betadex and alphaxalone

To systematically review the quality of evidence comparing the cardiopulmonary effects and quality of anesthesia after induction with alfaxalone vs. other anesthetic agents in dogs and cats. Studies published from 2001 until 20th May 2013 were identified with the terms 'alfaxan' OR 'alfaxalone' OR 'alphaxalone' in electronic databases: Discovery, PubMed, ScienceDirect, and Wiley Interscience. The study design and risk of bias of all included studies were assessed. Twenty-two studies from 408 (22 of 408, 5.39%) satisfied the inclusion criteria. Fourteen studies (14 of 22, 64%) focused on dogs and nine (9 of 22, 40%) on cats. One study had both dogs and cats as subjects. (Hunt et al., 2013) Twelve studies were rated an LOE1, and six of these as ROB1. One, seven, and two studies were rated as LOE2, LOE3, and LOE5, respectively. In dogs, strong evidence shows that induction quality with either alfaxalone-HPCD or propofol is smooth. Moderate evidence supports this finding in cats. In dogs, moderate evidence shows that there is no significant change in heart rate after induction with either alfaxalone-HPCD or propofol. In cats, moderate evidence shows no significant difference in postinduction respiratory rate and heart rate between alfaxalone-HPCD and propofol induction. Strong evidence shows dogs and cats have smooth recoveries after induction using either alfaxalone-HPCD or propofol, before reaching sternal recumbency.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Anesthesia, Inhalation; Anesthetics; Animals; beta-Cyclodextrins; Cats; Dogs; Heart Rate; Pregnanediones; Respiratory Physiological Phenomena

The objective of this study was to determine the pharmacodynamic effects in sheep of the anaesthetic alfaxalone in a 2-hydroxypropyl-β-cyclodextrin formulation. Seven Ripollesa sheep, weighing 43.0±6.6 kg, were used in the study. Twenty-four hours after instrumentation, the sheep were anesthetised with alfaxalone (2 mg/kg bodyweight IV) in cyclodextrin. Heart rate, arterial blood pressure, respiratory rate and arterial blood gases were recorded. Alfaxalone administration resulted in minimal cardio-respiratory depression. Time to standing from anaesthesia was 22.0±10.6 min. Apnoea was not observed in any of the sheep. Significant differences from baseline were not observed in respiratory rate or arterial blood pressure. Heart rate increased significantly (P<0.05) immediately after administration, returning to control values at 20 min. The calculated haemoglobin saturation (SO2) decreased significantly during the first 15 min after alfaxalone administration. The arterial pH decreased significantly during the first 30 min of the study, although no significant differences from basal values were observed in the arterial partial pressure of carbon dioxide (PaCO2). The results showed that alfaxalone in 2-hydroxypropyl-β-cyclodextrin administered as an IV bolus at 2 mg/kg produced minimal adverse effects and an uneventful recovery from anaesthesia in sheep.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acid-Base Equilibrium; Anesthesia, Intravenous; Anesthetics, Intravenous; Animals; beta-Cyclodextrins; Blood Pressure; Female; Heart Rate; Pregnanediones; Respiratory Rate; Sheep

Alphaxalone is a neuroactive steroid anesthetic that is poorly water soluble. It was formulated in 1972 as Althesin® using Cremophor® EL, a nonionic surfactant additive. The product was a versatile short-acting IV anesthetic used in clinical practice in many countries from 1972 to 1984. It was withdrawn from clinical practice because of hypersensitivity to Cremophor EL. In the investigations reported here, we compared the properties of 3 anesthetics: a new aqueous solution of alphaxalone dissolved in 7-sulfobutyl-ether-β-cyclodextrin (SBECD, a water-soluble molecule with a lipophilic cavity that enables drug solubilization in water); a Cremophor EL preparation of alphaxalone; and propofol.. Two solutions of alphaxalone (10 mg/mL) were prepared: one using 13% w/v solution of SBECD in 0.9% saline (PHAX) and the other a solution of alphaxalone prepared as described in the literature using 20% Cremophor EL (ALTH). A solution of propofol (10 mg/mL; PROP) in 10% v/v soya bean oil emulsion was used as a comparator anesthetic. Jugular IV catheters were implanted in male Wistar rats (180-220 g) under halothane anesthesia. Separate groups of 10 implanted rats each were given IV injections of PHAX, ALTH, or PROP from 1.2 mg/kg to lethal doses. Doses of each drug that caused anesthesia (loss of righting reflex and response to tail pinch) and lethality in 50% of rats were calculated by probit analysis. The drugs were also compared for effects on arterial blood pressure and heart rate.. IV PHAX, ALTH, and PROP caused dose-related sedation and anesthesia, with 50% effective dose (ED50) values for loss of righting reflex being 2.8, 3.0, and 4.6 mg/kg, respectively. PROP led to death in 10 of 10 rats at doses >30 mg/kg (50% lethal dose (LD50) = 27.7 mg/kg). A dose of alphaxalone 53 mg/kg as ALTH caused 10 of 10 rats to die (LD50 = 43.6 mg/kg), whereas none died when given the same doses of alphaxalone formulated in SBECD. PHAX caused 20% lethality at the maximal dose tested of 84 mg/kg. PHAX caused less cardiovascular depression than PROP. Control experiments with the 3 drug-free vehicles showed no effects.. Alphaxalone caused fast-onset anesthesia at the same dose for both formulations (PHAX and ALTH). The use of SBECD as a drug-solubilizing excipient did not alter the anesthetic effect of alphaxalone, but it did increase the therapeutic index of alphaxalone in PHAX compared with ALTH. PHAX has a higher safety margin than the propofol lipid formulation and also the alphaxalone formulation in Cremophor EL (ALTH).

Topics: Anesthetics, Intravenous; Animals; Arterial Pressure; beta-Cyclodextrins; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Excipients; Glycerol; Heart Rate; Lethal Dose 50; Male; Motor Activity; Pain Threshold; Pregnanediones; Propofol; Rats, Wistar; Reflex; Risk Assessment; Sleep; Solubility; Soybean Oil; Time Factors; Water

Topics: Anesthetics, Intravenous; Animals; beta-Cyclodextrins; Excipients; Glycerol; Male; Pregnanediones; Propofol; Water

Topics: Anesthetics, Intravenous; Animals; beta-Cyclodextrins; Excipients; Glycerol; Male; Pregnanediones; Propofol; Water

The objective of this study was to determine the pharmacodynamics effects of the anaesthetic alfaxalone in 2-hydroxypropyl- β -cyclodextrin in pregnant sheep after the intravenous injection of a 2 mg/kg weight dose. Six pregnant Ripollesa sheep, weighing 47.1 ± 4.4 kg, were used. Twenty-four hours after instrumentation, sheep were anaesthetized with intravenous alfaxalone in cyclodextrin. Time to standing from anaesthesia was 30.0 ± 10.81 min. Foetal heart rate increased significantly during the first 5 min after alfaxalone administration. Significant differences were observed in maternal diastolic arterial blood pressure between minute 10 and minutes 90, 120, 150, 180, 210, and 240. Significant differences were observed for foetal systolic arterial blood pressure between 5 and 30 min after alfaxalone administration. Significant differences in foetal pH were detected during the entire study period, whereas maternal pH returned to baseline values by 60 min after alfaxalone administration. The present study indicated that alfaxalone in 2-hydroxypropyl- β -cyclodextrin administered as an intravenous bolus at 2 mg/kg body weight produced minimal adverse effects and an uneventful recovery from anaesthesia in pregnant sheep and their foetus.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acid-Base Equilibrium; Anesthetics, Intravenous; Animals; Arterial Pressure; beta-Cyclodextrins; Blood Pressure; Female; Fetus; Heart Rate, Fetal; Injections, Intravenous; Pregnancy; Pregnanediones; Sheep, Domestic

Alfaxalone in a 2-hydroxypropyl-β-cyclodextrin (HPCD) formulation is an intravenous (IV) hypnotic agent characterised by the stability of cardiorespiratory effects after a single-bolus administration. The objective of this study was to investigate the cardiovascular, respiratory, and acid-base effects of alfaxalone-HPCD administered during a continuous rate infusion in six Ripollesa sheep. After instrumentation, a 2 mg/kg IV bolus of alfaxalone followed by a continuous infusion of 10 mg/kg/h was administered to the sheep. Heart rate, arterial blood pressure, respiratory rate and arterial blood gases were recorded. Occasional side effects and time to standing were also noted. No significant changes were observed in arterial blood pressure, but during the infusion and the initial stages of recovery, a significant increase in heart rate occurred during the last 120 min of the study. Significant respiratory depression was detected during the infusion period and the first 15 min of recovery. This study showed that a constant rate infusion alfaxalone in un-premedicated sheep produced clinically acceptable haemodynamic results and a mild respiratory depression that may require intermittent positive pressure ventilation.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acid-Base Equilibrium; Anesthetics; Animals; beta-Cyclodextrins; Blood Pressure; Carbon Dioxide; Female; Heart Rate; Pregnanediones; Sheep

The objective of this prospective study was to determine the effects of a single intravenous bolus of alfaxalone in 2-hydroxypropyl-β-cyclodextrin and propofol on the intraocular pressure (IOP) in sheep. Ten Ripollesa sheep with a bodyweight of 48.5 (6.8) kg (mean [sd]) were used in the study. Twenty-four hours before the experimental procedure, a complete ophthalmic examination was performed in all animals. The day of the study, intravenous alfaxalone (2 mg/kg) or propofol (6 mg/kg) was randomly administered in a cross-over design, with a washout period of two weeks. Measurements of IOP, globe position and pupil size were obtained at basal time, before induction (time 0) and at two, five, 10, 15, 20, 30, 45, 60, 90 and 120 minutes after drug administration. Occasional side effects and time to standing were also noted. Intravenous administration of alfaxalone and propofol in sheep resulted in no alteration of IOP. Nevertheless, a decrease in the pupil size was observed in both groups. This present study shows that alfaxalone and propofol, administrated as a single intravenous bolus, are good options for maintaining IOP during anaesthesia in sheep, although marked miosis was observed after administration.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Anesthetics, Intravenous; Animals; beta-Cyclodextrins; Cross-Over Studies; Infusions, Intravenous; Intraocular Pressure; Miosis; Pregnanediones; Propofol; Prospective Studies; Pupil; Sheep; Time Factors

To compare the cardiopulmonary effects of continuous rate infusions (CRIs) of alfaxalone-2-hydroxypropyl-beta-cyclodextrin (HPCD) and propofol in healthy dogs.. 6 young adult medium-sized healthy crossbred dogs.. A crossover design was used with a washout period of 6 days between anesthetic treatments. Each dog was sedated with acepromazine (0.02 mg/kg, IV) and hydromorphone (0.05 mg/kg, IV). Anesthesia was induced with propofol (4 mg/kg) or alfaxalone-HPCD (2 mg/kg). After endotracheal intubation, anesthesia was maintained with the same agent (propofol, 0.25 mg/kg/min; alfaxalone-HPCD, 0.07 mg/kg/min) for 120 minutes. Dogs spontaneously breathed 100% oxygen. Measurements included end-tidal partial pressure of carbon dioxide, heart and respiratory rates, mean arterial blood pressure, thermodilution-derived cardiac output, and body temperature. Paired arterial and mixed venous blood samples were collected for determination of blood pH, PaCO(2), and PaO(2). Data were recorded prior to induction; 5, 15, 30, 60, 90, and 120 minutes after induction of anesthesia; and 20 minutes after stopping the CRI, when feasible. Stroke volume and systemic vascular resistance were calculated. Quality of anesthetic induction and recovery and interval to recovery were recorded.. Both propofol and alfaxalone-HPCD produced excellent induction of anesthesia, maintenance, and recovery. Respiratory depression was evident with both anesthetics. Clinically acceptable, mild hemodynamic changes were similar for both anesthetics.. Alfaxalone-HPCD produced clinically acceptable anesthetic quality and hemodynamic values ideal for use as a CRI. Ventilation may need to be supported if hydromorphone is used at these propofol and alfaxalone-HPCD infusion rates.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Anesthetics, Intravenous; Animals; beta-Cyclodextrins; Blood Pressure; Body Temperature; Cardiac Output; Cross-Over Studies; Dogs; Heart Rate; Infusions, Intravenous; Pregnanediones; Propofol; Stroke Volume; Time Factors; Vascular Resistance