0·64; p<0·0001), need for epidural blood patch (0·50, 0·33-0·75; p=0·001), any headache (0·50, 0·43-0·57; p<0·0001), mild headache (0·52, 0·38-0·70; p<0·0001), severe headache (0·41, 0·28-0·59; p<0·0001), nerve root irritation (0·71, 0·54-0·92; p=0·011), and hearing disturbance (0·25, 0·11-0·60; p=0·002). Success of lumbar puncture on first attempt, failure rate, mean number of attempts, and the incidence of traumatic tap and backache did not differ significantly between the two needle groups. Prespecified subgroup analyses of postdural-puncture headache revealed no interactions between needle type and patient age, sex, use of prophylactic intravenous fluid, needle gauge, patient position, indication for lumbar puncture, bed rest after puncture, or clinician specialty. These results were rated high-quality evidence as examined using the grading of recommendations assessment, development, and evaluation. INTERPRETATION Among patients who had lumbar puncture, atraumatic needles were associated with a decrease in the incidence of postdural-puncture headache and in the need for patients to return to hospital for additional therapy, and had similar efficacy to conventional needles. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of atraumatic needles as a superior option for patients who require lumbar puncture. FUNDING None.

Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials

PurposeStress ulcer prophylaxis (SUP) is commonly prescribed in the intensive care unit. However, data from systematic reviews and conventional meta-analyses are limited by imprecision and restricted to direct comparisons. We conducted a network meta-analysis of randomized clinical trials (RCTs) to examine the safety and efficacy of drugs available for SUP in critically ill patients.MethodsWe searched MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials through April 2017 for randomized controlled trials that examined the efficacy and safety of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), and sucralfate for SUP in critically ill patients. No date or language restrictions were applied. Data on study characteristics, methods, outcomes, and risk of bias were abstracted by two reviewers.ResultsOf 96 potentially eligible studies, we included 57 trials enrolling 7293 patients. The results showed that PPIs are probably more effective for preventing clinically important gastrointestinal bleeding (CIB) than H2RAs [odds ratio (OR) 0.38; 95% confidence interval (95% CI) 0.20, 0.73], sucralfate (OR 0.30; 95% CI 0.13, 0.69), and placebo (OR 0.24; 95% CI 0.10, 0.60) (all moderate quality evidence). There were no convincing differences among H2RA, sucralfate, and placebo. PPIs probably increase the risk of developing pneumonia compared with H2RAs (OR 1.27; 95% CI 0.96, 1.68), sucralfate (OR 1.65; 95% CI 1.20, 2.27), and placebo (OR 1.52; 95% CI 0.95, 2.42) (all moderate quality). Mortality is probably similar across interventions (moderate quality). Estimates of baseline risks of bleeding varied significantly across studies, and only one study reported on Clostridium difficile infection. Definitions of pneumonia varied considerably. Most studies on sucralfate predate pneumonia prevention strategies.ConclusionsOur results provide moderate quality evidence that PPIs are the most effective agents in preventing CIB, but they may increase the risk of pneumonia. The balance of benefits and harms leaves the routine use of SUP open to question.

Development and internal validation of the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU)

Intensive care unit (ICU) mortality prediction scores deteriorate over time, and their complexity decreases clinical applicability and commonly causes problems with missing data. We aimed to develop and internally validate a new and simple score that predicts 90‐day mortality in adults upon acute admission to the ICU: the Simplified Mortality Score for the Intensive Care Unit (SMS‐ICU).

What's new with stress ulcer prophylaxis in the ICU?

What is known? Critically ill patients are at risk of stress-related mucosal erosions [1]. These are typically superficial and asymptomatic but may progress to ulceration and overt and clinically important gastrointestinal (GI) bleeding, a serious condition associated with increased morbidity and mortality [2]. The reported incidence of GI bleeding varies between 2 and 5% [3, 4], probably because of heterogeneous populations, varying definitions of GI bleeding, and difficulties in diagnosing stress ulcers [3, 4]. Importantly, stress ulcerations have been identified as the sole source of GI bleeding by endoscopy in fewer than 50% of patients with GI bleeding [5]. A number of risk factors for stress ulcer-related bleedings have been suggested, including mechanical ventilation, coagulopathy, acute kidney injury, hepatic failure, and disease severity [2–4, 6]. A protective effect of enteral nutrition has been proposed [1], however this has not been confirmed in subsequent studies [6]. In critically ill patients with risk of GI bleeding, use of stress ulcer prophylaxis (SUP) is recommended [7]. Accordingly, SUP is widely used in intensive care units (ICU) [3]. The most frequently prescribed SUP agents are proton-pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) [3]. It seems that PPIs are preferred and more efficient in preventing GI bleeding events than H2RAs [8]. However, in the latest systematic review comparing SUP with placebo or no treatment in general ICU patients, the quantity and quality of evidence supporting use of SUP was low, with no firm evidence for benefit or harm [6]. Importantly, accumulating evidence suggests that use of PPIs may increase the risk of nosocomial pneumonia, Clostridium difficile infections (CDIs) and cardiovascular events [4, 9]. Consequently, the current situation is one of clinical equipoise—the balance between benefits and harms of SUP is unknown [6].

Stress ulcer prophylaxis in the intensive care unit trial : detailed statistical analysis plan

In this statistical analysis plan, we aim to provide details of the pre‐defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP‐ICU) trial. The aim of the SUP‐ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU).

Predictive Performance of the Simplified Acute Physiology Score (SAPS) II and the Initial Sequential Organ Failure Assessment (SOFA) Score in Acutely Ill Intensive Care Patients: Post-Hoc Analyses of the SUP-ICU Inception Cohort Study

Purpose Severity scores including the Simplified Acute Physiology Score (SAPS) II and the Sequential Organ Failure Assessment (SOFA) score are used in intensive care units (ICUs) to assess disease severity, predict mortality and in research. We aimed to assess the predictive performance of SAPS II and the initial SOFA score for in-hospital and 90-day mortality in a contemporary international cohort. Methods This was a post-hoc study of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) inception cohort study, which included acutely ill adults from ICUs across 11 countries (n = 1034). We compared the discrimination of SAPS II and initial SOFA scores, compared the discrimination of SAPS II in our cohort with the original cohort, assessed the calibration of SAPS II customised to our cohort, and compared the discrimination for 90-day mortality vs. in-hospital mortality for both scores. Discrimination was evaluated using areas under the receiver operating characteristics curves (AUROC). Calibration was evaluated using Hosmer-Lemeshow’s goodness-of-fit Ĉ-statistic. Results AUROC for in-hospital mortality was 0.80 (95% confidence interval (CI) 0.77–0.83) for SAPS II and 0.73 (95% CI 0.69–0.76) for initial SOFA score (P<0.001 for the comparison). Calibration of the customised SAPS II for predicting in-hospital mortality was adequate (P = 0.60). Discrimination of SAPS II was reduced compared with the original SAPS II validation sample (AUROC 0.80 vs. 0.86; P = 0.001). AUROC for 90-day mortality was 0.79 (95% CI 0.76–0.82; P = 0.74 for comparison with in-hospital mortality) for SAPS II and 0.71 (95% CI 0.68–0.75; P = 0.66 for comparison with in-hospital mortality) for the initial SOFA score. Conclusions The predictive performance of SAPS II was similar for in-hospital and 90-day mortality and superior to that of the initial SOFA score, but SAPS II’s performance has decreased over time. Use of a contemporary severity score with improved predictive performance may be of value.

Simplified Mortality Score for the Intensive Care Unit (SMS-ICU): protocol for the development and validation of a bedside clinical prediction rule

Introduction Mortality prediction scores are widely used in intensive care units (ICUs) and in research, but their predictive value deteriorates as scores age. Existing mortality prediction scores are imprecise and complex, which increases the risk of missing data and decreases the applicability bedside in daily clinical practice. We propose the development and validation of a new, simple and updated clinical prediction rule: the Simplified Mortality Score for use in the Intensive Care Unit (SMS-ICU). Methods and analysis During the first phase of the study, we will develop and internally validate a clinical prediction rule that predicts 90-day mortality on ICU admission. The development sample will comprise 4247 adult critically ill patients acutely admitted to the ICU, enrolled in 5 contemporary high-quality ICU studies/trials. The score will be developed using binary logistic regression analysis with backward stepwise elimination of candidate variables, and subsequently be converted into a point-based clinical prediction rule. The general performance, discrimination and calibration of the score will be evaluated, and the score will be internally validated using bootstrapping. During the second phase of the study, the score will be externally validated in a fully independent sample consisting of 3350 patients included in the ongoing Stress Ulcer Prophylaxis in the Intensive Care Unit trial. We will compare the performance of the SMS-ICU to that of existing scores. Ethics and dissemination We will use data from patients enrolled in studies/trials already approved by the relevant ethical committees and this study requires no further permissions. The results will be reported in accordance with the Transparent Reporting of multivariate prediction models for Individual Prognosis Or Diagnosis (TRIPOD) statement, and submitted to a peer-reviewed journal.