RESUMEN
Because of insufficient soft-tissue conditions and variability in the size and mechanical friction of the stump treatment of upper leg amputees with an ordinary prosthesis might be difficult or even impossible. Alternatively, for such patients an endo-exo femoral prosthesis (EEFP) is sometimes the best treatment option. The use of EEFPs will be demonstrated as exemplified by the clinical course in a patient with a primary EEFP implantation including all relevant side-effects and associated problems.
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Amputación Quirúrgica/instrumentación , Amputación Quirúrgica/métodos , Fémur/cirugía , Prótesis de Cadera , Implantación de Prótesis/instrumentación , Implantación de Prótesis/métodos , HumanosRESUMEN
OBJECTIVE: Preconditioning with low doses of endotoxin has been shown to induce endotoxin hyporesponsiveness. The present study was designed to assess the metabolic response of various tissues during endotoxemia and after pretreatment with endotoxin. DESIGN: Controlled experimental animal study. SETTING: Research laboratory of a university hospital. MEASUREMENTS AND RESULTS: Ten pigs were randomly assigned to a control ( n = 5) or a treatment group ( n = 5), the latter receiving incremental doses of endotoxin 5-2 days prior the experiments. Apart from hemodynamics and oxygen transport variables, lactate, glucose, and glycerol were measured in muscle, subcutaneous fat, and hepatic tissue using microdialysis. Endotoxin was infused (1 micro g.kg.h) until the animals died. A significant increase in tissue lactate (eightfold) and glycerol (fivefold) was observed in the control animals. This effect was almost completely abolished in the endotoxin pretreated group. Endotoxin pretreatment had no significant effects on mean arterial pressure [56 (range 34-89) mmHg vs 70 (47-88) mmHg, n.s.] or cardiac output [4.8 (3.0-5.9) l/min vs 3.2 (2.1-4.2) l/min, n.s.], but significantly improved arterial pO(2) and pH ( P<0.05). Increase of oxygen extraction was higher in control animals [from 34% (range 24-47%) to 72% (range 61-79%)] compared to the pretreatment group [from 30% (range 22-42%) to 44% (range 34-50%), P<0.05]. Endotoxin pretreatment increased survival time from 5.3 h (5.0-5.8) to 8.0 h (7.0-8.5) ( P<0.05), respectively. CONCLUSIONS: Microdialysis monitoring revealed that endotoxin preconditioning ameliorates the increase in tissue metabolism during endotoxemia, accompanied by decreased systemic oxygen demand despite unchanged global hemodynamics.
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Endotoxinas/farmacología , Lipopolisacáridos/farmacología , Microdiálisis/métodos , Choque Séptico/metabolismo , Animales , Glucemia/metabolismo , Endotoxinas/administración & dosificación , Glicerol/sangre , Lactatos/sangre , Lipopolisacáridos/administración & dosificación , Oxígeno/sangre , Estadísticas no Paramétricas , PorcinosRESUMEN
BACKGROUND: In animal studies, gender differences were related to hormonal and immunologic changes that were associated with an increased susceptibility to sepsis in males. OBJECTIVE: In a prospective study, gender differences in patients with surgical sepsis were evaluated in terms of survival, sex hormones, and proinflammatory as well as anti-inflammatory mediators. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Fifty-two patients (19 women and 33 men) with surgical sepsis. MEASUREMENTS AND MAIN RESULTS: In a prospective study, tumor necrosis factor alpha and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), total testosterone, and 17-beta estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severity of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found in the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hospital-mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor necrosis factor continuously increased in men after diagnosis of sepsis, with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction), whereas no difference was found for interleukin 6 bioactivity. Women displayed enhanced interleukin 10 levels compared with men from day 1 to day 10 that reached a significant difference on days 3 and 5 (P<.05). Total testosterone levels were below the normal range for men, and estradiol levels were initially increased in both men and postmenopausal women, with higher levels for women. CONCLUSIONS: In this prospective study, gender differences were confirmed in human sepsis, with a significantly better prognosis for women, which may be related to increased levels of anti-inflammatory mediators. The hypothetical different ratio of proinflammatory and anti-inflammatory mediators may be important for further therapeutic interventions in sepsis.
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Complicaciones Posoperatorias/inmunología , Sepsis/inmunología , Caracteres Sexuales , APACHE , Estradiol/sangre , Femenino , Mortalidad Hospitalaria , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Complicaciones Posoperatorias/sangre , Pronóstico , Estudios Prospectivos , Sepsis/sangre , Sepsis/complicaciones , Análisis de Supervivencia , Testosterona/sangre , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To evaluate the effect of pentoxifylline on organ dysfunction, survival, and mediator response in patients with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Surgical intensive care units at 2 university hospitals. PATIENTS: Fifty-one surgical patients with severe sepsis were randomized to receive pentoxifylline continuously (27 patients) or saline infusion as placebo (24 patients). INTERVENTIONS: PATIENTS received pentoxifylline (1 mg/kg of body weight per hour; maximum, 1800 mg/d) during 28 days or until they were discharged from the intensive care unit or died. MEASUREMENTS AND MAIN RESULTS: Vital signs and organ function were determined at diagnosis; daily from day 1 to 7; on days 10, 14, 17, 21, and 24; and 28 days after diagnosis of sepsis. There were no differences in characteristics of patients at diagnosis in the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (mean+/-SEM, 17+/-4 points for the pentoxifylline group and 18+/-5 points for the placebo group), the multiple organ dysfunction score (mean+/-SEM, 11.0+/-0.8 vs 11.8+/-1.0 points), tumor necrosis factor alpha and interleukin 6 bioactivity, serum endotoxin levels, or organ dysfunction. At study entrance, 23 of 27 patients in the pentoxifylline group and 21 of 24 patients in the placebo group experienced septic shock. No adverse effects of pentoxifylline treatment were observed. The 28-day mortality rate was 30% (8/27) in pentoxifylline-treated patients and 33% (8/24) in the placebo group. Hospital mortality was 41% (11/27) in the pentoxifylline group and 54% (13/24) in the placebo group. The multiple organ dysfunction score decreased in patients receiving pentoxifylline 4 days after diagnosis of sepsis compared with placebo-treated patients; a significant difference was reached on day 14 (P<.05; Student t test, Bonferoni correction). The PaO2/FIO2 (fraction of inspired oxygen) ratio was significantly improved in pentoxifylline-treated patients on days 14 and 17 (P<.05), and the pressure-adjusted heart rate was significantly improved on day 6 (P<.05) compared with the placebo group. Serum endotoxin levels, tumor necrosis factor alpha and interleukin 6 bioactivity were not different between the groups during the study. CONCLUSIONS: Continuous intravenous administration of pentoxifylline beneficially influenced cardiopulmonary dysfunction in patients with sepsis without adverse effects. Larger trials are needed to evaluate the efficacy in improving organ function in relation to the outcome for patients with severe sepsis.
Asunto(s)
Pentoxifilina/uso terapéutico , Inhibidores de Fosfodiesterasa/uso terapéutico , Sepsis/tratamiento farmacológico , APACHE , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/prevención & control , Sepsis/clasificación , Sepsis/mortalidad , Choque Séptico/tratamiento farmacológico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Major vascular surgery with aortic cross-clamping is associated with temporary ischaemia of the lower limb due to lack of tissue blood flow. The present study was designed to determine if the short-term changes in cellular metabolism occurring during this situation can be detected by subcutaneous microdialysis. It was also hoped to ascertain if this new technique is useful in the continuous bedside monitoring of metabolism during aortic surgery. METHODS: In a controlled clinical study 20 patients undergoing elective aortic surgery were monitored using microdialysis probes that were inserted in the subcutaneous tissue of the left lower limb and a non-ischaemic region (shoulder). Interstitial fluid was obtained and the concentrations of glucose and lactate during lower limb ischaemia and during reperfusion were measured and compared with concentrations observed in fluid obtained from the non-ischaemic control tissue. RESULTS: Circulatory occlusion caused an immediate and significant decrease in the glucose/lactate ratio from 3.1+/-1.3 to 0.48+/-0.5 (P<0.05) that returned to preocclusion values within 2 h of commencing reperfusion. CONCLUSION: We suggest that microdialysis may be used both to assess acute changes in tissue metabolism during ischaemic periods and also to act as an additional tool for the detection of peri-operative acute variations in limb blood flow.
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Extremidades/irrigación sanguínea , Isquemia/prevención & control , Procedimientos Quirúrgicos Vasculares , Anciano , Glucemia/análisis , Glucosa/metabolismo , Humanos , Isquemia/metabolismo , Ácido Láctico/metabolismo , Microdiálisis , Persona de Mediana Edad , Atención Perioperativa , Reperfusión , Tejido Subcutáneo/metabolismoRESUMEN
The aim of this study was to examine the effect of decontamination as compared to placebo medication on post-gastrectomy treatment costs. The results of a prospective double-blind placebo-controlled multicenter trial indicate that perioperative i.v. prophylaxis with cefotaxim and topical decontamination with polymyxin B, tobramycin, vancomycin and amphotericin B from the day before surgery until the 7th postoperative day is most effective in the prevention of esophagojejunal anastomotic leakage following total gastrectomy. For the cost analysis, only patients who had been decontaminated according to the study protocol (n = 90) were compared to the non-decontaminated patients (n = 103). The esophagojejunal leakage rate was 10.6% in placebo patients (n = 103) and could be reduced significantly to 1.1% in decontaminated patients (n = 90, P = 0.0061; two-tailed Fisher's exact test). There was only one asymptomatic leakage detected on Gastrografin swallow. The pulmonary infection (P = 0.0173) and overall complication rates (p = 0.0238) were significantly reduced in the decontamination group as well. During the observation period, 9 (8.7%) patients in the placebo group and 3 (3.3%) in the decontaminated group died (P = n.s.). Patients were followed up for the initial 42 postoperative days and treatment costs were calculated for this time period only. The parameters compiled in the study pertaining to use of medical resources formed the basis for the determination of the postoperative treatment costs. These were the costs for decontaminating drugs, intravenous antibiotics, reoperations and non-surgical reinterventions as well as daily treatment costs of the general ward, the intensive care unit (ICU) and rehabilitation. The average costs per patient in the placebo group amounted to DM 20,000 while the costs for decontaminated patients were only DM 16,200, which was due to a significantly lower number of patients requiring treatment in the ICU (P = 0.0082), significantly fewer patients requiring i.v. antibiotics (P = 0.0232) and fewer patients with reoperations (P = 0.0909). The prophylaxis employing decontaminating drugs in the amount of DM 400 lowered post-gastrectomy treatment costs by DM 3800 or 19%. The prophylaxis can be recommended, because it lowers morbidity, mortality and the costs of total gastrectomy.
Asunto(s)
Profilaxis Antibiótica/economía , Gastrectomía/economía , Neoplasias Gástricas/cirugía , Dehiscencia de la Herida Operatoria/prevención & control , Infección de la Herida Quirúrgica/prevención & control , Anciano , Anfotericina B/administración & dosificación , Cefotaxima/administración & dosificación , Ahorro de Costo , Método Doble Ciego , Quimioterapia Combinada/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimixina B/administración & dosificación , Estudios Prospectivos , Neoplasias Gástricas/economía , Neoplasias Gástricas/mortalidad , Dehiscencia de la Herida Operatoria/economía , Dehiscencia de la Herida Operatoria/mortalidad , Infección de la Herida Quirúrgica/economía , Infección de la Herida Quirúrgica/mortalidad , Tasa de Supervivencia , Tobramicina/administración & dosificación , Vancomicina/administración & dosificaciónRESUMEN
A percutaneous osseointegrated anchoring device for above-knee implantation designed to enable permanent attachment of an artificial limb is described. In addition to a technical description, the two-stage operative procedure, together with the rehabilitation process in an 18-year-old man, is also detailed. Following amputation and complete healing of the soft tissues, a surface-structured metal pin capable of supporting large loads, is driven into the medullary canal of the thigh bone. A metal sleeve having an identical surface structure serves to close off the medullary canal and provide an interface with the soft tissues. Screwed to the end of the pin is a conical metal adapter to which is attached a silicone cylinder whose right-angled distal end is located subcutaneously and ends in a titanium mesh. The first part of the implantation procedure is concluded by closing the silicone cylinder with a plastic plug for 6 weeks to permit osseous integration and the ingrowth of tissue into the mesh. In a second step, the plastic plug is removed via a skin incision, and the permanent load-bearing metal adapter fitted. In the above-mentioned patient wound healing at the metal/tissue interface was complication-free, since the implanted silicone cylinder prevented the "wedge effect" caused by the build-up of "luxuriant" tissue. After a further healing phase of 6 weeks, rehabilitation with an exoprosthesis took only 2 weeks, after which time, the patient was able to walk without a walking aid, and returned to work.
Asunto(s)
Amputados/rehabilitación , Miembros Artificiales , Clavos Ortopédicos , Fémur/cirugía , Oseointegración/fisiología , Adolescente , Fémur/fisiopatología , Humanos , Masculino , Diseño de Prótesis , Soporte de Peso/fisiologíaRESUMEN
The incidence of fungal infection as well as fungal sepsis has increased dramatically during the last decade. Changes of local microbial flora after broad-spectrum antibiotic therapy allow overgrowth of Candida species. Prophylactic strategies to lower fungal infection and sepsis include adequate and restrictive antibiotic therapy. Concerning the treatment of the septic syndrome, supportive as well as adjunctive strategies like early-goal-directed cardiovascular therapy, hydrocortisone replacement therapy, intense insulin application to achieve normoglycemia as well as the application of activated Protein C besides a consequent source control regimen and standard intensive care therapy, are able to improve significantly the outcome of septic patients.
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Antifúngicos/uso terapéutico , Micosis , Sepsis , Quimioprevención , Humanos , Micosis/tratamiento farmacológico , Micosis/microbiología , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Sepsis/prevención & controlRESUMEN
Despite aggressive surgical treatment, prompt antibiotic therapy, and modern intensive care, up to one half of patients still die of diffuse peritonitis. There must be a distinction between infection as a microbiological phenomenon and sepsis as a complex, deleterious, inflammatory host response. Physiologic and metabolic changes during the latter process by taxonomically different organisms or different sources of infection are often clinically indistinguishable. Taurolidine, an amino acid derivate, seems to cover a variety of effects in peritonitis. As secondary peritonitis is associated with a significant cytokine release that is compartementalized in the peritoneal cavity, taurolidine is bactericidal, antiendotoxic, and antiadherent locally and, on the other hand, may modulate the systemic cytokine-mediated inflammatory response after being adsorbed systemically by the peritoneum. Current management of peritonitis can clear the peritoneal cavity of microorganisms and their products but patients continue to die of uncontrolled cytokine-induced systemic inflammation. In patients that undergo daily staged, planned relaparotomies they should not only be treated locally by taurolidine but also systemically by intravenous administration. The latter should, as a sort of sequential therapy, be continued, especially when the peritoneal cavity has been closed after a series of relaparotomies.
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Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Citocinas/sangre , Peritonitis/tratamiento farmacológico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Taurina/análogos & derivados , Tiadiazinas/uso terapéutico , Antiinfecciosos/efectos adversos , Infecciones Bacterianas/mortalidad , Infecciones Bacterianas/cirugía , Terapia Combinada , Humanos , Peritonitis/mortalidad , Peritonitis/cirugía , Reoperación , Infección de la Herida Quirúrgica/mortalidad , Infección de la Herida Quirúrgica/cirugía , Taurina/efectos adversos , Taurina/uso terapéutico , Tiadiazinas/efectos adversosRESUMEN
In three fatal cases of clostridial myonecrosis, the following criteria were found: repeated intramuscular injections over several years with anti-inflammatory substances, delay in diagnosis in outpatient care, and following uncontrollable systemic septic complications, despite radical surgical treatment. Only early, aggressive surgical interventions can stop the rapid course of necrotizing soft-tissue infections.
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Fascitis Necrotizante/cirugía , Gangrena Gaseosa/cirugía , Inyecciones Intramusculares/efectos adversos , Miositis/cirugía , Adulto , Anciano , Nalgas , Desbridamiento , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/mortalidad , Resultado Fatal , Femenino , Gangrena Gaseosa/diagnóstico , Gangrena Gaseosa/mortalidad , Humanos , Inyecciones Intramusculares/instrumentación , Masculino , Miositis/diagnóstico , Miositis/mortalidad , NecrosisRESUMEN
To evaluate the therapeutic effect of pentoxifylline (POF) on cardiopulmonary, renal and hepatic dysfunction, 51 patients with sepsis were randomized to receive POF or saline solution as placebo. Continuous intravenous administration of POF beneficially influenced cardiopulmonary organ function without adverse effects. PO2/FiO2-ratio as parameter of pulmonary dysfunction was significantly improved in the second week after diagnosis while parameter of cardial function were significantly different in the initial phase of sepsis. The clinical efficacy of POF in terms of organ dysfunction, however, did not result in improved survival.
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Insuficiencia Multiorgánica/tratamiento farmacológico , Pentoxifilina/administración & dosificación , Inhibidores de Fosfodiesterasa/efectos adversos , Choque Séptico/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Terapia Combinada , Cuidados Críticos , Humanos , Infusiones Intravenosas , Insuficiencia Multiorgánica/inmunología , Insuficiencia Multiorgánica/mortalidad , Pentoxifilina/efectos adversos , Estudios Prospectivos , Choque Séptico/inmunología , Choque Séptico/mortalidad , Tasa de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In a porcine endotoxin shock model using a continuous intravenous endotoxin infusion of 250 ng/kg body weight per hour, the cardiorespiratory and hematologic parameters were studied while applying a new on-line polymyxin B immobilized adsorption system. This preliminary report shows that the new adsorbent can remove endotoxin selectively from the circulation and confers a good amount of protection from endotoxin-induced cardiopulmonary decompensation as well as hematologic alterations. Survival time could be extended from 216 min to 313 min. Whereas cardiac output and mean arterial pressure declined critically after 3 h in the controls, the treated group remained stable for another 3 h. These data show that endotoxin adsorption by polymyxin B coupled covalently to acrylic spheres as an adjunctive on-line measure in the septic syndrome seems feasible.
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Endotoxinas/aislamiento & purificación , Hemoperfusión/métodos , Salmonella , Adsorción , Animales , Modelos Animales de Enfermedad , Endotoxinas/sangre , Estudios de Evaluación como Asunto , Femenino , Hemoperfusión/instrumentación , Microesferas , Tamaño de la Partícula , Polimixina B , Choque Séptico/sangre , Choque Séptico/fisiopatología , Choque Séptico/terapia , Porcinos , Factores de TiempoRESUMEN
After induction of early-phase endotoxin tolerance in a porcine endotoxin shock model over a period of 3-4 days a highly significant survival-time extension (p < or = 0.0001) was achieved. The protective effect of the unspecific tolerant state led to a significant enhancement of cardiorespiratory parameters during the continuous endotoxin challenge. However, the level of tolerance is relative and can be overcome by increasing the endotoxin challenge dose.
Asunto(s)
Toxinas Bacterianas/inmunología , Endotoxemia/inmunología , Endotoxinas/inmunología , Lipopolisacáridos/inmunología , Salmonella/inmunología , Choque Séptico/inmunología , Animales , Tolerancia Inmunológica/inmunología , PorcinosRESUMEN
BACKGROUND/AIMS: Procalcitonin (PCT) was shown to be related to the severity of bacterial infection and is recommended as a new parameter of inflammation and infection. To evaluate the prognostic value in septic shock, PCT levels were repeatedly determined and compared with tumour necrosis factor-alpha (TNF-alpha)- and interleukin (IL)-6 bioactivity as well as with C-reactive protein (CRP) serum levels. PATIENTS: Twenty-four surgical patients with septic shock were included. Eight patients died within the study period of 14 days. METHODS: Serum levels of TNF-(WEHI 164) and IL-6 (B13-29 subclone 9) bioactivity, CRP and PCT were determined on days 1, 3, 5, 7, 10 and 14 following diagnosis of septic shock. RESULTS: Survivors and non-survivors were comparable in terms of age and severity of sepsis characterized by the APACHE II score and multiple-organ-failure score. Predominant causes of sepsis were peritonitis and necrotiszing pancreatitis. TNF levels increased in non-survivors with no significant difference to survivors. IL-6 bioactivity was increased on day 1 (P = 0.06) and remained elevated in non-survivors, in whom it was significant on day 7 (P<0.05). CRP was constantly elevated with no difference between the groups. In nonsurvivors PCT remained increased, while the course of survivors was characterized by decreased values which were significantly lower (P<0.05) at every time point compared with those patients who died. A significant correlation could be found on day 1 (P<0.05) and at the end of the observation period (P<0.01) when comparing PCT levels with the multiple-organ-failure score. CONCLUSIONS: PCT seems to be a more reliable prognostic parameter in septic shock than IL-6, while TNF and CRP did not show any difference between survivors and non-survivors. These data indicate that PCT may represent a valuable parameter not only in the diagnosis of sepsis but also in the clinical course of the disease.
Asunto(s)
Biomarcadores/sangre , Calcitonina/sangre , Glicoproteínas/sangre , Precursores de Proteínas/sangre , Índice de Severidad de la Enfermedad , Choque Séptico/sangre , APACHE , Proteína C-Reactiva/análisis , Péptido Relacionado con Gen de Calcitonina , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Pancreatitis/complicaciones , Peritonitis/complicaciones , Pronóstico , Choque Séptico/diagnóstico , Choque Séptico/mortalidad , Factor de Necrosis Tumoral alfa/análisisRESUMEN
The induction of early-phase endotoxin tolerance in a procine endotoxin shock model by atoxic LPS from Rhodobacter sphaeroides led to a significant extension of the survival time (p < 0.0179). The protective effect of the non-specific tolerant state also led to an enhancement of cardiorespiratory parameters during the continuous endotoxin challenge. Non-specific stimulation of host defense mechanisms with atoxic endotoxin as prophylactic agent in surgical patients at risk may prove to be beneficial in the future.
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Lipopolisacáridos/inmunología , Rhodobacter sphaeroides/inmunología , Salmonella/inmunología , Choque Séptico/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Animales , Tolerancia Inmunológica/inmunología , Choque Séptico/prevención & control , Porcinos , Síndrome de Respuesta Inflamatoria Sistémica/prevención & controlRESUMEN
We studied the histomorphological changes of organs in an animal model of endotoxin tolerance (ETT). ETT was induced by pretreating pigs with increasing doses of endotoxin (ET) before challenging them with a continuous lethal ET infusion. In the ETT group the survival time was prolonged significantly versus controls, so that in the ETT group on an average double the ET challenge dose was administered. In this histomorphological study the lung, kidney, and intestine of almost all animals (ETT group n = 12, controls n = 11) showed about the same unspecific histological shock features. In the liver, however, we diagnosed partly disseminating, partly confluent, but obviously ET-induced, neutrophil liver cell necrosis in 10/12 ETT pigs and in 10/11 controls. We conclude that ETT in our model was not a protective factor against serious liver cell injury after ET administration. Our results may indicate that the ETT phenomenon can be overcome by raising the ET challenge dosage.
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Toxinas Bacterianas/toxicidad , Endotoxinas/toxicidad , Hígado/patología , Animales , Tolerancia a Medicamentos , Enterotoxinas/toxicidad , Intestinos/patología , Riñón/patología , Pulmón/patología , Miocardio/patología , Salmonella , PorcinosRESUMEN
In a porcine endotoxin shock model employing a continuous intravenous administration of Salmonella abortus equi endotoxin the cardiorespiratory and metabolic parameters were studied with main emphasis on the effect of hemofiltration (HF) as the only therapeutical measurement on the enhancement of survival time. Arachidonic acid (AA) metabolites Thromboxan B2 and 6-Keto-PGF 1-alpha could be lowered significantly by hemofiltration. Measuring the inadequacy of the supply and delivery systems in terms of O2-uptake, CO2 production, lung mechanics, TPR, CO, heart rate and MAP the control group seemed to be more severely compromised than the hemofiltrated groups, although the final outcome as for survival time could not be increased significantly. HF can nonselectively counteract some toxic effects of shock mediators without depriving the organism of beneficial components of a protective system being stimulated at the same time. Once the AA cascade is initiated, pharmacologic inhibition is of limited value as long as a direct specific therapeutic manipulation is still not available. Elimination of mediators by HF helps to combat the overstimulation of host defense mechanisms in ET shock which represents the ultimate threat to the host.
Asunto(s)
Modelos Animales de Enfermedad , Hemofiltración , Choque Séptico/terapia , 6-Cetoprostaglandina F1 alfa/sangre , Animales , Ácido Araquidónico , Ácidos Araquidónicos/sangre , Presión Sanguínea , Agua Corporal/fisiología , Dióxido de Carbono/metabolismo , Gasto Cardíaco , Frecuencia Cardíaca , Consumo de Oxígeno , Presión Esfenoidal Pulmonar , Choque Séptico/fisiopatología , Porcinos , Tromboxano B2/sangre , Resistencia VascularRESUMEN
OBJECTIVE: To investigate the relation of the biallelic Nco1 restriction fragment length polymorphism in the first intron of the tumor necrosis factor (TNF) beta gene with the development of severe sepsis in multiply injured patients. SUMMARY BACKGROUND DATA: The biallelic Nco1 polymorphism of the TNFbeta gene has been described to be associated with autoimmune diseases and with the mortality rate in severe sepsis. Therefore, the Nco1 polymorphism may be associated with the clinical finding that despite comparable risk factors, posttraumatic sepsis develops in some patients but not others. METHODS: The study group consisted of 110 patients with severe blunt trauma (Injury Severity Score > or = 17). Typing of each patient for the biallelic Nco1 polymorphism was performed by analyzing restriction fragments of an Nco1-digested DNA fragment obtained using polymerase chain reaction. Genotypes were then related to the occurrence of severe posttraumatic sepsis and TNFalpha serum concentrations. RESULTS: Fifty-seven patients showed an uncomplicated posttraumatic recovery, and severe sepsis developed in 53 patients. The overall allele frequency (TNFB1 0.29, TNFB2 0.71) and genotype distribution (TNFB1 homozygous 7.3%, TNFB1/TNFB2 42.7%, TNFB2 homozygous 50%) were in agreement with the distribution in healthy volunteers. Genotype distribution in patients with an uncomplicated clinical course was significantly different from that in patients with severe posttraumatic sepsis. Development of severe posttraumatic sepsis was significantly increased in patients homozygous for the allele TNFB2. In patients with severe posttraumatic sepsis, TNFalpha serum concentrations were significantly higher in TNFB2-homozygous individuals compared with heterozygous and TNFB1 -homozygous individuals. The age- and injury-matched odds ratio for the homozygous TNFB2 genotype compared with the heterozygous genotype was 5.22 (p = 0.007, 95% confidence interval 1.6 to 17.9). CONCLUSIONS: In multiply injured patients, the Nco1 polymorphism within the TNFbeta gene is associated with the development of severe posttraumatic sepsis and with increased TNFalpha serum levels when severe sepsis has occurred. This suggests a genetic determination of the individual inflammatory response after infection or tissue damage, which significantly influences susceptibility to severe nosocomial infections.
Asunto(s)
Polimorfismo de Longitud del Fragmento de Restricción , Sepsis/genética , Factor de Necrosis Tumoral alfa/genética , Heridas no Penetrantes/complicaciones , Adulto , Alelos , Antibacterianos/uso terapéutico , Femenino , Humanos , Masculino , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Índices de Gravedad del TraumaRESUMEN
OBJECTIVE: A prospective, randomized, double-blind, placebo controlled multicenter trial was undertaken in 205 patients treated with total gastrectomy for gastric malignancies to evaluate whether local antimicrobial measures reduce the incidence of esophagojejunal anastomotic leakage. SUMMARY BACKGROUND DATA: Anastomotic leakage of the esophagojejunostomy is always a septic complication of total gastrectomy for gastric malignancies, but it never has been attempted to prevent this complication with the administration of topical antimicrobial agents during the critical phase of anastomotic wound healing. METHODS: To evaluate the efficacy and safety of topical decontamination, the study was carried out as a prospective, randomized, double-blind and placebo-controlled clinical multicenter trial in patients with total gastrectomy for gastric cancer. Patients received either placebo or decontamination with polymyxin B (100 mg), tobramycin (80 mg), vancomycin (125 mg), and amphotericin B (500 mg) four times per day orally from the day before the operation until the seventh postoperative day. All patients received a perioperative intravenous prophylaxis with cefotaxime 2 x 2 g. Other interventions including the administration of antibiotics and fluids, were not affected by the study protocol. RESULTS: Of 260 patients who were randomized, total gastrectomy was not carried out in 55 patients. They dropped out of the study. Patients receiving an esophagojejunostomy were observed until day 42, when they were discharged from the clinic or died. An intention-to-treat analysis of the data was carried out. Among the 103 recipients of placebo, there were 11 (10.6%) with an anastomotic leakage of the esophagojejunostomy, and among the 102 recipients of decontamination, there were 3 (2.9%) with an anastomotic leakage of the esophagojejunostomy (p = 0.0492). Pulmonary infections were observed in 23 patients (22.3%) receiving placebo and in 9 patients (8.8%) who were decontaminated (p = 0.02). There were 11 deaths (10.6%) among the recipients of placebo and 5 deaths (4.9%) among the recipients of decontamination (p = 0.1). CONCLUSIONS: Decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B during anastomotic wound healing is safe and effective in the prevention of esophagojejunal anastomotic leakage after total gastrectomy.