KNOWLEDGE SUMMARY

In horses undergoing volatile anaesthesia, is recovery quality superior with sevoflurane compared to isoflurane?

Alexandra Robinson, DVM MANZCVS ^1*
Tsim Christopher Sun, BVSc GCert MPhil MANZCVS MRCVS ^{1, 2}
Eduardo Uquillas, BVM DVM DACVAA ²

¹ University Veterinary Teaching Hospital Sydney, 65 Paramatta Road, Camperdown 2050 NSW, Australia
² University Veterinary Teaching Hospital Camden, 410 Werombi Road, Brownlow Hill 2570 NSW, Australia
* Corresponding author email: arr945@outlook.com

Vol 8, Issue 1 (2023)
Submitted 20 Jan 2022; Published: 18 Jan 2023; next review: 26 May 2024
DOI: https://doi.org/10.18849/ve.v8i1.582

PICO question

In horses undergoing volatile anaesthesia, is recovery quality superior with the use of sevoflurane compared to isoflurane during the maintenance phase?

Clinical bottom line

Category of research

Treatment.

Number and type of study designs reviewed

Seven papers were available for critical appraisal. Of the seven papers, six were prospective, randomised trials and four of these were of crossover design. Of the same seven papers, three were experimental and four were clinical.

Strength of evidence

Moderate.

Outcomes reported

Five out of seven critically appraised articles found that there was no clinically significant improvement in recovery quality following volatile anaesthesia with sevoflurane compared to isoflurane. Two of the seven articles did find improvement in recovery quality following the use of sevoflurane over isoflurane, but both studies were of crossover design, one of these studies used non-blinded evaluators and the second study used both unblinded and blinded evaluators and a recovery quality scoring scale that did not show interobserver reliability.

Conclusion

In healthy horses presented for elective surgical and diagnostic imaging procedures in a clinical setting, there is no significant difference in recovery quality following the use of sevoflurane or isoflurane for the maintenance phase.

How to apply this evidence in practice

The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.

Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Clinical scenario

A 3-year-old Thoroughbred filly is presented to your clinic for a left carpal arthroscopy. The filly is race fit and is noted by her trainer to be highly strung. She comes with a history of having a ‘poor recovery’ following a previous anaesthetic required to facilitate the removal of an osteochondritis dissecans (OCD) lesion in a fetlock prior to beginning her race training. You are concerned about her demeanour and behaviour during the recovery phase and are interested in formulating an anaesthetic protocol for her that will minimise her fight-or-flight tendency during recovery. You have both isoflurane and sevoflurane available for use at your clinic, and you need to know if one volatile agent over the other will assist you in achieving a better recovery quality in this patient.

The evidence

Recovery quality following general anaesthesia in horses is a multifactorial process. There were seven articles discovered that were relevant to the PICO question. There was high quality evidence in the form of three prospective, randomised, controlled clinical trials. The last four articles were of crossover design, which introduces population bias in the evaluation of recovery quality, as recovery quality has been shown to improve following successive anaesthetic episodes (Platt et al., 2018). There is no compelling evidence available in the current literature to suggest that either sevoflurane or isoflurane has any significant benefit over the other in terms of improvement of recovery quality when used in healthy patients presenting for elective procedures.

Summary of the evidence

Brosnan et al. (2012)

 

Grosenbaugh & Muir (1998)

 

Leece et al. (2008)

 

Matthews et al. (1998)

 

Read et al. (2002)

 

Valverde et al. (2005)

 

White et al. (2021)

 

Appraisal, application and reflection

Equine anaesthesia is associated with an overall mortality rate of 1.0% (Gozalo-Marcilla et al., 2021) which is a modest improvement from mortality rates of 1.9% reported nearly 20 years ago (Johnston et al., 2002). Certain patient demographics are at higher risk of mortality than others, such as those with high American Society of Anaesthesiologists (ASA) physical status, extremes of age, body weight, fracture reparation, emergency laparotomy, increased anaesthetic time, procedures occurring out of hours, patients induced without premedication and maintenance with volatile agents (Johnston et al., 2002; and Johnston et al., 1995). Causes of anaesthetic-related mortality are variable and can include intraoperative cardiac arrest, fractures, luxations, neuropathy, myopathy, spinal cord malacia and respiratory obstruction (Dugdale & Taylor, 2016). Recovery from general anaesthesia has long been incriminated as the most dangerous part of the perianaesthetic period for equine patients, with 92% of overall morbidity and mortality occurring within this period (Laurenza et al., 2020). As such, the elucidation of specific anaesthesia-related factors for the improvement of recovery quality has been of considerable interest.

A review of the literature was carried out to answer the PICO question, followed by an article exclusion process resulting in seven peer-reviewed publications appropriate for critical appraisal. All seven articles have clear relevance to the PICO question. Of the seven articles, all are prospective, randomised trials. Four of these were crossover in design. There was, at least partial, blinding of recovery evaluators to treatment group in six of the articles. Four of the articles used client-owned horses, whereas the other three used research herds. The clinical trials, of which there were three, were most reflective of current standards in equine clinical anaesthesia. The articles retrieved were relatively recent, spanning only the last two decades.

In several large-scale multi- and single-centered epidemiological morbidity and mortality studies, volatile anaesthetic agents have been incriminated as a risk factor for mortality (Bidwell et al., 2007; Dugdale et al., 2016; and Johnston et al., 2002). The volatile anaesthetic agents are well known for their dose-dependent cardiorespiratory depression (Grosenbaugh & Muir, 1998). Such depression can lead to deleterious clinical sequelae such as hypotension, hypoventilation, hypercapnia and hypoxemia. Although direct causal relationships have not been identified, the presence of hypotension and hypoxemia have deleterious effects on muscle perfusion and tissue oxygenation, which could negatively impact recovery quality. Despite this, volatile agents are unlikely to be abandoned in equine anaesthesia due to their use during long and invasive procedures, minimal metabolism, ventilation-dependent elimination, titratability, and the ease with which their concentrations are monitored.

This critical appraisal was limited to sevoflurane and isoflurane, as they are the predominant volatile agents currently in use (Gozalo-Marcilla et al., 2021). Sevoflurane has been proposed to produce superior recovery quality in equine patients compared to isoflurane (Grosenbaugh & Muir, 1998). The pharmacokinetic and pharmacodynamic profile of sevoflurane suggests that it should have clinical advantages over isoflurane (Steffey, 2002). Sevoflurane has a lower blood / gas partition coefficient, indicating lower solubility of the agent in the blood. This results in a more rapid equilibration of partial pressure between the alveolar space and the blood and brain, leading to more rapid induction and recovery phases. This may increase the speed in which anaesthetic depth can be changed through titration of volatile agent delivery. Sevoflurane accumulated in the adipose tissue during long periods of general anaesthesia is also more rapidly eliminated than isoflurane, which may be an important factor during the recovery phase where horses can experience emergence delirium and dysphoria due to the continued presence of a volatile agent in their system. It may be that the advantage in using sevoflurane over isoflurane may only become evident after long (>3 hour) duration anaesthetics, although there are no comparative studies available that have investigated this.

Recoveries of good quality are characterised by the absence of emergence delirium, dysphoria or ataxia and the presence of adequate musculoskeletal strength. These characteristics lead to balanced and coordinated recoveries, reduced knuckling and falling events with fewer attempts to sternal recumbency and standing. Recoveries with these characteristics are likely to be qualitatively calm and smooth, reducing the opportunity for self-inflicted injury. Horses are prone to displaying fight-or-flight responses during emergence from general anaesthesia, and it has been postulated that the individual horse’s temperament may influence recovery (Brosnan et al., 2012; Leece et al., 2008; and Matthews et al., 1998). In addition, time spent in lateral recumbency, number of attempts to sternal recumbency, time spent in sternal recumbency, number of attempts to standing and time to standing are common objective variables used to characterise the recovery phase.

The assessment of recovery quality following use of a specific volatile agent is challenging. The use of ancillary anaesthetic agents is necessitated as part of a balanced anaesthetic technique and may include the use of injectable drugs for premedication, induction, rescue anaesthesia and the use of additional sedative and analgesic drugs in the recovery phase. The effects of ancillary agents in the recovery phase can be difficult to quantify, especially where long-lasting agents, such as acepromazine are involved in the anaesthetic protocol (Knych et al., 2018). Recovery quality will most likely be attributable to the volatile agent if the use of other ancillary agents within the protocol is standardised. Furthermore, it has become standard practice to administer additional sedative drugs during the recovery phase to improve recovery quality by decreasing opportunity for disorientation and volatile agent-related dysphoria (Santos et al., 2003; and White et al., 2021). Leece et al. (2008) and White et al. (2021) published results from prospective clinical trials using stringent anaesthesia protocolisation devoid of recovery sedatives. The results from each study concluded that there was no significant difference in recovery quality following sevoflurane versus isoflurane anaesthesia. There were no articles available for appraisal that evaluated volatile agents without the use of ancillary drugs.

The scoring of recovery quality following general anaesthesia is often subjectively assessed and qualitative in nature. Vettorato et al. (2010) investigated the reliability of four distinct recovery quality scoring systems (RQSS) through use of two groups of evaluators, 117 final-year veterinary students and 12 experienced equine anaesthetists. The four RQSS evaluated were a visual analogue scale originally reported by Hubbell in 1999, a composite scoring system (Donaldson et al., 2000), a simple descriptive scale (Young & Taylor, 1993) and the Edinburgh scoring system (Vettorato et al., 2010). Results revealed that the four RQSS exhibited moderate-high reliability, suggesting that there was significant interobserver agreement amongst scores given by blinded evaluators and that the scales were reliable even when used by inexperienced operators. Ideally, high interobserver agreement of recovery scales should be identified to reduce bias and enable meaningful comparisons between studies. Although a perfect RQSS has not yet been developed, recovery scales should be objective, sensitive in detecting recovery quality differences and be adapted to accommodate the conditions of the study facility (Valverde et al., 2005). In addition to this, researchers should seek to limit bias by blinding recovery evaluators to treatment groups.

Of the seven studies evaluated, four utilised RQSS that were recognised as being reliable by Vettorato et al. (2010). Valverde et al. (2005) utilised a modified composite scoring system, Leece et al. (2008) utilised a modified combination of a composite scoring system and simple descriptive scale, Brosnan et al. (2012) utilised a visual analogue scale and White et al. (2021) utilised a simple descriptive scale. Each of these scales had roots in the published grandfather articles referenced in Vettorato et al. (2010). All four articles used recovery evaluators that were blinded to treatment group, thus minimising the possibility of bias. Valverde et al. (2005) even proved the reliability of their modified composite scoring system by having one blinded and one unblinded evaluator to score recoveries. None of the RQSS used in these studies detected significant differences in recovery quality between sevoflurane and isoflurane recoveries. The remaining three articles used simple descriptive scales of their own manufacture that resulted in discrepant results (Matthews et al., 1998), had non-existent blinding processes (Grosenbaugh & Muir, 1998), and utilised hand-assisted recovery techniques (Read et al., 2002), thus increasing the potential for bias and possibly misleading results.

A recent publication by Platt et al. (2018) showed that habituation and learning during the recovery phase following sequential general anaesthetic episodes in equine patients occurs and culminates in improvement of recovery quality. This phenomenon may reduce the reliability of crossover designed research studies when determining recovery quality in horses. Four of the appraised articles were crossover designs. Interestingly, there were contrasting results. Two studies reported no difference in recovery quality when using sevoflurane versus isoflurane (Brosnan et al., 2012; and Read et al., 2002), while the other two suggested that sevoflurane recovery quality was superior (Grosenbaugh & Muir, 1998; and Matthews et al., 1998). Study participants were anaesthetised on as little as two (Read et al., 2002) to as many as five (Brosnan et al., 2012) separate occasions for study purposes. The crossover design and ample opportunity for learned behaviour development make the results of these articles difficult to interpret. Three of the four crossover designed studies had additional significant limitations that clouded their clinical relevance, such as unblinded recovery evaluators (Grosenbaugh & Muir, 1998), an insensitive and unreliable RQSS that may have precluded detection of specific aspects of recovery behaviour (Matthews et al., 1998) and hand-assisted recovery techniques (Read et al., 2002).

The use of anaesthesia-naïve animals may be the most logical population in which to study recovery quality. Of the articles appraised, three were clinical trials in which anaesthesia-naïve animals were enrolled (Leece et al., 2008; Valverde et al., 2005; and White et al., 2021). These three studies also had the strongest study designs, used reliable RQSS, had large sample sizes, reflected the general horse population and used anaesthetic protocols common in clinical practice. In addition to this, both Valverde et al. (2005) and White et al. (2021) cases were surgical procedures and those in Leece et al. (2008) involved diagnostic imaging, both scenarios of which are relevant to clinical practice. Furthermore, the studies produced by Leece et al. (2008) and White et al. (2021) were only concerned with recovery quality differences, thus making their results highly relevant to our analysis. For these reasons, these three articles likely offer the most accurate and unbiased information available to answer the PICO question. None of these studies detected any significant difference in recovery quality following sevoflurane versus isoflurane anaesthesia.

The finding from this critical appraisal was supported by the findings of a recent systematic review. Loomes & Louro (2021) deduced that there is no conclusive evidence that any given volatile agent is superior to another in terms of recovery quality. Loomes & Louro (2021) recognised that there is a relative dearth of literature on the topic, but the articles available typically have strong study designs with blinded recovery quality evaluators and the use of a validated RQSS. Limitations in the articles were the inconsistent use of sedatives prior to the recovery phase, general lack of power calculations, although Leece et al. (2008) did perform a post hoc power, and the presence of multiple study objectives. These limitations were also present in the currently appraised articles, and they seem to be common limitations in articles involving equine anaesthesia in general. Despite these limitations, Loomes & Louro (2021) suggest that there is moderate evidence to support their conclusion. A recently published expert opinion (Bettschart-Wolfensberger, 2021) combining extensive clinical experience and an independent dissection of the literature has culminated in the same conclusion.

After complete appraisal of the evidence, the authors conclude that there is moderate evidence in the literature to support that there is no clinical difference in recovery quality following sevoflurane versus isoflurane anaesthesia in healthy horses under clinical and experimental conditions. Sevoflurane and isoflurane both provide rapid, smooth recoveries of good quality. In the absence of clear and causal relationships between specific volatile anaesthetic agents and anaesthetic outcome, an individual clinician’s choice of volatile agent should be based on user familiarity, relative anaesthetic risk of the patient, anticipated duration of anaesthesia and the potential environmental impacts. Continued research into the benefits of administering additional sedative drugs in attempts to improve recovery quality are required. Further evaluation of volatile agent influence on recovery quality may require the use of sick horses and long (> 3 hour) durations of anaesthesia.

Methodology

Search Strategy

 

Exclusion / Inclusion Criteria

 

Search Outcome

 

Acknowledgements

The authors wish to acknowledge the assistance of Ms Monica Cooper in the process of formulating a literature search strategy for this review.

ORCID

Alexandra Robinson: https://orcid.org/0000-0003-4937-9552
Tsim Christopher Sun: https://orcid.org/0000-0003-1033-8251
Eduardo Uquillas: https://orcid.org/0000-0002-4227-2173

Conflict of Interest

The authors declare no conflicts of interest.

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