Fever in the intensive care unit
- Graeme MacLaren, MBBS, FCICM, FRACP, FCCP, FCCM
Graeme MacLaren, MBBS, FCICM, FRACP, FCCP, FCCM
- National University Hospital, Singapore
- The Royal Children's Hospital, Melbourne, Australia
- Denis Spelman, MBBS, FRACP, FRCPA, MPH
Denis Spelman, MBBS, FRACP, FRCPA, MPH
- Adjunct Professor, Monash University
- Alfred Hospital, Victoria, Australia
Fever is a common abnormality in the intensive care unit (ICU), which prompts important diagnostic and treatment decisions. The definition, differential diagnosis, diagnostic evaluation, and management of fever in the ICU are reviewed here. The pathophysiology of fever is discussed separately. (See "Pathophysiology and treatment of fever in adults".)
Normal body temperature is approximately 37ºC (98.6ºF), although this varies with the time of day and the method of measurement used. The definition of fever is arbitrary; as the temperature that defines fever is lowered, its sensitivity increases and its specificity decreases. A joint task force from the American College of Critical Care Medicine and the Infectious Diseases Society of America defined fever as a body temperature of 38.3ºC (101ºF) or higher . We adhere to this definition in this review because it is widely accepted. It is reasonable to use a lower temperature to define fever in immunocompromised patients.
Conventional means of measuring temperature in the ICU include intravascular, intravesicular (ie, bladder), rectal, and oral [1-6]. The gold standard is the thermistor on a pulmonary artery catheter, although these are used infrequently and may give unreliable temperature readings if the catheter is used to rapidly administer volume . Regardless of which method is chosen, the same method and site of measurement should be used repeatedly to facilitate the trending of serial measurements. Alternative methods, such as axillary, temporal artery, tympanic, and chemical dot monitors, should not be used because they are inaccurate during critical illness [1,6-12]. Despite this inaccuracy, these methods are still in widespread use in many ICUs around the world .
Fever complicates up to 70 percent of all intensive care unit (ICU) admissions and is often due to an infection or another serious condition [14,15]. In one observational study of 24,204 adult ICU admissions, fever ≥39.5ºC (103ºF) was associated with an increase in mortality (20 versus 12 percent) . Fever has also been associated with an increased length of stay, increased cost of care, and poorer outcomes in patients with traumatic head injury, subarachnoid hemorrhage, or pancreatitis [14,16-22]. The same associations probably exist with other conditions that have not been studied. Fever may prompt unnecessary investigations and lead to inappropriate antibiotic use.
The importance of fever as a pathophysiological process is poorly understood. Although regarded as a sign of clinical deterioration, fever can be an appropriate adaptive response to infection. For example, one study showed that elevated peak temperatures in ICU patients with infections were associated with decreased hospital mortality . Compared to patients with peak temperatures 36.5 to 36.9ºC, patients with peak temperatures 39 to 39.4oC had significantly lower hospital mortality (OR, 0.56; 95% CI 0.48-0.66). However, in non-infectious cases of fever, mortality increased with rising temperature (OR, 2.07; 95% CI 1.68-2.55).
- O'Grady NP, Barie PS, Bartlett JG, et al. 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. Crit Care Med 2008; 36:1330.
- Fallis WM. Monitoring urinary bladder temperature in the intensive care unit: state of the science. Am J Crit Care 2002; 11:38.
- Giuliano KK, Scott SS, Elliot S, Giuliano AJ. Temperature measurement in critically ill orally intubated adults: a comparison of pulmonary artery core, tympanic, and oral methods. Crit Care Med 1999; 27:2188.
- Schmitz T, Bair N, Falk M, Levine C. A comparison of five methods of temperature measurement in febrile intensive care patients. Am J Crit Care 1995; 4:286.
- Klein DG, Mitchell C, Petrinec A, et al. A comparison of pulmonary artery, rectal, and tympanic membrane temperature measurement in the ICU. Heart Lung 1993; 22:435.
- Nimah MM, Bshesh K, Callahan JD, Jacobs BR. Infrared tympanic thermometry in comparison with other temperature measurement techniques in febrile children. Pediatr Crit Care Med 2006; 7:48.
- Marik PE. Fever in the ICU. Chest 2000; 117:855.
- Romano MJ, Fortenberry JD, Autrey E, et al. Infrared tympanic thermometry in the pediatric intensive care unit. Crit Care Med 1993; 21:1181.
- Robinson JL, Seal RF, Spady DW, Joffres MR. Comparison of esophageal, rectal, axillary, bladder, tympanic, and pulmonary artery temperatures in children. J Pediatr 1998; 133:553.
- Lefrant JY, Muller L, de La Coussaye JE, et al. Temperature measurement in intensive care patients: comparison of urinary bladder, oesophageal, rectal, axillary, and inguinal methods versus pulmonary artery core method. Intensive Care Med 2003; 29:414.
- Hebbar K, Fortenberry JD, Rogers K, et al. Comparison of temporal artery thermometer to standard temperature measurements in pediatric intensive care unit patients. Pediatr Crit Care Med 2005; 6:557.
- Kimberger O, Cohen D, Illievich U, Lenhardt R. Temporal artery versus bladder thermometry during perioperative and intensive care unit monitoring. Anesth Analg 2007; 105:1042.
- Niven DJ, Laupland KB, Tabah A, et al. Diagnosis and management of temperature abnormality in ICUs: a EUROBACT investigators' survey. Crit Care 2013; 17:R289.
- Circiumaru B, Baldock G, Cohen J. A prospective study of fever in the intensive care unit. Intensive Care Med 1999; 25:668.
- Laupland KB, Shahpori R, Kirkpatrick AW, et al. Occurrence and outcome of fever in critically ill adults. Crit Care Med 2008; 36:1531.
- Stocchetti N, Rossi S, Zanier ER, et al. Pyrexia in head-injured patients admitted to intensive care. Intensive Care Med 2002; 28:1555.
- Oliveira-Filho J, Ezzeddine MA, Segal AZ, et al. Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome. Neurology 2001; 56:1299.
- Commichau C, Scarmeas N, Mayer SA. Risk factors for fever in the neurologic intensive care unit. Neurology 2003; 60:837.
- Brisinda G, Maria G, Ferrante A, Civello IM. Evaluation of prognostic factors in patients with acute pancreatitis. Hepatogastroenterology 1999; 46:1990.
- Bohidar NP, Garg PK, Khanna S, Tandon RK. Incidence, etiology, and impact of Fever in patients with acute pancreatitis. Pancreatology 2003; 3:9.
- Peres Bota D, Lopes Ferreira F, Mélot C, Vincent JL. Body temperature alterations in the critically ill. Intensive Care Med 2004; 30:811.
- Reaven NL, Lovett JE, Funk SE. Brain injury and fever: hospital length of stay and cost outcomes. J Intensive Care Med 2009; 24:131.
- Young PJ, Saxena M, Beasley R, et al. Early peak temperature and mortality in critically ill patients with or without infection. Intensive Care Med 2012.
- Cunha BA. Fever in the critical care unit. Crit Care Clin 1998; 14:1.
- Cunha BA. Fever in the intensive care unit. Intensive Care Med 1999; 25:648.
- Lucet JC, Bouadma L, Zahar JR, et al. Infectious risk associated with arterial catheters compared with central venous catheters. Crit Care Med 2010; 38:1030.
- Eggimann P, Pittet D. Infection control in the ICU. Chest 2001; 120:2059.
- George DL, Falk PS, Umberto Meduri G, et al. Nosocomial sinusitis in patients in the medical intensive care unit: a prospective epidemiological study. Clin Infect Dis 1998; 27:463.
- Holzapfel L, Chevret S, Madinier G, et al. Influence of long-term oro- or nasotracheal intubation on nosocomial maxillary sinusitis and pneumonia: results of a prospective, randomized, clinical trial. Crit Care Med 1993; 21:1132.
- Barie PS, Eachempati SR. Acute acalculous cholecystitis. Curr Gastroenterol Rep 2003; 5:302.
- Kalliafas S, Ziegler DW, Flancbaum L, Choban PS. Acute acalculous cholecystitis: incidence, risk factors, diagnosis, and outcome. Am Surg 1998; 64:471.
- Laurila J, Syrjälä H, Laurila PA, et al. Acute acalculous cholecystitis in critically ill patients. Acta Anaesthesiol Scand 2004; 48:986.
- Kaleya RN, Boley SJ. Acute mesenteric ischemia. Crit Care Clin 1995; 11:479.
- Kumar S, Sarr MG, Kamath PS. Mesenteric venous thrombosis. N Engl J Med 2001; 345:1683.
- Marik PE, Andrews L, Maini B. The incidence of deep venous thrombosis in ICU patients. Chest 1997; 111:661.
- Hirsch DR, Ingenito EP, Goldhaber SZ. Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995; 274:335.
- PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263:2753.
- Stein PD, Afzal A, Henry JW, Villareal CG. Fever in acute pulmonary embolism. Chest 2000; 117:39.
- Marik PE, Zaloga GP. Adrenal insufficiency in the critically ill: a new look at an old problem. Chest 2002; 122:1784.
- Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003; 348:727.
- Ringel MD. Management of hypothyroidism and hyperthyroidism in the intensive care unit. Crit Care Clin 2001; 17:59.
- Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med 2010; 38:1045.
- Uzzan B, Cohen R, Nicolas P, et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med 2006; 34:1996.
- Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007; 7:210.
- Marshall JC, Foster D, Vincent JL, et al. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis 2004; 190:527.
- Marshall JC, Walker PM, Foster DM, et al. Measurement of endotoxin activity in critically ill patients using whole blood neutrophil dependent chemiluminescence. Crit Care 2002; 6:342.
- Póvoa P, Almeida E, Moreira P, et al. C-reactive protein as an indicator of sepsis. Intensive Care Med 1998; 24:1052.
- Müller B, Becker KL, Schächinger H, et al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med 2000; 28:977.
- Claeys R, Vinken S, Spapen H, et al. Plasma procalcitonin and C-reactive protein in acute septic shock: clinical and biological correlates. Crit Care Med 2002; 30:757.
- Mackenzie I, Woodhouse J. C-reactive protein concentrations during bacteraemia: A comparison between patients with and without liver dysfunction. Intensive Care Med 2006; 32:1344.
- Jensen JU, Heslet L, Jensen TH, et al. Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 2006; 34:2596.
- Lobo SM, Lobo FR, Bota DP, et al. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003; 123:2043.
- van Zanten AR, Dixon JM, Nipshagen MD, et al. Hospital-acquired sinusitis is a common cause of fever of unknown origin in orotracheally intubated critically ill patients. Crit Care 2005; 9:R583.
- Vargas F, Bui HN, Boyer A, et al. Transnasal puncture based on echographic sinusitis evidence in mechanically ventilated patients with suspicion of nosocomial maxillary sinusitis. Intensive Care Med 2006; 32:858.
- Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34:1589.
- Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Clin Infect Dis 2005; 40 Suppl 4:S240.
- Topkara VK, Kondareddy S, Malik F, et al. Infectious complications in patients with left ventricular assist device: etiology and outcomes in the continuous-flow era. Ann Thorac Surg 2010; 90:1270.
- Gozzoli V, Schöttker P, Suter PM, Ricou B. Is it worth treating fever in intensive care unit patients? Preliminary results from a randomized trial of the effect of external cooling. Arch Intern Med 2001; 161:121.
- Ryan M, Levy MM. Clinical review: fever in intensive care unit patients. Crit Care 2003; 7:221.
- Schulman CI, Namias N, Doherty J, et al. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect (Larchmt) 2005; 6:369.
- Lee BH, Inui D, Suh GY, et al. Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study. Crit Care 2012; 16:R33.
- Cairns CJ, Andrews PJ. Management of hyperthermia in traumatic brain injury. Curr Opin Crit Care 2002; 8:106.
- Marion DW. Controlled normothermia in neurologic intensive care. Crit Care Med 2004; 32:S43.
- Bouchama A, Knochel JP. Heat stroke. N Engl J Med 2002; 346:1978.
- Suzuki S, Eastwood GM, Bailey M, et al. Paracetamol therapy and outcome of critically ill patients: a multicenter retrospective observational study. Crit Care 2015; 19:162.
- Schortgen F, Clabault K, Katsahian S, et al. Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med 2012; 185:1088.
- Young P, Saxena M, Bellomo R, et al. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med 2015.