How is Redman syndrome, also known as vancomycin flushing reaction, managed?

Management of Red Man Syndrome (Vancomycin Flushing Reaction)

The management of Red Man Syndrome involves immediately stopping or slowing the vancomycin infusion and administering antihistamines, with subsequent doses given at a slower infusion rate with antihistamine premedication. 1, 2

Understanding Red Man Syndrome

Red Man Syndrome (RMS) is a histamine-mediated reaction characterized by:

• Flushing of the upper body
• Pruritus (itching)
• Erythema (redness)
• Urticaria (hives)
• Potential hypotension in severe cases
• Wheezing or dyspnea in severe reactions

This reaction is distinct from true anaphylaxis as it is not IgE-mediated but rather caused by direct vancomycin-induced histamine release 1, 3.

Immediate Management

When RMS occurs:

1. Stop or slow the vancomycin infusion immediately 1, 2

   • Symptoms typically resolve within 20 minutes but may persist for several hours

2. Administer antihistamines

   • Diphenhydramine 50 mg IV/PO is the most commonly used antihistamine 4
   • H1 blockers are the mainstay of treatment

3. For severe reactions with hypotension:

   • IV fluids
   • Vasopressors if needed
   • Consider IV ephedrine in severe cases 5
   • In very severe cases, IV hydrocortisone may be added 5

Prevention and Subsequent Dosing

For patients who have experienced RMS:

1. Extend infusion time

   • Administer vancomycin over at least 2 hours 1, 2
   • The FDA warns that rapid bolus administration (over several minutes) may be associated with exaggerated hypotension, shock, and rarely cardiac arrest 2

2. Premedicate with antihistamines

   • Administer diphenhydramine 50 mg IV/PO 1 hour before vancomycin infusion 4
   • Pretreatment with diphenhydramine has been shown to significantly reduce the incidence of RMS (0% vs 47% in placebo group) 4

3. Consider dose adjustment

   • Lower doses (500 mg) are associated with significantly fewer RMS reactions than higher doses (1000 mg) when infused over the same time period 6
   • Consider dividing the total daily dose into smaller, more frequent administrations

Risk Factors and Special Considerations

• Higher vancomycin doses have greater risk of causing RMS when infused at the same rate 1, 6
• First-dose reactions are more common, but subsequent doses can still cause RMS 4
• RMS has been reported with local application of vancomycin powder in surgical wounds 7 and vancomycin-loaded bone cement 5, though this is rare

Important Caveats

• RMS must be distinguished from true anaphylaxis, which would contraindicate further vancomycin use
• Plasma histamine levels correlate with reaction severity 4, 6
• The frequency and severity of reactions typically decline with subsequent doses 6
• In rare cases, second-dose reactions can be more severe than first-dose reactions, even with premedication 4

By following these management strategies, most patients can continue to receive vancomycin safely even after experiencing Red Man Syndrome.