What is the management of septic shock in an adult patient with a severe underlying infection and hypotension?

Management of Septic Shock

Initiate aggressive resuscitation immediately upon recognition with 30 mL/kg crystalloid bolus within the first hour, administer broad-spectrum antibiotics within 60 minutes, and start norepinephrine if mean arterial pressure remains below 65 mmHg despite adequate fluid loading. 1

Immediate Actions (First Hour)

Fluid Resuscitation

• Administer a minimum 30 mL/kg of crystalloid fluids rapidly as an initial bolus for sepsis-induced tissue hypoperfusion—this is a floor, not a ceiling, and many patients will require substantially more 2, 1
• Use crystalloids (normal saline or lactated Ringer's) as first-line therapy; avoid hetastarch formulations entirely 2
• Consider albumin only if patients continue requiring massive crystalloid volumes to maintain adequate mean arterial pressure 2
• Continue fluid challenges as long as hemodynamic parameters improve based on dynamic (e.g., pulse pressure variation, stroke volume variation) or static variables (e.g., CVP, clinical examination) 2

Antimicrobial Therapy

• Obtain at least two sets of blood cultures (aerobic and anaerobic) before antibiotics, but never delay antimicrobial administration beyond 45 minutes 2, 1
• Draw one set percutaneously and one through each vascular access device if the device has been in place less than 48 hours 2
• Administer broad-spectrum intravenous antimicrobials within 1 hour of recognizing septic shock—every hour of delay directly increases mortality 2, 1
• Select agents with activity against all likely pathogens (bacterial, fungal, or viral) that achieve adequate tissue concentrations at the presumed infection source 2
• Ensure adequate dosing with high likelihood of killing suspected organisms 1

Hemodynamic Targets (First 6 Hours)

• Target mean arterial pressure ≥65 mmHg as the primary hemodynamic goal 2, 1
• Aim for central venous pressure 8-12 mmHg (12-15 mmHg if mechanically ventilated) 2
• Achieve urine output ≥0.5 mL/kg/hour 2
• Target central venous oxygen saturation (ScvO2) ≥70% or mixed venous oxygen saturation (SvO2) ≥65% 2
• Normalize lactate levels as rapidly as possible if elevated (lactate ≥4 mmol/L defines tissue hypoperfusion requiring aggressive resuscitation) 2, 1

Vasopressor Therapy

First-Line Agent

• Use norepinephrine as the first-choice vasopressor to maintain MAP ≥65 mmHg if hypotension persists despite adequate fluid resuscitation 2, 1, 3
• Place an arterial catheter as soon as practical in all patients requiring vasopressors for continuous blood pressure monitoring 2

Second-Line Agents

• Add vasopressin (0.03 units/min maximum) to norepinephrine to either raise MAP to target or decrease norepinephrine dose, but never use vasopressin as the initial vasopressor 2
• Add epinephrine when an additional agent is needed beyond norepinephrine to maintain adequate blood pressure 2
• Avoid dopamine except in highly selected circumstances (e.g., patients with low risk of tachyarrhythmias and absolute or relative bradycardia) 2
• Never use low-dose dopamine for renal protection—this practice is ineffective and should be abandoned 2

Inotropic Support

• Add dobutamine infusion (up to 20 mcg/kg/min) to vasopressor therapy if evidence of persistent hypoperfusion despite adequate intravascular volume and MAP, particularly with myocardial dysfunction suggested by elevated cardiac filling pressures and low cardiac output 2
• Titrate dobutamine to endpoints reflecting tissue perfusion and reduce or discontinue if worsening hypotension or arrhythmias develop 2

Source Control and Diagnostics

Infection Source Identification

• Perform imaging studies promptly to confirm potential infection sources 2
• Obtain detailed history focusing on recent procedures, indwelling devices, travel, exposures, and immunosuppression 1
• Sample fluid or tissue from suspected infection sites whenever feasible without causing patient harm 1
• Examine specimens by Gram stain, culture, and antibiogram when available 1

Source Control Interventions

• Implement definitive source control (drainage, debridement, device removal) as soon as possible after diagnosis, ideally within 12 hours when anatomically feasible 1
• Common sources include pulmonary (pneumonia), urinary tract (pyelonephritis, urosepsis), abdominal (peritonitis, cholangitis), and skin/soft tissue (necrotizing fasciitis, abscess) 4

Respiratory Support

Oxygenation

• Apply supplemental oxygen to achieve oxygen saturation ≥90% 1
• Avoid hyperoxia while maintaining adequate oxygenation 1
• Position patients semi-recumbent with head of bed elevated 30-45 degrees to reduce aspiration risk and prevent ventilator-associated pneumonia 2, 1

Mechanical Ventilation (if ARDS develops)

• Use low tidal volume ventilation at 6 mL/kg predicted body weight (not 12 mL/kg) in sepsis-induced ARDS 2
• Maintain plateau pressures ≤30 cm H2O in passively inflated lungs 2
• Apply positive end-expiratory pressure (PEEP) to prevent alveolar collapse at end-expiration 2
• Use higher PEEP strategies (rather than lower PEEP) for moderate to severe ARDS 2
• Consider recruitment maneuvers in severe refractory hypoxemia 2
• Use prone positioning in sepsis-induced ARDS with PaO2/FiO2 ratio <150 mm Hg (or ≤100 mm Hg) in facilities experienced with this practice 2
• Consider neuromuscular blockade for ≤48 hours in early ARDS with PaO2/FiO2 <150 mm Hg 2
• Implement a weaning protocol with daily spontaneous breathing trials 2

Adjunctive Therapies

Corticosteroids

• Do not use intravenous hydrocortisone if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability 2
• If hemodynamic stability cannot be achieved, administer hydrocortisone 200 mg/day as continuous infusion (not bolus dosing) 2, 1
• Taper hydrocortisone when vasopressors are no longer required 2
• Never administer corticosteroids for sepsis without shock 2
• Do not use ACTH stimulation testing to identify patients who should receive hydrocortisone 2

Glucose Management

• Target blood glucose 140-180 mg/dL (not <110 mg/dL) using protocolized insulin therapy 2, 1
• Commence insulin when two consecutive glucose levels exceed 180 mg/dL 2
• Avoid tight glycemic control targeting <110 mg/dL as this increases hypoglycemia risk without mortality benefit 1

Blood Products

• Transfuse red blood cells only when hemoglobin decreases to <7.0 g/dL, targeting 7-9 g/dL 2, 1
• Use higher hemoglobin thresholds only for active myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic coronary artery disease 2
• Do not use erythropoietin for sepsis-associated anemia 2
• Do not use antithrombin for treatment 2
• Avoid fresh frozen plasma to correct laboratory clotting abnormalities without active bleeding or planned invasive procedures 2
• Administer platelets prophylactically when counts <10,000/mm³ without bleeding, or <20,000/mm³ with significant bleeding risk 2

Prophylaxis

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

Ongoing Management

Antimicrobial Reassessment

• Reassess antimicrobial regimen daily for potential de-escalation based on culture results and clinical response 2, 1
• Use procalcitonin or similar biomarkers to assist in discontinuing empiric antibiotics when appropriate 2
• Administer antimicrobials for adequate but not prolonged duration 1

Sedation and Mobilization

• Minimize sedation to the absolute minimum necessary—avoid benzodiazepines entirely in septic patients 1
• Use protocolized sedation targeting specific titration endpoints 2
• Initiate early mobilization as soon as hemodynamically stable 1
• Resume oral nutrition after resuscitation and return of consciousness 1

Fluid Management After Stabilization

• Use a conservative fluid strategy for established sepsis-induced ARDS without evidence of tissue hypoperfusion 2

Critical Pitfalls to Avoid

• Never delay antimicrobial administration beyond 1 hour—each hour of delay increases mortality 2, 1
• The 30 mL/kg crystalloid bolus is a minimum starting point, not a maximum—many patients require substantially more fluid 2, 1
• Do not delay vasopressor initiation when MAP remains <65 mmHg despite adequate fluid challenge—prolonged tissue hypoperfusion worsens outcomes 1
• Never attempt extubation while patients still require vasopressors—hemodynamic stability without vasopressors is an absolute prerequisite 5
• Avoid excessive sedation, particularly benzodiazepines—this worsens delirium and outcomes 1
• Do not target tight glucose control <110 mg/dL—this increases hypoglycemia without benefit 1
• Do not use dopamine for renal protection—this is ineffective 2