1、多脏器功能障碍综合征及监护,MODS and intensive care,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 .19751977 MOFS，multiple organ failure syndrome-Baue，1975
2、 （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,3,Case 1Male 26yPost-subtotal excision of colonIleoco
3、lonic stoma leakageMultiple intestinal fistula,4,Abdominal abscess,5,Long-term application of high caloria parenteral nutrition ( fat emulsion) liver tumefaction liver dysfunction SGPT 36 SGOT 144 TB 167.9 DB 102.8,6,HR 170 RR 55PaCO2 23.8WBC 18700,Positive blood cultivation,7,Jan 16th septic shockJ
4、an 17th Renal function BUN 20.5 Cr 337 need inhalation of oxygen with mask continuous hemofiltration Jan 19th tracheotomy ventilator application,8,Case 2 male 59yExtensive anterior wall Myocardial infarction 20 days after onset (2002/3/6) continuous ventricular tachycardiaventricular fibrillation el
5、ectric defibrillation 5 times antiarrhythmic drugs counter shock drugs ventilator application,9,HR 120 RR 28PaCO2 26.8WBC 12600,10,Repeatedly ventricular tachycardia and fibrillation，totally 21 times electric defibrillationContinuous hyperpyrexia、high WBC、HR90、RR22Cultivation negative, antibiotics n
6、o effectivenessOrgan dysfunction came in crowdsshockRespiratory dysfunctionDeterioration of liver functionCast in urine routine test BUN、Cr oliguria、anuriaCoagulation abnormalitydeath,11,Acute onsetManifestatin of excessive inflammationDeteriotation of pts conditions despite active therapyMultiple o
7、rgan dysfunction,Different pts, Same progress,Case 1: infectious,Case 2:noninfectious,12,clinical behaviorAccumulativeSubstanceirreversibleMultiple organ low functioncaused by interaction between organs,Chronic disease Multiple organ low function,13,MODS followed by primary emergency disease in 24 h
8、ours,Clinical manifestationburst outSimultaneousdie quicklyprimary MODS Ischemiaischemia and reperfusionphysical and chemical injury factor,14,Sequential organ dysfunction after emergency disease,MODS,Clinical behaviorDelayedSequentialReversibleMODSExcessive inflammatory mediators,15,1.Direct injury
9、 of ischemia,Oxygen & nutrient insufficiency,Integrity of cell membrane ,organelle insult,ATP,Extracellular fluid in-flow,Hydrolase activation,Natrium in-flow,calcium in-flow,16,1.Direct injury of ischemia,Hypersensibitity in heart and brainSelective ischemiaEndothelial cell injury leads to high vas
10、cular permeability and low volume,17,permeability of cell membrane,Intracellular acidosis,Lower protein synthesis,Injury of ischemia and reperfusion,18,Vessel permeability WBC chemotaxis,monocyte/macrophage,neutrophil,elastinase PLA2 ODFR,TNF IL8 et al IL1 IL6,liver：acutephase reaction,Remote organ
11、injury,Tissue damage,etiological factor,neutrophil,Adherent molecule,2.Excessive inflammation SIRS MODS,Vascular endothelial cell,SIRS,MODS,19,Clinical progress,uncontrolled stress,SIRS,Capillary leakage syndrome,MODS,MSOF,20,Important molecule in MODS,Pro-inflammatory cytokines:TNF-, IL-1、2、6 etcSt
12、imulate synthesis and release of other cytokinesActivate neutrophiles,eosinophils and monocytes;activate T and B cell;chemotaxisIncrease the expression of adherent molecule Activate complement and coagulation systemIncrease permeability of vessels,decrease BPCause fever and catabolism of muscle,21,I
13、mportant molecule in MODS,Anti-inflammatory cytokines: IL-4、10 etcMaintain and enhance the function of activated NK cells,monocytes,B and T cells，Inhibit proliferation of T,B cellInhibit pro-inflammatory cytokines production , receptor expression and cytotoxicity of monocytesInhibit adherent molecul
14、e expression of vascular endothelial cells(VECs)Inhibit H2O2、NO production of macrophageInhibit antigen presentation and other assistant functions of monocytes and macrophage,22,Important cells in MODS,Polymorphonuclear leucocyte（PMN）：Effector cell of inflammatory response. Could release several pro
15、tein enzymes and ODFR to destroy VECs and stromaVECs：When activated, VECs express higher adherence to PMN and higher clotting competence;also they produce pro-inflammatory cytokines and vasodilating agent to magnify inflammatory response; finally, capillary leakage syndrome comes if VECs were destro
16、yed.,23,Important organ in MODS,IntestinesBecause 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 “m
17、otor” of inflammatory response,and are sources of late stage infectons of MODS pts.,24,uncontrolled stress,carbohydrate metabolism dysfunction, Insulin tolerance, without Ketonemia,hyperkinetic circulatory state, Hyperpyrexia, High Stroke volume,High oxygen consumption,Protein metabolism dysfunction
18、 , high katabolism, acute phase protein,25,T 38or 36HR90 beat/minRR20/min or PaCO232mmHgWBC12000mm3 or 4000mm3 or premature cells 10,Sepsis,Systemic InflammatoryResponse Syndrome (SIRS),(SIR+Positive Culture),(SIR without infection),Systemic Inflammatory Response syndrome SIRS,26,Chaotic internal mi
19、lieu during acute phase,Disturbance of electrolytes and acid-base balanceFeverCatabolism: emaciated,anemiaAcute disseminated intravascular coagulationArrhythmiaHyperglycemia, no ketonemia,27,Secondary aldosteronism -high density urine without Proteinuria, oliguria -prerenal azotemia -swollen,Plasma
20、protein leakage -Interstitial edema -Hypoproteinemia -blood inspissasion -Hypovolemia,Capillary leakage syndrome,CLS,28,Diagnosis of CLS,Positive body fluid balanceBlood volume deficiencyHypoproteinemiaOrgan and total body Interstitial edemalung Interstitial edemacerebral Interstitial edema,29,Organ
21、s dysfunction or failure,Organ or system,dysfunction,failure,lung,Liver,kidney,intestine,Blood,Hypoxemia, respirator at list 3-5days,ARDS,PEEP10cmH2O,FiO20.5,Bilirubin2-3mg/dL, Liver function2 normal value,Bilirubin2-3mg/dL, icterus,oliguria,dialysis,Untolerance of enteral nutrition5days,Curlingls u
22、lcer needs blood transfusion, Acalculous cholecystitis,PT or PTT elongation, platelet95%Kidney ARF only a few,32,Acute Respiratory Distress Syndrome, ARDS,Pathology of lungHigh capillary permeabilityInterstitial edemaVasoconstriction,micro thrombosis communicating branch openingAlveolar and small br
23、onchusAtelectasisDecreased alveolar surfactantEdemaI type epithelial cells instead by II type cellSymptomTachypnea, respiratory distress can not be eased by oxygen inhalationNo ralesNo lung x-ray abnormality,1.The early stage,33,PathologyDeteriorated lung Interstitial inflammation,usually complicate
24、d with SEPSISSymptomObviously dyspnoea and cyanosisneeds ventilatorIncreased respiratory tract secretion, ralesLung x-rayinfiltratesDisturbance of consciousnessFebrile or high leucocyte,.The second stage,34,3. Telophase,PathologyLung parenchyma fibrosisMicrovascular occlusionIncreased preload, hypox
25、iaSymptomDeep comaArrhythmiabradycardiacardiac arrest,35,Diagnosis,36,Acute Renal Failure, ARF,Etiology PrerenalHemorrhage, shock, fluid losing without appropriate fluid resuscitationpost renalboth side ureter or urinary flow blockedrenalkidney ischemia (hematorrhea,sepsis, allergic reaction)intoxic
26、ation(aminoglycoside antibiotic, biotic toxin, chemical),37,1.History and physical examinationEtiologyprerenal pathogenpostrenal pathogen,Diagnosis of ARF,38,2.Differentiation Diagnosis with prerenal ARF,39,3.Differentiation Diagnosis with Postrenal ARF,B type ultrasound(renal enlargement, ureter)Ab
27、dominal x-rays(calcification, calculus or Obstruction),40,4. Laboratory Urine test,Urinary catheter to record urine volumeUrine acidity/density(1.010-1.014)Urine microscopic examinationRBC and renal tubule epithelia(renal cortex and renal medulla necrosis)Large Brown casts(renal failure casts)Eosino
28、phil (interstitial nephritis)Red cell cast(glomerulonephritis)Normal(prerenal or postrenal failure earlier period),41,5. renal function examination,Urine urea nitrogen ( 175mmol/24h)Fractional excretion of filtrated sodium1 FENa（%）=（UNa/PNa）（PCr/UCr ）100osmotic pressure of urine *ARF- 400 mOsm/LBUN
29、(more than 3.89.4mmol/L per day) ,Cr Urine/Plasma Cr-1-ARF *1-prerenal,42,Intensive care,Organ and system function Monitoring and supportObjectameliorate oxygen metabolismameliorate nutrien stateTherapy aimed at stress and inflammatory MediatorsTreatment of capillary leakageTreatment of primary dise
30、ase,43,Oxygen metabolism Monitoring,Critical DO2Assay of plasma lactic acid/pyruvic acid,44,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
31、period. VO2Ca-vDO2CO10,45,Critical DO2,VO2,DO2,SepsisARDSMODS,Normal,Critical delivery oxygen,46,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 4-5 mmol/LSB and PH lactic acidosis
32、L/P rate - cells hypoxia L/P rate normal value- 10:1,47,Strategy of ameliorate oxygen metabolism,Improvement of oxygen deliveryrespiratory support-to improve arterial blood oxygen contenthigher inhalated oxygen concentration,ventilatorincrease cardiac output Heart rate, cardiac rhythm, cardiac contr
33、actility, preload/after loadBlood systemrise hemoglobin concentration,48,Strategy of ameliorate oxygen metabolism,Increase oxygen extraction ratioAmeliorate interstitial edemaReduce blood capilary permeabilityAmeliorate oxygen extraction of cells,49,Treatmen of CLS,Limitation of water-intakepremise:
34、 never get CO downInfusion volume decided by urine volume per hour when lung and brain interstitial edema happen.Rise colloid osmotic pressureUse powerful diureticUse glucocorticoid,50,Nutritional support,Metabolism supportOffer nutritional substrate but never increase organ loading.Metabolism modul
35、ationInhibition of catabolism hormonesPromote protein synthesis ,ease negative nitrogen balance,51,Nutritional support,Add accessoriesPromote protein synthesis and cell growthModulate immunologic response Enteral nutritionProtect bowel blood-mucosa barrier (prevent from infection ),52,Discussion of
36、therapy for stress and inflammatory mediators,Antagonism and clearanceAim at excessive cytokines - post-translation levelsReduction of synthesis keep the balance between pro- and anti- cytokines - in transcription levels - in translation level,53,Cytokines modulation,In transcription levelAnti-mRNA
37、expression (NF-B is in charge of many kinds of cytokine expression.)Translation levelReduce cytokines synthesisPost translation level Anti-cytokines(antibody or soluble receptor)Block receptor of cytokinesClearance of cytokines(plasmapheresis),54,Treatmen of ARDS,Correct hypoxemia quicklyuse ventila
38、tor as soon as possibleappropriate PEEP（regain alveolar function and functional residual capacity),55,Treatmen of ARDS,Maintain Circulation and lung interstitial edemaProper crystal/colloid rateDiureticNegative water balance (according to CVP/PAWP , urine output and lung auscultation),56,Treatmen of
39、 ARDS,Prevent and treat infectionBlock SIRScorticoid in the initial stagemediators inhibitor (Ibuprofen, Dentoxifylline,TNF antibody),57,Treatment of ARF,Oliguria or anuria stage (7-10days,average 5-6 and max. more than 1 month)confine water intakeEqual water intake and output fluid intake per day=(
40、dominant water losing )+ (non dominant water losing) - (endogeneous water)or 0.5kgnutrient Low protein, high calorie,high Vitaminprotein synthesis hormones,58,Treatment of ARF,correct electrolytes imbalaHyperkalemiaHyponatremiaHypocalcemiaAcidosisCounterinfection blood purification (CHF),59,Proper f
41、luid intake to prevent excessive losing of extracellular fluid: about 1/31/2 water loseCorrect electrolyte imbalanceElectrolytes test everydayIncrease protein intakeCounterinfection,Diuresis stage,60,Summary,(1) Differences between MODS and multiple organ low function,Low function,MODS,primary illne
42、ss Chronic acute,Pathogenesis interaction among organs hypoxia and Mediators,Pathology NO capillary dysfunction capillary dysfunction,Organ lesion accumulative subclinical,substantial functional,irreversible reversible,61,(2) Differences between MODS and primary MODS,The effect of ischemia , ischemi
43、a-reperfusion or other injury factor on cellsThe first strikeprimary MODSOrganell injuryCell edema and necrosisCell injury mediated by inflammatory mediators The second strike secondary MODSCell membrane injuryCell metabolism dysfunction, apoptosis,62,(3)Modern opinion of MODS development,Excessive
44、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.,
