RESUMEN
This study compared two methods of controlling the intracuff pressure in laryngeal mask airways. One hundred and eighty patients were randomly assigned into two groups. In the first group (n = 90), after training, the intracuff pressure was controlled using digital palpation of the pilot balloon. In the second group (n = 90), continuous manometry was used to control the intracuff pressure. An upper pressure limit of 60 cmH2 O was set. The median (IQR [range]) intracuff pressure in the palpation group was 130 (125-130 [120-130]) cmH2 O compared with 29 (20-39 [5-60]) cmH2 O in the manometry group (p < 0.001). In the palpation group, 37% of patients experienced pharyngolaryngeal complications vs. 12% in the manometry group (p < 0.001). We conclude that the digital palpation technique is not a suitable alternative to manometry in controlling the intracuff pressure in laryngeal mask airways.
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Máscaras Laríngeas , Monitoreo Fisiológico/métodos , Palpación/métodos , Complicaciones Posoperatorias/prevención & control , Método Doble Ciego , Femenino , Humanos , Masculino , Manometría/métodos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Since introduction of the German refined DRG system, the, in relation to other countries, relatively long hospital stay has been reduced significantly. The analyses presented here examine the hypothesis that only few impact factors allow for good hospital management and that length of stay is a performance indicator. The analyses were based on remuneration data of 20 German hospitals for 2007-2009, comprising details of 963 923 patient cases, and cost data for 2007-2010. Using simple and multiple linear regressions, the impact of hospital length of stay and case-based factors on case mix index (CMI) and cost categories were explained. The variance of the case mix index was best explained by the length of hospital stay, showing an adjusted regression coefficient ß=0.488 (p<0.001), followed by the number of coded procedures (ß=0.35, p<0.001). Other predictors played a minor role. The regression coefficient was higher for conservative (non-operative) than for surgery (operative) departments. In the regression on costs, the length of hospital stay explained the variance of total costs by ß=0.391 (p<0.001), among these personnel costs of the nursing staff correlated most highly (ß=0.595, p<0.001). The analyses confirm the working hypothesis with length of stay impacting CMI and costs most significantly. Treatment effort and complexity level, mortality rate, patient age or gender are well discussed factors but their joint impact on the CMI is minor. Consequently, cockpits for operational length of stay management comprising key data and ratios should be introduced on the department level.
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Atención a la Salud/economía , Honorarios y Precios/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Renta/estadística & datos numéricos , Tiempo de Internación/economía , Modelos Económicos , Alemania/epidemiologíaRESUMEN
OBJECTIVE: To report on presence of human EEG spindle oscillations on the cortical level within flat periods of the burst-suppression pattern during propofol-induced anesthesia; to search for corresponding oscillations and possible functional connections. METHODS: Artefact-free epochs of spindle activation were selected from the electroencephalograms of opiate-dependent patients undergoing rapid opiate detoxification. Power spectral analysis and source localization using low-resolution-brain-electromagnetic-tomography (LORETA(Key)) were performed. RESULTS: Sinusoidal rhythms with waxing and waning amplitudes appeared after propofol-induced narcosis but no direct correlations could be determined between individual dosage and characteristic spindle attributes. The power maximum stood midline over the cortical areas, especially around C(z). We calculated a peak frequency of 14(+/-1.2) Hz. Motor fields, particularly in the frontal, parietal, and various cingulate areas, were found to be the primary sources of spindle oscillations in the cortex. CONCLUSIONS: The frequent occurrence of these localized spindle sources demonstrates the preference for motor fields. Spindle oscillations observed during propofol-induced narcosis were similar in frequency and shape to those observed in natural sleep. SIGNIFICANCE: The results lend support to models that postulate a close link between the motor system and the organization of behavior. In addition, spindle rhythms under propofol bore some resemblance to spindle types which occur during sleep.
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Anestésicos Intravenosos/administración & dosificación , Corteza Cerebral/efectos de los fármacos , Electroencefalografía/efectos de los fármacos , Trastornos Relacionados con Opioides/fisiopatología , Periodicidad , Propofol/administración & dosificación , Adulto , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Femenino , Lateralidad Funcional , Humanos , Imagenología Tridimensional , Masculino , Análisis Espectral , Estadísticas no ParamétricasRESUMEN
Oxidation of unsaturated phosphatidylcholine (PC) produces fragmented phospholipids which have similar bioactivities as the platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-PC). Since a large number of molecular species are produced upon PC oxidation, the active ingredients have not been identified. We synthesized several short-chain PCs which are known to be characteristic PC oxidation products to test their PAF-like activity. The synthetic PCs contained palmitoyl or hexadecyl residues (both C16) in sn-1 position, and propionyl (C3), valeroyl (C5), succinyl (C4 with omega-carboxyl), glutaroyl (C5 with omega-carboxyl), or suberoyl (C8 with omega-carboxyl) residues in sn-2 position. Biological activity was measured by: (1) increase of intracellular calcium in human monocytes; (2) [3H]serotonin release from rabbit platelets; and (3) aggregation of human platelets. Specificity of the cellular response was tested by inhibition with the PAF-receptor antagonists BN 52021 and WEB 2086. Synthetic PC oxidation products activated both monocytes and platelets in a PAF-specific manner. The effective concentration varied with respect to assay system and chemical structure. In general, 1-hexadecyl-PCs were more effective than 1-palmitoyl-PCs, while increasing chain length in sn-2 position lowered biological activity. However, several 1-palmitoyl-PCs activated monocytes in concentrations between 10-8 and 10-6 M. In contrast, platelets were less susceptible to 1-palmitoyl-PCs. No significant difference was found between 2-valeroyl-PC (C5 with omega-methyl) and 2-glutaroyl-PC (C5 with omega-carboxyl). The data suggest that typical products of PC oxidation, containing propionyl, succinyl, or glutaroyl residues in sn-2 position, display PAF-like activity at micromolar concentrations.
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Plaquetas/efectos de los fármacos , Monocitos/efectos de los fármacos , Fosfatidilcolinas/farmacología , Animales , Plaquetas/metabolismo , Calcio/metabolismo , Humanos , Monocitos/metabolismo , Factor de Activación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Conejos , Serotonina/metabolismo , Relación Estructura-ActividadRESUMEN
BACKGROUND: Immunoparalysis is defined as a decrease in the level of HLA-DR expression on monocytes during the course of sepsis. OBJECTIVE: To evaluate whether interferon gamma-1b has an immunoregulatory effect in patients with immunoparalysis during the compensatory anti-inflammatory response syndrome. METHODS: Of the patients admitted consecutively to the intensive care unit for the management of sepsis, 10 received interferon gamma-1b, 100 micrograms per 0.5 mL, after confirmation of HLA-DR expression of less than 30% on 2 consecutive days. The therapy was continued until HLA-DR expression remained more than 50% for 3 days. RESULTS: Interferon gamma-1b therapy resulted in the recovery of diminished levels of HLA-DR expression on monocytes. Of the 10 patients, 8 responded to treatment within 1 day. On the first day of interferon gamma-1b therapy, HLA-DR expression increased from mean (+/- SEM) pretreatment levels of 27% +/- 6% to 62% +/- 8% (P < .01) and remained high during the 28-day study period in 8 patients. The therapy was given to 2 patients a second time when HLA-DR expression on monocytes was less than 30%. The recovery of monocytic HLA-DR expression levels after administration of interferon gamma-1b was associated with restitution of monocytic function, reflected by a significant increase of plasma interleukin-6 (P < .05) and tumor necrosis factor alpha (P < .05) levels in 9 patients. CONCLUSIONS: This study shows that HLA-DR expression is a good marker of compensatory anti-inflammatory response syndrome. It also shows that interferon gamma-1b not only restored the levels of HLA-DR expression but also reestablished the ability of monocytes to secrete the cytokines interleukin-6 and tumor necrosis factor alpha.
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Antivirales/uso terapéutico , Antígenos HLA-DR/metabolismo , Inflamación/inmunología , Interferón gamma/uso terapéutico , Monocitos/efectos de los fármacos , Adulto , Anciano , Femenino , Humanos , Interleucina-6/biosíntesis , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Síndrome , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Nitric oxide (NO.) can induce transient [Ca2+] changes in endothelial cells not different from receptor mediated signalling. Whether this Ca2+ signal may provide a link with IL-8 secretion induced by NO. donors was investigated in human endothelial cells. Sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose dependently increased IL-8 production in this cell type. Additive IL-8 secretion was found with TNFalpha. Buffering intracellular Ca2+ with MAPT/AM suppressed NO. induced [Ca2+]i changes and reduced subsequent IL-8 secretion. The additive effect of both NO. donors on TNFalpha induced IL-8 secretion was completely blocked in the presence of MAPT/AM. SKF 96365, which has been shown to block receptor mediated Ca2+ entry, and TMB-8, which blocks intracellular Ca2+ release, both inhibited IL-8 secretion, particularly when TNFalpha was used as a costimulator, indicating that [Ca2+]i changes are important components of IL-8 induction by NO..
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Calcio/metabolismo , Endotelio Vascular/metabolismo , Interleucina-8/metabolismo , Ácido Nítrico/farmacología , Línea Celular , Endotelio Vascular/citología , Colorantes Fluorescentes/metabolismo , Fura-2/metabolismo , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacología , Glicina/análogos & derivados , Glicina/farmacología , Humanos , Imidazoles/farmacología , Nitroprusiato/farmacología , Penicilamina/análogos & derivados , Penicilamina/farmacología , S-Nitroso-N-Acetilpenicilamina , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The measurement of the degree of oxidative stress in patients often causes problems because of the lack of useful parameters. Therefore, we used an ELISA technique to evaluate serum protein carbonyls as a parameter of oxidative stress in patients during coronary heart surgery. Protein carbonyls were detected in serum samples of 14 patients undergoing coronary surgery and cardiopulmonary artery bypass grafting. A clear 2- to 3-fold increase in protein carbonyls in serum samples taken from human venous coronary sinus could be detected in the reperfusion period of the heart. We compared these data with markers of oxidative stress previously used, such as the glutathione status and the lipid peroxidation product malondialdehyde (MDA). Strong correlations of the protein carbonyl formation with MDA (r2 = 0.86) and oxidized glutathione (r2 = 0.81) were found in the early reperfusion stage. Increased levels of oxidized glutathione and MDA were detected only in the early reperfusion period. In contrast, the serum protein carbonyl content remained elevated for several hours, indicating a considerably slower serum clearance of oxidized proteins compared with that of lipid peroxidation products and the normalization of the glutathione status. We therefore concluded that the measurement of serum carbonyls by this ELISA technique is suitable to detect oxidative stress in serum samples of patients. The relative stability of the parameter makes the protein carbonyl detection even more valuable for clinical purposes.
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Proteínas Sanguíneas/metabolismo , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Anciano , Biomarcadores/sangre , Puente Cardiopulmonar/efectos adversos , Glutatión/sangre , Humanos , Malondialdehído/sangre , Persona de Mediana Edad , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/etiología , Oxidación-Reducción , Estrés OxidativoRESUMEN
We hypothesized that in patients with chronic heart failure mesenteric venous congestion leads to increased bowel permeability, bacterial translocation, and thereby endotoxin release; the increased endotoxin challenge then causes immune activation with increased soluble CD14 levels and tumor necrosis factor (TNF)-alpha production. Patients with high soluble CD14 levels (indicative of endotoxin-cell interaction) have markedly increased plasma levels of TNF-alpha, soluble TNF receptors 1 and 2, and intracellular adhesion molecule-1, supporting this hypothesis.
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Gasto Cardíaco Bajo/sangre , Citocinas/sangre , Receptores de Lipopolisacáridos/sangre , Enfermedad Crónica , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Interferón gamma/sangre , Interleucinas/sangre , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/sangre , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Intra-abdominal infection is one of the major causes of septic shock and multiple organ failure. To date, what causes the disease's progression remains unclear and therefore the relevance of immune modulating therapies remains speculative. The primary outcome measure of this study was to investigate immune modulating mediators at the onset of peritonitis before the development of subsequent septic shock. The secondary outcome measure was to investigate the usefulness of these immune parameters in predicting progression from peritonitis to septic shock. Fifty-eight peritonitis patients were included in this study: 14 patients subsequently developed septic shock. All patients were examined on "diagnosis of peritonitis" (<4 h within establishment of diagnosis), during "early septic shock" (<12 h following the onset of septic shock), and once again during "late septic shock" (within 72-98 h following the onset of septic shock). The immune modulating parameters tumor necrosis factor-alpha (TNF-alpha), the soluble TNF-alpha receptors I and II (sTNF-alpha RI and sTNF-alpha RII), interleukines (IL) -1beta, -6, -8, and -10, and the adhesions molecules endothelial-leukocyte-adhesion-molecule (E-Selectin), intercellular-adhesion-molecule-1 (ICAM-1), and vascular-adhesion-molecule-1 (VCAM-1), in addition to nitrate and nitrite, were determined. In the peritonitis group with subsequent septic shock, TNF-alpha, sTNF-alpha RI + RII IL-1beta, IL-8, IL-10, and nitrate were significantly increased before the onset of septic shock. TNF-alpha had an area under the receiver operating characteristics curve (AUC) of 0.84 and was reliable in predicting the progression from peritonitis to septic shock. The AUC of the other immune modulating parameters, despite being significantly elevated, ranged from 0.71 to 0.76. The AUC of the conventional laboratory markers such as leukocytes and C-reactive protein ranged from 0.64 to 0.68. In peritonitis that progressed to septic shock, an early immune response had already occurred before the onset of septic shock. The progression was best predicted by TNF-alpha. Therefore, mediator therapy might be considered in high-risk peritonitis patients who show an exaggerated immune response before the progression to septic shock.
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Peritonitis/complicaciones , Peritonitis/inmunología , Choque Séptico/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Progresión de la Enfermedad , Femenino , Humanos , Interleucina-1/sangre , Interleucina-10/sangre , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Receptores del Factor de Necrosis Tumoral/sangre , Choque Séptico/etiología , Choque Séptico/microbiología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
After operations with cardiopulmonary bypass, patients often show early symptoms of the systemic inflammatory response syndrome (SIRS). Potential mediators of SIRS include the platelet-activating factor (PAF), which has been linked to septic shock and multiple organ dysfunction. We studied the effect of cardiac surgery on PAF acetylhydrolase, the PAF-degrading plasma enzyme, as well as the relationship between the enzyme and the postoperative state of the patients. PAF acetylhydrolase activity decreased by 38+/-8% after instituting cardiopulmonary bypass because of plasma dilution and returned to near-preoperative levels within 6 h postsurgery. After that, enzyme levels decreased again, resulting in a 24+/-12% reduction until at least 3 days postsurgery. Patients in poor postoperative condition (Acute Physiology Score >9) had a lower preoperative PAF acetylhydrolase activity than did normal patients (12+/-4 vs. 17+/-4 nmol min(-1) mL(-1); p < .05). Likewise, patients who developed postoperative SIRS had a lower preoperative PAF acetylhydrolase activity than did patients without SIRS (12+/-3 vs. 17+/-4 nmol min(-1) mL(-1); p < .05). The data suggest that PAF acetylhydrolase deficiency is among the factors associated with postoperative distress after cardiac surgery.
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Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Fosfolipasas A/sangre , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Apolipoproteínas A/sangre , Apolipoproteínas B/sangre , Colesterol/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Valores de Referencia , Análisis de RegresiónRESUMEN
STUDY OBJECTIVE: Recently, it was proposed that soluble intercellular adhesion molecule (sICAM)-1 plasma levels may allow subgroup identification of patients at risk for cardiovascular complications during sepsis. However, the impact of preexisting coronary artery disease (CAD) on these results has not yet been tested. The aim of this study was to investigate whether plasma levels of adhesion molecules, nitric oxide, and cytokines differ between septic patients with or without preexisting CAD. DESIGN: Prospective study. SETTING: Surgical ICU. PATIENTS: Forty-four septic patients, 24 of whom met the criteria of CAD. MEASUREMENT: Hemodynamic measurements were performed and blood samples were taken within 12 h after onset of sepsis (early sepsis) and again 72 h thereafter (late sepsis). Soluble adhesion molecules and cytokines were determined using commercially available enzyme-linked immunosorbent assay kits, cyclic guanosinomonophosphate (cGMP) by competitive radioimmunoassay, and nitrite/nitrate photometrically by Griess reaction. RESULTS: In CAD patients, sICAM-1 (p < 0.02) was significantly elevated in early and late sepsis, whereas soluble endothelial-linked adhesion molecule (sE-selectin; p < 0.01) and cGMP (p < 0.03) were only increased in late sepsis. Oxygen consumption did not significantly differ between groups. Oxygen delivery and mixed venous oxygen saturation during early and late sepsis were significantly diminished and the oxygen extraction ratio significantly increased in the CAD group (p < 0.05). CONCLUSIONS: Increased endothelial injury may be indicated by the elevated levels of sICAM-1, sE-selectin, and cGMP in septic patients with preexisting CAD. These parameters, however, failed to serve as predictors for unknown CAD or chances for survival in early sepsis.
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Moléculas de Adhesión Celular/sangre , Enfermedad Coronaria/complicaciones , Endotelio Vascular/patología , Molécula 1 de Adhesión Intercelular/sangre , Óxido Nítrico/sangre , Sepsis/complicaciones , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Enfermedad Coronaria/patología , GMP Cíclico/sangre , Citocinas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Estudios Prospectivos , Radioinmunoensayo , Sepsis/sangre , Sepsis/patología , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the impact of organizational procedures on intensive care unit (ICU) performance and cost-effectiveness after cardiac surgery. DESIGN: Prospective study. SETTING: Cardiothoracic ICU at a university hospital. PATIENTS: Thousand five hundred twenty-six consecutive patients over a period of 18 months. INTERVENTIONS: The first 6 months were used as the control period. Afterwards selected organizational changes were introduced, such as written standard procedures, time schedules and discharge reports. MEASUREMENTS: Demographic data, surgical procedures, length of ICU and hospital stay and hospital outcome were recorded. Severity of illness was assessed daily using Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS II) and Organ Failure Score (OFS). Intensity of treatment and nursing care was monitored by the Therapeutic Intervention Scoring System (TISS). RIYADH ICU Program (RIP 5.0) was used to determine the relationship of observed to predicted mortality (standardized mortality ratio SMR) and the effective costs per survivor. MAIN RESULTS: SMR decreased continuously after the establishment of new management procedures while all other factors all other factors remained unchanged. Comparing outcome according to APACHE II on ICU admission demonstrated a significantly increased ICU performance in high risk patients with an APACHE II of 20-30 points (p < 0.05) while effective costs per survivor decreased significantly from DM 29,988 to DM 13,568 DM (p < 0.05). CONCLUSIONS: Organizational changes can improve ICU performance and cost-effectiveness after cardiac surgery. The RIP may be used to monitor the clinical and economical effects of change.
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Unidades de Cuidados Intensivos/economía , Unidades de Cuidados Intensivos/normas , Evaluación de Procesos y Resultados en Atención de Salud/estadística & datos numéricos , Cuidados Posoperatorios/economía , Cuidados Posoperatorios/normas , APACHE , Adolescente , Adulto , Berlin , Niño , Preescolar , Puente de Arteria Coronaria , Análisis Costo-Beneficio , Femenino , Cardiopatías Congénitas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Costos de Hospital , Hospitales Universitarios , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To demonstrate bleeding complications encountered in patients after cardiac surgery on continuous venovenous haemofiltration (CVVH) treated with continuous versus intermittent r-hirudin for heparin-induced thrombocytopenia (HIT) type II. DESIGN: Case description. SETTING: Cardiothoracic intensive care unit at a university hospital. PATIENTS: 5 consecutive patients with proven HIT type II on CVVH after major cardiac surgery. INTERVENTIONS: Recombinant hirudin (r-hirudin) was given continuously at a dose of 0.01 mg/kg per h in three patients or in repeated bolus administration of 0.05 mg/kg in two patients. MEASUREMENTS AND RESULTS: Since the ecarin clotting time assay was not available at that time to monitor hirudin effects on coagulation, the activated partial thromboplastin time (normal range 26-38 s, target range 50-60 s) was used. The continuously treated patients suffered from major bleeding complications. Therefore, the regimen was changed to repeated bolus administration, reducing the incidence of bleeding complications probably due to a threefold diminished cumulative hirudin dose per day in comparison to continuous administration. CONCLUSIONS: If ecarin clotting time, the most suitable monitor for hirudin activation, is not available, we would prefer to give r-hirudin in repeated boluses to avoid major bleeding complications in cardiac surgery patients on CVVH.
Asunto(s)
Antitrombinas/efectos adversos , Hemofiltración , Hirudinas/efectos adversos , Hemorragia Posoperatoria/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Anciano , Anticoagulantes/efectos adversos , Antitrombinas/administración & dosificación , Válvula Aórtica/cirugía , Procedimientos Quirúrgicos Cardíacos , Puente de Arteria Coronaria , Resultado Fatal , Implantación de Prótesis de Válvulas Cardíacas , Heparina/efectos adversos , Hirudinas/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Trombocitopenia/inducido químicamenteRESUMEN
Two patients were admitted directly to our Intensive Care Unit in acute respiratory failure due to pneumonia with septicaemic shock, renal and hepatic impairment. Sputum and blood cultures failed to grow any organisms and despite broad spectrum antibiotic therapy for 7 days, neither patient improved. Diagnosis of the rare pneumonic form of psittacosis was made following a raised titre. After treatment with tetracyclines, both patients made a rapid recovery. Retrospective direct questioning revealed that they had close contact with psitacine birds.
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Insuficiencia Multiorgánica/etiología , Neumonía/diagnóstico , Psitacosis/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/tratamiento farmacológico , Neumonía/complicaciones , Neumonía/tratamiento farmacológico , Psitacosis/complicaciones , Psitacosis/tratamiento farmacológico , Pruebas Serológicas , Tetraciclina/uso terapéuticoRESUMEN
OBJECTIVES: To investigate leukocyte adherence in intestinal venules in experimental endotoxemia after treatment with the 21-aminosteroid U-74389G. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an experimental laboratory. SUBJECTS: Twenty-one male Wistar rats weighing 190 +/- 40 g. INTERVENTIONS: The rats were divided equally into three groups: (a) control group, (b) endotoxemia (5 mg/kg lipopolysacharide from Escherichia coli O55:B5), and (c) endotoxemia and U-74389G administration 30 min before (3 mg/kg) and 60 min after endotoxin challenge (1.5 mg/ kg). MEASUREMENTS AND MAIN RESULTS: The distal small intestine of the animals was examined using intravital fluorescence videomicroscopy 2 h after endotoxin challenge. Leukocytes were stained in vivo by means of rhodamine 6G. In the endotoxemic animals we observed a fourfold increase in the count of firmly adherent leukocytes in submucosal post-capillary and collecting venules. Treatment with the 21-aminosteroid U-74389G significantly attenuated the count of sticking leukocytes in the collecting venules (control, 61 +/- 10 cells/mm2; lipopolysaccharide, 237 +/- 42 cells/mm2; U-74389G 125 +/- 9 cells/mm2; p < 0.05). In these venules leukocyte rolling behavior was comparable to that in the control group without endotoxin challenge. CONCLUSIONS: Administration of U-74389G, which has radical scavenging properties, attenuates leukocyte adherence in selected populations of intestinal venules which is found increased during endotoxemia. Thus, 21-aminosteroids may have an impact in the treatment of endotoxin-induced intestinal injury.
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Antioxidantes/farmacología , Adhesión Celular/efectos de los fármacos , Leucocitos/efectos de los fármacos , Venas Mesentéricas/efectos de los fármacos , Pregnatrienos/farmacología , Toxemia/tratamiento farmacológico , Animales , Endotoxinas/toxicidad , Radicales Libres/metabolismo , Hemodinámica/efectos de los fármacos , Intestino Delgado/irrigación sanguínea , Intestino Delgado/efectos de los fármacos , Masculino , Venas Mesentéricas/inmunología , Microcirculación , Microscopía Fluorescente , Microscopía por Video , Estudios Prospectivos , Distribución Aleatoria , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Toxemia/etiología , Toxemia/inmunologíaRESUMEN
OBJECTIVES: To investigate microvascular water permeability (filtration capacity, Kf) in patients with septic and non-septic shock using a new non-invasive method for studying microvascular parameters in man. SETTING: Intensive Care Unit of a university hospital. PATIENTS AND METHODS: We investigated 28 patients, presenting with cardio-vascular instability due to either septic shock, or non-septic shock (haemorrhage, multiple trauma, respiratory and/or cardiac failure). INTERVENTIONS: We used standard invasive methods of monitoring (in-dwelling arterial lines and pulmonary artery flotation catheters) in combination with computer assisted venous congestion plethysmography (VCP) measurements, for a parallel assessment of peripheral microcirculatory parameters. RESULTS: On admission to the ICU, patients with septic shock revealed a significantly higher mean value of filtration capacity Kf = 6.1 +/- 0.4 x 10(-3) (mean value +/- standard error of the mean, ml.min-1.100 ml tissue-1.mmHg-1 = KfU) than non-septic patients Kf = 3.5 +/- 0.3 KfU (p < 0.02). The Kf values of the septic patients were significantly higher than those from age-matched patients with peripheral vascular disease (4.1 +/- 0.2 KfU, p < 0.001) and those of healthy controls (4.3 +/- 0.2 KfU, p < 0.001); the Kf values of the non-septic patients, however, were not significantly different. The highest mean Kf value observed during the stay on ICU was Kfmax 11.6 +/- 0.2 KfU in the septic group and 5.7 +/- 0.1 KfU in the non-septic group (p < 0.001). Pvi, a value reflecting the balance of hydrostatic and oncotic forces in the microcirculation, was elevated in both patient groups. On admission, in septic patients Pvi was 39.2 +/- 3.3 mmHg and in non-septic patients 35.1 +/- 2.7 mmHg, these values were not significantly different, but significantly higher than the Pvi value of healthy controls (Pvi 21.5 +/- 0.8) (p < 0.001). A weak, however significant, positive correlation was found between Kf and Pvi in both patient groups. No correlations were found between Kf, as well as Pvi, and cardiac index (CI), oxygen delivery index (DO2I), oxygen consumption index (VO2I) and systemic vascular resistance index (SVRI). CONCLUSIONS: An increase in permeability of microvessels will cause a loss of intravascular fluid and may therefore partially explain the large fluid requirements of patients in shock. It will also favour the development of oedema, which is often found in septic patients. We propose that changes in Kf are useful indices of microvascular malfunction and that VCP allows the non-invasive assessment of these parameters.
Asunto(s)
Permeabilidad Capilar , Hemodinámica , Pletismografía/métodos , Choque Séptico/fisiopatología , Agua , Adulto , Anciano , Femenino , Humanos , Masculino , Microcirculación/fisiopatología , Persona de Mediana EdadRESUMEN
Despite advances in critical care medicine, mortality from sepsis in ICU patients remains high. In response to several infectious and non-infectious stimuli, monocytes/ macrophages release a number of mediators, including cytokines, involved in the proinflammatory response that underlies sepsis. The excessive release of these mediators results in the development of whole body inflammation, and plays an important role in the pathogenesis of sepsis and septic shock. In addition, patients with sepsis also undergo an anti-inflammatory phase (the compensatory anti-inflammatory response syndrome) and at times, a mixed response with both pro-and anti-inflammatory components (the mixed antagonistic response syndrome). The initial systemic hyperinflammation is caused by production of inflammatory cytokines, especially tumour necrosis factor-a (TNF-alpha), and also interleukin-1 (IL-1), IL-6, and interferon gamma, which act synergistically with TNF-alpha in inducing shock in animal models. However, clinical trials aimed at downregulating these mediators using antibodies against endotoxin, TNF-alpha, antagonists of IL-1 or platelet activating factor have proved to be uniformly disappointing. Not only have these agents been found to have no effect, but they may also increase mortality. One of the reasons for such failure may be the lack of precise immunological monitoring during the course of sepsis. We have recently demonstrated that sepsis shows a biphasic immunological pattern during the initial and later phase: the early hyperinflammatory phase is counterbalanced by an anti-inflammatory response which may lead to a hypoinflammatory state. The latter is associated with immunodeficiency that is characterised by monocytic deactivation, so-called immunoparalysis. Interferon gamma-1 b has an immunoregulatory effect in patients with immunoparalysis during the compensatory anti-inflammatory response syndrome, not only restoring levels of HLA-DR expression but also reestablishing the ability of monocytes to secrete cytokines such as TNF-alpha. By monitoring immune status in septic patients, targeted intervention may lead to more success in immunomodulation of sepsis.
Asunto(s)
Citocinas/antagonistas & inhibidores , Citocinas/inmunología , Inmunoterapia , Monocitos/inmunología , Sepsis/inmunología , Sepsis/terapia , Animales , Cuidados Críticos , Enfermedad Crítica/terapia , Susceptibilidad a Enfermedades/inmunología , Humanos , InflamaciónRESUMEN
OBJECTIVE: To investigate the interleukin-6 (IL-6) to interleukin-10 (IL-10) ratio and levels of sE-selectin in patients undergoing elective surgery of the upper digestive tract and to define the differences in the perioperative immune response between chronic alcoholic and non-alcoholic patients. DESIGN: Prospective pilot study. SETTING: Single center, interdisciplinary intensive care unit (ICU) at a university hospital. MEASUREMENT AND MAIN RESULTS: The study compared chronic alcoholics ( n=25) and non-alcoholics ( n=20) before and after surgery for resection of upper digestive tract tumors. White blood cell counts, C-reactive protein and circulating levels of sE-selectin, the pro-inflammatory cytokine IL-6 and the inhibitory cytokine IL-10, were obtained at hospital admission, preoperatively, postoperatively at ICU admission and 2 and 4 days later. Rates of postoperative infectious complications including pneumonia and sepsis were determined. sE-selectin only differed between chronic alcoholics and non-alcoholics preoperatively. Compared to non-alcoholics, chronic alcoholic patients showed a fourfold increase in circulating levels of IL-10 ( p<0.01) and a suppression of the IL-6/IL-10 ratio ( p=0.001) immediately after surgery. Coincident with the immune alterations, chronic alcoholics had a prolonged ICU stay ( p<0.01) and a threefold increased rate of wound infections ( p<0.05) and pneumonia ( p<0.01). Lower IL-6/IL-10 ratios were associated with increased rates of infectious complications ( p<0.05). CONCLUSION: Chronic alcoholics had decreased IL-6/IL-10 ratios at ICU admission and increased rates of infectious complications in the postoperative ICU course. This may indicate immediate postoperative immune suppression before the onset of infections and may help to identify chronic alcoholic patients at risk.
Asunto(s)
Alcoholismo/complicaciones , Interleucina-10/sangre , Interleucina-6/sangre , Complicaciones Posoperatorias/etiología , Anciano , Anciano de 80 o más Años , Alcoholismo/inmunología , Alcoholismo/metabolismo , Proteína C-Reactiva/metabolismo , Femenino , Neoplasias Gastrointestinales/cirugía , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Infección de la Herida Quirúrgica/etiologíaRESUMEN
OBJECTIVES: To evaluate the effect of the stable prostacyclin analogue iloprost on the plasma disappearance rate of indocyanine green (PDR) in patients with septic shock. DESIGN AND SETTING: A prospective clinical study in a university hospital intensive care unit. PATIENTS AND INTERVENTIONS: 20 patients in septic shock. Patients received iloprost infusion (1 ng/kg per minute) for 24 h. MEASUREMENTS AND RESULTS: PDR was determined by a femoral arterial fiberoptic catheter before, 1, 6, and 24 h after start and 1 h after end of iloprost infusion. PDR increased significantly 24 h after start of iloprost infusion (baseline: 13.9 +/- 1.7% vs. 18.6 +/- 2.2%/min) and decreased 1 h after end of infusion (13.7 +/- 1.7%/min; p < 0.002). There was no change in pHi, cardiac index, mean arterial pressure, heart rate, central venous pressure, or intrathoracic blood volume index. CONCLUSION: Administration of the stable prostacyclin analogue iloprost significantly increases PDR, indicating improvement in liver function.
Asunto(s)
Colorantes/farmacocinética , Epoprostenol/análogos & derivados , Iloprost/uso terapéutico , Verde de Indocianina/farmacocinética , Choque Séptico/tratamiento farmacológico , Choque Séptico/metabolismo , Vasodilatadores/uso terapéutico , Adulto , Anciano , Monitoreo de Drogas/instrumentación , Monitoreo de Drogas/métodos , Técnica de Dilución de Colorante/instrumentación , Femenino , Hemodinámica , Humanos , Iloprost/farmacología , Infusiones Intravenosas , Hígado/metabolismo , Hígado/fisiopatología , Pruebas de Función Hepática , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Persona de Mediana Edad , Estudios Prospectivos , Choque Séptico/fisiopatología , Vasodilatadores/farmacologíaRESUMEN
OBJECTIVE: To identify the risk for prolonged mechanical ventilation in cardiac surgical patients. DESIGN: Prospective study with retrospective combination of a second database. PATIENTS: Six hundred and eighty-seven patients after cardiac surgery over a period of 12 months. MEASUREMENTS: Demographic data were recorded preoperatively, and surgical procedures intraoperatively using a surgical database designed for quality control. Length of ICU and hospital stay, and hospital outcome were recorded. Severity of illness was assessed daily using APACHE II, SAPS II, and Organ Failure Score. Intensity of treatment and nursing care was monitored by means of the Therapeutic Intervention Scoring System (TISS). Univariate and multivariate analyses were performed using logistic regression. The predictive value of the identified variables was tested by the Wilcoxon test using the receiver operating characteristic curve. MAIN RESULTS: Sixty-two patients (9.0%) were ventilated for > 48 h and accounted for 42.8% of the total costs in the ICU. The pre- and intraoperatively collected data produced a model with weak predictive capacity for prolonged ventilation [area under curve (AUC) 73.22 and 71.08, respectively]. The use of TISS and SAPS postoperatively resulted in an effective model of prediction (AUC 93.76). Adding the occurrence of reoperation, reintubation, emergency transfusion, intraaortic balloon pumping, and need for total parenteral nutrition to the model further improved its predictive capacity (AUC 94.74). CONCLUSIONS: The present results strongly suggest that data collected postoperatively using established scoring systems as well as documented events of high clinical impact for risk assessment and quality control are reliable predictors of prolonged ventilation.