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Systematic review of pharmacological therapies for the management of ischaemic pain in patients with non-reconstructable critical limb ischaemia

Laoire, Áine Ní; Murtagh, Fliss E.M.


Áine Ní Laoire



Background Critical limb ischaemia (CLI) is a severe manifestation of peripheral arterial disease, characterised by chronic ischaemic rest pain, ulcers or gangrene. Management of ischaemic pain is challenging in patients with no options for revascularisation and optimal pharmacological therapies have not been established.

Objectives To identify and evaluate the effectiveness of pharmacological therapies to treat ischaemic pain secondary to non-reconstructable CLI.

Methods This systematic review was reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Comprehensive searches of three electronic databases, a PubMed-related articles link search, grey literature search and hand-searches of the bibliographies of relevant papers and textbooks were performed. Studies recruiting adult patients with CLI of any aetiology were eligible for inclusion. Surgical and revascularisation procedures, and all invasive interventions were excluded.

Results Of 792 studies, six met full inclusion criteria. These studies researched the use of intravenous lidocaine, intravenous ketamine, oral gabapentin and the combination of transdermal buprenorphine and epidural morphine/ropivacaine infusion. All studies showed an improvement in severity of ischaemic pain in CLI but with varying side effect profiles and quality. The extracted studies showed substantial heterogeneity and therefore a meta-analysis was not performed.

Conclusion The pharmacological management of pain secondary to non-reconstructable CLI is a challenging review topic. No recommendations of pharmacological agents can be made following this review but a number of novel approaches to manage pain in this cohort have shown positive results and require further investigation.


Laoire, Á. N., & Murtagh, F. E. (2018). Systematic review of pharmacological therapies for the management of ischaemic pain in patients with non-reconstructable critical limb ischaemia. BMJ supportive & palliative care, 8(4), 400-410.

Journal Article Type Article
Acceptance Date Jul 19, 2017
Online Publication Date Aug 23, 2017
Publication Date 2018-12
Deposit Date Aug 23, 2018
Publicly Available Date Aug 23, 2018
Journal BMJ Supportive & Palliative Care
Print ISSN 2045-435X
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Issue 4
Pages 400-410
Public URL
Publisher URL
Contract Date Aug 23, 2018


Article (363 Kb)

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© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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