Dr CY Yung ICU, PYNEH 19 June 2009 Fever in ICU Dr CY Yung ICU, PYNEH 19 June 2009

Fever in ICU Definition Methods of measuring body temperature Commons causes Non-infective causes Use of antipyretics

Fever New hypothalamic set point due to cytokines production in inflammatory status Shivering and non-shivering thermogenesis Heat conservation in the peripheries

Body Temperature The traditional norm of 37°C is the mean axillary temperatures of 25000 healthy adults Wunderlich CA, Sequine E. Medical thermometry and human temperature. New York: William Wood, 1871. A more recent study revealed normal mean oral temperature of 36.8°C, with fever defined as >37.2 °C in the morning and >37.7°C in the afternoon by 99th percentile A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. Mackowiak PA; Wasserman SS; Levine MM JAMA 1992 Sep 23-30;268(12):1578-80

Definition of Fever A body temperature above 38.3°C represents a fever and deserves further evaluation to search for an infection Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. O'Grady NP, Barie PSAmerican College of Critical Care Medicine; Infectious Diseases Society of America. Crit Care Med. 2008 Apr;36(4):1330-49 Could be influenced by drugs, immune status, renal replacement therapy, etc.

Ways of Measure Pulmonary artery and bladder temperatures closely represent core body temperature Rectal, oral temperature are acceptable alternatives Rectal temperature is ~0.3-0.4°C higher than core temperature, risks of injury, transmitting infection Oral temperature shown to be reliable even in intubated patients Temperature measurement in critically ill orally intubated adults: a comparison of pulmonary artery core, tympanic, and oral methods.Giuliano KK et al. Crit Care Med. (1999)

Ways of Measure Infrared ear temperature is an acceptable way, but had shown poor agreement with PA temperature Accuracy of an infrared tympanic thermometer. Amoateng-Adjepong Y et al. Chest. (1999) Axillary and temporal artery measurement had unacceptable vairations Pulmonary artery > Intravesical > rectal > oral > tympanic

Post-operative Fever 15-40% after major surgery, but most are not associated with infection Freischlag J, Busuttil RW. The value of postoperative fever evaluation. Surgery 1983; 94: 358-363 Usually resolved after 24-48hrs Association with atelectasis, but no direct causal relationship Lack of association between atelectasis and fever Chest 107.n1 (Jan 1995): pp81(4). 

Bronchoscopy 5% of patients underwent FOB developed fever Mean duration of 14 hrs Maybe associated with underlying diagnosis and bleeding Prospective Analysis of Clinical Characteristics and Risk Factors of Postbronchoscopy Fever Chest - Volume 125, Issue 3 (March 2004)

Drug Fever Patient can be seriously ill Common association: amphotericin, cephalosporins, penecillins, phenytoin, procainamide, quinidine Less common: cimetidine, carbamaepine, hydralazine, rifampacin, streptokinase, vancomycin Mackowiak PA, LeMaister CF. Drug Fever: a critical apprasal of conventional concepts. Ann Intern Med 1987;106:728-733

Drug Fever Clinical features Rigors (53%) Myalgias (25%) Leukocytosis (22%) Eosinophillia (22%) Rash (18%) Hypotension (18%) Mackowiak PA, LeMaister CF. Drug Fever: a critical apprasal of conventional concepts. Ann Intern Med 1987;106:728-733 Mean lag time of starting drugs and manifestation is 21 days in one series Cunha B. Drug fever: the importance of recognition. Postgrad Med 1986;80: 123-129

Drug Fever Differentials include drug induced hyperthemia malignant hyperthermia, neuroleptic malignant syndrome, serotonin syndrome

Non-infectious Causes Blood transfusion: febrile reactions occurs in 5% of patients Acalculous cholecystitis: could be up to 1.5% of critically ill patients Venous thromboembolism Haemodialysis Cerebral and myocardial infarction

Treating Fever Mainly invitro evidence fever can increase immune response, by increasing production of antibodies and cytokines, activating T lymphocytes, enhancing phagocytosis by neutrophils High body temperature also decrease replication of bacteria in animal models Kluger M, Rothenburg BA. Fever and reduced iron: their interaction as a host defense response to bacterial infection. Science 1979;203:374-376 There is still definite proof of how fever affect course of infection

Treating Fever Role of systemic corticosteriods Postaglandin E2 mediates endogenous pyrogen production in pathogenesis of fever Aspirin was widely used as antipyretics before discovery of Reye’s Syndrome in 1980’s Acetaminophen and NSAID Ibuprofen was shown superior in mean temperature reduction in children (1.84°C Vs 1.24°C) Autret E. Comparative efficacy and tolerance of of ibuprufen syrup and acetaminophen syrup in children with pyrexia associated with infectious disesases and reated with antibiotics Role of systemic corticosteriods

Treating Fever Treating fever also reduced systemic symptoms of headache, myalagia and arthralgias Some evidence suggested uncontrolled cytokines production in fever will lead to adverse outcome Side effects of drugs

Stroke/Brain Injury Shown in both animal and human studies that worsened clinical outcome Combating hyperthermia in acute stroke: a significant clinical concern. Ginsberg MD; Busto R Stroke 1998 Feb;29(2):529-34 Effects of poststroke pyrexia on stroke outcome : a meta-analysis of studies in patients. Hajat C; Hajat S; Sharma P Stroke 2000 Feb;31(2):410-4. May also suggest underlying severity of brain damage Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Reith J; Jorgensen HS; Pedersen PM; Nakayama H; Raaschou HO; Jeppesen LL; Olsen TS Lancet 1996 Feb 17;347(8999):422-5 Suggested in AHA/ASA guideline for antipyretics