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IN-DEPTH: ANESTHESIA AND PAIN MANAGEMENT
Balancing Total Intravenous Anesthesia and
Inhalant Anesthesia in Horses
Ann E. Wagner, DVM, MS, Diplomate ACVA, ACVP
Author’s address: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical
Sciences, Colorado State University, Fort Collins, Colorado 80523; e-mail: [email protected].
© 2009 AAEP.
1.
Introduction
Intravenous drugs such as chloral hydrate, pentobarbital, and thiamylal were once commonly used
for general anesthesia of horses but were often associated with prolonged or violent recoveries. When inhalant anesthetics such as halothane
were introduced in the 1960s, the use of IV drugs for
maintenance of anesthesia became less common.1
In recent years, interest in IV anesthetic techniques
has been renewed, both by recognition of the relatively high risk of morbidity or mortality with inhalant techniques and by the development of injectable
drugs with fewer undesirable side effects and potentially improved recovery characteristics.2
In 2002, a large, multi-center prospective study
reported peri-anesthetic mortality for horses to be
0.9% (1 death per 111 anesthetized horses).3
Subsequently, one individual equine hospital reported a much lower mortality rate of 0.12– 0.24% (1
death per 417– 833 cases).4 In the multi-center
study, anesthesia induced and maintained using
only IV drugs (total intravenous anesthesia [TIVA])
was reported to be associated with a lower risk of
death (0.3%, or 1 death per 321 cases) than anesthesia induced with IV drugs and maintained with inhalant anesthesia.3 Recoveries from short-term IV
anesthesia are often smoother and more controlled
than recoveries from inhalant anesthesia.5 Other
advantages of TIVA include the minimal equipment
required compared with inhalant anesthesia and
potentially reduced stress.6 The development of reversible or shorter-acting drugs such as ␣2 agonists,
ketamine, and propofol has facilitated the use of
TIVA for longer procedures than previously considered safe.7
This article will review the current state of TIVA
in horses, as well as how certain IV sedatives, anesthetics, and analgesics are being used to supplement
and improve inhalant anesthesia.
2.
Short-Term IV Anesthesia (≤20 min)
In the United States, the most common technique
used for short-term IV anesthesia is xylazine sedation followed by ketamine induction, with or without
diazepam for improved muscle relaxation. Xylazine-ketamine or xylazine-diazepam-ketamine provides an average of 16 min of surgical anesthesia,
with recovery to standing in ⬃25–32 min.8 –10 It
has been suggested that duration of surgical anesthesia is longest in grade horses and shorter in Thoroughbreds.9 Most equine practitioners find both
induction and recovery with this drug regimen to be
satisfactory and reasonably safe. For good quality
NOTES
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Table 1.
Adjuncts for Improved Quality of Anesthesia
Listed below are suggested adjuncts for improving quality of anesthesia in horses that are too light or too tense after an ␣-2
agonist ⫹ ketamine ⫾ diazepam induction and do not respond sufficiently to additional increments of ␣-2 agonist or
ketamine
Systemically administered drugs
Thiopental ⬃1–2 mg/kg 关5–10 ml of 10% thiopental兴 IV (augments CNS depression and muscle relaxation)
Guaifenesin ⬃25–50 mg/kg 关250–500 ml of 5% guaifenesin兴 IV (augments muscle relaxation only)
Butorphanol ⬃0.01–0.02 mg/kg 关0.5–1 ml兴 augments analgesia (more noticeable during IV anesthesia than during gas
anesthesia)
Locally or regionally administered drugs
Castration
Lidocaine infiltration of testicle ⫾ spermatic cord augments analgesia, improves cremaster relaxation, and prolongs surgical
anesthesia time
15–20 ml 2% lidocaine injected directly into each testicle; some surgeons inject additional 5 ml into spermatic cord also
Wounds
Specific nerve blocks if applicable (digital, etc.)
Perilesional infiltration with lidocaine
Eye
Specific nerve blocks if applicable
Topical anesthetic on globe
of surgical anesthesia, it is important to ensure that
sedation and muscle relaxation are adequate; therefore, in general, a higher dose of xylazine (1.1 mg/kg
or ⬃500 mg per 450-kg horse) than would typically
be used for standing sedation is recommended. Additional methods for improving muscle relaxation
and quality of IV anesthesia are listed in Table 1.
Although xylazine is the most common pre-medication in the United States, other ␣2 agonists may
be used and may afford a slightly longer anesthesia
time. For example, detomidine (0.02 mg/kg, IV) followed by ketamine (2.2 mg/kg, IV) produced recumbency of slightly longer duration (average, 27 min)
than xylazine (1.1 mg/kg, IV) and ketamine (2.2
mg/kg, IV) (average, 23 min). However, muscle relaxation during anesthesia and recovery quality
were both slightly less satisfactory with detomidineketamine than with xylazine-ketamine.11
Romifidine is a newer ␣2 agonist associated with a
longer duration and purportedly less ataxia than
xylazine. Both of these characteristics could be
beneficial for short-term IV anesthesia. A comparison of romifidine (0.1 mg/kg, IV) to xylazine (1.1
mg/kg, IV), in combination with diazepam and ketamine, showed that both regimens produced excellent quality anesthesia, with good induction and
recovery quality, and good muscle relaxation. The
romifidine combination produced about 5 additional
min of surgical anesthesia (21 min) compared with
the xylazine combination (16 min). Recovery required about 44 min for the romifidine group compared with 32 min for the xylazine group.8
Butorphanol has been used as an adjunct for IV
anesthesia. A comparison of xylazine-ketamine or
detomidine-ketamine, with and without the addition
of butorphanol (0.04 mg/kg, IV, or 18 mg per 450-kg
horse), suggested that butorphanol may improve
muscle relaxation and surgical conditions and prolong recumbency time slightly.11
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Thiopental, once the “gold standard” of anesthetic
induction agents, is no longer commonly used for
short-term anesthesia in horses. Although with
appropriate premedication such as xylazine, thiopental inductions are quite predictable and smooth,
recoveries from short-term thiopental anesthesia
tend to be somewhat uncoordinated.10 In addition,
thiopental can be very irritating if accidentally injected perivascularly, and the volume typically required to anesthetize a 450-kg horse (⬃27 ml of 10%
solution) makes perivascular injection a considerable risk, unless an IV catheter is in place.
Interestingly, results of a controlled study suggested that thiopental produced better-quality inductions than did ketamine and that combining
either ketamine or thiopental in various proportions
with propofol improved both induction and recovery
quality.10 Propofol is an induction agent that has
become extremely popular both in humans and in
small animals, with generally smooth inductions
and particularly rapid and smooth recoveries, with
none of the residual “hangover” often associated
with other anesthetics. In the equine study, combinations of 1⁄4 induction dose of propofol with 3⁄4
induction dose of ketamine or thiopental produced
the smoothest inductions. However, the best-quality recoveries were achieved by combining 3⁄4 dose of
propofol with 1⁄4 dose of ketamine or thiopental.
One might then think that combining 1⁄2 dose of
propofol with 1⁄2 dose of the others would result in
both excellent inductions and excellent recoveries,
and indeed, the “1⁄2-1⁄2” combinations did result in
both induction and recovery quality that appeared to
be slightly better than either ketamine or thiopental
alone.10
Unfortunately, there are issues related to propofol
administration in horses that detract from its usefulness as a sole induction agent. Inductions by
propofol alone may be quite violent, with paddling of
IN-DEPTH: ANESTHESIA AND PAIN MANAGEMENT
the limbs and uncoordinated muscle activity.12
Premedication with either xylazine or detomidine
does not prevent excitatory behavior and muscle
activity.13 With the currently available propofol
concentration of 10 mg/ml, the required induction dose
(2 mg/kg) for a typical horse is nearly 100 ml, making
it inconvenient and time consuming to administer.
Respiratory depression may be profound and may necessitate assisted ventilation.12,13 Despite its reputation for rapid recoveries in most species, a single
induction dose of propofol in horses (after xylazine
premedication) is associated with slightly longer times
to standing (⬃33 min) than a single dose of ketamine
(⬃25 min).10,13
The use of tiletamine-zolazepam, another option
for induction of anesthesia of horses, was first described 20 yr ago.14 Tiletamine is a dissociative
anesthetic similar to ketamine, and zolazepam is a
benzodiazepine similar to diazepam. Tiletamine
and zolazepam are marketed in the United States as
the 50:50 combination Telazol,a formulated as a
powder that must be reconstituted before use. A
500-mg vial contains 250 mg of tiletamine and 250
mg of zolazepam, and the recommended doses are
given as milligram per kilogram of both drugs combined. After sedation with xylazine, anesthesia induced with tiletamine-zolazepam, at doses of 1.1,
1.65, or 2.2 mg/kg, IV, resulted in surgical anesthesia of ⬃20 min, lateral recumbency of 30- to 39-min
duration, and recovery to standing in 32– 46 min;
thus, tiletamine-zolazepam produces longer duration of anesthesia than does ketamine. Quality of
anesthesia was judged to be best with tiletaminezolazepam doses of 1.65 or 2.2 mg/kg, IV. However,
PaO2 decreased more than with xylazine-ketamine
anesthesia.14 In addition, recoveries from shortterm xylazine-tiletamine-zolazepam anesthesia
tend to be less satisfactory than recoveries from
xylazine-ketamine anesthesia.11 In the United
States, tiletamine-zolazepam is usually more expensive than ketamine-diazepam. Potential advantages of tiletamine-zolazepam include the slightly
longer duration of anesthesia and the very small
volume required for injection, which may be advantageous for certain situations, such as darting feral
horses.
A combination of tiletamine-zolaepam-ketaminedetomidine (TZKD) has been used for induction of
anesthesia in horses.15 The combination was pre-
Table 2.
pared by adding 4 ml of ketamine (100 mg/ml) and 1
ml of detomidine (10 mg/nl) to reconstitute a 5-ml
bottle of tiletamine-zolazepam. Horses were first
sedated with xylazine 0.44 mg/kg, IV (⬃200 mg for a
450-kg horse), and the combination TZKD was administered at 3 ml/450 kg, IV. This volume resulted in individual drug doses of tiletaminezolazepam at 0.67 mg/kg, ketamine at 0.53 mg/kg,
and detomidine 0.013 mg/kg. The authors reported
that advantages of this combination included the
small volume of drug to administer, predictable and
rapid induction, good muscle relaxation and analgesia that lasted longer than that associated with xylazine-ketamine, and acceptable cardiorespiratory
values. All horses stood satisfactorily in two or
fewer attempts within 40 min after induction.15
3.
TIVA (>20 min)
When a procedure requires ⬎15–20 min, surgical
anesthesia can be prolonged by administering additional IV anesthetics, either as intermittent boluses
or constant rate infusions (CRIs) (Table 2). To gain
an extra 3–5 min of surgical anesthesia, additional
␣2 agonist and ketamine can be administered at
approximately one third the original induction
doses. These boluses can be repeated several times
as needed.
When a procedure is anticipated to take ⬎30 min,
it is advisable to use a CRI to maintain anesthesia to
provide a more stable plane of anesthesia. Since
the early 1980s, the most common technique used
for this purpose has been “triple drip” or “GKX,” a
combination of guaifenesin (50 mg/ml), ketamine
(1–2 mg/ml), and xylazine (0.5 mg/ml).16 For more
painful or noxious procedures, the higher concentration of ketamine (2 mg/ml) is recommended, whereas
for restraint involving minimal stimulus, the lower
ketamine concentration (1 mg/ml) may suffice.
Although GKX can be used for induction of anesthesia, this induction involves a relatively prolonged
period of ataxia, and most practitioners prefer to
induce with xylazine-ketamine or xylazine-diazepam-ketamine and then use GKX for maintenance.
Typical infusion rates vary from 1.5 to 2.2 ml/kg/h,
depending on the procedure and the individual’s
response, as well as the concentration of ketamine in
the GKX.
Guaifenesin-ketamine-detomidine (GKD) is another combination used for TIVA. After sedation
Simplified Continuous Rate Infusions
A simple way to deliver CRIs without a fluid pump is to add 1 h worth of the appropriate drug(s), based on the individual
patient’s weight, to a 250-ml bag of IV fluid. At 1 drop/s (assuming an IV set that delivers 15 drops/ml), the contents of the bag
will be delivered in ⬃1 h.
For example, to achieve a xylazine-ketamine (XK) infusion in a 450-kg horse:
X: 450 kg ⫻ 2.1 mg/kg/h ⫽ 945 mg/h ⫽ 9.5 ml/h
K: 450 kg ⫻ 7.2 mg/kg/h ⫽ 3240 mg/h ⫽ 32.4 ml/h
Therefore, remove ⬃40–45 ml from a 250-ml bag of IV fluid; replace with 950 mg (9.5 ml) xylazine and 3240 mg (32.4 ml)
ketamine; and deliver at 1 drop/s (assuming 15 drops/ml).
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with detomidine (0.02 mg/kg, IV) and induction with
ketamine (2 mg/kg, IV), anesthesia was maintained
in ponies for 90 min with GKD (guaifenesin 100
mg/ml, ketamine 4 mg/ml, and detomidine 0.04 mg/
ml; note these concentrations of guaifenesin and
ketamine are about twice the usual concentrations
used in GKX), at an infusion rate of 0.8 ml/kg/h for
the first 60 min and 0.6 ml/kg/h for the final 30
min.17 The ponies took longer to stand (average, 46
min) compared with ponies anesthetized with halothane (33 min), but recovery quality was generally
good to excellent. Oxygen was supplemented during anesthesia.17
An alternative to guaifenesin-based combinations
is a CRI of xylazine and ketamine. After a standard induction, an infusion of xylazine at 35 ␮g/kg/
min (2.1 mg/kg/h) and ketamine at 120 ␮g/kg/min
(7.2 mg/kg/h) can be administered to maintain anesthesia for up to 70 min.18
Xylazine-ketamine CRIs are associated with very
smooth recoveries, but after 70 min of anesthesia,
the time required for the horse to recover to standing is generally longer (50 –55 min) compared with
recoveries from inhalation anesthesia (15– 40 min,
depending on the specific inhalant used).18
Other alternatives for TIVA include various combinations of ␣2 agonists with propofol. Detomidine
(0.015 mg/kg, IV) and propofol (2 mg/kg, IV) were
used to induce anesthesia in horses for experimental
abdominal surgery, with anesthesia maintained by
propofol infusion at an average of 0.18 mg/kg/min.
However, the combination was not recommended for
clinical use, because inductions were associated
with some excitement, and respiratory depression
and hypoxemia occurred.19
Medetomidine, an ␣2 agonist developed for use in
small animals, has also been combined with propofol
for TIVA in horses. In a clinical study of horses,
medetomidine (7 ␮g/kg, IV) was given for sedation,
and because of poor inductions with propofol, anesthesia was induced using ketamine (2 mg/kg, IV)
and diazepam (0.02 mg/kg, IV); anesthesia was
maintained by CRIs of medetomidine (3.5 ␮g/kg/h,
IV) and propofol (0.1 mg/kg/min, IV). Duration of
anesthesia averaged just under 2 h, but the longest
was nearly 4 h. About one half of the horses were
apneic and needed mechanical ventilation. Horses
were given an additional dose of medetomidine (2
Table 3.
␮g/kg, IV) 10 min after terminating the CRIs and
stood in an average of 42 min.20 In another study,
horses were sedated with medetomidine (5 ␮g/kg,
IV), induced with midazolam (0.04 mg/kg, IV) and
ketamine (2.5 mg/kg, IV), given a loading dose of
propofol (0.5 mg/kg, IV), and maintained on either
propofol (0.22 mg/kg/min) or a combination of ketamine (1 mg/kg/h), medetomidine (1.25 ␮g/kg/h),
and propofol (0.14 mg/kg/min). Most horses became apneic and hypoxemic and were therefore mechanically ventilated. After just under 2 h of
anesthesia, recoveries were actually better quality
and faster (average, 62 min) in the horses receiving
the combination compared with propofol only (average, 87 min), leading the authors to suggest that
propofol was the drug most responsible for prolonging recoveries.21
The time limit for safely maintaining anesthesia
using TIVA is uncertain. Ponies maintained with
GKX for 120 min were able to stand without help
within 30 min after terminating the infusion, “and
postanesthetic problems were not encountered.”
However, these ponies weighed only 150 –275 kg,
they were endotracheally intubated, and they received supplemental oxygen.16 Some of the other
CRI techniques described here have been used to
maintain anesthesia for ⬎2 h in full-size horses, but
again, the horses were intubated, breathing high
inspired oxygen, often mechanically ventilated, and
positioned on padded surgery tables. Without supplemental oxygen, an anesthetized, recumbent
horse is likely to be hypoxemic (arterial PO2 in the
range of 40 – 60 mm Hg),8,19 which increases the risk
of damage to muscles and other vital organs from
inadequate oxygen delivery (Table 3). Because
TIVA is often performed under field conditions,
without supplemental oxygen or a well-padded surface, a common recommendation is to limit anesthesia time to ⬃60 min.22
4.
Intravenous Adjuncts During Inhalant Anesthesia
Partly because inhaled anesthetics are associated
with several disadvantages—including cardiovascular depression, an increased stress response, and
variable recovery quality —and partly because of
increasing interest in improving pain management,
a number of anesthetic or analgesic adjuncts are
being used to augment inhalation anesthesia in
When to Supplement Oxygen During Anesthesia
During general anesthesia, supplementation of oxygen is recommended, although rarely used in field situations. Anesthesia and
recumbency cause ventilation-perfusion mismatch in the lungs that lowers PaO2 considerably. Even if you do not normally
supplement oxygen, consider doing it when:
Anesthesia and recumbency will be prolonged ⬎ 30 min
The horse has respiratory abnormalities such as COPD
The horse has cardiac abnormalities such as a murmur
The horse is very young (neonate) or very old
Although typically oxygen may be delivered by nasal insufflation (10 –15 l/min), intubation and manual or mechanical ventilation
may be necessary for some TIVA procedures, especially those involving propofol.
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IN-DEPTH: ANESTHESIA AND PAIN MANAGEMENT
horses. The use of multiple agents in this manner
is termed “balanced anesthesia” or “partial intravenous anesthesia” (PIVA). The usual goals of adding these adjuncts are to decrease the requirement
for the inhalant (therefore minimizing cardiovascular depressant effects), provide analgesia, and improve recoveries.
Intravenous lidocaine has been shown to decrease
the maximum alveolar concentration (MAC) for inhalant anesthetics in a dose-dependent fashion.
After a loading dose of 2.5 or 5 mg/kg, IV, lidocaine
infusions of either 50 or 100 ␮g/kg/min decreased
halothane MAC by 30 –70%.23 Because of the purported benefit of lidocaine infusions on gastrointestinal motility, lidocaine CRIs are frequently
administered to horses anesthetized for colic surgery but are also used during other surgeries. For
routine clinical use as an anesthetic adjunct, a loading dose is probably not necessary, because a lidocaine CRI reaches steady state in ⬃20 min.24
Because of concerns about potential residual ataxia
in recovery after IV lidocaine,25 it is recommended
that lidocaine CRI be terminated ⬃15 min before the
end of anesthesia.
Ketamine CRIs are also used to supplement inhalant anesthesia. A plasma ketamine concentration of
⬃11 ␮g/ml was associated with halothane MAC reduction of ⬃37% and corresponding improvement in cardiac output.26 Approximately 30% MAC reduction
might be achieved by administration of 50 ␮g/kg/min
(3 mg/kg/h).27 Because ketamine has antagonist
properties at spinal cord n-methyl-d-aspartate
(NMDA) receptors associated with the pain “wind-up”
phenomenon, even infusion rates ⬍50 ␮g/kg/min may
be associated with improved pain management, although evidence of this benefit specific to horses is not
available. Ketamine infusion rates of 10 –50 ␮g/kg/
min (0.6 –3 mg/kg/h) are typically used clinically.
Medetomidine CRIs have gained some popularity
as an adjunct to inhalant anesthesia in horses.
Infusion rates of 3.5–5 ␮g/kg/h (⬃1.6 –2.3 mg/h for a
450-kg horse) reduce MAC by ⬃25%.27 An added
benefit of medetomidine CRI as a supplement to
isoflurane anesthesia is reported to be improved recovery quality.28
In dogs, opioids are a mainstay of anesthesia and
perioperative pain management, but use of opioids in
horses is much more controversial, not only because of
undesirable side effects such as central nervous system excitation and impaired gastrointestinal function,
but also because of inconsistent results from studies of
various opioids’ effect on MAC for inhalants. Butorphanol (0.05 mg/kg or ⬃22.5 mg per 450-kg horse) had
no reliable effect: it increased halothane MAC in
three of six ponies tested, decreased it in one pony, and
did not change it in two others.29 Alfentanil and morphine likewise had no predictable beneficial effect on
the MAC for isoflurane in horses.30,31 A more recent
study reported that a high dose of fentanyl reduced
isoflurane MAC but that the effect was less than that
of fentanyl in humans or dogs.32
Some investigators have used multiple IV drugs
combined with inhalant anesthesia in a true “PIVA”
technique. One protocol supplemented halothane
anesthesia with a CRI of ketamine and guaifenesin
that was gradually decreased over time (mean infusion rates varied from 39 ␮g/kg/min and 1 mg/kg/
min at 20 min, respectively, to 13 ␮g/kg/min and 0.3
mg/kg/min at 120 min). This protocol was associated with a 50% reduction in halothane requirement, fewer “top-up” doses of ketamine, and less
need for dobutamine to support blood pressure.
Recovery times and quality were “acceptable” and
similar to horses recovering from halothane only.33
Another example of PIVA is infusion of guaifenesin, ketamine, and medetomidine in combination
with sevoflurane. A solution of guaifenesin (⬃50
g/l), ketamine (⬃2 g/l), and medetomidine (⬃2.4
mg/l) was administered at 0.5 ml/kg/h. Horses receiving this combination during sevoflurane anesthesia maintained excellent quality of anesthesia,
did not require dobutamine for blood pressure support, and required fewer attempts to stand in recovery compared with horses maintained with
sevoflurane only.34
5. Intravenous Anesthetics at the End of Inhalant
Anesthesia
Because inhalant anesthesia is often associated with
less-than-ideal recovery quality, a variety of techniques have been used in an attempt to improve
recoveries. The most common involve administration of an ␣2 agonist at the end of anesthesia or on
the horse’s arrival at the recovery stall. The use of
xylazine (0.1 mg/kg, IV), detomidine (2 ␮g/kg, IV), or
romifidine (8 ␮g/kg, IV) after isoflurane anesthesia
improved recovery and reduced ataxia compared
with isoflurane alone, with each of the drugs being
similarly effective.35 Clinically, a slightly higher
dose of xylazine (0.22 mg/kg, IV or ⬃100 mg per
450-kg horse) is often used to improve recovery.
Acepromazine is also used to modify recovery, although there is no documented proof of its benefit.
Clinical experience suggests that a very small dose
of acepromazine (0.007 mg/kg, IV, or ⬃3 mg per
450-kg horse), given about 20 min before the end of
anesthesia (to allow enough time for onset of effect),
may result in calmer, more controlled recoveries.
However, even after administration of acepromazine, many horses still benefit from additional sedation with xylazine in recovery.
Part of the recent interest in TIVA is attributable to
the good-to-excellent recovery quality typically associated with TIVA; however, as previously mentioned,
there is still concern about maintaining anesthesia
⬎1–1.25 h using TIVA. A compromise might be to
use inhalant anesthesia for maintenance during the
majority of a long procedure and then terminate delivery of the inhalant and continue anesthesia using IV
drugs for the last 30 min or so, the goal being to allow
the horse to eliminate the inhalant completely before
awakening from the IV anesthetics. A recent experAAEP PROCEEDINGS Ⲑ Vol. 55 Ⲑ 2009
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imental study of seven horses used CRIs of xylazine
(20 ␮g/kg/min) and ketamine (60 ␮g/kg/min) to continue anesthesia for 30 min after 90 min of isoflurane
anesthesia. Although no statistically significant improvement in recovery quality was shown, the average
scores for quality of standing and overall quality of
recovery suggested the technique might have benefit.36 The authors have continued to use this technique for specific clinical cases, such as horses that
have undergone orthopedic procedures in which a
smooth recovery is especially important.
6.
Summary
To date, there are numerous drug combinations that
can be used to produce general anesthesia in horses.
Currently, there is no single perfect method that is
uniformly reliable and safe, particularly for longterm anesthesia. However, the development of
newer injectable drugs and continuing studies into
their use for TIVA or PIVA promise further improvements in the near future.
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