??????????????SICU

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MODS and intensive care

• ??????????????SICU
• Surgical ICU of Ruijin Hospital
• Shanghai Second Medical University

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Denomination variation

• 1973 secondary system function failure---
  Tilney
• Summary data of 18 cases ARF patients after
  abdominal aortic aneurysm operation,and 17
  patients died from organ failure during dialysis
  .
• 1975-1977
• MOFS,multiple organ failure
  syndrome-----Baue,1975
• (Yet the treatment did not save the
  lives.)
• MOF ,multiple organ failure-----
  Eiseman,1977
• 1980s
• MSOF,multiple system organ failure-----
  Fry38/533
• point out the relationship between MSOF
  and severe infection
• 1990s ?MODS,multiple organ dysfunction
  syndrome?

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Case 1 Male 26y Post-subtotal excision of
colon Ileocolonic stoma leakage Multiple
intestinal fistula
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Abdominal abscess
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Long-term application of high caloria
parenteral nutrition ( fat emulsion) liver
tumefaction liver dysfunction SGPT 36
SGOT 144 TB 167.9 DB 102.8
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HR 170 RR 55 PaCO2 23.8 WBC 18700
Positive blood cultivation
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Jan 16th septic shock Jan 17th Renal function
BUN 20.5 Cr 337 need inhalation of oxygen
with mask continuous hemofiltration Jan 19th
tracheotomy ventilator application
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Case 2 male 59y Extensive anterior wall
Myocardial infarction 20 days after onset
(2002/3/6) continuous ventricular
tachycardia ?ventricular fibrillation
electric defibrillation 5 times
antiarrhythmic drugs counter shock drugs
ventilator application
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HR 120 RR 28 PaCO2 26.8 WBC 12600
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• Repeatedly ventricular tachycardia and
  fibrillation,totally 21 times electric
  defibrillation
• Continuous hyperpyrexia?high WBC?HR90?RR22
• Cultivation negative, antibiotics no
  effectiveness
• Organ dysfunction came in crowds
• shock
• Respiratory dysfunction
• Deterioration of liver function
• Cast in urine routine test? BUN?Cr ?
  ?oliguria?anuria
• Coagulation abnormality
• death

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Different pts, Same progress
Acute onset Manifestatin of excessive
inflammation Deteriotation of pts conditions
despite active therapy Multiple organ dysfunction
Case 2noninfectious
Case 1 infectious
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Chronic disease Multiple organ low function

• clinical behavior
• Accumulative
• Substance
• irreversible
• Multiple organ low function
• caused by interaction between organs

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MODS followed by primary emergency disease in 24
hours

• Clinical manifestation
• burst out
• Simultaneous
• die quickly
• primary MODS
• Ischemia
• ischemia and reperfusion
• physical and chemical injury factor

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Sequential organ dysfunction after emergency
disease,MODS

• Clinical behavior
• Delayed
• Sequential
• Reversible
• MODS
• Excessive inflammatory mediators

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1.Direct injury of ischemia
Oxygen nutrient insufficiency
ATP?
Integrity of cell membrane ?
organelle insult?

Natrium in-flow
calcium in-flow
Extracellular fluid in-flow
Hydrolase activation
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1.Direct injury of ischemia

• Hypersensibitity in heart and brain
• Selective ischemia
• Endothelial cell injury leads to high vascular
  permeability and low volume

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Injury of ischemia and reperfusion
permeability of cell membrane?
Intracellular acidosis
Lower protein synthesis
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2.Excessive inflammation SIRS MODS
etiological factor
Vessel permeability? WBC chemotaxis
neutrophil
monocyte/macrophage
elastinase PLA2 ODFR
TNF IL-8 et al IL-1 IL-6
Vascular endothelial cell
Adherent molecule
SIRS
Tissue damage
liveracutephase reaction
Remote organ injury
MODS
neutrophil
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Clinical progress
uncontrolled stress
SIRS
Capillary leakage syndrome
MODS
MSOF
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Important molecule in MODS

• Pro-inflammatory cytokinesTNF-aß, IL-1?2?6 etc
• Stimulate synthesis and release of other
  cytokines
• Activate neutrophiles,eosinophils and
  monocytesactivate T and B cellchemotaxis
• Increase the expression of adherent molecule
• Activate complement and coagulation system
• Increase permeability of vessels,decrease BP
• Cause fever and catabolism of muscle

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Important molecule in MODS

• Anti-inflammatory cytokines IL-4?10 etc
• Maintain and enhance the function of activated NK
  cells,monocytes,B and T cells,
• Inhibit proliferation of T,B cell
• Inhibit pro-inflammatory cytokines production ,
  receptor expression and cytotoxicity of monocytes
• Inhibit adherent molecule expression of vascular
  endothelial cells(VECs)
• Inhibit H2O2?NO production of macrophage
• Inhibit antigen presentation and other assistant
  functions of monocytes and macrophage

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Important cells in MODS

• Polymorphonuclear leucocyte(PMN)Effector cell of
  inflammatory response. Could release several
  protein enzymes and ODFR to destroy VECs and
  stroma
• VECsWhen activated, VECs express higher
  adherence to PMN and higher clotting
  competencealso they produce pro-inflammatory
  cytokines and vasodilating agent to magnify
  inflammatory response finally, capillary leakage
  syndrome comes if VECs were destroyed.

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Important organ in MODS

• Intestines
• Because of stress, fasting and catabolism,the
  blood-mucosa barrier of intestines could be
  destructed, the bacteria and toxin tranlocate to
  blood circulation and the latter could enhance
  inflammatory response to form vicious cycle. So
  intestines are called motor of inflammatory
  response,and are sources of late stage infectons
  of MODS pts.

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uncontrolled stress
carbohydrate metabolism dysfunction, Insulin
tolerance, without Ketonemia
hyperkinetic circulatory state, Hyperpyrexia,
High Stroke volume,High oxygen consumption
Protein metabolism dysfunction , high katabolism,
acute phase protein
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Systemic Inflammatory Response syndrome SIRS

• T gt38?or lt36?
• HRgt90 beat/min
• RRgt20/min or PaCO2lt32mmHg
• WBCgt12000mm3 or lt4000mm3 or premature cells gt10

Systemic Inflammatory Response Syndrome (SIRS)
Sepsis
(SIRPositive Culture)
(SIR without infection)
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Chaotic internal milieu during acute phase

• Disturbance of electrolytes and acid-base balance
• Fever
• Catabolism emaciated,anemia
• Acute disseminated intravascular coagulation
• Arrhythmia
• Hyperglycemia, no ketonemia

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Capillary leakage syndrome,CLS

• Secondary aldosteronism
• ---high density urine without Proteinuria,
  oliguria
• ---prerenal azotemia
• ---swollen

• Plasma protein leakage
• ---Interstitial edema
• ---Hypoproteinemia
• ---blood inspissasion
• ---Hypovolemia

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Diagnosis of CLS

• Positive body fluid balance
• Blood volume deficiency
• Hypoproteinemia
• Organ and total body Interstitial edema
• lung Interstitial edema
• cerebral Interstitial edema

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Organs dysfunction or failure
Organ or system
dysfunction
failure
Hypoxemia, respirator at list 3-5days
ARDS,PEEPgt10cmH2O,FiO2gt0.5
lung
Bilirubingt2-3mg/dL, Liver functiongt2 normal value
Bilirubingt2-3mg/dL, icterus
Liver
oliguria
dialysis
kidney
Curlingl's ulcer needs blood transfusion,
Acalculous cholecystitis
Untolerance of enteral nutritiongt5days
intestine
PT or PTT elongation, plateletlt50-80thousand,
Hypercoagulable state
Blood
DIC
central nervous system
Progressive deepen coma
Insanity,light orientation disorder
cardiovascular system
Ejection Fraction ? , capillary leakage
Irresponsivity to muscle strength drugs
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Glasgow Score
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Influenced organ

• Lung ARDS
• gt95
• Kidney ARF
• only a few

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Acute Respiratory Distress Syndrome, ARDS
1.The early stage

• Pathology of lung
• High capillary permeabilityInterstitial edema
• Vasoconstriction,micro thrombosis communicating
  branch opening
• Alveolar and small bronchusAtelectasis
• Decreased alveolar surfactant
• Edema
• I type epithelial cells instead by II type cell
• Symptom
• Tachypnea, respiratory distress can not be eased
  by oxygen inhalation
• No rales
• No lung x-ray abnormality

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1. .The second stage

• Pathology
• Deteriorated lung Interstitial inflammation,usuall
  y complicated with SEPSIS
• Symptom
• Obviously dyspnoea and cyanosisneeds
  ventilator
• Increased respiratory tract secretion, rales
• Lung x-rayinfiltrates
• Disturbance of consciousness
• Febrile or high leucocyte?

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3. Telophase

• Pathology
• Lung parenchyma fibrosis
• Microvascular occlusion
• Increased preload, hypoxia
• Symptom
• Deep coma
• Arrhythmiabradycardiacardiac arrest

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Diagnosis
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Acute Renal Failure, ARF

• Etiology
• Prerenal
• Hemorrhage, shock, fluid losing without
  appropriate fluid resuscitation
• post renal
• both side ureter or urinary flow blocked
• renal
• kidney ischemia (hematorrhea,sepsis, allergic
  reaction)
• intoxication(aminoglycoside antibiotic, biotic
  toxin, chemical)

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Diagnosis of ARF

• 1.History and physical examination
• Etiology
• prerenal pathogen
• postrenal pathogen

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2.Differentiation Diagnosis with prerenal ARF
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3.Differentiation Diagnosis with Postrenal ARF

• B type ultrasound(renal enlargement, ureter)
• Abdominal x-rays(calcification, calculus or
  Obstruction)

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4. Laboratory Urine test

• Urinary catheter to record urine volume
• Urine acidity/density(1.010-1.014)
• Urine microscopic examination
• RBC and renal tubule epithelia(renal cortex and
  renal medulla necrosis)
• Large Brown casts(renal failure casts)
• Eosinophil? (interstitial nephritis)
• Red cell cast(glomerulonephritis)
• Normal(prerenal or postrenal failure earlier
  period)

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5. renal function examination

• Urine urea nitrogen? (lt 180mmol/24)
• Urine Na? (gt 175mmol/24h)
• Fractional excretion of filtrated sodiumgt1
• FENa()(UNa/PNa)(PCr/UCr )100
• osmotic pressure of urine
• ARF------lt 400 mOsm/L
• prerenal ARF or glomerulonephritis------
  gt 400 mOsm/L
• BUN (more than 3.8-9.4mmol/L per day) ,Cr ?
• Urine/Plasma Cr------lt20
• renal failure index, RFI
• RFI Una( PCr/UCr )
• gt1------ARF
• lt1------prerenal

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Intensive care

• Organ and system function Monitoring and support
• Object
• ameliorate oxygen metabolism
• ameliorate nutrien state
• Therapy aimed at stress and inflammatory
  Mediators
• Treatment of capillary leakage
• Treatment of primary disease

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Oxygen metabolism Monitoring

• Critical DO2
• Assay of plasma lactic acid/pyruvic acid

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Oxygen associated index

• DO2 Oxygen Delivery---Oxygen offered to the body
  in a certain period by circulatory system
• DO2CO(1.38SaO2 0.003PaO2)
• VO2 Oxygen Consumption--- Oxygen consumpted by
  all cells in a certain period.
• VO2Ca-vDO2CO10

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Critical delivery oxygen
Sepsis ARDS MODS
Normal
VO2
Critical DO2
DO2
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Lactic Acid and cells hypoxia

• Lactic Acid?--latent cells hypoxia
• lactic acidosis --tissue perfusion deficiency
  and cells hypoxia
• Lactic Acid normal value--- 0.5-1.5 mmol/L
• gt4-5 mmol/L?SB and PH?? lactic
  acidosis
• L/P rate ? -- cells hypoxia
• L/P rate normal value--- 101

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Strategy of ameliorate oxygen metabolism

• Improvement of oxygen delivery
• respiratory support---to improve arterial blood
  oxygen content
• higher inhalated oxygen concentration,ventilator
• increase cardiac output
• Heart rate, cardiac rhythm, cardiac
  contractility, preload/after load
• Blood system
• rise hemoglobin concentration

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Strategy of ameliorate oxygen metabolism

• Increase oxygen extraction ratio
• Ameliorate interstitial edema
• Reduce blood capilary permeability
• Ameliorate oxygen extraction of cells

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Treatmen of CLS

• Limitation of water-intake
• premise never get CO down
• Infusion volume decided by urine volume per hour
  when lung and brain interstitial edema happen.
• Rise colloid osmotic pressure
• Use powerful diuretic
• Use glucocorticoid

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Nutritional support

• Metabolism support
• Offer nutritional substrate but never increase
  organ loading.
• Metabolism modulation
• Inhibition of catabolism hormones
• Promote protein synthesis ,ease negative nitrogen
  balance

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Nutritional support

• Add accessories
• Promote protein synthesis and cell growth
• Modulate immunologic response
• Enteral nutrition
• Protect bowel blood-mucosa barrier (prevent from
  infection )

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Discussion of therapy for stress and
inflammatory mediators

• Antagonism and clearance
• Aim at excessive cytokines
• --- post-translation levels
• Reduction of synthesis
• keep the balance between pro- and anti- cytokines
• --- in transcription levels
• --- in translation level

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Cytokines modulation

• In transcription level
• Anti-mRNA expression
• (NF-?B is in charge of many kinds of
  cytokine expression.)
• Translation level
• Reduce cytokines synthesis
• Post translation level
• Anti-cytokines(antibody or soluble receptor)
• Block receptor of cytokines
• Clearance of cytokines(plasmapheresis)

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Treatmen of ARDS

• Correct hypoxemia quickly
• use ventilator as soon as possible
• appropriate PEEP(regain alveolar function and
  functional residual capacity)

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Treatmen of ARDS

• Maintain Circulation and lung interstitial edema
• Proper crystal/colloid rate
• Diuretic
• Negative water balance (according to CVP/PAWP ,
  urine output and lung auscultation)

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Treatmen of ARDS

• Prevent and treat infection
• Block SIRS
• corticoid in the initial stage
• mediators inhibitor (Ibuprofen,
  Dentoxifylline,TNF antibody)

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Treatment of ARF

• Oliguria or anuria stage
• (7-10days,average 5-6 and max. more than 1
  month)
• confine water intake
• Equal water intake and output
• fluid intake per day(dominant water losing
  ) (non dominant water losing) - (endogeneous
  water)or 0.5kg
• nutrient
• Low protein, high calorie,high Vitamin
• protein synthesis hormones

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Treatment of ARF

• correct electrolytes imbala
• Hyperkalemia
• Hyponatremia
• Hypocalcemia
• Acidosis
• Counterinfection
• blood purification (CHF)

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Diuresis stage

• Proper fluid intake to prevent excessive losing
  of extracellular fluid about 1/3-1/2 water lose
• Correct electrolyte imbalance
• Electrolytes test everyday
• Increase protein intake
• Counterinfection

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Summary
(1) Differences between MODS and multiple organ
low function
Low function
MODS

• primary illness Chronic
  acute

• Pathogenesis interaction among organs
  hypoxia and Mediators

• Pathology NO capillary dysfunction
  capillary dysfunction

• Organ lesion accumulative
  subclinical

substantial
functional
irreversible
reversible
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(2) Differences between MODS and primary MODS

• The effect of ischemia , ischemia-reperfusion or
  other injury factor on cells
• The first strike?primary MODS
• Organell injury
• Cell edema and necrosis
• Cell injury mediated by inflammatory mediators
• The second strike ?secondary MODS
• Cell membrane injury
• Cell metabolism dysfunction, apoptosis

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(3)Modern opinion of MODS development

• Excessive inflammatory response runs through the
  course ,and is the main threaten to life.
• Once SIRS triggers single organ dysfunction, the
  pathophysiological state will get worse
  progressively, and finally MODS come up.
• SIRS ,sepsis and their complications construct a
  CONTINUM,and MOF is the most severe consequence.