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Journal Reading

Mortality Benefit of Vasopressor and Inotropic Agents in

Septic Shock : A Bayesian Network Meta Analysis of
Randomized Controlled Trials

Gina Ariani

Internal Medicine Department

Dr. M. Djamil Hospital, Padang
2016

Research Article

Background
Septic shock is a very common condition and
associated with a high mortality rate of 20 %
to 50 % in intensive care unit.
Important interventions for reducing sepsis
mortality
include
aggressive
fluid
resuscitation, early goal-directed therapy, and
early
administration
of
appropriate
antibiotics.

Research Article

Background
Vasopressors are often requires for severe
sepsis that does not respond to fluid
resuscitation.
Norepinephrine (NE), dopamine (DOP),
epinephrine (EPI), low-dose vasopressin
(LDVP), and phenylephrine (PHE) are most
commonly used vasopressor agents for
septic shock.

Research Article

Background
The current evidence-based guidelines
recommend NE as the first choice of
vasopressor (grade 1B).
EPI in addition to or possible substitution
for NE when necessary (grade 2B).
LDVP in addition to NE to decrease NE
dosage (ungraded), and
DOP in place of NE only in highly
selected patients (2C)

Research Article

Background
Current guideline s recommend a trial of DOB in
case of myocardial dysfunction or tissue
hypoperfusion (grade 1C).
The purpose of this study was to systematically
review the overall evidence on vasopressors and
inotropes in septic shock from randomized controlled
trials with a Bayesian network meta-analysis.

Research Article

Material and Methods

Identification of trials
Two authors independently searched the National
Library of Medicines Medline databasae for studies
published froma 1946 to September 11, 2013.
Use 28-day mortality as the outcome assessment
criterion for the purposes of our meta-analysis.

Research Article

Material and Methods

493 reports identified and titles and
abstracts screened againts inclusion
criteria
469 studies deemed not
relevant and excluded
24 full retrieved and
screened for detailed
evaluation

14 studies included in
quantitative
synthesis
(mixed-treatment
comparisons
and
meta
analyses)
(Table 1)

Excluded
: (n
Wrong outcome
Duration too short
Wrong population
Wrong design : 1

= 10)
:2
:5
:2

Research Article
Association between vasopressor and
mortality
28-day or nearest estimate mortality rates
with DOP as a referent treatment.
Norepinephrine and NE + LDVP but not
EPI significantly reduced mortality
compared with DOP in the network
analysis.

Research Article
Association between intropes and
mortality
The addition of DOB did not significantly
affect mortality compared with EPI or NE
alone in the network analysis.
The results were similiar when
dopexamine (DOPE) was added to NE
compared with EPI or NE alone.
.

Research Article

Discussion
With the current guidelines that NE is the first
choice vasopressor in septic shock.
It is reasonable ( and a coomon practice) to add
LDVP rather than EPI or DOP if NE alone does not
provide satisfactory hemodynamic support given
potential survival benefit as demonstrated in this
analysis.

Research Article

Discussion
No concrete data exist to recommend either EPI or
DOP if above measure fail to achieve target blood
pressure.
The choice for an additional agent, when needed,
may be based on side effect profile (ie, DOP for
patients with low risk for tachyarrhtymia and
ventricular arrhythmia or EPI for patients with low
risk for splanchnic ischemia.

Research Article

Discussion
Phenylephrine is recommended when combine
inotrope / vasopressor agents do not achieve target
blood pressure, and cardiac output is known to be
high (grade 1C).
Phenylephrine may be used as salvage therapy
when others measures fail to achieve hemodynamic
goals or tachyarrhythmias limit therapy, whereas
keeping the lack of evidence in mind.

Research Article

Discussion
Dobutamine infusion is an element of this
strategy for patients with low mixed venous
oxygen
saturation
despite
volume
resuscitation
and
vasopressor
administration, but its contribution to
observed improved outcomes with the use
of these bundles is unclear.

Research Article

Conclusion
Our bayesian network meta-analysis support
the use of NE with or without LDVP as the first
line vasopressor therapy in septic shock.
No concrete evidence exist to choose EPI over
DOP as the second line agent.
There is no evidence that the use of an
inotropic agent would improve survival in
septic patients in the presence or absence of
myocardial dysfunction.

The question (PICO) of the study

Population/ Problem
Intervention

Patient with septic shock

Intervention given during the
study ;
Norepinephrine (NE), dopamine
(DOP), epinephrine (EPI), lowdose vasopressin (LDVP), and

Comparison

phenylephrine (PHE).
Norepinephrine (NE), dopamine
(DOP), epinephrine (EPI), lowdose vasopressin (LDVP), and

Outcome

phenylephrine (PHE).
using of NE with or
LDVP

as

the

first

without
line

vasopressor therapy in septic

shock.

ICAL APPRAISAL
S THIS REVIEW ADDRESS A CLEAR QUESTION?
1. Did the review address a clearly
focused issue?

Yes

Cant

No

tell

Was there enough information on

The population studied

The intervention given

The outcomes considered

2.

Did

the

authors

look

for

the

appropriate sort of papers?

The best sort of studies would

Address the reviews question

Have an appropriate study design

ARE THE RESULT OF THIS REVIEW

VALID?
3.

Do

you

think

the

important, Yes Can

relevant studies were included?

Look for

Which bibliographic database were

used

Follow up from reference lists

Personal contact with experts

Search for unpublished as well as

published studies
Search for non English language
studies

t
tell

No

ARE THE RESULT OF THIS REVIEW

VALID?
4. Did the reviews authors do enough to Yes

Can

assess the quality of the included studies?

t tell

No

The authors need to consider the rigour of the

studies they have identified. Lack of rigour
may affect the studies results
5. If the results of the review have been
combined, was it reasonable to do so?

Consider whether

The results were similar from study to study

The result of all the included studies are clearly

displayed

The results of the different studies are similar

The reasons for any variations are discussed

WHAT ARE THE RESULTS?

6. What is the overall result of
the review?

Consider

Yes

If you are clear about the

reviews
bottom
line
results

What these are

Norepinephrine (NE) with or

without LDVP as the first line
vasopressor therapy in septic
shock.
No concrete evidence exist to
choose epinephrine (EPI) over
dopamine (DOP) as the second
line agent.

7. How precise are the results?

Are the results presented with Yes
confidence intervals?

Thank You