Pathophysiology of Septic & Septic Shock, Dr Christian a Johannes SpAn

8/10/2019 Pathophysiology of Septic & Septic Shock, Dr Christian a Johannes SpAn

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Dr. Christian A Johannes, SpAn, KIC

Tempat/ Tanggal Lahir : Jakarta, 27 November

Pendidikan : Dokter umum FK UNSRAT 1979

Anastesi logist FK UNDIP 1990Konsultan ICU IDSAI 1996

Pekerjaan : Kepala ICU RSPAD GS Jakarta

Team Dokter Kepresidenan RI


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Pathophysiology of Septic

and Septic Shock

Chris JohannesHead of Intensive Care Unit Centralrmy Hospital Gatot Subroto

JAKARTA


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ACCP/SCCM ConsensusDefinitions

Infection Inflammatory response to

microorganisms, or Invasion of normally sterile

tissues

Systemic InflammatoryResponse Syndrome(SIRS)

Systemic response to a variety

of processes

Sepsis Infection plus 2 SIRS criteria

Severe Sepsis Sepsis Organ dysfunction

Septic shock

Sepsis Hypotension despite fluidresuscitation

Multiple OrganDysfunction Syndrome

(MODS) Altered organ function in anacutely ill patient

Homeostasis cannot bemaintained withoutintervention

Bone RC et al. Chest. 1992;101:1644-55.


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Mortality of severe sepsis in most centers

remainsunacceptable highThe speed and appropriateness of therapy

administered in the initial hours after the

syndrome develops likely influenceoutcome


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Mortality

SepticShock

53-63%

20-53%Severe Sepsis300,000

7-17%Sepsis

400,000

Incidence

Balk, R.A. Crit Care Clin 2000;337:52

Mortality Increases in Septic Shock Patients


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INCIDENCE ANDMORTALITY


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0

50,000

100,000

150,000

200,000

250,000

D e a

t h s

/ Y e a r

Severe Sepsis:Comparison With Other Major Diseases

National Center for Health Statistics, 2001.American Cancer Society, 2001.

0

50

100

150

200

250

300

AIDS* Colon BreastCancer

CHF SevereSepsis

C a s e s

/ 1 0 0

, 0 0 0

Incidence of Severe Sepsis

AIDS* SevereSepsis

AMI BreastCancer

*American Heart Association. 2000.Angus DC et al. Crit Care Med 2001 In Press).

Mortality of Severe Sepsis


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Mortality Severe Sepsis:

Angus DC et al. Cr i t Ca re Med . 2001 (In Press). Sands KE et al. J A M A . 1997;278:234-40. Zeni F et al. Cri t Care Med . 1997;1095-100.

28% 34%

50%

0

20

40

60

M o r t a

l i t y

( % )

2001


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Brazilian Sepsis

Epidemiological Study

Mortalitas

Sepsis 33.9%

Severe sepsis 46.9%

Septic shock 52.2%


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Hospital mortality (%)


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The interrelationship between SIRS, sepsis, and infection

Chest 1992;101:1645

INFECTION SIRSSEPSIS

PANCREATITIS

BURNS

TRAUMA

OTHER

OTHER

VIREMIA

PARASITEMIA

FUNGEMIA

BACTERIEMIA


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Sepsis: A Complex DiseaseThis Venn diagram

provides a conceptualframework to viewthe relationships

between variouscomponentsof sepsis.

The inflammatory

changes of sepsis aretightly linked todisturbed hemostasis.

Adapted from: Bone RC et al. Chest. 1992;101:1644-55.

Opal SM et al. Crit Care Med . 2000;28:S81-2.


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SIRS: More Than Just a Systemic

Inflammatory ResponseSIRS: A clinical responsearising from a nonspecificinsult manifested by

2 of the following: Temperature

38C or 36C HR 90 beats/min Respirations 20/min WBC count 12,000/ mL or

4,000/ mL or >10% immatureneutrophils

Recent evidence indicatesthat hemostatic changes arealso involved

Adapted from: Bone RC et al. Chest. 1992;101:1644-55.Opal SM et al. Crit Care Med . 2000;28:S81-2.


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Sepsis: More Than JustInflammation

Sepsis : Known or suspected

infection Two or more

SIRS criteria

A significant linkto disorderedhemostasis

Adapted from: Bone RC et al. Chest. 1992;101:1644- 55.


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Severe Sepsis: Acute OrganDysfunction and DisorderedHemostasisSevere Sepsis:

Sepsis with signs oforgan dysfunction in 1of the followingsystems:

Cardiovascular Renal Respiratory Hepatic Hemostasis CNS Unexplained metabolic

acidosis Adapted from: Bone RC et al. Chest. 1992;101:1644- 55.


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Identifying Acute OrganDysfunction as a Marker ofSevere Sepsis

TachycardiaHypotension

CVPPAOP

JaundiceEnzymes Albumin

PT

AlteredConsciousness

ConfusionPsychosis

TachypneaPaO 2


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Angus DC et al. Crit Care Med . 2001; (In Press).

Zeni F et al. Crit Care Med . 1997;25:1095-100.Wheeler AP et al. N Engl J Med . 1999;340:207-14.

Severe Sepsis: A Complex and

Unpredictable Clinical SyndromeHigh mortality rate(28%-50%)

Heterogeneous patient population

Unpredictabledisease progression

Unclear etiologyand pathogenesis

SystemicInflammation

ImpairedFibrinolysis

Coagulation


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Sepsis: Defining a Disease Continuum

Bone et al. Chest. 1992;101:1644; Wheeler and Bernard. N Engl J M ed . 1999;340:207.

Sepsis SIRS Insult Severe Sepsis

Sepsis with 1 sign of organfailure

Cardiovascular (refractoryhypotension)

Renal

RespiratoryHepaticHematologicCNSMetabolic acidosis

Shock


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Initial Resuscitation Diagnosis Antibiotic therapy Source Control Fluid therapy Vasopressors Inotropic Therapy Steroids Recombinant Human

Activated Protein C(rhAPC) [drotrecoginalfa (activated)]

Blood Product Administration Mechanical Ventilation

Sedation, Analgesia, and NeuromuscularBlockade in Sepsis

Glucose Control

Renal Replacement

Bicarbonate Therapy

Deep Vein Thrombosis Prophylaxis

Stress Ulcer Prophylaxis

Limitation of Support

Index

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.


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SEPSIS

Systemic Inflammatory Response (SIRS) toINFECTION manifested by two or > of following:

Temp > 38 or < 36 centigrade HR > 90 RR > 20 or PaCO2 < 32

WBC > 12,000/cu mm or > 10% Bands (immature wbc)


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Risk Factors Associated with Septic

Shock Age

Malnutrition

General debilitation

Use of invasive

catheters

Traumatic wounds

Drug Therapy


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Pathophysiology of Septic shock

Initiated by gram-negative (most common) orgram positive bacteria, fungi, or virusesCell walls of organisms contain Endotoxins

Endotoxins release inflammatory mediators(systemic inflammatory response) causes... Vasodilation & increase capillary permeability leadstoShock due to alteration in peripheral circulation &massive dilation


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Pathophysiology of Septic Shock

IMMUNE / INFLAMMATORY RESPONSE

Microorganisms enter body

Mediator Release

Activation of Complement, kallikrein / kinin/ coagulation

& fibrinolytic factors platelets, neutrophils &macrophages>>damage to endothelial cells.

ORGAN DYSFUNCTION


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Sequelae of Septic Shock

The effects of the bacterias endotoxins cancontinue even after the bacteria is dead!!!


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ISF DEBATES:CONTROVERSIES IN SEPSIS

Vasopressor Therapyof Septic Shock:

Norepinephrine vs. DopamineSummary

Phillip Dellinger, MDJean-Louis Vincent, MD


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No high level evidence exists to

support better clinical outcomewith either dopamine ornorepinephrine when compared tothe other drug.


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Either dopamine or norepinephrine, as acombined inotrope/vasopressor, ispreferred over alternative drugs as firstline agents to treat hypotension in septicshock.


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Non-clinical outcome physiological

studies may be used to offer potentialadvantages of norepinephrine ordopamine, one over the other.


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In patients with poor contractility as a

major component of the hypotension,dopamine may be a better initialchoice.


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Some patients who do not achieveacceptable blood pressure with dopaminewill achieve that goal withnorepinephrine.


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Surviving Sepsis Campaign (SSC)Guidelines- Vasopressors

Either norepinephrine or dopamine(through a central line as soon as

available) is the first-choicevasopressor agent to correcthypotension in septic shock.

Grade D


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Low dose dopamine should not be used forrenal protection in severe sepsis

An arterial catheter should be placed as soonas practical in all patients requiringvasopressors Arterial catheters provide more accurate

and reproducible measurement of arterial pressure in shock states when compared tousing a cuff

Vasopressin may be cons idered in refractoryshock patients that are ref ractory to fluidresuscitation and high dose vasopressors

Vasopressors (cont)

Grade B

Grade E

Grade E


Hollenberg SM. Crit Care Med 1999; 27:639-660.Bellomo R. Lancet 2000; 356: 2139-2143 .Kellum J. Crti Care Med 2001; 29: 1526-1531.
http://www.sccm.org/professional_resources/guidelines/table_of_contents/index.asphttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11505120&itool=iconabstrhttp://www.sccm.org/professional_resources/guidelines/table_of_contents/index.asphttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11191541&itool=iconabstrhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11505120&itool=iconabstrhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11505120&itool=iconabstrhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11505120&itool=iconabstrhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11505120&itool=iconabstrhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11191541&itool=iconabstrhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11191541&itool=iconabstrhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11191541&itool=iconabstrhttp://www.sccm.org/professional_resources/guidelines/table_of_contents/index.asphttp://www.sccm.org/professional_resources/guidelines/table_of_contents/index.asphttp://www.sccm.org/professional_resources/guidelines/table_of_contents/index.asp


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In patients with low cardiac output despiteadequate fluid resuscitation, dobutamine may

be used to increase cardiac output Should be combined with vasopressor therapy

in the presence of hypotension It is not recommended to increase cardiacindex to target an arbitrarily predefinedelevated level Patients with severe sepsis failed to benefit from

increasing oxygen delivery t o supranormal levels by use of dobutamine

Inotropic TherapyGrade E

Grade A

Gattinoni L. N Eng J Med 1995;333:1025-1032.

Hayes MA. N Eng J Med 1994;330:1717-172 2.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7675044http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7675044http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7993413http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7993413http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7993413http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7993413http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7993413http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7993413http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7993413http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7675044http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7675044http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7675044


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Location of gun shoot N---------------------------------------------------------------

1. Abdomen 6

2. Thorax 23. Thoraco Abdominal 14. Head 25. Musculosceletal 1

--------------------------------------------------------------Total 12


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Clasification of Sepsis N---------------------------------------------------------------

1. Sepsis 3

2. Severe Sepsis 43. Septic Shock 5

--------------------------------------------------------------

Total 12


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Isolated micro organism from blood1. Klebsiella sp ( 4 pts )2. Enterobacter sp ( 2 pts )

3. Pseudomonas aerogenosa ( 2 pts )4, Escheria coli ( 1 pts )


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On Ventilator : 8 pts. ( e.c. ARDS ) All pts we give Fluid. ( Crystalloid an Colloid)Antibiotic : Meropenem

CefipimeSource ControlVasopressors ( Noerepinephrine, Dopamine,Dobutamine ) Glucocorticoid if there any indication.Glucose ControlNutrition Therapy


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Polyclonal IVIGTight Monitoring.

- Hemodynamic monitoring.

- SaO2- BGA

- Blood Glucose.

- Urine Output


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RESULT8 pts ( 66,6 % ) survived

4 pts ( 33,3 % ) died.


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CONCLUSION

IF WE USE THE GUIDELINES FROMSURVIVING SEPSIS CAMPAIGN, THEMORTALITY IN SEPSIS COULD BEDECREASED.


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Pathophysiology of Septic & Septic Shock, Dr Christian a Johannes SpAn

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