A global perspective on vasoactive agents in shock
- 2.6k Downloads
We set out to summarize the current knowledge on vasoactive drugs and their use in the management of shock to inform physicians’ practices.
This is a narrative review by a multidisciplinary, multinational—from six continents—panel of experts including physicians, a pharmacist, trialists, and scientists.
Results and conclusions
Vasoactive drugs are an essential part of shock management. Catecholamines are the most commonly used vasoactive agents in the intensive care unit, and among them norepinephrine is the first-line therapy in most clinical conditions. Inotropes are indicated when myocardial function is depressed and dobutamine remains the first-line therapy. Vasoactive drugs have a narrow therapeutic spectrum and expose the patients to potentially lethal complications. Thus, these agents require precise therapeutic targets, close monitoring with titration to the minimal efficacious dose and should be weaned as promptly as possible. Moreover, the use of vasoactive drugs in shock requires an individualized approach. Vasopressin and possibly angiotensin II may be useful owing to their norepinephrine-sparing effects.
KeywordsShock Cardiovascular system Adrenergic agonists Clinical trials Practice guidelines
ACG is funded by an NIHR Research Professorship award (RP-2015-06-018).
Compliance with ethical standards
Conflicts of interest
DA reports having received a grant from the French Ministry of Health to conduct a trial comparing epinephrine to norepinephrine plus dobutamine for septic shock (CATS). DDB reports that he acts as a consultant to and material for studies by Edwards Lifesciences. ACG reports that outside of this work he has received speaker fees from Orion Corporation Orion Pharma and Amomed Pharma. He has consulted for Ferring Pharmaceuticals, Tenax Therapeutics, Baxter Healthcare, Bristol-Myers Squibb and GSK, and received grant support from Orion Corporation Orion Pharma, Tenax Therapeutics and HCA International with funds paid to his institution. GH reports no financial conflict of interest. JR reports patents owned by the University of British Columbia (UBC) that are related to PCSK9 inhibitor(s) and sepsis and related to the use of vasopressin in septic shock. JR is an inventor on these patents. JR is a founder, Director and shareholder in Cyon Therapeutics Inc. (developing a sepsis therapy (PCSK9 inhibitor)). JR has share options in Leading Biosciences Inc. JR is a shareholder in Molecular You Corp. JR reports receiving consulting fees in the last 3 years from: (1) Asahi Kesai Pharmaceuticals of America (AKPA)(developing recombinant thrombomodulin in sepsis). (2) La Jolla Pharmaceuticals (developing angiotensin II; JR chaired the DSMB of a trial of angiotensin II from 2015 to 2017)—no longer actively consulting. (3) Ferring Pharmaceuticals (manufactures vasopressin and was developing selepressin)—no longer actively consulting. (4) Cubist Pharmaceuticals (now owned by Merck; formerly Trius Pharmaceuticals; developing antibiotics)—no longer 3 actively consulting. (5) Leading Biosciences (was developing a sepsis therapeutic that is no longer in development)—no longer actively consulting. (6) Grifols (sells albumin)—no longer actively consulting. (7) CytoVale Inc. (developing a sepsis diagnostic)—no longer actively consulting. JR reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that is provided to and administered by UBC.
- 1.Goodman and Gilman’s (2011) Pharmacological Basis of Therapeutics Twelfth (ed). New YorkGoogle Scholar
- 38.Wasilewski MA, Grisanti LA, Song J et al (2016) Vasopressin type 1A receptor deletion enhances cardiac contractility, β-adrenergic receptor sensitivity and acute cardiac injury-induced dysfunction. Clin Sci 130(22):2017–2027. https://doi.org/10.1042/CS20160363 CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Schumann J, Henrich EC, Strobl H et al. (2018) Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database of Systematic Reviews. Issue 1, Art. No.: CD009669Google Scholar
- 47.Cheng Y, Pan T, Ge M, et al. (2018) Evaluation of vasopressin for vasoplegic shock in patients with preoperative left ventricular dysfunction after cardiac surgery: a propensity-score analysis. Shock. Feb 7. 10.1097/shk.0000000000001114Google Scholar
- 101.Ponikowski P, Voors AA, Anker SD et al (2016) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC) Developed with the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J 37(27):2129–2200PubMedCrossRefGoogle Scholar
- 102.Excellence NIfHaC (2016) Sepsis : recognition, assessment and early management. In: sepsis: recognition, Assessment and early management. London.Google Scholar
- 109.Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA, Emergency Medicine Shock Research Network (EMShockNet) Investigators (2010) Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 303(8):739–746PubMedPubMedCentralCrossRefGoogle Scholar
- 114.Hammond DA, McCain K, Painter JT et al (2017) Discontinuation of vasopressin before norepinephrine in the recovery phase of septic shock. J Intensive Care Med 2017:885066617714209Google Scholar
- 115.Bissell BD, Magee C, Moran P, Bastin MLT, Flannery AH (2017) Hemodynamic instability secondary to vasopressin withdrawal in septic shock. J Intensive Care Med 2017:885066617716396Google Scholar