Approach to vasopressor medications in shock states

Approach to vasopressor medications in shock states

Dr Khaled Mohamed Aly

By Dr Khaled Mohamed Aly

Dr Khaled Mohamed Aly is a medical specialist MBBCH; M.S.C Cairo University; ACLS -EP; ATLS-SL (South Africa) Critical care course program-USA Disastrous medicine; STEMI-certificate AHA Hospital management and infection control diplomas Cairo University. Author of Critical Care Professional Handbook. Dr Khalad is Head of CME in Egypt for MEMP Ltd.

Vasopressors are medications that causes vasoconstriction; some of them have additional inotropic effect. By maintaining end-organ perfusion; the role of vasopressors remains critical to prevent irreversible organ injury and failure, and their use is usually accompanied by fluid resuscitation for adequate patient outcomes. Vasopressor agents are used clinically in the treatment of arterial hypotension in shock states. Shock is best defined as inadequate blood flow to meet the metabolic needs of the tissues. The most common reasons for shock are the cardiac output is low relative to the global demand, despite increased O2 extraction by the tissues; or perfusion pressure is inadequate such that blood flow distribution to metabolically active tissues is inadequate, despite an otherwise adequate cardiac output.

Shock states First-line agents Second-line-agents
Anaphylactic shock: is a serious life-threatening allergic reactions. Epinephrine; 1 ml of 1:10000 sol. (100 mg); can be given as slow IV push; then as 0.02 mg/kg/mininfusion (5-15 mg/min). Norepinephrine infusion 0.1-1 mg/kg/min (0.5-30 mg/min)
Cardiogenic shock-lt. ventricular: occurs if the heart suddenly can’t pump enough oxygen-rich blood to the body. The most common cause of cardiogenic shock is damage to the heart muscle from a severe heart attack. This damage prevents the heart’s main pumping chamber, the left Ventricle. SBP 70: norepinephrine infusion at 0.1-1 mg/kg/min (0.5-30 MG/MIN)- SBP 70-90:Dopamine infusion 15 mg/kg/min. if SBP 90: Dopamine infusion 2-20 mg/kg/min Amiodarone 0.75 mg/kg loading dose; then 5-10 mg/kg/min (not recommended post MI) – Milrinone 50 mg/kg loading dose; then 5-10 mg/kg/min (not recommended post MI)
Cardiogenic shock-pulmonary embolism: massive pulmonary embolism may produce cardiogenic shock by impeding blood flow in the pulmonary vessels, leading to volume overload of the right ventricle and a drastic reduction in left ventricular filling volume. In addition, the large pulmonary embolism produces a ventilation disorder by causing a perfusion/ventilation mismatch, which leads to hypoxemia. Arterial hypoxemia coupled with reduced coronary blood flow and subsequent systemic acidosis will have a deleterious effect on cardiac pump function. Dobutamine infusion at 5 mg/kg/min – norepinephrine infusion at 0.1-1 mg/kg/min Phenylephrine infusion at 10-20 mg/kg/min
Hemorrhagic shock: a form of hypovolemic shock in which severe blood loss (20% or more of blood or body fluids) leads to inadequate oxygen delivery at the cellular level. If hemorrhage continues unchecked, death quickly follows. Volume resuscitation Dopamine infusion at 5-15 mg/kg/min


Main uses of vasopressors

Inotropic and vasopressor agents are a mainstay of resuscitation therapy during cardiopulmonary arrest.1 Profound hypotension (Mean Arterial Pressure-MAP < 50 mm Hg) is associated with a pressure-dependent decrease in coronary and cerebral blood flow and can rapidly induce myocardial depression and cerebral ischemia. In patients in whom rapid fluid infusion and norepinephrine/dopamine therapies have failed to restore organ perfusion pressure and in whom emergent increases in MAP are required, epinephrine is the catecholamine of last resort.

Pulmonary hypertensionEpinephrine is a both a potent inotropic agent and vasopressor. Epinephrine produces venoconstriction that will increase the effective circulating blood volume, thereby increasing venous return. Although some increased peripheral edema formation will occur, anasarca is not a life- threatening condition, unlike hypotension. Additional disadvantages of epinephrine are its associated pulmonary hypertension and metabolic effects. Epinephrine induces hypermetabolism and glycolysis, resulting in lactic acidosis and hyperglycemia. Although these effects generally resolve quickly when epinephrine is discontinued, they can result in important clinical problems and make management more difficult. Other therapeutic options for patients who are unresponsive to catecholamines include vasopressin infusion; Vasopressin induces vasoconstriction by stimulating vasopressin receptors and by potentiating the actions of catecholamines.2

Main common vasopressors

Dopamine is the standard go-to anti-hypotensive for most prehospital systems. It’s a drug that has both inotropic and vasoconstrictive properties. These properties vary by dosing. Dosage starts at 5–10 mcg/kg/min, and at this dose dopamine primarily stimulates β1 receptors and increases cardiac output by increasing stroke volume. At > 10 mcg/kg/min—with 20 mcg/kg/min being the maximum dose—there’s modest α1 effects that cause an increase in systemic vasoconstriction, in turn causing an increase in afterload. Dopamine is generally one of the first-line drugs in patients with acute heart failure with mild hypotensive complication. However, caution should be exercised when using dopamine in the heart failure population at higher doses. An increase in afterload can further weaken the heart and lead to worsened heart failure and cardiovascular collapse. One of the main drawbacks from dopamine is its proclivity to cause exaggerated chronotropy and tachyarrhythmias. Dopamine should be used cautiously in patients with significant preexisting heart disease or current tachycardia. There’s currently little evidence to support dopamine as a first-line agent in shock states.2;3

Dobutamine Dobutamine is a synthetic adrenergic with purely β1 agonistic, inotropic effects. There’s also modest chronotropy observed. Different from dopamine, due to increasing stroke volume without any α1 effects, dobutamine causes a reflex peripheral vasodilation. This leads to increased cardiac output with decreased strain on heart muscle. Dobutamine use is generally reserved for advanced heart failure and low cardiac output states after hypotension is corrected, and is contraindicated for distributive shock states. Dobutamine is generally dosed at 2–20 mcg/kg/min. There’s some evidence to support dopamine/dobutamine dual-therapy in patients with severe acute heart failure. This increases cardiac output with minimal increased strain on the is used in stress echo.2;3

Norepinephrine (Levophed) acts on both α1 and β1 receptors, producing both potent vasoconstriction and a moderate increase in cardiac output. The primary vasoactive effect of norepinephrine is arterial and venous vasoconstriction. However, there are no inotropic effects with norepinephrine. Dosages for norepinephrine generally range from 5–30 mcg/min. There is measurable decrease in mortality when administered as first-line in both these conditions. Additionally, while the standard treatment for hypovolemic shock from hemorrhage is fluid and blood product administration, norepinephrine is generally the first-line choice until euvolemia can be achieved. Providers should be prepared to see a reflex bradycardia due to an increase in vasoconstriction and blood pressure cancelling the heart’s compensatory chronotropy in response to the shock-state. However, this decrease in heart rate is mitigated by the other effects of the drug and does not decrease overall perfusion.

Phenylephrine (Neo-Synephrine) has purely α1 agonistic qualities and is an extremely effective vasoconstrictor. This vasopressor is reserved primarily for patients suffering from distributive shock of a neurogenic origin such as spinal cord injury or other CNS illness/injury. However, phenylephrine can be used as a second-line agent in other hypoperfusion states that are refractory to norepinephrine or where norepinephrine in contraindicated due to a patient’s predisposition to arrhythmia. A possible reflex decrease in heart rate can also be seen with phenylephrine administration. Dosages of phenylephrine are titrated between 25–200 mcg/min.

Epinephrine affects both α1 and β1 receptors; however, it has very potent effects on the β1 receptors, in particular. At lower doses, epinephrine increases cardiac output via an increase in inotropy and chronotropy. At this lower dose, there can be a mild reflex vasodilation to the increase of cardiac output. This vasodilatory action along with the substantial increase in cardiac output is very beneficial in cardiogenic shock states. However, at higher doses, α1 effects predominate with profound vasoconstriction. Epinephrine is the strongest vasoconstrictor of all the vasopressors when all things are equal, thus making it first-line for anaphylaxis shock and generally second-line for septic and cardiogenic shocks. Epinephrine is typically dosed at 1–10 mcg/min with higher doses titrated as needed to maintain end-organ perfusion. It’s crucial to understand why epinephrine is the first-line agent for anaphylactic shock. Most importantly, with epinephrine being the strongest vasoconstrictor, it’s the best choice for reversing the catastrophic vasodilation that occurs in anaphylactic shock. Additionally, epinephrine is the best drug to prevent or stop the mast cells (white blood cells responsible for hypersensitivity reactions) from propagating the anaphylaxis. And lastly, epinephrine is the only drug that prevents or reverses upper and lower airway obstruction secondary to bronchoconstriction and angioedema.4

VasopressinVasopressin is a naturally occurring chemical in the body that’s also known as antidiuretic hormone. Its uses vary widely due to the unique properties and effects it has within the body. It can be used to stop free-water loss in diabetes insipidus and to stop gastrointestinal bleeding. In addition to these uses, it can also play a role in the shock setting. Vasopressin is a potent vasoconstrictor with no direct β1 effects. The increase in blood pressure that’s seen with vasopressin is due to its vasoconstricting action. While its efficacy as a vasopressor has yet to be completely established, vasopressin’s ability to cause peripheral vasoconstriction has led to its adoption as a second- and third-line drug in several shock pathologies, mainly those of distributive etiology. Particularly in anaphylactic shock refractory to epinephrine alone, vasopressin is the second-line choice. Also, when used as a second- or third-line agent in distributive shocks, vasopressin is able to reduce the amount of the previous agents used while maintaining the goal blood pressure. Vasopressin is traditionally dosed at 0.01–0.04 units/min.

Milrinone is a non-adrenergic inotrope used by patients at home with severe heart failure, in addition to its traditional in-hospital uses. Milrinone belongs to the class of drugs known as phosphodiesterase inhibitors. Its effects are similar to that of dobutamine with the exception of there being decreased risk for cardiac arrhythmia. Milrinone increases cardiac output via increased inotropy with very little chronotropic effect. Milrinone also decreases both preload and afterload via direct vasodilatory properties, which is different from many of the other medications reflex effects.

Additionally, there’s less of an increase in myocardial oxygen demand than that of its adrenergic counterparts. Milrinone is administered as an initial 50 mcg/kg bolus followed by a 0.375–0.75 mcg/kg/min maintenance infusion. Milrinone is administered for in-hospital and out-of-hospital patients waiting for heart transplants and advanced therapies like ventricular assist devices, or for those who aren’t candidates for more advanced therapies for which milrinone is the destination therapy. Although the current indication for milrinone is for advanced heart failure, there’s a pool of evidence beginning to support its use in the acute shock setting, especially in pediatrics and neonatology. When used in shock, an adrenergic vasopressor is typically also needed. However, the practice of using milrinone in most shock settings isn’t standard care and more research is needed.4, 5


Shock requires timely fluid resuscitation and vasopressor therapy that constitutes the cornerstone of therapy. Prompt recognition of reversible factors of refractory shock, such as metabolic and electrolyte derangements, source control for septic shock and lung-protective mechanical ventilation for respiratory failure are important therapeutic adjuncts; norepinephrine is indicated in septic shock.

In cardiogenic shock complicating AMI, current guidelines based on expert opinion recommend dopamine or dobutamine as first-line agents with moderate hypotension (systolic blood pressure 70 to 100 mm Hg) and norepinephrine as the preferred therapy for severe hypotension (systolic blood pressure <70 mm Hg).

Norepinephrine is considered the first-line vasopressor in vasodilatory shock, dobutamine the first- line inotrope in shock associated with decreased cardiac output, and their combination in vasodilatory shock with decreased cardiac output. Epinephrine is the first-line catecholamine in anaphylactic shock; in cardiopulmonary resuscitation and also as second line in shock that is unresponsive to other catecholamines. Vasopressin is emerging as a therapy in resistant vasodilatory shock.

View references

1. Jentzer JC, Coons JC, Link CB, Schmidhofer M. Pharmacotherapy update on the use of vasopressors and inotropes in the intensive care unit. Journal of cardiovascular pharmacology and therapeutics. 20(3):249-60. 2015.

2. Senz A, Nunnink L. Review article: inotrope and vasopressor use in the emergency department. Emerg Med Australas. 2009 Oct;21(5):342-51.

3. Bangash MN, Kong ML, Pearse RM. Use of inotropes and vasopressor agents in critically ill patients. Br J Pharmacol. 2012 Apr;165(7):2015-33.

4. Tisdale JE, Patel RV, Webb CR, Borzak S, Zarowitz BJ. Proarrhythmic effects of intravenous vasopressors. Ann Pharmacother. 1995 Mar. 29(3):269-81.

5. Hollenberg SM. Vasoactive drugs in circulatory shock. American journal of respiratory and critical care medicine. 183(7):847-55. 2011.

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