The minimum infusion rate of alfaxalone during its co-administration with lidocaine at three different doses by constant rate infusion in goats

OBJECTIVE : To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement in response to standardized stimulation while co-administered with lidocaine at three different doses by constant infusion rate infusion (CRI) in goats. STUDY DESIGN : Prospective, blinded, randomized crossover, experimental. ANIMALS : A total of eight healthy goats: four does and four wethers. METHODS: Anaesthetic induction was with lidocaine at 1 mg kg−1 [low dose of lidocaine (L-Lid)], 2 mg kg−1 [moderate dose (M-Lid)] or 4 mg kg−1 [high dose (H-Lid)] and alfaxalone at 2 mg kg−1. Anaesthetic maintenance was with alfaxalone initially at 9.6 mg kg−1 hour−1 combined with one of three lidocaine treatments: 3 mg kg−1 hour−1 (L-Lid), 6 mg kg−1 hour−1 (M-Lid) or 12 mg kg−1 hour−1 (H-Lid). The MIR of alfaxalone was determined by testing for responses to a stimulation in the form of clamping on a digit with a Vulsellum forceps every 30 minutes during lidocaine CRI. Basic cardiopulmonary parameters were measured. RESULTS : The alfaxalone MIRs were 8.64 (6.72–10.56), 6.72 (6.72–8.64) and 6.72 (6.72–6.72) mg kg−1 hour−1 during L-Lid, M-Lid and H-Lid, respectively, without any significant differences among treatments. Compared to the initial rate of 9.6 mg kg−1 hour−1, these reductions in MIR are equivalent to 10, 30 and 30%, respectively. Significant increases in heart rate (HR) and arterial carbon dioxide partial pressure (PaCO2) and decreases in arterial haemoglobin saturation (SaO2), arterial oxygen partial pressure (PaO2) and respiratory frequency (fR) immediately after induction were observed during all lidocaine treatments. CONCLUSIONS AND CLINICAL RELEVANCE : Lidocaine reduces the alfaxalone MIR by up to 30% with a tendency towards a plateauing in this effect at high CRIs. Immediate oxygen supplementation might be required to prevent hypoxaemia.The Beit Trust and National Research Foundation of South Africa.https://www.journals.elsevier.com/veterinary-anaesthesia-and-analgesia2019-05-01hj2018Companion Animal Clinical StudiesSchool of Health Systems and Public Health (SHSPH

The effects of midazolam and butorphanol, administered alone or combined, on the dose and quality of anaesthetic induction with alfaxalone in goats

Goats are rarely anaesthetised; consequently, scant information is available on the efficacy of anaesthetic drugs in this species. Alfaxalone is a relatively new anaesthetic agent, of which the efficacy in goats has not yet been studied. In this study, the sedative and alfaxalonesparing effects of midazolam and butorphanol, administered alone or concomitantly, in goats were assessed. Eight clinically healthy goats, four does and four wethers, were enlisted in a randomised crossover manner to receive intramuscular sedative treatments consisting of saline 0.05 mL/kg, or midazolam 0.30 mg/kg, or butorphanol 0.10 mg/kg, or a combination of midazolam 0.30 mg/kg with butorphanol 0.10 mg/kg before intravenous induction of general anaesthesia with alfaxalone. Following induction, the goats were immediately intubated and the quality of anaesthesia and basic physiological cardiorespiratory and blood-gas parameters were assessed until the goats had recovered from anaesthesia. The degree of sedation, quality of induction and recovery were scored. When compared with saline (3.00 mg/kg), midazolam, administered alone or with butorphanol, caused a statistically significant increased level of sedation and a reduction in the amount of alfaxalone required for induction (2.00 mg/kg and 1.70 mg/kg, respectively). Butorphanol alone (2.30 mg/kg) did not cause significant changes in level of sedation or alfaxalone-induction dose. During induction and recovery, the goats were calm following all treatments, including the control group. Cardiorespiratory and bloodgas parameters were maintained within clinically acceptable limits. The present study showed that midazolam, administered alone or combined with butorphanol, produces a degree of sedation that significantly reduces the dose of alfaxalone required for induction of general anaesthesia in goats, without causing any major adverse cardiorespiratory effects.The University of Pretoria and the Beit Trust.http://www.jsava.co.zaam201

Determination of the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to a standardised noxious stimulus in goats

OBJECTIVE : To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to noxious stimulation. STUDY DESIGN : Prospective, experimental.Animals Eight healthy goats; four does and four wethers. METHODS : Anaesthesia was induced with alfaxalone 3 mg kg 1 intravenously (IV). A continuous IV infusion of alfaxalone, initially at 0.2 mg kg 1 minute 1, was initiated. Following endotracheal intubation the goats breathed spontaneously via a circle breathing circuit delivering supplementary oxygen.The initial infusion rate was maintained for 30 minutes before testing for responses. The stimulus was clamping on the proximal (soft) part of one digit of the hoof with Vulsellum forceps for 60 seconds. In the absence or presence of purposeful movement of the extremities, the infusion ratewasreduced or increased by 0.02 mg kg 1 minute 1 and held constant for 30 minutes before claw-clamping again. Alfaxalone MIR was calculated as the mean of the infusion rates that allowed and abolished movement. Cardiorespiratory parameters were measured. Recovery from general anaesthesia was timed and quality scored. Results are presented as median (range). RESULTS : The MIR of alfaxalone was 0.16 (0.14– 0.18) mg kg 1 minute 1 or 9.6 (8.4–10.8) mg kg 1 hour 1. Induction of and recovery from anaesthesia were excitement-free. Cardio-respiratory changes were minimal, although compared to baseline HR increased, and at 2 minutes postinduction,(prior to oxygen supplementation), PaO2 decreased significantly from 84 (80–88) to 70 (51– 72) mmHg [11.2 (10.7–11.7) to 9.3 (6.8–9.6) kPa]. Sporadic muscle twitches, unrelated to depth of anaesthesia, were observed during the period of general anaesthesia. Time (minutes) to sternal recumbency and standing were 4.0 (3.0–10.0) and 41.5 (25.0–57.0) respectively. CONCLUSIONS AND CLINICAL RELEVANCE : Alfaxalone can be used for total intravenous anaesthesia (TIVA) in goats and is associated with minimal adverse effects. Oxygen supplementation is advised, especially when working at higher altitudes.Jointly funded by the National Research Foundation (NRF), the Beit Trust and the University of Pretoria.http://onlinelibrary.wiley.comjournal/10.1111/(ISSN)1467-29952016-01-31hb201

Antinociceptive effects of epidural magnesium sulphate alone and in combination with morphine in dogs

OBJECTIVE : To compare the antinociceptive effects of magnesium sulphate (MgSO4) when administered epidurally alone and in combination with morphine. STUDY DESIGN : Experimental, randomized, ‘blinded’, crossover study. ANIMALS : Six healthy adult Beagle dogs. METHODS : Evaluated treatments were MgSO4 (2.5 mg kg 1) alone (Mg), morphine (0.1 mg kg 1) alone (Mo), MgSO4 in combination with morphine (Mm), and sterile water (0.115 mL kg 1; Co) that were injected in the lumbosacral epidural space using an epidural catheter. Antinociception was measured using the von Frey mechanical threshold device applied to the carpal pads, both sides of the thorax and metatarsi. Measurements were obtained at time points: before treatment (baseline) and 0.5, 1, 2, 4, 6, 12, 18 and 24 hours after the epidural injection. Sedation, behaviour score and presence of motor deficits were assessed. Data were analyzed using a linear mixed model and Bonferroni adjustments, with significance set at p < 0.05. RESULTS : There were significant effects of treatment and time in all regions. Overall threshold values in grammes force [median (interquartile range)] when stimulation regions were combined were significantly higher in Mg [164 (135–200)], Mo 156 (129–195)] and Mm [158 (131–192)] compared to Co [145 (120–179)]. Thresholds were significantly higher compared to Co in Mg, Mo and Mm at the thorax and metatarsi, but only in Mg and Mo at the carpal pads. No motor deficits were observed at any time point. Thresholds (combined regions) were increased from baseline at one or more time points with all treatments, including control. CONCLUSION AND CLINICAL RELEVANCE : Epidural MgSO4 produced an antinociceptive effect characterised by an increase in the mechanical thresholds of similar magnitude to that produced by epidural morphine, compared with the control group, without causing any motor deficits. No potentiation of morphine antinociception was observed. The onset and offset times of antinociception could not be clearly established. To what extent these results can be extrapolated to clinical cases requires further investigation.Department of Companion Animal Clinical Studies of the University of Pretoria and the University of Pretoria Research Fund.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1467-29952016-05-31hb201

Anaesthetic induction and recovery characteristics of a diazepam-ketamine combination compared with propofol in dogs

Induction of anaesthesia occasionally has been associated with undesirable behaviour in dogs. High quality of induction of anaesthesia with propofol has been well described while in contrast variable induction and recovery quality has been associated with diazepam-ketamine. In this study, anaesthetic induction and recovery characteristics of diazepam-ketamine combination with propofol alone were compared in dogs undergoing elective orchidectomy. Thirty-six healthy adult male dogs were used. After habitus scoring (simple descriptive scale [SDS]), the dogs were sedated with morphine and acepromazine. Forty minutes later a premedication score (SDS) was allocated and general anaesthesia was induced using a combination of diazepam-ketamine (Group D/K) or propofol (Group P) and maintained with isoflurane. Scores for the quality of induction, intubation and degree of myoclonus were allocated (SDS). Orchidectomy was performed after which recovery from anaesthesia was scored (SDS) and times to extubation and standing were recorded. Data were analysed using descriptive statistics and Kappa Reliability and Kendall Tau B tests. Both groups were associated with acceptable quality of induction and recovery from anaesthesia. Group P, however, was associated with a poorer quality of induction (p = 0.014), prolonged induction period (p = 0.0018) and more pronounced myoclonus (p = 0.003), but had better quality of recovery (p = 0.000002) and shorter recovery times (p = 0.035) compared with Group D/K. Diazepam-ketamine and propofol are associated with acceptable induction and recovery from anaesthesia. Propofol had inferior anaesthetic induction characteristics, but superior and quicker recovery from anaesthesia compared with diazepam-ketamine.University of Pretoriahttp://www.jsava.co.zaam201

Genexpert MTB/RIF diagnostic and tuberculosis treatment initiation delays in Namibia

BACKGROUND : Early diagnosis and treatment of drug resistant tuberculosis are crucial in the control of the disease and treatment success. In Namibia, there is a gap in empirical data on the diagnosis and treatment initiation delay time since the roll-out of the GeneXpert MTB/RIF (Xpert) assay in 2017. This study aimed to determine Xpert pre-diagnosis and turnaround time at Namibian Institute of Pathology (NIP) as well as rifampicin resistant tuberculosis (RR-TB) treatment initiation delay on patients admitted at Katutura Intermediate Hospital TB clinic. METHODS : This was retrospective descriptive cross-sectional study which was conducted from 1 July 2018 to 31 March 2019. A total of seventy two participants comprising of twenty five RR-TB and forty seven non RR-TB patients were enrolled using consecutive sampling method. Laboratory information system (LIS) was utilized to determine Xpert median pre-analytical delay and turnaround time. Patients’ records and LIS were used to calculate median treatment initiation delay time post Xpert diagnosis. Data on continuous variables was summarized as median and interquartile range. RESULTS : The median pre-diagnostic, diagnostic and treatment initiation delay time were 7.5 (IQR: 0-14), 1 (IQR: 0-3) and 10 (IQR: 1-32) days respectively for RR-TB. For drug susceptible TB, the median pre-diagnostic, diagnostic and treatment initiation delay time were 5 (IQR: 1-8), 1 (IQR: 0-3) and 3 (IQR: 0-12) days respectively. Overall, median health system delay time was 21 (IQR: 2-32) days for RR-TB patients and 12 (IQR: 1-12) days for non RR-TB patients. CONCLUSION : Treatment initiation to appropriate second line regimes was long for many patients and may be attributable to poor interpretation of discordant results and increased number of RR-TB patients for treatment since Xpert adoption. Unnecessary referrals due to shortages of pulmonologists, cumbersome baseline investigations and outdated guidelines and policies could be the determinants of health system delay time. Interventions targeted at addressing identified factors should be implemented. Further studies should explore the actual treatment gap among RR-TB patients and further risk factors for delayed treatment.https://www.wjahr.comam2020School of Health Systems and Public Health (SHSPH

The effects of midazolam and butorphanol, administered alone or combined, on the dose and quality of anaesthetic induction with alfaxalone in goats

Goats are rarely anaesthetised; consequently, scant information is available on the efficacy of anaesthetic drugs in this species. Alfaxalone is a relatively new anaesthetic agent, of which the efficacy in goats has not yet been studied. In this study, the sedative and alfaxalonesparing effects of midazolam and butorphanol, administered alone or concomitantly, in goats were assessed. Eight clinically healthy goats, four does and four wethers, were enlisted in a randomised crossover manner to receive intramuscular sedative treatments consisting of saline 0.05 mL/kg, or midazolam 0.30 mg/kg, or butorphanol 0.10 mg/kg, or a combination ofmidazolam 0.30 mg/kg with butorphanol 0.10 mg/kg before intravenous induction of general anaesthesia with alfaxalone. Following induction, the goats were immediately intubated and the quality of anaesthesia and basic physiological cardiorespiratory and blood-gas parameters were assessed until the goats had recovered from anaesthesia. The degree of sedation, quality of induction and recovery were scored. When compared with saline (3.00 mg/kg), midazolam,administered alone or with butorphanol, caused a statistically significant increased level of sedation and a reduction in the amount of alfaxalone required for induction (2.00 mg/kg and 1.70 mg/kg, respectively). Butorphanol alone (2.30 mg/kg) did not cause significant changes in level of sedation or alfaxalone-induction dose. During induction and recovery, the goats were calm following all treatments, including the control group. Cardiorespiratory and blood gasparameters were maintained within clinically acceptable limits. The present study showed that midazolam, administered alone or combined with butorphanol, produces a degree of sedation that significantly reduces the dose of alfaxalone required for induction of general anaesthesia in goats, without causing any major adverse cardiorespiratory effects

Effects of chemical and mechanical stimulation on laryngeal motion during alfaxalone, thiopentone or propofol anaesthesia in healthy dogs

OBJECTIVE : To compare the effect of chemical and mechanical stimulation on arytenoid cartilage motion during anaesthetic induction with alfaxalone, thiopentone or propofol. STUDY DESIGN : Masked, randomized, crossover study. ANIMALS : A group of eight adult Beagle dogs. METHODS : Anaesthesia was induced with thiopentone (7.5 mg kg–1), propofol (3 mg kg–1) or alfaxalone (1.5 mg kg–1) intravenously (IV), which were concurrently paired with either chemical (doxapram at 2.5 mg kg–1 IV) or mechanical (gentle pressure to the corniculate process of the right arytenoid cartilage using a cotton bud) stimulation for enhanced assessment of laryngeal motion, in random order, with a 1 week wash-out period between treatments. If deemed inadequately anaesthetized, supplemental boli of thiopentone (1.8 mg kg–1), propofol (0.75 mg kg–1) or alfaxalone (0.4 mg kg–1) were administered. Assessment of number of arytenoid motions and vital breaths, among others, was initiated immediately after induction. Chemical (doxapram) and mechanical stimulation were begun 2 minutes after anaesthetic induction. Data were collected at 2, 3 and 5 minutes after anaesthetic induction and the Friedman rank-sum or repeated-measures analysis of variance tests were used when applicable for statistical analysis. RESULTS : The duration of examination time was shorter among treatments combined with chemical stimulation (p=0.001). Examination time during induction was longer for alfaxalone-chemical (8.9 minutes) and -mechanical (10.9 minutes) compared to both induction with thiopentone-chemical (3.8 minutes) and propofol-chemical (4.0 minutes). The median number of arytenoid motions for both thiopentone (67) and propofol (59) induction combined with chemical stimulation was significantly higher in comparison to that of alfaxalone (1), thiopentone (2) and propofol (2), when combined with mechanical stimulation at 3 minutes after induction. CONCLUSION AND CLINICAL RELEVANCE : Among the regimens for assessing laryngeal motion assessed in the present study, combinations of thiopentone or propofol with doxapram are the most effective means of stimulating arytenoid motion and could improve the accuracy of diagnosis of laryngeal paralysis in dogs.The National Research Foundation of South Africahttps://www.journals.elsevier.com/veterinary-anaesthesia-and-analgesia2020-07-01hj2020Companion Animal Clinical Studie