Br. J. Surg. VoI. 62 (1975) 364-372
Diagnosis, clinical course and treatment of acute dermal gangrene I. M c A . LEDINGHAM A N D M . A. TEHRANI* SUMMARY
Twenty patients with acute dermal gangrene jollowing surgery, trauma or sepsis are described. In 12 the skin became gangrenous secondary to a necrotizing process aflecting the subdermal fascia, and in 8 the condition arose primarily in the skin. In the first group mortality was high unless radical excision of the necrotic fascia was performed at an early stage; in 3 of the recent patients the overlying skin was removed, dejatted and stored .for later grafiing. Jn the second group, incision and adequate drainage combined with antibiotics seemed to sufice. Hyperbaric oxygen was of dubious value in the first group but appeared to contribute to arrest of the lesion in the second group.
ACUTEdermal gangrene, although relatively rare in modern surgical practice, can be very alarming. The rarity of the condition not infrequently causes delay in diagnosis and treatment, with the result that the mortality remains high. The multiplicity of terms used to describe variants of the condition further complicates understanding of the clinical problem (Meleney 1933; Crosthwait et al., 1964). With the advent of hyperbaric oxygen therapy, centres possessing hyperbaric facilities have tended to attract patients with various types of dermal gangrene on the basis that hypoxia and infection contribute to the progressive nature of the condition. Over the past 9 years a number of such patients have been referred to the Hyperbaric Unit at the Western Infirmary, Glasgow, and it is the purpose of this paper to present the accumulated clinical experience and to analyse the possible therapeutic implications, including the role of hyperbaric oxygen. The confusing terminology which exists in the current literature prompted the authors to simplify the classification of these conditions into two categories. Thus, the term ‘necrotizing fasciitis’ (Wilson, 1952) has been used to describe a progressive, usually rapid, necrotizing process affecting the subcutaneous fat, the superficial fascia and the superior surface of the deep fascia. The skin is initially intact but becomes gangrenous secondary to interruption of its deep blood supply. ‘Progressive bacterial gangrene’ describes a more slowly progressive lesion affecting the total thickness of skin but not involving deep fascia; pus formation is variable. In the patients of both categories almost all the lesions followed wounds or sepsis of the abdominal wall or perineum, although in some cases there was extensive spread to involve other areas of the body. N o patient in whom bacteriological culture revealed a predominant growth of clostridial organisms was included.
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Patients and methods The period of study extended from 1965 to 1974. Twenty patients were included in the series. Twelve were suffering from necrotizing fasciitis and 8 from progressive bacterial gangrene. Fourteen patients were referred from various parts of the United Kingdom and the remainder were from the surgical units of the Western Infirmary. The bacteriological, haematological and pathological laboratories were extensively used in the investigation and assessment of treatment of these patients. Medical and surgical care varied with the nature of the underlying disease process but most patients received hyperbaric oxygen at some stage of their illness. The general condition of several of the patients was serious enough to necessitate care in the Intensive Therapy Unit of the hospital (after 1967). Prolonged rehabilitation was required in a few of the survivors and it was the usual practice for this phase of the patient’s care to be conducted by the referring clinician. Clinical course, investigations and treatment The principal clinical details are summarized in Table 1 under the headings ‘Necrotizing fasciitis’ and ‘Progressive bacterial gangrene’. Necrotizing fasciitis : This condition followed drainage of ischiorectal sepsis (6 patients), abdominal surgery (2 appendicectomies, 1 closure of perforated duodenal ulcer, 1 Polya gastrectomy), fracture of the pelvis (1 patient) and diabetic peripheral vascular disease (1 patient). The mean age of the patients was 49 years (range 18-73 years). Five of the patients had preexisting systemic disease including diabetes mellitus (2 patients), actinomycosis, rheumatoid arthritis/ steroid therapy and carcinomatosis. The condition sometimes presented with nonspecific redness, swelling and oedema around the primary wound or area of sepsis. I n other instances the first sign was the appearance of cellulitis in an area some distance from the primarily affected region, the latter itself retaining a normal appearance. When incision was not performed at this stage the process became rapidly progressive and small areas of the skin became dusky, then blue with blister formation. Finally, overt gangrene of skin occurred, revealing in due course the characteristic grey, ragged and stringy appearance of the underlying fascia, The fascia1 involvement was always much more extensive than that of the related skin (Fig. 1). The average duration * University Department of Surgery and Division of Surgery, Western Infirmary, Glasgow.
Acute dermal gangrene
__
b
a
Fig. 1. a, Portion of excised apparently normal skin overlying an area affected by necrotizing fasciitis b, Undersurface of the sdme portion of skin showing the extent of fascia1 necrosis
Table I: CLINICAL FEATURES OF ACUTE DERMAL GANGRENE Case no. Age Sex Site involved Predispoqinp factors Necrotizing ,fasciitis I 50
M
Right flank, right lower limb
Actinomycosis in right iliac fossa, Polya gastrectomy Transrectal biopsy of cancer of prostate Appendicectomy (acute appendicitis) Left ischiorectal abscess, diabetes Left ischiorectal abscess, perforated sigmoid diverticulitis Left ischiorectal abscess
2
63
M
3
54
F
4
59
F
5
54
M
6
73
M
7
39
F
Right lower abdomen, upper thighs, penoscrotal Thorax, right flank, perineum Anterior abdominal wall, left buttock Both flanks, perineum, scrotum, both legs, left groin Lower abdominal wall, groin, left buttock, thigh, scrotum Left lower limb
8
67
F
Right flank, right iliac fossa
9
48
M
Left thigh, left leg
10
18
F
Thoraco-abdominal dorsolumbar region
11
44
M
12
18
F
Anterior abdominal wall, perineum Left leg and thigh, left lower abdomen
Progressioe bacterial gangrene 1 78 M Lower abdomen 2 70 F Left leg
Gangrene of left legbelow- knee amputation, diabetes Perforated duodenal ulcer, closure of perforation Left ischiorectal abscess, carcinoma of rectum, liver secondaries Appendicectomy, acute appendicitis Anal fissure, left ischiorectal abscess Fractured pelvis
3
77
F
4
23
F
5
27
M
Abdominal wall, upper right thigh Right lower abdomen, right groin, perineum Left iliac fossa, left buttock
6
50
M
Penoscrotal region
Left orchidectomy Diabetic gangrene, left below-knee amputation Diabetes, fractured neck of femur Lymphopoenia, biopsy of lymph node in right groin Road traffic accident, laceration of left buttock Urethral stricture
7
52
M
Perineum, scrotum
Left ischiorectal abscess
8
38
M
Lower abdomen, left groin
Left ischiorectal abscess, diahetes
Major associated factors Septic shock, respiratory failure, disseminated intravascular coagulation, heptocellular damage Toxaemia Peritonitis, septic shock, respiratory failure Toxaemia, bronchopneumonia Faecal peritonitis, septic shock, respiratory failure, renal failure Toxaemia, congestive cardiac failure Toxaemia, dehydration, respiratory failure Toxaemia, myocardial infarction, rheumatoid arthritis, steroid therapy Peritonitis, septic shock, subphrenic abscess, bronchopneumonia Septic shock, respiratory failure, disseminated intravascular coagulation, caecal fistula Toxaemia Toxaemia, acute pulmonary oedema, disseminated intravascular coagulation Toxaemia Toxaemia, respiratory failure Toxaemia, hypostatic pneumonia, pulmonary embolism, obesity Toxaemia, renal failure Toxaemia Septic shock, respiratory failure, obesity Toxaemia, atherosclerotic heart disease Toxaemia, relapsing pancreatitis
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I. McA. Ledingham and M. A. Tehrani Table 11: TREATMENT AND CLINICAL COURSE OF ACUTE DERMAL GANGRENE Initial response to treatment
Arrest of lesion
Good
No
Good
No
Poor
No
Fair
No
Good
Yes
Good
Yes
Survived
Fair
No
Good
No
Good
Yes
Died (day 30). Overwhelming toxaemia Died (day 18). ? Pulmonary embolism. No post-mortem Died (day 14). Bronchopneumonia
Good
Yes
Survived
Good
Yes
Survived
Good
Yes
Survived
Antibiotics, OHP (7 d)
Good
Yes
Survived
Good
No
Died (day 22). Overwhelming toxaemia
Good
Yes
Good
Yes
Treatment
Case no.
General
Local
1
Antibiotics, i.v. fluids
2
Antibiotics, i.v. fluids
3
Antibiotics, i.v. fluids
4
6
Antibiotics, i.v. fluids, transverse colostomy Antibiotics, i.v. fluids, laparotomy, transverse colostomy Antibiotics, i.v. fluids
7
Antibiotics, i.v. fluids
8
Antibiotics, i.v. fluids
9
Antibiotics, i.v. fluids, colostomy
10
Antibiotics, i.v. fluids, assisted ventilation
II
Antibiotics, i.v. fluids, transverse colostomy
12
Antibiotics, i.v. fluids, transverse colostomy
Multiple incisions, antibiotics, OHP (3 d) Multiple incisions, OHP ( 2 d) Exploration of wound, OHP (3 d) Multiple incisions, OHP (1 d) Multiple incisions, excision of necrotic fascia, OHP (8 d) Multiple incisions, excision of necrotic fascia, OHP (6 d) Desloughing, above-knee amputation, OHP (9 d) Multiple incisions, OHP ( 4 d ) Multiple incisions, excision of necrotic fascia and skin, OHP ( 2 d) Multiple incisions, excision of necrotic fascia and skin, multiple skin grafts Multiple incisions, excision of necrotic fascia and skin, multiple skin grafts Multiple incisions, excision of necrotic fascia and skin, multiple skin gralls
5
Progressice bacterial gangrene 1 Antibiotics, i.v. fluids.
Outcome, cause of death Died (day 4). Pulmonary embolism. No post-mortem Died (day 28). Overwhelming toxaemia. No post-mortem Died (day 16). Bronchopneumonia/ peritonitis Died (24 hours). Aspiration pneumonitis Died (day 17). Renal failure, bronchopneumonia
2
steroids Antibiotics, i.v. fluids
3
Antibiotics, i.v. fluids
Excision of necrotic tissue, above-knee amputation, OHP (3 d) OHP (4 d)
4
Antibiotics, i.v. fluids
Antibiotics, OHP (7 d)
5
Incision
Good
Yes
Excision of necrotic tissue, skin graft
Good
Yes
Survived
7
Antibiotics, i.v. fluids colostomy Antibiotics, i.v. fluids suprapubic cystostomy Antibiotics, i.v. fluids
Died (day 11). Pulmonary embolism Died (day 18). Massive bleeding from oropharynx Survived
Good
Yes
Survived
8
Antibiotics, i.v. fluids
Multiple incisions, excision of necrotic tissue Multiple incisions, excision of necrotic tissue. O H P (5 d )
Good
Yes
Survived
6
OHP, hyperbaric oxygen.
of time between the initiating factor and the first signs involving skin was 1 1 days (range 6-31 days). Coincident with the local features of progressive infection the general condition of the patient deteriorated, and toxaemia, dehydration and mental apathy rapidly ensued. In all 6 patients in whom analysis of plasma proteins was carried out hypo-albuminaemia and hypergamrnaglobulinaemia were found. In 10 of the 12 patients detailed bacteriological analyses were made on specimens obtained through 366
fresh incisions in the affected area. The commonest organisms isolated were coliforms in combination most frequently with enterococci ( 5 ) and streptococci (4); in only one case was the streptococcus of the alpha-haeniolytic variety. Other associated organisms included bacteroides (3), diphtheroids (2), Clostvidium welchii (2), proteus ( 2 ) , staphylococci (1) and Pseudomonaspyocyanea (1). After the initial surgical incisions had been made, bacteriological cultures most regularly revealed a mixed growth of coliforms and proteus or
Acute dermal gangrene
Ps. pyocyanea organisms, although numerous other organisms occurred as single isolates. Because of the frequency and severity of toxaemia and dehydration, treatment aimed at improving the general condition of the patient was often as immediately important as treatment of the local infection. Thus, the administration of intravenous fluids and large doses of the appropriate systemic antibiotics was routine; penicillin o r ampicillin and a broader spectrum antibiotic (usually gentamicin) formed the most frequent combination, although other antibiotics were added as indicated. Colostomy was performed in 5 patients to limit contamination of the infected area with bowel contents (and caecal fistula occurred spontaneously in a sixth). Treatment directed at the infection itself changed during the course of the study (Table 11). In 5 of the earlier patients (Cases 1, 2, 3, 4 and 8) multiple incisions were made in the affected areas and hyperbaric oxygen at 2 atm abs was administered intermittently over a period of 3 days (range 1-4 days). The response t o this combined treatment was initially good in 3 patients, fair in one and poor in another. However, all 5 patients died. Death was sudden in 3 cases (on days 2, 4 and 18) with the clinical features of pulmonary embolism, and gradual in 2 with progressive toxaemia. In 6 of the later patients (Cases 5, 6, 9, 10, 1 1 and 12) radical excision of the necrotic fascia (all 6 patients) and overlying skin (4 patients) was performed; 3 had hyperbaric oxygen. Four of these 6 patients survived. In both the other patients the local necrotic process had been arrested and skin grafting was awaited. One died suddenly following perforation of a sigmoid diverticulum and the second was found at laparotomy to have secondary carcinomatosis. The remaining patient (Cnse 7) was a severe diabetic who showed little or no response to early conservative surgical management and became progressively toxic in spite of later radical surgery including above knee amputation. She died of overwhelming toxaemia on day 30 of her illness. In 3 of the 4 patients (Cases 9, 10 and 12) treated by radical excision of skin overlying the involved area, the skin was preserved for later grafting. An illustrative example of one of these patients is outlined below:
This revealed gross undermining of the skin of a large area of the thoraco-abdominal wall and extensive necrosis of the subcutaneous tissue, although the skin itself appeared normal (Fig. 2). A diagnosis of necrotizing fasciitis with associated endotoxic shock was made. The skin and subcutaneous tissue of the involved part were completely excised (Fig. 3). Numerous bacteriological swabs were taken. The skin was defatted and preserved at 4 ‘C at the Regional Plastic Surgical Centre with a view to future grafting. The patient was transferred from the operating theatre to the Intensive Therapy Unit for subsequent care. In the Intensive Therapy Unit considerable therapeutic, psychiatric and nursing problems were encountered. Frequent blood gas estimations revealed a gradual deterioration in pulmonary gas exchange necessitating the use of intermittent positive pressure ventilation via an endotracheal tube. The patient was dehydrated and acidotic and there was haematological evidence of disseminated intravascular coagulation. Bacteriological cultures from the denuded area revealed a heavy growth of coliform organisms and bacteroides. A caecal fistula developed which did not respond to simple closure. With appropriate treatment the patient gradually improved and on day 16 the endotracheal tube was removed. The initially preserved skin was applied to the denuded area but little of the graft survived. Transfer to the Regional Plastic Surgical Centre was arranged on day 20 and multiple skin grafting was performed. Complete skin cover was achieved in 3 months. The appearance of the grafted areas at 1 year is illustrated in Fig. 4. The caecostomy was finally closed 18 months after the original appendiceetomy.
I n the most recent patient (Case 12) the skin overlying the involved area was completely excised 5 days after the onset of the condition; 80 per cent of this skin survived after grafting 1 week later. Progressiue bacterial gangrene: This form of gangrene followed ischiorectal sepsis (3 patients), lower abdominal surgery (1 orchidectomy and 1 lymph node biopsy), urethral stricture ( I patient), fractured neck of femur (1 patient) and diabetic peripheral vascular disease ( I patient). The mean age of these patients was 52 years (range 23-78 years). Five of the patients had pre-existing systemic disease including diabetes niellitus (3 patients), persistent lymphopoenia and severe atherosclerotic heart disease. In all 8 patients bacteriological cultures were taken from fresh incisions in the affected area. The commonest organisms isolated were coliforms. Other associated organisms included bacteroides (3), C/. welchii (2), haemolytic streptococci (1) and staphylococci (1). The most frequent colonizing organisms were coliforms (4) associated with proteus in 2 patients and Ctrse 10: P. H., an 18-year-old woman, underwent an Ps.pyocynnea and Staphylococcus aureirs in 1 patient emergency appendicectomy for histologically proved acute each. In one of the patients (Case 1) bacteriological appendicitis. Her postoperative recovery was complicated by cultures were consistently negative. continued pyrexia, vomiting and abdominal distension which The condition usually presented with a non-specific was initially treated conservatively with no improvement. At re-exploration 3 days later the wound showed signs of cellucellulitis around the wound o r near the site of sepsis. litis and it was noted that part of the external oblique apo- The abdominal wall lesions soon developed a characneurosis was necrotic. A large purulent pelvic collection was teristic appearance with a central necrotic zone, an encountered. The obviously necrotic portion of fascia was advancing, often serpiginous, purplish zone and a excised, and following evacuation of pus and irrigation of the pelvic cavity with noxytiolin a drain was inserted in the pelvic peripheral erythematous margin fading gradually cavity and the wound closed loosely, leaving a subcutaneous towards normal skin. In the case of penoscrotal lesions drain. Culture from the pus revealed growth of lactoseskin gangrene was rapidly progressive and the purplish fermenting coliform organisms and enterococci sensitive to marginal zone was not obvious. Irrespective of site, gentamicin. In spite of adequate drainage of the pelvic cavity and the whole skin thickness was primarily involved and intravenous administration of the appropriate antibiotics and there was little or n o invasion of subcutaneous tissues. fluids, the patient remained very toxic, with a gradual fall in Unlike necrotizing fasciitis this form of acute dermal urine output and progressive anaemia. Because of lack of gangrene followed the initiating factor without an improvement, further exploration was carried out on day I I . 367
I. McA. Ledingham and M. A. Tehrani
b
a
Fig. 2. Case 10. Relatively normal appearance of abdominal (a) and dorsolumbar ( 6 ) skin on day 11 when radical excision was performed.
b
a
Fig. 3. Case 10. Posterior (a) and anterolateral (b) extent of excision of skin and necrotic fascia.
a Fig. 4. Case 10. Appearance of the grafted posterior (a) and anterolateral (b) area at 1 year.
368
b
Acute dermal gangrene
a
b
Fig. 5. Case 3. a, Lower abdominal wall and pubis showing a gangrenous lesion. b, Distant lesions affecting the upper right thigh showing characteristic purplish advancing margins.
a
b
Fig. 6. Case 1. a, Extensive area of the left abdominal wall involved in a progressive gangrenous lesion. h, Spontaneous epithelization several weeks later.
apparent quiescent interval. The patient’s general condition deteriorated with spread of the local infection but rarely to the same degree of severity as in the patients with necrotizing fasciitis. Hypo-albuminaemia and hypergammaglobulinaemia were marked in 3 of the 4 patients in whom analysis of plasma proteins was performed. Treatment of the patient’s general condition was of major importance and consisted of the administration of intravenous fluids and antibiotics; colostomy and suprapubic cystostomy were performed in 2 of the patients. In 6 of the patients (Cases 2, 3, 5, 6, 7 and 8) it was obvious from the outset that all the layers of the skin were involved, and in these, local treatment consisted of either incision or early excision of necrotic tissue. Three of the most severely ill of these patients received hyperbaric oxygen. The initial response to the combination of treatment was good in all 6 patients although in 1 patient the lesion was not finally arrested. Four survived with complete healing of the skin lesions One patient died suddenly on day 1 1 from pulmonary embolism, and the other, an elderly diabetic, succumbed to progressive overwhelming toxaemia on day 22.
In 2 of the patients (Cases 1 and 4) the condition seemed to be limited clinically to the epidermal layers of skin, and in these, local treatment consisted of non-adherent dressings and hyperbaric oxygen. In both patients the initial response to treatment was good and the local condition was arrested. The younger patient died suddenly on day 18 after massive oropharyngeal bleeding, probably aggravated by severe thrombocytopenia. The older patient survived with spontaneous healing of the affected area. Illustrative examples of 2 of the patients in this group are outlined below. Case 3 : G . H., a 78-year-old woman, was admitted to another hospital with a fracture of the neck of the right femur. At the time of admission the patient was noted to have a small patch of gangrenous skin in the suprapubic region which spread rapidly during the course of the next 2 days with surrounding inflammatory oedema and surgical emphysema. Bacteriological studies revealed heavy growth of coliform and bacteroides organisms. In spite of the administration of appropriate antibiotics, her condition deteriorated. She became toxic and a rapidly spreading cellulitis was noted. Further bacteriological studies revealed a heavy growth of bacteroides, anaerobic streptococci and proteus organisms. At this stage diabetes mellitus was discovered for the first time and treatment with soluble insulin was started. Transfer to the Hyperbaric Unit was arranged on the eighth day by which time there was an extensive area of
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I. McA. Ledingham and M. A. Tehrani necrosis of the lower abdominal wall and upper right thigh (Fig. 5). Hyperbaric oxygen therapy was started at 2.5 atm abs in sessions not exceeding 28 hours continuously. The patient’s condition improved and 48 hours after hyperbaric oxygen therapy it was considered that the progress of the infection had been halted. Over the next 24 hours, however, the improvement was not sustained and the patient died suddenly o n the eleventh day. A post-mortem examination revealed organizing ante-mortem thrombi in the pulmonary arteries. Case 1 : W. W., a 78-year-old man, underwent a left orchidectomy through an inguinal incision for a benign testicular mass. Six days later an ischaemic lesion appeared in the wound. In spite of local treatment the lesion extended over the lower abdomen during the next few days, and at the time of admission to the Western Infirmary (day 22) the greater part of the left lower quadrant of the abdomen was involved (Fig.6u). An incision into the affected area suggested that the deeper layers of the skin and subcutaneous tissues were not involved in the process, but histological examination of biopsy material indicated some spread to deeper layers. The initial bacteriological studies fciled to reveal any growth, an observation which was confirmed on ten subsequent wound cultures. The patient was subjected to an intensive course of hyperbaric oxygen over the next week. In addition, p a r e n t e d and local antibiotics were administered in spite of the negative bacteriological reports. The patient’s progress following this combined therapy wdS satisfactory and gradual spontaneous epithelization occurred over the subsequent weeks (FiK. 66).
Discussion The clinical conditions described in this study readily fell into two categories: one in which skin gangrene succeeded a major infective process in the subcutaneous tissues, and the other in which skin gangrene related directly to infection of the skin.
Necvotizing fasciitis The first of these two clinical conditions was described many years ago (Meleney, 1924), but the term ‘necrotizing fasciitis’ was not used until relatively recently (Wilson, 1952). The term is appropriate since the primary condition is a progressive necrosis of the superficial fascia, subcutaneous fat and superior surface of the deep fascia with death of skin secondary to thrombosis of the subcutaneous blood vessels. Tissues deep to the fascia are not normally involved. The diagnosis of necrotizing fasciitis is not difficult to establish once the characteristic necrotic appearance of the fascia is visualized, but in the early stages the relatively normal appearance of the skin conceals the severity and extent of the underlying disease. The diagnosis can only be confirmed with certainty by immediate exploratory incisions. The condition is readily distinguished from ‘gas gangrene’ which normally occurs in association with penetrating wounds following major trauma and involves, in its florid form, invasion of muscle by clostridia organisms. Crepitus and a ‘mousy’ smelling discharge are characteristic. The patient becomes rapidly toxic and is often restless and delirious. Although the original description of necrotizing fasciitis has survived the passage of time some of the features of the condition appear to have changed. In some, predominantly early, reports (Meleney, 1924, 1933; Wilson, 1952; Strasberg andsilver, 1968)the disease commonly occurred in the extremities, often after minor trauma, whereas in several recent publications 370
(Rea and Wyrick, 1970; Wilson and Haltalin, 1973) the trunk, and in particular the lower abdomen, was the most commonly affected site. The bacteriological pattern appears also to have undergone a change with the passage of time. In Meleney’s (1924) series haemolytic streptococci were exclusively isolated, but later the bacterial flora included haernolytic staphylococci (Wilson, 1952) and various Gram-negative organisms (Crosthwait et al., 1964; Meade and Mueller, 1968; Rea and Wyrick, 1970). I n the present series the bacteriological cultures taken directly from the necrotic fascia through freshly incised wounds revealed a wide variety of organisms. In all but one case haemolytic streptococci were absent. Two factors may have prevented the demonstration of these organisms on bacteriological culture: the early use of antibiotics, including topical applications, prior to consideration of the diagnosis of necrotizing fasciitis, and rapid overgrowth with essentially faecal organisms in wounds predominantly of the lower abdomen and perineum. Nevertheless, it is surprising that only one isolate of haemolytic streptococci was made, and it is possible that while these organisms may be important in initiating the disease process, their presence may not be critical for its subsequent progression. The effect of treatment also appears to have changed over the years. In early reports, incision of the affected area together with frequent antiseptic soaks and careful debridenient of necrotic tissue was attended by excellent results, with the reported mortality as low as 9 per cent (Wilson, 1952). Nowadays such relatively conservative procedures appear less effective unless used at a very early stage, and mortality in some series ranges between 30 and 40 per cent (Crosthwait et al., 1964; Rea and Wyrick, 1970; Wilson and Haltalin, 1973). It is possible that only the most resistant infections are now reported and that infections involving the extremities in young, otherwise healthy individuals respond rapidly to incision, debridement and antibiotics. Infections of the trunk and perineum are more difficult to drain adequately and diagnostic incisions may be delayed in the elderly or very sick patient. On the basis of present experience the best results appear to follow early, multiple and extensive incisions into the affected area with complete excision of the underlying necrotic fascia. Whether the large flaps of skin thus created should simply be reflected or excised and stored is debatable, but if there is any doubt about the adequacy of drainage the latter alternative is preferable and is best done at one operation. This policy was adopted in 4 of the most recent patients and the excised skin later regrafted in 2. The role of hyperbaric oxygen in the treatment of this condition is uncertain. The patient’s general condition normally improved after hyperbaric oxygen but the latter was usually only one of the therapeutic changes introduced on initial referral. Other factors, e.g. alterations in the antibiotic regimen or in intravenous fluid administration, may have played an equally important role. Certainly hyperbaric oxygen did not halt spread of the necrotic process in patients whose skin flaps were not reflected. This pattern of
Acute dermal gangrene response to hyperbaric oxygen was readily distinguishable from that in most patients with ‘gas gangrene’ treated at this centre in whom hyperbaric oxygen combined with simple incision is usually associated with rapid cessation of the primary condition. The patient with the most extensive involvement (Case 10) survived because of the radical nature of the surgical procedure; she did not have hyperbaric oxygen treatment. Present experience would suggest, therefore, that surgical treatment is of prime importance. Whether hyperbaric oxygen adds anything to surgical management remains to be determined. Antibiotics were usually administered early in the course of the illness and appear to have been the appropriate choice in most cases. Like hyperbaric oxygen, however, the role of antibiotics seems to be secondary to radical surgical treatment.
Progressive bacterial gangrene The conditions included under this heading have in the past been considered as separate clinical entities. For example, ‘postoperative progressive synergistic gangrene’ was so called because lesions answering the clinical description of 4 of the patients in the present series (Cases I, 3, 4 and 5) appeared to be caused by a pair of organisms which were more active in combination than alone. Originally the pair most frequently incriminated were a non-haemolytic microaerophilic streptococcus and Staph. aureus (Meleney, 1933), but subsequently several synergistic pairs have been demonstrated, including proteus and Staph. albus (Lyall and Stuart, 1948) and coliforms and Ps. aeruginosa (Webb and Berg, 1966). ‘Fournier’s gangrene’ was the original name attached to lesions similar t o those described in 3 of the patients of the present series (Cases 6, 7 and 8). These gangrenous lesions of the scrotum and penis were considered to be due to invasion by haemolytic streptococcus (Meleney, 1933). ‘Synergistic necrotizing cellulitis’ might well have been the name applied to the final patient of this series (Case 2), in whom widespread invasion of a n amputation stump was attributed to a synergistic combination of aerobic Gram-negative rods and an anaerobic streptococcus, with bacteroides as a frequently associated organism (Stone and Martin, 1972). Recently, the justification for these separate subgroups has been questioned since they are almost certainly at most variants of a single process (Pillsbury et al., 1956; Rook et al., 1972). Examination of the bacteriological pattern reported in the present study does not support the concept that one specific combination of organisms underlies this condition. In only one of the patients, with scrota1 gangrene, did culture reveal haemolytic streptococci ; the majority of the remainder of the series had a mixture of coliform organisms with one of the bacteroides or clostridial family-not an unexpected combination in wounds of the lower abdomen and perineum. Synergism between some of these groups may exist but presumably not more so than in many other wounds similarly infected.
Although there may have been historically valid reasons for separating the subgroups on the grounds of differing therapy, this does not now seem to be necessary. Whereas the earlier literature suggested the need for wide and radical excision of the affected area in the case of so-called ‘progressive synergistic gangrene’, in recent years simple incision and drainage combined with appropriate antibiotics in adequate doses seem to suffice. The use of hyperbaric oxygen in 5 of the 8 patients in the present series appeared to contribute to the arrest of the lesion in all but one. Apparent disappearance of the anaerobic organisms from the wounds may, in part, explain the role of hyperbaric oxygen in this condition.
General comments Both these forms of acute dermal gangrene are relatively rare in modern surgical practice. The advent of antibiotics has presumably helped to reduce the incidence of the condition and there seems little doubt that the cases reported in the current literature represent a group in which infection is only one of the factors involved. Ischaemia and reduced host defence mechanism may be equally important factors. In necrotizing fasciitis the relative avascularity of the fascia1 planes may favour the subcutaneous spread of infection, particularly with anaerobic organisms. A number of the patients had underlying systemic illness to which was added hypoproteinaemia and presumably other deficiencies as the illness progressed. The patient’s ability to resist sustained infection was thus substantially reduced. In progressive bacterial gangrene avascularity of the wound and reduced host defence mechanisms appear to have contributed to the progress of the lesion in some instances, although specific immunological defects were not adequately investigated. Thus, while earlier reports describing acute dermal gangrene stressed the importance and apparent specificity of the invading organisms, it now seems clear that the main problems confronting the surgeon is a vicious cycle of infection, local ischaemia and reduced host defence mechanisms. Which of these factors predominates in the inidividual patient will vary, but it is vital that all three are considered simultaneously if arrest of the progress of these lesions is to be achieved and lives saved. Acknowledgements We gratefully acknowledge the collaboration of the many colleagues, both a t the Western Infirmary, Glasgow, and elsewhere in the United Kingdom, who have referred patients to us. We are also grateful to D r J. D. Sleigh, Consultant Bacteriologist, Western Infirmary, Glasgow, who read and criticized the bacteriological component of the paper. References CROSTHWAlT R. W. jUn., CROSTHWAlT R. W. and JORDAN G. L. jun. (1964) Necrotizing fasciitis.
J. Trauma 4, 148-157.
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I. McA. Ledingham and M. A. Tehrani and STUART R. D. (1948) PrOgeSSiVe postoperative gangrene of the skin. Observations on aetiology and treatment in two cases. Glasg. Med. J . 29, 1-18. MEADE J. w. and MUELLER c. B. (1968) Necrotizing infections of subcutaneous tissues and fascia. A i m Surg. 168, 274-280. MELENEY F. L. (1924) Haemolytic streptococcus gangrene. Arch. Surg. 9, 317-364. MELENEY F. L. (1933) A differential diagnosis between certain types of infectious gangrene of the skin. Surg. Gynecol. Obstet. 56, 847-867. PILLSRURY D. M., SHELLEY w. B. and KLIGMAN A. M. (1956) Dermatology. Philadelphia, Saunders, pp. 492496. REA w. J. and WYRICK w. J. jun. (1970) Necrotizing fasciitis. Ann. Surg. 172, 957-964. LYALL A.
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s. and EBLING F. J. G. (1972) Textbook of Dermatology. Oxford, Blackwell, p. 498. STONE H. H. and MARTIN J. D. jun. (1972) Synergistic necrotizing cellulitis. Ann. Surg. 175, 702-710. STRASBERG S. M. and SILVER M. S. (1968) Haemolytic streptococcus gangrene. 115, 763-768. WEBB R. and BERG E. (1966) Symbiotic gangrene due to Pseudomonas pyocyanea and E. coli. Aust. NZ J. Surg. 36, 159-160. WILSON B. (1952) Necrotizing fasciitis. Am. Surg. 18, 41 6-43 1. WILSON H. D. and HALTALIN K. (1973) Acute necrotizing fasciitis in childhood. Am. J . Dis. Child. 125, 591-595. ROOK A., WILKINSON D.
Diagnosis, clinical course and treatment of acute dermal gangrene I. M c A . LEDINGHAM A N D M . A. TEHRANI* SUMMARY
Twenty patients with acute dermal gangrene jollowing surgery, trauma or sepsis are described. In 12 the skin became gangrenous secondary to a necrotizing process aflecting the subdermal fascia, and in 8 the condition arose primarily in the skin. In the first group mortality was high unless radical excision of the necrotic fascia was performed at an early stage; in 3 of the recent patients the overlying skin was removed, dejatted and stored .for later grafiing. Jn the second group, incision and adequate drainage combined with antibiotics seemed to sufice. Hyperbaric oxygen was of dubious value in the first group but appeared to contribute to arrest of the lesion in the second group.
ACUTEdermal gangrene, although relatively rare in modern surgical practice, can be very alarming. The rarity of the condition not infrequently causes delay in diagnosis and treatment, with the result that the mortality remains high. The multiplicity of terms used to describe variants of the condition further complicates understanding of the clinical problem (Meleney 1933; Crosthwait et al., 1964). With the advent of hyperbaric oxygen therapy, centres possessing hyperbaric facilities have tended to attract patients with various types of dermal gangrene on the basis that hypoxia and infection contribute to the progressive nature of the condition. Over the past 9 years a number of such patients have been referred to the Hyperbaric Unit at the Western Infirmary, Glasgow, and it is the purpose of this paper to present the accumulated clinical experience and to analyse the possible therapeutic implications, including the role of hyperbaric oxygen. The confusing terminology which exists in the current literature prompted the authors to simplify the classification of these conditions into two categories. Thus, the term ‘necrotizing fasciitis’ (Wilson, 1952) has been used to describe a progressive, usually rapid, necrotizing process affecting the subcutaneous fat, the superficial fascia and the superior surface of the deep fascia. The skin is initially intact but becomes gangrenous secondary to interruption of its deep blood supply. ‘Progressive bacterial gangrene’ describes a more slowly progressive lesion affecting the total thickness of skin but not involving deep fascia; pus formation is variable. In the patients of both categories almost all the lesions followed wounds or sepsis of the abdominal wall or perineum, although in some cases there was extensive spread to involve other areas of the body. N o patient in whom bacteriological culture revealed a predominant growth of clostridial organisms was included.
364
Patients and methods The period of study extended from 1965 to 1974. Twenty patients were included in the series. Twelve were suffering from necrotizing fasciitis and 8 from progressive bacterial gangrene. Fourteen patients were referred from various parts of the United Kingdom and the remainder were from the surgical units of the Western Infirmary. The bacteriological, haematological and pathological laboratories were extensively used in the investigation and assessment of treatment of these patients. Medical and surgical care varied with the nature of the underlying disease process but most patients received hyperbaric oxygen at some stage of their illness. The general condition of several of the patients was serious enough to necessitate care in the Intensive Therapy Unit of the hospital (after 1967). Prolonged rehabilitation was required in a few of the survivors and it was the usual practice for this phase of the patient’s care to be conducted by the referring clinician. Clinical course, investigations and treatment The principal clinical details are summarized in Table 1 under the headings ‘Necrotizing fasciitis’ and ‘Progressive bacterial gangrene’. Necrotizing fasciitis : This condition followed drainage of ischiorectal sepsis (6 patients), abdominal surgery (2 appendicectomies, 1 closure of perforated duodenal ulcer, 1 Polya gastrectomy), fracture of the pelvis (1 patient) and diabetic peripheral vascular disease (1 patient). The mean age of the patients was 49 years (range 18-73 years). Five of the patients had preexisting systemic disease including diabetes mellitus (2 patients), actinomycosis, rheumatoid arthritis/ steroid therapy and carcinomatosis. The condition sometimes presented with nonspecific redness, swelling and oedema around the primary wound or area of sepsis. I n other instances the first sign was the appearance of cellulitis in an area some distance from the primarily affected region, the latter itself retaining a normal appearance. When incision was not performed at this stage the process became rapidly progressive and small areas of the skin became dusky, then blue with blister formation. Finally, overt gangrene of skin occurred, revealing in due course the characteristic grey, ragged and stringy appearance of the underlying fascia, The fascia1 involvement was always much more extensive than that of the related skin (Fig. 1). The average duration * University Department of Surgery and Division of Surgery, Western Infirmary, Glasgow.
Acute dermal gangrene
__
b
a
Fig. 1. a, Portion of excised apparently normal skin overlying an area affected by necrotizing fasciitis b, Undersurface of the sdme portion of skin showing the extent of fascia1 necrosis
Table I: CLINICAL FEATURES OF ACUTE DERMAL GANGRENE Case no. Age Sex Site involved Predispoqinp factors Necrotizing ,fasciitis I 50
M
Right flank, right lower limb
Actinomycosis in right iliac fossa, Polya gastrectomy Transrectal biopsy of cancer of prostate Appendicectomy (acute appendicitis) Left ischiorectal abscess, diabetes Left ischiorectal abscess, perforated sigmoid diverticulitis Left ischiorectal abscess
2
63
M
3
54
F
4
59
F
5
54
M
6
73
M
7
39
F
Right lower abdomen, upper thighs, penoscrotal Thorax, right flank, perineum Anterior abdominal wall, left buttock Both flanks, perineum, scrotum, both legs, left groin Lower abdominal wall, groin, left buttock, thigh, scrotum Left lower limb
8
67
F
Right flank, right iliac fossa
9
48
M
Left thigh, left leg
10
18
F
Thoraco-abdominal dorsolumbar region
11
44
M
12
18
F
Anterior abdominal wall, perineum Left leg and thigh, left lower abdomen
Progressioe bacterial gangrene 1 78 M Lower abdomen 2 70 F Left leg
Gangrene of left legbelow- knee amputation, diabetes Perforated duodenal ulcer, closure of perforation Left ischiorectal abscess, carcinoma of rectum, liver secondaries Appendicectomy, acute appendicitis Anal fissure, left ischiorectal abscess Fractured pelvis
3
77
F
4
23
F
5
27
M
Abdominal wall, upper right thigh Right lower abdomen, right groin, perineum Left iliac fossa, left buttock
6
50
M
Penoscrotal region
Left orchidectomy Diabetic gangrene, left below-knee amputation Diabetes, fractured neck of femur Lymphopoenia, biopsy of lymph node in right groin Road traffic accident, laceration of left buttock Urethral stricture
7
52
M
Perineum, scrotum
Left ischiorectal abscess
8
38
M
Lower abdomen, left groin
Left ischiorectal abscess, diahetes
Major associated factors Septic shock, respiratory failure, disseminated intravascular coagulation, heptocellular damage Toxaemia Peritonitis, septic shock, respiratory failure Toxaemia, bronchopneumonia Faecal peritonitis, septic shock, respiratory failure, renal failure Toxaemia, congestive cardiac failure Toxaemia, dehydration, respiratory failure Toxaemia, myocardial infarction, rheumatoid arthritis, steroid therapy Peritonitis, septic shock, subphrenic abscess, bronchopneumonia Septic shock, respiratory failure, disseminated intravascular coagulation, caecal fistula Toxaemia Toxaemia, acute pulmonary oedema, disseminated intravascular coagulation Toxaemia Toxaemia, respiratory failure Toxaemia, hypostatic pneumonia, pulmonary embolism, obesity Toxaemia, renal failure Toxaemia Septic shock, respiratory failure, obesity Toxaemia, atherosclerotic heart disease Toxaemia, relapsing pancreatitis
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I. McA. Ledingham and M. A. Tehrani Table 11: TREATMENT AND CLINICAL COURSE OF ACUTE DERMAL GANGRENE Initial response to treatment
Arrest of lesion
Good
No
Good
No
Poor
No
Fair
No
Good
Yes
Good
Yes
Survived
Fair
No
Good
No
Good
Yes
Died (day 30). Overwhelming toxaemia Died (day 18). ? Pulmonary embolism. No post-mortem Died (day 14). Bronchopneumonia
Good
Yes
Survived
Good
Yes
Survived
Good
Yes
Survived
Antibiotics, OHP (7 d)
Good
Yes
Survived
Good
No
Died (day 22). Overwhelming toxaemia
Good
Yes
Good
Yes
Treatment
Case no.
General
Local
1
Antibiotics, i.v. fluids
2
Antibiotics, i.v. fluids
3
Antibiotics, i.v. fluids
4
6
Antibiotics, i.v. fluids, transverse colostomy Antibiotics, i.v. fluids, laparotomy, transverse colostomy Antibiotics, i.v. fluids
7
Antibiotics, i.v. fluids
8
Antibiotics, i.v. fluids
9
Antibiotics, i.v. fluids, colostomy
10
Antibiotics, i.v. fluids, assisted ventilation
II
Antibiotics, i.v. fluids, transverse colostomy
12
Antibiotics, i.v. fluids, transverse colostomy
Multiple incisions, antibiotics, OHP (3 d) Multiple incisions, OHP ( 2 d) Exploration of wound, OHP (3 d) Multiple incisions, OHP (1 d) Multiple incisions, excision of necrotic fascia, OHP (8 d) Multiple incisions, excision of necrotic fascia, OHP (6 d) Desloughing, above-knee amputation, OHP (9 d) Multiple incisions, OHP ( 4 d ) Multiple incisions, excision of necrotic fascia and skin, OHP ( 2 d) Multiple incisions, excision of necrotic fascia and skin, multiple skin grafts Multiple incisions, excision of necrotic fascia and skin, multiple skin grafts Multiple incisions, excision of necrotic fascia and skin, multiple skin gralls
5
Progressice bacterial gangrene 1 Antibiotics, i.v. fluids.
Outcome, cause of death Died (day 4). Pulmonary embolism. No post-mortem Died (day 28). Overwhelming toxaemia. No post-mortem Died (day 16). Bronchopneumonia/ peritonitis Died (24 hours). Aspiration pneumonitis Died (day 17). Renal failure, bronchopneumonia
2
steroids Antibiotics, i.v. fluids
3
Antibiotics, i.v. fluids
Excision of necrotic tissue, above-knee amputation, OHP (3 d) OHP (4 d)
4
Antibiotics, i.v. fluids
Antibiotics, OHP (7 d)
5
Incision
Good
Yes
Excision of necrotic tissue, skin graft
Good
Yes
Survived
7
Antibiotics, i.v. fluids colostomy Antibiotics, i.v. fluids suprapubic cystostomy Antibiotics, i.v. fluids
Died (day 11). Pulmonary embolism Died (day 18). Massive bleeding from oropharynx Survived
Good
Yes
Survived
8
Antibiotics, i.v. fluids
Multiple incisions, excision of necrotic tissue Multiple incisions, excision of necrotic tissue. O H P (5 d )
Good
Yes
Survived
6
OHP, hyperbaric oxygen.
of time between the initiating factor and the first signs involving skin was 1 1 days (range 6-31 days). Coincident with the local features of progressive infection the general condition of the patient deteriorated, and toxaemia, dehydration and mental apathy rapidly ensued. In all 6 patients in whom analysis of plasma proteins was carried out hypo-albuminaemia and hypergamrnaglobulinaemia were found. In 10 of the 12 patients detailed bacteriological analyses were made on specimens obtained through 366
fresh incisions in the affected area. The commonest organisms isolated were coliforms in combination most frequently with enterococci ( 5 ) and streptococci (4); in only one case was the streptococcus of the alpha-haeniolytic variety. Other associated organisms included bacteroides (3), diphtheroids (2), Clostvidium welchii (2), proteus ( 2 ) , staphylococci (1) and Pseudomonaspyocyanea (1). After the initial surgical incisions had been made, bacteriological cultures most regularly revealed a mixed growth of coliforms and proteus or
Acute dermal gangrene
Ps. pyocyanea organisms, although numerous other organisms occurred as single isolates. Because of the frequency and severity of toxaemia and dehydration, treatment aimed at improving the general condition of the patient was often as immediately important as treatment of the local infection. Thus, the administration of intravenous fluids and large doses of the appropriate systemic antibiotics was routine; penicillin o r ampicillin and a broader spectrum antibiotic (usually gentamicin) formed the most frequent combination, although other antibiotics were added as indicated. Colostomy was performed in 5 patients to limit contamination of the infected area with bowel contents (and caecal fistula occurred spontaneously in a sixth). Treatment directed at the infection itself changed during the course of the study (Table 11). In 5 of the earlier patients (Cases 1, 2, 3, 4 and 8) multiple incisions were made in the affected areas and hyperbaric oxygen at 2 atm abs was administered intermittently over a period of 3 days (range 1-4 days). The response t o this combined treatment was initially good in 3 patients, fair in one and poor in another. However, all 5 patients died. Death was sudden in 3 cases (on days 2, 4 and 18) with the clinical features of pulmonary embolism, and gradual in 2 with progressive toxaemia. In 6 of the later patients (Cases 5, 6, 9, 10, 1 1 and 12) radical excision of the necrotic fascia (all 6 patients) and overlying skin (4 patients) was performed; 3 had hyperbaric oxygen. Four of these 6 patients survived. In both the other patients the local necrotic process had been arrested and skin grafting was awaited. One died suddenly following perforation of a sigmoid diverticulum and the second was found at laparotomy to have secondary carcinomatosis. The remaining patient (Cnse 7) was a severe diabetic who showed little or no response to early conservative surgical management and became progressively toxic in spite of later radical surgery including above knee amputation. She died of overwhelming toxaemia on day 30 of her illness. In 3 of the 4 patients (Cases 9, 10 and 12) treated by radical excision of skin overlying the involved area, the skin was preserved for later grafting. An illustrative example of one of these patients is outlined below:
This revealed gross undermining of the skin of a large area of the thoraco-abdominal wall and extensive necrosis of the subcutaneous tissue, although the skin itself appeared normal (Fig. 2). A diagnosis of necrotizing fasciitis with associated endotoxic shock was made. The skin and subcutaneous tissue of the involved part were completely excised (Fig. 3). Numerous bacteriological swabs were taken. The skin was defatted and preserved at 4 ‘C at the Regional Plastic Surgical Centre with a view to future grafting. The patient was transferred from the operating theatre to the Intensive Therapy Unit for subsequent care. In the Intensive Therapy Unit considerable therapeutic, psychiatric and nursing problems were encountered. Frequent blood gas estimations revealed a gradual deterioration in pulmonary gas exchange necessitating the use of intermittent positive pressure ventilation via an endotracheal tube. The patient was dehydrated and acidotic and there was haematological evidence of disseminated intravascular coagulation. Bacteriological cultures from the denuded area revealed a heavy growth of coliform organisms and bacteroides. A caecal fistula developed which did not respond to simple closure. With appropriate treatment the patient gradually improved and on day 16 the endotracheal tube was removed. The initially preserved skin was applied to the denuded area but little of the graft survived. Transfer to the Regional Plastic Surgical Centre was arranged on day 20 and multiple skin grafting was performed. Complete skin cover was achieved in 3 months. The appearance of the grafted areas at 1 year is illustrated in Fig. 4. The caecostomy was finally closed 18 months after the original appendiceetomy.
I n the most recent patient (Case 12) the skin overlying the involved area was completely excised 5 days after the onset of the condition; 80 per cent of this skin survived after grafting 1 week later. Progressiue bacterial gangrene: This form of gangrene followed ischiorectal sepsis (3 patients), lower abdominal surgery (1 orchidectomy and 1 lymph node biopsy), urethral stricture ( I patient), fractured neck of femur (1 patient) and diabetic peripheral vascular disease ( I patient). The mean age of these patients was 52 years (range 23-78 years). Five of the patients had pre-existing systemic disease including diabetes niellitus (3 patients), persistent lymphopoenia and severe atherosclerotic heart disease. In all 8 patients bacteriological cultures were taken from fresh incisions in the affected area. The commonest organisms isolated were coliforms. Other associated organisms included bacteroides (3), C/. welchii (2), haemolytic streptococci (1) and staphylococci (1). The most frequent colonizing organisms were coliforms (4) associated with proteus in 2 patients and Ctrse 10: P. H., an 18-year-old woman, underwent an Ps.pyocynnea and Staphylococcus aureirs in 1 patient emergency appendicectomy for histologically proved acute each. In one of the patients (Case 1) bacteriological appendicitis. Her postoperative recovery was complicated by cultures were consistently negative. continued pyrexia, vomiting and abdominal distension which The condition usually presented with a non-specific was initially treated conservatively with no improvement. At re-exploration 3 days later the wound showed signs of cellucellulitis around the wound o r near the site of sepsis. litis and it was noted that part of the external oblique apo- The abdominal wall lesions soon developed a characneurosis was necrotic. A large purulent pelvic collection was teristic appearance with a central necrotic zone, an encountered. The obviously necrotic portion of fascia was advancing, often serpiginous, purplish zone and a excised, and following evacuation of pus and irrigation of the pelvic cavity with noxytiolin a drain was inserted in the pelvic peripheral erythematous margin fading gradually cavity and the wound closed loosely, leaving a subcutaneous towards normal skin. In the case of penoscrotal lesions drain. Culture from the pus revealed growth of lactoseskin gangrene was rapidly progressive and the purplish fermenting coliform organisms and enterococci sensitive to marginal zone was not obvious. Irrespective of site, gentamicin. In spite of adequate drainage of the pelvic cavity and the whole skin thickness was primarily involved and intravenous administration of the appropriate antibiotics and there was little or n o invasion of subcutaneous tissues. fluids, the patient remained very toxic, with a gradual fall in Unlike necrotizing fasciitis this form of acute dermal urine output and progressive anaemia. Because of lack of gangrene followed the initiating factor without an improvement, further exploration was carried out on day I I . 367
I. McA. Ledingham and M. A. Tehrani
b
a
Fig. 2. Case 10. Relatively normal appearance of abdominal (a) and dorsolumbar ( 6 ) skin on day 11 when radical excision was performed.
b
a
Fig. 3. Case 10. Posterior (a) and anterolateral (b) extent of excision of skin and necrotic fascia.
a Fig. 4. Case 10. Appearance of the grafted posterior (a) and anterolateral (b) area at 1 year.
368
b
Acute dermal gangrene
a
b
Fig. 5. Case 3. a, Lower abdominal wall and pubis showing a gangrenous lesion. b, Distant lesions affecting the upper right thigh showing characteristic purplish advancing margins.
a
b
Fig. 6. Case 1. a, Extensive area of the left abdominal wall involved in a progressive gangrenous lesion. h, Spontaneous epithelization several weeks later.
apparent quiescent interval. The patient’s general condition deteriorated with spread of the local infection but rarely to the same degree of severity as in the patients with necrotizing fasciitis. Hypo-albuminaemia and hypergammaglobulinaemia were marked in 3 of the 4 patients in whom analysis of plasma proteins was performed. Treatment of the patient’s general condition was of major importance and consisted of the administration of intravenous fluids and antibiotics; colostomy and suprapubic cystostomy were performed in 2 of the patients. In 6 of the patients (Cases 2, 3, 5, 6, 7 and 8) it was obvious from the outset that all the layers of the skin were involved, and in these, local treatment consisted of either incision or early excision of necrotic tissue. Three of the most severely ill of these patients received hyperbaric oxygen. The initial response to the combination of treatment was good in all 6 patients although in 1 patient the lesion was not finally arrested. Four survived with complete healing of the skin lesions One patient died suddenly on day 1 1 from pulmonary embolism, and the other, an elderly diabetic, succumbed to progressive overwhelming toxaemia on day 22.
In 2 of the patients (Cases 1 and 4) the condition seemed to be limited clinically to the epidermal layers of skin, and in these, local treatment consisted of non-adherent dressings and hyperbaric oxygen. In both patients the initial response to treatment was good and the local condition was arrested. The younger patient died suddenly on day 18 after massive oropharyngeal bleeding, probably aggravated by severe thrombocytopenia. The older patient survived with spontaneous healing of the affected area. Illustrative examples of 2 of the patients in this group are outlined below. Case 3 : G . H., a 78-year-old woman, was admitted to another hospital with a fracture of the neck of the right femur. At the time of admission the patient was noted to have a small patch of gangrenous skin in the suprapubic region which spread rapidly during the course of the next 2 days with surrounding inflammatory oedema and surgical emphysema. Bacteriological studies revealed heavy growth of coliform and bacteroides organisms. In spite of the administration of appropriate antibiotics, her condition deteriorated. She became toxic and a rapidly spreading cellulitis was noted. Further bacteriological studies revealed a heavy growth of bacteroides, anaerobic streptococci and proteus organisms. At this stage diabetes mellitus was discovered for the first time and treatment with soluble insulin was started. Transfer to the Hyperbaric Unit was arranged on the eighth day by which time there was an extensive area of
369
I. McA. Ledingham and M. A. Tehrani necrosis of the lower abdominal wall and upper right thigh (Fig. 5). Hyperbaric oxygen therapy was started at 2.5 atm abs in sessions not exceeding 28 hours continuously. The patient’s condition improved and 48 hours after hyperbaric oxygen therapy it was considered that the progress of the infection had been halted. Over the next 24 hours, however, the improvement was not sustained and the patient died suddenly o n the eleventh day. A post-mortem examination revealed organizing ante-mortem thrombi in the pulmonary arteries. Case 1 : W. W., a 78-year-old man, underwent a left orchidectomy through an inguinal incision for a benign testicular mass. Six days later an ischaemic lesion appeared in the wound. In spite of local treatment the lesion extended over the lower abdomen during the next few days, and at the time of admission to the Western Infirmary (day 22) the greater part of the left lower quadrant of the abdomen was involved (Fig.6u). An incision into the affected area suggested that the deeper layers of the skin and subcutaneous tissues were not involved in the process, but histological examination of biopsy material indicated some spread to deeper layers. The initial bacteriological studies fciled to reveal any growth, an observation which was confirmed on ten subsequent wound cultures. The patient was subjected to an intensive course of hyperbaric oxygen over the next week. In addition, p a r e n t e d and local antibiotics were administered in spite of the negative bacteriological reports. The patient’s progress following this combined therapy wdS satisfactory and gradual spontaneous epithelization occurred over the subsequent weeks (FiK. 66).
Discussion The clinical conditions described in this study readily fell into two categories: one in which skin gangrene succeeded a major infective process in the subcutaneous tissues, and the other in which skin gangrene related directly to infection of the skin.
Necvotizing fasciitis The first of these two clinical conditions was described many years ago (Meleney, 1924), but the term ‘necrotizing fasciitis’ was not used until relatively recently (Wilson, 1952). The term is appropriate since the primary condition is a progressive necrosis of the superficial fascia, subcutaneous fat and superior surface of the deep fascia with death of skin secondary to thrombosis of the subcutaneous blood vessels. Tissues deep to the fascia are not normally involved. The diagnosis of necrotizing fasciitis is not difficult to establish once the characteristic necrotic appearance of the fascia is visualized, but in the early stages the relatively normal appearance of the skin conceals the severity and extent of the underlying disease. The diagnosis can only be confirmed with certainty by immediate exploratory incisions. The condition is readily distinguished from ‘gas gangrene’ which normally occurs in association with penetrating wounds following major trauma and involves, in its florid form, invasion of muscle by clostridia organisms. Crepitus and a ‘mousy’ smelling discharge are characteristic. The patient becomes rapidly toxic and is often restless and delirious. Although the original description of necrotizing fasciitis has survived the passage of time some of the features of the condition appear to have changed. In some, predominantly early, reports (Meleney, 1924, 1933; Wilson, 1952; Strasberg andsilver, 1968)the disease commonly occurred in the extremities, often after minor trauma, whereas in several recent publications 370
(Rea and Wyrick, 1970; Wilson and Haltalin, 1973) the trunk, and in particular the lower abdomen, was the most commonly affected site. The bacteriological pattern appears also to have undergone a change with the passage of time. In Meleney’s (1924) series haemolytic streptococci were exclusively isolated, but later the bacterial flora included haernolytic staphylococci (Wilson, 1952) and various Gram-negative organisms (Crosthwait et al., 1964; Meade and Mueller, 1968; Rea and Wyrick, 1970). I n the present series the bacteriological cultures taken directly from the necrotic fascia through freshly incised wounds revealed a wide variety of organisms. In all but one case haemolytic streptococci were absent. Two factors may have prevented the demonstration of these organisms on bacteriological culture: the early use of antibiotics, including topical applications, prior to consideration of the diagnosis of necrotizing fasciitis, and rapid overgrowth with essentially faecal organisms in wounds predominantly of the lower abdomen and perineum. Nevertheless, it is surprising that only one isolate of haemolytic streptococci was made, and it is possible that while these organisms may be important in initiating the disease process, their presence may not be critical for its subsequent progression. The effect of treatment also appears to have changed over the years. In early reports, incision of the affected area together with frequent antiseptic soaks and careful debridenient of necrotic tissue was attended by excellent results, with the reported mortality as low as 9 per cent (Wilson, 1952). Nowadays such relatively conservative procedures appear less effective unless used at a very early stage, and mortality in some series ranges between 30 and 40 per cent (Crosthwait et al., 1964; Rea and Wyrick, 1970; Wilson and Haltalin, 1973). It is possible that only the most resistant infections are now reported and that infections involving the extremities in young, otherwise healthy individuals respond rapidly to incision, debridement and antibiotics. Infections of the trunk and perineum are more difficult to drain adequately and diagnostic incisions may be delayed in the elderly or very sick patient. On the basis of present experience the best results appear to follow early, multiple and extensive incisions into the affected area with complete excision of the underlying necrotic fascia. Whether the large flaps of skin thus created should simply be reflected or excised and stored is debatable, but if there is any doubt about the adequacy of drainage the latter alternative is preferable and is best done at one operation. This policy was adopted in 4 of the most recent patients and the excised skin later regrafted in 2. The role of hyperbaric oxygen in the treatment of this condition is uncertain. The patient’s general condition normally improved after hyperbaric oxygen but the latter was usually only one of the therapeutic changes introduced on initial referral. Other factors, e.g. alterations in the antibiotic regimen or in intravenous fluid administration, may have played an equally important role. Certainly hyperbaric oxygen did not halt spread of the necrotic process in patients whose skin flaps were not reflected. This pattern of
Acute dermal gangrene response to hyperbaric oxygen was readily distinguishable from that in most patients with ‘gas gangrene’ treated at this centre in whom hyperbaric oxygen combined with simple incision is usually associated with rapid cessation of the primary condition. The patient with the most extensive involvement (Case 10) survived because of the radical nature of the surgical procedure; she did not have hyperbaric oxygen treatment. Present experience would suggest, therefore, that surgical treatment is of prime importance. Whether hyperbaric oxygen adds anything to surgical management remains to be determined. Antibiotics were usually administered early in the course of the illness and appear to have been the appropriate choice in most cases. Like hyperbaric oxygen, however, the role of antibiotics seems to be secondary to radical surgical treatment.
Progressive bacterial gangrene The conditions included under this heading have in the past been considered as separate clinical entities. For example, ‘postoperative progressive synergistic gangrene’ was so called because lesions answering the clinical description of 4 of the patients in the present series (Cases I, 3, 4 and 5) appeared to be caused by a pair of organisms which were more active in combination than alone. Originally the pair most frequently incriminated were a non-haemolytic microaerophilic streptococcus and Staph. aureus (Meleney, 1933), but subsequently several synergistic pairs have been demonstrated, including proteus and Staph. albus (Lyall and Stuart, 1948) and coliforms and Ps. aeruginosa (Webb and Berg, 1966). ‘Fournier’s gangrene’ was the original name attached to lesions similar t o those described in 3 of the patients of the present series (Cases 6, 7 and 8). These gangrenous lesions of the scrotum and penis were considered to be due to invasion by haemolytic streptococcus (Meleney, 1933). ‘Synergistic necrotizing cellulitis’ might well have been the name applied to the final patient of this series (Case 2), in whom widespread invasion of a n amputation stump was attributed to a synergistic combination of aerobic Gram-negative rods and an anaerobic streptococcus, with bacteroides as a frequently associated organism (Stone and Martin, 1972). Recently, the justification for these separate subgroups has been questioned since they are almost certainly at most variants of a single process (Pillsbury et al., 1956; Rook et al., 1972). Examination of the bacteriological pattern reported in the present study does not support the concept that one specific combination of organisms underlies this condition. In only one of the patients, with scrota1 gangrene, did culture reveal haemolytic streptococci ; the majority of the remainder of the series had a mixture of coliform organisms with one of the bacteroides or clostridial family-not an unexpected combination in wounds of the lower abdomen and perineum. Synergism between some of these groups may exist but presumably not more so than in many other wounds similarly infected.
Although there may have been historically valid reasons for separating the subgroups on the grounds of differing therapy, this does not now seem to be necessary. Whereas the earlier literature suggested the need for wide and radical excision of the affected area in the case of so-called ‘progressive synergistic gangrene’, in recent years simple incision and drainage combined with appropriate antibiotics in adequate doses seem to suffice. The use of hyperbaric oxygen in 5 of the 8 patients in the present series appeared to contribute to the arrest of the lesion in all but one. Apparent disappearance of the anaerobic organisms from the wounds may, in part, explain the role of hyperbaric oxygen in this condition.
General comments Both these forms of acute dermal gangrene are relatively rare in modern surgical practice. The advent of antibiotics has presumably helped to reduce the incidence of the condition and there seems little doubt that the cases reported in the current literature represent a group in which infection is only one of the factors involved. Ischaemia and reduced host defence mechanism may be equally important factors. In necrotizing fasciitis the relative avascularity of the fascia1 planes may favour the subcutaneous spread of infection, particularly with anaerobic organisms. A number of the patients had underlying systemic illness to which was added hypoproteinaemia and presumably other deficiencies as the illness progressed. The patient’s ability to resist sustained infection was thus substantially reduced. In progressive bacterial gangrene avascularity of the wound and reduced host defence mechanisms appear to have contributed to the progress of the lesion in some instances, although specific immunological defects were not adequately investigated. Thus, while earlier reports describing acute dermal gangrene stressed the importance and apparent specificity of the invading organisms, it now seems clear that the main problems confronting the surgeon is a vicious cycle of infection, local ischaemia and reduced host defence mechanisms. Which of these factors predominates in the inidividual patient will vary, but it is vital that all three are considered simultaneously if arrest of the progress of these lesions is to be achieved and lives saved. Acknowledgements We gratefully acknowledge the collaboration of the many colleagues, both a t the Western Infirmary, Glasgow, and elsewhere in the United Kingdom, who have referred patients to us. We are also grateful to D r J. D. Sleigh, Consultant Bacteriologist, Western Infirmary, Glasgow, who read and criticized the bacteriological component of the paper. References CROSTHWAlT R. W. jUn., CROSTHWAlT R. W. and JORDAN G. L. jun. (1964) Necrotizing fasciitis.
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I. McA. Ledingham and M. A. Tehrani and STUART R. D. (1948) PrOgeSSiVe postoperative gangrene of the skin. Observations on aetiology and treatment in two cases. Glasg. Med. J . 29, 1-18. MEADE J. w. and MUELLER c. B. (1968) Necrotizing infections of subcutaneous tissues and fascia. A i m Surg. 168, 274-280. MELENEY F. L. (1924) Haemolytic streptococcus gangrene. Arch. Surg. 9, 317-364. MELENEY F. L. (1933) A differential diagnosis between certain types of infectious gangrene of the skin. Surg. Gynecol. Obstet. 56, 847-867. PILLSRURY D. M., SHELLEY w. B. and KLIGMAN A. M. (1956) Dermatology. Philadelphia, Saunders, pp. 492496. REA w. J. and WYRICK w. J. jun. (1970) Necrotizing fasciitis. Ann. Surg. 172, 957-964. LYALL A.
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s. and EBLING F. J. G. (1972) Textbook of Dermatology. Oxford, Blackwell, p. 498. STONE H. H. and MARTIN J. D. jun. (1972) Synergistic necrotizing cellulitis. Ann. Surg. 175, 702-710. STRASBERG S. M. and SILVER M. S. (1968) Haemolytic streptococcus gangrene. 115, 763-768. WEBB R. and BERG E. (1966) Symbiotic gangrene due to Pseudomonas pyocyanea and E. coli. Aust. NZ J. Surg. 36, 159-160. WILSON B. (1952) Necrotizing fasciitis. Am. Surg. 18, 41 6-43 1. WILSON H. D. and HALTALIN K. (1973) Acute necrotizing fasciitis in childhood. Am. J . Dis. Child. 125, 591-595. ROOK A., WILKINSON D.
