Corticosteroids and risk of gastrointestinal bleeding in critically ill adults: Protocol for a systematic review.

BACKGROUND: Corticosteroids are frequently prescribed to critically ill patients. However, their use may increase the risk of gastrointestinal (GI) bleeding, which is associated with morbidity and mortality. Accordingly, we aim to assess whether continued administration of corticosteroids for >24 hours increases the rate of GI bleeding in adult critically ill patients compared to placebo or no treatment. METHODS/DESIGN: We will conduct a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis. The participants will be adult (as defined in the included trials) critically ill patients. The intervention will be any corticosteroid administered systematically for >24 hours and the comparator will be placebo or no treatment. The primary outcome will be rate of clinically important GI bleeding. We will systematically search EMBASE, MEDLINE, Medline In-Process, Cochrane Library, Epistemonikos and trial registries for relevant literature, as well as perform a hand search. We will follow the recommendations by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors (bias) and random errors will be assessed and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION: The risk of GI bleeding in adult critically ill patients treated with corticosteroids is unknown. Hence, there is need for a robust systematic review to assess this risk and provide clinicians with a clearer understanding of the strength and limitations of existing data.

Factors associated with non-response at health-related quality of life follow-up in a septic shock trial.

BACKGROUND: Follow-up of intensive care unit (ICU) patients often includes health-related quality of life (HRQoL) surveying, but non-responders hamper the interpretation. Our aim was to assess factors for non-response to HRQoL survey in ICU patients with septic shock at follow-up in a clinical trial. METHODS: In a post hoc follow-up registry study, we assessed all the Danish survivors in the Transfusion-Requirements in Septic Shock trial patients, who were mailed the Short Form 36-item Survey (SF-36) 1-year after randomization. We used covariates from the trial database merged with covariates from nation-wide registries using the unique national identification number to explore possible factors for not responding. Five covariates were pre-specified to be included in the primary multivariate analysis: age, number of days in hospital from randomization to follow-up, level of education, cohabitation and employment status at follow-up. We compared the mortality from 1-year survival (2012-2014) till end of final follow-up (January 2016) between non-responders and responders. RESULTS: We assessed 308 survivors of whom 108 (35%) were non-responders. In the primary analysis lower age (odds ratio 1.03, 95% CI [1.01-1.05]), more admission days in hospital (1.006 [1.001-1.011]) and living alone (4.33 [2.46-7.63]) were associated with non-responding, whereas the level of education and employment status were not. Non-responders had a hazard ratio of 1.63 [0.97-2.72] for mortality from 1-year follow-up to final follow-up as compared to the responders. CONCLUSION: Being younger, spending more days in hospital and living alone were all associated with non-response at 1-year HRQoL follow-up among ICU patients with septic shock.

Effects of red blood cell storage time on transfused patients in the ICU-protocol for a systematic review.

BACKGROUND: Patients in the intensive care unit (ICU) are often anaemic due to blood loss, impaired red blood cell (RBC) production and increased RBC destruction. In some studies, more than half of the patients were treated with RBC transfusion. During storage, the RBC and the storage medium undergo changes, which lead to impaired transportation and delivery of oxygen and may also promote an inflammatory response. Divergent results on the clinical consequences of storage have been reported in both observational studies and randomised trials. Therefore, we aim to gather and review the present evidence to assess the effects of shorter vs. longer storage time of transfused RBCs for ICU patients. METHODS: We will conduct a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials, and also include results of severe adverse events from large observational studies. Participants will be adult patients admitted to an ICU and treated with shorter vs. longer stored RBC units. We will systematically search the Cochrane Library, MEDLINE, Embase, BIOSIS, CINAHL and Science Citation Index for relevant literature, and we will follow the recommendation by the Cochrane Collaboration and the Preferred Reporting Items for Systemtic Review and Meta-Analysis (PRISMA)-statement. We will assess the risk of bias and random errors, and we will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the overall quality of evidence. CONCLUSION: We need a high-quality systematic review to summarise the clinical consequences of RBC storage time among ICU patients.

Higher vs. lower haemoglobin threshold for transfusion in septic shock: subgroup analyses of the TRISS trial.

BACKGROUND: Using a restrictive transfusion strategy appears to be safe in sepsis, but there may be subgroups of patients who benefit from transfusion at a higher haemoglobin level. We explored if subgroups of patients with septic shock and anaemia had better outcome when transfused at a higher vs. a lower haemoglobin threshold. METHODS: In post-hoc analyses of the full trial population of 998 patients from the Transfusion Requirements in Septic Shock (TRISS) trial, we investigated the intervention effect on 90-day mortality in patients with severe comorbidity (chronic lung disease, haematological malignancy or metastatic cancer), in patients who had undergone surgery (elective or acute) and in patients with septic shock as defined by the new consensus definition: lactate above 2 mmol/l and the need for vasopressors to maintain a mean arterial pressure above 65 mmHg. RESULTS: The baseline characteristics were mostly similar between the two intervention groups in the different subgroups. There were no differences in the intervention effect on 90-day mortality in patients with chronic lung disease (test of interaction P = 0.31), haematological malignancy (P = 0.47), metastatic cancer (P = 0.51), in those who had undergone surgery (P = 0.99) or in patients with septic shock by the new definition (P = 0.20). CONCLUSION: In exploratory analyses of a randomized trial in patients with septic shock and anaemia, we observed no survival benefit in any subgroups of transfusion at a haemoglobin threshold of 90 g/l vs. 70 g/l.