Should beta (beta blockers) be avoided in patients with sepsis, particularly those with a history of heart failure or arrhythmias who are already on medications like metoprolol (metoprolol)?

Beta-Blockers in Sepsis: Continuation vs. Avoidance

Beta-blockers should NOT be routinely avoided in sepsis patients, and chronic beta-blocker therapy (such as metoprolol) should be continued in patients with established indications like heart failure or arrhythmias, unless contraindications develop during the acute septic episode. 1, 2

Key Principle: Continue Chronic Beta-Blocker Therapy

• Patients already taking beta-blockers for heart failure or other cardiovascular conditions should have their therapy continued during sepsis. 1
• Abrupt discontinuation of metoprolol in patients with coronary artery disease can cause severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias. 2
• When discontinuation is necessary, dosage should be gradually reduced over 1-2 weeks with careful monitoring. 2

Evidence Supporting Beta-Blocker Use in Sepsis

Mortality Benefits

• Chronic beta-blocker prescription prior to sepsis is associated with reduced 28-day mortality (17.7% vs 22.1%, adjusted OR 0.81,95% CI 0.68-0.97, p=0.025) in a large cohort of 9,465 ICU patients with sepsis. 3
• Multiple trials demonstrate beneficial effects on heart rate control without detrimental effects on blood pressure. 4
• Of six trials assessing mortality, four showed substantial benefits from beta-blocker use in sepsis. 4

Physiologic Rationale

• Beta-blockers may provide metabolic and immunomodulatory benefits in sepsis, including effects on glucose homeostasis, cytokine expression, and myocardial function. 5
• Catecholaminergic hyperactivity and excessive tachycardia in sepsis may be mitigated by beta-blockade. 6

Critical Contraindications During Acute Sepsis

Hold or reduce beta-blockers if the following develop:

• Heart rate <45-50 bpm or significant bradycardia 1, 2
• Systolic blood pressure <100 mmHg or clinically significant hypotension 1, 2
• Signs of cardiogenic shock or high risk for shock (oliguria, low output state) 1
• Decompensated heart failure (new rales, S3 gallop) 1
• Second- or third-degree heart block without pacemaker 2
• Marked first-degree AV block (PR interval ≥0.24 sec) 2

Important Clinical Caveat: Sepsis as Alternative Cause of Tachycardia

• The POISE trial found increased mortality from sepsis in patients receiving perioperative beta-blockade, suggesting that persistent tachycardia may indicate infection rather than inadequate beta-blockade. 1
• Perform thorough search for alternative causes of tachycardia (sepsis, hypovolemia, pulmonary embolism, anemia) before escalating beta-blocker doses. 1
• Patients with persistent tachycardia may warrant short-term down-titration or discontinuation of beta-blocker therapy. 1

Specific Recommendations for Metoprolol in Sepsis

For Patients Already on Metoprolol

• Continue metoprolol unless specific contraindications develop (bradycardia, hypotension, shock, heart block). 1, 2
• Monitor heart rate, blood pressure, and signs of heart failure closely. 2
• If severe bradycardia develops, reduce or stop metoprolol. 2

Dosing Adjustments

• Hold metoprolol if heart rate consistently <45-50 bpm or systolic BP <100 mmHg. 1
• Consider reducing to lower doses (e.g., 12.5 mg) rather than complete discontinuation if hemodynamic instability is mild. 1, 7
• For patients with concerns about tolerance, short-acting metoprolol allows easier titration than longer-acting agents. 1

Special Populations

Patients with Heart Failure

• Beta-blockers are strongly recommended before discharge in patients with compensated heart failure or LV systolic dysfunction for secondary prevention, even after sepsis. 1
• Beta-blockers reduce mortality and hospitalization risk in heart failure patients with or without CAD, diabetes, and across demographic groups. 1
• Three beta-blockers proven effective in chronic HFrEF: bisoprolol, metoprolol succinate, and carvedilol. 1

Patients with Arrhythmias

• Beta-blockers remain appropriate for rate control in atrial fibrillation or other arrhythmias during sepsis, unless contraindications develop. 1
• Metoprolol can be used cautiously for rate control in multifocal atrial tachycardia, avoiding use in respiratory decompensation. 1

Patients with Reactive Airway Disease

• Metoprolol may be used cautiously in patients with mild reactive airway disease or COPD, starting with reduced doses (12.5 mg). 1, 7
• Beta-1 selectivity is not absolute; bronchodilators should be readily available. 2
• Active asthma is an absolute contraindication. 7
• If concerns exist about beta-blocker intolerance, consider short-acting esmolol for easier titration. 1, 8

Guideline Limitations on Beta-Agonists (Not Beta-Blockers)

Important distinction: The 2012 Surviving Sepsis Campaign guidelines recommend against beta-AGONISTS (albuterol, salbutamol) in sepsis-induced ARDS due to increased mortality, but this does not apply to beta-BLOCKERS. 1

Algorithm for Beta-Blocker Management in Sepsis

1. Assess if patient is on chronic beta-blocker therapy (metoprolol, carvedilol, bisoprolol, etc.)
2. If YES, continue therapy unless:
   • HR <45-50 bpm
   • SBP <100 mmHg
   • Signs of cardiogenic shock
   • Decompensated heart failure
   • High-degree AV block
3. If contraindications develop:
   • Hold doses temporarily
   • Do NOT abruptly discontinue
   • Reassess daily for resolution
   • Resume at lower dose when stable
4. Search for alternative causes of tachycardia (infection, hypovolemia, PE, anemia) before attributing to inadequate beta-blockade
5. Before discharge, ensure beta-blocker is restarted in patients with heart failure or CAD indications

Common Pitfalls to Avoid

• Do not abruptly discontinue chronic beta-blocker therapy due to fear of hypotension in sepsis—this causes worse outcomes in patients with CAD or heart failure. 2
• Do not confuse beta-AGONIST recommendations (avoid in sepsis-ARDS) with beta-BLOCKER management (continue chronic therapy). 1
• Do not ignore alternative causes of tachycardia (sepsis itself, hypovolemia) when considering beta-blocker escalation. 1
• Do not use beta-blockers to treat sepsis-induced tachycardia de novo—evidence supports continuation of chronic therapy, not initiation during acute sepsis. 4, 9

Current Evidence Limitations

• While observational data and small trials suggest potential benefits of beta-blockers in sepsis, there is insufficient evidence to justify routine initiation of beta-blockers specifically for sepsis treatment. 9
• Most positive data comes from continuation of chronic therapy or highly selected patients. 3
• Large multicenter randomized controlled trials are needed to definitively establish efficacy, optimal agent, dosing, and timing. 9, 6