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Multiple Organ Failure after CPR
 唐高駿
 Gau-Jun Tang,
MD, MHS
– 台北榮民總醫院
– 重症加護中心
Primary
Injury
Tissue
Lactacidosis :
vasoparalysis
osmolality
tissue pH
LIVING CELL
(Cerebral and Extracerebral Tissues)
Ischemic Anoxia
Mitochondrial Energy Failure
Ionic Fluxes
K+ efflux*
Na+ influx
H2O influx
cytotoxic edema
Ca++ influx*
Lipid
Peroxidation :
membrane
phospholipids
phospholipase
free fatty acids
+O2
Free Radicals
protease
proteolysis
leakage of lysosomes
Electrical pump failure
 Outflux
of potassium
 influx of sodium
 Voltage dependent Ca channel activate
 Large uncontrollable Ca influx
The relationship of lactate to shock, SIRS and MODS
Bacteria translocation
Shock
Vasodilation
Hepatic failure
Tissue perfusion
Capillary Leak
ARDS
DIC
Bacteria
Renal failure
Intestine mucosa
Endotoxermea
Bacteremia
Bacterial Translocation
Activation of inflammation
Brain is very vulnerable to
ischemia and hypoxia
 High
metabolic rate
– 60% electrophysiological activity
– membrane potential
– neurotransmitter synthesis and uptake
 2%
body weigh
 15% cardiac output
 jugular vein oxygen saturation 55-70
PANORGANIC
DEATH
CIRCULATORY
ARREST
CLINICAL DEATH
APPROXIMATE
TIME, MIN.
?
5
10
15
20
RESTORATION OF CIRCULATION
SPONTANEOUS
BREATHING
SPONTANEOUS
BREATHING
SPONTANEOUS
BREATHING
APNEA
CONSCIOUS
CONSCIOUS
OR
STUPOR
UNCONSCIOUS
UNCONSCIOUS
NEUROL
NORMAL
NEUROL
DEFICIT
VEGETATIVE
STATE
EEG
ABNORMAL
BRAIN
DEATH
EEG
ISOELECTRIC
Cessation of circulation
 10
seconds
– Unconsciousness
 15-25
sec
– Isoelectric
2
to 4 minutes
– Glucose and glycogen store of the brain are
depleted
3
to 5 minutes
– ATP is exhausted
– Electrical pump failure
Lung
 Injury
to rib cage and intrathoracic viscera
– chest compression
 Aspiration
pneumonia
– 24%, 96 patients
 Rello,
Clin Infect Dis, 1995
 Pulmonary
edema
– 30%
 Dohi,
Crit Care Med, 1983
– Similar to ARDS
massive pneumoperitoneum gastric disruption
pneumothorax results from a break in the parietal pleura
Barotrauma
Kidney
 Acute
tubular necrosis (ATN)
– Hypotension
– Hypovolumea
– Shock
– Poor renal perfusion
Hepatic changes after cardiac arrest
 Markedly
elevated transaminases 20 to 100
times of normal
 Jaundice appeared 2 or 3 days latter
 Albumin lost
 Biopsy
–
–
–
–
central lobular necrosis with
centrilobular congestion, hemorrhage & necrosis
acute inflammation
cholestasis
Coagulopathy
 Increased
blood coagulability
 microvascular thrombosis
 small emboli in pulmoanry circuit
 consumption of Hageman facor
 acitivation of intrinsic pathway
Coagulopathy
 Formation
of fibrin
 Formation of thrombin antithrombin
complex
 figrin monomers
– Fibrolytic process was not activated
 D-
dimer
 plasminogen activator inhibitor
– Bottiger, Circulation, 1995
Acute adrenal insufficiency
 hyponatremia
 hyperkalemia
 hypotension
 weakness
or fatigue
 Pathology
– bilateral adrenal cortex hemorrhage
Sick euthyroid syndrome
Thyroxine
(T4) level is low
Thyrotropin (TSH) normal
No sign or sympatom of
hypothyroidism
No treatment is indicated
Postresuscitation myocardial
dysfunction
 Global
impairment in myocardial function
– last for hrs, days or weeks
 myocardial
 Low
BP
 CI
 SVI
 LVSWI
stunning
Circulation failure
 CNS
dysfunction
 Renal failure
 Hepatic dysfunction
 Gut failure
 Lactic acidosis
– Presence of Anarobic respiration
– Related to mortality
TCA Cycle
Pyruvic acid (3C)
Coenzyme A
Acetyl Co A (2C)
Oxaloacetic acid (4C)
NADH + H+
NAD
Malic acid (4C)
H2O
Fumaric acid (4C)
FADH2
FAD
citric acid (6C)
NAD+
NADH + H+
CO2
a-ketoglutaric acid (5C)
CoA-SH
NAD+
Succinic acid (4C)
ATP
NADH + H+
Succinyl
CoA (4C)
CO2
Vascular failure
Endothelial and cell membrane disruption
Gastrointestinal failure
 Stress
ulcer
 Achaculus Cholecystitis
 Poor perfusion of mucosa
Tonometer catheter
Tonometer
Determinant of Cardiac output and Blood pressure
Afterload
Contractility
Preload
Myocardial
fiber
shortening
Left
ventricular
size
Stroke
volume
Heart
rate
Cardiac
output
Peripheral
resistance
Arterial
pressure
Cardiac failure
 Treatment
–
–
–
–
–
–
underlying disease
Myocaridal infarction
cardiac tamponade
aortic dissection
pulmonary embolism
pneumothorax
hypovolumia
Circulatory support
 Optimize
preload
 Dobutamine
– (5-15 ug/kg/min)
 Vasopressor
action
– dopamine (5-20 ug/kg/min)
 norepinephrine,
Epinephrine
– increase in myocardial consumption
 milrinone
– phosphodiasterase inhibitor
CVP/PCWP
(Low)
Hemodynamic
management
Volume
(NL or High)
Volume
Flow
Cardiac Output
(Low)
(NL or High)
Volume,
Dobutamine
O2 Transport
O2 Uptake
(Low)
(NL or High)
Volume
Lactate
(NL)
Observe
Tissue
oxygenation
(High)
supranormal VO2
Mechanical support
IABP,
ECMO
Respiration
 Endotracheal
tube
 Mechanical ventilation
 PEEP
 Oxygen
 Keep PaCO2 30 to 35 mmHg
How we protect the Brain?
 Adequate
cerebral blood flow
 Adequate oxygen in the blood
Brain ischemia
 No
flow
– Cardiac arrest
 Incomplete
ischemia
– CPR
 No
reflow
– BP normal, vasospasma
 Ischemic
penumbra (缺血半影)
– Transition zone between infarct and normal
brain
– Ischemia
– Electrical silence
– No cytolysis
Regulation of cerebral blood flow
 Cerebral
metabolism
– matched well with blood flow
 Carbon
dioxide
 Oxygen
 Hypothermia
 Anesthetics
 Cerebral
blood flow
– dependent on cerebral perfusion pressure
Maintain cerebral perfusion
pressure
 Autoregulation
of cerebral blood flow
 Lost after extended hypoxemia or
hypercarbia
 cerebral blood flow depend on cerebral
perfusion pressure
 Cerebral perfusion pressure = mean arterial
pressure - intracranial pressure
Optimize cerebral perfusion
pressure
 Mean
arterial pressure
– Maintaining a normal or slightly elevated mean
arterial pressure
– Hypertension after arrest
 Reducing
intracranial pressure
– head elevated to 30
 increase
cerebral venous drainage
– hyperventilation
 PaCO2 25-30
 Reduce
cerebral blood flow
Brain Protection
 Hypertension
– SBP 150-200mmHg 1 to 5 min
– Normal or hypertension, absolutely no
hypotension
 Hematocrit:
33~35 mg %
 Glucose
– Lactic acidosis
– 100 至 200 g/dl
Reduce cerebral metabolism
 Seizures
– phenobarbital, phenytoin, diazepam
 Hyperthermia
 Barbiturate
coma
– EEG isoelectric
– Clinical not significant ?
– Reduce metabolism also reduce cerebral blood
flow
 Hypothermia
Hypothermia
 Moderate
Hypothrmia (28-32)
– protect the brain during heart surgery
 Deep
Hypothermia (<25)
– cardiac arrest
Rapid brain cooling methods:
 Head-neck-trunk
surface
 Nasopharyngeal
 Esophagogastric
 IV
cold infusion
 Venovenous shunt with pump, heat
exchange
 Arteriovenous shunt, heat exchange
 Peritoneal cold lavage
 Intracarotid cold flush
 Cardiopulmonary bypass
加護病房中對CPR後昏迷病患之處理
 將血中值維持正常
–
–
–
–
–
–
Hematocrit 30%-35%
Electrolytes normal
Plasma COP >15 mmHg
Serum albumin >3g/dl
Serum osmolality 280-330 mOsm/liter
Glucose 100-300mg/dl
加護病房中對CPR後昏迷病患之處理
 使用高滲透壓液體以降低腦壓
 正常體溫或適量的低體溫(>34ºC)
– 避免高燒
 靜脈注射
– 不要單獨給予葡萄糖水
– 使用葡萄糖水5%-10% 在0.25%-0.5% 的生理
食鹽水中靜脈方式給予
– 給予營養輸液 (24 to 48 hr)
維持顱內恆定
 必須排除出血或腦瘤(電腦斷層)
 監測ICP
– 維持ICP<15mmHg
 降低CO2
 腦脊髓液引流
 Mannitol
0.5g/kg iv plus 0.3g/kg/hr iv, short-term;or mannitol
1g/kg once iv
 Loop diuretic (eg.furosemide,0.5-1.0mg/kg iv)
 Thiopental or pentobarbital 2-5mg/kg iv;repeat as needed
 Corticosteroid
Electrolyte balance
 Hypernatremea
 Hyperosmolality
 Hyperkelemea
 Hypokelemea
 Hypomegnesia
Mg in head and spinal injury
Mg++ as a Channel Blocker
Post resuscitation
 Heart
failure
 recurrent cardiac arrest
 ischemia encephalopathy
 intercurrent infection
 multiple organ failure
Determinants of MOF after primary insult
Initiating factor
Host response
Impact
Clinical manifestation
Outcome
Microbial
Tissue trauma
Shock
Pro- inflammatory (genetics)
Anti-inflammatory
Endothelial integrity
Endothelial function
Cell signalling/mitochondrial function
Tissue edema
Tissue hypoperfusion
Direct effect on cell metabolism
Survival
OSF
Death
Determinants of MOF after surgical
infection
 Some
patients recover without complications
while others develop septic shock
 Cause
– Difference in the degree of inflammatory response
to the infection
 Tumor
necrosis factor-alpha (TNF-a) - principal
mediator of septic shock
 Mortality and hemodynamic derangement closely
correlated with the TNF-a level
TUMOR NECROSIS FACTOR
 20 ug/m2/24 hr
– Fever
– Tachcardia
– Elevated acute-phase protein
– Elevated stress hormone
 >620 ug/m2/24 hr
– Hypotension
– Concious change
– Profound hypotension
– Pulmonary edema
– Oliguria

Michie HR, Wilmore DW. Sepsis, signal and surgical
sequelae (a hypothesis), Arch Surg, 125, 1990
Survival vs Non-Survival
Tang, 1996, CCM
Survival (n=6)
Age
55 ± 6.7
APACHE II(pre-op)
18.7 ± 2.1
APACHE II(post-op) 21.0 ± 2.2
TNF (pre-op)
106.8 ± 29.5
TNF (post-op)
115.7 ± 28.0
Peak TNF (pg/ml)
494.1 ± 268
IL-6 (pg/ml) (pre-op) 28.7 ± 10.0
IL-6 (pg/ml) (post-op) 154.5 ± 53.5
Peak IL-6 (pg/ml)
269.9 ± 67.6
Non-Survival (n=9)
57 ± 5.3
21.4 ± 1.7
26.8 ± 2.4
144.2 ± 78.5
213 ± 93.7
2061.1 ± 543.3*
72.4 ± 40.8
312.5 ± 102.4
889.9 ± 278.5
Synergistic effect of surgery and
infection on TNF
Why TNF level are different
with similar infection
 Genetic
factor modulating the production of
TNF-a
– C3H/HeJ genetic defect mice resistance to
lethal action of endotoxin
 Macrophages
from do not produce TNF-a in
response to endotoxin
– Beutler, Science, 1986
– In vitro secretion of TNF-a were lower in HLADR2-positive individuals
– TNF2 polymorphism increase TNF -a synthesis
 Wilson.
Proc Natl Acad Sci U S A. 1997
TNF2: bi-allelic polymorphism
 Located
at promotor region of TNF gene
 Gambia children infected with malaria
– homozygotes for the TNF2 allele,
– relative risk of 7 for death or severe neurological
sequelae due to cerebral malaria
 McGuire,
 Allele
Nature, 1994
frequency of TNF2 in Taiwan
– 5.1% in school children
– 18.2% in the bronchitis patients
– 2.3% in the non-bronchitis control
 Huang, AJRCCM,
1997
Hypothesis and Purpose of study
 TNF2
individuals are at higher risk to develop
septic shock after bacterial infection
 Evaluate
the genotype distribution of TNF2
allele with regard to the development of septic
shock, mortality and plasma TNF concentration
in critically ill surgical infected patients
Determination of Gene polymorphism
 White
blood cell
 The 5’ region of TNF gene (-331 to 14) was
amplified by PCR
 digested with NcoI (Boehringer Mannheim,
Mannhein, Germany)
 analysed on a 2% MetaPhor agarose gel
 TNF1 allele would be digested into two
fragments (325 and 20 bp base pairs)
 TNF2 allele would not be digested (345 bp base
pairs)
Distribution of Genetic polymorphism
26(23.2%)
86(76.8%)
TNF1/TNF1
Allele frequency:
5.1% Taiwan school children
16 % in Gambia
TNF1/TNF2
Mortality between TNF 1 and TNF
2 alleles in shock patients
TNF1/TNF1 (n=29) TNF1/TNF2 (n=13)
Mortality
18(62%)
12(92%)
Survive
11(38%)
1(8%)
<0.05