[Respiratory dysfunction in burned patients]. / Lésions respiratoires et brûlures.

INTRODUCTION: Smoke inhalation and respiratory complications are still the major causes of mortality in severely burned patients. STATE OF THE ART: The diagnosis is suspected clinically on the basis of history and physical examination and can be confirmed bronchoscopically. Respiratory failure in burned patients occurs through a number of associated mechanisms. Pneumonitis and adult respiratory distress syndrome (ARDS) are common early complications. New pulmonary treatments and advances in ventilation have reduced the incidence of both barotrauma and infectious complications. Tracheal stenosis can occur as a late complication of prolonged mechanical ventilation. PERSPECTIVES: Clinical and experimental studies have shown that damage to the mucosal barrier and the release of inflammatory mediators are the most important pathophysiological events following smoke inhalation. Manipulation of the inflammatory response following inhalation may be a treatment option in the distant future. CONCLUSION: Inhalation injury occurring in burned patients can produce severe respiratory and systemic complications.

[Inflammatory reaction and infection in severe burns]. / Réaction inflammatoire et infection chez le brûlé grave.

Major burn injury is a lesion where the inflammatory reaction is exported to the whole body. After a short time of hemodynamic changes, this inflammation is kept by necrotic tissues, persistence of an opened wound, and by the pulmonary and gut reactions. When infection starts, it becomes difficult to distinguish its symptoms among the inflammatory signals. The main point of the care of burn patient consists in trying to control this reaction and the immuno-depression it leads to: early excision and grafts, early enteral nutrition, perfect nursing care. There is no specific medical treatment of this state. The antibiotic use must be well weighed up. Infection is often the trigger of the multiple organ dysfunction which is the way the burn patient dies but is not mandatory.

Ornithine alpha-ketoglutarate improves wound healing in severe burn patients: a prospective randomized double-blind trial versus isonitrogenous controls.

OBJECTIVE: To compare the effectiveness on wound healing time in severe burn patients of ornithine alpha-ketoglutarate supplementation of enteral feeding vs. an isonitrogenous control. Previous clinical and experimental studies suggest a beneficial effect of enterally administered ornithine alpha-ketoglutarate supplementation on protein metabolism in burn patients, but few data deal with clinical outcome. DESIGN: Prospective double-blind randomized trial. SETTING: Burn treatment center of an army hospital. PATIENTS: Forty-seven severe burn patients with total burned body surface areas of 25% to 95% and presence of full thickness burn who were prescribed early exclusive enteral nutrition. Either ornithine alpha-ketoglutarate or isonitrogenous control (soy protein mixture, Protil-1) were administered twice a day as a bolus (2 x 10 g) at 9 am and 9 pm for 3 wks. The patients were evaluated for wound healing time (primary end point), antibiotic use, tolerance, duration of enteral nutrition, and nutritional status. INTERVENTIONS: Serial blood samples were collected in each patient for determination of serum transthyretin and plasma phenylalanine, and urine sampling was performed for determination of 3-methylhistidine excretion at day 4 and day 21 after burn injury. MEASUREMENTS AND MAIN RESULTS: Wound healing times in patients receiving ornithine alpha-ketoglutarate or Protil-1 were 60 +/- 7 and 90 +/- 12 days, respectively (p < .05) for similar grafted surfaces. Based on increased serum transthyretin concentrations, both groups showed an improvement of nutritional status at day 21 after burn. Taking a cut-off value of 110 unit burn standard for severity of injury, plasma phenylalanine concentrations, and urinary 3-methylhistidine/creatinine ratio were significantly reduced (p < .05) in the less severe burn patients (<110 unit burn standard) supplemented with ornithine alpha-ketoglutarate. CONCLUSIONS: Ornithine alpha-ketoglutarate supplementation of enteral feeding significantly shortens wound healing time in severe burn patients. In addition, ornithine alpha-ketoglutarate administration was safe and well tolerated and decreased protein hypercatabolism in the less severe burn patients.

Cultured epithelial autografts in extensive burn coverage of severely traumatized patients: a five year single-center experience with 30 patients.

OBJECTIVE: We report recent five-year experience in a large, single center series of severely burned and otherwise traumatized patients given cultured epithelial autografts (CEA) from a single commercial laboratory. SUMMARY BACKGROUND DATA: Initial optimism over CEA application has been tempered by subsequent reports asserting that this modality is unreliable and expensive. Discussion continues over its clinical role. METHODS: From 1991 to 1996, CEA were applied to a mean 37+/-17% of total body surface area (TBSA) of 30 patients. These patients had 78+/-10% average burn size, 65+/-16% average third-degree burn size, 90% prevalence of endoscopically confirmed inhalation injury and 37% prevalence of other serious conditions. RESULTS: CEA achieved permanent coverage of a mean 26+/-15% of TBSA, an area greater than that covered by conventional autografts (a mean 25+/-10% of TBSA). Survival was 90% in these severely burned and otherwise traumatized patients. Final CEA take was a mean 69+/-23%. In subset analyses, only younger age was significantly associated with better CEA take (p = 0.0001 in univariate analysis, p<0.04 in multivariate analysis, Student's t-test). CONCLUSIONS: Epicel CEA successfully provided extensive, permanent burn coverage in severely traumatized patients, proving an important adjunct to achievement of a high survival rate in a patient population whose prognosis previously had been poor. In our experience CEA appear to have a very high beneficial value in the management of bur ns >60% TBSA. In some cases studied it is very likely that CEA was a life-saving treatment.

[Ambulatory treatment of burns in children]. / Traitement ambulatoire des brûlures de l'enfant.

A majority of burns in children may have an ambulatory management for which the paediatrician has an important role. He must assess the severity of the burn by quoting extent, depth and localization of the burn injuries and then send the most severe to a specialized burn centre. The circumstances and the social situation are important in the decision of either hospitalization or ambulatory care, remembering that the burn may correspond to child abuse. The treatment consists of initially refreshing the burn to limit the extension, then washing the lesions using topical antiseptic soap, finally applying standard silver sulfadiazine cream. Local care is accomplished daily the first few days, then every three days to follow the healing and to keep a watch on possible complications such as infections or failure to heal, which must be treated in burn units. Pain relief treatment is an important part of the management.

[Pharmacokinetics of fusidic acid in patients with seriously infected burns]. / Pharmacocinétique de l'acide fusidique administré au sujet gravement brûlé infecté.

The pharmacokinetics of fusidic acid (FA) were studied in 10 infected severe burns patients (35 +/- 5 yrs, 81 +/- 17 kg) i.e. 43 +/- 10% in 3rd degree. Treatment was given at the dose of 500 mg/8 hours (2-hour infusion). The kinetics of FA were evaluated on D1 (1st infusion) and at steady state on D4 (10th infusion), each sequence involving 9 whole blood samples. Samples were assayed by high-performance liquid chromatography. Data were analysed by a non-compartmental method. Mean duration of treatment, considered effective in all cases, was 5.9 +/- 2.1 days. The systemic safety of FA was felt to be good. Kinetic analysis revealed the existence of significant differences between D1 and D4 concerning the parameters Cmax, Cmin, AUC, Cl and Vss. These events are attributable to the non-linear nature of the human kinetics of FA. Accumulation ratios R1 and R2 did not differ i.e. 1.51 +/- 0.25 and R2 = 2.44 +/- 0.68. Kinetic modelling based upon the experimental tracing obtained on D1 revealed good coincidence of the predictive tracing in relation to data determined on D4. The dosage algorithm of 500 mg/8 hours was microbiologically satisfactory with Cmin measured on D1 and at steady state constantly greater than the MIC of the main organisms concerned (< to 2 micrograms/ml). Reduction in the parameters Cmax and AUC in comparison with a group of healthy subjects ultimately led to shortening of the mean T1/2 of FA. In the absence of impaired liver function, this is attributable to the known increase in hepatic clearances in burns patients and, to a certain extent, to the existence of translesional extra-hepatic clearance, which could contribute to the success of treatment.

Evolution and significance of circulating procalcitonin levels compared with IL-6, TNF alpha and endotoxin levels early after thermal injury.

To determine the evolution and significance of circulating procalcitonin (ProCT), IL-6 TNF alpha and endotoxin levels early after thermal injury, we performed a prospective, single unit, longitudinal study. Forty burn patients with total body surface area (TBSA) > 30 per cent were studied, of whom 33 suffered an inhalation injury. Blood samples were taken on the day of admission, every 4 h during the first day and daily during the first week. All patients had increased ProCT and IL-6 levels without any proven infection. Endotoxin and TNF alpha levels remained very low or undetectable. ProCT and IL-levels correlated well with the severity of skin burn injury (respectively, p < 0.006 and p < 0.028, using the non-parametric Kruskal-Wallis test). ProCT levels are not associated with smoke inhalation. ProCT and IL6 are prognostic factors of mortality at the time of admission but less reliable than the clinical UBS (unit burn standard) score. Endotoxin and TNF alpha were undetectable, suggesting that the problem of the early gut bacterial translocation remains to be proven.

[Therapeutic monitoring of teicoplanin in a severely burned patient]. / Suivi thérapeutique de la teicoplanine chez un sujet gravement brûlé.

The authors report the study of the kinetics in serum and urine and the clinical safety of a high dose of teicoplanin administered in a 19 year-old patient with major burns (60% of body surface area, the half of which consisting of third-degree burns and UBS at 150) and S aureus meticillin-resistant infection. At day 1, he was given two loading infusions of 12 mg.kg-1 teicoplanin followed by 12 mg.kg-1 per day of treatment. At all times, Cmin concentrations were below the limit value of 8 mg.mL-1. Therefore the therapeutic regimen was increased on several occasions. On days 5, 8 and 15, Cmin were measured by FPIA. Pharmacokinetic analysis was performed at day 16, (i.e., 20 mg.kg-1) and urine was also collected over at least 12 hours. At day 16, serum and urine samples were assayed by HPLC. Data were analyzed with a noncompartmental method. The duration of treatment was 20 days and no adverse events were noted. Bacteriological tests performed at the end of treatment demonstrated the elimination of the agent responsible over the infection. While pharmacokinetics were not assessed at plateau, Cmin remained very low. Vss was similar to values obtained in healthy subjects while total clearance was increased. This phenomenon was explained by the increase of total clearance and a nonrenal translesional diffusion suggested by the body surface area affected by third-degree burns. Finally, the cost of increasing doses of teicoplanin must be taken in account.

[Objectives, results and future prospects of burn treatment in 1997]. / Objectifs, résultats et perspectives du traitement des brûlés en 1997.

When burn injuries to the skin are extensive, delays in wound closure contribute to multiple organ failure because the availability of donor sites does not allow early and permanent coverage of excised wounds. From 1991 to 1996, 30 patients with a mean burn size of 78% total body surface area (65% full-thickness) underwent skin grafting with autologous cultured epidermis (AEC) performed in the labs of Genzyme Tissue Repair Company. Twenty three were adults and seven children under 15 (mean age 29, range 2.5 to 70); 27 suffered inhalation injury; 3 presented with multiple trauma and 2 with blast injury. As soon as possible wound beds were excised and temporarily covered with allografts or with sandwich or meshed autografts; the mean surface covered with autografts was 28 +/- 12%. Keratinocytes grafts were applied to a mean of 37 +/- 16.5%, an average of 210 grafts of 25 to 30 cm2. Three patients died respectively at day 67, 81 and 90. At time of gaze backing removal, the mean percentage of culture engraftment was 69% (range 25 to 95); this engraftment was higher for children (74%) and very bad above 60 (25%). The mean length of hospitalisation was 114 +/- 30 days. The definitive coverage by AEC was evaluated through the percentage of secondary autografted area: 10 +/- 9.5% (range 0 to 46). The average cost by patient was 98,500$ or 16$ by cm2 of culture. The weakness of epithelialisation makes essential a dermal support to the keratinocytes cultures, allodermis is now currently used, perhaps the new skin substitutes will give the ideal missing piece.

Clinical pharmacokinetics of piperacillin-tazobactam combination in patients with major burns and signs of infection.

The pathophysiology associated with major burns is complex and subject to a state of flux. The combination of beta-lactamase inhibitors with powerful penicillins is an interesting and an attractive potential solution to the emergence of bacterial resistance. The kinetics in serum and urine and the clinical safety of a fixed combination of 4 g of piperacillin (PPR) and 0.5 g of tazobactam (TZB) were studied in 10 patients (22 to 50 years old and weighing 45 to 105 kg) with major burns who were infected with Pseudomonas aeruginosa and various entero-bacteria. All of them received additional antimicrobial drugs. Treatment involved one dose every 6 h. The mean body surface area affected by third-degree burns was 30.0% +/- 4.0%. The study took place in accordance with current ethical guidelines. Two series of blood samples were drawn after the first (day 1) and ninth (day 3 at steady state) doses; urine was collected during the same periods. Levels of PPR and TZB in serum and urine were measured by high-pressure liquid chromatography. A noncompartmental method was used for kinetic and graphic analysis of concentration-time pairs. The safety of the treatment was excellent. There was no systemic accumulation of the beta-lactam combination. Residual concentrations measured on days 1 and 3 [mean (standard error of the mean)] were above the MIC for the organism responsible for infection; i.e., C(min)day1 = 26.3 (8.5) and C(min)day3 = 21.0 (9.1) for PPR and C(min)day1 = 1.9 (0.6) and C(min)day3 = 1.4 (0.3) for TZB. There was no statistically significant difference between pharmacokinetic parameters determined for day 1 and day 3. Evidence was found in burn patients, in contrast to healthy subjects, of a marked increase in apparent volumes of distribution, in such a way that the apparent elimination half-lives of the combination were notably prolonged, i.e., 1.8 (0.3) versus 1.5 (0.3) h for PPR in patients and healthy subjects, respectively, and 1.7 (0.3) versus 1.4 (0.3) h for TZB. These findings indicate the possibility of nonrenal translesional diffusion of PPR-TZB in burn patients. The polarity of the association would further support this hypothesis. It has been shown here that the recommended dosage regimen for administration of PPR-TZB must be high in major-burn patients, i.e., 4 g/0.5 g every 6 h. The data obtained provide valuable information, which is suitable for immediate application in everyday clinical practice.

[Nosocomial infections in a burns unit. Results of a prospective study over a year]. / Infections nosocomiales dans un service de brûlés. Résultats d'une enquête prospective d'un an.

OBJECTIVES: To assess nosocomial infections in a burn care centre, to identify patients' infection risk factors at the time of admission and factors of monthly variations of infection incidence. STUDY DESIGN: Prospective survey, from October 1992 to September 1993. PATIENTS AND METHOD: The study included 140 patients staying for more than two days in a 22-bed burn unit. Nosocomial infection criteria were derived from the 1988 CDC criteria. Incidence rates of infection were calculated. Infected and noninfected patients were compared. Each monthly infection incidence was compared with six unit activity indicators. RESULTS: Fifty-six patients developed 132 infections. The overall incidence was 94%. Incidence density was 25 infections per 1,000 days of care. The distribution of infected sites was: skin (30%), intravascular catheters (25%), blood (22%), urinary tract (18%), respiratory tract (5%). The most frequent pathogens were Pseudomonas sp (49%), Staphylococcus sp (18%), Escherichia coli (18%), and Streptococcus faecalis (10%). They were characterized by a good antibiotic sensitivity. Each common burn severity index was predictive of nosocomial infections. Facial, perineal and respiratory lesions were also linked to infection. There was a positive correlation between the peak of nosocomial infections in the unit during a month and the peak of activity during the foregoing one. CONCLUSION: Incidence rates of infection were high, as 40% of the population was concerned. Choosing reliable infection criteria was the most difficult problem to solve.

[Multiple trauma and burns]. / Le brûlé polyagressé.

In peace time, burn injury combined with traumatic, chemical or radioactive casualties is rarely encountered and often unrecognized; during disasters, burn injury is unlikely the only trauma. The authors try to bring out the main pathophysiological, diagnostic and therapeutic characteristics of changes induced by combined lesions on burn injury and vice-versa.

[Polytraumatized burnt patients]. / Le brûlé polyagressé.

In peace time, burn injury combined with traumatic, chemical or radioactive casualties, is rarely encountered and often unrecognised; during disasters, burn injury is unlikely the only trauma. The authors try to bring out the great physiopathologic, diagnostic and therapeutic principles of changes due to combined lesions on burn injury and vice-versa.

[Surgery of acoustic neurinoma in the elderly]. / Chirurgie des neurinomes de l'acoustique du vieillard.

Eleven patients, between 70 and 85 years old, with acoustic neurinoma, were operated by translabyrinthic approach. The size of the tumor was between 2 and 4 cm in five cases, 4 cm or more in six cases. Complete tumor removal was possible in six cases (55%), in five cases (45%) residual tumor was left behind. Complications included cerebrospinal fluid leakage (2 cases), meningitis (1 case), and hemorrhage (1 case, fatal four days later). Anesthetic management is described.

[Nasopharyngeal fibroma. Excision under hemodilution and delayed autotransfusion]. / Le fibrome naso-pharyngien. Exérèse sous hémodilution et autotransfusion différée.

The surgical treatment of juvenile naso-pharyngeal angiofibroma involved a potential haemorrhagic risk: the average intra-operative blood loss was estimated at between 1,300 and 2,800 ml in many reports. Two cases are reported in which haemodilution and autologous blood transfusion were used. The method consisted in pre-operative repeated phlebotomies ("leap-frog") and normovolaemic acute haemodilution; thus, 1,700 ml of autologous blood was collected in the first case, and 2,300 ml in the second one. Autotransfusion was carried out and no homologous blood transfusion was used in the peri-operative period. The use of this method, although compelling, had many advantages (financial saving, suppression of adverse reactions with homologous transfusion, transfusion of fresh blood, reduction of postoperative oedema).

[Nosocomial Candida albicans septicemia in parenteral alimentation through a peripheral vein]. / Septicémie nosocomiale à Candida albicans au cours d'une alimentation parentérale sur veine périphérique.

Fungal septicaemias during total parenteral nutrition are frequent, but their occurrence during parenteral nutrition via a peripheral vein is uncommon. A case of disseminated candidemia with ocular and renal localizations during parenteral nutrition via a peripheral vein is reported in a 24 year old patient hospitalized for primary cerebellar haemorrhage. The case history showed the importance of early ophthalmologic examination in all septicaemic cases. The diagnosis was confirmed by nine positive blood cultures and immunological tests, but the dosage of soluble antigens remained negative. The part played by a contaminated perfusion bottle out-of-date was suggested, but could not be proved absolutely. The assessment of the immune state could wrongly suggest an acquired immunodeficiency syndrome, for it has been demonstrated that Candida albicans itself had an immunosuppressive activity.