Effects of gabapentin on morphine consumption and pain in severely burned patients.

OBJECTIVE: Nociception is the major cause of burn pain and leads to central hyperalgesia. Gabapentin (Gp) is an antihyperalgesic drug that selectively affects central sensitization. We studied the opioid-sparing and analgesic effects of Gp in severely burned patients. METHODS: Ten patients (mean total burned body surface area (TBSA), 25%), received 2400 mg of oral Gp daily from after burn days 3-24 in addition to standard pain therapy. They were compared to a retrospective matching group. Outcomes were cumulative morphine consumption and mean daily pain scores. Outcomes were recorded during treatment (21 days) and 21 days after treatment. RESULTS: During treatment and post-treatment phases, patients receiving Gp had cumulative morphine consumption and a mean daily pain score significantly lower than controls. CONCLUSION: Gp use reduced opioid consumption and lowered pain scores that seemed to extend beyond its pharmacologic action probably result from the ability of Gp to prevent central hyperalgesia induced by burns.

Analytical quantification of the inflammatory cell infiltrate and CD95R expression during treatment of drug-induced toxic epidermal necrolysis.

The treatment of drug-induced toxic epidermal necrolysis (TEN) remains unsatisfactory. Intravenous immunoglobulins (IVIg) and intravenous cyclosporin A (CsA) have shown some efficacy in short series of patients. We assessed the effects of IVIg and CsA on TEN lesional and apparently uninvolved skin using standard histology and immunohistochemistry. Cutaneous biopsies were taken from necrotic and clinically uninvolved TEN skin at admission (D1) before any treatment, and after a 5-day treatment (D5). Two IVIg-treated patients (0.75 g/kg/day), two CsA-treated patients (5 mg/kg/day) and two control patients only receiving supportive care were compared. Biopsies were examined by standard histology and immunohistochemistry using antibodies directed to CD68 antigen (macrophages), CD45R0 antigen (activated T lymphocytes), Factor XIIIa (dermal dendrocytes) and the CD95 receptor (apoptosis marker). The different cell densities were evaluated by computerized image analysis. The clinical outcomes with the different treatments were also recorded. There was no obvious difference in the duration of hospitalization in intensive care unit between the three groups but one patient passed away in each of the IVIg- and CsA-groups. At D5, no differences were found between the three groups in the histological and clinical rate of re-epithelialization, and in the evolution of T lymphocyte, macrophage and dendrocyte densities in the epidermis and dermis. However, the expression of the CD95 receptor was similarly and strongly abated at D5 in the epidermis of IVIg- and CsA-treated patients, while it was conversely increased in the two patients under supportive care only. Such a difference was found both in necrotic and uninvolved sites. IVIg and CsA treatments thus appeared to exert no obvious effect on the inflammatory infiltrate, but both abated the expression of the CD95 receptor in the skin of TEN patients. This effect did not seem sufficient to fully reverse the clinical evolution of the disease. It is inferred that IVIg and CsA do not completely abate the TEN process.

Drug-induced toxic epidermal necrolysis and pancytopenia: a puzzling association.

The molecular mechanisms involved in the pathogenesis of toxic epidermal necrolysis (TEN) remain not fully understood. We report a unique case of antibiotic-induced TEN developed in a patient who also suffered from prolonged severe methotrexate-induced pancytopenia. The objective of the study was to explore the nature of the cutaneous inflammatory infiltrate and the density in dermal dendrocytes (DD). Immunohistochemistry was used to identify activated T lymphocytes (CD45R0), monocyte-macrophages (Mac 387, CD68), DD (Factor XIIIa), and Langerhans cells (CD1a). The proliferation marker (Ki67) and the antibody to Fas receptor (CD95R) were also used to assess the distribution of the germinative pool of keratinocytes and the FAS-related apoptotic process, respectively. Numerous Factor XIIIa+ DD were present in the papillary dermis with only sparce perivascular CD45RO+ T lymphocytes and scattered CD68+ or Mac 387+ macrophages. Double immunostainings revealed that a minority of Factor XIIIa+ DD co-expressed the CD68 glycoprotein (a marker of phagocytic activity). No cells co-expressed factor XIIIa and Mac 387 immunoreactivities. CD45RO+ T lymphocytes, CD68+ and Mac 387+ macrophages were absent in the epidermis. The expression of CD95R was present although restricted to the basal keratinocytes, while the L1-protein (Mac 387+) was diffusely present in the epidermis. Langerhans cells (CD1a+) were sparce, but normal in distribution. The presence of a great number of Factor XIIIa+ DD without any possible recent recruitment from bone marrow suggests that these cells differentiated from resident cells of the skin. Indeed, there was no co-expression of Factor XIIIa and L1-protein, thus showing the absence of recruitment from monocytes. The simultaneous over-expression of Factor XIIIa and CD68 in some DD indicates some phagocytic activity. In view of the absence of inflammatory cells in the epidermis, keratinocytes appeared responsible for their own destruction through CD95-mediated and/or calcium-dependent apoptotic pathways. This finding entails that TEN treatments should target the keratinocyte metabolism rather than the circulating inflammatory cells which presumably play a limited role, if any, in the epidermal destructive process.

The efficacy of continuous fascia iliaca compartment block for pain management in burn patients undergoing skin grafting procedures.

UNLABELLED: Postoperative pain from split skin donor sites is often more intense than the pain at the grafted site. In this prospective, randomized, double-blind study we assessed the efficacy of a continuous fascia iliaca compartment block (FICB) in reducing the pain at the thigh donor site. Twenty patients, with a total burn surface area of 16% +/- 13% (mean +/- SD) were randomized 1:1 to receive either ropivacaine 0.2% or saline 0.9%. All patients received a general anesthesic followed by preincision continuous FICB with 40 mL of the randomized solution, then an infusion of 10 mL/h of either ropivacaine or saline until the first dressing change (72 h later). Postoperative analgesia consisted of propacetamol 2g/6h, IV patient-controlled analgesia of morphine chlorhydrate (2 mg/mL), and morphine hydrochlorate 0.5 mg/kg PO once 60 min before first dressing change. The visual analog scale (VAS) scores were compared using the Mann-Whitney U-test preoperatively, 24 and 48 h postoperatively, and during the first dressing change. The cumulative morphine consumption was compared with repeated-measures analysis of variance followed by Scheffé's method if indicated. Patients with continuous FICB had significantly reduced postoperative morphine consumption at all time points (23 +/- 20 versus 88 +/- 29 mg after 72 h, study versus control groups, respectively; P < 0.05). In both groups, VAS scores remained low but were only significantly lower for patients with continuous FICB during the first dressing change (3 [1] versus 7 [3]; median [interquartile range]; P < 0.05). We conclude that continuous FICB is an efficient method for diminishing pain at the thigh donor site. (250 words) IMPLICATIONS: Postoperative pain at the split skin donor sites is often more intense than the pain at the grafted site. This prospective, randomized, double-blind study assessed the efficacy of a continuous fascia iliaca compartment block in reducing the pain at the thigh donor site.

Aeromedical transfer to Belgium of severely burned patients during the initial days following the Volendam fire.

Nineteen critical burn patients were transferred to burn centers in Belgium soon after an indoor fire in The Netherlands. This evacuation was done by helicopter and by ambulance. The first arterial blood gases and pH measurements of the patients on arrival in the burn centers were analyzed and compared. All patients were in metabolic acidosis, but the respiratory component to the pH and the resulting pH was variable. Although an efficient fluid resuscitation to maintain an adequate urine output and arterial pressure is essential, the arterial blood gases and pH should also be monitored during the early evacuation of severe burn patients. Because hyperkaliemia is associated with a low pH value, we suggest that during the evacuation of these patients the ventilation setting should maintain the pH between 7.35 and 7.45. The comparison of the measurements between the group of patients transferred by air and the group transferred by road showed here differences in favor of a road transfer.

Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone.

To study the epidemiology of Pseudomonas aeruginosa colonization in a 32-bed burn wound center (BWC), 321 clinical and 45 environmental P. aeruginosa isolates were collected by prospective surveillance culture over a 1-year period and analyzed by serotyping, drug susceptibility testing, and amplified fragment length polymorphism (AFLP) analysis. Among 441 patients treated at the center, 70 (16%) were colonized with P. aeruginosa, including 12 (17%) patients who were colonized on admission and 58 (83%) patients who acquired the organism during their stay. Of the 48 distinct AFLP genotypes found, 21 were found exclusively in the environment, 15 were isolated from individual patients only, and 12 were responsible for the colonization of 57 patients, of which 2 were also isolated from the environment, but secondary to patient carriage. Polyclonal P. aeruginosa colonization with strains of two to four genotypes, often with different antibiotic susceptibility patterns, was observed in 19 patients (27%). Two predominant genotypes were responsible for recurrent outbreaks and the colonization of 42 patients (60% of all colonized patients). The strain with one of those genotypes appeared to be endemic to the BWC and developed multidrug resistance (MDR) at the end of the study period, whereas the strain with the other genotype was antibiotic susceptible but resistant to silver sulfadiazine (SSD(r)). The MDR strain was found at a higher frequency in sputum samples than the SSD(r) strain, which showed a higher prevalence in burn wound samples, suggesting that anatomic habitat selection was associated with adaptive resistance to antimicrobial drugs. Repeated and thorough surveys of the hospital environment failed to detect a primary reservoir for any of those genotypes. Cross-acquisition, resulting from insufficient compliance with infection control measures, was the major route of colonization in our BWC. In addition to the AFLP pattern and serotype, analysis of the nucleotide sequences of three (lipo)protein genes (oprI, oprL, and oprD) and the pyoverdine type revealed that all predominant strains except the SSD(r) strain belonged to recently identified clonal complexes. These successful clones are widespread in nature and therefore predominate in the patient population, in whom variants accumulate drug resistance mechanisms that allow their transmission and persistence in the BWC.