What are the Canadian guidelines for initial management of severe sepsis?

Canadian Guidelines for Initial Management of Severe Sepsis

The Canadian guidelines for initial management of severe sepsis recommend early quantitative resuscitation within the first 6 hours after recognition, with specific hemodynamic targets including central venous pressure of 8-12 mmHg, mean arterial pressure ≥65 mmHg, urine output ≥0.5 mL/kg/hr, and central venous oxygen saturation ≥70%. 1, 2

Initial Resuscitation Protocol

• Implement protocolized, quantitative resuscitation as soon as tissue hypoperfusion is recognized (defined as hypotension persisting after initial fluid challenge or blood lactate >4 mmol/L) 1, 2
• Target the following goals during the first 6 hours of resuscitation:
  • Central venous pressure 8-12 mmHg
  • Mean arterial pressure (MAP) ≥65 mmHg
  • Urine output ≥0.5 mL/kg/hr
  • Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively 1
• For patients with elevated lactate levels, target normalization of lactate as rapidly as possible 1, 2
• Perform routine screening of potentially infected seriously ill patients for severe sepsis to enable earlier intervention 1, 2

Diagnostic Measures

• Obtain appropriate cultures before starting antimicrobial therapy if no significant delay (<45 minutes) will occur 1, 2
• Collect at least 2 sets of blood cultures (both aerobic and anaerobic bottles) with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless inserted <48 hours prior 1
• Consider using 1,3 β-D-glucan assay, mannan and anti-mannan antibody assays if invasive candidiasis is in the differential diagnosis 1
• Perform imaging studies promptly to confirm potential sources of infection 1, 2

Antimicrobial Therapy

• Administer effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock 1, 2
• Initial empiric anti-infective therapy should include one or more drugs active against all likely pathogens (bacterial, fungal, or viral) and that penetrate in adequate concentrations into the presumed source of sepsis 1
• Reassess antimicrobial regimen daily for potential de-escalation to prevent resistance, toxicity, and minimize costs 1, 2
• Consider using procalcitonin or similar biomarkers to assist in discontinuing empiric antibiotics when no subsequent evidence of infection exists 1, 2
• For neutropenic patients or those with multidrug-resistant pathogens, use combination empirical therapy 1
• Limit empiric combination therapy to 3-5 days and de-escalate to the most appropriate single therapy once susceptibility profile is known 1
• Typical duration of therapy is 7-10 days, with longer courses for slow clinical response, undrainable foci of infection, S. aureus bacteremia, fungal/viral infections, or immunologic deficiencies 1

Fluid Therapy

• Use crystalloids as the initial fluid of choice for resuscitation of severe sepsis and septic shock 1
• Avoid hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock 1
• Consider albumin when patients require substantial amounts of crystalloids to maintain adequate mean arterial pressure 1
• Administer an initial fluid challenge of at least 30 mL/kg of crystalloids for patients with sepsis-induced tissue hypoperfusion and suspected hypovolemia (more rapid administration and greater amounts may be needed in some patients) 1
• Continue fluid challenge technique as long as hemodynamic improvement occurs based on either dynamic or static variables 1

Vasopressors and Inotropic Support

• Target a mean arterial pressure (MAP) of 65 mmHg with vasopressor therapy 1
• Use norepinephrine as the first-choice vasopressor 1
• Consider epinephrine as an additional agent when needed to maintain adequate blood pressure 1
• Vasopressin (0.03 units/minute) can be added to norepinephrine to either raise MAP to target or decrease norepinephrine dosage, but should not be used as the initial vasopressor 1
• Dopamine is not recommended except in highly selected circumstances (e.g., patients with low risk of tachyarrhythmias and absolute or relative bradycardia) 1
• Administer dobutamine infusion or add to vasopressor in the presence of myocardial dysfunction (elevated cardiac filling pressures and low cardiac output) or ongoing signs of hypoperfusion despite adequate intravascular volume and MAP 1

Additional Supportive Measures

• Avoid intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy can restore hemodynamic stability 1
• Target hemoglobin of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage 1
• Use low tidal volume ventilation for patients requiring mechanical ventilation 1
• Implement blood glucose management with insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL 1

Implementation Considerations

• Studies have shown that even short delays in implementing these recommendations can adversely impact outcomes, with significant increases in mortality risk after delays of 20 minutes for lactate measurement, 50 minutes for blood cultures, 100 minutes for crystalloid administration, and 125 minutes for antibiotic therapy 3
• Implementation of standardized order sets for the management of severe sepsis has been associated with greater fluid administration, improved antibiotic therapy, decreased incidence of organ failure, and improved survival 4

Common Pitfalls and Caveats

• Delaying antimicrobial therapy beyond one hour from recognition of severe sepsis or septic shock significantly increases mortality 5, 3
• Inadequate initial fluid resuscitation can lead to persistent hypoperfusion and increased vasopressor requirements 4
• Failure to obtain appropriate cultures before antimicrobial administration can hinder pathogen identification and targeted therapy 1, 2
• Overuse of broad-spectrum antibiotics without appropriate de-escalation can drive antimicrobial resistance 6
• Relying solely on static hemodynamic variables without considering dynamic responses to fluid challenges may lead to volume overload 1, 7