RESUMEN
BACKGROUND: Pregabalin, an antiepileptic and chronic pain medication, has been used by various authors for preoperative analgesia. We have assessed the effect of pre-emptive administration of the drug to patients scheduled for elective abdominal hysterectomy. METHODS: Seventy-four ASA I and II patients were included in this prospective, double blind study. They were randomised to receive 75, 150, or 300 mg of pregabalin, or 7.5 mg of midazolam as a placebo, one hour before anaesthesia and surgery. Anaesthesia was induced with propofol and maintained with sevoflurane or desflurane. Fentanyl was used for analgesia and rocuronium for muscle relaxation. Immediately after surgery, patients received morphine intravenously in 2 mg increments until the NRS score was below 3. This was then followed by PCA. RESULTS: Morphine consumption and pain scores were only significantly lower in the 300 mg pregabalin group, when compared to the placebo and other treatment groups; there were no differences between placebos and lower doses of pregabalin. CONCLUSION: We conclude that pre-emptive administration of 300 mg pregabalin reduces postoperative pain and morphine consumption. Further studies on higher doses would appear to be justified.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Analgésicos/uso terapéutico , Morfina/uso terapéutico , Dolor Postoperatorio/prevención & control , Medicación Preanestésica , Premedicación , Ácido gamma-Aminobutírico/análogos & derivados , Método Doble Ciego , Femenino , Humanos , Histerectomía , Dimensión del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Pregabalina , Estudios Prospectivos , Resultado del Tratamiento , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Morphine is the first choice of treatment of severe post-operative pain, despite the occurrence of often discomforting (post-operative nausea or vomiting (PONV)) and sometimes dangerous (sedation, respiratory depression) side effects. Literature data indicate that morphine's active metabolite, morphine-6-glucuronide (M6G), is a powerful analgesic with a possibly more favourable side-effect profile. In this multi-centre randomised controlled clinical trial patients undergoing major abdominal surgery were randomised to M6G or morphine treatment. Treatment started 30-60 min prior to the end of surgery and was continued postoperatively, after patients were titrated to comfort, via patient-controlled analgesia (PCA) for 24-48 h. Pain intensity, nausea, vomiting and sedation scores were collected at regular intervals. In the study 268 patients were randomised to M6G and 249 to morphine. Withdrawal due to insufficient pain relief occurred predominantly just after surgery and was higher in the M6G group (16.8%) than in the morphine group (8.8%), suggesting a slower onset of analgesia for M6G compared to morphine. Subjects who continued on PCA remained equi-analgesic throughout the study. During the first 24h, nausea levels showed a 27% difference in favour of M6G which narrowly failed to reach statistical significance (P=0.052). Sub-analysis showed a significant reduction in nausea levels in females on M6G (30% difference, P=0.034). In all patients, similar reductions of 30-35% were observed in anti-emetic use, vomiting, PONV (a combined measure of nausea and vomiting) in favour of M6G, persisting for the first 24h postoperatively. Reductions in sedation were observed in the first 4h post-operative period for M6G patients.
Asunto(s)
Abdomen/cirugía , Analgésicos Opioides/uso terapéutico , Derivados de la Morfina/uso terapéutico , Morfina/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Náusea y Vómito Posoperatorios/epidemiología , Procedimientos Quirúrgicos Operativos , Adulto , Anciano , Analgésicos Opioides/efectos adversos , Anestesia , Área Bajo la Curva , Interpretación Estadística de Datos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derivados de la Morfina/efectos adversos , Dimensión del Dolor/efectos de los fármacos , Fases del Sueño/efectos de los fármacos , Resultado del TratamientoRESUMEN
This study was aimed at determining the analgesic effect of gabapentin and tiagabine, two antiepileptic drugs that were administered alone and in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice. Linear regression analysis was used to evaluate the dose-response relationships between logarithms of antiepileptic drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, we calculated doses that increased the antinociceptive effect by 50% (ED(50) values) for gabapentin, tiagabine and their combination. The type of interaction between gabapentin and tiagabine was assessed using the isobolographic analysis. Results indicated that both antiepileptic drugs produced the definite antinociceptive effect, and the experimentally derived ED(50) values for gabapentin and tiagabine, when applied alone, were 504.4 mg/kg and 5.67 mg/kg, respectively. With isobolography, the experimentally derived ED(50 mix) value for the fixed ratio combination of 1:1 was 139.31 mg/kg and significantly differed from the theoretically calculated ED(50 add) value, which was 255.04 mg/kg (p < 0.05), indicating the synergistic interaction between gabapentin and tiagabine in the hot-plate test in mice. In conclusion, the combination of tiagabine with gabapentin at a fixed ratio of 1:1 exerted a synergistic interaction in the mouse model of nociceptive pain. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial for pain relief in humans.
Asunto(s)
Aminas/farmacología , Anticonvulsivantes/farmacología , Ácidos Ciclohexanocarboxílicos/farmacología , Ácidos Nipecóticos/farmacología , Dimensión del Dolor/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacología , Aminas/administración & dosificación , Animales , Anticonvulsivantes/administración & dosificación , Ácidos Ciclohexanocarboxílicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Gabapentina , Masculino , Ratones , Modelos Estadísticos , Ácidos Nipecóticos/administración & dosificación , Tiagabina , Ácido gamma-Aminobutírico/administración & dosificaciónRESUMEN
The aim of this study was to determine the analgesic effect of gabapentin and tiagabine - two antiepileptic drugs, administered alone and in combination at the fixed-ratio of 1:1, in two phases of the formalin test in mice. Log-probit analysis was used to evaluate dose-response effects and calculate the ED(50) values for gabapentin, tiagabine, and their combination at the fixed-ratio of 1:1 in the phases I and II of the formalin test in mice. The types of interactions between both antiepileptic drugs were characterized using the isobolographic analysis. Results indicated that gabapentin and tiagabine produced the antinociceptive effect in both phases of the formalin test. The ED(50) values for gabapentin and tiagabine, administered singly, in the phase I of the formalin test were 29.59 and 2mg/kg, whereas in the phase II of the formalin test were 8.22 and 0.50 mg/kg, respectively. With isobolography, the ED(50 mix) values at the fixed-ratio combination of 1:1 were 7.30 mg/kg (phase I) and 0.48 mg/kg (phase II), indicating both additive and supra-additive (synergistic) interactions between gabapentin and tiagabine in the formalin test in mice. In conclusion, the combination of gabapentin with tiagabine at the fixed-ratio of 1:1 exerted additive interaction in the phase I and synergistic interaction in the phase II of the formalin test in mice. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial in the pain relief in humans.
Asunto(s)
Aminas/farmacología , Analgésicos/farmacología , Ácidos Ciclohexanocarboxílicos/farmacología , Formaldehído , Agonistas del GABA/farmacología , Ácidos Nipecóticos/farmacología , Dimensión del Dolor/efectos de los fármacos , Ácido gamma-Aminobutírico/farmacología , Animales , Relación Dosis-Respuesta a Droga , Gabapentina , Masculino , Ratones , Desempeño Psicomotor/efectos de los fármacos , TiagabinaRESUMEN
BACKGROUND: Gynaecological laparoscopic (GL) surgery can be prolonged and may be associated with significant cardiovascular compromise. Recent experimental studies suggest that prolonged pneumoperitoneum can cause cardiac depression and a decrease in cardiac index. The goal of the study was to compare haemodynamics before and after CO2 desufflation, performed at the end of surgery. METHODS: This study included ASA I and II women undergoing GL under general anaesthesia. After induction, an oesophageal Doppler device (TED) probe (Arrow HemoSonic 100) was inserted and the following values were recorded every 5 min: aortic blood flow (ABF), total systemic vascular resistance (TSVRa), mean acceleration (Acc), peak velocity (PV) heart rate (HR) and mean arterial pressure (MAP). RESULTS: Fifty-seven patients were enrolled in the study. MAP and TSVRa increased after CO2 insufflation, and decreased at the end of GL in all groups. TSVRa significantly increased at the end of GL, before CO2 desufflation in all procedures lasting more that 60 min, when compared to those lasting less than 60 min. A significant decrease in ABF was observed before desufflation in GL lasting more than 60 min vs. those lasting less than 30 min. CO2 desufflation was associated with an increase in ABF in all groups. Contractility (Acc, PV) significantly decreased during surgery and increased after desufflation in operations lasting 30-60 min or those lasting more than 60 min, compared to short procedures (<30 min). DISCUSSION AND CONCLUSION: Prolonged pneumoperitoneum caused significant, time-dependent compromise of aortic blood flow and heart contractility. Changes were directly related to increased abdominal pressure and increased with prolonged surgery. This may be of special importance in patients with cardiovascular diseases.
Asunto(s)
Enfermedades Cardiovasculares/fisiopatología , Enfermedades de los Genitales Femeninos/fisiopatología , Enfermedades de los Genitales Femeninos/cirugía , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Hemodinámica , Laparoscopía/efectos adversos , Neumoperitoneo Artificial/efectos adversos , Adulto , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Femenino , Enfermedades de los Genitales Femeninos/epidemiología , Humanos , Contracción MiocárdicaRESUMEN
Anesthetics depress the autonomic nervous system. The effects of thiopental and propofol on heart rate variability (HRV) during fentanyl-based induction of general anesthesia were studied in one hundred patients. We observed different effects of fentanyl, thiopental and propofol on HRV. Fentanyl decreased total power of HRV and low frequency power (LF), but not high frequency power (HF), indicating a greater reduction of cardiac sympathetic activity. Thiopental and propofol caused the further reduction of HRV and decreased HF power. Thiopental increased LF power and LF/HF ratio, indicating that the vagolytic effect is associated with the increase in sympathetic activity. Propofol preserved the LF power, indicating that the cardiac parasympathetic activity is reduced more than the sympathetic activity.
Asunto(s)
Anestesia General , Anestésicos Intravenosos/farmacología , Fentanilo , Frecuencia Cardíaca/efectos de los fármacos , Propofol/farmacología , Tiopental/farmacología , Adulto , Femenino , Humanos , MasculinoRESUMEN
Topiramate, unlike gabapentin, lamotrigine and tiagabine, resembles phenytoin and carbamazepine since it had been used as an antinociceptive drug in empirical treatment of neuropathic pain in humans, before its systemic and planned research was conducted in animal models of pain. Chronic administration of topiramate, at the dose of 50 mg/kg/day, significantly diminished the mechanical sensitivity and shortened the period of allodynia in the Seltzer mononeuropathy model in rats.
Asunto(s)
Modelos Animales de Enfermedad , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Dolor/tratamiento farmacológico , Neuropatía Ciática/tratamiento farmacológico , Animales , Masculino , Ratas , Ratas Wistar , TopiramatoRESUMEN
BACKGROUND: Postoperative bleeding may be complicated by failure to identify the site of bleeding, multiple bleeding points, and persistent hemorrhage despite surgical intervention. CASE: Activated recombinant factor VII was used successfully in a patient with life-threatening postsurgical bleeding after resection of two large extraperitoneal pelvic sarcomas. CONCLUSION: In severe hemorrhage, hemostasis can be achieved with activated recombinant factor VII.
Asunto(s)
Factor VIIa/uso terapéutico , Hemorragia Posoperatoria/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Pélvicas/cirugía , Proteínas Recombinantes/uso terapéutico , Sarcoma/cirugíaRESUMEN
Gabapentin and baclofen at doses not affecting motor performance, produced dose-dependent inhibition of both phases in the formalin test in mice. Isobolographic analysis revealed an additive interaction between the studied drugs in the second phase of the formalin test. Gabapentin given at doses effective in both phases of the formalin test significantly potentiated baclofen-induced motor impairment.