1、多脏器功能障碍综合征及监护,上海第二医科大学附属瑞金医院SICUSurgical ICU of Ruijin Hospital Shanghai Second Medical University,MODS and intensive care,2,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
2、 organ failure during dialysis .19751977 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,mu
3、ltiple organ dysfunction syndrome,3,Case 1Male 26yPost-subtotal excision of colonIleocolonic 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.
4、8,6,HR 170 RR 55PaCO2 23.8WBC 18700,Positive blood cultivation,7,Jan 16th septic shockJan 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 da
5、ys after onset (2002/3/6) continuous ventricular tachycardiaventricular fibrillation electric 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 defi
6、brillationContinuous hyperpyrexia、high WBC、HR90、RR22Cultivation negative, antibiotics no effectivenessOrgan dysfunction came in crowdsshockRespiratory dysfunctionDeterioration of liver functionCast in urine routine test BUN、Cr oliguria、anuriaCoagulation abnormalitydeath,11,Acute onsetManifestatin of
7、 excessive inflammationDeteriotation of pts conditions despite active therapyMultiple organ dysfunction,Different pts, Same progress,Case 1: infectious,Case 2:noninfectious,12,clinical behaviorAccumulativeSubstanceirreversibleMultiple organ low functioncaused by interaction between organs,Chronic di
8、sease Multiple organ low function,13,MODS followed by primary emergency disease in 24 hours,Clinical manifestationburst outSimultaneousdie quicklyprimary MODS Ischemiaischemia and reperfusionphysical and chemical injury factor,14,Sequential organ dysfunction after emergency disease,MODS,Clinical beh
9、aviorDelayedSequentialReversibleMODSExcessive inflammatory mediators,15,1.Direct injury 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,Hyperse
10、nsibitity in heart and brainSelective ischemiaEndothelial cell injury leads to high vascular permeability and low volume,17,permeability of cell membrane,Intracellular acidosis,Lower protein synthesis,Injury of ischemia and reperfusion,Vessel permeability WBC chemotaxis,monocyte/macrophage,neutrophi
11、l,elastinase PLA2 ODFR,TNF IL8 et al IL1 IL6,liver：acutephase reaction,Remote organ 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,MOD
12、S,MSOF,20,Important molecule in MODS,Pro-inflammatory cytokines:TNF-, IL-1、2、6 etcStimulate 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 systemI
13、ncrease permeability of vessels,decrease BPCause fever and catabolism of muscle,21,Important 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 pr
14、oduction , receptor expression and cytotoxicity of monocytesInhibit adherent molecule 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,Polymorphonucl
15、ear leucocyte（PMN）：Effector cell of inflammatory response. Could release several protein 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
16、inflammatory response; finally, capillary leakage syndrome comes if VECs were destroyed.,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 co
17、uld 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.,24,uncontrolled stress,carbohydrate metabolism dysfunction, Insulin tolerance, without Ketonemia,hyperkinetic circulatory state, Hyp
18、erpyrexia, High Stroke volume,High oxygen consumption,Protein metabolism dysfunction , 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 wi
19、thout infection),Systemic Inflammatory Response syndrome SIRS,26,Chaotic internal milieu during acute phase,Disturbance of electrolytes and acid-base balanceFeverCatabolism: emaciated,anemiaAcute disseminated intravascular coagulationArrhythmiaHyperglycemia, no ketonemia,27,Secondary aldosteronism -
20、high density urine without Proteinuria, oliguria -prerenal azotemia -swollen,Plasma protein leakage -Interstitial edema -Hypoproteinemia -blood inspissasion -Hypovolemia,Capillary leakage syndrome,CLS,28,Diagnosis of CLS,Positive body fluid balanceBlood volume deficiencyHypoproteinemiaOrgan and tota
21、l body Interstitial edemalung Interstitial edemacerebral Interstitial edema,29,Organs 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
22、-3mg/dL, icterus,oliguria,dialysis,Untolerance of enteral nutrition5days,Curlingls ulcer 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 edem
23、aVasoconstriction,micro thrombosis communicating branch openingAlveolar and small bronchusAtelectasisDecreased 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 ea
24、rly stage,33,PathologyDeteriorated lung Interstitial inflammation,usually complicated with SEPSISSymptomObviously dyspnoea and cyanosisneeds ventilatorIncreased respiratory tract secretion, ralesLung x-rayinfiltratesDisturbance of consciousnessFebrile or high leucocyte,.The second stage,34,3. Teloph
25、ase,PathologyLung parenchyma fibrosisMicrovascular occlusionIncreased preload, hypoxiaSymptomDeep comaArrhythmiabradycardiacardiac arrest,35,Diagnosis,36,Acute Renal Failure, ARF,Etiology PrerenalHemorrhage, shock, fluid losing without appropriate fluid resuscitationpost renalboth side ureter or uri
26、nary flow blockedrenalkidney ischemia (hematorrhea,sepsis, allergic reaction)intoxication(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.Differe
27、ntiation Diagnosis with Postrenal ARF,B type ultrasound(renal enlargement, ureter)Abdominal 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(
28、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),41,5. renal function examination,Urine urea nitrogen ( 175mmol/24h)Fractional excretion of filtrated
29、sodium1 FENa（%）=（UNa/PNa）（PCr/UCr ）100osmotic pressure of urine *ARF- 400 mOsm/LBUN (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 stre
30、ss and inflammatory MediatorsTreatment of capillary leakageTreatment of primary disease,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（1.38S
31、aO2 + 0.003PaO2）VO2 Oxygen Consumption- Oxygen consumpted by all cells in a certain 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 h
32、ypoxia Lactic Acid normal value- 0.5-1.5 mmol/L 4-5 mmol/LSB and PH lactic acidosis 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 conce
33、ntration,ventilatorincrease cardiac output Heart rate, cardiac rhythm, cardiac contractility, preload/after loadBlood systemrise hemoglobin concentration,48,Strategy of ameliorate oxygen metabolism,Increase oxygen extraction ratioAmeliorate interstitial edemaReduce blood capilary permeabilityAmelior
34、ate oxygen extraction of cells,49,Treatmen of CLS,Limitation of water-intakepremise: 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
35、supportOffer nutritional substrate but never increase organ loading.Metabolism modulationInhibition of catabolism hormonesPromote protein synthesis ,ease negative nitrogen balance,51,Nutritional support,Add accessoriesPromote protein synthesis and cell growthModulate immunologic response Enteral nut
36、ritionProtect bowel blood-mucosa barrier (prevent from infection ),52,Discussion of 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 le
37、vels - in translation level,53,Cytokines modulation,In transcription levelAnti-mRNA 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 o
38、f cytokines(plasmapheresis),54,Treatmen of ARDS,Correct hypoxemia quicklyuse ventilator 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
39、 balance (according to CVP/PAWP , urine output and lung auscultation),56,Treatmen of 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 t
40、han 1 month)confine water intakeEqual water intake and output fluid intake per day=(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 imbalaHyperkalemiaH
41、yponatremiaHypocalcemiaAcidosisCounterinfection blood purification (CHF),59,Proper fluid 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) Diff
42、erences 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 reversib
43、le,61,(2) Differences between MODS and primary MODS,The effect of ischemia , ischemia-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 m
44、etabolism dysfunction, apoptosis,62,(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.,
