Multi-Organ Dysfunction Syndrome (MODS)
Define multi-organ system (MODS) failure within the context of critical care. (often happens with ARDS, Sepsis et
Shock)
Clarify major sequelae associated with MODS.
Define key concepts and treatment regiments associated with MODS
Multiple Organ Failure Syndrome
Defined - “Failure of multiple organs of biological systems following any severe metabolic insult such as trauma,
shock, surgery, or sepsis.” (Kreis, 2006)
Systems that may fail - CV, Pulmonary, Renal, Liver, GI, metabolic, immune system and coagulation.
Primary cause - Cell death related to severe ischemia or sepsis.
Systemic low blood flow and/or isolated ischemia with cellular and humoral effects leading to organ injury.
Chemical mediators - Major contributor to organ failure.
Respiratory system may be the first to fail.**
Temporary shock states lead to result in varying degrees of cell ischemia.
What Organs Fail?
• Pulmonary, Renal, Cardiovascular, Hepatic, GI
• Poor prognosis
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Mortality rate
•
- One organ/systems 40%
•
- Two organ/systems 60%
•
- Four or more
100%
Risk Factors
• Major Cause: Chemical Mediators
• Respiratory system is the first the fail: Cellular metabolism Preexisting disease: cirrhosis, ESRD, COPD, cancer,
CAD, sepsis, coagulopathies, necrotic tissue, massive transfusions, steroids, malnutrition, drug overdose,
immobilization, trauma, major surgery, hypotension, hypothermia, acidosis.
• Most frequent: temporary shock state resulting in varying degrees or body cell ischemia.
Clinical Progression
Injury
Low Grade Fever
Tachycardia
Dyspnea
Infiltrates on CXR
ARDS
Hyperdynamic/Hypermetabolic
state
Increased Urea
Nitrogen excretion
Increased Bilirubin
Increased Creatinine
Bacteremia/poor
wound healing/skin
breakdown
Compensatory Mechanisms fail/renal
failure/Death
Multiple Organ Dysfunction Syndrome (4 phases)
• 1. General increased capillary permeability.
•
- increased edema, decreased albumin, protein 3rd spacing, decreased urine production, ARDS.
• Malperfusion (Global Ischemia)
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- Blood flow falls below required metabolic demand
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- Blood flow fails to provide adequate oxygen to meet demand
•
- Capillary perfusion is altered by the influx of chemical mediators.
2. Hypermetabolic state. – system overdrive
•
- inflammatory/stress response, increased VO2 (must have compensatory mechanism to meet increased
demand)
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- Mild hyperglycemia secondary to insulin resistance.
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- Increased lactate levels.*** causing metabolic acidosis
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- Increased protein metabolism.
3. Organ Malfunction.
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- Localized injury secondary to cellular death, bacterial and endotoxin translocation from GI tract.
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- Blood flow is not evenly distributed to all organs.
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- GI mucosa, skeletal muscles.
4. Organs return to normal an/or permanent damage (death)
Chemical Mediators
1. Chemical Mediators
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- Vasopressin (ADH) - antidiuretic effects (V2 receptors), vasoconstriction (V1 receptors)
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- ADH increases
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- Stimulus for release; baroreceptors, osmoreceptors
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- hemorrhage promotes marked release of ADH
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- dehydration: long- term stimulus depletes stores
2. Renin Angiotensin-Aldosterone System.
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- Renin acts on angiotensinogen (plasma protein) and converts angiotensin I to angiotensin II in the lung. (ACE)
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- Stimulus for release is decreased renal perfusion. catecholamines/sympathetic.
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- angiotensin II potent vasoconstrictor, primarily in the intestine.
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- Cardiac effects - + inotropic, + chronotropic, coronary vasoconstriction
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- meds that block the renin-angiotensin system
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- ACE inhibitors (Captopril, Vasotec)
3. Myocardial Depressant Factor
• - Primarily in the pancreas but may be release from other organs
• - decreased blood flow to abdominal viscera, especially pancreas.
• - ischemic or hemorrhagic pancreatitis.
• - hypoperfusion leads to acidosis, hypoxia, and ischemia to pancreas.
• - decrease inotropic effect and constriction of blood vessels
4. Cytokines (Humoral Mediators)
• - endogenous proteins that exist and form within monocytes or macrophages.
• - thought to be responsible for “acute phase reaction” or “acute reactive proteins.”
• - inflammatory response by the liver by initial insult (infection, trauma)
• - Interleukin, Tumor Necrosis Factor (TNF), Platelet Activating Factor (PAF).
• - Interrelated and stimulate each other leading to increase metabolism, aggregation of platelets, increased
vascular permeability.
5. Free Oxygen Radicals
• - produces ischemia to tissue leading to inflammatory response.
• - injury to cells, mitochondrial function and endothelial layers.
• - decreased ATP production, decreased Ca transport by sarcoplasmic reticulum, changes action potential.
• - endothelial damage leads to CAD.
Liver Response to Ischemia and Mediators
• - Hepatic artery and portal vein secondary to shock state.
• - In early shock - catecholamine release, increased gluconeogenesis, increased elevated blood sugar.
• - important to control blood glucose.
• - increased bilirubin, PT, AST, ALT, and later...ammonia
Liver Failure
• - decreased function, decreased gluconeogenesis (late sign-hypoglycemia), increased bilirubin, depressed
metabolism.
• - increased ammonia - lack of urea metabolism after GI bacteria convert urea to ammonia.
• - encephalopathy.
• - altered fat metabolism leads to elevated triglycerides increasing measured osmolality.
• - albumin levels are effected (effecting hydrostatic pressure – causing fluid in interstitial space: fluid overload,
but intravascular depletion)and plasma proteins effected.
Pancreas (angry organ!)
• - Low blood flow leads to ischemia, edema, necrosis, inflammation, microvascular thrombi.
• - cell damage leads to release of cellular proteases and lipases which trigger autodigestion and release of
enzymes into circulation.
• - myocardial depressant factor (MDF) and accelerates shock.
• - abdominal pain.
• - Lab: elevated- amylase, lipase
• Tx: attempt to maintain adequate blood flow.
GI Tract
• - GI tract effected by septic shock, hypovolemic, or hemorrhagic shock.
• - Low blood flow causes increased ADH activates the renin-angiotensin system causes severe vasoconstriction
to GI tract.
• - GI wall breaks down (Mucosal Barrier) causing bacteria and other toxins to be released (bacterial
translocation).
• - Sympathetic stimulation slows activity.
• - Mucosal damage causes loss of water, electrolytes, and proteins.
• GI Mucosa
Anaerobic metabolism
Increased levels / decreased pH - acidotic
Tissue beds
• - Decreased blood flow leads to increased coagulation and microclots.
• - necrotic bowel – metabolic acidosis
• - Steroids potentiate bowel wall breakdown and bleeding.
• - H2 antagonists, Proton Pump Inhibitors to slow acid production and decrease GI regurgitation. May result in
pneumonia with enteric bacteria if not treated.
• - Tx: monitor for GI bleeding, maintain adequate blood flow and BP, enteral feeding to maintain wall integrity.
• - use of broad spectrum antibiotics.
• - Caution: possible overgrowth of Clostridium Difficile.
• - Brown-green watery diarrhea (may lead to increased hypovolemia, increased fever, leukocytosis)
• - stool culture.
• - Caution with drugs that decrease GI motility.
Renal System
• - pre-renal and infrarenal failure
• - Hypotension or low CO leads to low renal blood flow, autoregulation lost.
• - Autoregulation is lost when MAP is below 60 mmHg for 40 mins.
• - usually involves toxic damage to the tissue by endotoxins.
• - vasoactive mediators, O2 radicals.
• - rhabdomyolysis (myoglobin release – causing crystalization in urine – kidney blockage) or hemolysis (free Hgb).
Neurological
• - Brain - Vulnerable to lack of O2 from ischemic shock.
• - hypotension (MAP < 60 mmHg) causes autoregulation begins to fail. Below 40, brain is ischemic.
• - liver and renal compromise leads to encephalopathy.
• - tight glucose control to maintain brain glucose levels.
• - Tx: maintain adequate BP and CPP (cerebral perfusion pressure). Monitor osmolality.
Pulmonary System
• - Lungs are important because of secondary hypoxic effects.
• - Lungs receive the first chemical mediators and create more ischemic tissue.
• - Thus, the lungs are one of the first organs to show signs of MODS.
• - May be primary injury (aspiration, contusion, inhalation injury)
• - May be secondary injury (sepsis, shock, inflammation)
• - Stress causes a hypermetabolic state in attempt to compensate for higher O2 demand.
• - Injury to the lungs potentiates oxygen free radicals from multiple sources.
• - ARDS frequently develops.
• - Platelet activation causes increased aggregation and microclotting.
• - Endotoxins - bradykinin, TNF, histamines - increase capillary permeability
• - Pulmonary edema.
• - Platelet activation causes bronchoconstriction
• - Microclotting occurs.
• - Ventilator induced lung injury.
• - High FIO2, volutrauma.
• - Potentiate chemical mediators.
Cardiac Function
• - Reminders:
•
- cardiac cells tolerate approximately 15-30 ischemia using energy sources (ATP and Creatnine Phosphate use
while ischemic).
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- once used, contractility drops.
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- Low CO contributes to other body tissue ischemia, injury and death with more chemical mediators.
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- increased dysrhythmia’s and cardiac depression.
• - Injured cells get excess influx of calcium.
• - impairs relaxation and diastolic filling, coronary flow and increases demands.
• - Ca Channel Blockers may be helpful to prevent myocardial overload to maintain ATP metabolism.
• - Reduction in dysrhythmia’s, reduce vasospasm, reduce negative inotrope and decrease afterload.
• - Oxygen radicals - releases from ischemic cardiac tissue.
Cardiac effects from sepsis.
• - dialation of ventricles, decreased contractility, low ejection fraction but high CO due to dialation.
• - pulmonary hypertension from ARSD adds to right heart strain.
• - high metabolic demand - increased HR - increased O2 demand - more ischemia.
Shock (review)
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- Initial stage - Pre-shock (compensated, warm)
- S/S - tachy, cool, clammy, metabolic acidosis, low BP, oliguria, decreased LOC.
-Types: Anaphylaxis, Neurogenic, Cardiogenic, Obstructive, Hypovolemic, Septic.
- First 8-12 hours of any high risk patient is critical.
• - BP is not an early indicator.
• - Good history, assessment, diagnostic tests.
O2 Transport
Oxygen Supply vs. Demand
Perfusion pressure or gradient (MAP-CVP)
Maintain 60-80.
Limited in oxygen distribution to tissues and other organs.
• - Tissue swelling
• - Capillary microclotting / vasoconstriction
Shock and MODS
Major Treatments: Underlying Cause:
• - Adequate fluid resuscitation (Maintain CI, DO2I, preload pressures and prevent vasoconstriction.
• - Support cardiac function (prevent acidosis, low inotropic support, provide adequate O2 without overload).
• - Support ventilation (maintain O2 and decreased WOB)
• - Adequate nutritional support.*** helps prevent GI breakdown
• - Sedation (decrease high O2 demands)
Hypovolemic Shock
• - Decreased circulating volume (hemorrhage, third spacing)
• - Compensatory Mechanisms:
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- early shift from interstitial to vascular.
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- low venous return causing low CO.
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- Renin-angiotensin activation (autonomic stimulation) Vasoconstriction
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- Redistribution of blood flow to vital organs
Hypovolemic Shock Signs and Symptoms
• - 10 % Volume Loss (approx. 750cc) minimal or no change in BP, HR, CVP.
• - 20 % Volume Loss (1000-1250cc) mild hypotension, increased HR, slight narrow in pulse pressure.
• - 30-35% Volume Loss (1500-1750cc) severe hemorrhage, hypotension, narrow pulse pressure, tachypnea.
• - SVR increased.
Hypovolemic Shock Tx:
• - Fluid resuscitation
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- LR (composition close to plasma, slightly hypotonic, may lower blood viscosity)
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- NS (slightly hypertonic, preferred in hypovolemia not due to bleeding)
• - Maximize O2 transport.
• - Monitor Lactate levels.
• - Use caution with analgesics. (due to effects of BP)
• - May require colloids or blood products.(especially in DIC)
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Septic Shock
- Infection (microorganism invasion with an inflammatory response)
- SIRS (Systemic Inflammatory Response Syndrome) (If no organism identified)
- Fever + Leukocytosis
- Recognized by two of the following:
1. Temp > 38 C or <36 C.
2. HR > 90 bpm.
3. RR > 20 breaths per minute or PaCO2 < 32
4. WBC > 12,000 cells/mm, < 4000 cells/mm or > 10% bands**
SIRS
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Complex Inflammatory Pathways
Triggered by
• Injury
• Hypoxia
• Hypoperfusion
• No organism identified
Septic Shock
• - Refractory hypotension.
• - Sepsis with hypotension despite fluid resuscitation.
• - Defined as SBP < 90mmHg or a reduction of > 40 mmHg from baseline in the absence of other causes.
• Hyperdynamic Phase:
• - Early phase (release of endotoxins causing damage to blood vessel endothelium)
• - Causes vasodialation and increased permeability.
• - Warm, flushed
• - High demand on respiratory system.
• - Tachycardia with normal or low BP.
• Hypodynamic Phase
• - Late phase (hypovolemia from fluid shifts, high sympathetic response, tachy, low CO, WBC’s may drop*)
• - Tx. - Early Antibiotics, fluid resuscitation and/or vasopressors (norepinephrine).
Septic Shock Treatments:
• - Early recognition of potential sources (lines, wounds, lungs, urine, bowels).
• - Maintain fluid volume (MAP > 60mmHg).
• - Vasopressors - Levophed to maintain SVR with fluids. More CO support.
• - Maintain adequate O2 delivery, intubate, oxygenate, treat ARDS, Hgb levels.
• - nutritional support with high caloric requirement.
• - Prevent secondary complications (DVT, PE, stress related GI bleeding, nosocomial infection. Oral Care. Skin
integrity and cross contamination.
Summary of Treatment Goals
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Control of hemorrhage
Rapid correct of hypoperfusion
Halt oxygen debt accumulation
Appropriate antibiotic administration
Resuscitative efforts must focus on stopping development of cellular dysfunction resulting in the downward
spiral to MODS and death.