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La terapia antibiotica,i fluidi, il sostegno emodinamico nella sepsi

severa

Roberto Fumagalli Ospedale Niguarda Ca Granda Universt degli Studi Milano Bicocca

Financial disclosure: none

Inappropriate Antimicrobial Therapy: Prevalence among Intensive Care Patients

Source: Kollef M, et al: Chest 1999;115:462-74

Community-onset infection Hospital-onset infection Hospital-onset infection after initial community-onset infection

Inappropriate Antimicrobial Therapy (n = 655 ICU patients with infection)

Patient Group

17.1%

34.3%

45.2%

Terapia antibiotica adeguata vs inadeguata: batteriemia e sepsi severa/shock settico

RAHAL et Al. Critical Care 2008, 12(suppl 4): S5

Early antibiotics are good... Author n Setting Median time

(mins) Odds Ratio for death

Gaieski Crit Care Med 2010; 38:1045-53

261 ED, USA (Shock)

119 0.30 (first hour vs all times)

Daniels Emerg Med J 2010; doi:10.1136

567 Whole hospital, UK

121 0.62 (first hour vs all times)

Kumar Crit Care Med 2006; 34(6):1589-1596

2154 ED, Canada (Shock)

360 0.59 (first hour vs second hour)

Appelboam Critical Care 2010; 14(Suppl 1): 50

375 Whole hospital, UK

240 0.74 (first 3 hours vs delayed)

Levy Crit Care Med 2010; 38 (2): 1-8

15022 Multi-centre 0.86 (first 3 hours vs delayed)

ANTIBIOTICOTERAPIA Somministrazione ev di ATB entro la prima

ora dal riconoscimento della sepsi grave o dello shock settico

Utilizzare un ampio spettro ATB (uno o pi) empirico contro il possibile patogeno, che penetri bene nel sito di infezione

RACCOMANDATO

ANTIBIOTICOTERAPIA

La restrizione degli antibiotici per ridurre le resistenze e i costi non la strategia iniziale appropriata per questi pz.

Limitare la durata della terapia a 7-10 gg; durata maggiore se risposta clinica lenta, immunodeficienza o se foci non

drenabili Stop ATB se confermata causa non infettiva Terapia di combinazione

Se Pseudomonas Pz neutropenico Per < di 3-5 gg poi de-escalation dopo aver ottenuto lantibiogramma

DE-ESCALATION THERAPY

Stage 1 Administering the broadest-spectrum

antibiotic therapy to improve outcomes (decrease mortality, prevent organ dysfunction, and decrease length of stay)

Stage 2 Focusing on de-escalating as a means to

minimize resistance and improve cost-effectiveness

Conclusions: De-escalation appears feasible in most cases without any obvious negative clinical impact in a medical ICU.

Esse sono, insieme, conseguenza e causa di eventi metabolici e danno tissutale

Le alterazioni circolatorie hanno un ruolo centrale nello SHOCK settico

Levento emodinamico principale nello shock settico la

MODS INSUFFICIENZA CARDIOCIRCOLATORIA

vasodilatazione arteriosa

COMPONENTI:

Vasodilatazione arteriosa

Ipovolemia - perdite verso lesterno - aumentata permeabilit

Depressione miocardica - ridotta compliance - ridotta frazione deiezione

MODS INSUFFICIENZA CARDIOCIRCOLATORIA

COMPONENTI:

Vasodilatazione arteriosa

Ipovolemia - perdite verso lesterno - aumentata permeabilit

Depressione miocardica - ridotta compliance - ridotta frazione deiezione

MODS INSUFFICIENZA CARDIOCIRCOLATORIA

Types of Colloids

Types B

VISEP Study (Volume Substitution and Insulin Therapy in Severe Sepsis)

P=0.14 P=0.001

Normal Over

Low dose: 22 mL/kg BW/d; High dose: > 22 mL/kg BW/d Brunkhorst FM et al. NEJM 2008;358:12539

Cumulative Effect of Volume Resuscitation on the Need for Renal-Replacement Therapy and the Rate of Death at 90 Days

Brunkhorst FM et al. N Engl J Med 2008;358:125-139

6S Study (Scandinavian Starch for Severe Sepsis/Septic Shock)

Investigation in haemodynamically mostly stabilized patients no indication for HES!

Volumen replacement was not goal-directed. Criteria for renal replacement therapy

(a secondary outcome variable) were not defined! Use of potato-derived starch solution

Perner A et al. N Engl J Med 2012;367:124-34

6S Study Main limitations

CHEST Study (Crystalloid versus Hydroxyethyl Starch Trial)

HES Saline Relative Risk (95% CI) P Value

Myburgh JA et al. N Engl J Med 2012;367:1901-11

Criteria for begin of renal replacement therapy (RRT) were not defined ( such therapy was initiated at the discretion of the attending clinicians ). RRT was merely a secondary endpoint adequate power only for primary endpoint lack of statistical validity regarding RRT data

BUT!

Mortality and Hydroxyethyl Starch

Zarychanski R, et al. JAMA 2013;309:67888

N Engl J Med. 2014 Apr 10;370(15):1412-21.

METHODS

During the early phase of volume resuscitation, fluids were administered in both groups according to early goal-directed therapy

In the a. g. 20% from day 1 until day 28 albumin was administered on a daily basis, to mantain a serum albumin level of 30 g/L or more (300 ml if

OUTCOMES (subgroup analysis)

*post-hoc subgroup analysis

*

N Engl J Med. 2014 Apr 10;370(15):1412-21.

COMPONENTI:

Vasodilatazione arteriosa

Ipovolemia - perdite verso lesterno - aumentata permeabilit

Depressione miocardica - ridotta compliance - ridotta frazione deiezione

MODS INSUFFICIENZA CARDIOCIRCOLATORIA

Meccanismi fisiopatologici della vasodilatazione

Donald, N Eng J Med, 2001

Receptor Physiology

Receptor Location Effect

Alpha-1 Adrenergic Vascular wall Vasoconstriction

Heart Increase duration of contraction without

increased chronotropy

Beta Adrenergic Beta-1 Heart Inotropy and chronotropy

Beta-2 Blood vessels Vasodilation

Dopamine Renal Vasodilation

Splanchnic (mesenteric)

Coronary Cerebral

Subtype Vasoconstriction

Drug Alpha-1 Beta-1 Beta-2 Dopaminergic Predominant Clinical Effects

(Neosynephrine) Phenylephrine *** 0 0 0 SVR , CO /

(Levophed) Norepinephrine *** ** 0 0 SVR , CO /

(Adrenalin) Epinephrine *** *** ** 0

CO , SVR (low dose) SVR/ (higher dose)

(Intropin) Dopamine

(mcg/kg/min)

0.5 to 2 0 * 0 ** CO

5 to 10 * ** 0 ** CO , SVR

10 to 20 ** ** 0 ** SVR

Dobutamine 0/* *** ** 0 CO , SVR

Isoproterenol 0 *** *** 0 CO , SVR

*** Very Strong Effect, ** Moderate effect, * Weak effect, 0 No effect.

Vasoactive Medication Receptor Activity and Clinical Effects

Original Article Vasopressin versus Norepinephrine Infusion

in Patients with Septic Shock James A. Russell, M.D., Keith R. Walley, M.D., Joel Singer, Ph.D., Anthony C. Gordon, M.B., B.S., M.D., Paul C. Hbert, M.D., D. James Cooper, B.M.,

B.S., M.D., Cheryl L. Holmes, M.D., Sangeeta Mehta, M.D., John T. Granton, M.D., Michelle M. Storms, B.Sc.N., Deborah J. Cook, M.D., Jeffrey J.

Presneill, M.B., B.S., Ph.D., Dieter Ayers, M.Sc., for the VASST Investigators

N Engl J Med Volume 358(9):877-887

February 28, 2008

Kaplan-Meier Survival Curves for Patients Who Underwent Randomization and Infusion

Russell JA et al. N Engl J Med 2008;358:877-887

INTERACTIONS BETWEEN FLUIDS AND VASOACTIVE AGENTS ON MORTALITY IN

SEPTIC SHOCK: A MULTICENTER OBSERVATIONAL STUDY

J Waecher et al: CCM Oct 2014, 42,10:2158-2168

Retrospective evaluation using a multivariate logistic regression to evaluate the association between

mortality, timing and amount of fluid resuscitation in septic shock

The focus during the first hour of resuscitation should be aggressive

fluid administration only thereafter starting vasoactive drugs

INTERACTIONS BETWEEN FLUIDS AND VASOACTIVE AGENTS ON MORTALITY IN SEPTIC SHOCK: A MULTICENTER OBSERVATIONAL STUDY

J Waecher et al: CCM Oct 2014, 42,10:2158-2168

Thank you roberto.fumagalli@unimib.it

La terapia antibiotica,i fluidi, il sostegno emodinamico nella sepsi severaInappropriate Antimicrobial Therapy: Prevalence among Intensive Care PatientsTerapia antibiotica adeguata vs inadeguata: batteriemia e sepsi severa/shock setticoDiapositiva numero 4Early antibiotics are good...ANTIBIOTICOTERAPIAANTIBIOTICOTERAPIADE-ESCALATION THERAPYDiapositiva numero 9Diapositiva numero 10Diapositiva numero 11Diapositiva numero 12Diapositiva numero 13Diapositiva numero 14Types of ColloidsTypes BDiapositiva numero 17Diapositiva numero 18Diapositiva numero 19Diapositiva numero 20Diapositiva numero 21Diapositiva numero 22Diapositiva numero 23Diapositiva numero 24Diapositiva numero 25Diapositiva numero 26Diapositiva numero 27Diapositiva numero 28METHODSOUTCOMES (subgroup analysis)Diapositiva numero 31Diapositiva numero 32Diapositiva numero 33Diapositiva numero 34Diapositiva numero 35Diapositiva numero 36Diapositiva numero 37Diapositiva numero 38Diapositiva numero 39Diapositiva numero 40Diapositiva numero 41Diapositiva numero 42Diapositiva numero 43Diapositiva numero 44Diapositiva numero 45INTERACTIONS BETWEEN FLUIDS AND VASOACTIVE AGENTS ON MORTALITY IN SEPTIC SHOCK: A MULTICENTER OBSERVATIONAL STUDYINTERACTIONS BETWEEN FLUIDS AND VASOACTIVE AGENTS ON MORTALITY IN SEPTIC SHOCK: A MULTICENTER OBSERVATIONAL STUDYDiapositiva numero 48Diapositiva numero

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