Sepsis resident survival guide

Sepsis Resident Survival Guide
Diagnostic Criteria
Causes
Focused Initial Rapid Evaluation
Empiric Therapy
Dos
Don'ts

Main article: Sepsis

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]

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

Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.

Abbreviations: CBC, complete blood count; CI, cardiac index; CK-MB, creatine kinase MB isoform; CVP, central venous pressure; DC, differential count; ICU, intensive care unit; INR, international normalized ratio; LFT, liver function test; MAP, mean arterial pressure; PCWP, pulmonary capillary wedge pressure; PT, prothrombin time; PTT, partial prothrombin time; SaO2, arterial oxygen saturation; SBP, systolic blood pressure; ScvO2, central venous oxygen saturation; SvO2, mixed venous oxygen saturation; SMA-7, sequential multiple analysis-7.

Suspected sepsis (details) Signs and Symptoms 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) Hypotension (SBP <90 mm Hg, MAP <70 mm Hg, or an SBP decrease >40 mm Hg) Hypoxemia (PaO2/FiO2 <300) Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Ileus (absent bowel sounds) Diminished capillary refill or mottling Laboratory Findings Hyperglycemia (plasma glucose >140mg/dL or 7.7 mmol/L) in the absence of diabetes Leukocytosis (WBC count >12,000 μL–1) Leukopenia (WBC count <4000 μL–1) Bandemia >10% immature forms C-reactive protein more than two SD above the normal value Procalcitonin greater than two SD above the normal value Creatinine increase >0.5mg/dL or 44.2 μmol/L Coagulation abnormalities (INR >1.5 or aPTT >60 s) Thrombocytopenia (platelet count <100,000 μL–1) Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 μmol/L) Hyperlactatemia (>1 mmol/L)

Early Goal-Directed Therapy Supplemental oxygen ± intubation / ventilatory support ± sedation to maintain SaO2 ≥93% Arterial and central venous line placement Rivers Protocol Infuse a 500 ml bolus of crystalloid q 30 minutes to maintain CVP at 8–12 mm Hg. If MAP <65 mm Hg, administer vasopressors to maintain MAP at ≥65 mm Hg. If MAP >90 mm Hg, administer vasodilators until MAP ≤90 mm Hg. If ScvO2 <70%, transfuse RBC to maintain Hct at ≥30%. Once CVP/MAP/Hct are optimized, if ScvO2 is still <70%, load dobutamine 2.5 μg/kg/min. Titrate dobutamine by 2.5 μg/kg/min q 30 minutes until 20 μg/kg/min or ScvO2 ≥70%. Taper or discontinue dobutamine if MAP <65 mm Hg or HR >120 bpm. Surviving Sepsis Campaign Care Bundles To Be Completed Within 3 Hours: Measure lactate level Obtain ≥2 sets of blood cultures prior to administration of antibiotics Administer 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L Administer empiric antibiotics (details) To Be Completed Within 6 Hours: Administer vasopressors for persistent hypotension to maintain MAP ≥65 mm Hg For septic shock or initial lactate ≥4 mmol/L (36 mg/dL): — Measure CVP — Measure ScvO2 Remeasure lactate if initial lactate was elevated Goals of Initial Resuscitation CVP 8–12 mm Hg MAP ≥65 mm Hg Urine output ≥0.5 mL/kg/hr ScvO2 ≥70% or MvO2 ≥65% Normalization of lactate

Antimicrobial Therapy Source Control Infection Prevention Corticosteroids Blood Product Administration Mechanical Ventilation of Sepsis-Induced ARDS Sedation, Analgesia, and Neuromuscular blockade Glucose Control Renal Replacement Therapy Deep Vein Thrombosis Prophylaxis Stress Ulcer Prophylaxis Nutrition Setting Goals of Care

Empiric Antibiotic Therapy

History of intravenous drug use with high prevalence of MRSA

Vancomycin 1 gm IV q12h

Sepsis associated with petechiae

Ceftriaxone 2 gm IV q12h

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 GNB

Piperacillin-Tazobactam 3.375 gm IV q4h

AND

Vancomycin 1 gm IV q12h

High prevalence of ESBL and/or carbapenemase-producing aerobic GNB

Colistin 2.5 mg/kg then 1.5 mg/kg IV q12h

AND

Meropenem 1 gm IV q8h

AND

Vancomycin 1 gm IV q12h

Dos

Initial Resuscitation

• Commence protocolized, quantitative resuscitation for patients with sepsis-induced tissue hypoperfusion. Goals during the first 6 hrs of resuscitation:

• CVP 8–12 mm Hg
• MAP ≥65 mm Hg
• Urine output ≥0.5 mL/kg/hr
• ScvO2 ≥70% or MvO2 ≥65%

• In mechanically ventilated patients or those with known preexisting decreased ventricular compliance, a higher target CVP of 12–15mm Hg should be achieved to account for the impediment in filling.

Diagnosis

• Perform routine screening for severe sepsis in potentially infected seriously ill patients to allow earlier implementation of therapy.
• Cultures as clinically appropriate before antimicrobial therapy if no significant delay (>45 mins) in the start of antimicrobials.
• At least 2 sets of blood cultures (both aerobic and anaerobic bottles) should be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted. The volume of blood drawn with the culture tube should be ≥ 10 mL.
• The Gram stain can be useful, in particular for respiratory tract specimens, to determine if inflammatory cells are present (>5 PMNs/HPF and &lt:10 squamous cells/LPF) and if culture results will be informative of lower respiratory pathogens.
• Rapid influenza antigen testing during periods of increased influenza activity in the community is also recommended.
• The use of the 1,3 β-d-glucan assay, mannan and anti-mannan antibody assays may be useful when suspecting invasive candidiasis.
• Perform imaging studies promptly to confirm a potential source of infection. Diagnostic imaging may identify a source of infection that requires removal of a foreign body or drainage.

Antimicrobial Therapy

• Administration of intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock.
• Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens and that penetrate in adequate concentrations into presumed source of sepsis.
• If treatment of candidiasis is warranted, the selection of empirical therapy (eg, an echinocandin, triazoles such as fluconazole, or amphotericin B) should be tailored to the local pattern of the most prevalent Candida species and any recent exposure to antifungal drugs.
• Antiviral therapy should be initiated as early as possible in patients with severe sepsis or septic shock of viral origin.
• For selected patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is suggested for Pseudomonas aeruginosa bacteremia. A combination of beta-lactam and a macrolide is suggested for patients with septic shock from Streptococcus pneumoniae bacteremia.
• The duration of therapy should typically be limited to 7–10 days if clinically indicated. Longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, Staphylococcus aureus bacteremia; some fungal and viral infections, or immunologic deficiencies including neutropenia.
• Antimicrobial regimen should be reassessed daily for potential deescalation.

Source Control

• A specific anatomical diagnosis of infection requiring consideration for emergent source control should be sought and diagnosed or excluded as rapidly as possible.
• Control infection source within the first 12 hours after the diagnosis is made.
• Intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess).
• If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established.
• If infected peripancreatic necrosis is a potential infection source, definitive intervention should be delayed until adequate demarcation of viable and nonviable tissues has occurred.

Infection Prevention

• Oral chlorhexidine gluconate should be used as a form of oropharyngeal decontamination to reduce the risk of VAP in ICU patients with severe sepsis.

Fluid Therapy of Severe Sepsis

• Use crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock.
• Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids.

Vasopressors

• Initiate vasopressor therapy (norepinephrine as the first choice) to target a mean arterial pressure of 65 mm Hg.
• Consider epinephrine when an additional agent is required to maintain adequate blood pressure. Vasopressin may be added to norepinephrine with intent of either raising MAP or decreasing norepinephrine dosage.
• Phenylephrine is not recommended in the treatment of septic shock except:

• Norepinephrine is associated with serious arrhythmias
• Cardiac output is known to be high and blood pressure persistently low
• As salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target

Inotropic Therapy

• A trial of dobutamine infusion up to 20 micrograms/kg/min can be administered or added to vasopressor in the presence of:

• Myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output
• Ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP

• Cardiac index should be maintained at predetermined supranormal levels.

Corticosteroids

• Steroids may be indicated in the presence of a history of steroid therapy or adrenal dysfunction.
• When low-dose hydrocortisone is administered, continuous infusion rather than repetitive bolus injections should be used.

• Steroid therapy should be tapered when vasopressors are no longer required.

Blood Product Administration

• Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, RBC transfusion should be considered when Hb <7.0 g/dL to target a concentration of 7.0–9.0 g/dL in adults.
• In patients with severe sepsis, administer prophylactic platelets when:

• PLT <10,000/mm3 (10 x 10⁹/L) in the absence of apparent bleeding
• PLT <20,000/mm3 (20 x 10⁹/L) in the presence of bleeding risks
• PLT ≥50,000/mm3 (50 x 10⁹/L) for active bleeding, surgery, or invasive procedures

Mechanical Ventilation of Sepsis-Induced ARDS

• Target a tidal volume of 6 mL/kg predicted body weight in patients with sepsis-induced ARDS.
• Measure plateau pressures in patients with ARDS. Initial upper limit for plateau pressures in a passively inflated lung should be ≤30 cm H2O.
• Positive end-expiratory pressure (PEEP) should be applied to avoid alveolar collapse at end expiration. A PEEP >5 cm H2O is usually required to avoid lung collapse.
• Higher rather than lower levels of PEEP should be used for patients with sepsis-induced moderate to severe ARDS. Strategies to titrate PEEP include:

• Titrate PEEP and tidal volume according to bedside measurements of thoracopulmonary compliance with the objective of obtaining the best compliance.
• Titrate PEEP based on severity of oxygenation deficit and guided by the FiO2 required to maintain adequate oxygenation.

• Mechanically ventilated sepsis patients should be maintained with the head of the bed elevated to 30–45 degrees to limit aspiration risk and to prevent the development of ventilator-associated pneumonia.
• Prone positioning may be considered in sepsis-induced ARDS patients with a PaO2/FiO2 ratio ≤100 mm Hg.
• Undertake a conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypo perfusion.
• Mechanically ventilated patients with severe sepsis should undergo spontaneous breathing trials regularly to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria:

• Arousable
• Hemodynamically stable without vasopressor agents
• No new potentially serious conditions
• Low ventilatory and end-expiratory pressure requirements
• Low FiO2 requirements which can be met safely delivered with a face mask or nasal cannula.

Sedation, Analgesia, and Neuromuscular blockade in Sepsis

• Continuous or intermittent sedation should be minimized in mechanically ventilated sepsis patients, targeting specific titration endpoints.
• If neuromuscular blocking agents must be maintained, either intermittent bolus as required or continuous infusion with train-of-four monitoring of the depth of blockade should be used.
• A short course of NMBA of not greater than 48 hours may be considered for patients with early sepsis-induced ARDS and a PaO2/FiO2 of <150 mm Hg.

Glucose Control

• A protocolized approach should be undertaken for ICU patients with severe sepsis when 2 consecutive blood glucose levels are >180 mg/dL. This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL.
• Blood glucose values should be monitored every 1–2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter

Renal Replacement Therapy

• Either continuous renal replacement therapy or intermittent hemodialysis may be used in patients with severe sepsis and acute renal failure.
• Continuous therapies may be considered to facilitate management of fluid balance in hemodynamically unstable septic patients.

Deep Vein Thrombosis Prophylaxis

• Patients with severe sepsis should receive daily prophylaxis against venous thromboembolism (VTE).
• VTE prophylaxis should be accomplished with daily subcutaneous low-molecular weight heparin (LMWH). If creatinine clearance is <30 mL/min, use dalteparin or another form of LMWH that has a low degree of renal metabolism or UFH.
• Patients with severe sepsis should be treated with a combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible.
• Septic patients who have a contraindication for heparin use (eg, thrombocytopenia, severe coagulopathy, active bleeding, recent intracerebral hemorrhage) should not receive prophylaxis, but receive mechanical prophylactic treatment, such as compression stockings or intermittent compression devices, unless contraindicated.

Stress Ulcer Prophylaxis

• Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor should be given to patients with severe sepsis/septic shock who have bleeding risk factors.
• When stress ulcer prophylaxis is used, use proton pump inhibitors rather than H2 blockers.

Nutrition

• Administer oral or enteral feedings as tolerated, rather than either complete fasting or only intravenous glucose within the first 48 hours after a diagnosis of severe sepsis/septic shock.
• Use intravenous glucose and enteral nutrition rather than total parenteral nutrition alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock.
• Use nutrition with no specific immunomodulating supplementation rather than nutrition providing specific immunomodulating supplementation in patients with severe sepsis.

Setting Goals of Care

• Discuss goals of care and prognosis with patients and families.
• Incorporate goals of care into treatment and end-of-life care planning, utilizing palliative care principles where appropriate.
• Address goals of care as early as feasible, but no later than within 72 hours of ICU admission.

Don'ts

Antimicrobial Therapy

• Empiric combination therapy should not be used for more than 3–5 days. De-escalation to the most appropriate monotherapy should be performed as soon as the susceptibility profile is ascertained.
• Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause.

Fluid Therapy of Severe Sepsis

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

Vasopressors

• Do not use low dose vasopressin as the single vasopressor.
• Do not use low-dose dopamine for renal protection.

Corticosteroids

• Do not administer corticosteroids for the treatment of sepsis in the absence of shock.
• Do not use intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability.
• ACTH stimulation test is not recommended for identifying adults with septic shock who should receive hydrocortisone.

Blood Product Administration

• Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis.
• Do not use fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedure.

Immunoglobulins and Selenium

• Do not use intravenous immunoglobulins in adult patients with severe sepsis or septic shock.
• Do not use intravenous selenium for the treatment of severe sepsis.

Mechanical Ventilation of Sepsis-Induced ARDS

• Do not routinely place the pulmonary artery catheter for patients with sepsis-induced ARDS.
• Do not use beta 2-agonists for treatment of sepsis-induced ARDS in the absence of specific indications such as bronchospasm.

Sedation, Analgesia, and Neuromuscular blockade in Sepsis

• Neuromuscular blocking agents (NMBAs) should be avoided if possible in the septic patient without ARDS due to the risk of prolonged neuromuscular blockade following discontinuation.

Bicarbonate Therapy

• Sodium bicarbonate should not be used for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15.

Stress Ulcer Prophylaxis

• Patients without risk factors should not receive stress ulcer prophylaxis.

Nutrition

• Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (eg, up to 500 calories per day), advancing only as tolerated.

References