Vasopressors
Jennifer & Joshua Chalk Talk
1/17/2014
Go Hawks!
Vasopressors
What?
When?
Why?
Wprecautions?
Vasopressors
Definitions
Pressor: Increases blood pressure by
stimulating constriction of blood vessels

Increases vascular tone
Definitions
Inotrope: Alters force or energy of
muscular contractions

Positive: Increases myocardial contractility
Definitions
Shock: Inability of oxygen delivery to meet
tissue oxygen requirements



Hypovolemia (decreased circulating volume)
Cardiac function impairment (decreased
myocardial contractility)
Inappropriate distribution of cardiac output
secondary to abnormal vasodilatation
Pathophysiology
Cardiac output

Heart Rate
Sympathetic and
Parasympathetic tone
Circulating
chatecolamines

Preload
Changes in venous
return
Changes in plasma
volume

Contractility
Sympathetic tone
Circulating
catecholamines
Progression to Late Shock
Septic Shock
Hypotension despite adequate fluid
resuscitation
Presence of hypoperfusion or organ
dysfunction
Acidosis / alteration in mental status

Sepsis: temp >38°C or <36°C; HR> 90 bpm*
respiratory rate>20 breaths/min, need for
mechanical ventilation; WBC 12,000*
Hemorrhagic Shock
Rapid reduction in blood volume
Heart rate and blood pressure responses
can be variable
Vasopressors may be harmful if pt is
hypovolemic; Despite improvement in
blood pressure, renal blood flow
decreases and renal vascular resistance
rises
Cardiogenic Shock
Pump failure
Results when more than 40% of
myocardium damaged
Similar circulatory and metabolic changes
to hemorrhagic shock
Treatment
1. Fluids / Procedures
2. DRUGS!


Vasopressors
Inotropes
Fluid Requirements
“There is no evidence-based support for
one fluid-type over another”(surviving
sepsis)
Early fluid administration more important
than fluid type

HES/Albumin/Gelatin/LR; Rivers et al
Pharmacology
Pharmacology
Adrenergic System

Alpha adrenergic
Increases vascular tone
May decrease cardiac output
May decrease regional blood flow (renal, spleen,
cutaneous)

Beta adrenergic
Maintains blood flow
May increase cellular metabolism
May decrease immune system
Pharmacology
Dopaminergic




Increases splanchnic and renal perfusion
Facilitates resolution of lung edema
Associated with harmful immunological effects
May decrease prolactin, human growth
hormone
Vasopressors
Norepinephrine
Dopamine
Epinephrine
Vasopressin
Phenylephrine
Vasopressors
Phenylephrine
Vasopressors
Vasopressors
Vasopressin
Receptors
Receptors
Norepinephrine
Historically considered a poor choice in
shock due to excessive vasoconstriction
and end-organ hypoperfusion
This opinion began to change recently
Benefits: raise arterial pressure and
systemic vascular resistance
Maintain cardiac function / improve renal
function
Dopamine
More potential for arrhythmias/increased
heart rate
May increase both blood pressures and
flow; may be best used in patient with low
heart rate and inadequate fluid
resuscitation
Epinephrine
Epi often used as 3rd line after NE and DA
failed
Epi always first line in Anaphylactic Shock
Vasopressin
Vasopressin works on V1,V2,V3 receptors
Increases bp / may improve mortality
May decrease NE requirements
May improve renal function
Avoid in MI; in cardiac ischemia may
decrease contractility/lower CO/increase
mortality
At doses > 0.04 units/hr may decrease GI
blood flow
Studies
VASST





Vasopressin (0.03 un/hr) v. NE in septic shock
No significant difference in mortality at 28
days
Decreased mortality in patients with less
severe septic shock (lowest quartile of arterial
lactate)
Vaso + corticosteroids decreased mortality v.
NE + corticosteroids
Conclusion: May be effective in patients with
less severe septic shock already receiving NE
Studies
Martin: Norepi in Septic Shock



97 patients in septic shock
Dopamine started at 5mcg/kg/min, titrated to
15mcg/kg/min
If hypotension persisted:
DA increased to 25mcg/kg/min OR
NE added at 0.5mcg/kg/min
Martin et al
Patients receiving NE had best survival
rate on all days of hospital stay (p<0.001)
Mortality strongly associated with high
lactate and low urine output
“NE was associated with a highly significant
decrease in hospital mortality. The data
contradict the notion that norepinephrine
potentiates end organ hypoperfusion through
excessive vasoconstriction
Studies
De Backer: Norepi v Dopamine in Shock.




Multicenter study, 1679 patients
DA with 52.5% mortality
NE with 48.5% mortality (p=0.10)
More arrhythmic events with DA (207v102)
DeBacker et al
Included Septic (62.2%), Cardiogenic
(16.7%), and Hypovolemic (15.7%) shock.
More patients in DA group required 2nd
pressor
Subgroup: DA in cardiogenic shock
increased mortality significantly (p=0.03)
Conclusion: “This study raised serious
concern about the safety of Dopamine”
Practical Considerations
•
•
•
•
•
Vascular Access
Access to drug
Compatibilities
Titration
Adverse effects
Central vs. Peripheral line
Central always preferred
Peripheral

Line
Must flush well
As big as possible
Preferred infusion site = forearm (basilic, cephalic, and
median antebrachial)


Caution with dorsum of hand, wrist, feet
Decision: life vs. limb
MD must be aware

Guardrails alert: pressor must go through central line
Override with MD approval documented

Slower titration with obese patients
Central vs. Peripheral line
Jean-Damien, R et al. Central or peripheral catheters for
initial venous access of ICU patients

Patients randomized: peripheral (N=128) or central access
(N=135)
Included epinephrine/norepinephrine doses up ~0.4 mcg/kg/min (for 75 kg
patient); Dopamine/dobutamine doses up to 10 mcg/kg/min

Less major complications with central rather than peripheral
access (0.64 vs. 1.04, p<0.02)
Majority of complications in PIV group were inability to insert PIV

Subcutaneous diffusion (aka extravasation)
More with peripheral rather than central access


19/128 (~15%) vs. 2/135 (~1.5%)
Average length of stay ~12 days
All patients managed with “observation and conservative
management”
http://emcrit.org/podcasts/peripheral-vasopressors-extravasation/
Ricard JD, et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med. 2013 Sep;41(9):2108-15
Extravasation
Drug
Dobutamine
Dopamine,
Epinephrine,
Phenylephrine
Norepinephrine
, Vasopressin
Effect
Irritant; Rare reports of
vesicant effects
Vesicants
Mechanism(s) of
tissue injury
Cytotoxicity, acidic
pH
Vasoconstriction
Extravasation
Phentolamine





Short-term alphaadrenergic blocking
activity
Administration
→vasodilatation of
vascular smooth muscle
Administer ASAP
Infiltrate area of
extravasation with
phentolamine: 5 mg
diluted in 9 mL NS
Should see near
immediate effects;
otherwise consider
additional dose (Max =
Getting a Drip Up and On
Sequence of events









Hypotensive patient
Recognize pressor needed
Physician orders
Order recognized in ORCA
Pharmacy technician makes drip
Pharmacist checks drip
Pharmacy technician tubes drip
Nurse collects from tube station
Nurse starts drip
Getting a Drip Up and On
Dopamine,
Dobutamine

Premixed and in
PYXIS!
Epinephrine,
Phenylephrine,
Norepinephrine,
Vasopressin

Mixed by technician
after order received in
inpatient pharmacy
Getting a Drip Up and On
Persistent hypotension → Ask MD if drip should
be sent to bedside

Cost to hospital per bag: $1.56 – 7.23
Call pharmacy



Ask for pharmacist STAT (state you are calling from
ED)
State patient scenario briefly
Request pharmacy to start making drip
ONLY Physician may give verbal order with U#, drug
and dose
Otherwise MD must place order in ORCA before drip is
sent

Request pharmacy to notify PSS when drip sent
Compatibilities
Variable – Call pharmacy
Most likely to be compatible: Epinephrine,
dobutamine, dopamine, vasopressin
Maybe: Phenylephrine
Generally not tested: Norepinephrine
Titration
Starting a drip


MD must order
Generally best to start low and increase
Adverse effects frequently dose related
Switching a patient from OSH

Check patient weight and dosing UNITS
If the same, transition to UW pump and drug
If different:


Call pharmacy to convert
Start in the low to mid range of dosing and titrate
Adverse Reactions
Phenylephrin
Epinephrine Norepinephrine Dopamine Dobutamine Vasopressin e
Tachycardia
x
x
Arrhythmias
Increased
myocardial O2
x
demand
Decreased
perfusion to
x
vital organs
Nausea/vomitin
g
Metabolic
x
acidosis
High doses x
High doses x
x
x (ventricular)
x
x
x (less)
x
x
x
Hypersensitivity
Extravasation
x
x
x
x
x
x
x
(contains
sulfites)
x
References
De Backer D et al. Comparison of dopamine and norepinephrine in
the treatment of shock. N Engl J Med 2010;362:779-89.
Martin C et al. Effect of norepinephrine on the outcome of shock.
Crit Care Med 2000; 28:2758 –2765
Perel A. The initial hemodynamic resuscitation of the septic patient
according to Surviving Sepsis Campaign guidelines – does one size
fit all? Critical Care 2008, 12:223
Russel J. Vasopressin in the management of septic shock. Critical
Care 2011, 15:226
Russell JA, et al. Vasopressin versus norepinephrine infusion in
patients with septic shock. N Engl J Med 2008, 358:877-887.
Ricard JD, et al. Central or peripheral catheters for initial venous
access of ICU patients: a randomized controlled trial. Crit Care Med.
2013 Sep;41(9):2108-15