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

Septic Shock
Hypotension despite adequate fluid
resuscitation
Presence of hypoperfusion or organ
dysfunction
Acidosis / alteration in mental status

Sepsis: temp >38C or <36C; 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

Phenylephrin
e

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 2 nd
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

Effect
Irritant; Rare reports of
vesicant effects

Dopamine,
Vesicants
Epinephrine,
Phenylephrine
Norepinephrine
, Vasopressin

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 (less)
x

x
x

Hypersensitivity
Extravasation

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