This document discusses the fundamentals of using vasopressors. It outlines the steps to determine when to start vasopressors: 1) Is the patient's blood pressure too low? 2) Why is the blood pressure low? 3) How to raise the blood pressure? Norepinephrine is generally the first-line vasopressor. Adjuncts like vasopressin and steroids may be considered if norepinephrine dose is high. Peripheral intravenous lines can be used for vasopressors in the short term but central lines are preferable at higher doses due to risk of extravasation from peripheral lines.

1. Vasopressors:
Fundamentals
Brian Locke, MD
P/CCM Fellow
University of Utah Affiliated Hospitals and Clinics

2. IDENTIFY HYPOTENSION
GIVE VOLUME IF HYPOVOLEMIC
USE NOREPINEPHRINE
DOSE FOR MAP 65
PIV IS FINE, BP CUFF IS FINE*usually

3. Road Map
• When to start vasopressors
1. Is this patient’s BP too low?
2. Why is this patient’s BP low?
3. How should I bring this patient’s BP up?
• What vasopressor to use (the easy part)
• Practical considerations
• When to use adjuncts to NE
• How to use peripheral pressors

4. Case 1
• 64M with T2DM and chronic dry flaky skin on his feet. He comes in
with R non-purulent cellulitis. Receives 30cc/kg LR in the ED, then is
admitted to medicine.
• 1h after admission, RN pages you that his BP is 90 / 40 (MAP 60).
What do you want to do?

5. When to start vasopressors
Steps to decide when to start vasopressors:
1. Is this patient’s BP too low?
2. Why is this patient’s BP low?
3. How should I bring this patient’s BP up?

6. Is this patient’s BP too low?
BP target = open question in ICU
medicine
• Mean Arterial Pressure of 65 mmHg =
classic teaching (e.g. Surviving Sepsis)
• Should we tailor to baseline
BP/comorbidities?
• Mechanistic rationalization but has not
been demonstrated empirically.
Beware: BP =/= Perfusion
Can you think of a way BP can go up and
perfusion goes down?

7. Is it real?
• Assess Mental status, urine output, cap refill,
lactate, gestalt.
• Avoid sedating meds in patients with borderline BP
• lose ability to monitor (and often cause hypotension)
• You probably don’t need an arterial line…
Duration of hypotension is important
• “[Ischemic] Time is Brain”
• “[Hypotensive] Time is Organ Function”
Increasing time with perfusion
deficit = increased risk of adverse
kidney event. MPP = Mean
Perfusion Pressure
Am J Respir Crit Care Med, 2020
https://www.atsjournals.org/doi/ab
s/10.1164/rccm.201912-2316OC

9. When to start vasopressors
Steps to decide when to start vasopressors:
1. Is this patient’s BP too low?
2. Why is this patient’s BP low?
3. How should I bring this patient’s BP up?

10. Why is this patient’s BP low?
Obstructive Shock
• Tamponade
• PE
• Tension Pneumothorax
Distributive Shock
• Sepsis
• Pancreatitis
• Neurogenic
• Anaphylactic
Hypovolemic Shock
• Hemorrhagic shock
• Diarrhea
• Insensible Losses
Cardiogenic Shock
• Valve
• Arrythmia
• Cardiomyopathy

11. When to start vasopressors
Steps to decide when to start vasopressors:
1. Is this patient’s BP too low?
2. Why is this patient’s BP low?
3. How should I bring this patient’s BP up?

12. Case 1b
• 64M with T2DM and chronic dry flaky skin on his feet. He comes in
with R non-purulent cellulitis syncope and BRBPR, which is ongoing.
Receives 30cc/kg LR in the ED, then is admitted to medicine.
• 1h after admission, RN pages you that his BP is 85 / 50 (MAP 60).
What do you want to do?

13. Why is this patient’s BP low?
Obstructive Shock
• Tamponade
• PE
• Tension Pneumothorax
Remove the obstruction
Distributive Shock
• Sepsis – Antibiotics, Source Control
• Pancreatitis
• Neurogenic
• Anaphylactic
Vasopressors
Hypovolemic Shock
• Hemorrhagic shock
• Diarrhea
• Insensible Losses
Replace volume
Cardiogenic Shock
• Valve
• Arrythmia
• Cardiomyopathy
Fix or augment the pump

14. Case 2
• 70M presents with urinary retention, fever, AMS. Initially normal BP.
UA with WBC and bacteriuria – started on broad spectrum antibiotics.
BP tanks after the patient is admitted despite 2L LR. You suspect E
Coli bacteremia, with worsening shock as endotoxin is released.
Lactate is 5 mmol/l. You have a trainee on your team who asks…
• “Lactate is elevated because not enough O2 is being delivered to the
tissues… LR doesn’t carry any oxygen, and NE works by raising
vascular resistance which ought to lower flow… how would either of
these help?”
• How would you respond?

15. Mechanism of improved DO2
(SV * HR) = CO = MAP-CVP / SVR:
• Isolated increase in SVR would make CO drop?
Non-LV-cardiogenic shock states, Venous return is
commonly the limiting step (blood pools in dilated
veins)
• Unstressed volume: no increase in pressure as more
added.
• In health: 85% of total volume
• Stressed volume: pressure increases as volume
added, so increases venous return.
• In health: 15% of volume.

16. Mechanism of improved DO2
Venous return is
proportional to the stressed
volume
• Fluids: increase stressed
volume by increasing
overall volume
• Vasopressors: move
unstressed volume to
stressed volume
(venoconstricting =
tightening the tube)
DOI: 10.4103/ija.IJA_209_17
MSFP: mean systemic filling pressure (in the venules)
VR: Venous return

17. Case 3
• 70F with OA on NSAIDs who has reduced PO intake for 1 week due to
epigastric pain. Acute onset 10/10 abd pain night of presentation.
Rigid on the gurney
• Taken to OR – perf’ed ulcer, gets Gram Patch, admitted afterward with
secondary peritonitis. 30cc/kg LR. Lactate is 8 mmol/L. MAP is 60
mmHg
• What do you do? Fluids or vasopressors?

18. Sepsis: how much fluids?
• Hypovolemia due to: reduced PO, increased insensible losses/fever,
3rd space losses due to vascular permeability).
• Replete based on duration of symptoms, severity of reduced intake, etc.
• Vasodilated due to: endothelial injury, altered vascular tone
• Surviving Sepsis: 30 ml/kg. However, this has not (yet) been tested
• Comes from Observational data, trial protocols (e.g. Early Goal Directed
Therapy – PROCESS, ARISE trials), and common practice

19. Sepsis
• Paradigm: ”Fluids first, then NE if refractory hypotension”
• CENSER Trial: Should patients get both (fluids, pressors) up front?
• blinded RCT
• 0.05 mcg/kg/min NE x 24h through PIV vs placebo & std of care (surviving
sepsis)
• Outcome: Improvement in shock
• 65+ MAP and 0.5L/kg/hr UOP or 10% drop in lactate in 6h
• 76.1% NE vs 48.4% Placebo. No problem with adverse effects.
Clovers: June 2021. PETAL Network RCT
of Vasopressors first with rescue fluids vs
fluids first vs rescue vasopressors

20. Case 3
• 70F with OA on NSAIDs who has reduced PO intake for 1 week due to
epigastric pain. Acute onset 10/10 abd pain night of presentation.
Rigid on the gurney
• Taken to OR – perf’ed ulcer, gets Gram Patch, admitted afterward with
secondary peritonitis. 30cc/kg LR. Lactate is 8 mmol/L. MAP is 60
mmHg
• You decide to give another 1L of fluids. MAP increases to 70, then
trends down to 60 mmHg over then next hour.
• Do you continue to give more fluids?

21. ‘Fluid responsiveness’, Resuscitation Targets
• Organizational and mental barriers to starting vasopressors
• Sepsis 3 septic shock definition: ‘Requires vasopressors’
• If BP increases with fluids (or + NICOM), should you give more?
• To maintain 20% increase in intravascular volume (1L), 2-3L of fluid are going
to end up in the interstitium and tissues
More fluids = Worse outcomes (observational)
• Malbrain et al, 2014 meta-analysis
Resuscitation targets: unknown if helpful
• Lactate (if elevated, give more IVF?)
• Mixed Venous O2 (invasive, no better)
• Cap Refill (as good as lactate,
ANDROMEDA-SHOCK)

22. Road Map
• When to start vasopressors
1. Is this patient’s BP too low?
2. Why is this patient’s BP low?
3. How should I bring this patient’s BP up?
• What vasopressor to use (the easy part)
• Practical considerations
• When to use adjuncts to NE
• How to use peripheral pressors

23. Use Norepinephrine
Norepinephrine Epinephrine Vasopressin Phenylephrine
Action Alpha1 - vasoconstriction
Beta1 - contractility
Alpha1 - “
Beta1 – “
Beta2 – inotropic
effect.
V1 receptor Alpha1 – “
*Beta1 – “
Use First line, generally • Relative bradycardia
• Low cardiac output
• Anaphylaxis
• Pure
vasoconstrictor.
• Used as adjunct
Physiologically VERY
similar to NE
Dosage • Start at 0.04 mcg/kg/min
• There is no maximum dose
Gtt: same as NE
Push dose: 1mg (only
for use in arrest, 5-
10min)
0.04 U (no titration
because half-life is 30
minutes)
Push dose: 100 mcg
(10-20 min)

24. Use Norepinephrine
No solid evidence suggesting NE is
best
• Vaso 1st: VANISH trial, equivalent
• Epi 1st: CAT trial, equivalent
NE is logistically convenient.
Titrate q5-15 minutes

25. Road Map
• When to start vasopressors
1. Is this patient’s BP too low?
2. Why is this patient’s BP low?
3. How should I bring this patient’s BP up?
• What vasopressor to use (the easy part)
• Practical considerations
• When to use adjuncts to NE
• How to use peripheral pressors

26. Adjuncts
Common practice pattern: once NE at 0.20 mcg/kg/min.
• consider adding Vasopressin 0.04U, no titration, based on VASST trial
(no benefit, but post-hoc analysis most useful in that range)
• Stress dose steroids (hydrocortisone 100 mg q8 or 50 mg q6)
• Consider central venous catheter and arterial line

27. Do you need a central line?
• Pittard, 2013: RCT of 135 vs 128 pts randomized peripheral vs
central. Most frequent PIV complication = couldn't start.
Allowed 33.3+ mcg/min
NE. DOI: 10.1177/0310057X1704500614
• Tian, 2019: Systematic review extravasation rate: 3.4%, but
no true adverse outcomes in about 1500 patients. DOI
10.1111/1742-6723.13406
• Cardenas-Garcia, 2015: Cohort of 734 ICU received mean
duration 49+/- 22 hours, max 72h of peripheral pressors: 2%
had extravasation , none had lasting damage, 13% eventually
needed central line. DOI: 10.1002/jhm.2394
• Loubani, 2015: Systematic review: average time to
extravasation = 35h DOI: 10.1016/j.jcrc.2015.01.014
• Midlines: controversial. Data soon.
Compared to central venous catheter complication rates:
3SITES study, NEJM

28. How to do peripheral pressors
• You need to know about the IV
• Best: 18g or 20g in AC fossa or proximal (less risk, and less
risk of damage)
• protocoled extremity check (e.g. q2h)
• must flush and draw without pain
• Not US guided placement (this means was hard, and is
usually deeper and thus harder to monitor for
extravasation)
• Don't have BP cuff on that arm.
• If extravasation: administer SQ phentolamine (0.1-
0.2 mg/kg up to 10) and possibly nitroglycerin paste.
• If their BP drops: Check their arm
• This is the main reason to place CVC as dose increases –
reliable access
PIV

29. IDENTIFY HYPOTENSION
GIVE VOLUME IF HYPOVOLEMIC
USE NOREPINEPHRINE
DOSE FOR MAP 65
PIV IS FINE, BP CUFF IS FINE*usually

30. Questions?
Brian.locke@hsc.utah.edu