PATRICK DUFF, M.D. SEPTIC SHOCK TREATMENT WITH

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SEPTIC SHOCK

• PATRICK DUFF, M.D.

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SEPTIC SHOCKOVERVIEW

• Etiology
• Microbiology
• Pathophysiology
• Diagnosis
• Management

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SEPTIC SHOCKIMPACT

• Results in approximately 215,000 deaths annually
  in the U.S.
• Similar in frequency to MI as a cause of death

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SEPTIC SHOCKPREDISPOSING FACTORS

• Extended hospitalization
• Advanced age
• Debilitating illness
• Immunodeficiency disorder
• Ventilator gt 48 h

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SEPTIC SHOCKPREDISPOSING FACTORS

• Disseminated malignancy
• Hyperalimentation
• Biliary tract surgery
• Genital tract surgery

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SEPTIC SHOCKMORTALITY
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SEPTIC SHOCKMICROBIOLOGY
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SEPTIC SHOCKPATHOPHYSIOLOGY
The Perfect Storm
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SEPTIC SHOCKPATHOPHYSIOLOGY

• Endotoxin?stimulation of humoral and cellular
  immune systems?activation of complement sequence
  and coagulation cascade

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SEPTIC SHOCKPATHOPHYSIOLOGY

• Activation of coagulation cascade? activation of
  fibrinolytic system? DIC

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SEPTIC SHOCKPATHOPHYSIOLOGY

• Complement activation?chemotaxis of PMNs,
  degranulation of mast cells, and release of
  histamine and inflammatory mediators?increased
  capillary permeability

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SEPTIC SHOCKPATHOPHYSIOLOGY

• INFLAMMATION? release of catecholamines and
  prostaglandins? generalized vasoconstriction

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SEPTIC SHOCKPATHOPHYSIOLOGY

• VASOCONSTRICTION? decreased perfusion of vital
  organs? tissue hypoxia? metabolic acidosis

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SEPTIC SHOCKPATHOPHYSIOLOGY

• METABOLIC ACIDOSIS? capillary pooling? decreased
  circulating blood volume? decreased venous
  return? decreased cardiac output

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SEPTIC SHOCKPATHOPHYSIOLOGY

• DECREASED CARDIAC OUTPUT? decreased coronary and
  cerebral blood flow? intractable hypotension,
  coma, multiorgan failure? DEATH

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SEPTIC SHOCKCLINICAL MANIFESTATIONS

• Altered mental status
• Thermal instability
• Cardiac dysfunction
• Respiratory compromise

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SEPTIC SHOCKCLINICAL MANIFESTATIONS

• Bleeding
• Jaundice
• Ileus
• Skin changes

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SEPTIC SHOCKDIFFERENTIAL DIAGNOSIS

• Cardiogenic shock
• Hypovolemic shock
• Venous or AF embolism
• Cardiac tamponade

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SEPTIC SHOCKDIFFERENTIAL DIAGNOSIS

• Hemorrhagic pancreatitis
• Diabetic ketoacidosis
• Aortic dissection

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SEPTIC SHOCKDIAGNOSTIC TESTS
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SEPTIC SHOCKDIAGNOSTIC TESTS
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SEPTIC SHOCKDIAGNOSTIC TESTS
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SEPTIC SHOCKMICROBIOLOGY STUDIES

• Urine culture
• Blood culture
• Culture of peritoneal fluid
• Culture of abscess
• Sputum culture

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SEPTIC SHOCKIMAGING STUDIES

• Chest x-ray
• Abdominal films
• IVP
• CT
• MRI
• Ultrasound

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SEPTIC SHOCKOTHER DIAGNOSTIC STUDIES

• ECG
• Right heart catheterization

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SEPTIC SHOCKMANAGEMENT

• Monitoring
• CO
• PCWP
• BP
• ABGs
• Urine output

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SEPTIC SHOCKMANAGEMENT

• Restore circulating blood volume
• Packed red blood cells
• Maintain hemoglobin of 7 to 9 g/l
• Crystalloid
• Ringers lactate
• Normal saline

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SEPTIC SHOCKMANAGEMENT

• 7 3 rule for fluid replacement
• Infuse 150-200 ml/10 minutes
• If PCWP increases gt 7mm Hg, discontinue infusion
  temporarily
• If PCWP increases lt 3 mm Hg, infuse a second
  increment

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SEPTIC SHOCKGOALS OF FLUID RESUSCITATION

• Central venous pressure of 8 to 12 mm Hg
• Mean arterial pressure gt 65 mm Hg
• Urine output gt 0.5 ml/kg/h
• Central venous or mixed venous oxygen saturation
  gt 70

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SEPTIC SHOCKVASOPRESSORS

• Dopamine
• Starting dose 1-3 mcg/kg/min
• Norepinephrine
• 5 to 15 mcg/min
• Vasopressin
• 0.01 to 0.03 U/min

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SEPTIC SHOCKVASOPRESSORS

• In patients with septic shock, there is no
  difference in mortality in patients treated with
  dopamine vs norepinephrine vs vasopressin
• Dopamine is associated with more arrhythmic
  events than norepinephrine
• Events serious enough to require discontinuation
  of medication

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SEPTIC SHOCKINOTROPIC THERAPY

• Dobutamine - first choice inotrope for patients
  with low CO in the presence of adequate LV
  filling pressure
• Dose
• 0.5 to 1 mcg/kg/min
• Maximum 40 mcg/kg/min

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SEPTIC SHOCKMANAGEMENT

• Corticosteroids

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SEPTIC SHOCKTREATMENT WITH HYDROCORTISONE

• Dose 200-300 mg/day for 7 days in 3 or 4
  divided doses or by continuous infusion
• Reverses shock more rapidly
• Variable effect on mortality
• Increases frequency of superinfection

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SEPTIC SHOCKSURGICAL INTERVENTION

• Drainage of abscess
• Debridement of infected wound
• Removal of infected organ

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SEPTIC SHOCKANTIBIOTIC THERAPY

• Antibiotics should be started within one hour of
  diagnosis of sepsis/hypotension? improved
  survival
• Initial empiric regimen should target most likely
  pathogens, e
• Reassess regimen after 48-72 hours
• Total duration of treatment- 7 to 10 days

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SEPTIC SHOCKSPECIALIZED ANTIBIOTICS

• Anti-staphylococcal agents
• Linezolid
• Quinupristin plus dalfopristin
• Vancomycin
• Anti-fungal agents

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SEPTIC SHOCKPOSSIBLE MODIFICATIONS IN ANTIBIOTIC
ADMINISTRATION

• Prolong the intravenous infusion to 3 to 4 hours
• For ventilator-related infections, administer
  nebulized antibiotics

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SEPTIC SHOCKMINIMIZING INFLAMMATION

• Recombinant human activated protein C (rhAPC)
• Inflammatory response is integrally linked to
  procoagulant activity and endothelial activation
• rhAPC is an endogenous anticoagulant with
  anti-inflammatory properties

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SEPTIC SHOCKMINIMIZING INFLAMMATION

• Recombinant human activated protein C
• Inhibits thrombin
• Inhibits neutrophil recruitment
• Inhibits apoptosis
• Improves survival in patients with multi-organ
  dysfunction
• Dose - 24 micrograms/kg/min x 96 hours

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SEPTIC SHOCKRESPIRATORY SUPPORT

• Administer oxygen
• Monitor ABGs
• Initiate mechanical ventilation early
• Avoid barotrauma
• Use PEEP as indicated

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EFFECT OF ARDS ON MORTALITY IN SEPTIC SHOCK
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MANAGEMENT OF SEPTIC SHOCKOTHER SUPPORTIVE
MEASURES

• Maintain normal temperature
• Correct coagulation abnormalities
• Maintain glucose lt 150 mg/dl
• Administer WBC transfusion
• DVT prophylaxis

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SEPTIC SHOCKPREVENTIVE MEASURES

• Stabilize pre-existing illnesses prior to surgery
• Avoid unnecessary preoperative hospitalization

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SEPTIC SHOCKPREVENTIVE MEASURES

• Diagnose and treat operative site infections
  immediately
• Be ever vigilant

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SEPTIC SHOCKCONCLUSIONS

• Predisposing factors
• Microbiology
• Fluid resuscitation
• Surgical intervention
• Antibiotic therapy
• Importance of early intervention

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REFERENCES

• Dellinger RP, et al. Surviving sepsis campaign
  guidelines for management of severe sepsis and
  septic shock. Crit Care Med 2004 32 858-73.
• Russell JA. Management of sepsis. N Engl J Med
  2007 3551699-713.
• Sprung CL, et al. Hydrocortisone therapy for
  patients with septic shock. N Engl J Med 2008
  358111-24.

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REFERENCES

• Parrillo JE. Septic shock vasopressin,
  norepinephrine, and urgency. N Engl J Med 2008
  358 954-55
• DeBacker D, et al. Comparison of dopamine and
  norepinephrine in the treatment of shock. N Engl
  J Med 2010 362779-89.
• Peleg AY, Hooper DC. Hospital-acquired infections
  due to gram-negative bacteria. N Engl J Med 2010
  3621804-13.