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O&P Library > POI > 1999, Vol 23, Num 3 > pp. 195 - 208

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Factors affecting wound healing after major amputation for vascular disease: a review

M. Eneroth *

Introduction

There has been a continuous increase in the incidence of major lower limb amputations from the beginning of the century until the mid-1980s (Table 1). This increase has been attributed to the increasing number of elderly persons, diabetics and smokers (Liedberg and Persson, 1983). During the last decade, several reports from Scandinavia have mentioned a decreased incidence of major amputations (Larsson et al., 1995; Larsson and Risberg, 1988; Persson et al., 1989; Pohjolainen and Alaranta, 1988; Sernbo et al., 1996; Wahlberg et al., 1994). Others have reported a reduction in the number of major amputations (Ebskov et al., 1994; Eickhoff, 1993; Lindholt et al., 1994; Luther, 1994; Lääperi et al., 1993; Pedersen et al., 1994; Pell et al., 1994; Stenström et al., 1992). The reduction has been attributed to better foot care among diabetics (Gibbons et al., 1993; Larsson et al., 1995), and an increase and improvement in vascular surgery (Ebskov et al., 1994; Eickhoff, 1993; Giddings et al., 1993; Jeans et al., 1994; Lindholt et al., 1994; Pedersen et al., 1994; Pomposelli et al., 1995; Shah et al., 1992). The decreased prevalence of smoking in the Western world (Centers for Disease Control, 1989; Fielding, 1985; Stachnik and Hoppe, 1986), also probably play an important role.

Despite these promising findings of a reduction in the incidence and numbers of major amputations in various countries in the Western world, the number of patients with critical leg ischemia will probably increase because of growing numbers of elderly people (Lindblad et al., 1991) and the increased prevalence of diabetes mellitus (Basore and Lewis, 1993; Midthjell et al., 1995; Wetterhall et al., 1992). Therefore, despite advances in limb salvage treatment, there will still be patients who are unsuitable for vascular procedures, and many of them ultimately face major amputation.

In a prospective multicentre study of 713 trans-tibial amputations for vascular disease, only 42% of the stumps were judged to have healed without complication (Dormandy et al., 1994). In a review of 18 articles published during the last two decades and covering more than 4,400 major amputations, 20% of trans-tibial amputations (TTAs), 22% of knee disarticulations (KDs) and 8% of trans-femoral amputations (TFAs) had to undergo a revision or a reamputation, because of complications with healing (Eneroth et al., 1997). Inclusion of those having delayed or failed healing, without the need for further surgery would increase the failure rate by an average of 15% after TTAs (Dormandy and Ray, 1994).

Furthermore, despite improvements in amputation techniques (Burgess et al., 1971; Jain et al., 1995; Persson, 1974; Robinson et al., 1982), and in the management of major amputations (Bunt et al., 1984; Sonne-Holm et al., 1985), the reamputation rate after major amputations has remained unchanged over the past 20 years (Table 2). The reasons for the absence of any significant reduction of reamputation rate are unknown. The increasing mean age at surgery (Eneroth and Persson, 1992; Kald et al., 1989; Liedberg and Persson, 1983) may play a role. With an increasingly older amputee population, it seems likely that their general health will become worse and their arterial disease more extensive (Pell et al., 1993), leading to a higher prevalence of complications and associated morbidity and resulting in a slower rehabilitation, longer hospital stays and increasing costs. In this review, factors have been suggested to affect wound healing after major amputation for vascular disease (Table 3) are discussed.

Factors suggested to affect wound healing after amputation

Smoking

Smoking has been described as the main risk factor for development of intermittent claudication (Hughson et al., 1978a; Kannel et al., 1976), and amputation has been shown to occur more frequently, at a younger age, and at higher levels in smokers (Liedberg and Persson, 1983; Stewart, 1987). In a review of the peripheral vascular consequences of smoking, its negative effects have been ascribed to a combination of cardiovascular, vessel wall, metabolic, biochemical, lipid and hematological effects (Krupski, 1991). The smoking of a single cigarette reduces the velocity of the digital skin blood flow in healthy subjects by 29-42% (Sarin et al., 1974; van Adrichem et al., 1992) and it has been shown that smoking impairs wound healing (Reus et al., 1984). Cessation of smoking improves intermittent claudication (Birkenstock et al., 1975; Hughson et al., 1978b; Quick and Cotton, 1982), increases patency rates of vascular reconstruction's (Myers et al., 1978; Ameli et al., 1989) and reduces the risk of rest pain and the need for vascular surgery (Jonason and Bergström, 1987) as well as the risk of amputation (Juergens et al., 1960). Major amputation after reconstructive arterial surgery was needed more often in heavy compared to moderate smokers (Ameli et al., 1989; Lassila and Lepäntalo, 1988). Liedberg and Persson (1983) and Eneroth and Persson (1993) found that smokers were significantly younger than non-smokers at amputation, while previous smokers and those who had never smoked were about the same age at amputation. This implies that even a late stop in smoking is useful in preventing amputation. In the only study analysing the effects of continued smoking in the postoperative period after a major amputation, smoking increased the risk of infection and reamputation (Lind et al., 1991). Although the relationship between smoking and the risk of a contralateral amputation has not been described, previous findings about the effects of smoking (Juergens et al., 1960; Liedberg and Persson, 1983; Lind et al., 1991; Stewart, 1987), indicate the need for continuing active anti-smoking campaigns, even after the first amputation wound has been healed.

Hemorrheology

A preoperative hemoglobin >130g/l has been reported to be an important risk factor for healing complications in forefoot amputations among diabetics (Bailey et al., 1979). Kacy et al. (1982) observed a higher preoperative hematocrit in complicated trans-tibial amputations among diabetics. Hansen et al. (1988) found gradually increasing rates of healing complications with rising levels of preoperative hemoglobin and hematocrit in arteriosclerotic amputations, while no such association was found in diabetics. Dormandy et al. (1994) observed that a high preoperative hematocrit was a risk factor for reamputation in prospective study of 713 TTAs. In a multi-variate analysis Eneroth and Persson (1993) found that a preoperative hemoglobin >120g/l was related to a significant increase in healing complications after major amputation. However, whether or not a high hematocrit and/or hemoglobin value is a risk factor for complicated healing in amputees is controversial. Several authors were not able to show that the level of the hematocrit or hemoglobin was a valuable predictor of stump failure (Falstie-Jensen and Christensen, 1990; Lepntalo et al., 1987; Tripses and Pollak, 1981; Weiss et al., 1990). This inconsistency may depend on the fact that it was the preoperative value that was related to healing. Obviously postoperative values are also important, although Lepäntalo et al. (1987) found no differences in pre- and postoperative values.

High hematocrit and/or hemoglobin values may be secondary to dchydration and the mechanism underlying the suggested association between hemoglobin values above 120-130g/l and healing complications may be a compromised micro-circulation secondary to increased whole blood viscosity (Messmer et al., 1982). Lowering the hematocrit by normovolemic hemodilution has been shown to increase blood flow in the leg and the pain-free walking distance in patients with stable intermittent claudication (Ernst et al., 1987; Yates et al., 1979). In the Second European Consensus Document on Chronic Critical Leg Ischemia (1991) it was recommended that if the hematocrit remains equal to or above 50% despite cessation of smoking and rehydration in patients with CLI, hemodilution should be considered. Although hemodilution has not been shown to benefit patients with CLI or amputees, it most likely is important to rehydrate dehydrated patients, not only to optimise preparation before amputation but also to reduce blood viscosity and thereby possibly increase blood flow in the leg.

Malnutrition

There is a growing interest concerning the occurrence and effects of malnutrition in hospitalised patients (Cederholm, 1994; Unosson, 1993). Malnutrition increases the risk of delayed wound healing, decubitus, infections, congestive heart failure, progressive weakness, apathy and death (Ek et al., 1991; Haydock and HiH, 1987; Jensen et al., 1982; Pedersen and Pedersen, 1992; Warnold and Lundholm, 1984). Malnutrition is common in hospitalised patients undergoing orthopaedic surgery (Delmi et al., 1990; Jensen et al., 1982; Older et al., 1980), especially among amputees (Dickhaut et al., 1984; Kay et al., 1987; Pedersen and Pedersen, 1992; Eneroth et al., 1997). Amputees are at particular risk of becoming malnourished because of a decreased intake of nutrients (due to pain, nausea and/or confusion), increased losses of nutrients (through wounds) and increased nutrient requirements (due to major surgery and infection).

Normal values of serum albumin and total lymphocyte count, indication a well-nourished patient, were predictive of a successful Syme amputation in a retrospective study of 23 diabetics (Dickhaut et al., 1984) and in a study of 41 major lower limb amputations, patients with a normal serum albumin level and total lymphocyte count had a lower risk of healing complications (Kay et al., 1987). Pedersen and Pedersen (1982) noted that malnourished amputees had a higher frequency impaired wound healing and an increased risk of postoperative cardiopulmonary and septic complications. Eneroth et al. (1997) found that 88% who underwent a TTA were malnourished before surgery and the healing rate was better in patients receiving pre- and postoperative supplementary nutrition than in a matched control group. The healing rate after supplementary nutrition was found to be higher in the nutrition group than in the control group in diabetics, whereas there was no difference in non-diabetics (Eneroth et al., 1997). Due to the small number of patients, these findings have to be considered with caution and have to be confirmed in further studies. Supplementary nutrition provides a satisfactory energy-protein intake and rchydrates the patient. Whether it is extra energy-protein intake or the rehydration or both that are responsible for the improved healing is uncertain.

Previous vascular surgery

The apparent aggravation in the degree of ischemia after graft failure in some cases has been attributed to an interruption in the collateral pathways at the time of operative dissection or to propagation of a thrombus after graft occlusion (Kazmers et al., 1980). Multiple incisions have been thought to be important regarding healing complications (Kazmers et al., 1980; Stirnemann et al., 1992). However, whether or not a failed attempt at limb-salvage affects wound healing after an amputation and/or leads to a higher level of amputation than in persons having a primary amputation is a matter of controversy (Table 3). Most studies are retrospective and include patients with great variations in the degree and onset of ischemia and the types of procedures performed, making comparisons uncertain and a direct comparison of patients with primary amputations to those with secondary amputations after failed vascular surgery is thus not valid, since the two groups are different (Tsang et al., 1991).

Although in some elderly patients with a questionable quality of distal vessels and rehabilitation potential, the surgeon should always consider the serious risk of deterioration of the patient's health due to repeated surgery, and instead consider a primary major amputation in some cases (Stirnemann et al., 1992), there is a consensus that the associated risk of wound healing complications after amputation and/or conversion from TTA to TFA level in some patients with a failed attempt at limb-salvage should not detract from the overall value of arterial reconstructions (Pedersen et al., 1994).

Diabetes mellitus

Whether diabetic patients have fewer healing complications following major amputations than those with ischemic disease alone remains controversial (Borssén and Lithner, 1983; Dormandy et al., 1994; Fearon et al., 1985; Finch et al., 1980; McCollum et al., 1984; Stewart, 1987). Several studies report better healing rate in diabetics, while others have not demonstrated any differences (Table 3). Variations in the extent and localisation of vascular disease, patient characteristics and treatment strategies may be responsible for the inconsistencies. Furthermore, many diabetics who in the past had a major amputation with a high healing rate might have been amputated below the ankle if treated today (Larsson et al., 1995).

An increased risk of amputation has been correlated to the inadequacy of metabolic control (Moss et al., 1992; Nelson et al., 1988; Reiber et al., 1992; Selby and Zhang, 1995). However, to the author's knowledge, no study has analysed the relationship between metabolic control and healing complications after a major amputation. Hemorrheological disturbances often occur in diabetics and may interfere with wound healing. Hypercoagulability, impaired fibrinolysis and changes in the microvessels impair the micro-circulation (Levin et al., 1993; McMillan, 1984). Low molecular weight heparin improves the local capillary circulation and healing of chronic foot ulcers in diabetic patients (Jörneskog et al., 1993). The mechanisms underlying this effect are not fully understood, but the increase in fibrinolytic activity and the anti-inflammatory and antithrombotic effects of herapin may be important (Jörneskog et al., 1993). Whether low molecular weight heparin can improve wound healing after major amputation is still not known.

Absence of preoperative gangrene

Patients without gangrene or ulceration (i.e. intact skin) just before amputation had an increased risk of healing complications (Eneroth and Persson, 1993). Major amputation when no preoperative ulceration or gangrene was present is thus paradoxically not a good but a bad prognostic factor for healing of the amputation stump. The absence of a demarcation (i.e. ulceration and/or gangrene), may be responsible for the poor clinical judgement in the selection of amputation level in such patients. Based on these findings, it is recommended that a patient with severe rest pain but with intact skin, for whom no vascular operation is possible, should have his/her amputation delayed until a level of demarcation becomes visible. If ischemia is present on the thigh as well, renal failure may develop if one waits too long, and acute amputation should be performed.

Level of amputation

As mentioned earlier, about one fifth of TTAs and KDs and 8% of TFAs had to undergo a revision of reamputation, because of complications with healing (Eneroth, 1997). When comparing the total reoperation rate in relation to the primary amputation level (Table 2) no difference was found between TTAs and KDs (p=0.4), whereas the reoperation rate after TFAs is lower than after TTAs (p<0.0001) and KDs (p<0.0001).

Healing will not occur when the tissue blood flow is insufficient at the attempted level of amputation. Clinical judgement alone cannot adequately predict the likelihood of healing (Dormandy and Ray, 1994), but remains the commonest approach (McCollum and Walker, 1992). The single most readily available test is the Doppler-derived measurement of systolic pressure. Some evidence supports the use of a thigh and/or ankle pressure of 50-70mmHg as a criterion for successful healing after major amputation (Barnes et al., 1976; Dean et al., 1975; Evans et al., 1990; Holstein, 1973; McCollum and Walker, 1992; Pollock et al., 1980; Schwartz et al., 1982), although calcified non-compressible arteries, often found in diabetic patients, give falsely elevated values for thigh and ankle pressures (Gibbons et al., 1979; Raines et al., 1976). Various other tests, such as segmental systolic pressure (Baker et al., 1977; Dean et al. 1975), skin perfusion pressure and/or blood flow (Adera et al., 1995; Dwars et al., 1992; Holloway and Burgess, 1983; Holstein et al., 1979: Karanfilian et al. 1986; Lantsberg and Goldman, 1991; Malone et al., 1981) and TcPo2 (Burgess et al., 1982; Padberg et al., 1996; Wutschert and Bounameaux, 1997; Weiss et al., 1988) have been described as predictors of healing after amputation. Most of these techniques are expensive and difficult to perform correctly, and none has gained wide acceptance (Falstie-Jensen et al., 1989; Sarin et al., 1991; Wagner et al., 1988). The author believes that there will be no "golden standard test" to predict the likelihood of healing after a major amputation, since it is not only the tissue blood flow that is related to wound healing. All other factors, mentioned in this review may also be of importance. The combination of clinical judgement and various tests therefore will be the commonest approach also in the future

Prophylactic antibiotics

Prophylactic antibiotic treatment reduces the frequency of wound infections after major ampufations compared to no prophylaxis at all (Møller and Krebs, 1985; Robbs and Ray, 1982; Sonne-Holm et al., 1985). In a randomised trial, prophylactic treatment with a broad-spectrum antibiotic (cefoxitin) lowered the frequency of infected wounds and reamputations more than placebo treatment (Sonne-Holm et al., 1985). A few other studies have compared various antibiotics (Friis, 1987; Huizinga et al., 1982; Huizinga et al., 1983; Thomsen et al., 1990), and although penicillin G and cefuroxim were equally effective in one study (Friis, 1987), a broad-spectrum antibiotic is often recommended as the treatment of choice (Huizinga et al., 1983; Sonne-Holm et al., 1985; Thomsen et al., 1990). Although these findings are based on small samples there is a general agreement that prophylactic antibiotics should be used as a standard treatment. However, there is no consensus as to which antibiotic to use or the number of treatment days needed.

Surgical technique and experience

Various techniques are used for TTAs and there is some controversy as to which technique has the best healing potential. The long posterior myofascio-cutaneous flap with a short anterior flap (Burgess et al., 1971; Ghormley, 1946), the sagittal technique with mediolateral flaps (Persson, 1974; Tracy, 1966) and the skew flap technique (Robinson et al., 1982) are the most widely used. The sagittal flap technique resulted in better healing than the conventional equal anterior and posterior flaps (Alter et al., 1978; Persson, 1974) and than the long posterior flap technique in diabetics (Falstie-Jensen et al., 1989), while others found no such difference (Holstein 1982; Termansen. 1977). The skew flap technique and the medially-based flap technique (Jain et al., 1995) seem to be as good as those previously described (Harrison et al., 1987; Jain et al., 1995; Ruckley et al., 1991). The various types of operative technique used in TTAs thus seem about equally effective with regard to healing as long as sagittal, skew or long posterior flaps are used.

Not only the surgical technique used is of importance. Falstie-Jensen and Christensen (1990) found that experienced surgeons had a failure rate of 2%, while less experienced surgeons had a failure rate of 29% in a Danish study of major amputations. White et al. (1997) found no difference in healing, but fewer patients whose amputation was performed by a junior trainee could walk with a prosthetic limb than those whose amputation was performed by a senior trainee or a consultant. The authors recommend that a major amputation should always be performed or supervised by an experienced surgeon.

Drains and dressings

A higher incidence of wound infections has been reported in patients with drains in amputation stumps for vascular disease (Berardi and Keonin, l978; Kacy et al., 1982; Tripses and Pollak, 1981). In spite of this, drainage still seems to be a standard treatment in many European countries (Dormandy et al., 1994). The role of drains in avoiding the formation of hematomas in amputation stumps in vascular disease is at most minor and the best prophylaxis for the formation of a hematoma is good operative hemostasis (Tripses and Pollak, 1981).

Soft, semi-rigid or rigid dressings have been used after TTAs in various series (Baker et al., l977; Barber et al., 1983; Burgess and Zettl, 1969; Fylling and Knighton, 1989; MacLean and Fick, 1994; Mooney et al., 1971; Nicholas and DeMuth, 1976). The main advantages of rigid compared to soft dressings often is described as the reduction of pain and stump edema. protection of the stump, prevention of knee flexion contracture and prevention of casual inspection of the wound. However, the literature in this field is scarce. In five comparative studies, a rigid or semi-rigid dressing was preferred to a soft dressing, because of less pain, shorter hospital stay and shorter time to prosthetic fitting (Baker et al., 1977; Barber et al., 1983, Burgess and Zettl, 1969; Condie et al., 1996; MacLean and Fick, 1994). Only one study has noted fewer wound healing problems among patients with a rigid dressing (Mooney et al., 1971).

Discussion

Healing complications and reamputation are very common after major amputations for vascular disease. These complications constitute a major trauma to an already traumatised patient and lead to high costs for society. A number of factors have been related to wound healing complications in patients having a major amputation. However the literature relies mainly on studies evaluating prognostic factors with univariate analysis in small numbers of patients. Thus, since so many factors influence wound healing after amputation, the results can be distorted by a chance imbalance between the groups if univariate analysis is used. Therefore, prognostic factors should be analysed simultaneously. Furthermore, most clinical studies reporting about this are based on clinical characteristics and signs, which are more or less defined. Differences in or absence of definitions make comparisons difficult. There is a great need for uniform definitions to permit comparison results. Pending further prospective, randomised, multicentre studies, using clear-cut definitions and questions, analysing not only variations in management but also taking into consideration other known risk factors, the question at to which parameters are related to healing after a major amputation will remain partly unanswered.

It is likely that a number of factors are of importance and although it may by unrealistic to expect high success rates in elderly amputees with extensive co-morbidities, one must try to promote healing or even postpone amputation by correcting these risk factors and by strict attention to pre- and postoperative management. Achievements in the management of amputees therefore represent not only a challenge to the medical profession, but are of great importance, since the consequences of failed treatment are so serious for both the patient and the community.

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O&P Library > POI > 1999, Vol 23, Num 3 > pp. 195 - 208

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