RESUMO
Isoflurane is a halogenated ether which is used for general anesthesia. To stabilize a new formulation in order to evaluate the potential to reduce the dose required for general anesthesia, an isoflurane-loaded nanoemulsion was proposed. A high-pressure homogenization technique was used to develop drug-loaded nanoemulsions which presented droplet size of 150 +/- 0.78 nm with a narrow size distribution and low polydispersity index (0.08 +/- 0.01). The zeta potential was -18 +/- 2.4 mV and pH was 6.03 +/- 0.04. Rheological analysis showed Newtonian behavior for the formulations, whose physical stability was confirmed by multiple light scattering. It was verified that isoflurane volatilization did not occur in these formulations. The preclinical evaluation, carried out via the end-tidal isoflurane concentration, showed that the dose required for anesthetic maintenance significantly decreased when the nanostructured formulation was administered compared to inhaled isoflurane. There was no significant difference (p < 0.05) between experimental groups (inhaled isoflurane and intravenous isoflurane-loaded nanoemulsion) in terms of the cardiac rate, oxygen hemoglobin saturation, and arterial blood pressure, as well as the biomarkers of renal, hepatic and skeletal muscle system functionalities. Slight tachypnea, edema, and erythema were observed after isoflurane-loaded or unloaded-nanoemulsion. The stability and significant dose reduction observed for drug-loaded nanoemulsion render this formulation a promising option for intravenous delivery of isoflurane.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Isoflurano/administração & dosagem , Isoflurano/química , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Taxa Respiratória/efeitos dos fármacos , Anestésicos Gerais/administração & dosagem , Anestésicos Gerais/química , Animais , Cães , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Emulsões/química , Feminino , Masculino , PressãoRESUMO
OBJECTIVE: To evaluate the extent sensory and motor blocks produced by the epidural injection of different volumes of 0.25% bupivacaine (Bu) with methylene blue (MB), in dogs. STUDY DESIGN: Prospective experimental trial. ANIMALS: Twenty healthy adult mongrel dogs, weighing 9.9 +/- 1.9 kg. METHODS: Dogs were randomly allocated into one of four groups that received 0.2, 0.4, 0.6 or 0.8 mL kg(-1) of an epidural solution containing 0.25% Bu and MB. Sensory block was evaluated against time by pinching the tail, hind limb interdigital web, toenail bases and the skin over the vertebral dermatomes. Motor block was assessed by ataxia, hind limb weight-bearing ability and by loss of muscle tone of the tail and pelvic limbs. Data were collected at 2, 5, 10, 15 and 30 minutes after the end of epidural injection. After the final time point, dogs were euthanatized and laminectomies were conducted to expose the extent of the dural dye staining. RESULTS: The volumes 0.2, 0.4, 0.6 and 0.8 mL kg(-1) of 0.25% Bu and MB blocked a mean of 5, 14.2, 20.2 and 21 dermatomes, respectively. The extent of the sensory block increased up to a volume of 0.6 mL kg(-1). Motor block was longer-lasting and more intense than sensory block. Complete dyeing of the spinal cord with MB was achieved in some dogs at 0.4 mL kg(-1) and all dogs at 0.6 mL kg(-1). CONCLUSIONS: The volume of anesthetic injected into the epidural space plays an important role in the quality of the epidural anesthesia. At 0.25%, bupivacaine provided an efficient sensory block at 0.6 mL kg(-1). CLINICAL RELEVANCE: Relatively high volumes (0.6 mL kg(-1)) of 0.25%, BU and MB were needed to produce an effective sensory and motor block caudal to the umbilicus, but all spinal cord segments were reached by MB at this dose.