What are the current management strategies for septic shock?

Septic Shock Management Update

Administer IV antimicrobials within 60 minutes of recognizing septic shock, initiate aggressive fluid resuscitation with 30 mL/kg crystalloids, and start norepinephrine as first-line vasopressor to target MAP ≥65 mmHg—these three interventions form the cornerstone of septic shock management and directly impact mortality. 1, 2, 3

Immediate Recognition and Diagnostic Actions (First Hour)

Obtain blood cultures before antibiotics but never delay antimicrobials beyond 45-60 minutes if cultures cannot be obtained immediately. 2, 4 The single most critical intervention is antibiotic administration within one hour—every hour of delay increases mortality. 5, 2

• Measure serum lactate as a marker of tissue hypoperfusion to guide resuscitation intensity. 2, 4
• Perform focused ultrasonography to identify complicating physiology such as hypovolemia or cardiogenic shock. 6
• Identify and diagnose the anatomic source of infection as rapidly as possible using clinical examination and imaging. 1, 4

Antimicrobial Therapy Strategy

Use broad-spectrum empiric therapy covering all likely pathogens (bacterial, fungal, viral) with adequate tissue penetration to the presumed infection source. 1, 2 Piperacillin/tazobactam is specifically recommended as a preferred broad-spectrum option for septic shock. 5

Dosing and Administration

• Administer piperacillin/tazobactam via extended (4-hour) or continuous infusion rather than intermittent bolus dosing—this reduces mortality from 31.6% to 12.2% in critically ill patients with APACHE II ≥17. 5
• Standard dosing: 4.5 g every 6-8 hours as extended or continuous infusion after loading dose. 5

Combination and De-escalation

• Consider combination therapy (two antibiotics from different classes) for septic shock, particularly for Pseudomonas aeruginosa or in neutropenic patients. 1, 2
• De-escalate to narrower therapy within 3-5 days once susceptibility results are available—this minimizes resistance and toxicity. 1, 5
• Typical duration is 7-10 days; longer courses are appropriate for slow clinical response, undrainable foci, S. aureus bacteremia, or immunodeficiency. 1, 2
• Reassess antimicrobial therapy daily for potential narrowing. 1, 2

Fluid Resuscitation

Administer 30 mL/kg IV crystalloids within the first 3 hours for sepsis-induced hypoperfusion (hypotension or lactate ≥4 mmol/L). 1, 2, 7 More rapid administration and greater amounts may be needed in some patients. 1

• Use crystalloids (either balanced crystalloids or normal saline) as the fluid of choice—both are reasonable options with weak evidence favoring balanced crystalloids. 1, 3, 7
• Consider albumin in addition to crystalloids when patients require substantial amounts of crystalloids. 1
• Never use hydroxyethyl starches—they are contraindicated in septic shock. 1, 6
• Apply fluid challenge technique: continue fluid administration as long as hemodynamic factors improve based on dynamic (pulse pressure variation, stroke volume variation) or static (arterial pressure, heart rate) variables. 1

Pitfall to Avoid

After initial resuscitation, use a conservative fluid strategy in established septic shock without tissue hypoperfusion to avoid fluid overload. 1, 7

Vasopressor Therapy

Target MAP ≥65 mmHg in patients requiring vasopressors. 1, 2, 3 Early vasopressor initiation is appropriate in patients who are not fluid-responsive. 3

Vasopressor Algorithm

1. Norepinephrine is the first-choice vasopressor (strong recommendation). 1, 2, 3
2. If hypotension persists, add vasopressin 0.03 units/minute to raise MAP or decrease norepinephrine dosage. 1, 3, 7
3. Add epinephrine if additional agent needed (vasopressin is preferred over epinephrine as second agent). 1, 3, 7
4. Dopamine is only appropriate in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia. 1

Practical Consideration

Peripheral administration of vasopressors through a 20-gauge or larger IV line is safe and effective—do not delay vasopressors waiting for central access. 3

Source Control

Implement source control interventions as soon as medically and logistically practical after diagnosis, ideally within 12 hours. 1, 2

• Use the intervention with the least physiologic insult (e.g., percutaneous rather than surgical drainage). 1
• Remove intravascular access devices promptly if they are a possible source, after establishing other vascular access. 1
• For infected peripancreatic necrosis, delay definitive intervention until adequate demarcation of viable and nonviable tissues occurs. 1

Adjunctive Therapies

Corticosteroids

Administer hydrocortisone (up to 300 mg/day) or prednisolone (up to 75 mg/day) to patients with refractory septic shock requiring escalating vasopressor dosages. 4, 3, 7 Use continuous flow when hydrocortisone is given. 1 Do not use corticosteroids for sepsis without shock. 1

Blood Products

• Target hemoglobin 7-9 g/dL once tissue hypoperfusion resolves, in the absence of myocardial ischemia, severe hypoxemia, or acute hemorrhage. 1, 2, 4
• Administer platelets prophylactically when counts <10,000/mm³ without bleeding, or <20,000/mm³ with significant bleeding risk. 1

Glycemic Control

Maintain blood glucose ≤180 mg/dL using a protocolized approach—avoid targeting <150 mg/dL after initial stabilization due to hypoglycemia risk. 2, 4, 8

Mechanical Ventilation (If Required)

Use low tidal volume ventilation (6 mL/kg predicted body weight) for sepsis-induced ARDS, targeting plateau pressures ≤30 cm H₂O. 1, 2, 4

• Apply PEEP to avoid alveolar collapse at end-expiration. 1
• Use higher rather than lower PEEP levels for moderate-to-severe ARDS. 1
• Position patients semi-recumbent (head of bed 30-45°) to reduce aspiration risk and prevent ventilator-associated pneumonia. 1, 2, 4
• Consider prone positioning for PaO₂/FIO₂ ratio ≤100 mmHg in facilities with experience. 1
• Implement weaning protocols with daily spontaneous breathing trials when patients are arousable, hemodynamically stable without vasopressors, and have low ventilatory requirements. 1

Performance Improvement

Implement hospital-wide sepsis screening programs and multidisciplinary teams including physicians, nurses, pharmacy, and respiratory therapy. 2, 4 Use sepsis bundles and protocols with regular education and performance feedback. 2, 4

Critical Pitfall

Recent evidence demonstrates that protocolized care offers little advantage compared with management without rigid protocols—focus on the core interventions (antibiotics, fluids, vasopressors) rather than strict protocol adherence. 6