What is the best approach to manage a patient in septic shock?

Management of Septic Shock

Immediately administer broad-spectrum intravenous antibiotics within 1 hour of recognizing septic shock, rapidly infuse at least 30 mL/kg of crystalloids, and start norepinephrine as the first-line vasopressor if mean arterial pressure remains below 65 mmHg despite adequate fluid resuscitation. 1, 2

Initial Resuscitation (First Hour - "The Golden Hour")

The speed of intervention directly impacts mortality in septic shock. 2

Antimicrobial Therapy

• Administer intravenous broad-spectrum antibiotics within 1 hour of recognizing septic shock—delays beyond this window directly increase mortality. 1, 2
• Obtain at least two sets of blood cultures before starting antibiotics, but do not delay antimicrobial administration beyond 45 minutes even if cultures cannot be obtained. 2
• Use antibiotics with high likelihood of activity against all suspected pathogens at adequate dosages. 1, 2

Fluid Resuscitation

• Immediately infuse a minimum of 30 mL/kg of crystalloids for initial resuscitation—this is a minimum threshold, not a maximum, and many patients require substantially more. 1, 2
• Use crystalloids as the first-line fluid of choice (either balanced crystalloids or normal saline). 1
• Consider adding albumin when patients require substantial amounts of crystalloids. 1
• Strongly avoid hydroxyethyl starches—they are contraindicated in septic shock. 1
• Continue aggressive fluid administration as long as hemodynamic parameters continue to improve, guided by dynamic or static variables. 1

Vasopressor Therapy

• Initiate norepinephrine as the first-choice vasopressor if mean arterial pressure remains below 65 mmHg despite adequate fluid resuscitation. 1, 2
• Target a mean arterial pressure (MAP) of 65 mmHg as the initial hemodynamic goal. 1, 2
• Add epinephrine as a second agent when additional vasopressor support is needed beyond norepinephrine. 1
• Vasopressin (0.03 units/minute) can be added to norepinephrine to raise MAP or decrease norepinephrine dosage, but should not be used as the sole initial vasopressor. 1
• Avoid dopamine except in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia. 1
• Measure arterial blood pressure and heart rate frequently in patients requiring vasopressors. 1

Source Control and Diagnosis

Identifying the Infection Source

• Perform detailed patient history and thorough clinical examination to identify the infection source. 1, 2
• Use imaging techniques when available to localize the infection. 1, 2
• Sample fluid or tissue from the suspected infection site whenever possible without harming the patient. 1, 2
• Examine sampled material by Gram stain, culture, and antibiogram when available. 1, 2

Source Control Interventions

• Implement source control interventions as soon as medically and logistically practical after diagnosis is made, ideally within 12 hours when anatomically feasible. 1, 2
• Use the least physiologically invasive effective intervention (e.g., percutaneous drainage rather than surgical drainage when appropriate). 1
• Promptly remove intravascular access devices that are possible sources of infection after establishing alternative vascular access. 1

Hemodynamic Monitoring and Targets

Resuscitation Endpoints

Target the following within the first 6 hours: 2

• Mean arterial pressure ≥65 mmHg 1, 2
• Urine output ≥0.5 mL/kg/hour 2
• Central venous oxygen saturation ≥70% 2
• Normal capillary refill time, absence of skin mottling, warm and dry extremities 1, 2
• Return to baseline mental status 1, 2

Lactate Monitoring

• Measure serum lactate levels as a marker of tissue hypoperfusion. 2

Respiratory Support and Mechanical Ventilation

Oxygenation

• Apply oxygen to achieve oxygen saturation ≥90%—if pulse oximetry is unavailable, administer oxygen empirically. 1, 2
• Maintain adequate oxygenation without hyperoxia. 3, 2

Positioning and Non-Invasive Support

• Place patients in semi-recumbent position with head of bed elevated 30-45 degrees to prevent aspiration and ventilator-associated pneumonia. 1, 3, 2
• Use non-invasive ventilation in select patients with dyspnea and/or persistent hypoxemia despite oxygen therapy if staff is adequately trained. 1

Mechanical Ventilation (If ARDS Develops)

• Use lung-protective ventilation with tidal volumes of 6 mL/kg predicted body weight (not 12 mL/kg). 1, 2
• Target plateau pressures ≤30 cm H₂O in passively inflated lungs. 1
• Apply positive end-expiratory pressure (PEEP) to avoid alveolar collapse at end-expiration. 1
• Use higher rather than lower PEEP strategies for moderate or severe ARDS. 1
• Consider prone positioning for PaO₂/FiO₂ ratio ≤100 mm Hg in facilities with experience. 1
• Perform daily spontaneous breathing trials when patients meet weaning criteria (arousable, hemodynamically stable without vasopressors, no new serious conditions, low ventilatory requirements). 1, 2

Adjunctive Therapies

Corticosteroids

• Administer intravenous hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) to adult patients requiring escalating dosages of vasopressors. 1, 2

Glucose Control

• Target blood glucose 140-180 mg/dL using protocolized insulin therapy. 3, 2
• Avoid tight glucose control targeting <110 mg/dL—this increases hypoglycemia risk without mortality benefit. 3, 2

Blood Product Management

• Target hemoglobin 7-9 g/dL unless active myocardial ischemia, acute hemorrhage, or severe coronary artery disease is present. 1, 2
• Transfuse red blood cells only when hemoglobin decreases to <7.0 g/dL. 1
• Do not use fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures. 1

Thromboprophylaxis and Stress Ulcer Prevention

• Provide pharmacological or mechanical deep vein thrombosis prophylaxis. 1, 2
• Use H₂-blockers or proton pump inhibitors in patients with bleeding risk factors. 1, 2

Sedation and Delirium Management

Sedation Minimization

• Minimize sedation to the absolute minimum necessary—this is a critical intervention for outcomes. 3, 2
• Avoid benzodiazepines entirely in septic shock patients. 3, 2
• Use continuous or intermittent sedation targeting specific titration endpoints when necessary. 1
• Avoid neuromuscular blocking agents if possible due to risk of prolonged blockade. 1

Early Mobilization

• Initiate early mobilization as soon as patients are hemodynamically stable. 3, 2

Conservative Fluid Strategy Post-Resuscitation

• Use a conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of ongoing tissue hypoperfusion. 1

Critical Pitfalls to Avoid

• Delaying antimicrobial administration beyond 1 hour—each hour of delay increases mortality. 2
• Inadequate initial fluid resuscitation—the 30 mL/kg bolus is a minimum starting point, not a ceiling. 1, 2
• Failing to initiate vasopressors when MAP remains <65 mmHg despite adequate fluids—this prolongs tissue hypoperfusion and worsens outcomes. 1, 2
• Using excessive sedation, particularly benzodiazepines—this significantly worsens delirium and mortality. 3, 2
• Using dopamine as first-line vasopressor—norepinephrine has superior outcomes. 1
• Using hydroxyethyl starches for fluid resuscitation—these are contraindicated. 1
• Tight glucose control targeting <110 mg/dL—this increases hypoglycemia without benefit. 3, 2