What’s the Squeeze: Role of

Vasopressin in Shock
Nicholas Corbin, PharmD
PGY1 Pharmacy Resident
Franciscan Health-Indianapolis
Interior titleStatement
Disclosure goes here

The speaker has no actual or potential conflict of

interest in relation to this presentation.
Interior title goes here
Clinical Case

• 54-year-old male presents to the Emergency

Department unresponsive, febrile, tachycardic,
and tachypneic
• Vital signs:
• BP: 65 mmHg/30 mmHg
• HR: 134 beats/minute
• RR: 30 breaths/minute
• SpO2= 70%
Interior title goes here
Clinical Case
• Labs
Na: 129 Cl: 100 BUN: 80 Glucose: 160 WBC: 20
RBC: 2.01
Hgb: 8
K: 3.5 CO2: 8 Cr: 2 Lactate: 5
Plt: 200

• The patient was diagnosed with sepsis and is started

on 30 mL/kg IV bolus of lactated ringers and 10
micrograms/minute of norepinephrine
• The physician asks you what other treatment options
are available
Interior title goes here
Objectives
• List four different types of shock and the differences
in treatment
• Compare vasopressors and their role in treatment of
shock
• Recognize the current role of vasopressin in the
treatment of shock
• Discuss vasopressin’s mechanism of action and why
it has been studied in shock
• Compare clinical trials and appraise statistical
significance of end-points
Interior title goes here
Objectives
• List four different types of shock and the differences
in treatment
• Compare vasopressors and their role in treatment of
shock
• Recognize the current role of vasopressin in the
treatment of shock
• Discuss vasopressin’s mechanism of action and why
it has been studied in shock
• Compare clinical trials and appraise statistical
significance of end-points
Interior
What is title goes here
Shock?

Life threatening medical

condition that leads to
decreased blood flow
and oxygenation of vital
organs

Moranville MP, et al. Journal of Pharmacy Practice. 2010;24(1):44-60.

Interior title goesofhere
Pathophysiology Shock

Hypoxia
• Decreased tissue perfusion and oxygen delivery
• Increased oxygen consumption

Metabolism shift
• Shift from aerobic to anaerobic metabolism
• Lactate and carbon dioxide levels increase

Moranville MP, et al. Journal of Pharmacy Practice. 2010;24(1):44-60.

Procter LD. Merck Manual. Shock. Accessed December 1, 2021
Interior title goesofhere
Pathophysiology Shock

Cellular changes
• Ion pump malfunction
• Intracellular edema
• Intracellular contents leak into
extracellular space

Multi-organ system failure

Moranville MP, et al. Journal of Pharmacy Practice. 2010;24(1):44-60.

Procter LD. Merck Manual. Shock. Accessed December 1, 2021
Interior title goesQuestion
Poll Everywhere here #1

Question Images – Browse 838,316 Stock Photos, Vectors, and Video | Adobe Stock
Interior
Subtypes title
of goes
Shockhere
Type Potential Causes
Distributive Sepsis
Anaphylaxis
Hypovolemic Hemorrhagic
Non-hemorrhagic
Cardiogenic Ventricular dysrhythmias
Pharmacological
Obstructive Pulmonary Embolism
Cardiac Tamponade

Moranville MP, et al. Journal of Pharmacy Practice. 2010;24(1):44-60.

Interior
How Do WetitleTreat?
goes here

Cardiogenic Distributive
Diuretics IV Antibiotics
Anticoagulation Steroids
IV Fluids
Vasopressor
s Obstructive
Hypovolemic Thrombolytics
Blood products Pressure Relieving
Devices

Moranville MP, et al. Journal of Pharmacy Practice. 2010;24(1):44-60.

Interior title goes here
Objectives
• List four different types of shock and the differences
in treatment
• Compare vasopressors and their role in treatment of
shock
• Recognize the current role of vasopressin in the
treatment of shock
• Discuss vasopressin’s mechanism of action and why
it has been studied in shock
• Compare clinical trials and appraise statistical
significance of end-points
Interior title goes
Vasopressors Usedhere
in Shock

• Dopamine
Catecholamines • Epinephrine
• Norepinephrine

Catecholamine- • Phenylephrine
mimetic

Non- • Angiotensin II
catecholamines • Vasopressin

Jentzer JC, et al. Cardiovascular Pharmacology Core Review. 2015; 20(3):249-60

VanValkinburg D, et al. Stat Pearls. Inotropes and Vasopressors
Interior title goes
Vasopressors Usedhere
in Shock

Drug Effect on Effect on Effect on

Contractility Heart Rate Arterial
Constriction

Angiotensin II - - +++

Dopamine ++ ++ ++

Epinephrine +++ +++ ++

Jentzer JC, et al. Cardiovascular Pharmacology Core Review. 2015; 20(3):249-60

VanValkinburg D, et al. Stat Pearls. Inotropes and Vasopressors
Interior title goes
Vasopressors Usedhere
in Shock

Drug Effect on Effect on Effect on

Contractility Heart Rate Arterial
Constriction

Norepinephrine ++ ++ +++

Phenylephrine - - +++

Vasopressin - - +++

Jentzer JC, et al. Cardiovascular Pharmacology Core Review. 2015; 20(3):249-60

VanValkinburg D, et al. Stat Pearls. Inotropes and Vasopressors
Interior title goes
Vasopressors Usedhere
in Shock

Drug Adverse Effects

Angiotensin II Delirium
Tachycardia
Thrombosis
Dopamine Arrhythmias
Hyperglycemia
Polyuria
Epinephrine Headache
Hyperglycemia
Lactic acidosis

Moranville MP, et al. Journal of Pharmacy Practice. 2010;24(1):44-60.

VanValkinburg D, et al. Stat Pearls. Inotropes and Vasopressors
Interior title goes
Vasopressors Usedhere
in Shock

Drug Adverse Effects

Norepinephrine Dyspnea
Peripheral ischemia
Tachycardia
Phenylephrine Bradycardia
Reduced cardiac output
Reduced urinary output
Vasopressin Hyponatremia
Renal insufficiency
Thrombocytopenia

Moranville MP, et al. Journal of Pharmacy Practice. 2010;24(1):44-60.

VanValkinburg D, et al. Stat Pearls. Inotropes and Vasopressors
Interior
Example: title goes here
Sepsis

Pathophysiolog • Infection causing inflammatory

y response and vasodilation

• Altered mental status

• Fever
Presentation • Hypotension
• Pallor

Angus DC, et al. NEJM. 2013; 369:840-51.

Example: Sepsis
Interior title goes here

Angus DC, et al. NEJM. 2013; 369:840-51.

Interior
Survivingtitle goesGuidelines
Sepsis here 2021

• Remeasure if initial lactate

Measure serum
>2 mmol/L
lactate

• Two separate anatomical

Obtain blood
sites
cultures

• Broad-spectrum
Start IV
antibiotics

Evans L, et al. Critical Care Medicine. 2021;49(11):1063-143.

 Interior title
Surviving goes
Sepsis here
Guidelines 2021

• Goal: 30 ml/kg
• Balanced crystalloids are
Start IV crystalloid preferred

• Goal: MAP ≥ 65 mmHg

• First line: norepinephrine
IV vasopressors • Second line: vasopressin

Evans L, et al. Critical Care Medicine. 2021;49(11):1063-143.

Interior title goesQuestion
Poll Everywhere here #2

Question Images – Browse 838,316 Stock Photos, Vectors, and Video | Adobe Stock
Interior title goes here
Objectives
• List four different types of shock and the differences
in treatment
• Compare vasopressors and their role in treatment of
shock
• Recognize the current role of vasopressin in the
treatment of shock
• Discuss vasopressin’s mechanism of action and why
it has been studied in shock
• Compare clinical trials and appraise statistical
significance of end-points
Interior title goes here
Vasopressin

• Synthesized in the hypothalamus and

released by the post-pituitary gland
• Released in response to:
• Decreased atrial volume
• Activation of carotid baroreceptors

Demiselle J, et al. Ann. Intensive Care. 2020; 10(9):1-7.

Interior title goes
Vasopressin here of Action
Mechanism

Receptor Effect
V1a agonist Vasoconstriction
V1b agonist Increased cortisol and
insulin secretion
V2 agonist Increased water
reabsorption

Demiselle J, et al. Ann. Intensive Care. 2020; 10(9):1-7.

Vasopressin Mechanism of Action
Interior title goes here

https://www.cvphysiology.com/Blood%20Pressure/BP016
Interior
Why Has title goes here
Vasopressin Been Studied in Shock?

Depletion of endogenous vasopressin

Landry et al.
• Measured vasopressin levels in 19 patients with septic
shock
• Found to have eight times lower levels compared to
patients with cardiogenic shock (3.1 pg/mL vs. 22.7
pg/mL)
• Given 0.04 units/minute of vasopressin
• Average SBP increased from 92 mmHg to 146 mmHg

Landry DW, et al. Circulation. 1997; 95: 1122-25.

Interior title goesQuestion
Poll Everywhere here #3

Question Images – Browse 838,316 Stock Photos, Vectors, and Video | Adobe Stock
Interior title goes here
Objectives
• List four different types of shock and the differences
in treatment
• Compare vasopressors and their role in treatment of
shock
• Recognize the current role of vasopressin in the
treatment of shock
• Discuss vasopressin’s mechanism of action and why
it has been studied in shock
• Compare clinical trials and appraise statistical
significance of end-points
Interior
VASST title goes here
Study Vasopressin versus Norepinephrine (NE)
Infusion in Patients with Septic Shock

Intervention • All patients received 5 mcg/minute of NE

• Randomized to vasopressin or NE
• Dose: vasopressin 0.01-0.03 units/minute or
NE 5-15 mcg/minute
Population • N=799
• Diagnosed with septic shock
• Not responsive to 500 mL of normal saline
• Required vasopressor therapy

Russell JA, et al. NEJM. 2008;358:877-87

 Interior title goes here
VASST-Methods
• Multicenter, randomized, double blind, active-controlled
• Primary endpoint: mortality rate 28 days after the start
of the infusion
• Secondary endpoints:
90-day mortality Days alive and free of
end-organ dysfunction
Days alive and free of Length of stay in hospital
vasopressor use or ICU
Rate of mechanical Incidence of initiation of
ventilation renal replacement therapy

Russell JA, et al. NEJM. 2008;358:877-87

Interior title goes here
VASST-Results
• 28-day mortality: 39.3% in NE group versus 35.4%
in vasopressin group; P=0.26
• 90-day mortality: 49.6% in NE group versus 43.9%
in vasopressin group; P=0.11
• Days alive free of organ dysfunction: 0 days in
both groups
• Length of hospital stay: 26 days in NE group versus
27 days in vasopressin group; P=0.23
• Length of ICU stay: 16 days in NE group versus 15 days
in vasopressin group; P=0.14

Russell JA, et al. NEJM. 2008;358:877-87

VASST – Results
Interior title goes here

Russell JA, et al. NEJM. 2008;358:877-87

VASST –title
Interior Results
goes here

Russell JA, et al. NEJM. 2008;358:877-87

Interior title goes here
VASST-Conclusion

• Vasopressin in patients with septic shock is

not associated with improved 28-day or
90-day mortality
• Vasopressin was not associated with
reduced length of hospital/ICU stay or end
organ dysfunction
• Of note, patients assigned to the vasopressin
group received statistically significant less
norepinephrine

Russell JA, et al. NEJM. 2008;358:877-87

 Interior
VANCS title goes here
Study Vasopressin versus Norepinephrine in
Patients with Vasoplegic Shock After
Cardiac Surgery
Intervention • Randomized to either vasopressin or
norepinephrine
• Vasopressin dose: 0.01-0.06 units/minute
• Norepinephrine dose: 10-60 mcg/minute
Population • N=300
• Post-cardiac surgery
• Vasopressor therapy needed within 48
hours after taking off cardiopulmonary
bypass
Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93.
Interior
VANCS title goes here
- Methods
• Prospective, randomized, superiority, double-blind,
and controlled trial
• Primary objective: Composite endpoint of death
and severe surgical complications within 30 days
after surgery
• Secondary objectives:
Incidence of: Length of:
• Atrial fibrillation • Hospital stay
• Infection • ICU stay
• Septic shock
• Ventricular arrhythmias
Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93.
Interior
VANCS title
Trialgoes here

Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93.

 Interior
VANCS title goes here
- Conclusion
• The incidence of acute kidney injury occurred
more often in patients that received
norepinephrine

• Patients receiving norepinephrine were

statistically more likely to develop atrial fibrillation

• Length of stay in the hospital and ICU

were shorter in the vasopressin group

Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93.

Interior title goes
VASST versus here
VANCS

VASST VANCS

Population ≥18 years old and ≥18 years old and

diagnosed with septic diagnosed with
shock vasoplegic shock
after cardiac surgery

Intervention Vasopressin (0.01 to Vasopressin (0.01 to

0.03 units/minute) or 0.06 units/minute) or
NE (5 to 15 NE (10 to 60
mcg/minute) mcg/minute)

Russell JA, et al. NEJM. 2008;358:877-87

Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93.
Interior title goes
VASST versus here
VANCS

VASST VANCS

Primary No statistical Composite outcome:

outcome difference in 28-day Main difference was
mortality increased rate of AKI
in NE group

Secondary No statistical Increased rate of

outcome difference in 90-day A. fib and length of
mortality, length of stay in hospital/ICU in
hospital/ICU stay NE group

Russell JA, et al. NEJM. 2008;358:877-87

Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93
Interior title goesQuestion
Poll Everywhere here #4

Question Images – Browse 838,316 Stock Photos, Vectors, and Video | Adobe Stock
 Interior
VANCS title goes here
2 Trial
Trial Vasopressin versus Norepinephrine for the
Management of Septic Shock in Cancer
Patients
Intervention • Patients randomized to either norepinephrine
or vasopressin
• Norepinephrine dose: 10-60 mcg/minute
• Vasopressin dose: 0.01-0.06 units/minutes

Population • N=250
• Had current diagnosis of cancer
• Documented or suspected infection
• Met at least 2 of 4 SIR criteria

Hajjar LA, et al. Crit Care Med. 2019;47(12):1743-50

Interior
VANCS title goes here
2 – Methods

• Single center, double-blind, randomized controlled trial

• Primary objective: 28-day all cause mortality rate
• Secondary objectives:

90-day all cause mortality Number of days alive and

off vasopressors
Incidence of mechanical Need for renal replacement
ventilation therapy at day 28

Hajjar LA, et al. Crit Care Med. 2019;47(12):1743-50

Interior
VANCS title goes here
2 – Results

• 28-day mortality: 56.9% in vasopressin group versus

52.8% in norepinephrine group; P=0.525
• 90-day mortality: 72% in vasopressin group versus
75.2% in norepinephrine group; P=0.566
• No statistical difference in days alive and free of
mechanical ventilation, vasopressor therapy, or renal
replacement therapy
• Patients in the vasopressin group were statistically more
likely to need open label norepinephrine (53.6% versus
40.8%; P=0.043)

Hajjar LA, et al. Crit Care Med. 2019;47(12):1743-50

Interior
VANCS title goes here
2 – Conclusion
• Vasopressin is not associated with an improvement
in 28-day mortality, or 90-day mortality compared to
norepinephrine in patients with a history of cancer
• Patients who were randomized to the vasopressin
group were more likely to require open label
norepinephrine use
• Unlike the original VANCS trial, norepinephrine was
not associated with a statistically significant nor
numerical cause of acute kidney injury
• There were more patients in the vasopressin group
that developed hyponatremia

Hajjar LA, et al. Crit Care Med. 2019;47(12):1743-50

 Interior
VANCS title goes
versus here II
VANCS
VANCS VANCS II

Population ≥18 years old and ≥18 years old with

diagnosed with history/current
vasoplegic shock diagnosis of cancer
after cardiac surgery and diagnosed with
septic shock
Intervention Vasopressin (0.01 to 0.06 units/minute) or
NE (10 to 60 mcg/minute) with goal mean
arterial pressure ≥ 65 mmHg

Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93.

Hajjar LA, et al. Crit Care Med. 2019;47(12):1743-50
Interior
VANCS title goes
versus here II
VANCS
VANCS VANCS II
Primary Composite outcome: No difference in 28-day
Outcome Main difference was mortality but patients in
increased rate of AKI NE group had higher
in NE group mortality rate

Secondary Increased rate of Vasopressin had

Outcome A. fib and length of greater incidence of
stay in hospital/ICU in open-label vasopressor
NE group requirement and
hyponatremia

Hajjar LA, et al. Anesthesiology. 2017;126(1):85-93.

Hajjar LA, et al. Crit Care Med. 2019;47(12):1743-50
 Interior
Low title goesinhere
Dose Vasopressin Trauma/Hemorrhagic Shock

Study Effect of Low Dose Supplementation of

Arginine Vasopressin on Need for Blood
Product Transfusions in Patients with
Trauma and Hemorrhagic Shock

Intervention • Received a four-unit vasopressin bolus or

placebo
• Randomized to ≤0.04 units/minute of
vasopressin or placebo

Population • N=100
• Trauma patients
• Received at least six units of blood within 12
hours of injury
Sim CA, et al. JAMA Surgery. 2019;154(11):994-1003.
LowInterior
Dose Vasopressin
title goesin here
Trauma/Hemorrhagic Shock
Methods
• Randomized, double-blind, placebo-controlled, single
center trial
• Primary Objective: total volume of blood products
transfused
• Secondary Objective:

Total volume of Total amount of

crystalloids transfused vasopressors required
Secondary complications 30-day mortality

Sim CA, et al. JAMA Surgery. 2019;154(11):994-1003.

Low Dose Vasopressin in Trauma/Hemorrhagic Shock
Results
Interior title goes here

Sim CA, et al. JAMA Surgery. 2019;154(11):994-1003.

LowInterior
Dose Vasopressin in here
title goes Trauma/Hemorrhagic Shock
Conclusion
• In patients who were diagnosed with
trauma/hemorrhagic shock, patients receiving
vasopressin were more likely to require less blood
products
• Vasopressin supplementation was associated with less
required 48-hour total crystalloid requirement or
vasopressor supplementation but was not deemed
statistically significant
• Hospital length of stay was numerically lower in the
treatment group versus placebo group

Sim CA, et al. JAMA Surgery. 2019;154(11):994-1003.

Interior title goesQuestion
Poll Everywhere here #5

Question Images – Browse 838,316 Stock Photos, Vectors, and Video | Adobe Stock
Interior
Summarytitle goes here

• Shock is a life-threatening condition that can

ultimately lead to multi-organ failure and
death
• IV fluids and vasopressors are at the center
of treatment for all types of shock
Interior
Summarytitle goes here
(continued)

• Vasopressin is an endogenous hormone that

causes vasoconstriction and decreases
diuresis
• Endogenous vasopressin has been shown to
be decreased in states of shock
• While vasopressin has been shown as a
catecholamine sparing agent, it has not been
shown to reduce mortality
What’s the Squeeze: Role of
Vasopressin in Shock
Nicholas Corbin, PharmD
PGY1 Pharmacy Resident
Franciscan Health-Indianapolis