Clinical Practice Guideline :

End Point of Resuscitation

Hasanul Arifin

The 3rd Symposium on Critical Care and Emergency Medicine

From Pre Hospital to ER and ICU
03-05 May 2007, Medan
Severely injured trauma victims

SHOCK

MODS or DEATH
 SHOCK

COMPLETELY
RESUSCITATION

SURVIVE
COMPLETE RESUSCITATION

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

™ BloodPressure
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 ?

Endpoints of Resuscitation
DO2

SvO2

RVEDV

LVSWI
Global Endpoints
LVP(O)

Base Deficit

Lactate Level

Gastric Intramucosal pH (pHi)

Gap Intramucosal & Arterial PCO2

Skeletal Intramucosal pH &PCO2

Regional Endpoints
Near Infra Red Spectroscopy

Tissue Electrodes
 A. Oxygen Delivery
™ SupranormalOxygen (Shoemaker)
™ DO2 and CI higher in survivors than non-
survivors
™ CI≥4.5 L/min/m² (2.8-4.2)
™ DO2 ≥ 600 mL/min/m² ( 600)
™ VO2≥ 170 mL/min/m² (150)

complications, LOS, hospital costs

“ABCDE OF Resuscitation”
™A = Airway
™ B= Breathing support
™ C = Circulation
™ D = Delivery of oxygen
™ E = Extraction and Utilization of O2
by tissue
 A. Oxygen Delivery, cont’
Studied by : Conclusion
Fleming et al MODS, Hosp.stay, < 24 hrs of injury

Bishop et al MODS, death (volume loading, dobutamine,

transfusion Hb 14 gm/dL)
Moore et al No improve the rate MODS and death
Durham et al
Heyland et al Benefit if the goals are achieved preoperatively
Kern & Shoemaker Benefit if interventions initiated before the
onset of organ failure .
 A. Oxygen Delivery, cont’
9Optimization of the hemodynamic
variables should be initiated as early
as possible during resuscitation
( timing is the key point)
9 the greatest benefit seems to be in
the sickest groups of patients
B. 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%
Parameter Oksigenasi di Jaringan
™ Keseimbangan antara suplay dan pemakaian
oksigen di jaringan dapat dilihat pada 2 parameter
oksigenasi, yaitu:
1. Oxygen utilization coefficient (OUC) atau Oxygen
extraction ratio (O2ER): persentasi oksigen delivery yg
terpakai oleh tubuh.

2. Mixed venous oxygen saturation (SvO2): Oksigen

yang masih tersisa didalam vena setelah diambil oleh
jaringan.
Global Tissue Oxygenation
 Mixed Venous Oxygen Saturation (SvO2)

™ Nilai normal SvO2 adalah 75%, hal ini berarti dalam kondisi
normal, jaringan mengambil/menggunakan (ekstraksi) oksigen
sebesar 25% dari oksigen yang ditransport (DO2).

™ Jika ekstraksi oksigen meningkat, maka saturasi mixed vena akan

terlihat menurun; hal ini menyebabkan CaO2 akan menurun.
Tubuh akan mengkompensasi dengan cara meningkatkan flow/CO
 Mixed Venous Oxygen Saturation (SvO2)

™ Jika SvO2 kurang dari 30%, berarti ambilan oksigen oleh jaringan
sangat tinggi, hal ini menyebabkan terjadinya ketidakseimbangan
suplay dan demandÆ metabolik anaerobik Æ laktat ↑.

™ SvO2 normal belum tentu kondisi metabolik normal, karena bisa

saja terjadi mekanisme kompensasi
 Aorta

SvO2
= 75%

Pulmonary

Pulmonary artery
vein
Left Atrium

Sa O2 = 98%
Right PaO2 = 92%
Atrium Left CaO2 = 20 ml/dl
ventricle

Right
ventricle

organ
PvO2 = 40%
CvO2 = 15 ml/dl
 C. Additional Invasive Hemodynamic
Monitoring Parameters
™ Trauma patients Æ occult cardiac dysfunction
™ Early invasive hemodynamic monitoring (Scalea, et al)
™ Early monitoring Æ identified occult shock Æ may helped to
prevent MODS and death
™ Volume resuscitation, inotropes, and blood transfusions Æ DO2
until lactate concentration normalized.

CVP, PCWP
limitations Ævariable ventricular compliance &
intrathoracic pressure
 C. Additional Invasive Hemodynamic
Monitoring Parameters
RVEDVI
™ May more accurately reflect LV-preload than CVP
or PCWP
™ Determined by using a right ventricular ejection
fraction /oximetry volumetric catheter.
™ RVEDVI , better corelation with CI, pHi
™ Normalized pHi and high RVEDVI were strongly
associated with better outcome
 C. Additional Invasive Hemodynamic
Monitoring Parameters
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
 D. Arterial Base Deficit
™ Inadequate DO2 leads to anaerobic metabolism
™ Degree of anaerobiosis ~ depth and severity of
hemorrhagic 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
 D. Arterial Base Deficit, cont’
™ Straficationof patient’s level of illness by base
deficit (Davis, et al)
strafication Base Deficit
mild 2 - 5 mmol/L
moderate 6 -14 mmol/L
severe > 14 mmol/L
 D. Arterial Base Deficit, cont’
Studied by Conclusion
Davis, et al Higher base deficit , lower BP and greater fluid
requirement
Rutherford, et al BD correlated with mortality and enhanced the
predictive value of the TRISS methodology
Sauaia, et al BD, lactate, transfusion requirement were predictive
of the development of MOF
Kincaid, et al Normal lactate level, but persistenly high BD Æ
lower VO2 and OUC, MODS and death
Krishna, et al Severe hypothermia (<330C) , BD > 12mmol/L and
Combination of temp. <35.50C + BD >5 mmol/L Æ
were strong predictors of death
 D. Arterial Base Deficit
Davis, et al Admission BD ≥ 6 mmol/L Æ 72% cases need
blood transfusion vs 18% cases if BD < 6 mmol/L,
and LOS, ARDS, RF, MODS
Botha, et al BD correlated with neutrophil CD11b expression
Æ inflammatory & MODS.
Kincaid et al, & Randolph et al Pediatric patients, BD reflect injury severity and
risk of mortality . BD >8mmol/L Æ 25% mortality
risk.
 E. 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 Æ survived
™ 24-48 hours Æ 25% mortality
™ >48 hours did not normalize Æ 86% mortality
 Targeting: Blood Lactate

Nguyen et al. Crit Care Med 2004

™ serial lactate levels may improve the prognostic value and
help guide therapy
 F. End-tidal Carbon Dioxide Levels
™ Reduced cardiac output and/or abnormal distribution of
pulmonary blood flow Æ pulmonary dead space
™ Æ a-A CO2 (measured by P-etCO2)
™ Tyburski. et al, 106 trauma patients undergoing surgery.
™ Survivors vs Nonsurvivors
™ Higher PetCO2
™ Lower a-etCO2
™ Decreased alv.dead space ratio (a-etCO2)/PaCO2 )
 G. Gastric tonometry
™ The stomach has been called the canary of the
body. Since it is usually the first organ system
affected by inadequate systemic perfusion.
™ The theory : detection of subclinical ischemia to
skin, gut, kidney (2nd organ) would allow
identification of patients who require additional
resuscitation despite seemingly normalized vital
organs.
 G. Gastric tonometry, cont’
™ Gastric tonometry is based on the finding that
tissue ischemia leads to an increase in tissue
PCO2 and decrease in tissue pH.

Intramucosal pH
(pHi)
Gastric Tonometer pHi (H-H equation)

™ Tissue ischemia Æ increase

PCO2 Æ decrease tissue pH
™ CO2 diffuses across tissue &
fluids
™ PCO2 in gastric secretion ==
PCO2 gastric mucosa

saline

Semipermiable baloon
 Why the Gut?
™ splanchnic circulation sensitive to changes in
blood flow
™ countercurrent exchange in the villus →
especially vulnerable to hypoxia & reduced
blood flow
™ mucosa highly susceptible to ischemic injury
during sepsis
™ blood shunted away from gut mucosa to deeper
layers
 G. Gastric tonometry, cont’
Gys, et al 59 surgical ICU patients, pHi < 7.32 Æ mortality of
37%, higher pHi all survived
Doglio, et al Lower pHi Æ development of MODS and increased
of mortality in critically ill patients, particularly if the
low pHi persisted > 12 hours.
Boyd, et al Base deficit and bicarbonate levels correlated well
with pHi. Finding BD >4.65 had a 77% sensitivity
and 96% specificity of predicting pHi of <7.32
Gutierrez, et al Survivor and nonsurvivors had similar DO2, but non
survivors had greater of VO2, OER, lactate, and had
lower pHi, mixed venous pH, PvO2, all died at pHi
<7.32
 G. Gastric tonometry, cont’
Roumen, et al 15 blunt trauma undergoing surgery, 8 had
pHi ≤7.32 , Æ 3 complications, 2 died , all 7
with normal pHi had uncomplicated
recoveries
 G. Gastric tonometry, cont’
™ Technologic Limitations.
™ Original Æ manual technique
™ Fibreoptic systems using a spectrophotometric method
for continuous monitorig

™ Sublingual PCO2 monitoring.

™ Weil, et al , sublingual PCO2 correlates with lactate
levels, presence of shock, and survival in a small group
of acutely ill patients.
 H. Tissue oxygen and carbon dioxide
electrodes.

™ Same principles of gastric tonometry

™ Optical sensor (optode) placed into subcutaneous
tissues to examine peripheral tissue
 H. Tissue oxygen and carbon dioxide
electrodes.
Drucker, et al 18 trauma patients, still had low
subcutaneous PO2 levels despite adequate
resuscitation by traditional criteria.
Gote, et al 10 patients undergoing emergency intestinal
surgery , subcutaneous PO2 levels were
higher in the survivors
Tatevossian, Patients who died had lower transcutaneous
et al PO2 , higher transcutaneous PCO2 , all
patients died who had transcutaneous PCO2
>60 torr for >30 min.
 I. Near infrared spectroscopy (NIRS)
™ Examine tissue oxygenation
™ NIRS technology allows the simultaneous
measurement of tissue PO2, PCO2 and pH.
™ Mc Kinley, et al. during resuscitation in trauma
patients, StO2 correlated with systemic O2 delivery,
base deficit, and lactate . This correlation was better
than that found with gastric mucosal PCO2 and
PCO2 gap (gastric-arterial PCO2)
 I. Near infrared spectroscopy (NIRS)
™ Inaddition to monitoring tissue oxygenation, NIRS
can provide information regarding mitochondrial
function.
 J. 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.”
 J. 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.
 WARM
COOL

GOOD
HAEMODYNAMIC Shock ?
 Summary
™ During resuscitation from traumatic hemorrhagic
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, gastic tonometry, and
regional measures of tissue O2 and levels have
beeen 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.
 Resuscitation End Points
™ Regional
™ Tissue oxygenation and PCO2
™ Tissue oxygen and CO2 electrodes
™ Near infrared spectroscopy (NIRS)

™ Gastric mucosal ischemia

™ Gastrictonometry
™ Sublingual monitoring of PCO2
 Traditional end points
™ Basic indices ™ Advance indices
‰ Mental status ‰ CVP
‰ HR ‰ CO
‰ BP ‰ PAOP
‰ PP ‰ RVEF
‰ Urine output
‰ Skin perfusion
Optimal End-Points of Resuscitation

™ Lactate levels (normal : 2 mMol/L)

‰ Produced from pyruvate by lactate dehydrogenase
‰ Aerobic metabolism : pyruvate Æ acetyl-co-A Æ ATP
‰ An-aerobic metabolism : pyruvate Æ lactate (acid)
Resuscitation End Points
™ Global
™ Oxygen delivery
™ Supranormal oxygen
™ SvO2

™ Hemodynamic profiles
™ CVP
™ PCWP
™ RVEDVI

™ Acid-base status
™ Bicarbonate concentrations
™ Arterial lactate
™ EtCO2 levels
O2 Extraction Rate (O2 ER)

O2ER = VO2I / DO2I

= ~0.25
= 1- SvO2
Human-based studies:
Early goal-directed therapy has unequivocally been shown to
positively affect outcome in human patients experiencing
cardiovascular shock. However, specific endpoints of resuscitation to
target in critically ill patients remain controversial. Reliance on
traditional endpoints of resuscitation (heart rate [HR], blood pressure
[BP]) appears insufficient in detection of ongoing tissue hypoxia in
shock states. A multitude of publications exist suggesting that indirect
indices of global (lactate, base deficit, mixed/central venous oxygen
saturation), regional (gastric intramucosal pH [pHi]) and cellular
(transcutaneous oxygen) oxygenation are more successful in outcome
prediction and in assessing adequacy of resuscitative efforts in this
patient population.