Multiple Organ Failure after CPR
description
Transcript of Multiple Organ Failure after CPR
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