1Vasopressors in shockDiane J Lum, PharmD, BCACP

Stony Brook University Hospital

9/30/15

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

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

4 Patient Case

Patient given Normal Saline 30 mL/kg

BP 84/65

MAP 55

5 Patient case

What is the vasopressor of choice in septic shock in a patient not responding to fluids?

6 Septic Shock

10th 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

7 Vasopressors

Drug Receptors Dosing Side effects

Phenylephrine α1 0.5 to 6 mcg/kg/min Reflex bradycardia, decrease stroke volume

Norepinephrine α1, β1 > β2 0.1 to 3 mcg/kg/min Urinary retention

Epinephrine α1, β1, β2 Infusion: 1 to 20 mcg/minBolus: 1 mg IV q3 to 5 minIM: (1:1000): 0.1 to 0.5 mg

Tachyarrhythmia

Dopamine (low dose) D, β1 5 to 15 mcg/kg/min Tachyarrhythmia

Dopamine (high dose)

D, α1, β1 > β2

>15 mcg/kg/min

Vasopressin V1, V2 0.03 units/min Splanchnic vasoconstriction

Overgaard C, et al. Circulation. 2008;118:1047-1056Micromedex. Micromedexsolutions.com

8 Septic Shock Treatment Guidelines

First line: Norepinephrine

Adjunct/add on therapy: Epinephrine, vasopressin, phenylephrine

Dopamine alternative to norepinephrine in highly selective patients

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;118:1047-1056Micromedex. Micromedexsolutions.com

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

Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83afIntensive 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

Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83afIntensive 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

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?

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

Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83afIntensive 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

Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83afIntensive 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

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;118:1047-1056Micromedex. Micromedexsolutions.com

18 Phenylephrine

Onset: within a minutes

Duration of action: 1 to 2 hours

Excretion: Primarily kidneys

Cost: $33.58 for one 50 mg vial

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

Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83afIntensive 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

21 Vasopressin

Adjunct for septic shock

Augments adrenergic vasopressors effects

Pressor effects of vasopressin relatively preserved during acidic conditions

Dellinger R et al. Surviving Sepsis Campaign 2012. DOI: 10.1097/CCM.0b013e31827e83afIntensive 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

Loubani et al. J Crit Care, 2015;30(3):653e9-e17Ricard 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

24 Patient Case

BP dropped to 68/42

Diagnosis: Cardiogenic shock secondary to ACS

What vasopressor would you start?

25 Cardiogenic shock

Occurs in 5 to 8% of patients hospitalized for STEMI

Diagnosis: SBP <90 mm Hg for 30 min, MAP <65 mm Hg for 30 min, or

vasopressors required to achieve 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)

Reynolds et al. 2008. Circulation;117:686-697

26 Cardiogenic shock and low cardiac output

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

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

29 Patient Case

Which vasopressor would you give this patient?

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

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

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

33Vasopressors in shockDiane J Lum, PharmD, BCACP

Stony Brook University Hospital

9/30/15