septic shock

SEPTIC SHOCK SEPTIC SHOCK PREDISPOSING FACTORS  Disseminated malignancy - Hyperalimentation  Biliary tract surgery - Genital tract surgery  Extended hospitalization - Advanced age  Debilitating illness - Immunodeficiency disorder  Ventilator > 48 h - Disseminated malignancy  Hyperalimentation - Biliary tract surgery  Genital tract surgery SEPTIC SHOCK MORTALITY SEPTIC SHOCK MICROBIOLOGY Underlying Illness Mortality % Rapidly fatal 80 Ultimately fatal 40 Non-fatal <10 SEPTIC SHOCK PATHOPHYSIOLOGY  Endotoxinàstimulation of humoral and cellular immune systemsàactivation of complement sequence and coagulation cascade  Activation of coagulation cascadeà activation of fibrinolytic systemà DIC  Complement activationàchemotaxis of PMNs, degranulation of mast cells, and release of histamine and inflammatory mediatorsàincreased capillary permeability  INFLAMMATIONà release of catecholamines and prostaglandinsà generalized vasoconstriction  VASOCONSTRICTIONà decreased perfusion of vital organsà tissue hypoxiaà metabolic acidosis  METABOLIC ACIDOSISà capillary poolingà decreased circulating blood volumeà decreased venous returnà decreased cardiac output  DECREASED CARDIAC OUTPUTà decreased coronary and cerebral blood flowà intractable hypotension, coma, multiorgan failureà DEATH SEPTIC SHOCK CLINICAL MANIFESTATIONS  Altered mental status - Thermal instability  Cardiac dysfunction - Respiratory compromise  Bleeding - Jaundice  Ileus - Skin changes SEPTIC SHOCK DIFFERENTIAL DIAGNOSIS  Cardiogenic shock - Hypovolemic shock  Venous or AF embolism - Cardiac tamponade  Hemorrhagic pancreatitis - Diabetic ketoacidosis  Aortic dissection SEPTIC SHOCK DIAGNOSTIC TESTS Laboratory Test Result WBC Decreased, then increased HCT Variable PLT Decreased with DIC Fibrinogen Decreased with DIC Fibrin degradation products Increased with DIC PT, PTT, TT Prolonged with DIC pH Decreased Lactic acid Increased (poor prognostic factor) pO2 Decreased pCO2 Increased HCO3 Decreased K+ Increased SEPTIC SHOCK MICROBIOLOGY STUDIES  Urine culture - Blood culture  Culture of peritoneal fluid - Culture of abscess  Sputum culture - Chest x-ray  Abdominal films - IVP  CT - MRI  Ultrasound - ECG  Right heart catheterization SEPTIC SHOCKMANAGEMENT  Monitoring --> CO , PCWP, BP, ABGs, Urine output  Restore circulating blood volume  Packed red blood cells; Maintain hemoglobin of 7 to 9 g/l ; Crystalloid ; Ringer’s lactate ; Normal saline  “7 – 3 rule” for fluid replacement  Infuse 150-200 ml/10 minutes  If PCWP increases > 7mm Hg, discontinue infusion temporarily  If PCWP increases < 3 mm Hg, infuse a second increment SEPTIC SHOCK GOALS OF FLUID RESUSCITATION  Central venous pressure of 8 to 12 mm Hg  Mean arterial pressure > 65 mm Hg  Urine output > 0.5 ml/kg/h  Central venous or mixed venous oxygen saturation > 70% SEPTIC SHOCK VASOPRESSORS  Dopamine  Starting dose 1-3 mcg/kg/min  Norepinephrine  5 to 15 mcg/min  Vasopressin  0.01 to 0.03 U/min  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 SEPTIC SHOCK INOTROPIC 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 SEPTIC SHOCK TREATMENT 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 SEPTIC SHOCK SURGICAL INTERVENTION  Drainage of abscess  Debridement of infected wound  Removal of infected organ SEPTIC SHOCK ANTIBIOTIC THERAPY  Antibiotics should be started within one hour of diagnosis of sepsis/hypotensionà 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 SEPTIC SHOCK SPECIALIZED ANTIBIOTICS  Anti-staphylococcal agents  Linezolid  Quinupristin plus dalfopristin  Vancomycin  Anti-fungal agents SEPTIC SHOCK POSSIBLE MODIFICATIONS IN ANTIBIOTIC ADMINISTRATION  Prolong the intravenous infusion to 3 to 4 hours  For ventilator-related infections, administer nebulized antibiotics SEPTIC SHOCK MINIMIZING 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  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 SEPTIC SHOCK RESPIRATORY SUPPORT  Administer oxygen  Monitor ABGs  Initiate mechanical ventilation early  Avoid barotrauma  Use PEEP as indicated EFFECT OF ARDS ON MORTALITY IN SEPTIC SHOCK Condition Mortality % Septic shock without ARDS 50 Septic shock with ARDS 90 MANAGEMENT OF SEPTIC SHOCK OTHER SUPPORTIVE MEASURES  Maintain normal temperature  Correct coagulation abnormalities  Maintain glucose < 150 mg/dl  Administer WBC transfusion  DVT prophylaxis SEPTIC SHOCK PREVENTIVE MEASURES  Stabilize pre-existing illnesses prior to surgery  Avoid unnecessary preoperative hospitalization  Diagnose and treat operative site infections immediately  Be ever vigilant SEPTIC SHOCK CONCLUSIONS  Predisposing factors  Microbiology  Fluid resuscitation  Surgical intervention  Antibiotic therapy  Importance of early intervention 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: 355:1699-713.  Sprung CL, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358:111-24.  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; 362:779-89.  Peleg AY, Hooper DC. Hospital-acquired infections due to gram-negative bacteria. N Engl J Med 2010; 362:1804-13.