III Corso Nazionale Teorico Pratico

Emergenze in Infettivologia (CEI)

12-13 maggio 2011

Shock settico: cosa c di nuovo?

M.Verri
U.O. Anestesia e Rianimazione Universitaria
Dir.Prof.R.Alvisi

sono guarito !!!

proteina C attivata
ricombinante ?
(Drotrecogin)

steroidi ?

supporto respiratorio
sostituz.funzione renale
controllo glicemico
nutrizione
sedazione
prevenzione complicanze
ecc.

microbiologia
antibioticoterapia
rimozione sorgente

Ottimizzazione perfusione
volemia
cristalloidi
colloidi
emocomponenti
emoderivati
tono vascolare
vasocostrittori
contrattilit miocardica
dobutamina

S.M.A.R.T. maggio 2011

sono guarito !!!

Coupled Plasma Filtration Adsorption

CPFA

steroidi ?

supporto respiratorio
sostituz.funzione renale
controllo glicemico
nutrizione
sedazione
prevenzione complicanze
ecc.

microbiologia
antibioticoterapia
rimozione sorgente

Ottimizzazione perfusione
volemia
cristalloidi
colloidi
emocomponenti
emoderivati
tono vascolare
vasocostrittori
vasodilatatori ??
contrattilit miocardica
dobutamina
(dopamina)

Sepsis is very complex!

Infectious
agent?

Pro inflammatory
mediator

Other
factors?

early
inhibitors

Receptor
activation

Signal pathway
activation

Inflammatory
cascade

Coagulation
cascade
ROS

Pro- inflammatory
mediators

Anti- inflammatory
mediators

inhibitors

Protein synthesis

Da EMC 2010

Ideal therapy for sepsis

Plasma
bad molecules

Hyper-inflammation
good molecules

Normal
UF out

Immunoparalysis

SIRS =
Systemic inflammatory response
syndrome

Reinfusate in

CARS =
Compensatory anti-inflammatory
response syndrome

CPFA used successfully in non-ARF

patients
Hemodynamic response to coupled
plasmafiltration-adsorption in human
septic shock
Marco Formica, Carlo Olivieri, Sergio Livigni, Giulio
Cesano, Antonella Vallero, Mariella Maio and Ciro Tetta
Intensive Care Med (2003) 29: 703-708

Objective: The objective was to examine the effect of repeated

applications of coupled plasmafiltration-adsorption on the
hemodynamic response in septic shock patients hospitalized in
intensive care units (ICUs).
Conclusion: Coupled plasmafiltration-adsorption was a feasible and
safe extracorporeal treatment and exerted a remarkable improvement
in the hemodynamics, the pulmonary function, and the outcome in
septic shock patients with or without concomitant ARF.

Anne-Cornelie J. M. de Pont, MD, PhD Adult Intensive Care Unit Academic Medical
Center University of Amsterdam Amsterdam, The Netherlands

The improvement of blood purification techniques and membranes has

generated new opportunities for the use of extracorporeal techniques in
sepsis. Removal of both pro- and anti-inflammatory mediators by means of
these new techniques is feasible and might add to the restoration of
homeostasis by controlling excessive cytokine production (the so-called
peak concentration hypothesis). Whether this approach will result in a
better clinical outcome for patients with severe sepsis remains to be
investigated.

Steroids
Consider intravenous hydrocortisone for adult septic shock when
hypotension remains poorly responsive to adequate fluid
resuscitation and vasopressors. (2C)
ACTH stimulation test is not recommended to identify the subset
of adults with septic shock who should receive hydrocortisone.
(2B)
Hydrocortisone is preferred to dexamethasone. (2B)
Fludrocortisone (50g orally once a day) may be included if an
alternative to hydrocortisone is being used which lacks
significant mineralocorticoid activity. Fludrocortisone is optional
if hydrocortisone is used. (2C)
Steroid therapy may be weaned once vasopressors are no longer
required. (2D)
Hydrocortisone dose should be 300 mg/day. (1A)
Do not use corticosteroids to treat sepsis in the absence of shock
unless the patients endocrine or corticosteroid history warrants
it. (1D)

Nov.2008

Steroids
Negli ultimi anni luso dei corticosteroidi nello shock settico
risultato controverso
Pro:
miglioramento emodinamico con pi rapida sospensione dei vasopressori
> rapidit di risoluzione della disfunzione dorgano
< mortalit (?)

Con:

mortalit tra responder e non responder

= rapidit nella sospensione dei vasopressori
> superinfezioni
debolezza neuromuscolare
intolleranza glucidica

Steroids
Annane D, et al. Effect of treatment with
low doses of hydrocortisone and
fludrocortisone on mortality in patients
with septic shock. JAMA 2002;288:862870
S steroidi nello shock settico che
richiede vasopressori
SprungCL, et al. The CORTICUS
randomized, double-blind, placebocontrolled study of hydrocortisone
therapy in patients with septic shock. N
Engl J Med 2008;358:111-124
NO steroidi nello shock settico

Steroids
Recommendations for the diagnosis and management of corticosteroid
insufficiency in critically ill adult patients: Consensus statements from
an international task force by the American College of Critical Care
Medicine
Crit Care Med 2008; 36:19371949

Recommendation 6:
Hydrocortisone should be considered in the
management strategy of patients with septic shock,
particularly those patients who have responded
poorly to fluid resuscitation and vasopressor
agents.
Strength of Recommendations: 2B

Corticosteroids in the Treatment of Severe Sepsis and Septic

Shock in Adults
Annane D, Bellissant E, Bollaert PE, et al.
JAMA. 2009; 301:2362-2375

28-day mortality was modestly reduced (relative risk [RR] = 0.84, P = .05)
and was also modestly reduced in the subset of studies reporting prolonged
corticosteroid administration (RR = 0.84, P = .02). Treatment increased the
proportion of patients achieving reversal of shock and reduced the length of
intensive care unit stay without a detectable increase in gastrointestinal
bleeding, superinfection, or neuromuscular complications. Corticosteroids
did increase the risk for hyperglycemia and hypernatremia. The authors
concluded that the prolonged use of corticosteroids safely reduces shortterm mortality in patients with severe sepsis or septic shock.
Until a definitive clinical trial answers this question, corticosteroid use will
continue to be highly variable and at the discretion of intensivists
worldwide

Conclusions:

Based on clinically meaningful thresholds (RRR[1525%) for

mortality reduction in severe sepsis or septic shock, the Bayesian approach to all
three meta-analyses consistently showed that low-dose steroids were not
associated with survival benefits.
The probabilities of developing
steroid- induced side effects
(superinfections, bleeding,
and hyperglycemia)
were high for all analyses.

Special admission paths: sepsis

R Ferrer, A.Navas, ML Martinez, A.Artigas
The key to success involves the implementation of a
hospital wide system that recognizes septic patients
early, and at the same time rapidly administers
effective therapy ( sepsis-rapid response team)(?)
The results of the meta-analysis are very consistent
in showing that sepsis bundles improve survival by
improving the way sepsis treatments are delivered
Health care organizations traditionally favour
investing in new technology and drugs, but are
reluctant to invest in organizational development. For
sepsis care bundles to succeed, this must change
Barochia AV, Cui X, Vitberg D, Suffredini AF, OGrady NP, Banks SM. Bundled care for septic shock:
an analysis of clinical trial. Crit Care Med 2010; 38(2).668-78
Ferrer R, Artigas A, et al. Effectiveness of treatments for severe sepsis: a prospective,
multicenter, observational study. Am J Respir Crit Care Med 2009; 180(9):861-6
Levy MM, Dellinger RP, Bion J. The Surviving Sepsis Campaign: results of an international
guideline-based performance improvement program targeting severe sepsis. Intensive Care
Med 2010;36(2):222-31

Overall Conclusions
CPFA appears to be a safe and well-tolerated
treatment for treatment of septic patients
CPFA improved hemodynamics, reduced some
pro- and anti- inflammatory cytokines and
restored immune balance
More clinical studies are needed to determine
target septic patient population and
treatment indications

Da Intensive Care Med 2010;36(12): 2019-2029