RESUMEN
OBJECTIVE: To determine how hemoglobin (Hb), platelet, and serotonin concentrations change during cardiopulmonary bypass (CPB) in sequestered blood from the pulmonary artery compared with circulating systemic blood; and to determine the correlation between platelet and serotonin variability at the two sites and clinical outcome measurements related to hemodynamics and blood loss. DESIGN: A prospective clinical study. SETTING: A university hospital. PARTICIPANTS: Twenty patients undergoing elective aortocoronary bypass. INTERVENTIONS: Measurements of Hb, platelet, and serotonin concentrations were performed before, during, and after CPB on paired blood samples from the pulmonary artery and the radial artery. Hemodynamic measurements were recorded before and after CPB and chest tube drainage was recorded postoperatively. MEASUREMENTS AND MAIN RESULTS: The Hb, platelet, and serotonin concentrations were all significantly different between radial artery and pulmonary artery samples at the different measurement times (p < 0.001, analysis of variance [ANOVA] for repeated measures). Hb, platelet, and serotonin concentrations were all significantly increased in the pulmonary artery at the time of aortic cross-clamping compared with the corresponding radial artery blood samples (p < 0.0005, ANOVA). During the period of ischemic arrest, Hb was unchanged in the pulmonary artery and remained significantly increased compared with systemic blood (p < 0.0005, ANOVA). Serotonin concentrations in both systemic and sequestered pulmonary artery blood had significant correlation with cardiac index (CI), right ventricular ejection fraction (REF), and systemic vascular resistance index (SVRI; p < or = 0.006, least squares analysis). Postoperative chest tube drainage most closely correlated with the platelet counts measured in both the radial and pulmonary arteries at the start of CPB (p < 0.05, least squares analysis). CONCLUSION: During CPB, there were significant differences in Hb, platelet, and serotonin concentrations in sequestered pulmonary artery blood compared with circulating systemic blood. The initial differences and subsequent changes were most likely attributable to decreased hemodilution and a different pattern of platelet activation in the pulmonary artery blood compared with the systemic blood. Despite the hematologic differences, serotonin concentration and platelet counts in the pulmonary artery blood had significant correlation to indices of cardiac function and postoperative chest tube drainage, respectively. Platelet and serotonin changes in sequestered pulmonary artery blood were also associated with some of the adverse consequences of CPB.
Asunto(s)
Puente Cardiopulmonar , Hemoglobinas/análisis , Recuento de Plaquetas , Serotonina/sangre , Análisis de Varianza , Pérdida de Sangre Quirúrgica , Gasto Cardíaco/fisiología , Tubos Torácicos , Puente de Arteria Coronaria , Drenaje , Procedimientos Quirúrgicos Electivos , Femenino , Paro Cardíaco Inducido , Hemodilución , Hemodinámica , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Activación Plaquetaria/fisiología , Estudios Prospectivos , Arteria Pulmonar , Arteria Radial , Volumen Sistólico/fisiología , Factores de Tiempo , Resultado del Tratamiento , Resistencia Vascular/fisiología , Función Ventricular Derecha/fisiologíaRESUMEN
OBJECTIVE: This study evaluated platelet effects on thromboelastography to determine how morphologically abnormal platelets affected native whole blood analysis. DESIGN: Prospective, controlled comparison. SETTING: Tertiary care university hospital. PARTICIPANTS: Volunteer cardiac surgery patients. INTERVENTIONS: Fresh platelets were obtained from volunteers and were either treated normally or cryodisrupted with liquid nitrogen. Fresh platelets, liquid nitrogen-treated platelets, or an equivalent quantity of the patient's blood were added to whole blood samples obtained from cardiac surgery patients before heparinization. Thromboelastographic parameters sensitive to platelet effects were measured in each of the three groups. MEASUREMENTS AND MAIN RESULTS: Maximum amplitude and alpha-angle significantly increased in the two groups receiving added platelets. There were no differences between the fresh platelet and the liquid nitrogen-treated platelet groups (Student's paired t-test). The R-time decreased significantly in both platelet-treated groups compared with the group that did not receive additional platelets. CONCLUSIONS: Viscoelastic changes in whole blood coagulation after the addition of platelet concentrates are not dependent on morphologically intact or functionally normal platelets. This in vitro study predicts that transfusion of poorly preserved platelet concentrates as well as fresh platelets would increase clot strength on thromboelastography if the recipient's blood were tested immediately after administration.
Asunto(s)
Plaquetas/fisiología , Tromboelastografía , Coagulación Sanguínea , Humanos , Transfusión de Plaquetas , Estudios ProspectivosRESUMEN
Sevoflurane administration can result in increased serum inorganic fluoride ion concentrations, which have been associated with inhibition of renal concentrating ability. We measured serum fluoride levels, renal function, and recovery variables as a function of time in ASA grade I-III patients administered general anesthesia with isoflurane or sevoflurane for at least 1 h. Fifty patients were exposed to sevoflurane (< or = 2.4% inspired concentration) or isoflurane (< or = 1.9% inspired concentration) for maintenance of anesthesia as part of a multicenter trial. Blood was collected for determination of serum fluoride ion concentration, electrolytes, blood urea nitrogen, and creatinine at various time points pre- and postoperatively. Mean serum fluoride levels were significantly increased in sevoflurane versus isoflurane groups at all time points; the mean peak serum levels were 28.2 +/- 14 mumol/L at 1 h for sevoflurane and 5.08 +/- 4.35 mumol/L at 12 h for isoflurane. Sevoflurane-mediated increases in serum fluoride levels peaked at 1 h and, in general, decreased rapidly after discontinuation of the anesthesia. Three of 24 patients exposed to sevoflurane had one or more fluoride levels > 50 mumol/L. One of these patients had a serum inorganic fluoride ion level > 50 mumol/L at 12 h after sevoflurane, and an additional patient had fluoride levels > 33 mumol/L for up to 24 h after sevoflurane discontinuation. Those two patients also demonstrated an increase in serum blood urea nitrogen and creatinine at 24 h after sevoflurane administration compared with baseline. The elimination half-life of serum fluoride ion was 21.6 h. The results of this study suggest the possibility of sevoflurane induced nephrotoxicity.
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Anestesia por Inhalación/métodos , Anestésicos por Inhalación , Éteres , Fluoruros/sangre , Isoflurano , Éteres Metílicos , Adulto , Anciano , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Femenino , Humanos , Riñón/fisiología , Masculino , Persona de Mediana Edad , Sevoflurano , Factores de TiempoRESUMEN
The purpose of this study was to compare the accuracy of conductivity, adjusted conductivity, photometric, and centrifugation methods of measuring or estimating hemoglobin (Hb) with Coulter measured HB as the reference. These bedside methods were studied in 25 cardiac surgery patients during euvolemia and hemodilution and after salvaged autologous red blood cell transfusion. In vivo patient blood samples were obtained before induction, at the start of cardiopulmonary bypass (CPB), after CPB, and after blood transfusion. In 10 patients, blood was sampled in vitro from units of processed blood. Hb values were determined using conductivity by Stat-Crit, adjusted conductivity by Nova Stat Profile 9, bedside photometry by HemoCue, and centrifugation methods. The calculated bias values of Coulter test method Hb (mean +/- SD) for in vivo patient blood samples (n = 90) were: Stat-Crit = 0.6 +/- 0.8 g/dL; Nova Stat Profile 9 = -0.7 +/- 0.4 g/dL; HemoCue = -0.1 +/- 0.2 g/dL; and centrifuge = 0.1 +/- 0.5 g/dL (P < 0.0001). Hb bias values (g/dL) for in vitro samples (n = 10) obtained from processed blood were Stat-Crit = 5.1 +/- 0.6; Nova Stat Profile 9 = 3.0 +2- 0.6; HemoCue = 0.4 +/- 0.4; and centrifuge = 0.6 +/- 0.3 (P < 0.0001). Hb assessment by different test methods may be significantly affected during hemodilution and after blood transfusion. In vitro conditions exaggerated the inaccuracy of conductivity and adjusted conductivity Hb estimates. The rank order of closest approximation to the Coulter measurement for all in vivo blood samples was provided by bedside photometry, followed by centrifugation, adjusted conductivity, and uncorrected conductivity methods.
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Procedimientos Quirúrgicos Cardíacos , Hemoglobinas/análisis , Monitoreo Intraoperatorio , Análisis de Varianza , Sesgo , Proteínas Sanguíneas/análisis , Transfusión Sanguínea , Transfusión de Sangre Autóloga , Volumen Sanguíneo , Puente Cardiopulmonar , Centrifugación , Cloruros/sangre , Conductividad Eléctrica , Transfusión de Eritrocitos , Fluidoterapia , Hemodilución , Humanos , Soluciones Isotónicas/uso terapéutico , Modelos Lineales , Fotometría , Sodio/sangreRESUMEN
This study was designed to evaluate effects of enalaprilat, an angiotensin-converting enzyme inhibitor, on hemodynamic and hormonal responses during surgery at endotracheal intubation, incision, and limb-tourniquet inflation. Thirty patients undergoing limb procedures with general anesthesia (N2O/narcotic technique) and a pneumatic tourniquet were randomized to receive either preoperative enalaprilat (1.25 mg intravenously [i.v.] 20 min prior to induction) or intraoperative enalaprilat (0.625 mg i.v. at the onset of tourniquet-associated hypertension), with appropriate placebo controls. Arterial blood pressure and heart rate increased significantly in response to intubation in the placebo group. Although there were no significant differences in catecholamine levels, plasma renin activity was significantly increased at postincision in the preoperative-enalaprilat group versus the placebo group. This suggests that activation of the renin-angiotensin system may play a key role in mediation of intraoperative hemodynamic responses to endotracheal intubation. With respect to tourniquet hypertension, preoperative or intraoperative treatment with enalaprilat reduced neither the pressor response to tourniquet inflation nor the amount of enflurane subsequently required to control arterial blood pressure. These findings suggest that this response is mediated by pain pathways, and may be treated more effectively with anesthesia/analgesia.
Asunto(s)
Catecolaminas/sangre , Enalaprilato/administración & dosificación , Renina/sangre , Procedimientos Quirúrgicos Operativos , Adolescente , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Enalaprilato/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Periodo Intraoperatorio , Persona de Mediana Edad , Cuidados PreoperatoriosRESUMEN
OBJECTIVE: Our objective was to compare the effect of protein and electrolyte changes associated with hemodilution on the accuracy of photometric and conductivity hemoglobin determination methods. METHODS: Blood samples from 10 patients with normal preoperative serum electrolytes and total protein levels were studied. From an indwelling arterial line, 20 ml of blood were removed; hemoglobin values were measured pre-(Baseline) and postdilution by Coulter counter, conductivity, and photometric methods. Blood samples were diluted by placing 4 ml of blood into three test tubes, and adding 1 ml of either 25% albumin, 0.9% sodium chloride, or 5% dextrose in water. RESULTS: Blood sample dilution resulted in a reported conductivity hemoglobin that was significantly different from the Coulter value (p = 0.0004) when 25% albumin, 0.9% sodium chloride, and 5% dextrose in water solution was used. Using the same dilutions, the photometric method accurately reflected Coulter hemoglobin values. The correlation between photometric and Coulter hemoglobin measurements was R2 = 0.97, p = 0.0001. Correcting the conductivity hemoglobin values for changes in total protein, chloride and sodium significantly improved correlation with Coulter hemoglobin (R2 of uncorrected versus corrected = 0.37 and 0.72; p = 0.0001). CONCLUSIONS: In the range of electrolyte and protein concentrations found in this study, the photometric method of hemoglobin assessment was more accurate than either corrected or uncorrected conductivity hemoglobin determinations, as compared to Coulter-based measurements.
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Proteínas Sanguíneas/análisis , Electrólitos/sangre , Hemoglobinas/análisis , Cloruros/sangre , Conductividad Eléctrica , Pruebas Hematológicas/instrumentación , Humanos , Fotometría , Sodio/sangreRESUMEN
STUDY OBJECTIVE: To examine the safety and efficacy of intravenous fenoldopam as compared to placebo for the treatment of postoperative hypertension. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: Community hospital. PATIENTS: 16 ASA I-III hypertensive patients scheduled for noncardiac surgical procedures. INTERVENTIONS: Treatment with fenoldopam or placebo was initiated immediately after other causes of hypertension had been ruled out. Hypertension was defined as a supine systolic blood pressure (SBP) or diastolic blood pressure (DBP) greater than 20% over the patient's preoperative baseline, which was obtained 6 hours prior to the procedure with the patient lying quietly. The baseline consisted of 3 consecutive blood pressure (BP) measurements obtained at 5-minute intervals and not varying by more than 10%. Fenoldopam or placebo infusion was initiated at 0.1 microgram/kg/min and increased and decreased as necessary until the therapeutic goal BP was reached or treatment failure had occurred. The therapeutic goal BP was a decrease to at least 10% above the preoperative baseline, and failure of treatment was defined as inability to reach this BP level after 15 minutes at 1.5 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: BP and heart rate (HR) data were collected consistently throughout the study and 1 hour after termination of infusion. Laboratory studies and 12-lead electrocardiographic results were obtained at the start of the study and repeated 24 hours after termination of infusion. Blood samples were obtained for the measurement of epinephrine, norepinephrine, and dopamine levels and were analyzed using high-performance liquid chromatography with electrochemical detection. Pretreatment BP measurements were significantly elevated from baseline in both groups. Fenoldopam treatment significantly reduced BP to the therapeutic goal in 8 of 8 patients; placebo reduced BP to this goal in only 4 of 8 patients (p < 0.05). At the end of the titration period, the therapeutic goal BP was not significantly different from baseline in the fenoldopam group. HR was significantly elevated (p < 0.05) at goal in the fenoldopam group as compared with the placebo group. Fenoldopam administration lowered SBP and DBP to goal in a mean time of 28 minutes versus 42.5 minutes in the placebo group. There were no significant differences in catecholamine levels at any of the measurement periods. CONCLUSION: Fenoldopam is an effective drug for reducing BP following hypertensive episodes in the postoperative setting. Fenoldopam use is associated with an increase in HR versus placebo.
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2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/análogos & derivados , Dopaminérgicos/administración & dosificación , Hipertensión/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/administración & dosificación , Adulto , Anciano , Presión Sanguínea/fisiología , Método Doble Ciego , Epinefrina/sangre , Femenino , Fenoldopam , Frecuencia Cardíaca/fisiología , Humanos , Hipertensión/fisiopatología , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Complicaciones Posoperatorias/fisiopatología , Procedimientos Quirúrgicos OperativosRESUMEN
Despite the wide use of droperidol to reduce nausea and vomiting in children, its pharmacokinetics have not been described in pediatric patients. Twelve ASA Class I-II children, undergoing tonsillectomy and adenoidectomy, received standardized anesthesia; none of the children received premedication. After induction of general anesthesia, droperidol (0.05 mg/kg) was injected intravenously as a bolus. Droperidol plasma concentrations were determined by radioimmunoassay. Pharmacokinetic data were analyzed by model-independent methods. The pharmacokinetic parameters (mean +/- SD) for the studied population were elimination half-life: 101.5 +/- 26.4 min, mean residence time: 127.2 +/- 28.6 min, volume of distribution at steady state: 0.58 +/- 0.29 L/kg and clearance: 4.66 +/- 2.28 mL.kg-1 x min-1. The clearance and volume of distribution at steady state values are lower than those reported for the adult population, and they apparently decreased in a parallel fashion. The smaller volume of distribution at steady state is consistent with the lipophilic distribution of droperidol and the reduced content of adipose tissue in children. The elimination half-time and mean residence time values are similar to those reported previously for adults. The relatively short half-life of droperidol for our pediatric population does not explain its extended antiemetic action. It does, however, reaffirm that the pharmacokinetic duration of a drug's action is only one of the determinants of its clinical duration.
Asunto(s)
Anestesia por Inhalación , Droperidol/farmacocinética , Halotano , Náusea/prevención & control , Óxido Nitroso , Complicaciones Posoperatorias/prevención & control , Vómitos/prevención & control , Niño , Preescolar , Droperidol/sangre , Droperidol/uso terapéutico , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos OperativosRESUMEN
Complement-dependent antibody-mediated damage to multilamellar lipid vesicles (MLVs) normally results in a maximum release of 50-60% of trapped aqueous marker. The most widely accepted explanation for this is that only the outermost lamellae of MLVs are attacked by complement. To test this hypothesis, complement damage to two different types of large unilamellar vesicles (LUVs), large unilamellar vesicles prepared by the reverse-phase evaporation procedure (REVs) and large unilamellar vesicles prepared by extrusion techniques (LUVETs), were determined. In the presence of excess antibody and complement the LUVs released a maximum of only approx. 25 to 40% of trapped aqueous marker, instead of close to 100% that would be expected. Since small unilamellar vesicles apparently differ from LUVs in that they can release 100% of trapped aqueous marker it appeared that the size of the vesicles was an important factor. Because of these observations the influence of MLV size on marker release was examined. Three populations of MLVs of different sizes were separated by a fluorescence activated cell sorter. Assays of the separated MLV populations showed that the degree of complement-dependent marker release was inversely related to MLV size. No detectable glucose was taken up by MLVs when glucose was present only outside the liposomes during complement lysis. Our results can all be explained by the closing, or loss, of complement channels. We conclude that complement channels are only transiently open in liposomes, and that loss of channel patency may be due to either channel closing or to loss of channels.
Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos , Proteínas del Sistema Complemento/inmunología , Dimiristoilfosfatidilcolina , Liposomas , Surfactantes Pulmonares , Animales , Complejo Antígeno-Anticuerpo , Bovinos , Cerebrósidos , Colesterol , Sueros Inmunes , Espectrometría de Fluorescencia , Relación Estructura-ActividadRESUMEN
The ability of trehalose and other sugars to maintain the integrity of large unilamellar vesicles subjected to dehydration and rehydration has been investigated. It is shown, employing freeze-fracture techniques, that large unilamellar vesicles prepared in the presence of trehalose at 125 mM or higher concentration do not exhibit significant structural changes during the dehydration-rehydration cycle. Further, up to 90% of entrapped 22Na or [3H]inulin is retained during this process. Other sugars also exhibited similar protective effects where trehalose was most effective, followed by sucrose, maltose, glucose and lactose. It is demonstrated that proton or Na+/K+ electrochemical gradients can be maintained during the dehydration-rehydration process, which can subsequently be used to drive the uptake of lipophilic cationic drugs such as adriamycin. The implications for long-term storage of liposomal systems for use in drug-delivery protocols are discussed.
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Disacáridos , Liposomas , Fosfatidilcolinas , Trehalosa , Desecación , Liofilización , Inulina , Microscopía Electrónica , Modelos Biológicos , Radioisótopos de Sodio , TritioRESUMEN
The entry of immunoglobulin-coated liposomes into human leukocytes bearing Fc receptors was evaluated using two methods: (i) the cellular association of liposomal markers (3H-labelled phosphatidylcholine, lipid phase; [14C]inulin, aqueous phase), and (ii) the ultrastructural cytochemistry of cells following incubation of cells with liposomes containing a cytochemical marker (horseradish peroxidase) in the aqueous spaces. The entry of liposomes into a cell population composed predominantly of neutrophils was linear for 10--15 min and was mediated by an active process that appeared to be both energy- and surface-dependent. This uptake could be largely inhibited by incubation at 0 degrees C, and by exposure to glutaraldehyde, iodoacetamide, N-ethylmaleimide, and an excess of aggregated immunoglobulins. Entry into cells of multilamellar liposomes was saturable, displaying affinity constants of 1.1 and 1.7 mM. Ultrastructural analysis of the heterogeneous leukocyte population showed that monocytes took up liposomes more actively than neutrophils and lymphocytes. Moreover, liposomes were almost always found within the leukocytes, rather than adherent to the outer plasma membrane. The relative avidity of monocytes was confirmed by comparing the uptake of radiolabelled liposomes by a 'pure' neutrophil population, a 'mixed' neutrophil population, and a 'mononuclear cell' population. Precoating liposomes with high molecular weight aggregates of human immunoglobulin G resulted in enhanced serum-independent uptake. The fraction of aggregated immunoglobulin G which was most effective in provoking uptake of coated liposomes also stimulated the greatest amount of lysosomal enzyme secretion. These data suggest that the interaction (precoating) of liposomes with either high molecular weight aggregates of immunoglobulin G or with serum enhances their subsequent uptake by human leukocytes.
Asunto(s)
Inmunoglobulina G/metabolismo , Leucocitos/metabolismo , Liposomas/metabolismo , Proteínas Sanguíneas/metabolismo , Membrana Celular/metabolismo , Humanos , Técnicas In Vitro , Cinética , Leucocitos/ultraestructura , Propiedades de SuperficieRESUMEN
Large unilamellar vesicles, prepared by a petroleum ether vaporization method, were compared to multilamellar vesicles with respect to a number of physical and functional properties. Rotational correlation time approximations, derived from ESR spectra of both hydrophilic (3-doxyl cholestane) and hydrophobic (3-doxyl androstanol) steroid spin probes, indicated similar molecular packing of lipids in bilayers of multilamellar and large unilamellar liposomes. Light scattering measurements demonstrated a reduction in apparent absorbance of large unilamellar vesicles, suggesting loss of multilamellar structure which was confirmed by electron microscopy. Furthermore, large unilamellar vesicles exhibited enhanced passive diffusion rates of small solutes, releasing a greater percentage of their contents within 90 min than multilamellar vesicles, and reflecting the less restricted diffusion of a unilamellar system. The volume trapping capacity of large unilamellar vesicles far exceeded that of multilamellar liposomes, except in the presence of a trapped protein, soy bean trypsin inhibitor, which reduced the volume of the aqueous compartments of large unilamellar vesicles. Finally, measurement of vesicle diameters from electron micrographs of large unilamellar vesicles showed a vesicle size distribution predominantly in the range of 0.1--0.4 micron with a mean diameter of 0.21 micron.