RESUMEN
AIM: To evaluate the efficacy and safety of treatment with recombinant growth hormone (rGH) in patients with cystic fibrosis (CF). METHODS: Twenty patients with CF (aged 10-23 years) were randomised to age and sex matched treatment and control groups. The treatment group received daily subcutaneous injections of 1 IU/kg/wk rGH for 12 months. Pulmonary function (forced expiratory volume in one second (FEV1) and airway resistance), exercise capacity measured with a bicycle ergometer, body composition (dual energy x ray absorptiometry), and weight were assessed at the beginning of the study and after 6 and 12 months. RESULTS: rGH treatment did not improve weight and pulmonary function, but lean body mass increased significantly in the treatment group. Exercise capacity increased in the treatment group from 143 (16) W (mean (SD)) to 164 (19) W after 12 months of rGH treatment. CONCLUSION: Treatment of CF patients with rGH for one year improved the exercise capacity significantly but not pulmonary function. The improved exercise capacity needs confirmation in a larger population before such an expensive treatment is justified.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Fármacos del Sistema Respiratorio/uso terapéutico , Adolescente , Adulto , Índice de Masa Corporal , Niño , Tolerancia al Ejercicio , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Consumo de Oxígeno/fisiología , Estudios Prospectivos , Resultado del Tratamiento , Capacidad Vital/fisiologíaRESUMEN
Inflammation and proteolytic processes play an important role in the progression of cystic fibrosis (CF) lung disease. The goal of this study was to describe bronchoalveolar lavage fluid (BALF) protein pattern of CF patients in comparison to controls and to assess if there is proteolytic degradation of surfactant protein A (SP-A), an important innate host defence component of the lungs. BALFs from 17 clinically stable CF patients and from eight healthy children were separated by two-dimensional gel electrophoresis. Silver staining was used to show BALF proteins and Western blotting to detect SP-A isoforms. In CF, BALF proteins of a low molecular weight < or = 20 kD were more abundant than in controls. Various proteins were seen in CF which were not present in controls and vice versa. Degradation of SP-A was present in 15 of 17 CF BALFs but in none of the controls, in contrast polymeric isoforms were seen in all controls and in four of 17 CF patients. Proteolytic damage to surfactant protein A and significant changes of normal bronchoalveolar lavage fluid proteins occur in lungs of cystic fibrosis patients. Identification of altered bronchoalveolar lavage fluid proteins may give new insights into pathogenic mechanisms and provide new targets for therapy.
Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Fibrosis Quística/metabolismo , Proteínas/análisis , Proteolípidos/análisis , Surfactantes Pulmonares/análisis , Adolescente , Niño , Electroforesis en Gel Bidimensional , Humanos , Elastasa de Leucocito/análisis , Proteína A Asociada a Surfactante Pulmonar , Proteínas Asociadas a Surfactante PulmonarRESUMEN
In cystic fibrosis (CF), the chronic neutrophilic inflammation of the airways results in proteolytic degradation of lung tissue early in the course of the disease. Inhalation of alpha 1-protease inhibitor (alpha 1-PI) may restore the protease-antiprotease imbalance and thus lead to less tissue damage. To monitor its impacts on bronchoalveolar lavage (BAL) fluid protein pattern (proteome) and on surfactant protein A (SP-A), eight young adults with CF inhaled 100 mg of alpha 1-PI twice daily over eight weeks. BAL fluids were obtained before and after inhalation. Total protein, the number and amount of proteins with a molecular mass < 20 kDa were reduced compared to pretreatment values. Degradation products of SP-A were shown by immunoblotting, being reduced after alpha 1-PI treatment. This pilot study demonstrates that inhalation of alpha 1-PI is associated with biochemical changes consistent with reduced proteolysis. The display of the BAL proteome by two-dimensional electrophoresis may be helpful to quantify the overall molecular changes associated with proteolytic or other lung injuries and offers the possibility to monitor directly therapeutic interventions.
Asunto(s)
Fibrosis Quística/metabolismo , Proteolípidos/metabolismo , Proteoma/metabolismo , Surfactantes Pulmonares/metabolismo , alfa 1-Antitripsina/uso terapéutico , Administración por Inhalación , Adolescente , Líquido del Lavado Bronquioalveolar , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/microbiología , Endopeptidasas/metabolismo , Femenino , Humanos , Masculino , Proteína A Asociada a Surfactante Pulmonar , Proteínas Asociadas a Surfactante Pulmonar , Soluciones , alfa 1-Antitripsina/administración & dosificaciónRESUMEN
The inhalation of alpha(1)-protease inhibitor (alpha(1)-PI) was assessed in a pilot study to restore the protease-antiprotease balance in the lungs of cystic fibrosis (CF) patients. In addition, the effect of this treatment on the surface active properties of lung surfactant and the metabolic conversion of aggregate forms was studied. Eight young adults with CF inhaled 100 mg of alpha(1)-PI twice daily over 8 weeks and bronchoalveolar lavages (BAL) were obtained before and 12 h after the last inhalation. Large aggregate (LA) forms of surfactant were isolated from the in vivo material by ultracentrifugation and their conversion into small aggregates (SA) was assessed by an in vitro surface area cycling assay. Although alpha(1)-PI partially restored the protease-anti-protease imbalance and reduced BAL protein content, no effects were noted on the impaired minimal surface tension and on the in vivo and in vitro conversion of LA to SA. Antiserum against the specific carboxyl esterase ES-2, previously identified in mice and rats as the putative surfactant convertase, did not detect a protein of the appropriate size in CF BAL. Whereas short-term inhalation of alpha(1)-PI was beneficial for the proteolytic aspects of CF lung injury, this appeared not to be the case for surfactant conversion and surface activity.
Asunto(s)
Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Inhibidores de Serina Proteinasa/farmacología , alfa 1-Antitripsina/farmacología , Administración por Inhalación , Adolescente , Femenino , Humanos , Pulmón/efectos de los fármacos , Pulmón/fisiología , Masculino , Surfactantes Pulmonares/farmacología , Inhibidores de Serina Proteinasa/administración & dosificación , Tensión Superficial , alfa 1-Antitripsina/administración & dosificaciónRESUMEN
A neonatal case of severe, ventilator-dependent tracheobronchomalacia (TBM) is described. The extent of the malacic segment was determined by endoscopy and tracheobronchography. Additionally, relevant and ever increasing reversible peripheral airway obstruction was documented by measuring the mechanical properties of the respiratory system before and after salbutamol. With the combination of endoscopically guided aortopexy and salbutamol infusion, the infant was eventually weaned from mechanical ventilation at the age of 86 days. We speculate that in ventilator-dependent infants with severe TBM the determination of bronchodilator responsiveness may have clinical consequences.
Asunto(s)
Albuterol/uso terapéutico , Enfermedades Bronquiales/terapia , Broncodilatadores/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Mecánica Respiratoria/efectos de los fármacos , Enfermedades de la Tráquea/terapia , Albuterol/farmacología , Enfermedades Bronquiales/complicaciones , Broncodilatadores/farmacología , Broncografía , Femenino , Humanos , Recién Nacido , Respiración con Presión Positiva , Respiración Artificial , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Enfermedades de la Tráquea/complicacionesRESUMEN
The relationship between the most common disease-causing mutations, the clinical manifestation, and lung function was prospectively assessed in 60 infants (33 females, 27 males) with cystic fibrosis at time of diagnosis (age: 7.2 months; range: 0.8-23.8 months). Lung function was assessed by infants whole-body plethysmography. Age at time of diagnosis was independent from the genotype. Weight gain from birth until the time of diagnosis expressed in percent predicted of a normal population was lower in the 3905insT group (57.9 +/- 19.0%) compared with deltaF508 homozygotes (62.5 +/- 20.6%; n.s.) and the R553X group (85.9 +/- 10.9%; p < 0.005). Differences regarding lung function within the genetic groups are mainly related to pulmonary hyperinflation, measured by thoracic gas volume (TGV), present in 8 of 9 infants with 3905insT, differentiating this frameshift mutation (TGV of 7.0 +/- 3.6 SD-S) from the R553X mutation (TGV 2.1 +/- 4.6 SD-S; p < 0.02). It is concluded that the variable disease findings in infants with cystic fibrosis is clinically and functionally reflected by features already present at time of diagnosis. The degree of pulmonary hyperinflation is, at least partly, influenced by the genotype.
Asunto(s)
Fibrosis Quística/genética , Fibrosis Quística/fisiopatología , Bacterias/aislamiento & purificación , Fibrosis Quística/patología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Genotipo , Humanos , Lactante , Masculino , Mutación , Fenotipo , Pruebas de Función Respiratoria , Mecánica Respiratoria , Aumento de PesoRESUMEN
Cystic fibrosis (CF) leads to a chronic inflammation of the airways with significant air flow limitations developing early in the course of the disease. As a well-functioning pulmonary surfactant is necessary to keep the alveoli and the small conducting airways open during expiration, we hypothesized that the biochemical and biophysical properties of surfactant may be impaired in CF. Bronchoalveolar lavage fluid obtained during a clinically stable period was analysed from 20 CF patients (5.9-20 yrs) and 17 healthy children and adults. CF patients had significantly elevated total and polymorphonuclear neutrophil cell counts, whereas the concentrations of total protein and phospholipids did not differ from controls. The percentage of surface active phospholipids, phosphatidylcholine and phosphatidylglycerol, and the concentration of surfactant protein A were significantly reduced in CF patients. Surfactant protein B was unchanged. Although the relative proportion of large aggregates was higher in CF, their surface active properties were inferior, as assessed in the pulsating bubble surfactometer. Because the capacity of CF lavage fractions to inhibit surfactant function was the same as that of controls, impaired minimal surface tension was more likely to be due to the biochemical alterations detected, than to inhibition of a well-functioning surfactant. The impaired pulmonary surfactant system in clinically stable patients with cystic fibrosis is in agreement with the view that surfactant dysfunction may contribute to lung disease in cystic fibrosis.
Asunto(s)
Fibrosis Quística/metabolismo , Surfactantes Pulmonares/metabolismo , Adolescente , Adulto , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Niño , Preescolar , Fibrosis Quística/patología , Humanos , Persona de Mediana Edad , Fosfolípidos/análisis , Proteínas/análisis , Proteolípidos/análisis , Proteínas Asociadas a Surfactante Pulmonar , Surfactantes Pulmonares/análisis , Surfactantes Pulmonares/química , Tensión SuperficialRESUMEN
A syndrome involving periodic fever, pharyngitis, adenitis and aphthous stomatitis is described in 8 children. Attacks are characterized by abrupt onset of fever and, in addition to the above symptoms, by malaise, headache and abdominal pain. Mild leukocytosis and elevation of the erythrocyte sedimentation rate are found in the laboratory. Patients exhibit normal growth and development and are otherwise healthy. PFAPA is clinically benign, with no long-term sequelae. Recognition and diagnosis of the syndrome eliminate the need for intensive work-up. The cause remains unknown. No evidence linking bacterial, viral, or fungal pathogens to this syndrome has been found. No patient has exhibited atypical lymphocytosis or neutropenia, and all patients had normal levels of immunoglobulin. All had received antibiotics early in the course of their illness but without effect. Cimetidine has been discussed in the literature as a possible treatment, but the results are controversial.
Asunto(s)
Fiebre de Origen Desconocido/etiología , Linfadenitis/etiología , Periodicidad , Faringitis/etiología , Estomatitis Aftosa/etiología , Preescolar , Diagnóstico Diferencial , Pruebas Diagnósticas de Rutina , Femenino , Fiebre de Origen Desconocido/diagnóstico , Humanos , Lactante , Linfadenitis/diagnóstico , Masculino , Faringitis/diagnóstico , Recurrencia , Estomatitis Aftosa/diagnóstico , SíndromeRESUMEN
The antipyretic efficacy of propacetamol, an intravenous prodrug of paracetamol, was evaluated in two pediatric prospective randomized studies. In the first, we-compared one standard intravenous dose of propacetamol (30 mg/kg) to one standard intravenous dose of acetylsalicylic acid (ASA, 15 mg/kg) in 10 nononcologic patients with bacterial illnesses. In the second study, we compared two intravenous doses of propacetamol (30 mg/kg versus 15 mg/kg) in 24 oncologic patients with fever and neutropenia. No statistically significant differences in antipyretic efficacy were found between standard doses of propacetamol and ASA; even when half-doses of propacetamol (15 mg/kg) were used, good antipyretic efficacy was observed, which was not statistically different from that observed with the full dose. The use of propacetamol seems promising for patients (such as oncologic patients) who cannot receive enteral paracetamol formulas.
Asunto(s)
Acetaminofén/uso terapéutico , Analgésicos no Narcóticos/uso terapéutico , Aspirina/uso terapéutico , Fiebre/tratamiento farmacológico , Neoplasias/complicaciones , Acetaminofén/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Aspirina/efectos adversos , Infecciones Bacterianas/complicaciones , Niño , Preescolar , Fiebre/etiología , Humanos , Infusiones Intravenosas , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Estudios ProspectivosRESUMEN
UNLABELLED: Twenty-nine of initially 42 infants with recurrent wheeze (20 male and 9 female) with an age range of 2.1-25.2 months were randomly assigned to receive either 100 micrograms beclomethasone dipropionate (BDP) combined with 200 micrograms salbutamol (group BDP-S, n = 9), 200 micrograms salbutamol (group S, n = 8), or placebo (group P, n = 6) 3 times daily for a 6 weeks' treatment period. Six infants had to be treated openly with BDP-S (group O, n = 6) because of deterioration in the disease state. Ten babies were excluded because of incomplete data and poor drug compliance and further 3 because of needed rescue medication. The drugs were inhaled from a metered dose inhaler through a baby-adapted spacer device, the Babyhaler. Control was assessed by symptom diaries, and infant whole-body plethysmography. Values of thoracic gas volume (TGV), airway conductance (Gaw) and specific airway conductance (sGaw) were calculated numerically independent of age and body length in percent predicted and in standard deviation scores using regression equations taken from healthy infants previously evaluated. Functional improvement was considered to have occurred when either TGV, and/or Gaw improved more than 2 SD from baseline. There was a significant improvement in the symptom score (p < 0.05), particularly concerning cough, in addition to a significant decrease in pulmonary hyperinflation (TGV: p < 0.05) and improvement of Gaw (p < 0.01) and sGaw (p < 0.01) in the BDP-S group when compared to the P group. No significant differences were found between the BDP-S and S group and/or between the S and P groups. CONCLUSIONS: In wheezy infants BDP improves clinical status and lung function, when given in combination with salbutamol by a baby-adapted spacer device.
Asunto(s)
Albuterol/administración & dosificación , Asma/tratamiento farmacológico , Beclometasona/administración & dosificación , Broncodilatadores/administración & dosificación , Glucocorticoides/administración & dosificación , Administración por Inhalación , Análisis de Varianza , Asma/fisiopatología , Distribución de Chi-Cuadrado , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Lactante , Masculino , Pruebas de Función Respiratoria , Ruidos Respiratorios/efectos de los fármacos , Resultado del TratamientoRESUMEN
BACKGROUND: Pseudomonas aeruginosa sepsis, well known in immunocompromised patients, is rare in previously healthy children. CASE REPORT: A previously healthy 4 month-old boy was admitted with the suspicion of meningococcal septicemia. Three days prior to admission, he had developed high fever and two 4 cm-diameter skin lesions on his right leg, with dark red colour and a central haemorrhagic blister. He subsequently developed generalized seizures; meningitis and urinary tract infection were excluded. Despite topical therapy with an antistaphylococcal drug skin lesions extended, particularly at the level of the head. The patient was given oral amoxicillin-clavulanate, but his condition worsened; he was transferred to our intensive care unit with septic shock and a diagnosis of meningococcemia. Blood cultures grew Pseudomonas aeruginosa. Despite intensive therapy and appropriate antibiotic therapy, the patient died. CONCLUSION: To allow early diagnosis and adequate treatment, it is mandatory to diagnose Ecthyma gangrenosum as the most frequent manifestation of invasive infection with Pseudomonas aeruginosa.
Asunto(s)
Bacteriemia/complicaciones , Ectima Contagioso/complicaciones , Infecciones por Pseudomonas/complicaciones , Bacteriemia/diagnóstico , Ectima Contagioso/diagnóstico , Humanos , Lactante , Masculino , Infecciones por Pseudomonas/diagnósticoRESUMEN
The acid-base balance of 199 patients with cystic fibrosis, seen from 1987 through 1992 at the Bern Outpatient Clinic, were evaluated. Simple metabolic alkalosis was demonstrated in 16 and mixed metabolic alkalosis and respiratory acidosis in 9 patients. When compared with 10 patients with simple respiratory acidosis and 16 with normal hydrogen ion balance, those with simple metabolic alkalosis were significantly younger. The need for pancreatic enzymes was significantly higher and the relative underweight significantly more severe in patients with either simple or mixed metabolic alkalosis and respiratory acidosis. The results indicate the rather common occurrence of chronic metabolic alkalosis in cystic fibrosis. It is observed in young patients, in patients who need high doses of pancreatic enzymes and in the those with poor nutritional status.
Asunto(s)
Alcalosis/complicaciones , Fibrosis Quística/complicaciones , Acidosis Respiratoria/complicaciones , Acidosis Respiratoria/epidemiología , Acidosis Respiratoria/metabolismo , Adolescente , Factores de Edad , Alcalosis/epidemiología , Alcalosis/metabolismo , Peso Corporal , Estudios de Casos y Controles , Niño , Preescolar , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/metabolismo , Femenino , Humanos , Lactante , Lipasa/administración & dosificación , Masculino , Extractos Pancreáticos/administración & dosificación , PancrelipasaRESUMEN
The association between abnormal chloride transport, resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, and the immunologic processes involved in the development of CF lung disease is poorly understood. However, neutrophil-dominated inflammation on the respiratory epithelial surface is a common finding in CF patients and suggests a mechanism for the immunologic abnormalities described in CF. Of particular importance for the pathophysiology of CF are proteases such as neutrophil elastase (NE) which are released from neutrophils in CF airways and cause direct structural damage to respiratory tissue. In healthy individuals, the deleterious effects of excess protease activity in the respiratory system are inhibited by antiproteases such as alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI). However, in CF, antiproteases are outnumbered by proteases and this protective mechanism is rendered ineffective. Restoration of this protease/antiprotease balance through antiprotease replacement therapy is currently under clinical investigation and preliminary results are promising.
Asunto(s)
Fibrosis Quística/metabolismo , Endopeptidasas/metabolismo , Enfermedades Pulmonares/etiología , Neutrófilos/enzimología , Inhibidores de Proteasas/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Fibrosis Quística/inmunología , Fibrosis Quística/fisiopatología , Humanos , Elastasa de Leucocito , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/metabolismo , Neutrófilos/efectos de los fármacos , Elastasa Pancreática/antagonistas & inhibidoresRESUMEN
Mycobacterium genavense is a rare cause of opportunistic infection in immunocompromised hosts. Follow up of two cases of M. genavense invasive infection in children with haemophilia A and AIDS are presented. One patient died 18 months after diagnosis of M. genavense infection of an indirectly related cause, probably of Pneumocystis carinii pneumonia. The second patient still attends our outpatient clinic and the infection is under control. Both presented with abdominal lymphomas and pain and a wasting syndrome. A combination of several drugs against atypical mycobacteria is used for treatment.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Síndrome de Inmunodeficiencia Adquirida/microbiología , Infecciones por Mycobacterium no Tuberculosas , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Neoplasias Abdominales/complicaciones , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Caquexia/complicaciones , Caquexia/microbiología , Resultado Fatal , Estudios de Seguimiento , Humanos , Lactante , Linfoma/complicaciones , Masculino , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Micobacterias no Tuberculosas/aislamiento & purificaciónRESUMEN
Cystic fibrosis (CF) is characterized in the lung by chronic purulent bronchitis culminating in pulmonary insufficiency. There is evidence to suggest that neutrophil elastase (NE) released by neutrophils on the respiratory epithelial surface plays a major role in the pathogenesis of this lung disease. This study sought to determine the age of onset of the chronic neutrophil-dominated inflammation in CF and the consequences to the NE-anti-NE screen on the respiratory epithelial surface of the CF lung. NE and anti-NE defensive molecules were evaluated in respiratory epithelial lining fluid (ELF) in 27 children with stable CF (1 to 18 yr of age). Despite normal antigenic concentrations of alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI), 25 of 27 children with CF had neutrophil-dominated inflammation (> 500 neutrophils/microliters ELF). Active NE was found in ELF in 20 of 27 children, including two of four aged 1 yr. Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded. These observations demonstrate that a chronic imbalance of the NE-anti-NE protective screen develops early on the respiratory epithelial surface in persons with CF and is likely well established by 1 yr of age, with resultant potential for lung damage.
Asunto(s)
Fibrosis Quística/enzimología , Pulmón/enzimología , Elastasa Pancreática/análisis , Proteínas , Inhibidores de Serina Proteinasa/análisis , alfa 1-Antitripsina/análisis , Adolescente , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Niño , Preescolar , Fibrosis Quística/patología , Femenino , Humanos , Lactante , Elastasa de Leucocito , Masculino , Neutrófilos/patología , Elastasa Pancreática/antagonistas & inhibidores , Proteínas Inhibidoras de Proteinasas Secretoras , Inhibidor Secretorio de Peptidasas LeucocitariasRESUMEN
Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, serves as the major inhibitor of neutrophil elastase (NE) on the epithelial surface of the upper airways. As a control for studies to evaluate the aerosol administration of recombinant SLPI (rSLPI) to augment the anti-NE defenses of the lung, the status of antioxidants in respiratory epithelial lining fluid (ELF) was evaluated. Unexpectedly, aerosol administration of rSLPI caused an elevation in ELF glutathione, a major component of the epithelial antioxidant screen; i.e., rSLPI may provide not only augmentation of anti-NE defenses but also antioxidant defenses. To evaluate this concept, rSLPI (100 mg) was aerosolized to sheep, and SLPI, glutathione, anti-NE capacity, and anti-H2O2 capacity were evaluated in respiratory ELF over a 30-h period. As expected, aerosolization of rSLPI increased ELF SLPI levels and anti-NE capacity. Strikingly, postaerosol levels of glutathione in ELF were also increased (5-fold 24 h after aerosol), with a concomitant increase in ELF anti-H2O2 capacity; i.e., the rSLPI augmented the antioxidant screen of ELF. This suggests that rSLPI may be particularly well suited for therapy in lung diseases characterized by excess of both serine proteases and oxidants on the respiratory epithelial surface.
Asunto(s)
Glutatión/metabolismo , Pulmón/metabolismo , Proteínas , Inhibidores de Serina Proteinasa/farmacología , Aerosoles , Animales , Cisteína/farmacología , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Técnicas In Vitro , Pulmón/efectos de los fármacos , Neutrófilos/enzimología , Oxidación-Reducción , Elastasa Pancreática/metabolismo , Proteínas Inhibidoras de Proteinasas Secretoras , Proteínas Recombinantes/farmacología , Inhibidores de Serina Proteinasa/administración & dosificación , OvinosRESUMEN
STUDY HYPOTHESIS: In a model of near-fatal hemorrhage that incorporates a vascular injury, stepwise increases in blood pressure associated with aggressive crystalloid resuscitation will result in increased hemorrhage volume and mortality. DESIGN: This study used a swine model of potentially lethal hemorrhage in the presence of a vascular lesion to compare the effects of resuscitation with mean arterial pressures of 40, 60, and 80 mm Hg. Twenty-seven fully instrumented immature swine (14.8 to 20 kg), each with a surgical-steel aortotomy wire in place, were bled continuously from a femoral artery catheter to a mean arterial pressure of 30 mm Hg. At that point the aortotomy wire was pulled, producing a 4-mm aortic tear and uncontrolled intraperitoneal hemorrhage. When the animal's pulse pressure reached 5 mm Hg, the femoral artery hemorrhage was discontinued and resuscitation was begun. INTERVENTIONS: Saline infusion was begun at 6 mL/kg/min and continued as needed to maintain the following desired endpoints: group 1 (nine) to a mean arterial pressure of 40 mm Hg, group 2 (nine) to a mean arterial pressure of 60 mm Hg, and group 3 (nine) to a mean arterial pressure of 80 mm Hg. After 30 minutes or a total saline infusion of 90 mL/kg, the resuscitation fluid was changed to shed blood infused at 2 mL/kg/min as needed to maintain the desired mean arterial pressure or to a maximum volume of 24 mL/kg. Animals were observed for 60 minutes or until death. MEASUREMENTS AND MAIN RESULTS: Data were compared using repeated-measures analysis of variance with a post hoc Tukey-Kramer, Fisher's exact test, and Kruskal-Wallis. Mortality was significantly greater in group 3 (78%) compared with either group 1 (11%; P = .008) or group 2 (22%; P = .028). Mean survival times were significantly shorter in group 3 (44 +/- 12 minutes) compared with either group 1 (58 +/- 6 minutes; P = .007) or group 2 (59 +/- 3 minutes; P = .006). The average intraperitoneal hemorrhage volumes were 13 +/- 14 mL/kg, 20 +/- 25 mL/kg, and 46 +/- 11 mL/kg for groups 1, 2, and 3, respectively (group 1 versus 2, P = .425; group 1 versus 3, P < .001; group 2 versus 3, P = .014). Group 2 animals demonstrated significantly greater oxygen deliveries compared with groups 1 and 3. CONCLUSION: In a model of near-fatal hemorrhage with a vascular injury, attempts to restore blood pressure with crystalloid result in increased hemorrhage volume and markedly higher mortality.
Asunto(s)
Aorta/lesiones , Presión Sanguínea , Fluidoterapia/efectos adversos , Choque Hemorrágico/fisiopatología , Animales , Volumen Sanguíneo , Soluciones Cristaloides , Hemorragia/fisiopatología , Soluciones Isotónicas , Modelos Biológicos , Sustitutos del Plasma/uso terapéutico , Choque Hemorrágico/mortalidad , Choque Hemorrágico/terapia , Tasa de Supervivencia , PorcinosRESUMEN
STUDY OBJECTIVE: To compare the efficacy of diazepam and midazolam when used for conscious sedation in emergency department patients. DESIGN: Prospective, randomized, double-blind, multicenter trial. SETTING: Three university EDs. TYPE OF PARTICIPANTS: Patients requiring one of the following procedures: abscess drainage, joint reduction, extensive suturing, chest tube insertion, or lumbar puncture. INTERVENTIONS: Diazepam (2.5 mg/mL) or midazolam (1 mg/mL) was administered until the desired level of sedation was achieved to a maximum of 5 mL. Fentanyl citrate was administered if needed for pain. MEASUREMENTS AND MAIN RESULTS: Thirty-three patients received diazepam and 36 received midazolam. Patients receiving midazolam had a greater degree of early sedation (P < .05), a higher 90-minute alertness scale score (P < .05), more patients ready for discharge at 90 minutes (P = .05), significantly less recall for the procedure (P < .02), and less pain on injection (P < .01) than patients who were given diazepam. CONCLUSIONS: Diazepam and midazolam are both effective for conscious sedation in ED patients. Midazolam causes less pain on injection, a significantly greater degree of early sedation, and a more rapid return to baseline function.