Fever in the Neuro-ICU

  • Marc-Alain BabiEmail author


Fever is defined by elevation in core body temperature above the daily range for an individual. It is a characteristic feature of a number of noninfectious diseases such as inflammatory, autoimmune, and autoregulatory disorder, as well as numerous infectious conditions. Fever is a recognized disorder in the setting of acute brain and nervous system disorders. The pathogenesis of fever, etiology, evaluation, and management are discussed in this chapter.


Fever Hyperthermia Brain injury Hyperemia Hyperpyrexia Stroke Traumatic brain injury Subarachnoid hemorrhage Cardiac arrest Neuronal injury 


  1. 1.
    Lee-Chiong TL Jr, Stitt JT. Disorders of temperature regulation. Compr Ther. 1995;21:697–704.PubMedGoogle Scholar
  2. 2.
    Mortola JP. Gender and the circadian pattern of body temperature in normoxia and hypoxia. Respir Physiol Neurobiol. 2017;245:4–12.CrossRefGoogle Scholar
  3. 3.
    Mackowiak PA, Wasserman SS, Levine MM. A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA. 1992;268:1578–80.CrossRefGoogle Scholar
  4. 4.
    Niven DJ, Gaudet JE, Laupland KB, et al. Accuracy of peripheral thermometers for estimating temperature: a systematic review and meta-analysis. Ann Intern Med. 2015;163:768–77.CrossRefGoogle Scholar
  5. 5.
    Horowitz HW. Fever of unknown origin or fever of too many origins? N Engl J Med. 2013;368:197–9.CrossRefGoogle Scholar
  6. 6.
    de Kleijn EM, Vandenbroucke JP, van der Meer JW. Fever of unknown origin (FUO). I A. prospective multicenter study of 167 patients with FUO, using fixed epidemiologic entry criteria. The Netherlands FUO Study Group. Medicine (Baltimore). 1997;76:392–400.CrossRefGoogle Scholar
  7. 7.
    Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res. 2004;10:201–22.PubMedGoogle Scholar
  8. 8.
    Schlievert PM, Shands KN, Dan BB, Schmid GP, Nishimura RD. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis. 1981;143:509–16.CrossRefGoogle Scholar
  9. 9.
    Parsonnet J, Gillis ZA, Pier GB. Induction of interleukin-1 by strains of Staphylococcus aureus from patients with nonmenstrual toxic shock syndrome. J Infect Dis. 1986;154:55–63.CrossRefGoogle Scholar
  10. 10.
    Albrecht RF, Wass CT, Lanier WL. Occurrence of potentially detrimental temperature alterations in hospitalized patients at risk for brain injury. Mayo Clin Proc. 1998;73:629–35.CrossRefGoogle Scholar
  11. 11.
    Ginsberg MD, Busto R. Combating hyperthermia in acute stroke: a significant clinical concern. Stroke. 1998;29:529–34.CrossRefGoogle Scholar
  12. 12.
    Thompson HJ, Pinto-Martin J, Bullock MR. Neurogenic fever after traumatic brain injury: an epidemiological study. J Neurol Neurosurg Psychiatry. 2003;74:614–9.CrossRefGoogle Scholar
  13. 13.
    Thompson HJ, Tkacs NC, Saatman KE, et al. Hyperthermia following traumatic brain injury: a critical evaluation. Neurobiol Dis. 2003;12:163–73.CrossRefGoogle Scholar
  14. 14.
    Kinoshita K, Chatzipanteli K, Vitarbo E, et al. Interleukin-1beta messenger ribonucleic acid and protein levels after fluid-percussion brain injury in rats: importance of injury severity and brain temperature. Neurosurgery. 2002;51:195–203; discussion 203.CrossRefGoogle Scholar
  15. 15.
    Dietrich WD, Chatzipanteli K, Vitarbo E, et al. The role of inflammatory processes in the pathophysiology and treatment of brain and spinal cord trauma. Acta Neurochir Suppl. 2004;89:69–74.PubMedGoogle Scholar
  16. 16.
    Suehiro E, Fujisawa H, Ito H, et al. Brain temperature modifies glutamate neurotoxicity in vivo. J Neurotrauma. 1999;16:285–97.CrossRefGoogle Scholar
  17. 17.
    Takagi K, Ginsberg MD, Globus MY, et al. Effect of hyperthermia on glutamate release in ischemic penumbra after middle cerebral artery occlusion in rats. Am J Phys. 1994;267:H1770–6.Google Scholar
  18. 18.
    Morimoto T, Ginsberg MD, Dietrich WD, et al. Hyperthermia enhances spectrin breakdown in transient focal cerebral ischemia. Brain Res. 1997;746:43–51.CrossRefGoogle Scholar
  19. 19.
    Kim Y, Truettner J, Zhao W, et al. The influence of delayed postischemic hyperthermia following transient focal ischemia: alterations of gene expression. J Neurol Sci. 1998;159:1–10.CrossRefGoogle Scholar
  20. 20.
    Sharma HS, Hoopes PJ. Hyperthermia induced pathophysiology of the central nervous system. Int J Hyperth. 2003;19:325–54.CrossRefGoogle Scholar
  21. 21.
    Rossi S, Zanier ER, Mauri I, et al. Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage. J Neurol Neurosurg Psychiatry. 2001;71:448–54.CrossRefGoogle Scholar
  22. 22.
    Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med. 2004;30:2126–8.CrossRefGoogle Scholar
  23. 23.
    Hovdenes J, Laake JH, Aaberge L, Haugaa H, Bugge JF. Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand. 2007;51:137–42.CrossRefGoogle Scholar
  24. 24.
    Skulec R, Kovarnik T, Dostalova G, Kolar J, Linhart A. Induction of mild hypothermia in cardiac arrest survivors presenting with cardiogenic shock syndrome. Acta Anaesthesiol Scand. 2008;52:188–94.CrossRefGoogle Scholar
  25. 25.
    Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med. 2001;161:2007–12.CrossRefGoogle Scholar
  26. 26.
    Gebhardt K, Guyette FX, Doshi AA, et al. Prevalence and effect of fever on outcome following resuscitation from cardiac arrest. Resuscitation. 2013;84:1062–7.CrossRefGoogle Scholar
  27. 27.
    Grossestreuer AV, Gaieski DF, Donnino MW, Wiebe DJ, Abella BS. Magnitude of temperature elevation is associated with neurologic and survival outcomes in resuscitated cardiac arrest patients with postrewarming pyrexia. J Crit Care. 2017;38:78–83.CrossRefGoogle Scholar
  28. 28.
    Writing Group Members, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133:e38–360.Google Scholar
  29. 29.
    Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.CrossRefGoogle Scholar
  30. 30.
    Polderman KH. Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality, part 1: indications and evidence. Intensive Care Med. 2004;30:556–75.CrossRefGoogle Scholar
  31. 31.
    Kliegel A, Losert H, Sterz F, et al. Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest--a feasibility study. Resuscitation. 2005;64:347–51.CrossRefGoogle Scholar
  32. 32.
    Al-Senani FM, Graffagnino C, Grotta JC, et al. A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest. Resuscitation. 2004;62:143–50.CrossRefGoogle Scholar
  33. 33.
    Wang Y, Lim LL, Levi C, et al. Influence of admission body temperature on stroke mortality. Stroke. 2000;31:404–9.CrossRefGoogle Scholar
  34. 34.
    Schwarz S, Hafner K, Aschoff A, et al. Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology. 2000;54:354–61.CrossRefGoogle Scholar
  35. 35.
    Frosini M, Sesti C, Valoti M, et al. Rectal temperature and prostaglandin E2 increase in cerebrospinal fluid of conscious rabbits after intracerebroventricular injection of hemoglobin. Exp Brain Res. 1999;126:252–8.CrossRefGoogle Scholar
  36. 36.
    Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010;41(10):2265–70.CrossRefGoogle Scholar
  37. 37.
    Guluma KZ, Oh H, Yu SW, Meyer BC, Rapp K, Lyden PD. Effect of endovascular hypothermia on acute ischemic edema: morphometric analysis of the ICTuS trial. Neurocrit Care. 2008;8(1):42–7.CrossRefGoogle Scholar
  38. 38.
    Krassioukov AV, Karlsson AK, Wecht JM, Wuermser LA, Mathias CJ, Marino RJ, et al. Assessment of autonomic dysfunction following spinal cord injury: rationale for additions to international standards for neurological assessment. J Rehabil Res Dev. 2007;44:103–12.CrossRefGoogle Scholar
  39. 39.
    Beraldo PS, Neves EG, Alves CM, et al. Pyrexia in hospitalised spinal cord injury patients. Paraplegia. 1993;31:186–91.PubMedGoogle Scholar
  40. 40.
    Dietrich WD, Bramlett HM. Hyperthermia and central nervous system injury. Prog Brain Res. 2007;162:201–17.CrossRefGoogle Scholar
  41. 41.
    Montgomerie JZ. Infections in patients with spinal cord injuries. Clin Infect Dis. 1997;25:1285–90.CrossRefGoogle Scholar
  42. 42.
    Sugarman B, Brown D, Musher D. Fever and infection in spinal cord injury patients. JAMA. 1982;248:66–70.CrossRefGoogle Scholar
  43. 43.
    Commichau C, Scarmeas N, Mayer SA. Risk factors for fever in the neurologic intensive care unit. Neurology. 2003;60:837–41.CrossRefGoogle Scholar
  44. 44.
    Weir B, Disney L, Grace M, et al. Daily trends in white blood cell count and temperature after subarachnoid hemorrhage from aneurysm. Neurosurgery. 1989;25:161–5.CrossRefGoogle Scholar
  45. 45.
    Simpson RK Jr, Fischer DK, Ehni BL. Neurogenic hyperthermia in subarachnoid hemorrhage. South Med J. 1989;82:1577–8.CrossRefGoogle Scholar
  46. 46.
    Oliveira-Filho J, Ezzeddine MA, Segal AZ, et al. Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome. Neurology. 2001;56:1299–304.CrossRefGoogle Scholar
  47. 47.
    Dorhout Mees SM, Luitse MJ, van den Bergh WM, et al. Fever after aneurysmal subarachnoid hemorrhage: relation with extent of hydrocephalus and amount of extravasated blood. Stroke. 2008;39:2141–3.CrossRefGoogle Scholar
  48. 48.
    Badjatia N, Fernandez L, Fernandez A, et al. Impact of therapeutic normothermia on outcome after subarachnoid hemorrhage. Paper presented at: 60th Annual Meeting of the American Academy of Neurology, April 16, 2008, Chicago.Google Scholar
  49. 49.
    Badjatia N, Fernandez L, Schmidt JM, Lee K, Claassen J, Connolly ES, Mayer SA. Impact of induced normothermia on outcome after subarachnoid hemorrhage: a case-control study. Neurosurgery. 2010;66(4):696–700; discussion 700–1.CrossRefGoogle Scholar
  50. 50.
    Fernandez A, Schmidt JM, Claassen J, et al. Fever after subarachnoid hemorrhage: risk factors and impact on outcome. Neurology. 2007;68:1013–9.CrossRefGoogle Scholar
  51. 51.
    Andrews PJ, Sleeman DH, Statham PF, et al. Predicting recovery in patients suffering from traumatic brain injury by using admission variables and physiological data: a comparison between decision tree analysis and logistic regression. J Neurosurg. 2002;97:326–36.CrossRefGoogle Scholar
  52. 52.
    Konstantinidis A, Inaba K, Dubose J, et al. The impact of nontherapeutic hypothermia on outcomes after severe traumatic brain injury. J Trauma. 2011;71:1627–31.PubMedGoogle Scholar
  53. 53.
    Andrews PJ1, Sinclair HL, Rodriguez A, et al. Eurotherm3235 trial collaborators. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2015;373(25):2403–12.CrossRefGoogle Scholar
  54. 54.
    Cairns CJ, Andrews PJ. Management of hyperthermia in traumatic brain injury. Curr Opin Crit Care. 2002;8:106–10.CrossRefGoogle Scholar
  55. 55.
    Stocchetti N, Rossi S, Zanier ER, et al. Pyrexia in head-injured patients admitted to intensive care. Intensive Care Med. 2002;28:1555–62.CrossRefGoogle Scholar
  56. 56.
    Yokobori S, Frantzen J, Bullock R, Gajavelli S, Burks S, Bramlett H, Dietrich WD. The use of hypothermia therapy in traumatic ischemic/reperfusional brain injury: review of the literatures. Ther Hypothermia Temp Manag. 2011;1:185–92.CrossRefGoogle Scholar
  57. 57.
    Yokobori S, Gajavelli S, Mondello S, Mo-Seaney J, Bramlett HM, Dietrich WD, Bullock MR. Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model. J Neurosurg. 2013;118:370–80.CrossRefGoogle Scholar
  58. 58.
    Vane JR. Inhibition of prostaglandin synthesis as a mechanisms of action for the aspirin-like drugs. Nature. 1971;231:232–5.Google Scholar
  59. 59.
    Mackowiak PA. Concepts of fever. Arch Intern Med. 1998;158:1870–81.CrossRefGoogle Scholar
  60. 60.
    van Breda EJ, van der Worp HB, van Gemert M, et al. Reduction of body temperature with paracetamol in patients with acute stroke: randomised clinical trials are needed. Cerebrovasc Dis. 2004;18:350.CrossRefGoogle Scholar
  61. 61.
    Cormio M, Citerio G. Continuous low dose diclofenac sodium infusion to control fever in neurosurgical critical care. Neurocrit Care. 2007;6:82–9.CrossRefGoogle Scholar
  62. 62.
    Dippel DW, van Breda EJ, van der Worp HB, et al. Timing of the effect of acetaminophen on body temperature in patients with acute ischemic stroke. Neurology. 2003;61:677–9.CrossRefGoogle Scholar
  63. 63.
    Dippel DW, van Breda EJ, van der Worp HB, et al. Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]. BMC Cardiovasc Disord. 2003;3:2.CrossRefGoogle Scholar
  64. 64.
    Callaway CW, Elmer J, Guyette FX, et al. Dexmedetomidine reduces shivering during mild hypothermia in waking subjects. PLoS One. 2015;10:e0129709.CrossRefGoogle Scholar
  65. 65.
    Badjatia N, Bodock M, Guanci M, Rordorf GA. Rapid infusion of cold saline (4 degrees C) as adjunctive treatment of fever in patients with brain injury. Neurology. 2006;66:1739–41.CrossRefGoogle Scholar
  66. 66.
    Diedrich DA, Brown DR. Analytic reviews: propofol infusion syndrome in the ICU. J Intensive Care Med. 2011;26:59–72.CrossRefGoogle Scholar
  67. 67.
    Fong JJ, Sylvia L, Ruthazer R, et al. Predictors of mortality in patients with suspected propofol infusion syndrome. Crit Care Med. 2008;36:2281–7.CrossRefGoogle Scholar
  68. 68.
    Kim F, Olsufka M, Longstreth WT Jr, et al. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline. Circulation. 2007;115:3064–70.CrossRefGoogle Scholar
  69. 69.
    Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation. 2007;73:29–39.CrossRefGoogle Scholar
  70. 70.
    Rittenberger JC, Guyette FX, Tisherman SA, et al. Outcomes of a hospital-wide plan to improve care of comatose survivors of cardiac arrest. Resuscitation. 2008;79:198–204.CrossRefGoogle Scholar
  71. 71.
    Gaieski DF, Band RA, Abella BS, DeVita MA, Alvarez RJ, Callaway CW. Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest. Resuscitation. 2009;80:418.CrossRefGoogle Scholar
  72. 72.
    Moore TM, Callaway CW, Hostler D. Core temperature cooling in healthy volunteers after rapid intravenous infusion of cold and room temperature saline solution. Ann Emerg Med. 2008;51:153–9.CrossRefGoogle Scholar
  73. 73.
    Hostler D, Northington WE, Callaway CW. High-dose diazepam facilitates core cooling during cold saline infusion in healthy volunteers. Appl Physiol Nutr Metab. 2009;34:582–6.CrossRefGoogle Scholar
  74. 74.
    Badjatia N, Strongilis E, Gordon E, et al. Metabolic impact of shivering during therapeutic temperature modulation: the bedside shivering assessment scale. Stroke. 2008;39:3242–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of FloridaGainesvilleUSA

Personalised recommendations