Can skin testing be performed for allergy to rocuronium and sugammadex?

Skin Testing for Rocuronium and Sugammadex Allergy

Yes, skin testing can and should be performed for both rocuronium and sugammadex when anaphylaxis to either agent is suspected, using established non-irritant concentrations and proper technique by trained personnel.

Rocuronium Skin Testing

Skin testing for rocuronium is well-established and recommended. If anaphylaxis to a neuromuscular blocking agent (NMBA) like rocuronium is suspected, the patient should undergo skin prick testing with all NMBAs in current use 1. The guidelines are clear that:

• Skin tests are most useful for NMBAs including rocuronium 1
• Both skin prick tests (SPT) and intradermal tests (IDT) should be performed
• Testing should occur as soon as the patient has fully recovered clinically and antihistamine effects have worn off 1

Validated Concentrations for Rocuronium

Recent research has established specific non-irritant concentrations 2:

• SPT: Undiluted stock concentration is non-irritant
• IDT: Maximum non-irritant concentration is 0.05 mg/mL

These concentrations were validated in 187 participants with 78% being NMBA-tolerant, providing robust safety data.

Sugammadex Skin Testing

Skin testing for sugammadex is feasible and clinically relevant, though less extensively studied than NMBA testing. The evidence demonstrates:

• Sugammadex can cause IgE-mediated anaphylaxis 3, 4, 5
• Intradermal testing has successfully identified sugammadex as the causative agent in confirmed anaphylaxis cases 5
• Positive skin responses have been documented at 1:100 and 1:1000 dilutions of the standard 100 mg/mL solution 5

Validated Concentrations for Sugammadex

The 2023 study established 2:

• SPT: Undiluted stock concentration is non-irritant
• IDT: Maximum non-irritant concentration is 50 mg/mL

Critical Consideration: The Sugammadex-Rocuronium Complex

A unique and clinically important finding is that the sugammadex-rocuronium inclusion complex itself can be allergenic, separate from either agent alone 6. This means:

• Patients may test negative to both sugammadex and rocuronium individually but positive to the premixed complex 6
• When testing patients with suspected reactions after sugammadex administration for rocuronium reversal, test the complex in addition to individual agents 5, 6
• The recommended ratio for complex testing is sugammadex 7.14 mg/mL + rocuronium 2 mg/mL 2

Interestingly, some research suggests the complex may actually attenuate skin reactions in certain patients 5, 7, adding complexity to interpretation.

Testing Protocol

Timing

• Perform testing as soon as possible after clinical recovery 1
• Discontinue antihistamines several days before testing
• No need to stop corticosteroids 1

Technique

1. Start with skin prick testing using undiluted concentrations 2
2. Proceed to intradermal testing if SPT is negative, using validated dilutions 1
3. Include testing of the sugammadex-rocuronium complex if the reaction occurred after sugammadex reversal 5, 6
4. Use histamine as positive control and saline as negative control 1
5. Read results at 15-20 minutes for SPT and 20-30 minutes for IDT 1

Interpretation Caveats

Important limitations to recognize:

• A negative skin test does not guarantee that anaphylaxis will not occur with future exposure 1
• Skin tests must be interpreted within the clinical context 1
• Cross-sensitivity between NMBAs is common due to shared quaternary ammonium epitopes 1
• Testing must be performed by suitably trained and experienced personnel 1

Clinical Implications

If skin testing is positive to rocuronium:

• Warn the patient against future exposure to all NMBAs if possible due to cross-reactivity 1
• If an NMBA is mandatory for future anesthesia, use one with a negative skin test, acknowledging residual risk 1

If skin testing is positive to sugammadex:

• Avoid sugammadex for future rocuronium reversal
• Consider alternative reversal strategies (neostigmine for non-steroidal NMBAs, or spontaneous recovery)

The evidence strongly supports skin testing for both agents, with established protocols and validated concentrations now available for safe clinical use.