Журнал «Медицина неотложных состояний» Том 20, №2, 2024

Розвиток гіпертермії (≥ 38,3 °C) при тяжкій черепно-мозковій травмі (ЧМТ) асоціюється з підвищенням рівня інвалідизації та смертності, оскільки критично впливає на розвиток вторинного пошкодження головного мозку. На клітинному рівні гіпертермія викликає структурно-функціональні зміни нейронів у вигляді порушення деполяризації, трансмембранного іонного транспорту, механізмів передачі клітинних сигналів та функції мітохондрій. Гіпертермія може призводити до некрозу чи апоптозу нейронів. До системних ефектів гіпертермії відносять підвищення проникності гематоенцефалічного бар’єра, що зумовлює розвиток внутрішньочерепної гіпертензії. У цій публікації розглядаються патофізіологічні механізми розвитку гіпертермії, її участь у пошкодженні головного мозку при тяжкій ЧМТ, діагностичні критерії гіпертермії центрального генезу та сучасні підходи до забезпечення конт-рольованої нормотермії.

The development of hyperthermia (≥38.3 °C) in severe traumatic brain injury (TBI) is associated with increased levels of disability and mortality, since it critically affects the development of secondary brain damage. At the cellular level, hyperthermia causes structural and functional changes in neurons through disruption of depolarization, transmembrane ion transport, cell signaling mechanisms, and damage to mitochondrial function. Hyperthermia can lead to necrosis or apoptosis of neurons. Among the systemic effects of hyperthermia is an increase in the permeability of the blood - brain barrier, causing the development of intracranial hypertension. This publication presents the pathophysiological mechanisms of the development of hyperthermia and its participation as a factor of brain damage in severe TBI, diagnostic criteria for hyperthermia of central origin and modern methods of controlled normothermia.

черепно-мозкова травма; гіпертермія; лихоманка; цільовий температурний менеджмент; контрольована нормотермія; інтенсивна терапія

traumatic brain injury; hyperthermia; fever; target temperature management; controlled normothermia; intensive care

1. Nyholm L., Howells T., Lewén A. et al. The influence of hyperthermia on intracranial pressure, cerebral oximetry and cerebral metabolism in traumatic brain injury. Ups. J. Med. Sci. 2017 Aug. 122(3). 177-184. doi: 10.1080/03009734.2017.1319440. 
2. Meier K., Lee K. Neurogenic Fever. J. Intensive Care Med. 2017 Feb. 32(2). 124-129. doi: 10.1177/0885066615625194. 
3. Handbook of Clinical Neurology, Vol. 156 (3rd series). Thermoregulation: From Basic Neuroscience to Clinical Neurology, Part I. A.A. Romanovsky (Ed.). Elsevier, 2018. https://doi.org/10.1016/B978-0-444-63912-7.00001-1. 
4. Garami A., Szekely M. Body temperature its regulation in framework of energy balance. Temperature. 2014 Apr. 1(1). 28-29. doi.org/10.4161/temp.29060.
5. Flouris A.D. A unifying theory for the functional architecture of endothermic thermoregulation. Temperature. 2014 Oct. 1(3). 162-163. doi.org/10.4161/23328940.2014.980138.
6. Kiyatkin E.A. Brain temperature could affect neurochemical evaluation. Temperature. 2014 Apr-Jun. 1(1). 12-13. doi: 10.4161/temp.27831.
7. O’Grady N.P., Alexander E., Alhazzani W. et al. Society of Critical Care Medicine and the Infectious Diseases Society of America Guidelines for evaluating new fever in adult patients in the ICU. Critical Care Medicine. 2023 Nov. 51(11). 1570-1586. doi: 10.1097/CCM.00000000000006022.
8. Marik P.E. Fever in the ICU. Chest. 2000 Mar. 117(3). 855-69. doi: 10.1378/chest.117.3.855. 
9. Kilpatrick M.M., Lowry D.W., Firlik A.D. et al. Hyperthermia in the neurosurgical intensive care unit. Neurosurgery. 2000 Oct. 47(4). 850-855. doi: 10.1097/00006123-200010000-00011.
10. Diringer M.N., Reaven N.L., Funk S.E., Uman G.C. Elevated body temperature independently contributes to increased length of stay in neurologic intensive care unit patients. Crit. Care Med. 2004 Jul. 32(7). 1489-1495. doi: 10.1097/01.ccm.0000129484.61912.84. 
11. Zawadzka M., Szmuda M., Mazurkiewicz-Bełdzińska M. Thermoregulation disorders of central origin — how to diagnose and treat. Anaesthesiol. Intensive Ther. 2017. 49(3). 227-234. doi: 10.5603/AIT.2017.0042.
12. Walter E.J., Hanna-Jumma S., Carraretto M. et al. The pathophysiological basis and consequences of fever. Crit. Care. 2016. 20(200). doi.org/10.1186/s13054-016-1375-5.
13. Beverly A., Walter E., Carraretto M. Management of hyperthermia and hypothermia in sepsis: A recent survey of current practice across UK intensive care units. J. Intensive Care Soc. 2016 Feb. 17(1). 88-89. doi: 10.1177/1751143715601124. 
14. Roti J.L. Cellular responses to hyperthermia (40–46 °C): cell killing and molecular events. Int. J. Hyperther. 2008. 24(1). 3-15. 
15. Rabinstein A., Sandhu K. Non-infectious fever in the neurological intensive care unit: іncidence, causes and predictors. J. Neurol. Neurosurg. Psychiatr. 2007. 78. 1278-1280.
16. Honig A., Michael S., Eliahou R. et al. Central fever in patients with spontaneous intracerebral hemorrhage: predicting factors and impact on outcome. BMC Neurol. 2015. 15(6). doi: 10.1186/s12883-015-0258-8. 
17. Hocker S.E., Tian L., Li G. et al. Indicators of central fever in the neurologic intensive care unit. JAMA Neurol. 2013. 70(12). 1499-1504. doi: 10.1001/ jamaneurol.2013.4354.
18. Sung C.Y., Lee T.H., Chu N.S. Central hyperthermia in acute stroke. Eur. Neurol. 2009. 62(2). 86-92. doi: 10.1159/000222778. 
19. Rincon F., Hunter K., Schorr C. The epidemiology of spontaneous fever and hypothermia on admission of brain injury patients to intensive care units: a multicenter cohort study. J. Neurosurg. 2014 Oct. 121(4). 950-60. doi: 10.3171/2014.7.JNS132470. 
20. Niven D.J., Laupland K.B. Pyrexia: aetiology in the ICU. Crit. Care. 2016. 247(20). doi: 10.1186/s13054-016-1406-2.
21. Laupland K.B., Gregson D.B., Zygun D.A. Severe bloodstream infections: a population-based assessment. Crit. Care Med. 2004 Apr. 32(4). 992-997. doi: 10.1097/01.ccm.0000119424.31648.1e. 
22. Mackowiak P.A., Wasserman S.S., Levine M.M. 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 Sep. 268(12). 1578-1580. 
23. Weinmann E.E., Salzman E.W. Deep-vein thrombosis. N. Engl. J. Med. 1994 Dec. 331(24). 1630-1641. doi: 10.1056/NEJM199412153312407. 
24. Laupland K.B. Fever in the critically ill medical patient. Crit. Care Med. 2009 Jul. 37(7 Suppl). S273-278. doi: 10.1097/CCM.0b013e3181aa6117.
25. Crompton M.R. Hypothalamic lesions following closed head injury. Brain. 1971. 94(1). 165-72. doi: 10.1093/brain/94.1.165. 
26. Shibata M. Hyperthermia in brain hemorrhage. Med. Hypotheses. 1998 Mar. 50(3). 185-190. doi: 10.1016/s0306-9877(98)90016-0. 
27. 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 May. 126(2). 252-258. doi: 10.1007/s002210050734. 
28. Mrozek S., Vardon F., Geeraerts T. Brain temperature: physiology and pathophysiology after brain injury. Anesthesiol. Res. Pract. 2012. 2012. 989487. doi: 10.1155/2012/989487. 
29. Siwicka-Gieroba D., Robba C., Gołacki J. et al. Cerebral oxygen delivery and consumption in brain-injured patients. J. Pers. Med. 2022. 12. 1763. doi.org/10.3390/jpm12111763.
30. Spiotta A.M., Stiefel M.F., Heuer G.G. Brain hyperthermia after traumatic brain injury does not reduce brain oxygen. Neurosurgery. 2008 Apr. 62(4). 864-872. doi: 10.1227/01.neu.0000316900.63124.ce.
31. Birg T., Ortolano F., Wiegers E.J.A. et al. Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study. Neurocrit. Care. 2021 July. 35. 651-661. https://doi.org/10.1007/s12028-021-01294-1.
32. Sharma H.S., Hoopes P.J. Hyperthermia induced pathophy-siology of the central nervous system. Int. J. Hyperthermia. 2003 May-Jun. 19(3). 325-354. doi: 10.1080/0265673021000054621. 
33. Walter E.J., Carraretto M. The neurological and cognitive consequences of hypothermia. Critical Care. 2016. 20. 199. doi: 10.1186/s13054-016-1376-4.
34. Handbook of Clinical Neurology, Vol. 157 (3rd series). Thermoregulation: From Basic Neuroscience to Clinical Neurology, Part II. A.A. Romanovsky (Ed.). Elsevier, 2018. https://doi.org/10.1016/B978-0-444-64074-1.00049-5. 
35. Kasdorf E., Perlman J.M. Hyperthermia, inflammation, and perinatal brain injury. Pediatric Neurology. 2013. 49(1). 8-14. https://doi.org/10.1016/j.pediatrneurol.2012.12.026.
36. Greer D.M., Funk S.E., Reaven N.L. et al. Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis. Stroke. 2008 Nov. 39(11). 3029-35. doi: 10.1161/STROKEAHA.108.521583. 
37. Sacho R.H., Vail A., Rainey T. et al. The effect of spontaneous alterations in brain temperature on outcome: a prospective observational cohort study in patients with severe traumatic brain injury. J. Neurotrauma. 2010 Dec. 27(12). 2157-2164. doi: 10.1089/neu.2010.1384. 
38. Rumana C.S., Gopinath S.P., Uzura M. et al. Brain temperature exceeds systemic temperature in head-injured patients. Crit. Care Med. 1998 Mar. 26(3). 562-567. doi: 10.1097/00003246-199803000-00032. 
39. Rossi S., Zanier E.R., Mauri I. et al. Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage. J. Neurol. Neurosurg. Psychiatry. 2001 Oct. 71(4). 448-54. doi: 10.1136/jnnp.71.4.448. 
40. Greer D.M., Ritter J., Helbok R. et al. Impact of Fever Prevention in Brain-Injured Patients (INTREPID): Study Protocol for a Randomized Controlled Trial. Neurocrit. Care. 2021 March. 35. 577-589. https://doi.org/10.1007/s12028-021-01208-1.
41. Bhatti F., Naiman M., Tsarev A., Kulstad E. Esophageal temperature management in patients suffering from traumatic brain injury. Therapeutic Нypothermia and Тemperature Мanagement. 2019. 9(4). 238-242. doi.org/10.1089/ther.2018.0034.
42. Tsarev A.V., Ussenko L.V. Comparative assessment of the controllability and safety of therapeutic hypothermia in the complex of intensive care of severe traumatic brain injury. Medicni Perspektivi. 2017. 22(4). 56-61. doi: 10.26641/2307-0404.2017.4.117669 (In Ukrainian).
43. Tsarev A.V. Targeted temperature management in intensive care of severe traumatic brain injury. Emergency Medicine. 2017. (7). 59-64. doi: 10.22141/2224-0586.7.86.2017.116881 (In Ukrainian).
44. Tsarev A.V. Controlled normothermia in critically states patients with traumatic brain injury. Emergency Medicine. 2017. (3). 66-72. doi: 10.22141/2224-0586.3.82.2017.102326 (In Ukrainian).