Matt Harmon

Chapter four 78 and interventional data were collected daily by trained research physicians. The plausibility of an infection was assessed using a four-point scale (none, possible, probable or definite) using Centers for Disease Control and Prevention and International Sepsis Forum consensus definitions 14,15 as described previously. 12 We included patients diagnosed with sepsis and having blood microarray data obtained within the first 24 hours of ICU admission. Sepsis was defined on ICU admission as having definite or probable infection 12 , combined with at least one parameter of inflammatory dysfunction, hemodynamic dysfunction, organ dysfunction or deranged tissue perfusion. 16 To limit the occurrence of iatrogenic hypothermia, patients admitted from the operating room (OR), ICU readmissions, patients undergoing active cooling, patients transferred from another ICU and patients with immunosuppression were excluded from this study. 7 Shock was defined as hypotension requiring treatment with vasopressors at a dose of 0.1 mcg/kg/min during at least 50% of the day. Clinical severity was assessed by Acute Physiology and Chronic Health Evaluation (APACHE) IV and Sequential Organ Failure Assessment (SOFA) scores. To control for body temperatures that may have been inadvertently entered in the database (i.e. a rectal sensor that has been displaced and is exposed to ambient temperature), patients with unreliably low measurements of temperature (below 33°C) were excluded. Also, patients with only one registered temperature measurement during the first 24 hours were not included. Temperature was measured using a rectal, nasal, inguinal or tympanic temperature probes. Core temperatures were used in preference to inguinal or tympanic measurements. Hypothermia was defined as a minimum body temperature <36.0°C and a maximum body temperature <38.3°C in the first 24 hours of ICU admission. Conversely, fever was defined as a maximum body temperature ³38.3°C and a minimum body temperature ³36.0°C as defined in previous studies. 10,17 Normothermia was defined a minimum and maximum body temperature between ³36.0°C and <38.3°C. Patients were defined as ‘both’ if they had both hypothermia and fever in the first 24 hours of ICU admission. Blood Gene Expression Microarrays and bioinformatics Whole blood was collected in PAXgene tubes (Becton-Dickinson, Breda, the Netherlands) within 24 hours after ICU admission and total RNA was isolated using the PAXgene blood mRNA kit (Qiagen, Venlo, the Netherlands) in combination with QIAcube automated system (Qiagen), as previously described. 13,18,19 Microarray data (Affymetrix Human Genome U219 96-array plates) are accessible to the public via the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) accession GSE65682.