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JOURNAL READING
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Systemic immune response leads to activation of
inammatory, coagulation, and brinolysis
cascades and consequently leads to collateraltissue damage and multiple organ failure
Anti-inammatory response secondary
infections
Worldwide, up to 19 million cases of severe sepsis
eac year, and increasing by !"#$ per year
bundle care decreased ris% of immediate deatassociated wit severe sepsis and septic soc%,
and as a result, imminent deat rate declinedfrom !&$ to '&$-(&$
INTRODUCTIO
N
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)roper sedation for patients wit sepsis needof mecanical ventilation *+ to reduce te
stress and an.iety associated wit tracealintubation and oter invasive interventions
/-aminobutyric acid *0AA receptor agonistssuc as ben2odia2epines and propofol are
commonly administered sedative agents inte 345
6ecently, studies ave igligted sedativeand analgesic properties of selective 7'receptor agonists suc as dexmedetomidine
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de.medetomidine inibits protein %inase A andleads to posporylation of downstream en2ymessuc as adenylate cyclase after its binding totransmembrane 0 protein adrenoreceptors
sedative e8ects come from yperpolari2ation of
noradrenergic neurons in te locus ceruleus andanalgesic e8ect is a result of modulation of painimpulses in te noradrenergic patways in teposterior orns of te spinal cord
evidence suggests tat de.medetomidine as asedative agent in intensive care sedative givene.cellent
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:e.medetomidine as an e8ect as anti-apoptosis, and modulation of te immunesystem tat may ave an important role in tepatogenesis of sepsis
de.medetomidine as te side e8ect ofypotension and bradycardia, wic may a8ectte stability of emodynamics in patients wit
septic soc%
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GOALS
to evaluate the effectiveness and
safety of dexmedetomidine used forsedation of patients with sepsis
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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 shoc!
• Then searched "edline #copus TRI$ and CENTR%& '%RT
(pen)rey and $ro*uestwithout applying any language filter up to
+uly ,- /,-.
• Two of the authors independently reviewed search results for
irrelevant and duplicate studies and extracted data and assessed
methodological 0uality of the studies• used tabulation to synthesi1e the findings of the studies and
transformed data into a common rubric and calculated a weighted
treatment effect across studies using Review "anager
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#T2'3 4&(5 'I%)R%"
6 patients with sepsis or septic
shoc! were identified and included in
this systematic review
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Result
•
founded ,6 references in 7 databases and afterexclusion of irrelevant and duplicate studies 8 studies
with total number of 6 patients with sepsis
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• Based on 8 studies with total number of 6 patients with
sepsis were included. The ris! ratio for 9:day mortality
was /.6; <;-= confidence interval /.6:/.;;> $ ? ./-@
for the dexmedetomidine group vs the control group. The
weighted mean difference for the length of stay in theintensive care unit was ,.-6 <;-= confidence interval
A,.7 to 6.9,> $ ? .8@.
• No adverse effect including hypertensive hypotensive or
bradycardia response was reported in any studies.
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'I#C2##I(N 8 studies showed that dexmedetomidine had beneficial effects on9:day mortality <based on )R%'E approach@ and deliriumcoma<based on )R%'E approach@ in patients with sepsis
no significant effect on length of IC2 stay or duration of "D<based on )R%'E approach@
dexmedetomidine enhances nonrapid eye movement sleep andinduces a more natural sleep cycle dexmedetomidine effect onsleep 0uality may improve clinical outcomes such as delirium:free
days and mortality
dexmedetomidine can decrease levels of TN4:F I&:,G and I&:8in patients with sepsis after 6 and 69 hours of treatment. Thisanti:inflammatory effect of dexmedetomidine can suppress theexaggerated production of inflammatory cyto!ines in septic shoc!
Both I%$ after 6 hours and I%$ 69 hours were significantlylower in / patients treated with dexmedetomidine compared withthose treated with propofol. Increase in I%$ not only has negativeeffectson splanchnic respiratory cardiovascular renal andneurologic functionbut is also associated with high mortality
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• 'exmedetomidine further enhance mucosal immunity and bacterial
clearance by promoting macrophage phagocytosis andbactericidal
!illing properties that are clinically importantin sepsis and septic
shoc!
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CONCLUSION
• In a small group of studies of patients with sepsis
dexmedetomidine improved short:term mortality
compared with other sedatives without affecting theintensive care unit length of stay.
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