What is the approach to using beta (beta blockers) in patients with sepsis, particularly those with underlying cardiovascular disease who are already on chronic beta blocker therapy?

Beta-Blocker Management in Sepsis

Continue beta-blockers in patients with sepsis who are already on chronic therapy for cardiovascular disease, but hold or reduce the dose if heart rate drops below 45-50 bpm or systolic blood pressure falls below 100 mmHg. 1

Approach to Chronic Beta-Blocker Therapy During Sepsis

For Patients Already Taking Beta-Blockers

The most critical principle is continuation rather than abrupt discontinuation. 1 Patients with underlying cardiovascular disease who are chronically on beta-blockers should have their therapy continued during sepsis, as abrupt discontinuation can precipitate rebound effects including severe exacerbations of angina, myocardial infarction, and ventricular arrhythmias. 2

Key hemodynamic thresholds for dose adjustment:

• Hold or reduce dose if heart rate <45-50 bpm 1, 3
• Hold or reduce dose if systolic blood pressure <100 mmHg 4, 1, 3
• Consider dose reduction rather than complete discontinuation for mild hemodynamic instability 1

Critical Monitoring Parameters

Before each dose administration, assess:

• Heart rate (target 50-60 bpm for optimal benefit) 1
• Systolic blood pressure 3
• Signs of tissue hypoperfusion or organ dysfunction 3
• Alternative causes of tachycardia (infection progression, hypovolemia, pulmonary embolism, anemia) 4

A crucial caveat: The association between death due to sepsis and beta-blocker use in the POISE trial suggests that persistent tachycardia may indicate worsening sepsis or other complications rather than inadequate beta-blockade. 4 A thorough search for alternative causes of tachycardia is essential before attributing it solely to inadequate beta-blocker dosing.

Evidence for Mortality Benefit in Specific Populations

Patients with absolute tachycardia (HR ≥100 bpm) during sepsis may derive particular benefit from continued beta-blocker therapy. 5 An observational cohort study demonstrated that long-term beta-blocker therapy was associated with decreased 30-day mortality in septic patients exhibiting tachycardia (odds ratio 0.406,95% CI 0.177-0.932). 5

Selective beta-1 blockers appear superior to non-selective agents in this setting. 5 This finding aligns with the need to avoid excessive hemodynamic depression while still providing heart rate control and potential metabolic/immunomodulatory benefits.

Mechanism of Potential Benefit

Beta-blockers may provide benefit through multiple pathways beyond heart rate control:

• Modulation of excessive catecholaminergic hyperactivity characteristic of sepsis 6
• Anti-inflammatory effects 6, 7
• Improved myocardial oxygen supply/demand balance 6
• Metabolic and immunomodulatory properties 7

When to Avoid or Discontinue

Absolute contraindications during sepsis include: 1

• Cardiogenic shock or high risk for shock
• Active bronchospasm
• Symptomatic bradycardia
• Heart rate consistently <45 bpm
• Decompensated heart failure
• Advanced heart block

Relative contraindications requiring careful assessment:

• Hypotension with systolic blood pressure <100 mmHg (may require temporary dose reduction or holding) 4, 3
• Signs of tissue hypoperfusion despite adequate fluid resuscitation 3

Practical Algorithm

1. Assess baseline status: Confirm patient is hemodynamically stable (not requiring IV inotropes, not in cardiogenic shock) 1

2. Check vital signs before each dose:

   • If HR <45 bpm → Hold dose 1, 3
   • If HR 45-50 bpm → Consider holding or reducing dose 1
   • If SBP <90 mmHg → Hold dose 3
   • If SBP 90-100 mmHg → Use caution, consider dose reduction 3

3. Investigate alternative causes if tachycardia persists:

   • Worsening sepsis/infection
   • Hypovolemia
   • Pulmonary embolism
   • Anemia
   • Pain or agitation 4

4. Reassess after 2-4 hours if dose held for hypotension 3

5. If hemodynamic instability persists, consider dose reduction rather than complete discontinuation 1

Important Caveats

The risk-benefit calculation differs from initiating beta-blockers in sepsis. While the Surviving Sepsis Campaign guidelines do not specifically recommend initiating beta-blockers for sepsis treatment 4, the evidence supports continuation of chronic therapy in patients with cardiovascular indications. 1

Clinically significant hypotension from beta-blockers carries substantial risk. In the perioperative setting, hypotension was associated with an adjusted odds ratio for death and stroke of 4.97 (95% CI 3.62-6.81). 4, 3 This underscores the importance of vigilant hemodynamic monitoring.

Beta-blockers reduce mortality by 23% in post-MI patients, with greatest benefit in those with heart failure, systolic dysfunction, or ventricular arrhythmias. 1 This cardiovascular protection must be weighed against potential hemodynamic compromise during acute sepsis.