Jean-Daniel Chiche, MD PhD

History and Basics of Shock Shock & Tissue Hypoxia

MICU & Dept of Host-Pathogen Interaction Hôpital Cochin & Institut Cochin, Paris-F

What defines shock today?

66 % 16 % 16 % 2 %

Shoemaker WC et al, Arch Surg 1973;106:630-6

We believe that almost any reasonable plan is better than no plan at all

We need strategies!

Hopkins JA et al, Arch Surg 1980;115:745-50

Hemodynamics of Septic Shock

Decreased vascular tone Hyperdynamic shock Myocardial depression Capillary leak syndrome Altered microcirculation Impaired O2 extraction

N Engl J Med 2001;345:1368-77

Individuals are unique!

Photo credit: Kallel Koven

differing host response to insult

different trajectory of disease progression

different severity of disease progression

affected not just by genes but by age, comorbidity, drugs...

Host protection from infectious disease is

voidance

esistance

olerance

Factors affecting the tolerance level

MEDZHTOV R, SCIENCE 2012

Can we define ideal resuscitation targets ?

Septic Shock Bundle

Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) > 65 mm Hg.

In the event of persistent arterial hypotension despite volume resuscitation (septic shock) and/or initial lactate > 4 mmol/L (36 mg/dl): Insert central line Achieve central venous pressure (CVP)>8 mmHg. Achieve central venous oxygen saturation

(ScvO2) of > 70%.*

(To be started immediately & completed within 6 hours)

Resuscitation targets in septic shock

The physiological evidence 1

CO CVP

SvO2

DO2

Lactacte clearance

Microcirculation

MAP

∆down

Respiratory changes of Arterial Pressure - derived parameters

- Systolic Arterial Pressure

∆SAP

- Pulse pressure

∆PP

- Stroke Volume variations

∆SV

10 mmHg or 9 %

5 mmHg

10 %

13 % Cut-off values for prediction

of fluid responsiveness

Prediction of Fluid Responsiveness

Positive Uncertain Negative Response to fluid challenge

Improving MAP in Sepsis: rationale

Sepsis is associated with decreased vascular tone

Profound hypotension worsens organ hypoperfusion

Correction of hypotension may improve organ perfusion and microcirculation

Profound hypotension is an independent risk factor for death

• Retrospective cohort study • 111 pts: data from PDMS

MAP<65 mmHg was the strongest predictor of 30-day mortality

Systemic hemodynamics

Systemic O2 metabolism

Regional perfusion

Blood lactate (meq.L-1) Urine output (mL.h-1)

O2 delivery (mL.min-1.m-2) Serum creatinine (µmol.L-1)

N Engl J Med, 2014

Norepinephine doses significantly higher in the high MAP group

N Engl J Med, 2014

N Engl J Med, 2014

Thinking beyond blood pressure

CO CVP

SvO2

DO2

Lactacte clearance

Microcirculation

MAP

Which parameter do you use to guide septic shock resuscitation ?

European cross-sectional, self-reported questionnaire-based survey

Mean arterial blood pressure (87%) ScvO2 (65%) CVP (59%) Systolic arterial blood pressure (48%) SvO2 (42%) Cardiac index (42%)

Torgersen C et al. European Journal of Anaesthesiology 2011

Optimizing DO2 to Prevent Tissue Hypoxia

EGDT: Ventilate (O2) + Fill + Pump + Perfuse Tissue Hypoxia

The DO2-VO2 relationship

Oxygen extraction

Oxygen delivery

Oxy

gen

upta

ke

Sepsis

Critical DO2 threshold

SvO2

Lact

ate

Oxygen extraction

Tested whether increasing cardiac index to a supra-normal level (CI group) or increasing mixed venous oxygen saturation to a normal level (SvO2 group) would decrease morbidity and mortality in ICU patients, as compared with a control group (normal cardiac index)

PCRT with 762 patients randomized CTL group 252 pts – target reached 94.3 % CI group 253 pts – target reached 44.9 % SvO2 257 pts – target reached 66.7 %

Target

single organ (renal) perfusion

Target tissue perfusion-based

endpoints irrespective of MAP<65mmHg

Target minimum MAP (45-50 mmHg) to preserve heart

and brain perfusion

3

2

1

DO2

VO2

CVP

MAP

GEDV ScvO2

SvO2

CO HR PAOP

PAP

Urine output Lactate

v-a ∆CO2

Microcirculation (Capillary perfusion, StO2…)

Mottling, Capillary refill ∆Temperature

35.5%

17.5%

33.9%

13.1%

• prospective, multicentre, observational study; 363 pts

DO2

VO2

CVP

MAP

GEDV ScvO2

SvO2

CO HR PAOP

PAP

Urine output

v-a ∆CO2

Microcirculation (Capillary perfusion, StO2…)

Mottling, Capillary refill ∆Temperature

Resuscitation targets in septic shock

The physiological evidence 1

Next generation trials: what’s new? 2