PATRICK DUFF, M.D. SEPTIC SHOCK

PATRICK DUFF, M.D.

SEPTIC SHOCKOVERVIEW

EtiologyMicrobiologyPathophysiology

DiagnosisManagement

SEPTIC SHOCKIMPACT

Results in approximately 215,000 deaths annually in the U.S.

Similar in frequency to MI as a cause of death

SEPTIC SHOCKPREDISPOSING FACTORSExtended hospitalizationAdvanced ageDebilitating illnessImmunodeficiency disorderVentilator > 48 h

SEPTIC SHOCKPREDISPOSING FACTORSDisseminated malignancyHyperalimentationBiliary tract surgeryGenital tract surgery

SEPTIC SHOCKMORTALITY

Underlying Underlying IllnessIllness

Mortality %Mortality %

Rapidly fatalRapidly fatal 8080

Ultimately fatalUltimately fatal 4040

Non-fatalNon-fatal <10<10

SEPTIC SHOCKMICROBIOLOGY

The Perfect Storm

SEPTIC SHOCKPATHOPHYSIOLOGYEndotoxinstimulation of humoral and cellular immune systemsactivation of complement sequence and coagulation cascade

SEPTIC SHOCKPATHOPHYSIOLOGYActivation of coagulation cascade activation of fibrinolytic system DIC

SEPTIC SHOCKPATHOPHYSIOLOGYComplement activationchemotaxis of PMNs, degranulation of mast cells, and release of histamine and inflammatory mediatorsincreased capillary permeability

SEPTIC SHOCKPATHOPHYSIOLOGYINFLAMMATION release of catecholamines and prostaglandins generalized vasoconstriction

SEPTIC SHOCKPATHOPHYSIOLOGYVASOCONSTRICTION decreased perfusion of vital organs tissue hypoxia metabolic acidosis

SEPTIC SHOCKPATHOPHYSIOLOGYMETABOLIC ACIDOSIS capillary pooling decreased circulating blood volume decreased venous return decreased cardiac output

SEPTIC SHOCKPATHOPHYSIOLOGYDECREASED CARDIAC OUTPUT decreased coronary and cerebral blood flow intractable hypotension, coma, multiorgan failure DEATH

SEPTIC SHOCKCLINICAL MANIFESTATIONS

Altered mental status

Thermal instability

Cardiac dysfunction

Respiratory compromise

SEPTIC SHOCKCLINICAL MANIFESTATIONS

BleedingJaundiceIleusSkin changes

SEPTIC SHOCKDIFFERENTIAL DIAGNOSISCardiogenic shockHypovolemic shockVenous or AF embolismCardiac tamponade

SEPTIC SHOCKDIFFERENTIAL DIAGNOSISHemorrhagic pancreatitis

Diabetic ketoacidosisAortic dissection

SEPTIC SHOCKDIAGNOSTIC TESTSLaboratory TestLaboratory Test ResultResult

WBCWBC Decreased, then Decreased, then increasedincreased

HCTHCT VariableVariable

PLTPLT Decreased with DICDecreased with DIC

FibrinogenFibrinogen Decreased with DICDecreased with DIC


Fibrin degradation Fibrin degradation productsproducts

Increased with DICIncreased with DIC

PT, PTT, TTPT, PTT, TT Prolonged with DICProlonged with DIC

pHpH DecreasedDecreased

Lactic acidLactic acid Increased (poor Increased (poor prognostic factor)prognostic factor)


pO2pO2 DecreasedDecreased

pCO2pCO2 IncreasedIncreased

HCO3HCO3 DecreasedDecreased

K+K+ IncreasedIncreased

SEPTIC SHOCKMICROBIOLOGY STUDIES

Urine cultureBlood cultureCulture of peritoneal fluid

Culture of abscess

Sputum culture

SEPTIC SHOCKIMAGING STUDIES

Chest x-rayAbdominal filmsIVPCTMRIUltrasound

SEPTIC SHOCKOTHER DIAGNOSTIC STUDIES

ECG

Right heart catheterization

SEPTIC SHOCKMANAGEMENTMonitoring

COPCWPBPABGsUrine output

SEPTIC SHOCKMANAGEMENTRestore circulating blood volumePacked red blood cells

Maintain hemoglobin of 7 to 9 g/lCrystalloid

Ringer’s lactateNormal saline

SEPTIC SHOCKMANAGEMENT“7 – 3 rule” for fluid replacement

Infuse 150-200 ml/10 minutesIf PCWP increases > 7mm Hg, discontinue infusion temporarily

If PCWP increases < 3 mm Hg, infuse a second increment

SEPTIC SHOCKGOALS OF FLUID RESUSCITATIONCentral venous pressure of 8 to 12 mm Hg

Mean arterial pressure > 65 mm Hg

Urine output > 0.5 ml/kg/hCentral venous or mixed venous oxygen saturation > 70%

SEPTIC SHOCKVASOPRESSORS

DopamineStarting dose 1-3 mcg/kg/min

Norepinephrine5 to 15 mcg/min

Vasopressin0.01 to 0.03 U/min

SEPTIC SHOCKVASOPRESSORSIn 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 norepinephrineEvents serious enough to require discontinuation of medication

SEPTIC SHOCKINOTROPIC THERAPY

Dobutamine - first choice inotrope for patients with low CO in the presence of adequate LV filling pressure

Dose0.5 to 1 mcg/kg/minMaximum – 40 mcg/kg/min

SEPTIC SHOCKMANAGEMENTCorticosteroids

SEPTIC SHOCKTREATMENT WITH HYDROCORTISONEDose – 200-300 mg/day for 7 days in 3 or 4 divided doses or by continuous infusion

Reverses shock more rapidlyVariable effect on mortalityIncreases frequency of superinfection

SEPTIC SHOCKSURGICAL INTERVENTION

Drainage of abscess

Debridement of infected wound

Removal of infected organ

SEPTIC SHOCKANTIBIOTIC THERAPYAntibiotics 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

SEPTIC SHOCKSPECIALIZED ANTIBIOTICSAnti-staphylococcal agentsLinezolidQuinupristin plus dalfopristin

VancomycinAnti-fungal agents

SEPTIC SHOCKPOSSIBLE MODIFICATIONS IN ANTIBIOTIC ADMINISTRATION

Prolong the intravenous infusion to 3 to 4 hours

For ventilator-related infections, administer nebulized antibiotics

SEPTIC SHOCKMINIMIZING INFLAMMATIONRecombinant 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

SEPTIC SHOCKMINIMIZING INFLAMMATIONRecombinant human activated protein CInhibits thrombinInhibits neutrophil recruitmentInhibits apoptosisImproves survival in patients with multi-organ dysfunction

Dose - 24 micrograms/kg/min x 96 hours

SEPTIC SHOCKRESPIRATORY SUPPORT

Administer oxygen

Monitor ABGsInitiate mechanical ventilation earlyAvoid barotraumaUse PEEP as indicated

EFFECT OF ARDS ON MORTALITY IN SEPTIC SHOCK

ConditionCondition Mortality %Mortality %

Septic shock Septic shock without ARDSwithout ARDS

5050

Septic shock Septic shock with ARDSwith ARDS

9090

MANAGEMENT OF SEPTIC SHOCKOTHER SUPPORTIVE MEASURES

Maintain normal temperatureCorrect coagulation abnormalities

Maintain glucose < 150 mg/dlAdminister WBC transfusionDVT prophylaxis

SEPTIC SHOCKPREVENTIVE MEASURESStabilize pre-existing illnesses prior to surgery

Avoid unnecessary preoperative hospitalization

SEPTIC SHOCKPREVENTIVE MEASURESDiagnose and treat operative site infections immediately

Be ever vigilant

SEPTIC SHOCKCONCLUSIONS

Predisposing factorsMicrobiologyFluid resuscitationSurgical

interventionAntibiotic therapyImportance of early

intervention

REFERENCESDellinger 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.

REFERENCESParrillo 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.

Technology

PATRICK DUFF, M.D. SEPTIC SHOCK