JOURNAL READING

INTRODUCTIO
N
Systemic immune response leads to activation of

inflammatory, coagulation, and fibrinolysis

cascades and consequently leads to collateral
tissue damage and multiple organ failure
Anti-inflammatory response
secondary
infections
Worldwide, up to 19 million cases of severe sepsis
each year, and increasing by 8.7% per year
bundle care decreased risk of immediate death
associated with severe sepsis and septic shock,
and as a result, imminent death rate declined
from 80% to 20%-30%

Proper sedation for patients with sepsis need

of mechanical ventilation (MV) to reduce the

stress and anxiety associated with tracheal
intubation and other invasive interventions
-aminobutyric acid (GABA) receptor agonists
such as benzodiazepines and propofol are
commonly administered sedative agents in
the ICU

Recently, studies have highlighted sedative

and analgesic properties of selective 2

receptor agonists such as dexmedetomidine

 dexmedetomidine inhibits protein kinase A and

leads to phosphorylation of downstream enzymes

such as adenylate cyclase after its binding to
transmembrane G protein adrenoreceptors
sedative effects come from Hyperpolarization of

noradrenergic neurons in the locus ceruleus and

analgesic effect is a result of modulation of pain
impulses in the noradrenergic pathways in the
posterior horns of the spinal cord
evidence suggests that dexmedetomidine as a

sedative agent in intensive care sedative given

excellent

Dexmedetomidine has an effect as anti-

apoptosis, and modulation of the immune

system that may have an important role in the
pathogenesis of sepsis
dexmedetomidine has the side effect of

hypotension and bradycardia, which may affect

the stability of hemodynamics in patients with
septic shock

to evaluate the effectiveness and

safety of dexmedetomidine used for
sedation of patients with sepsis

GOALS

METHODS
accordaning BITERN guidelines and general methods recommended
by Cochrane collaboration.
included all clinical trials, investigating dexmedetomidine in patients
with sepsis, severe sepsis, or septic shock
Then searched Medline, Scopus, TRIP and CENTRAL, DART,
OpenGrey, and ProQuestwithout applying any language filter up to
July 15, 2015.
Two of the authors independently reviewed search results for
irrelevant and duplicate studies and extracted data and assessed
methodological quality of the studies
used tabulation to synthesize the findings of the studies and
transformed data into a common rubric and calculated a weighted
treatment effect across studies using Review Manager

STUDY FLOW DIAGRAM

242 patients with sepsis or septic

shock were identified and included in
this systematic review

Result
founded 124 references in 7 databases, and after
exclusion of irrelevant and duplicate studies, 6 studies
with total number of 242 patients with sepsis

 Based on 6 studies with total number of 242 patients with

sepsis were included. The risk ratio for 28-day mortality
was 0.49 (95% confidence interval, 0.24-0.99; P = .05)
for the dexmedetomidine group vs the control group. The
weighted mean difference for the length of stay in the
intensive care unit was 1.54 (95% confidence interval,
1.73 to 4.81; P = .36).
No adverse effect including hypertensive, hypotensive, or
bradycardia response was reported in any studies.

DISCUSSION

6 studies showed that dexmedetomidine had beneficial effects on

28-day mortality (based on GRADE approach) and delirium/coma
(based on GRADE approach) in patients with sepsis
no significant effect on length of ICU stay or duration of MV
(based on GRADE approach)
dexmedetomidine enhances nonrapid eye movement sleep and
induces a more natural sleep cycle, dexmedetomidine effect on
sleep quality may improve clinical outcomes such as delirium-free
days and mortality
dexmedetomidine can decrease levels of TNF-, IL-1, and IL-6
in patients with sepsis after 24 and 48 hours of treatment. This
anti-inflammatory effect of dexmedetomidine can suppress the
exaggerated production of inflammatory cytokines in septic shock
Both IAP after 24 hours and IAP 48 hours were significantly
lower in 20 patients treated with dexmedetomidine compared with
those treated with propofol. Increase in IAP not only has negative
effectson splanchnic, respiratory, cardiovascular, renal, and
neurologic functionbut is also associated with high mortality

 Dexmedetomidine further enhance mucosal immunity and bacterial

clearance by promoting macrophage phagocytosis andbactericidal
killing, properties that are clinically importantin sepsis and septic
shock

 In a small group of studies of patients with sepsis,

dexmedetomidine improved short-term mortality
compared with other sedatives without affecting the
intensive care unit length of stay.

CONCLUSION

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