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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