Pharmacokinetics of intramuscular alfaxalone and its echocardiographic, cardiopulmonary and sedative effects in healthy dogs

Cruz-Benedetti, Inga-Catalina; Bublot, Isabelle; Ribas, Thibault; Fourel, Isabelle; Vogl, Claus; Dubois, Claire M.; Milani, Mathilde; Ida, Keila Kazue; Portier, Karine

doi:10.1371/journal.pone.0204553

Cited by 26 publications

(31 citation statements)

References 31 publications

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“…In the ALF group, the level of SpO 2 remained > 90%, similar to that observed in previous studies [ 27 , 32 ]. The XYL-ALF group showed a decrease SpO 2 with mean values varying from 82% to 87% for 25 min post-induction; however, no significant clinical signs of cyanosis were observed.…”

Section: Discussionsupporting

confidence: 90%

“…These findings were similar to those observed in previous studies in sheep [ 6 , 7 ]; however, in the XYL-ALF group, SAP and MAP were decreased but remained within the clinically acceptable range. In this study, the stability of arterial blood pressures suggested that increased HR was not a baroreceptor response to hypotension, as previously reported [ 30 , 32 ]. However, it was hypothesized that increased HR acts as a compensatory reflex to maintain CO within the normal range [ 29 , 33 ].…”

Section: Discussionsupporting

confidence: 86%

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The Effect of Xylazine Premedication on the Dose and Quality of Anesthesia Induction with Alfaxalone in Goats

Abouelfetouh

Liu

Salah

et al. 2021

Animals

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Goats have been used as animal models in research and are increasingly kept as companion animals. However, information about effective anesthetic drugs is scarce in this species. The objective of this study was to evaluate the effect of xylazine premedication on alfaxalone induction. Twelve clinically healthy goats weighing 18.5 ± 2 kg were randomly assigned to two groups. Induction was performed with alfaxalone alone intravenously (ALF group) or with xylazine premedication before alfaxalone administration (XYL-ALF group). The quality of induction was scored, induction doses of alfaxalone were determined, and cardiorespiratory parameters and nociceptive thresholds were measured before any treatment(s) (baseline) and at 5, 15, 25 and 35 min after alfaxalone administration. The mean dose of alfaxalone required for induction in the ALF group was greater than that in the XYL-ALF group (p < 0.001). There were no significant changes in diastolic arterial pressure (DAP), mean arterial pressure (MAP) or systolic arterial pressure (SAP) compared to baseline in either group, while hemoglobin oxygen saturation (SpO2) was lower from 5 to 25 min (p < 0.5) in the XYL-ALF group. The nociceptive threshold was significantly higher at 5 min in the XYL-ALF group than in the ALF group (p = 0.0417). Xylazine premedication reduced the required dose of alfaxalone for anesthetic induction and produced better antinociception than alfaxalone alone. In addition, the combination of xylazine and alfaxalone allowed for successful induction; however, oxygen supplementation is necessary to counteract xylazine-associated hypoxemia.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 86%

The Effect of Xylazine Premedication on the Dose and Quality of Anesthesia Induction with Alfaxalone in Goats

Abouelfetouh

Liu

Salah

et al. 2021

Animals

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“…Finally, alfaxalone gets benefits from its high safety, its fast clearance, and short half-life, following the quick hepatic metabolism by esterases and the very efficient renal excretion, without massive accumulations in body tissues [34,35]. Nevertheless, at term of pregnancy, the maternal hemodynamic status undergoes a physiological overload due to gestation itself, especially in giant-size dogs [52,53,54], and the low cardio-circulatory impact of alfaxalone at standard dosages (up to 3 mg/kg) [55] on the maternal side is of paramount advantage.…”

Section: Discussionmentioning

confidence: 99%

Effects of Alfaxalone or Propofol on Giant-Breed Dog Neonates Viability During Elective Caesarean Sections

Melandri

Alonge

Peric

et al. 2019

Animals

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Simple SummaryNowadays, thanks to the increased awareness of owners and breeders and to the most recent techniques available to veterinarians, the management of parturition, especially of C-sections, has become a topic of greater importance. Anesthesia is crucial and must be targeted to both the mother and neonates. The present study aimed to evaluate the effect of the induction agent alfaxalone on the vitality of puppies born from elective C-section, in comparison to propofol. After inducing general anesthesia for elective C-section, puppies from the mothers induced with alfaxalone had higher 5-min Apgar scores than those induced with propofol. The concentration of cortisol in fetal fluids collected at birth is neither influenced by the anesthetic protocol used, nor does it differ between amniotic and allantoic fluids. Nevertheless, the cortisol concentration in fetal fluids affects the relationship between anesthesia and the Apgar score: the present study highlights a significant relationship between the anesthetic protocol used and Apgar score in puppies, and fetal fluids cortisol concentration acts as a covariate of this relationship. Alfaxalone is a safe and effective drug for the induction of anesthesia in dogs, and it can be successfully employed for elective C-section, with neonatal wellbeing improvements.AbstractAttention must be paid to C-section anesthesia effects on mother and offspring. Alfaxalone induction results in improved puppy viability when compared to propofol. The present study aims to evaluate effects of alfaxalone or propofol induction for elective C-section on newborns, expressed as Apgar score and fetal fluids cortisol concentration. Anesthesia was induced with alfaxalone 3 mg/kg iv in 5 bitches (group A), and propofol 4 mg/kg iv in another 5 (group P), maintained with isoflurane. Amniotic and allantoic fluids were collected to determine cortisol concentration. Apgar score, litter size, newborn gender, birth-weight, maternal age, and parity were recorded. ANOVA, U Mann-Whitney test and ANCOVA assessed the effects of drugs on the Apgar score and fetal fluids cortisol. Thirty-six puppies were randomly selected for the study: 16 from group A and 20 from group P. Only the Apgar score significantly differed between groups. ANCOVA confirmed a significantly higher Apgar score in group A underlining the influence of fetal fluids cortisol concentrations, both resulting in covariates. Present results confirm the effect of anesthesia on the Apgar score of newborns, which is significantly higher for alfaxalone than propofol, suggesting the use of fetal fluids cortisol as a covariate. These findings could be a starting point for further investigations when less viable puppies are detected or expected, such as during an emergency C-section.

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“…Tamura et al [ 24 ] reported that hypoxemia associated with a decrease in RR was observed in a dose-dependent manner following the IM administration of 5, 7.5, and 10 mg/kg alfaxalone, while the cardiovascular status was well-maintained. In contrast, Maney [ 13 ] reported that low IM doses of alfaxalone alone at 1 and 2 mg/kg produced no change in RR in dogs, and Cruz-Benedetti et al [ 1 ] reported that there were no significant changes in oxygenation even though the RR decreased significantly in dogs that received 4 mg/kg alfaxalone IM. Lee et al [ 11 ] reported that a combination of 10 µg/kg medetomidine, 0.1 mg/kg butorphanol, and 1.5 mg/kg alfaxalone caused severe hypoxemia associated with a decrease in RR in healthy dogs.…”

Section: Discussionmentioning

confidence: 99%

The anesthetic effects of intramuscular alfaxalone in dogs premedicated with low-dose medetomidine and/or butorphanol

et al. 2021

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We aimed to evaluate the induction, anesthesia, and cardiorespiratory effects of intramuscular (IM) anesthetic protocol with alfaxalone following premedication with low-dose medetomidine, butorphanol, or a combination of both (medetomidine–butorphanol) in dogs. Six healthy beagles were administered 1, 2.5, or 5 mg/kg alfaxalone IM following premedication with low-dose medetomidine (5 µg/kg; MA-IM), butorphanol (0.3 mg/kg; BA-IM), or medetomidine-butorphanol (5 µg/kg and 0.3 mg/kg, respectively; MBA-IM). Each dog received 9 treatments with minimum 7-day washout period between treatments. Dogs were allowed to breath room air during anesthetic induction. We attempted endotracheal intubation after alfaxalone administration. Alfaxalone produced a dose-dependent anesthetic effect in each anesthetic protocol. Intubation was achieved in 4 out of 6 dogs that received MA-IM and BA-IM with 2.5 mg/kg alfaxalone and in all dogs that received MBA-IM with 1, 2.5, and 5 mg/kg alfaxalone. The median durations [minimum–maximum] of accepting intubation were 79 [0–89], 97 [84–120], and 117 [84–217] min, respectively. Hypotension (mean arterial blood pressure <60 mmHg) did not develop, but bradycardia (heart rate <60 beats/min) was observed in all dogs that received the MA-IM and MBA-IM protocols. Severe hypoxemia (percutaneous arterial oxygen saturation <90%) developed in 2 dogs that received MBA-IM with 5 mg/kg alfaxalone. We consider that the MA-IM and BA-IM protocols with ≥2.5 mg/kg alfaxalone and the MBA-IM protocol with 1–2.5 mg/kg alfaxalone could provide clinically useful and effective anesthesia without causing severe cardiorespiratory depression in healthy dogs.

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Pharmacokinetics of intramuscular alfaxalone and its echocardiographic, cardiopulmonary and sedative effects in healthy dogs

Cited by 26 publications

References 31 publications

The Effect of Xylazine Premedication on the Dose and Quality of Anesthesia Induction with Alfaxalone in Goats

The Effect of Xylazine Premedication on the Dose and Quality of Anesthesia Induction with Alfaxalone in Goats

Effects of Alfaxalone or Propofol on Giant-Breed Dog Neonates Viability During Elective Caesarean Sections

The anesthetic effects of intramuscular alfaxalone in dogs premedicated with low-dose medetomidine and/or butorphanol

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