Sepsis resident survival guide

Sepsis Resident Survival Guide
Overview
Diagnostic Criteria
Causes
Focused Initial Rapid Evaluation
Do's
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]; Vidit Bhargava, M.B.B.S [3]

Overview

Diagnostic Criteria

Systemic Inflammatory Response Syndrome

Systemic inflammatory response syndrome (SIRS) represents the complex findings resulting from systemic activation of the innate immune response triggered by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes. However, criteria for SIRS are considered to be too nonspecific to be of utility in diagnosing a cause for the syndrome or in identifying a distinct pattern of host response.

SIRS is considered to be present when patients have two or more of the following clinical findings:

Body temperature >38 °C (100.4 °F) or <36 °C (96.8 °F) Heart rate >90 beats per minute Hyperventilation evidenced by a respiratory rate of >20 breaths per minute or a PaCO2 <32 mm Hg White blood cell count of >12000 cells/mm³ or <4000 cells/mm³ (>12 x 109 cells/L or <4 x 109 cells/L) or bandemia (>10% band forms)

Sepsis

Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of infection. Diagnostic criteria for sepsis are as follows:

Sepsis = infection (documented or suspected) and some of the following:

General variables Fever (>38.3°C) Hypothermia (core temperature <36°C) Heart rate >90/min–1 or more than two SD above the normal value for age Tachypnea Altered mental status Significant edema or positive fluid balance (>20 mL/kg over 24 hr) Hyperglycemia (plasma glucose >140mg/dL or 7.7 mmol/L) in the absence of diabetes

Inflammatory variables Leukocytosis (WBC count >12,000 μL–1) Leukopenia (WBC count <4000 μL–1) Normal WBC count with greater than 10% immature forms Plasma C-reactive protein more than two SD above the normal value Plasma procalcitonin more than two SD above the normal value

Hemodynamic variables Arterial hypotension (SBP <90mm Hg, MAP <70mm Hg, or an SBP decrease >40mm Hg in adults or less than two SD below normal for age)

Organ dysfunction variables Arterial hypoxemia (Pao2/Fio2 <300) Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Creatinine increase >0.5mg/dL or 44.2 μmol/L Coagulation abnormalities (INR >1.5 or aPTT >60 s) Ileus (absent bowel sounds) Thrombocytopenia (platelet count <100,000 μL–1) Hyperbilirubinemia (plasma total bilirubin >4mg/dL or 70 μmol/L)

Tissue perfusion variables Hyperlactatemia (>1 mmol/L) Decreased capillary refill or mottling

Severe Sepsis

Severe sepsis is defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion.

Severe sepsis = sepsis-induced tissue hypoperfusion or organ dysfunction (any of the following thought to be due to the infection)

Sepsis-induced hypotension (SBP of <90 mm Hg or MAP <70 mm Hg or a SBP decrease >40 mm Hg or <2 SD below normal for age in the absence of other causes of hypotension) Lactate above upper limits laboratory normal Urine output <0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation Acute lung injury with PaO2/FIO2 <250 in the absence of pneumonia as infection source Acute lung injury with PaO2/FIO2 <200 in the presence of pneumonia as infection source Creatinine >2.0 mg/dL (176.8 μmol/L) Bilirubin >2 mg/dL (34.2 μmol/L) Platelet count <100,000 μL Coagulopathy (international normalized ratio >1.5)

Septic Shock

Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation, in the absence of other causes for hypotension.

• Septic shock in adult patients refers to a state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes.
• Septic shock in pediatric patients is defined as a tachycardia (may be absent in the hypothermic patient) with signs of decreased perfusion including decreased peripheral pulses compared with central pulses, altered alertness, flash capillary refill or capillary refill 􏰀2 seconds, mottled or cool extremities, or decreased urine output.

Causes

Sepsis is a life-threatening condition and must be treated immediately irrespective of the underlying cause.

• If associated with community-acquired pneumonia

• Streptococcus pneumoniae
• Staphylococcus aureus and MRSA
• Legionella
• Gram-negative bacilli

• If associated with urinary tract infection

• Aerobic gram-negative bacilli
• Enterococcus

• If associated with intra-abdominal infection

• Aerobic gram-negative bacilli
• Anaerobic gram-negative bacilli

• If associated with intravenous drug use

• Staphylococcus
• Nocardia

• If associated with petechiae

• Neisseria meningitidis
• Rocky Mountain spotted fever

FIRE: Focused Initial Rapid Evaluation

Characterize the symptoms: ❑ Fever ❑Hypothermia ❑ Altered mental status ❑ Mottling ❑ Ileus ❑ Oliguria

Examine the patient: ❑ Tachycardia ❑ Tachypnea ❑ Edema ❑ Hyperglycemia ❑ Hypotension after an initial 30 ml/Kg bolus ❑ Decreased capillary refill

Order labs: ❑ Random blood sugar (RBS) ❑ Complete blood count (CBC) ❑ Plasma C reactive protein (CRP) ❑ Plasma procalcitonin ❑ Pulse oximetry ❑ Urinalysis/Renal function tests ❑ PT/INR ❑ Liver function tests ❑ Serum lactate ❑ Central venous pressure (CVP)

Consider alternative diagnosis: ❑ Infections ❑ Acute pancreatitis ❑ Diabetic ketoacidosis Lower gastrointestinal bleeding Myocardial infarction

Initial resuscitation: Goals to achieve in first 6 hours ❑ Central venous pressure (CVP) 8-12 mm Hg ❑ Mean arterial pressure (MAP) ≥ 65 mm Hg ❑ Urine output ≥ 0/5 mL/Kg/hr ❑ Central venous O2 sat. 70% ❑ If lactate levels elevated, target is normalization

Diagnosis: ❑ Perform 2 sets of blood cultures (aerobic and anaerobic) atleast, before starting antibiotics Drawn percutaneously Drawn through each vascular access device present for > 48 hours ❑ Perform 1,3 beta-D-glucan assay, mannan, anti-mannan antibody assay if available ❑ Perform imaging studies as appropriate to locate a source

Antimicrobial therapy: ❑ Initiate within 1st hour of diagnosis Reassess regimen daily ❑ Use low procalitonin levels for prognosis ❑ Usual duration of therapy 10 days ❑ Longer in neutropenics, slow responders, undrainable foci, immunologically compromised

Choice of antibiotics

Unknown organism ❑ Empiric therapy with broad spectrum antbiotic with good tissue penetrance

Neutropenic pt with severe sepsis (goal is to cover Acinetobacter & Pseudomonas spp) ❑ Use combination empirical therapy

Severe infections + resp failure + septic shock ❑ Extended spectrum beta lactam andaminoglycoside/fluoroquinolone

Streptococcus pneumoniae ❑ beta lactam + macrolide

Culture specific organism ❑ Shift to appropriate anti-bacterial, antiviral or antifungal

Remove source/foci of infection: ❑ Use minimally invasive process ❑ Source removal best done in first 12 hours ❑ Remove intravascular access devices if they are a possible source ❑ Oral chlorhexidine gluconate to reduce oral contamination as a risk factor for ventilator associated pneumonia

Hemodynamic support Fluid therapy: ❑ Administer crystalloids, use albumin when demand for fluids is too high ❑ Use dynamic variables (change in pulse pressure, stroke volume) and static variables (arterial pressure,heart rate) to assess status Vasopressors (to achieve target MAP ≥ 65 mm Hg): ❑ Place arterial line as soon as feasible ❑ Administer norepinephrine as 1st choice drug ❑ Use epinephrine - when additional agent needed ❑ Use vasopressin 0.03 units/minute to raise MAP or decrease norepinephrine usage ❑ Selective dopamine (absolute or relative bradycardia) and phenylephrine usage Inotropic therapy: ❑ Trial of dobutamine infusion 20 μg/Kg if cardiac output low with elevated cardiac filling pressure

Corticosteroids: ❑ Use continuous flow IVhydrocortisone 200 mg/day if shock doesn’t improve with fluids & vasopressor ❑ Taper when vasopressors no longer required

Blood products: ❑ Transfuse blood when hemoglobin < 7.0 g/dL ❑ Transfuse platelets if < 10,000/mm3 or < 20,000/mm3 in those with high risk

Mechanical ventilation for sepsis induced ARDS': ❑ Target tidal volume of 6 mL/Kg ❑ Target plateau pressure ≤ 30 mm Hg ❑ Use PEEP (positive end expiratory pressure) to avoid alveolar collapse ❑ Raise patients bed to 30-45° ❑ Attempt weaning when all foll. criteria are met: ❑ Pt arousable ❑ Hemodynamics stable ❑ No new complications ❑ Low ventilatory/fiO2 requirements ❑ Extubate when weaning successful

Other supportive therapy Sedation & neuromuscular blockade: ❑ Use minimal sedation/neuromuscular blockade in mechanically ventilated patients Glucose control: ❑ Blood glucose target value should be ≤ 180 mg/dL ❑ Use insulin infusion and 1-2 hourly monitoring to achieve target Renal replaement therapy: ❑ May be used for management of fluid balance in hemodynamically unstable patients ❑ Use for septic patients withacute renal failure DVT prophylaxis: ❑ Do pharmacoprophylaxis with low molecular weight heparin (LMWH), if no contraindications present ❑ Use pneumatic compression devices whenever possible Stress ulcer prophylaxis ❑ Consider prophylaxis if risk factors are present Feeding: ❑ Enteral & oral feeding preferred over total parenteral feeding (TPN) ❑ Adjust calorie requirement in subsequent days, as tolerated Goals of care: ❑ Discuss goals or care, patient aspirations and future directives with family with 72 hours of admission

Empiric Antibiotic Therapy

Biliary source

Ampicillin-Sulbactam 3 gm IV q6h OR Piperacillin-Tazobactam 3.375 gm IV q4h OR Ticarcillin-Clavulanate 3.1 gm IV q4h

Community-acquired pneumonia

Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h AND Piperacillin-Tazobactam 3.375 gm IV q4h AND Vancomycin 1 gm IV q12h

Unclear infection source

Doripenem 500 mg IV q8h OR Ertapenem 1 gm IV q24h OR Imipenem 0.5 gm IV q6h OR Meropenem 1 gm IV q8h AND Vancomycin 1 gm IV q12h

Low prevalence of ESBL and/or carbapenemase producing aerobic gram-negative bacilli

Piperacillin-Tazobactam 3.375 gm IV q4h AND Vancomycin 1 gm IV q12h

High prevalence of ESBL and/or carbapenemase producing aerobic gram-negative bacilli

Colistin 2.5 mg/kg then 1.5 mg/kg IV q12h AND Meropenem 1 gm IV q8h AND Vancomycin 1 gm IV q12h

History of intravenous drug use with high prevalence of MRSA

Vancomycin 1 gm IV q12h

Sepsis associated with petechiae

Ceftriaxone 2 gm IV q12h

Do's

• Patients who are suspected of being severely infected, should be routinely screened for sepsis.

• Administer antimicrobial therapy within 1 hour of diagnosis of sepsis.

• Delay intervention, if source/foci of infection is peri-pancreatic necrosis.

Dont's

• Do not use empiric combination therapy for more than 3-5 days.

• Do not use antimicrobial agents in severely inflamed patients, from a non-infectious cause.

• Do not use hydroxyethyl starch for fluid therapy resuscitation of severe sepsis and septic shock.

• Do not use low dose vasopressin/dopamine/phenylephrine as monotherapy.

• Do not use low dose dopamine for renal protection.

• Do not use corticosteroids in the absence of shock.

• Do not use erythropoietin as a specific treatment of anemia associated with sepsis.

• Do not use antithrombin.

• Do not use fresh frozen plasma to correct clotting abnormalities in the absence of bleeding or planned invasive procedure.

• Do not use following supportive therapies as their role is not clear:

IV immunoglobulins

IV selenium

• Do not routinely use pulmonary artery catheters.

• Do not use bicarbonate therapy as prophylaxis of hypoperfusion induced lactic acidosis if pH > 7.15.

References