Septic Shock

Maternal MortalityMaternal Mortality-- Safe Motherhood Initiative Safe Motherhood Initiative --

In 2002 the “Safe Motherhood Initiative” was

launched as a joint venture between NYS Dept

of Health and ACOG District II. of Health and ACOG District II.

The goals of the program :

1. - Overall decrease in maternal mortality:

2. - Eliminates the disparity between white and black women

Maternal MortalityMaternal Mortality-- Safe Motherhood Initiative Safe Motherhood Initiative --

Reporting Maternal Deaths through the S.M.I.

was on a voluntary basis � from 8/03 through

6/05 there were 37 Maternal Deaths reported6/05 there were 37 Maternal Deaths reported

to ACOG District II through the S.M.I.

Maternal MortalityMaternal Mortality-- Safe Motherhood Initiative Safe Motherhood Initiative --

Embolism 24%

Most common causes of M.M.

PIH 24%

Hemorrhage 15%

Infectious 15%

Cardiac 6%

Maternal MortalityMaternal Mortality-- Safe Motherhood Initiative Safe Motherhood Initiative --

1.- Hemorrhage Protocol

2.- Preconceptional counselling2.- Preconceptional counselling

3.- Management of Sepsis and septic shock

4.- Obesity

5.- Critical Care in Obstetrics

Septic Shock- Case presentation -

C/O - Fever, nausea, vomiting 2-3d

- Other fam members � same symptoms

Mrs X , 36y old P2 at 34wks

V.S. -Temp 104, BP 97/57, Pulse 150, R.R. 22

P.E. - Non-focal: Lungs clear, Abd non-tender

Labs - WBC 8,000 Hct 33%, Hb 11g

Fever etiology ?? - Hydration, �Temp, EFM

- Sepsis workup

Septic Shock- Case presentation -

Initial FHR:

- Bseline 200bpm, �variability, no decels

Hospital Course

- Bseline 200bpm, �variability, no decels

2hrs after Adm:

- Temp 102, BP 94/45, Pulse 150, R.R. 18, O Sat 95%

4 hrs after Adm:

- FHR Decelerations

430 hrs after Adm:

- Decision for C/S

Adhesion molecules

Septic Shock- Case presentation -

Septic Shock-Case presentation –

Septic Shock- Case presentation -

Delivery 401 A.M. (EBL=800cc)

To R.R. 430 A.M.

4:45A.M. Temp 98.9o F

5:00A.M. BP 80/40 Ephedrine BP 100/55

6:45A.M. O2 Sat 85%, -75% � O2 � Rpt Sat 95%

7:00A.M. pH=7.27 pO2=47 pCO2=41 HCO3=18

7:30A.M. Temp 99.5o F, CxR Bil pleural effusion

Septic Shock- Case presentation -

Delivery 401 A.M. (EBL=800cc)

To R.R. 430 A.M. Urinary Output

5A.M. 50cc5 50cc6A.M. 50cc7A.M. 45cc8A.M. 25cc9A.M. 25cc10A.M. 20cc11A.M. 10cc 12P.M. 30cc1P.M. 60cc

� Fluids

Septic Shock- Case presentation -

PregnancyPost surgery Ac resp distress

R/O Pulmonary Embolus

- 8A.M. Heparin theray started

- 2P.M. CT - No evidence of Emboli- Infiltrates sugg of pulm. edema

- 8A.M. Heparin theray started- CT of chest requested

Temp 99-101o F, O2 Sat 95-97%, UO > 30cc/h

Septic Shock- Case presentation -

CT � Bil Infiltrates

Rpt WBC � 15,000

Fever 1010 F

O2 desaturation

Pneumonia – Sepsis -ARDS

O2 desaturation

Low BP’s- 5P.M. Antibiotic Rx � ICU

-10P.M. Respiratory DistressIntubated � Vent (PEEP=15cm H2 O)Rpt CxR � ARDS

Septic Shock- Case presentation -

No improvement Pulmonary StatusLevophed Maintain BP’sBlood Culture Strep PneumoniaRx Imipenem, Gentamycin

Day 1-7

Rx Imipenem, GentamycinXigris (APC) started

WBC’s 18-33,000Temp 102-103 F

Day 8-9

2nd Septic Source ?

Septic Shock- Case presentation -

CxR No empyemaNo other studies done (Pat unstable)

#9 Explor laparotomy � TAH* in ICU

2nd Septic Source

#9 Explor laparotomy � TAH* in ICU

Temp’s � 98-100 FWBC’s � 17,000

Pulmonary – No ChangePressor agents – No Change

#14 Cardiac Arrest � Death

* Endomyometritis with abcess formation

Septic Shock- Case presentation -

-Delay in Dg

-Delay in initiation of antibiotic therapy

Mrs X , 36y old P2 at 34wks ���� 2A.M.

-Delay in initiation of antibiotic therapy

-Delay in initiation of hemodynamic monitoring

- Delay in initiation of aggressive fluid management

ICU Admission in Septic Shock � 5 P.M.

Maternal Mortality 2wks later

Septic Shock

Consensus conference of American College of Chest Physicians and Society of Critical Care Medicine on Sepsis and related disorders – 1992

- Systemic inflamatory response syndrome- Systemic inflamatory response syndrome

- Sepsis

- Severe Sepsis

- Septic Shock

- Multiple Organ Dysfunction Syndrome

Systemic Inflamatory Response Syndrome

Septic Shock

The organisms response to any insult

SIRS*

- Infectious, Trauma, Toxic

>2 of the following :

Definition

Diagnosis

*Systemic Inflamatory Response Syndrome

>2 of the following :-Temperature >380C or <360C- Heart Rate > 90 bpm- Respiratory Rate >20/min-WBC >12,000 or <4,000- Organ dysfunction

(Neuro, Renal, Clotting, Acidosis, etc)

Diagnosis

Septic Shock

BacteremiaPresence of bacteria in the blood

SIRSSystemic Inflamatory Response Syndrome

Sepsis

Severe sepsis

Septic Shock

Documented infection + Evidence of SIRS

SIRS

Sepsis associated with organ dysfunction (MODS)

Sepsis induced hypotension despite adequate hydration

Response Syndrome

Septic Shock

1.- Individual entities ?Increasingly severe responses to same insult

2.- Do they develop sequentially ?

Progression after 2.- Do they develop sequentially ?

3.- Risk of specific end-organ failure ?

4.- Mortality Rates ?

Progression after hospitalization ?

ARDS, DIC, ARF

Septic Shock

A large study of 2,527 patients that met at least 2 criteria for SIRS and were followed for 28d in the hospital or until discharge/death.28d in the hospital or until discharge/death.

Rangel-Fausto et al JAMA-1995

Septic Shock

SIRS 1301 (52%)

Sepsis 649 (26%)

Final Diagnosis

Rangel-Fausto et al JAMA-1995

Sepsis 649 (26%)

Severe Sepsis 467 (18%)

Septic Shock 110 (4%)

Septic Shock

Final Dg Present on Admission

Progressed in Hospital

Sepsis 56% 44%

Rangel-Fausto et al JAMA-1995

Sepsis 56% 44%

Severe Sepsis 42% 58%

Septic Shock 29% 71%

Septic Shock

SIRS Advance to higher level

Advance to Septic Shock

Rangel-Fausto et al JAMA-1995

2 criteria 32% 11%

3 criteria 36% 21%

4 criteria 45% 27%

Septic Shock

Sepsis 16%

⊕⊕⊕⊕ Blood Cultures

Rangel-Fausto et al JAMA-1995

Sepsis 16%

Severe Sepsis 25%

Septic Shock 69%

Septic Shock

Dg ARDS DIC ARF

SIRS-2 2% 8% 9%

SIRS-3 3% 15% 13%

Rangel-Fausto et al JAMA-1995

SIRS-3 3% 15% 13%

SIRS-4 6% 19% 19%

Sepsis 6% 16% 19%

Severe Sepsis 8% 18% 23%

Septic Shock 18% 38% 31%

Septic Shock

Septic Shock

SIRS and related conditions represent a hierarchical continuum of increased inflammatory response to infection

Conclusions

Rangel-Fausto et al JAMA-1995

response to infection

End organ failure rates blood culture rates and mortality rates are all increased with each subsequent stage of systemic inflamatory response.

Septic Shock

Diagnosis- Clinical presentation

- Lab workupPathophysiology

- Lab workup

Treatment

Septic Shock- Pathophysiology -

Infection

Bacteremia Release of toxins

Complex Complex inflammatory response

Multiple Organ Dysfunction

Death

Septic Shock- Pathophysiology -

Coagulation system

Endothelium

Cell metabolismBacterial toxins

Bacteremia

Cell metabolism

Lungs

Kidney

Cardio-vascular

Bacterial toxins

Inflamatory Response

Septic Shock-Coagulation –

Procoagulants Anticoagulants

- Coagulation cascade

- Platelet Activation Factor

- Vasoconstriction

- TF Inhibitor

- AT Complex

- Prot C Complex

- Fibrinolysis

Septic Shock- Coagulation -

Activated Protein C

- Inhibits Factor VIII-a, V-a

- � TF expression

- Inhibits PAI – 1

Anticoagulant

Fibrinolysis- Inhibits PAI – 1

- � Leukocytes adhesion

- � TNF levels

Fibrinolysis

Anti-Inflamatory

Low Prot C and APC Mortality Rates

Septic Shock

Septic Shock- Coagulation -

���� Procoagulants

� AnticoagulantsBacterial Toxins

Bacterial Toxins

-� Expression of TF- Edothelial damage-� Platelet agregation

-� levelTF Inhibitor

- � level ofAT

- � level of Prot C

- � Prot C to APC

- � Fibrinolysis

Microvascular thrombosis

Septic Shock- Cellular metabolism -

Sepsis

-Hypoxemia

- Hypotension

-Microvascular abn Microvascular thrombosis

Tissue hypoxia

-Microvascular abn Microvascular thrombosis

Shunting

Mitochondrial dysfunction

Anaerobic metabolism� ATP � Lactic ac

Septic Shock- Cellular metabolism -

Acidosis ( pH < 7.35 )

Respiratory� pCO2 > 45mmHg

Metabolic � HCO3 < 22mEq/L� pCO2 > 45mmHg

� HCO3 22-26 mEq/L� HCO3 < 22mEq/L

⊕Anion Gap-Lactic ac-Ketoacidosis-Intoxication

∅ Anion Gap-Renal ac

Anion Gap = (Na + K ) – (Cl + HCO3 ) ⊕ Anion Gap >14mEq/L

Septic Shock- Endothelial Cell -

Endothelial cell

- Prevent coagulation

- Prevent migration of cells

TM,, APC receptors �TF

� Adhesion molecules- Prevent migration of cells

- Regulate vasopermeability

- Regulate microcirculation

� Adhesion molecules

� Leukocyte activation

Vasoactive substances

Septic Shock- Endothelial Cell -

�Adhesion molecules

Complement activation� Permeability

Sepsis Endothelial cells

Complement activation

� TF, � PAF

� Permeability

� Coagulation

Leakage � Edema

Microvascular thrombosis

Cell death

Septic Shock

Endothelial cell injury

Alveolar flooding

� Lung compliance

� Capillary permeability

- ARDS -

� Lung compliance

Shunting

Hypoxemia

Recovery DeathPulmonary fibrosis

Pulmonary HTN

Septic Shock- ARDS -

Onset Acute

PaO / FiO < 200mmHgHypoxemia PaO2 / FiO2 < 200mmHg

Chest X-ray Bilateral alveolar or interstitial infiltrates

PCWP < 18mmHg

Septic Shock- Cardio-vascular -

Myocardial Depression

Refractory Vasodilation

Sepsis

Hypotension

Tissue perfusion

Capillary permeability

Loss of intravascular volume

Cell Death

Septic Shock- Diagnosis -

Coagulation - Hypoxemia- CxR changes

- Metabolic ac. Renal

Pulmonary

Tissue -Ac renal failure

-D.I.C.- Thrombosis

-Decreased E.F.-Hypotension

- Metabolic ac.(Anion gap)

- � Lactic acid

RenalTissue metabolism

Cardio vascular

-Ac renal failure

-Hepatic failureLiver

-Alteration of mental status

C.N.S.

Septic Shock- Diagnosis -

Fever - Common symptom- Viral syndrome- Non infectious

-Regional anesthesia

- Anxiety- Pain

Pulse

BP

- Pregnancy- Steroids (FLM)- Labor

-Regional anesthesia-Supine hypotension

- NPO- Nausea/Vomiting

WBC’s

BP

Output

Septic Shock- Diagnosis -

Coagulation

-Low BP (Refractory), PCWP, EF

- pH, HCO3 BD, Anion gap, LactateTissue metabolism

Cardio-vascular

-Fibrinogen, FSP, PT, PTT, INR, Plts

-Low BP (Refractory), PCWP, EF

- O2 Sat, CxR

Renal

Pulmonary

Cardio-vascular

- Urinary Output, BUN, CR, Lytes

- Liver function tests

C.N.S.

Liver

- Physical exam

Septic Shock- Diagnosis -

Acidosis

Oliguria

Hypotension

Hypoxemia

FeverAbn WBC’s�BP, �Pulse Hypoxemia

Coagulopathy

Abn mental status

�Pulse� R.R.

Prompt Dg andManagement

Septic Shock- Management -

Patients seen in the E.R. with the Dg of septic shock were randomly allocated to

Rivers et al NEJM 2001

1.- Standard therapy (n=133)

2.- Early goal-directed therapy (n=130)

Septic Shock- Management -

“Early goal directed therapy” is a complex approach to septic shock involving manipulation of cardiac preload afterload and contractility to achieve a balance between O2delivery and O2 demand.delivery and O2 demand.

End points used to confirm that balance

- Mixed venous O2 Sat- Lactate level- Base Deficit- pH

Rivers et al NEJM 2001

Septic Shock- Management -

Controls A-lines, CVP placed

Management of fluids, drugs up to MD’s

Study A-line, CVP placed

Rivers et al NEJM 2001

StudyFluids 500cc q 30min � CVP = 8-12mmHg

If MAP < 65mmHg � Vasopressors

If CV O2 Sat < 70% � Blood Hct > 30%

If CV O2 Sat still < 70% � Dobutamine

During the 1st 6hrs

Septic Shock- Management -

Therapy 0-6hrs 0-72hrs

Fluids-Control 3,499ml 13,300ml

Fluids-Study 4,981ml* 13,400mlns

Rivers et al NEJM 2001

Fluids-Study 4,981ml* 13,400ml

Blood-Control 18% 44%

Blood-Study 64%* 68%*

Dobutamine-Control 1% 9%

Dobutamine-Study 14%* 15%ns

*p< 0.01

Septic Shock- Management -

End-Point Baseline 0-6hrs 7-72hrs

CVP-C 6.1 11.8 11.6

CVP-S 5.3ns 13.8* 11.9ns

MAP-C 76 81 80

Rivers et al NEJM 2001

MAP-C 76 81 80

MAP-S 74ns 95* 87*

Lactate-C 6.9 4.9 3.9

Lactate-S 7.7ns 4.3* 3.0*

Base Deficit-C 8.9 8.0 5.1

Base deficit-S 8.9ns 4.7* 2.0*

C � Control, S � Study *p< 0.01

Septic Shock- Management -

End-Point Baseline 0-6hrs 7-72hrs

PT-C 16.5 17.5 17.3

PT-S 15.8ns 16.0* 15.4ns

PTT-C 32.9 37.6 37.0

Rivers et al NEJM 2001

PTT-C 32.9 37.6 37.0

PTT-S 33.3ns 32.6* 34.6*

FSP-C 39 54.9 62.0

FSP-S 44ns 45.8ns 39.2*

MODS-C 7.3 6.8 6.4

MODS-S 7.6ns 5.9* 5.1*

C � Control, S � Study *p< 0.01

Septic Shock- Management -

Mortality Controls(n=133)

Study(n=130)

All inpatients 59(46%) 38(30%)*

Rivers et al NEJM 2001

All inpatients 59(46%) 38(30%)*

28 day 61(49%) 40(33%)*

60 Day 70(57%) 50(44%)*

*p< 0.01

Septic Shock- Management -

To determine the impact of delays in initiating

Objective

Kumar et al Crit Care Med, 2006

To determine the impact of delays in initiating adequate antibiotic therapy on mortality rates of patients in septic shock

Septic Shock- Management -

A retrospective cohort study including 14 ICU’s

Methods

Kumar et al Crit Care Med, 2006

A retrospective cohort study including 14 ICU’s in the USA and Canada. A total of 2,731 adult patients with documented septic shock were included.

Septic Shock- Management -

A. The primary outcome variable was survival to hospital discharge.

Methods

Kumar et al Crit Care Med, 2006

hospital discharge.

B. The primary independent variable was the time to initiation of effective antimicrobial therapy relative to the first occurrence of shock (persistent hypotension)

Septic Shock- Management -

A. Mortality for the entire population � 56%

B. Survival was similar:

Outcome

Kumar et al Crit Care Med, 2006

B. Survival was similar:

- Infection documented or suspecetd

- A plausible pathogen identified or not

- Bacteremia present or absent

Septic Shock- Management -

Antibiotics Rx(from onset of shock)

Mortality Rates

< 1hr 82%

Kumar et al Crit Care Med, 2006

At 6hrs 42%

< 1hr 82%

Septic Shock- Management -

Antibiotics Rx(from onset of shock)

Mortality Rates

< 1hr 82%

Kumar et al Crit Care Med, 2006

At 6hrs 42%

Each hour of delay was associated with a � in survival of 7.6%

Septic Shock- Management -

Antibiotic Rx and Intensive therapy (goal directed therapy ) started at the earliest stages of severe sepsis/septic shockstages of severe sepsis/septic shock

Lower mortality rates