TOPLINE:

Patients with Ehlers-Danlos syndrome experienced reduced anesthetic effectiveness with subcutaneous lidocaine compared with healthy control individuals, with a lower proportion experiencing anesthesia at 15 and 30 minutes after injection.

METHODOLOGY:

• Researchers investigated the effectiveness of local anesthetic lidocaine in 91 patients with Ehlers-Danlos syndrome (median age, 34 years; 93% female) and 44 healthy control individuals (median age, 37 years; 80% female) recruited from an Ehlers-Danlos Society Global Learning Conference in Nashville, Tennessee, and the University of Calgary, Calgary, Alberta, Canada.
• Two standardized injection sites were located horizontally on the forearm. A control site was marked at least 1.5 inches distal to the antecubital fossa, and two testing sites were labeled at least 2 inches below the control site and 2 inches apart from each other.
• Participants received a subcutaneous injection of 0.5 mL of 2% lidocaine without epinephrine at one site and 0.5 mL of 0.9% saline at another site on the right forearm, with the assignment of agents to sites randomized and blinded to both participants and assessors. No injection occurred at the control site.
• Sensation testing was performed before injection and at 5, 15, and 30 minutes after injection using a standardized 10 g monofilament pressed three times at each site. Participants rated sensation at the test site vs the control site on a 0-3 scale (0 = no sensation; 1 = dull, non-sharp sensation; 2 = sharp sensation but less intense than at the control site; and 3 = sharp sensation equal to or more intense than at the control site).
• Ratings were converted to a delta sensation score to assess the incremental increase in the effectiveness of lidocaine vs saline; scores ranging from 0 to 3 indicated no anesthetic effect to full anesthetic effect, and negative scores indicated a greater anesthetic effect of saline than of lidocaine.

TAKEAWAY:

• The median delta sensation scores at 5 minutes and the proportion of participants experiencing anesthesia at 5 minutes did not differ between the Ehlers-Danlos syndrome and healthy control groups.
• However, delta sensation scores were lower in the Ehlers-Danlos syndrome group than in the healthy control group at 15 (P = .002) and 30 minutes (P = .003) after injection.
• Fewer patients with Ehlers-Danlos syndrome vs healthy individuals experienced adequate anesthesia at 15 (60% vs 84%; P = .006) and 30 minutes (53% vs 80%; P = .003).
• Among women, a smaller proportion in the Ehlers-Danlos syndrome group vs the healthy control achieved anesthesia at 15 (61% vs 94%; P < .001) and 30 minutes (52% vs 89%; P < .001); delta sensation scores were also lower at 15 (P = .001) and 30 minutes (P < .001). No such differences were observed among men.

IN PRACTICE:

The results offer “objective evidence that patients with EDS [Ehlers-Danlos syndrome] do experience a shorter duration of local anesthetic effect when using lidocaine, confirming the common anecdotal reports by patients with EDS. This study can help inform clinical choices in anesthesia for both healthcare providers and patients with EDS,” the researchers of the study reported.

SOURCE:

The study was led by Kate M. Bourne, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada. It was published online on March 3, 2026, in Regional Anesthesia & Pain Medicine.

LIMITATIONS:

Most participants had hypermobile Ehlers-Danlos syndrome, constraining inference to other subtypes. The study used lidocaine, which acts faster and has a shorter duration (0.5-2 hours), and responses to other local anesthetics might differ. Forearm subcutaneous injections do not mirror typical clinical procedures.

DISCLOSURES:

The study was supported by the Libin Cardiovascular Institute, the Canerector Foundation, and the National Center for Advancing Translational Sciences. One author was supported partially by a grant from the National Institutes of Health. Three authors reported consulting for therapeutic and pharmaceutical companies, and one of them reported receipt of funding.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.