sepsissepsisDr.AbdulWAHID M SalihDr.AbdulWAHID M Salih

Ph.D. SurgeryPh.D. Surgery

How to manage ?How to manage ?►54yr male54yr male►24 hr 24 hr FeverFever and delirium and delirium► Initial ObsInitial Obs

HR 162, RR 30HR 162, RR 30,O2 sats 95% , BP ,O2 sats 95% , BP 116/82, GCS 13/15116/82, GCS 13/15

►HistoryHistory Migratory abdominal pain and fever 1/7Migratory abdominal pain and fever 1/7

►Past HistoryPast History Left ureteric stone, 6mm Left ureteric stone, 6mm

Differential DiagnosisDifferential Diagnosis► PancreatitisPancreatitis► Ischeamic GutIscheamic Gut► Hypovolaemic shockHypovolaemic shock

GI bleed / AAA rupture / ectopic / dehydrationGI bleed / AAA rupture / ectopic / dehydration► Cardiogenic shockCardiogenic shock

AMI / Myocarditis / TamponadeAMI / Myocarditis / Tamponade► PEPE► Toxic ShockToxic Shock► Addisonian crisis (note relative adrenocorticoid Addisonian crisis (note relative adrenocorticoid

insufficiency in many septic patients)insufficiency in many septic patients)► Thyroid StormThyroid Storm

Consensus Consensus DefinitionsDefinitions

► eithereither►Bacteraemia Bacteraemia (or (or

viraemia/fungaemia/protozoan)viraemia/fungaemia/protozoan)is the presence of bacteria within the bloodstreamis the presence of bacteria within the bloodstream

►Septic focus Septic focus (abscess / cavity / tissue mass)(abscess / cavity / tissue mass)

InfectionInfection

► 2/4 2/4 ofof;;►TempTemp >38 or <36 >38 or <36►HRHR >90 >90►Respiratory Rate Respiratory Rate >20 or >20 or PaCO2PaCO2

<32 (4.3kPa)<32 (4.3kPa)►WCCWCC >12 or <4 or >10% >12 or <4 or >10% bandsbands

(immature forms)(immature forms)

SIRSSIRS

•Is the systemic response to infection

Sepsis

Sepsis - SIRS + Infection

Severe Sepsis- Sepsis+ Organ dysfunction

Septic shock– Sepsis+ Hypotension despite fluid resuscitation

Complications

Organ System InvolvementOrgan System Involvement►CirculationCirculation

Hypotension, Hypotension, increases in microvascular permeabilityincreases in microvascular permeability ShockShock

►LungLung Pulmonary Edema, Pulmonary Edema, hypoxemia,hypoxemia, ARDSARDS

►HematologicHematologic DIC, coagulopathyDIC, coagulopathy (DVT)(DVT)

Organ System InvolvementOrgan System Involvement

►GI tractGI tract stress ulcer stress ulcer Translocation of bacteria, Translocation of bacteria, Liver Failure,Liver Failure, Gastroparesis and ileus,Gastroparesis and ileus, CholestasisCholestasis

►KidneyKidney Acute tubular necrosis, Acute tubular necrosis, Renal FailureRenal Failure

Organ System InvolvementOrgan System Involvement

►Nervous SystemNervous System EncephalopathyEncephalopathy

►Skeletal MuscleSkeletal Muscle RhabdomyolysisRhabdomyolysis

►EndocrineEndocrine Adrenal insufficiencyAdrenal insufficiency

Sources of SepsisSources of SepsisThe International Cohort The International Cohort

StudyStudySevere Severe SepsisSepsis

Septic Septic ShockShock

Respiratory 66 53

Abdomen 9 20

Bacteremia 14 16

Urinary 11 11

Multiple - -

35% mortality

PathophysiologyPathophysiology

►Excessive Excessive anti-inflammatoryanti-inflammatory responseresponse

►Sepsis: Sepsis: auto-destructiveauto-destructive process process allowing normal responses to allowing normal responses to infection/injury to involve normal infection/injury to involve normal tissuestissues

Severe Sepsis: Severe Sepsis: The Final Common PathwayThe Final Common Pathway

Endothelial Dysfunction and Microvascular Thrombosis

Hypoperfusion/Ischemia

Acute Organ Dysfunction (Severe Sepsis)

Death

High Risk PatientsHigh Risk PatientsFor Sepsis and DyingFor Sepsis and Dying

Middle-aged, Middle-aged, elderlyelderly Post op Post op / post trauma/ post trauma Post Post splenectomysplenectomy TransplantTransplant immuneimmune supressed supressed AlcoholicAlcoholic / Malnourished / Malnourished Genetic predispositionGenetic predisposition DelayedDelayed appropriate antibiotics appropriate antibiotics ComorbiditiesComorbidities : : AIDS, renal or liver failure, neoplasmsAIDS, renal or liver failure, neoplasms

Identification of septic focusIdentification of septic focus

►history history ►physical examinationphysical examination

► imagingimaging► culturescultures

Blood cultures, urine culture, sputum culture, abscess culture.Blood cultures, urine culture, sputum culture, abscess culture.

InvestigationsInvestigations

► BasicBasic► WBCWBC► PlateletsPlatelets► CoagsCoags► Renal functionRenal function► GlucoseGlucose► AlbuminAlbumin► LFTLFT► ABGABG

► Specific ?SourceSpecific ?Source

► UrineUrine► CxRCxR► Blood Cultures Blood Cultures ► BiopsyBiopsy

May all be normal early on!

Differentiate sepsis from Differentiate sepsis from noninfectious SIRS noninfectious SIRS

►ProcalcitoninProcalcitonin►C-reactive protein (CRP) C-reactive protein (CRP) ►IL-6IL-6►protein complement C3aprotein complement C3a►LeptinLeptin

test is test is not yet not yet readily available for readily available for clinical practice clinical practice

Treatment of SepsisTreatment of Sepsis► AntibioticsAntibiotics

► Early aggressive fluid Early aggressive fluid resuscitationresuscitation

► InotropesInotropes for BP for BP support (Dopamine, support (Dopamine, vasopressin, vasopressin, norepinephrine)norepinephrine)

► Source Source controlcontrol

► SteroidSteroid therapy (adrenal therapy (adrenal insufficiency)insufficiency)

► Activated protein CActivated protein C

► VentilatoryVentilatory Strategies Strategies

► GlycemicGlycemic control control

► Newer therapies.Newer therapies.

I.V. antibioticsI.V. antibiotics► Initiated as soon as Initiated as soon as cultures cultures are drawn.are drawn.

►Severe sepsis should receive Severe sepsis should receive broadspectrum broadspectrum antibiotic.antibiotic.

►Empiric Empiric antifungalantifungal drug; drug; Neutropenic patients, DM, chronic steroids.Neutropenic patients, DM, chronic steroids.

AntibioticsAntibiotics

• Abx within 1 hr hypotension: Abx within 1 hr hypotension: 79.9% survival79.9% survival

• Survival decreased Survival decreased 7.6% 7.6% with each with each hour of delayhour of delay

• Mortality increased by 2Mortality increased by 2ndnd hour post hypotension hour post hypotension • Time to initiation of Antibiotics was the single Time to initiation of Antibiotics was the single

strongest predictor of outcomestrongest predictor of outcome

Antibiotics dosing Antibiotics dosing

► Dosage for intravenous administration (normal Dosage for intravenous administration (normal renal function).renal function).

► Imipenem-cilastin 0.5g q 6hImipenem-cilastin 0.5g q 6h► Meropenem 1.0g q 8hMeropenem 1.0g q 8h► Piperacillin-tazobactam 3.375gq 4h or 4.5 g q 6hPiperacillin-tazobactam 3.375gq 4h or 4.5 g q 6h► Cefepime1-2 q 8hrCefepime1-2 q 8hr► Gatifloxacin 400mg iv q dGatifloxacin 400mg iv q d► Ceftriaxone 2.0g q 24hrCeftriaxone 2.0g q 24hr► Levofloxacin500mg q dLevofloxacin500mg q d

Source controlSource control►Early recognition Early recognition of the Sepsis syndrome.of the Sepsis syndrome.

►SurgicalSurgical intervention when indicated. intervention when indicated.

► Aggressive supportive care in Aggressive supportive care in intensive care intensive care unitsunits..

SurgerySurgery►Get the Get the pus outpus outabscessesabscesses or foci of infection should be or foci of infection should be

drained drained

►Early definitive care ;Early definitive care ;e,.g; ruptured appendix, cholecystitise,.g; ruptured appendix, cholecystitis

SupportiveSupportive Oxygenate / VentilateOxygenate / Ventilate

VolumeVolume

Electrolyte homeostasisElectrolyte homeostasis

InotropesInotropes

(DVT) and stress ulcer prophylaxis(DVT) and stress ulcer prophylaxis

ARDS causes respiratory failureARDS causes respiratory failurein patients with severe Sepsis in patients with severe Sepsis

► Assess the Assess the airwayairway, respiration, and perfusion, respiration, and perfusion

► Supplemental Supplemental oxygenationoxygenation, ,

► VentilatorVentilator for respiratory failure for respiratory failure

Sepsis-induced hypotensionSepsis-induced hypotensionsystolic less than systolic less than 9090 mm Hg mm Hg or a reduction of more than or a reduction of more than 40 mm Hg 40 mm Hg from from

baseline in the absence of baseline in the absence of other causes other causes of hypotension."of hypotension."

1.1.A loss of plasma A loss of plasma volume into the volume into the interstitial spaceinterstitial space,,1.1. Decreases in vascular Decreases in vascular tonetone, , 2.2. Myocardial depressionMyocardial depression..

Treatment of HypotensionTreatment of Hypotension► Intravenous fluids : Crystalloids vs. Colloids.Intravenous fluids : Crystalloids vs. Colloids.► need more than ‘maintenance’ + replace need more than ‘maintenance’ + replace

losseslosses

Fluid TherapyFluid Therapy

► No mortality difference between;No mortality difference between;

colloid vs. crystalloidcolloid vs. crystalloid

Goals for initial resuscitation Goals for initial resuscitation

►Central venous pressure Central venous pressure 8 to 12 8 to 12 mmHg.mmHg.

►Mean arterial pressure Mean arterial pressure 65 65 mmHg.mmHg.

►Urine output Urine output 0.5 0.5 mL per kg per hr.mL per kg per hr.

►Pulmonary capillary wedge Pulmonary capillary wedge pressure exceeds pressure exceeds 18 18 mmHgmmHg

SteroidsSteroids For Non-respondersFor Non-responders;;

► Improved Improved refractory hypotensionrefractory hypotension► Reduced Reduced mortality 10%mortality 10%

50mg of hydrocortisone iv q 6hrs 50mg of hydrocortisone iv q 6hrs With fludrocortisone 50mcg ngtfor 7 days With fludrocortisone 50mcg ngtfor 7 days

Stress hyperglycemiaStress hyperglycemiain critically ill patients in critically ill patients Due to;Due to;

1.1. A decreased A decreased releaserelease of insulinof insulin

2.2. increased release of hormones with effects increased release of hormones with effects countering insulincountering insulin

3.3. increased increased insulin resistance insulin resistance

4.4. Hyperglycemia diminishes the ability of Hyperglycemia diminishes the ability of neutrophils neutrophils and macrophagesand macrophages to combat infections. to combat infections.

Tight Glycemic controlTight Glycemic control

► Continuous Continuous insulin infusioninsulin infusion

► Maintaining serum glucose levels between Maintaining serum glucose levels between 80 80 and 110 mg/dland 110 mg/dl

► Decreased Decreased mortalitymortality development of development of renal renal failurefailure

Failed therapiesFailed therapies

►CorticosteroidsCorticosteroids——high dose methylprednisolonehigh dose methylprednisolone

►Anti-endotoxin antibodiesAnti-endotoxin antibodies

►TNF antagonistsTNF antagonists—soluble TNF —soluble TNF receptorreceptor

►IbuprofenIbuprofen

MortalityMortality

Sepsis: Sepsis:

30% - 50%30% - 50%

Septic Shock: Septic Shock:

50% - 60%50% - 60%