Resuscitation End Point

Resuscitation End Point

ofof
Macro and Microcirculation
Macro and Microcirculation

Prof. dr. Achsanuddin Hanafie, SpAn, KIC

Departemen / SMF – Anestesiologi dan Terapi Intensif
FK-USU/RSUP H. Adam Malik Medan
Resuscitation End Points
Resuscitation End Points
Determining when resuscitation is
Determining when resuscitation is
complete can be challenging, as
complete can be challenging, as
tissue hypoperfusion can persist
tissue hypoperfusion can persist
despite normal vital sign.
despite normal vital sign.
 PATHOGENESIS
PATHOGENESIS
OF SHOCK
OF SHOCK
Shock is an imbalance between
Shock is an imbalance between
oxygen supply and demand, which
oxygen supply and demand, which
result in a systemic clinical syndrome
result in a systemic clinical syndrome
characterized by hypotension leading
characterized by hypotension leading
to cellular dysfunction
to cellular dysfunction
Septic Shock
Septic Shock
 Pathogenesis of Sepsis Mediated
Hemodynamic Dysfunction
NIDUS OF INFECTION ORGANISMS EXOGENEOUS TOXINS ENDOGENOUS
Pneumonia MEDIATORS
Organism
Peritonitis Structural Component CYTOKINES
Cellulitis Exotoxin (TSST-1, Toxin A) *Interleukin 1,2,….6
Abscess Endotoxin *Tumor Necrosis Factor
Other Infection Sites
PLATELET ACT FACTOR
ARACHID ACID METAB
HUMORAL CASCADES
*Complement
*Kinins
*Coagulation
Severe Decrease
SVR
MYOCARDIUM
HYPOTENSION *Depression
Depressed CO *Dilatation
CARDIOVASCULAR
DEATH INSUFFICIENCY
Multiple Organ VASCULATURE
*Vasodilation
MOSF System
*Vasoconstriction
Failure *Endothelial Damage
*Maldistribution of flow
RECOVERY
Hemodynamic
Hemodynamic supportsupport
ininseptic shock:
septic shock:
IsIsrestoring a normal
restoring a normal
blood pressure the right
blood pressure the right
target?
target?
Bracco D, Dubois MJ
Crit Care Med 2005 Vol.33, No.9
 Resuscitation End Points

Traditional Global Organ

Clinical Parameters Specific
Parameters Parameters

Macrocirculation Microcirculation
Resuscitation End Points
Resuscitation End Points
Traditional Clinical Parameter :
Heart Rate
Blood Pressure
Urine output
Body temperature
Hemodynamic measurement :
CVP
PAWP
RVEDVI
Resuscitation End Points
Resuscitation End Points
Global Parameters :
Oxygen Delivery Index (DO2I)
Oxygen Consumption Index (VO2I)
Mixed Venous Oxygen Saturation (SvO2)
Serum Lactate
Base Deficit
Arterio Venous Carbon Dioxide Gradient
(AVPaCO2)
Resuscitation End Points
Resuscitation End Points
Organ-Specific Parameters :

Gastric Tonometry

Sublingual Capnometry

Near-Infrared Spectroscopy
 WARM
COOL

GOOD
HAEMODYNAMIC Shock ?
 SHOCK

COMPLETELY
RESUSCITATION

SURVIVE
COMPLETE RESUSCITATION
COMPLETE RESUSCITATION

?
 OXYGEN DEBT HAS BEEN REPAID
 OXYGEN DEBT HAS BEEN REPAID
 TISSUE ACIDOSIS ELIMINITAED
 TISSUE ACIDOSIS ELIMINITAED
 NORMAL AEROBIC METABOLISM
 NORMAL AEROBIC METABOLISM
TRADITIONAL MARKERS OF SUCCESSFUL
RESUSCITATION

Blood Pressure
NORMAL
Heart Rate
Urine Output

Compensated
Shock
 Compensated Shock

 Up to 85% still have evidence of

inadequate tissue oxygenation
 Ongoing metabolic acidosis
 Gastric mucosal ischemia
 Splanchnic blood flow  40%

Which end point of resuscitation ?

Goal-directed Therapy

O2 O2
Demand Supply
 Oxygen Delivery & Mortality in Septic Shock

100
90
80
70
% Mortality

60
50
40
30
20
10
0
0 - 8.5 9.0 - 12.9 3.0 - 16.9 17.0 - 20.9 21.0 - 24.9 25 +

Oxygen Delivery (ml/kg/min)

Tuchsmidt J, Fried J, Astiz M, Rackow E, Chest 1992; 102: 216-220

 Goal-directed Therapy Microcirculation

O2 O2
Supply Demand

SvO2 Lactate

Hemodynamic parameters DO22 parameters (a-v) CO2

-Preload (CVP, PCWP) -PaO22
-Afterload (MAP, SVR) -Hemoglobin
-Contractility (SV) CELL Base
-Cardiac output Deficit
-Heart rate (BPM)
-Shock index (HR/SBP)
-Coronary perfusion pressure pHi

PslCO2
Mediators

“Downstream”
“Downstream” markers
markers ofof the
the
“Upstream”
“Upstream” endpoints
endpoints of
of resuscitation
resuscitation effectiveness
effectiveness of
of resuscitation
resuscitation
 GOAL- directed Therapy
GOAL- directed Therapy
“Upstream” endpoints MACROCIRCULATION
of Resuscitation

DO2 parameter
DO2 parameter
Hemodynamic parameters
Hemodynamic parameters
 PaO2
 PaO
Hemoglobin
2
 Preload (CVP, PCWP)  Hemoglobin
 Preload (CVP, PCWP) Cardiac output
Afterload (MAP, SVR)  Cardiac output
 Afterload (MAP,
Contractility (SV)SVR)
 Contractility (SV)
Heart rate (BPM)
 Heart
Shock rate
index(BPM)
(HR/SBP)
 Shock index
Coronary (HR/SBP)
perfusion
 Coronary
pressure perfusion MICROCIRCULATION
pressure
 INDIRECT INVESTIGATION
“Downstream” markers of the
effectiveness of resuscitation SvO2

Lactate

(a-v)CO2

CELL
Base
Deficit

pHi
Mediators PslCO2
Hemodynamic Monitoring
Parameters

 Blood Pressure
 Blood Pressure
 MAP (Mean Arterial Pressure)
 MAP (Mean Arterial Pressure)
 HR (Heart Rate)
 HR (Heart Rate)
Additional Invasive Hemodynamic
Monitoring Parameters

CVP, PCWP, RVEDVI

limitations variable ventricular
compliance & intrathoracic pressure
Additional Invasive Hemodynamic
Monitoring Parameters

LVSWI , LVP
LVSWI , LVP
LVSWI = stroke index x MAP x 0.0144
LVP = cardiac index x (MAP-CVP)
LVP ( > 320 mmHg x L/min/m2 )
Lactate clearance and survival significantly
correlated with HR, LVSWI and LVP
Mixed Venous Oxygen Saturation
(SvO2)

SvO2 levels should reflect the adequacy

of O2 delivery to tissue in relation to
global tissue O2 demands

SvO2 ≥ 70%
Mixed Venous Oxygen Saturation (SvO2)
Mixed Venous Oxygen Saturation (SvO2)
Right atrium
Venous O2 Saturation
Superior vena cava
(SvO2)
Pulmonary artery

Hyperdynamic state SvO2 < 65% (Rare)

Splanchnic O2 Central Mixed venous

Central
venous O2
saturation venous O2 OMixed
2
venous
saturation
saturation O2 saturation
(SspO2) saturation (SvO2)
(ScvO2) (SvO2)
15% lower (ScvO2) 5-13% lower
5-13% lower
 Arterial Base Deficit

Inadequate DO2 leads to anaerobic

metabolism
Degree of anaerobiosis ~ depth and
severity of septic shock
Should be reflected in the base deficit
and lactate level
pH is not as useful as it will be
defended by the body’s compensatory
mechanism
 Arterial Base Deficit, cont’

• Stratification of patient’s level of

illness by base deficit (Davis, et al)

Stratification Base Deficit

mild 2 - 5 mmol / L
moderate 6 -14 mmol / L
severe > 14 mmol / L
 Arterial Lactate

Level lactate at initial and response to intervention

(fluid resuscitation) , as predictive value. (Vincent et, al)
Normal level 2 mMol/L
Time needed to normalize serum lactate level as an
important prognostic factor for survival (Abramson et al.)

24 hours  survived
24 - 48 hours  25% mortality
> 48 hours did not normalize  86% mortality
 Is oxygen consumption
Is oxygen consumption
adequate for demand?
adequate for demand?
Check a lactic acid level
if > 2,5 mmol /L, lactic acid is being produced
secondary to anaerobic metabolism and attempts
to increase CO and DO2I should be undertaken
if the lactic acid is high and SvO2 is normal, the
elevation in lactic acid is probably due to a previous
episode of anaerobic metabolism and oxygen debt
if the lactic acid is high and SvO2 is low, anaerobic
metabolism is likely still occurring and must be
treated aggressively
Targeting: Blood Lactate

Nguyen et al. Crit Care Med 2004

serial lactate levels may improve the prognostic value
and help guide therapy
 Physical Examination
Despite all the interest in laboratory values,
as well as data from invasive and non
invasive monitoring devices, used to
determine the adequacy of resuscitation,
“one should not discount the value of
a good physical examination.”
 Physical Examination

Kaplan, et al examined the ability of 2

intensivists to diagnose hypoperfusion by
physical examination of patients’ extremities.
Warm or Cool ?
Compared with warm extremities, those
with cool extremities had lower CI, pH,
bicarbonate levels, SvO2 , and higher lactate
levels.
 Surviving Sepsis
Campaign
“Guidelines for Management of
Severe Sepsis and Septic Shock”

Dellinger RP, Carlet JM, Masur H, et al. for the Surviving Sepsis Campaign
Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
Optimizing Oxygen Delivery in Shock
Transfusi 

DO2 = CO x Hb x SaO2 x 1,34

Oxygenation/

HR x SV ventilation MV

 
Fluid Preload Afterload Vasopressor
Contractility Inotrop 
 Hemodynamic monitoring - Physiology

CO ~ SV x HR SvO2 ~ 75 %
CO ~ 70ml x 70 beats/min (O2) ~ 1.0 ml/g Hgb
CO ~ 5 L / min CvO2 ~ 150 ml/min
O2
O2 Hgb O2
O2
O2 Hgb O2 O2
O2
SaO2 ~ 100% CELL
(O2) ~ 1.34 ml/g Hgb
O2 extraction ~ 50 ml
Hgb ~ 150 g/l
VO2 ~ 250 ml/min
CaO2 ~ 200 ml/l
DO2 ~ 1000 ml/min
 Hemodynamic monitoring - Techniques

Preload
Pulse pressure variations
PiCCO
TEDM SvO2
CVP (and waveform) O2 PAC

PAC
CO O2 O2 SVC venous oxymetry
PAC Hgb
TEDM
PiCCO O2 debt
LiDCO Lactate
O2 TEB
O2 O2 NICO O2 Base excess

Hgb
O2
SaO2 CELL
Pulse oxymetry Vo2
Co - oxymetry (ABG) PAC
NICO
Initial Resuscitation
Resuscitation should begin as
soon as severe sepsis or sepsis
induced tissue hypoperfusion is
recognized

-
Elevated Serum lactate identifies
tissue hypoperfusion in patients
at risk who are not hypotensive
 Fluid Therapy: Choice of Fluid
Fluid resuscitation may consist of natural or
artificial colloids or crystalloids
No evidenced-based support for one type of
fluid over another
Crystalloids have a much larger volume of
distribution compared to colloids
Crystalloid resuscitation requires more fluid to
achieve the same endpoints as colloid
Crystalloids result in more edema

Grade C Choi PTL. Crit Care Med 1999;27:200-210.

Cook D. Ann Intern Med 2001;135:205-208.
Dellinger, et. al. Crit Care Med 2004, 32: 858-873. Schierhout G. BMJ 1998;316:961-964.
 Goals of therapy within first 6
hours are:
CVP 8-12 mm Hg (12-15 in MV pts)
MAP > 65 mm Hg
Urine output > 0.5 mL/kg/hr
ScvO2 or SvO2 ≥ 70%;
if not achieved with fluid resuscitation during first 6
hours:
- Transfuse PRBC to hematocrit > 30%
and/or
- Administer dobutamine (max 20 mcg/kg/min)
to goal
Grade B
Dellinger, et. al. Crit Care Med 2004, 32: 858-873. Rivers E. N Engl J Med 2001;345:1368-77.
 Ventilation Volume replacement Pharmacotherapy

baseline
VO22 oxygen consumption
MAP

DO22 oxygen delivery

CI cardiac index
COP colloid osmotic pressure
infusion BV
BV blood volume

organ failure
survival critical
 Vasopressors
Initiate vasopressor therapy if appropriate fluid
challenge fails to restore adequate blood
pressure and organ perfusion

Vasopressor therapy should also be used

transiently in the face of life-threatening
hypotension, even when fluid challenge is in
progress
Grade E
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
LeDoux D. Crit Care Med 2000;28:2729-2732. Regnier B. Intensive Care Med 1977;3:47-53.
Martin C. Chest 1993;103:1826-1831. Martin C. Crit Care Med 2000;28:2758-2765.
DeBacker D. Crit Care Med 2003;31:1659-1667. Hollenberg SM. Crit Care Med 1999; 27: 639-660.
 Vasopressors
Either norepinephrine or dopamine are first line
agents to correct hypotension in septic shock

Norepinephrine is more potent than dopamine

and may be more effective at reversing
hypotension in septic shock patients

Dopamine may be particularly useful in patients

with compromised systolic function but causes
more tachycardia and may be more arrhythmogenic
LeDoux D. Crit Care Med 2000;28:2729-2732. Regnier B. Intensive Care Med 1977;3:47-53.
Grade D
Martin C. Chest 1993;103:1826-1831. Martin C. Crit Care Med 2000;28:2758-2765.
DeBacker D. Crit Care Med 2003;31:1659-1667. Hollenberg SM. Crit Care Med 1999; 27: 639-660.
 Cardiac and vascular effect
Inotropic/
vasoactive
+ inotropic + chronotrop vasoconstr vasodilatation Total effect

Inotropic/
Dobutamine 4x 1x - 2-3x vasodilator

Dose Inotropic/
Dopamine 3x 1x 3x dependent vasopressor

Nor Inotropic/
epinephrine
2x - 4x -
vasopressor

4x 3x 3x Inotropic/
Isoproterenol - vasodilator
 E
ENND
DPPO
OIIN
NTTS
S
1. CVP = 15 mm Hg
2. Wedge pressure = 10 - 12 mmHg
3. Cardiac index > 3 L/min/m2
4. Oxygen uptake (Vo2) > 100 mL/min/m2
5. Blood lactate , 4 mmol/L
6. Base deficit - 3 - + 3 mmol/L
 Summary
Volume resuscitation remains the
cornerstone of treatment for the
hypotensive patient.

Norepinephrine is more potent than

dopamine and may be more effective
at reversing hypotension in septic shock
patients
 Summary
During resuscitation from septic shock,
normalization of standard clinical parameters
such as BP, HR, and urine output are not
adequate to guarantee survival without organ
system dysfunction.
Numerous parameters including hemodynamic
profiles, acid base status, gastric tonometry,
and regional measures of tissue O2 and levels
have been studied
 Summary
Many can be useful for predicting risk of organ
failure and death.
Studies comparing use of these parameters as
endpoints for resuscitation protocols,
however, have failed to show clear benefit in
terms of patient outcomes.
At present, it seems prudent to use one of
these endpoints rather than relying on
standard clinical parameters.
Despite all the interest in above values, one
should not discount the value of a good
physical examination.
horas lae

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