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The landscape of veterinary anaesthesia has undergone a significant transformation in recent years. The traditional approach of relying on a single or dual anaesthetic drug for sedation and general anaesthesia is giving way to a more refined practice—balanced anaesthesia. The concept of balanced anaesthesia revolves around the careful selection and combination of multiple drugs, each contributing its own targeted effect on neuronal pathways. This method offers the advantage of minimizing the risks and side effects of individual drugs while enhancing the desired outcomes, making it a safer and more effective approach for anaesthesia. While the theory of balanced anaesthesia is gaining global recognition among veterinary anaesthetists, there are practical challenges that hinder its widespread adoption, especially in regions like India. Many veterinary practitioners in India face significant barriers when it comes to implementing this advanced technique. Lack of resources, such as access to veterinary anaesthesiologists, as well as difficulties in managing the pharmacological dosing of multiple anaesthetic agents, create a complex environment for practitioners. The challenge of memorizing the correct doses and calculating injection volumes—particularly when drugs are measured in different units—further complicates the process. Additionally, the frequent need to open multiple ampoules for each surgery leads to wastage of valuable anaesthetic agents, time, and resources. This often forces practitioners to revert to familiar but suboptimal anaesthetic protocols, relying on just one or two drugs for all procedures, which can increase the risk of adverse effects. The purpose of this book is to address these challenges by offering a practical and accessible guide to balanced anaesthesia for small animal practitioners. Drawing from both evidence-based research and hands-on clinical experience, this guide proposes a simplified yet effective method for creating balanced anaesthetic cocktails—mixtures of multiple drugs formulated to achieve the desired anaesthetic endpoints. These cocktails are designed to be pharmacologically compatible, easy to administer, and flexible enough to accommodate variations in drug availability across regions. Each chapter presents a range of anaesthetic cocktail formulations, designed to achieve key behavioural endpoints such as anti-nociception, amnesia, muscle relaxation, and loss of consciousness. The use of lower doses of individual drugs, combined in a balanced manner, reduces the likelihood of side effects and enhances the overall safety of the procedure. Furthermore, the simplified approach

The yesteryear concept of employing one or two acclaimed anaesthetic drugs to produce sedation and general anaesthesia is now switching over to the era of balanced sedation and balanced anaesthesia. The theory of balanced anaesthesia entails achieving the state of general anaesthesia with the proportionate administration of a mixture of small amounts of several neuronal depressant drugs which summates the advantages of the individual drugs but not their disadvantages (Bettschart-Wolfensberger and Larenza, 2007). Knowledge about balanced anesthesia and targeted effects of drugs on neuronal pathways has started to influence veterinary anaesthetists worldwide. But there are many constraints for a vast majority of veterinary practitioners in India to follow this emerging modality of anaesthetic practice. It is almost impractical for most of them to get the assistance of a veterinary anaesthesiologist every time. So they experience complexities to deal with the pharmacological dosing of multiple component drugs of balanced anaesthetic protocols. Memorising the doses and calculating the volume of injection of multiple component drugs where the doses of some drugs has to be calculated in milligram per kilogram body weight while others have to be calculated in microgram per kilogram body weight becomes a cumbersome task for the practitioner. Moreover, many of these anaesthetic drugs are available in ampoules, and hence multiple ampoules have to be broken for every single surgery; consuming a lot of time. Wastage of the leftover anaesthetic in opened ampoules is another concern. Unavailability of some drugs at some areas is another issue the practitioner faces. These challenges constrain the practitioner from practicing balanced anaesthesia and most of them lean on the verily familiar conventional anaesthetic protocol, based exclusively on one or two frequently used drugs, for almost all the surgical procedures of varying depth. Since only one or two anaesthetic drugs are involved in the protocol, the drugs have to be used at its upper limit of pharmacological doses to achieve the desired endpoints of anaesthesia. This will increase the probable risk of undesired side effects of these drugs. The challenges that restrict our practitioners from advancing beyond the era of sole reliance on one or two drugs for producing the state of anaesthesia has to be addressed and measures to resolve these issues have to be evolved to promote and equip our veterinary practitioners to practice the safer technique of balanced anaesthesia. Encompassing these objectives, and based on evidence and

The drug conventionally used for sedation is xylazine, which is an alpha-2 agonist (Dugdale, 2010; Rankin, 2015). Dexmedetomidine is the latest drug of the same class used for sedation, and is more specific to alpha2 receptors than xylazine (Ishyama et al., 1995). Doses of 1-2 mg per kg body weight of xylazine (Hall and Clarke, 2001) and upto 20 mcg per kg body weight of dexmedetomidine (Ko, 2013) are required for sedation when used alone (Hall and Clarke, 2001; Rankin, 2015). Similar degrees of sedation could still be achieved at lower doses of xylazine (0.2 to 0.4 mg per kg body weight) and dexmedetomidine (2.5 to 5 mcg per kg) if administered in combination with any opioid drug like hydromorphone / oxymorphone / fentanyl / buprenorphine / butorphanol / nalbuphine / tramadol at their usual doses (Hunt et al., 2013). Another drug - acepromazine, which is a phenothiazine tranquiliser, is used at its doses of 0.01 to 0.05 mg/kg combined with an opioid for achieving sedation (Smith et al., 2001; Dugdale, 2020; Ko, 2013). Combination of an opioid with either a phenothiazine tranquiliser or an alpha2 agonist sedative drug provides neurolept anaesthesia/analgesia (Dugdale, 2020; Rankin, 2015). An anticholinergic drug - glycopyrrolate is administered in combination with acepromazine and opioid to prevent bradycardia (Dyson and James-Davies, 1999). Anticholinergics are generally not recommended with sedative cocktails containing dexmedetomidine, but preferred with sedative cocktails containing xylazine (Congdon et al., 2011; Billah et al., 2017). If sedation is to be achieved with acepromazine alone, higher doses need to be administered where there will be an increase in its dose dependent side effects, and hence not preferred (Simon and Steagall, 2020). Benzodiazepines are another class of sedative drugs, which generally doesn’t provide predictable sedation in animals. Paradoxical excitement is caused in healthy adults when these drugs are used alone (Herron et al., 2008). Predictable sedation is achieved when these drugs are administered in combination with any opioids (KuKanich and Wiese, 2015). Also, benzodiazepines can be combined with an alpha2-opioid combination to enhance the overall sedation (Maze et al., 1992). Various balanced sedative cocktails prepared with the drugs available for a veterinary practitioner in India, are presented. The balanced sedative cocktails are prepared with either

Ketamine and Propofol - “Ketofol” “Ketofol’’ is a 1:1 (w:w) combination of ketamine and propofol (Taboada and Leece, 2014; Thejasree et al., 2018). The advantages of using both ketamine and propofol in combination (Ketofol) include analgesia, rapid recovery, preservation of airways and maintenance of spontaneous respiration and haemodynamic stability (Saeed, 2011). The admixture has benefits of both drugs, while reducing the side effects of the individual drugs when administered alone (Amornyotin, 2014; Lee and Lee, 2016; Mirfazaelian et al., 2016). Propofol-induced respiratory depression is less with the admixture, while analgesia and cardiorespiratory functions are good due to ketamine (Amornyotin, 2014; Mirfazaelian et al., 2016). Since the adverse effects are dose dependent, the combination helps reduce the dose of the individual drug needed to cause the desired anaesthetic effects. This combination of ketamine and propofol can be used to induce anaesthesia following sedation with any of the previously mentioned balanced sedative cocktails. Induction should be “titrated to effect” based on the depth of sedation achieved from the administration of the balanced sedative cocktails. Thiopentone and Propofol - “Thio-propofol” Thio-propofol is a 1:1 vol:vol mixture of 2.5% thiopentone and 1% propofol (Ko et al., 1999; Evans et al., 2002; Larisa et al., 2008). Since the mechanisms of action of propofol and thiopentone are similar, the mixture provides an additive hypnotic interaction (Vinik et al., 1999) and behaves in-between to that of the

Combination of an opioid (butorphanol/buprenorphine) and an alpha-2 agonist (xylazine/dexmedetomidine) along with an NMDA antagonist and benzodiazepine (tiletamine-zolazepam or ketamine-midazolam) will make up a balanced anaesthetic cocktail. Examples for balanced anaesthetic cocktails are xylazine/dexmedetomidine-butorphanol-midazolam-ketamine and butorphanol/ buprenorphine-tiletamine zolazepam-dexmedetomidine/xylazine (Ko, 2013; Cagle et al., 2017; Sooryadas et al., 2019; Verma et al., 2020). The latter ones are costly due to the tiletamine-zolazepam and dexmedetomidine in them, while the former ones are cost effective alternatives. Xylazine/Dexmedetomidine-Butorphanol-Midazolam-Ketamine (XBMK/DBMK) Anaesthetic Cocktail The preparation can be made by drawing 0.1 ml/kg of ketamine (50 mg/ml presentation) along with 0.1 to 0.2 ml/kg of the xylazine-butorphanol-midazolam (XBM) or dexmedetomidine-butorphanol-midazolam (DBM) sedative cocktail in a single syringe. For intravenous administration, 0.1 ml/kg each of ketamine and the sedative cocktail is to be chosen, while for intramuscular administration 0.1 ml/kg of ketamine and 0.2 ml/kg of the sedative cocktail is preferred. The volume of the cocktail that needs to be administered intramuscularly will be larger by 0.1 ml/kg when compared to the tiletamine-zolazepam based anaesthetic cocktails. Anticholinergic premedication is preferred prior to administration of anaesthetic cocktail containing xylazine (Nesgash et al., 2016), particularly if given intravenously. The XBMK/DBMK anaesthetic cocktails will induce anaesthesia in a few minutes, which last for 20 to 40 minutes (Ko, 2013; Verma et al., 2019; Verma et al., 2020). Intravenous administration of the anaesthetic cocktail provides shorter duration of surgical plane of anaesthesia. When administered as said above, the combination provides xylazine @ 0.2 - 0.4 mg/kg or dexmedetomidine @ 2.5 - 5 mcg/kg, butorphanol @ 0.1 - 0.2 mg/kg, midazolam @ 0.125 - 0.25 mg/kg and ketamine @ 5 mg/kg body weight which is as per their recommended doses when given in combination (Verma et al., 2019; Verma et al., 2020).

Total Intravenous Anaesthesia Maintenance of anaesthesia, conventionally, is done either with inhalants, or as intermittent boli of injectable anaesthetics. The pharmacological complexity of the uptake and elimination of inhalant anaesthetic agents, and the need of technical and functional knowhow, of inhalant anaesthesia machine, either restricts its use in majority clinical practice, or is not used in an ideal manner. Injectable anaesthetic drugs as intermittent boli “as and when needed” is the practice by majority practitioners for maintenance of anaesthesia. Intermittent bolus injections of anaesthetic drugs creates intermittent peaks of anaesthesia and thereby increased side effects due to high doses. Instead, a continuous rate infusion of the anaesthetic drugs, in smaller quantities is employed in TIVA, providing balanced anaesthetic maintenance. These drugs act through different pathways, providing analgesia, muscle relaxation and unconsciousness, in a synergistic manner. TIVA is thus a technique in which anaesthesia is maintained solely through the use of intravenous drugs, without reliance on inhaled anaesthetics (Kennedy, 2016). Total intravenous anaesthesia is commonly achieved using a combination of sedative-hypnotics, analgesics and even muscle relaxation drugs, often administered via continuous rate infusion (CRI) to maintain stable drug levels (Verma et al., 2020). The key advantage of TIVA is that it provide stable haemodynamics because it maintains the sympathetic tone well. Also, this procedure promises less environmental contamination avoiding exposure to anaesthetic gas in the operating rooms. TIVA is emerging as a popular option in a range of surgical procedures due to its benefits in patient comfort, recovery, and control over anaesthesia depth. Few examples of anaesthetic cocktails for total intravenous anaesthesia in dogs through constant rate infusion are mentioned below. Easy understanding on how to calculate and prepare CRI is mentioned later. 1. Dexmedetomidine (2 mcg/kg/hr), midazolam (3 mcg/kg/min), lignocaine (50 mcg/kg/min) and ketamine (40 mcg/kg/min) as a cocktail intravenous infusion in normal saline. Anaesthesia is induced by intramuscular administration of a cocktail of DBMK mentioned in earlier chapter, followed by an intravenous loading dose of lignocaine at the rate of 2 mg/kg prior to the cocktail intravenous infusion (Verma et al., 2020). 2. Xylazine (1 mg/kg/hr), midazolam (3 mcg/kg/min), lignocaine (50 mcg/kg/ min) and ketamine (40 mcg/kg/min) as a cocktail intravenous infusion in