Evaluation of serum procalcitonin concentration in the ICU following severe burn.

The goal of the study was to analyse plasma procalcitonin (PCT) concentrations during infectious events of burns in ICU. Clinical and laboratory data were collected at admission and twice a week in burned patients admitted with a total body surface area (TBSA) >20%. Procalcitonin was determined using both a semi-quantitative detection (PCT-Q) and a quantitative immunoluminometric method (PCT-Lumi). A total of 359 time points in 25 consecutive patients with 40+/-17% (20-86%) TBSA burned, defined as a procalcitonin concentration associated with an inflammatory status according to society critical care medicine definition, were made. The principal site of infection was the respiratory tract (84% of patients required mechanical ventilation). PCT-Lumi values corresponded to the four semi-quantitative ranges of PCT-Q and statistically reflected the simultaneously observed inflammatory status (Kruskall-Wallis test). The area under the receiver operating characteristic curve for C-reactive protein (CRP) was higher than those for PCT and white blood cell (WBC) count, but this difference was not significant. The optimum PCT cut-off value was 0.534 ng/ml with sensitivity and specificity of 42.4% and 88.8%, respectively. However, PCT does not appear to be superior to C-reactive protein (CRP) and white blood count (WBC) as diagnosis marker of sepsis in burns. PCT is not sufficient to diagnose and to follow infection in burns admitted in ICU.

[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.

Long-term regeneration of human epidermis on third degree burns transplanted with autologous cultured epithelium grown on a fibrin matrix.

BACKGROUND: Extensive third degree burn wounds can be permanently covered by the transplantation of autologous cultured keratinocytes. Many modifications to Green and colleagues' original technique have been suggested, including the use of a fibrin matrix. However, the properties of the cultured cells must be assessed using suitable criteria before a modified method of culture for therapeutic purposes is transferred to clinical use, because changes in culture conditions may reduce keratinocyte lifespan and result in the loss of the transplanted epithelium. METHODS: To evaluate the performances of human keratinocytes grown on a fibrin matrix, we assay for their colony-forming ability, their growth potential and their ability to generate an epidermis when grafted onto athymic mice. The results of these experiments allowed us to compare side by side the performance for third degree burn treatment of autologous cultured epithelium grafts grown according to Rheinwald and Green on fibrin matrices with that of grafts grown directly on plastic surfaces. RESULTS: We found that human keratinocytes cultured on a fibrin matrix had the same growth capacity and transplantability as those cultured on plastic surfaces and that the presence of a fibrin matrix greatly facilitated the preparation, handling, and surgical transplantation of the grafts, which did not need to be detached enzymatically. The rate of take of grafts grown on fibrin matrices was high, and was similar to that of conventionally cultured grafts. The grafted autologous cells are capable of generating a normal epidermis for many years and favor the regeneration of a superficial dermis. CONCLUSION: We have demonstrated that: 1) fibrin matrices have considerable advantages over plastic for the culture of skin cells for grafting and that it is now possible to generate and transplant enough cultured epithelium from a small skin biopsy to restore completely the epidermis of an adult human in 16 days; and 2) the generated epidermis self-renews itself for years. The use of fibrin matrices thus significantly improves the transplantation of cultured epithelium grafts for extensive burns as recently demonstrated in a follow-up work.

PCC-FISH in skin fibroblasts for local dose assessment: biodosimetric analysis of a victim of the Georgian radiological accident.

We propose a new method of biodosimetry that could be applied in cases of localized irradiation. The approach is based on excess chromosome segments determination by the PCC-FISH technique in fibroblasts isolated from skin biopsy. Typically, 0 to 10 Gy ex vivo gamma-irradiated human skin biopsies were dissociated and fibroblasts were isolated and grown for several days. Cells next underwent PCC-FISH painting of whole chromosome 4, and the number of excess chromosome segments per metaphase was determined. An ex vivo reference curve correlating the number of excess chromosome segments per metaphase to the radiation dose was established and used to assess the dose delivered to the skin of one of the victims of the radiological accident that occurred at Lia in Georgia in December 2001. Specifically, the victim suffering from moist desquamation underwent skin excision in Hospital Percy (France). Measurement of excess chromosome segments per metaphase was done in fibroblasts isolated and grown from removed wounded skin and subsequent conversion to radiation doses was performed. The radiation dose map obtained was shown to be in accordance with clinical data and physical dosimetry as well as with conventional biodosimetry. These results demonstrated that PCC-FISH painting applied to skin fibroblasts may be a suitable technique for dose estimation. To assess its worth, this approach needs to be extended to future accidents involving localized radiation exposure.

Bronchopulmonary distress associated with toxic epidermal necrolysis.

We describe here a patient with severe TEN and respiratory distress and we review the subject of bronchopulmonary symptoms in TEN. Even if pseudostratified ciliated involvement is uncommon, bronchial lesions in the absence of other known causes, should be specifically related to TEN. The mechanisms of pulmonary involvement and ARDS associated with TEN are discussed.

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.

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.

Initial general management and surgery of six extensively burned children treated with cultured epidermal autografts.

PURPOSE: The aim of this study was to document the surgical and intensive care methods used in six extensively burned children (EBC), ie, total body surface area (TBSA) burned over 70% or TBSA with deep burns over 60%, treated with cultured epidermal autografts (CEA). METHODS: Six EBC, with a mean age of 7.5 years (range, 2.5 to 12) received CEA. Their mean TBSA burned was 82% (range, 70-94) with 74% (range, 60-90) of TBSA with deep burns. All sustained flame burns and inhalation injuries. RESULTS: The survival rate was six of six. The average initial and final engraftment rates of CEA were, respectively, 79% (range, 70 to 95) and 84% (range, 72 to 100). CEA definitively covered 45% (range, 18 to 57) of TBSA for a mean cost per child of $80,000 (range, 55,000 to 110,000). CONCLUSION: Even if CEA are expensive, such engraftment rates and survival ratio results make them an excellent alternative wound covering method for EBC when donor sites for widely meshed autografts are exhausted.

A silver sulphadiazine-impregnated lipidocolloid wound dressing to treat second-degree burns.

OBJECTIVE: To evaluate the efficacy and tolerance of Urgotul SSD dressing (Laboratoires Urgo) in the treatment of second-degree burns. METHOD: This was a national multicentre phase III non-comparative open-label prospective study involving 10 burns units. The 41 subjects were non-immunosuppressed adults with second-degree thermal burn(s), which were clinically non-infected, less than 24 hours old, had a surface area less than 500 cm2 and warranted the local use of silver sulphadiazine. For four weeks, subjects were followed up weekly with a clinical assessment, bacteriological swabs and photographic recording. RESULTS: Of the 41 patients, 24 healed within a mean of 10.8 days and 13 had a skin graft on the study burn within a mean of 11.5 days. There were four premature study withdrawals. The total number of cumulative treatment days was 445, and 298 treatments were performed (including 257 dressing changes). Mean dressing wear time was 1.73 days. None of the subjects acquired a secondary infection. Researchers took 121 bacteriological samples, and wound colonisation with Staphylococcus aureus was found in only one patient. At follow-up nursing staff reported that dressing acceptability was good. CONCLUSION: Use of Urgotul SSD led to a good wound outcome--wounds healed or were grafted.

[Pharmacokinetics of antibiotics in burn patients]. / Pharmacocinétique des antibiotiques chez le sujet brûlé.

The pathophysiology associated with major burns is complex and subject to a state of flux (coexistence of pain, infectious diseases, multiple trauma, disturbances of metabolism and acid-base status, etc) which could affect the disposition and the pharmacokinetic behaviour of drugs. In current clinical practice, practitioners often use powerful antimicrobial agents; however, few pharmacokinetic studies are available in burns patients (of the order of 30 studies). Furthermore, the methods used are sometimes questionable. After dealing with the ethical and physiological context in which such research is undertaken, the authors report a review of the pharmacokinetic studies done during the last 15 years. Concerning both aminoglycosides and glycopeptides, no therapeutic recommendations are available (therapeutic schedules). However, in this case, therapeutic monitoring is available and represents a suitable tool to better master their use. In the case of beta-lactam antibiotics and quinolones, more data are available. Some investigations have shown the possibility of translesional diffusion of certain agents in burns (such as gentamicin, piperacillin/tazobactam combination, or fosfomycin). This phenomenon could be a co-factor of success in treatment. Considering the relatively meager pharmacokinetic and pharmacodynamic data available in burns, it is important in the future to refine our knowledge of the distribution and metabolism of drugs in burns patients in order to better master their use. Finally, ethical and methodological considerations need to be taken in account.

[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.

[Burns and pregnancy. A case of severe burn occurring at the beginning of pregnancy. Maternal and fetal survival]. / Brûlures et grossesse. Une observation de brûlure grave survenue en début de grossesse. Survies maternelle et foetale.

The authors report a case of a severe thermal burn (70% of the surface of the body) in a pregnant woman who had 15 weeks amenorrhoea. The survival of the mother and the continuation of the pregnancy to term allowed a normal live baby to be born. As far as the authors know this is the fourth case history of a severe (more than 60% of the body) burn published occurring in the first trimester of pregnancy and carried through successfully to term. A study of the literature has shown that the physiopathological results of severe burns do explain the usually poor prognosis for mother and fetus. Large quantities of prostaglandins are released into the circulation of the mother because of the thermal insult to tissues and because of the infection that usually accompanies such burns. These prostaglandins can stimulate the myometrium, which gives rise to fatal obstetric complications. The urgent acute treatment for a severe burn in a pregnant woman, which should preferably be carried out in a special centre, consists in water and electrolyte resuscitation, assisted respiration and prevention of bacterial contamination. These measures are just as important for the fetus. At the same time obstetric care should be started. Good collaboration between the obstetricians and those who carry out the resuscitation all bring about the measures that are needed to allow the mother and fetus to survive.

[Use of Diprivan in burn patients]. / Utilisation du Diprivan chez le brûlé. Use of diprivan in the burned patient.

The use of propofol should be avoided in the first 48 hours after a burn injury, as a major haemodynamic instability characterizes this period. For excision and/or grafting, propofol is mainly used as an induction agent. Maintenance of anaesthesia requires higher doses, often in the range of 15 mg.kg-1.h-1, and varying with each patient and the stage of the burn. Propofol is most appropriate in anaesthesia for dressing changes, considering the repetition of the procedures, interfering least with enteral nutrition and the quality of recovery, considered as essential. Combined with alfentanil or fentanyl, the dose of propofol is titrated to obtain the desired effect, from a simple sedation with patient co-operation to total anaesthesia.

[Human albumin solutions in the treatment of burned patients. Current indications]. / Solutions d'albumine humaine dans le traitement des brûlés. Indications actuelles.

A KEY ROLE: Albumin is a large molecule which plays an essential role in generating colloido-osmotic pressure which facilitates fluid retention in the intravascular space. HYPOALBUMINEMIA IN BURNED PATIENTS: Excessive loss is followed by deficient synthesis in the liver (preferential production of inflammatory proteins, insufficient protein intake). HUMAN ALBUMIN IN BURNED PATIENTS: By maintaining fluid in the vascular sector and favoring inflow from the interstitial space, human albumin maintains blood volume. Despite its value as the reference substance, reasonable use as become necessary because of cost-containment. Human albumin should be reserved for severely burned patients whose albuminemia falls to approximately 20 g/l (or proteinemia to 35 g/l).

[Role of Pseudomonas aeruginosa in infection in burn patients]. / Place du pyocyanique dans l'infection des brûlés.

The regular finding of Pseudomonas aeruginosa in Burns Units has always been a source of worries. Following a brief review of the natural history of this micro-organism, the authors examine all possible therapeutic measures. They underline the importance of measures aimed at controlling environmental and epidemiological factors and at improving surveillance. These measures, together with baths, topical applications of antibacterial agents and prophylactic vaccination and serotherapy tend to circumscribe the infection. When therapeutic measures are not as effective as expected and natural defences collapse, sepsis develops with clinical features that male diagnosis uneasy. The conditions in which antibiotics are given are peculiar in burned patients, and the therapeutic approach to Pseudomonas infections is particularly difficult in such cases.

[Fatal Lyell's syndrome caused by griseofulvin]. / Syndrome de Lyell d'évolution fatale après prise de griséofulvine.

A case of toxic epidermolysis (TE) with a fatal outcome is reported. It occurred after administration of 500 mg griseofulvin twice daily in a 19-year-old female patient. She developed the first skin lesions on the sixth day of treatment. All the body surface was involved, except for the scalp. Several complications arose in the course of the disease, thrombocytopaenia, lymphocytopaenia, rhabdomyolysis, and non cardiogenic pulmonary oedema. Death occurred as a result of multiple organ failure following septic shock associated with adult respiratory distress syndrome. The pathogenesis of these complications and the major therapeutic difficulties encountered are discussed. The involvement of griseofulvin in TE has only been reported once before. The arguments in favour of its involvement in the present case are discussed.

[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.

[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.

[Inhalation burns: apropos of 198 cases. Incidence of laryngotracheal involvement]. / Les brûlures par inhalation: à propos de 198 cas incidence de l'atteinte laryngo-trachéale.

Inhalation burns and laryngotracheal involvement were studied in a retrospective series of 635 patients hospitalized for skin burns at the Center for Burn Treatment from January 1993 to January 1997. Inhalation burns were observed in 31.1% of the cases. Exclusive laryngeal involvement occurred in 19.6% of the inhalation burns. Both tracheobronchial and laryngeal burns were observed in 27.2%. Patients with inhalation burns also had facial burns (90.9%) and extensive (> 50%) or severe (UBS > 200) skin burns in 39.8% and 29.7% of the cases respectively. Mortality of skin burns was increased six-fold to 19.1% in patients who also had inhalation burns. Intubation was used alone in 60.1% and was followed by tracheotomy in 27.2%. The decision for tracheotomy was essentially based on the probable duration of ventilatory assistance. Tracheotomy was required in case of severe inhalation burns and the predictable duration of intubation was over 8 days. Laryngotracheal stenosis occurring after inhalation burns is complex and extensive, with great variability over time. Laryngotracheal calibration is indicated as first intention therapy.

[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.