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Lesson 8 of10
In Progress

Literature Review for Vasopressin

Jimmy September 14, 2021

Summary of Data for Vasopressin For Cardiac Arrest

Author Design Intervention ComparisonOutcome
Lindner et al.
(1997)
Prospective, randomized trial

n=40

OHCA
Vasopressin (40 IU), one
dose, followed by
standard ACLS
treatment
Standard ACLS
treatment.
Survival to hospital
admission: 70 vs. 35%
(P = 0.06) and
survival to hospital
discharge: 40 vs. 15%
in the intervention
and control groups,
respectively
(P = NS)
Stiell et al.
(2001)
Prospective, randomized trial

n=200

IHCA
Vasopressin (40 mg) one
dose, followed by
standard ACLS
treatment
Standard ACLS
treatment
Survival to hospital
discharge: 12 vs. 14%
in the intervention
and control groups,
respectively
(P = NS)
Wenzel et al.
(2004)
Prospective,
randomized
trial

n= 1219

OHCA
Two injections of 40 IU of
vasopressin followed
by additional
treatment w/
adrenaline if needed
Standard ACLS
treatment
ROSC: 25 vs. 28%
(P =0.19) and
survival to hospital
admission: 36 vs. 31%
(P=0.06) in the
intervention and
control groups,
respectively
Grmec et al.
2006
Observational cohort study

n= 109

OHCA
Vasopressin 40 IU x 1 after three doses of 1 mg epinephrine

Vasopressin 40 IU as first-line therapy
Epineprhine 1 mg every 3 minutes The rate of restoration of spontaneous circulation (ROSC) with hospital admission, and the 24-hour survival rate were significantly higher among patients in the vasopressin groups (< 0.05)
Callaway et al.
(2008)
Prospective,
randomized
trial

n=325

OHCA
Vasopressin (40 IU), one
dose, followed by
standard ACLS
treatment
One dose saline
placebo in addition
to standard ACLS
treatment
ROSC: 31 vs. 30% and
survival to hospital
admission: 19 vs. 23%
in the intervention
and control groups,
respectively
(P = NS)
Gueugniaud et al.
(2008)
Prospective, randomized trial

n=2894

OHCA
Epinephrine (1 mg) and
vasopressin (40 IU),
maximum two doses,
followed by standard
ACLS treatment
1 mg adrenaline and
saline placebo,
maximum two
doses, followed by
standard ACLS
treatment
ROSC: 28.6 vs. 29.5%
and survival to
hospital admission
20.7 vs. 21.3%; in the
intervention group
and control groups,
respectively
(P = NS)
Mentzelopoulos
et al.
(2009)
Prospective,
randomized
trial

n=100

IHCA
Vasopressin (20 IU) +
Epinephrine (1 mg) in
repeated doses
(maximum 5 cycles)
+ methylprednisolone (40 mg) on the first cycle.

Additional adrenaline
if needed. Post-
resuscitation shock
treated w/
hydrocortisone
Epinephrine (1 mg) +
saline placebo for
maximum five
cycles.

Saline
placebo for
patients w/ post-
resuscitation shock
ROSC: 81 vs. 52%
(P =0.003) and
survival to hospital
discharge 19 vs. 4%
(P=0.02) in the
intervention and
control groups,
respectively
Mukoyama et al.
(2009)
Prospective,
randomized trial

n= 336

OHCA
Vasopressin (40 IU)
repeated every
5– 10 min until
cumulative dose of
160 IU
Epinephrine (1 mg),
repeated every
5 –10 min until
cumulative dose of
4 mg
ROSC: 28.7 vs. 26.6%
and survival to
hospital discharge 5.6
vs. 3.8% in the
intervention and
control groups,
respectively
(P = NS)
Carroll et al.
(2012)
Prospective intervention vs. historical control group

n= 30

IHCA
Vasopressin (0.8 mg/kg),
one dose, followed by
standard ACLS
treatment
Historical control
group (pediatric
patients in the ICU
that received at
least two doses of
vasopressor
medication, but not
vasopressin)
24-h survival: 80 vs. 30%,
(P = 0.05) and
survival to discharge:
60 vs. 25% (P = 0.07)
in the intervention
and control groups,
respectively
Ong et al. (2012)Prospective,
randomized trial

n= 727

OHCA
Vasopressin (40 IU), one
dose, followed by
standard ACLS
treatment
Standard ACLS
treatment
ROSC: 30 vs. 31% and
survival to discharge:
2.3 vs. 2.9% in the
intervention and
control groups,
respectively
(P =NS)
Mentzelopoulos
et al. (2013)
Prospective,
randomized trial

n=268

IHCA
Vasopressin (20 IU) +
Epinephrine (1 mg) in
repeated doses
(maximum 5 cycles)
+ methylprednisolone (40 mg) on the first cycle.

Additional adrenaline
if needed. Post-
resuscitation shock
treated w/
hydrocortisone
Epinephrine (1 mg) +
saline placebo for
maximum five
cycles.

Saline
placebo for
patients w/ post-
resuscitation shock
ROSC: 83.9 vs. 65.9%
(P = 0.005) and
neurologically
favorable survival
13.9 vs. 5.1%
(P =0.02) in the
intervention and
control groups,
respectively
Turner et al.
2014
Prospective,
randomized trial

n=268

OHCA+IHCA
Vasopressin + Epinephrine
Epinephrine AloneROSC: 56% in the vasopressin plus epinephrine group vs 60% in the epinephrine
alone group; P = 0.68; odds ratio [OR] = 0.83; 95% CI =0.37-1.85

Survival to hospital discharge did not differ significantly between groups (9% vs 5%; P = 0.46; OR = 1.88;
95% CI = 0.40-8.88).

Patients in the vasopressin plus epinephrine group had a significantly higher rate of ROSC compared with patients in the epinephrine alone group (63% vs 37%; P = 0.01; OR = 0.16; 95% CI =0.04-0.69).
IHCA= In-hospital cardiac arrest; OHCA= out-of-hospital cardiac arrest; OR= Odd ratio; ROSC= Return of Spontaneous Circulation

Mentzelopoulos SD, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013

Design

  • Randomized, double-blind, placebo-controlled,parallel-group trial
    • September 1, 2008, to October 1, 2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients

Primary Outcome

  • ROSC for 20 minutes or longer (adjusted to Utstein style) and survival to hospital discharge with favorable neurological recovery (ie, Glasgow-Pittsburgh Cerebral PerformanceCategory [CPC] score of 1 or 2).

Secondary Outcomes

  • Arterial pressure during and approximately 20minutes after CPR
  • Arterial pressure and central venous oxygen saturation (ScvO2) during days 1 through 10 after randomization
  • The number of organ failure–free days during days 1 through 60
  • Potentially corticosteroid-associated complications
    • Hyperglycemia,infections, bleeding peptic ulcers, and paresis

Intervention

  • IV Arginine vasopressin 20 IU/CPR cycle upt to 5 cycles
    • IV Epinephrine 1 mg/CPR cycle
    • IV methylprednisolone sodium succinate IV
      • At 4hours after resuscitation, surviving patients in theVSE group with postresuscitation shock received stress-dose hydrocortison(300mg/d for ≤7 days and gradual taper)

Comparison

  • IV Epinephrine 1 mg/CPR cycle

Baseline Characteristics

CharacteristicControl Group
(n = 138)
VSE Group
(n = 130)
Age, mean (SD), y62.8 (18.6)63.2 (17.6)
Male sex, No. (%88 (63.8)95 (73.1)
Body mass index, mean (SD)a25.4 (3.8)25.8 (4.6)
Hospital stay before the arrest, median (IQR), d2 (1-6)5 (1-11)
Cardiovascular comorbidity, No. (%)
-Hypertension
-Coronary artery disease
-Diabetes
-Peripheral vascular disease
-Cardiac arrhythmia
-Valvular heart disease
-Cardiac conduction disturbances


77 (55.8)
44 (31.9)
30 (21.7)
24 (17.4)
27 (19.6)
18 (13.0)
6 (4.3)
64 (49.2)
44 (33.8)
34 (26.2)
34 (26.2)
25 (19.2)
21 (16.2)
15 (11.5)
Noncardiovascular comorbidity, No. (%77 (55.8)74 (56.9)
Cause of cardiac arrest, No.(%)
-Hypotension
-Respiratory depression or failure
-Myocardial ischemia/infarction
-Metabolic
-Life-threatening/lethal arrhythmia
-Other
51 (37.0)
52 (37.7)
24 (17.4)
21 (15.2)
11 (8.0)
1 (0.7)
61 (46.9)
42 (32.3)
30 (23.1)
11 (8.5)
8 (6.2)
2 (1.5)

Secondary Outcome Results

OutcomeVSE
n [%]
EpinephrineOR
95% CI
P-Value
ROSC for 20+ minutes 109/130 [83.9%]91/138 [65.9%]OR, 2.98
95% CI,1.39-6.40

P = .005
Survival to hospital discharge with favorable neurological recovery18/130 [13.9%]7/138 [5.1%]OR, 3.28
95% CI, 1.17-9.20

P = .02

Secondary Outcome Results

  • VSE patients had shorter ALS duration and higher mean arterial pressure during and after CPR compared to the control group.
  • VSE patients had no difference in blood gas analysis during and after CPR compared to the control group.
  • VSE patients had improved mean arterial pressure and ScvO2 during days 1 through 10 after randomization, compared to the control group
  • VSE patients had significantly more neurologic, ventilator, and renal failure–free days, compared to the control group
  • The incidence of complications and eventual causes of death among patients who survived >4 h were not significantly different between the two groups

Commentary

  • Strengths
    • Multisite study
    • Randomized, double-blind, placebo-controlled, parallel-group trial
    • Readily available medications and ease of administration
    • Author confirms the results of previous study with same drug regimen
    • Vast amount of data during the post-resuscitation phase
  • Limitations
    • Small Patient population
    • Lack of sample size analysis
    • Excluded patients that had a life expectancy of <6 weeks
    • Lack of endogenous vasopressin and cortisol levels to test hypothesis
    • In-Hopsital Cardiac arrest which has more favorable results compared to out-of-hospital cardiac arrest

This is the first data to support that uses a pharmacological combination therapy with vasopressin, steroids, and epinephrine not only increases ROSC but discharge with good neurological outcomes. These results should be confirmed in a large multicenter, multinational randomized controlled trial prior to widespread adoption.