Inotropes and vasopressors
1Department of Anesthesiology, Reanimatology and Intensive Medicine, University Hospital Center Split, Split, Croatia
2 University of Split, School of Medicine
DOI: 10.22514/SV131.032017.6 Vol.13,Issue S1,May 2017 pp.46-52
Published: 08 May 2017
Inotropic agents are used to increase myo-cardial contraction while vasopressors are used to increase vascular tone. They are often used for treatment of patients whose tissue perfusion is insufficient to meet metabolic requirements. Therefore, these agents are usually administered in inten-sive care units where continuous and inva-sive monitoring of cardiac function can be applied.
Inotropic agents can be divided into those that increase cAMP levels and those that do not. Adrenergic receptor agonists and phosphodiesterase inhibitors (PDEi) in-crease cAMP levels and are currently the mainstay of positive inotropic therapy. Le-vosimendan acts as calcium sensitizer and increases myocardial contraction force without increasing intracellular calcium levels. In addition to existing inotropic agents, new promising inotropes are be-ing developed. These include sarcoplasmic reticulum calcium pump (istaroxime), cardiac myosin activators (omecamtivme-carbil), gene therapy, nitroxyl donors and ryanodine receptor stabilizers.
Current treatments of heart failure are aimed at prolonging survival and not just alleviating symptoms. This review pro-vides a short description of the physiology of myocardial contraction and adrenergic receptors. We also provide a short descrip-tion of commonly used inotropic agents and vasopressor drugs as well as a short re-view of agents that are expected are in use in the future.
Inotropes are agents used to increase myo-cardial contractility, while vasopressors are administered to increase vascular tone (1). Their use ismostly confined to critically ill patients whose hemodynamic impairment is such that tissue perfusion is insufficient to meet metabolic requirements (2). Pa-tients in need of inotropic or vasopressor support are often presented with septic or cardiogenic shock and severe heart failure, and are victims of major trauma or un-dergoing major surgery.These drugs are therefore administered usually to patients treated in intensive care settings where continuous monitoring of cardiac rhythm, arterial oxygenation, urine output and other invasive hemodynamic monitoring can be applied.Inotropic and vasopressor drugs should be administered through a central venous catheter via infusion pumps that can deliver precise flow rates. These agents are mostly short acting with rapid onset and offset of action. Therefore, they can be used without an initial bolus and can be titrated frequently. Abrupt dis-continuation should be avoided because of possible hypotension.
Inotropes, Vasopressor Agents, Intensive Care, Heart Failure
LENKO SARIC,IVANA PRKIC,NENAD KARANOVIC. Inotropes and vasopressors. Signa Vitae. 2017. 13(S1);46-52.
1. Bangash MN, Kong ML, Pearse RM. Use of inotropes and vasopressor agents in critically ill patients. Br J Pharmacol 2012;165(7):2015-33.
2. Jessup M AW, Casey DE, et al. ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collabo-ration with the International Society for Heart and Lung Transplantation. Circulation 2009(119):1977-2016.
3. Bers DM. Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol 2008;70:23-49.
4. Hasenfuss G, Teerlink JR. Cardiac inotropes: current agents and future directions. Eur Heart J 2011;32(15):1838-45.
5. Alexander SP, Mathie A, Peters JA. Guide to Receptors and Channels (GRAC), 5th edition. Br J Pharmacol 2011;164 Suppl 1:S1-324.
6. Glick DB. The Autonomic Nervous System. In: Miller RD, Eriksson LA, Fleisher LA, Wiener-Kronish JP, Young WL, editors. Miller’s Anesthesia, 7th ed. USA: Elsevier; 2009.
7. Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 2011;63(1):182-217.
8. Izumi Y, Miura K, Iwao H. Therapeutic potential of vasopressin-receptor antagonists in heart failure. J Pharmacol Sci 2014;124(1):1-6.
9. Royster RL, Groban L, Grosshans DW, Jones-Haywood MM, Slaughter TF. Cardiovascular Pharmacology. In: Kaplan JA, Reich DL, Savino JS, editors. Kaplan’s Cardiac Anesthesia: The Echo Era, 6th ed. USA: Elsevier; 2011.
10. Levy JH, Ramsay JG, Tanaka K, Bailey JM. Postoperative Cardiovascular Management. In: Kaplan JA, Reich DL, Savino JS, editors. Kaplan’s Cardiac Anesthesia: The Echo Era, 6th ed. USA: Elsevier; 2011.
11. Metra M, Bettari L, Carubelli V, Cas LD. Old and new intravenous inotropic agents in the treatment of advanced heart failure. Prog Cardiovasc Dis 2011;54(2):97-106.
12. Levy JH, Bailey JM, Deeb GM. Intravenous milrinone in cardiac surgery. Ann Thorac Surg 2002;73(1):325-30.
13. Weishaar RE, Burrows SD, Kobylarz DC, Quade MM, Evans DB. Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets. Isolation, characterization, and effects of various reference phosphodiesterase inhibitors and cardiotonic agents. Biochem Pharmacol 1986;35(5):787-800.
14. Francis GS, Bartos JA, Adatya S. Inotropes. J Am Coll Cardiol 2014;63(20):2069-78.
15. Francis GS. The contemporary use of digoxin for the treatment of heart failure. Circ Heart Fail 2008;1(3):208-9.
16. Toller W, Heringlake M, Guarracino F, Algotsson L, Alvarez J, Argyriadou H, et al. Preoperative and perioperative use of levosi-mendan in cardiac surgery: European expert opinion. Int J Cardiol 2015;184C:323-36.
17. Biolo A, Colucci WS, Givertz MM. Inotropic and Vasoactive Agents in the Cardiac Intensive Care Unit. In: Jeremias A, Brown DL, editors. Cardiac Intensive Care, 2nd ed. USA: Elsevier; 2010.
18. Toller WG, Stranz C. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology 2006;104(3):556-69.
19. Petersen JW, Felker GM. Inotropes in the management of acute heart failure. Crit Care Med 2008;36(1 Suppl):S106-11.
20. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a pla-cebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000;356(9248):2139-43.
21. Holmes CL, Walley KR. Bad medicine: low-dose dopamine in the ICU. Chest 2003;123(4):1266-75.
22. Jones D, Bellomo R. Renal-dose dopamine: from hypothesis to paradigm to dogma to myth and, finally, superstition? J Intensive Care Med 2005;20(4):199-211.
23. Tzimas KN, Papadakos PJ. An updated review of sepsis for the anesthesiologist. Semin Cardiothorac Vasc Anesth 2013;17(4):262-8.
24. Givertz MM, Fang JC. Approach to the Patient with Hypotension and Hemodynamic Instability. In: Irwin RS, Rippe JM, editors. Irwin and Rippe’s Intensive Care Medicine, 7th ed. USA: Lippincott Williams and Wilkins 2011.
25. Oba Y, Lone NA. Mortality benefit of vasopressor and inotropic agents in septic shock: a Bayesian network meta-analysis of rand-omized controlled trials. J Crit Care 2014;29(5):706-10.
26. 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. Crit Care Med 2017;45.
27. Layek A, Maitra S, Pal S, Bhattacharjee S, Baidya DK. Efficacy of vasopressin during cardio-pulmonary resuscitation in adult patients: a meta-analysis. Resuscitation 2014;85(7):855-63.
28. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, et al. Part 7: Adult Advanced Cardiovascular Life Sup-port: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132(18 Suppl 2):S444-64.
29. Pathak A, Lebrin M, Vaccaro A, Senard JM, Despas F. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther 2013;38(5):341-9.
30. Nagy L, Pollesello P, Papp Z. Inotropes and inodilators for acute heart failure: sarcomere active drugs in focus. J Cardiovasc Pharma-col 2014;64(3):199-208.
31. Bove T, Matteazzi A, Belletti A, Paternoster G, Saleh O, Taddeo D, et al. Beneficial impact of levosimendan in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials. Heart Lung Vessel 2015;7(1):35-46.
32. Farmakis D, Alvarez J, Gal TB, Brito D, Fedele F, Fonseca C, et al. Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper. Int J Cardiol 2016;222:303-12.
33. Zangrillo A, Putzu A, Monaco F, Oriani A, Frau G, De Luca M, et al. Levosimendan reduces mortality in patients with severe sepsis and septic shock: A meta-analysis of randomized trials. J Crit Care 2015;30(5):908-13.
34. Gordon AC, Perkins GD, Singer M, McAuley DF, Orme RM, Santhakumaran S, et al. Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis. N Engl J Med 2016;375(17):1638-48.
35. Garg V, Frishman WH. A new approach to inotropic therapy in the treatment of heart failure: cardiac myosin activators in treatment of HF. Cardiol Rev 2013;21(3):155-9.
36. Shen YT, Malik FI, Zhao X, Depre C, Dhar SK, Abarzua P, et al. Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail 2010;3(4):522-7.
37. Cleland JGF MF. The Selective Cardiac Myosin activator, CK-182752, Increases Systolic Function in Heart Failure. J Card Fail 2008;14.
38. Teerlink JR, Felker GM, McMurray JJ, Ponikowski P, Metra M, Filippatos GS, et al. Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study. J Am Coll Cardiol 2016;67(12):1444-455.
39. Sivakumaran V, Stanley BA, Tocchetti CG, Ballin JD, Caceres V, Zhou L, et al. HNO enhances SERCA2a activity and cardiomyocyte function by promoting redox-dependent phospholamban oligomerization. Antioxid Redox Signal 2013;19(11):1185-197.
40. Marks AR. Calcium cycling proteins and heart failure: mechanisms and therapeutics. J Clin Invest 2013;123(1):46-52.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.
IndexCopernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.
Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.
Scopus: CiteScore 0.5(2019) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.