Septic shock Dr. M. A. Sofi MD; FRCP (London); FRCPEdin; FRCSEdin

What is shock? Shock is a state of acute circulatory failure characterized by persistent arterial hypotension despite adequate fluid resuscitation or by tissue hypoperfusion (manifested by a lactate concentration >4 mg/dL) unexplained by other causes. “Sepsis is a clinical syndrome characterized by systemic inflammation due to infection. There is a continuum of severity ranging from sepsis to severe sepsis and septic shock” Septic shock refers to sepsis with cardiovascular dysfunction (i.e., hypotension, reliance on administration of vasoactive drug to maintain a normal blood pressure, or two of the following: “prolonged capillary refill, oliguria, metabolic acidosis, or elevated arterial lactate) that persists despite the administration of ≥40 mL/kg of isotonic fluid in one hour.”

Organ dysfunction secondary to Sepsis. Terminology Severe Sepsis Organ dysfunction secondary to Sepsis. e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy. Septic Shock Hypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion. Systemic Inflammatory Response Syndrome (SIRS) Temp > 38 or < 36 HR > 90 RR > 20 or PaCO2 < 32 WBC > 12 or < 4 or Bands > 10% Sepsis The systemic inflammatory response to infection. Two out of four criteria acute change from baseline

Comparable global Epidemiology SSC The incidence of sepsis syndrome is between 51 – 95 cases per 100,000 in several countries  Over 1,665,000 cases of sepsis occur in the United States each year, with a mortality rate up to 50 percent . Even with optimal treatment, mortality due to severe sepsis or septic shock is approximately 40 percent and can exceed 50 percent in the sickest patients September 2005 Comparable global Epidemiology The increased incidence of sepsis syndrome is a global phenomenon with a documented incidence between 51 – 95 cases per 100,000 in several countries.

SIRS SIRS – systemic inflammatory response syndrome Must have at least 2 of the following: Temperature >38.5ºC or <36ºC Heart rate >90 beats/min Respiratory rate >20 breaths/min or PaCO2 <32 mmHg WBC >12,000 cells/mm3, <4000 cells/mm3, or >10 % immature (band) forms SIRS is the body’s response to infection, inflammation, stress. Definitions according to the American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM) in 1992

Sepsis and Severe Sepsis Sepsis – SIRS + suspected or confirmed infection (documented via cultures or visualized via physical exam/imaging) Severe Sepsis – Sepsis + at least one sign of organ hypo-perfusion or dysfunction Areas of mottled skin Disseminated intravascular coagulation Capillary refill > 3 secs AKI UOP < 0.5cc/kg /hr ARDS or acute lung injury (ALI) Lactate > 2mmol /L Cardiac dysfunction on echo Altered mental status Plt < 100 Abnormal EEG Troponin Leak

Septic Shock Septic Shock - Severe sepsis plus one of the following conditions: MAP <60 mm Hg (<80 mm Hg if previous hypertension) after adequate fluid resuscitation Need for vasopressors to maintain BP after fluid resuscitation Adequate fluid resuscitation = 40 to 60 mL/kg saline solution (NS 5L- 10L) Lactate > 4mmol /L HIGHEST RISK OF MORTALITY

 26-year-old woman developed rapidly progressive shock associated with purpura and signs of meningitis.

Sepsis Pathogenesis An incompletely understood pathogenesis: hallmarks are microvascular thrombosis, vasodilation, free radical damage, Capillary Leak Unbalanced Immune Reaction Mediators of Inflammation Tissue Factor An incompletely understood pathogenesis: hallmarks are microvascular thrombosis, vasodilation, free radical damage, Capillary Leak Procoagulant State ROS Microvascular Thrombosis Vasodilation CapillaryLeak

Shock Classification, Terminology, and Staging Hypovolemic shock results from the loss of blood volume caused by GI bleeding, extravasation of plasma, major surgery, trauma Obstructive shock from an intrinsic or extrinsic obstruction of circulation. PE embolism and pericardial tamponade. Distributive shock is caused by excessive vasodilation and impaired distribution of blood flow.  Patients have hyperdynamic shock with high cardiac output, hypotension. Cardiogenic shock is caused by primary myocardial dysfunction. The patients have cool clammy extremities,

Clinical Manifestations. Staging of Septic Shock: I. Compensated / Pre-shock / Hyperdynamic II. Decompensated / Organ hypoperfusion III. End organ failure / Irreversible

Clinical Manifestations. Recognition of Septic Shock: Early compensated, hyperdynamiic state Clinical signs Warm extremities Bounding pulses Tachycardia Warm shock tachypnoea confusion flushed skin Decreased systemic vascular resistance

Clinical Manifestations. Hypotension Cold and clammy skin Mottling Tachycardia Cyanosis Cold shock Narrow pulse pressure Hypoxemia Acidosis.

Where is infection?

Noninfectious mimics of sepsis Acute myocardial infarction Overzealous diuresis Acute pulmonary embolus Transfusion reactions Acute pancreatitis Adverse drug reactions Fat emboli syndrome Procedure-related transient bacteremia Acute adrenal insufficiency Amniotic fluid embolism Acute gastrointestinal hemorrhage

Investigations Sepsis work up: CBC, ABG, Lactate PCT, CRP Metabolic panel/Electrolytes Coagulation profile Urine, Sputum, Blood, Stools, Throat swab cultures Viral cultures Gastric aspirate/ET aspirate CIE/Latex agglutination Imaging: CXR, CT, MRI, PET Scan, Echo. Ultrasound

Goals and principles of treatment Management principles: Early recognition Early and adequate antibiotic therapy Source control Early hemodynamic resuscitation and continued support Proper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS) Pharmacotherapy Alpha-/beta-adrenergic agonists (eg, dopamine, dobutamine, epinephrine) Isotonic crystalloids Volume expanders Antibiotics (eg, cefotaxime, piperacillin-tazobactam, ceftriaxone, ciprofloxacin, levofloxacin, vancomycin) Corticosteroids (hydrocortisone, dexsamethasone)

Management Steps Central Line Access (Fluid hydration +/- pressor) 1st line therapy – fluids, fluids, fluids! Crystalloid equivalent to colloid Initial 1-2 Liters (20mg /kg) crystalloid or 500 ml colloid Careful in CHF patients !! Establish a 2nd IV line for Dopamine infusion (Draw blood for culture) IV antibiotics Ampicillin + gentamicin or Ampicillin+ Ceftriaxone/Cefataxime Ceftriaxone or Cefotaxime alone or Ampicillin + Chloramphenicol

Correct metabolic derangement: Metabolic acidosis. Hyperglycemia Management Steps DIC: Restoration of normovolemia: Reverses abnormal activation. ‘Component replacement’ (Goal - Normal PT, PTT, fibrinogen, PC = 40,000 to 100000 /cu mm.) a. FFP - most beneficial in early stages. b. Cryo- consider 1 unit/3 units of FFP transfused. c. Platelet concentrate Correct metabolic derangement: Metabolic acidosis. Hyperglycemia hypoglycemia (always correct hypoglycemia)

Management Steps Gastrointestinal: Antacids, sucralfate, early enteral nutrition Renal: Volume replacement Low dose dopamine ?diuretic with volume expansion Indications for dialysis: Hyperkalemia Refractory metabolic acidosis Anuria despite diuresis BUN>100mg% Recognize and manage organ failure: Cardiovascular support: Rate & rhythm- correct 02, acidosis, Ca, Mg, K variations Stroke volume - fluid correction & replace losses Inotrope support. Respiratory support: Supplement 02, Early intubation and PPV (PEEP)

Antibiotics Cultures / Antibiotics / Labs Cultures PRIOR to Antibiotics ( 2 Sets, one peripheral and one from any line older than 48hrs) IV Abx within 3 hrs in the ED, within 1 hr in the ICU Broad Spectrum, combination therapy for neutropenic and patients with pseudomonas risk factors Vancomycin PLUS Zosyn (Piperacillin and tazobactam) Consider need for Source Control ! Drainage of abscess or cholangitis, removal of infected catheters, debridement or amputation of osteomyelitis Stress importance of early cultures and IV antibiotics (BROAD). Think Source control if relevant for your patient and possible need for surgery evaluation.

Vasopressor agents used in septic shock Typical intravenous dose range Dopamine 6 – 25 µg/Kg/min Epinephrine 1 – 10 µg/min Norepinephrine 1 – 30 µg/min Phenylpherine 40 – 180 µg/min Vasopressin 0.01 – 0.04 units/min

Corticosteroids Use in Septic Shock, if NO response to vasopressors and fluids HYDROCORTISONE 200mg -300mg / day Divided doses (Q6hrs) Initial Dose 100mg IV x1 Consider for patients who received etomidate Wean Steroids QUICKLY once off vasopressors 2 Trials Annane et al, JAMA 2002; 228: 862-871 Corticus Trial, NEJM 2008; 358: 111-124

Parameters for monitoring organ system function in patients with sepsis Respiratory system PaO2/FiO2 ratio Renal system Urine output and serum creatinine Hematologic system Platelet count Central nervous system Glasgow coma score Hepatobiliary system Serum bilirubin and liver enzymes Cardiovascular system Blood pressure, arterial lactate Gastrointestinal system Gastric intramucosal pH (pHi), ileus, blood in nasogastric aspirate

Management- summary. Five important points 1. ABC, supplement 02 always. 2. IV or IO access and fluid resuscitation up to 60 mL/Kg. 3. Early dopamine infusion @10µg/Kg/min 4. Empirical antibiotic. 5. Frequent monitoring.

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