What medications are used to treat acute sepsis in a crashing patient?

Medications for Treating Acute Sepsis in a Crashing Patient

In a crashing patient with acute sepsis, immediate administration of broad-spectrum antibiotics within 1 hour of sepsis recognition and norepinephrine as the first-line vasopressor are the most critical pharmacological interventions to reduce mortality. 1

Initial Pharmacological Management

Antimicrobial Therapy

• Broad-spectrum antibiotics: Must be administered within 1 hour of sepsis recognition 1, 2
  • Select antibiotics covering all likely pathogens based on:
    • Suspected infection source
    • Local epidemiology
    • Patient risk factors
  • Obtain blood cultures before antibiotic administration (at least 2 sets) but do not delay antibiotics 1
  • For septic shock: Use empiric combination therapy (at least two antibiotics of different classes) 1

Vasopressors and Hemodynamic Support

After initial fluid resuscitation of at least 30 mL/kg of crystalloids:

1. Norepinephrine: First-choice vasopressor to maintain mean arterial pressure (MAP) ≥65 mmHg 2, 1

   • Start when fluid resuscitation fails to restore adequate blood pressure and organ perfusion

2. Vasopressin: Can be added as second-line agent (up to 0.03 U/min) to either:

   • Raise MAP to target
   • Decrease norepinephrine requirements 1
   • Should not be used as initial vasopressor 2

3. Epinephrine: Can be added when an additional agent is needed to maintain adequate blood pressure 2

4. Dobutamine: Consider adding when there is:

   • Myocardial dysfunction (elevated cardiac filling pressures with low cardiac output)
   • Ongoing signs of hypoperfusion despite adequate volume and MAP 2, 1

5. Dopamine: Not recommended except in highly selected circumstances (patients with low risk of tachyarrhythmias) 2

Adjunctive Pharmacological Therapies

Corticosteroids

• Consider IV hydrocortisone (200 mg/day) only if adequate fluid resuscitation and vasopressor therapy cannot restore hemodynamic stability 2
• Avoid routine use in septic shock patients who are responding to fluid and vasopressor therapy 2

Blood Products

• Target hemoglobin of 7-9 g/dL in the absence of:
  • Tissue hypoperfusion
  • Ischemic coronary artery disease
  • Acute hemorrhage 2

Glucose Control

• Initiate insulin therapy when blood glucose levels exceed 180 mg/dL
• Target an upper blood glucose level ≤180 mg/dL 2

Monitoring Response to Treatment

• Reassess frequently after initial interventions:

  • Vital signs
  • Lactate clearance (if initially elevated)
  • Urine output
  • Signs of tissue perfusion 1

• For high-risk patients (NEWS2 score ≥7): Reassess every 30 minutes 1

• For moderate-risk patients (NEWS2 score 5-6): Reassess every hour 1

Common Pitfalls to Avoid

1. Delayed antibiotic administration: Mortality increases significantly when antibiotics are delayed beyond 1 hour in septic shock 3

   • Multivariate analysis shows antibiotic delay >4.5 hours increases mortality odds ratio to 5.54 3

2. Inadequate fluid resuscitation: Initial fluid challenge should be at least 30 mL/kg of crystalloids within first 3 hours 1

   • Avoid hydroxyethyl starches for volume replacement 1

3. Inappropriate vasopressor selection: Using dopamine as first-line instead of norepinephrine can increase arrhythmia risk 2

4. Failure to reassess: Continuous reassessment and adjustment of treatment is essential as patient status evolves 1

5. Overlooking source control: Identifying and controlling the infection source (e.g., draining abscesses, removing infected devices) is critical within 12 hours when feasible 1

Implementation of sepsis protocols emphasizing early antibiotic therapy and adequate fluid resuscitation has been shown to significantly reduce 28-day mortality from 61% to 33% in patients with septic shock 3.