title: Assessment of the safety and feasibility of administering anti-pyretic therapy in critically ill adults: study protocol of a randomized trial.
abstract: BACKGROUND
  Fever is one of the most commonly observed abnormal signs in patients with critical illness. However, there is a paucity of evidence to guide the management of febrile patients without acute brain injury and little is known about the biologic response to treatment of fever. As such, observational studies suggest that the treatment of fever is inconsistent. This pilot clinical trial will assess the safety and feasibility of treating febrile critically ill adult patients with an aggressive versus a permissive temperature control strategy. The biologic response to these two different temperature control strategies will also be assessed through analysis of a panel of inflammatory mediators.
  
  
  RESULTS
  The study population will include febrile adult patients admitted to one of two general medical-surgical intensive care units (ICUs) in Calgary, Alberta, Canada. Patients will be randomized to either an aggressive or permissive fever treatment strategy. The aggressive group will receive acetaminophen 650 mg enterally every 6 hours upon reaching a temperature ≥ 38.3 °C and external cooling will be initiated for temperatures ≥ 39.5 °C, whereas the permissive group will receive acetaminophen 650 mg every 6 hours upon reaching a temperature ≥ 40.0 °C and external cooling for temperatures ≥ 40.5 °C. The study will take place over 12 months with the goal of enrolling 120 patients. The primary outcome will be 28-day mortality after study enrolment, with secondary outcomes that will include markers of feasibility (e.g. the enrolment rate, and the number of protocol violations), and levels of select inflammatory and anti-inflammatory mediators.
  
  
  CONCLUSIONS
  Results from this study will lead to a better understanding of the inflammatory effects of anti-pyretic therapy and will evaluate the feasibility of a future clinical trial to establish the best treatment of fever observed in nearly one half of patients admitted to adult ICUs.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01173367.
authors.affiliation: Department of Critical Care Medicine, University of Calgary, and Alberta Health Services, Calgary, Alberta, Canada. daniel.niven@albertahealthservices.ca
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Niven
authors.forename: Caroline
authors.initials: C
authors.lastname: Léger
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
authors.forename: H Tom
authors.initials: HT
authors.lastname: Stelfox
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Laupland
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000416:Alberta; D058633:Antipyretics / Q000008:administration & dosage*; D001831:Body Temperature; D016638:Critical Illness / Q000401:mortality / Q000628:therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D058633:Antipyretics; D000082:Acetaminophen