Vasopressors induce vasoconstriction and raise the mean arterial pressure (MAP). Inotropes increase myocardial contractility. There are several synthetic and endogenous agents with inotropic and vasopressor effects, and they often need to be combined in order to optimise or correct the haemodynamics. Most agents exert both vasopressor and inotropic effects (Figure 1). What follows is a quick reference for their use in the emergency department, the intensive care or coronary care unit, and the operating theatre. Careful electrocardiographic and haemodynamic monitoring with ECG, a central venous catheter and an arterial line is necessary to achieve an optimal result.
Overview of vasopressors and inotropes
Figure 1. The approximate position of each drug according to its vasoconstrictor effect (vertical axis) and its positive inotropic effect (horizontal axis). Grey = pure vasopressors, orange = phosphodiesterase inhibitors, blue/turquoise = calcium sensitisers and a beta agonist without vascular effect.
Catecholamine receptors
- Alpha-1 adrenergic receptors: expressed in vascular smooth muscle. Activation results in vasoconstriction and an increase in systemic vascular resistance (SVR).
- Beta-1 adrenergic receptors: expressed in the myocardium. Activation results in increased contractility and increased chronotropy (heart rate).
- Beta-2 adrenergic receptors: expressed in vascular smooth muscle. Activation results in vasodilatation.
- D1 and D2 (dopamine receptors): activation of D1 and D2 in the kidneys and the splanchnic vascular bed leads to renal and mesenteric vasodilatation.
Dobutamine is a synthetic catecholamine.
Indications, dosing and effects
Note that abrupt changes in blood pressure activate autonomic reflexes that influence the haemodynamic result. Reflex tachycardia is the rule after a rapid fall in blood pressure.
| Drug | Indications | Dosing | α1 | β1 | β2 | D1/D2 | Effect | Adverse effects |
|---|---|---|---|---|---|---|---|---|
| Dopamine — low dose | Rarely used | 0.5–3.0 μg/kg/min | + | + | + | +++++ | Low-dose dopamine stimulates D1 receptors and induces vasodilatation in the coronary, renal, cerebral and mesenteric vessels. | Few |
| Dopamine — intermediate dose | Cardiogenic shock. Vasodilatory shock. Heart failure, acute or chronic. Bradycardia (second-line option). | 3.0–10.0 μg/kg/min | + | ++++ | + | +++++ | Intermediate-dose dopamine activates β1, releases noradrenaline and thereby increases contractility and chronotropy, with a slight rise in SVR. | Ventricular arrhythmias. Myocardial ischaemia. Tissue ischaemia (high doses or extravasation). |
| Dopamine — high dose | Cardiogenic shock. Vasodilatory shock. Heart failure, acute or chronic. Bradycardia (second-line option). | 10.0–20.0 μg/kg/min | ++++ | ++++ | ++ | +++++ | High-dose dopamine additionally induces α1 stimulation and thereby vasoconstriction with a marked rise in SVR. | As for the intermediate dose, together with marked hypertension (caution during non-selective beta blockade). |
| Dobutamine | Cardiogenic shock. Bradycardia (second-line treatment). Stress testing (it increases myocardial oxygen consumption). | Usual: 2.0–20 μg/kg/min. Maximum: 40 μg/kg/min | + | +++++ | +++ | 0 | A potent inotrope with a mild chronotropic effect. Doses < 5 μg/kg/min produce slight vasodilatation. Doses > 5 μg/kg/min produce vasoconstriction, which predominates at doses > 15 μg/kg/min. | Tachycardia. An increased ventricular rate in atrial fibrillation. Ventricular arrhythmias. Myocardial ischaemia. Hypertension (in patients on non-selective beta blockade). Tolerance after a few days. |
| Noradrenaline (norepinephrine) | Shock (all types). Hypotension (all types). | 0.01–3.0 μg/kg/min. Safe peripherally. | +++++ | +++ | ++ | 0 | A potent vasoconstrictor with a mild inotropic effect. It raises the systolic pressure, the diastolic pressure and the pulse pressure with minimal effect on cardiac output. Minimal chronotropic effect. It increases coronary blood flow. | Atrial or ventricular arrhythmias. Bradycardia. Peripheral (digital) ischaemia. Hypertension (particularly during non-selective beta blockade). Prolonged use may be cardiotoxic. |
| Adrenaline (epinephrine) | Shock (all types). Cardiac arrest. Bronchospasm. Anaphylaxis. Bradycardia (second-line option). | Infusion: 0.01–0.10 μg/kg/min. Bolus: 1 mg IV every 3–5 min (maximum 0.2 mg/kg). IM (1:1000): 0.1–0.5 mg (maximum 1 mg). Safe peripherally. | +++++ | ++++ | +++ | Not applicable | The beta effect is more marked at low doses, the alpha effect more marked at higher doses. Increased coronary flow. Pulmonary vasoconstriction. Increased pulmonary blood flow. | Ventricular arrhythmias. Severe hypertension with a risk of cerebrovascular haemorrhage. Myocardial ischaemia. Sudden cardiac death. Prolonged use may be cardiotoxic. |
| Isoprenaline (isoproterenol) | Bradycardia (first-line treatment). Bradycardia-induced torsades de pointes. Brugada syndrome. | 2.0–10.0 μg/min. Safe peripherally. | 0 | +++++ | +++++ | 0 | A powerful chronotropic and inotropic effect. Potent systemic vasodilatation. Slight pulmonary vasodilatation. Increases cardiac output through both heart rate and contractility. | Ventricular arrhythmias. Myocardial ischaemia. Hypertension. Hypotension. |
| Phenylephrine | Typically used as an emergency bolus to correct acute hypotension. Hypotension (all types). It raises the MAP in hypotension in patients with aortic stenosis. It reduces the LVOT gradient in hypertrophic cardiomyopathy. It corrects hypotension caused by concurrent intake of sildenafil and nitrates. | Bolus: 0.1–0.5 mg IV every 10–15 min. Infusion: 0.4–9.1 μg/kg/min. Safe peripherally. | +++++ | 0 | 0 | Not applicable | An immediate and marked rise in MAP. | Reflex bradycardia. Hypertension (particularly during non-selective beta blockade). Severe peripheral and visceral vasoconstriction. Tissue necrosis on extravasation. |
| Milrinone | Acute heart failure. Decompensated chronic heart failure. | Bolus: 50 μg/kg over 10–30 min. Infusion: 0.375–0.75 μg/kg/min. | 0 | 0 | 0 | 0 | A phosphodiesterase inhibitor. A potent inotrope. It induces vasodilatation and reduces preload, afterload and SVR. | Ventricular arrhythmias. Hypotension. Myocardial ischaemia. Torsades de pointes. It accumulates in renal failure (dose adjustment necessary). |
| Amrinone | Acute heart failure. Decompensated chronic heart failure. | Bolus: 0.75 mg/kg over 2–3 min. Infusion: 5–10 μg/kg/min. | 0 | 0 | 0 | 0 | A phosphodiesterase inhibitor. Rarely used because of its adverse effects. | Arrhythmias, enhanced AV conduction. Hypotension. Thrombocytopenia. Hepatotoxicity. |
| Vasopressin | Shock (all types); in practice as an adjunct to noradrenaline in septic shock. | Infusion: 0.01–0.04 units/min as a fixed dose, usually 0.03 units/min. It is not titrated as the principal vasopressor; above 0.04 units/min the risk of digital and splanchnic ischaemia increases with no further benefit. A 40-unit bolus in cardiac arrest is not part of the current European resuscitation guidelines, in which adrenaline is the first choice. | 0 | 0 | 0 | 0 | Vasopressin stimulates V1 receptors (vascular smooth muscle) and V2 receptors (kidney). V1 stimulation produces vasoconstriction; V2 increases renal water reabsorption. Vasopressin raises SVR without a significant effect on cardiac output, and it potentiates the vascular effect of noradrenaline. | Arrhythmias. Hypertension. A reduced cardiac output (at doses > 0.04 units/min). Myocardial ischaemia. Severe peripheral vasoconstriction with a risk of ischaemia (particularly of the skin). Splanchnic vasoconstriction. |
| Levosimendan (Simdax) | Decompensated chronic heart failure. | Loading dose: 6–12 μg/kg over 10 min (omitted in hypotension). Infusion: 0.1 μg/kg/min, adjustable between 0.05 and 0.2 μg/kg/min for 24 h. | 0 | 0 | 0 | 0 | Levosimendan is a calcium sensitiser that enhances ventricular contractility and induces peripheral arteriolar and venous vasodilatation. | Enhanced AV conduction. Hypotension. |
References
- Overgaard CB, Dzavik V. Inotropes and Vasopressors: Review of Physiology and Clinical Use in Cardiovascular Disease. Circulation 2011.
- Jentzer JC, et al. Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit. J Cardiovasc Pharmacol Therap 2014.
- Müllner M, Urbanek B, Havel C, et al. Vasopressors for shock. Cochrane Database Syst Rev 2004.
- Ballieu P, Besharatian Y, Ansari S. Safety and Feasibility of Phenylephrine Administration Through a Peripheral Intravenous Catheter in a Neurocritical Care Unit. J Intensive Care Med 2021;36:101.
- Lherm T, Troché G, Rossignol M, et al. Renal effects of low-dose dopamine in patients with sepsis syndrome or septic shock treated with catecholamines. Intensive Care Med 1996;22:213.
- Unverferth DA, Blanford M, Kates RE, Leier CV. Tolerance to dobutamine after a 72 hour continuous infusion. Am J Med 1980;69:262.
- Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 1995;333:1025.
- Gregory JS, Bonfiglio MF, Dasta JF, et al. Experience with phenylephrine as a component of the pharmacologic support of septic shock. Crit Care Med 1991;19:1395.
- De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Crit Care Med 2003;31:1659.
- MacGregor DA, Smith TE, Prielipp RC, et al. Pharmacokinetics of dopamine in healthy male subjects. Anesthesiology 2000;92:338.
- Löllgen H, Drexler H. Use of inotropes in the critical care setting. Crit Care Med 1990;18:S56.
- Steel A, Bihari D. Choice of catecholamine: does it matter? Curr Opin Crit Care 2000;6:347.
- Hannemann L, Reinhart K, Grenzer O, et al. Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock. Crit Care Med 1995;23:1962.
- Al-Hesayen A, Azevedo ER, Newton GE, Parker JD. The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure. J Am Coll Cardiol 2002;39:1269.
- De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779.
- Mutlu GM, Factor P. Role of vasopressin in the management of septic shock. Intensive Care Med 2004;30:1276.
- Sharshar T, Blanchard A, Paillard M, et al. Circulating vasopressin levels in septic shock. Crit Care Med 2003;31:1752.
- Tsuneyoshi I, Yamada H, Kakihana Y, et al. Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Crit Care Med 2001;29:487.
- Dünser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 2003;107:2313.
- Kill C, Wranze E, Wulf H. Successful treatment of severe anaphylactic shock with vasopressin. Two case reports. Int Arch Allergy Immunol 2004;134:260.
- Schummer C, Wirsing M, Schummer W. The pivotal role of vasopressin in refractory anaphylactic shock. Anesth Analg 2008;107:620.
- McIntyre WF, Um KJ, Alhazzani W, et al. Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-Analysis.
- Albanèse J, Leone M, Delmas A, Martin C. Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. Crit Care Med 2005;33:1897.
- Kam PC, Williams S, Yoong FF. Vasopressin and terlipressin: pharmacology and its clinical relevance. Anaesthesia 2004;59:993.
- O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet 2002;359:1209.
- Leone M, Albanèse J, Delmas A, et al. Terlipressin in catecholamine-resistant septic shock patients. Shock 2004;22:314.
- Rodríguez-Núñez A, Fernández-Sanmartín M, Martinón-Torres F, et al. Terlipressin for catecholamine-resistant septic shock in children. Intensive Care Med 2004;30:477.
- Morelli A, Rocco M, Conti G, et al. Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock. Intensive Care Med 2004;30:597.
- Polito A, Parisini E, Ricci Z, et al. Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis. Intensive Care Med 2012;38:9.
- Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA 2016;316:509.
- Malay MB, Ashton JL, Dahl K, et al. Heterogeneity of the vasoconstrictor effect of vasopressin in septic shock. Crit Care Med 2004;32:1327.
- Kahn JM, Kress JP, Hall JB. Skin necrosis after extravasation of low-dose vasopressin administered for septic shock. Crit Care Med 2002;30:1899.
- Leather HA, Segers P, Berends N, et al. Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension. Crit Care Med 2002;30:2548.
- Dünser MW, Mayr AJ, Tür A, et al. Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med.
- Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008;358:877.
- Jeon K, Song JU, Chung CR, et al. Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS). Crit Care.
- Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021;49:e1063.
- Landoni G, Lomivorotov VV, Alvaro G, et al. Levosimendan for Hemodynamic Support after Cardiac Surgery. N Engl J Med 2017.
- Mehta RH, Leimberger JD, van Diepen S, et al. Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery. N Engl J Med 2017.
- Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017;377:419.
