Infracoccygeal Botox for Dyssynergia
Condition: Dyssynergic Defaecation; Evacuation Disorder; Anismus; Defecation Disorder
Study type: Observational

Summary: 
      Background:

      Constipation is a common problem, affecting up to 20% of the population during their
      lifetime. Some patients respond poorly to standard treatments such as laxatives. A subgroup
      of these have dyssynergic defaecation where the muscles that control bowel movements fail to
      relax during pushing, preventing evacuation of stools. Currently, the mainstay of treatment
      requires muscle retraining by a therapist using a technique called biofeedback. Patients in
      whom biofeedback has failed are left with few options, one of which includes Botox injection
      into the pelvic floor muscles involved in the defaecation process. However, current method of
      injection is inaccurate and often requires anaesthesia. The investigators propose a novel
      technique for Botox delivery which reduces the risks and associated costs.

      Objectives:

        1. The primary objective is to demonstrate technical feasibility of percutaneous
           infracoccygeal Botox injection as an alternative to transanal puborectalis muscle
           injection for the treatment of dyssynergic defaecation.

        2. The secondary objectives are to assess the safety and acceptability of this technique,
           and to derive pilot clinical effectiveness data to inform future studies.

      Methods:

      The investigators will carry out Botox injection into the puborectalis muscle under
      ultrasound guidance in the outpatient department. This will be done by percutaneous injection
      below the coccyx where the puborectalis has been demonstrated to be easily accessible. An
      electromyography of the puborectalis is obtained before the injection to demonstrate proof of
      mechanism. The investigators will collect data using a combination of questionnaires, patient
      baseline data, and anorectal physiology test results before and after the treatment.

      Outcomes:

        -  Feasibility: procedure duration, rate of identification of puborectalis by ultrasound
           scan and pre-injection EMG, procedure limitations, and successful injection rate

        -  Safety: rate of adverse events

        -  Acceptability: patient pain and comfort, willingness to undergo repeat procedure

        -  Preliminary data on effectiveness: Cleveland Clinic constipation score, anorectal
           physiology test results
    

Detailed description: 
      Patients with dyssynergic defaecation represent a subgroup of a larger group of patients
      presenting with symptoms of chronic constipation. The disorder is characterised by impaired
      stool expulsion as a result of inappropriate contraction of the pelvic floor musculation
      despite normal propulsive force during attempted defaecation. Failure of the puborectalis
      and/or anal sphincter muscles to relax during evacuation leads to a closed anal canal which
      prevents the emptying of stools.

      A Cochrane review in 2014 on the treatment of chronic constipation in adults demonstrated a
      high prevalence of dyssynergic defaecation and a variety of treatments. In this group,
      biofeedback was found to be superior to oral diazepam, sham treatment, and laxatives; while
      surgical procedures such as partial division of the puborectalis muscle were more
      efficacious, the risks of adverse reaction, namely incontinence, were high. Thus, biofeedback
      therapy is the current gold-standard for the treatment of dyssynergia. The success rate of
      biofeedback in correcting or improving the symptoms in patients with dyssynergia varies
      between 33% and 80%. Difficulty arises in those in whom biofeedback is unsuccessful, as there
      is little, and conflicting, low quality evidence on alternative therapies.

      One further therapeutic option uses injection of Botulinum toxin type A (BTXA) into the
      puborectalis and/or external anal sphincter muscles. This is currently the second-line
      treatment for dyssynergic defaecation in whom biofeedback has failed. A systematic review in
      2016 on the use of BTXA in patients with 'anismus', a term previously used to describe
      dyssynergic defaecation, demonstrated initial clinical improvement in symptoms in 77.4% of
      patients. Two of the seven studies were conducted on participants in whom biofeedback therapy
      had failed. Complications were reported in 7.4% of patients (0 to 22.6%) and included faecal
      incontinence, which was minor and transient, posterior anal fissure, and rectal prolapse. The
      effect of BTXA was not permanent, with clinical improvement declining to 46% at four months
      after the injection. For this reason, several studies offered repeated treatments.

      The delivery of BTXA injection varied between studies and institutions in terms of dosage and
      position of injection, but all were performed via perianal or transanal approaches, often
      requiring sedation or anaesthesia. There are several disadvantages of this approach including
      cost (operating theatre utilisation) and risks associated with anaesthesia and infection from
      passing the needle through a contaminated operative field. In addition, the injection site is
      defined blind by the surgeon's finger (an issue of accuracy of injection and hazard of needle
      stick injury).

      The proposed study aims to demonstrate the technical feasibility of an alternative approach
      to delivering BTXA injection in adult patients with dyssynergic defaecation. This novel
      technique injects BTXA into the puborectalis muscle percutaneously using an infracoccygeal
      approach under ultrasound guidance. This allows the procedure to be performed in an
      outpatient radiology setting without the need for any form of anaesthesia or analgesia. The
      injection is performed in a clean operative field away from the anus, minimising risk of
      infection and the muscle can be clearly visualised (see below). These advantages will be
      particularly valuable in patients who require repeated procedures or those with multiple
      co-morbidities at high anaesthetic risk.

      The utilisation of BTXA in human is well established. This medication is licensed for use in
      focal spasticity with well-established side-effects and interactions. Current evidence for
      the use of BTXA in dyssynergic defaecation is based on the conventional transanal approach,
      with report on efficacy and complications as previously stated.

      The puborectalis is easily accessible below the coccyx, and is the site for ultrasonic
      assessment in the paediatric population. The identification of puborectalis muscle in the
      infracoccygeal position has not been described in the literature in the adult population.
      However, pilot imaging studies on a small number of non-obese subjects have been successful
      in easily identifying the puborectalis using ultrasound scan. This approach has the potential
      to allow accurate administration of BTXA injection under ultrasonic guidance in the
      outpatient setting without the need for anaesthesia or operating theatre utilisation. The
      general aim of this study is to demonstrate that percutaneous infracoccygeal BTXA injection
      is a valid alternative approach to transanal injection for the treatment of dyssynergic
      defaecation. Specifically, the investigators will determine technical feasibility (including
      pilot proof of mechanism), patient acceptability, safety, and pilot efficacy outcomes for a
      future definitive trial.
    

Intervention name(s): Percutaneous infracoccygeal Botulinum toxin injection to puborectalis
Intervention type(s): Procedure
Intervention description(s): The intervention is an injection of 200 units of Botulinum toxin type A in to the puborectalis muscle under ultrasound guidance.
In the prone position, the puborectalis muscle will be identified below the coccyx using ultrasound. After skin preparation using 70% Isopropyl Alcohol Pad, and up to 5ml of local anaesthetic (1% lidocaine), an electromyography (EMG) needle will be inserted and the puborectalis muscle stimulated using a current to confirm correct needle position. 200 units of BTXA (Botox, Allergan, Ireland) prepared in 2 ml of saline solution and drawn up using a 2ml syringe. 1ml (100 units) of BTXA solution is injected through the EMG needle into the puborectalis muscle to each side of the midline, achieving a total of 200 units. The needle is withdrawn, and the procedure is complete.
Intervention MeSH terms: Botulinum Toxins
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adult patients diagnosed with dyssynergic defaecation using Rome IV criteria
      
Keywords: Botulinum toxin type A; Botox