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<meta name="robots" content="NOINDEX,NOFOLLOW,NOARCHIVE,NOIMAGEINDEX" /><meta name="citation_inbook_title" content="Lower Limb Peripheral Arterial Disease: Diagnosis and Management [Internet]" /><meta name="citation_title" content="Management of ischaemic pain in critical limb ischaemia" /><meta name="citation_publisher" content="Royal College of Physicians (UK)" /><meta name="citation_date" content="2012/08" /><meta name="citation_author" content="National Clinical Guideline Centre (UK)" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK327432/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Management of ischaemic pain in critical limb ischaemia" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="Royal College of Physicians (UK)" /><meta name="DC.Contributor" content="National Clinical Guideline Centre (UK)" /><meta name="DC.Date" content="2012/08" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK327432/" /><meta name="DC.Language" content="en" /><meta name="description" content="Critical limb ischaemia (CLI) is characterised by persistent and severe ischaemic rest pain associated with poor tissue perfusion, tissue loss and ulceration. 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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>National Clinical Guideline Centre (UK). Lower Limb Peripheral Arterial Disease: Diagnosis and Management [Internet]. London: Royal College of Physicians (UK); 2012 Aug. (NICE Clinical Guidelines, No. 147.)</p></div><div class="bk_msg_box bk_bttm_mrgn clearfix bk_noprnt"><div class="iconblock clearfix"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/nicecg147guid/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-nicecg147guid-lrg.png" alt="Cover" height="100px" width="80px" /></a><div class="icnblk_cntnt"><ul class="messages"><li class="info icon"><span class="icon"><a href="/books/n/nicecg147guid/">See 2020 Partial Update</a></span></li></ul></div></div></div><div class="messagearea bk_noprnt" style="margin-bottom:1.3846em "><ul class="messages"><li class="warn icon"><span class="icon">Update information: This guideline was updated by a NICE standing committee in February 2018 and 2 new recommendations were added on diagnosing peripheral arterial disease in people with diabetes. The recommendations are in section 1.3 of the guidance. The evidence for these recommendations is in evidence reviews A: determining the diagnosis and severity of peripheral arterial disease in people with diabetes. December 2020: NICE added links in the recommendation on pain relief to other NICE guidelines and resources that support discussion with patients about opioid prescribing and safe withdrawal management. For the current recommendations, see www.nice.org.uk/guidance/CG147/chapter/recommendations. October 2018: The antiplatelet therapy link in recommendation 1.2.1 was updated.</span></li></ul></div><div class="bk_prnt"><p style="color:red;"><strong>Update information: This guideline was updated by a NICE standing committee in February 2018 and 2 new recommendations were added on diagnosing peripheral arterial disease in people with diabetes. The recommendations are in section 1.3 of the guidance. The evidence for these recommendations is in evidence reviews A: determining the diagnosis and severity of peripheral arterial disease in people with diabetes. December 2020: NICE added links in the recommendation on pain relief to other NICE guidelines and resources that support discussion with patients about opioid prescribing and safe withdrawal management. For the current recommendations, see www.nice.org.uk/guidance/CG147/chapter/recommendations. October 2018: The antiplatelet therapy link in recommendation 1.2.1 was updated.</strong></p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/nicecg147/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-nicecg147-lrg.png" alt="Cover of Lower Limb Peripheral Arterial Disease" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>Lower Limb Peripheral Arterial Disease: Diagnosis and Management [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK327432_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK327432_dtls__"><div>NICE Clinical Guidelines, No. 147.</div><div>National Clinical Guideline Centre (UK).</div><div>London: <a href="http://www.rcplondon.ac.uk/Pages/index.aspx" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">Royal College of Physicians (UK)</a>; 2012 Aug.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/nicecg147/">Contents</a></li></ul></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/nicecg147/ch10/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/nicecg147/ch12/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK327432_"><span class="label"> 11</span><span class="title" itemprop="name">Management of ischaemic pain in critical limb ischaemia</span></h1></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="ch11.s1"><h2 id="_ch11_s1_">11.1. Introduction</h2><p>Critical limb ischaemia (CLI) is characterised by persistent and severe ischaemic rest pain associated with poor tissue perfusion, tissue loss and ulceration. The preferred option is to improve tissue perfusion through endovascular or surgical treatment, therefore reducing the pain. In some cases, however, such treatment is not possible. This may be due to un-reconstructable disease or degree of tissue loss. Treatment to reperfuse the limb may have been attempted but have been unsuccessful, or the patient’s preferences may be towards conservative treatment. This results in continued pain. Whilst amputation is sometimes required, this outcome may be prevented or delayed if it is possible to adequately control pain.</p><p>The impact of pain can vary between patients as pain is a very personal experience. Pain is typically worse at night in bed because when the limb is elevated perfusion does not have gravity to assist it. This results in sleep deprivation. It is common for patients to attempt sleep with their leg hanging out of the bed or to choose to sleep in a chair. Ischaemic pain is often described by patients as a relentless, unbearable, deep burning pain. It impacts on all aspects of their life as they are unable to function properly. They are unlikely to pursue their normal activities and may well need help with daily tasks. They often become irritable with strains placed on their relationships. Appetite is compromised so they suffer nutritionally. Studies have highlighted that people with PAD have a fear about increasing pain.<a href="/books/n/nicecg147/references/#ch14.r17" data-bk-pop-rid="/books/n/nicecg147/references/def-item/ch14.r17/" data-bk-pop-others="" class="bk_pop"><sup>17</sup></a><sup>,</sup><a href="/books/n/nicecg147/references/#ch14.r19" data-bk-pop-rid="/books/n/nicecg147/references/def-item/ch14.r19/" data-bk-pop-others="" class="bk_pop"><sup>19</sup></a><sup>,</sup><a href="/books/n/nicecg147/references/#ch14.r20" data-bk-pop-rid="/books/n/nicecg147/references/def-item/ch14.r20/" data-bk-pop-others="" class="bk_pop"><sup>20</sup></a></p><p>Appropriate pain management is dependent on the accurate diagnosis of the cause of foot pain (see <a href="/books/n/nicecg147/ch7/">chapter 7</a>). This chapter deals with the management of ischaemia pain. Neuropathic pain, although sometimes associated with CLI, will not be dealt with in this guideline and is covered in Neuropathic pain: Pharmacological management, NICE clinical guideline CG96.<a href="/books/n/nicecg147/references/#ch14.r155" data-bk-pop-rid="/books/n/nicecg147/references/def-item/ch14.r155/" data-bk-pop-others="" class="bk_pop"><sup>155</sup></a></p></div><div id="ch11.s2"><h2 id="_ch11_s2_">11.2. Management options for pain in critical limb ischaemia</h2><div id="ch11.s3"><h3>11.2.1. Review question</h3><p>What is the clinical and cost effectiveness of chemical sympathectomy, opioids, gabapentin, pregabalin or tricyclic antidepressants compared to each other in any combination for the management of ischaemic pain in adults with critical limb ischemia?</p><p>To improve patient outcomes and quality of life, the GDG sought to identify RCT and observational evidence for interventions to manage ongoing or escalating ischaemic pain. Spinal cord stimulation was not included in the evidence review as the NICE technology appraisal 159<a href="/books/n/nicecg147/references/#ch14.r156" data-bk-pop-rid="/books/n/nicecg147/references/def-item/ch14.r156/" data-bk-pop-others="" class="bk_pop"><sup>156</sup></a> does not recommend its use for ischaemic pain outwith the context of a clinical trial. The treatments considered in the review were: chemical sympathectomy, opioids, gabapentin, pregabalin or tricyclic antidepressants (amitriptyline, nortiptyline and imipramine). The literature search was limited to studies with a follow-up duration of more than one week and indirect populations were excluded.</p><div id="ch11.s4"><h4>11.2.1.1. Clinical evidence</h4><p>No RCTs or observational studies which compared chemical sympathectomy, opioids, gabapentin, pregabalin or tricyclic antidepressants to each other in any combination were identified.</p></div><div id="ch11.s5"><h4>11.2.1.2. Economic evidence</h4><p>No cost-effectiveness evidence comparing chemical sympathectomy, opioids, gabapentin, pregabalin or tricyclic antidepressants to each other or in combination was identified in the literature. In the absence of relevant published evidence, the GDG were presented with current UK costs to inform decision making (<a class="figpopup" href="/books/NBK327432/table/ch11.t1/?report=objectonly" target="object" rid-figpopup="figch11t1" rid-ob="figobch11t1">Table 98</a> and <a class="figpopup" href="/books/NBK327432/table/ch11.t2/?report=objectonly" target="object" rid-figpopup="figch11t2" rid-ob="figobch11t2">Table 99</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch11t1"><a href="/books/NBK327432/table/ch11.t1/?report=objectonly" target="object" title="Table 98" class="img_link icnblk_img figpopup" rid-figpopup="figch11t1" rid-ob="figobch11t1"><img class="small-thumb" src="/books/NBK327432/table/ch11.t1/?report=thumb" src-large="/books/NBK327432/table/ch11.t1/?report=previmg" alt="Table 98. Cost of drugs for the treatment of ischaemic pain in critical limb ischaemia." /></a><div class="icnblk_cntnt"><h4 id="ch11.t1"><a href="/books/NBK327432/table/ch11.t1/?report=objectonly" target="object" rid-ob="figobch11t1">Table 98</a></h4><p class="float-caption no_bottom_margin">Cost of drugs for the treatment of ischaemic pain in critical limb ischaemia. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch11t2"><a href="/books/NBK327432/table/ch11.t2/?report=objectonly" target="object" title="Table 99" class="img_link icnblk_img figpopup" rid-figpopup="figch11t2" rid-ob="figobch11t2"><img class="small-thumb" src="/books/NBK327432/table/ch11.t2/?report=thumb" src-large="/books/NBK327432/table/ch11.t2/?report=previmg" alt="Table 99. Cost of chemical sympathectomy." /></a><div class="icnblk_cntnt"><h4 id="ch11.t2"><a href="/books/NBK327432/table/ch11.t2/?report=objectonly" target="object" rid-ob="figobch11t2">Table 99</a></h4><p class="float-caption no_bottom_margin">Cost of chemical sympathectomy. </p></div></div></div></div><div id="ch11.s6"><h3>11.2.2. Evidence statements</h3><div id="ch11.s7"><h4>11.2.2.1. Clinical</h4><p>No clinical evidence was identified.</p></div><div id="ch11.s8"><h4>11.2.2.2. Economic</h4><p>No cost-effectiveness evidence was identified.</p></div></div><div id="ch11.s9"><h3>11.2.3. Recommendations and link to evidence</h3><div id="ch11.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK327432/table/ch11.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch11.tu1_lrgtbl__"><table><thead><tr><th id="hd_h_ch11.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Recommendations</th><th id="hd_h_ch11.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">
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<dl class="temp-labeled-list"><dt>25.</dt><dd><p class="no_top_margin">Offer paracetamol, and either weak or strong opioids depending on the severity of pain, to people with critical limb ischaemic pain.</p></dd><dt>26.</dt><dd><p class="no_top_margin">Offer drugs such as laxatives and anti-emetics to manage the adverse effects of strong opioids, in line with the person’s needs and preferences.</p></dd><dt>27.</dt><dd><p class="no_top_margin">Refer people with critical limb ischaemic pain to a specialist pain management service if any of the following apply:</p><ul><li class="half_rhythm"><div>their pain is not adequately controlled or revascularisation is inappropriate or impossible</div></li><li class="half_rhythm"><div>ongoing high doses of opioids are required for pain control</div></li><li class="half_rhythm"><div>pain persists after revascularisation or amputation.</div></li></ul></dd><dt>28.</dt><dd><p class="no_top_margin">Do not offer chemical sympathectomy to people with critical limb ischaemic pain, except in the context of a clinical trial.</p></dd></dl></th></tr></thead><tbody><tr><td headers="hd_h_ch11.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Relative values of different outcomes</td><td headers="hd_h_ch11.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For patients with pain associated with critical limb ischaemia, the GDG considered pain relief and quality of life as the most important outcomes. Improved quality of life which would include the ability to sleep, maintain normal activities of daily living, maintaining a level of independence is of high importance to the patient. No data on these outcomes were found.<br /><br />In addition to considering various drugs with analgesic properties, the GDG were particularly interested to look at evidence relating to chemical sympathectomy, an old established operation which is still performed in some centres. No satisfactory evidence was found.</td></tr><tr><td headers="hd_h_ch11.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Trade off between benefits and harms</td><td headers="hd_h_ch11.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The GDG considered the side effects associated with each type of analgesia (such as constipation, nausea and drowsiness). The group agreed that a tiered approach to pain management would minimise adverse events associated with stronger preparations while ensuring that adequate pain relief was provided. The adequate management of pain can improve a patient’s quality of life.<br /><br />The GDG noted that prolonged use of pain medication is often associated with side-effects, and that tolerance and dependence to pain relief need to be considered. Patients should therefore be reviewed on a regular basis. Particular note was taken of the potential risks of prolonged strong opioid use, and the GDG felt that this situation should be one in which advice from, and monitoring by, a pain specialist should be sought.</td></tr><tr><td headers="hd_h_ch11.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Economic considerations</td><td headers="hd_h_ch11.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The GDG considered the cost of each analgesic treatment and the cost of treating their associated side effects (e.g. laxatives for constipation). They thought that a tiered approach to pain management would likely be the most cost effective treatment strategy as mild preparations are generally the least costly, have the fewest side effects and are often effective in providing adequate pain relief.<br /><br />The GDG considered the potential for improved pain management and the cost of ineffective analgesics alongside the cost associated with referral to specialist pain management services. The group agreed that for people who require strong analgesic preparations, are taking a maximum dosage and/or have poorly managed pain, the potential for improved quality of life would be likely to justify the cost of specialist treatment.</td></tr><tr><td headers="hd_h_ch11.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Quality of the evidence</td><td headers="hd_h_ch11.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No RCT or observational evidence was identified to allow comparison of chemical sympathectomy, opioids, gabapentin, pregabalin or tricyclic anti-depressants in any combination for managing CLI pain. The recommendations were based on GDG consensus and expert opinion.</td></tr><tr><td headers="hd_h_ch11.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other considerations</td><td headers="hd_h_ch11.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The GDG recognised that the management of CLI pain is often poor, sometimes due to ischaemic pain being misdiagnosed but also because the root cause is difficult to treat. Pain occurs through out the disease process. Patients require increasing pain management towards the end of the care pathway. Such patients may have had a failed revascularisation procedure or are not considered suitable for revascularisation. Pain management should be considered before referral for amputation<br /><br />The GDG agreed that the principles of pain management for CLI are not intrinsically different from managing pain in other chronic conditions. Other NICE guidance such as Low back pain <a href="/books/n/nicecg147/references/#ch14.r157" data-bk-pop-rid="/books/n/nicecg147/references/def-item/ch14.r157/" data-bk-pop-others="" class="bk_pop"><sup>157</sup></a> and Osteoarthritis<a href="/books/n/nicecg147/references/#ch14.r158" data-bk-pop-rid="/books/n/nicecg147/references/def-item/ch14.r158/" data-bk-pop-others="" class="bk_pop"><sup>158</sup></a> have used a stepped approach in pain management. The WHO pain ladder is widely used in the management of pain for various conditions. Pain relief is escalated in cases of persistent or increasing pain. The GDG were of the opinion, particularly in the absence of strong evidence, that a stepped approach would also be appropriate for ischaemic leg pain.<br /><br />The GDG agreed by consensus that pain management should begin with paracetamol. Where this is insufficient, weak opioids such as Tramadol or codeine should be given alongside paracetamol. Strong opioids such as morphine or oxycodone are recommended for short term use only. Other medications such as laxatives and anti-emetics should be offered alongside strong opioids.<br /><br />Patients should be commenced on a dose that suits their individual needs. Dosing can be escalated where pain is not controlled. The optimal dosing required for pain relief can differ between individuals and this must be taken into account during the decision-making process.<br /><br />These patients will have been managed in secondary care but are often referred back to primary care for the management of their pain. It is important, therefore, that there is clear guidance for pain management for primary care representatives including when to refer to a pain specialist.<br /><br />The GDG suggested that the following good practice principles of pain management:
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<ul><li class="half_rhythm"><div>The person should be regularly reviewed when on pain medication to ensure that it is giving adequate pain relief and no serious side effects. Patient preference must also be considered.</div></li><li class="half_rhythm"><div>Any pain relief used without marketing authorisation for the treatment of pain associated with must be documented and informed consent taken.</div></li><li class="half_rhythm"><div>All pain relief measures must be monitored as per local protocols and in accordance with the BNF.</div></li></ul><b>Chemical sympathectomy</b><br />The GDG noted that observational evidence is available on chemical sympathectomy, but this does not compare the procedure to the other interventions of interest for this review question.<br /><br />In current practice, chemical sympathectomy is undertaken where revascularisation has not succeeded or is not an option and after other pain relief options have failed, but usually prior to amputation. The patients concerned tend to be those with non-healing ulcers, severe rest pain or not responding to strong opioids. The GDG debated the concern that there may be a minority of such patients who would benefit from chemical sympathectomy and that any recommendation against offering this may be harmful to these patients. They also acknowledged that the technique for undertaking a chemical sympathectomy has changed; the treatment is now performed using imaging to guide the needle. This new technique has not been fully explored and may be more effective. However, the GDG were also aware that the availability of chemical sympathectomy varies around the country. It is not performed in some areas because it is thought to be ineffective, and those who hold this view regard sympathectomy as a procedure which delays the initiation of more effective pain relief. The placebo effect was also noted to be common in pain management techniques and without randomised controlled trials, the true effect of a pain treatment can not be known.<br /><br />The issue of chemical sympathectomy was discussed at length by the GDG because of difficulty in obtaining consensus. It was agreed that practice is variable, there is a reduction in overall usage and many centres do not provide this treatment. It was also agreed that there was no convincing formal evidence of benefit, but disagreement on the consequences of this lack of evidence, some holding that use of sympathectomy should not be discouraged until lack of benefit is proven, while others felt that it would be wrong to continue the practice without obtaining proper outcome evidence. The majority view was that sympathectomy should only be offered in the context of a clinical trial, and that this was the best way to ensure that practice was consistent and that there would be the development of evidence to support future guidance in this area.</td></tr></tbody></table></div></div></div><div id="ch11.s10"><h3>11.2.4. Research recommendation</h3><p>What is the clinical and cost effectiveness of chemical sympathectomy in comparison with other methods of pain control for managing critical limb ischaemic pain?</p><div id="ch11.s11"><h4>Why this is important</h4><p>Approximately 1 in 5 people with critical limb ischaemia cannot be offered procedures to improve the blood supply to their leg because of either the pattern of their disease or other comorbidities. In this group the therapeutic options are pain control or primary amputation. Chemical lumbar sympathectomy, which involves the destruction of the lumbar sympathetic chain (usually the L2 and L3 ganglia), has been suggested to reduce pain and improve wound healing, and may prevent amputation in some patients. Initially achieved surgically, it is now most commonly performed using chemical agents such as phenol to destroy the lumbar sympathetic chain. Despite having been used for over 60 years, the role of chemical lumbar sympathectomy remains unclear. Improvement in skin blood flow and modification of pain perception control have been demonstrated, and this has prompted the use of chemical lumbar sympathectomy for treating a range of conditions such as regional pain syndrome, vasospastic conditions and critical limb ischaemia. However, in critical limb ischaemia the use of chemical lumbar sympathectomy varies widely between units in England, the mode of action and indications are unclear, and there is currently no randomised controlled trial evidence demonstrating its clinical value. Therefore a randomised control trial comparing chemical lumbar sympathectomy with other methods of pain relief is recommended.</p></div></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK327432/?report=reader">PubReader</a></li><li><a href="/books/NBK327432/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK327432" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK327432" style="display:none" title="Cite this Page"><div class="bk_tt">National Clinical Guideline Centre (UK). Lower Limb Peripheral Arterial Disease: Diagnosis and Management [Internet]. London: Royal College of Physicians (UK); 2012 Aug. (NICE Clinical Guidelines, No. 147.) 11, Management of ischaemic pain in critical limb ischaemia.<span class="bk_cite_avail"></span></div></div></li><li><a href="/books/n/nicecg147/pdf/">PDF version of this title</a> (3.4M)</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#ch11.s1" ref="log$=inpage&link_id=inpage">Introduction</a></li><li><a href="#ch11.s2" ref="log$=inpage&link_id=inpage">Management options for pain in critical limb ischaemia</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Other titles in this collection</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/n/nicecollect/">
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