Multiple Organ Failure after CPR

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Multiple Organ Failure after CPR

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• Gau-Jun Tang, MD, MHS
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• ??????

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LIVING CELL
(Cerebral and Extracerebral Tissues) Ischemic
Anoxia Mitochondrial Energy Failure
Primary Injury
Tissue Lactacidosis vasoparalysis
osmolality tissue pH
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
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Electrical pump failure

• Outflux of potassium
• influx of sodium
• Voltage dependent Ca channel activate
• Large uncontrollable Ca influx

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The relationship of lactate to shock, SIRS and
MODS
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Bacteria translocation
Shock
Vasodilation
Hepatic failure
Tissue perfusion
Capillary Leak
ARDS
DIC
Bacteria
Renal failure
Endotoxermea Bacteremia
Intestine mucosa
Bacterial Translocation
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Activation of inflammation
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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

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PANORGANIC DEATH
CLINICAL DEATH
CIRCULATORY ARREST
?
APPROXIMATE TIME, MIN.
5
10
15
20
RESTORATION OF CIRCULATION
APNEA UNCONSCIOUS
SPONTANEOUS BREATHING UNCONSCIOUS
SPONTANEOUS BREATHING CONSCIOUS
SPONTANEOUS BREATHING CONSCIOUS OR STUPOR
NEUROL NORMAL
NEUROL DEFICIT
VEGETATIVE STATE EEG ABNORMAL
BRAIN DEATH EEG ISOELECTRIC
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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

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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

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massive pneumoperitoneum gastric disruption
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pneumothorax results from a break in the parietal
pleura
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Barotrauma
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Kidney

• Acute tubular necrosis (ATN)
• Hypotension
• Hypovolumea
• Shock
• Poor renal perfusion

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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

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Coagulopathy

• Increased blood coagulability
• microvascular thrombosis
• small emboli in pulmoanry circuit
• consumption of Hageman facor
• acitivation of intrinsic pathway

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Coagulopathy

• Formation of fibrin
• Formation of thrombin antithrombin complex
• figrin monomers
• Fibrolytic process was not activated
• D- dimer
• plasminogen activator inhibitor
• Bottiger, Circulation, 1995

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Acute adrenal insufficiency

• hyponatremia
• hyperkalemia
• hypotension
• weakness or fatigue
• Pathology
• bilateral adrenal cortex hemorrhage

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Sick euthyroid syndrome

• Thyroxine (T4) level is low
• Thyrotropin (TSH) normal
• No sign or sympatom of hypothyroidism
• No treatment is indicated

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Postresuscitation myocardial dysfunction

• Global impairment in myocardial function
• last for hrs, days or weeks
• myocardial stunning
• Low BP
• CI
• SVI
• LVSWI

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Circulation failure

• CNS dysfunction
• Renal failure
• Hepatic dysfunction
• Gut failure
• Lactic acidosis
• Presence of Anarobic respiration
• Related to mortality

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TCA Cycle
Pyruvic acid (3C)
Coenzyme A
Acetyl Co A (2C)
Oxaloacetic acid (4C)
citric acid (6C)
NADH H
NAD
NAD
Malic acid (4C)
H2O
NADH H
CO2
Fumaric acid (4C)
a-ketoglutaric acid (5C)
FADH2 FAD
CoA-SH
NAD
Succinic acid (4C)
NADH H
CO2
Succinyl CoA (4C)
ATP
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Vascular failureEndothelial and cell membrane
disruption
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Gastrointestinal failure

• Stress ulcer
• Achaculus Cholecystitis
• Poor perfusion of mucosa

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Tonometer catheter
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Tonometer
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Determinant of Cardiac output and Blood pressure
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Cardiac failure

• Treatment underlying disease
• Myocaridal infarction
• cardiac tamponade
• aortic dissection
• pulmonary embolism
• pneumothorax
• hypovolumia

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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

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Hemodynamic management
CVP/PCWP
Volume
(NL or High)
(Low)
Volume
Flow
Cardiac Output
(Low)
(NL or High)
Volume, Dobutamine
O2 Transport
O2 Uptake
(Low)
(NL or High)
Tissue oxygenation
Volume
Lactate
(NL)
(High)
Observe
supranormal VO2
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Mechanical supportIABP, ECMO
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Respiration

• Endotracheal tube
• Mechanical ventilation
• PEEP
• Oxygen
• Keep PaCO2 30 to 35 mmHg

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How we protect the Brain?

• Adequate cerebral blood flow
• Adequate oxygen in the blood

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Brain ischemia

• No flow
• Cardiac arrest
• Incomplete ischemia
• CPR
• No reflow
• BP normal, vasospasma
• Ischemic penumbra (????)
• Transition zone between infarct and normal brain
• Ischemia
• Electrical silence
• No cytolysis

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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

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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

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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

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Brain Protection

• Hypertension
• SBP 150-200mmHg 1 to 5 min
• Normal or hypertension, absolutely no hypotension
• Hematocrit 3335 mg
• Glucose
• Lactic acidosis
• 100 ? 200 g/dl

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Reduce cerebral metabolism

• Seizures
• phenobarbital, phenytoin, diazepam
• Hyperthermia
• Barbiturate coma
• EEG isoelectric
• Clinical not significant ?
• Reduce metabolism also reduce cerebral blood flow
• Hypothermia

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Hypothermia

• Moderate Hypothrmia (28-32)
• protect the brain during heart surgery
• Deep Hypothermia (lt25)
• cardiac arrest

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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

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• Hematocrit 30-35
• Electrolytes normal
• Plasma COP gt15 mmHg
• Serum albumin gt3g/dl
• Serum osmolality 280-330 mOsm/liter
• Glucose 100-300mg/dl

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• ??????5-10 ?0.25-0.5 ?????????????
• ?????? (24 to 48 hr)

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• ??ICP
• ??ICPlt15mmHg
• ??CO2
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• Mannitol 0.5g/kg iv plus 0.3g/kg/hr iv,
  short-termor mannitol 1g/kg once iv
• Loop diuretic (eg.furosemide,0.5-1.0mg/kg iv)
• Thiopental or pentobarbital 2-5mg/kg ivrepeat as
  needed
• Corticosteroid

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Electrolyte balance

• Hypernatremea
• Hyperosmolality
• Hyperkelemea
• Hypokelemea
• Hypomegnesia

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Mg in head and spinal injury
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Mg as a Channel Blocker
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Post resuscitation

• Heart failure
• recurrent cardiac arrest
• ischemia encephalopathy
• intercurrent infection
• multiple organ failure

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Determinants of MOF after primary insult
Microbial Tissue trauma Shock
Initiating factor
Pro- inflammatory (genetics) Anti-inflammatory
Host response
Endothelial integrity Endothelial function Cell
signalling/mitochondrial function
Impact
Clinical manifestation
Tissue edema Tissue hypoperfusion Direct effect
on cell metabolism
Survival
Outcome
OSF
Death
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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-?) - principal
  mediator of septic shock
• Mortality and hemodynamic derangement closely
  correlated with the TNF-? level

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TUMOR NECROSIS FACTOR

• 20 ug/m2/24 hr
• Fever
• Tachcardia
• Elevated acute-phase protein
• Elevated stress hormone
• gt620 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

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Survival vs Non-SurvivalTang, 1996, CCM
Survival (n6)
Non-Survival (n9) Age
55 6.7 57
5.3 APACHE II(pre-op) 18.7 2.1
21.4 1.7 APACHE II(post-op) 21.0
2.2 26.8 2.4 TNF
(pre-op) 106.8 29.5
144.2 78.5 TNF (post-op) 115.7
28.0 213 93.7 Peak TNF
(pg/ml) 494.1 268 2061.1
543.3 IL-6 (pg/ml) (pre-op) 28.7 10.0
72.4 40.8 IL-6 (pg/ml)
(post-op) 154.5 53.5 312.5
102.4 Peak IL-6 (pg/ml) 269.9 67.6
889.9 278.5
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Synergistic effect of surgery and infection on TNF
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Why TNF level are different with similar infection

• Genetic factor modulating the production of TNF-?
  
• C3H/HeJ genetic defect mice resistance to lethal
  action of endotoxin
• Macrophages from do not produce TNF-? in response
  to endotoxin
• Beutler, Science, 1986
• In vitro secretion of TNF-? were lower in
  HLA-DR2-positive individuals
• TNF2 polymorphism increase TNF -? synthesis
• Wilson. Proc Natl Acad Sci U S A. 1997

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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, Nature, 1994
• Allele 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

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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

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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)

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Distribution of Genetic polymorphism
26(23.2) TNF1/TNF2
86(76.8) TNF1/TNF1
Allele frequency 5.1 Taiwan school children 16
in Gambia
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Mortality between TNF 1 and TNF 2 alleles in
shock patients

TNF1/TNF2 (n13)
TNF1/TNF1 (n29)
Mortality
18(62)
12(92)
lt0.05
11(38)
Survive
1(8)