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Manifestations of mof
- 1. MOF …. Continued. SINTAYEHU (GSR1)
- 2. Clinical manifestations Does not occur as “a non or all rule” A range of organ dysfunction resulting in clinical organ failure Post traumatic syndrome of MOF follows a predictable course Lung dysfunction precedes Cardiac by 0.6 days Hepatic by 4.8 days Renal by 5.5 days on average This sequential pattern is affected by pre-existing diseases or the nature of clinical event
- 3. Contd. Clinical manifestation and temporal evolution of MOF is influenced by Host factors Advanced age Comorbid diseases Immunosuppressive drugs Genetic factors influence severity and progression genetic polymorphisms in genes controlling the synthesis of cytokines (eg, TNF, IL-10) or TLR receptors manifest an excessive inflammatory response to acute injury or sepsis …… higher risk for MODS
- 4. Early MOF usually manifests within first 72hrs of the physiologic insult in one of these ways Physiologic derangement Need for specific organ supportive therapy Separate clinical syndrome
- 5. Pulmonary dysfunction: ARDS Acute respiratory failure with formation of non-cardiogenic PE reduced lung compliance and hypoxaemia which is refractory to oxygen therapy. Characterized by Diffuse pulmonary infiltrates seen on CXR Pulmonary wedge pressure of < 18mmHg, PaO2/FiO2 ratio of < 26.6 kPa (200 mmHg)
- 6. Causes of ARDS Direct Pulmonary insults Lung contusion, pneumonia, smoke inhalation etc. Indirect Severe extra pulmonary diseases like bacteremia, trauma, pancreatitis Two phases Initiator: release of pro-inflammatory mediators Effector phase: activated leukocytes release proteolytic enzymes and ROS…..degradation of components of basement membrane……alveolar flooding and surfactant deactivation
- 7. management Predisposing insult Nutritional support Low tidal volume MV Prognosis MR 50-60% and when with sepsis, MR increases to 90%
- 8. Ventilator induced lung injury VILI develops during treatment of ARDS and fuels failure of other organs Characterized by PaO2/FIO2 200 to 300 May or may not progress to ARDS
- 9. Hepatic dysfunction Circulatory shock Hepatic hypoperfusion Ischemic hepatic injury Gut derived cathecolamines activate adrenoceptors on kupffer cells TNF and NO production Acute hepatic dysfunction Diffuse hepatic inflammation circulation Lung injury
- 10. 1, Ischemic hepatitis or shock liver Hepatic hypo perfusion decreased protein synthesis, lactate clearance, gluconeogenesis and glycogenolysis Characterized by elevations in aminotransferase level, prothrombin time, INR Significant lactic acidosis Profound hypoglycemia Centrilobular necrosis on histology Successful reversal of the shock state with aggressive resuscitation often reverses the biochemical abnormalities.
- 11. ICU jaundice Typically conjugated hyperbilirubinemia Develops days after the physiologic insult and more common Histologic features include intrahepatic cholestasis, steatosis, and Kupffer cell hyperplasia Causes Ongoing ischemia TPN cholestasis Drug toxicity Damage to bile canaliculi by infla.mediators or bact.toxin
- 12. GI dysfunction Likely results from interacting effects of reduced regional blood flow, impaired motility, and change in normal microbial flora Manifestations include Stress gastritis ileus and intolerance of enteral feeding, pancreatitis, and acalculous cholecystitis Stress bleeding frequency has decreased recently due to Improved resuscitation Stress ulcer prophylaxis
- 13. Renal dysfunction Reflected by Decrease in UOP <0.5ml/kg/hr Increased creatinine level Need for replacement therapy or dialysis Early onset: hypotension, decreased RBF Late onset: multifactorial Pre-renal factors like d CO and hypovolemia Nephrotoxic agents( drugs and radiocontrast) release of cytokines (TNF induces apoptosis of renal cells) Aggravated by vasoactive agents used in shock treatment
- 14. Metabolic dysfunction Severe physiologic stress induces a syndrome of metabolic alterations termed hypermetabolic stress response Occurs in 60 to 65% of stressed patients Changes include: Increased VO2 Hyperglycemia Hyperlactatemia Protein catabolism 15 to 20% of patients have inappropriate hypometabolic response Stratifying severity of stress to identify significant hypermetabolism
- 15. Adrenocortical insufficiency Serum cortisol inadequate for ongoing stress response Cytokine mediated decrease in synthesis or release of corticotropin releasing hormone, ACTH or cortisol May also result from long term administration of glucocorticoids Characterized by Decreased SVR, CO and hypovolemia Considered in critically ill patients vasopressor dependent despite adequate resuscitation and source control Dx Random serum cortisol<10micg/dl or increase <9micg/dl after 250micg/dl iv ACTH stimulation test
- 16. Glucose disorders Hyperglycemia Develops early following insult Causes Increased glycogenolysis and gluconeogenesis Due to increase in stress hormones ACTH,glucocorticoids, glucagon, cathecolamines and insulin resistance Hypoglycemia occurs late Depletion of glycogen store Failure of gluconeogenesis in liver
- 17. Cardiovascular dysfunction Altered peripheral vascular and myocardial function in the absence of pre existing dysfunction Clinically manifests with Peripheral edema with hypotension refractory to volume challenge Need for vasoactive agents to support circulation Early hyper dynamic phase Late hypo daynamic phase NO is implicated in both the peripheral vasodilatation and the myocardial depression. Dilation of ventricles-----increase LVEDV…..maintain SV despite impaired contractility
- 18. Despite correction of macrovascular hemodynamic parameters, persistent microvascular dysfunction is associated with organ dysfunction and death Endothelial activation mediated by Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) …. induces superoxide generation, and enhances endothelial adhesiveness to leukocytes and chemokine production….endothelial dysfunction ……MODs LOX_1 a novel target for modulation of inflammation in microcirculation
- 19. Neurologic dysfunction CNS dysfunction In 70% of critically ill patients Confusion, disorientation, decreased level of consciousness Without focal signs Recently known to be independent predictor of poor out come Complex phenomenon involving Alteration of BBB Entry of circulating cytokines Endotoxemia stimulating local production of TNF by microglia and astrocytes TNF induces brain edema, neutrophil infiltration, astrocytosis, and apoptotic cellular death
- 20. PNS dysfunction (critical illness polyneuropathy) clinical presentation tends to be more subtle than that of CNS Diffuse weakness, depressed reflex, distal sensory loss Limb weakness with spared cranial nerves Suspected when failure of weaning from MV despite improvement of underlying critical illness
- 21. Pathology axonal degeneration Cause is not well understood Inflammatory mediators thought to play a role Preventable aspects Unnecessary and prolonged NM blockade Prolonged or high dose glucocorticoids Excessive propofol use Electrolyte abnormalities, glycemic control
- 22. Hematologic dysfunction DIC or Thrombohemorrhagic disorders Most fulminant hematologic dysfunction in MOF results from a massive activation of the clotting cascade Activation of hemostasis leading to formation of thrombin Compensatory thrombolysis( secondary fibrolysis) Degrade fibrinogen and other clotting factors, causing consumption coagulopathy, exacerbating the bleeding diathesis
- 23. Thrombocytopenia the most common hematologic abnormality critical illness -in 20% 0f all ICU pts -causes .↑sed consumption .impaired thrombopoiesis from BM suppression Others Mild anemia Leucopenia from overwhelming inflammatory stimulus
- 24. Laboratory examinations No specific test for MODs Abnormalities in the following tests are commonly seen Acid-base: d anion gap ….associated with increased mortality CBC: normocytic anemia, high or low WBC, thrombocytopenia LFTs insensitive to diagnose early liver dysfunction in MODs Serum albumin: in MODs hypoalbuminemia results from cytokine induced suppression of synthesis, albumin catabolism, dilutional and 3rd space losses. Adverse px but poor sensitivity and specificity Procalcitonin: plasma marker of sepsis. Septic vs nonseptic, not specific
- 25. Hemodynamic monitors of tissue perfusion Global SvO2/ ScvO2>70% Esophageal Doppler probe…measure CO during resuscitation after trauma Regional perfusion Gastric tonometry PHi and PCO2 Siblingual capnometry
- 26. Modifiable Delay in resuscitation Amount of RBC transfusion Age of transfused products High base deficit Uncorrected lactate at 12- 24hrs post injury Abdominal compartment syndrome Missed injury Non modifiable High injury severity Age >55years old Obesity Male gender Genetics Comorbidities Predictors of MOF
- 27. Biomarker Disease conditions Role Neutrophil gelatinase- Lipocalin (NGAL) acute kidney injury Detects 36-48hrs earlier than creatinine Serum glutamate/glutamine Sepsis Marks liver dysfunction Cytokeratin-18 (CK-18) Sepsis with hepatic dysfunction Early predictor of survival Procalcitonin (PCT) Sepsis and infection Early marker Adrenomedullin (AM) Acute cardiac injury Elevated in early septic shock Pentraxin-3 (PTX3) Acute lung and heart injury Correlate with severity NT-pro-BNP severe sepsis and septic shock Marks myocardial dysfunction VCAM-1(vascular cell adhesion molecule 1) Mediates adhesion of cells to endothelium Cytokines (interleukine; IL) 6 Myocardial disfunction Predictor of mortality Endothelial cell-specific molecule 1 (ESM-1 sepsis Endocan increase indicate poor prognosis
- 28. Scoring of MOF No gold standard system Most organ failure assessment systems assign values to six organ systems Respiratory Cardiovascular Renal Hematology, Hepatic Central nervous system Sauaia et al. reported Denver and Marshall MODS perform well as indicators of unfavorable outcomes in critically ill patients
- 29. Marshall MOF scores Evaluate 6 systems each scored 0-4 Parameters recorded at same time of day always Does not consider specific values as indicators of MOF Establishes degree of severity defined by observed mortality
- 30. Denver scale evaluates 4 systems each scored 0-3 OF defined as score>0 , MOF is defined as failure of 2 or more organs with score of 4 or more as determined 48hrs after trauma Ciesla et al, The role of the lung in postinjury multiple organ failure Surgery 01-OCT-2005; 138(4): 749-57
- 31. Management principles Early aggressive resuscitation and physiologic monitoring Avoid additional insults and control sources Prevent nosocomial infection Supportive therapy for dysfunctional organ Glycemic control and early enteral nutrition Prophylaxis: DVT , Stress ulcer Minimize blood transfusion when possible Use agents that can disrupt end organ injury Activated protein C Current Therapy of Trauma and Surgical Critical Care eds Asensio and Trunkey 2008
- 32. Prognosis of MOF Depends on Number of failing organs MR 27-100% Duration of organ dysfunction Advanced age Premorbid illness Knaus
- 33. References Mastery of Surgery, 5th Edition ACS surgery: principles and practices, 2007 edition Subston text book of surgery, 19th edition International Journal of Clinical Medicine, 2012, 3, 722-730 de Montmollin and Annane Critical Care2011, 15:236 Can J Surg, Vol. 51, No. 2, April 2008 EDWIN A. DEITCH, M.D.
- 34. Thank you
Editor's Notes
- Th e authors showed that LOX-1 neutraliza tion reduced endotoxin-induced leukocyte adher ence and reduced plasma levels of monocyte chemoattractant protein-1 (MCP-1), a major chemokine.