How to use norepinephrine (Levophed) in patients with sepsis and congestive heart failure (CHF)?

Norepinephrine Use in Septic Shock with Congestive Heart Failure

Norepinephrine remains the first-line vasopressor for septic shock even in patients with preexisting heart failure, and should be initiated early after adequate fluid resuscitation to restore mean arterial pressure to at least 65 mmHg. 1, 2

Initial Vasopressor Strategy

Start norepinephrine as the mandatory first-choice agent once hypotension persists after initial fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours), targeting MAP ≥65 mmHg. 1, 3 The presence of CHF does not change this fundamental approach—norepinephrine is the most well-supported vasopressor specifically in patients with sepsis and preexisting heart failure. 2

Administration Protocol

• Administer through central venous access whenever possible to minimize risk of tissue necrosis from extravasation. 4, 5
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors. 1, 3
• Start with 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70-kg adult), then titrate to achieve MAP target. 4
• Standard dilution is 4 mg in 1000 mL of 5% dextrose (4 mcg/mL), with initial infusion rates of 2-3 mL/min (8-12 mcg/min). 5

Critical Considerations in Heart Failure Patients

Do not withhold adequate fluid resuscitation due to CHF. Evidence demonstrates that traditional fluid resuscitation targets do not increase adverse events in heart failure patients with sepsis and likely improve outcomes. 2 However, monitor closely for fluid overload and consider earlier vasopressor initiation if profound hypotension exists (diastolic BP ≤40 mmHg or diastolic shock index ≥3). 6

Hemodynamic Nuances

• Norepinephrine may increase myocardial oxygen requirements, mandating cautious use in patients with ischemic heart disease, but this concern does not contraindicate its use. 4
• In sepsis specifically, norepinephrine improves renal blood flow and urine output despite typically causing renal vasoconstriction in other contexts. 4
• Norepinephrine increases cardiac output in early septic shock by transforming unstressed blood volume into stressed blood volume and increasing mean systemic filling pressure. 6, 7

Escalation Protocol for Refractory Hypotension

When MAP target cannot be achieved with norepinephrine alone (typically at doses >15 mcg/min):

Add vasopressin at 0.03 units/minute to either raise MAP to target or decrease norepinephrine requirements. 1, 8 This is the preferred second-line agent. Do not exceed 0.03-0.04 units/minute as higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit. 1, 8

If hypotension persists, add epinephrine (0.05-2 mcg/kg/min) as the third vasopressor rather than escalating vasopressin further. 1, 8

What NOT to Do

• Avoid dopamine in CHF patients with sepsis—it induces more cardiac adverse events, increases risk of tachyarrhythmias, and is associated with higher mortality compared to norepinephrine. 1, 8, 2, 9
• Do not use phenylephrine as first-line therapy—it may raise blood pressure numbers while actually worsening tissue perfusion and should only be used when norepinephrine causes serious arrhythmias or as salvage therapy. 1, 3
• Never use low-dose dopamine for "renal protection"—this is strongly discouraged and has no benefit. 4, 1

Managing Concurrent Cardiac Dysfunction

If persistent hypoperfusion exists despite adequate MAP and fluid resuscitation, add dobutamine (2.5-20 mcg/kg/min) to improve cardiac output, particularly when myocardial dysfunction is evident. 4, 1 However, use dobutamine cautiously as it generally has detrimental effects and may worsen outcomes. 2, 10

Beta-Blocker Management

• Continue chronic beta-blockers in the absence of acute hemodynamic decompensation or cardiogenic shock. 4, 2
• Temporarily reduce or omit beta-blockers if the patient is clinically unstable with signs of low cardiac output, but generally do not stop them completely. 4

Common Pitfalls to Avoid

• Do not delay norepinephrine waiting for "complete" fluid resuscitation in profoundly hypotensive patients—prolonged hypotension worsens outcomes and early norepinephrine administration is beneficial. 6, 7
• Avoid excessive fluid administration attempting to avoid vasopressors—fluid overload is particularly harmful in CHF patients and norepinephrine rapidly stabilizes blood pressure more effectively than fluids alone. 6, 2
• Do not use norepinephrine plus vasopressin combination as initial therapy—this combination may actually reduce survival compared to norepinephrine alone in heart failure patients with sepsis. 9
• Monitor for extravasation—if it occurs, infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into the site immediately to prevent tissue necrosis. 4