Sepsis & Septic Shock

60
Sepsis & Septic Shock Mario M. Panaligan, MD, FPCP, FPSMID

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Sepsis & Septic Shock. Mario M. Panaligan, MD, FPCP, FPSMID. REFERENCES. Harrison’s Principles of Internal Medicine, 17 th ed Severe Sepsis and Septic Shock (Chapter 265, pp. 1695-1702) Treatment and Prophylaxis of Bacterial Infections (Chapter 127, pp. 851-864) - PowerPoint PPT Presentation

Transcript of Sepsis & Septic Shock

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Sepsis &Septic Shock

Mario M. Panaligan, MD, FPCP, FPSMID

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REFERENCES • Harrison’s Principles of Internal Medicine, 17th ed

– Severe Sepsis and Septic Shock (Chapter 265, pp. 1695-1702)– Treatment and Prophylaxis of Bacterial Infections (Chapter 127, pp.

851-864)– Antiviral Chemotherapy, Excluding Antiretroviral Drugs (Chapter

171, pp. 1087-1095)– Diagnosis and Treatment of Fungal Infection (Chapter 191, pp.

1242-1244)– Agents Used to Treat Parasitic Infections (Chapter 201, pp. 120-

1275)

Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2008. Critical Care Med 2008; 36 (1): 296-327

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“Sepsis is a disease of

medical progress…”

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SEPSIS

• 10th leading cause of death in the US • Estimated 751, 000 cases of severe sepsis

each year in the US– With a mortality rate of 28.6% and an annual cost

of US$16.7 billion

• Worldwide, 18 million cases of severe sepsis occur annually, killing approximately 1400 people each day and incurring a healthcare cost of US$9.4 billion in Europe alone

Nguyen HB, Rivers EP. The Clinical Practice of Early Goal-Directed Therapy in Severe Sepsis and Septic Shock. Adv Sepsis 2005;4(4):126–33.

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Sepsis

• Prospective observational study at UP-PGH in 1998 involving 1,270 patients– Prevalence rate: 25%– Mortality rate: 34%

• Sepsis-related: 77%• Septic shock: 42%

Alejandria MM, Phil J Microbiol Infec Dis, 2000

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Risk Factors for Progressing to Severe Sepsis and Poor Outcome

Progression RR

Physiologic variables 1.45

Pneumonia 1.47

Abdominal Infection 1.51

Primary bacteremia 1.81

Aerobic gram - bacilli 1.38

Outcome RR

Initial Severity 1.41

Renal dysfunction 1.31

ICU-acquired Infection 1.53

Aerobic gram - bacilli 1.49

Alberti C et al. Am J Respir Crit Care Med 2005; 171: 461Alberti C et al. Am J Respir Crit Care Med 2003; 168: 77

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SIRSSIRS

OtherOther

TraumaTrauma

BurnsBurnsSEPSISSEPSIS

INFECTIONINFECTION

BacteremiaBacteremia

FungemiaFungemia

ParasitemiaParasitemia

ViremiaViremia

OthersOthers PancreatitisPancreatitis

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• A clinical response arisingfrom a nonspecific insult, including 2 of the following:

– Temperature >38oC or <36oC

– HR >90 beats/min– Respiratory rate >20/min

or PaCO2 < 32 mmHg– WBC count >12,000/mm3

or <4,000/mm3 or >10% immature neutrophils

SIRS = systemic inflammatory response SIRS = systemic inflammatory response syndrome.syndrome.

Bone et al. Bone et al. Chest.Chest. 1992;101:1644. 1992;101:1644.

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis

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SIRS = systemic inflammatory response SIRS = systemic inflammatory response syndrome.syndrome.

• SIRS with a presumed or

confirmed infectious process

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis

Bone et al. Chest. 1992;101:1644.

• A clinical response arisingfrom a nonspecific insult, including 2 of the following:

– Temperature >38oC or <36oC

– HR >90 beats/min– Respiratory rate

>20/min or PaCO2 < 32 mmHg

– WBC count >12,000/mm3 or <4,000/mm3 or >10% immature neutrophils

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

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis

• Sepsis with ≥1 sign of organ failure

– Cardiovascular (refractory hypotension)

– Renal– Respiratory– Hepatic– Hematologic– CNS– Unexplained metabolic

acidosis

ShockShock

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Severe Sepsis

WITH

Hypoperfusion abnormalities

AND

Persistent Hypotension

Despite adequate fluid resuscitation

Bone RC, Chest 1992;101:1644-1655 Rangel-Frausto M, JAMA, 1995; 273: 117

SEPTIC SHOCKSEPTIC SHOCK

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SEPTIC SHOCK

PLUS

Altered organ function

such that homeostasis cannot be

maintained without intervention

Bone RC, Chest 1992;101:1644-1655 Rangel-Frausto M, JAMA, 1995; 273: 117

MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS)

MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS)

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Multiple Organ Dysfunction Multiple Organ Dysfunction Syndrome (MODS)Syndrome (MODS)

SEPTIC SHOCKSEPTIC SHOCK

SEPSIS-INDUCEDSEPSIS-INDUCEDHYPOTENSIONHYPOTENSION

SEVERE SEVERE SEPSIS SEPSIS

SEPSISSEPSIS

Sepsis: A Disease Continuum

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PathogenesisTrigger (organism-derived, e.g. endotoxin)

Release of tumor necrosis factor α / other proinflammatory cytokines

Inflammatory cascade

Hypothalamus Capillary endothelial cell Vessel wall

FeverTachycardiaTachypnea

Neutrophil migrationPlatelet adherence

DICDepletion of intravascular vol

Nitric oxide synthesis

Vasodilatation

Cellular hypoxia

Organ dysfunction/hypoperfusion HypotensionDeath

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Signs and symptoms suggestive of sepsis

• Primary– Fever and chills– Hypothermia– Hyperventilation– Skin lesions– Change in mental

status

• Complications– Hypotension– Bleeding– Leukopenia– Organ failure

• Lungs: cyanosis, acidosis

• Kidney: oliguria, acidosis

• Heat: congestive heart failure

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Management of Patients with Sepsis

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DIAGNOSTIC WORK-UP

• HISTORY• Thorough PE

– Search for source/s of infection– Identify signs of systemic organ dysfunction

• Diagnostic tests– Ancillary laboratory exams

• ABGs, Renal and liver function tests, CBC

– Appropriate microbiologic examinations• Specimens are obtained before antibiotic therapy• Consideration for immediate administration of antibiotic/s

Dellinger RP, et al. Crit Care Med, 2008

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Biomarkers of sepsis?

• Utility?– Ability to influence or affect a

diagnostic or therapeutic decision• To identify a subgroup of patients who

are more likely to benefit from a given intervention and to maximize clinical benefit of that therapy

To predict response to therapy

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Biomarkers of sepsis?

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

The PIRO Model

Marshall JC, Current Infect Dis Reports 2006, 8: 351Levy MM, Intensive Care Med 2003, 29: 530

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Surviving Sepsis Campaign: International Guidelines for

Management of Severe Sepsis and Septic Shock: 2008

Dellinger RP, Levy MM, Carlet JM, et al. Critical Care Med 2008; 34: 17-60.

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Issues in Improving Outcome of Patients with Severe Sepsis

• The surviving sepsis guidelines– Early goal-directed therapy (EGDT)

– Low-dose intravenous steroids

– Strict blood glucose level control

– Recombinant activated protein C

– Appropriate early antimicrobial therapy

Dellinger RP et al. Crit Care Med 2008; 32, Suppl

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GRADE System of Recommendations

• Quality of Evidence (Grade)– A (High quality): RCT– B (Moderate): Downgraded RCT or upgraded

observational studies– C (Low): Well done observational studies– D (Very Low): Case series or expert opinion

• Strength of Recommendation– 1: Strong– 2: Weak

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CURRENT MANAGEMENT OF SEVERE SEPSIS AND SEPTIC SHOCK

• Immediate stabilization procedures

• Definitive therapeutic intervention

Dellinger RP, et al. Crit Care Med, 2008

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Recognition Initial Resuscitation

Diagnosis ManagementSupportive Management

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INITIAL RESUSCITATION

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INITIAL RESUSCITATION

• First 6 hours– Begin resuscitation immediately in patients with

hypotension or elevated serum lactate >4mmol/l; do not delay pending ICU admission (1C)

– Resuscitation goals: (1C) • Central venous pressure (CVP) 8 - 12 mm Hg • Mean arterial pressure > 65 mm Hg• Urine output > 0.5 mL/kg/hr• Central venous (superior vena cava) oxygen saturation >

70%, or mixed venous > 65%

Dellinger RP, et al. Crit Care Med, 2008

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IMMEDIATE STABILIZATION

• Reversal of life-threatening abnormalities• Special attention for the ABCs

– Airway protection for patients with depressed level of consciousness

• MV support

– Circulatory support to optimize organ perfusion• Aggressive fluid management• Inotropics or vasopressors when necessary• Hemodynamic monitoring • Urine output

Dellinger RP, et al. Crit Care Med, 2008

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FLUID THERAPY

• Fluid-resuscitate using crystalloids or colloids (1B)– Target a CVP of > 8 mmHg (>12 mmHg if

mechanically ventilated) (1C)– Use a fluid challenge technique while associated

with hemodynamic improvement (1D)• Give fluid challenges of 1000 ml of crystalloids or 300-

500 ml of colloids over 30 minutes

– Rate of fluid administration should be reduced if cardiac filling pressures increase without concurrent hemodynamic improvement (1D)

Dellinger RP, et al. Crit Care Med, 2008

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VASOPRESSORS / INOTROPIC SUPPORT

• Maintain MAP > 65mmHg (1C)• Norepinephrine (NE) or dopamine (DOP)

centrally administered are the initial vasopressors of choice (1C)

• Epinephrine, phenylephrine or vasopressin should not be administered as the initial vasopressor in septic shock (2C)– Use epinephrine as the first alternative agent in

septic shock when BP is poorly responsive to NE or DOP (2B)

Dellinger RP, et al. Crit Care Med, 2008

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VASOPRESSORS / INOTROPIC SUPPORT

• Use dobutamine (DOB) in patients with myocardial dysfunction as supported by elevated cardiac filling pressures and low cardiac output (1C)

• Do not increase cardiac index (CI) to predetermined supranormal levels (1B)

• Do not use low-dose dopamine for renal protection (1A)

• In patients requiring vasopressors, insert an arterial catheter as soon as practical (1D)

Dellinger RP, et al. Crit Care Med, 2008

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DIAGNOSIS AND MANAGEMENT

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DIAGNOSIS

• Obtain appropriate cultures before starting antibiotics provided this does not significantly delay antimicrobial administration (1C)– Obtain two or more blood cultures (BCs)

• One or more BCs should be percutaneous • One BC from each vascular access device in place > 48

hours

– Culture other sites as clinically indicated– Perform imaging studies promptly in order to

confirm; and– Sample any source of infection; if safe to do so

Dellinger RP, et al. Crit Care Med, 2008

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Antimicrobial Therapy

• Mainstay of treatment for patients with infection and sepsis

Dellinger RP, et al. Crit Care Med, 2008

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EMPIRIC ANTIMICROBIAL THERAPY

• Broad-spectrum– Selection based on the presumed site of infection

and the likely pathogens involved• Gram stain result if available• Local susceptibility patterns

– To be started within an hour after performance of important microbiologic exams

• Other factors to consider include– Host’s immune status– Allergies– Renal or hepatic dysfunction

Dellinger RP, et al. Crit Care Med, 2008

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Definitive Antibiotic Therapy

• Pathogen-directed

• Pharmacokinetic – pharmacodynamic properties of the antibiotic

• Site of Infection

Dellinger RP, et al. Crit Care Med, 2008

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PREDICTORS OF POOR OUTCOME

• Age

• Severity of the underlying condition

• Presence of complications at the onset of treatment

• Grade (severity) of bacteremia

• Source of infection

• Inappropriate antimicrobial therapy

Mandell GL, Principles of Infectious Diseases, 2005

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Impact of Inadequate Antibiotic Treatment on All-Cause Mortality

• All-cause mortality: more than twice as high among patients who received inadequate antibiotic treatment compared to those who received adequate antibiotic treatment

52.1

23.5

-5

5

15

25

35

45

55

65

All-cause Mortality (%)

P<0.001

Adapted from MH Kollef et al. Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality. Chest 1999; 115: 462-474

Inadequate AntibioticTreatment

(n=169 patients)

Adequate AntibioticTreatment

(n=486 patients)

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• Infection-related mortality: more than twice as high among patients who received inadequate antibiotic treatment compared to those who received adequate antibiotic treatment

Impact of Inadequate Antimicrobial Treatment on Infection-related Mortality

Adapted from MH Kollef et al. Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality. Chest 1999; 115: 462-474

42

17.7

05

10

1520253035

404550

Infection-related Mortality (%)

P<0.001

Adequate AntibioticTreatment

(n=486 patients)

Inadequate AntibioticTreatment

(n=169 patients)

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Risk factors for mortality

• Non-modifiable– Presence of

malignancy– Severe underlying

condition (High MSOF and MPM scores)

– Gram-negative bacteremia

• Modifiable– Inappropriate

antimicrobial therapy– Use of alternative

antibiotics– Nosocomial

acquisition of infection

Alejandria MM, Phil J Microbiol Infect Dis, 2000

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Timing of antimicrobial therapy• Review of 3 cohorts of adult patients with septic shock

(N=2731)– 58% community-acquired; 42% nosocomial– Documented infection seen in 78%

• 50% received effective antimicrobial treatment within 6 hours of documented hypotension

– Overall mortality was 56%– Survival rate: 82.7% in patients receiving effective

antimicrobials within 30 minutes VS 42% in patients receiving antimicrobials 6 hours after the onset of septic shock

• Mean 7.6% decrease in survival for every hour of delay in the initiation of antibiotic therapy

Kumar A, Crit Care Med 2006; 34: 1589

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Source Control

• Definite identification of site of infection– Drainage of an abscess or local focus of

infection– Debridement of infected necrotic tissue– Removal of a potentially infected device– Definitive control of a source of ongoing

microbial contamination

Dellinger RP, et al. Crit Care Med, 2008

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Sou

rce

Con

trol

Source Control Technique

Examples

DRAINAGE Intraabdominal abscess

Thoracic empyema

Septic arthritis

Cholangitis

DEBRIDEMENT Necrotizing fasciitis

Infected pancreatic necrosis

Intestinal infarction

Mediastinitis

DEVICE REMOVAL Infected vascular catheter

Urinary catheter

Colonized endotracheal tube

Infected intrauterine contraceptive device

DEFINITIVE CONTROL

Sigmoid resection for diverticulitis

Cholecystectomy for gangerenous cholecystitis

Amputation for clostridial myonecrosis

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Supportive ManagementAdjunctive Measures

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Glucose Control

• Use of IV insulin to control hyperglycemia in patients with severe sepsis following stabilization in the ICU (1B)– Aim to keep blood glucose < 8.3 mmol/L (150

mg/dl) using a validated protocol for insulin dose adjustment (2C)

– Provide a glucose calorie source and monitor blood glucose values every 1-2 hrs (4 hrs when stable) in patients receiving IV insulin (1C)

Dellinger RP, et al. Crit Care Med, 2008

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Renal Replacement and Bicarbonate Therapy

• Intermittent hemodialysis (HD) and continuous veno-venous hemofiltration (CVVH) are considered equivalent (2B)

• CVVH offers easier management in hemodynamically unstable patients (2D)

• Do not use bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements when treating hypoperfusion-induced lactic acidemia with pH > 7.15 (1B)

Dellinger RP, et al. Crit Care Med, 2008

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Use of Steroids• Do not use steroids to treat sepsis in the absence

of shock unless the patient’s endocrine or hydrocortisone history warrants it (1D)

• IV hydrocortisone for adult septic shock when hypotension remains poorly responsive to adequate fluid resuscitation and vasopressors (2C)– Hydrocortisone dose is usually < 300 mg/day (1A)– Hydrocortisone is preferred to dexamethasone (2B)– Fludrocortisone (50 ug orally OD) may be included if an

alternative is being used which lacks significant mineralocorticoid activity (2C)

Dellinger RP, et al. Crit Care Med, 2008

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Annane D, BMJ Aug 2004

Use of Steroids

• Meta-analysis of 16 trials (n=2063) on the effects of corticosteroids on mortality in patients with severe sepsis or septic shock– Analysis of 15 trials (n=2022)

• No reduction of all cause mortality in 28 days (RR=0.92, 95% CI 0.75, 1.14)

– Subgroup analysis of 5 trials (long duration > 5 days and low dose corticosteroid therapy)

• All cause mortality: RR=0.8, 95% CI 0.67, 0.95)

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• ACTH stimulation test is not recommended to identify the subset of adults with septic shock who should receive hydrocortisone (2B)

• Steroid therapy may be weaned once vasopressors are no longer required (2D)

Use of Steroids

Dellinger RP, et al. Crit Care Med, 2008

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DVT prophylaxis

• Use either low dose unfractionated heparin (UFH) or low-molecular weight heparin (LMWH), unless contraindicated (1A)

• Use a mechanical prophylactic device such as compression stockings or an intermittent compression device, when heparin is contraindicated (1A)

• Use a combination of pharmacologic and mechanical therapy for patients who are at very high risk for DVT (2C)

• In patients at very high risk, LMWH should be used rather than UFH (2C)

Dellinger RP, et al. Crit Care Med, 2008

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Stress Ulcer Prophylaxis

• Provide stress ulcer prophylaxis using H2 blocker (1A) or PPI (1B)* Benefits of preventing UGIB must be

weighed against the potential for development of VAP

Dellinger RP, et al. Crit Care Med, 2008

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Blood Product Administration

• Give red blood cells when hgb decreases to < 7 g/dl to target a hgb of 7-9 g/dl in adults (1B)

• Do not use erythropoietin to treat sepsis-related anemia (1B)

Dellinger RP, et al. Int Care Med, 2008

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Blood Product Administration

• Only when bleeding leads to hemodynamic compromise

• Potential deleterious effects– Increased viscosity impede blood flow– Decreased unloading of oxygen due to reduced 2,3-DPG

levels in transfused cells– Tissue ischemia due to decreased deformability of

transfused cells– Depress immune status

• No difference in outcome between patients maintained on Hgb levels > 7 g/dl OR 10 g/dl

(Herbert PC, JAMA 1995; 273:1439)

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Blood Product Administration

• Do not use FFP to correct laboratory clotting abnormalities unless there is bleeding or planned invasive procedures (2D)

• Do not use antithrombin therapy (1B)• Administer platelets when: (1B)

– Counts are < 5,000/mm3 regardless of bleeding– Counts are 5,000 to 30,000/mm3 and there is

significant bleeding risk– Higher platelet counts > 50,000/mm3 are typically

required for surgery or invasive procedures

Dellinger RP, et al. Crit Care Med, 2008

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Drotrecogin alfa activated (recombinant activated protein C)

• Significantly reduced mortality in patients with severe sepsis (30.8% vs 24.7%) based on an RCT involving 1690 patients– Higher rate of serious bleeding (3.5% vs 2 %)

• Recommended in patients at high risk of death (APACHE II 25, sepsis-induced multiple organ failure, septic shock, or sepsis-induced ARDS) and no absolute contraindication related to bleeding risk (2B; 2C for post-operative patients)

• Adult patients with severe sepsis and low risk of death should not receive rhAPC (1A)

Dellinger RP, et al. Crit Care Med, 2008

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Prevention of Sepsis

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Preventive Measures

• Appropriateness of the antibiotics

Mandell GL, Principles of Infectious Diseases, 2005

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Preventive Measures

• Risk identification

• Modify host factors for infection– Control underlying illness– Improve immune status through

immunization

EBCPG, ASCO, J Clin Oncol 1996; 14: 1957 Mandell GL, Principles of Infectious Diseases, 2005

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Preventive Measures

• Prevent acquisition or transmission of pathogens– Adherence to infection control policies– Appropriate isolation procedures– Chemoprophylaxis for high risk individuals

Mandell GL, Principles of Infectious Diseases, 2005

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SUMMARY

• Early clinical suspicion• Assessment of disease severity• Rigorous diagnostic work-up• Immediate administration of appropriate

antibiotic therapy• Comprehensive supportive care• Preventive measures particularly for high risk

individuals