We tested this hypothesis by conducting a prospective multicenter observational study in a heterogeneous group of medical and surgical critically ill patients.Materials and methodsStudy www.selleckchem.com/products/Y-27632.html designWe performed a prospective multicenter observational study in Australian and New Zealand ICUs. All sites that were members of the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group were invited to participate, and 47 centers agreed to collect data. Each center obtained local Institutional Ethics Committee approval. Informed consent was waived at all sites. Over a 5-week period (August to September 2008) all new adult patients admitted to the ICU who received RBCs were included. Patients remained in the study until hospital death or discharge.

Patient-specific data included the following: date and time of hospital and ICU admission, gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) III diagnostic code and score, and pre-existing or currently active co-morbidities. Any type of blood component given within 24 hours prior to ICU admission or during the ICU stay was recorded. The date, time and patient status (alive or dead) at hospital discharge were also noted. RBC-specific data included the age of the RBC unit at the time of transfusion and the leukodepletion status. The age of the blood was determined by subtracting the date of collection from the date of transfusion. The donation number (this number is unique to each blood donation) for every unit transfused was noted: these numbers were used to gather information specific to each RBC unit from the Australian Red Cross Blood Service and the New Zealand Blood Service.

Data managementData were collected using case report forms, which were completed at sites and then faxed to the study coordinating centre at the ANZIC Research Centre, Monash University, Melbourne, Australia. The case report forms were subsequently scanned to a database using an optical reader. After checking the data and repeated queries to the study sites, the missing data related to RBC transfusions constituted <1%.Statistical methods regarding analysis of age of RBCsMaximum age of RBCsThe relationship between hospital mortality and maximum age of RBCs received was determined using logistic regression.

We chose Entinostat the maximum age of RBCs transfused as the independent variable to be tested because we reasoned that exposure to even a single transfusion of old RBCs may have a toxic effect and contribute to increased mortality. Furthermore, we reasoned that once exposure to red cells with storage lesions occurs, it may cause irreversible damage and influence morbidity and mortality. The association, if present, may therefore not be linear in nature. First, we tested the age of RBCs as a continuous variable.