RESUMO
BACKGROUND: Intranasally administered midazolam was compared with sufentanil as a premedicant for 60 patients, aged 1/2 to 6 years, undergoing outpatient surgery of 2 hours or less. METHODS: Thirty minutes before anesthetic induction (halothane in 50% nitrous oxide/oxygen), patients were randomly assigned to receive either intranasal midazolam (0.2 mg/kg) or sufentanil (2 microg/kg). A "blinded" observer evaluated preoperative emotional state, response to premedication, induction, and emergence from anesthesia and side effects. RESULTS: Children who had not previously cried were more likely to cry when midazolam was administered compared with sufentanil (71% versus 20%, p = 0.0031). Of 31 midazolam patients, 20 experienced nasal irritation. Approximately 15 to 20 minutes after drug administration, most patients in both groups could be comfortably separated from their parents. The sufentanil group appeared to be more sedated and more cooperative during induction of anesthesia. Vital signs and oxygen saturation did not change significantly with either medication before or after surgery, although two sufentanil patients had a moderate reduction in ventilatory compliance after anesthetic induction. Sufentanil was associated with more nausea and vomiting than midazolam (34% versus 6%, p < 0.02). CONCLUSION: Both intranasal midazolam and sufentanil provide rapid, safe, and effective sedation in small children before anesthesia for ambulatory surgery. Sufentanil provided somewhat better conditions for induction and emergence. Midazolam causes more nasal irritation during instillation, and sufentanil causes more postoperative nausea and vomiting. Both drugs enabled patients to be separated from their parents with a minimum of distress. Patients in the midazolam group were discharged approximately 40 minutes earlier (p <0.005).
Assuntos
Adjuvantes Anestésicos/uso terapêutico , Procedimentos Cirúrgicos Ambulatórios , Ansiolíticos/uso terapêutico , Midazolam/uso terapêutico , Sufentanil/uso terapêutico , Adjuvantes Anestésicos/administração & dosagem , Administração Intranasal , Ansiolíticos/administração & dosagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Midazolam/administração & dosagem , Método Simples-Cego , Sufentanil/administração & dosagem , Resultado do TratamentoRESUMO
The cardiopulmonary effects of epinephrine and terbutaline were compared in a doubleblind crossover study in 23 subjects with chronic obstructive airway disease. On each of three days each subject received a single subcutaneous dose of saline, 0.25 mg of epinephrine or 0.5 mg of terbutaline. Treatment with epinephrine produced significant increases in forced vital capacity (FVC), forced expiratory volume in one second (FEV-1), maximal expiratory flow rate (MEFR) and maximal mid-expiratory flow (MMEF). Terbutaline caused even more pronounced increases in all four parameters and exhibited a longer duration of action. Neither drug altered arterial pH, arterial oxygen pressure (PaO-2), or arterial carbon dioxide pressure (PaCO-2). With regard to cardiovascular effects, no alterations in either systolic or diastolic pressure were observed. Administration of epinephrine and terbutaline caused statistically significant increases in heart rate. The effect of terbutaline was more pronounced that that of epinephrine. In addition, terbutaline caused a heart rate-related depression of the T-wave of the lead 2 ECG. Neither drug altered any of the hematologic, hemochemical or urinary parameters monitored before and after treatment. Side effects were seen in eight subjects after administration of saline solution, in 13 subjects after epinephrine and in 19 subjects after terbutaline. None of these side effects was considered clinically serious and none required treatment. It is concluded from this study that subcutaneously administered terbutaline is a more effective bronchodilator than epinephrine.
Assuntos
Obstrução das Vias Respiratórias/tratamento farmacológico , Epinefrina/uso terapêutico , Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Terbutalina/uso terapêutico , Adulto , Idoso , Artérias , Sangue , Dióxido de Carbono/sangue , Eletrocardiografia , Epinefrina/administração & dosagem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Espirometria , Terbutalina/administração & dosagem , Capacidade VitalRESUMO
Prostacyclin (PGI2) infusion was studied in patients during cardiopulmonary bypass for coronary artery bypass grafting to assess its capacity to protect platelet hemostatic function. Twelve patients received PGI2 at doses ranging from 20 to 70 ng/kg/min by continuous infusion directly into the bubble oxygenator. Nine control patients were also studied. Platelet counts were not different in the two groups; the platelet count at the completion of the operation was decreased by a mean of 29% in treated patients and 40% in control patients (p greater than 0.15). Bleeding times were uniformly greater than 30 minutes following 30 minutes on bypass in both groups (p greater than 0.5). Also there was no difference in the bleeding times between the treated and untreated groups in the immediate postbypass period (p greater than 0.05). In addition, no difference in transfusion requirements was observed between the treated and control groups. However, plasma levels of platelet factor 4 were lower in the treated patients (p less than 0.05), and, more significantly, blood pressure was lower at all time points in the treated patients (p less than 0.001) despite the greater use of vasopressors. We conclude that PGI2 infusion in this study was of no hemostatic benefit but produced significant hypotension, a potential source of morbidity.
Assuntos
Plaquetas/efeitos dos fármacos , Ponte de Artéria Coronária , Epoprostenol/administração & dosagem , Hemostasia Cirúrgica/métodos , Adulto , Idoso , Tempo de Sangramento , Pressão Sanguínea/efeitos dos fármacos , Creatinina/urina , Avaliação de Medicamentos , Feminino , Humanos , Hipotensão/induzido quimicamente , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Fator de Ativação de Plaquetas/análise , Contagem de Plaquetas , Fator Plaquetário 4/análise , Fatores de Tempo , beta-Tromboglobulina/análiseRESUMO
BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage in a number of clinical settings. The purpose of this investigation was to determine the correlation between cerebral microemboli and S100beta levels during cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were divided into five time periods: (1) incision to aortic cannulation; (2) aortic cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release; (4) cross-clamp release to decannulation; and (5) decannulation to chest closure. The level of S100beta (n = 156) was measured at baseline, at the end of cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release. RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time, cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary bypass time was univariately associated with S100beta level, it became nonsignificant in a multivariable model that included age and cross-clamp time. CONCLUSIONS: The correlation of S100beta level with emboli measured during cannulation (time period 2) supports the hypothesis that cannulation is a high-risk time period for cerebral injury.
Assuntos
Proteínas de Ligação ao Cálcio/sangue , Ponte de Artéria Coronária/efeitos adversos , Embolia e Trombose Intracraniana/etiologia , Proteínas S100/sangue , Fatores Etários , Análise de Variância , Aorta/cirurgia , Biomarcadores/sangue , Ponte Cardiopulmonar , Artérias Cerebrais/diagnóstico por imagem , Constrição , Feminino , Seguimentos , Humanos , Embolia e Trombose Intracraniana/sangue , Embolia e Trombose Intracraniana/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Crescimento Neural , Fatores de Risco , Subunidade beta da Proteína Ligante de Cálcio S100 , Fatores de Tempo , Ultrassonografia Doppler TranscranianaRESUMO
Development of a safe and effective oral form of testosterone has been inhibited by the rapid hepatic metabolism of nonalkylated androgens. Since triglycerides are absorbed via lymphatics and bypass the liver, we hypothesized that a testosterone-triglyceride conjugate (TTC) might allow for safe and effective oral testosterone therapy. Therefore, we studied the single-dose pharmacokinetics of oral administration of TTC in rabbits. Female New Zealand rabbits were administered 2, 4, or 8 mg/kg of TTC in sesame oil by gastric lavage. Testosterone undecanoate (TU) by gastric lavage was used as a positive control. Blood was sampled from a catheter in the auricular artery at 0, 15, 30, 60, 90, 120, 180, 240, 360, 480, and 600 minutes after drug administration. Samples were assayed for testosterone by a fluoroimmunoassay. Mean serum testosterone, area under the curve (AUC), and terminal half-life were calculated. Oral TTC administration resulted in rapid and marked increases in serum testosterone. Oral TTC resulted in higher maximum serum testosterone concentrations than oral TU at 8 mg/kg (TTC: 28.6 +/- 7.9 nmol/L vs TU: 11.9 +/- 2.1 nmol/L; P <.001) and 4 mg/kg (TTC: 11.5 +/- 4.2 nmol/L vs TU: 3.6 +/- 1.0 nmol/L; P <.001). In addition, the AUC was 1.8 to 2.6 times greater for TTC than TU at both doses (P <.05). The terminal half-life for both TU and TTC was between 3 and 5 hours and was not significantly different. We conclude that oral TTC is rapidly absorbed from the rabbit intestine and results in elevated concentrations of serum testosterone. The absorption of TTC appears to be superior to that of TU; however, the in vivo persistence of the 2 compounds is similar. TTC may offer an alternative to the use of TU for oral testosterone therapy. Further testing of this compound is warranted.
Assuntos
Androgênios/farmacocinética , Testosterona/análogos & derivados , Testosterona/farmacocinética , Administração Oral , Androgênios/sangue , Androgênios/química , Animais , Hipogonadismo/tratamento farmacológico , Masculino , Modelos Animais , Coelhos , Testosterona/sangue , Testosterona/química , Triglicerídeos/sangue , Triglicerídeos/química , Triglicerídeos/farmacocinéticaRESUMO
STUDY OBJECTIVE: To determine the hemodynamic effects of famotidine in patients undergoing cardiac surgery. DESIGN: A prospective, randomized, double-blinded, placebo-controlled study. SETTING: A large university teaching hospital. PATIENTS: Twenty-one patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: The patients received a rapid intravenous bolus injection of famotidine 20 mg or saline placebo after anesthesia induction. A second dose was given 12 hours after surgery in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Serial hemodynamic measurements (heart rate, arterial blood pressure, cardiac index, pulmonary arterial pressure, central venous pressure, systemic vascular resistance) were obtained after each famotidine or placebo dose and analyzed by ANOVA: The values were not altered (p > 0.05) after intraoperative or postoperative famotidine or placebo administration. CONCLUSIONS: Rapid intravenous bolus administration of famotidine does not alter patient hemodynamics after anesthesia induction or in the intensive care unit after cardiac surgery.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Famotidina/farmacologia , Hemodinâmica/efeitos dos fármacos , Idoso , Anestesia , Pressão Sanguínea/efeitos dos fármacos , Ponte Cardiopulmonar , Método Duplo-Cego , Famotidina/administração & dosagem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hospitais Universitários , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Pressão Venosa/efeitos dos fármacosRESUMO
This randomized, open-label study compared the investigational inhalational anesthetic sevoflurane with isoflurane in 47 healthy women undergoing elective ambulatory surgery. The women were randomized to receive either sevoflurane or isoflurane in 60% nitrous oxide-oxygen. Induction with thiopental 3-6 mg/kg was followed by vecuronium 0.1 mg/kg and fentanyl 0-200 micrograms. Duration of anesthesia, time to emergence, orientation, length of stay in the surgical unit, and hospital discharge were recorded. The emergence, length of stay, and discharge times after discontinuation of sevoflurane were 9.7 +/- 0.7, 120.6 +/- 8.0, and 244 +/- 15 minutes, respectively, and for isoflurane were 11.9 +/- 1.4, 106.8 +/- 7.1, and 282 +/- 24 minutes, respectively (NS). The isoflurane group had a higher frequency of postoperative cough. At the end of surgery, the sevoflurane group received a deeper level of anesthesia (minimum alveolar concentration 1.5 vs 1.3), however, these patients were oriented earlier (13.6 +/- 1.1 min vs 17.0 +/- 1.5 min isoflurane; p = 0.02) after discontinuation of anesthesia, although this difference is of little clinical significance.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Anestésicos Inalatórios/farmacologia , Éteres/farmacologia , Isoflurano/farmacologia , Éteres Metílicos , Adulto , Período de Recuperação da Anestesia , Feminino , Humanos , SevofluranoRESUMO
STUDY DESIGN: A case series in which the halo-Milwaukee brace was used for postoperative immobilization in children with complex congenital and developmental spinal deformities. OBJECTIVES: To describe the use of halo-Milwaukee orthosis in a pediatric population for stabilization of the cervical and upper thoracic spine. SUMMARY AND BACKGROUND DATA: Postoperative immobilization of the neck and upper thorax can be achieved with cervical orthoses, cervicothoracic lumbar orthosis, halo cast, Minerva jacket, or halo vest. In the young child or in individuals with severe deformities, prefabricated braces often do not provide adequate stability or predictable fit. The halo-Milwaukee brace has proven to be an effective and versatile technique in the management of complex pediatric spinal deformities. METHODS: Halo-Milwaukee brace immobilization was used in 12 patients after surgical stabilization of the upper thoracic or cervical spine. Technique and indications are discussed in this report. Surgical outcomes and complications were reviewed retrospectively in all cases. RESULTS: Application of the halo-Milwaukee brace was a clinically effective and safe means of controlling the upper thoracic and cervical spine. The orthosis was well tolerated and allowed access to the posterior incision. The brace is easily converted to a standard Milwaukee brace with neck ring. The pelvic segment of the brace is molded before surgery, and in most instances did not require postoperative modification. CONCLUSION: The halo-Milwaukee brace is a simple and convenient method of intraoperative and postoperative immobilization. The technique is applicable in patients who cannot be treated with more conventional off-the-shelf orthoses. The brace was well tolerated and allowed for early patient mobilization.
Assuntos
Braquetes , Fixadores Externos , Cifose/cirurgia , Escoliose/cirurgia , Coluna Vertebral/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Radiografia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/fisiopatologia , Resultado do TratamentoRESUMO
Use of omental flaps is well documented in soft tissue reconstruction of the head and neck, chest wall, and abdomen. Three cases of omental transfer for soft tissue reconstruction of the lower extremities are presented. In two patients, free vascularized omental flaps were used to cover deep soft tissue defects over the lower leg and in one patient, a pedicle flap was used to cover a deep groin defect extending into the hip joint. In all patients, use of an omental graft allowed revascularization and subsequent wound healing with good cosmetic results.
Assuntos
Úlcera do Pé/cirurgia , Pé/irrigação sanguínea , Isquemia/cirurgia , Úlcera da Perna/cirurgia , Perna (Membro)/irrigação sanguínea , Omento/transplante , Retalhos Cirúrgicos , Idoso , Amputação Cirúrgica , Artérias/cirurgia , Virilha/irrigação sanguínea , Humanos , Masculino , Microcirurgia , Pessoa de Meia-Idade , Reoperação , Retalhos Cirúrgicos/irrigação sanguínea , Infecção da Ferida Cirúrgica/cirurgia , Técnicas de SuturaRESUMO
STUDY OBJECTIVE: To compare the efficacy of patient-controlled analgesia (PCA) to physician-controlled analgesia in patients undergoing extracorporeal shock wave lithotripsy (ESWL). DESIGN: Prospective, randomized trial. SETTING: New Jersey Kidney Stone Treatment Center at Robert Wood Johnson University Hospital, New Brunswick, NJ. PATIENTS: 62 ASA I, II, and III patients undergoing ESWL. INTERVENTIONS: The control group (n = 29) received physician-controlled analgesia with continuous infusions (0.75 mcg/kg/min) and intermittent boluses (5 mcg/kg) of alfentanil. PCA patients (n = 33) initially received alfentanil 0.5 mcg/kg followed by a continuous background infusion (0.2 to 0.5 mcg/kg/min) and self-administered alfentanil (3 to 5 mcg/kg) with a 5-minute lockout period. Bolus doses and infusion rates were determined by patient comfort and cardiorespiratory response to alfentanil. MEASUREMENTS AND MAIN RESULTS: Prior to the procedure, the patients completed two questionnaires (State-Trait Anxiety Inventory and Multidimensional Health Locus of Control Scales). During ESWL, blood pressure, heart rate, respiratory rate, oxygen saturation, end-tidal CO2, and pain and sedation levels were measured at 0, 800, 1,600, 2,400, and 3,000 shock waves. The total doses of alfentanil administered were calculated. PCA patients received 31% less alfentanil than control group patients (p < 0.0001). Patients with more preoperative anxiety required larger doses of alfentanil (p < 0.05). The pain level was slightly higher in the patients receiving PCA (p > 0.05) but most patients reported either no or only mild pain. Side effects from the therapy, such as nausea and vomiting, were either not present or were mild in both groups, with one patient (3% to 4%) in each group reporting mild nausea. Both patients and urologists were very satisfied with the pain management in both groups. CONCLUSIONS: PCA is a useful alternative to physician-controlled analgesia during ESWL since it provides equivalent pain control while using less alfentanil.
Assuntos
Alfentanil/administração & dosagem , Litotripsia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Autoadministração , Inquéritos e QuestionáriosAssuntos
Embolia e Trombose Intracraniana/etiologia , Terapia a Laser , Revascularização Miocárdica/métodos , Idoso , Ecocardiografia Transesofagiana , Feminino , Humanos , Embolia e Trombose Intracraniana/diagnóstico por imagem , Terapia a Laser/efeitos adversos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Revascularização Miocárdica/efeitos adversos , Espectroscopia de Luz Próxima ao Infravermelho , Ultrassonografia Doppler TranscranianaAssuntos
Expedições/história , Escorbuto/história , Regiões Antárticas , História do Século XIX , HumanosRESUMO
Polymorphonuclear leukocyte (PMN) numbers were determined in samples of central venous or pulmonary artery blood and in simultaneously drawn samples of systemic arterial blood 5 min before institution of cardiopulmonary bypass (CPB) and 5 min after the termination of CPB in 10 adult patients. In only 2 of 10 patients was the systemic arterial PMN number lower than that in central venous or pulmonary arterial blood in the post-CPB period. The results suggest that intrapulmonary PMN sequestration, reported to be a frequent consequence of complement activation during CPB, is a transient and self-limited phenomenon in most persons.
Assuntos
Ponte Cardiopulmonar , Neutrófilos , Adulto , Ativação do Complemento , Feminino , Humanos , Contagem de Leucócitos , Pulmão/imunologia , MasculinoRESUMO
Some previous reports indicate that the excitability of the brain may be increased for days following enflurane anesthesia. The authors investigated this possibility in cats by determining whether or not pentylenetetrazol- (Metrazol) or lidocaine-seizure thresholds decreased after repeated enflurane exposure. The lidocaine-seizure threshold was bracketed in 4 cats, and the pentylenetetrazol-seizure threshold was bracketed in another 4 cats. Each cat was then exposed to 4 per cent enflurane for 2 hours on 4 successive days. Twenty-four hours after the last enflurane exposure, the cats were injected with the previously determined subthreshold dose of pentylenetetrazol (6.4 mg/kg, on the average) or lidocaine (7.8 mg/kg, on the average). No cat convulsed. It was therefore concluded that under our experimental conditions, repeated enflurane exposure does not increase the sensitivity to drugs which nonselectively excite the central nervous system (e.g., pentylenetetrazol) or to drugs which mimic temporal lobe epilepsy (e.g., lidocaine). This finding cast doubt that brain excitability is increased in the post-enflurane anesthetic period.
Assuntos
Anestesia , Enflurano/farmacologia , Lidocaína/antagonistas & inibidores , Pentilenotetrazol/antagonistas & inibidores , Animais , Encefalopatias/induzido quimicamente , Gatos , Feminino , Masculino , Convulsões/induzido quimicamenteRESUMO
The interaction of sympathetic blockade and decreased mean arterial pressure on plasma renin activity during surgery was studied in dogs. Plasma renin activity was measured during lumbar laminectomy before and after sympathetic blockade produced by subarachnoid spinal anaesthesia. Plasma renin activity was significantly increased during laminectomy. Twenty minutes after sympathetic blockade there were marked decreases in mean arterial pressure and plasma renin activity; but with mean arterial pressure continuing to decline, plasma renin activity showed moderate increases at 50 minutes after sympathetic blockade. It is concluded that increases in plasma renin activity seen during surgical operations can be attenuated by sympathetic blockade produced by subarachnoid or epidural spinal anaesthesia, although decreases in mean arterial pressure resulting from the sympathetic blockade continue to provide a stimulus for renin secretion.
Assuntos
Bloqueio Nervoso Autônomo , Renina/sangue , Procedimentos Cirúrgicos Operatórios , Sistema Nervoso Simpático/fisiologia , Animais , Pressão Sanguínea , Cães , LaminectomiaRESUMO
We studied the effects of two dosage levels of glucagon infusion on systemic hemodynamic and regional blood flow measurements during experimental cardiogenic shock in monkeys. Cardiogenic shock was induced in monkeys by embolization of coronary arteries with glass microspheres. Glucagon 1 microgram/kg/min was infused in five monkeys and five remaining monkeys received glucagon infusion at 10 micrograms/kg/min. Radioactive microsphere technique was used to measure regional blood flows. During cardiogenic shock, there were significant decreases in heart rate, mean arterial pressure, cardiac output and rate of rise of left ventricular pressure and significant increases in total peripheral resistance. Blood flows to the heart, brain, kidney and splanchnic bed were markedly reduced. Neither dosage level of glucagon produced any significant improvement in systemic hemodynamic or regional blood flow values. Glucagon produced only nonsignificant increases in splanchnic blood flow during cardiogenic shock. These findings suggest that glucagon infusions in dosages of 1 microgram/kg/min and 10 micrograms/kg/min do not improve systemic or regional hemodynamic status in severe cardiogenic shock.
Assuntos
Glucagon/farmacologia , Hemodinâmica/efeitos dos fármacos , Choque Cardiogênico/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Glucagon/administração & dosagem , Haplorrinos , Frequência Cardíaca/efeitos dos fármacos , Fígado/irrigação sanguínea , Macaca mulatta , Fluxo Sanguíneo Regional/efeitos dos fármacos , Resistência VascularRESUMO
In monkeys anesthetized with 70% nitrous oxide and 0.5% inspired halothane in oxygen, we measured changes in systemic hemodynamics and regional blood flows produced by nitroprusside and trimethaphan. Regional blood flow measurements were made using the radioactive microsphere technique. Control measurements were made before infusion of nitroprusside and trimethaphan into each animal in sequence in amounts adequate to reduce mean arterial pressure to approximately 55 +/- 5 mm Hg. Measurements were made during each drug infusion after a stable period of hypotension lasting at least 30 min. During nitroprusside infusion, cerebral blood flow remained unchanged, but myocardial blood flow increased significantly. However, pressure-rate product, an indirect measure of myocardial oxygen consumption, was unchanged, implying that myocardial blood flow exceeded myocardial oxygen requirement. During trimethaphan infusion, cerebral blood flow decreased, although cerebral metabolic rate for oxygen was unchanged due to increased oxygen extraction by the brain. Trimethaphan also produced a decrease in myocardial blood flow that was in proportion to the decrease in myocardial oxygen requirement as indicated by pressure-rate product. Neither drug produced changes in renal or total hepatic blood flows. We conclude that brain oxygen reserve is decreased during hypotension induced by trimethaphan. Blood flows to other organs are not significantly impaired in monkeys during hypotension to a mean arterial pressure of approximately 55 mm Hg induced by either nitroprusside or trimethaphan.