Injectable Anesthetic Agents and Techniques in Ruminants and Swine

Anesthesia

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Injectable Anesthetic Agents and Techniques in Ruminants and Swine John C. Thurmon, D.V.M., M.S.*

Injectable anesthetic agents and techniques have an important place in the practice of food-animal medicine and surgery. However, in cattle, a large number of surgeries are conducted in the field with local or regional analgesia. The effectiveness of this form of anesthesia is possible because of the ruminant's willingness to accept mechanical restraint without inflicting severe injury on itself. However, there are numerous situations in which general anesthesia is required for completion of surgery. The injectable agents are most appropriate for field use for several reasons. With injectable agents, a minimum of equipment is required, so the investment is small. This is of major importance owing to the economic value of most food animals. All supplies and drugs can be transported easily to the patient, which is in direct contrast to the use of an inhalation machine, which is expensive and difficult to transport to a field location. These comments are not meant to imply that all major surgical procedures can be performed with local or regional analgesia or injectable anesthesia under field conditions. Certainly, major surgical intervention (for example, thoracic, orthopedic, and extensive abdominal procedures) can best be performed in large animal hospitals equipped with inhalation anesthesia, respiratory support equipment, and other devices essential for performing state-of-the-art anesthesia and surgery. The veterinarian must keep in mind that general statements on doses and rates of administration made in this article are for the average animal. Individual patients may vary greatly in their response to a given dose of drug administered by the same route under nearly the same circumstances. Such variability suggests the need for further investigation of these agents in food-producing animals and dictates that the veterinarian exercise his or her professional judgment when administering potentially lethal drugs such as anesthetics.

* Diplomate,

American College of Veterinary Anesthesiologists; Professor, and Head of the Anesthesiology Section, Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, Illinois

Veterinary Clinics of North America: Food Animal Practice-Vol. 2, No.3, November 1986

567

568

JOHN

C.

THUR~10N

INJECTABLE AGENTS The injectable anesthetics are often divided into two groups: barbiturates and nonbarbiturates. The barbiturates are numerous, but only pentobarbital (Nembutal), thiopental (Pentothal), thiamylal (Biotal), and methohexital (Brevital) are used with any frequency in food animals. Of this group, thiamylal is used most widely in the United States, followed by thiopental. Because of the prolonged action of pentobarbital, it is used less frequently than thiamylal as a general anesthetic. However, it still remains one of the most effective sedatives for treating animals with seizures, convulsions, or excitement resulting from CNS-stimulating drugs. Because it is less irritating to tissues than either thiamylal or thiopental, it may be administered intramuscularly (6 to 10 mg per kg) when diluted to a 2.5 to 3 per cent solution to induce deep sedation. When given by this route, pentobarbital is an effective drug for controlling excitement in older swine recovering from intramuscularly administered ketamine. Barbiturates as a group are poor analgesics, and although the period of surgical anesthesia is brief from a single injection, sedation with a lengthy recovery is most often encountered when pentobarbital is used to maintain anesthesia by repeated injection. Close patient surveillance during the recovery period is essential to ensure a safe and satisfactory outcome. Although barbiturates have stood the test of time for safety and reliability, their undesirable properties (for example, poor muscle relaxant qualities, respiratory depression, poor analgesia) prevent them from fulfilling all the criteria of the ideal anesthetic. As a result, the search continues for reliable short-acting agents that may be used alone or in combination with other drugs to meet the demand for a superior injectable anesthetic agent. This desire has led to the evaluation of a large number of agents often referred to as the nonbarbiturates. The nonbarbiturate group includes cyclohexamines (ketamine), steroid anesthetics (Saffan), opiates (fentanyl), chloral hydrate, benzodiazepines (diazepam), imidazoles (etomidate), and alkylphenols (di-isopropyl phenol). The latter two agents have not been used to any extent in veterinary anesthesia and are not discussed in this chapter. Xylazine is similar in structure and action to the imidazoles and is included here because of its frequent use in ruminants and swine. In the latter, sedative response to xylazine is not as profound as in ruminants. As a result, xylazine is frequently combined with other agents (for example, ketamine) in order to take full advantage of its superior clinical properties. Combinations of anesthetic agents administered in appropriate doses are often superior to anyone agent. Combining ketamine for its analgesic and immobilizing effect with xylazine for its sedative, analgesic, and skeletal muscle-relaxing qualities is often cited as effective in a variety of species. Recently, guaifenesin has been shown to enhance muscle relaxation, while having only minimal effect on re-

INJECTABLE ANESTHETIC AGENTS AND TECHNIQUES

569

covery time, when given with ketamine and xylazine as a continuous infusion. In order to conserve space in this article, doses and comments from a large number of reports have been summarized in Table 1.

Pentobarbital Sodium Although pentobarbital has been used safely in food-producing animals for decades, it must not be used indiscriminately. Pentobarbital is a potent central nervous system depressant, which often results in respiratory arrest when administered rapidly or in high dose. This effect on respiration may be further compounded by placing the patient in recumbency or in a steep head-down tilt (for example, in hernia repair in pigs). If hypoventilation is effectively relieved by mechanical ventilation, pentobarbital is remarkably safe. Cardiovascular function, although depressed by an apneic dose of pentobarbital, remains rather stable, and prevention of hypoxia and hypercapnia is all that is required to insure a safe outcome. Analeptic agents (for example, doxapram) are effective temporary central nervous system stimulants in barbiturate-depressed patients and can be used in emergency situations. Action of these agents is of short duration, and the aroused animal may later relapse into a state of life-threatening respiratory depression. Under most circumstances, treatment of respiratory depression with mechanical ventilation is preferred to the use of analeptics. Effective mechanical support of ventilation requires that an endotracheal tube be in place. Tracheal intubation should be an integral part of all general anesthetic techniques in food animals. The majority of catastrophic outcomes of general anesthesia, whether with barbiturates or other agents, occur because of apnea, often compounded by absence of a patent airway. Cattle and Swine. Pentobarbital is not a suitable agent for general anesthesia in adult cattle. It may be used in calves and swine, but because young animals do not have the hepatic metabolic capacity of adults, pentobarbital should not be used as a general anesthetic in calves less than 1 month of age or young piglets. Pentobarbital can be used satisfactorily in adult sheep, goats, and swine. An intravenous dose of 15 to 30 mg per kg will provide 20 to 30 minutes of relatively safe anesthesia provided a patent airway is established and maintained until swallowing and other airway protective reflexes have returned. In swine, pentobarbital is generally given by injection into a dorsal auricular vein although the intraperitoneal route has been used. Restraint problems are common in mature swine, and head movement is often encountered in smaller animals, complicating intravenous injection. Placement of an over-the-needle Teflon or polyethylene catheter ensures an intravenous route for injection. However, catheter expense may not be justified under many circumstances. Pentobarbital is more often used for complete anesthesia in young swine than in mature animals. Preanesthetic medication (promazine, xylazine, Innovar-Vet, diazepam, and so on) will decrease the amount of pentobarbital required for surgical anesthesia. When Innovar-Vet, 1 ml per

Young cattle

Sheep and goats

Swine

Cattle

Cattle

Sheep and goats Sheep and goats

Swine

Swine

Swine

Pentobarbital

Pentobarbital

Pentobarbital

Thiopental

Thiamylal

Thiopental

Thiopental

Thiamylal

Methohexital

Thiamylal

SPECIES

DRUG(S)

IV

2-4

5

6-18

10-20

8-14

10-16

4-8

IV

IV

IV

IV

IV

IV

IV

Intratesticular

45

6-12

IV

10-30

IV

IV

15-30

28-33

ROUTE

5

41

41

41

41

41

41

21

31

21 31

41

21 31

REFERENCE

Short duration of action acceptable for procedures (e.g., detusking, castration) not requiring more than a few minutes. Excitement may occur during recovery.

Seldom given as a bolus because of small hagile auricular veins. Surgical anesthesia of 15 to 20 minutes duration. Full recovery in approximately 60 minutes. Anesthesia time may be extended by supplemental doses, but recovery will be greatly prolonged.

Induction dose will be increased if drug is given slowly. Apnea of short duration occurs with rapid injection. Tracheal intubation recommended. Anesthesia extended with repeated incremental doses. Used most often for induction. Maintenance with inhalation agent.

The smaller dose is used in premedicated cattle and the larger in unpremedicated thrifty animals. Apnea is of short duration. Surgical anesthesia for 5 to 10 minutes. Recovery in 30 to 40 minutes. Should not be used in young calves.

Analgesia of short duration (15 to 45 minutes), prolonged with incremental doses. Apnea often encountered with supplemental doses. Anesthesia adequate for castration occurs in 10 minutes.

Pentobarbital is rapidly metabolized; anesthesia is of short duration (20 to 60 minutes). May prolong anesthesia with incremental doses (6 to 36 mg/kg/hour). Trachea must be intubated.

Seldom used in adult cattle and should not be used in calves under 1 month of age because of prolonged recovery. Must intubate trachea to protect airway. U sed for preanesthetic sedation or to control excitement during recovery from ketamine.

COMMENTS

I njectable Anesthetic Agents: A Summary of Doses and Comments

DOSE (MG/KG)

Table 1.

~

Z

0

3::

:::0

c-:

::t

0 ...,

S Z

........

0

-..:t

Cattle

Calves

Cattle

Cattle

Adult cattle

Calves

Calves

Calves

Calves

Sheep

Methohexital

Methohexital

Ketamine

Ketamine and xylazine

Guaifenesin, ketamine, and xy lazine

Ketamine and xylazine

Ketamine and xylazine

Ketamine and xylazine

Ketamine and xylazine

Ketamine and ace promazine

0.088

0.55

22 1M

1M

1M

1M

0.22

4.4

1M

1M

0.2

11

1M

1M

0.2

lO

IV or 1M

5 or lO

IV

IV

0.1

0.55 ml

IV

IV

IV

IV

2

2

5.5

42

35

25

52

51

41

15

14

21

21

Atropine, 0.22 mg/kg 1M, will decrease salivation. Anesthesia may be extended by incremental injection of ketamine 2 to 4 mg/kg as required. Tracheal intubation advised.

Ketamine and xylazine mixed in same syringe. Safe chemical restraint of short duration. Supplemental oxygen recommended.

Surgical anesthesia ranged from 40 to 55 minutes.

Anesthesia prolonged with incremental doses of ketamine, 0.5 to 1.0 mg/kg.

Five or lO mg dose was given IV or 1M, respectively. Anesthesia was prolonged with 5 mg/kg ketamine 1M.

Solution made in 5% dextrose in water. Each ml contains 50 mg guaifenesin, I mg ketamine, and 0.1 mg xylazine. Anesthesia induced with 0.55 mg/kg, maintained with 2.2 mllkg/hour.

Xylazine administration is followed by ketamine. Anesthesia may be prolonged by repeating 1/2 the original dose of each drug or by infusion of ketamine as above. The xylazine dose is doubled (0.2 mg/kg) when given 1M.

Induction was followed by maintenance with ketamine in saline (2 mg/m!) given at a rate of lO mllmin IV.

Rapid IV injection induces anesthesia sufficient for tracheal intubation.

Anesthesia has been induced in adult cows receiving 2.5 gm of methohexital IV. Recovery was smooth and rapid.

Z

-

~

~

-1

rJl

tTl

Zc:

z

::r:

n

tTl

~

0

Z

>-

'Jl

...,Z

tTl

:» 0

n

...,tTl

::r:

[f;

...,

tTl

:» Z

t:O l' tTl

>-

n...,

~

SPECIES

Sheep

Sheep

Sheep

Sheep

Sheep or goats

Goats

Goats

Goats

Sheep and goats

DRUG(S)

Ketamine

Ketamine

Ketamine and xylazine

Ketamine and xylazine

Ketamine and diazepam

Ketamine and diazepam

Ketamine and xylazine

Ketamine and xylazine

Guaifenesin, ketamine, and xylazine

1M 1M 1M

0.22

11

0.22 IV

1M

11

0.55 ml

1M

0.88

1M

IV

2

22

IV

4

1M

0.1

41

22

27

27

19

Drugs mixed in 5% dextrose in water. Each ml contained 50 mg guaifenesin, 1 mg ketamine, and 0.1 mg xylazine. Anesthesia induced with 0.55 mllkg and maintained by continuous infusion of 2.2 mllkg/hour.

Atropine not given, goats not fasted. Analgesia ranged from 50 to 85 minutes.

Atropine (0.44 mg/kg) and xylazine followed in 10 minutes by ketamine. Duration of analgesia approximately 45 minutes.

Atropine (0.44 mg/kg) and diazepam followed in 10 minutes by ketamine. Duration of analgesia approximately 22 minutes.

Diazepam given 15 minutes prior to ketamine. To maintain anesthesia, ketamine infused IV to effect.

Xylazine given 10 minutes before ketamine. Anesthesia of short duration.

19

IV

4

0.22

Drugs mixed in the same syringe. Duration of analgesia vary at different body sites, extending to 46.8 minutes at horn hase hut only to 32.7 minutes in the flank area.

7

1M

11

Dosages from .5 to 22 mg/kg induce anesthesia ranging hom approximately 10 to 40 minutes in duration.

Anesthesia maintained hy infusing 5% glucose in water containing 2 mg/ml of ketamine at a rate of 4 mllmin. Preanesthetic medication not given.

49

40

IV

COMMENTS

IV

REFERENCE

ROUTE

5 to 22

2

DOSE (MG/KG)

Table 1. (Continued)

~

0 2

?::

c ::e

:r:

~

n

2

:r:

'---" 0

t-:J

-:t

Swine

Swine

Swine

Swine

Swine

Swine

Swine

Swine

Swine

Ketamine

Ketamine and xylazine

Ketamine and acepromazine

Ketamine and xylazine

Ketamine, fentanyl, and droperidol

Ketamine and diazepam

Guaifenesin, ketamine, and xylazine

Ketamine and thiopental

Ketamine, xylazine, and oxymorphone

2 2 0.075

20 6 to 11

0.5 to 1 mllkg

10 to 18 1 to 2

11

IV IV IV

1M IV

IV

1M IV

lM

1M

1M

0.39

15 to 20

1M

1M

2

15

1M

1M

20

20

6

43

44

21

4

3

17

28

43

Excellent analgesia of 20 to 30 minutes duration. Doubling dose and administering 1M increased duration of action with nearly the same degree of anesthesia.

Adequate for short minor procedures. Muscle relaxation fair. Recovery smooth.

Drugs mixed in 5% dextrose in water. Each ml contained 50 mg guaifenesin, 1 mg ketamine, and 1 mg xylazine. Anesthesia induced with 0.5 to 1 mg/kg and maintained by continuous infusion at a rate of 2.2 mllkg/hour.

Analgesia not as profound as with xylazine. Recovery generally smooth.

Innovar-Vet (1 mll14 kg) given 1M following 0.044 mg/kg of atropine. Anesthesia prolonged with ketamine, 2 to 6 mg/kg IV or 1M. Use should be restricted to young swine less than 45 kg.

Ketamine (100 mg/ml) and xylazine (100 mg/ml) combined in a 1: 1 rate and given as a single injection to feral pigs. The dose reported here appears to be optimal for immobilization. Swine immobilized for approximately 48 minutes. Level of analgesia not reported.

Acepromazine followed in 30 minutes with ketamine. Immobilization 5 minutes after receiving ketamine. Recovery 65 to 80 minutes.

Anesthesia may be extended or depth increased by administering V2 the original dose. Xylazine does not induce deep sedation in swine when used alone.

Atropine (0.044 mg/kg) relieved salivation. Poor muscle relaxation, minimal analgesia, rough recovery. Supplementation recommended.

~

-l eN

'J1

trI

c::

Z

Z

::r:

n

trl

~

;:.. Z 0

'J1

..,Z

trl

> 0

n

'J1

.., ::r: trl ..,

trl

> Z

t:P l' trl

;:..

Cl >-:

Z

M

SPECIES

Calves, sheep, and goats

Sheep

Swine

Swine

Swine

DRUC(S)

Saffan

Saffan

Saffan

Saffan and azaperone

Saffan

2 to 3

2 4 1M

IV 1M

IV

IV

3

6

IV

ROUTE

3 to 6

DOSE (MC/KC)

21

Induced deep sedation in neonatal pigs (7 days of age). Anesthesia induced with an additional 2 to 3 mg/kg IV Saffan and "safely maintained for up to 2 hours by incremental injections."

Surgical anesthesia of 10 to 15 minutes in small pigs. Good surgical anesthesia may be extended with small increments of Saffan IV to effect.

21

18

Anesthesia maintained by continuous infusion of a dilute solution (0.234 mg/kg/minute). Recovery rapid when infusion discontinued.

Short period of excellent anesthesia (10 to 20 minutes) extended by 1 to 2 mg/kg IV as required. Lambs taken by cesarean no more difficult to revive than when taken from halothane-anesthetized ewes.

COMMENTS

50

8

REFERENCE

Table 1. (Continued)

~

c z

Z

(5

';("

::0

c:

--3 ::r:

n

::r:

'--;

~

-l.

INJECTABLE ANESTHETIC AGENTS AND TECHNIQUES

575

15 kg, is administered 20 to 30 minutes before pentobarbital (intramuscularly), swine are much easier to manage for intravenous injection. In mature swine, less than an anesthetic dose of pentobarbital (that is, deep sedation, 10 mg per kg intravenously) may also be supplemented with local analgesia. This technique requires n1echanical restraint because reflex responses appear to be enhanced and swine are often prone to resist even nonpainful manipulations with vigorous movement of the rear limbs. Such response is often encountered when alcohol or some other antiseptic is applied to the freshly scrubbed surgical site. Pentobarbital may be given safely to large boars for castration. With all surgical equipment prepared, intravenous injection of 10 to 12 mg per kg of pentobarbital provides a brief period of surgical anesthesia sufficient for castration. Pentobarbital may also be injected directly into the testicle for castration. The amount required is quite large (40 to 50 mg per kg). One half of the total dose is injected into each testicle. Light anesthesia occurs in 15 to 20 minutes. The first testicle injected should be the first surgically removed in order to shorten recovery time. For intratesticularly induced anesthesia, a ketamine-xylazine combination (ketamine 6 mg per kg, xylazine 2 mg per kg) has, for the most part, replaced pentobarbital. Sheep and Goats. Pentobarbital is acceptable for brief periods (15 to 30 minutes) of surgical anesthesia in small ruminants. Because of the likelihood of regurgitation, particularly if intra-abdominal manipulations are performed, a cuffed endotracheal tube should be put into place immediately after induction. Small increments of pentobarbital (totaling approximately one half of induction dose) may be safely given to prolong surgical anesthesia. When pentobarbital supplementation is used to extend anesthesia, it must be given very slowly to effect or respiratory arrest may occur. Provided an endotracheal tube is in place and an Ambu bag or other respiratory support device is close by, apnea is of little concern because mechanical ventilation is all that is required until spontaneous breathing resumes. Sheep, goats, and swine recover much more rapidly from an anesthetic dose of pentobarbital than do dogs. Signs of recovery in the various species, although occurring at different times, occur at the same plasma concentration of pentobarbital. This suggests that small ruminants and swine metabolize pentobarbital more rapidly than dogs. Thiobarbiturates Thiopental (Pentothal) and thiamylal (Biotal) are the most commonly used thiobarbiturates in veterinary practice. Of these two agents, thiamylal is the most popular. Popularity of thiamylal over thiopental is related to its greater potency, which appears to be approximately 1.25 to 1.50 times that of thiopental. The margin of safety of these two agents with respiratory support is considerable. The most common untoward responses are respiratory depression and benign cardiac dysrhythmias. The latter usually take the form of a bigeminal rhythm, which is of short duration and goes unnoticed unless the elec-

576

JOHN

C.

THUR~10N

trocardiogram (ECG) is being monitored. These dysrhythmias are of minor concern in the calm, physically fit patient. However, in patients with cardiovascular disease or in healthy individuals excited and experiencing critical circulating levels of endogenously released catecholamines, thiobarbiturates should be given with extreme caution. Drugs that antagonize alpha-l receptor sites (for example, acetylpromazine) ameliorate the bigeminal rhythm but may enhance thiobarbiturate-induced cardiovasculur depression. Thus, the dosage of all agents becomes critical in the unhealthy or excited patient. The thiobarbiturates depress myocardial function, as do most other anesthetics. Systemic blood pressure is a function of cardiac output and peripheral vascular resistance. Thus, blood pressure may be directly affected by decreasing or increasing either or both of these variables. Although there is disagreement about the effects of barbiturates on peripheral vascular tone, it is generally accepted that they depress myocardial contractility; thus, vascular pressure tends to follow directional changes in cardiac output. The controversial effects on cardiovascular function appear to be influenced by preanesthetic medication, rate and route of administration, total dose, species variability, and temporal effects. In spite of the existing controversies and their myocardial and respiratory depressing effects, the thiobarbiturates have stood the test of time and are safe agents for induction and maintenance of short-term anesthesia in food-producing animals. In adult cattle, a single dose of thiopental or thiamylal may be safely used to induce surgical anesthesia of short duration (10 to 20 minutes) or for tracheal intubation and maintenance of anesthesia with an inhalation agent (for example, halothane in oxygen). Incremental injections of thiamylal may be given to maintain anesthesia but must be expected to greatly prolong recovery time. Once tissue stores (for example, muscle tissue) have become saturated by repeated administration, recovery time is directly related to the animal's ability to metabolize and eliminate the drug. Fortunately, ruminants (particularly sheep and goats) metabolize thiobarbiturates rather rapidly. This ability, coupled with the natural phenomenon of rapid redistribution from brain tissue and blood to other well-perfused body tissues, appears in major part to be responsible for the short duration of thiobarbiturate anesthesia in ruminants. Deaths occurring after thiobarbiturate administration most commonly arise from respiratory depression, which is often a direct response to overdose, and, in ruminants, from aspiration of regurgitated ruminal contents deeply into the respiratory passages. Therefore, tracheal intubation and respiratory support by artificial ventilation (that is, with apnea) are all that is required to ensure a desirable response to thiobarbiturate anesthesia in the majority of cases. Taking the shortcut of deleting tracheal intubation inevitably leads to disaster. Administration. The thiobarbiturates are administered as a 5 or 10 per cent solution in water or saline in mature cattle. A 2.5 to 5 per cent solution is appropriate for younger animals and mature swine, sheep, and goats. If a 10 per cent solution is injected perivascularly,

INJECTABLE ANESTHETIC AGENTS AND TECHNIQUES

577

it results in extensive tissue necrosis at the site of injection. Further, when a 10 per cent solution is given in the dorsal auricular vein of swine, even if given slowly and none is injected perivascularly, ear tissue necrosis may occur. Thus, a 2.5 or 5 per cent solution is recommended for young and mature swine, respectively. These agents should be administered by the intravenous route only. In adult cattle, the jugular vein is most commonly used. The milk vein has been used; however, perivascular injection at this site is potentially dangerous in the producing dairy cow. The tail vein should never be used. In healthy adult cattle, the dose is calculated and given as an intravenous bolus. This is referred to as a "crash induction" and is employed to prevent the excitatory stage of anesthesia that is possible with a slow rate of injection. Tracheal intubation is quickly completed to protect the airway from regurgitated ruminal contents and provide a route for respiratory support should apnea or serious respiratory depression occur. Anesthesia may be continued by incremental injection of the barbiturate or the animal may be connected to an inhalation machine for maintenance (for example, halothane in oxygen). In sheep and goats, either a crash induction or the method more commonly used in dogs and cats (that is, one half of the calculated dose given as a bolus followed by small increments given to effect) may be used. It appears that the incidence of regurgitation before tracheal intubation is decreased when the crash induction technique is employed. In addition, a smaller dose of barbiturate is required to induce anesthesia with the rapid injection technique. Thus, recovery will occur more quickly. The rapid induction technique, which employs a smaller total dose, may be used advantageously in young animals that have not developed fully their hepatic enzyme capacity to metabolize and eliminate thiobarbiturates. However, it is generally accepted that barbiturates should not be used to maintain anesthesia in calves under 2 months of age. Swine are not easily restrain~d for venipuncture and intravenous injection. The auricular veins are very fragile, and excessive injection pressure can easily cause vessel wall rupture and perivascular injection. Thus, cannulating the vein with an over-the-needle catheter or a needle affixed to a short length of tubing (butterfly intravenous injection set) helps ensure successful intravenous injection. Thiobarbiturate anesthesia in swine is accomplished by quickly injecting one half of the calculated dose. When the animal sinks to its sternum, incremental amounts are injected until the desired plane of anesthesia is achieved. Small increments of the thiobarbiturate can easily be given to prolong basal anesthesia, but it must be remembered that apnea commonly occurs when surgical anesthesia is attained. Thus, this cannot be recommended unless the pig's trachea has been intubated and means for respiratory support are readily at hand. The recommended dose of thiobarbiturates is quite variable. I have found the following dose to be acceptable. The higher doses are used in vigorous light animals, and lower doses are employed in older heavier animals. It should be pointed out that premedication with a sedative

578

JOHN

C.

THURMON

or tranquilizer (for example, xylazine) will decrease the induction dose of thiobarbiturate by one fourth to one half. Doses are as follows: Thiopental C attle-6 to 12 mg per kg Sheep and goats-l0 to 16 mg per kg Swine-l0 to 20 mg per kg Thiamylal C attle-4 to 8 mg per kg Sheep and goats-8 to 14 mg per kg Swine-6 to 18 mg per kg Methohexital (Brevital) Methohexital is an ultrashort-acting, methylated oxybarbiturate that is considerably more potent than either thiopental or thiamylal. Although its short duration of action is due in part to redistribution from the brain to other body tissues, rapid hepatic metabolism appears to play an important role in early recovery from anesthesia. Methohexital may be given to induce surgical anesthesia of short duration (complete recovery occurring in 20 to 30 minutes) or for tracheal intubation to be followed by inhalation anesthesia. Recovery from methohexital is generally accompanied by excitement. This undesirable response may be decreased by premedication with a tranquilizer (for example, azaperone in swine) or a sedative (for example, xylazine). The dose of methohexital is decreased accordingly when one of these agents is employed. When methohexital induction is followed by inhalation maintenance, recovery is generally smooth. Exceptions to this observation may occur when patients experience major pain or hypoxemia during the recovery period. Methohexital has been used to induce anesthesia for castration of large boars (6 to 10 mg per kg intravenously). In calves, sheep, and goats, 3 to 5 mg per kg intravenously is satisfactory for induction of anesthesia. For induction of anesthesia in adult cattle, a dose of 6 mg per kg intravenously has been suggested. As with the other barbiturates, apnea of short duration may occur. The thiobarbiturates or methohexital may be combined with guaifenesin for safe short-term anesthesia. Guaifenesin is a muscle relaxant thought to act centrally upon the internuncial neurons of the spinal cord and brainstem of polysynaptic fibers, which innervate the extremities. In clinical doses, it appears to have very little effect on diaphragmatic function, so it affects respiration minimally. Cardiovascular function is well maintained. Guaifenesin is clearly a muscle relaxant and not an anesthetic agent. When surgery is performed, guaifenesin should be used only in combination with an agent that induces analgesia or unconsciousness. Death from guaifenesin overdose is most likely to occur when it is administered alone. When it is combined with a barbiturate, stages and planes of anesthesia with which the veterinarian is familiar are induced, allowing assessment of anesthetic depth and timely adjustment of rate of administration.

INJECTABLE ANESTHETIC AGENTS AND TECHNIQUES

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Guaifenesin solution is prepared by adding 50 gm of guaifenesin powder to 1 L of 5 per cent dextrose in water, which is heated until the guaifenesin is added. Two grams of thiamylal or 3 gm of thiopental are added just prior to administration. The guaifenesin-thiobarbiturate (G-T) mixture is given intravenously to effect. In a physically fit unpremedicated adult cow or bull, 1.5 to 2 ml per kg of the G-T solution induces surgical anesthesia of 15 to 20 minutes duration provided it has been given rapidly (that is, through a 12-gauge needle or catheter). When muscle relaxation and light general anesthesia are achieved, the trachea should be intubated. Administration of oxygen relieves hypoxemia associated with recumbency. Surgical anesthesia may be extended by continuous infusion of G-T solution at a slow rate, given to effect. For induction, the total dose of G-T should not exceed 2 ml per kg. Extended anesthesia time should not exceed 1 to 13/4 hours, and for safe administration, the total dose of G-T should not exceed 4 ml per kg of body weight. When used appropriately, G-T is a safe and useful combination of drugs for induction of anesthesia for short minor surgical procedures or tracheal intubation for inhalation maintenance. Long periods of surgical anesthesia in adult ruminants are more safely achieved with inhalation agents. Ketamine Over the last decade, ketamine has become a very widely used anesthetic agent in food animals. It has virtually replaced the barbiturates as the primary component in most injectable anesthetic regimens. This has been possible because it may be given by either the intravenous or the intramuscular route. Objectional but characteristic responses (for example, poor muscle relaxation with increased myotatic reflexes, poor visceral analgesia, rough recovery, cardiovascular effects) to ketamine may be ameliorated or eliminated by selected adjuncts given peri- or intraoperatively. Ketamine induces rapid onset of a peculiar state of unconsciousness often described as dissociative or cataleptoid anesthesia. The anesthetic state is characterized by profound somatic analgesia, but visceral analgesia is poor. The latter is generally ameliorated by supplemental administration of an analgesic (for example, xylazine, oxymorphone). Muscle tone is increased, and tendinous reflexes are often exaggerated, resulting in frequent involuntary muscular movement. The eyelids remain open, with the cornea becoming susceptible to drying and abrasions. Oral and upper respiratory protective reflexes remain intact but suppressed enough that tracheal intubation is advised. Excitement during the recovery period is rather common in adults receiving ketamine by the intramuscular route and/or handled roughly during the perianesthetic period. Excitement may be prevented by pretreatment with xylazine or easily controlled by intravenous administration of pentobarbital (2 to 6 mg per kg) or diazepam (0.25 to 0.5 mg per kg). The latter is expensive and no more effective than pentobarbital. Gentle handling and appropriate preanesthetic

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medication are generally all that is required to circumvent these problems. Respiratory function is depressed in patients receiving ketamine, and respiratory pattern becomes apneustic. These responses are associated with mild hypoxemia and hypercapnia. Rapid intravenous administration often results in apnea. This latter effect should also be borne in mind when supplemental ketamine is given intravenously to prolong surgical anesthesia. Ketamine tends to dilate the bronchi and thus may have a beneficial effect in anesthesia of animals suffering from bronchial constrictive conditions. The cardiovascular effects of ketamine result from its central stimulation of the sympathetic nervous system and direct myocardial depression. These responses are doserelated, with moderate doses associated with the former and high doses with the latter. In a physically fit nonpremedicated patient, one would expect to observe tachycardia, increased cardiac output, and hypertension. Systemic vascular resistance and pulmonary artery pressure are transiently increased. When ketamine is given alone and in moderate dosage, its net effect is reflected in cardiovascular stimulation, apparently as a result of central stimulation of the sympathetic nervous system. Ketamine possesses direct antidysrhythmic properties. However, its central action may augment myocardial sensitization to increased circulating catecholamines induced by other agents. Overall, myocardial oxygen consumption is increased. In food-animal anesthesia, ketamine is most often combined with some other adjunctive agent, so its effects on the cardiovascular system are variable, depending to a large extent on pre- or concomitantly administered agents. Ketamine is seldom administered as the sole anesthetic agent, because it is not very satisfactory other than for brief procedures (for example, dis budding of kid goats, suturing lacerations). However, when combined with other agents and used judiciously, ketamine is unquestionably a safe and reliable anesthetic agent. The large number of favorable reports in the veterinary literature fully support this conclusion. Administration. Ketamine may be given by either the intravenous or the intramuscular route. In adult cattle, the intravenous route is most commonly used. Premedicating adult cattle with xylazine (0.2 mg per kg intramuscularly) followed by ketamine (2 to 3 mg per kg intravenously) induces anesthesia sufHcient for tracheal intubation or for minor surgical intervention. Anesthesia may be safely prolonged by small intravenous increments ofketamine (1 to 2 mg per kg) given slowly to effect. An alternative is to add ketamine (2 mg per ml) to 5 per cent dextrose or saline. This solution is then given to effect by continuous infusion at a rate of 10 ml per minute. Clinical experience has shown that constant-rate intravenous infusion of a guaifenesin, ketamine, and xylazine (GKX) mixture is an effective anesthetic combination in cattle, sheep, and goats. The mixture is prepared by adding 500 mg of ketamine and 50 mg of xylazine to each 500 ml of 5 per cent guaifenesin (prepared in 5 per cent dex-

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trose). The final mixture is infused initially at a rate of 0.55 ml per kg. The onset of anesthesia is gradual but smooth. The initial loading dose is followed by continuous infusion of 2.2 ml per kg per hour in adults and 1.65 ml per kg per hour in calves, kids, and lambs. Infusion is easily maintained at a constant rate using a disposable intravenous fluid administration set with a clear drip chamber. The rate may be calculated as follows for a 250 kg animal: Initially, the animal would receive 138 ml of GKX (250 kg x 0.55 ml per kg), the loading or induction dose. Infusion would be continued at a rate of 138 drops per minute (15 drops per ml x 2.2 ml x 250 kg -;- 60 minutes). In the University of Illinois Large Animal Hospital, surgical procedures performed with GKX have ranged up to 2.5 hours in length and have included femoral fracture plating and pinning, penile surgery, umbilical hernia repair, cesarean section, and other procedures requiring laparotomy. Muscle relaxation with GKX is excellent, easily allowing tracheal intubation. Patients breathe relatively well, but as with other anesthetic regimens, dose-related hypoventilation does occur. Administration of oxygen (5 to 15 L per minute), although not absolutely essential in physically fit animals, helps to prevent the hypoxemia that accompanies hypoventilation. In my experience, recoveries have been very smooth. When anesthesia has been extended up to 2 hours, recovery may be hastened by administration of yohimbine or tolazoline. Because the agents in GKX have relatively short half-lives, this combination lends itself well to continuous intravenous infusion in the food-animal species. Dose and administration in swine are discussed later. Ketamine (11 mg per kg intramuscularly) and xylazine (0.22 mg per kg intramuscularly) are a very useful combination of drugs in calves. Ketamine and xylazine are miscible and may be mixed and administered from the same syringe. The onset of anesthesia is rapid and without excitement. Muscle relaxation and analgesia are quite satisfactory for most surgical procedures in calves, lasting not more than 30 minutes. Anesthesia may be extended by repeat administration of each drug at one fourth to one half of the original dose. The smaller dose may be given intravenously for rapid onset and short duration; the larger dose given intramuscularly has a considerably longer effect. Bradycardia is seldom a problem in calves receiving ketamine and xylazine at the same time, but when xylazine administration is followed in 5 to 10 minutes by ketamine, persistent bradycardia may be of concern. Bradycardia and profuse salivation (which usually accompany ketamine-xylazine administration) may be safely controlled with atropine (0.1 to 0.2 mg per kg intramuscularly). Diazepam (1 to 2 mg per kg intravenously) is a reasonable substitute for xylazine in calves. However, diazepam is more expensive, induces very little analgesia, and requires strict accounting of its use. Recovery from ketamine-xylazine or ketamine-diazepam anesthesia is without excitement but somewhat more prolonged with the latter combination. Calves given one injection of ketamine-xylazine by the intramuscular route are usually able to stand in 11/2 to 2 hours. Stand-

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ing time is considerably shorter when smaller doses (ketamine 6.0 mg per kg, xylazine 0.11 mg per kg) are given intravenously. Recovery time may be hastened by administration of yohimbine (0.125 mg per kg intravenously) or tolazoline (2.5 to 5 mg per kg intraveneously), particularly when calves have received large supplemental doses of xylazine. In sheep and goats, ketamine has been used as the sole anesthetic and in combination with a variety of adjunctive agents. Alone, ketamine, as in most other animal species, is not satisfactory for other than the briefest of surgical procedures. Although it is profoundly analgesic, muscle relaxation, increased myotatic reflex responses, and eNS stimulation all detract from its usefulness. These undesirable responses may be eliminated or decreased by pre- or concomitant administration of agents such as xylazine, diazepam, or acepromazine. A very desirable combination of drugs for short-term anesthesia in sheep and goats is xylazine (0.22 mg per kg intramuscularly) and ketamine (11 mg per kg intramuscularly). The degree of analgesia may vary from one body site to another, but it is generally satisfactory for most surgical procedures not extending beyond 25 to 30 minutes. Operations on or about tendinous structures may result in reflex movement that mayor may not be associated with painful manipulation. Although xylazine or diazepam (2 mg per kg intravenously) increases the degree of muscle relaxation, only xylazine appears to increase the degree of analgesia. Local analgesia at the surgical site may be required when diazepam is chosen for its central muscle relaxing qualities. When teaching students to use injectable anesthetic techniques in small ruminants in the surgical laboratory, I have placed considerable emphasis on an atropine (0.11 to 0.22 mg per kg intramuscularly), xylazine (0.22 mg per kg intramuscularly), and ketamine (11 mg per kg intramuscularly) technique. Atropine is given, followed in 15 to 20 minutes by xylazine. Ketamine is administered as soon as the sedative effect of xylazine is evident. If anesthesia must be prolonged to finish the surgical procedure, ketamine is given at a rate of 4 mg per kg intravenously or 6 to 8 mg per kg intramuscularly. The intravenous route is used for rapid onset and short duration; the intramuscular route is employed for longer duration. In these animals, the trachea is intubated for respiratory support and to prevent aspiration of ruminal contents should regurgitation occur. This anesthetic technique has proven to be very satisfactory for a variety of minor and major surgical procedures in goats and sheep. As was described under the administration of ketamine in cattle, the GKX regimen is very satisfactory in sheep and goats when given at the same dose rate. Ketamine has become the major component of most injectable anesthetic regimens for swine. However, when given alone, ketamine does not induce satisfactory anesthesia. Pigs (particularly mature swine) not receiving preanesthetic medication (for example, xylazine, diazepam, or acepromazine) often react violently to intramuscular ketamine. Muscle relaxation and analgesia are poor, and minor surgery

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often requires injection of a local analgesic. Several drugs have been found to relieve effectively the excitatory and exaggerated myotatic responses of swine to ketamine. Those used most commonly include xylazine, diazepam, azaperone, or acepromazine. Of these agents, xylazine is the most popular. Ironically, xylazine, when given intramuscularly in rather high doses (1 to 2 mg per kg intramuscularly), does not induce the degree of sedation that occurs in ruminants at one tenth of this dose. Satisfactory short-term anesthesia may be achieved in swine by administering atropine (0.044 mg per kg intramuscularly) followed by xylazine (2.2 mg per kg intramuscularly) and ketamine (12 to 20 mg per kg intramuscularly). Anesthesia may be extended by intravenous supplementation with a xylazine-ketamine mixture from the same syringe given to effect. The mixture is made by adding 1/2 to 1 ml of 100 mg xylazine to each 1 ml of ketamine. An intravenous ketamine-xylazine mixture must be given slowly and to eflect. It is wise to have an endotracheal tube in place should apnea occur. Diazepam (1 to 2 mg per kg intramuscularly) may be used in combination with ketamine. It ensures a smooth recovery and has a longer effect than xylazine. However, it does not enhance analgesia as much as does xylazine. Further, it is more expensive than xylazine, and accurate records of its use must be kept. A combination ofxylazine (2 mg per kg), oxymorphone (0.075 mg per kg), and ketamine (2 mg per kg) mixed in the same syringe and given intravenously induces satisfactory surgical anesthesia. By doubling each drug dose, a satisfactory response may be achieved by the intramuscular route. Analgesia and muscle relaxation are good. Recovery is smooth and may be hastened by administration of yohimbine and naloxone. Major drawbacks to this drug combination are expense and required accurate record keeping of oxymorphone. Pretreating pigs (up to 45 kg in weight) with atropine (0.05 mg per kg intramuscularly) and Innovar-Vet (1 ml per 15 kg intramuscularly) followed by ketamine (12 to 16 mg per kg intramuscularly) provides 30 to 40 minutes of surgical anesthesia. Anesthesia may be prolonged by supplemental doses of ketamine (2.2 mg per kg intravenously or 6.6 mg per kg intramuscularly). Acepromazine (0.4 mg per kg intramuscularly) followed in 30 minutes by ketamine (15 mg per kg intramuscularly) immobilizes swine for 1 to I1f2 hours, but analgesia is rather poor. Azaperone (2 to 8 mg per kg intramuscularly) may be given to tranquilize or immobilize swine. Ketamine (10 to 20 mg per kg intramuscularly) increases analgesia, but 20 to 30 minutes should be allowed to pass, ensuring deep tranquilization before ketamine is given. If swine are handled roughly during the administration process, they may respond unfavorably to this drug combination. It is not uncommon for pigs to reveal outwardly an excitatory response to azaperone before becoming tranquil or immobilized. Azaperone and metomidate (the latter not presently available in the United States) have been used extensively for anesthesia of swine in European countries. Azaperone (1 to 2 mg per kg intramuscularly)

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followed in 10 to 15 minutes by metomidate (10 mg per kg intraperitoneally or 4 mg per kg intravenously) induces anesthesia. Reports on analgesia are conflicting. Some suggest that cesarean section is possible with the two drugs alone, while others report that local analgesia is required for adequate surgical analgesia. As described earlier, GKX is a very workable combination of drugs in swine of all ages. Its major drawback is the requirement of intravenous administration. In swine, the xylazine concentration in GKX is increased tenfold over that used in ruminants. The combination is mixed by adding 500 mg of ketamine and 500 mg of xy lazine to each 500 ml of 5 per cent guaifenesin in 5 per cent dextrose in water. I refer to this combination as "Triple 500." The mixture is administered rapidly via a catheter placed into a central auricular vein at a dose of 0.5 to 1 ml per kg for induction. Anesthesia is maintained by continuous infusion at a rate of 2.2 mg per kg per hour. Analgesia and muscle relaxation are adequate for most surgical procedures. Although swine receiving GKX breathe well, tracheal intubation as with other anesthetic regimens seems prudent. I have observed pigs to vomit occasionally during recovery from 2 to 3 hours of GKX anesthesia. For the most part, recovery is smooth, occurring 20 to 40 minutes after discontinuing infusion. As with other regimens employing xylazine, recovery time may be hastened by intravenous administration of yohimbine (0.125 mg per kg) or tolazoline (2.5 to 5 mg per kg). To avoid ketamine-induced exicitement, neither of these agents should be administered prior to 20 to 30 minutes following discontinuation of GKX infusion. Recently in the University of Illinois Large Animal Hospital, a combination of ketamine (11 mg per kg intramuscularly), xylazine (2 mg per kg intramuscularly), and butorphanol (0.22 mg per kg intramuscularly) has been shown to induce satisfactory anesthesia in pigs (5 to 20 kg) for abdominal surgery (for example, hernia repair). Butorphanol appears to enhance analgesia greatly without causing noticeable respiratory depression. A laboratory study to validate further the safety and efficacy of this drug combination is under way. Steroidal Anesthetics Saffan (12 mg per ml) is an injectable anesthetic composed of two steroids, alphaxalone (9 mg per ml) and alphadalone (3 mg per ml). Because alphaxalone and alphadalone are poorly water-soluble, a polyoxyethylated castor oil compound (Cremophor EL) is used to increase the solubility of these agents. Because hypersensitive reactions are rather numerous and appear to be associated with the solubilizing agent, approval of Saffan for use in the United States has been delayed. This is unfortunate, because published reports and personal clinical experience suggest that Saffan is a useful anesthetic in calves, sheep, goats, and swine. Saffan is approved for use in the United Kingdom and European countries from which most reports have come on its use in food animals. Saffan may be given by either the intramuscular or the intra-

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venous route. The latter is preferred because induction of anesthesia is rapid, and the dose is approximately one half of that required by the intramuscular route. Anesthesia by the intramuscular route is of longer duration, but a large volume of Saffan is required. The optimal intravenous induction dose appears to be 3 to 6 mg per kg. The higher dose gives about 20 minutes of anesthesia characterized by a high degree of analgesia and muscle relaxation, which may be safely extended by supplemental increments of 1 to 2 mg per kg, as required. Cardiopulmonary function is well maintained and animals recover rather rapidly and smoothly, being able to stand in approximately 30 minutes, even after repeated administration. As with all other general anesthetics, tracheal intubation is advised because regurgitation of ruminal contents and pulmonary aspiration have been observed. In swine, Saffan is a very suitable anesthetic. Because of cost and the large volume required by the intramuscular route, it is most often given intravenously through an auricular ear vein. A dosage of 4 to 6 mg per kg given intravenously induces 10 to 15 minutes of surgical anesthesia. Premedicating swine with azaperone (4 mg per kg intramuscularly) decreases the induction dose of Saffan by 50 per cent. Anesthesia may be prolonged with incremental injections. Recovery is smooth and rapid. When a preanesthetic tranquilizer or sedative has been administered, recovery may be prolonged. In neonatal pigs, Saffan (2 to 3 mg per kg intramuscularly) induces deep sedation and muscle relaxation. Anesthesia can then be induced by further administering 2 to 3 mg per kg intravenously. Incremental injections may be used to maintain anesthesia safely for up to 2 hours.

Chloral Hydrate Chloral hydrate is an excellent sedative that may be given intravenously or orally to ruminants and occasionally to swine. Because of its poor analgesic qualities and narrow margin of safety in high doses, it is seldom used as the sole anesthetic. The compound is highly irritating to tissues, and care must be taken to ensure intravascular administration because perivascular injection will result in massive tissue necrosis. Chloral hydrate may be used to induce light narcosis safely and may be supplemented with local or regional analgesia for minor surgeries. The sedative effect of chloral hydrate is slow in onset, so the drug must be injected slowly, allowing sufficient time to achieve the desired state of narcosis without approaching an overdose. Full effects of an intravenous dose of chloral hydrate occur in approximately 5 minutes. Chloral hydrate has been used effectively to sedate confined animals that could not otherwise be approached for handling. When animals are starved of water for 24 to 36 hours, they often become thirsty enough to drink water containing chloral hydrate in a concentration of 100 to 150 gm per 8 to 10 L. Light to medium narcosis may be achieved by 5 to 7 gm per 100 kg, intravenously. Sedation for purposes of transporting mature boars and sows may be safely achieved by administration of 10 to 15 gm per 100 kg of chloral hydrate by

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stomach tube. Intraperitoneal administration of chloral hydrate induces peritonitis; therefore, I can not recommend sedation of pigs for surgical repair of abdominal hernias and so forth via this route. Mixtures of chloral hydrate and pentobarbital are commercially available. These mixtures satisfactorily induce sedation or light narcosis that is not accompanied by analgesia.

IMMOBILIZING AGENTS FOR CAPTURE OF FERAL ANIMALS Drugs most readily available to the veterinarian for immobilization of feral ruminants are ketamine and xylazine. Either of these agents effectively immobilizes cattle if given in high enough dose. However, if they are given in combination, induction and recovery are smoother. The disadvantage of the combination is that the total volume required in the adult cow is somewhat too large for delivery with most systems (that is, Cap-Chur-type gun). There have been attempts to overcome this problem by increasing the concentration of each of these drugs. Presently, ketamine and xylazine can be purchased in concentrations of 100 mg per ml. Through freeze-drying of these agents, powder can be obtained. With ketamine and xylazine powder, a small volume of a highly concentrated drug mixture can be delivered to immobolize a large animal. Ketamine appears to be soluble in a concentration of 200 to 300 mg per ml, while xylazine concentration can easily be tripled (that is, 300 mg per mI). Thus, concentrated ketamine and xylazine may be easily combined in the same syringe for more effective use in the capture of feral cattle. The profound sedative effect induced by 1 mg per kg xylazine (five times the normal sedative dose in cattle) has been safely antagonized with yohimbine (0.125 mg per kg intravenously) and 4-aminopyridine (0.30 mg per kg intravenously). In my experience, yohimbine alone has been effective in reversing xylazine sedation. Another readily available xylazine antagonist that has proven to be effective in goats, sheep, and swine in the laboratory is tolazoline (2 to 5 mg per kg intravenously). When administration of a large dose of xylazine is anticipated, a supply of yohimbine or tolazoline should be readily available. Likewise, equipment for tracheal intubation, oxygen administration, and relief of ruminal tympany should be immediately at hand. Etorphine (M-99), an opiate derivative, is presently the most widely used drug for capture of wild animals of large size. This compound is extremely potent, and an immobilizing dose can easily be delivered in standard capture devices. For this reason, extreme caution should be exercised when M-99 is used. In all instances, the antagonist (diprenorphine [M-5050] or naloxone) should be drawn into a syringe and readied for injection before M-99 is loaded into the delivery syringe. Accidental self-injection can quickly lead to death unless the antagonist is given immediately. In cattle, the immobilizing dose of M -99 is 0.022 mg per kg when

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given with acepromazine (0.10 mg per kg). To antagonize the effects of M-99, M-5050 is given at a rate of 0.030 to 0.040 mg per kg intravenously. Adult moose have been effectively immobilized with M-99 (0.016 mg per kg) and xylazine (0.60 mg per kg). Xylazine is a much more potent immobilizing adjunct than is acepromazine; thus, 0.10 to 0.20 mg per kg of xylazine would quite likely decrease the dose of M-99 required to immobilize a feral cow. Because specific antagonists for M-99 (diprenorphine) and xylazine (yohimbine) are available, minor overdosing of these agents is not of major concern. Carfentanil is an extremely potent synthetic opiate closely related to fentanyl (the narcotic component of Innovar-Vet). It has been used to immobilize elk and moose in doses of 0.00125 to 0.012 mg per kg. Elk injected with 0.00125 to 0.0066 mg per kg were immobilized in 3.8 minutes. Less than 2 minutes was required when the dose was increased. Antagonism is rapid and complete when M-5050 is given at seven times the total carfentanil dose. There is every reason to believe that carfentanil can be used effectively and safely to immobilize feral cattle. The compound is presently undergoing scrutiny by the Food and Drug Administration for approval as an immobilizing agent for wild animals. In addition to the potent opioid derivatives (for example, M-99, fentanyl, carfentanil, and others) used to immobilize wild and feral ruminants, a group of central serotonin receptor blocking compounds has been shown to have profound "tranquilizing-taming" effects in elk and "aggressive bovine species." A peripheral serotonin (S-2) receptor blocker (ketanserin, 0.4 mg per kg intravenously) has been shown to decrease hypertension and "stress-hyperthermia" mortality associated with increased circulating catecholamines and serotonin in elk. A compound labeled R51703, a central serotonin inhibitor, closely related to ketanserin has a strong tranquilizing and taming effect. R51703 (0.4 mg per kg intramuscularly) does not immobilize but induces a calm state so profound that even aggressive animals of the bovine species may be easily approached and handled. A combination of R51703 and carfentanil is reportedly safe and effective for immobilizing elk. Further development of agents designed to manipulate endogenous neurotransmitters and development of additional specific agonists and antagonists appear to be important to the establishment of effective injectable immobilizing anesthesia techniques for wild animals. Undoubtedly, discovery and development of such agents will play a major role in the future trends of veterinary anesthesia.

ELECTRO IMMOBILIZATION Recently, the techniques of electroimmobilization and electroacupuncture anesthesia have been advanced for use in food animals. AI-

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though the term electroanesthesia has frequently been used, electroimmobilization is a more appropriate term for this technique. Electroimmobilization has been advocated for minor surgery, although there is strong evidence that the technique is aversive and does not eliminate pain of surgery in most patients. Although cardiopulmonary function is not severely depressed in most animals, it is generally agreed that electroimmobilization techniques do not induce the major components of anesthesia. Work completed by Grandin and colleagues convincingly demonstrated that recall of electroimmobilization occurs in sheep.16 These results show that amnesia or unconsciousness is not achieved with electroimmobilization. Because unconsciousness, amnesia, and analgesia are essential components of general anesthesia, electroimmobilization can not be considered acceptable for surgery. In conclusion, electroimmobilization is aversive, may in fact be painful, and can not be equated with the term anesthesia. Electroacupuncture has shown some promise as a means of inducing local or regional analgesia and may be a legitimate alternative to local or regional nerve block in the hands of experienced individuals. The induction of general anesthesia in cattle with electroacupuncture has not been reported in the United States. The technique requires precise placement of needles along the course of major nerve trunks or so-called anesthetic lines and continual electrical stimulation to achieve and maintain excitation of the CNS and damping of painful stimuli. It is possible that electroacupuncture, in contrast to electroimmobilization, may serve as an effective alternative to druginduced anesthesia in the skilled acupuncturist's hands.

DRUG SOURCES Acepromazine (Acetyl promazine): Ayerst Laboratories, Division of American Home Products Corp., New York, New York 10017 Alphaxalone-alphadalone (Saffan): Glaxo Laboratories, Greenford, Middlesex, England 4-Aminopyridine: Sigma Chemical Co., St. Louis, Missouri 63178 Atropine: Med. Tech. Inc., Elwood, Kansas 66024 Azaperone (Stresnil): Pitman-Moore, Inc., Washington Crossing, New Jersey 08560 Butorphanol (Torbugesic): Bristol Laboratories, Syracuse, New York 13201 Carfentanil : Wildlife Laboratories Inc., Fort Collins, Colorado 80524 Chloral Hydrate: Veterinary Laboratories, Inc., Lenexa, Kansas 66215 Diazepam (Valium): Hoffman-LaRoche, Inc., Nutley, New Jersey 07110

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Diprenorphine (M-5050): Lemmon Co., Sellersville, Pennsylvania 18960 Doxapram (Dopram): A. H. Robins Company, Richmond, Virginia 23220 Etorphine (M-99): Lemmon Co., Sellersville, Pennsylvania 18960 Fentanyl-droperidol (Innovar-Vet): Pitman-Moore, Inc., Washington Crossing, New Jersey 08560 Glyceryl guaiacolate (Guaifenesin): A. H. Robins Company, Richmond, Virginia 23220 Ketamine (Ketaset): Bristol Laboratories, Syracuse, New York 13201 Methohexital (Brevital): Eli Lilly and Co., Indianapolis, Indiana 46285 Metomidate (Hypnodil): Janssen Pharmaceutical Beerse, Belgium Naloxone: Pitman-Moore Inc., Washington Crossing, New Jersey 08560 Oxymorphone (N umorphan): Endo Laboratories Inc., Garden City, New York 11530 Pentobarbital (Nembutal): Abbott Laboratories, North Chicago, Illinois 60064 Thiamylal (Biotal): Bio-Ceutic, Division Boehringer Ingelheim, St. Joseph, Missouri 64502 Thiopental (Pentothal): Abbott Laboratories, North Chicago, Illinois 60064 Tolazoline (Priscoline): Ciba, Summit, New Jersey 07901 Xylazine (Rompun): BayVet, Division Miles Laboratories, Shawnee, Kansas 66201 Yohimbine (Antagenil): Wildlife Laboratories Inc., Fort Collins, Colorado 80524

REFERENCES J. V., Wheatley, A. M., et al.: Althesin as an anesthetic in experimental animals susceptible to halothane-initiated malignant hyperthermia. Br. J. Pharmacol., 63:425, 1979. Anderson, I. L.: Anesthesia of swine. N. Z. Vet. J., 25:319-321, 1977. Baber, D. W., and Coblentz, B. E.: Immobilization of feral pigs with a combination ofketamine and xylazine. J. Wildl. Manage., 46:557-559,1982. Benson, C. J., and Thurmon, J. C.: Anesthesia of swine under field conditions. J. Am. Vet. Med. Assoc., 174:594-596, 1979. Booth, N. H.: Intravenous and other parenteral anesthetics. In Veterinary Pharmacology and Therapeutics. Edition 5. Ames, Iowa State University Press, 1982, pp. 203-254. Breeze, C., and Dodman, N. H.: Xylazine-ketamine-oxymorphine: An injectable anesthetic combination in swine. J. Am. Vet. Med. Assoc., 184:182-183, 1984. Byagagaire, S. D., and Mbiuki, S. M.: Duration of analgesia in sheep under xylazineketamine anesthesia. Vet. Rec., 114:15-16, 1984.

1. Ahern, C. P., McLaughlin,

2. 3. 4. 5. 6. 7.

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