Cold Injury.

Cold injury has been documented for centuries and remains a concern for military personnel, winter recreationalists, and urban homeless populations. Treatment advances in the last decades have included thrombolytic and prostaglandin therapies however the mainstay remains early recognition and rapid rewarming. This chapter focuses on frostbite, with a brief overview of other cold related conditions.

A preliminary study of the thermal strain experienced by dive support boat personnel.

Anecdotal evidence indicated some British military dive support boat personnel suffer from uncomfortably cold hands and feet, which could impair their performance and be associated with reductions in core body temperature. This study collected preliminary data on thermal stress and cognitive performance of personnel taking part in a cold-weather training exercise. Six men were monitored during four boat transits in a range of climatic conditions (air temperature +1.2°C to -10.5°C, wind chill -4.5°C to 19.3°C). Core body temperature was measured with a radio pill and 12 skin sites (ISO 9886 plus hand, finger, foot and toe) with iButtons or thermistors. Self-reported thermal comfort and thermal sensation was also recorded. Reaction time and selective attention were measured pre- and post-transit. Participants' physical characteristics and personal clothing ensembles were recorded. No participant became hypothermic. Most participants' hand, foot and digit temperatures fell to below 15°C, indicating a risk of impaired dexterity, in addition to that arising from gloves. During the trial, hand and digit temperatures occasionally fell below 10°C. The limited data collected showed personal clothing choices could provide adequate thermal protection for these conditions and temperatures, and highlighted inter-individual variation and the need to allow for significant variation of day-to-day environmental conditions.

Extremity cooling during an arctic diving training exercise.

A field study was conducted to examine the vulnerability of military divers to non-freezing cold injury (NFCI) during Arctic ice-diving operations. Participants were instrumented with temperature sensors on the back of their hands and on the bottom of their big toe for each dive to measure cooling of their extremities. While NFCI was not diagnosed in any of the participants during this field study, the data indicate that the feet were particularly vulnerable during the dives given that they were mostly in a temperature zone that could cause pain and performance decrements. The data also show that for short term dives, the dry and wet suits with wet gloves in both configurations were thermally more comfortable for the hands than the dry suit with dry glove configuration; however, the latter would be more protective against potential NFCI during longer dives. Features such as hydrostatic pressure and repetitive diving that are unique to diving but not previously considered as risk factors for NFCI are examined herein and warrant deeper investigation given that symptoms of NFCI might be mistaken as decompression sickness.

Abstracts from The Cold Weather Operations Conference 2021.

A common effort for both military and civil healthcare is to achieve knowledge-based health care in cold weather injuries and fatal accidents in harsh arctic environment. The Cold Weather Operations Conference in November 2021, having more than 300 participants from 20 countries, was addressing the prevention and treatment of injuries and trauma care in cold weather conditions and the challenges for military prehospital casualty care. The intention of the programme was to stimulate further research and systematic knowledge-based clinical work. The abstracts from the conference present cold weather research and clinical experience relevant for readers of the International Journal of Circumpolar Health.

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

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.

Increased cold injuries and the effect of body mass index in patients with peripheral vascular disease.

BACKGROUND: Exposure to extremely or moderate low temperatures is associated with increased morbidity and mortality risk. Peripheral vascular disease (PVD) is a slow and progressive circulation disorder. Given that cold temperature causes constriction of the small arteries and veins in the skin, patients who suffer from peripheral circulation problems, like PVD, may be vulnerable to cold injuries. This study aimed to investigate the association between PVD and cold-induced injuries in the winter among Korean adults. We further analyzed the association stratified by body mass index (BMI) classification. METHODS: We used the 2002-2015 National Health Insurance Service-National Sample Cohort data and included a total of 535,186 adults as the study population. Patients with underlying PVD were identified by ICD-10 code I73. Cold-related illnesses were defined by ICD-10 codes (T690, T691, T698, T699, T330 ~ T339, T340 ~ T349, and T350 ~ T357). Body mass index (BMI) was categorized into underweight, normal weight, overweight, and obese. RESULTS: A total of 23.21% (n = 124,224) were PVD patients, and 0.59% (n = 3154) had cold-induced injuries. PVD patients were more likely to be diagnosed with cold injuries, but it was valid only in the underweight or normal weight groups. After adjusting for age, sex, income, cigarette smoking, alcohol consumption, regular exercise, high blood pressure, and hyperglycemia, PVD patients had a significantly increased odds ratio (OR) for cold injuries [adjusted OR = 1.11; 95% confidence intervals (95% CI): 1.01-1.21]. Increased OR for cold injuries in PVD patients was also observed in adults (adjusted OR = 1.14; 95% CI: 1.03-1.25 in Model 2), but not in the elderly. When we classified study subjects into the four BMI groups, the adjusted OR of cold injuries in PVD patients was significant in the underweight group (OR = 1.83; 95% CI, 1.26-2.66) and normal weight group (OR = 1.15; 95% CI, 1.03-1.27), not in those with overweight and obese. In adults, a consistent result was found in adults in the underweight group (OR = 1.63; 95% CI, 1.08-2.47 in Model 2) and normal weight group (OR = 1.19; 95% CI, 1.07-1.33 in Model 2). In the elderly, the adjusted OR for cold injuries was only significant in the underweight group (OR = 3.37; 95% CI, 1.08-10.53 in Model 2). CONCLUSIONS: We found a significant association between PVD and cold-induced injuries in the general population. BMI modified the association. Thus, the association observed appears to be clinically applicable to PVD patients being low to normal BMI.

Previous recreational cold exposure does not alter endothelial function or sensory thermal thresholds in the hands or feet.

NEW FINDINGS: What is the central question of this study? Does recreational cold exposure result in cold sensitivity and is this associated with endothelial dysfunction and impaired sensory thermal thresholds? What is the main finding and its importance? Previous cold exposure was correlated with cold sensitivity of the foot, which might indicate the development of a subclinical non-freezing cold injury. Endothelial function and thermal detection were not impaired in cold-sensitive individuals; therefore, further research is required to understand the pathophysiology of subclinical and clinical forms of non-freezing cold injury. ABSTRACT: In this study, we investigated whether cold-sensitive (CS) individuals, who rewarm more slowly after a mild cold challenge, have impaired endothelial function and sensory thermal thresholds (STTs) and whether this is related to reported cold exposure. Twenty-seven participants with varying previous cold exposure undertook three tests: an STT test, i.e. determination of warm and cold STTs of the fingers and dorsal foot; an endothelial function test, i.e. measurement of cutaneous vascular conductance (CVC) during iontophoresis of ACh on the forearm, finger and foot; and a CS test, involving immersion of a foot for 2 min in water at 15°C followed by 10 min of rewarming in air at 30°C. Toe skin temperature (Tsk ) measured during the CS test was used to form a CS group (<32°C before and 5 min after immersion) and an otherwise closely matched control group [Tsk >32°C; n = 9 (four women) for both groups]. A moderate relationship was found between cold exposure ranking and Tsk rewarming (r = 0.408, P = 0.035, n = 27) but not STT or endothelial function. The Tsk and blood flow were lower in CS compared with control subjects before and after foot immersion [Tsk , mean (SD): 30.3 (0.9) versus 34.8 (0.8) and 27.9 (0.8) versus 34.3 (0.8)°C, P < 0.001; and CVC: 1.08 (0.79) versus 3.82 (1.21) and 0.79 (0.52) versus 3.45 (1.07) flux mmHg-1 , n = 9, P < 0.001, respectively]. However, no physiologically significant differences were observed between groups for endothelial function or STT. A moderate correlation between previous cold exposure and toe Tsk rewarming after foot immersion was observed; however, CS was not associated with impaired endothelial function or reduced thermal detection.

Case series of non-freezing cold injury: the modern clinical syndrome.

BACKGROUND: Non-freezing cold injury (NFCI) occurs when peripheral tissue is damaged by cold exposure but not to the extent of freezing. Historically, the phenotype of NFCIs sustained was severe, whereas today the spectrum of injury represented in the UK military predominantly comprises subtler injuries. The diagnostic challenge of recognising these injuries, both in the acute and chronic settings, can lead to mismanagement and subsequent morbidity. METHODS: We characterised a recent case series of 100 UK Service Personnel referred with suspected NFCI to a Military UK NFCI clinic. We characterised the acute and chronic phenotype of those diagnosed with NFCI (n=76) and made comparison to those who received alternate diagnoses (n=24), to find discriminatory symptoms and signs. RESULTS: The most common acute symptoms of NFCI were the extremities becoming cold to the point of loss of feeling for more than 30 min (sensitivity 96%, specificity 90%, p<0.001), followed by a period of painful rewarming (sensitivity 81%, specificity 67%, p<0.001). In-field foot/hand inspections took place in half of the NFCI cases. Importantly, remaining in the field and undergoing multiple cycles of cooling and rewarming after an initial NFCI was associated with having double the risk of the NFCI persisting for more than a week. The most common and discriminant chronic symptoms and signs of NFCI were having extremities that behave differently during cold exposures (sensitivity 81%, specificity 75%, p<0.001) and having abnormal pinprick sensation in the affected extremity (sensitivity 88%, specificity 88%, p<0.001). CONCLUSIONS: A small collection of symptoms and signs characterise acute and chronic NFCIs and distinguish this vasoneuropathy from NFCI mimics.

[Erythromelalgia: skin redness and pain]. / Erythromelalgie: rote Haut und Schmerz.

Erythromelalgia is a rare disease that is associated with hemato-oncological diseases or after taking certain drugs and toxins, but it can also occur as an independent clinical picture, for example, due to mutations in the sodium channel NaV1.7. Clinically, there is a characteristic triad of attack-like burning pain and skin redness in the area of the distal extremities, which can be alleviated by excessive cooling. The attacks are triggered by heat, exertion, and stress. The diagnosis is primarily made clinically and can be confirmed by genetic testing if a sodium channel NaV1.7 mutation is present. Important differential diagnoses are complex regional pain syndrome, the non-freezing cold injury, and small fiber neuropathies. Therapy is multidisciplinary and has to be planned individually and include physical therapy and psychotherapy as well as drug therapy as integral components.

A 4-year follow-up of non-freezing cold injury with cold allodynia and neuropathy in 26 naval soldiers.

Background and aims Non-freezing cold injuries (NFCI), which typically may occur in military personnel, may result from exposure to cold, at temperatures around 0 °C or above, and worsened by wind and moisture. The injury is due to cooling but not freezing of tissue like in frostbite. NFCI may result in in chronic neuropathy and cold hypersensitivity. A recent retrospective study of small-and large fibres has suggested that NFCI results in neuropathic pain due to a sensory neuropathy and question a longitudinal study to verify a possible observation of improvement of NFCI over time. The present study is a 4-year follow-up investigation of large - and small-fibre function in 26 naval cadets and officers who were exposed to cold injury during the same military expedition. Methods The 26 soldiers were investigated clinically (with investigation of motor function, reflexes, sensibility), with nerve conduction studies (NCS) of major nerves in upper- and lower extremity, small fibre testing (QST, measurement of thermal thresholds), measurements of subcutaneous fat tissue and maximal O2 uptake. Investigations found place 2 months following the actual military expedition, with follow-up investigations of affected soldiers at 6-12 months and up to 3-4 years. In order to elucidate possible mechanisms (disinhibition of cold pain by myelinated nerve fibres) of cold allodynia, cold pain thresholds were measured following an ischemic block of conduction of large and small myelinated nerve fibres. Results Of 26 soldiers, 19 complained of numbness in feet and a large majority of 16 of cold hypersensitivity 2 months following injury. There were significant alterations of both large- and small-fibre function, indicating a general large- and small-fibre neuropathy. The most prominent finding was a pronounced cold allodynia, inversely correlated with the amount of subcutaneous fat. During the first year, results of NCS and thermal testing gradually normalized in most. Seven soldiers developed chronic symptoms in the form of cold hypersensitivity and with findings of cold allodynia, which was not further enhanced, but abolished following block of conduction of myelinated nerve fibres. Seven soldiers were free of symptoms from that start of the investigation, probably because they had been more eager to keep their legs moving during the exposure to cold. Conclusions Of a total of 26 soldiers, only seven developed chronic symptoms of cold hypersensitivity, corresponding to the finding of cold allodynia by thermal testing. The cold allodynia may not be explained by disinhibition of cold pain by myelinated fibres as in healthy subjects. A large majority recovered from an initial large-and small fibre neuropathy, demonstrating that recovery from NFCI may occur. Implications Although large-and small fibre neuropathy may be restored following cold injury, there is a risk of a permanent and disabling cold hypersensitivity, corresponding to the findings of cold allodynia. It is of uttermost importance to secure military personnel from the risk of cold injuries. It seems important to avoid immobilisation of extremities during exposure to cold.

Case series of non-freezing cold injury: epidemiology and risk factors.

BACKGROUND: Non-freezing cold injury (NFCI) occurs when the peripheral tissue is cooled sufficiently that damage occurs, but not to the point of tissue freezing. Historically, the phenotype of the injuries studied was often severe, and it is unclear whether knowledge gained from these cases is entirely relevant to the frequently subtle injuries seen today. METHODS: We therefore sought to characterise a recent case series of 100 patients referred with suspected NFCI to a military UK NFCI clinic. Their demographics, medical history and situational risk factors leading to their injuries were analysed, and comparison was made between those subsequently diagnosed with NFCI (n=76) and those receiving alternate diagnoses (n=24). RESULTS: Statistically significant predisposing factors for NFCI in the UK service personnel (SP) were being of African-Caribbean ethnicity and having a short duration of service in the Armed Forces. Past or current smoking was not identified as a risk factor. Injuries were almost always suffered on training exercises (most commonly in the UK); being generally cold and being on static duties were statistically significant situational risk factors. Non-significant trends of risk were also found for having wet clothing, wet boots and immersion. Self-reported dehydration was not found to be a risk factor for NFCI. CONCLUSIONS: Our demographic findings are in general agreement with those of previous studies. Our situational risk factor findings, however, highlight a pattern of NFCI risk factors to the modern UK SP: winter training exercises, when troops are generally cold and extremities often wet, with static duties frequently implicated in the disease mechanism.

Distal limb pathologic conditions in horses treated with sleeve-style digital cryotherapy (285 cases).

Digital cryotherapy (DC) is frequently used as laminitis prophylaxis for horses. While DC with ice-water slurries is reported to be safe for up to 48 h, the safety of sleeve-style digital cryotherapy (SSDC) with ice in direct contact with the distal limb has not been evaluated. Our objective was to determine the incidence of distal limb pathologic conditions (DLPC) among horses treated with SSDC. A retrospective study of cases from 2011 to 2015 identified 285 horses treated with SSDC for a minimum of 12 h. Data collected from medical records included demographic, treatment, diagnostic, and SSDC treatment parameters. Bivariate statistics and a generalized linear regression model were created to evaluate risk factors associated with increased incidence of DLPC. Among horses treated with SSDC, 7% had tissue injury of the distal limb. Increasing duration of SSDC was associated with increased incidence of DLPC. Lesions observed included dermatitis, cellulitis, alopecia, coronitis, tissue necrosis, and distal limb edema. These lesions were similar to frostbite, non-freezing cold injury, and prolonged water immersion injuries seen in other species. While the incidence of DLPC was low, the authors recommend that horses undergoing SSDC with ice in direct contact with the skin should be monitored closely for injury when prolonged cryotherapy is clinically indicated. Further studies to improve safety, efficacy, and convenience of alternative methods of DC for horses are warranted.

Trench Foot or Non-Freezing Cold Injury As a Painful Vaso-Neuropathy: Clinical and Skin Biopsy Assessments.

BACKGROUND: Trench foot, or non-freezing cold injury (NFCI), results from cold exposure of sufficient severity and duration above freezing point, with consequent sensory and vascular abnormalities which may persist for years. Based on observations of Trench foot in World War II, the condition was described as a vaso-neuropathy. While some reports have documented nerve damage after extreme cold exposure, sensory nerve fibres and vasculature have not been assessed with recent techniques in NFCI. OBJECTIVE: To assess patients with chronic sensory symptoms following cold exposure, in order to diagnose any underlying small fibre neuropathy, and provide insight into mechanisms of the persistent pain and cold hypersensitivity. METHODS: Thirty soldiers with cold exposure and persistent sensory symptoms (>4 months) were assessed with quantitative sensory testing, nerve conduction studies, and skin biopsies. Immunohistochemistry was used to assess intraepidermal (IENF) and subepidermal (SENF) nerve fibres with a range of markers, including the pan-neuronal marker protein gene product 9.5 (PGP 9.5), regenerating fibres with growth-associated protein 43 (GAP43), and nociceptor fibres with transient receptor potential cation channel subfamily V member 1 (TRPV1), sensory neuron-specific receptor (SNSR), and calcitonin gene-related peptide (CGRP). von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) were used for assessing blood vessels, and transient receptor potential cation channel, subfamily A member 1 (TRPA1) and P2X purinoceptor 7 (P2X7) for keratinocytes, which regulate nociceptors via release of nerve growth factor. RESULTS: Clinical examination showed pinprick sensation was abnormal in the feet of 20 patients (67%), and between 67 and 83% had abnormalities of thermal thresholds to the different modalities. 7 patients (23%) showed reduced sensory action potential amplitude of plantar nerves. 27 patients (90%) had decreased calf skin PGP 9.5 IENF (p < 0.0001), the remaining 3 patients had decreased nerve markers in subepidermis or foot skin. There were marked increases of all vascular markers (for vWF in calf skin, p < 0.0001), and increased sensory or regenerating SENF (for calf skin, GAP43, p = 0.002). TRPA1 (p = 0.0012) and P2X7 (p < 0.0001) were increased in basal keratinocytes. CONCLUSION: A range of skin biopsy markers and plantar nerve conduction studies are useful objective assessments for the diagnosis of peripheral neuropathy in NFCI. Our results suggest that an increase in blood vessels following tissue ischaemia/hypoxia could be associated with disproportionate and abnormal nerve fibres (irritable nociceptors), and may lead to NFCI as a "painful vaso-neuropathy."

Effects of dietary nitrate supplementation on the response to extremity cooling and endothelial function in individuals with cold sensitivity. A double blind, placebo controlled, crossover, randomised control trial.

Individuals with cold sensitivity have low peripheral skin blood flow and skin temperature possibly due to reduced nitric oxide (NO•) bioavailability. Beetroot has a high concentration of inorganic nitrate and may increase NO-mediated vasodilation. Using a placebo-controlled, double blind, randomised, crossover design, this study tested the hypotheses that acute beetroot supplementation would increase the rate of cutaneous rewarming following a local cold challenge and augment endothelium-dependent vasodilation in cold sensitive individuals. Thirteen cold sensitive participants completed foot and hand cooling (separately, in 15 °C water for 2 min) with spontaneous rewarming in 30 °C air whilst skin temperature and cutaneous vascular conductance (CVC) were measured (Baseline). On two further separate visits, participants consumed 140 ml of either concentrated beetroot juice (nitrate supplementation) or nitrate-depleted beetroot juice (Placebo) 90 min before resting seated blood pressure was measured. Endothelial function was assessed by measuring CVC at the forearm, finger and foot during iontophoresis of 1% w/v acetylcholine followed by foot and hand cooling as for Baseline. Plasma nitrite concentrations significantly increased in nitrate supplementation compared to Placebo and Baseline (502 ± 246 nmol L-1; 73 ± 45 nmol L-1; 74 ± 49 nmol L-1 respectively; n = 11; P < 0.001). Resting blood pressure and the response to foot and hand cooling did not differ between conditions (all P > 0.05). Nitrate supplementation did not alter endothelial function in the forearm, finger or foot (all P > 0.05) compared to Placebo. Despite a physiologically meaningful rise in plasma nitrite concentrations, acute nitrate supplementation does not alter extremity rewarming, endothelial function or blood pressure in individuals with cold sensitivity.

Role of cyclooxygenase in the vascular responses to extremity cooling in Caucasian and African males.

NEW FINDINGS: What is the central question of this study? Compared with Caucasians, African individuals are more susceptible to non-freezing cold injury and experience greater cutaneous vasoconstriction and cooler finger skin temperatures upon hand cooling. We investigated whether the enzyme cyclooxygenase is, in part, responsible for the exaggerated response to local cooling. What is the main finding and its importance? During local hand cooling, individuals of African descent experienced significantly lower finger skin blood flow and skin temperature compared with Caucasians irrespective of cyclooxygenase inhibition. These data suggest that in young African males the cyclooxygenase pathway appears not to be the primary reason for the increased susceptibility to non-freezing cold injury. Individuals of African descent (AFD) are more susceptible to non-freezing cold injury (NFCI) and experience an exaggerated cutaneous vasoconstrictor response to hand cooling compared with Caucasians (CAU). Using a placebo-controlled, cross-over design, this study tested the hypothesis that cyclooxygenase (COX) may, in part, be responsible for the exaggerated vasoconstrictor response to local cooling in AFD. Twelve AFD and 12 CAU young healthy men completed foot cooling and hand cooling (separately, in 8°C water for 30 min) with spontaneous rewarming in 30°C air after placebo or aspirin (COX inhibition) treatment. Skin blood flow, expressed as cutaneous vascular conductance (as flux per millimetre of mercury), and skin temperature were measured throughout. Irrespective of COX inhibition, the responses to foot cooling, but not hand cooling, were similar between ethnicities. Specifically, during hand cooling after placebo, AFD experienced a lower minimal skin blood flow [mean (SD): 0.5 (0.1) versus 0.8 (0.2) flux mmHg-1 , P < 0.001] and a lower minimal finger skin temperature [9.5 (1.4) versus 10.7 (1.3)°C, P = 0.039] compared with CAU. During spontaneous rewarming, average skin blood flow was also lower in AFD than in CAU [2.8 (1.6) versus 4.3 (1.0) flux mmHg-1 , P < 0.001]. These data provide further support that AFD experience an exaggerated response to hand cooling on reflection this appears to overstate findings; however, the results demonstrate that the COX pathway is not the primary reason for the exaggerated responses in AFD and increased susceptibility to NFCI.

A new treatment for frostbite sequelae; Botulinum toxin.

Frostbite sequelae are a relevant occupational injury outcome for soldiers in arctic environments. A Caucasian male soldier suffered frostbite to both hands during a military winter exercise. He developed sensory-motor disturbances and cold hypersensitivity. Angiography and thermography revealed impaired blood flow while Quantitative Sensory Testing indicated impaired somato-sensory nerve function. Two years after the initial event, he received an off label treatment with Botulinum toxin distributed around the neurovascular bundles of each finger. After treatment, cold sensitivity was reduced while blood flow and somato-sensory nerve function improved. The successful treatment enabled the soldier to successfully pursue his career in the army.

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

INTRODUCTION: Non-freezing cold injury (NFCI) remains largely under-reported, and is of particular importance in the armed forces where its prevalence is greatest. Iloprost, a synthetic prostaglandin I2 analogue, has previously been used with some success in the treatment of vasospastic and freezing cold injuries, although its role in NFCI remains unclear. CASE REPORT: An Iloprost infusion was used to treat the long-term sequelae of an ex-soldier suffering with ongoing pedal pain and loss of function 20 years after the initial NFCI insult sustained on military exercise. Following 5 days of iloprost infusion, he reported 4 weeks of markedly reduced pain and increased mobility before symptom relapse. A second infusion was thus given 3 months later, which resulted in increased pain and analgesic requirements. DISCUSSION: 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.

Role of cyclooxygenase in the vascular response to locally delivered acetylcholine in Caucasian and African descent individuals.

INTRODUCTION: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury (NFCI) compared with Caucasian individuals (CAU). Vasodilatation to acetylcholine (ACh) is lower in AFD compared with CAU in the non-glabrous foot and finger skin sites; the reason for this is unknown. Prostanoids are responsible, in part, for the vasodilator response to ACh, however it is not known whether the contribution differs between ethnicities. METHODS: 12 CAU and 12 AFD males received iontophoresis of ACh (1 w/v%) on non-glabrous foot and finger skin sites following placebo and then aspirin (600mg, single blinded). Aspirin was utilised to inhibit prostanoid production by inhibiting the cyclooxygenase (COX) enzyme. Laser Doppler flowmetry was utilised to measure changes in skin blood flow. RESULTS: Not all participants could receive iontophoresis charge due to high skin resistance; these participants were therefore excluded from the analyses. Foot: ACh elicited greater maximal vasodilatation in CAU than AFD following placebo (P=0.003) and COX inhibition (COXib) (P<0.001). COXib did not affect blood flow responses in AFD, but caused a reduction in the area under the curve for CAU (P=0.031). Finger: ACh elicited a greater maximal vasodilatation in CAU than AFD following placebo (P=0.013) and COXib (P=0.001). COXib tended to reduce the area under the curve in AFD (P=0.053), but did not affect CAU. CONCLUSIONS: CAU have a greater endothelial reactivity than AFD in both foot and finger skin sites irrespective of COXib. It is concluded that the lower ACh-induced vasodilatation in AFD is not due to a compromised COX pathway.

Dexamethasone prevents vascular damage in early-stage non-freezing cold injury of the sciatic nerve.

Non-freezing cold injury is a prevalent cause of peripheral nerve damage, but its pathogenic mechanism is poorly understood, and treatment remains inadequate. Glucocorticoids have anti-inflammatory and lipid peroxidation-inhibiting properties. We therefore examined whether dexamethasone, a synthetic glucocorticoid compound, would alleviate early-stage non-freezing cold injury of the sciatic nerve. We established Wistar rat models of non-freezing cold injury by exposing the left sciatic nerve to cold (3-5°C) for 2 hours, then administered dexamethasone (3 mg/kg intraperitoneally) to half of the models. One day after injury, the concentration of Evans blue tracer in the injured sciatic nerve of rats that received dexamethasone was notably lower than that in the injured sciatic nerve of rats that did not receive dexamethasone; neither Evans blue dye nor capillary stenosis was observed in the endoneurium, but myelinated nerve fibers were markedly degenerated in the injured sciatic nerve of animals that received dexamethasone. After dexamethasone administration, however, endoneurial vasculopathy was markedly improved, although damage to the myelinated nerve fiber was not alleviated. These findings suggest that dexamethasone protects the blood-nerve barrier, but its benefit in non-freezing cold injury is limited to the vascular system.