1
Vasopressors in shock
Diane 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/min
Bolus: 1 mg IV q3 to 5 min
IM: (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
0.03 units/min
V1, V2
Overgaard C, et al. Circulation. 2008;118:1047-1056
Micromedex. Micromedexsolutions.com
Splanchnic
vasoconstriction
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;118:1047-1056
Micromedex. 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.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
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
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.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
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
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
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.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
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.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
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
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
33
Vasopressors in shock
Diane J Lum, PharmD, BCACP
Stony Brook University Hospital
9/30/15