RESUMO
BACKGROUND: Venous disease presents an extremely complex problem with various clinical manifestations. This is an epidemiological study of venous disease as it occurs in an area of Brazil. For the first time in Brazil the CEAP classification is used. METHODS: A total of 2104 people, were randomly recruited at the registration desks of the General Policlinic Department of the University Hospital and public health centers. The "C" of the CEAP classification was used to classify the clinical features of the venous diseases. The subjects were categorized according to sex and age. In addition, women were also subdivided according to number of their pregnancies. RESULTS: In the age group of females aged 14 to 22, we found 46.42% without symptoms and obvious veins (CEAP 0A/0A). Only 12.29% were symptomatic, and 41.25% of all patients in this group presented with visible veins or telangiectasias, though without symptoms. In the age group of women ranging from 23 to 48, 66.47% had had up to 3 pregnancies. In this group 10.43% were (CEAP 0A/0A). Those who had symptoms with prominent veins totaled 37.53% and those who presented with prominent veins without symptoms, 51.83%. In the female group over 48 years of age, only 4.67% were (CEAP 0A/0A). The majority (62.79%) had symptoms and prominent veins. In the male group, the greater part (65.54%) was (CEAP 0A/0A). Only 13.97% were considered symptomatic with some kind of prominent veins. CONCLUSIONS: This large epidemiological study is the first in Brazil to validate the CEAP classification as an important tool in the epidemiology of venous pathology: a method allowing an objective approach to venous disease. The data in this study were similar to those of western countries. Venous disease was found to be much more frequent in females than males. Age and number of pregnancies are important factors in the development of the disease. Over 50% of young women presented with visible veins in their legs but were without symptoms and this was considered a purely esthetic problem.
Assuntos
Insuficiência Venosa/classificação , Insuficiência Venosa/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Brasil/epidemiologia , Criança , Estudos Epidemiológicos , Feminino , Número de Gestações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Distribuição por SexoRESUMO
OBJECTIVE: To test whether patients require less volatile anesthetic after cardiopulmonary bypass (CPB). DESIGN: Prospective, observational clinical study. SETTING: Cardiovascular operating rooms of a large teaching hospital. PARTICIPANTS: Twenty adult patients undergoing surgery with CPB. INTERVENTIONS: Subjects received a computer-controlled fentanyl infusion designed to maintain effect site concentrations of 3 ng/mL, combined with a variable amount of isoflurane. MEASUREMENTS AND MAIN RESULTS: The end-tidal isoflurane concentration associated with a target bispectral index of 55 was recorded during skin preparation, after sternotomy, during rewarming, and after separation from CPB. Adjusted, geometric mean (95% confidence intervals), end-tidal isoflurane concentrations associated with a bispectral index of 55 were 0.46% (0.38% to 0.58%) during skin preparation, 0.47% (0.39% to 0.58%) after sternotomy, 0.35% (0.29% to 0.42%) during rewarming, and 0.36% (0.31% to 0.43%) after separation from CPB. The last 2 concentrations (recorded near the end and after CPB) were significantly (p < 0.05) less than the first 2 concentrations (recorded before CPB). CONCLUSION: Because the level of surgical stimulation was relatively constant and minimal at the times of the measurements, these results are consistent with a reduced need for isoflurane after compared with before CPB.
Assuntos
Anestésicos Inalatórios/farmacologia , Ponte Cardiopulmonar , Eletroencefalografia , Isoflurano/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
UNLABELLED: Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for "rescue" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy. IMPLICATIONS: Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.
Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estimulação Elétrica Nervosa Transcutânea , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Because no completely effective antiemetic exists for the prevention of postoperative nausea and vomiting (PONV), we hypothesize that a multimodal approach to management of PONV may reduce both vomiting and the need for rescue antiemetics in high-risk patients. After IRB approval, women undergoing outpatient laparoscopy were randomized to one of three groups. Group I (n = 60) was managed by using a predefined multimodal clinical care algorithm. Patients undergoing the same surgical procedure who received a standard balanced outpatient anesthetic with ondansetron 4 mg (Group II, n = 42) or placebo (Group III, n = 37) prophylaxis were chosen to establish baseline incidence of nausea and vomiting. None of the Group I patients vomited before discharge, compared with 7% in Group II (P = 0.07) and 22% in Group III (P = 0.0003). However, one patient (2%) in Group I required treatment for symptoms in the postanesthesia care unit, compared with 24% in Group II (P<0.0001) and 41% in Group III (P< 0.0001). Time to discharge-ready was significantly shorter in Group I (128, 118-139 min; mean, 95% confidence interval) versus Group II (162, 145-181 min; P = 0.0015) and Group III (192, 166-222 min; P = 0.0001). Patient satisfaction with control of PONV was not different between Group I and Group II. Return to normal daily activity and overall satisfaction were not different among groups. Multimodal management resulted in a 98% complete response rate and a 0% incidence of vomiting before discharge; however, this improvement did not result in an increased level of patient satisfaction when compared with routine monotherapy prophylaxis. We conclude that both multimodal management and routine monotherapy antiemetic prophylaxis resulted in an increased level of patient satisfaction than symptomatic treatment in this high-risk population.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Antieméticos/uso terapêutico , Procedimentos Cirúrgicos em Ginecologia , Laparoscopia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adulto , Algoritmos , Antieméticos/administração & dosagem , Feminino , Humanos , Dor Pós-Operatória/tratamento farmacológico , Método Simples-Cego , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The safety and antiemetic efficacy of CP-122,721, a novel neurokinin-1 antagonist, was evaluated when administered alone or in combination with ondansetron. METHODS: Using a randomized, double-blind, placebo-controlled study design, CP-122,721 was initially compared with placebo and subsequently to ondansetron alone and in combination for prophylaxis against postoperative nausea and vomiting in 243 women undergoing abdominal hysterectomy. In the dose-ranging studies (n = 86), patients received either CP-122,721 100 mg (vs. placebo) or 200 mg (vs. placebo) orally 60-90 min before induction of anesthesia. In the interaction study (n = 157), patients received CP-122,721 200 mg or placebo 60-90 min before induction of anesthesia, and ondansetron 4 mg or saline 2 ml intravenously 15-30 min before the end of surgery. Patients assessed their level of nausea and pain on arrival in the postanesthesia care unit and at 0.5-, 1-, 1.5-, 2-, 4-, 8-, 12-, and 24-h intervals postoperatively. Emetic episodes, need for rescue antiemetic-antinausea medication, postoperative complications, and patient satisfaction were recorded. RESULTS: In the initial dose-ranging study, only 10% of the patients experienced emesis within the first 8 h after surgery with CP-122,721 200 mg compared with 50% in the placebo group. CP-122,721 200 mg also decreased the need for rescue medication (25% vs. 48%). CP-122,721 100 mg was less effective than 200 mg in decreasing the incidence of repeated episodes of emesis. In the interaction study, 6% of the patients receiving CP-122,721 200 mg orally experienced emesis less than 2 h after surgery compared with 17% with ondansetron alone. With combined therapy, only 2% experienced emesis. In addition, the median times for 75% of patients to remain free from postoperative nausea and vomiting were 82, 75, and 362 min in the ondansetron, CP-122,721, and combination groups, respectively. CONCLUSIONS: Oral CP-122,721 200 mg decreased emetic episodes compared with ondansetron (4 mg intravenously) during the first 24 h after gynecologic surgery; however, there was no difference in patient satisfaction.
Assuntos
Antieméticos/uso terapêutico , Histerectomia/efeitos adversos , Ondansetron/uso terapêutico , Piperidinas/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Antagonistas da Serotonina/uso terapêutico , Substância P/antagonistas & inibidores , Administração Oral , Adulto , Antieméticos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Histerectomia/métodos , Injeções Intravenosas , Antagonistas dos Receptores de Neurocinina-1 , Piperidinas/efeitos adversos , Placebos , Medicação Pré-Anestésica , Fatores de RiscoRESUMO
BACKGROUND: Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model. METHODS: Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine. RESULTS: Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion. CONCLUSIONS: Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.
Assuntos
Dopamina/farmacocinética , Adulto , Dopamina/administração & dosagem , Dopamina/sangue , Meia-Vida , Humanos , Infusões Intravenosas , Masculino , Modelos BiológicosRESUMO
OBJECTIVE: Pulse oximetry (SpO2) is the non-invasive standard for monitoring arterial oxygen saturation in patients undergoing anesthesia, but is subject to external interference by motion artifact, peripheral vasoconstriction, and low cardiac output. We hypothesized that oximetry signals could be acquired from the esophagus when peripheral pulse oximetry is unobtainable. Therefore, we tested an esophageal stethoscope which incorporates transverse oximetry photodetectors and emitters in patients undergoing coronary bypass surgery. METHODS: Immediately after induction of general anesthesia in 10 coronary artery bypass (CABG) patients, Criticare and Nellcor digital probes were positioned on the left hand, concurrent with placement of an esophageal SpO2 probe. A computer recorded 5,910 matched oximetry signals every 15 sec during an average of 2.5 hrs. All SpO2 measurements were before, and immediately after non-pulsatile, hypothermic cardiopulmonary bypass. Data represent the percentage (median value [range]) of the total monitored time that a SpO2 value was displayed. RESULTS: The Nellcor (99.8%, range 6.5-100%) and Criticare (99.7%, range 36.6-100%) acquired and displayed saturation signals more frequently (p = 0.003) than the esophageal monitor (75.3%, range 42.1-95.8%). The two standard digital oximeters had a mean difference of 0.9%, with a standard deviation of the differences of 0.9. The esophageal probe had a mean difference of -5.2% and -4.8%, with standard deviation of differences of 8.0 and 7.7 (compared to the Nellcor and Criticare monitors, respectively). A second-generation prototype shielded from electrocautery interference was tested in an additional 4 patients. The shielded prototype displayed signals more frequently (96.7%, range 68.4-100%) than the original esophageal prototype. CONCLUSIONS: Digital pulse oximetry failure is common in CABG patients, probably because of marginal cardiac output and peripheral vasoconstriction associated with hypothermia. Our study could not confirm that esophageal technology, which utilizes the esophagus as a site of transflectance oximetry, was superior to conventional digital pulse oximetry.
Assuntos
Ponte de Artéria Coronária , Esôfago , Monitorização Fisiológica , Oximetria/instrumentação , Adulto , Idoso , Anestesia Geral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Monitorização Fisiológica/instrumentação , Oximetria/métodos , Oxiemoglobinas/análise , Processamento de Sinais Assistido por ComputadorRESUMO
BACKGROUND: Although prophylactic administration of antiemetics reduces the incidence of postoperative nausea, vomiting, or both (PONV), there is little evidence to suggest this improves patient outcomes. The authors hypothesized that early symptomatic treatment of PONV will result in outcomes, including time to discharge, unanticipated admission, patient satisfaction, and time to return to normal daily activities, that are similar to those achieved with routine prophylaxis. METHODS: Men and women (n = 575) scheduled for outpatient surgery during general anesthesia were randomized to receive either 4 mg intravenous ondansetron or placebo before operation and either 1 mg intravenous ondansetron or placebo if postoperative symptomatic treatment of PONV was necessary. Patients were stratified into subgroups by risk factors for PONV. RESULTS: No differences occurred in the time to discharge, rate of unanticipated admission, or time to return to normal activity between the prophylaxis and treatment groups. The reported level of satisfaction with control of PONV was 93% in the treatment arm and 97% in the prophylaxis arm, which fall within the limits defined a priori as clinically equivalent. Female patients with a history of motion sickness or PONV who were undergoing highly emetogenic procedures had a higher reported level of satisfaction with prophylaxis than with treatment (100% vs. 90%, P = 0.043); however, the level of satisfaction with the overall outpatient surgical experience was not different. CONCLUSION: Although PONV is unpleasant, the data indicate little difference in outcomes when routine prophylactic medications are administered versus simply treating PONV should symptoms occur.
Assuntos
Anestesia Geral/efeitos adversos , Antieméticos/administração & dosagem , Ondansetron/administração & dosagem , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adolescente , Adulto , Idoso , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Hospital acquired renal dysfunction, most commonly caused by renal hypoperfusion, dramatically increases mortality in intensive care patients. Glomerular filtration rate (GFR) is rapidly altered during renal hypoperfusion, and a more rapid means of GFR measurement may prompt institution of renal-specific therapy. We hypothesized that a transcutaneous renal function monitor can rapidly and accurately assess acute changes in GFR within a time frame much shorter than the 2-4 hours currently available. METHODS: The study design was a prospective determination of the capability to measure GFR transcutaneously. In three different studies, concurrent transcutaneous measurement of GFR, using the rate of disappearance of 99mTc-diethylenetriaminepentaacetic acid (DTPA), was compared by correlation and standard deviation (SD) to reference standards of DTPA plasma clearance, serum inulin clearance, or serum creatinine. RESULTS: Continuous transcutaneous clearance (TC) measurement correlated with standard DTPA plasma clearance techniques (r = 0.93). Acute pharmacologically induced changes in GFR are detectable by TC measurement within 12-20 min, a time interval significantly affected by the data acquisition interval. Excess patient movement in the ICU patients created clearance artifacts in 50% of clearance traces. Retrospective analysis of ICU patient data reveal TC measurements are 93% specific and 92% sensitive for serum creatinine levels in critically ill patients. CONCLUSIONS: TC monitoring provides prompt indication of directional changes in GFR and may provide the clinician warning of inadequate resuscitation. Prospective analysis of the specificity, sensitivity, and TC guided renal-specific resuscitation is needed.
Assuntos
Taxa de Filtração Glomerular , Hemodinâmica , Falência Renal Crônica/diagnóstico , Monitorização Fisiológica/métodos , Estado Terminal , Humanos , Rim/irrigação sanguínea , Rim/fisiopatologia , Ácido Pentético/metabolismo , Ácido Pentético/uso terapêutico , Complicações Pós-Operatórias/diagnóstico , Valores de ReferênciaRESUMO
UNLABELLED: We evaluated the safety and efficacy of RS-25259, a potent and long-acting selective 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) in women undergoing hysterectomy procedures. In this randomized, double-blind, placebo controlled, dose-ranging study, 218 healthy, consenting women were assigned to one of the six treatment groups: placebo or RS-25259 0.1, 0.3, 1.0, 3.0, or 30 microg/kg. All patients underwent a standardized general anesthetic technique. The study medication was administered i.v. 20-30 min before the end of surgery. During the initial 24-h period after surgery, the incidence of vomiting, the need for rescue antiemetics, the time to the first episode of emesis, and administration of rescue antiemetic medication, as well as a nausea visual analog scale and verbal categorical scale scores were recorded. In addition, recovery times from the end of anesthesia and the incidences of perioperative side effects were noted. Only 30 microg/kg RS-25259 significantly decreased the incidence of vomiting and the requirement for rescue antiemetics. The largest dose of RS-25259 also delayed the time to the first emetic episode and reduced the number of treatment failures. However, no differences were found in the severity of postoperative nausea (versus saline), and postoperative headaches were more common after the administration of RS-25259 0.3-30 microg/kg i.v. In conclusion, RS-25259 30 microg/kg i.v. was effective in reducing the incidence of PONV after major gynecologic surgery, but the occurrence of headaches with the larger doses of RS-25259 is a concern. IMPLICATIONS: RS-25259, a long-acting 5-HT3 antagonist, was effective in reducing postoperative vomiting only at the largest dose studied (30 microg/kg). However, RS-25259 had no antinausea activity, and the larger doses were associated with an increased incidence of headaches in the postoperative period.
Assuntos
Antieméticos/uso terapêutico , Histerectomia , Isoquinolinas/uso terapêutico , Náusea/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Antagonistas da Serotonina/farmacologia , Vômito/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversosRESUMO
STUDY OBJECTIVE: To compare the efficacy of ondansetron, droperidol, or metoclopramide with placebo in preventing postoperative vomiting following strabismus surgery. STUDY DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University outpatient surgery center. PATIENTS: 160 ASA physical status I and II children ages 1 to 12 years who were scheduled for strabismus surgery. INTERVENTIONS: Administration of either ondansetron 100 mcg/kg, metoclopramide 250 mcg/kg, droperidol 75 mcg/kg, or placebo intravenously after induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Both ondansetron and droperidol were superior to metoclopramide and placebo in preventing predischarge vomiting, with incidences of 5%, 5%, 32%, and 25%, respectively. However, there was no difference in the incidence of postdischarge vomiting among the groups (ondansetron 25%, droperidol 25%, metoclopramide 20%, and placebo 25%). CONCLUSIONS: While both ondansetron and droperidol are more effective than metoclopramide when compared with placebo in decreasing the incidence of predischarge vomiting, none of these drugs was more effective than placebo in decreasing the incidence of postdischarge vomiting. Recovery from anesthesia was not significantly different among the groups as assessed by time to awakening, initial Steward score, and time to discharge.
Assuntos
Antieméticos/uso terapêutico , Droperidol/uso terapêutico , Metoclopramida/uso terapêutico , Ondansetron/uso terapêutico , Estrabismo/cirurgia , Vômito/prevenção & controle , Procedimentos Cirúrgicos Ambulatórios , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/prevenção & controle , Estudos ProspectivosRESUMO
UNLABELLED: This study was conducted to determine the efficacy and safety of four intravenous (I.V.) doses of dolasetron, an investigational 5-HT3 receptor antagonist, for the treatment of postoperative nausea and/or vomiting (PONV) after outpatient surgery under general anesthesia. This multicenter, randomized, double-blind trial compared the antiemetic efficacy of 12.5, 25, 50, or 100 mg I.V. dolasetron with placebo over 24 h using complete response (no emetic episodes and no rescue medication), time to first emetic episode or rescue medication, and patient nausea and satisfaction with antiemetic therapy as rated by visual analog scale (VAS). Of 1557 patients enrolled, 620 patients were eligible for treatment. Complete response rates for all dolasetron doses--12.5 mg (35%), 25 mg (28%), 50 mg (29%), and 100 mg (29%)--were significantly more effective than placebo (11%, P < 0.05). There was a significant gender interaction for complete response (P < 0.01). Of the patients in the 25-mg and 100-mg dose groups, 12% and 13%, respectively, experienced no nausea (VAS score < 5 mm) versus 5% in the placebo group (P < 0.05). There were no clinically relevant changes in vital signs or laboratory values and no trends with dose for adverse events. Dolasetron is effective for treating PONV and has an adverse event profile similar to that of placebo. The 12.5-mg dose was as effective as larger doses for complete response. IMPLICATIONS: Nausea and vomiting are common problems for postsurgical patients. In this study of 620 patients undergoing surgery, a 12.5-mg dose of intravenous dolasetron, a new serotonin-receptor blocker, was significantly more effective than placebo in treating established postoperative nausea and vomiting. Dolasetron 12.5 mg was as safe as placebo.
Assuntos
Antieméticos/administração & dosagem , Indóis/administração & dosagem , Náusea/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Quinolizinas/administração & dosagem , Vômito/tratamento farmacológico , Adulto , Procedimentos Cirúrgicos Ambulatórios , Anestesia Geral , Antieméticos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Indóis/efeitos adversos , Injeções Intravenosas , Modelos Logísticos , Masculino , Satisfação do Paciente , Quinolizinas/efeitos adversosRESUMO
OBJECTIVES: To determine the optimal dosing of doxacurium as a continuous infusion in neurosurgical patients with traumatic brain injury; to determine the effects of bolus administration of doxacurium on heart rate (HR), blood pressure (BP), and intracranial pressure (ICP); to monitor neuromuscular recovery after discontinuation of prolonged doxacurium infusion; and to compare the cost of doxacurium with other current neuromuscular blocking drugs. DESIGN: Prospective, open-label study. SETTING: Neurosurgical intensive care unit (ICU) of a university-affiliated teaching hospital. PATIENTS: Eight critically ill, mechanically ventilated patients with traumatic head injury and normal renal and hepatic function. Patients had ICP monitoring. INTERVENTIONS: A bolus injection of doxacurium (0.05 mg/kg) followed by a continuous infusion (0.015 mg/kg/hr), adjusted to maintain one twitch during Train-of-Four nerve stimulation of the adductor pollicis muscle. MEASUREMENTS AND MAIN RESULTS: Bolus injections of doxacurium did not alter the HR, BP, or ICP. Patients were paralyzed 66 +/- 12 (SEM) hrs, with recovery of the fourth twitch occurring 118 +/- 19 mins after infusion of the doxacurium was discontined. There were no incidences of prolonged weakness, myopathy, or other adverse events. CONCLUSIONS: Continuous infusion of doxacurium provides stable neuromuscular blockade for neurosurgical patients with traumatic brain injury. Doxacurium is devoid of clinically important interactions with HR, BP, or ICP and is less costly than other neuromuscular blockers used in the ICU.
Assuntos
Lesões Encefálicas/cirurgia , Cuidados Críticos , Isoquinolinas/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Lesões Encefálicas/fisiopatologia , Cuidados Críticos/economia , Cuidados Críticos/métodos , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Pressão Intracraniana/efeitos dos fármacos , Isoquinolinas/economia , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares não Despolarizantes/economia , Fármacos Neuromusculares não Despolarizantes/uso terapêutico , Neurocirurgia , Estudos Prospectivos , Respiração ArtificialRESUMO
The death-inducing receptor Fas is activated when cross-linked by the type II membrane protein Fas ligand (FasL). When human soluble FasL (sFasL, containing the extracellular portion) was expressed in human embryo kidney 293 cells, the three N-linked glycans of each FasL monomer were found to be essential for efficient secretion. Based on the structure of the closely related lymphotoxin alpha-tumor necrosis factor receptor I complex, a molecular model of the FasL homotrimer bound to three Fas molecules was generated using knowledge-based protein modeling methods. Point mutations of amino acid residues predicted to affect the receptor-ligand interaction were introduced at three sites. The F275L mutant, mimicking the loss of function murine gld mutation, exhibited a high propensity for aggregation and was unable to bind to Fas. Mutants P206R, P206D, and P206F displayed reduced cytotoxicity toward Fas-positive cells with a concomitant decrease in the binding affinity for the recombinant Fas-immunoglobulin Fc fusion proteins. Although the cytotoxic activity of mutant Y218D was unaltered, mutant Y218R was inactive, correlating with the prediction that Tyr-218 of FasL interacts with a cluster of three basic amino acid side chains of Fas. Interestingly, mutant Y218F could induce apoptosis in murine, but not human cells.
Assuntos
Glicoproteínas de Membrana/metabolismo , Receptor fas/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação , Cromatografia em Gel , Ensaio de Imunoadsorção Enzimática , Proteína Ligante Fas , Glicosilação , Humanos , Células Jurkat , Ligantes , Glicoproteínas de Membrana/genética , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese , Prolina/metabolismo , Alinhamento de Sequência , Solubilidade , Especificidade da Espécie , Tirosina/metabolismoRESUMO
OBJECTIVE: To evaluate the risk of phlebitis associated with chlorhexidine-coated polyurethane catheters in peripheral veins. DESIGN: A randomized, double-blinded trial comparing chlorhexidine-coated polyurethane catheters with uncoated polyurethane catheters. SETTING: A university hospital. PATIENTS: Adult medicine and surgery patients. INTERVENTIONS: Certified registered nurse anesthetists or an infusion team consisting of nurses and physicians inserted the catheters. Catheter insertion sites were scored twice daily for evidence of phlebitis. At the time catheters were removed, a quantitative blood culture was performed, and catheters were sonicated for quantitative culture. RESULTS: Of 221 evaluable catheters, phlebitis developed in 18 (17%) of 105 coated catheters, compared to 27 (23%) of 116 uncoated catheters (relative risk [RR], 0.74; 95% confidence interval [CI95], 0.43-1.26; P = .32). By survival analysis, chlorhexidine-coated catheters had a lower risk of phlebitis during the first 3 days (P = .06), but not when all catheters were considered in both patient groups (P = .31). In the absence of catheter colonization, the incidence of phlebitis was 21% (16/76) and 24% (20/86) for coated and uncoated catheters, respectively (P = .85), whereas in the presence of catheter colonization, the incidence of phlebitis was 14% (1/7) and 80% (4/5) for coated and uncoated catheters, respectively (RR, 0.18; CI95, 0.03-1.15; P = .07). CONCLUSION: The risk of phlebitis in the presence of catheter colonization was 82% lower for chlorhexidine-coated polyurethane catheters compared to otherwise identical uncoated catheters.
Assuntos
Anti-Infecciosos Locais/administração & dosagem , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/microbiologia , Clorexidina/administração & dosagem , Infecção Hospitalar/prevenção & controle , Contaminação de Equipamentos/prevenção & controle , Flebite/prevenção & controle , Adulto , Cateterismo Periférico/métodos , Cateteres de Demora/efeitos adversos , Intervalos de Confiança , Método Duplo-Cego , Feminino , Humanos , Controle de Infecções/métodos , Controle de Infecções/normas , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Tamanho da Amostra , Staphylococcus/isolamento & purificação , Análise de SobrevidaRESUMO
Intercellular adhesion molecule-1 (ICAM-1) is the cell surface receptor for the major class of human rhinoviruses, and tICAM453, a truncated, soluble form of ICAM-1, has been shown previously to be a potent in vitro inhibitor of rhinovirus. In this report, we have investigated the in vivo efficacy of tICAM453 for the prophylaxis of rhinovirus serotype 16 infection in the chimpanzee. Because chimpanzees do not show clinical symptoms of infection after rhinovirus challenge, infection was followed by measuring antirhinovirus serum antibody responses and detection of virus shedding. By both of these measures, intranasal application of tICAM453 was efficacious in preventing rhinovirus infection in chimpanzees subsequently challenged with infectious doses of virus. These results suggest that the use of soluble rhinovirus receptor to inhibit virus binding to host cells should be feasible in humans.
Assuntos
Resfriado Comum/prevenção & controle , Molécula 1 de Adesão Intercelular/uso terapêutico , Rhinovirus , Administração Intranasal , Animais , Anticorpos Antivirais/análise , Resfriado Comum/imunologia , Molécula 1 de Adesão Intercelular/administração & dosagem , Pan troglodytes , Rhinovirus/imunologia , Eliminação de Partículas ViraisRESUMO
The purpose of this study was to test the hypothesis that using a 1:4 ratio of remifentanil to alfentanil, a remifentanil infusion would provide better suppression of intraoperative responses and comparable recovery profiles after ambulatory laparoscopic surgery than an alfentanil infusion, as part of total intravenous anesthesia. Two hundred ASA physical status I, II, or III adult patients participated in this multicenter, double-blind, parallel group study. Patients were randomly assigned 2:1 to either the remifentanil-propofol or alfentanil-propofol regimens. The anesthesia sequence was propofol (2 mg/kg intravenously [IV] followed by 150 micrograms.kg-1.min-1), and either remifentanil (1 microgram/kg IV followed by 0.5 microgram.kg-1.min-1)of alfentanil (20 micrograms/kg IV followed by 2 micrograms.kg-1.min-1), and vecuronium. After trocar insertion, infusion rates were decreased (propofol to 75 micrograms.kg-1.min-1; remifentanil to 0.25 microgram.kg-1.min-1; alfentanil to 1 microgram.kg-1.min-1). Alfentanil and propofol were discontinued at 10 and 5 min, respectively, before the anticipated end of surgery (last surgical suture); remifentanil was discontinued at the end of surgery. Recovery times were calculated from the end of surgery. The median duration of surgery was similar between groups (39 min for remifentanil versus 34 min for alfentanil). A smaller proportion of remifentanil patients than alfentanil patients had any intraoperative responses (53% vs 71%, P = 0.029), had responses to trocar insertion (11% vs 32%, P < 0.001), or required dosage adjustments during maintenance (24% vs 41%, P < 0.05). Early awakening times were similar. Remifentanil patients qualified for Phase 1 discharge later and were given postoperative analgesics sooner than alfentanil patients (P < 0.05). Actual discharge times from the ambulatory center were similar between groups (174 min for remifentanil versus 204 min for alfentanil) (P = 0.06). In conclusion, remifentanil can be used for maintenance of anesthesia in a 1:4 ratio compared with alfentanil, for total IV anesthesia in ambulatory surgery. This dose of remifentanil provides more effective suppression of intraoperative responses and does not result in prolonged awakening.
Assuntos
Alfentanil/uso terapêutico , Assistência Ambulatorial/métodos , Laparoscopia/métodos , Piperidinas/uso terapêutico , Adulto , Anestesia Intravenosa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Remifentanil , Fatores de TempoRESUMO
This study was designed to test the hypothesis that there is a direct prophylactic antiemetic effect of small-dose propofol given by continuous infusion. Sixty female patients undergoing outpatient laparoscopy under general anesthesia were randomized to receive, in a double-blind fashion, either a bolus of 0.1 mg/kg followed by a constant infusion of 1 mg.kg-1.h-1 of propofol or an equivalent volume of 10% Intralipid (placebo) beginning 30 min before induction of anesthesia and continuing until discharge from Stage I postanesthesia care unit (PACU). Anesthesia was induced and maintained in a standard fashion in all patients. The number of emetic episodes before and after discharge from PACU, nausea scores (11-point numerical scale), and time to discharge were evaluated. No significant differences between Intralipid and propofol were found for any of the outcome variables tested. While small-dose propofol is an effective adjuvant in reducing chemotherapy-induced emesis, we were unable to demonstrate any beneficial effect of propofol in reducing postoperative nausea and vomiting when used as the sole prophylactic medication in this patient population. Propofol may have a synergistic effect when administered with other antiemetics, or the specific antiemetic effect of propofol, if it exists, may be dose-dependent and the dose used in this study was below the efficacy threshold.