Instillagel, lipid rescue and the Medicines and Healthcare products Regulatory Agency

Abstract

Lipid rescue for the treatment of local anaesthetic toxicity is becoming increasingly recognised. The first published case reports of its use in humans appeared in 2006, and by December 2007, more than 80% of hospitals surveyed had adopted lipid rescue [1]. Instillagel® (Farco-Pharma, Koln, Germany) is a 2% lidocaine gel, commonly used to aid catheterisation. It comes in both 6-ml (120 mg) and 11-ml (220 mg) prefilled syringes. The maximum advised lidocaine dosage for injection is 200 mg, or 500 mg for adrenaline-containing solutions [2]. Regarding topical application, the product information states that for doses of up to 800 mg (equates to 40 ml) instilled in the urethra, blood concentration remains in the low range and below toxic levels [3]. Traumatic catheterisation can increase absorption. The manufacturer states that Instillagel should not be used in patients with damaged or bleeding mucous membranes because of the risk of systemic absorption [3]. During difficult urethral catheterisation, trauma may occur and several doses of Instillagel may have been used, running the risk of systemic toxicity. Anecdotal evidence suggests this has resulted in cardiac arrest. The product guidelines for overdose recommend ‘arresting the convulsions and ensuring adequate ventilation with oxygen’ [3]. However, lipid rescue, which is recommended by the UK Resuscitation Council in suspected local anaesthetic toxicity and induced cardiac arrest, is not mentioned [4]. One distributor for Instillagel recommends suxamethonium for local anaesthetic-induced convulsions [5]. We asked the UK Instillagel distributor, CliniMed (CliniMed Ltd., High Wycombe, Bucks., UK) why lipid rescue was not mentioned. They contacted their manufacturers, Farco-Pharma, and they informed us that any amendments to the summary of product characteristics were made following advice from the Medicines and Healthcare products Regulatory Agency (MHRA). We then contacted the MHRA, which told us that lipid rescue was an interesting new treatment strategy but one that should still be regarded as experimental. They felt that the use of lipid emulsions in this way is ‘off-label’, and the MHRA would not expect distributors to include lipid therapy in the summary of product characteristics. We would suggest that many practitioners are not fully aware of the risks associated with Instillagel, seeing it more as a lubricant than as a local anaesthetic. The MHRA does not feel that manufacturers of any local anaesthetic containing products need to update their product characteristic advice to include lipid rescue in treatment of overdose. We believe that this should now be amended. No external funding and no competing interests declared.