1. Giving our patients the best chance to survive shock Erik Diringer, DO Intensivist – Kenmore Mercy Hospital

2. Disclosures None

3. Vasopressors Powerful class of IV medications that induce vasoconstriction Not to be confused with inotropes Surprisingly a dearth of studies exist comparing their use in different shock states 2

4. Shock States (Adult) “The rude unhinging of the machinery of life” 2 Significant reduction of systemic tissue perfusion Oxygen consumption > Oxygen delivery (VO 2 > DO 2 ) Cellular effect Systemic effects Cell death, end-organ damage, MSOF, death Often happens prior to hypotension

5. Shock States MAP = (CO x SVR) + CVP CO = HR x SV SV influenced by preload, afterload, contractility

6. Systemic Tissue Perfusion Cardiac Output (CO) Heart Rate (HR) Stroke Volume (SV) PreloadAfterloadContractility Systemic Vascular Resistance (SVR)

7. Shock States Types: Distributive: dec. SVR Eg) septic shock, SIRS, anaphylaxis, neurogenic, toxins Cardiogenic: dec. contractility (inc. SVR, HR) Eg) CMP, arrhythmia, mechanical, obstructive Hypovolemic: dec. preload (inc. SVR, HR) Eg) fluid loss, hemorrhage

8. Vasopressor/Inotrope Receptors Alpha adrenergic α -1 in vessels, induces vasoconstriction Beta adrenergic β -1 in heart, increases inotropy and chronotropy, mild vasoconstriction β -2 in vessels induces vasodilation Dopamine: renal, splanchnic, coronary, cerebral vascular beds Generally induce vasodilation Subtype induces vasoconstriction by inducing NE release

9. Vasopressor Choices Norepinephreine (Levophed) – 0.02-1 mcg/kg/min IV α -1 and β -1 activity Potent vasoconstriction, modest inc. CO Phenylephrine (Neo-Synephrine) – 40-60 mcg/min IV α -1 activity Potent vasoconstriction, dec. SV Epinephrine – 2-10 mcg/min IV Potent β -1 activity, modest α -1, β -2 inc. CO, dec. SVR α -1 predominates at higher doses Beware of arrhythmias, splanchnic vasoconstriction

10. Vasopressor Choices Dopamine 1-2 mcg/kg/min: selective renal, splanchnic, cerebral, coronary vasodilation 5-10 mcg/kg/min: β -1 activity >10 mcg/kg/min: α -1 activity Beware of arrhythmias

11. Vasopressor Choices Vasopressin (ADH) Second-line agent in distributive shock Doses >0.03 U/min associated with coronary and mesenteric ischemia

12. Inotrope Choices Dobutamine (Dobutrex) β -1 activity: inc. contractility, dec. SVR Isoproterenol (Isuprel) β -1, β -2 activity: inc. HR, dec. SVR Milrinone PDE inhibitor Non-adrenergic, but similar physiological effect to dobutamine

14. Pre-Pressor Problems ABCs Volume resuscitation Central access, monitoring Why is my patient in shock? What determinant of tissue perfusion is being adversely affected? HR, preload, afterload, contractility, SVR

15. Distributive Shock

16. Systemic Tissue Perfusion Cardiac Output (CO) Heart Rate (HR) Stroke Volume (SV) PreloadAfterloadContractility Systemic Vascular Resistance (SVR)

17. Distributive Shock dec. SVR Compensatory inc. HR Often dec. contractility in septic shock Goal is to maintain adequate SVR without adversely affecting CO Septic shock most common cause EGDT, volume resuscitation Norepinephrine is first-line vasopressor therapy in septic shock despite adequate fluid resuscitation 3 (Grade 1B) Epinephrine second-line (Grade 2B) Vasopressin (0.03 U/min) to achieve MAP goal, decrease NE (UG) Dopamine only in low-risk for arrhythmia, absolute/relative bradycardia (grade 2C)

18. Septic Shock Phenylephrine is not recommended, except (grade 1C): When norepinephrine is associated with serious arrhythmias When CO is high and BP persistently low As salvage therapy when combined inotrope/vasopressor drugs and low-dose vasopressin have failed to achieve the MAP target Phenylephrine is an appropriate pressor in neurogenic shock

19. Cardiogenic Shock

20. Systemic Tissue Perfusion Cardiac Output (CO) Heart Rate (HR) Stroke Volume (SV) PreloadAfterloadContractility Systemic Vascular Resistance (SVR)

21. Cardiogenic Shock dec. contractility Compensatory inc. SVR and HR Only vasopressors with β activity are indicated! Avoid α -1 agents that only increase SVR Inotropes preferred when BP adequate Sometime secondary to dec. HR Provide optimal supportive care (pH, temp, O 2 ) May require device (VA-ECMO, IABP, VAD, TVP)

22. Cardiogenic Shock – Obstructive Generally no role for vasopressors Treatment aimed specifically at underlying cause Cardiac tamponade, tension pneumothorax, massive PE

23. Hypovolemic Shock

24. Systemic Tissue Perfusion Cardiac Output (CO) Heart Rate (HR) Stroke Volume (SV) PreloadAfterloadContractility Systemic Vascular Resistance (SVR)

25. Hypovolemic Shock dec. preload Compensatory inc. SVR and HR Why is my patient hypovolemic? Fluid loss, hemorrhage Treat the underlying cause Generally vasopressors indicated as temporizing support ie) BP support during intubation, procedures Specific cases Esophageal varices: Vasopressin decreases portal blood flow and improves hemostasis

26. Take Home Messages Shock often occurs before hypotension Oxygen consumption > Oxygen delivery (VO 2 > DO 2 ) Tissue perfusion influence by CO and SVR CO influenced by HR, preload, afterload and contractility Shock can be distributive, cardiogenic, hypovolemic or a combination Vasopressor choice directed at mechanism of shock

27. Take Home Messages Always ask “Why?” Direct your therapy based upon the answer

29. References 1. Müllner M, Urbanek B, Havel C, et al. Vasopressors for shock. Cochrane Database Syst Rev 2004; :CD003709. Müllner M, Urbanek B, Havel C, et al. Vasopressors for shock. Cochrane Database Syst Rev 2004; :CD003709. 2. Simeone FA: Shock, trauma and the surgeon. Ann Surg 1963; 158: 759–774. 3. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 ​​ (http://www.survivingsepsis.org/Guidelines). Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 ​​http://www.survivingsepsis.org/Guidelines