Lidocaine - topical

Additional information

The scientific literature indicates that pain behavior and pain perception may vary between men and women. This could be influenced by differences in pharmacokinetics, sex hormones, differences in stress response, or type of pain test. Also, many variables other than a person’s sex/gender account for individual differences in pain sensitivity. The prevalence of several clinical pain conditions is higher in women than in men, which suggests that either different clinical pain mechanisms may operate in men vs. women, or different or additional risk factors are relevant in one sex, or a combination of differences [1]. Therefore, sex differences of pain releasing medication might thus be difficult to interpret [2].

Pharmacokinetics and dosing

A study in 52 volunteers (20 men, 32 women) measuring S-lidocaine levels after a standardized application of 23% lidocaine/7% tetracaine compounded anesthetic to the face found higher concentrations in men and also in persons with greater facial surface and non-white ethnicity [14]. In contrast to this, a study in persons with mild to moderate asthma, the lidocaine concentration after local administration in the upper airways before bronchoscopy (21 men, 30 women) was similar in men and women [15].

Effects

Studies analyzing sex differences in reduced pain after topical lidocaine treatment (alone or in combination) report contradictory results.

A chart review of patients undergoing phacoemulsification (40 men, 84 women) found a reduction in fentanyl requirements with the addition of intracameral lidocaine to topical anesthesia during cataract surgery independent of patient’s sex [16].  A randomized study in patients being subjected to peripheral i.v. cannulation (149 men, 141 women) showed less patient discomfort, measured with a visual analogue scale (VAS), in both men and women after administration of 0.1 mL of intradermal 1% lidocaine [17].  There are two small studies showing sex differences in the groups treated with topical lidocaine but not in the placebo groups. One randomized study used an algometer to test pressure pain in healthy volunteers (23 men, 21 women) and found men but not women to experience less pain in the lidocaine but not in the placebo group [18]. Together with age above 40 years and lower anxiety level before procedure, male sex was found to be associated with lower estimated pain on the VAS scale over-all in a randomized double-blind placebo-controlled study of the effect of local lidocaine before gastroscopy (119 men, 79 women) [19].

 Lidocaine/prilocaine combination

Studies report conflicting results regarding sex differences in pain scores from EMLA.

In a randomized trial in children 6-12 years (13 boys, 18 girls), EMLA (2.5% each of lidocaine and prilocaine [3, 4]) treatment before dental dam placement was found to be more effective than placebo in both boys and girls regardless of age [5]. Another placebo controlled pediatric study on the effect of EMLA to reduce pain during intravenous catheter insertion (26 boys, 31 girls aged 4-12) found a positive effect, regardless of patient’s age or sex [6]. In children with cerebral palsy (31 boys, 19 girls) undergoing botulinum toxin injections,no significant correlations were found between the patient’s sex and the pain rating scale CHEOPS Max [7].

Topical anaesthesia with EMLA or placebo during cardiac biopsy after cardiac transplantation (50 men, 19 women) did not affect pain differently in men vs women [8]. In a double-blind, placebo-controlled clinical trial the effect on 2,5 g of EMLA administration to patients undergoing fine needle aspiration of the thyroid nodules was evaluated (44 men, 6 women). EMLA treated patients experienced less pain regardless of patient’s sex. Although the male group was small, women reported more pain overall [9]. Similarly, a double-blind placebo controlled, randomized, prospective study on the effect of EMLA before digital ring block for surgery for ingrown big toenail (42 men, 39 women) found no effect of EMLA treatment over all but less pain in men in the EMLA group [10].

The opposite was found in a study of the effect of EMLA before cryotherapy for Human papillomavirus (HPV) (20 men, 20 women) where men reported higher pain scores in the EMLA group [11]. Also, in a cross-over study (20 women, 20 men) women treated with EMLA had significantly lower VAS for pain in association with insertion of a 30G needle and injection of a local anaesthetic compared to men [12]. Women demonstrated lower pain scores with EMLA than men in a double-blind randomized study (40 men, 24 women) over a 6-month period on pain caused by hair removal with a Nd:YAG 1,064 nm laser [13].

Adverse effects

In the pharmacokinetic study mentioned above (20 men, 32 women) cutaneous side effects after a standardized application of 23% lidocaine/7% tetracaine compounded anesthetic to the face was also evaluated. No difference between men and women in reporting of side effects was found [14].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

In a randomized, blinded study comparing topical amethocaine with EMLA before Port-a-Cath procedures in children (27 boys, 12 girls aged 5-16) no difference between boys or girls were found in their own or their parents pain assessment. However, nurses estimated the pain to be worse for boys and younger children [20].