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

LIVING CELL(Cerebral and Extracerebral Tissues)

Ischemic AnoxiaMitochondrial Energy Failure

TissueLactacidosis : vasoparalysis osmolality tissue pH

Ionic Fluxes K+ efflux*

Na+ influxH2O influx cytotoxic edemaCa++ influx*

LipidPeroxidation :membrane phospholipids phospholipase free fatty acids +O2

Free Radicals protease proteolysisleakage of lysosomes

PrimaryInjury

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

Shock

Tissue perfusion

Bacterial Translocation

EndotoxermeaBacteremia

Vasodilation

Hepatic failure

Capillary Leak

ARDS

DIC

Renal failureBacteria

Intestine mucosa

Bacteria 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

CIRCULATORYARREST 5 10 15 20

?CLINICAL DEATH

APPROXIMATETIME, MIN.

RESTORATION OF CIRCULATION

SPONTANEOUSBREATHING

CONSCIOUS

SPONTANEOUSBREATHING

CONSCIOUSOR

STUPOR

SPONTANEOUSBREATHING

UNCONSCIOUS

APNEA

UNCONSCIOUS

NEUROLNORMAL

NEUROLDEFICIT

VEGETATIVE STATE

EEG ABNORMAL

BRAINDEATHEEG

ISOELECTRIC

PANORGANICDEATH

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 compl

ex 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 hypothyroidis

m No treatment is indicated

Postresuscitation myocardial dysfunction

Global impairment in myocardial function– last for hrs, days or weeks

myocardial stunning Low BP CI SVI LVSWI

Circulation failure

CNS dysfunction Renal failure Hepatic dysfunction Gut failure Lactic acidosis

– Presence of Anarobic respiration – Related to mortality

Pyruvic acid (3C)

Coenzyme A

Acetyl Co A (2C)

citric acid (6C)

NAD+

NADH + H+

CO2

-ketoglutaric acid (5C)

NAD+

NADH + H+

CO2

CoA-SH

Succinyl CoA (4C)

ATP

Succinic acid (4C)

FADH2

FAD

Fumaric acid (4C)H2O

Malic acid (4C)

Oxaloacetic acid (4C)

NADNADH + H+

TCA Cycle

Vascular failure

Endothelial and cell membrane disruption

Gastrointestinal failure

Stress ulcer Achaculus Cholecystitis Poor perfusion of mucosa

Tonometer catheter

Tonometer

Leftventricularsize

H e a rtra te

S tro k evo lum e

M yocard ialfibershortening

C a rd ia co utp ut

P e rip h e ra lre s is ta nc e

A rte ria lp re ssure

A fte rlo a d C o ntra c tility P re lo a d

Determinant of Cardiac output and Blood 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) (NL or High)

VolumeCardiac Output

(Low)

Volume,Dobutamine

(NL or High)

O2 Uptake

(Low) (NL or High)

VolumeLactate

(NL) (High)

Observe supranormal VO2

Volume

Flow

O2 Transport

Tissue oxygenation

Hemodynamic management

Mechanical supportIABP, 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

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

Brain ischemia

Cerebral metabolism– matched well with blood flow

Carbon dioxide Oxygen Hypothermia Anesthetics Cerebral blood flow

– dependent on cerebral perfusion pressure

Regulation of cerebral blood flow

Autoregulation of cerebral blood flow Lost after extended hypoxemia or hypercarb

ia cerebral blood flow depend on cerebral perf

usion pressure Cerebral perfusion pressure = mean arterial

pressure - intracranial pressure

Maintain cerebral perfusion pressure

Mean arterial pressure– Maintaining a normal or slightly elevated mean arterial pr

essure– Hypertension after arrest

Reducing intracranial pressure– head elevated to 30

increase cerebral venous drainage

– hyperventilation PaCO2 25-30

Reduce cerebral blood flow

Optimize cerebral perfusion pressure

Hypertension– SBP 150-200mmHg 1 to 5 min– Normal or hypertension, absolutely no hypoten

sion Hematocrit: 33~35 mg % Glucose

– Lactic acidosis– 100 至 200 g/dl

Brain Protection

Seizures– phenobarbital, phenytoin, diazepam

Hyperthermia Barbiturate coma

– EEG isoelectric– Clinical not significant ?– Reduce metabolism also reduce cerebral blood flow

Hypothermia

Reduce cerebral metabolism

Moderate Hypothrmia (28-32)– protect the brain during heart surgery

Deep Hypothermia (<25)– cardiac arrest

Hypothermia

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

Rapid brain cooling methods:

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 mannito

l 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

Initiating factor

Pro- inflammatory (genetics) Anti-inflammatory

Endothelial integrityEndothelial functionCell signalling/mitochondrial function

Tissue edemaTissue hypoperfusionDirect effect on cell metabolism

Survival OSF

Death

Host response

Impact

Clinical manifestation

Outcome

Determinants of MOF after primary insultMicrobial

Tissue trauma

Shock

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

TUMOR NECROSIS FACTOR 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 (n=6) Non-Survival (n=9) Age 55 ± 6.7 57 ± 5.3APACHE II(pre-op) 18.7 ± 2.1 21.4 ± 1.7APACHE II(post-op) 21.0 ± 2.2 26.8 ± 2.4TNF (pre-op) 106.8 ± 29.5 144.2 ± 78.5TNF (post-op) 115.7 ± 28.0 213 ± 93.7Peak TNF (pg/ml) 494.1 ± 268 2061.1 ± 543.3*IL-6 (pg/ml) (pre-op) 28.7 ± 10.0 72.4 ± 40.8IL-6 (pg/ml) (post-op) 154.5 ± 53.5 312.5 ± 102.4Peak IL-6 (pg/ml) 269.9 ± 67.6 889.9 ± 278.5

Survival vs Non-SurvivalTang, 1996, CCM

Synergistic effect of surgery and infection on TNF

Why TNF level are different with similar infection

Genetic factor modulating the production of TNF- – C3H/HeJ genetic defect mice resistance to leth

al action of endotoxin Macrophages from do not produce TNF- in respon

se 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

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 d

ue 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

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 ampl

ified by PCR digested with NcoI (Boehringer Mannheim, Man

nhein, Germany) analysed on a 2% MetaPhor agarose gel TNF1 allele would be digested into two fragment

s (325 and 20 bp base pairs) TNF2 allele would not be digested (345 bp base p

airs)

Distribution of Genetic polymorphism

26(23.2%)

TNF1/TNF286(76.8%)

TNF1/TNF1

Allele frequency: 5.1% Taiwan school children16 % in Gambia

TNF1/TNF1 (n=29) TNF1/TNF2 (n=13)

Mortality

Survive

18(62%)

11(38%)

12(92%)

1(8%)

<0.05

Mortality between TNF 1 and TNF 2 alleles in shock patients