Single and Combination Agents for General Anesthesia

A variety of injectable and inhalant anesthetic agents have been used successfully in goats to achieve chemical restraint or general anesthesia. Each anesthetist seems to prefer a different protocol or combination of drugs.

Short-Acting Barbiturates

Thiopental sodium (5-20 mg/kg in a 2.5% solution given rapidly IV) can be used for induction of anesthesia; ideally the low dose is given initially, with additional small doses given rapidly if the desired effect is not achieved in 30 sec­onds. It produces 30-50 seconds of apnea; intubation is easiest to perform during this period, as long as a stylet is used to stiffen the tube. Thiamylal sodium (Surital*, Parkedale Pharmaceuticals, Rochester, MI, USA) has simi­lar effects at 10 mg/kg (Gray and McDonell 1986b), but is no longer available in the United States. Methohexital sodium (Brevital, Par Pharmaceutical, Dublin, Ireland) at 4 mg/kg IV is said to provide five to seven minutes of anes­thesia (Hall et al. 2001). Excitement during recovery can be avoided by premedication with midazolam, diazepam, medetomidine, or xylazine, and the latter two permit use of a lower barbiturate dose for induction. When xylazine has been used, recovery time to standing is shortened by rever­sal with IV yohimbine at 0.125 mg/kg (Mora et al. 1993) or atipamezole, which is more alpha-2 selective.

Other Barbiturates

The IV dose of pentobarbital for adult goats is 30 mg/kg (Linzell 1964) or 20-30 mg/kg (Clarke et al. 2014). The ani­mal regains its feet in 20-60 minutes unless additional doses to total 6-36 mg/kg per hour are administered. Animals vary in their response to this drug, and recovery may be prolonged. Commercial solutions of pentobarbital often contain propylene glycol, which causes hemolysis and hematuria in goats and sheep (Linzell 1964).

Laryngospasm sometimes occurs shortly after the administration of barbiturates, especially pentobarbital, and particularly during anesthesia of young goats (Bryant 1969). The animal exhibits gasping, ineffective ventilation, and dilated pupils. The emergency requires intubation with a smaller-size tube or an emergency tra­cheostomy. Spraying a local anesthetic on the larynx sim­plifies intubation in this instance.

Xylazine

Xylazine is an excellent drug for sedating goats, although it is not approved for this purpose in the United States. For many minor procedures such as oral and ocular exams, 0.03-0.04 mg/kg IV provides a brief (10 minutes) period of complacency. For painful procedures, it is safest to use a modest dose (0.05 mg/kg IV or 0.10 mg/kg IM) in combination with local analgesia (Gray and McDonell 1986a). Dosages should be calculated carefully; a 20 mg/ mL solution and a tuberculin syringe with a plunger make it easier to draw up the correct quantity, and otherwise beware of extra xylazine in the hub of the needle when the injection is given IV. Alternatively, a 1 mg/mL solu­tion can be prepared in advance by diluting 0.5 mL of 20 mg/mL xylazine in 9.5 mL of saline in a clot tube. The author (MCS) has found that male goats and those with central nervous system diseases such as listeriosis seem to be especially susceptible to overdosing. Salivation, bloat, and hyperglycemia are expected complications whenever xylazine is used. The drug has been shown to cause increased myometrial activity, depression of maternal and fetal heart rates, and marked depression of maternal and fetal arterial oxygen partial pressure (PaO2) when given to late-pregnant Rambouillet cross ewes at a dosage of 10 mg IM. The fetuses recovered within 60 minutes (Jansen et al. 1984). Conservative doses of xylazine are not contraindicated in healthy pregnant goats and are preferable to the stress associated with physically restrain­ing an excited or painful goat.

Doses of xylazine more than 0.15 mg/kg IV are not rec­ommended for sheep and goats, because these doses may cause severe cardiovascular and respiratory depression (Gray and McDonell 1986b). Even at the 0.15 mg/kg dosage, clinically important respiratory depression and hypoxemia have been reported in sheep (Doherty et al. 1986), though less consistently in goats (Kutter et al. 2006). PaO₂ decreases by approximately half, and a paradoxical respiratory rhythm has been observed where the thoracic cage collapses on inspiration. The sheep become cyanotic. Later research in sheep has explained how the hypoxemia develops by dem­onstrating that xylazine at 0.15 mg/kg IV causes damage to the capillary endothelium; intra-alveolar hemorrhage; and interstitial, and alveolar edema, changes that clear within 12 hours (Celly et al. 1999). This is believed to be the result of activation of pulmonary intravascular macrophages that release prostaglandins and other vasoactive substances (Seddighi and Doherty 2016). Dexmedetomidine has a simi­lar effect on the lungs of sheep (Kastner et al. 2007).

The adverse effects of xylazine can be partially reversed by the α₂-adrenergic receptor antagonists yohimbine at 0.125 mg/kg or tolazoline at 1.5 mg/kg IV and administra­tion of oxygen. Yohimbine produces a more rapid and per­sistent reversal of xylazine than does doxapram (0.4 mg/kg IV). Tolazoline may be more effective than yohimbine in ruminants (Gross and Tranquilli 1989). Yohimbine at 0.25 mg/kg in combination with 4-aminopyridine at 0.4 mg/kg, both given IV, is more effective than either drug alone (Ndeereh et al. 2001). Atipamezole is the most α2- adrenergic receptor selective reversal agent available, and is given at a dose of 125-175 pg/kg, half IV and half IM (Matthews 2016).

Ketamine, Ketamine plus Diazepam

Ketamine alone may be used for anesthetic procedures where muscle relaxation is not important (Kellar and Bauman 1978).

Xylazine and Ketamine

Xylazine and ketamine are frequently combined for gen­eral anesthesia in goats when inhalation anesthesia is not available. The period of analgesia is prolonged, but so is the recovery time relative to ketamine alone. A frequently quoted regimen in the older literature is 0.22 mg/kg xyla- zine followed by 11 mg/kg ketamine 10 minutes later; both drugs are given IM (Kumar et al. 1976; Thurmon 1986). Also possible is a single IM injection of 0.22 mg/kg xyla- zine and 11 mg/kg ketamine, although the time until immobilization occurs is increased. Anesthesia lasts approximately 45 minutes and recovery to standing occurs in approximately 90 minutes (Kumar et al. 1983). Increments of 6 mg/kg ketamine are given IM if prolonga­tion of anesthesia is necessary. An IM combination of 0.1 mg/kg xylazine plus 10 mg/kg ketamine is reported to provide 30-40 minutes of surgical anesthesia (Clarke et al. 2014). A decreased IV dosage rate (0.10 mg/kg xyla- zine followed by 5 mg/kg ketamine) is more appropriate for procedures that require 15-20 minutes of anesthesia (Gray and McDonell 1986b).

A xylazine/ketamine/atropine combination has been recommended for disbudding of kids (Pieterse and van Dieten 1995), but is not ideal. The dosages are 0.04 mg/kg xylazine, 10 mg/kg ketamine, and 0.1 mg/kg atropine, all in one IM injection, providing onset of surgical anesthesia in an average of 12 minutes. Note that the combination of xylazine and atropine has been found to cause hyperten­sion and infarction in small animal species, and atropine makes respiratory secretions more viscous. Another IM combination is created by adding 1 mL = 10 mg of butorphanol and 1 mL = 100 mg equine xylazine to a 10 mL vial of 100 mg/mL ketamine. The dose of the cocktail is 1 mL/45 kg IV or 1 ml/23 kg IM. Create a new controlled substance recording form for this vial, to simplify required paperwork.

Time to standing (but not to eating) is shortened by IV administration of 0.25 mg/kg yohimbine and 0.6 mg/kg 4-aminopyridine (Kruse-Elliott et al. 1987). IV tolazoline at 2.1 mg/kg also significantly shortens the period of recum­bency in goats anesthetized with xylazine-ketamine (Dew 1988). As discussed above under xylazine, atipame- zole is now preferred by many anesthetists.

More recently, a combination called the ketamine stun has been developed for short-term anesthesia of small ruminants (Abrahamsen 2013). For the IV recumbent keta­mine stun, a combination of xylazine (0.025-0.05 mg/kg), butorphanol (0.05-0.1 mg/kg), and ketamine (0.3-0.5 mg/ kg) is administered (usually the upper end of the range is used) and onset takes approximately one minute. Local anesthetic should be administered immediately, if feasible. The animal remains awake but unconcerned and unmov­ing; duration of effect is approximately 15-25 minutes. If the upper end of the range for these drugs is given IM or SC, onset is slower but duration longer.

Xylazine Congeners

Clonidine, romifidine, medetomidine, dexmedetomidine, and detomidine are alpha-2 adrenergic agonists similar in action to xylazine. IV clonidine doses of 0.2-7 pg/kg in goats cause dose-dependent sedation, ranging from quiet behavior with maintenance of appetite to a sleep-like state (Eriksson and Tuomisto 1983). IV medetomidine at 5 pg/kg causes deep clinical sedation, metabolic alkalosis, and hyperglycemia (Raekallio et al. 1994). IM medetomidine at 15 pg/kg results in sedation and lateral recumbency, begin­ning at approximately 10 minutes and lasting approxi­mately 1 hour. Side effects include bradycardia, hypothermia, rumen stasis, bloating, frequent urination, salivation, and dyspnea, but disappear within two hours after return to standing (Mohammad et al. 1991). Dexmedetomidine (the active d-enantiomer of medetomi- dine) at 2 ug/kg has been shown to severely decrease PaO₂ in goats (Kutter et al. 2006). A commonly used dose of dex­medetomidine in goats is 5-10 ug/kg IV or 10-30 ug/kg IM (Seddighi and Doherty 2016). The same authors propose a dose of detomidine for goats of 5-20 ug/kg IV or 20-30 ug/ kg IM. Detomidine causes mild to moderate sedation and analgesia approximately 15 minutes after IM injection at 10-20 ug/kg (Clark et al. 1993).

IM medetomidine at 15 ug/kg (15 minutes after 0.1 mg/ kg atropine) provides sedation that begins approximately 7 minutes after injection and lasts approximately 40 min­utes. When the same doses of medetomidine are followed 10 minutes later with 5 mg/kg ketamine IM, anesthesia onset is rapid and lasts approximately 45 minutes. Salivation and diuresis are marked. When atipamezole is given intravenously at 15 ug/kg as a reversal agent 30 min­utes after medetomidine, the goats are able to walk nor­mally in 2-3 minutes (Tiwari et al. 1997). Similarly, when an intravenous medetomidine dose of 20 ug/kg was reversed 25 minutes later with intravenous atipamezole at 100 ug/kg, the goats stood up an average of 1.5 minutes later, but were agitated and vocalized (Carroll et al. 2005).

Tiletamine and Zolazepam

Telazol (Zoetis, Parsippany, NJ, USA) is a non-narcotic, non-barbiturate anesthetic agent approved in the United States for IM injection in dogs and cats. It is a combination of a ketamine-like drug, tiletamine (50 mg/mL), and the anxiolytic muscle relaxant zolazepam (50 mg/mL). It pro­duces cataleptoid or dissociative anesthesia. Analgesia may be insufficient for laparotomy (Clarke et al. 2014). Few reports are published on its use in small ruminants, but the drug is effective in sheep and goats. IM injection of a dos­age of 7.5-10 mg/kg provides anesthesia within 10 minutes and lasting 15-35 minutes (Clark et al. 1995). A dosage of 8-16 mg/kg was used IV to anesthetize 80 laboratory sheep for various surgeries, including celiotomies. The average duration of surgical anesthesia was 2.5 hours, and the aver­age time from injection to recovery was prolonged, at 5.6 hours (Conner et al. 1974). A 5.5 mg/kg dosage IV pro­vides rapid induction of goats, and additional doses of 0.5-1 mg/kg can be used to prolong the surgical anesthesia as needed. Adding butorphanol at 0.1 mg/kg IV is not ben­eficial (Carroll et al. 1997).

Premedication with atropine decreases salivation, but is not necessary because the swallowing reflex is preserved and not desirable because respiratory secretions become more viscous. Intubation or at the very least positioning the head low is advised in case regurgitation of rumen con­tents occurs. An oxygen source and means of assisted ven­tilation are also desirable (Carroll et al. 1997). Initial screening suggested that doxapram HCl is useful for arous­ing dogs that have been overdosed with Telazol (Hatch et al. 1988). An approximate dose is 5 mg/kg IV. There are no reports available of similar testing in goats.

Althesin

Althesin (Saffan*, Schering-Plough, Kenilworth, NJ, USA) was previously approved as an anesthetic for sheep and goats in New Zealand. This agent contained 9 mg alphax- alone and 3 mg alphadolone per mL. The drug is no longer marketed in the United States or New Zealand. The dosage for healthy adult sheep and goats is 2.2-3 mg/kg given IV to produce 10 minutes of surgical anesthesia. Recovery to standing occurs about 20 minutes after injection. An increased dose (6 mg/kg) has been used for disbudding kids (McKeating and Pilsworth 1984; Williams 1985). Althesin causes depression of myocardial contractility in goats (Foex and Prys-Roberts 1972) and has been reported to cause anaphylaxis in dogs and cats due to the castor oil-based vehicle.

Propofol

Propofol is another injectable induction agent with rapid onset of anesthesia, short duration of action, and smooth recovery. Apnea is a common outcome, and airway equip­ment (laryngoscope, bougie, endotracheal tubes, oxygen, etc.) should be available whenever propofol is used. In a dose titration study, 5.1 mg/kg given rapidly IV was the median effective dose required for induction of anesthesia adequate for intubation in unpremedicated goats (Pablo et al. 1997). The mean induction time was 23 seconds, and 27 of 28 goats experienced apnea (mean duration 73 sec­onds). Another study found a dose of 4 mg/kg adequate for induction, with only 1 of 5 goats experiencing apnea (Reid et al. 1993). Additional doses of propofol should be availa­ble if needed to complete induction, and ventilation should be supported if apnea persists. The dose of propofol can be reduced in sedated animals (Branson and Gross 1994). One such protocol uses IM detomidine at 10 gg/kg combined with butorphanol at 0.1 mg/kg before induction with 3-4 mg/kg propofol IV (Carroll et al. 1998). Anesthesia can be maintained with intermittent boluses of propofol. An alternative protocol reported is induction with IV ketamine (3 mg/kg) and propofol (1 mg/kg), followed by infusion of ketamine (0.03 mg/kg/min) and propofol (0.3 mg/kg/min) and 100% inspired oxygen for maintenance of anesthesia (Larenza et al. 2005). Combining ketamine with propofol is useful to prevent apnea. Yet another method of total IV anesthesia involves giving fentanyl at 0.02 mg kg/kg or midazolam at 0.3 mg/kg IV, followed one minute later by IV induction with propofol at 4 mg/kg, followed by a con­stant rate infusion of propofol at 12.0 mg/kg/hour and fen­tanyl 0.02 mg kg/hour or propofol at 12.0 mg/kg/hour and midazolam 0.3 mg kg/hour (Dzikiti et al. 2010).

Opioid Immobilization

Etorphine and carfentanil, more commonly used for cap­ture or immobilization of exotic species, have been evalu­ated in domestic goats at 5-40 gg/kg. IM carfentanil provides faster catatonic immobilization (5 minutes or less) than does etorphine (5-10 minutes; transient struggling occurs attributed to injection site pain). Recovery is slower after carfentanil, as the goat remains recumbent for more than two hours. Blood pressure increases while heart rate decreases (Heard et al. 1996). Pulmonary hypertension induced by etorphine contributes importantly to hypoxia when the drug is given to goats (Meyer et al. 2015). Oral administration of carfentanil combined with detomidine results in an undesirable prolonged induction time and excitement phase (Sheeman et al. 1997).

Halothane

Halothane has been largely supplanted by newer agents, but was once a popular non-explosive anesthetic among practitioners owning a gas anesthesia machine. Halothane takes effect quickly enough that a small goat can be induced through a mask, though more often an injectable drug such as xylazine or thiamylal sodium is used in older animals (Dhindsa et al. 1970). Recovery from the effects of the gas anesthesia is rapid, and fetal depression is minimal. In light of this, halothane could be used for cesarean section when general anesthesia is desired, although isoflurane is a safer choice.

During mask induction, 4% halothane solution is admin­istered. This takes 3-4 minutes with a tightly fitting face mask. A canine face mask is suitable, or a mask can be fashioned by cutting the bottom out of a 500 mL plastic bottle and padding the edges with cotton and tape. After intubation, the goat is maintained on a 1-2% halothane vaporizer setting at a flow rate of 1 L of oxygen per minute. Semi-closed circuits require a greater oxygen flow rate than do completely closed circuits.

Occasionally, an acute, massive liver necrosis occurs after halothane anesthesia of seemingly healthy goats (Fetcher 1983; O'Brien et al. 1986). Signs usually occur within 24 hours and include depression, inappetence, sali­vation, teeth grinding, head pressing, and icterus. Serum levels of aspartate aminotransferase (AST), bilirubin, alka­line phosphatase, creatinine, and blood urea nitrogen lev­els are increased. Death typically occurs within four days. Necropsy reveals centrilobular or massive liver necrosis. In some cases there is necrosis of the proximal renal tubules, abomasal ulceration, and hepatic encephalopathy. It has been postulated that hypotension and liver hypoxia encour­age reductive metabolism of halothane, leading to produc­tion of toxic free radicals. Although unproven, use of xylazine in conjunction with halothane may be a contrib­uting factor because of depressive effects on the circulatory system. Prolonged anesthesia is also a risk factor. Halothane administered for 45-125 minutes did not cause liver injury in young healthy goats premedicated with xylazine at 0.1 mg/kg IM (McEwen et al. 2000).

Methoxyflurane

Methoxyflurane has no advantage over halothane unless the practitioner owns only a Metophane machine. Induction and recovery are slower than with halothane.

Methoxyflurane can be used to supplement nitrous oxide (4 L/min) and oxygen (2 L/min) in a non-rebreathing system.

Isoflurane and Other Inhalants

More modern inhalants are preferred to halothane. Depending on availability and personal preferences of the anesthetist, other agents may be used in goats. These include enflurane (Antognini and Eisele 1993), isoflurane (Ewing 1990), sevoflurane (Larenza et al. 2005), and desflu- rane (evaluated in sheep by Mohamadnia et al. 2008). Mask induction can be done with 3-5% isoflurane or 4-6% sevoflu- rane, with or without nitrous oxide at 50% of the total gas flow (Riebold 2015). Nitrous oxide should be discontinued after induction, to avoid accumulation in the rumen. Anesthesia is maintained with a lower concentration, such as 1-2% isoflurane in oxygen. The concentration of isoflu- rane needed can be further reduced by IV morphine at 2 mg/ kg (Doherty et al. 2004). Because these agents cause some respiratory depression, controlled ventilation is preferable to spontaneous breathing (Antognini and Eisele 1993). Portable tabletop isoflurane anesthesia units are now avail­able and appropriate for field anesthesia situations.

Ether is undesirable because it produces profuse saliva­tion and a prolonged, unpleasant induction and is highly flammable.

Electroanesthesia

There are several reports of the use of an alternating electri­cal current to anesthetize goats. For instance, a 700Hz alter­nating sine wave current of 25milliamps and 10 V was used for bone plating in one pregnant doe (Vijaykumar and Ramakrishna 1983). It has been suggested that electroimmo­bilization (the use of electrical current to restrain conscious animals by causing paralysis) is unpleasant to ruminants (they show aversion in behavior trials), and also that the tech­nique is inhumane if surgery is performed without additional local analgesia (Thurmon 1986; Trim 1987; AVMA 2008).

Acupuncture Analgesia

Beginning in the 1970s, acupuncture stimulation has been used in Western countries in both small animal and human medicine to decrease the amount of anesthetic needed or to control postoperative pain. Complex mechanisms of action have been proposed (Janssens et al. 1988), and release of endorphins and encephalins is involved. Because acupuncture lacks sedative effects, goats with a quiet tem­perament or those extremely depressed because of illness presumably are most suitable for acupuncture analgesia. Otherwise, mild sedation, as with xylazine, should be considered. Few specific reports of the use of either body­point or earpoint acupuncture for surgery in goats have been published. One recent report describes electroacu­puncture anesthesia for laparotomy in goats (Ashour et al. 2021). Practitioners should fall back on their experi­ence with other species.