Intrapyloric botulinum toxin injection as treatment for diabetic gastroparesis

Résumé fourni par la source

A 38-year-old man with a 25-year history of type 1 diabetes, complicated by peripheral neuropathy, retinopathy and end-stage renal failure (he had recently started haemodialysis) had been troubled by nausea, vomiting, loss of appetite and severe heartburn for the past three years. His symptoms had worsened in the past year and he had lost 17kg in weight and had had eight hospital admissions in the past year. His blood glucose was erratic. A gastroscopy was normal and radioisotope study confirmed delayed gastric empty-ing. Domperidone and amitriptyline were of no benefit. Erythromycin suspension was helpful but did not control his symptoms. Following intrapyloric botu-linum toxin injection (100 U Botox diluted in 10ml N/Saline injected as 4 x 20 U aliquots into four quadrants about 1–2cm proximal to the pyloric ring), his symptoms improved and he gained 7kg over eight weeks. His blood glucose went up requir-ing an increase in his insulin requirement. He reported that the treatment had dra-matically changed his life. His symptoms were controlled for about four months. He did not derive similar benefit from further intrapyloric Botox injections and he has now been referred for gastric pacing. Delayed gastric emptying is not uncommon in patients with diabetes but diabetic gastroparesis is a relatively rare complication. In gastroparesis, gastric emptying is severely delayed. The relation-ship between upper GI symptoms and the rate of gastric emptying is relatively weak.1 Symptomatic gastroparesis is often diffi-cult to manage. It may result in poor gly-caemic control, poor nutrition, and dehy-dration, which in turn may lead to poor quality of life and frequent hospitalisation. The goal of management is to control symptoms, ensure adequate hydration and nutrition, maintain adequate glucose control and improve gastric emptying. Small, low-fibre and low-fat meals are advised but this advice is largely anec-dotal. Liquid nutritional supplements may be needed. The number of therapies with proven efficacy is limited. The use of pro-kinetic drugs forms the mainstay of ther-apy. Erythromycin is more effectively given intravenously than orally, and has decreased efficacy with long-term use. Attempts should be made to maintain blood glucose levels close to the eugly-caemic range since it is known that hyperglycaemia slows gastric emptying. Elevated pyloric pressures may be responsible for delayed gastric emptying in patients with diabetes.2 Botulinum toxin inhibits the release of acetylcholine and produces transient paralysis when injected into smooth muscle. Thus, injection of botulinum toxin into the pylorus would produce transient paraly-sis of the pylorus, thereby accelerating gastric emptying and improving symp-toms of nausea and vomiting. In an open-label trial, Lacy et al.3 injected 200 U of botulinum toxin into the pylorus of eight patients with type 1 dia-betes and gastroparesis who had failed standard therapy. Four of the seven patients who completed the study noted an increase in insulin use of >5 U/day. Six patients gained weight and gastric emp-tying time improved in four patients. The largest published report on Botox use for gastroparesis is a retrospective series by Bromer et al.4 who reported that 27 out of 63 patients (43%) achieved a sympto-matic response. The mean duration of the response was five months. Recently, in a single-institution, randomised, double-blind, placebo-controlled trial 16 patients were randomised to intrapyloric botu-linum toxin and 16 patients to saline placebo.5 At one-month follow up, 37.5% randomised to botulinum toxin and 56.3% randomised to placebo achieved improvement. There were no identifiable clinical predictors of response. The botu-linum toxin group demonstrated improve-ment in gastric emptying. However, this was not superior to placebo. Thus, larger controlled trials are needed before this therapy can be widely recommended.6 The efficacy of botulinum injection tends to diminish with subsequent injec-tions. In patients who benefit from the treatment, pyloroplasty/gastrojejunos-tomy may be considered but a system-atic review of surgical therapy for gastro-paresis reported that surgical procedures intended to improve gastric emptying have generally not been successful in managing these patients.7 Gastric electrical stimulation has been found to benefit some patients with severe gastroparesis not responsive to standard therapy.8 However, it is very costly but it may prove cost-effective in patients with prolonged, recurrent hospi-tal admissions. It is only available in a few specialist centres in the UK. There are no conflicts of interest.

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