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Erythromycin: prophylaxis against recurrent small bowel obstruction
  1. Emily Rea1 and
  2. Emma Husbands2
  1. 1Palliative Medicine, St Anne's Hospice, Newport, UK
  2. 2Department of Palliative Care, Gloucestershire Royal Hospital, Gloucester, UK
  1. Correspondence to: Dr Emily Rea, Palliative Medicine, St Anne's Hospice, Harding Avenue, Malpas, Newport NP20 6ZE, UK; elbrooke{at}doctors.org.uk

Abstract

We describe three cases where erythromycin suspension has been used successfully in preventing recurrence of small bowel obstruction in patients with terminal illness and for whom it proved more effective than standard preparations such as metoclopramide and domperidone. These patients also experienced a longer term benefit over some months. With recent alerts over longer term use of metoclopramide and domperidone, we demonstrate that erythromycin is a viable alternative prokinetic in patients with terminal illness at risk of small bowel obstruction instead of or alongside metoclopramide and domperidone. More research is required to establish the point at which erythromycin should be considered in the management of symptoms. In addition, research into the possibility of a viable alternative to erythromycin is needed.

  • Drug administration
  • Supportive care

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Background

Nausea and vomiting secondary to small bowel obstruction is a commonly seen presentation in palliative medicine and is distressing for those experiencing it. Use of erythromycin as a prokinetic agent is widely recognised. Erythromycin has been recommended as treatment for constipation and in a number of conditions including diabetic gastroparesis, myotonic dystrophy, critical care patients receiving nutritional support, following surgery, and in the management of pseudo-obstruction. A recent case report discussed the use of erythromycin in the management of refractory nausea and vomiting secondary to paraneoplastic gastroparesis.1 Here the authors report the successful use of initially intravenous, and then oral erythromycin, alongside temporary insertion of a nasogastric tube. The patients nausea and vomiting have completely resolved.

Case descriptions

Here are three cases where erythromycin was used with good effect in terminally-ill patients to manage and reduce recurrence of small bowel obstruction.

Case 1

A woman in her 60s with ovarian cancer had received carboplatin chemotherapy followed by debulking surgery and then further carboplatin chemotherapy. During her treatment, she was admitted on three occasions with subacute bowel obstruction, managed conservatively each time. She presented a fourth time with a recurrence of her small bowel obstruction 9 weeks after formation of a defunctioning loop colostomy. A CT scan showed widespread disease throughout her omentum. She was started on dexamethasone (8 mg subcutaneously) and metoclopramide (80 mg subcutaneously via syringe driver). Her stoma functioned periodically but a nasogastric tube was still necessary to prevent her from vomiting.

At this point erythromycin suspension 250 mg two times per day orally was started. Her stoma function improved, and nasogastric aspirate decreased. Two weeks later the nasogastric tube was removed, and the patient was able to manage fluids and soft diet. On the two occasions when the erythromycin was stopped in order to reduce the burden of medication that she was taking her symptoms reoccurred within 24 hours. Metoclopramide was stopped without ill-effect, and she continued to take erythromycin until shortly before she died from global effects of disease progression 3 months later.

Case 2

A woman in her 40s with metastatic ovarian cancer had been treated with a hysterectomy and omentectomy at her initial presentation 16 years earlier. She received chemotherapy when her disease reoccurred but then presented with severe abdominal pain occurring intermittently associated with feelings of fullness. Her pain seemed to be triggered by eating and so consequently she skipped meals to avoid this. Imaging showed extensive peritoneal disease with adhesions. She was taking metoclopramide 20 mg three times daily as well as laxatives. Functionally in between episodes of pain her performance status was one.

A trial of erythromycin suspension 250 mg two times per day orally was started, and the patient's pain and feelings of fullness completely disappeared. Subsequently the metoclopramide and laxatives were stopped without any complications. She continued on erythromycin for 16 months when the dose was increased to 250 mg four times a day as some mild discomfort reoccurred. The increased dose was continued with benefit for a further 2 months until shortly before her death from disease progression.

Case 3

A man in his 60s with rectal cancer was treated with chemotherapy and an anterior resection. He then developed lung and retroperitoneal metastases and was given further chemotherapy. He started to experience recurrent episodes of colicky abdominal pain, associated with constipation and bloating, on a weekly basis. At the point of referral to specialist palliative care, he had already tried metoclopramide with regular laxatives but with little change in his symptoms.

Erythromycin oral suspension was introduced at 250 mg two times per day with a good result. His symptoms resolved, and this continued for 7 months with him reporting a marked improvement in his quality of life. After 7 months his symptoms began to worsen again, and a CT scan showed a marked progression of his disease and a complete revision of his medications was then required during the terminal phase where efforts to promote prokinesis were abandoned prior to his death.

Discussion

Erythromycin was effective in managing and preventing further small bowel obstruction in the three cases described where other treatments, such as metoclopramide and laxatives, had been only partially beneficial. A recent alert from the Medicines and Healthcare products Regulatory Agency (MHRA) has raised concerns about metoclopramide and neurological side effects such as extrapyramidal disorders and tardive dyskinesia.2 Erythromycin does not cause these neurological side effects and additionally seems to be more effective than metoclopramide in stimulating gastric emptying. It has also been found to be more effective than domperidone and cisapride.3 It comes in a suspension form and is potentially only administered twice a day unlike domperidone and metoclopramide. In two of the cases described, there also appeared to be enough laxative effect from the erythromycin to allow standard ‘laxatives’ to be stopped, reducing medication burden.

As with any medication long-term use must be carefully considered. The main concerns with long-term use of erythromycin are development of antibiotic resistance to bacteria, prolongation of the QT interval and consequently sudden cardiac death and tachyphylaxis (reduced efficacy of the erythromycin). Given the limited life expectancy of our patient population, the long-term risk of bacterial resistance seems to be outweighed by the benefit in symptom control. The population is small but observation of the long-term effects would be important.

Erythromycin can cause prolonged QT syndrome, particularly in those patients who are also taking a CYP3A4 inhibitor such as clarithromycin.4 The risk of causing a prolonged QT syndrome, potentially resulting in death, must be seriously considered. The risk can be reduced by avoiding prescribing erythromycin alongside CYP3A4 inhibitors. Unfortunately prolongation of the QT interval does not seem to be dose dependent so although in our patients we have used less than maximum dose of erythromycin the risk of prolonged QT remains. The benefits of ongoing erythromycin use should be balanced against the risks to the individual patient.

There is a suggestion that tolerance to erythromycin may occur over time with associated reduction in efficacy, known as tachyphylaxis. Anecdotal evidence is that this does not always occur, and many palliative patients have remained on the drug for several months or more without loss of efficacy. In our second case, the dose of erythromycin was increased from 250 mg two times per day to four times daily after the patient had been on the drug for 16 months. The increased dose continued to be effective up until her death a further 2 months later.

The financial cost of erythromycin suspension seems small compared to the cost of repeated admissions to hospital, investigations and interventions for small bowel obstruction. Not to mention the emotional and psychological costs to the patient which are more difficult to quantify.

Conclusion

Erythromycin can be used as an alternative to or alongside metoclopramide and domperidone in the management of recurrent small bowel obstruction. The consequences of long-term use will need further study. Azithromycin has been suggested as an alternative to erythromycin for use as a prokinetic. It has a longer half-life and fewer side effects although currently there is limited evidence to support its use this way.5 Further work over its role in comparison with erythromycin would be of value.

References

Footnotes

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.