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Pralidoxime-Induced Potentiation of the Pressor Effect of Adrenaline and Hastened Successful Resuscitation by Pralidoxime in a Porcine Cardiac Arrest Model

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Abstract

Purpose

Pralidoxime potentiated the pressor effect of adrenaline and facilitated restoration of spontaneous circulation (ROSC) after prolonged cardiac arrest. In this study, we hypothesised that pralidoxime would hasten ROSC in a model with a short duration of untreated ventricular fibrillation (VF). We also hypothesised that potentiation of the pressor effect of adrenaline by pralidoxime would not be accompanied by worsening of the adverse effects of adrenaline.

Methods

After 5 min of VF, 20 pigs randomly received either pralidoxime (40 mg/kg) or saline, in combination with adrenaline, during cardiopulmonary resuscitation (CPR). Coronary perfusion pressure (CPP) during CPR, and ease of resuscitation were compared between the groups. Additionally, haemodynamic data, severity of ventricular arrhythmias, and cerebral microcirculation were measured during the 1-h post-resuscitation period. Cerebral microcirculatory blood flow and brain tissue oxygen tension (PbtO2) were measured on parietal cortices exposed through burr holes.

Results

All animals achieved ROSC. The pralidoxime group had higher CPP during CPR (P = 0.014) and required a shorter duration of CPR (P = 0.024) and smaller number of adrenaline doses (P = 0.024). During the post-resuscitation period, heart rate increased over time in the control group, and decreased steadily in the pralidoxime group. No inter-group differences were observed in the incidences of ventricular arrhythmias, cerebral microcirculatory blood flow, and PbtO2.

Conclusion

Pralidoxime improved CPP and hastened ROSC in a model with a short duration of untreated VF. The potentiation of the pressor effect of adrenaline was not accompanied by the worsening of the adverse effects of adrenaline.

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References

  1. Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med. 2018;379:711–21.

    Article  CAS  Google Scholar 

  2. Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche JD, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive Care Med. 2013;39:1972–80.

    Article  Google Scholar 

  3. Eddleston M, Eyer P, Worek F, Juszczak E, Alder N, Mohamed F, et al. Pralidoxime in acute organophosphorus insecticide poisoning–a randomised controlled trial. PLoS Med. 2009;6:e1000104.

    Article  Google Scholar 

  4. Jung YH, Ryu DH, Jeung KW, Na JY, Lee DH, Lee BK, et al. Effect of pralidoxime on coronary perfusion pressure during cardiopulmonary resuscitation in a pig model. Clin Exp Emerg Med. 2019;6:204–11.

    Article  Google Scholar 

  5. Jung YH, Lee HY, Jeung KW, Lee BK, Youn CS, Yun SW, et al. Pralidoxime administered during cardiopulmonary resuscitation facilitates successful resuscitation in a pig model of cardiac arrest. Clin Exp Pharmacol Physiol. 2020;47:236–46.

    Article  CAS  Google Scholar 

  6. Jung YH, Mamadjonov N, Lee HY, et al. Effects of different doses of Pralidoxime administered during cardiopulmonary resuscitation and the role of α-adrenergic receptors in its Pressor action. J Am Heart Assoc. 2020;9:e015076.

    PubMed  PubMed Central  Google Scholar 

  7. Wenzel V, Lindner KH, Krismer AC, Miller EA, Voelckel WG, Lingnau W. Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs. Circulation. 1999;99:1379–84.

    Article  CAS  Google Scholar 

  8. Jeung KW, Ryu HH, Song KH, Lee BK, Lee HY, Heo T, et al. Variable effects of high-dose adrenaline relative to standard-dose adrenaline on resuscitation outcomes according to cardiac arrest duration. Resuscitation. 2011;82:932–6.

    Article  CAS  Google Scholar 

  9. Berg RA, Otto CW, Kern KB, Hilwig RW, Sanders AB, Henry CP, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxial cardiac arrest. Crit Care Med. 1996;24:1695–700.

    Article  CAS  Google Scholar 

  10. Tang W, Weil MH, Sun S, Noc M, Yang L, Gazmuri RJ. Epinephrine increases the severity of postresuscitation myocardial dysfunction. Circulation. 1995;92:3089–93.

    Article  CAS  Google Scholar 

  11. Ristagno G, Sun S, Tang W, Castillo C, Weil MH. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation. Crit Care Med. 2007;35:2145–9.

    Article  CAS  Google Scholar 

  12. Ristagno G, Tang W, Huang L, Fymat A, Chang YT, Sun S, et al. Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation. Crit Care Med. 2009;37:1408–15.

    Article  CAS  Google Scholar 

  13. Schmitz B, Fischer M, Bockhorst K, Hoehn-Berlage M, Hossmann KA. Resuscitation from cardiac arrest in cats: influence of epinephrine dosage on brain recovery. Resuscitation. 1995;30:251–62.

    Article  CAS  Google Scholar 

  14. Berg RA, Otto CW, Kern KB, et al. High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs: a prospective, randomized study. Crit Care Med. 1994;22:282–90.

    Article  CAS  Google Scholar 

  15. Gedeborg R, Silander HC, Ronne-Engström E, Rubertsson S, Wiklund L. Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation. Crit Care Med. 2000;28:1423–30.

    Article  CAS  Google Scholar 

  16. Cho YC, Cho SW, Chung SP, Yu K, Kwon OY, Kim SW. How can a single rescuer adequately deliver tidal volume with a manual resuscitator? An improved device for delivering regular tidal volume. Emerg Med J. 2011;28:40–3.

    Article  Google Scholar 

  17. Curtis MJ, Hancox JC, Farkas A, Wainwright CL, Stables CL, Saint DA, et al. The Lambeth Conventions (II): guidelines for the study of animal and human ventricular and supraventricular arrhythmias. Pharmacol Ther. 2013;139:213–48.

    Article  CAS  Google Scholar 

  18. Le Roux P, Menon DK, Citerio G, et al. Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine. Intensive Care Med. 2014;40:1189–209.

    Article  Google Scholar 

  19. Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002;360:1395–6.

    Article  Google Scholar 

  20. Boerma EC, Mathura KR, van der Voort PH, Spronk PE, Ince C. Quantifying bedside-derived imaging of microcirculatory abnormalities in septic patients: a prospective validation study. Crit Care. 2005;9:R601–6.

    Article  Google Scholar 

  21. Serné EH, Gans RO, ter Maaten JC, Tangelder GJ, Donker AJ, Stehouwer CD. Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction. Hypertension. 2001;38:238–42.

    Article  Google Scholar 

  22. Reynolds JC, Frisch A, Rittenberger JC, Callaway CW. Duration of resuscitation efforts and functional outcome after out-of-hospital cardiac arrest: when should we change to novel therapies? Circulation. 2013;128:2488–94.

    Article  Google Scholar 

  23. Iqbal MB, Al-Hussaini A, Rosser G, et al. Predictors of survival and favorable functional outcomes after an out-of-hospital cardiac arrest in patients systematically brought to a dedicated heart attack center (from the Harefield Cardiac Arrest Study). Am J Cardiol. 2015;115:730–7.

    Article  Google Scholar 

  24. Dumas F, Bougouin W, Geri G, Lamhaut L, Bougle A, Daviaud F, et al. Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol. 2014;64:2360–7.

    Article  CAS  Google Scholar 

  25. Sigal AP, Sandel KM, Buckler DG, Wasser T, Abella BS. Impact of adrenaline dose and timing on out-of-hospital cardiac arrest survival and neurological outcomes. Resuscitation. 2019;139:182–8.

    Article  Google Scholar 

  26. Zarro VJ, Dipalma JR. The sympathomimetic effects of 2-pyridine aldoxime methylchloride (2-PAM CL). J Pharmacol Exp Ther. 1965;147:153–60.

    CAS  PubMed  Google Scholar 

  27. Stavinoha WB, Hinshaw LB, Smith PW, Rieger JA Jr. Cardiovascular effects of 2-pyridine aldoxime methylchloride (pralidoxime and blood pressure). Arch Int Pharmacodyn Ther. 1970;187:52–65.

    CAS  PubMed  Google Scholar 

  28. Carrier GO, Peters T, Bishop VS. Alteration in calcium metabolism as a mechanism for pyridine aldoxime methochloride (2-PAM) cardiac action in rabbit atria. J Pharmacol Exp Ther. 1975;193:218–31.

    CAS  PubMed  Google Scholar 

  29. Vandycke C, Martens P. High dose versus standard dose epinephrine in cardiac arrest - a meta-analysis. Resuscitation. 2000;45:161–6.

    Article  CAS  Google Scholar 

  30. Lin S, Callaway CW, Shah PS, Wagner JD, Beyene J, Ziegler CP, et al. Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation. 2014;85:732–40.

    Article  CAS  Google Scholar 

  31. Yang L, Wang S, Li CS. Effect of continuous compression and 30:2 cardiopulmonary resuscitation on cerebral microcirculation in a porcine model of cardiac arrest. Scand J Trauma Resusc Emerg Med. 2013;21:55.

    Article  Google Scholar 

  32. Sekhon MS, Gooderham P, Menon DK, Brasher PMA, Foster D, Cardim D, et al. The burden of brain hypoxia and optimal mean arterial pressure in patients with hypoxic ischemic brain injury after cardiac arrest. Crit Care Med. 2019;47:960–9.

    Article  CAS  Google Scholar 

  33. Elmer J, Flickinger KL, Anderson MW, Koller AC, Sundermann ML, Dezfulian C, et al. Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest. Resuscitation. 2018;129:121–6.

    Article  Google Scholar 

  34. Sekhon MS, Ainslie PN, Menon DK, Thiara SS, Cardim D, Gupta AK, et al. Brain hypoxia secondary to diffusion limitation in hypoxic ischemic brain injury postcardiac arrest. Crit Care Med. 2020;48:378–84.

    Article  CAS  Google Scholar 

  35. Markstaller K, Karmrodt J, Doebrich M, Wolcke B, Gervais H, Weiler N, et al. Dynamic computed tomography: a novel technique to study lung aeration and atelectasis formation during experimental CPR. Resuscitation. 2002;53:307–13.

    Article  Google Scholar 

  36. Cha KC, Kim YW, Kim HI, Kim OH, Cha YS, Kim H, et al. Parenchymal lung injuries related to standard cardiopulmonary resuscitation. Am J Emerg Med. 2017;35:117–21.

    Article  Google Scholar 

  37. Tang W, Weil MH, Gazmuri RJ, Sun S, Duggal C, Bisera J. Pulmonary ventilation/perfusion defects induced by epinephrine during cardiopulmonary resuscitation. Circulation. 1991;84:2101–7.

    Article  CAS  Google Scholar 

  38. Berk JL, Hagen JF, Koo R, et al. Pulmonary insufficiency caused by epinephrine. Ann Surg. 1973;178:423–35.

    Article  CAS  Google Scholar 

  39. Ferrari W, Baggio G, Guarini S. Studies on epinephrine-induced lung edema in the rat. I. Selective alpha 1-adrenoceptor involvement. Arch Int Pharmacodyn Ther. 1986;281:89–99.

    CAS  PubMed  Google Scholar 

  40. Laurent I, Monchi M, Chiche JD, Joly LM, Spaulding C, Bourgeois B, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol. 2002;40:2110–6.

    Article  Google Scholar 

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Acknowledgements

We would like to thank Editage (www.editage.co.kr) for English language editing.

Availability of Data and Material

The data that support the findings of this study are included in electronic supplementary material (Online Resource 1).

Code Availability

Not applicable.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A2B6001388). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank Editage (www.editage.co.kr) for English language editing.

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Authors and Affiliations

  1. Department of Emergency Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea

    Hyoung Youn Lee, Yong Hun Jung, Byung Kook Lee, Tag Heo & Yong Il Min

  2. Department of Medical Science, Chonnam National University Graduate School, Gwangju, Republic of Korea

    Najmiddin Mamadjonov

  3. Department of Emergency Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeollanam-do, Republic of Korea

    Kyung Woon Jeung

  4. Department of Emergency Medicine, Chonnam National Univeristy Medical School, Gwangju, Republic of Korea

    Kyung Woon Jeung, Yong Hun Jung, Byung Kook Lee, Kyung-Sub Moon, Tag Heo & Yong Il Min

  5. Department of Neurosurgery, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeollanam-do, Republic of Korea

    Kyung-Sub Moon

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  1. Hyoung Youn Lee
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Contributions

Conceptualisation: Kyung Woon Jeung; Methodology: Hyoung Youn Lee, Najmiddin Mamadjonov, Kyung Woon Jeung, Yong Hun Jung, and Kyung-Sub Moon; Formal analysis: Byung Kook Lee; Investigation: Hyoung Youn Lee, Najmiddin Mamadjonov, Kyung Woon Jeung, and Yong Hun Jung; Writing-original draft preparation: Hyoung Youn Lee, Najmiddin Mamadjonov, and Kyung Woon Jeung; Funding acquisition: Kyung Woon Jeung; Resources: Yong Hun Jung and Kyung-Sub Moon; Supervision: Tag Heo and Yong Il Min; Writing-review and editing: Tag Heo and Yong Il Min.

Corresponding author

Correspondence to Kyung Woon Jeung.

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Ethics Approval

This study was approved by the Animal Care and Use Committee of Chonnam National University Hospital (CNUH IACUC-18004). Animal care and experiments were conducted according to the author’s Institutional Animal Care and Use Committee guidelines.

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Lee, H.Y., Mamadjonov, N., Jeung, K.W. et al. Pralidoxime-Induced Potentiation of the Pressor Effect of Adrenaline and Hastened Successful Resuscitation by Pralidoxime in a Porcine Cardiac Arrest Model. Cardiovasc Drugs Ther 34, 619–628 (2020). https://doi.org/10.1007/s10557-020-07026-5

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