Septic Shock

Maternal Mortality
- Safe Motherhood Initiative In 2002 the Safe Motherhood Initiative was launched as a joint venture between NYS Dept 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 Mortality
- 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 reported to ACOG District II through the S.M.I.

Maternal Mortality
- Safe Motherhood Initiative Most common causes of M.M.
Embolism PIH Hemorrhage Infectious Cardiac 24% 24% 15% 15% 6%

Maternal Mortality
- Safe Motherhood Initiative 1.- Hemorrhage Protocol 2.- Preconceptional counselling 3.- Management of Sepsis and septic shock 4.- Obesity 5.- Critical Care in Obstetrics

Septic Shock
- Case presentation Mrs X , 36y old P2 at 34wks C/O - Fever, nausea, vomiting 2-3d

- Other fam members same symptoms 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 Hospital Course
Initial FHR:

- Bseline 200bpm,
2hrs after Adm:

variability, no decels

- 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

Septic Shock
- Case presentation -

Adhesion molecules

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 7:00A.M. Ephedrine BP 100/55 O2 Rpt Sat 95% HCO3=18 pCO2=41 6:45A.M. O2 Sat 85%, -75% pH=7.27 pO2=47 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. 50cc 6A.M. 50cc 7A.M. 45cc 8A.M. 25cc 9A.M. 25cc 10A.M. 20cc 11A.M. 10cc 12P.M. 30cc 1P.M. 60cc

Fluids

Septic Shock
- Case presentation Pregnancy Post surgery Ac resp distress

R/O Pulmonary Embolus

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

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

- 2P.M. CT - No evidence of Emboli

- Infiltrates sugg of pulm. edema

Septic Shock
- Case presentation CT Bil Infiltrates Rpt WBC 15,000 Fever 1010 F O2 desaturation Low BPs

Pneumonia Sepsis -ARDS

- 5P.M. Antibiotic Rx

ICU

-10P.M. Respiratory Distress

Intubated Vent (PEEP=15cm H2 O) Rpt CxR ARDS

Septic Shock
- Case presentation Day 1-7

No improvement Pulmonary Status Levophed Maintain BPs Blood Culture Strep Pneumonia Rx Imipenem, Gentamycin Xigris (APC) started
Day 8-9

WBCs 18-33,000 Temp 102-103 F

2nd Septic Source ?

Septic Shock
- Case presentation 2nd Septic Source
CxR No empyema No other studies done (Pat unstable) #9 Explor laparotomy Temps WBCs 98-100 F 17,000 TAH* in ICU

Pulmonary No Change Pressor agents No Change

#14 Cardiac Arrest

* Endomyometritis

Death

with abcess formation

Septic Shock
- Case presentation Mrs X , 36y old P2 at 34wks -Delay in Dg -Delay in initiation of antibiotic therapy -Delay in initiation of hemodynamic monitoring - Delay in initiation of aggressive fluid management 2A.M.

ICU Admission in Septic Shock Maternal Mortality 2wks later

5 P.M.

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 - Sepsis - Severe Sepsis - Septic Shock - Multiple Organ Dysfunction Syndrome

Systemic Inflamatory Response Syndrome

Septic Shock
SIRS*
Definition Diagnosis The organisms response to any insult
- Infectious, Trauma, Toxic

>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)

*Systemic

Inflamatory Response Syndrome

Septic Shock
Bacteremia SIRS Sepsis Severe sepsis Septic Shock
Presence of bacteria in the blood Systemic Inflamatory Response Syndrome Documented infection + Evidence of SIRS Sepsis associated with organ dysfunction (MODS) Sepsis induced hypotension despite adequate hydration

Septic Shock
1.- Individual entities ? 2.- Do they develop sequentially ? 3.- Risk of specific end-organ failure ? 4.- Mortality Rates ?
Increasingly severe responses to same insult 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.

Rangel-Fausto et al JAMA-1995

Septic Shock
Final Diagnosis
SIRS Sepsis Severe Sepsis Septic Shock 1301 (52%) 649 (26%) 467 (18%) 110 (4%)
Rangel-Fausto et al JAMA-1995

Septic Shock
Final Dg Present on Admission 56% 42% 29% Progressed in Hospital 44% 58% 71%

Sepsis Severe Sepsis Septic Shock

Rangel-Fausto et al JAMA-1995

Septic Shock
SIRS Advance to higher level 32% 36% 45% Advance to Septic Shock 11% 21% 27%

2 criteria 3 criteria 4 criteria

Rangel-Fausto et al JAMA-1995

Septic Shock
Blood Cultures
Sepsis Severe Sepsis Septic Shock 16% 25% 69%

Rangel-Fausto et al JAMA-1995

Septic Shock
Dg SIRS-2 SIRS-3 SIRS-4 Sepsis Severe Sepsis Septic Shock ARDS 2% 3% 6% 6% 8% 18% DIC 8% 15% 19% 16% 18% 38% ARF 9% 13% 19% 19% 23% 31%

Rangel-Fausto et al JAMA-1995

Septic Shock

Septic Shock
Conclusions SIRS and related conditions represent a hierarchical continuum of increased inflammatory response to infection End organ failure rates blood culture rates and mortality rates are all increased with each subsequent stage of systemic inflamatory response.
Rangel-Fausto et al JAMA-1995

Septic Shock

Diagnosis
Pathophysiology
- Clinical presentation - Lab workup

Treatment

Septic Shock
- Pathophysiology Infection Bacteremia Release of toxins Complex inflammatory response Multiple Organ Dysfunction Death

Septic Shock
- Pathophysiology Coagulation system Endothelium Cell metabolism Lungs Kidney Cardio-vascular

Bacteremia 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 Leukocytes adhesion TNF levels Septic Shock - Inhibits PAI 1

Anticoagulant Fibrinolysis Anti-Inflamatory

Low Prot C and APC

Mortality Rates

Septic Shock
- Coagulation Bacterial Toxins Bacterial Toxins
Anticoagulants

Procoagulants
- 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 Tissue hypoxia

Microvascular thrombosis Shunting Mitochondrial dysfunction

Anaerobic metabolism ATP Lactic ac

Septic Shock
- Cellular metabolism Acidosis ( pH < 7.35 ) Respiratory
pCO2 > 45mmHg HCO3 22-26 mEq/L
Anion Gap

Metabolic
HCO3 < 22mEq/L

Anion Gap

-Lactic ac -Ketoacidosis -Intoxication

-Renal ac

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

Septic Shock
- Endothelial Cell Endothelial cell
- Prevent coagulation - Prevent migration of cells - Regulate vasopermeability - Regulate microcirculation

TM,, APC receptors TF Adhesion molecules Leukocyte activation Vasoactive substances

Septic Shock
- Endothelial Cell Sepsis
Endothelial cells Adhesion molecules Complement activation TF, PAF Leakage

Permeability Coagulation

Edema

Microvascular thrombosis

Cell death

Septic Shock
- ARDS Endothelial cell injury
Capillary permeability Alveolar flooding Lung compliance Shunting Hypoxemia

Recovery

Pulmonary fibrosis Pulmonary HTN

Death

Septic Shock
- ARDS -

Onset Hypoxemia Chest X-ray PCWP

Acute PaO2 / FiO2 < 200mmHg Bilateral alveolar or interstitial infiltrates

< 18mmHg

Septic Shock
- Cardio-vascular Sepsis
Myocardial Depression Refractory Vasodilation

Capillary permeability

Hypotension

Loss of intravascular volume

Tissue perfusion Cell Death

Septic Shock
- Diagnosis Coagulation -D.I.C. - Thrombosis Pulmonary - Hypoxemia - CxR changes -Ac renal failure

Tissue - Metabolic ac. metabolism (Anion gap) - Lactic acid Cardio vascular -Decreased E.F. -Hypotension

Renal Liver C.N.S.

-Hepatic failure -Alteration of mental status

Septic Shock
- Diagnosis Fever - Common symptom - Viral syndrome - Non infectious - Pregnancy - Steroids (FLM) - Labor Pulse - Anxiety - Pain -Regional anesthesia -Supine hypotension

BP WBCs

Output - NPO - Nausea/Vomiting

Septic Shock
- Diagnosis Coagulation Tissue metabolism Cardio-vascular Pulmonary Renal Liver C.N.S. -Fibrinogen, FSP, PT, PTT, INR, Plts - pH, HCO3 BD, Anion gap, Lactate -Low BP (Refractory), PCWP, EF - O2 Sat, CxR - Urinary Output, BUN, CR, Lytes

- Liver function tests - Physical exam

Septic Shock
- Diagnosis Fever Abn WBCs BP, Pulse R.R.

Acidosis Oliguria Hypotension Hypoxemia Coagulopathy Abn mental status

Prompt Dg and Management

Septic Shock
- Management -

Patients seen in the E.R. with the Dg of septic shock were randomly allocated to 1.- Standard therapy (n=133) 2.- Early goal-directed therapy (n=130)

Rivers et al NEJM 2001

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 O2 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 Study
A-lines, CVP placed Management of fluids, drugs up to MDs A-line, CVP placed Fluids 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
Rivers et al NEJM 2001

Septic Shock
- Management Therapy
Fluids-Control Fluids-Study Blood-Control Blood-Study Dobutamine-Control Dobutamine-Study
*p<

0-6hrs
3,499ml 4,981ml* 18% 64%* 1% 14%*

0-72hrs
13,300ml 13,400mlns 44% 68%* 9% 15%ns

0.01

Rivers et al NEJM 2001

Septic Shock
- Management End-Point
CVP-C CVP-S MAP-C MAP-S Lactate-C Lactate-S Base Deficit-C Base deficit-S
C Control, S Study *p< 0.01

Baseline
6.1 5.3ns 76 74ns 6.9 7.7ns 8.9 8.9ns

0-6hrs
11.8 13.8* 81 95* 4.9 4.3* 8.0 4.7*

7-72hrs
11.6 11.9ns 80 87* 3.9 3.0* 5.1 2.0*

Rivers et al NEJM 2001

Septic Shock
- Management End-Point
PT-C PT-S PTT-C PTT-S FSP-C FSP-S MODS-C MODS-S
C Control, S Study *p< 0.01

Baseline
16.5 15.8ns 32.9 33.3ns 39 44ns 7.3 7.6ns

0-6hrs
17.5 16.0* 37.6 32.6* 54.9 45.8ns 6.8 5.9*

7-72hrs
17.3 15.4ns 37.0 34.6* 62.0 39.2* 6.4 5.1*

Rivers et al NEJM 2001

Septic Shock
- Management Mortality
All inpatients 28 day 60 Day

Controls
(n=133)

Study
(n=130)

59(46%) 61(49%) 70(57%)

38(30%)* 40(33%)* 50(44%)*

*p<

0.01

Rivers et al NEJM 2001

Septic Shock
- Management -

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

Kumar et al Crit Care Med, 2006

Septic Shock
- Management -

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

Kumar et al Crit Care Med, 2006

Septic Shock
- Management -

Methods
A. The primary outcome variable was survival to 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)
Kumar et al Crit Care Med, 2006

Septic Shock
- Management -

Outcome
A. Mortality for the entire population B. Survival was similar: - Infection documented or suspecetd

56%

- A plausible pathogen identified or not - Bacteremia present or absent

Kumar et al Crit Care Med, 2006

Septic Shock
- Management -

Antibiotics Rx
(from onset of shock)

Mortality Rates
82%

< 1hr

At 6hrs

42% Kumar et al Crit Care Med, 2006

Septic Shock
- Management -

Antibiotics Rx
(from onset of shock)

Mortality Rates
82%

< 1hr
Each hour of delay was associated with a in survival of 7.6%
At 6hrs

42% Kumar et al Crit Care Med, 2006

Septic Shock
- Management -

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

Lower mortality rates