pathophysiology of sepsis phil(2) · 3angus dc, et al. crit care med 2001;29:1303-10. ... major...
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The Magnitude and Pathophysiologyof Severe Sepsis
R. Phillip Dellinger, MDR. Phillip Dellinger, MDProfessor of MedicineProfessor of Medicine
Robert Wood Johnson Medical SchoolRobert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyUniversity of Medicine and Dentistry of New Jersey
Head, Division of Critical Care MedicineHead, Division of Critical Care MedicineCooper University HospitalCooper University Hospital
Camden, New JerseyCamden, New Jersey
* Based on data for septicemia * Based on data for septicemia ††Reflects hospitalReflects hospital--wide cases of severe sepsis as defined by infection in the presewide cases of severe sepsis as defined by infection in the presence of organ dysfunction nce of organ dysfunction 11Sands KE, et al. Sands KE, et al. JAMAJAMA 1997;278:2341997;278:234--40.40.22Murphy SL. National Vital Statistics Reports. 1998.Murphy SL. National Vital Statistics Reports. 1998.33Angus DC, et al. Angus DC, et al. CritCrit Care MedCare Med 2001;29:13032001;29:1303--10. 10.
SEVERE SEPSIS:A Significant Healthcare Challenge
Major cause of morbidity and mortality Major cause of morbidity and mortality worldwideworldwide
Leading cause of death in Leading cause of death in noncoronarynoncoronary ICU (US)ICU (US)11
1111thth leading cause of death overall (US)leading cause of death overall (US)22**More than 750,000 cases of severe sepsis in More than 750,000 cases of severe sepsis in the US annuallythe US annually33
In the US, more than 500 patients die of In the US, more than 500 patients die of severe sepsis dailysevere sepsis daily33††
0
50
100
150
200
250
300
Severe Sepsis Stroke Breast Cancer Lung Cancer
IncidenceMortality
*Calculated data based on information compiled from the American Heart Association, American Cancer Society, National Center for Health Statistics and the US Census Bureau (1995-1999).
†Severe sepsis mortality rates range from 28%-50% (79/100,000 to 141/100,000 population).
SEVERE SEPSIS IS COMMON*R
ate
per
100,
000
Pop
ulat
ion
†
Patient Characteristics and Costof Severe Sepsis and
Septic Shock in Quebec
LetarteLetarte J, Longo CJ, Pelletier J, et alJ, Longo CJ, Pelletier J, et alJ J CritCrit Care Care 2002; 17(1):392002; 17(1):39--4949
Nonsurvivor$7,584 total/$1,724 daySurvivor$16,228 total/$877 day
Pathogenesis of Severe Sepsis
Infecting organismInfecting organism↓↓
Initiators (Initiators (endotoxin/exotoxinendotoxin/exotoxin))↓↓
MediatorsMediators↓↓
Organ dysfunction and shockOrgan dysfunction and shock
Balk RA. Crit Care Clin 2000;16:337-52.
IDENTIFYING ACUTE ORGAN DYSFUNCTION AS MARKERS OF SEPSIS AND SEVERE SEPSIS
TachycardiaTachycardiaHypotensionHypotensionAlteredAltered CVPCVP
AlteredAltered PAOPPAOP
OliguriaOliguriaAnuriaAnuria
↑↑ CreatinineCreatinine
↓↓ PlateletsPlatelets↑↑ PT/APTTPT/APTT↓↓ Protein CProtein C↑↑ DD--dimerdimer
JaundiceJaundice↑↑ EnzymesEnzymes↓↓ AlbuminAlbumin
↑↑ PTPT
Altered Altered ConsciousnessConsciousness
ConfusionConfusionPsychosisPsychosis
TachypneaTachypneaPaOPaO22 <70 mm Hg<70 mm Hg
SaOSaO22 <90%<90%PaOPaO22/FiO/FiO22 ≤≤300300
Figure B, page 948, reproduced with permission from Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955.
Schrier R and Wang W. N Engl J Med 2004;351:159-169
Arterial Vasodilatation and Renal Vasoconstriction in Patients with Sepsis
Predictive value of microalbuminuria in medical ICU patients
Abid O, Sun, Q, Sugimoto K, et al.Abid O, Sun, Q, Sugimoto K, et al.Chest Chest 2001; 120:19842001; 120:1984--19881988
High Perfused Vessel Density (Sublingual OPS High Perfused Vessel Density (Sublingual OPS in normal individual)in normal individual)
Organ Dysfunction and Mortality:Baseline and Dynamic Values
Marshall et al. Marshall et al. CCMCCM 1995; 23(10):16381995; 23(10):1638--16521652
ICU Outcome According to theMaximum Number of SIRS Criteria at Admission
Sprung et al. Intensive Care Med 2006; 32:421-427
The PIRO Model of Sepsis
OO
RR
II
PPGeneticsChronic Illness
Cultural Attitudes
ShockARDS, etc.
PhysiologicSpecific MediatorsGeneric Markers
INFECTION
Type of Organism
PREDISPOSITION
ORGAN DYSFUNCTION
RESPONSE
Site
Extent
Levy MM et al, CCM 2003; 31(4):1250-1256
37
38
39
40
[°C
]
0
10
20
30
40
[G/l]
0
6
12
18
24[n
g/m
l]
050
100150200250300350
[mg/
l]
NoneSIRS
Sepsis
Sev. Sepsis
Sept. Shock NoneSIRS
Sepsis
Sev. Sepsis
Sept. Shock
CRPPCT
LeukocytesTemperature
[n.s.]
[<0.0001]
[<0.0001]
[<0.0001]
20% 8% 7% 20% 72%
Outcome of Sepsis is Related to Severity of the Host Response
Rangel-Frausto et al. JAMA 1995.
3 7 1017 16 20
46
0
10
20
30
40
50
60M
orta
lity
(%)
NoSIRS
SIRS2 SIRS3 SIRS4 Sepsis SevereSepsis
SepticShock
Severity
Diagnostic Dilemma:Heart Attack vs. Sepsis
Heart AttackHeart AttackEKGEKGCardiac EnzymesCardiac Enzymes
CPKCPKMBMB
TroponinTroponinCRPCRPEchocardiogramEchocardiogramCardiac Cardiac CatheterizationCatheterization
SepsisSepsisSigns and symptomsSigns and symptoms
Fever, chills, Fever, chills, elevated WBC, elevated WBC, difficulty breathingdifficulty breathing
““Look sickLook sick””Objective Objective measurementsmeasurements……
The Future
More precise and earlier More precise and earlier identificationidentificationPrevention of organ dysfunction Prevention of organ dysfunction from occurringfrom occurringTargeting newly recognized and still Targeting newly recognized and still poorly understood mediatorspoorly understood mediators
Such as heat shock proteinSuch as heat shock protein