Benedikt Heidinger

Safety of off-label erythropoiesis stimulating agents in critically ill patients: a meta-analysis

PurposeErythropoiesis stimulating agents (ESAs) are used to treat anemia in critically ill patients. This indication is off-label, because it is not licensed by regulatory authorities. Recently ESAs were suspected to harm critically ill patients. Our objective was to assess the safety of ESAs in off-label indications in critically ill patients.MethodsEleven databases were searched up to April 2012. We considered randomized controlled trials (RCTs) and controlled observational studies in any language that compared off-label ESAs treatment with other effective interventions, placebo or no treatment in critically ill patients. Two authors independently screened and evaluated retrieved records, extracted data and assessed risk of bias and quality of reporting.ResultsWe used frequentist and Bayesian models to combine studies, and performed sensitivity and subgroup analyses. From 12,888 citations, we included 48 studies (34 RCTs; 14 observational), involving 944,856 participants. Harm reporting was of medium to low quality. There was no statistically significant increased risk of adverse events in general, serious adverse events, the most frequently reported adverse events, and death in critically ill patients treated with ESAs. These results were robust against risk of bias and analysis methods. There is evidence that ESAs increase the risk of clinically relevant thrombotic vascular events, and there is some less certain evidence that ESAs might increase the risk for venous thromboembolism.ConclusionsIn critically ill patients, administration of ESAs is associated with a significant increase in clinically relevant thrombotic vascular events but not with other frequently reported adverse events and death.

Admission blood pressure and 1-year mortality in acute myocardial infarction

Arterial hypertension is a well‐established factor for increased risk of cardiovascular diseases, but low admission blood pressure has also been suggested as predictor for increased mortality. We hypothesised that in patients with acute myocardial infarction admission blood pressure at the Emergency Department predicts long‐term mortality.

Different Mortality Time Points in Critical Care Trials: Current Practice and Influence on Effect Estimates in Meta-Analyses.

Objective:Mortality is frequently used as an outcome in critical care trials, being a patient-orientated variable and robust against information/selection bias. Mortality frequency, however, should be measured at a defined time point of follow-up. Practice of meta-analysis shows that follow-up times of trials in critical care medicine differ substantially. This may have substantial implications on potential pooling of effect estimates. We aimed to describe the current practice of mortality follow-up time definitions in a representative sample of published critical care randomized controlled trials and to analyze the influence of different follow-up times on subsequently pooled effect estimates. Data Sources:Cochrane CENTRAL, EMBASE, MEDLINE, PASCAL Biomed, and PsycINFO. Study Selection:Databases were searched for critical care randomized controlled trials published after 2000. A random sample of 50% was drawn for further review. Data Extraction:Study characteristics were extracted, as well as the number and time points of mortality ascertainment. Additional data were extracted from Kaplan-Meier plots, as available. Data Synthesis:Meta-regression and multilevel mixed-effects linear regression were used to analyze the influence of follow-up time (independent variable) on deviation of pooled risk ratios from study baseline (dependent variable). From 9,246 retrieved references, we included 106 studies representing 63,713 participants. Among these, 45 studies (43%) reported more than one time point, with 24 different time points at all, only three (28, 30, and 90 d) being reported in more than 10% of studies. Limiting meta-analyses to only one predefined time point would reduce the number of eligible studies by at least 60%. No influence of time points on meta-analytic summary effect estimates was found. Conclusions:In a large sample of critical care randomized controlled trials, numerous different mortality time points are reported. Mortality time points did not influence pooled point estimates of the effects. Consequently, it seems possible to pool effect estimates, which in turn will increase the precision of these effect estimates.

An electrocardiogram technician improves in-hospital first medical contact-to-electrocardiogram times: a cluster randomized controlled interventional trial ☆,☆☆,★

BACKGROUND In the case of chest pain, the current guidelines require electrocardiogram (ECG) recording and patient assessment within 10 minutes upon arrival in the emergency department. METHODS We investigated the effect of an ECG technician (ECG-T) on in-hospital first medical contact-to-ECG times (iFMC-to-ECG) investigated in a cluster randomized, controlled trial. Allocation of intervention was concealed. Staff satisfaction and feasibility was defined as a secondary outcome. Delays between ECG and the availability of an emergency physician and the assessment of ECG were additionally evaluated. RESULTS A total of 163 (44 clusters) and 191 (47 clusters) patients were allocated to control and intervention, respectively. Twenty-seven (17%) of 163 patients in the control group vs 110 (58%) of 191 patients in the intervention group received ECG registration within 10 minutes (risk ratio, 3.40 [2.24-5.15]; P < .001). The iFMC-to-ECG time was 23 (95% confidence interval [CI], 20-27) minutes for the control group vs 9 (95% CI, 8-11) minutes for the intervention group (P < .001). Nursing staff judged the feasibility of intervention with a median of 1 (interquartile range [IQR], 1-1 (on a scale of 1 [best] to 5 [worst]), perceived workload alleviation with a median of 1 (IQR, 1-1), and improvement of quality of care with a median of 1 (IQR, 1-2). The ECG-to-EP time was 78 (95% CI, 64-92) seconds, and diagnosis was made within 17 (95% CI, 16-18) seconds. CONCLUSIONS Delays of iFMC-to-ECG can be effectively addressed by implementation of an ECG-T. The service of an ECG-T is feasible and improves staff satisfaction. Both ECG-to-EP time and ECG assessment constitute no relevant delay.