1. Vasopressors in shock Diane J Lum, PharmD, BCACP Stony Brook University Hospital 9/30/15 1

2. Objectives  Review the different types of shock (septic, cardiogenic, and neurogenic)  Describe the mechanism of action of vasopressors  Discuss guideline recommendations and literature on septic, cardiogenic, and neurogenic shock 2

3. Patient case  AB is a 80 year old M who presents to ED with AMS  Vitals: Temp: 38.8°C, HR 104, RR 23, BP 84/60  Labs: WBC 20, Scr 2.2  Cultures: pending  Home medications: Amlodipine 10 mg, zolpidem 10 mg, metformin 500 mg 3

4. Patient Case  Patient given Normal Saline 30 mL/kg  BP 84/65  MAP 55 4

5. Patient case  What is the vasopressor of choice in septic shock in a patient not responding to fluids? 5

6. Septic Shock  10 th leading cause of death in the United States  Mortality rates 28 to 50%  Defined as sepsis induced hypotension despite adequate fluid resuscitation  Mean arterial pressure (MAP) goal >65 6

7. Vasopressors DrugReceptorsDosingSide effects Phenylephrineα1α10.5 to 6 mcg/kg/minReflex bradycardia, decrease stroke volume Norepinephrineα1, β1 > β20.1 to 3 mcg/kg/minUrinary retention Epinephrineα1, β1, β2Infusion: 1 to 20 mcg/min Bolus: 1 mg IV q3 to 5 min IM: (1:1000): 0.1 to 0.5 mg Tachyarrhythmia Dopamine (low dose)D, β15 to 15 mcg/kg/minTachyarrhythmia Dopamine (high dose)D, α1, β1 > β2>15 mcg/kg/min VasopressinV1, V20.03 units/minSplanchnic vasoconstriction Overgaard C, et al. Circulation. 2008;118:1047-1056 Micromedex. Micromedexsolutions.com 7

8. Septic Shock Treatment Guidelines  First line: Norepinephrine  Adjunct/add on therapy: Epinephrine, vasopressin, phenylephrine  Dopamine alternative to norepinephrine in highly selective patients 8 Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83af

9. Norepinephrine  α-adrenergic agonist and β1 agonist  Onset: 1 to 2 min, Duration of action: 5 to 10 min  Dosing: Initial: 0.1 to 0.5 mcg/kg/min and increase by 1 to 2 mcg/min every 3 to 5 min until MAP goal  Max dose: Not well defined, some studies go up to 3 mcg/kg/min Overgaard C, et al. Circulation. 2008;118:1047-1056 Micromedex. Micromedexsolutions.com 9

10. Dopamine  Receptor agonist is dose dependent  Low dose (<5 mcg/kg/min): Dopaminergic receptors activated  vasodilation of splanchic and renal blood flow  Medium dose (5 to 10 mcg/kg/min): β1 stimulation  increase CO and HR  High dose (>10 mcg/kg/min): αlpha effects  vasoconstriction  Clinical significance of renal dose is controversial 10 Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83af Intensive Care Med. 2013;39(2):165-228

11. Dopamine  Onset: 5 minutes  Duration of action: <10 min  Adverse effects: tachyarrhythmia  Cost: $13.67 for 400 mg IVPB 11 Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83af Intensive Care Med. 2013;39(2):165-228

12. Norepinephrine versus Dopamine  Multicenter RCT in patients with septic shock to receive norepinephrine or dopamine  Primary outcome:  Rate of death at 28 days: Dopamine (52%) v. norepinephrine (48%), P=0.10  Secondary outcome:  Arrhythmic events: Dopamine (24.1%) v. norepinephrine (12.4%), P<0.001 12 DeBacker et al. 2010. N Engl J Med;362:779-89

13. Patient Case  AB is a 80 year old M who presents to ED with AMS  Vitals: Temp: 38.8°C, HR 104, RR 23, BP 84/60, MAP 55, weight 50 kg  Labs: WBC 20, Scr 2.2, BG 450, Lactic Acid 5.5  Patient is on norepinephrine 35 mcg/min  Which vasopressor would you add onto norepinephrine? 13

14. Epinephrine  Effects α1, β1, β2  β adrenergic > at low doses (< 10 mcg/min)  α1 adrenergic > at high doses  Doses > 20 mcg/min pure alpha effects 14 Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83af Intensive Care Med. 2013;39(2):165-228

15. Epinephrine  Duration of action: <5 min  Excretion: Renal  Adverse effect: Increase serum lactate, decrease splanchnic flow tachyarrhythmia 15 Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83af Intensive Care Med. 2013;39(2):165-228

16. Epinephrine Indications  Second line vasopressor in septic shock in addition to norepinephrine  Cardiac arrest: epinephrine 1:10,000   1 mg q3 to 5 min  Anaphylaxis: epinephrine 1:1000   0.1 to 0.5 mg IM q5 to 10 min PRN 16

17. Phenylephrine  α1 adrenergic agonist  Increases systemic vascular resistance (SVR) and BP  Rapid bolus for immediate correction of severe hypotension  Dose for push dose pressor: 50 to 100 mcg  Dose for continuous infusion: 0.5 to 6 mcg/kg/min or 100 to 180 mcg/min Overgaard C, et al. Circulation. 2008;118:1047-1056 Micromedex. Micromedexsolutions.com 17

18. Phenylephrine  Onset: within a minutes  Duration of action: 1 to 2 hours  Excretion: Primarily kidneys  Cost: $33.58 for one 50 mg vial 18

19. Vasopressin  Stored in posterior pituitary gland  released after increase in plasma osmolality or hypotension  V1 stimulation causes vasoconstriction in vascular smooth muscle  V2 (renal collecting ducts) mediate water reabsorption  Dose: 0.03 units/min in septic shock 19 Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83af Intensive Care Med. 2013;39(2):165-228

20. Vasopressin  Onset: Rapid, peak effect within 15 min  Duration: 20 min  Metabolism: both kidneys and liver  Cost: $116 for one 20 units/mL vial 20

21. Vasopressin  Adjunct for septic shock  Augments adrenergic vasopressors effects  Pressor effects of vasopressin relatively preserved during acidic conditions 21 Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83af Intensive Care Med. 2013;39(2):165-228

22. Administration of vasopressors  Central versus peripheral line  Systematic review showed complications occurred from peripheral line administration with infusions running >4 hours  Treatment: Phentolamine 22 Loubani et al. J Crit Care, 2015;30(3):653e9-e17 Ricard et al. Crit Care Med, 2013;41:2108-15

23. Patient Case  BB is a 55 year old M who presents to ED with SOB and CP  PMH: MI, dyslipidemia, diabetes, HTN  Vitals: Temp 37°C, HR 100, BP 96/68  Patient given morphine for CP 23

24. Patient Case  BP dropped to 68/42  Diagnosis: Cardiogenic shock secondary to ACS  What vasopressor would you start? 24

25. Cardiogenic shock  Occurs in 5 to 8% of patients hospitalized for STEMI  Diagnosis:  SBP 90 mm Hg  Pulmonary congestion or elevated left ventricular filling pressures  Signs of impaired organ perfusion (AMS, cold clammy skin, oliguria, increased serum lactate) 25 Reynolds et al. 2008. Circulation;117:686-697

26. Cardiogenic shock and low cardiac output 26 Antman et al. 2004. ACC/AHA Practice Guidelines

27. Cardiogenic Shock  De Backer et al. cohort study showed mortality reduction with norepinephrine versus dopamine  Norepinephrine and dopamine have inotropic properties  Epinephrine alternative to norepinephrine 27 Levy et al. Annals of Intensive Care.2015;5:17

28. Patient Case  DJ is a 40 year old male who presents to the ED with spinal injury from MVA  DJ was intubated by EMS  Vitals: Temp: 37°C, HR 45, BP 70/55  Diagnosis: neurogenic shock 28

29. Patient Case  Which vasopressor would you give this patient? 29

30. Neurogenic Shock  Defined: Reduced BP from neurologic causes  Must exclude other causes of hypotension first  Bradycardia common symptom of neurogenic shock  First ensure intravascular volume is restored 30 J Spinal Cord Med. 2008; 31(4)

31. Neurogenic Shock  Dopamine, norepinephrine, or phenylephrine can treat hypotension  Norepinephrine may increase BP and HR due to alpha and beta properties  Dopamine may be favored over phenylephrine in bradycardic patients  Phenylephrine pure alpha1 agonist and increase peripheral tone 31 J Spinal Cord Med. 2008; 31(4)

32. Summary  Norepinephrine is first line treatment for septic shock  Norepinephrine has lower incidence of arrhythmias compared to dopamine  Dopamine and norepinephrine have inotropic properties and are used for cardiogenic shock  First line treatment for neurogenic shock unclear 32

33. Vasopressors in shock Diane J Lum, PharmD, BCACP Stony Brook University Hospital 9/30/15 33