VANCOMYCIN AND RED MAN SYNDROME
Vancomycin is an antibiotic belonging to the glycopeptide group that has been in use since 1958. Since then, vancomycin has become the first-line choice for treating Gram-positive bacteria resistant to betalactam, notably methicillin-resistant Staphylococcus aureus (MRSA). In addition to nephrotoxicity, red-man syndrome (RMS) is one of the ADRs of concern with this antibiotic. In Vietnam, according to a summary from the National Center for Drug Information and Adverse Drug Reactions from 2006 to 2014, there were 364 ADR reports related to vancomycin, of which 125 (34.3%) reported symptoms of redness in the head, face, neck, and upper body (accompanied by itching and hypotension).
1. MECHANISM AND MANIFESTATIONS OF RED-MAN SYNDROME (RMS)
Mechanism: RMS is not an allergic reaction but has signs and symptoms similar to an allergic reaction. The mechanism of this reaction is due to the depletion of mast cells and basophils, leading to the release of histamine independent of previously formed IgE antibodies or the complement pathway. It may be difficult to distinguish between the anaphylactic form related to intravenous infusion and IgE-mediated allergic reactions.
Manifestations: The reaction can occur early within 4-10 minutes after starting the infusion.patients experiencing symptoms of Red Man Syndrome (RMS). The incidence of RMS was significantly lower when vancomycin was administered over a longer period, such as 60 minutes. Therefore, it is recommended to infuse vancomycin slowly to minimize the risk of this syndrome.
Management of Red Man Syndrome: If RMS occurs, the infusion should be stopped immediately. Antihistamines can be administered to alleviate symptoms, and the infusion can be resumed at a slower rate once symptoms have resolved. In severe cases, corticosteroids may be considered. It is important to monitor the patient closely during and after the infusion of vancomycin to ensure their safety and comfort.
Conclusion: Red Man Syndrome is a notable reaction associated with the administration of vancomycin, particularly when infused rapidly. Awareness of this syndrome and its management is crucial for healthcare providers to ensure patient safety during treatment.Patients with severe skin reactions, 5 individuals experienced hypotension and need to stop the infusion immediately. This is the most common hypersensitivity reaction to vancomycin, dose-dependent and related to rapid infusion rates when using high doses. Other risk factors include the concentration of the infusion solution (≥5 mg/ml), a history of Red Man Syndrome (RMS), and Caucasian ethnicity. RMS occurs in 5-50% of hospitalized patients receiving vancomycin and up to 90% in healthy volunteers. The incidence of RMS varies widely between studies, possibly due to differences in infusion rates, infusion solution concentrations, study design, subject characteristics, and concomitant medications. RMS has also been reported in patients receiving intravenous vancomycin and oral administration.
2. MANAGEMENT OF RED MAN SYNDROME ON FIRST USE
Management will be considered based on the severity and manifestations of the Red Man Syndrome that the patient experiences clinically.
| Severity – Manifestations | Management |
| Mild reaction (flushing but not uncomfortable. Symptoms resolve within a few minutes and do not require antihistamines) | Infuse at a rate of 1/2 the previous infusion rate |
| Moderate reaction (uncomfortable, flushing but stable blood pressure, no chest pain or muscle spasms) | Administer diphenhydramine* (50mg orally or intravenously) and Famotidine (20 mg IV)
Symptoms gradually decrease, infuse again at a rate of 1/2 the initial rate or 10mg/min (choose the slower rate) |
| Severe reaction (with muscle spasms, chest pain, or hypotension) | Stop vancomycin infusion
Administer diphenhydramine* (50mg IV) and famotidine (20 mg IV) Infuse fluids if hypotension occurs When symptoms decrease, re-infuse vancomycin within 4 hours or more. If subsequent doses are given, use antihistamines before each vancomycin infusion and infuse vancomycin over 4 hours, monitoring blood pressure during the infusion |
*Diphenhydramine: the drug at the hospital is commercially known as Dimedrol
3. PREVENTION OF RED MAN SYNDROME WHEN USING VANCOMYCIN
To minimize adverse reactions related to infusion, each dose of vancomycin should be infused over at least 60 minutes at a maximum rate of 10 mg/min and alternate infusion sites. To reduce the risk of RMS, a dose of 1g is generally recommended to be infused over 2 hours. According to a study, infusing vancomycin (1 g) over 2 hours significantly reduced the frequency, severity of RMS, and the amount of histamine released into the plasma compared to infusing over 1 hour. However, RMS has also been noted with slow infusion of vancomycin. Patients should be closely monitored, and vancomycin should be discontinued immediately if hypotension, chest pain, muscle pain, or any adverse events occur during the infusion.
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INSTRUCTIONS FOR DILUTING VANCOMYCIN INFUSION SOLUTION For a vial containing 500mg of vancomycin: – Reconstitute the lyophilized powder with 10ml of sterile water for injection. – Dilute with at least 100ml of solvent (0.9% NaCl or 5% glucose) to achieve a concentration of 2.5g/L to 5.0g/L and administer continuously for at least 60 minutes. For a vial containing 1g of vancomycin**: – Reconstitute the lyophilized vancomycin powder with 20ml of sterile water for injection. – Dilute with at least 200ml of solvent (0.9% NaCl or 5% glucose) to achieve a concentration of 2.5g/L to 5.0g/L and administer continuously for at least 100 minutes. Note: after reconstitution, it should be used immediately, can be stored at 2-8 degrees Celsius for 24 hours. |
**Vancomycin 1g: at the hospital, it is commercially known as Voxin 1g
References:
- National Center for Drug Information and Adverse Drug Reaction Monitoring, Vancomycin and Red Man Syndrome, http://magazine.canhgiacduoc.org.vn/Magazine/Details/144, accessed on 01/03/2024.
- Uptodate, Vancomycin hypersensitivity accessed on 01/03/2024.
