多脏器功能障碍综合征及监护

1. 多脏器功能障碍综合征及监护 MODS and intensive care 上海第二医科大学附属瑞金医院SICU Surgical ICU of Ruijin Hospital Shanghai Second Medical University

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 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 • 1980‘s MSOF，multiple system organ failure----- Fry38/533 point out the relationship between MSOF and severe infection • 1990‘s ※MODS,multiple organ dysfunction syndrome※

3. Case 1 Male 26y Post-subtotal excision of colon Ileocolonic stoma leakage Multiple 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 55 PaCO2 23.8 WBC 18700 Positive blood cultivation

7. 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

8. 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

9. HR 120 RR 28 PaCO2 26.8 WBC 12600

10. Repeatedly ventricular tachycardia and fibrillation，totally 21 times electric defibrillation • Continuous hyperpyrexia、high WBC、HR≥90、RR≥22 • 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

11. Different pts, Same progress Acute onset Manifestatin of excessive inflammation Deteriotation of pts’ conditions despite active therapy Multiple organ dysfunction Case 2:noninfectious Case 1: infectious

12. Chronic disease Multiple organ low function • clinical behavior • Accumulative • Substance • irreversible • Multiple organ low function • caused by interaction between organs

13. 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

14. Sequential organ dysfunction after emergency disease,MODS • Clinical behavior • Delayed • Sequential • Reversible • MODS • Excessive inflammatory mediators

15. 1.Direct injury of ischemia Oxygen & nutrient insufficiency ATP↓ Integrity of cell membrane ↓ organelle insult↓ calcium in-flow Natrium in-flow Hydrolase activation Extracellular fluid in-flow

16. 1.Direct injury of ischemia • Hypersensibitity in heart and brain • Selective ischemia • Endothelial cell injury leads to high vascular permeability and low volume

17. ADP Na+ AMP adenosine Ca++ IMP hypoxanthine riboside H2O hypoxanthine xanthine oxidase Xanthine dehydrogenase xanthine oxygen-derived free radidicals xanthine oxidase Uric Acid Injury of ischemia and reperfusion permeability of cell membrane↑ Intracellular acidosis Lower protein synthesis

18. 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 liver：acutephase reaction Remote organ injury MODS neutrophil

19. Clinical progress uncontrolled stress SIRS Capillary leakage syndrome MODS MSOF

20. Important molecule in MODS Pro-inflammatory cytokines:TNF-αβ, IL-1、2、6 etc • Stimulate synthesis and release of other cytokines • Activate neutrophiles,eosinophils and monocytes;activate T and B cell;chemotaxis • Increase the expression of adherent molecule • Activate complement and coagulation system • Increase permeability of vessels,decrease BP • Cause fever and catabolism of muscle

21. Important molecule in MODS Anti-inflammatory cytokines: IL-4、10etc • 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

22. Important cells in MODS • Polymorphonuclear leucocyte（PMN）：Effector cell of inflammatory response. Could release several protein enzymes and ODFR to destroy VECs and stroma • VECs：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 destroyed.

23. 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.

24. 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

25. Systemic Inflammatory Response syndromeSIRS • T ＞38℃or ＜36℃ • HR＞90 beat/min • RR＞20/min or PaCO2＜32mmHg • WBC＞12000mm3 or ＜4000mm3 or premature cells ＞10％ Systemic Inflammatory Response Syndrome (SIRS) Sepsis (SIR+Positive Culture) (SIR without infection)

26. 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

27. Capillary leakage syndrome,CLS • Secondary aldosteronism • ---high density urine without Proteinuria, oliguria • ---prerenal azotemia • ---swollen • Plasma protein leakage • ---Interstitial edema • ---Hypoproteinemia • ---blood inspissasion • ---Hypovolemia

28. Diagnosis of CLS • Positive body fluid balance • Blood volume deficiency • Hypoproteinemia • Organ and total body Interstitial edema • lung Interstitial edema • cerebral Interstitial edema

29. Organs dysfunction or failure Organ or system dysfunction failure Hypoxemia, respirator at list 3-5days ARDS,PEEP>10cmH2O,FiO2>0.5 lung Bilirubin>2-3mg/dL, Liver function>2 normal value Bilirubin>2-3mg/dL, icterus Liver oliguria dialysis kidney Curlingl's ulcer needs blood transfusion, Acalculous cholecystitis Untolerance of enteral nutrition>5days intestine PT or PTT elongation, platelet<50-80thousand, 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

30. Glasgow Score

31. Influenced organ • Lung ——ARDS >95% • Kidney—— ARF only a few

32. Acute Respiratory Distress Syndrome, ARDS 1.The early stage • Pathology of lung • High capillary permeability——Interstitial edema • Vasoconstriction,micro thrombosis ——communicating branch opening • Alveolar and small bronchus——Atelectasis • 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

33. .The second stage • Pathology • Deteriorated lung Interstitial inflammation,usually complicated with SEPSIS • Symptom • Obviously dyspnoea and cyanosis——needs ventilator • Increased respiratory tract secretion, rales • Lung x-ray——infiltrates • Disturbance of consciousness • Febrile or high leucocyte↑

34. 3. Telophase • Pathology • Lung parenchyma fibrosis • Microvascular occlusion • Increased preload, hypoxia • Symptom • Deep coma • Arrhythmia—bradycardia—cardiac arrest

35. Diagnosis

36. Acute Renal Failure, ARF • Etiology • Prerenal • Hemorrhage, shock, fluid losing without appropriate fluid resuscitation • post renal • both side ureter or urinary flow blocked • renal • kidneyischemia (hematorrhea,sepsis, allergic reaction) • intoxication(aminoglycoside antibiotic, biotic toxin, chemical)

37. Diagnosis of ARF 1.History and physical examination • Etiology • prerenal pathogen • postrenal pathogen

38. 2.Differentiation Diagnosis with prerenal ARF

39. 3.Differentiation 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 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)

41. 5. renal function examination • Urine urea nitrogen↓(< 180mmol/24) • Urine Na↑ (> 175mmol/24h) • Fractional excretion of filtrated sodium>1 FENa（%）=（UNa/PNa）×（PCr/UCr ）×100 • osmotic pressure of urine *ARF------< 400 mOsm/L *prerenal ARF or glomerulonephritis------ > 400 mOsm/L • BUN (more than3.8－9.4mmol/L per day) ,Cr ↑ • Urine/Plasma Cr------<20 • renal failure index, RFI RFI＝ Una×（ PCr/UCr ） *>1------ARF *<1------prerenal

42. 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

43. Oxygen metabolism Monitoring • Critical DO2 • Assay 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 DO2＝CO×（1.38×SaO2 + 0.003×PaO2） • VO2 Oxygen Consumption--- Oxygen consumpted by all cells in a certain period. VO2＝Ca-vDO2×CO×10

45. Critical delivery oxygen Sepsis ARDS MODS Normal VO2 Critical DO2 DO2

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/L→SB and PH↓→ lactic acidosis • L/P rate ↑ -- cells hypoxia L/P ratenormal value--- 10:1

47. 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

48. Strategy of ameliorate oxygen metabolism • Increaseoxygen extraction ratio • Ameliorate interstitial edema • Reduce blood capilary permeability • Ameliorate oxygen extraction of cells

49. 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

50. 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