RESUMEN
OBJECTIVE: To investigate the safety, biological effects, and efficacy of the anti-tumor necrosis factor (TNF) antibody fragment, MAK 195F, in a phase II trial in patient with severe sepsis. DESIGN: Prospective, randomized, open label, placebo-controlled, dose-ranging, multicenter, multinational clinical trial. SETTING: Sixteen academic medical centers' intensive care units in six European countries. PATIENTS: One hundred twenty-two patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy. INTERVENTIONS: Patients received one of three different doses of the anti-TNF antibody (0.1 mg/kg, 0.3 mg/kg, or 1.0 mg/kg) or placebo; the antibody or placebo was given in nine doses at 8-hr intervals over 3 days. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in mortality rates among the groups receiving various doses of the anti-TNF antibody or placebo, but patients with baseline serum interleukin (IL)-6 concentrations of > 1000 pg/mL appeared to benefit from MAK 195F in a dose-dependent fashion. Increased circulating IL-6 concentrations, but not TNF concentrations, were found to be important prognostic indicators for mortality for the patients in the placebo and the two lower dosage groups but not in the high dosage group (1 mg/kg). IL-6 concentrations decreased during the first 24 hrs of treatment in all three anti-TNF groups but not in the placebo group. MAK 195F was well tolerated by all patients. Human antimurine antibodies developed in 40% of the patients receiving the antibody. CONCLUSIONS: There was no increase in survival from sepsis for the patients receiving anti-TNF treatment in the overall study population. Retrospective stratification of patients by IL-6 concentrations suggests beneficial effects of the drug for patients with baseline circulating IL-6 concentrations of > 1000 pg/mL. This hypothesis requires validation in a larger, blinded, prospective study.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Sepsis/terapia , Factor de Necrosis Tumoral alfa/inmunología , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Interleucina-6/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Sepsis/sangre , Sepsis/inmunología , Sepsis/mortalidad , Análisis de Supervivencia , Factores de TiempoAsunto(s)
Antifúngicos/administración & dosificación , Infección Hospitalaria/tratamiento farmacológico , Micosis/tratamiento farmacológico , Antifúngicos/efectos adversos , Candidiasis/tratamiento farmacológico , Candidiasis/mortalidad , Candidiasis/transmisión , Infección Hospitalaria/mortalidad , Infección Hospitalaria/transmisión , Humanos , Unidades de Cuidados Intensivos , Micosis/mortalidad , Micosis/transmisión , Factores de Riesgo , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/mortalidad , Infección de la Herida Quirúrgica/transmisión , Tasa de SupervivenciaRESUMEN
Two groups of 13 patients, randomly allocated to receive either enflurane or neurolept anaesthesia for cholecystectomy, were compared in their cardiovascular and neuroendocrine response to surgery and in the postoperative period. There were no significant differences in blood pressure or heart rate. Catecholamine values were higher under neurolept anaesthesia towards the end of surgery and postoperatively. Median values for adrenaline during suture of peritoneum were 342 pg/ml and 88 pg/ml, respectively, P less than 0.05. In contrast, ACTH and cortisol rose to higher levels in enflurane treated patients. At the end of surgery median ACTH values were 75 pg/ml in NLA patients and 322 pg/ml in enflurane patients (P less than 0.01). Vasopressin increments during surgery were similar under both regimens, while prolactin was higher following induction of neurolept anaesthesia. It is discussed whether the differences in stress hormone secretion patterns under either form of anaesthesia reflect different stress protective properties or direct pharmacological effects of certain anaesthetics. We conclude that the hormonal stress response to surgery is critically dependent on the type of anaesthesia and may be discordant in different hormonal systems.
Asunto(s)
Anestesia , Colecistectomía , Enflurano , Hormonas/sangre , Neuroleptanalgesia , Hormona Adrenocorticotrópica/sangre , Adulto , Epinefrina/sangre , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Hidrocortisona/sangre , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Prolactina/sangre , Vasopresinas/sangreRESUMEN
UNLABELLED: Intraoperative autotransfusion provides several advantages over homologous transfusion for the recipient. Since the harvested red cells have a normal 2,3-DPG concentration [15, 18], the decreased oxygen affinity of hemoglobin [26] that occurs in the recipient after the transfusion of stored blood is thought to be avoidable by intraoperative autotransfusion. In a study on the influence of harvested cells on oxygen affinity in patients by Orr and Blenko [18], however, it was not possible to demonstrate the superiority of these erythrocytes over stored red cells in the recipient: whereas 2,3-DPG remained at the preoperative level in both groups after transfusion, oxygen affinity increased postoperatively in the study group but not in the control group. In this study we directly determined oxygen affinity in addition to 2,3-DPG in the harvested cells after processing. The influence on the recipients' oxygen affinity after transfusion was analyzed and compared to that of a group of patients who received only stored blood. PATIENTS AND METHODS: Three groups of patients were studied: Group 1 received only autotransfusion blood, group 2 autotransfusion and stored blood, and group 3 only stored blood. For harvesting, centrifugation, and washing of the red cells the Haemonetics Cell Saver (CS III) was used. The p50 value - which is generally accepted as a measurement of oxygen affinity - was determined as described by Müller-Plathe and Müller-Plathe [17]. For analysis of these data, blood was drawn from patients pre- and postoperatively and for the majority of cases also one or more days postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)