13 Jul 2021
Kate Loomes BVSc(Hons), MSc, CertAVP(EP), CertAVP(VA), CertAVP(EM), DipECVAA, MRCVS IN this article, the author fully explains partial IV anaesthesia – the maintaining of anaesthesia with a combination of IV and inhalational agents.
Kate Loomes
Job Title
During general anaesthesia in horses, maintaining and preserving good cardiorespiratory function and optimising recovery quality are two important considerations.
A contributory cause for the cardiovascular depression in horses is the use of inhalational agents and, therefore, reducing the concentration of delivered inhalational agent is one of the general principles to prevent and treat cardiopulmonary depression (Kalchofner et al, 2006; Gozalo-Marcilla et al, 2014).
Due to their lack of inherent analgesic properties, it may not be possible to reduce the concentration of inhalational agents and maintain an adequate plane of anaesthesia during surgery (Gozalo-Marcilla et al, 2014) without the provision of adequate analgesia.
The recovery phase is a time of increased risk for horses after general anaesthesia. It has recently been reported that the majority of equine anaesthetic-related complications occur during recovery (Laurenza et al, 2020) and, therefore, optimising recovery quality and safety is paramount in reducing equine anaesthetic morbidity and mortality.
Intraoperative pain can negatively influence recovery quality and has been identified as a potential risk factor for poor recovery quality in horses (Young and Taylor, 1993; Gozalo-Marcilla et al, 2014).
Partial IV anaesthesia (PIVA) describes maintaining anaesthesia with a combination of IV and inhalational agents, which may also be termed “balanced anaesthesia” (White, 2015).
The co-administration of IV anaesthetic or sedative agents during general anaesthesia maintained with an inhalational agent may enable a reduction in inhalational agent requirements, therefore reducing the magnitude of the cardiorespiratory depression. Additionally, the co-administration of certain IV agents can improve analgesia and anaesthetic stability (Nannarone and Spadavecchia, 2012) and improve recovery quality (Gozalo-Marcilla et al, 2015).
The use of PIVA in equine anaesthesia has gained in popularity in the past few years. In 2010, a survey of the American Association of Equine Practitioners reported that 45 per cent of respondents performed long-term anaesthesia (more than 30 minutes); however, PIVA protocols were not stated as a method of maintaining general anaesthesia (Hubbell et al, 2010).
By 2015, an international survey of veterinary surgeons reported that the use of drugs including PIVA and total IV anaesthesia were frequently mentioned when respondents were asked about perceived areas of recently implemented or additionally needed (future) improvements in equine anaesthesia (Wohlfender et al, 2015).
Furthermore, almost 80 per cent of respondents used continuous rate infusions (CRIs) of various anaesthetic and analgesic drugs during inhalational agent anaesthesia (Wohlfender et al, 2015).
Supplemental IV anaesthesia/analgesia is alternative terminology referring to the additional use of analgesic or anaesthetic agents with an inhalational agent (White, 2015). For the purposes of this article, maintaining general anaesthesia with an inhalational agent and an IV anaesthetic, sedative or analgesic agent is referred to as PIVA.
Potential benefits of PIVA include:
Potential disadvantages of PIVA include:
The use of PIVA has several aims. The administration of an IV anaesthetic or sedative agent may provide a “MAC-sparing” effect and, therefore, allow a reduction in the delivered concentration of inhalational agent while maintaining an adequate “depth” of anaesthesia and surgical conditions.
Commonly used inhalational agents isoflurane and sevoflurane have no analgesic properties and, therefore, the delivery of higher concentrations of inhalational agent during invasive or “painful” surgical procedures may reduce the perception of pain, but this does not moderate or reduce intraoperative pain pathway activation.
The lack of intraoperative analgesia also may lead to pain at the end of anaesthesia, which, in turn, may influence the recovery negatively (Gozalo-Marcilla et al, 2014). PIVA protocols may enhance intraoperative analgesia and improve recovery quality.
Agents that are most commonly reported and used as part of PIVA protocols include alpha-2 adrenoreceptor agonists (detomidine, romifidine, xylazine, medetomidine and dexmedetomidine), lidocaine, ketamine and morphine.
Alpha-2 adrenoceptor agonists are potent sedatives with good analgesic properties and are frequently utilised in combination with other drugs during equine anaesthesia (Gozalo-Marcilla et al, 2015).
All alpha-2 adrenoceptor agonists produce adverse cardiovascular effects, including bradycardia and first or second-degree atrioventricular blocks attributable to decreased sympathetic outflow from the CNS and increased vagal tone from baroreceptor response to hypertension (Yamashita et al, 2000). The resulting bradycardia may be one of the causes for the reduction in cardiac output seen after bolus administration of alpha-2 adrenoceptor agonists (England and Clarke, 1996).
An initial transient hypertension occurs after bolus administration, followed by a longer period of mild hypotension (England and Clarke, 1996). Blood pressure may be better maintained when an infusion of alpha-2 adrenoceptor agonists is used due to the increased peripheral vascular resistance (Yamashita et al, 2000); however, this should not be confused with good muscle perfusion.
The low infusion rates of certain alpha-2 adrenoceptor agonists utilised in PIVA protocols have been associated with minimal cardiovascular effects, which appear to be tolerated in healthy horses (Kalchofner et al, 2006; 2009; Devisscher et al, 2010; Gozalo-Marcilla et al, 2012).
Urine production also increases in response to administration of alpha-2 adrenoceptor agonists. After longer anaesthetic times – and, therefore, durations of alpha-2 adrenoceptor agonist infusions (greater than 30 minutes) – the volume of urine produced may be significant. To avoid excessive distention of the bladder, monitor urine output and prevent premature attempts to rise; catheterisation during alpha-2 adrenoceptor agonist CRIs is considered very important (Kalchofner et al, 2006; Bettschart-Wolfensberger and Larenza, 2007).
The administration of intraoperative detomidine CRI (10.8µg kg-1 hour-1) reduced the MAC of halothane by 33 per cent in healthy horses (Wagner et al, 1992). Schauvliege et al (2011) reported that the use of intraoperative detomidine infusions in isoflurane-anaesthetised horses was associated with typical cardiovascular effects of alpha-2 adrenoceptor agonists, but that the recovery quality was good.
The administration of an intraoperative romifidine CRI (18µg kg-1 hour-1) in isoflurane-anaesthetised horses reduced the isoflurane requirement during elective surgery in one study (Kuhn et al, 2004), while another study showed no such effect (Devisscher et al, 2010).
An intraoperative infusion of romifidine (40µg kg-1 hour-1) in isoflurane-anaesthetised horses resulted in a lower cardiac output compared to a saline infusion in one prospective study; however, cardiac index and arterial blood pressure were not affected (Devisscher et al, 2010). When compared with an intraoperative detomidine CRI, romifidine (40µg kg-1 hour-1) resulted in better recovery quality in isoflurane-anaesthetised horses undergoing elective surgery (Alonso et al, 2020).
While this study was retrospective and the recovery scoring was not blinded to the treatment, 87 per cent of horses receiving a romifidine intraoperative CRI were standing after one attempt with little or no ataxia (Alonso et al, 2020).
Xylazine is the least selective alpha-2 adrenoceptor agonist, and has a short half-life and rapid onset of action (Wiederkehr et al, 2021). When an intraoperative xylazine infusion (0.69mg kg-1 hour-1) was compared to medetomidine (3.5µg kg-1 hour-1 IV) in isoflurane-anaesthetised horses undergoing elective surgery, mean arterial pressure was slightly higher, dobutamine requirements slightly lower and recovery times shorter in horses receiving xylazine (Wiederkehr et al, 2021). However, the isoflurane “sparing effect” and recovery quality was not different between groups in this study.
Similarly, when isoflurane-anaesthetised horses receiving an intraoperative xylazine CRI (1mg kg-1 hour-1) were compared to those receiving isoflurane alone or an intraoperative ketamine CRI, mean arterial pressure was higher and dobutamine requirements lower in those receiving xylazine (Pöppel et al, 2014).
In the same study, recovery times were not different between groups, but recovery quality was significantly better in horses that had received an intraoperative xylazine CRI compared to those receiving a ketamine CRI (Pöppel et al, 2014).
Medetomidine has a short elimination half-life and rapid clearance (Bettschart-Wolfensberger et al, 1999), which makes its particularly suitable as a CRI. Medetomidine intraoperative CRI (3.5µg kg-1 hour-1 ) has been shown to reduce desflurane requirements (Bettschart-Wolfensberger et al, 2001).
As with all alpha-2 adrenoceptor agonists, medetomidine reduced cardiac output and Ringer et al (2005) reported the reduction in cardiac output associated with medetomidine in isoflurane-anaesthetised horses was greater than that associated with lidocaine infusion. However, when medetomidine and lidocaine CRI was compared to lidocaine CRI alone in isoflurane-anaesthetised horses, the combination of medetomidine and lidocaine did not adversely affect cardiovascular function, and recovery quality was better compared to lidocaine CRI alone (Valverde et al, 2010).
In another study in healthy adult horses undergoing elective surgery, cardiopulmonary function was generally well maintained when general anaesthesia was maintained using isoflurane and medetomidine CRI (3.5μg kg-1 hour-1), and recoveries were generally calm and smooth, with 86 per cent of horses scored as having a good-to-excellent quality of recovery with two or fewer attempts to stand (Kalchofner et al, 2006).
Dexmedetomidine is the dextrorotatory and active enantiomer of medetomidine (Sacks et al, 2017). Compared to medetomidine, a bolus of dexmedetomidine had shorter-lasting cardiopulmonary effects without a decrease in heart rate (Bettschart-Wolfensberger et al, 1999; 2005).
Dexmedetomidine has a shorter plasma elimination half-life and more rapid clearance compared to medetomidine (Grimsrud et al, 2012; Rezende et al, 2015). As with all alpha-2 adrenoceptor agonists, typical cardiovascular effects of dexmedetomidine include an increase in systemic vascular resistance and arterial blood pressure, and a reduction in heart rate and cardiac output (Gozalo-Marcilla et al, 2010; Risberg et al, 2016).
Administration of dexmedetomidine CRI reduced sevoflurane requirements by 12 per cent in one experimental crossover study, although no cardiovascular advantage was conferred (Simeonova et al, 2017). In the same study, while horses did not undergo surgery, the anaesthetic duration was relatively long (three hours) and horses receiving dexmedetomidine CRI had better recovery scores than those receiving sevoflurane alone (Simeonova et al, 2017).
Administration of dexmedetomidine CRI (1.75mg kg-1 hour-1) in isoflurane-anaesthetised horses undergoing elective surgery was associated with limited cardiopulmonary effects and significantly improved recovery qualities compared to isoflurane alone (Gozalo-Marcilla et al, 2012).
In contrast, another study showed that cardiovascular function in horses receiving isoflurane and dexmedetomidine CRI (1.75µg kg-1 hour-1) was more compromised than in horses receiving a higher concentration of isoflurane and saline CRI, despite a reduction in isoflurane requirements (Risberg et al, 2016). However, horses receiving dexmedetomidine had significantly better recoveries compared to those receiving isoflurane alone (Risberg et al, 2016).
When medetomidine CRI and dexmedetomidine CRI were compared in isoflurane-anaesthetised horses undergoing elective surgery, cardiopulmonary function was comparable between the two groups, but recovery scores following dexmedetomidine were better compared to medetomidine (Sacks et al, 2017). When two dexmedetomidine CRI dose rates (0.5µg kg-1 hour-1 versus 1.75µg kg-1 hour-1) were compared In horses undergoing castration under isoflurane anaesthesia, no differences were seen between cardiovascular parameters or recovery quality between groups (Bettembourg et al, 2019).
It is important to note that medetomidine and dexmedetomidine remain unlicensed for use in horses in the UK.
Lidocaine is a local anaesthetic of the amide group (Enderle et al, 2008). It offers an inhalational agent-sparing effect (Doherty and Frazier, 1998; Dzikiti et al, 2003), and also provides intrinsic analgesic properties (Murrell et al, 2005; Robertson et al, 2005).
Lidocaine CRI resulted in minimal effects on cardiac output in healthy isoflurane-anaesthetised horses undergoing elective surgery (Ringer et al, 2007) and may also be beneficial for horses undergoing colic surgery due to anti-endotoxaemic (Cassuto et al, 1985; Rimback et al, 1988; Cassutto and Gfeller, 2003) and prokinetic properties (Brianceau et al, 2002; Driessen, 2005; Torfs et al, 2009).
In horses undergoing elective surgery, administration of an IV infusion of lidocaine (loading dose 1.5mg kg -1 IV followed by 2mg kg -1 hour-1 to 2.4mg kg-1 hour-1) during isoflurane anaesthesia allowed a reduction in isoflurane requirement by 24 per cent, but no differences in cardiovascular parameters were detected (Schuhbeck et al, 2012). However, in horses undergoing colic surgery receiving a lidocaine CRI (50µg kg-1 min-1 IV), preloading with a lidocaine bolus (1.5mg kg-1 IV) did not decrease isoflurane requirements over extended periods of time compared to the CRI with no preloading given (Nannarone et al, 2015).
The administration of an intraoperative lidocaine CRI may cause ataxia in recovery, and despite stopping the lidocaine infusion 15 to 20 minutes prior to recovery, recovery quality was worse in horses receiving lidocaine CRI compared to those receiving saline (Schuhbeck et al, 2012).
It is, therefore, recommended that lidocaine infusion is ceased 30 minutes prior to recovery, since continuation of the infusion for longer can cause ataxia and detrimental recovery effects (Valverde et al, 2005). Intraoperative lidocaine infusions can also be co-administered with other infusions, including ketamine, opioids and alpha-2 adrenoceptor agonists (White, 2015).
Ketamine, a dissociative anaesthetic agent, induces analgesic effects by antagonising N-methyl-D-aspartate receptors (Chizh et al, 2007) and low-dose infusions have been recommended to decrease nociception during surgery in horses (Correll et al, 2004; Levionnois et al, 2010). Ketamine CRI in halothane-anaesthetised horses may reduce halothane requirements by 37 per cent and resulted in improved haemodynamics, including cardiac output, in one study (Muir and Sams, 1992).
Racemic (R-/S-) ketamine CRIs have been widely used in equine anaesthesia as part of the balanced anaesthesia concept aiming to improve analgesia, reduce inhalational agent requirements and preserve cardiac function (Bettschart-Wolfensberger and Larenza, 2007).
However, despite several beneficial effects, racemic ketamine has been associated with muscular tremor and rigidity, involuntary limb movements, excitation, and ataxia in the recovery phase, which may result in a negative outcome (Muir and Sams, 1992). These negative effects may be related to ketamine and the active metabolite of ketamine, norketamine, plasma concentrations and the duration of infusion, which restricts the use of ketamine infusions to low dose rates and shorter procedures (lower than two hours; Muir and Sams, 1992; Larenza et al, 2009).
Since the anaesthetic potency of S-ketamine is twice that of the racemic mixture, the dose needs to be adjusted for S-ketamine to provide equipotent doses (Larenza et al, 2009). When infusions of racemic ketamine and S-ketamine were compared in isoflurane-anaesthetised horses, recovery quality was better, with fewer attempts to stand and no signs of excitement in horses receiving S-ketamine (Larenza et al, 2009).
Opioids may be used as part of a PIVA protocol for analgesic properties; however, their anaesthetic-sparing effect in horses is unpredictable (Steffey et al, 2003; Thomasy et al, 2006; Knych et al, 2009). Gastrointestinal motility may be reduced after administration of opioids, so attention must be paid to monitoring postoperative faecal output.
In an experimental study, administration of dexmedetomidine alone, or combined with remifentanil or morphine, did not cause clinically significant adverse cardiorespiratory effects when compared with baseline – and no detectable gastrointestinal problems were identified in the post-anaesthetic period (Benmansour et al, 2014).
At high doses (2mg kg-1), morphine can cause dangerous unpredictable behaviour and undesirable recoveries (Steffey et al, 2003). At lower doses (0.1mg kg-1 to 0.17mg kg-1), morphine has been more recently shown to have no effect or a positive effect on recovery quality. Better recovery qualities were recorded on a composite scoring scale in horses undergoing elective surgery after administration of morphine (0.1mg kg-1 hour-1) following a loading dose of 0.15mg kg-1 during halothane anaesthesia (Clark et al, 2008).
In an experimental crossover study, a combined lidocaine and ketamine (LK) CRI afforded a 49 per cent reduction in isoflurane requirements, and when morphine (MLK) was added to this combination, the isoflurane sparing effect was 53 per cent (Villalba et al, 2011).
Mean arterial pressure was lower in horses where general anaesthesia was maintained with isoflurane alone, compared to when accompanied by LK and MLK infusions, which may be due to an increased isoflurane requirement. No differences were detected in recovery quality between the groups, although no surgery was carried out as part of the experimental protocol (Villalba et al, 2011).
Butorphanol is a synthetic agonist-antagonist (μ-receptor antagonist and k-receptor agonist) opioid, and is used to enhance sedation and provide short-lived visceral analgesia in adult horses (Kalpravidh et al, 1984). Butorphanol has minimal cardiorespiratory effects (Robertson et al, 1981) and contributes to the management of balanced anaesthesia; however, it does reduce gastrointestinal motility and may contribute to behavioural changes such as increased locomotor activity (Caure et al, 2010; Skarda and Muir, 2003).
Cardiorespiratory variables and recovery quality were not influenced by a butorphanol CRI (13μg kg-1 hour-1) in isoflurane-anaesthetised horses compared to a saline CRI (Dias et al, 2014). However, gastrointestinal motility was reduced for 60 minutes in horses receiving a butorphanol CRI (Dias et al, 2014).
The administration of an intraoperative butorphanol CRI in horses under isoflurane-medetomidine anaesthesia did not reduce isoflurane requirements, or have any effect on cardiopulmonary function or recovery quality (Bettschart-Wolfensberger et al, 2011).
A combination of lidocaine and ketamine infusion in horses undergoing elective surgery improved anaesthetic and cardiovascular stability during isoflurane anaesthesia lasting up to two hours in mechanically ventilated horses, with comparable quality of recovery compared to isoflurane alone (Enderle et al, 2008). Enderle et al (2008) reported that isoflurane requirements were reduced by 40 per cent in horses receiving lidocaine-ketamine CRI compared to those receiving isoflurane alone, which indicates an additive effect.
The authors reported recoveries were subjectively smoother in horses receiving isoflurane alone, but no statistical difference was seen when numerical scores were compared; however, the statistical power of the analysis was weak (Enderle et al, 2008).
Considering the known negative effects of ketamine and lidocaine in the recovery phase, it has been recommended that these infusions are ceased at least 15 to 20 minutes prior to recovery after durations of anaesthesia and infusion lower than 1 to 2 hours to reduce ataxia in the recovery period (Enderle et al, 2008).
Other combinations of PIVA agents in isoflurane-anaesthetised horses, such as romifidine-ketamine and guaifenesin-ketamine combinations, allowed a reduction in isoflurane requirements to 0.75 MAC in horses undergoing surgery (Nannarone and Spadavecchia, 2012). However, some horses receiving guaifenesin were reported to have poor and ataxic recoveries, which may be due to persistent muscle weakness (Nannarone and Spadavecchia, 2012).
Romifidine-ketamine PIVA combinations resulted in haemodynamic stability and good recovery quality in isoflurane-anaesthetised horses undergoing surgery, which may be due to romifidine’s analgesic and sedative effects (Nannarone and Spadavecchia, 2012).
Another combination of agents utilised in a PIVA technique resulting in an inhalational agent sparing effect included guaifenesin-ketamine-medetomidine in sevoflurane-anaesthetised horses (Yamashita et al, 2002). Cardiovascular function was reported to be better, with less dobutamine required and fewer attempts to stand in horses where general anaesthesia was maintained using guaifenesin-ketamine-medetomidine CRI and sevoflurane compared to those receiving sevoflurane alone (Yamashita et al, 2002).
Certain agents in PIVA protocols in equine anaesthesia can reduce inhalational agent requirements, and improve analgesia and recovery quality; however, it is important to consider the individual properties of the agents and potential side effects.
