Pressor Selection for Hypotensive Patients on Linezolid (Zyvox)
Norepinephrine is the recommended first-line vasopressor for patients on linezolid who develop hypotension, with careful monitoring for enhanced pressor response due to linezolid's monoamine oxidase inhibitor properties. 1, 2
Critical Drug Interaction Concern
Linezolid is a reversible, nonselective monoamine oxidase inhibitor, which creates a significant interaction risk with adrenergic vasopressors 2. The FDA label specifically warns that "a significant pressor response has been observed in normal adult subjects receiving linezolid" when combined with adrenergic agents 2. Studies with pseudoephedrine and phenylpropanolamine demonstrated mean maximum increases in systolic blood pressure of 32 mm Hg (range: 20-52 mm Hg) and 38 mm Hg (range: 18-79 mm Hg), respectively, when co-administered with linezolid 2.
First-Line Vasopressor Choice
Norepinephrine remains the preferred first-line vasopressor despite the linezolid interaction, starting at 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70-kg adult). 1 The 2016 Surviving Sepsis Campaign guidelines provide strong recommendation for norepinephrine as first-choice vasopressor, and this remains applicable even with linezolid use 1. The 2016 European Society of Cardiology guidelines similarly recommend norepinephrine for severe hypotension with low total peripheral resistance 1.
Dosing Strategy with Linezolid
- Start at the lower end of the dosing range (0.1 mcg/kg/min or 7 mcg/min in a 70-kg adult) due to potential enhanced pressor response 1, 2
- Titrate slowly with close bedside monitoring, as the enhanced pressor effect may require lower-than-typical doses 1, 2
- Target mean arterial pressure (MAP) of 65 mm Hg initially 1
- Administer through central line whenever possible to prevent tissue necrosis from extravasation 1
Second-Line Vasopressor Options
If MAP remains inadequate despite low-to-moderate dose norepinephrine (0.1-0.2 mcg/kg/min), add vasopressin at 0.03-0.04 units/min 1. Vasopressin is advantageous in this scenario because it works through non-adrenergic V1 receptors and does not interact with linezolid's MAO inhibitor properties 1.
Alternatively, epinephrine (0.05-0.5 mcg/kg/min) can be added to or substituted for norepinephrine, though the same enhanced pressor response concerns apply 1, 2.
Vasopressors to Use with Extreme Caution
Dopamine should be avoided or used only in highly selected patients (e.g., those with absolute or relative bradycardia and low risk of tachyarrhythmias) 1. The 2012 Surviving Sepsis Campaign comparison of dopamine versus norepinephrine suggested norepinephrine has fewer side effects and lower mortality in septic shock subgroup analysis 1. Given linezolid's MAO inhibitor properties, dopamine's enhanced pressor response would be even more pronounced and unpredictable 2.
Phenylephrine (0.5-2.0 mcg/kg/min) should be reserved for exceptional circumstances where norepinephrine causes serious arrhythmias or when cardiac output is known to be high with persistently low blood pressure 1. The pure alpha-agonist effects combined with linezolid's MAO inhibition create substantial risk for excessive vasoconstriction 2.
Essential Monitoring Requirements
- Measure blood pressure continuously via arterial line when possible 1
- Monitor for excessive pressor response (systolic BP increases >30-40 mm Hg above target) 2
- Assess heart rate for reflex bradycardia from excessive vasoconstriction 1, 2
- Evaluate tissue perfusion (lactate clearance, urine output, mental status) 1
- Check for signs of end-organ hypoperfusion from excessive vasoconstriction 1
Critical Pitfalls to Avoid
Do not use typical vasopressor doses without considering the enhanced pressor response from linezolid. The FDA label documents that combination treatment with adrenergic agents produces substantially higher blood pressure elevations than either agent alone 2. Starting at lower doses and titrating more cautiously is essential 1, 2.
Do not mix adrenergic vasopressors with sodium bicarbonate or alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions 1.
Do not overlook the need for adequate fluid resuscitation before or concurrent with vasopressor initiation. Norepinephrine is relatively contraindicated in hypovolemia and may increase myocardial oxygen requirements 1. The Surviving Sepsis Campaign recommends initial fluid resuscitation with crystalloids (minimum 30 mL/kg) before or concurrent with vasopressor therapy 1.
Alternative Non-Adrenergic Approach
For patients requiring prolonged vasopressor support on linezolid, consider vasopressin as a primary agent (up to 0.03 units/min) to minimize reliance on adrenergic vasopressors and their enhanced pressor response 1. However, vasopressin should not be used as the sole initial vasopressor; it should be added to low-dose norepinephrine 1.