Both lidocaine and prilocaine are amide local anaesthetics with similar pharmacological properties, speed of onset and duration of action (EMLA SPC 2016). They are released from the topical anaesthetic cream into the epidermal and dermal layers of the skin near dermal pain receptors and nerve endings (EMLA SPC 2016). They work by blocking voltage-gated sodium channels, which prevents membrane depolarisation and so blocks nerve impulse transmission (David et al. 2014).
EMLA is a commonly-used brand of lidocaine/prilocaine cream. EMLA stands for Eutectic Mixture of Local Anaesthetics. A eutectic mixture is a combination of two ingredients that has a lower melting point than either alone (Martindale 2017). This property allows the preparation of a topical formulation from which the local anaesthetics can be better absorbed into the skin.
There are several creams available for human use containing 2.5% lidocaine and 2.5% prilocaine (or 25mg/g) with polyoxyethylene hydrogenated castor oil (Joint Formulary Committee 2017):
- Denela 5% cream (Teva UK Ltd.)
- EMLA 5% cream (Aspen Pharma Trading Ltd.)
- generic lidocaine 2.5% plus prilocaine 2.5% cream (manufacturers include: AM Distributions [Yorkshire] Ltd; Colorama Pharmaceuticals Ltd.; Ennogen Healthcare Ltd.; Niche Pharma Ltd.).
Therapeutic indications in human medicine include topical anaesthesia of:
- the skin during needle insertion (for example, intravenous catheters or blood sampling) and superficial surgical procedures (all ages)
- the genital mucosa (for example, before superficial surgical procedures or infiltration anaesthesia in people 12 years and over)
- leg ulcers during mechanical cleansing or debridement (in adults only) (EMLA SPC 2016).
In humans, the recommendations are that a thick layer of the cream should be applied to intact skin (for example, around 1.5g/10cm2 ) under an occlusive dressing (EMLA SPC 2016). The time needed to achieve reliable anaesthesia of intact skin is 1–2 hours, depending on the type of procedure (EMLA SPC 2016). Less time is needed for thinner skin. For example, maximum local anaesthesia occurs after 30–60 minutes on the face and after 15 minutes on male genitalia; for procedures on the genital mucosa no occlusive dressing is required (EMLA SPC 2016).
The BSAVA Small Animal Formulary states that lidocaine/prilocaine cream is very useful to facilitate venous catheter placement in small puppies and kittens. It recommends placing the cream on the skin for around 40 to 60 minutes before the procedure, and that covering the skin with an occlusive dressing promotes absorption (BSAVA 2017). For skin anaesthesia, Plumb’s Veterinary Drugs recommends applying thin layers of the cream every 3–4 hours as needed (Plumb’s 2017).
Trials showing a beneficial effect
- In a blinded non-randomised controlled study in laboratory animals (involving 24 dogs, 32 cats, 18 rabbits, 20 rats), applying lidocaine/prilocaine cream under a thin plastic wrap and an adhesive bandage for 60 minutes did result in a statistically significant reduction in pain compared with aqueous cream in the dogs, cats and rabbits (p<0.05) (Flecknell et al 1990). It enabled percutaneous insertion of catheters into the cephalic vein in dogs and cats and the marginal ear vein in rabbits with good anaesthesia. However, applying the cream to rats’ tails before percutaneous cannulation of the lateral tail vein did not produce a statistically significant reduction in the behavioural responses to venepuncture compared with the control group (p>0.1). In rats, the study’s authors considered that the stress caused by restraint for venepuncture appeared to outweigh any reactions to the needle puncture itself.
- A non-randomised controlled study compared lidocaine/prilocaine cream (with occlusion) with a cream containing 20% benzocaine, 6% lidocaine and 4% tetracaine, a cream of 0.5% proparacaine, and a control (petroleum jelly), on tactile sensitivity in the paws of newborn rats (16 in each group) (Strain et al 2014). It showed that touch thresholds statistically significantly increased after treatment with lidocaine/prilocaine cream compared with petroleum jelly (p=0.01). There were no statistically significant differences between the anaesthetic groups. The researchers concluded that lidocaine/prilocaine cream appears to be a slightly effective topical anaesthetic for reducing tactile sensitivity in newborn rats.
- A crossover study compared pain behaviours, and physiological and endocrine responses, in eight rabbits having pinnas tattooed with or without lidocaine/prilocaine cream (Keating et al 2012). A 1mm thick layer of the cream was applied to both the inner and outer surfaces of the ear and covered with an occlusive dressing for 15–20 minutes. Rabbits that did not have the local anaesthetic cream had statistically significantly greater struggling behaviour and vocalisation (p<0.001), greater facial expression scores of pain (p=0.004), higher peak heart rate (p=0.002), and higher systolic (p=0.001) and mean arterial blood pressure (p=0.004) than the rabbits with the cream.
Trials showing no effect or less effect than other methods
- A double-blind randomised controlled trial in 36 laboratory mice found that applying topical lidocaine/prilocaine cream had no effect on the aversive behaviours induced by lateral tail vein injection (David et al. 2014).
- In a randomised controlled trial, lidocaine/prilocaine cream was compared with intradermal infiltration of lidocaine 1% (with or without 1 in 100,000 adrenaline) for obtaining skin biopsy specimens from 25 dogs with skin disease (Henfrey et al. 1991). Results showed that lidocaine/prilocaine cream, applied and covered with an occlusive dressing for 60 minutes, provided moderate to good analgesia for biopsy of the skin in 75% of the dogs tested compared with good analgesia in 100% of the dogs having lidocaine infiltration (no statistical analysis included). The researchers concluded that their study showed that analgesia suitable for skin biopsy was not reliably produced with the lidocaine/prilocaine cream.
- A double-blind randomised placebo-controlled trial compared the effects of lidocaine/prilocaine cream with a placebo cream during placement of jugular venous catheters in 31 hospitalised cats (Wagner et al. 2006). The cream was applied to a 10cm2 area over the jugular vein and covered for 1 hour with an occlusive dressing. Struggling during catheter placement was not statistically significantly less in the lidocaine/prilocaine group than the group that received placebo cream (p=0.06), nor was aggression score (p=0.51), vocalisation score (p=0.98) or total discomfort score (p=0.31).
In humans, a burning sensation, itching, swelling, blanching, redness and warmth at the application site are common adverse reactions (that is, reported in 1–10%); irritation and application site paraesthesia (such as tingling) are uncommon (in 0.1–1%); and hypersensitivity, methaemoglobinaemia, purpura and petechiae are rare (in 0.01–0.1%) (EMLA SPC 2016). It has been suggested that methaemoglobinaemia is caused by a metabolite of lidocaine and prilocaine (Martindale 2017). The effect is more frequently seen (often in connection with overdose) in newborns and infants aged 0 to 12 months (EMLA SPC 2016). Methaemoglobinaemia is reported to be rare in animals (Plumb’s Veterinary Drugs). The likelihood may be increased if it is used in conjunction with methaemoglobin-inducing medicines (such as sulphonamides, nitrofurantoin, phenytoin and phenobarbital) (EMLA SPC 2016).
In a blinded non-randomised controlled study in nine rabbits (involving 36 incisions), histopathology showed that there were no adverse tissue or foreign body reactions in any of the lacerations treated with lidocaine/prilocaine cream (Al-Asfour et al 2008).
In another study, blanching of the skin was detected in six of 24 dogs treated with lidocaine/prilocaine cream, and histological examination of the skin revealed loss of surface keratin in two dogs with possible seborrhoea (Henfrey et al. 1991).
A pilot study in 10 healthy young adult cats assessed lidocaine/prilocaine cream applied in a thick layer to a 2cm by 5cm area of close-shaved skin over a jugular vein, and covered in an occlusive bandage for 1 hour (Gibbon et al. 2003). Jugular vein catheters were then inserted. There were no signs of redness, swelling, blanching or itching, gastrointestinal upset, neurological signs, cyanosis or distress in any of the cats.
Topical lidocaine may be absorbed systemically, but systemic toxicity (that is, effects on the central nervous and cardiovascular systems [EMLA SPC 2017]) is unlikely to occur in animals unless it is used on a significant percentage of body area, for prolonged times or at high concentrations (Plumb’s Veterinary Drugs). The maximum therapeutic dose of lidocaine in dogs is reported to be about 10mg/kg (Lemo et al. 2007).
Contact with eyes can cause irritation and should be avoided (Plumb’s Veterinary Drugs 2017; EMLA SPC 2017). Tests on laboratory animals have shown that lidocain/prilocaine cream has an ototoxic effect when instilled into the middle ear. Animals with an intact tympanic membrane show no abnormality when exposed to the cream in the external auditory canal (EMLA SPC 2017).
In a pharmacokinetic study, the absorption of lidocaine and prilocaine was rapid after application of cream to intact mouse skin, and statistically significantly increased when applied to lacerated skin. (Al-Musawi et al 2012) In theory, rapid absorption across diseased skin, broken skin or mucous membranes means onset time will be faster, but could also lead to more systemic absorption and tendency towards toxic levels. Extra vigilance is needed in patients also receiving Class-I antiarrhythmics (for example, lidocaine, mexiletine) (Plumb’s Veterinary Drugs 2017).
People frequently applying or removing the cream should ensure that contact is avoided to prevent hypersensitivity developing (EMLA SPC 2017).
Lidocaine 2.5% plus prilocaine 2.5% cream is not licensed in veterinary medicine. It should only be used in accordance with the veterinary prescribing cascade (VMD 2015).
There is a paucity of published evidence on the effects of lidocaine/prilocaine cream in small animals. The results of a few small studies suggest that it has some topical anaesthetic effect and might be useful during superficial skin procedures such as venous catheterisation and blood sampling in dogs, cats and rabbits. The cream does not appear to be useful for deeper skin procedures such as skin biopsies, or placing of jugular catheters in cats. Research also suggests that the cream needs to be applied for about an hour under occlusion to be effective, but less time may be adequate for thinner skin, such as on rabbits’ ears. More research is needed to assess the most effective doses, duration of application, and need or not for occlusion in different species.
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