Hydrocortisone versus vasopressin

in septic shock

Hannah Klemm, PharmD

PGY1 Pharmacy Resident
Franciscan Health Indianapolis
 Objectives

01 Identify the current

guideline
02 Compare the efficacy of
vasopressin and
recommendations for hydrocortisone within this
shock study
 1-Hour Septic Shock Bundle

Broad- 30 mg/kg
Cultures Lactate spectrum crystalloid
antibiotics fluids

Evans L, et al. Executive Summary: Surviving Sepsis Campaign. Crit Care Med. 2021 Nov 1;49(11):1974-1982. doi: 10.1097/CCM.0000000000005357.
 Current Guidelines
If patients are not responsive to fluid resuscitation, vasopressors can be used

1 2 3 4
Norepinephrine Vasopressin Corticosteroid Epinephrine
First line vasopressor Started when NE is in For those on a dose of For those with an
the range of 0.25-0.5 NE ≥ 0.25 mcg/kg/min inadequate MAP
mcg/kg/min at least 4 hours after despite NE and
initiation vasopressin

Strong Recommendation Weak Recommendation Weak Recommendation Weak Recommendation

Evans L, et al. Executive Summary: Surviving Sepsis Campaign. Crit Care Med. 2021 Nov 1;49(11):1974-1982. doi: 10.1097/CCM.0000000000005357.
 Rationale
• Low vasopressin levels contribute to hypotension
• Exogenous vasopressin will restore blood pressure
Vasopressin while decreasing catecholamine requirement

• Sepsis induces nitric oxide mediated vasodilation and

steroids inhibit nitric oxide synthase
Corticosteroid • Improve adrenal insufficiency and hyperinflammatory
state
 • Multicenter, randomized, double-blind trial
VASST Meth
ods

Trial • 16 years of age

Inclu • Had septic shock that was resistant to fluids and required vasopressors
sion

• Norepinephrine 5-15 mcg/min

Study • Vasopressin 0.01-0.03 units/min + norepinephrine 5 mcg/min
group
s

• Mortality rate 28 days after the start of the infusions

Endp
oints

• No difference in 28-day mortality between the two groups (39.3% vs 35.4%)

• Patients in the vasopressin group had increased plasma vasopressin levels allowing for a
Resul
ts
decrease in NE dose (3.2 pmol/L vs 73.6 pmol/L at 6 hours)
 • Multicenter, factorial, double-blind, randomized trial

VANISH Met
hods
• Received vasopressin or norepinephrine

Trial
Incl • ≥16 years of age, had septic shock and requiring vasopressors
usio
n

• Received vasopressors prior to study enrollment, ongoing systemic steroid treatment, end
Excl stage kidney disease, and pregnant
usio
n

• Kidney failure free days

End • 28-day mortality and duration of RRT
poin
ts

• No difference in kidney failure between groups (57% vs 59.2%)

Res • Clinical benefit with vasopressin due to increased vasopressin plasma levels
ults
 • Investigator-initiated, international, double-blind, parallel-group, randomized,
controlled trial
ADRENAL Met
hods

Trial • ≥18 years of age, mechanical ventilation, current infection, have been treated with
Incl vasopressors for at least 4 hours up to randomization
usio
n

• Received steroids for another indication besides sepsis or received etomidate

Excl during admission
usio
n

• 90-day mortality
End • Time to resolution of shock, length of stay, duration of mechanical ventilation, and
poin recurrence of shock
ts

• No difference in 90-day mortality (P=0.5)

• Quicker time to shock resolution (P<0.001), decrease in ICU length of stay
Res
(P<0.001), fewer days requiring mechanical ventilation (P<0.001)
ults
Hydrocortisone versus vasopressin for the management of
adult patients with septic shock refractory
to norepinephrine: A multicenter retrospective study

Kulesza S, et al. Hydrocortisone versus vasopressin for the management of adult patients with septic shock
refractory to norepinephrine: A multicenter retrospective study. Pharmacotherapy. 2023 Aug;43(8):787-794. doi:
10.1002/phar.2811.
 Study Design
Type of study Setting Data collection Purpose

• Retrospective, • 10 Ascension • December 2015 – • Compare

multicenter, Health hospitals August 2021 outcomes
observational, associated with
cohort study the use of
vasopressin and
hydrocortisone in
shock
 Outcomes
Primary
1 Mortality within 28 days of study drug initiation

Secondary
2 Hemodynamic responsiveness
Resolution of shock
Recurrence of shock within 72 hours
Duration of vasopressor therapy
ICU length of stay
Incidence of new renal replacement therapy
28-day ventilator free days
Incidence of adverse events
 Inclusion Criteria
• Receipt of vasopressin (0.03 or 0.04
units/min) OR receipt of hydrocortisone (200
or 300 mg/day)
• Receipt of norepinephrine prior to study drug
• 30 mL/kg of IV fluid bolus prior to study drug
• Receipt of antibiotics for septic shock
• Baseline lactate > 2 mmol/L
Exclusion Criteria
• Pregnant or incarcerated
• Received other vasopressors prior to
norepinephrine
• Required mechanical circulatory support
• History of glucocorticoid use within 6 months
• Simultaneous initiation of norepinephrine and
study drug
• Initiation of vasopressin and hydrocortisone were
within 6 hours of each other
 768 patients
included

Hydrocortisone Vasopressin
(384) (384)

Due to there being differences in patient characteristics, a propensity score

matched was used resulting in 290 patients in each group
 Vasopressin Hydrocortisone
Variable
N=290 N=290
Age, years 70 (61-79) 70 (61-77)

Male 148 145

Caucasian 216 (74.5%) 202 (69.7%)

BMI, kg/m2 26.9 (22.3-32.7) 27.1 (22.5-31.7)

SOFA score 11 (9-12) 10 (9-13)

Lactate, mmol/L* 3.9 (2.6-6.9) 3.5 (2.3-5.9)

Mechanical Ventilation* 199 (68.6) 166 (57.2)

Norepinephrine dose, mcg/kg/min* 0.4 (0.23-0.6) 0.19 (0.1-0.35)

MAP, mmHg* 64 (56-70) 68 (64-75)

Time to initiation of study drug, hrs 7.1 (3.3-16.8) 8.1 (4.2-16.3)

*Significant difference in the unmatched cohort

Statistical Analysis

A p-value less than 0.05 was considered to indicate

statistical significance

Categorical data is described using frequency

Continuous data is described using mean with interquartile

range
 Primary Outcome

Vasopressin Hydrocortisone
Outcome P-value
N=290 N=290
28-day mortality 194 (66.9%) 136 (46.9%) < 0.01
 Secondary Outcomes
Vasopressin Hydrocortisone
Outcome P-value
N=290 N=290
Hemodynamic response 215 (74.1%) 264 (91%) < 0.01

Resolution of shock 109 (37.6%) 189 (65.2%) < 0.01

Recurrence of shock within 72 hours 20/109 (18.3%) 22/189 (11.6) 0.11

28-day ventilator free days 0 (0-19) 8 (0-25) < 0.01

New RRT 45 (15.5%) 38 (13.1%) 0.41

ICU length of stay 8.5 (5.5-16.5) 5.5 (3.5-10.5) <0.01

 Secondary Outcomes Cont.
Vasopressin Hydrocortisone
Adverse Event P-value
N=290 N=290
Hyperglycemia 46 (15.9%) 53 (18.3%) 0.44

Hyponatremia 24 (8.3%) 30 (10.3%) 0.39

Hypernatremia 39 (13.4%) 51 (17.6%) 0.17

Gastrointestinal bleeding 10 (3.4%) 14 (4.8%) 0.4

New bacteremia 8 (2.8%) 12 (4.1%) 0.36

Cardiac arrest 36 (12.4%) 24 (8.3%) 0.1

 Strengths Limitations

• Subjects received • Retrospective

guideline recommended • Variety in providers
therapies resulting in variability
• Propensity score in prescribing practices
matched
 Conclusion
Adding hydrocortisone to norepinephrine in patients with septic
shock decreased 28-day mortality

Hydrocortisone also decreased ICU length of stay and shock

recurrence

An improvement in resolution of shock and hemodynamic

responsiveness was seen in the hydrocortisone group
 My Key Takeaway

• There is a benefit to adding steroids to vasopressors in septic shock

and therefore I believe that majority of patients should be given
stress-dose steroids to help shock resolution
• There are some patient specific factors that may indicate more
harm than benefit with steroid use
Hydrocortisone versus vasopressin
in septic shock

Hannah Klemm, PharmD

PGY1 Pharmacy Resident
Franciscan Health Indianapolis