RESUMEN
We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2-12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg.kg(-1) following oral placebo premedication, i. v. flurbiprofen 1 mg.kg(-1) following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg.kg(-1) following clonidine, and i.v. flurbiprofen 1 mg.kg(-1) following clonidine. The children received clonidine (4 microg.kg(-1)) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg.kg(-1) i.v. flurbiprofen 1 mg.kg(-1), oral clonidine 4 microg.kg(-1) provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery.
Asunto(s)
Analgésicos/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Clonidina/administración & dosificación , Diclofenaco/administración & dosificación , Flurbiprofeno/administración & dosificación , Procedimientos Quirúrgicos Oftalmológicos , Dolor Postoperatorio/prevención & control , Administración Oral , Administración Rectal , Niño , Quimioterapia Combinada , Procedimientos Quirúrgicos Electivos , Humanos , Inyecciones Intravenosas , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
OBJECTIVE: Acute severe pancreatitis is often associated with acute lung injury, including acute respiratory distress syndrome. Acute lung injury induced by phospholipase A2 (PLA2) or trypsin, a pancreatic enzyme, is an experimental model resembling acute respiratory distress syndrome. Neutrophils and platelets are thought to play a pivotal role in the pathogenesis of acute respiratory failure. Lidocaine inhibits some aspects of neutrophil and platelet functions. We conducted the current study to assess the effects of pretreatment with lidocaine on acute lung injury induced by a combination of PLA2 and trypsin. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one adult male Japanese White rabbits (weight range, 2.0-2.4 kg). INTERVENTIONS: The animals were mechanically ventilated with a tidal volume of 10 mL/kg and an Fio2 of 0.4, and thereafter, they were randomly assigned to three groups. Acute lung injury was induced by a combination of PLA2 (1000 units/kg/hr) and trypsin (5000 units/kg/hr) infused intravenously for 4 hrs. Immediately before induction of the acute lung injury, the lidocaine treatment group received intravenous lidocaine (2 mg/kg bolus followed by 2 mg/kg/hr) until they were killed. In the nontreatment group, saline was given instead of lidocaine. Rabbits in the nonlung-injury group received saline infusion instead of the pancreatic enzymes. MEASUREMENTS AND MAIN RESULTS: During the experimental period (4 hrs), arterial blood gases, lung mechanics, and peripheral neutrophil and platelet counts were measured. Immediately after killing, the wet weight/dry weight ratio of the lung was recorded. Light microscopic findings (lung injury score and number of neutrophils) were compared between the three groups. The combination of PLA2 and trypsin decreased Pao2, lung compliance, and peripheral counts of neutrophils and platelets and increased alveolar/arterial oxygen tension difference, lung resistance, wet weight/dry weight ratio, and the number of neutrophils in the lung. Lidocaine treatment attenuated these changes. The two pancreatic enzymes caused extensive morphologic lung damage, which was lessened by lidocaine. CONCLUSIONS: We conclude that pretreatment with intravenous lidocaine attenuated the lung injury induced by the pancreatic enzymes. However, further studies are required to determine whether this drug has a therapeutic effect once the lung injury has developed.
Asunto(s)
Modelos Animales de Enfermedad , Lidocaína/uso terapéutico , Fosfolipasas A , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Tripsina , Animales , Análisis de los Gases de la Sangre , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Infusiones Intravenosas , Recuento de Leucocitos/efectos de los fármacos , Lidocaína/farmacología , Masculino , Neutrófilos/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Fosfolipasas A2 , Recuento de Plaquetas/efectos de los fármacos , Conejos , Distribución Aleatoria , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/patología , Mecánica Respiratoria/efectos de los fármacosRESUMEN
Accumulation of L-kynurenine and 3-hydroxyanthranilic acid (3HAA) occurs in the monocyte-derived cells following immune stimulation, and may derive from L-tryptophan following induction of indoleamine-2,3-dioxygenase. In the present study, we evaluate the possibility that 3HAA acts as an endogenous inducer of monocyte/macrophage apoptosis. Supplementation with 200 microM of 3HAA, but not other L-tryptophan metabolites tested, significantly increased the number of apoptotic cells in both THP-1 and U937 cells. Catalase, superoxide dismutase and manganese ions markedly enhanced apoptosis in the presence of 3HAA in these cells. The present results suggest that 3HAA induces the macrophage/monocyte apoptosis under certain conditions, which may be relevant to pathophysiology of inflammatory conditions.
Asunto(s)
Ácido 3-Hidroxiantranílico/metabolismo , Ácido 3-Hidroxiantranílico/farmacología , Apoptosis/fisiología , Quinurenina/metabolismo , Macrófagos/citología , Macrófagos/fisiología , Triptófano/metabolismo , Apoptosis/efectos de los fármacos , Humanos , Quinurenina/análogos & derivados , Quinurenina/farmacología , Macrófagos/efectos de los fármacos , Células Tumorales Cultivadas , Células U937RESUMEN
PURPOSE: Intravenous flurbiprofen, a non-steroidal antiinflammatory drug (NSAID), has been used recently for postoperative pain relief in adults. The drug is also likely to have antiemetic property. The present study was undertaken to investigate the effect of flurbiprofen on postoperative pain and emesis in children undergoing strabismus surgery, which is well known to produce postoperative nausea and vomiting. METHODS: In a prospective, randomised, controlled clinical trial, 90 children aged 2-11 yr received saline (control), flurbiprofen 0.5 mg.kg-1, or flurbiprofen 1 mg.kg-1. Saline and flurbiprofen were administered i.v. immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). No opioids or antiemetics were administered throughout the study. The incidence and frequency of vomiting were compared among groups. RESULTS: Flurbiprofen 1 mg.kg-1 provided lower OPS (highest) scores during the eight hours after surgery and a reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. The two doses of flurbiprofen failed to decrease the incidence and frequency of vomiting. CONCLUSION: These data suggest that preoperative flurbiprofen 1 mg.kg-1 iv is a simple and effective approach to postoperative pain relief but not to the prevention of emesis following paediatric strabismus surgery.
Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Antieméticos/uso terapéutico , Flurbiprofeno/uso terapéutico , Éteres Metílicos , Dolor Postoperatorio/prevención & control , Estrabismo/cirugía , Vómitos/prevención & control , Analgésicos/administración & dosificación , Anestesia por Inhalación , Anestésicos por Inhalación/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Antieméticos/administración & dosificación , Niño , Preescolar , Diclofenaco/administración & dosificación , Diclofenaco/uso terapéutico , Relación Dosis-Respuesta a Droga , Éteres/administración & dosificación , Flurbiprofeno/administración & dosificación , Humanos , Incidencia , Inyecciones Intravenosas , Náusea/prevención & control , Óxido Nitroso/administración & dosificación , Dimensión del Dolor , Placebos , Premedicación , Estudios Prospectivos , Sevoflurano , Método Simple CiegoRESUMEN
To explore the effects of oral omeprazole on preoperative gastric fluid pH and volume in children, 104 healthy in-patients aged 4-9 yr were randomly allocated to four groups (n = 26). Subjects in the Omeprazole-Omeprazole Group received two doses of omeprazole (20 mg per dose), those in the Placebo-Placebo Group, two doses of placebo, those in the Placebo-Omeprazole and Omeprazole-Placebo Groups, one dose each of the two preparations by mouth. For each treatment regimen, the first medication was administered at 9:00 p.m. on the night before surgery and the second at 5:30 a.m. on the morning of the day of surgery (three hours preoperatively). Children undergoing elective surgery were offered 10 ml.kg-1 of apple juice three hours before induction of anaesthesia. After induction of anaesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube and analyzed for pH and total fluid volume. The administration of omeprazole at bedtime before surgery increased gastric pH (3.3 +/- 1.3 vs 2.0 +/- 0.6, P < 0.05) in comparison with placebo, as did two doses of omeprazole (pH = 4.8 +/- 1.6, P < 0.05). A single dose of omeprazole administration on the morning of the day of surgery failed to increase gastric pH. There was a reduction in the number of children with a pH < 2.5 and a volume > 0.4 ml.kg-1 in the Omeprazole-Omeprazole and Omeprazole-Placebo Groups, compared with the Placebo-Placebo or Placebo-Omeprazole Groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Ácido Gástrico/metabolismo , Jugo Gástrico/efectos de los fármacos , Jugo Gástrico/metabolismo , Omeprazol/uso terapéutico , Premedicación , Administración Oral , Anestesia por Inhalación , Bebidas , Niño , Preescolar , Procedimientos Quirúrgicos Electivos , Frutas , Determinación de la Acidez Gástrica , Humanos , Concentración de Iones de Hidrógeno , Intubación Gastrointestinal , Intubación Intratraqueal , Omeprazol/administración & dosificación , Placebos , Estudios ProspectivosRESUMEN
The effect of nitrendipine on the cardiovascular responses to tracheal intubation was studied in a placebo-controlled, randomised, double-blind trial. Thirty patients (ASA physical status 1) undergoing elective surgery received either 5 or 10 mg nitrendipine, or a placebo orally 3 h before induction of anaesthesia (n = 10 for each group). Anaesthesia was induced with sodium thiopentone 5 mg/kg i.v. and tracheal intubation was facilitated with vecuronium 0.2 mg/kg i.v. Patients receiving the placebo showed a significant increase in the mean arterial pressure and the rate-pressure product in response to tracheal intubation. These increases following intubation were reduced in nitrendipine-treated patients compared with the placebo group (P < 0.05). Oral administration of nitrendipine (5 or 10 mg, 3 h before induction of anaesthesia) was able to attenuate the hypertensive response to tracheal intubation in ASA 1 patients under light anaesthesia. We propose this pharmacological technique with supplementary doses of opioids and/or benzodiazepines for the management of patients with hypertension or coronary artery disease.
Asunto(s)
Hemodinámica/efectos de los fármacos , Intubación Intratraqueal/efectos adversos , Nitrendipino/uso terapéutico , Administración Oral , Adulto , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Método Doble Ciego , Procedimientos Quirúrgicos Electivos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Nitrendipino/administración & dosificaciónRESUMEN
Ultraviolet-B and PUVA share several biological events with phorbol ester tumor promoters. The effects of ultraviolet-B irradiation and topical PUVA treatment on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity, which are known to be induced or activated by phorbol ester tumor promoter, were investigated in hairless mouse skin. Ornithine decarboxylase activity was remarkably enhanced by ultraviolet-B and PUVA. Although PUVA did not affect DNA synthesis significantly, ultraviolet-B stimulated epidermal DNA synthesis approximately 5-fold over control values at 48 h. However, unexpectedly, neither cytosolic nor membrane-bound protein kinase C activity showed any change during the 2 h after either treatment. These results suggest that the protein kinase C system is not involved in the initial signal transduction system of ultraviolet-B or PUVA, unlike the case with phorbol ester tumor promoter.
Asunto(s)
ADN/efectos de la radiación , Ornitina Descarboxilasa/efectos de la radiación , Terapia PUVA , Proteína Quinasa C/efectos de la radiación , Piel/efectos de la radiación , Rayos Ultravioleta , Animales , Bromodesoxiuridina , Membrana Celular/enzimología , Membrana Celular/efectos de la radiación , Citosol/enzimología , Citosol/efectos de la radiación , ADN/biosíntesis , Femenino , Ratones , Ratones Pelados , Ornitina Descarboxilasa/metabolismo , Proteína Quinasa C/metabolismo , Fase S/efectos de la radiación , Piel/citología , Piel/enzimología , Piel/metabolismo , Factores de TiempoRESUMEN
The effects of butylated hydroxyanisole (BHA), a representative phenolic antioxidant, on the activity of ornithine decarboxylase (ODC, an indicator of tumor promotion and epidermal hyperproliferation) induced by ultraviolet-B (UVB) or PUVA in mouse skin were investigated. By topical application of BHA (55 mumol), PUVA-induced ODC activity was suppressed by about 60% at both 12 h and 24 h after treatment. In contrast, BHA failed to suppress UVB-induced ODC activity in mouse skin. These results suggest that the induction of ODC activity by UVB or PUVA is mediated by different pathways.
Asunto(s)
Hidroxianisol Butilado/farmacología , Ornitina Descarboxilasa/metabolismo , Terapia PUVA , Piel/enzimología , Piel/efectos de la radiación , Rayos Ultravioleta , Animales , Femenino , Ratones , Ratones Pelados , Ornitina Descarboxilasa/efectos de la radiaciónRESUMEN
STUDY OBJECTIVE: To evaluate the efficacy of nilvadipine given orally in attenuating the hypertensive response to laryngoscopy and intubation. DESIGN: Controlled, randomized, double-blind study. SETTING: Induction of anesthesia for elective surgery at a university hospital. PATIENTS: Thirty normotensive patients (ASA physical status I) undergoing elective surgery were divided into three groups of ten patients each. INTERVENTIONS: Either 2 mg of nilvadipine, 4 mg of nilvadipine, or a placebo (control) was administered orally 90 minutes before induction of anesthesia. Anesthesia was induced with thiopental sodium 5 mg/kg intravenously, and tracheal intubation was facilitated with vecuronium 0.2 mg/kg. During anesthesia, ventilation was assisted or controlled with 1% enflurane and 50% nitrous oxide (N2O) in oxygen. Laryngoscopy lasting 30 seconds was attempted 2 minutes after administration of thiopental sodium and vecuronium. MEASUREMENTS AND MAIN RESULTS: Patients receiving the placebo showed a significant increase in mean arterial pressure (MAP) and heart rate associated with tracheal intubation. The increase in MAP following tracheal intubation was significantly lower in nilvadipine-treated patients than in the control group (p less than 0.05). However, neither dose of nilvadipine attenuated the tachycardic response to intubation. CONCLUSIONS: Oral administration of nilvadipine before induction of anesthesia is a simple and practical method for attenuating pressor response to laryngoscopy and tracheal intubation after standard elective induction under additional 1% enflurane-N2O anesthesia.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Intubación Intratraqueal , Laringoscopía , Nifedipino/análogos & derivados , Administración Oral , Adulto , Anestesia Intravenosa , Presión Sanguínea/fisiología , Bloqueadores de los Canales de Calcio/administración & dosificación , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Hipertensión/prevención & control , Intubación Intratraqueal/efectos adversos , Laringoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Nifedipino/administración & dosificación , Nifedipino/uso terapéutico , Placebos , Premedicación , Taquicardia/prevención & control , Tiopental , Bromuro de VecuronioRESUMEN
STUDY OBJECTIVE: To evaluate the efficacy and safety of nisoldipine given orally in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Induction of anesthesia for elective surgery at a university hospital. PATIENTS: Thirty normotensive patients (ASA physical status I) undergoing elective surgery were assigned to one of three groups; placebo, nisoldipine 5 mg, or nisoldipine 10 mg. Each group consisted of ten patients. INTERVENTIONS: Either 5 mg of nisoldipine, 10 mg of nisoldipine, or a placebo was administered orally 2 hours before induction of anesthesia. Anesthesia was induced with thiopental sodium 5 mg/kg intravenously, and tracheal intubation was facilitated with vecuronium 0.2 mg/kg. During anesthesia, ventilation was assisted or controlled with 1% enflurane and 50% nitrous oxide in oxygen. Laryngoscopy lasting 30 seconds was attempted 2 minutes after administration of thiopental sodium and vecuronium. MEASUREMENTS AND MAIN RESULTS: Patients receiving the placebo showed a significant increase in mean arterial pressure associated with tracheal intubation. These increases following tracheal intubation were significantly reduced in patients receiving nisoldipine 10 mg compared with patients receiving the placebo (p less than 0.05). CONCLUSIONS: Oral administration of nisoldipine before induction of anesthesia is a simple, practical, and safe method for attenuating pressor response to laryngoscopy and tracheal intubation.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Intubación Intratraqueal , Laringoscopía , Nisoldipino/uso terapéutico , Administración Oral , Adulto , Anestesia Intravenosa , Presión Sanguínea/fisiología , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Intubación Intratraqueal/efectos adversos , Laringoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Nisoldipino/administración & dosificación , Placebos , Tiopental , Factores de Tiempo , Bromuro de VecuronioRESUMEN
A 54-year-old Japanese male was treated with a single shot of cisplatin-phosphatidylcholine-lipiodol (CPL) suspension due to bladder tumour (stage T2N0M0). Seven months later, a right lower ureteral stenosis developed. The possible cause of ureteral stenosis due to intra-arterial chemotherapy is discussed.