Emergency Ultra-Deep Hypothermia in Cardiac Arrest Induced by Blood Loss (Experimental Study on Nonhuman Primates)
https://doi.org/10.15360/1813-9779-2025-1-62-74
Abstract
The survival rate of critically injured individuals with severe blood loss and cardiac arrest is close to zero.
Aim. To evaluate the feasibility of using emergency ultra-deep hypothermia (EUDH) in an experimental model of cardiac arrest induced by blood loss in nonhuman primates.
Materials and Methods. Five male olive baboons (Papio anubis), weighing 19.8 (18.8–23.8) kg, were subjected to severe blood loss leading to cardiac arrest. After 1 minute of observation and 3 minutes of cardiopulmonary resuscitation (CPR), aortic arch cooling was initiated using extracorporeal membrane oxygenation (ECMO) with a 4°C solution to achieve a nasopharyngeal temperature of 10°C. Whole-body cooling followed until a rectal temperature of 16°C was reached. Balloon catheters were used to disconnect the upper and lower halves of the body. Once the target temperatures were reached, the ECMO circuit was turned off and an open laparotomy was performed to simulate damage control strategies. One hour after cardiac arrest, slow rewarming began at a rate of 1°C per 10 minutes to 1°C per hour, accompanied by reinfusion of previously collected blood. After return of spontaneous circulation (ROSC), sustained breathing, and tracheal extubation, the animals were transferred to a vivarium.
Results. During deep hypothermia, cerebral oximetry values remained within normal limits in all animals. Sustained ROSC was recorded in 4 of 5 animals at temperatures between 22–25°C. Two animals survived to the end of the experiment but died after extubation, 44 and 19 hours after the start of the experiment. Cooling rates for survivors were 7–11 minutes compared to 23–37 minutes for non-survivors. Causes of death included systemic hypoperfusion with subsequent reperfusion syndrome as evidenced by progressive lactate elevation, elevated creatine phosphokinase levels, cerebral edema, myocardial ischemia, and transient coagulopathy.
Conclusion. EUDH supports adequate cerebral perfusion during temporary circulatory arrest. Recovery of cardiac activity and, in some cases, awakening are achievable during the rewarming phase. Causes of death and possible corrective measures require further investigation.
About the Authors
Victor A. RevaRussian Federation
Victor A. Reva
6 Academician Lebedev Str., B, 194044 St. Petersburg
Anastasia R. Samakaeva
Russian Federation
Anastasia R. Samakaeva
6 Academician Lebedev Str., B, 194044 St. Petersburg
Daniil A. Shelukhin
Russian Federation
Daniil A. Shelukhin
4 A Finlandsky Prospekt, 191186 Str. Petersburg
Sergey V. Orlov
Russian Federation
Sergey V. Orlov
177 Academician Lapina Str., Vesyoloye vil., 354376 Sochi
Vladimir D. Potemkin
Russian Federation
Vladimir D. Potemkin
6 Academician Lebedev Str., B, 194044 St. Petersburg
Dmitry V. Bulgin
Russian Federation
Dmitry V. Bulgin
177 Academician Lapina Str., Vesyoloye vil., 354376 Sochi
Galina Y. Gracheva
Russian Federation
Galina Y. Gracheva
10 Lvovskaya Str., 195176 St. Petersburg
Alexey V. Shchegolev
Russian Federation
Alexey V. Shchegolev
6 Academician Lebedev Str., B, 194044 St. Petersburg
References
1. Konesky K. L., Guo W. A. Revisiting traumatic cardiac arrest: should CPR be initiated? Eur J Trauma Emerg Surg. 2018; 44 (6): 903. DOI: 10.1007/s00068-017-0875-6. PMID: 29177620.
2. Gräsner J. T., Wnent J., Herlitz J., Perkins G. D., Lefering R., Tjelmeland I., Koster R. W., et al. Survival after out-ofhospital cardiac arrest in Europe — Results of the EuReCa TWO study. Resuscitation. 2020; 148: 218–226. DOI: 10.1016/j.resuscitation.2019.12.042. PMID: 32027980.
3. Rhee P. M., Acosta J., Bridgeman A., Wang D., Jordan M., Rich N. Survival after emergency department thoracotomy: review of published data from the past 25 years. J Am Coll Surg. 2000; 190 (3): 288–298. DOI: 10.1016/s1072-7515(99)00233-1. PMID: 10703853.
4. Beske R. P., Obling L., Bro-Jeppesen J., Nielsen N., Meyer M., Kjaergaard J., Johansson P. I., et al. The effect of targeted temperature management on the metabolome following out-of-hospital cardiac arrest. Ther Hypothermia Temp Manag. 2023; 13 (4): 208–215. DOI: 10.1089/ther.2022.0065. PMID: 37219970.
5. Negovsky V. A. The resuscitation of the body and artificial hypothermia. M.: Medgiz; 1960: 302.
6. Marchand P., Allan J. C. An experimental study of the effect of hypothermia on the heart and brain. S Afr J Med Sci. 1956; 21 (3–4): 127–141. DOI: 10.1097/00132586-195810000-00002. PMID: 13442723.
7. Bigelow W. G., Lindsay W. K., Greenwood W. F. Hypothermia; its possible role in cardiac surgery: an investigation of factors governing survival in dogs at low body temperatures. Ann Surg. 1950; 132 (5): 849–866. DOI: 10.1097/00000658-195011000-00001. PMID: 14771796.
8. Moroz V. V. On the occasion of the100th anniversary of V. A. Negovsky academician of the Russian Academy of Medical Sciences. General Reanimatology = Obshchaya Reanimatologiya. 2009; 5 (1): 3–11. (In Russ.&Eng.). DOI: 10.15360/1813-9779-2009-1-5.
9. Chamberlain D. «Vladimar Negovsky: The Father of reanimatology». The Negovsky memorial lecture, given at the seventh scientific congress of the European Resuscitation Council, Budapest September 2004. Общая реаниматология. General Reanimatology = Obshchaya Reanimatologiya. 2005; 1 (2): 57–69. DOI: 10.15360/1813-9779-2005-2-57-69.
10. Safar P. J., Tisherman S. A. Suspended animation for delayed resuscitation. Curr Opin Anaesthesiol. 2002; 15 (2): 203–210. DOI: 10.1097/00001503-200204000-00010. PMID: 17019202.
11. Wu X., Drabek T., Tisherman S. A., Henchir J., Stezoski S. W., Culver S., Kochanek P. M. Emergency preservation and resuscitation with profound hypothermia, oxygen, and glucose allows reliable neurological recovery after 3 h of cardiac arrest from rapid exsanguination in dogs. J Cereb Blood Flow Metab. 2008; 28 (2): 302–311. DOI: 10.1038/sj.jcbfm.9600524. PMID: 17622254.
12. Usenko L. V., Tsarev A. V. Artificial hypothermia in modern reanimaology. General Reanimatology = Obshchaya Reanimatologiya. 2009; 5 (1): 21–23. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2009-1-21.
13. Capone A., Safar P., Radovsky A., Wang Y. F., Peitzman A., Tisherman S. A. Complete recovery after normothermic hemorrhagic shock and profound hypothermic circulatory arrest of 60 minutes in dogs. J Trauma. 1996; 40 (3): 388–395. DOI: 10.1097/00005373-199603000-00011. PMID: 8601855.
14. Alam H. B., Chen Z., Honma K., Koustova E., Querol R. I. L. C., Jaskille A., Inocencio R., et al. The rate of induction of hypothermic arrest determines the outcome in a swine model of lethal hemorrhage. J Trauma. 2004; 57 (5): 961–969. DOI: 10.1097/01.ta.0000149549.72389.3f. PMID: 15580018.
15. Tisherman S. A. Emergency preservation and resuscitation for cardiac arrest from trauma. Ann N Y Acad Sci. 2022; 1509 (1): 5–11. DOI: 10.1111/nyas.14725. PMID: 34859446.
16. Castellini G., Gianola S., Biffi A. Resuscitative endovascular balloon occlusion of the aorta (REBOA) in patients with major trauma and uncontrolled haemorrhagic shock: a systematic review with meta-analysis. World J Emerg Surg. 2021; 16 (1): 41. DOI: 10.1186/s13017-021-00386-9. PMID: 34384452.
17. Alam H. B., Rhee P., Honma K., Chen H., Ayuste E. C., Lin T., Toruno K., et al. Does the rate of rewarming from profound hypothermic arrest influence the outcome in a swine model of lethal hemorrhage? J Trauma. 2006; 60 (1): 134–146. DOI: 10.1097/01.ta.0000198469.95292.ec. PMID: 16456447.
18. Liu Y., Li S., Zhang J., Han J., Zhang Y., Yin Z., Wang H. A safety evaluation of profound hypothermia-induced suspended animation for delayed resuscitation at 90 or 120 min. Mil Med Res. 2017; 4: 16. DOI: 10.1186/s40779-017-0127-4. PMID: 28573043.
19. Thevathasan T., Gregers E., Mørk S. R., Degbeon S., Linde L., Andreasen J. B., Smerup M., et al. Lactate and lactate clearance as predictors of one-year survival in extracorporeal cardiopulmonary resuscitation — An international, multicentre cohort study. J Resuscitation. 2024; 198: 110149. DOI: 10.1016/j.resuscitation.2024.110149. PMID: 38403182.
20. Reva V. A., Goncharov S. F., Potemkin V. D., Baranov M. I., Vertiy A. B., Sazhneva M. Y., Samakaeva A. R., et al. Emergency superdeep hypothermia in circulatory arrest caused by massive blood loss: from the experience of tactical and special exercises. Disaster Medicine = Meditsina Katastrof. 2023; 4: 57–64. (in Russ.). DOI: 10.33266/2070-1004-2023-4.
Supplementary files
Review
For citations:
Reva V.A., Samakaeva A.R., Shelukhin D.A., Orlov S.V., Potemkin V.D., Bulgin D.V., Gracheva G.Y., Shchegolev A.V. Emergency Ultra-Deep Hypothermia in Cardiac Arrest Induced by Blood Loss (Experimental Study on Nonhuman Primates). General Reanimatology. 2025;21(1):62-74. https://doi.org/10.15360/1813-9779-2025-1-62-74