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Safety of alfaxalone and propofol as anaesthetic agents for bitches undergoing caesarean section

The current limited evidence suggests that alfaxalone may provide better anaesthetic quality for the bitch and result in better puppy viability

07 December 2020, at 6:45am

You want to ensure your practice has a safe anaes­thetic protocol in place for caesarean sections (c-sec­tions) in bitches, as anaesthesia can be a risk to both bitch and puppies. Previous research has shown signifi­cantly lower Apgar scores for puppies born from c-section (Silva et al., 2009), for which anaesthesia may be partially responsible. Propofol is frequently used as an induction agent in c-sections, though alfaxalone is becoming more commonly used. What is the evidence comparing the safety of propofol and alfaxalone as anaesthetic induction agents in bitches and their puppies?

The evidence

Six studies were critically appraised, including four ran­domised controlled trials and two non-comparative studies. Two studies directly compared the use of alfaxalone and propofol as induction agents, so offer high-quality evidence. The other four studies assess propofol as an induction agent in one of their experimental groups. Alfaxalone’s use in c-sections is only recently becoming more common, so was only investigated in the two comparative studies.

Metcalfe et al. (2014) investi­gated 74 bitches undergoing c-section and their puppies. Cases were randomised, so two in three received alfax­alone induction and one in three received propofol induction. Outcomes meas­ured were quality of anaes­thetic induction, maintenance and recovery, as well as puppy survival and puppy vigour. Of bitches in the alfax­alone group, 98 percent scored a top score for induction, 81 percent for anaesthetic effectiveness and 73 percent for recovery, compared with 88 percent, 65 percent and 69 percent respectively for the same measures with propofol. A greater percentage of alfaxalone group puppies were positive for all health vigour assessments compared with the propofol group. Survival percentages at birth and at 24 hours did not differ between groups. Limitations include that the group sizes were unequal, and 46 percent of the propofol group were brachycephalic breeds, compared to 29 percent of the alfaxalone group. Brachycephalic breeds tend to be more unstable under anaesthesia so this could impact the findings.

In a second blinded study (Doebeli et al., 2013), 22 bitches and 81 puppies were placed in either an alfaxalone group or propofol group. Puppy survival did not differ between the alfaxalone and propofol groups at any time interval. Five minutes after birth, the proportion of pup­pies in the alfaxalone group with high, medium and low Apgar scores were 68 percent, 15 percent and 17 percent respectively, compared to 19 percent, 31 percent and 50 percent respectively for the propofol group (Apgar scores are used to evaluate new-born human babies. The score is based on five simple criteria on a scale from zero to two, then summing up the five values thus obtained to give a score of zero to ten. The five criteria are appearance, pulse, grimace, activity, respiration). Pre- and intraopera­tive parameters in bitches, including anaesthesia duration and delivery time, did not differ between groups. Limi­tations include the small sample size and the unknown value of Apgar scores in pre­dicting short-term survival of puppies.

A study by Vilar et al. (2018), in which a group of 14 bitches were induced with propofol and maintained with sevoflu­rane, reported 98.1 percent of puppies were born alive, with 7.7 percent of puppies classi­fied as critical neonates. The mean Apgar score 60 minutes after birth was 9.0 ± 1, classi­fied as high. Limitations include that bitches were premedi­cated with morphine, which may have affected puppy vitality, and longer-term outcomes were not recorded.

In a non-comparative retrospective study of a population at an increased obstetric risk, bitches were induced with propo­fol (De Cramer et al., 2017). The percentage of puppies live at delivery was 97.39 percent for Boerboel Mastiff bitches, 96.67 percent for English Bulldogs and 91.69 percent for other pure breeds. The average Apgar scores for the Boerboels, English Bulldogs and other pure-breed puppies respectively were 9.77, 9.35 and 9.68. All bitches were fully ambulatory 15 minutes after extubation. Limitations include that the study was non-comparative, and the population is not representa­tive of the full clinical population.

Another non-comparative study studying propofol induction found induction and maintenance of anaesthe­sia were uneventful in all 141 bitches, and all recovered quickly despite 40/141 being lethargic for one to two days (Funkquist et al., 1997). Out of the 412 puppies delivered by c-section, 306 were born alive of which 13 died within 20 minutes, and a further 36 were euthanised or died during the three-month post-operative period. Limitations include that it was a non-comparative study and follow-ups were done by telephone, so relied on owner assessment.

The final study critically appraised was a non-blinded randomised controlled trial with four experimental groups, one of which included propofol induction (Luna et al., 2004). Puppy vitality and mortality were measured; mortality was 4 percent and the percentage of puppies testing positive for each of the reflexes tested was as follows: pain: 96 percent, sucking: 88 percent, anogenital: 88 percent, magnum: 58 percent, flexion: 46 percent. Limitations include that the study was not blinded, there were small sample sizes and safety for bitches was not evaluated.

Conclusion

Overall, the evidence suggests that puppy mortality, bitch mortality and anaesthetic complications were in acceptable proportions, highlighting that propofol and alfaxalone are safe to use with only one bitch dying among all the studies cited. As all six studies investigated the use of a propofol induction, and only two investigated alfaxalone induction, there is more evidence supporting the use of propofol for this purpose. However, current evidence suggests that alfaxalone is a safe alternative, but further research is necessary.

The best evidence came from the two randomised controlled trials (Doebeli et al., 2013; Metcalfe et al., 2014), which suggested that there may be small differences between the safety of alfaxalone and propofol induction. Metcalfe et al. (2014) found that alfaxalone may provide a slightly better quality of anaesthesia for bitches. While there was no significant difference in puppy mortality, Doebeli et al. (2013) found significantly higher Apgar scores in the alfaxalone group compared to the propofol group in the first 60 minutes of life, although there was no impact on long-term viability. This may be of clinical relevance when performing a c-section out of hours with limited support to observe puppy recovery. Further investigation of alfaxo­lone’s impact on neonatal viability is required.

Future research should further investigate the safety of alfaxalone for induction of anaesthesia for c-sections for both bitches and puppies compared to other anaesthetic agents.

References
Author Year Title
De Cramer, K. G. M., Joubert, K. E. and Nöthling, J. O. 2017 Puppy survival and vigor associated with the use of low dose medetomidine premedication, propofol induction and maintenance of anesthesia using sevoflurane gas-inhalation for cesarean section in the bitch. Theriogenology, 96, 10-15
Doebeli, A., Michel, E., Bettschart, R., Hartnack, S. and Reichler, I. M. 2013 Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol. Theriogenology, 80, 850-854
Funkquist, P. M., Nyman, G. C., Löfgren, A. J. and Fahlbrink, E. M. 1997 Use of propofol-isoflurane as an anesthetic regimen for cesarean section in dogs. Journal of the American Veterinary Medical Association, 211, 313-317
Luna, S. P. L., Cassu, R. N., Castro, G. B., Teixeira Neto, F. J., Silva, J. R. and Lopes, M. D. 2004 Effects of four anaesthetic protocols on the neurological and cardiorespiratory variables of puppies born by caesarean section. Veterinary Record, 154, 387-389
Metcalfe, S., Hulands-Nave, A., Bell, M., Kidd, C., Pasloske, K., O’Hagan, B., Perkins, N. and Whittem, T. 2014 Multicentre, randomised clinical trial evaluating the efficacy and safety of alfaxalone administered to bitches for induction of anaesthesia prior to caesarean section. Australian Veterinary Journal, 92, 333-338
Silva, L., Lúcio, C., Veiga, G., Rodrigues, J. and Vannucchi, C. 2009 Neonatal clinical evaluation, blood gas and radiographic assessment after normal birth, vaginal dystocia or caesarean section in dogs. Reproduction in Domestic Animals, 44, 160-163
Vilar, J. M., Batista, M., Pérez, R., Zagorskaia, A., Jouanisson, E., Díaz-Bertrana, L. and Rosales, S. 2018 Comparison of 3 anesthetic protocols for the elective cesarean-section in the dog: Effects on the bitch and the newborn puppies. Animal Reproduction Science, 190, 53-62

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