pmb department of medicine : sepsis, what is it › medicine › presentation33.pdf · survival...
TRANSCRIPT
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Sepsis
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What is it?The ACCP/SCCM Consensus Conference Committee. 1992
Continuum: from systemic inflammatory response to sepsis-associated organ dysfunction.SIRS : inflammatory process independent of its causeConfirmed infectious process: SepsisSevere sepsis: associated with:
organ dysfunctionhypoperfusion abnormalitysepsis-induced hypotension
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SIRSSystemic inflammatory response syndrome(SIRS): The systemic inflammatory response to a wide variety of severe clinical insults manifests by 2 or more of the following conditions: Temperature greater than 38°C or less than 36°C Heart rate greater than 90 beats per minute (bpm) Respiratory rate greater than 20 breaths per minute or PaCO2 less than 32 mm Hg White blood cell count greater than 12,000/mL, less than 4000/L, or 10% immature (band) forms
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SepsisThis is a systemic inflammatory response to a documented infection. The clinical features include 2 or more of the following conditions as a result of a documented infection: Rectal temperature greater than 38°C or less than 36°CTachycardia (>90 bpm) Tachypnea (>20 breaths per min)With sepsis, at least 1 of the following manifestations of inadequate organ function/perfusion also must be included:
Alteration in mental state Hypoxemia (PaO2 <72 mm Hg at FiO2 [fraction of inspired oxygen] 0.21; overt pulmonary disease not the direct cause of hypoxemia)Elevated plasma lactate levelOliguria (urine output <30 mL or 0.5 mL/kg for at least 1 h)
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Severe Sepsis:Sepsis and SIRS associated with:
organ dysfunctionhypoperfusion (lactic acidosis, oliguria, or an acute alteration in mental status)hypotension
Sepsis-induced hypotension (ie, systolic blood pressure <90 mm Hg or a reduction of >40 mm Hg from baseline)Septic shockMODS: presence of altered organ function, acutely ill, homeostasis cannot be maintained without intervention.
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How does it work?
Uncontrolled inflammatory response: Lewis Thomas theory – TNF-α, IL-1Compensatory antiinflammatoryresponse syndrome (CARS) may antagonize SIRS and restore homeostasisIf successful prognosis is excellent
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If proinflammatory condition persists or excessive anti-inflammation :MODS is likely to develop as the
patient transitions through the mixed antagonist response syndrome (MARS).
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Trials to block the inflammmatorycascade. Failure of antiinflammatory agents.Frequency of exaggerated inflammatory response is lower than was originally thought to be.
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Failure of the Immune system?
Sepsis patients have features consistent with immunosuppression
Loss of delyaed hypersensitivityInability to clear infectionPredisposition to nosocomil infections
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Apoptosis and AnergyApoptosis – programmed cell death
May be due to endogenous release of glucocorticoids
Necrotic cells cause immune stimulation and enhance antimicrobial defensesApoptotic cell death, induces anergy orantiinflammatory cytokines that impair the response to pathogensAnergy – state of nonresponsiveness to antigen.Immune response seated in T-cells fails to proliferate or secrete cytokines.
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Current Research Indications
Initially increase in inflammatory mediatorsShift toward an anti-inflammatory immunosuppressive sateMech: shift to anti-inflammatory cytokines - interlukin 4 and 10
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The dead speak
Autopsy studies:Profound loss of cells in the adaptive immune systemOnly cells dying are lymphocytes and gastrointestinal epithelial cellsCell death in the heart, kidneys, liver, and lung does not correlate with clinical evidence. ? Much organ dysfunction can be explained by cell hibernation or cell stunning
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New Postulate Normal stress response – activation of antiinflammatory mechanisms outside of affected tissues – antiinflammatory responses predominate. Survival among patients with sepsis correlates with the recovery of the inflammatory but not the immunosuppresive functionImmunosupression is a primary rather than a compensatory response to sepsis.
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Who
Mortality/Morbidity: 21.6-50.8%Sex: male preponderance 52-66%most often in elderly patients
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So What?
Prevention is better than cureEarly goal-directed therapyFind the site of infection – treat itVentilationMetabolic supportSteroids
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Prevention is better than cure
Identify patients with impaired host defense mechanismsVentilatory support and invasive catheters worsen the risk of infection. Avoiding the use of catheters. Add topical antibiotics around invasive catheters Prophylactic antibiotics in the perioperativephase, particularly following gastrointestinal surgery, may be beneficial
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Early goal directed therapy
Work to specific goals – pre/intra opcentral venous pressure of 8 to 12 mm HgMAP 65 to 90 mm Hgurine output of 0.5 ml/kg/hr or greatercentral venous oxygen saturation 70%cardiac index greater than 2.5 L/min/m2use of vasocative drug dose necessary to achieve these goals.lactate, base deficit, pH
Standardize these goals
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Further resuscitationIntubation and assisted ventilation Large volumes of fluid.
Administer fluid therapy with predetermined boluses (500 mL or 10 mL/kg)2-4 times more volume of crystalloids than colloids may increase extravascular fluid fluxes
CVP - sustained rise in filling pressure of more than 5 mm Hg indicates that the compliance of the vascular system is decreasing
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Inotropes
MAP required for adequate splanchnicand renal perfusion When?
does not respond to several liters usually 4 L or moreevidence of volume overload
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Norepinephrine - preferred drug in sepsisDopamine or norepinephrine - first line agents to correct hypotension in septic shockDobutamine first line in decreasing cardiac output
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Adequate fluid resuscitation, followed bynorepinephrine using dobutamine if inotropicsupport is needed.Epinephrine as a single agent - not recommended
impairs splanchnic circulation and tissue perfusionCombination of dopamine and norepinephrinebetter tolerated than epinephrine
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Newer InotropesVasopressin:
redistributes blood flow away from the muscle, skin, and gut to the brain and heartmay be useful withrefractory septic shock
Dopexamine: This agent has beta2-adrenergic and dopaminergic effects without any alpha-adrenergic activityPhosphodiesterases inhibitors:
Inamrinone (formerly amrinone) and milrinone
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Find the site of infection –treat it
Autopsy:Failure to diagnose and treat infectionswith antibiotics or surgical drainage most common avoidable error
Source of infection can be identifiedwith the exception of patients who areimmunocompromised with neutropenia.
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Respiratory tract, urinary tract, abdominal, soft tissueintravascular devices - nosocomially-acquired sepsis. Multiple sites: 6-15% Empiricalantimicrobial therapy Empirical antibiotic therapy
Initiate early
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VentilationLung protective and pressure-limitedventilatory strategy
improved survival rates and lower rates of barotrauma
Recommendationstidal volume of 5-8 mL/kg,longer inspiratory timeDo not exceed transpulmonary pressure of 30 cm H20Permissive hypercapnia may ensue.
PEEP measuring plateau pressures and calculation of lung compliance at different levels of PEEP.
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Prone positioning, nitric oxide beneficial in the short termnot shown to improve survival rates
Trials of spontaneous breathing identified as possibly being able to breathe spontaneously 2-hour trials of spontaneous breathing
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Metabolic Support
Hypokalemia, hypomagnesemia, andhypophosphatemia Hemoglobin - 8.0 g/dL Thrombocytopenia and coagulopathycommonLactic acidosis - anion gap metabolic acidosis.
bicarbonate therapy worsens intracellular acidosis. Correction does not improve hemodynamics used for pH of less than 7.2 or bicarbonate of less than 9 mmol/L, no data to support
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Glucose
Serum glucose should be maintained in the reference range with insulin infusion Intensive insulin therapy (4.4 –6.1mmol)
Critically ill patients: reduced morbidity, mortality and episodes of sepsisBacteremia – lower mortalitySepsis – lower rate of death from MODS
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Steroids??
CorticosteroidsHigh dose – out Adrenal/physiologic doses - yes
Hydrocortisone, 50 mg IV every 6 hours, plus fludrocortisone, 50 µg/day orally, for 7 days.
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Sepsis specificRecombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Recombinant human activated protein C (drotrecogin-alfa, activated)antithrombotic, profibrinolytic, and anti-inflammatory propertiesreduces the level of IL-6 and otherproinflammatory cytokines.
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Future management
Interleukin 12 – immune stimulantAntibodies against C5a activator decreases apoptosisNitric oxide inhibitors
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References
NEJM 348;2 Jan 9 2003 Review article : The Pathophysiology and Treatment of SepsisEmedicine – septic shock review article 2001Intensive Care Medicine 2001