Randomized trial of novel tetracaine patch to provide local anaesthesia in neonates undergoing venepuncture.

BACKGROUND: Procedures such as venepuncture or heel prick are painful and may cause considerable stress to newborn infants. Topical local anaesthetics are effective for venepuncture but need to be applied for at least 60 min and the delivered dose will vary. We assessed a novel tetracaine-based self-adhesive patch in providing controlled local anaesthesia before venepuncture. METHODS: A placebo-controlled, double-blind trial was conducted using a tetracaine patch formulated from hydroxypropylcellulose discs (0.283 cm(2)) containing tetracaine (1 mg x cm(-2)) surrounded by a low tack pressure-sensitive adhesive backing layer. Thirty-two newborn infants of gestation 32-42 weeks (median 36 weeks), aged 3-18 days (median 6 days) were randomized to receive a tetracaine-containing patch or a placebo device applied to the dorsum of the hand 30 min before venepuncture to obtain blood samples. Pain was assessed in response to needle insertion using a validated adaptation of the neonatal facial coding score (NFCS) and the presence of crying. RESULTS: Of 15 tetracaine-treated neonates, 14 (93%) presented little or no pain in response to the procedure compared with six of 17 (35%) who had the placebo patch applied (P=0.01). CONCLUSIONS: The tetracaine patch produced effective pain relief during the venepuncture procedure in both term and pre-term infants. There were no adverse effects, either local or systemic.

Effect of percutaneous local anaesthetics on pain reduction during pulse dye laser treatment of portwine stains.

We have used EMLA, 4% amethocaine gel and placebo for facial portwine stains, for a period of 1 h, in a double-blind study. After removal of the preparations from the skin surface, each area was treated with six pulses of the laser, each 5 mm in diameter. Any pain noted immediately after treatment was recorded using both visual analogue (VAS) and verbal rating (VRS) scores. Twenty nine patients completed the study and statistical analysis of the results indicated that both EMLA and 4% amethocaine gel were superior to placebo (P < 0.001). However, when EMLA and 4% amethocaine gel were compared, the amethocaine preparation was significantly better (P < 0.05, VAS; P < 0.005 VRS) than EMLA in reducing pain caused by the laser treatment.

New patch delivery system for percutaneous local anaesthesia.

We have assessed the release of amethocaine from a new patch delivery system and subsequent drug diffusion through human stratum corneum and whole skin. We found that the patch system was more efficient than an amethocaine gel preparation. It was also observed, both in vitro and in vivo, that the stratum corneum acted as a reservoir for amethocaine. A double-blinded clinical trial, using 30- and 60-min application times, indicated that there was no statistical difference between patch and gel formulations in onset of percutaneous local anaesthesia. Furthermore, a 30-min application of the patch was sufficient to provide profound and prolonged topical anaesthesia in all volunteers. In contrast, although a 60-min application of EMLA was necessary to ensure satisfactory onset of percutaneous anaesthesia, the duration of action was much shorter than that of the amethocaine patch.

Local anaesthesia of the skin.

Local anaesthesia of intact skin is of growing importance given the increased use of minor surgical procedures on an out-patient basis. Specific pain receptors (nociceptors) are responsible for sensing cutaneous pain. Mechanisms of pain perception and the role of local anaesthetics in reversibly blocking nociception are considered. Effective routes of administration are dermal infiltration or, more recently, anaesthesia by topical application of specifically formulated preparations which promote percutaneous absorption of the drug (percutaneous local anaesthesia). Although many other topical anaesthetic products are also available these do not permit the anaesthetic to reach the nociceptors underlying the stratum corneum and are therefore only suitable for mucosal anaesthesia or for application to damaged skin. The chemical characteristics of local anaesthesia drugs are identified. Those agents suitable for cutaneous anaesthesia are reviewed with respect to potency, onset and duration of anaesthesia and possible systemic or local adverse reactions.

In vivo assessment of percutaneous local anaesthetic preparations.

This study has demonstrated greater efficacy of a new percutaneous amethocaine preparation relative to Eutectic Mixture of Local Anaesthetics (EMLA). Initially, a double-blinded trial was undertaken on each preparation individually against placebo, as the recommended method of application was different for EMLA (2.5 g applied for 60 min under an occlusive dressing) and the amethocaine formulation (0.5 g applied for 30 min). Thereafter, the two preparations were compared directly, in a double-blinded study using a standardized application for both formulations. The results indicated that both preparations provided significant (chi-square; P less than 0.001) percutaneous local anaesthesia when compared with placebo. The amethocaine preparation produced significant anaesthesia (chi-square, P less than 0.001) after 30 min application. Furthermore, the amethocaine formulation demonstrated both increased rapidity of action and increased duration of effect, as determined by a two-tailed unpaired t test, in comparison with EMLA when application times of both 30 and 60 min were used for each preparation. The results of this study indicate that the amethocaine preparation provided more rapid and prolonged anaesthesia than EMLA.

Concentration-response analysis of percutaneous local anaesthetic formulations.

The percutaneous absorption of amethocaine has been measured for different concentrations of the drug in three different formulations, A, B and C. Statistical analysis indicated that a concentration of 4% produced effective percutaneous local anaesthesia to pin-prick, together with an acceptable onset time of approximately 40 min. Increasing the concentration did not reduce the onset time further, although there was some increase in the duration of anaesthesia. Formulations A and B were hydrophilic, whereas C was an oil-in-water cream. Effective anaesthesia with formulation C required a higher drug concentration (12%), perhaps because of partitioning of the lipophilic anaesthetic into the lipid phase of the vehicle. The rate-limiting step was considered to be diffusion by the lipophilic anaesthetic through the stratum corneum, shown by onset of anaesthesia after removal of the formulation from the test site.

Comparative in vivo and in vitro assessment of the percutaneous absorption of local anaesthetics.

The percutaneous absorption of local anaesthetics in a standard formulation has been compared in vitro and in vivo. In vitro data were obtained with a modified Sartorius absorption system and silastic as a lipophilic barrier membrane. With this system the greatest steady-state flux values and permeability coefficients were obtained with amethocaine and lignocaine. These drugs also performed best in an in vivo volunteer trial. However, statistical analysis revealed that amethocaine was significantly better at producing full-depth anaesthesia to the challenge of insertion of a sterile needle. An optimized amethocaine formulation may therefore be expected to meet most closely the ideal profile for a percutaneous local anaesthetic preparation.