Nitric oxide production in burns: plasma nitrate levels are not increased in patients with minor thermal injuries.

BACKGROUND: Recent studies have suggested that adults who sustain burns of less than 15% total body surface area display elevated plasma nitrate levels, indicating increased production of nitric oxide. The present study was initiated to confirm whether plasma nitrate is elevated in minor burn injury and, if so, whether it heralds the onset of a systemic inflammatory response to that injury. METHODS: Plasma samples were taken from 98 control and 10 burns patients. RESULTS: The mean plasma nitrate level for nine burns patients with a mean total body surface area burnt of 7.65% (range, 4-15%) was 42.83 micromol/L on day 1. This was not significantly different from that of a control population of 98 preoperative plastic surgery patients: 36.91 micromol/L (p = 0.162). Eight of 10 burns patients showed a decrease in plasma nitrate to 27.47 micromol/L by day 3 (p = 0.046). Elevated nitrate levels were seen in 2 of 10 burns patients. One had concurrent smoke-inhalation injury preceding multiple organ dysfunction, and one was treated with a cream containing cerium nitrate (Flammacerium, Duphar Laboratories, Southhampton, United Kingdom). CONCLUSIONS: For patients who sustain minor burns, plasma levels of nitrate decrease from those of mean normal controls with time unless there is multiple organ dysfunction or the patient receives extraneous nitrate.

Plasma concentrations of tumour necrosis factor-alpha and interleukin-6 during burn wound surgery or dressing.

BACKGROUND: Clinical deterioration after burn wound manipulation may be related to the release of cytokines including tumour necrosis factor-alpha (TNF) and interleukin-6 (IL-6). METHODS: The two cytokines were assayed by immunoenzymetric assay in blood samples taken before and during manipulation of the burn wound. An antibiotic, teicoplanin, was administered to half the patients at the start of the procedure in a randomized fashion as part of a separate trial. FINDINGS: Sixty patients with a median burn size of 8% (range 1-56%) were studied during dressing change (n = 40) or burn excision (n = 20). There was little change in TNF levels between preoperative and recovery samples but IL-6 concentrations increased three-fold, particularly in those with large recent burns or bacteraemia, and were correlated with poor clinical outcome. The presence of teicoplanin did not significantly affect the levels of either cytokine. INTERPRETATION: The systemic cytokine response to burn wound dressing or debridement is predominantly that of IL-6 and it is not significantly reduced by preventing Gram-positive bacteraemia during the procedure.

Randomized placebo-controlled trial of teicoplanin in the antibiotic prophylaxis of infection following manipulation of burn wounds.

BACKGROUND: Burn wound surgery or change of dressings commonly causes bacteraemia. The use of antibiotic prophylaxis has not been tested adequately in a controlled trial. METHODS: A randomized double-blind placebo-controlled study was performed to determine the effect on Gram-positive bacteraemia and clinical outcome of a single dose of teicoplanin (12 mg/kg intravenously) given at burns surgery or change of dressings. RESULTS: A total of 134 patients were entered into the study, representing 220 episodes of dressing or debridement (110 episodes in each group). There was a significant difference between the groups with respect to perioperative Gram-positive bacteraemia: eight episodes (7 per cent) in the teicoplanin group versus 51 (46 per cent) in the placebo group (P < 0.001). However, good clinical outcome was similar in both groups (80 of 110 versus 77 of 110 respectively, P = 0.7). Only eleven patients had bacteraemia caused by Gram-negative species alone. Bacteriological response in terms of wound culture showed no significant difference between the groups: 63 (57 per cent) of 110 episodes versus 58 (53 per cent) of 110 respectively respectively. CONCLUSION: Prevention of Gram-positive bacteraemia did not affect postoperative recovery.

Teicoplanin versus flucloxacillin in the treatment of infection following burns.

Antibiotic treatment of patients developing infection after burns is principally based on experience with other surgical patients. Few comparative trials have been performed in burns patients despite the altered pharmacokinetics of antibiotics and the high incidence of Gram-positive infection in the first week. A randomized trial was performed to compare the cure rates of presumed Gram-positive infection in burns patients given teicoplanin (6 mg/kg every 12 h for three doses then daily) or flucloxacillin (1 g every 6 h i.v./p.o.). Both groups received gentamicin if additional Gram-negative infection was thought likely. A total of 64 patients were entered into the study representing 65 episodes of treatment of which 55 were completed. Clinical success was achieved in 22 (73%) of 30 evaluable patients given teicoplanin and in 21 (68%) of 31 evaluable patients given flucloxacillin (not significant). Of 51 patients assessable for bacteriological efficacy, clearance was achieved in 15 (63%) of 24 patients given teicoplanin and in 15 (56%) of 27 patients given flucloxacillin (not significant). Serum trough concentrations of teicoplanin were 9 mg/L in five patients at the steady state. Adverse events were recorded in 15 (48%) of episodes in the teicoplanin group and in 14 (41%) of episodes in the flucloxacillin group. Teicoplanin demonstrated similar efficacy and safety to flucloxacillin with or without gentamicin.

Quantitative microbiology in the management of burn patients. I. Correlation between quantitative and qualitative burn wound biopsy culture and surface alginate swab culture.

The diagnosis and treatment of burn wound infection is commonly determined by clinical impression and the qualitative results of surface swabs. It has been suggested that quantitative bacteriology from burn wound biopsies confirms burn wound infection and improves patient management. Methods for quantitating surface flora have been described, but comparisons with biopsy specimens have been contradictory. The quantitative and qualitative results of 141 pairs of biopsies and surface swabs, from 74 burn patients, were compared. Staph. aureus was the commonest organism isolated (29 per cent of biopsies and 35 per cent of swabs). Recovery of the same set of species from biopsy and swab occurred in 54 per cent of pairs. There was a significant correlation between the bacterial count obtained by biopsy and by surface swab (P < 0.001), but using various threshold values, the predictive value of the counts obtained by one method to predict the counts obtained by the other was poor. Parallel cultures taken on 18 occasions, showed a significant correlation between bacterial counts obtained from two biopsies or two swabs taken simultaneously (P < 0.002), but there was wide variation in bacterial densities from the same burn wound at the same time. Recovery of the same set of species from both biopsies occurred in 56 per cent of pairs, and from both swabs in 50 per cent of pairs. The use of quantitative microbiology in burns is limited by the unreliability of a single surface swab or biopsy to represent the whole burn wound.

Quantitative microbiology in the management of burn patients. II. Relationship between bacterial counts obtained by burn wound biopsy culture and surface alginate swab culture, with clinical outcome following burn surgery and change of dressings.

The use of quantitative bacteriology in the burns unit has been thought to be efficient in predicting sepsis or graft loss. To examine the relationship between clinical outcome and bacterial densities on and in the burn wound, 69 biopsy/surface swab pairs were collected from 47 patients on 64 occasions, either immediately prior to excision and grafting, or at routine change of dressings. The mean per cent TBSA burn was 16 (range 1-65). There was a significant correlation between log total bacterial count by biopsy with total white cell count and age (P = 0.028), and a significant negative correlation between total bacterial count by swab with per cent TBSA (P = 0.006). There was no significant difference in bacterial counts between patients judged to be a clinical success or clinical failure (72 h follow-up), either after undergoing excision and grafting, or change of dressings, and no difference in counts between patients with perioperative bacteraemia and those without. With burns > 15 per cent TBSA, a relationship between bacterial counts and subsequent sepsis or graft loss still was not demonstrated. It is suggested that quantitative bacteriology by burn wound biopsy or surface swab does not aid the prediction of sepsis or graft loss.

Pharmacokinetics of a single dose of teicoplanin in burn patients.

Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients. This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns. Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%). Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h). Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h). The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration. A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.

Wound management in burn centres in the United Kingdom.

Despite advances in the use of topical and parenteral antimicrobial therapy, and the practice of early tangential excision, infection of the burn wound remains a leading cause of morbidity and mortality. The aim of this study was to survey and compare wound management and antibiotic usage in burn surgery in all UK burn centres. A postal questionnaire was used, followed up by telephone. Answers were obtained from all 39 units treating burns in the UK. A written policy on antibiotic usage was used by 13 centres. Excisions were covered routinely by prophylactic antibiotic therapy in 18 units, and three of these used antibiotic cover during all procedures in which the wound was manipulated. No routine antibiotic cover was given in 21 units. All units obtained surface swab cultures, but only two performed punch biopsy of the wounds. Quantitative bacteriology (counting colony forming units) was employed by three centres. Most units cleaned the burn with saline (17 of 39) or chlorhexidine (eight of 39) but combinations of these and other agents were also used. Nearly half (17 of 37) of those who replied had not seen any cases of proven or suspected toxic shock syndrome in the past 2 years. Four units gave prophylaxis against Staphylococcus aureus, and four gave antibiotics against Streptococcus pyogenes, despite recommendations in the literature. Twenty-nine units gave no prophylaxis. This study has revealed that there is no consensus on antibiotic usage amongst centres treating burns in the UK and that most units rely on surface swab cultures to monitor infection.

The early management of large burns.

The first article in this series (Vol 52 (11), p.583) discussed the pathophysiological processes involved in burn injury. This article describes the early management of large burns, in which treatment is considered in four stages: resuscitation, assessment, further care and transfer. The mnemonic 'RAFT' is suggested as a means of assisting recall of the management process.

Pathophysiological basis of burn management.

Despite increased public awareness of the dangers of fire, burns remain a part of everyday life. Most accident departments will see one or more burn victims each day and, although not common, major burns still occur. In this and a second article we review the pathophysiology of thermal injury and describe the early treatment of a major burn victim.

Neuropeptide-containing nerves in painful hypertrophic human scar tissue.

Specimens of hypertrophic scar tissue (n = 9), non-hypertrophic, flat scar tissue (n = 5) and control skin (n = 3) were obtained from eight adult females (aged 22-56) and three adult males (aged 22-59). The specimens were studied histologically and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, substance P, somatostatin, [Met]enkephalin, [Leu]enkephalin, and the enzyme dopamine beta-hydroxylase. The non-hypertrophic scar tissues were not dissimilar to the control tissue, but contained connective tissue in bundles with a greater number of collagen fibres. In the hypertrophic scar tissue of some patients, the dermis contained adipose tissue displaced upwards from the hypodermis. The connective tissue contained densely packed collagen fibres and fibroblasts; this region was devoid of hair follicles, sweat glands and blood vessels, although they were observed in the region of loosely packed connective tissue. The normal skin contained all the neuropeptides studied, except somatostatin-, and dopamine beta-hydroxylase-immunoreactive nerves, which were seen as single fibres or in nerve bundles, and were associated with blood vessels in the dermis. Neuropeptide Y-immunoreactive nerves were found in the arrector pili muscle, and neuropeptide Y-, vasoactive intestinal polypeptide-, calcitonin gene-related peptide-, [Met]enkephalin- and dopamine beta-hydroxylase-containing nerves were found within sweat glands. In patients with flat, non-hypertrophic scar tissue, neuropeptides and dopamine beta-hydroxylase-containing nerves were absent. In patients with hypertrophic scars, the density of neuropeptide Y-, vasoactive intestinal polypeptide-, substance P-, calcitonin gene-related peptide- and dopamine beta-hydroxylase-immunoreactive nerves was greater in the dermis when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Basaloid squamous carcinoma of the buccal cavity.

Basaloid-squamous carcinoma was first recognized as a separate pathologic entity in 1986. It has been described in the hypopharynx, larynx, base of tongue, and nasal cavity. We report the first case of this rare tumor occurring in the buccal cavity and review the atypical squamous cell carcinomas that occurred in these sites.

The use of streptokinase in replant salvage.

This is the first report of the clinical use of direct intra-arterial streptokinase infusion to promote the salvage of a failing thumb replant. Anastomotic revision was performed on two occasions following thrombosis in the vein grafts used to replant an avulsed thumb. Recurrent thrombosis was treated successfully with conservative thrombolytic therapy consisting of a direct infusion of streptokinase, 20,000 I.U. per hour into the radial artery for 32 hours, followed by intravenous heparin, 40,000 I.U. for 24 hours. The thumb survived, with no tissue loss. Thrombolytic therapy is the only non-surgical means of dissolving intraluminal thrombus, and should be considered when thrombosis occurs in a replanted extremity.