A proof-of-concept assessment in healthy volunteers of stimulated skin wrinkling to determine the presence or absence of digital nerve blockade

Abstract

To the Editor, Skin wrinkling of the palms and digits after exposure to water is a familiar human experience caused by a rather complex physiologic process. Water entering sweat pores is thought to create an electrolyte imbalance across the membranes of the dense network of sympathetic neurons, increasing their firing and causing the vasoconstriction of vascular structures called glomus bodies. The reduced pulp volume causes wrinkling of the overlying epidermis. Stimulated skin wrinkling (SSW) has been utilized to assess the function of the sympathetic nervous system in a wide variety of pathologic states for over 85 years and was reviewed most recently in 2015. Eutectic mixture of local anesthetic (EMLA; lidocaine 2.5% and prilocaine 2.5%) cream has been shown to be equivalent to a circulating warm water bath as a standardized wrinkling agent and is more clinically practical. Because SSW has been shown to be a reliable test of sympathetic nerve function in disease states, we considered the possibility that it could be utilized specifically to assess the success of regional nerve blockade. We conducted a proof-of-concept study to examine if blinded observers could differentiate the presence or absence of a digital nerve block in healthy volunteers by assessing photographs of skin-wrinkling taken during the use of the SSW test with EMLA cream. Following approval from the Newfoundland and Labrador Health Research Ethics Authority (HREB # 2018.207) and registration at ClinicalTrials.gov (NCT03873896), we recruited four healthy volunteers (three males and one female aged [mean (standard deviation)] 29.5 (1.5) yr, all Caucasian). We performed a digital nerve block on a randomly chosen hand with sterile technique using 3 mL of lidocaine 2% and a two-injection dorsal approach. Baseline photographs were taken (time zero) and then 1 mL of EMLA cream was applied to the ventral aspect of both ring fingers and covered by an occlusive dressing. Both were removed before photos were taken of the blocked and contralateral unblocked digits at ten, 20, and 30 min from baseline (Figure). Two blinded observers independently scored these randomized photos and ranked the extent of wrinkling using a validated fivepoint ordinal scale. The inter-rater reliability of the observers’ assessments for wrinkling was assessed using Cohen’s linearly weighted kappa. There was moderate agreement between the observers (j = 0.614; 95% confidence interval, 0.465 to 0.763; P \\ 0.001). The ordinal scores were dichotomized into ‘‘no significant wrinkling’’ (wrinkling assessment score, \\ 3) and ‘‘significant wrinkling’’ (wrinkling assessment score, 3 or 4) and analyzed using Fisher’s exact test to examine the difference between observers’ assessments of ‘‘significant wrinkling’’ (unblocked) vs ‘‘no significant wrinkling’’ (blocked) for all time intervals. The results showed that observers identified significant differences in wrinkling following the application of the EMLA cream between blocked and unblocked digits at all time intervals. At ten minutes, 13/16 images were identified correctly (81% accuracy; P = 0.026); at 20 and 30 min, 14/16 images were identified correctly (88% accuracy; P = 0.01), respectively. When combining all observations from both observers over all time intervals, a total of 41/48 images were correctly identified (85% accuracy; P\\ 0.001). This proof-of-concept study showed that blinded observers were able to identify the presence/absence of a P. A. W. Collins, MD, FRCPC (&) R. M. DiDonato, PhD K. Thomson, MD M. Brazil, MD, FRCPC Memorial University of Newfoundland, St. John’s, NL, Canada e-mail: [email protected]; [email protected]