versión On-line ISSN 2224-9435
J. S. Afr. Vet. Assoc. vol.84 no.1 Cape Town ene. 2013
T. Brighton Dzikiti
Department of Companion Animal Clinical Studies, University of Pretoria, Onderstepoort campus, South Africa
Intravenous anaesthesia is gradually becoming populär in veterinary practice. Traditionally, general anaesthesia is induced with intravenous drugs and then maintained with inhalation agents. Inhalation anaesthetic agents cause more significant dose-dependent cardiorespiratory depression than intravenous anaesthetic drugs, creating a need to use less of the inhalation anaesthetic agents for maintenance of general anaesthesia by supplementing with intravenous anaesthesia drugs. Better still, if anaesthesia is maintained completely with intravenous anaesthetic drugs, autonomic functions remain more stable intra-operatively. Patient recovery from anaesthesia is smoother and there is less pollution of the working environment than happens with inhalation anaesthetic agents. Recently, a number of drugs with profiles (pharmacokinetic and pharmacodynamic) suitable for prolonged intravenous anaesthesia have been studied, mostly in humans and, to a certain extent, in dogs and horses. There is currently very little scientific information on total intravenous anaesthesia in goats, although, in the past few years, some scholarly scientific articles on drugs suitable for partial intravenous anaesthesia in goats have been published. This review article explored the information available on drugs that have been assessed for partial intravenous anaesthesia in goats, with the aim of promoting incorporation of these drugs into total intravenous anaesthesia protocols in clinical practice. That way, balanced anaesthesia, a technique in which drugs are included in anaesthetic protocols for specific desired effects (hypnosis, analgesia, muscle relaxation, autonomic stabilisation) may be utilised in improving the welfare of goats undergoing general anaesthesia.
Total intravenous anaesthesia (TIVA) is becoming a vital technique for general anaesthesia and a well-established anaesthetic concept for some animal species, notably dogs and horses. Information on TIVA protocols for goats is very scarce at the moment; yet, there are situations (field anaesthesia, anaesthesia for MRI, research) when TIVA might be the only practically possible way to achieve general anaesthesia in goats (Carroll, Hartsfield & Hambleton 1997; Larenza et al. 2005). This review article highlights the latest developments in intravenous anaesthesia in goats, paying attention to outcomes of recent scientific articles on sedatives, analgesic and/or hypnotic drugs that can be used for TIVA in goats.
In veterinary practice, intravenous anaesthetic drugs are commonly used as induction agents to facilitate endotracheal intubation, whilst inhalation anaesthetic agents form the foundation for maintenance of general anaesthesia (McKenzi 2008; Reid, Nolan & Welsh 1993). Inhalation anaesthesia may not be applicable in all situations where anaesthesia is required. General anaesthesia can then be maintained by intravenous drugs in those situations (Hofer et al. 2003). Intravenous anaesthesia (IVA), instead of inhalation anaesthesia, could soon become an established means of anaesthetic provision for both induction and maintenance of anaesthesia in veterinary practice. During early historical times, anaesthesia could only be achieved by inhalation of vapours such as chloroform and ether (Askitopoulou, Ramoutsaki & Konsolaki 2000; Griffith 1934). Following the invention of the hypodermic needle, independently by Charles Gabriel Pravaz in France and by Alexander Wood in England in 1853 (Harvinder & Prausnitz 2007; Kravetz 2005), the technique of intravenous anaesthesia has subsequently grown over the years to a point today, where, propelled by recent major developments in volumetric pump technology and a broader understanding of the pharmacokinetic and pharmacodynamic profiles of relevant drugs, it has become the preferred anaesthetic technique in some instances, especially in commonly anaesthetised animals such as dogs (Mani & Morton 2010; McKenzi 2008; Moens 2004). TIVA is a technique that involves the use of only intravenous anaesthetic drugs to maintain an adequate depth of anaesthesia for a targeted level of central nervous system depression, for example, hypnosis for diagnostic procedures or surgical anaesthesia for noxious interventions (Suarez et al. 2012; Waelbers, Vermoere & Polis 2009).
Why intravenous anaesthesia?
There are several advantages of TIVA, especially if the drugs are administered as continuous infusions. These advantages include rapid onset of action independent of ventilation status, reduction of adverse effects of other anaesthetic drugs if used in balanced anaesthesia protocols, allowing for provision of continuous analgesia if needed, smoother recovery from anaesthesia, low costs considering that the minimum requirement is a needle and a syringe, and reduction of the hazards of occupational health and atmospheric pollution (Dundee & McMurray 1984; Hasley 1991; Mani & Morton 2010; Waelbers et al. 2009). It must be noted that TIVA anaesthesia also contributes to decreased environmental pollution, to a largely unaccounted extent, through disposal of surplus drugs and excreted metabolites into the environment (Briggs 2003). In remote settings, TIVA would be a very useful method of restraint because it does not necessarily require bulky, sophisticated and expensive equipment such as the anaesthesia machine for inhalation anaesthesia (McKenzi 2008; Waelbers et al. 2009).
There are some disadvantages to the use of TIVA that include the need for infusion pumps as the ideal modality of IVA delivery, difficulty of aligning infusion rates to depth of anaesthesia, tendency for the drug plasma concentrations to increase with duration of IVA time, and pain on injection of some drugs (Mani & Morton 2010; Waelbers et al. 2009). Even though the equipment required to deliver inhalation anaesthetic agent is expensive, the cost of IVA drugs used could prove more expensive, especially for very long anaesthetic procedures. Yet, in the author's opinion, when all is considered, the advantages of TIVA far outweigh the disadvantages, especially when patient comfort is considered.
Basic requirements for anaesthesia in goats
Anaesthetic management in goats is usually uncomplicated, with the primary notable risk being regurgitation with potentially fatal pulmonary aspiration (Hall, Clarke & Trim 2001). Mature goats have a multi-compartmental stomach with a large rumen that does not empty easily (Riebold 2007). Withholding food for 12-18 h may decrease rumen fermentation and decrease the risk of regurgitation, but does not result in a real reduction in the volume of ruminal contents (Abrahamsen 2008; Taylor 1991; Valverde & Doherty 2008). Water can be withheld for 6-12 h (Fulton, Clarke & Farris 1994). It is essential to prevent aspiration of rumen contents, even after following the precautions suggested above, by prompt placement of an endotracheal tube and inflation of the cuff of the tube after induction of general anaesthesia in mature goats (Abrahamsen 2008; Galatos 2011; Riebold 2007). Endotracheal intubation in goats is difficult because of the long, narrow oral cavity and distant laryngeal opening. Using a long-bladed laryngoscope to facilitate visualisation and a non-flexible stylet makes placement of the tube into the trachea much easier (Caulkett 2003; Taylor 1991).
Prior to an anaesthestic procedure, a physical examination should be performed. It is not uncommon for goats to develop hypoxaemia with general anaesthesia (Hall et al. 2001). Normal eructation in the goat is hampered by anaesthesia and by dorsal or lateral recumbent positioning. As a result, gas accumulates in the rumen, causing ruminal tympany or bloat, and the distended rumen exerts pressure on the diaphragm causing the lung capacity to decrease (Fulton et al. 1994; Galatos 2011). Pressure on the major vessels then impedes venous return to the heart. Cardiac output, blood pressure and tissue perfusion are also compromised and this can lead to possible ventilation-perfusion mismatch. Hypoxaemia and hypercarbia may result and can be life threatening. Passing a stomach tube after intubation can help resolve gaseous distension (Riebold 2007).
Supportive therapy during anaesthesia should ideally include intravenous fluid administration for maintenance and replacement needs, heat conservation and supplementation and oxygen supplementation (Abrahamsen 2008). Fluid maintenance can be achieved with a balanced electrolyte solution such as Lactated Ringers at a flow rate of 4 mL/kg/h - 6 mL/kg/h through an intravenous catheter placed in the cephalic vein (Fulton et al. 1994).
Techniques for intravenous anaesthesia
Intravenous anaesthetic drugs are usually first administered as a large bolus to fill the volume of distribution of the central compartment, which is then followed by continuous lower dosages to maintain effective drug plasma concentrations for the duration of the anaesthetic procedure (Beths 2008; Waelbers et al. 2009). Administration of intravenous anaesthetic drugs for maintenance of anaesthesia can be achieved by multiple bolus injections or continuous infusion at a fixed or variable rate (Beths 2008; Waelbers et al. 2009). Intermittent multiple bolus injection of IVA drugs is very simple, but is characterised by inconsistent drug plasma concentrations, variable anaesthetic depth and may result in poor and/or prolonged recovery from anaesthesia (Beths 2008; Joubert 2009). Continuous administration of intravenous anaesthetic drugs can be achieved by using a drug-spiked intravenous fluid bag, buretrol or a syringe controlled by a basic volumetric pump (syringe driver) or computer-controlled pump (Beths 2008; Waelbers et al. 2009). If intravenous anaesthetic drugs are administered from a drug-spiked fluid bag or a buretrol, the rate of administration is calculated to drops per second and adjusted over time to achieve a desired anaesthetic effect (analgesia, hypnosis, surgical anaesthesia). However, administration of intravenous anaesthetic drugs can be undertaken in a more sophisticated manner by the constant rate infusion (CRI) technique using the conventional syringe driven by a pump, or by the target-controlled infusion (TCI) technique using a highly sophisticated computer-controlled pump that adjusts the rate of drug administration so as to maintain a user-defined target plasma or effect site drug concentration (Mani & Morton 2010; Waelbers et al. 2009).
In human practice, a number of TCI systems have been developed for popular IVA drugs (Beths 2008; Sneyd 2004), but, in veterinary practice, research towards development of TCI system for propofol has only been conducted for dogs (Beths 2008; Joubert 2009). Ideally, the effect of a selected drug and the dose or plasma concentration at which the effect occurs should be known (Mama 2006). However, administration of intravenous anaesthetic drugs by the TCI technique is still a far-fetched wish in ruminant anaesthesia practice because of unavailability of infusion systems and limited population pharmacokinetics of suitable drugs (Hatschbach et al. 2008). The rate of intravenous anaesthetic drug administration will continue to be influenced by less sophisticated and cheaper equipment for years to come in veterinary practice.
Drugs available for prolonged intravenous anaesthesia in goats
To avoid misunderstandings, prolonged intravenous anaesthesia is defined, in this review article, as an anaesthetic procedure lasting at least 60 min, or long enough to require a drug or drugs to be topped up more than once to maintain general anaesthesia at a desired level.
For an anaesthetic drug to be deemed suitable for prolonged IVA it should, (1) be stable in solution, (2) water soluble, (3) lipid soluble and potent as an anaesthetic agent, (4) have a rapid onset of action, (5) have few adverse effects, (6) be rapidly cleared from body tissues and (7) cause short, smooth and predictable recovery from anaesthesia (Beths 2008;
Dzikiti 2010; Joubert 2009; McKenzi 2008). Based on these criteria, drugs that can currently be used in prolonged IVA include general anaesthetics (propofol, ketamine, alfaxalone), opioids (fentanyl, remifentanil), benzodiazepines (diazepam, midazolam) and some anaesthetic adjuncts (lidocaine, glycerol guaicolate). In food animals such as goats, it is essential for administered drugs to have short half-lives to ensure short withdrawal times and that way restrict presence of excess drug residues in meat or milk to a very short period of time (Fajt 2011).
General anaesthetic agents for intravenous anaesthesia in goats
Goats are not amongst the commonly anaesthetised animals, which is partly why information on goat anaesthesia is scarce. General anaesthesia can be induced in goats using the same drugs commonly used in other species. These induction agents include thiopentone, propofol and ketamine, which can be administered with or without premedication at dosages of 5 mg/kg - 20 mg/kg, 3 mg/kg - 7 mg/kg and 4 mg/kg - 15 mg/kg, respectively (Dzikiti et al. 2010; Dzikiti et al. 2009; Galatos 2011; Prassinos, Galatos & Raptopoulos 2005; Taylor 1991). It is recommended to premedicate goats so that they are calm before administering these induction agents (Galatos 2011). Once induced, goats should have their tracheas intubated with a cuffed endotracheal tube to protect against aspiration of regurgitated ruminal contents (Dzikiti 2010; Galatos 2011; Reid et al. 1993; Taylor 1991). Of these induction agents, propofol and possibly ketamine possess pharmacokinetic profiles that make them suitable for TIVA for maintenance of general anaesthesia in goats.
Propofol provides a rapid and smooth onset of induction that easily facilitates intubation in the goat (Dzikiti et al. 2010; Dzikiti et al. 2009; Larenza et al. 2005; Prassinos et al. 2005; Reid et al. 1993). Propofol causes induction apnoea more frequently than other general anaesthetics (Bettschart-Wolfensberger et al. 2000; Carroll et al. 1998; Langley & Heel 1988; Pablo, Bailey & Ko 1997), especially if administered too rapidly and at a high dose (Galatos 2011). Propofol causes dose-dependent cardiovascular and respiratory depression, implying a need to monitor these systems and take necessary corrective measures (intravenous fluid infusion, ventilation support) if required (Hodgkinson & Dawson 2007). Rapid metabolism and high body clearance make propofol suitable for IVA in goats either by intermittent incremental boluses or continuous infusion (Reid et al. 1993). In goats, propofol can be administered for TIVA on its own at a dose of 0.3 mg/kg/min - 0.6 mg/kg/min (12 mg/kg/h -36 mg/kg/h), or in combination with other anaesthetic drugs at lower dosages adjusted to the effect required (Carroll et al. 1998; Dzikiti et al. 2010; Dzikiti, Stegmann, Cromarty, Dzikiti & Hellebrekers 2011; Larenza et al. 2005). Propofol should be combined with analgesic drugs in anaesthesia protocols for noxious procedures because it is devoid of any substantial analgesic effects (Beths 2008; Langley & Heel 1988; Sneyd 2004).
Ketamine is a commonly used general anaesthetic agent in veterinary practice that has recently gained greater popularity because of its suitability for use as an analgesic agent to prevent development of chronic pain when administered at sub-anaesthetic doses by continuous infusion (Valverde & Gunkel 2005; White, Way & Trevor 1982). It is a dissociative anaesthetic agent which has major advantages in comparison with other general anaesthetic agents because it mildly stimulates cardiovascular function via sympathomimetic effects and also provides analgesia as already stated (White et al. 1982). The major drawback with ketamine is inability to relax skeletal muscles, which has given rise to a need to always co-administer it with benzodiazepines to facilitate adequate muscle relaxation to enable intubation and minimise muscle excitation (Ghurashi et al. 2009; Prassinos et al. 2005). Ketamine causes less induction apnoea and respiratory depression in comparison with propofol in goats (Prassinos et al. 2005). Ketamine possesses most of the characteristics required for suitability for continuous IVA, lending itself well for field anaesthesia, but is longer acting and slightly more cumulative than propofol (Hodgkinson & Dawson 2007). Goats regain the swallowing reflex after more than 11 min following an intravenous bolus of ketamine (Prassinos et al. 2005), in comparison with less than 5 min following a bolus of propofol (Dzikiti et al. 2009; Prassinos et al. 2005). Ketamine is used extensively in dogs (Aguado, Benito & Gomez de Segura 2011; Wilson et al. 2008) and horses (Enderle et al. 2008; Kruger & Stegmann 2009; Vallaba, Santiago & Gomez de Segura 2011) in sub-anaesthetic doses for partial intravenous anaesthesia (PIVA), but there are very few scientific reports on its use for the same purpose in goats. Previous studies report administration of ketamine for PIVA at doses of 0.03 mg/kg/min - 0.05 mg/kg/min (1.8 mg/kg/h - 3.0 mg/kg/h) in goats (Doherty et al. 2007; Larenza et al. 2005). Studies in other species have demonstrated that the major metabolic product of ketamine, norketamine, possesses significant anaesthetic effects, but has a shorter half-life than racemic ketamine (Hijazi & Boulieu 2002; Larenza et al. 2007). Following prolonged intravenous infusion, this active metabolite might accumulate and result in more pronounced anaesthetic effects. It is prudent therefore to monitor depth of anaesthesia carefully and consider reducing the infusion rate during very long ketamine infusions.
Alfaxalone (previously a component of saffan)
Intravenous administration of alfaxalone is characterised by a rapid onset of action, rapid redistribution and a short terminal half-life (Ferre et al. 2006; Suarez et al. 2012). It fulfils most properties of an ideal intravenous infusion anaesthetic agent and has several advantages over other drugs, including a very high therapeutic index that is even greater than that of propofol (Muir et al. 2008). Alfaxalone has recently been used as an induction agent in sheep (Andaluz et al. 2012). In that study, alfaxalone administered as an intravenous bolus at 2 mg/kg produced minimal adverse effects and uneventful recovery from anaesthesia. The few publications leaning towards alfaxalone in goats (Amer et al. 1989, 1990; Camburn 1982; Gibbons 1986) are outdated, as they are based on saffan, which has since been discontinued because of the histamine release that was linked to its stabiliser (Child et al. 1971; Dodman 1980; Sear et al. 1983). Alfaxalone was first introduced in 1971 as althesin and saffan, which were composed of a mixture of the two neurosteroids, alfaxalone and alfadolone acetate (Child et al. 1971; Sear et al. 1983), solubilised in 20% polyethoxylated castor oil (Cremophor-EL). A new formulation has since been developed for use in dogs and cats from alfaxalone (without alfadolone) solubilised in 2-hydroxypropyl-beta cyclodextrin (HPCD) (Ferre et al. 2006; Suarez et al. 2012). In future, alfaxalone could become useful for prolonged IVA in goats as well, if more research-based data on its pharmacokinetic profile in this species become available and its cost decreases.
Thiopentone's pharmacokinetic profile makes it unsuitable for prolonged IVA. Maintaining general anaesthesia with thiopentone for any longer than 15 min progressively results in its accumulation in body tissues, which might result in delayed recovery from anaesthesia (Galatos 2011). For this reason, thiopentone should be used only for intravenous induction that would be followed by maintenance of general anaesthesia with other anaesthetic drugs, usually inhalation anaesthetic agents (Taylor 1991).
Sedative and analgesic agents for intravenous anaesthesia in goats
Opioids are used extensively for premedication, for analgesic supplementation during regional and general anaesthesia, as primary anaesthetic agents and as analgesics for postoperative pain (Clutton 1998; Stanski 2000). Whilst many opioids of high analgesic potency are suitable for prolonged IVA, fentanyl is currently commonly preferred in veterinary practice as it offers clinically desirable effects over a wide dose range and has a wide therapeutic margin (Mama 2006). Fentanyl, a synthetic µ-opioid agonist, is commonly used for the treatment of moderate to severe pain (Carroll et al. 1999; Lamont & Mathews 2007; Plumb 2005).
The onset of action of fentanyl is rapid following intravenous administration, with analgesia, sedation, ataxia, respiratory depression and hyperaesthesia developing in 3 min - 8 min (Carroll et al. 1999; Lamont & Mathews 2007). It has a short duration of action, with the peak effect lasting less than 30 min (Carroll et al. 1999; Lee, Papich & Hardie 2000).
Fentanyl has been administered intravenously as an adjunct to general anaesthetic drugs at doses of 0.002 mg/kg/h -0.030 mg/kg/h in mechanically ventilated goats and at 0.020 mg/kg/h in spontaneously breathing goats without severely affecting vital physiological functions, although some insignificant signs of excitement (specifically tail-wagging) were observed at high dose rates (Andel et al. 2000; Dzikiti et al. 2010; Dzikiti, Stegmann, Dzikiti & Hellebrekers 2011a). Studies in humans and dogs have shown that fentanyl alone does not result in complete general anaesthesia, but can be combined with benzodiazepines or sub-anaesthetic doses of a general anaesthetic agent such as propofol to achieve satisfactory levels of general anaesthesia (Carroll et al. 1999; Stanski 2000).
The plasma concentration of fentanyl declines mainly as a result of redistribution to a large volume following a single bolus or a brief intravenous infusion (Mani & Morton 2010; Roberts & Freshwater-Turner 2007). If fentanyl is administered at a constant rate for a period longer than 3 h in humans, it attains a steady state (elimination occurring at the same rate as administration), in which case redistribution becomes less important and a rise in context-sensitive half-life (plasma half-life after a specified period of time) ensues (Roberts & Freshwater-Turner 2007). It is therefore not recommended to administer fentanyl at a constant rate for periods longer than 3 h, but rather by the TCI technique to avoid fentanyl accumulation in tissues (Mani & Morton 2010; Roberts & Freshwater-Turner 2007). For opioids with small volumes of distribution, such as remifentanil, redistribution is very limited and the context-sensitive half-life changes very little even after very long periods of CRI (Roberts & Freshwater-Turner 2007; Sneyd 2004).
Benzodiazepines: Midazolam and Valium
Midazolam and diazepam are the most commonly used benzodiazepines (Galatos 2011; Posner 2007). Both benzodiazepines are fast-acting with short elimination half-lives (Lemke 2007; Posner 2007) making them suitable for prolonged IVA. Being water-soluble, midazolam can be administered by the intramuscular route as well as the intravenous route as it is non-irritant to tissues, unlike diazepam (Kanto 1985; Posner 2007). Diazepam, being insoluble in water, is delivered in propylene glycol, an organic solvent that causes pain with subcutaneous, intramuscular and intravenous injections and makes absorption after subcutaneous or intramuscular administration unpredictable (Posner 2007). Midazolam also has a shorter context-sensitive half-life than diazepam making it a better choice for prolonged IVA (Posner 2007). For premedication in goats, both midazolam and diazepam are usually administered at doses of 0.1 mg/kg - 0.5 mg/kg (Dzikiti et al. 2009; Ghurashi et al. 2009; Lemke 2007). Benzodiazepines cause mild and transient cardiovascular and respiratory effects and are commonly used as mild tranquillisers, potent muscle relaxants and anticonvulsants (Galatos 2011; Lemke 2007). The sedative and hypnotic effects of benzodiazepines are dose-dependent, with hypnosis attainable at intravenous doses of about 0.6 mg/kg following midazolam administration (Stegmann & Bester 2001). Midazolam has been administered intravenously as an adjunct to general anaesthetic drugs at doses of 0.1 mg/kg/h - 0.9 mg/kg/h in mechanically ventilated goats and at 0.3 mg/kg/h in spontaneously breathing goats, without adversely affecting vital physiological functions (Dzikiti et al. 2010; Dzikiti, Stegmann, Dzikiti & Hellebrekers 2011b).
Alpha-2 adrenergic agonists
Use of α2-adrenoceptor agonists in small ruminants is highly controversial at the moment. Development of profound hypoxaemia in goats, but especially in sheep, has been documented with anaesthetic protocols that included α2-adrenoceptor agonists such as xylazine, romifidine, detomidine and medetomidine (Celly et al. 1997; Kumar & Thurmon 1979; Mogoa, Stegmann & Guthrie 2000). For this reason, it is recommended to exercise caution when using these drugs in small ruminants (Carroll et al. 2005; Galatos 2011). Because the suitability of use of (α-adrenoceptor agonists in goats is currently debatable, the author decided not to include literature on IVA with these drugs in goats in this review.
Intravenous anaesthesia adjuncts
In addition to the drugs discussed above, there are other non-anaesthesia specific drugs that can be incorporated into TIVA protocols for specific purposes in goats. Lidocaine and glycerol guaicolic ether (GGE) are amongst these adjuncts.
Lidocaine is traditionally used as a local analgesic and anti-arrhythmic agent (Cassutto & Gfeller 2003; Gintant, Hoffman & Naylor 1983), but has lately been administered by intravenous infusion in various species as an antioxidant and inflammatory modulator useful in preventing reperfusion injury (Cassutto & Gfeller 2003) and for reduction of requirements of inhalation anaesthetic agents during general anaesthesia in various species, including rats (DiFazio, Niederlehner & Burney 1976), ponies (Doherty & Frazier 1998), horses (Dzikiti, Hellebrekers & Van Dijk 2003), dogs (Mannarino et al. 2012; Valverde et al. 2004), cats (Pypendop & IIkiw 2005) and calves (Vesal et al. 2011). Intravenously administered lidocaine depresses the central nervous system, specifically causing sedative, analgesic and anti-epileptic effects (Rademaker & De Vries 2008). In goats, intravenous lidocaine, administered as a bolus dose at 2.5 mg/kg followed by a CRI dose of 6.0 mg/kg/h, was reported to cause a clinically significant reduction in the concentration of isoflurane required for maintenance of general anaesthesia (Doherty et al. 2007).
Glycerol guaicolate is a central-acting muscle relaxant with a role in equine and bovine anaesthesia that is similar to that of the benzodiazepines (Galatos 2011; Hall et al. 2001; Riebold 2007). It is usually used in combination with induction agents such as ketamine to induce and maintain IVA of short duration (less than 1 h) (Riebold 2007). When it is administered for muscle relaxation just before induction of anaesthesia, the dose of GGE is about 50 mg/kg, whilst the infusion rate for PIVA is 50 mg/kg/h - 100 mg/kg/h (Hall et al. 2001; Riebold 2007). Endotracheal intubation and oxygen supplementation are recommended when GGE-incorporating anaesthetic protocols are used to minimise development of respiratory depression and hypoxaemia (Hall et al. 2001; Riebold 2007). Not much scientific information exists at present on the effects of GGE in goats, but its profile makes it suitable for continuous PIVA of short duration (up to 1 h long) if artificial ventilation cannot be provided.
Drug combinations for total intravenous anaesthesia in goats
In practical terms, the groups of drugs described above as suitable for IVA in goats can be used to achieve TIVA-based, balanced anaesthesia by utilising specific combinations to target individual components of the anaesthetic state (unconsciousness, analgesia, muscle relaxation) to achieve any desired purpose of anaesthesia in goats. Unconsciousness can be obtained from the propofol and ketamine, analgesia from fentanyl, ketamine and lidocaine, and muscle relaxation from benzodiazepines and possibly GGE. For TIVA in goats, propofol or ketamine can be combined with midazolam and fentanyl for both induction and maintenance of general anaesthesia. Table 1 summarises the dosages at which these drugs can be administered for the initial bolus and subsequent intermittent boluses or continuous infusion.
Monitoring the total intravenous anaesthesia -anaesthetised goat
Anaesthetised goats should be carefully monitored to ensure an appropriate anaesthetic depth and assessment of associated peri-anaesthetic complications, mostly involving the digestive system (tympany, regurgitation, excessive salivation) and the cardiorespiratory system (choking, hypercarbia, hypotension, hypoxaemia) (Galatos 2011; Taylor 1991). An appropriately anaesthetised goat may display sluggish palpebral and pedal reflexes as well as stable autonomic responses (Galatos 2011; Garcia 2012). If a goat is too deeply anaesthetised, the palpebral reflex and even corneal reflex will be absent, the cornea will dry up and severe bradypnoea and even apnoea may be observed. On the other hand, a lightly anaesthetised goat might blink, lachrymate, vocalise, salivate excessively, breathe more rapidly, swallow or even move its extremities (Galatos 2011; Garcia 2012). The rate of administration of intravenous drugs for maintenance of general anaesthesia should be guided by the signs of anaesthetic depth displayed by individual patients and not necessarily by known theoretical infusion rates.
Other basic parameters that can be monitored include heart rate, colour of the mucous membranes, capillary refill time, respiratory rate and body temperature (Galatos 2011; Garcia 2012; Taylor 1991). Symptomatic corrective therapy, which might include oxygen, fluids, electrolytes, specific drugs and patient therapy, should be instituted, where necessary, especially to ensure that circulation, respiration and body temperature stay within normal physiologic limits (Galatos 2011; Garcia 2012; Taylor 1991). During recovery from general anaesthesia, it is still essential to monitor the goat throughout, especially to avoid complications associated with the digestive and respiratory systems. The goat should be supported to sternal recumbency and the endotracheal tube only removed after the swallowing and coughing reflexes return (Galatos 2011; Garcia 2012; Taylor 1991).
This is a literature review article summarising observations from several scientific papers that were published in journals that require that the involvement of animals in research be conducted in accordance with relevant national and international ethical guidelines and that the research protocols be approved by the authors' institutional and relevant ethics committee.
General anaesthesia is used to produce unconsciousness, analgesia and muscle relaxation, but might also suppress autonomic reflex activities and consequently lead to inadequate function of vital physiological systems such as the cardiovascular and respiratory system (Antognini & Carstens 2002; Rees & Gray 1950). Use of inhalation anaesthetic agents to maintain general anaesthesia is associated with dose-dependent depression of the cardiopulmonary systems (Antognini & Eisele 1993; Hall et al. 2001; Hikasa et al. 2002).
Balanced anaesthesia, a technique in which several drugs are combined at reduced dosages to decrease adverse effects of each drug, is used to limit cardiopulmonary depression associated with use of inhalation anaesthetic agents at high dosages to maintain general anaesthesia (Toner 2005). Incorporation of intravenous anaesthetic drugs in goat anaesthetic protocols would go a long way towards attaining balanced anaesthesia because the currently available inhalation anaesthetic agents do not have any significant muscle-relaxing or analgesic effects in goats. When applying balanced anaesthesia techniques, it is important to define the purpose of each drug used. Recent scientific papers have provided information on dosages of some drugs that can be successfully utilised for prolonged IVA in goats. It is envisaged that future scientific research will be conducted to provide more information on pharmacokinetic and pharmacodynamics profiles of currently suitable IVA drugs and other potential IVA drugs such as alfaxalone and remifentanil in goats.
The University of Pretoria is acknowledged for providing the technical resources and time that made it possible for me to gather the scientific information used in this article. My wife, Loveness, and my two children, Kayla and Carlin, are also greatly appreciated for their moral support and understanding during the time that I was away from them whilst preparing this article.
The author declares that he has no financial or personal relationships which may have inappropriately influenced him in writing this article.
Aguado, D., Benito, J. & Gömez de Segura, I.A., 2011, 'Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl', Veterinary Journal 189, 63-66. http://dx.doi.org/10.1016/j.tvjl.2010.05.029, PMid:20594878 [ Links ]
Amer, H.A., Ahmed, A.S., Gohar, H.M. & Abdel Mamid, M.A., 1989, 'Effects of steroid anaesthesia on some liver function tests in goats', Journal of Steroid Biochemistry 32, 475-476. http://dx.doi.org/10.1016/0022-4731(89)90225-2 [ Links ]
Amer, H.A., Ahmed, A.S., Gohar, H.M. & Abdel Mamid, M.A., 1990, 'Biochemical effect of steroid anaesthesia on some liver function tests in goats', Archiv fur Experimentelle Veterinärmedizin 44, 361-366. PMid:2241474 [ Links ]
Andaluz, A., Felez-Ocana, N., Santos, L., Fresno, L. & Garcia, F., 2012, 'The effects on cardio-respiratory and acid-base variables of the anaesthetic alfaxalone in a 2-hydroxypropyl-β-cyclodextrin (HPCD) formulation in sheep', Veterinary Journal 191, 389-392. http://dx.doi.org/10.1016/j.tvjl.2011.03.017, PMid:21543243 [ Links ]
Andel, H., Bayer, G.S., Ciovica, R., Monsivais, J., Bacso, M., Zimpfer, M. et al., 2000, 'Depressive effect of isoflurane on motor evoked potentials in the Nubian goat', Canadian Journal of Anaesthesia 47, 81-86. http://dx.doi.org/10.1007/BF03020739 PMid:10626726 [ Links ]
Antognini, J.F. & Carstens, E., 2002, 'In vivo characterization of anaesthesia and its components', British Journal of Anaesthesia 89, 156-166. http://dx.doi.org/10.1093/bja/aef156, PMid:12173227 [ Links ]
Antognini, J.F. & Eisele, P.H., 1993, 'Anaesthetic potency and cardiopulmonary effects of enflurane, halothane and isoflurane in goats', Laboratory Animal Science 43, 607-610. PMid:8158989 [ Links ]
Askitopoulou, H., Ramoutsaki, I.A. & Konsolaki, E., 2000, 'Analgesia and anesthesia: Etymology and literary history of related Greek words', Anesthesia Analgesia 91, 486-491. PMid:10910873 [ Links ]
Beths, T., 2008, 'Total intravenous anaesthesia in dogs: Development of a target-controlled infusion (TCI) scheme for propofol', PhD thesis, Department of Companion Animal Sciences, University of Glasgow, viewed 14 June 2012, from http://theses.gla.ac.uk/354/01/2008bethsphd.pdf [ Links ]
Bettschart-Wolfensberger, R., Semder, A., Alibhai, H., Demuth, D., Aliabadi, F.S. & Clarke, K.W., 2000, 'Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (Disoprivan) in comparison to propofol solved in polysorbate 80 in Goats', Journal of Veterinary Medicine A 47, 341-350. http://dx.doi.org/10.1046/j.1439-0442.2000.00289.x [ Links ]
Carroll, G.L., Hartsfield, S.M., Champney, S.M., Geller, S.C., Martinez, E.A. & Haley, E.L., 2005, 'Effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and mechanical threshold in goats', Veterinary Anaesthesia and Analgesia 32, 147-157. http://dx.doi.org/10.1111/j.1467-2995.2005.00187.x, PMid:15877661 [ Links ]
Carroll, G.L., Hartsfield, S.M. & Hambleton, R., 1997, 'Anesthetic effects of tiletamine-zolazepam, alone or in combination with butorphanol, in goats', Journal of the American Veterinary Medical Association 211, 593-597. PMid:9290827 [ Links ]
Carroll, G.L., Hooper, R.N., Boothe, D.M., Hartsfield, S.M. & Randoll, L.A., 1999, 'Pharmacokinetics of fentanyl after intravenous and transdermal administration in goats', American Journal of Veterinary Research 60, 986-991. PMid:10451210 [ Links ]
Carroll, G.L., Hooper, R.N., Slater, M.R., Hartsfield, S.M. & Matthews, N.S., 1998, 'Detomidine-butorphanol-propofol for carotid artery translocation and castration or ovariohysterectomy in goats', Veterinary Surgery 27, 75-82. http://dx.doi.org/10.1111/j.1532-950X.1998.tb00101.x, PMid:9449181 [ Links ]
Cassutto, B.H. & Gfeller, R.W., 2003, 'Use of intravenous lidocaine to prevent reperfusion injury and subsequent multiple organ dysfunction syndrome', Journal of Veterinary Emergency and Critical Care 13, 137-148. http://dx.doi.org/10.1046/j.1435-6935.2003.00080.x [ Links ]
Celly, C.S., McDonell, W.N., Young, S.S. & Black, W.D., 1997, 'The comparative effect of four α2-adrenoceptor agonists (xylazine, romifidine, detomidine and medetomidine) in sheep', Journal of Veterinary Pharmacology and Therapeutics 20, 464-471. http://dx.doi.org/10.1046/j.1365-2885.1997.00097.x, PMid:9430770 [ Links ]
Child, K.J., Currie, J.P., Dis, B., Dodds, M.G., Pearce, D.R. & Twissell, D.J., 1971, 'The pharmacological properties in animals of CT1341 - A new steroid anaesthetic agent', British Journal of Anaesthesia 43, 2-13. http://dx.doi.org/10.1093/bja/43.1.2-a, PMid:4251319 [ Links ]
Clutton, R.E., 1998, 'New drugs in companion animal anesthesia', Waltham Focus 8, 9-16. [ Links ]
DiFazio, C.A., Niederlehner, J.R. & Burney, R.G., 1976, 'The anesthetic potency of lidocaine in the rat', Anesthesia and Analgesia 55, 818-821. http://dx.doi.org/10.1213/00000539-197611000-00016, PMid:1033700 [ Links ]
Doherty, T.J. & Frazier, D.L., 1998, 'Effect of lidocaine on halothane minimum alveolar concentration in ponies', Equine Veterinary Journal 30, 300-303. http://dx.doi.org/10.1111/j.2042-3306.1998.tb04101.x, PMid:9705112 [ Links ]
Doherty, T., Redua, M.A., Queiroz-Castro, P., Egger, C., Cox, S.K. & Rohrbach, B.W., 2007, 'Effect of intravenous lidocaine and ketamine on the minimum alveolar concentration of isoflurane in goats', Veterinary Anaesthesia and Analgesia 34, 125-131. http://dx.doi.org/10.1111/j.1467-2995.2006.00301.x, PMid:173 1 6393 [ Links ]
Dundee, J.W. & McMurray, T.J., 1984, 'Clinical aspects of total intravenous anaesthesia: Discussion paper', Journal of the Royal Society of Medicine 77, 669672. PMid:6148418 [ Links ]
Dzikiti, T.B., 2010, 'Total intravenous anaesthesia (TIVA) in goats', PhD thesis, Department of Companion Animal Clinical Studies, University of Pretoria, viewed 12 June 2012, from http://upetd.up.ac.za/thesis/available/etd-05312011-150533/ [ Links ]
Dzikiti, T.B., Hellebrekers, L.J. & Van Dijk, P., 2003, 'Effects of intravenous lidocaine on isoflurane concentration, physiological parameters, metabolic parameters and stress-related hormones in horses undergoing surgery', Journal of Veterinary Medicine A 50, 190-195. http://dx.doi.org/10.1046/j.1439-0442.2003.00523.x [ Links ]
Dzikiti, T.B., Stegmann, G.F., Dzikiti, L.N. & Hellebrekers, L.J., 2010, 'Total intravenous anaesthesia (TIVA) with propofol-fentanyl and propofol-midazolam combinations in spontaneously breathing goats', Veterinary Anaesthesia and Analgesia 37, 519-525. http://dx.doi.org/10.1111/j.1467-2995.2010.00568.x, PMid:21072973 [ Links ]
Dzikiti, T.B., Stegmann, G.F., Dzikiti, L.N. & Hellebrekers, L.J., 2011a, 'Effects of fentanyl on isoflurane minimum alveolar concentration and cardiovascular function in mechanically-ventilated goats', Veterinary Record 168, 429. http://dx.doi.org/10.1136/vr.d999, PMid:21493442 [ Links ]
Dzikiti, T.B., Stegmann, G.F., Dzikiti, L.N. & Hellebrekers, L.J., 2011b, 'Effects of midazolam on isoflurane minimum alveolar concentration and cardiovascular function goats', Small Ruminant Research 97, 104-109. http://dx.doi.org/10.1016/j.smallrumres.2011.01.011 [ Links ]
Dzikiti, T.B., Stegmann, G.F., Hellebrekers, L.J. & Dzikiti, L.N., 2009, 'Sedative and cardiopulmonary effects of acepromazine, midazolam, butorphanol, acepromazine-butorphanol and midazolam-butorphanol on propofol anaesthesia in goats', Journal of the South African Veterinary Association 80, 10-16. PMid:19653513 [ Links ]
Dzikiti, T.B., Stegmann, G.F., Cromarty, D., Dzikiti, L.N. & Hellebrekers, L.J., 2011, 'Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats', Veterinary Anaesthesia and Analgesia 38, 44-53. http://dx.doi.org/10.1111/j.1467-2995.2010.00585.x, PMid:21214709 [ Links ]
Enderle, A.K., Levionnois, O.L., Kuhn, M. & Schatzmann, U., 2008, 'Clinical evaluation of ketamine and lidocaine intravenous infusions to reduce isoflurane requirements in horses under general anaesthesia', Veterinary Anaesthesia and Analgesia 35, 297-305. http://dx.doi.org/10.1111/j.1467-2995.2007.00391.x, PMid:19522888 [ Links ]
Ferre, P.J., Pasloske, K., Whittem, T., Ranasinghe, M., Li, Q. & Lefebvre, H.P., 2006, 'Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU', Veterinary Anaesthesia and Analgesia 33, 229-236. http://dx.doi.org/10.1111/j.1467-2995.2005.00264.x, PMid:16764587 [ Links ]
Fulton, L.K., Clarke, M.S. & Farris, H.E., 1994, 'The goat as a model for biomedical research and teaching', Institute for Laboratory Animal Research 36, 21-29. [ Links ]
Garcia, M., 2012, Laboratory animal anesthesia and analgesia, viewed 29 October 2012, from http://www.research.ucsb.edu/compliance/animal-subjects/veterinary-care/laboratory-animal-anesthesia-and-analgesia/ [ Links ]
Ghurashi, M.A.H., Seri, H.I., Bakheit, A.H., Ashwag, E.A.M. & Abakar, J.A., 2009, 'Evaluation of ketamine/diazepam anaesthesia for performing surgery in desert goats under field conditions', Australian Journal of Basic and Applied Sciences 3, 455-459. [ Links ]
Gintant, G.A., Hoffman, B.F. & Naylor, R.E., 1983, 'The influence of molecular form of local anesthetic-type antiarrhythmic agents on reduction of minimum upstroke velocity of canine Purkinje fibers', Circulation Research 52, 735-746. http://dx.doi.org/10.1161/01.RES.52.6.735, PMid:6305532 [ Links ]
Griffith, H.R., 1934, 'John Snow, pioneer specialist in anesthesia', Anesthesia and Analgesia 13, 45. http://dx.doi.org/10.1213/00000539-193401000-00019 [ Links ]
Hall, L.W., Clarke, K.W. & Trim, C.M., 2001, Veterinary anaesthesia, 10th edn., WB Saunders, London. [ Links ]
Harvinder, S.G. & Prausnitz, M.R., 2007, 'Does size matter?', Journal of Diabetes Science and Technology 1, 725-729. [ Links ]
Hasley, M.J., 1991, 'Occupational health and pollution from anaesthetics. A report of a seminar', Anaesthesia 46, 486-488. http://dx.doi.org/10.1111/j.1365-2044.1991.tb11692.x [ Links ]
Hatschbach, E., Silva, F.C., Beier, S.L., Lima, A.F. & Massone, F., 2008, 'Comparative study between target-controlled infusion and continuous-infusion anesthesia in dogs treated with methotrimeprazine and treated with propofol and remifentanil', Acta Cirurgica Brasileira 23, 65-72. http://dx.doi.org/10.1590/S0102-86502008000100011, PMid:18278395 [ Links ]
Hijazi, J. & Boulieu, R., 2002, 'Contribution of CYP3A4, CYP2B6 and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes', Drug Metabolism and Disposition 30, 853-858. http://dx.doi.org/10.1124/dmd.30.7.853, PMid:12065445 [ Links ]
Hikasa, Y., Hokushini, S., Takase, K. & Ogasawara, S., 2002, 'Cardiopulmonary, haematological, serum biochemical and behavioural effects of sevoflurane compared with isofurane or halothane in spontaneously ventilating goats', Small Ruminant Research 43, 167-178. http://dx.doi.org/10.1016/S0921-4488(02)00002-0 [ Links ]
Hofer, C.K., Zollinger, A., Buchi, S., Klaghofer, R., Serafino, D., Buhlmann, S. et al., 2003, 'Patient well-being after general anaesthesia: A prospective, randomized, controlled multi-centre trial comparing intravenous and inhalation anaesthesia', British Journal of Anaesthesia 91, 631-637. http://dx.doi.org/10.1093/bja/aeg243, PMid:14570783 [ Links ]
Joubert, K.E., 2009, 'Computer simulations of propofol infusions for total intravenous anaesthesia in dogs', Journal of the South African Veterinary Association 80, 2-9. PMid:19653512 [ Links ]
Kanto, J.H., 1985, 'Midazolam: The first water-soluble benzodiazepine. Pharmacology, pharmacokinetics and efficacy in insomnia and anesthesia', Pharmacotherapy 5, 138-155. PMid:3161005 [ Links ]
Kravetz, R.E., 2005, 'Hypodermic syringe', American Journal of Gastroenterology 100, 2614-2615. http://dx.doi.org/10.1111/j.1572-0241.2005.00397.x, PMid:16393208 [ Links ]
Kruger, K. & Stegmann, G.F., 2009, 'Partial intravenous anaesthesia in 5 horses using ketamine, lidocaine, medetomidine and halothane', Journal of the South African Veterinary Association 80, 233-236. PMid:20458864 [ Links ]
Kumar, A. & Thurmon, J.C., 1979, 'Cardiopulmonary, haematocytologic and biochemical effects of xylazine in goats', Laboratory Animal Science 29, 486-491. PMid:513619 [ Links ]
Lamont, A. & Mathews, K.A., 2007, 'Opioids, non-steroidal anti-inflammatories, and analgesic adjuvants', in W.J. Tranquilli, J.C. Thurmon & K.A. Grimm (eds.), Lumb and Jones's veterinary anaesthesia and analgesia, 4th edn., pp. 241-271, Blackwell Publishing, Ames. [ Links ]
Langley, M.S. & Heel, R.C., 1988, 'Propofol: A review of its pharmacodynamics and pharmacokinetic properties and use as an intravenous anaesthetic', Drugs 35, 334372. http://dx.doi.org/10.2165/00003495-198835040-00002, PMid:3292208 [ Links ]
Larenza, M.P., Bergadano, A., Iff, I., Doherr, M.G. & Schatzmann, U., 2005, 'Comparison of the cardiopulmonary effects of anaesthesia maintained by continuous infusion of ketamine and propofol with anaesthesia maintained by inhalation of sevoflurane in goats undergoing magnetic resonance imaging', America Journal of Veterinary Research 66(12), 2135-2141. http://dx.doi.org/10.2460/ajvr.2005.66.2135, PMid:16379659 [ Links ]
Larenza, M.P., Landoni, M.F., Levionnois, O.L., Knobloch, M., Kronen, P.W., Theurillat, R. et al., 2007, 'Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies', British Journal of Anaesthesia 98, 204-212. http://dx.doi.org/10.1093/bja/ael336, PMid:17218377 [ Links ]
Lee, D.D., Papich, M.G. & Hardie, E.M., 2000, 'Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats', America Journal of Veterinary Research 61, 672-677. http://dx.doi.org/10.2460/ajvr.2000.61.672, PMid:10850844 [ Links ]
Lemke, K.A., 2007, 'Anticholinergics and sedatives', in W.J. Tranquilli, J.C. Thurmon & K.A. Grimm (eds.), Lumb and Jones's veterinary anaesthesia and analgesia, 4th edn., pp. 203-239, Blackwell Publishing, Ames. [ Links ]
Mama, K., 2006, 'Clinical application of pharmacokinetics for balanced anaesthesia in small and large animals', 9th World Congress of Veterinary Anaesthesia 2006 proceedings, Santos SP, Brazil, 12-16 September 2006, pp. 89-91. [ Links ]
Mani, V. & Morton, N.S., 2010, 'Overview of total intravenous anaesthesia in children', Pediatric Anesthesia 20, 211-222. [ Links ]
Mannarino, R., Luna, S.P.L., Monteiro, E.R., Beier, S.L. & Castro, V.B., 2012, 'Minimum infusion rate and haemodynamic effects of propofol, propofol-lidocaine and propofol-lidocaine-ketamine in dogs', Veterinary Anaesthesia and Analgesia 39, 160-173. http://dx.doi.org/10.1111/j.1467-2995.2011.00679.x, PMid:22248386 [ Links ]
McKenzi, G., 2008, 'Total intravenous anesthesia - TIVA', Iranian Journal of Veterinary Surgery suppl. 2 (2nd ISVS and 7th ISVSAR), 108-117. [ Links ]
Moens, Y., 2004, 'Syringe pumps for anaesthesia/analgesia: Toy or tool?', 29th World Congress of the World Small Animal Veterinary Association proceedings, Rhodes, Greece, 06-09 October 2004, viewed 12 June 2012, from http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2004&PID=8565&Print=1&O=Generic [ Links ]
Mogoa, E.G.M., Stegmann, G.F. & Guthrie, A.J., 2000, 'Effects of xylazine on acid-base balance and arterial blood-gas tensions in goats under different environmental temperature and humidity conditions', Journal of the South African Veterinary Association 71, 229-231. PMid:11212933 [ Links ]
Muir, W., Lerche, P., Wiese, A., Nelson, L., Pasloske, K. & Whittem, T., 2008, 'Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs', Veterinary Anaesthesia and Analgesia 35, 451-462. http://dx.doi.org/10.1111/j.1467-2995.2008.00406.x, PMid:18793290 [ Links ]
Pablo, L.S., Bailey, J.E. & Ko, J.C.H., 1997, 'Median effective dose of propofol required for induction of anaesthesia in goats', Journal of the American Veterinary Medical Association 211, 86-88. PMid:9324507 [ Links ]
Plumb, D.C., 2005, Plumb's veterinary drugbook, 5th edn., PharmaVet Inc., Stockholm. [ Links ]
Posner, L.P., 2007, 'Midazolam or diazepam - Which should I choose in my practice?', viewed 14 February 2008, from http://www.ivis.org/proceedings/navc/2007/SAE/031.asp?LA=1 [ Links ]
Prassinos, N.N., Galatos, A.D. & Raptopoulos, D., 2005, 'A comparison of propofol, thiopental or ketamine as induction agents in goats', Veterinary Anaesthesia and Analgesia 32, 289-296. http://dx.doi.org/10.1111/j.1467-2995.2005.00204.x, PMid:16135210 [ Links ]
Pypendop, B.H. & IIkiw, J.E., 2005, 'The effects of intravenous lidocaine administration on the minimum alveolar concentration of isoflurane in cats', Anesthesia and Analgesia 100, 97-101. http://dx.doi.org/10.1213/01.ANE.0000139350.88158.38, PMid:15616060 [ Links ]
Rademaker, C.M.A. & De Vries, L.S., 2008, 'Pharmacology review: Lidocaine for neonatal seizure management', Neoreviews 9, e585-e589, viewed 22 June 2012, from http://neoreviews.aappublications.org/content/9/12/e585.full.pdf [ Links ]
Reid, J., Nolan, A.M. & Welsh, E., 1993, 'Propofol as an induction agent in the goat: A pharmacokinetic study', Journal of Veterinary Pharmacology and Therapeutics 16, 488-493. http://dx.doi.org/10.1111/j.1365-2885.1993.tb00215.x, PMid:8126766 [ Links ]
Riebold, T.W., 2007, 'Ruminants', in W.J. Tranquilli, J.C. Thurmon & K.A. Grimm (eds.), Lumb and Jones's veterinary anaesthesia and analgesia, 4th edn., pp. 731-746, Blackwell Publishing, Ames. [ Links ]
Roberts, F. & Freshwater-Turner, D., 2007, 'Pharmacokinetics and anaesthesia', Continuing Education in Anaesthesia, Critical Care and Pain 7, 25-29. http://dx.doi.org/10.1093/bjaceaccp/mkl058 [ Links ]
Sear, J.W., Phillips, K.C., Andrews, C.J.H. & Prys-Roberts, C., 1983, 'Dose-response relationships of infusions of althesin or methohexitone', Anesthesia 38, 931. http://dx.doi.org/10.1111/j.1365-2044.1983.tb12021.x [ Links ]
Stanski, D.R., 2000, 'Monitoring depth of anaesthesia', in R.D. Miller, Anaesthesia, 5th edn., pp. 1087-1113, Churchill Livingstone, New York. [ Links ]
Stegmann, G.F. & Bester, L., 2001, 'Sedative-hypnotic effects of midazolam in goats after intravenous and intramuscular administration', Veterinary Anaesthesia and Analgesia 28, 49-55. http://dx.doi.org/10.1046/j.1467-2987.2000.00034.x [ Links ]
Suarez, M.A., Dzikiti, B.T., Stegman, F.G. & Hartman, M., 2012, 'Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs', Veterinary Anaesthesia and Analgesia 39, 236-244. http://dx.doi.org/10.1111/j.1467-2995.2011.00700.x, PMid:22405473 [ Links ]
Vallaba, M., Santiago, I. & Gömez de Segura, I.A., 2011, 'Effects of constant rate infusion of lidocaine and ketamine, with or without morphine on isoflurane minimum alveolar concentration in horses', Equine Veterinary Journal 43, 721726. http://dx.doi.org/10.1111/j.2042-3306.2010.00355.x, PMid:21668490 [ Links ]
Valverde, A. & Doherty, T.J., 2008, 'Anesthesia and analgesia in ruminants', in R. Fish, P.J. Danneman, M. Brown & A. Karas (eds.), Anesthesia and analgesia in laboratory animals, 2nd edn., pp. 385-411, Academic Press, London. http://dx.doi.org/10.1016/B978-012373898-1.50018-8 [ Links ]
Valverde, A., Doherty, T.J., Hernändez, J. & Davies, W., 2004, 'Effect of lidocaine on halothane minimum alveolar concentration in dogs', Veterinary Anaesthesia and Analgesia 31, 264-271. http://dx.doi.org/10.1111/j.1467-2995.2004.00165.x, PMid:15509291 [ Links ]
Valverde, A. & Gunkel, C.I., 2005, 'Pain management in horses and farm animals', Journal of Emergency and Critical Care 15, 295-307. http://dx.doi.org/10.1111/j.1476-4431.2005.00168.x [ Links ]
Vesal, N., Spadavecchia, C., Steiner, A., Kirscher, F. & Levionnois, O.L., 2011, 'Evaluation of the isoflurane-sparing effects of lidocaine infusion during umbilical surgery in calves', Veterinary Anaesthesia and Analgesia 38, 451-460. http://dx.doi.org/10.1111/j.1467-2995.2011.00636.x, PMid:21831050 [ Links ]
Waelbers, T., Vermoere, P. & Polis, I., 2009, 'Total intravenous anaesthesia in dogs. A review', Vlaams Diergeneeskundie Tijdschrift 78, 160-169. [ Links ]
White, P.F., Way, W.L. & Trevor, A.J., 1982, 'Ketamine - Its pharmacology and therapeutic uses', Anesthesiology 56, 119-136. http://dx.doi.org/10.1097/00000542-198202000-00007, PMid:6892475 [ Links ]
Wilson, J., Doherty, T.J., Egger, C.M., Fidler, A., Cox, S. & Rohrbach, B., 2008, 'Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs', Veterinary Anaesthesia and Analgesia 35, 289-296. http://dx.doi.org/10.1111/j.1467-2995.2007.00389.x, PMid:18363578 [ Links ]
Postal address: Private Bag X04
Onderstepoort 0110, South Africa
Received: 28 June 2012
Accepted: 02 Nov. 2012
Published: 13 Feb. 2013