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Non-adrenergic Vasopressors in Septic Shock: Overview and Update

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Annual Update in Intensive Care and Emergency Medicine 2021

Part of the book series: Annual Update in Intensive Care and Emergency Medicine ((AUICEM))

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Abstract

Septic shock is a medical emergency and vasoactive medications must be promptly used to achieve hemodynamic stabilization if fluid therapy is not sufficient to achieve this goal. Current guidelines recommend norepinephrine as the first-choice vasopressor in this context; however, some conditions, such as refractory septic shock, may require high doses of norepinephrine, which may be associated with various adverse effects and increased mortality rates. Indeed, vascular hyporesponsiveness, a condition defined as a decreased pressure response to vasopressor agents, often occurs in septic patients and usually requires progressive administration of increasing doses of norepinephrine to achieve hemodynamic stabilization. The pathophysiology underlying this disorder is linked to an imbalance between vasoconstrictor and vasodilator mediators. Therefore, administration of non-adrenergic vasopressors has been proposed as a possible therapeutic option in patients with septic shock requiring high norepinephrine doses. These non-adrenergic vasopressors include arginine vasopressin (AVP) and its derivatives (terlipressin and selepressin), as well as angiotensin II. Few studies have investigated the role of these agents, leaving no conclusive evidence about their possible beneficial effects on outcome. The current evidence does not support the routine use of these agents; however, AVP may be a safe adjunct to reduce norepinephrine requirements in patients with septic shock.

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References

  1. Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care. 2019;23:196.

    Article  Google Scholar 

  2. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–77.

    Article  Google Scholar 

  3. Auchet T, Regnier MA, Girerd N, Levy B. Outcome of patients with septic shock and high-dose vasopressor therapy. Ann Intensive Care. 2017;7:43.

    Google Scholar 

  4. Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358:877–87.

    Google Scholar 

  5. Liu ZM, Chen J, Kou Q, Lin Q, Huang X, Tang Z, et al. Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial. Intensive Care Med. 2018;44:1816–25.

    Article  CAS  Google Scholar 

  6. Laterre PF, Berry SM, Blemingset A, Carlsen JE, François B, Graves T, et al. Effect of selepressin vs placebo on ventilator- and vasopressor-free days in patients with septic shock: The SEPSIS-ACT Randomized Clinical Trial. JAMA. 2019;322:1476–85.

    Article  CAS  Google Scholar 

  7. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377:419–30.

    Google Scholar 

  8. Levy B, Collin S, Sennoun N, Ducrocq N, Kimmoun A, Asfar P, et al. Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med. 2010;36:2019–29.

    Article  CAS  Google Scholar 

  9. Bucher M, Hobbhahn J, Taegeret K, Kurtz A. Cytokine-mediated downregulation of vasopressin V(1A) receptors during acute endotoxemia in rats. Am J Physiol Regul Integr Comp Physiol. 2002;282:979–84.

    Article  Google Scholar 

  10. Antonucci E, Fiaccadori E, Donadello K, Taccone FS, Franchi F, Scolletta S. Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care. 2014;29:500–11.

    Article  Google Scholar 

  11. Reddi BAJ, Beltrame JF, Younget RL, Wilson DP. Calcium desensitisation in late polymicrobial sepsis is associated with loss of vasopressor sensitivity in a murine model. Intensive Care Med Exp. 2015;3:36.

    Article  Google Scholar 

  12. Wolfe KS, Patel BK, MacKenzie EL, Giovanni SP, Pohlman AS, Churpek MM, et al. Impact of vasoactive medications on ICU-acquired weakness in mechanically ventilated patients. Chest. 2018;154:781–7.

    Article  Google Scholar 

  13. Stolk RF, van der Poll T, Angus DC, van der Hoeven JG, Pickkers P, Kox M. Potentially inadvertent immunomodulation: Norepinephrine use in sepsis. Am J Respir Crit Care Med. 2016;194:550–8.

    Article  CAS  Google Scholar 

  14. Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370:1583–93.

    Article  CAS  Google Scholar 

  15. Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med. 2008;34:2226–34.

    Article  Google Scholar 

  16. Avni T, Lador A, Lev S, Leibovici L, Paul M, Grossman A. Vasopressors for the treatment of septic shock: systematic review and meta-analysis. PLoS One. 2015;10:e0129305.

    Article  Google Scholar 

  17. Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007;370:676–84.

    Article  CAS  Google Scholar 

  18. Zhong L, Ji XW, Wang HL, Zhao GM, Zhou Q, Xie B. Non-catecholamine vasopressors in the treatment of adult patients with septic shock – evidence from meta-analysis and trial sequential analysis of randomized clinical trials. J Intensive Care. 2020;8:83.

    Article  Google Scholar 

  19. Barrett LK, Singer M, Clappet LH. Vasopressin: mechanisms of action on the vasculature in health and in septic shock. Crit Care Med. 2007;35:33–40.

    Article  CAS  Google Scholar 

  20. O’Callaghan DJP, Gordon AC. What’s new in vasopressin? Intensive Care Med. 2015;41:2177–9.

    Article  Google Scholar 

  21. Landry DW, Levin HR, Gallant EM, Ashton RC Jr, Seo S, D'Alessandro D, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95:1122–5.

    Article  CAS  Google Scholar 

  22. Gordon AC, Wang N, Walley KR, Ashby D, Russell JA. The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock. Chest. 2012;142:593–605.

    Article  CAS  Google Scholar 

  23. Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: The VANISH Randomized Clinical Trial. JAMA. 2016;316(5):509–18.

    Article  CAS  Google Scholar 

  24. Lange M, Ertmer C, Rehberg S, Morelli A, Köhler G, Kampmeier TG, et al. Effects of two different dosing regimens of terlipressin on organ functions in ovine endotoxemia. Inflamm Res. 2011;60:429–37.

    Article  CAS  Google Scholar 

  25. Albanese J, Leone M, Delmas A, Martin C. Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. Crit Care Med. 2005;33:1897–902.

    Article  CAS  Google Scholar 

  26. Morelli A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, et al. Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized controlled pilot study. Crit Care. 2009;13:R130.

    Article  Google Scholar 

  27. He X, Su F, Taccone FS, Laporte R, Kjølbye AL, Zhang J, et al. A selective V(1A) receptor agonist, selepressin, is superior Arginine Vasopressin and to Norepinephrine in ovine septic shock. Crit Care Med. 2016;44:23–31.

    Article  Google Scholar 

  28. Russell JA, Vincent JL, Kjølbye AL, Olsson H, Blemings A, Spapen H, et al. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Crit Care. 2017;21:213.

    Article  Google Scholar 

  29. Antonucci E, Gleeson PJ, Annoni F, Agosta S, Orlando S, Taccone FS, et al. Angiotensin 2 in refractory septic shock. Shock. 2017;47:560–6.

    Article  CAS  Google Scholar 

  30. Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014;18:534.

    Article  Google Scholar 

  31. Ostermann M, Boldt DW, Harper MD, Lim GW, Gunnerson K. Angiotensin in ECMO patients with refractory shock. Crit Care. 2018;22:288.

    Article  Google Scholar 

  32. Tumlin JA, Murugan R, Deane AM, Ostermann M, Busse LW, Ham KR, et al. Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous Angiotensin II. Crit Care Med. 2018;46:949–57.

    Article  CAS  Google Scholar 

  33. Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care. 2015;19(Suppl. 3):S8.

    Article  Google Scholar 

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Authors and Affiliations

  1. Intermediate Care Unit, Emergency Department, Ospedale Guglielmo da Saliceto, Piacenza, Italy

    E. Antonucci & M. Giovini

  2. Department of Anesthesiology and Intensive Care Medicine, Uniklinikum Jena, Jena, Germany

    Y. Sakr

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  1. E. Antonucci
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  2. M. Giovini
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  3. Y. Sakr
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Correspondence to Y. Sakr .

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Editors and Affiliations

  1. Department of Intensive Care, Erasme University Hospital, Université libre de Bruxelles, Brussels, Belgium

    Jean-Louis Vincent

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Antonucci, E., Giovini, M., Sakr, Y. (2021). Non-adrenergic Vasopressors in Septic Shock: Overview and Update. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2021. Annual Update in Intensive Care and Emergency Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-73231-8_7

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  • DOI: https://doi.org/10.1007/978-3-030-73231-8_7

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