Vassopressors and Inotropes

Basics of Hypotension, physiology and pharmacology of Vassopressores and Inotropes role.

1. Vasopressors & Inotropes Runal Shah MEM PGY-2

2. Objectives Physiology of vascular receptors Principles of use of vasoactive agents Individual drugs Complications

3. Adrenergic Receptor Physiology Alpha-1 Beta-1 Beta-2 Dopamine

4. α -1 Adrenergic receptors Located in arteriolar walls Induces significant vasoconstriction Present in heart Slight positive Inotropic effect (increased intracellular Calcium ).

5. β - Adrenergic receptors β -1 adrenergic receptors are most common in the heart positive inotropy and chronotropy with minimal vasoconstriction. β -2 adrenergic receptors in blood vessels induce vasodilatation; bronchodilation.

6. Dopamine receptors Present in the renal, splanchnic, coronary, and cerebral vascular beds. Stimulation of these receptors leads to vasodilatation. Second subtype of dopamine receptors causes vasoconstriction by inducing nor-epinephrine release.

7. Principles Of Use Of Vasopressors and Inotropes Hypotension may result from: Hypovolemia Pump failure Pathologic misdistribution of blood flow Vasopressors are indicated for: Decrease of >30 mmHg/20% from baseline SBP or MAP <60 mmHg Evidence of end-organ dysfunction due to hypoperfusion Hypovolemia must be corrected first

8. Use of vasopressors and inotropes is guided by three fundamental concepts: One drug, many receptors Dose-response curve Direct versus reflex actions Principles Of Use Of Vasopressors and Inotropes

9. Volume resuscitation Repletion of adequate intravascular volume, when time permits, is crucial prior to the initiation of vasopressors. Vasopressors will be ineffective or only partially effective in the setting of coexisting hypovolemia. Fluids may be withheld in patients with significant pulmonary edema due to ARDS or CHF.

10. Tachyphylaxis Responsiveness to these drugs can decrease over time due to tachyphylaxis. Doses must be constantly titrated to adjust for this phenomenon and for changes in the patients clinical condition.

11. Nor-epinephrine Acts on both α -1 and β -1 receptors Potent vasoconstriction as well as a less pronounced increase in cardiac output Paradoxical decrease in HR can occur as a reflex increase in Parasympathetic tone. Drug of choice to treat septic shock

12. Nor-epinephrine Norepinephrine is traditionally used as the last measure for cases of hypotension that are refractory to volume infusion and other hemodynamic drugs (e.g., dobutamine, dopamine). Norepinephrine is the vasopressor of choice in septic shock and should be added when hypotension is not corrected by appropriate volume infusion.

13. Epinephrine Potent β -1 receptor activity and β -2 and α - 1 receptor effects. Result is an increased CO, with decreased SVR and variable effects on the MAP. β -1 receptor stimulation may provoke dysrhythmias. Greater degree of splanchnic vasoconstriction. Most often used in ACLS, treatment of anaphylaxis, as a second line agent in septic shock and for management of hypotension.

14. Dopamine At low doses (0.5-5 mcg/kg/min) dopamine acts predominately on dopamine-1 receptors in the renal, mesenteric, cerebral, and coronary beds, resulting in selective vasodilatation. At moderate doses (5-10 mcg/kg/min) dopamine also stimulates β - 1 receptors and increases CO, predominately by increasing SV with variable effects on HR. Can result in dose-limiting dysrhythmias At higher doses (>10 mcg/kg/min) dopamine stimulates α receptors and produces vasoconstriction with an increased SVR.

15. Dopamine Dopamine is indicated for reversing hemodynamically significant H ypotension caused by myocardial infarction Trauma heart failure renal failure when fluid resuscitation is unsuccessful or not appropriate.

16. Dobutamine Dobutamine is a synthetic catecholamine that is used as a positive inotropic agent, to increase cardiac stroke output in patients with severe, decompensated heart failure. Predominant β -1 receptor effect increases inotropy and chronotropy and reduces LV filling pressures. Minimal α and β -2 receptor effects result in overall vasodilatation, complemented by reflex vasodilatation to the increased CO. Net effect is increased CO, with decreased SVR with or without a small reduction in BP, HR.

17. Dobutamine Indicated in short-term positive inotropic support for the treatment of cardiovascular decompensation secondary to ventricular dysfunction or low-output heart failure. It is the preferred agent in septic shock with depressed cardiac output despite adequate left ventricular filling pressures. Dobutamine is also usually the preferred agent in the management of cardiogenic shock.

18. Vasopressin Acts like ADH; directly stimulates smooth muscle V1 receptors, resulting in vasoconstriction Often used in the setting of DI or esophageal variceal bleeding. May be useful in the treatment of refractory septic shock, particularly as a second pressor agent.

19. Vasopressin For the treatment of refractory hypotension, vasopressin is infused at a rate of 0.01 to 0.04 unit per minute

20. Inamrinone and Milrinone MoA : Phosphodiesterase inhibitor , increase intracellular c-AMP, Calcium – Increased FoC, Myocardiac contractility, Positive Inotropic and Vasodilator property ( Inodilator ) Indication : for short term use of Decompensated Heart Failure S/E : Supraventricular arrhythmias, Hypotension, Headache, Rare : Thrombocytopenia

21. Inamrinone and Milrinone Inamrinone Milrinone Onset 2-5 min 5-15min Action duration 0.5-2 hours 2.5 hours Dose Bolus : 0.75 mcg/kg IV x 2-3 min Maintenance : 5-10mcg/kg/min IV Infusion Bolus : 50 mcg/kg IV x 10 min Maintenance : 0.5-0.75mcg/kg/min IV Infusion

22. Phenylephrine MoA : α effects predominate, minimal β effects, vasoconstriction of vascular beds resulting in increase of SBP, DBP. Dose : 100-200 mcg/min IV infusion then tapered according to BP. S/E : Severe Bradycardia

23. Doses and infusions Agent Dose Dopamine 5-10 mcg/kg/min Nor-Adrenaline 0.1-0.5 mcg/kg/min Adrenaline 0.1-0.5 mcg/kg/min Vasopressin 0.01-0.04 units/min

24. Complications Hypoperfusion Commonly occurs in the setting of inadequate cardiac output or inadequate volume resuscitation. Dusky skin changes at the tips of the fingers and toes, renal insufficiency and oliguria, and possible limb ischemia. Increase the risk of gastritis, shock liver, intestinal ischemia, or translocation of gut flora with resultant bacteremia.

25. Complications Dysrhythmias Stimulation of β -1 receptors. Increases the risk of sinus tachycardia, atrial fibrillation, AVnRT, or ventricular tachyarrhythmias. Limit the maximal dose and necessitate switching to another agent with less prominent β -1 effects.

26. Complications Local effects Peripheral extravasation of vasopressors into the surrounding connective tissue can lead to excessive local vasoconstriction with subsequent skin necrosis. Vasopressors should be administered via a central line. Local treatment with Phentolamine minimize local vasoconstriction.

27. Complications Hyperglycemia May occur due to inhibition of insulin secretion. Magnitude of hyperglycemia generally is mild. More pronounced with Nor-epinephrine and epinephrine than dopamine. β >> α (Decreases insulin, Hyperglycemia by Glycogenolysis and Gluconeogenesis)

28. Vasopressor Use in Septic Shock Patients with hyperdynamic septic shock (hypotension, low SVR, and high CI) tend to have warm extremities due to inappropriate hyperperfusion of the skin and soft tissues. Norepinephrine and Phenylephrine appear more potent in hyperdynamic sepsis. Patients with hypodynamic septic shock (hypotension, low SVR, and low CI) manifest hypoperfusion of the extremities. Dopamine may be preferable in patients with hypodynamic sepsis.

29. Thank You… Ref: Tintinalli’s Emergency Medicine, 7/e The ICU book, by Paul Marino, 3/e Google