Search PubMed⌕ Search

Biomedical subjects

Pierre Damas

Publications and source records attributed to Pierre Damas.

10 recordsLinked to original sources

Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779].

INTRODUCTION: Combination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy. METHODS: Patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter. RESULTS: Seventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No significant difference was observed regarding the time course of temperature, leukocytosis or C-reactive protein level. There were no differences between length of stay in the intensive care unit after infection, nor in ventilator free days within 28 days after infection. No difference in mortality was observed. CONCLUSION: Antibiotic combination using a fourth generation cephalosporin with either an aminoside or a fluoroquinolone is not associated with a clinical or biological benefit when compared to cephalosporin monotherapy against common susceptible pathogens causing VAP.

Adult↗

Selection of resistance during sequential use of preferential antibiotic classes.

OBJECTIVE: To determine the effect of antibiotic class pressure on the susceptibility of bacteria during sequential periods of antibiotic homogeneity. DESIGN AND SETTING: Prospective study in a mixed ICU with three separated subunits of eight, eight, and ten beds. PATIENTS AND PARTICIPANTS: The study examined the 1,721 patients with a length of stay longer than 2 days. INTERVENTIONS: Three different antibiotic regimens were used sequentially over 2 years as first-choice empirical treatment: cephalosporins, fluoroquinolone, or a penicillin-beta-lactamase inhibitor combination. Each regimen was applied for 8 months in each subunits of the ICU, using "latin square" design. RESULTS: We treated 731 infections in 546 patients (32% of patients staying more than 48 h). There were 25.5 ICU-acquired infections per 1,000 patient-days. Infecting pathogens and colonizing bacteria were found in 2,739 samples from 1,666 patients (96.8%). No significant change in global antibiotic susceptibility was observed over time. However, a decrease in the susceptibility of several species was observed for antibiotics used as the first-line therapy in the unit. Selection pressure of antibiotics and occurrence of resistance during treatment was documented within an 8-month rotation period. CONCLUSIONS: Antibiotic use for periods of several months induces bacterial resistance in common pathogens.

Anti-Bacterial Agents↗

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.

Adult↗

Liver transplantation in Jehovah's witnesses.

For religious reasons, Jehovah's witnesses refuse transfusion of blood products (red cells, platelets, plasma), but may accept organ transplantation. The authors developed a multidisciplinary protocol for liver transplantation in Jehovah's witnesses. In a 6-year period, nine Jehovah's witness patients were listed for liver transplantation. They received preoperative erythropoietin therapy, with iron and folic acid that allowed significant haematocrit increase. Two patients underwent partial spleen embolization to increase platelet count. Seven patients underwent cadaveric whole liver transplantation, and two right lobe living-related liver transplantation, using continuous circuit cell saving system and high dose aprotinin. No patient received any blood product during the surgical procedure. One patient suffering from deep anaemia after living-related liver transplantation was transfused as required by his family, but died from aspergillus infection. One 6-year-old child was transfused against her parent's will. The authors demonstrated that it is possible to increase haematocrit and platelet levels in cirrhotic patients awaiting liver transplantation. They were able to reduce intraoperative need for blood products, allowing liver transplantation in prepared Jehovah's witness patients. This experience may be beneficial for non-Jehovah's witness liver transplant recipients.

Adolescent↗

Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state.

BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness. OBJECTIVE: To study auditory processing among patients who are in an MCS, patients who are in a PVS, and healthy control subjects. METHODS: By means of (15)O-radiolabeled water-positron emission tomography, we measured changes in regional cerebral blood flow induced by auditory click stimuli in 5 patients in an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients in an MCS and the healthy controls, auditory stimulation activated bilateral superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed that, compared with patients in a PVS, patients in an MCS demonstrated a stronger functional connectivity between the secondary auditory cortex and temporal and prefrontal association cortices. CONCLUSIONS: Although assumptions about the level of consciousness in severely brain injured patients are difficult to make, our findings suggest that the cerebral activity observed in patients in an MCS is more likely to lead to higher-order integrative processes, thought to be necessary for the gain of conscious auditory perception.

Acoustic Stimulation↗

Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study.

OBJECTIVE: To compare the efficacy and safety of adjusted-dose unfractionated heparin with that of regional citrate anticoagulation in intensive care patients treated by continuous venovenous hemofiltration (CVVH). DESIGN AND SETTING: Prospective, randomized, clinical trial in a 32-bed medical and surgical ICU in a university teaching hospital. PATIENTS: ICU patients with acute renal failure requiring continuous renal replacement therapy, without cirrhosis, severe coagulopathy, or known sensitivity to heparin. INTERVENTIONS: Before the first CVVH run patients were randomized to receive anticoagulation with heparin or trisodium citrate. Patients eligible for another CVVH run received the other study medication in a cross-over fashion until the fourth circuit. MEASUREMENTS AND RESULTS: Forty-nine circuits (hemofilters) were analyzed: 23 with heparin and 26 with citrate. The median lifetime of hemofilters was 70 h (interquartile range 44-140) with citrate anticoagulation and 40 h (17-48) with heparin (p=0.0007). One major bleeding occurred during heparin anticoagulation and one metabolic alkalosis (pH=7.60) was noted with citrate after a protocol violation. Transfusion rates (units of red cells per day of CVVH) were, respectively, 0.2 (0.0-0.4) with citrate and 1.0 (0.0-2.0) with heparin (p=0.0008). CONCLUSIONS: Regional citrate anticoagulation seems superior to heparin for the filter lifetime and transfusion requirements in ICU patients treated by continuous renal replacement therapy.

Acute Kidney Injury↗

Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study.

OBJECTIVES: To re-examine the epidemiology of acute lung injury (ALI) in European intensive care units (ICUs). DESIGN AND SETTING: A 2-month inception cohort study in 78 ICUs of 10 European countries. PATIENTS: All patients admitted for more than 4 h were screened for ALI and followed up to 2 months. MEASUREMENTS AND MAIN RESULTS: Acute lung injury occurred in 463 (7.1%) of 6,522 admissions and 16.1% of all mechanically ventilated patients; 65.4% cases occurred on ICU admission. Among 136 patients initially presenting with "mild ALI" (200< PaO2/FiO2 < or =300), 74 (55%) evolved to acute respiratory distress syndrome (ARDS) within 3 days. Sixty-two patients (13.4%) remained with mild ALI and 401 had ARDS. The crude ICU and hospital mortalities were 22.6% and 32.7% (p<0.001), and 49.4% and 57.9% (p=0.0005), respectively, for mild ALI and ARDS. ARDS patients initially received a mean tidal volume of 8.3+/-1.9 ml/kg and a mean PEEP of 7.7+/-3.6 cmH2O; air leaks occurred in 15.9%. After multivariate analysis, mortality was associated with age (odds ratio (OR) =1.2 per 10 years; 95% confidence interval (CI): 1.05-1.36), immuno-incompetence (OR: 2.88; Cl: 1.57-5.28), the severity scores SAPS II (OR: 1.16 per 10% expected mortality; Cl: 1.02-1.31) and logistic organ dysfunction (OR: 1.25 per point; Cl: 1.13-1.37), a pH less than 7.30 (OR: 1.88; Cl: 1.11-3.18) and early air leak (OR: 3.16; Cl: 1.59-6.28). CONCLUSIONS: Acute lung injury was frequent in our sample of European ICUs (7.1%); one third of patients presented with mild ALI, but more than half rapidly evolved to ARDS. While the mortality of ARDS remains high, that of mild ALI is twice as low, confirming the grading of severity between the two forms of the syndrome.

Age Distribution↗

Recurrent fatal drug-induced toxic epidermal necrolysis (Lyell's syndrome) after putative beta-lactam cross-reactivity: Case report and scrutiny of antibiotic imputability.

OBJECTIVE: A series of antibiotics may be responsible for toxic epidermal necrolysis. We report two successive episodes of toxic epidermal necrolysis in the same patient. Drug imputability criteria designate a cross-reactivity between two antibiotics of different chemical classes but sharing the beta-lactam ring in common. DESIGN: Descriptive case report and review of the literature. SETTING: Medical intensive care unit in a university medical center. PATIENT AND MAIN RESULTS: A 75-yr-old woman developed a first episode of toxic epidermal necrolysis (involving 40% of the body surface) after intake of cefotaxime, a third-generation cephalosporin. Perfusions of high-dose immunoglobulins rapidly improved the lesions, followed by partial reepithelialization in 5 days. Sepsis required the administration of meropenem, which is a carbapenem antibiotic. The epidermal destruction immediately recurred, with extension to previously uninvolved skin areas and fatal consequences. CONCLUSIONS: The beta-lactam ring present in cephalosporins and carbapenems represents the putative chemical structure responsible for the presently reported cross-reactivity to two antibiotics of different classes. Drugs having any chemical similarity to the initial culprit compound should be strictly avoided when possible in the management of toxic epidermal necrolysis.

Aged↗

Brain function in the vegetative state.

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.

Cerebral Cortex↗