Potential new treatment for non-freezing cold injury: is Iloprost the way forward?

Ionescu, Anne-Marie; Hutchinson, Sarah; Ahmad, Mehtab; Imray, Christopher

doi:10.1136/jramc-2016-000672

Cited by 10 publications

(10 citation statements)

References 9 publications

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“…The symptoms of NFCI are generally treated with current oral medications used for chronic pain, including neuropathic pain, though some studies have assessed the efficacy of new treatments ( 23 ). A range of nerve fibre, vascular and ion channel mechanisms have been reported by us to underlie chronic NFCI ( 3 ), which represent potential new targets for pain relief.…”

Section: Discussionmentioning

confidence: 99%

Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration

et al. 2021

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Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application.Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment.Results: Participants showed significant decrease in spontaneous pain (mean NPRS: −1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (−1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001).Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019).Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.

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Section: Discussionmentioning

confidence: 99%

Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration

et al. 2021

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“…NFCI forms part of the spectrum of cold weather injury (CWI) that includes FCI and frostnip [ 10 , 12 ]. Deployed populations are at risk when operating in areas below 15°C or with periods of immersion in wet conditions where prolonged exposure can trigger maximal vasoconstriction and limb ischaemia [ 10 , 13 ].…”

Section: Non-freezing Cold Injurymentioning

confidence: 99%

“…Arguably of most significance to this review is the case report by Ionescu et al . discussing the use of iloprost in the treatment of an established NFCI patient for the management of chronic pain [ 13 ]. The patient received iloprost treatment for chronic pain secondary to NFCI following initial injury 20 years prior to presentation.…”

Section: The Remote Iloprost Use In Non-freezing Cold Injurymentioning

confidence: 99%

Can iloprost be used for treatment of cold weather injury at the point of wounding in a forward operating environment? A literature review

Lowe

Warner

2023

International Journal of Circumpolar Health

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Introduction: Cold Weather Injury (CWI) represents a spectrum of pathology, the two main divisions being Freezing Cold Injury (FCI) and Non-Freezing Cold Injury (NFCI). Both are disabling conditions associated with microvascular and nerve injury often treated hours after initial insult when presenting to a healthcarestablishment. Given that iloprost is used for the treatment of FCI, could it be used in a forward operating environment to mitigate treatment delay? Is there a role for its use in the forward treatment of NFCI? This review sought to evaluate the strength of evidence for the potential use of iloprost in a forward operating environment. Methods: Literature searches were undertaken using the following question for both FCI and NFCI: in [patients with FCI/NFCI] does [the use of iloprost] compared to [standard care] reduce the incidence of [long-term complications]. Medline, CINAHL and EMBASE databases were searched using the above question and relevant alternative terminology. Abstracts were reviewed before full articles were requested. Results: The FCI search yielded 17 articles that were found to refer to the use of iloprost and FCI. Of the 17, one referred to pre-hospital treatment of frostbite at K2 base camp; however, this was utilising tPA. No articles referred to pre-hospital use in either FCI or NFCI. Discussion: Although evidence exists to support the use of iloprost in the treatment of FCI, its use to date has been in hospital. A common theme is delayed treatment due to the challenges of evacuating casualties from a remote location. There may be a role for iloprost in the treatment of FCI; however, further study is required to better understand the risk of its use.

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“…Neuropathic pain and CRPS are common sequelae of NFCI. In one reported case, iloprost, a vasodilator that is an analog of prostaglandin I 2 , was used to treat a 41-year old military veteran who suffered from foot pain with decreased mobility 20 years after sustaining a NFCI [ 20 ]. A five-day infusion of iloprost led to a month of decreased pain with increased mobility.…”

Section: Treatmentmentioning

confidence: 99%

Nonfreezing Cold Injury (Trench Foot)

Zafren

2021

IJERPH

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Nonfreezing cold injury (NFCI) is a modern term for trench foot or immersion foot. Moisture is required to produce a NFCI. NFCI seldom, if ever, results in loss of tissue unless there is also pressure necrosis or infection. Much of the published material regarding management of NFCIs has been erroneously borrowed from the literature on warm water immersion injuries. NFCI is a clinical diagnosis. Most patients with NFCI have a history of losing feeling for at least 30 min and having pain or abnormal sensation on rewarming. Limbs with NFCI usually pass through four ‘stages.’ cold exposure, post-exposure (prehyperaemic), hyperaemic, and posthyperaemic. Limbs with NFCI should be cooled gradually and kept cool. Amitriptyline is likely the most effective medication for pain relief. If prolonged exposure to wet, cold conditions cannot be avoided, the most effective measures to prevent NFCI are to stay active, wear adequate clothing, stay well-nourished, and change into dry socks at least daily.

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Potential new treatment for non-freezing cold injury: is Iloprost the way forward?

Abstract: The use of iloprost in the treatment of NFCI is discussed and its use in a condition which physicians consistently struggle to treat effectively is considered. Careful counselling is recommended as symptoms may be worsened.

Cited by 10 publications

References 9 publications

Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration

Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration

Can iloprost be used for treatment of cold weather injury at the point of wounding in a forward operating environment? A literature review

Nonfreezing Cold Injury (Trench Foot)

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