Nonfreezing Cold Injury

Summary

Nonfreezing cold injury may occur when peripheral tissues, almost always the feet, are exposed to cold and/or wet conditions but tissue fluids do not freeze. Very common among infantry soldiers, it typically produces only mild symptoms during exposure, but profuse and chronic problems for many years afterwards. Sequelae are protean, including cold sensitization, pain, and hyperhidrosis. Little treatment is effective, and sympathectomy is discouraged.

Introduction

Whilst cold injury in general has a long military medical history, it was not until the First World War that nonfreezing forms were distinguished from those in which freezing of tissues had occurred. Even as recently as the Second World War and the Korean War, terminology and field diagnosis were confusing, for instance lumping most cases of nonfreezing cold injury (NFCI) with some of freezing cold injury (FCI) under the term ‘cold injuries, ground type.’ What is clear is that NFCI has accounted for very large numbers of casualties in most infantry wars fought in cold-wet climates, including the First World War, the European and other Theaters towards the end of the Second World War, and most recently the Falklands Conflict. Conditions usually taken to imply NFCI include ‘trench foot’ and ‘immersion foot,’ although in strict historical usage the former should be applied to very severe mixed injuries resulting in massive tissue destruction.

Clinical and laboratory studies of NFCI have increasingly shown its overlap with similar conditions. These include ‘paddy foot,’ described in soldiers whose feet have been immersed in warm water for long periods, and ‘shelter limb,’ which occurred in Londoners taking refuge in the Underground system during the Blitz, whose feet were neither wet nor cold, but remained dependent and immobile for long periods. There are also remarkable similarities with conditions including ‘deprivation hands and feet,’ which appears to be NFCI in infants, and ‘reflex sympathetic dystrophy,’ a relatively recently described group of disorders involving chronic pain and vascular instability following diffuse trauma. In view of this, it is perhaps best to consider NFCI as part of a spectrum of diseases which are marked by ischaemia at the time of the primary injury, hyperaemia on cessation of that insult, and chronic neurological and vascular consequences – ‘ischaemia, hyperaemia, neuro-vascular’ or IHNV syndromes.

In distinction to FCI, and in common with other IHNV disorders, the early evolution of cases of NFCI is usually unimpressive, and often even sub-clinical; this contrasts with the long-term consequences, which are frequently sustained and more severe. Even when victims have been provided with a high standard of accessible medical care at the time of the primary injury, it is usual for them to present many weeks, months or even years afterwards, complaining of sequelae. The clinician may then be posed the problem of trying to reconstruct dimly-remembered events from the distant past in an effort to establish whether current signs and symptoms result from NFCI, or whether they reflect a more conventional Raynaud’s disorder.

Definition

Nonfreezing cold injury is defined as being an injury of peripheral tissues resulting from exposure to cold and/or wet conditions, such that the tissue fluids do not freeze at any time.

In cases where an adequate history can be obtained, the key diagnostic criterion is of a sensory neurological disturbance during the period of exposure. This usually amounts to local anaesthesia, and is distinct from sensations of prolonged or extreme cold.

Occurrence

NFCI is most commonly reported in military personnel who are exposed to suitably cold-wet environments for sufficiently long periods, typically infantry soldiers in static positions, such as in defensive trenches. Surveys undertaken of personnel involved in the Falklands Conflict showed that front-line personnel almost invariably sustained NFCI, whilst it was much less common in headquarters, logistic support, and similar staff; however rear echelon personnel working in water and mud for prolonged periods were more liable, and anyone who becomes soaked during an amphibious operation is clearly at risk. Certain ethnic groups, particularly Afro-Caribbeans, show increased incidences, as do tobacco smokers. There is insufficient information to comment on gender differences, although the low-grade peripheral vascular problems common in women suggest that they should be more prone.

Civilian personnel do suffer from NFCI, but seldom present; when they do, the absence of overt primary injury and the nature of sequelae often cause confusion. In the extreme, such patients may have had long careers following a relentless progression from vascular surgeon to neurologist, ending with psychiatrist. Establishing a physical diagnosis may then result in immense relief to the patient, and restoration of self-esteem, even though they have been warned that little treatment is available for the condition. NFCI may be not uncommon in mountaineers, participants in water-sports, divers, and year-round outdoor workers.

The feet are almost universally the affected periphery, although occasionally the hands may be involved. Anecdotal reports of NFCI to the male genitalia appear not to have been investigated. Whilst exceptional injuries may occur to any area of skin, nonfreezing injuries of the face or ears seem very rare indeed, in contrast to FCI.

Clinical Course

Although the grading of cold injuries by severity is becoming increasingly deprecated, the progression in time of NFCI is usefully divided into stages. Most generally accepted are those originally employed by Ungley, in his classic description of immersion foot during the Second World War. It is strongly recommended that this staging is adopted for all descriptions of NFCI.

Stage One: Ischaemia

Prior to the start of the first stage, the periphery feels cold, but sensation and function remain essentially intact. This stage is marked by loss of sensation in the affected part, to a varying degree. The majority of patients admit to complete loss of feeling in the most distal extremity (toes), although some employ more colorful and distinctive descriptions, including the feeling that their feet were made of cotton wool, or that they were ‘wearing someone else’s feet.’ The latter phrase is almost characteristic, and neatly summarizes the consequences of loss of proprioception as well. If the affected part is examined at this time, it is very cold indeed, but unfrozen (e.g. there is no ice in the socks), white, and apparently ischemic. This stage ends once rewarming commences; such rewarming may be as little as that occurring during massage and routine foot care, in which case the feet may cycle between stages one and two several times before final rewarming.

Stage Two:

Early reperfusion Once rewarming has started, the periphery undergoes transition from ischaemia to hyperaemia, exhibiting a fleeting intermediate which, although rarely observed, is distinctive. The return of color starts with a blue-mottled appearance, with swelling beginning but rarely prominent. Tissue temperatures start to rise, and that rewarming is accompanied by pain in the face of the numbness remaining from stage one. In some more severe cases, the skin remains wet, as if from profuse sweating. This stage ends once hyperaemia commences, which is normally within a few minutes or hours of starting rewarming.

Stage Three:Hyperaemia

The most overt signs of NFCI are paradoxically the hyperaemia, swelling, and pain which ensue soon after the extremity is rewarmed. As tissue temperatures continue to rise during rewarming, the skin flushes and remains pinker than usual for the remainder of this stage. Pulses become full and bounding, and slowed capillary refill can be demonstrated (rest a fingertip on the skin to blanch it - on removal, the blanching is slow to disappear). Early swelling which may have appeared during stage two continues to grow, to the point where the patient may be unable to wear conventional footwear. Pitting oedema is not normally present, although the most severe cases may develop blistering not unlike that of FCI.

Early loss of sensation usually remains, to be accompanied by pain which may be exquisite and severe. In milder cases, the pain is mainly nocturnal and confined to the region of the metatarsal heads, under the sole of the foot, and may mimic metatarsalgia. This commonly prevents or disrupts sleep, and is exacerbated by contact with bedclothes and footwear. More severe pain is uncommon, but when it does occur it may be unremitting and resistant to all conventional analgesics (including narcotics, which simply remove the distress which the pain was causing), although it can be abolished by regional analgesia such as spinal or epidural administration of local anesthetics. At its worst, such pain can be relentless, and last for several weeks.

Other sensory abnormalities are less common, but distinctive when they do occur. Some complain of formication, or other similar dysthesiae. Painful paraethesiae are more common but usually transient. Conventional assessment of gross motor function and reflexes are normal.

The hyperemic stage usually lasts several days or weeks, and gradually gives way to the final stage.

Stage Four: Sequelae

For an apparently minor initial injury, NFCI is notorious for its severe and long-lasting consequences. Long-term follow-up of small numbers of patients from the Second World War and many more from recent conflicts suggests that some suffer from lifelong sequelae, whilst others recover spontaneously from three months to 12 years after the injury. Resolution is unpredictable, although serial thermography can provide tentative prognosis.

The most common and significant consequence is the symptom of cold sensitivity, which is an indicator of the presence of cold sensitization. Patients complain of an increased sensitivity to cold exposure in the cold-injured extremity, in particular that once it has become cold, it is very slow to rewarm. It is not uncommon for a mild cold stress (such as immersion in 15º C. for two minutes) to require more than six hours of exposure to warm air before the patient feels that the toes have fully rewarmed. Objective evidence of such protracted vasoconstriction has been provided by both infra-red thermography (see below) and laser Doppler blood flow measurement. As a consequence, those who are cold sensitized may be unwilling to go outdoors during the winter, may require to heat their homes excessively, and sometimes even during the summer, and undergo social and occupational restrictions. Although sometimes described as a secondary Raynaud’s condition, it is sufficiently distinctive to accord it the name of ‘cold sensitization.’ A typical and almost diagnostic remark is that a sensitized male’s female partner complains of his cold feet in bed, rather than him complaining about hers.

Pain and other disturbances of sensation (ranging from numbness to hyperaesthesia) are also common, and may be associated with cold sensitization and episodes of cooling. Patterns are very variable, and range from random shooting pains higher in the foot or ankle, to dull aches on exposure to the cold. They may mimic causalgia, and some patients appear to be suffering from allodynia. Partial or complete loss of sensation usually resolves slowly, but certain modalities may never recover. Two characteristic instances are a rare permanent loss of proprioception, which in turn alters gait and may severely limit walking, and almost complete loss of warm thermal sensation. The latter can be confirmed by the measurement of thermal sensory thresholds.

Many who have suffered from NFCI complain of excessive local sweating, or hyperhidrosis. The high evaporative heat loss from affected feet, coupled with profound resting vasoconstriction, can lower skin temperatures well below ambient, down to as low as 22º C. when conditioned to 30º C. air. Sustained sweating leads to the accumulation of sweat within footwear: this causes social problems because of odor, can rot leather footwear (some sufferers have to throw their shoes away every three months), and may lead to further NFCI. In contrast, the skin may become dry and cracked, particularly along skinfolds, with fissures opening and weeping periodically. Stubborn, deep-seated and recurrent fungal infection may take hold, aided by the moist environment resulting from hyperhidrosis. This can affect the nails too, leading to thickening and in the worst cases onychogryposis. Other patients complain that they shed and regrow toe nails two or three times a year.

Other sequelae are more unusual, and may include joint involvement similar to ‘frostbite arthritis,’ although this does not appear to have been studied in those who have had NFCI alone. The most severely injured may undergo amputation and suffer problems common to those with the worst freezing injuries.

Special Investigations

Taking a careful history and performing a thorough medical examination should enable the non-specialist physician to arrive at the correct diagnosis in the great majority of cases. Equivocal findings, disputes, and when there is a need to assess change (perhaps in response to treatment, or to offer a prognosis) merit the greater rigor of investigation. Although there is as yet no single measure which can act as a diagnostic criterion, two techniques have shown themselves to be of value in assessing cold sensitization and thermal sensory impairment.

Assessing cold sensitization

Many different techniques have been employed to try to demonstrate the prolonged vasoconstriction which results from exposure to a cold stress. For a method to be successful, the stress must be sufficiently mild as to avoid causing too many false positives, the method of assessing change must be reproducible, and the whole test conducted in an environment warm enough to support resting vasodilatation in normal subjects.

The current method used at INM has been developed from the original work of Golden, Gallimore and Francis in 1982. Testing is conducted in an environmental chamber providing still air at a dry-bulb temperature of 30º C., in which patients are rested recumbent for at least 30 minutes before starting. A control infrared thermogram is then taken, of the sole of an affected foot (or palm of hand). The extremity is put into a plastic bag (which keeps it dry during immersion) and plunged into a waterbath maintained at 15º C. for two minutes. On removal, the plastic bag is discarded, and a second thermogram taken. Five minutes after removal from the water, the third and final thermogram is taken.

Normal and mildly cold-sensitized subjects show warm (surface temperatures above 32º C.) extremities in the first infrared image, whilst those with moderate and severe degrees of sensitization have digits at around 30º C. and below. The third image is the most discriminatory: in normal subjects, skin temperatures have returned to normal, warm pre-immersion values. The mildly cold-sensitized will only have achieved 29º–30º C., moderate cases around 27º C., and severe cases 25º C. and below. The distribution of temperatures usually gives insight into the digits which are worst affected, and may sometimes show demarcated deficits, although these are more usual in FCI, vibration injuries, etc.

The requirement to use a tightly-controlled environmental chamber limits the use of this technique to specialist centers. Variant methods have been used by some workers in their attempts to perform assessments elsewhere: some have focussed on trying to follow cold-induced vasodilatation during longer cold exposures, whilst others have tried short periods of alcohol spraying. Although these may be of value in experienced hands, they can also produce very high false positive rates, and are not as easy to interpret as results from the INM protocol. Other methods of assessing blood flow have been used: Francis tried photoplethysmography, whilst Oakley has more recently performed many studies using laser Doppler systems, but they are more demanding and only of value as research tools.

Assessing sensory impairment

Anecdotal reports of impaired warm sensation (see above) were married in 1986 with Fowler’s development of simple apparatus to measure thermal sensory thresholds in those with diabetic peripheral neuropathy. Oakley demonstrated that those with NFCI of the feet commonly had unrecordably high (> 6º C.) warm sensory thresholds in the toes, whilst cool thresholds were little altered (< 3º C.) from normal. Since then Fowler’s Middlesex Hospital Thermal Testing System has been used to assess those presenting with NFCI. Although it is not a direct measure of cold sensitization, this differential pattern of damage remains a common objective finding in stage four. Because the measurement of thermal sensory thresholds is much less demanding of facilities, and several commercial systems are available and in use in neurological departments worldwide, it is a more accessible means of investigation than infrared thermography.

Treatment

The very limited understanding of the pathophysiological mechanisms responsible for NFCI and its sequelae have severely limited its treatment. Current understanding focuses on three main causes of tissue damage: exposure to cold, prolonged ischaemia accompanying that exposure, and the action of free radicals during reperfusion. There are as yet no proven treatment regimes for any of these modes of injury.

Acute management

The critical difference in management between FCI and NFCI is that nonfreezing injuries should only ever be rewarmed slowly. Laboratory and clinical evidence has shown that the rapid rewarming preferred for freezing injuries will at the very least result in more severe symptoms and signs during stage three, if applied to nonfreezing injuries. Beyond that, management is conservative, with topical anti-bacterials, avoidance of further trauma including any further cold exposure, and early mobilization.

Pain relief is usually the greatest problem during stage three. Mild analgesics and non-steroidal anti-inflammatory drugs are usually completely ineffective; as remarked above, even narcotic analgesics do not alleviate the pain, but just affect the reaction to pain. Oakley found that nocturnal doses of quinine salts (e.g. quinine sulphate 200 mg rising to 400 mg hs) were effective, but subsequent experience has been unfavorable. More recent approaches have been based on amitriptyline (50 to 150 mg Hs) which does afford most patients some degree of relief without significant side-effects. It can also be used in those suffering residual pain in stage four.

Amelioration of sequelae

Once the hyperaemia of stage three changes into the vasoconstriction of stage four, the administration of vasodilators may have a sounder rationale. Unfortunately, experience has shown that results are disappointing. The only approach which has so far shown any promise is the long-term use of sustained-release preparations of nifedipine. These need to be given for several weeks or months before there is demonstrable benefit, but side-effects are sufficiently common and significant that this is of no use in those remaining in the military, or otherwise leading an active life. Thymoxamine has not been of any value.

There is much controversy surrounding the use of sympathectomy. Whilst it can undoubtedly lead to short-term improvements, after six months most patients have worse symptoms than before. It also lacks any sound pathophysiological basis. Surgical sympathectomy therefore should never be considered, and chemical techniques should be avoided.

Keeping the feet warm and dry, through the use of suitable footwear, remains the mainstay of long-term treatment. Military and other personnel who want to return to cold and wet environments should be strongly discouraged from doing so until symptomatic cold sensitization has resolved. Serial thermographic assessment can be particularly valuable in deciding when it is safe to allow re-exposure, although the severity of symptoms does not always accord with the assessed severity of sensitization. Recurrent minor injury is common, and may result in the most severe degrees of cold sensitization; FCI may also occur in those who are cold-sensitized, readily causing massive tissue loss and high levels of amputation.

Prevention

Although NFCI can be postponed by good foot care and hygiene, and careful choice of footwear, fieldcraft and equipment appear unable to overcome fundamental physiological limitations to cold/wet exposure. Much of the success achieved in prevention has resulted from measures such as troop rotation, which were first applied during the First World War.

Training injuries are a particularly intransigent problem. The arguments for training realism might need to be tempered with increased risk of NFCI. On the other hand, the value of a very high standard of fieldcraft, as can only be achieved by long and demanding training, is also apparent. Provided that the objective is always training and not selection by natural wastage, better training could still result in less severe and obtrusive NFCI.

Future Developments

Efforts continue to try to unravel the complex pathophysiology of this protean group of conditions. Recent hypotheses that cold sensitization results from sympathetic denervation supersensitivity have not been borne out by the latest research. Instead, attention is being focussed on changes in the vascular endothelium, and in trained reductions in peripheral perfusion capacity. Experimental models have shown that small local blood vessels are quite severely damaged following NFCI, and groups are now examining neuro-endothelial function. It is also possible that cold sensitization is the reverse of the neovascularisation seen as a result of physical training in the heat, leading to a loss of peripheral vessels. If this is the case, sending patients to the tropics during stage three may prevent the appearance of cold sensitization.

Bibliography