Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial.

BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS/DESIGN: The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point. DISCUSSION: The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.

[Drug-drug interactions in intensive care patients]. / Laegemiddelinteraktioner hos intensivpatienter.

INTRODUCTION: The purpose of this study was to investigate the frequency of potential drug-drug interactions (DDIs) within the first 24 hours of admission to an intensive care unit, and to determine which drugs were involved in potential DDIs along with the clinical relevance of the identified DDIs. METHODS: Drug data from all intensive care patients (n = 102) admitted during a three-month period in the spring 2007 were investigated. Potential DDIs were evaluated using the drug interaction system of Micromedex. RESULTS: Four patients were excluded because their treatment only included one drug. A total of 98 patients were treated with an average of ten drugs per patient. Among the enrolled patients, we found 242 potential DDIs, corresponding to an average of 2.5 DDIs per patient. The drugs most frequently involved in potential DDIs included antithrombotic drugs, opioids, loop diuretics, ACE inhibitors, beta blockers, NSAIDs, corticosteroids, quinolon antibiotics, cardiac glycosides, thiazide diuretics, -anaesthetics, antidepressants, anticonvulsants and sedatives. DISCUSSION: The number of DDIs per patient found in this study is high compared with the results of a recent Norwegian study. The majority of the identified DDIs were normal combinations of drugs, which are managed through monitoring of the patient and discontinuing of the offending drug if necessary. It is therefore important to revise the patient's medication daily. CONCLUSION: A total of 71% of the 98 enrolled patients were exposed to one or more potential DDIs. We found an average of 2.5 potential DDIs per patient. Antithrombotic drugs, opioids and loop diuretics were most frequently involved in potential DDIs. The clinical relevance varied because the majority of the identified potential DDIs were normal drug combinations.