RESUMO
BACKGROUND AND OBJECTIVE: Postoperative nausea and vomiting (PONV) is a frequent and unpleasant experience that may increase postoperative complications and costs. For surgical procedures with a high risk of PONV, prevention is preferable to treatment. In this study, the authors explore the dose-response relationship between granisetron administered just prior to the end of surgery and post-operative nausea and vomiting in patients undergoing abdominal hysterectomy. METHODS: This was a randomized, double-blind, placebo-controlled, pilot study of post-operative nausea and vomiting prevention. Patients undergoing elective open abdominal hysterectomy requiring general anaesthesia received a single dose of granisetron 0.1, 0.2 or 0.3 mg or placebo administered approximately 15 min prior to the end of surgery. The primary efficacy end-point was the proportion of patients with no vomiting in the 0--6 h interval following medication administration. No inferential statistics were planned. RESULTS: The proportion of patients with no vomiting episode in the 0--6 h interval after administration of study medication was higher in each granisetron treatment group (>90%) than in the placebo group (77%). Proportions of patients with no vomiting episodes in the 0--24 h interval were similar across treatment groups. Results of analyses of proportions of patients with no moderate or severe nausea episodes, proportions of those requiring rescue medication and times to first use of rescue medication suggested a treatment effect of granisetron relative to placebo in both the 0--6 and 0--24 h intervals. Similar proportions of patients in each treatment group reported at least one adverse event. CONCLUSIONS: Granisetron at doses of 0.1, 0.2 and 0.3 mg administered just prior to the end of surgery suggested a trend of improved efficacy compared to placebo in preventing postoperative nausea and vomiting in the first 6 h after abdominal hysterectomy. This pilot study did not identify a dose-response relationship.
Assuntos
Antieméticos/uso terapêutico , Granisetron/uso terapêutico , Histerectomia , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Adulto , Antieméticos/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Granisetron/administração & dosagem , Humanos , Injeções Intravenosas , Pessoa de Meia-Idade , Projetos PilotoRESUMO
OBJECTIVE: We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass. METHODS: Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated. RESULTS: In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%). CONCLUSIONS: In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion.
Assuntos
Aprotinina/efeitos adversos , Ponte de Artéria Coronária , Oclusão de Enxerto Vascular/induzido quimicamente , Hemostáticos/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Aprotinina/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Ponte Cardiopulmonar , Feminino , Oclusão de Enxerto Vascular/mortalidade , Hemostáticos/administração & dosagem , Heparina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Fatores de Risco , Taxa de Sobrevida , Veias/transplanteRESUMO
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
There are well-recognized adverse interactions between the monoamine oxidase inhibitors and anesthetic drugs, particularly narcotics. Patients having cardiopulmonary bypass procedures are commonly anesthetized using high-dose narcotic techniques. We describe an uneventful perioperative course in a parkinsonian patient who required urgent coronary artery bypass graft surgery while he was taking selegiline, a selective inhibitor of monoamine oxidase type B.
Assuntos
Anestésicos Gerais/efeitos adversos , Ponte de Artéria Coronária , Hemodinâmica/efeitos dos fármacos , Inibidores da Monoaminoxidase/efeitos adversos , Entorpecentes/efeitos adversos , Selegilina/efeitos adversos , Idoso , Antiparkinsonianos/efeitos adversos , Interações Medicamentosas , Humanos , Masculino , Doença de Parkinson/tratamento farmacológicoRESUMO
During the past decade a new syndrome has been recognized: cerebral hypoxia secondary to cardiopulmonary bypass, resulting in impairment of cognitive memory. The incidence of the syndrome appears to be no less that 30% in patients over 65 years of age undergoing cardiac surgery. There are several factors contributing to hypoxia produced by cardiopulmonary bypass. One of these factors is crystalloid pump prime and replacement solutions devoid of (1) oxygen carrying capacity and (2) devoid of protein and its colloid osmotic pressure. This shortcoming of cardiopulmonary crystalloid solutions is partially responsible for two of the three major pathologic effects of cardiopulmonary bypass: (1) hypoxia (2) interstitial fluid accumulation (anasarca, water-logging, edema). This report describes an oxygen carrying hyperosmolar solution which enhances brain p0(2) and diminishes interstitial fluid accumulation. This blood substitute consists of perfluorcarbons and saccharides, but could consist of a hemoglobin variant plus hyperosmolar ingredients other than saccharides. The advantage of a perfluorochemical is its ability to access small channels and to be centrifuged off the patient post-operatively with a cell saver. The advantage of saccharides is that they can be metabolized by the patient for energy, and they produce a moderate diuresis coming off bypass.
Assuntos
Encéfalo/irrigação sanguínea , Ponte Cardiopulmonar/métodos , Fluorocarbonos/farmacologia , Hipóxia Encefálica/prevenção & controle , Oxigênio/sangue , Animais , Gasometria , Substitutos Sanguíneos/farmacologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Ponte Cardiopulmonar/efeitos adversos , Relação Dose-Resposta a Droga , Cabras , Hipóxia Encefálica/etiologia , Concentração Osmolar , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
Eleven goats (mean weight, 69 +/- 16 kg) underwent 5 hrs of normothermic nonpulsatile cardiopulmonary bypass (CPB) using as priming fluid either a Ringer's based crystalloid priming solution (CP, n = 5) of a hyperosmolar oxyreplete hemosubstitute (HS, n = 6). The HS contained 20% w/v perfluorocarbon (perfluorodecalin), its osmolarity was 800-900 mOsm/1, and the administered dose of perfluorocarbon was 30-50 ml/kg. Otherwise, the experimental procedure was identical for both groups. PaCO2 was maintained above 35 mmHg and blood flow rate at 65 ml/kg. Brain tissue pH, PO2, and PCO2, cerebral blood flow (CBF), arterial and venous blood gases, and other systemic variables were monitored. During CPB, PVO2 and brain tissue PO2 were increased significantly in the HS group. The CBF per kilogram of weight also was significantly higher in the HS group. Metabolic acidosis developed in both groups and, surprisingly, brain tissue pH and pHV were lower in the HS group. The mean values of PVCO2 and brain tissue PCO2 indicate that brain tissue hypercapnia also occurred in both groups. The HS provided long-term stability and compatibility with electrolytes, and did not cause major complications or allergic reactions during CPB. Perfluorocarbon based HSs improve tissue oxygenation, eliminate the risk of infection due to homologous transfusions, do not require blood type matching, have a shelf life longer than that of blood, and, therefore, they can be an important factor in diminishing the incidence of complications after CPB.
Assuntos
Substitutos Sanguíneos/farmacologia , Encéfalo/metabolismo , Dióxido de Carbono/sangue , Ponte Cardiopulmonar , Circulação Cerebrovascular/efeitos dos fármacos , Fluorocarbonos/farmacologia , Oxigênio/sangue , Animais , Cabras , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting, but the safety and effectiveness of smaller doses is unclear. Furthermore, patient selection criteria for optimal use of the drug are not well defined. METHODS: Seven hundred and four first-time coronary artery bypass grafting patients were randomized to receive one of three doses of aprotinin (high, low, and pump-prime-only) or placebo. The patients were stratified as to risk of excessive bleeding. RESULTS: All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements. Consistent efficacy was not, however, demonstrated in the subgroup of patients at low risk for bleeding. There were no differences in mortality or the incidences of renal failure, strokes, or definite myocardial infarctions between the groups, although the pump-prime-only dose was associated with a small increase in definite, probable, or possible myocardial infarctions (p = 0.045). CONCLUSIONS: Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens. Although safe, aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding. The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infarctions.
Assuntos
Aprotinina/administração & dosagem , Ponte de Artéria Coronária , Hemostáticos/administração & dosagem , Idoso , Aprotinina/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Método Duplo-Cego , Feminino , Hemostáticos/efeitos adversos , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Fatores de RiscoAssuntos
Raquianestesia/efeitos adversos , Anestésicos Locais/efeitos adversos , Lidocaína/efeitos adversos , Anestésicos Locais/administração & dosagem , Fatores de Confusão Epidemiológicos , Humanos , Incidência , Lidocaína/administração & dosagem , Exame Neurológico , Postura , Pressão , Estudos Prospectivos , Transtornos de Sensação/etiologia , Procedimentos Cirúrgicos OperatóriosRESUMO
BACKGROUND: Protamine sulfate reversal of heparin anticoagulation may be associated with adverse cardiovascular side effects. The purpose of this study was to determine whether diminished systemic oxygen consumption and hemodynamic changes were more likely to accompany rapid versus slow protamine administration. METHODS: Fifteen patients undergoing abdominal aortic aneurysm resection in a prospective randomized double-blinded study received intravenous protamine (1.5 mg/kg) rapidly during a 3-minute period (group I, n = 7) or slowly during a 15-minute period (group II, n = 8). Systemic oxygen consumption (VO2) and hemodynamic parameters were assessed for up to 20 minutes after protamine administration began. RESULTS: Blood pressure declines (millimeters of mercury) were greatest in group I with rapid protamine administration (-19 systolic and -9 diastolic) compared with group II with slow protamine administration (-12 systolic and -1 diastolic). Heart rate fell markedly in both groups I and II. Cardiac output (CO) declined in group I at virtually all time periods. Similar CO declines in group II occurred 10 minutes after protamine infusion had begun and persisted for 3 minutes after protamine administration was complete. Maximum VO2 decreases were -16% (60 seconds into protamine infusion) and -13% (1.5 minutes after protamine infusion) in groups I and II, respectively, with statistically significant declines (p < 0.05) occurring only in group I compared with baseline values. Statistically significant differences (p < 0.01), however, were found when mean declines during and after protamine infusion were compared with controls for both CO and VO2 in both groups. CONCLUSIONS: Significant declines in systemic VO2 and hemodynamic perturbations accompany protamine reversal of heparin anticoagulation during aortic surgery. Rapid protamine administration increases the magnitude of these adverse responses.
Assuntos
Anticoagulantes/antagonistas & inibidores , Aneurisma da Aorta Abdominal/cirurgia , Hemodinâmica/efeitos dos fármacos , Antagonistas de Heparina/uso terapêutico , Heparina/uso terapêutico , Protaminas/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Heparina/efeitos adversos , Antagonistas de Heparina/administração & dosagem , Antagonistas de Heparina/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Estudos Prospectivos , Protaminas/administração & dosagem , Protaminas/efeitos adversos , Fatores de TempoRESUMO
This study compares effects of equipotent concentrations of halothane, enflurane, and isoflurane on atrioventricular (AV) function in dogs. Enflurane anesthesia was associated with more AV nodal depression, only at faster heart rates than either halothane or isoflurane. These rate-related effects are important in the genesis of supraventricular reentrant tachyarrhythmias. Subsidiary pacemaker function exhibited marked variability between and within animals with no demonstrable difference between anesthetic drugs. Enflurane has more depressant effects on AV nodal recovery properties than halothane or isoflurane; however, there were no differences demonstrated on slow AV nodal conduction. This suggests that enflurane would be the most effective volatile anesthetic in converting or slowing supraventricular tachyarrhythmias, while carrying no more risk of causing advanced heart block.
Assuntos
Nó Atrioventricular/efeitos dos fármacos , Enflurano/farmacologia , Halotano/farmacologia , Isoflurano/farmacologia , Marca-Passo Artificial , Animais , Nó Atrioventricular/fisiologia , CãesRESUMO
Previously we have described impaired myocardial conduction in patients receiving diltiazem and enflurane. The present study examines the possible mechanism(s) which may account for our clinical observation and presents methods of reversing adverse interactions. Nineteen mongrel dogs were randomized into two exposure groups: enflurane or chloralose anesthesia. Stepwise increasing doses of diltiazem were administered until predetermined endpoints were reached. Sinus and atrioventricular (AV) node function was assessed at all levels of diltiazem infusions, and after reversal drugs. Depression of AV nodal conduction and refractoriness after diltiazem administration was greater during enflurane anesthesia when compared with chloralose. There was severe sinus node dysfunction in enflurane-anesthetized animals. These effects were only reversed by isoproterenol. Patients may be at increased risk for severe sinus node depression when diltiazem is administered during enflurane anesthesia. This is due to a potent interaction between diltiazem and enflurane on the sinoatrial node.
Assuntos
Anestesia por Inalação , Nó Atrioventricular/efeitos dos fármacos , Cloralose/farmacologia , Diltiazem/farmacologia , Enflurano/farmacologia , Nó Sinoatrial/efeitos dos fármacos , Anestesia Intravenosa , Animais , Nó Atrioventricular/fisiologia , Depressão Química , Cães , Sinergismo Farmacológico , Eletrocardiografia/efeitos dos fármacos , Eletrofisiologia , Distribuição Aleatória , Nó Sinoatrial/fisiologiaAssuntos
Angioplastia Coronária com Balão/efeitos adversos , Arritmias Cardíacas/etiologia , Complicações Intraoperatórias/etiologia , Idoso , Anestesia Geral , Angioplastia Coronária com Balão/instrumentação , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Ponte de Artéria Coronária , Desenho de Equipamento , Feminino , Humanos , Complicações Intraoperatórias/fisiopatologia , Complicações Intraoperatórias/terapiaRESUMO
In 1990, the NIH formally recognized the need for investigation of the problem of damaging the effects of cardiopulmonary bypass, issuing RFA HL-90-12-H, which emphasized production of neurologic defects in the very young and the elderly. The authors were at that time involved in comparison of pulsatile flow to steady flow cardiopulmonary bypass in large ungulates. The world literature recognizes five damaging effects of steady flow cardiopulmonary bypass that can be mitigated by pulsatile flow: metabolic acidosis, interstitial fluid accumulation, elevated systemic vascular resistance, arteriovenous shunting, and impaired brain oxygenation. To maximize the beneficial effect of pulsatile flow, however, it is necessary that its morphology be physiologic. It has been stated in the past that this goal may not be possible using standard size aortic cannulas. The purpose of this publication is to describe a method by which this feat has been achieved in 150 pound ungulates undergoing prolonged cardiopulmonary bypass.
Assuntos
Cateterismo Cardíaco/instrumentação , Ponte Cardiopulmonar/instrumentação , Animais , Ponte Cardiopulmonar/efeitos adversos , Estudos de Avaliação como Assunto , Feminino , Cabras , Hemodinâmica/fisiologia , Fluxo Pulsátil/fisiologia , Traumatismos do Sistema NervosoRESUMO
Protamine reversal of heparin anticoagulation is associated with adverse hemodynamic effects that may be attenuated with protamine pretreatment (PP). This study assesses the role of complement activation during these phenomena in adult cardiac surgery patients. Sixteen individuals undergoing cardiopulmonary bypass were given intravenous normal saline or protamine (2 mg/kg) as a randomized pretreatment prior to undergoing heparin anticoagulation (400 IU/kg), coronary artery revascularization, and subsequent reversal of the anticoagulated state with protamine (4 mg/kg). Blood pressure, pulmonary artery diastolic pressure (PAD), heart rate, and cardiac output (CO) were measured during and after pretreatment, prior to heparin reversal by protamine, and for 10 min after reversal. Total hemolytic complement (CH50), C3 conversion to C3b, C3a/C5a, platelet count, and white blood cell count (WBC) were also measured at the same time periods. No significant correlation existed between complement activation and hemodynamic events, as might have been evident by decreased CH50, increased C3 conversion to C3b, or elevations in C3a/C5a levels. PP significantly prevented the CO decrease occurring at 1 and 3 min following heparin reversal by protamine (-0.8 and -1.4 liters/min vs 0.1 and -0.2 liters/min, P less than 0.05 and P less than 0.01, respectively). Reversal hypotension was less with PP, although PAD fell equally in both groups. WBC decreases after heparin reversal were less after PP (-25% vs -7%, P = 0.06). These data support the conclusion that, contrary to earlier reports, adverse hemodynamic and hematologic responses accompanying protamine reversal of heparin anticoagulation do not appear to be correlated with activation of complement. In fact, those patients having the greatest C3a generation exhibited the least hemodynamic changes.
Assuntos
Anticoagulantes/antagonistas & inibidores , Proteínas do Sistema Complemento/fisiologia , Antagonistas de Heparina/farmacologia , Protaminas/farmacologia , Adulto , Idoso , Débito Cardíaco/efeitos dos fármacos , Ponte Cardiopulmonar , Ativação do Complemento , Complemento C3/metabolismo , Complemento C3b/metabolismo , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The hemodynamic consequences and myocardial blood flow alterations associated with cross-clamping of the thoracic aorta were studied during pentobarbital (control), halothane (1 MAC), and isoflurane (1 MAC) anesthesia in dogs with a critical stenosis of the left circumflex coronary artery. Aortic clamping at the level of the diaphragm resulted in significant and equivalent increases in mean aortic pressure and left atrial pressure during the control clamp, halothane clamp, and isoflurane clamp periods. Likewise, aortic clamping resulted in a significant and equivalent decrease in cardiac output during control-clamp, halothane clamp, and isoflurane clamp. Myocardial contractility as assessed by dP/dt was depressed during halothane and isoflurane anesthesia when compared with control, but no further change in contractility was associated with aortic clamping. No significant alterations in regional or transmural myocardial blood flow were found with halothane or isoflurane anesthesia, or with aortic clamping during halothane or isoflurane anesthesia. It is concluded that there are significant hemodynamic consequences associated with aortic clamping, that neither halothane nor isoflurane anesthesia alters these consequences when compared with pentobarbital anesthesia alone, and that the deterioration in myocardial function observed during aortic clamping with halothane and isoflurane anesthesia cannot be attributed to any maldistribution of myocardial blood flow.