Colchicine for Constipation

Postoperative pain relief in the setting of total hip or knee arthroplasty (replacement) has two essential purposes; first, as an act of compassion towards the suffering patient and second, to allow for accelerated postoperative physiotherapy. The former attribute results in an improvement in the patient’s overall quality of life during their hospital stay. The second benefit of postoperative analgesia is a swifter return to full utility of the replaced joint and a reduced length of stay in hospital. Importantly, medication-assisted early postoperative mobility reduces the frequency of a deep vein thrombosis 30 fold. Early mobilisation is defined as “starting to walk within 24 hours after surgery.”

Opioids are the mainstay of postoperative analgesia. While highly effective, they also cause opioid-induced constipation (OIC) in 40% to 95% of patients. The underlying cause of OIC is opioid binding to the μ-receptors in the enteric system. To reduce the incidence of OIC, opioid analgesics may be administered with an opioid antagonist such as naloxone. Naloxone moderates the constipating effects of opioids by acting as a competitive antagonist at opioid receptors in the gastrointestinal system. It does not diminish the analgesic effect of co-administered opioids due to poor oral bioavailability. Targin® is a medication that combines naloxone with the opioid analgesic oxycodone for the management of chronic pain.

Other medications commonly utilised include docusate + sennoside B 50mg + 8mg (two tablets taken once or twice daily), macrogol 3350 sachets (one to three sachets daily), Senokot with Agarol “milkshakes,” and bisacodyl tablets (two tablets at night), suppositories, and enemas. However, the use of aperients to alleviate OIC can cause diarrhoea in up to 38% of patients. Non-drug treatments such as increasing dietary fibre, fluids, and physical activity are unlikely to provide relief from OIC.

A patient at Campbelltown Private Hospital, who was in rehabilitation following a total knee replacement, alerted me to the benefits of colchicine as an effective alternative for patients with a history of treatment-resistant constipation. He had been prescribed this therapy by his gastroenterologist. Diarrhoea is a common side effect of colchicine therapy. While OIC is not an approved indication for colchicine, this is an interesting therapeutic use of what is normally a troublesome side effect.

Sandyk et al. (1984) reported that a dose of 0.3-0.6mg daily was beneficial in three patients with refractory constipation in Parkinson’s disease.

Verne and colleagues (1997) trialled colchicine 0.6mg three times daily for eight weeks in an open-label pilot study for patients with constipation refractory to medical treatment (n=7). Spontaneous bowel movements increased significantly from 1.7 +/- 0.5 per week when treated with laxatives and enemas to 6.4 +/- 0.7 per week while taking colchicine. Importantly “symptoms of abdominal pain, nausea, and bloating significantly (P < 0.05) improved during therapy with colchicine.”

A further study by Verne et al. (2003) assessed colchicine use in 16 patients with chronic idiopathic constipation refractory to standard medical therapies. Patients randomly received either colchicine 0.6 mg three times daily or an identical placebo three times daily for four weeks in a double-blind, crossover study. Mean colonic transit was calculated at baseline, week six, and week twelve. Colchicine increased the number of bowel movements and accelerated colonic transit time compared to baseline and placebo. Abdominal pain in the colchicine group was greater than that seen at baseline or with placebo use. However, the pain decreased significantly by week four.

A more recent double-blind placebo-controlled trial conducted by Taghavi and co-workers (2010) investigated the use of colchicine in patients with refractory slow transit constipation. The 60 participants were allocated to either colchicine 1mg four times daily or placebo for two months. The validated KESS (Knowles Eccersley Scott Symptoms) score, used to assist in the diagnosis and evaluation of the symptoms of constipation, was applied to the case and control groups. A significant benefit (p=0.0001) in favour of colchicine to treat refractory constipation was reported.
The results of these trials suggest that colchicine may be underutilised in the orthopaedic rehabilitation setting for patients with OIC. A clinical trial to further test the validity of these earlier studies is justified.Save

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