Skip to main content
SpringerLink
Log in

Modified Glucose-insulin-potassium Therapy for Hemorrhage-induced Traumatic Cardiac Arrest in Rabbits

  • Original Articles
  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

Objective

Resuscitation with whole blood is known to be better than that with saline in attaining the return of spontaneous circulation (ROSC) and improving the short-term survival rate for hemorrhage-induced traumatic cardiac arrest (HiTCA). However, the resuscitation with whole blood alone fails to address the pathophysiological abnormalities, including hyperglycemia, hyperkalemia and coagulopathy, after HiTCA. The present study aimed to determine whether the modified glucose-insulin-potassium (GIK) therapy can ameliorate the above-mentioned pathophysiological abnormalities, enhance the ROSC, improve the function of key organs, and reduce the mortality after HiTCA.

Methods

HiTCA was induced in rabbits (n=36) by controlled hemorrhage. Following arrest, the rabbits were randomly divided into three groups (n=12 each): group A (no resuscitation), group B (resuscitation with whole blood), and group C (resuscitation with whole blood plus GIK). The GIK therapy was administered based on the actual concentration of glucose and potassium. The ROSC rate and survival rate were obtained. Hemodynamical and biochemical changes were detected. Thromboelastography (TEG) was used to measure coagulation parameters, and enzyme-linked immunosorbent assay to detect parameters related to inflammation, coagulation and the function of brain.

Results

All animals in groups B and C attained ROSC. Two rabbits died 24–48 h after HiTCA in group B, while no rabbits died in group C. The GIK therapy significantly reduced the levels of blood glucose, potassium, and biological markers for inflammatory reaction, and improved the heart, kidney, liver and brain function in group C when compared to group B. Furthermore, the R values of TEG were significantly lower in group C than in group B, and the maximum amplitude of TEG was slightly lower in group B than in group C, with no significant difference found.

Conclusion

Resuscitation with whole blood and modified GIK therapy combined can ameliorate the pathophysiological disorders, including hyperglycemia, hyperkalemia and coagulopathy, and may improve the function of key organs after HiTCA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Xu J, Shen P, Gao Y, et al. The Effects of the Duration of Aortic Balloon Occlusion on Outcomes of Traumatic Cardiac Arrest in a Porcine Model. Shock, 2019,52(3):e12–e21

    Article  PubMed  Google Scholar 

  2. Barnard EBG, Hunt PAF, Lewis PEH, et al. The outcome of patients in traumatic cardiac arrest presenting to deployed military medical treatment facilities: data from the UK Joint Theatre Trauma Registry. J R Army Med Corps, 2018,164(3):150–154

    Article  PubMed  Google Scholar 

  3. Rall J, Cox JM, Maddry J. The Use of the AbdominalAortic and Junctional Tourniquet During Cardiopulmonary Resuscitation Following Traumatic Cardiac Arrest in Swine. Mil Med, 2017,182(9):e2001–e2005

    Article  PubMed  Google Scholar 

  4. Smith JE, Rickard A, Wise D. Traumatic cardiac arrest. J R Soc Med, 2015,108(1):11–16

    Article  PubMed  PubMed Central  Google Scholar 

  5. Watts S, Smith JE, Gwyther R, et al. Closed chest compressions reduce survival in an animal model of haemorrhage-induced traumatic cardiac arrest. Resuscitation, 2019,140:37–42

    Article  PubMed  Google Scholar 

  6. Jeffcoach DR, Gallegos JJ, Jesty SA, et al. Use of CPR in hemorrhagic shock, a dog model. J Trauma Acute Care Surg, 2016,81(1):27–33

    Article  PubMed  Google Scholar 

  7. Lockey DJ, Lyon RM, Davies GE. Development of a simple algorithm to guide the effective management of traumatic cardiac arrest. Resuscitation, 2013,84(6):738–742

    Article  PubMed  Google Scholar 

  8. Hoops HE, Manning JE, Graham TL, et al. Selective Aortic Arch Perfusion with fresh whole blood or HBOC-201 reverses hemorrhage-induced traumatic cardiac arrest in a lethal model of non-compressible torso hemorrhage. J Trauma Acute Care Surg, 2019,87(2):263–273

    Article  PubMed  Google Scholar 

  9. McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin, 2001,17(10):107–124

    Article  CAS  PubMed  Google Scholar 

  10. Kerby JD, Griffin RL, MacLennan P, et al. Stress-induced hyperglycemia, not diabetic hyperglycemia, is associated with higher mortality in trauma. Ann Surg, 2012,256(3):446–452

    Article  PubMed  Google Scholar 

  11. Bosarge PL, Shoultz TH, Griffin RL, et al. Stress-induced hyperglycemia is associated with higher mortality in severe traumatic brain injury. J Trauma Acute Care Surg, 2015,79(2):289–294

    Article  CAS  PubMed  Google Scholar 

  12. Tsai YW, Wu SC, Huang CY, et al. Impact of stress-induced hyperglycemia on the outcome of children with trauma: A cross-sectional analysis based on propensity score-matched population. Sci Rep, 2019,9(1):16311

    Article  PubMed  PubMed Central  Google Scholar 

  13. Nehme Z, Nair R, Andrew E, et al. Effect of diabetes and pre-hospital blood glucose level on survival and recovery after out-of-hospital cardiac arrest. Crit Care Resusc, 2016,18(2):69–77

    PubMed  Google Scholar 

  14. Mentzelopoulos SD, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA, 2013,310(3):270–279

    Article  PubMed  Google Scholar 

  15. Russo JJ, James TE, Hibbert B, et al. CAPITAL Investigators. Hyperglycaemia in comatose survivors of out-of-hospital cardiac arrest. Eur Heart J Acute Cardiovasc Care, 2018,7(5):442–449

    Article  PubMed  Google Scholar 

  16. Kim SH, Choi SP, Park KN, et al. Association of blood glucose at admission with outcomes in patients treated with therapeutic hypothermia after cardiac arrest. Am J Emerg Med, 2014,32(8):900–904

    Article  PubMed  Google Scholar 

  17. Zhao K, Zhang Y, Li J, et al. Modified Glucose-Insulin-Potassium Regimen Provides Cardioprotection With Improved Tissue Perfusion in Patients Undergoing Cardiopulmonary Bypass Surgery. J Am Heart Assoc, 2020,9(6):e012376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Festing MF. On determining sample size in experiments involving laboratory animals. Lab Anim, 2018,52(4):341–350

    Article  CAS  PubMed  Google Scholar 

  19. Duan K, Yu W, Lin Z, et al. A time course study of acute traumatic coagulopathy prior to resuscitation: from hypercoagulation to hypocoagulation caused by hypoperfusion? Transfus Apher Sci, 2014,50(3):399–406

    Article  PubMed  Google Scholar 

  20. Jin PY, Zhang HS, Guo XY, et al. Glucose-insulin-potassium therapy in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord, 2014,14:169

    Article  PubMed  PubMed Central  Google Scholar 

  21. Molnar M, Bergquist M, Larsson A, et al. Hyperglycaemia increases S100beta after short experimental cardiac arrest. Acta Anaesthesiol Scand, 2014,58(1):106–113

    Article  CAS  PubMed  Google Scholar 

  22. Kreutziger J, Schmid S, Umlauf N, et al. Association between Blood Glucose and cardiac Rhythms during pre-hospital care of Trauma Patients — a retrospective Analysis. Scand J Trauma Resusc Emerg Med, 2018,26(1):58

    Article  PubMed  PubMed Central  Google Scholar 

  23. Diebel LN, Diebel ME, Martin JV, et al. Acute hyperglycemia exacerbates trauma-induced endothelial and glycocalyx injury: An in vitro model. J Trauma Acute Care Surg, 2018, 85(5):960–967

    Article  CAS  PubMed  Google Scholar 

  24. Zhao XD, Qin YH, Ma JX, et al. Influence of intensive insulin therapy on vascular endothelial growth factor in patients with severe trauma. J Huazhong Univ Sci Technolog Med Sci, 2013,33(1):107–110

    Article  CAS  PubMed  Google Scholar 

  25. Kahn NN. Platelet-stimulated thrombin and PDGF are normalized by insulin and Ca2+ channel blockers. Am J Physiol, 1999,276(5):E856–E862

    CAS  PubMed  Google Scholar 

  26. Chen S, Hu M, Shen M, et al. IGF-1 facilitates thrombopoiesis primarily through Akt activation. Blood, 2018,13(2):210–222

    Article  Google Scholar 

  27. Moore EE, Moore HB, Kornblith LZ, et al. Trauma-induced coagulopathy. Nat Rev Dis Primers, 2021,7(1):30

    Article  PubMed  PubMed Central  Google Scholar 

  28. Koami H, Sakamoto Y, Sakurai R, et al. Thromboelastometric analysis of the risk factors for return of spontaneous circulation in adult patients with out-of-hospital cardiac arrest. PLoS One, 2017,12(40):e0175257

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cicero L, Fazzotta S, Palumbo VD, et al. Anesthesia protocols in laboratory animals used for scientific purposes. Acta Biomed, 2018,89(3):337–342

    CAS  PubMed  Google Scholar 

  30. Kiefer D, Müller-Wirtz LM, Maurer F, et al. Intravenous propofol, ketamine (ketofol) and rocuronium after sevoflurane induction provides long lasting anesthesia in ventilated rats. Exp Anim, 2022,71(2):231–239

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Both authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Trauma, Burn and Combined Injury, Department for Combat Casualty Care Training, Training Base for Army Health Care, Army Medical University, Chongqing, 400038, China

    Lin Zhang, Wen-qiong Du, Zhao-wen Zong, Xin Zhong, Yi-jun Jia, Ren-qing Jiang & Zhao Ye

  2. Department of Orthopedics, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    Zhao-wen Zong

Authors
  1. Lin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wen-qiong Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhao-wen Zong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi-jun Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ren-qing Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhao Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhao-wen Zong.

Ethics declarations

The authors declare that they have no competing interests.

Additional information

This work was supported by the Key Clinical Innovation Project of Army Medical University and Xinqiao Hospital (CX2019JS107/2018JSLC0023).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, L., Du, Wq., Zong, Zw. et al. Modified Glucose-insulin-potassium Therapy for Hemorrhage-induced Traumatic Cardiac Arrest in Rabbits. CURR MED SCI 43, 1238–1246 (2023). https://doi.org/10.1007/s11596-023-2796-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-023-2796-4

Key words

Search

Navigation