Shock 2011

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  • Shock 2011

    1. 1. Eval & Rx of Shock Frank W Meissner, MD, RDMSFACP, FACC, FCCP, FASNC, CPHIMS, CCDS
    2. 2. Case Study58 y/o male Day 1 S/P CABGPersistent Shock @ 18 hrs post CABGShock developed about 8 hr after off-pump -Nursing followed post CABG protocols, butDoubutamine @ 12 mcg/kg/min & freq ectopyHemodynamic parameters: RAP 4, PA 28/5,PAOP 10, C.O. 12 l/min, SVR 400, P 110, T98.4°F, SVO2 85Thoughts?
    3. 3. Hemodynamic profiles of shock states Physiologic Preload Pump function Afterload Tissue perfusion variable Cardiac output SVR MV O2Sat Clinical PCWP/PAOP Myocardial Myocardial pHmeasurement IVC Dimensions Contractility Contractility Lactic AcidHypovolemicCardiogenicDistributive
    4. 4. IntroductionDefinition: a physiologic state caused byinadequate tissue perfusion leading todecreased tissue oxygen delivery (DO2) &decreased tissue oxygen uptake (VO2)Not a blood pressure or an isolated vital signabnormalityA pattern of physiological dysfunction =inadequate tissue perfusion
    5. 5. IntroductionEffects are initially reversible, but lead to cellularhypoxia with: Cell membrane and ion pump dysfunction Intracellular edema Leak intracellular contents into extracelluar space Dysregulation of intracellular pH
    6. 6. Cellular Shock
    7. 7. MOSFRapid Progression to deathPrompt recognition early syms key to survival
    8. 8. PrognosisDespite extensive research, mortality ratesremain high in the published literature Septic: 35-40% Cardiogenic: 60-90% Hypovolemic: variable, depends on etiology and time to treatment
    9. 9. StagesPre-shockShockEnd-organ dysfunction
    10. 10. Stages: Pre-shockWarm or compensated shockRegulatory mechanisms are able tocompensate for diminished perfusion.
    11. 11. Stages: Cold ShockCompensatory mechanisms becomeoverwhelmed, resulting in: Tachycardia Tachypnea Metabolic acidosis Oilguria Cool, clammy skin High SVR
    12. 12. Stages: shockUsually occur with: Loss of 20-25% of effective blood volume Fall in cardiac index to 2.5 L/min/M2 Activation of mediators of the sepsis syndrome
    13. 13. Sepsis: end-organ dysfunction Decreasing urine output Restlessness =>agitation =>obtundation =>coma Mutiple organ system failure than death
    14. 14. Physiologic Determinants Systemic Vascular Resistance (SVR) Vessel length - or length of vessel bed Blood viscosity - incr Hgb => incr resistance Vessel diameter - majority of resistance in small arteriolar vessels (resistance vessels) - 450 to 100 µm SG definition = 80*[(MAP-MPAOP)/CO]
    15. 15. Physiologic determinantsCardiac Output (CO) = HR x SVStroke volume ∫ (preload, myocardialcontractility, afterload)
    16. 16. Pre-Load
    17. 17. Myocardial Contractility Slope of End-systolic pressure volume relationship = Emax or Ees independent measure of contractility
    18. 18. Newer Non-Invasive Hemodynamic MeasuresSystolic Pressure Variation (MaxSBP-MinSBP)Pulse Pressure Variation[(MaxArterialPulsePressure-MinArterialPulsePressure)/MeanArterialPulsePressure]Stroke Volume Variation [(MaxSV-MinSV)/MeanSV]Measurements made during one controlled vent breathIf SPV>10, SVV>10%, PPV>13% => Volume Responsiveness
    19. 19. Do Hemodynamics Matter?Maybe NOT in Septic Shock
    20. 20. ClassificationHypovolemicCardiogenicDistributive
    21. 21. Physiologic Determinants SVR & CO can reliably differentiate shock states Assuming SVR is accurate
    22. 22. Hypovolemic shock#1 Cause of Death Worldwide Hemorrhage Trauma GI bleeding Ruptured aneurysm or hematoma Hemorrhagic pancreatitis Fractures
    23. 23. Hypovolemic shockFluid loss Diarrhea Vomiting Heat stroke Inadequate repletion of insensible losses Burns
    24. 24. Cardiogenic shock2ndary 2 pump failure & decreasedcardiac outputMain categories: Myopathies Arhythmia Mechanical Obstructive
    25. 25. Cardiogenic shockCardiomyopathies: Infarction > 40% of LV mass RV infarction Dilated cardiomyopathies Stunned myocardium 2ndary prolonged ischemia or cardiopulmonary bypass
    26. 26. Cardiogenic shockArrhythmia Lost synchrony of filling of atria & ventricles 2ndary atrial fibrillation (Atrial Kick) Complete loss of CO with ventricular fibrillation Symptomatic bradycardia & heart block with decrease in CO (CO = HR * SV)
    27. 27. Cardiogenic shockMechanical Mitral regurgitation from chordae tendineae rupture Aortic insufficiency due to dissection of ascending aorta into the aortic valve ring Critical aortic stenosis
    28. 28. Cardiogenic shockObstructive Pulmonary embolism Tension pneumothorax Constrictive pericarditis Pericardial tamponade Severe pulmonary hypertension
    29. 29. Distributive shockCauses: Sepsis Activation of systemic inflammatory response system (pancreatitis, burns, multiple trauma) Anaphylaxis Drug or toxin reactions (insect bites, transfusion reactions, heavy metal poisoning)
    30. 30. Distributive shockCauses: Addisonian crisis Myxedema coma Neurogenic shock 2ndary spinal cord trauma MI + SIRS Cardiopulmonary bypass
    31. 31. Common featuresHypotension SBP < 90, MAP < 60 Occurs in most shock patients Initially relative to patient’s baseline blood pressure Drop in SBP > 40 early indicator Progresses profound hypotension, often requiring vasopressors
    32. 32. Common featuresCool, clammy skin Regulatory processes compensate 4 decreased effective tissue perfusion Blood flow redirected to vital organs maintain coronary, cerebral and splanchnic perfusion Lack of peripheral flow leads to classic cool, clammy picture of shock
    33. 33. Common featuresOliguria Result of shunting of renal bloodflow to other vital organs Objective measure of intravascular volume depletion Related signs: tachycardia, orthostatic hypotension, poor skin turgor, absent axillary sweat, dry mucous membranes
    34. 34. Common featuresMental status changes Begins with agitation Progresses to confusion/delirium Ends in obtundation/coma
    35. 35. Common features Metabolic acidosis Initially unexplained respiratory alkalosis Acidosis eventually prevails Accumulation of lactate due to lack of clearance by liver, kidneys and skeletal muscle Increased anaerobic metabolism 2ndary tissue hypoxia in later stages
    36. 36. Initial approachHistory: Food/medicine allergies Recent medication changes Potential acute/chronic drug intoxication Preexisting diseases
    37. 37. Initial approachPhysical exam: HEENT Scleral icterus Dry conjunctivae Dry mucous membranes Pinpoint pupils Fixed/dilated pupils
    38. 38. Initial approachPhysical exam: Neck JVD Delayed carotid upstroke Carotid bruits Meningeal signs
    39. 39. Initial approachPhysical exam: lungs Tachypnea Shallow respirations Crackles/rales Consolidation Egophony
    40. 40. Initial approachPhysical exam: cardiovascular Arrhythmia Murmurs or S3 gallop Diffuse PMI Right or left ventricular heave
    41. 41. Initial approachPhysical exam: Abdomen Tenseness Distension Tenderness Rebound/guarding Absent bowel sounds
    42. 42. Initial approachPhysical exam: rectal Decreased tone Blood (hematochezia or melena)
    43. 43. Initial approachPhysical exam: extremities Calf swelling/palpable cords Unequal pulses Disparity of blood pressure between upper extremities
    44. 44. Initial approachPhysical exam: neurologic Agitation Confusion Delirium Obtundation
    45. 45. Initial approachPhysical exam: skin Cold, clammy Warm, hyperemic Rashes Petechiae Urticara
    46. 46. Initial approachLab evaluation CBC with manual differential Basic chemistries Liver function tests Amylase/lipase Fibrinogen & fibrin split products
    47. 47. Initial approachLab evaluation ABG’s & SVO2 Toxicology screen Chest x-ray Abdominal x-ray
    48. 48. Factors influencing mixed & central venous SO2 75% _ + ↑VO2 ↓DO2 ↑ DO2 ↓VO2 Stress ↓ PaO2 ↑ PaO2 Hypothermia Pain ↓ Hb ↑ Hb Anesthesia Hyperthermia ↓ Cardiac output ↑ Cardiac output Shivering
    49. 49. Interp of SVO2• Like the CO, a low SvO2 tells you something is wrong, but not what and what should be done (fluids? inotropes?).• If SvO2 is normal or high - in septic patients ScvO2 may be elevated 2ndary low O2 extraction
    50. 50. InsertCVP/SvcO2
    51. 51. Insert CVP/SvcO2SvO2 >70%
    52. 52. Insert CVP/SvcO2 SvO2 >70%CVP N or low
    53. 53. Insert CVP/SvcO2 SvO2 >70%CVP N or low Sepsis?
    54. 54. Insert CVP/SvcO2 SvO2 >70%CVP N or low Sepsis? Repeat Fluid challenge 250ml/ 5mins
    55. 55. Insert CVP/SvcO2 SvO2 >70%CVP N or low Sepsis? Repeat Fluid challenge 250ml/ 5mins Haemodynamic improvement ?
    56. 56. Insert CVP/SvcO2 SvO2 >70% CVP N or low Sepsis? Repeat Fluid challenge 250ml/ 5minsContinue untilnormal values obtained Haemodynamic improvement ? Yes
    57. 57. Insert CVP/SvcO2 SvO2 >70% CVP N or low Sepsis? Repeat Fluid challenge 250ml/ 5minsContinue untilnormal values obtained Haemodynamic improvement ? Yes No Vasopressors
    58. 58. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP N or low Sepsis? Repeat Fluid challenge 250ml/ 5minsContinue untilnormal values obtained Haemodynamic improvement ? Yes No Vasopressors
    59. 59. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP low CVP N or low Sepsis? Repeat Fluid challenge 250ml/ 5minsContinue untilnormal values obtained Haemodynamic improvement ? Yes No Vasopressors
    60. 60. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP low CVP N or low Hypovolaemic/ Sepsis? Haemorrhagic/ cause? Repeat Fluid challenge 250ml/ 5minsContinue untilnormal values obtained Haemodynamic improvement ? Yes No Vasopressors
    61. 61. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP low CVP N or low Hypovolaemic/ Sepsis? Haemorrhagic/ cause? Repeat fluid Repeat Fluid challenge challenge (250ml/5mins) 250ml/ 5mins or transfusion if necessary.Continue untilnormal values obtained Haemodynamic improvement ? Yes No Vasopressors
    62. 62. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP low CVP N or low Hypovolaemic/ Sepsis? Haemorrhagic/ cause? Repeat fluid Repeat Fluid challenge challenge (250ml/5mins) 250ml/ 5mins or transfusion if necessary.Continue untilnormal values obtained Continue until normal Haemodynamic values obtained improvement ? Yes Haemodynamic No improvement Vasopressors
    63. 63. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP low CVP N or low Hypovolaemic/ Sepsis? Haemorrhagic/ cause? Repeat fluid Repeat Fluid challenge challenge (250ml/5mins) 250ml/ 5mins or transfusion if necessary.Continue untilnormal values obtained Continue until normal Haemodynamic values obtained improvement ? No response Yes Haemodynamic No improvement Vasopressors
    64. 64. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP low CVP N or low Hypovolaemic/ Sepsis? Haemorrhagic/ cause? Repeat fluid Repeat Fluid challenge challenge (250ml/5mins) 250ml/ 5mins or transfusion if necessary.Continue untilnormal values obtained Continue until normal Haemodynamic values obtained improvement ? No response Yes Haemodynamic No improvement Echocardiography that preceeds Vasopressors CO monitoring
    65. 65. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP high CVP low CVP N or low Hypovolaemic/ Sepsis? Haemorrhagic/ cause? Repeat fluid Repeat Fluid challenge challenge (250ml/5mins) 250ml/ 5mins or transfusion if necessary.Continue untilnormal values obtained Continue until normal Haemodynamic values obtained improvement ? No response Yes Haemodynamic No improvement Echocardiography that preceeds Vasopressors CO monitoring
    66. 66. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP high CVP low CVP N or low Hypovolaemic/ Sepsis? Consider global/right Haemorrhagic/ ventricular failure cause? Repeat fluid Repeat Fluid challenge challenge (250ml/5mins) 250ml/ 5mins or transfusion if necessary.Continue untilnormal values obtained Continue until normal Haemodynamic values obtained improvement ? No response Yes Haemodynamic No improvement Echocardiography that preceeds Vasopressors CO monitoring
    67. 67. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP high CVP low CVP N or low Hypovolaemic/ Sepsis? Consider global/right Haemorrhagic/ ventricular failure cause? Repeat fluid Repeat Fluid challenge challenge Echocardiography that preceeds (250ml/5mins) 250ml/ 5mins cardiac output monitoring or transfusion if necessary.Continue untilnormal values obtained Continue until normal Haemodynamic values obtained improvement ? No response Yes Haemodynamic No improvement Echocardiography that preceeds Vasopressors CO monitoring
    68. 68. Insert CVP/SvcO2 SvO2 >70% SvO2 <70% CVP high CVP low CVP N or low Hypovolaemic/ Sepsis? Consider global/right Haemorrhagic/ ventricular failure cause? Repeat fluid Repeat Fluid challenge challenge Echocardiography that preceeds (250ml/5mins) 250ml/ 5mins cardiac output monitoring or transfusion if necessary.Continue untilnormal values obtained Continue until normal Haemodynamic values obtained improvement ? No response Yes Haemodynamic No improvement Echocardiography that preceeds Vasopressors CO monitoring
    69. 69. PA CatheterizationCan be used to providehemodynamic measurements such as: Cardiac output Pulmonary artery wedge pressure SVRHelpful in determining a cause whenthe differential is broad
    70. 70. PA CatheterizationCan also help with: Monitoring fluid resuscitation Titration of vasopressors Measuring effects of changes in ventilator settings (PEEP) on hemodynamics
    71. 71. PA CatheterizationPA catheters entail significantclinical risks & have never beenproven to improve clinicaloutcomes in a RCTBedside PA Cath ≠ Right HeartCatheterization
    72. 72. Hemodynamic Shock profiles Physiologic Preload Pump function Afterload Tissue perfusion variable Pulmonary Clinical Systemic vascular Mixed venous capillary wedge Cardiac outputmeasurement resistance oxygen saturation pressure Hypovolemic Decreased Decreased Increased Decreased Cardiogenic Increased Decreased Increased Decreased Distributive Decreased Increased Decreased Increased
    73. 73. PA Cath Vs US Measurement PA Cath US RAP + + CO + + (Pulm CO & Aortic CO) PAOP + + LAP ≠ + RV + + PVR + ± SVR + ± SVO2 + - Core body temp + -Cardiac Chamber Sizes - + Ccontractile State - + Valve Function ± + Detection of Shunts ± + Pericardial Dz ± +
    74. 74. Pressure Measurements Doppler US
    75. 75. RUSH Exam
    76. 76. maximal impulse of the heart. It is important for the EP to know RUSH Exam - Probe Sites “The Pump”d Ultrasound in SHock (RUSH) step 1. Evaluation of the pump.
    77. 77. “The Pump”SubCostal View 4-V Enlargement
    78. 78. “The Pump”Large Pericardial Effusion
    79. 79. Studies examining the incidence of pericardial effusions in Emergency Department or “The Pump”Fig. 4. Subxiphoid view: cardiac tamponade. Cardiac Tamponade
    80. 80. “The Pump”Acute RV Strain => Massive PE
    81. 81. a et al “The Pump” Thrombus in RA Apical view: floating thrombus in right atrium.
    82. 82. T RUSH Exam - Probe Sitesstep 2. Evaluation of the tank. IVC exam, inferior vena ca “The Tank”graphy in Trauma), right upper quadrant, left upper quadran
    83. 83. change of the IVC with respiratory variation to central venous pressure (CVP) using anindwelling catheter. A smaller caliber IVC (<2 cm diameter) with an inspiratory collapse “The Tank”Fig. 8. Inferior vena cava sniff test: low cardiac filling pressures. Eval IVC with “Sniff Test”
    84. 84. “The Tank”Perera et alFig. 9. Inferior vena cava sniff test: M-mode Doppler showing collapsible IVC. Eval IVC with “Sniff Test” m-modegreater than 50% roughly correlates to a CVP of less than 10 cm of water. This
    85. 85. reversed. In these patients, the IVC is also less compliant and more distended “The Tank”throughout all respiratory cycles. However, crucial physiologic data can still beFig. 10. Inferior vena cava sniff test: high cardiac filling pressures.Eval IVC with “Sniff Test” High Filling Pressures
    86. 86. Perera et al “The Tank”Fig. 11. Right upper quadrant/hepatorenal view: free fluid.FAST Eval Liver/Kidney R-hypochondrium view
    87. 87. “The Tank” The RUSH ExamFig. 12. Left upper quadrant: pleural effusion. e-FAST Eval L-pleural space Free fluid in the peritoneal or thoracic cavities in a hypotensive patient in whom
    88. 88. repeating horizontal linear lines, demonstrating a lack of lung sliding or absence of “The Tank”the ‘‘beach’’ (see Fig. 14). Although the presence of lung sliding is sufficient to rule The RUSH Exam 45Fig. 13. Long-axis view: normal lung. Fig. 14. M-mode: normal lung versus pneumothorax. e-FAST Eval R/O PTX out pneumothorax, the absence of lung sliding may be seen in other conditions in addition to pneumothorax, such as a chronic obstructive pulmonary disease bleb,
    89. 89. as ruptured abdominal 14). Although the presence of lung dissections, are life-threat- the ‘‘beach’’ (see Fig. aortic aneurysms (AAA) and aortic sliding is sufficient to rule “The Tank”ening causes of hypotension. The survival of such patients may often be measured inminutes, and the ability to quickly diagnose these diseases is crucial. A ruptured AAA is classically depicted as presenting with back pain, hypotension,and a pulsatile abdominal mass. However, fewer than half of cases occur with thistriad, and some cases will present with shock as the only finding.84 A large or rupturingAAA can also mimic a kidney stone, with flank pain and hematuria. Fortunately for theEP, ultrasound can be used to rapidly diagnose both conditions.85 Numerous studieshave shown that EPs can make the diagnosis of AAA using bedside ultrasound, witha high sensitivity and specificity.86–89 The sensitivity of EP-performed ultrasound forthe detection of AAA ranges from 93% to 100%, with specificities approaching100%.86–88 A complete ultrasound examination of the abdominal aorta involves imaging fromthe epigastrium down to the iliac bifurcation using a phased-array or curvilinearFig. 13. Long-axis view: normal lung. e-FAST Eval Pulmonary EdemaFig. 15. Lung ultrasound: edema with B lines.
    90. 90. The RUSH RUSH Exam - Probe Sites6. RUSH step 3. Evaluation of the pipes. “The Pipes”
    91. 91. larger than 5 cm.90 Studies have also confirmed that the EP can reliably make a correct “The Pipes”determination of the size of an AAA.87,91Fig. 17. Short-axis view: large abdominal aortic aneurysm. Abdominal Aorta
    92. 92. “The Pipes”Fig. 18. Short-axis view: aortic dissection. Acute Aortic Dissection
    93. 93. “The Pipes” The RUSH ExamFig. 19. Suprasternal view: aortic dissection. Acute Aortic Dissection‘‘Clogging of the pipes’’: venous thromboembolismBedside ultrasound for DVT In the patient in whom a thromboembolic event is sus-
    94. 94. walls of the vein (Fig. 20).98,99 In contrast, a normal vein will completely collapse with “The Pipes”simple compression. Most distal deep venous thromboses can be detected throughFig. 20. Femoral vein deep venous thrombosis with fresh clot. Femoral Vein U/S Eval
    95. 95. Macro Vs Micro Assessment of ShockResuscitation
    96. 96. Why the microcirculation is important in shock! 1. It is where oxygen exchange takes place. 2. It plays a central role in the immune system. 3. During septic shock it is the first to go and last to recover. 4. Rescue of the microcirculation = resuscitation end-point.
    97. 97. Capillary flow in sepsis
    98. 98. Orthogonal polarizationspectral (OPS) imaging
    99. 99. Shunting model of sepsis Implication : that active recruitment of the microcirculation is an important component of resuscitation. O2 a v lactate CO2Ince C & Sinaasappel M (1999) Crit Care Med 27:1369-1377
    100. 100. Sepsis is a disease of the microcirculation Spronk P, Zandstra D, Ince C (2004) Critical Care 8:462-468
    101. 101. Mitochondrial Dysfunction in Cell Injury Increased cytosolic Ca2+, oxidative stress, lipid peroxidation Mitochondrial Cytochrome c and other PermeabilityTransition pro-apoptotic proteinsRobbins & CotranPathologic Basis of Disease: 2005 Apoptosis
    102. 102. Functional and Morphologic Consequences of Decreased ATP During Cell InjuryIschemia Oxidative Phosphorylation ATP
    103. 103. Functional and Morphologic Consequences of Decreased ATP During Cell InjuryIschemia Oxidative Phosphorylation ATP Anaerobic glycolysis Glycogen pH Clumping chromatin
    104. 104. Functional and Morphologic Consequences of Decreased ATP During Cell InjuryIschemia Oxidative Phosphorylation ATP Anaerobic Na pump glycolysisInflux of Ca2+ GlycogenH20, and Na+ pHEfflux of K+ER swelling ClumpingCell swelling chromatinBlebs
    105. 105. Functional and Morphologic Consequences of Decreased ATP During Cell InjuryIschemia Oxidative Phosphorylation ATP Anaerobic Detachment Na pump glycolysis of ribosomesInflux of Ca2+ Glycogen Protein synthesisH20, and Na+ pHEfflux of K+ER swelling Clumping Lipid depositionCell swelling chromatinBlebs
    106. 106. Hemodynamic Vs mitochondrial failure Energy failureBE - Lactate
    107. 107. Hemodynamic Vs mitochondrial failure Energy Volume failure testBE - Lactate
    108. 108. Hemodynamic Vs mitochondrial failure VO2 ↑ Lactate ↓ Energy Volume failure testBE - Lactate
    109. 109. Hemodynamic Vs mitochondrial failure Hemodynamic failure VO2 ↑ Lactate ↓ Energy Volume failure testBE - Lactate
    110. 110. Hemodynamic Vs mitochondrial failure Hemodynamic failure VO2 ↑ Lactate ↓ Energy Volume failure testBE - Lactate VO2 →↓ Lactate →↓
    111. 111. Hemodynamic Vs mitochondrial failure Hemodynamic failure VO2 ↑ Lactate ↓ Energy Volume failure testBE - Lactate VO2 →↓ Lactate →↓ Pump failure or mitochondrial dysfunction
    112. 112. Hemodynamic Vs mitochondrial failure Hemodynamic failure VO2 ↑ Lactate ↓ Energy Volume failure testBE - Lactate VO2 →↓ Dobutamine Lactate →↓ test Pump failure or mitochondrial dysfunction
    113. 113. Hemodynamic Vs mitochondrial failure Hemodynamic failure VO2 ↑ Lactate ↓ VO2 ↑ Energy Volume Lactate ↓ failure testBE - Lactate VO2 →↓ Dobutamine Lactate →↓ test Pump failure or mitochondrial dysfunction
    114. 114. Hemodynamic Vs mitochondrial failure Hemodynamic failure Pump failure VO2 ↑ Lactate ↓ VO2 ↑ Energy Volume Lactate ↓ failure testBE - Lactate VO2 →↓ Dobutamine Lactate →↓ test Pump failure or mitochondrial dysfunction
    115. 115. Hemodynamic Vs mitochondrial failure Hemodynamic failure Pump failure VO2 ↑ Lactate ↓ VO2 ↑ Energy Volume Lactate ↓ failure testBE - Lactate VO2 →↓ Dobutamine Lactate →↓ test Pump failure or VO2 → mitochondrial Lactate →↑ dysfunction
    116. 116. Hemodynamic Vs mitochondrial failure Hemodynamic failure Pump failure VO2 ↑ Lactate ↓ VO2 ↑ Energy Volume Lactate ↓ failure testBE - Lactate VO2 →↓ Dobutamine Lactate →↓ test Pump failure or VO2 → mitochondrial Lactate →↑ dysfunction Mitochondrial dysfunction
    117. 117. Nitroglycerin promotes microvascular recruitment in septic and cardiogenic shock patients Sublingual OPS imaging in a patient Same patient after subsequent with septic shock after pressure nitroglycerin 0.5 mg IV bolus guided volume resuscitationSpronk, Ince, Gardien, Mathura, Oudemans-van Straaten, Zandstra DF. (2002) The Lancet 360:1395-1396.
    118. 118. Early Goal-Directed Therapy Results 28-day Mortality 60 49.2% 50 P = 0.01* 40 33.3% 30 20 10 0 Standard Therapy EGDT n=133 n=130 *Key difference was in sudden CV collapse, not MODSRivers E. N Engl J Med 2001;345:1368-77.
    119. 119. Therapeutic prioritiesSupportive measures to treat hypoxemia,hypotension and impaired tissue oxygenationDistinguish between sepsis and SIRS (systemicinflammatory response syndrome) so medical/surgical treatment of the source of infection canbe startedAssess for adequate tissue perfusion
    120. 120. Initial management Resuscitation Assess airway, respiration, perfusion Supplemental O2 to all patients Intubation often required to protect airway Mechanical ventilation often needed => development of lung injury or ARDS is common - ‘Shock Lung’
    121. 121. Initial managementMonitoring of tissue perfusion Hypotension is typically present Prompt volume resuscitation & restoration of perfusion pressure can limit end organ damage Arterial catheterization if restoration of perfusion pressure is expected to be protracted process
    122. 122. Initial managementSigns of inadequate organ perfusion: Cool, vasoconstricted skin due to redirection of bloodflow to vital organs Obtundation/restlessness Oliguria/anuria Lactic acidosis
    123. 123. Initial managementRestoration of tissue perfusion - Goal Directed Therapy CVP 8 - 12 MAP > 65 Urine output > 0.5 ml/kg/hr Mixed venous O2 > 70% Use IV fluids, PRBC’s & pressors to achieve goals depending on patient’s intravascular volume, cardiac status & severity of shock
    124. 124. Physiologic Classification ofAcute Circulatory Insufficiency Volume Vessel Heart tone function Fluids / blood Vasopressors Inotropes
    125. 125. Initial management IV fluids Rapid, large volume infusions CHF is primary relative contraindication Relative hypovolemia is often severe Not unusual for a patient to require 10 liters within the first 24 hours
    126. 126. Initial managementIV fluids Should be given in well-defined, rapidly infused boluses (Preferably within 15min) Effects of 1Liter/hr =25% effects of 1liter/15 min = 4liters an hr without the longterm volume effects Assess volume status, tissue perfusion, blood pressure, and for pulmonary edema before/after each bolus Colloids have not been proven to be superior to crystalloids - but have a role in hypoalbuminemia
    127. 127. PRELOAD Assessment-Volume • LOOK @ CVP/ PAOP • Always Eval CVP in relation to CO Volume unresponsive Preload OKVolumeresponsive Failing Heart Add dopamine or dobutamine
    128. 128. “Will my patient respond to fluids?”CO Preload
    129. 129. “Will my patient respond to fluids?” Fluid Responsiveness is a dynamic parameter that reflects the degree by which the CO responds to changes in preloadCO Preload
    130. 130. Initial management May repeat IV fluid boluses until: B/P, tissue perfusion & oxygen delivery are @ goal PAWP > 18 Development of pulmonary edema Septic patients can develop pulmonary edema with normal wedge pressures due to capillary leak
    131. 131. Initial managementIV fluids: how much? Central venous catheters monitor central venous pressures - Continuous SVO2 monitoring sheaths - SVV measurements + continuous C.O. monitors Also can estimate mixed venous oxygen content Simultaneous MV 02 & Arterial O2 sats + Hgb measurement allow 4 calculation of C.O. by Fick eq
    132. 132. Initial management Vasopressors Second-line agents Useful in patients who fail to reach adequate blood pressures despite adequate volume resuscitation Also useful in patients who develop cardiogenic pulmonary edema
    133. 133. Initial management Vasopressors Dopamine & levophed recommended are first-choice drugs - RCT neither superior Phenylephrine (pure α-adrenergic) useful when tachycardia or arrhythmia with β- adrenergic activity limit their use- no data showing efficacy in septic shock Vasopressin is added to patients refractory to first-choice agents
    134. 134. Properties of Vasopressors Arterial Drug HR Contractility constriction Dobutamine + +++ - Dopamine ++ ++ ++ Epinephrine +++ +++ ++Norepinephrine ++ ++ +++Phenylephrine 0 0 +++ Amrinone + +++ --
    135. 135. Monitoring therapy response All patients require close monitoring Evidence of deterioration => prompt re-evaluation
    136. 136. Monitoring therapy response Monitoring parameters: Respiratory: PaO2/FiO2 ratio Renal: hrly U/O, BUN, creatinine Hematologic: CBC, %Bands, platelet counts CNS: Glascow coma scale Hepatobiliary: bilirubin, LFT’s CV: P, B/P, arterial lactate, SVO2 GI: ileus, blood in NG aspirate
    137. 137. Monitoring therapy response Ebb phase: Restore arterial perfusion pressures to pre- sepsis levels Flow phase: Maintain oxygen delivery to meet ongoing tissue needs
    138. 138. Monitoring therapy response Detection of tissue hypoxia Arterial lactate concentration is most useful measure of tissue perfusion Limited in that it is a global measure and can miss significant injury to a specific organ system
    139. 139. Monitoring therapy response Treatment of tissue hypoxia Study compared standard treatment (MAP>65, CVP>8, urine output>0.5 ml/kg/ hr) to maintaining central venous O2 saturation > 70%
    140. 140. Monitoring therapy response Results: Decreased in-hospital mortality (30% vs. 46%) Lower arterial lactate concentration following 6 hours of therapy Lower APACHE II and SAPS II scores Decreased evidence of multiple organ dysfunction
    141. 141. Monitoring therapy response Red blood cell transfusions were used aggressively in this study to maintain DO2 (70% in study arm vs. 45% in control arm) Recommend maintaining Hct > 30 to maintain adequate tissue oxygen delivery
    142. 142. Monitoring therapy response If arterial lactate concentrations fail to fall with adequate transfusion, cardiac output must be increased Further IV fluid therapy can be given Dobutamine is given when arterial pressures are adequate to tolerate afterload reduction (phenylephrine/norepineprhine can be added if needed)
    143. 143. Control of septic focus Prompt identification & treatment infectious source is critical All previously discussed treatments are supportive - not definitive
    144. 144. Control of septic focus Identification of septic focus: Blood cultures (2 sets, aerobic and anaerobic) Urine Gram stain and culture Sputum in a patient with productive cough Intra-abdominal collection in post-operative patients
    145. 145. Control of septic focusInvestigational methods: TREM-1 (triggering receptor expressed on myeloid cells) Elevated serum procalcitonin
    146. 146. Control of septic focus Eradication of infection Potentially infected foreign bodies (vascular access devices) Percutaneous or surgical drainage of abscesses Soft-tissue debridement or amputation if necessary
    147. 147. AntibioticsAntimicrobial regimen Started promptly after cultures are obtained Inappropriate antibiotic selection is depressingly common & can increase mortality Time to initiation of treatment is shown to be the strongest predictor of mortality
    148. 148. AntibioticsIf pseudomonas is not likely, vancomycin (+) 3rd/4th generation cephalosporin β-lactam/β-lactamase inhibitor CarbapenemUp to 60% Septic Shock patient’s with negativecultures
    149. 149. AntibioticsIf pseudomonas likely, vancomycin and 2 of thefollowing (Synergistic Pseudomona Coverage): Antipseudomonal cephalosporin Antipseudomonal penicillin/β-lactamase inhibitor Antipseudomonal carbepenem Floroquinolone with good antipseudomonal activity Aminolgycoside
    150. 150. Recombinant HumanActivated Protein C (Xigris) Coagulation abnormalities are common in septic shock Several reports have suggested that protein C supplementation may produce clinical benefit, esp with purpura fulminans
    151. 151. Recombinant HumanActivated Protein C (Xigris) PROWESS trial: Lower 28-day mortality rate (24.7 vs. 30.8%) Non-significant increase in serious bleeding Was of greater benefit in the most acutely ill patients (APACHE II > 25)
    152. 152. Recombinant HumanActivated Protein C (Xigris) PROWESS trial limitations: Excluded patients with chronic renal failure Patients with metastatic cancer, pancreatitis and organ transplant recipients were excluded after 720 patients were enrolled Cell line used to produce drug was changed during the trial
    153. 153. Recombinant HumanActivated Protein C (Xigris) ENHANCE trial: Similar 28-day all-cause mortality rates Increase in incidence of serious bleeding (specifically intracranial hemorrhage) was significant Treatment within 24 hours of first sepsis- related organ dysfunction showed significantly lower mortality than those treated after 24 hours
    154. 154. Recombinant HumanActivated Protein C (Xigris) ADDRESS trial Patients with APACHE II scores < 25 Designed to enroll 11,000 patients Stopped after 2,600 patients were enrolled because it was unlikely to show any benefit
    155. 155. NutritionEssential for optimal immune functionBeneficial in both treatment of & prevention ofsepsisEarly enteral nutrition offers > benefit thanparenteral nutrition & less risk + maintains gutintegrity & lowers risk of GIBResults in higher neutrophil counts and higheralbumin levels
    156. 156. Glucose controlCritically ill patients can develop hyperglycemiaand insulin resistance regardless of a history ofdiabetesSeveral papers have shown improvement inoutcome with aggressive glucose control (goalGlucose = 80-110 mg/dl)
    157. 157. Concluding Advice
    158. 158. Concluding Advice• Fluid resuscitation to keep a CI > 2.5 l/min/m2 with a Ppao < 20 mm Hg
    159. 159. Concluding Advice• Fluid resuscitation to keep a CI > 2.5 l/min/m2 with a Ppao < 20 mm Hg• Add inotropic support if unable to sustain CI within this Ppao limit
    160. 160. Concluding Advice• Fluid resuscitation to keep a CI > 2.5 l/min/m2 with a Ppao < 20 mm Hg• Add inotropic support if unable to sustain CI within this Ppao limit• Vasopressors to maintain a mean arterial pressure > 65 mm Hg
    161. 161. Concluding Advice• Fluid resuscitation to keep a CI > 2.5 l/min/m2 with a Ppao < 20 mm Hg• Add inotropic support if unable to sustain CI within this Ppao limit• Vasopressors to maintain a mean arterial pressure > 65 mm Hg• If measures of organ perfusion available (urine output, ΔPCO2, tissue blood flow, Serum lactate, base deficit ) use them to guide response to therapy.
    162. 162. Concluding Advice• Fluid resuscitation to keep a CI > 2.5 l/min/m2 with a Ppao < 20 mm Hg• Add inotropic support if unable to sustain CI within this Ppao limit• Vasopressors to maintain a mean arterial pressure > 65 mm Hg• If measures of organ perfusion available (urine output, ΔPCO2, tissue blood flow, Serum lactate, base deficit ) use them to guide response to therapy.• Trends may be more important than absolute values

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