Evaluation of cardiovascular effects of total intravenous anesthesia
with propofol or a combination of ketamine-medetomidine-propofol
in horses
Mohammed A. Umar, DVM, MVSc; Kazuto Yamashita, DVM, PhD; Tokiko Kushiro, DVM, PhD;
William W. Muir III, DVM, PhD
Objective⎯To evaluate the cardiovascular effects of total IV anesthesia with propofol (P-TIVA) or ketamine-medetomidine-propofol (KMP-TIVA) in
horses.
Animals⎯5 Thoroughbreds. Procedures⎯Horses were anesthetized twice for 4 hours, once with P-TIVA and once with KMP-TIVA. Horses were
medicated with medetomidine (0.005 mg/kg, IV) and anesthetized with ketamine (2.5 mg/kg, IV) and midazolam (0.04 mg/kg, IV). After receiving a
loading dose of propofol (0.5 mg/kg, IV), anesthesia was maintained with a constant rate infusion of propofol (0.22 mg/kg/min) for P-TIVA or with a
constant rate infusion of propofol (0.14 mg/kg/min), ketamine (1 mg/kg/h), and medetomidine (0.00125 mg/kg/h) for KMP-TIVA. Ventilation was
artificially controlled throughout anesthesia. Cardiovascular measurements were determined before medication and every 30 minutes during
anesthesia, and recovery from anesthesia was scored.
Results⎯Cardiovascular function was maintained within acceptable limits during P-TIVA and KMP-TIVA. Heart rate ranged from 30 to 40
beats/min, and mean arterial blood pressure was > 90 mm Hg in all horses during anesthesia. Heart rate was lower in horses anesthetized with
KMP-TIVA, compared with P-TIVA. Cardiac index decreased significantly, reaching minimum values (65% of baseline values) at 90 minutes during
KMP-TIVA, whereas cardiac index was maintained between 80% and 90% of baseline values during P-TIVA. Stroke volume and systemic vascular
resistance were similarly maintained during both methods of anesthesia. With P-TIVA, some spontaneous limb movements occurred, whereas with
KMP-TIVA, no movements were observed.
Conclusions and Clinical Relevance⎯Cardiovascular measurements remained within acceptable values in artificially ventilated horses during
P-TIVA or KMP-TIVA. Decreased cardiac output associated with KMP-TIVA was primarily the result of decreases in heart rate. (Am J Vet Res
2007;68:121–127)
rolonged general anesthesia in horses is generally accomplished by administering inhalation anes-thetics. The concentration of inhalation
anesthetics required to provide a surgical plane of anesthesia fre-quently contributes to the intraoperative development of hypotension and
hypoventilation. On the other hand, findings during the infusion of injectable anes-thetic drug combinations to horses suggests that
car-diopulmonary parameters are better maintained during TIVA, compared with inhalation anesthesia. A variety of TIVA techniques have been
investigated during short
1
2-4
5
Received May 17, 2006.
Accepted September 14, 2006.
From the Department of Small Animal Clinical Sciences, School
of Veterinary Medicine, Rakuno Gakuen University, Ebetsu,
Hokkaido 069-8501, Japan (Umar, Yamashita, Kushiro) and
the Department of Veterinary Clinical Sciences, College of
Veterinary Medicine, The Ohio State University, Columbus,
OH 43210 (Muir). Dr. Kushiro’s present address is Department
of Veterinary Clinical Sciences, College of Veterinary
Medicine, Washington State University, Pullman, WA
99164-6610.
Dr. Umar was supported by a study fellowship awarded by
Monbukagakusho, Tokyo.
Address correspondence to Dr. Umar.
AbbreviAtions
TIVA
MAP
P-TIVA
KMP-TIVA
Total
Mean
TIVA
TIVA
IV
anesthesia
arterial blood
pressure
with
propofol
with
ketamine-medetomi
dineIPPV
propofol
Intermittent
positive-pressure
ventilation
MPAP
SVR
Mean
pulmonary
artery pressure
Systemic
vascular
resistance
surgical procedures in horses. The use of TIVA for
lon-ger surgical procedures has been limited to
combina-tions of muscle relaxants or α -adrenoceptor
agonists
or
both
with
ketamine
and
medetomidine-propofol combination.
Propofol is a rapid-acting, short-duration, relative-ly
noncumulative anesthetic for IV administration that
could be useful for providing short-term or extended
(infusion) TIVA in horses. Propofol has been used for induction and
2
4,6,7
8
9
maintenance of anesthesia in horses, providing safe anesthesia with rapid and uneventful recovery even
10,11
The principal disadvantages of propofol are that it is a
poor analgesic and causes substantial respiratory
de-pression. Propofol is currently considered to be
unsat-isfactory as the sole anesthetic for horses because
the volume of drug required is too large to enable rapid
in-jection, the quality of anesthetic induction is
unpredict-able, and respiratory depression is common
following IV bolus administration.
The combination of propofol with analgesic agents
could provide an alternative method for improving the
quality and safety of anesthesia achieved in horses with
propofol (ie, more-effective analgesia) and decreasing
the total dose of drug required. Although propofol has
been used for TIVA in horses, adequate anesthesia
enabling
surgical
procedures
and
acceptable
cardiovas-cular function was only achieved when
propofol was administered with an infusion of ketamine,
medetomi-dine, or both.
We previously reported that the combination of
ketamine-medetomidine-propofol for TIVA provided
better maintenance of surgical anesthesia for carotid
artery translocation and decreased the requirement of
when used as a continuous infusion.
9
12
10,13,14
8,14,15
propofol, compared with propofol infusion alone, in
horses. In that study, heart rate and MAP were
ade-quately maintained during surgery; however,
detailed measurement of cardiovascular function was
not at-tempted. The purpose of the study reported here
was to evaluate the cardiovascular effects of the
combination of ketamine-medetomidine-propofol for
TIVA and to compare these effects with those of
propofol alone for TIVA in horses premedicated with
medetomidine and induced for anesthesia with ketamine
and midazolam.
15
Materials and Methods
m
incorporated a ventilator and delivered 100% oxygen (5
L/min). A loading dose of propofol (0.5 mg/kg, IV) was
administered to all horses in both groups, and a constant
rate infusion of propofol alone at 0.22 mg/kg/min
(P-TIVA group) or propofol (0.14 mg/kg/min) and a
ketamine-medeto-midine drug combination (ketamine at
1 mg/kg/h and medetomidine at 0.00125 mg/kg/h;
KMP-TIVA group) was started and maintained for 4
hours. The ketamine-medetomidine drug combination
was administered with a syringe infusion pump, and
propofol was ad-ministered with an infusion pump.
Rates of propofol and ketamine-medetomidine infusions
were chosen on the basis of findings in a previous
study.
On the basis of the results of our previous report,
breathing was controlled with IPPV initiated when
ap-nea of > 60 seconds occurred and continued to the
end of anesthesia in the present study. All horses were
venti-lated with IPPV; respiratory rate was set at 6
breaths/min and 20 to 25 cm H O peak airway pressure
to maintain a Paco of 40 to 50 mm Hg. During
anesthesia, lactated Ringer’s solution was administered
IV at 10 mL/kg/h to all horses. The urinary bladder was
catheterized to maintain an empty bladder during
anesthesia.
The monitoring equipment and catheters were
dis-connected at the end of 4 hours, and the infusion of
the ketamine-medetomidine drug combination and
propo-fol was discontinued. Horses were transported to
a 3.5 X 3.5-m padded recovery stall. All horses were
recov-ered with assistance by use of head and tail ropes.
n
o
p
15
Animals⎯Five healthy Thoroughbred mares
weighing (mean ± SD) 501 ± 44 kg (range, 451 to 580
kg) and aged 12.8 ± 4.4 years (range, 5 to 18 years)
were used for this study. Right carotid arteries of these
horses had been relocated to a subcutaneous position at
least 1 month prior to study. Each horse had been
anesthetized for 4 hours on 2 occasions as follows: once
with P-TIVA and once with KMP-TIVA. The protocol
used was randomly chosen. There was a minimum of 28
days between treatments. Food but not water was
withheld from horses for 12 hours before anesthesia.
Horses were cared for according to the principles of the
Guide for the Care and Use of Laboratory Animals
pre-pared by Rakuno Gakuen University. The Animal
Care and Use Committee of Rakuno Gakuen University
ap-proved this study.
Instrumentation⎯Horses were restrained in a
wooden stockade to facilitate placement of vascular
catheters and measurement of baseline hemodynamic
data. Areas over the relocated right carotid artery and
right and left jugular furrows were clipped and prepared
aseptically, and approximately 1 mL of 2% lidocaine
was injected SC at each introducer site. A 14-gauge,
13.3-cm jugular venous catheter was placed
percutaneously in the left jugular vein. An 18-gauge,
2.5-cm catheter was placed in the repositioned right
carotid artery. An 8-F introducer was placed in the right
jugular vein, and a 9-F introducer was also placed in the
right jugular vein 30 cm proximal to the 8-F introducer.
A
triple-lumen,
7-F,
100-cm,
Swan-Ganz,
ballooned-tipped thermistor catheter was placed in the
pulmonary artery via the 8-F introducer by advancing it
along the jugular vein and into the pulmonary artery.
The position was confirmed by the characteristic
pressure wave. An 8-F, 100-cm catheter was placed in
the right atrium via the 9-F introducer. The distance
between the tip of the Swan-Ganz catheter and the 8-F
catheter was adjusted to 40 to 50 cm. Ends of the
Swan-Ganz, right atrial, and carotid arterial catheters
were connected through saline (0.9% NaCl)
solution–filled lines to pressure transducers and a
hemodynamic monitor. Transducers were placed at the
level of the shoulder for standing horses and the sternum
for anesthetized horses.
a
b
c
d
e
f
g
h
Anesthesia⎯Each horse was premedicated with
medetomidine (0.005 mg/kg, IV) via the 14-gauge,
13.3-cm catheter placed in the left jugular vein. Five
minutes later, anesthesia was induced by administering
midazolam (0.04 mg/kg, IV) and ketamine (2.5 mg/ kg,
IV). All horses were orotracheally intubated and
po-sitioned in left lateral recumbency on an inflated
airbed surgical table. The endotracheal tube was
connected to a large animal circle system that
i
j
k
l
15
2
2
q
Measurements⎯Hemodynamic
and
arterial
blood-gas tension data were recorded before
premedication administration (baseline values) and
every 30 minutes during 4 hours of anesthesia. Baseline
hemodynamic and arterial blood-gas tension data were
obtained in all hors-es while horses stood in a stockade.
Heart
rate
(beats/
min),ECG(base-apexlead),MAP(mmHg),MPAP(mm
Hg), and mean right atrial pressure (mm Hg) were
de-termined. Cardiac output (L/min) was measured by a
thermodilution technique with 40 mL of a 5% dextrose solution at
0 C that was injected manually for approxi-mately 2
seconds through the 8-F catheter placed in the right
atrium. Fluctuation in temperature was detected with the
Swan-Ganz catheter placed in the pulmonary artery.
Cardiac output was measured at least 3 times, and the
mean value was calculated. Cardiac index (mL/kg/ min),
stroke volume (mL/beat), and SVR (dynes/s/cm ) were
calculated with standard formulas.
Arterial blood samples were
collected from the translocated carotid ar-tery
anaerobically into heparinized syringes for immedi-ate
blood-gas tension and pH analyses by use of a blood-gas
analyzer.
16
o
5
17
r
Quality of recovery⎯The quality of recovery was
categorized by use of a scoring system. Recovery was
considered to begin after the cessation of the drug
infu-sion. Times to extubation, first movement, sternal
po-sitioning, and standing after the cessation of
anesthesia were recorded. Recovery scores were
assigned as fol-lows: 0 = unable to stand (horse cannot
stand for > 2 hours after multiple attempts to stand,
excitement is evident, injury or high risk of injury), 1 =
poor (mul-tiple attempts to stand, excitement is evident,
high risk of injury), 2 = fair (multiple attempts to stand,
substan-tial ataxia), 3 = satisfactory (horse stands after 1
to 3 at-tempts, prolonged ataxia but no excitement), 4 =
good (horse stands after 1 or 2 attempts; mild,
short-term ataxia), and 5 = excellent (horse stands on
first attempt, minimal or no ataxia). Observers were
aware of the group allocation of each horse.
18
Statistical analysis⎯Data were recorded as mean ±
SD. A repeated-measures ANOVA was used to analyze
changes in hemodynamic and respiratory data. When
appropriate, a Student paired t test was used to
deter-mine differences between time points and to
compare characteristics of recovery from anesthesia
between groups. The quality of recovery from anesthesia
for P-TIVA and KMP-TIVA was analyzed with the
Mann-Whitney U test. Values of P < 0.05 were
considered significant.
Results
Cardiovascular effects⎯The heart rate remained
between 30 and 40 beats/min during P-TIVA and
KMP-TIVA. The MAP was maintained at > 90 mm Hg
throughout 4 hours of anesthesia in both groups. The
MPAP was significantly lower during KMP-TIVA than
during P-TIVA from 120 to 240 minutes of anesthesia.
Cardiac index was significantly lower during
KMP-TIVA than during P-TIVA from 60 to 150
Table 1⎯Mean ± SD cardiovascular values during 4 hours of
KMP-TIVA or P-TIVA in 5 horses.
Minutes after
Variable Baseline*
120
150
inductionof
anesthesia
30
180
90
240
60
210
HR (beats/min) KMP-TIVA 38 5 34 2 34 3 35 5 34
4 34 4 33 3 33 3 31 3 P-TIVA 39 4 40 5 39 4
41 7 40 4 40 6 39 5 39 5 39 5
MAP (mm Hg) KMP-TIVA 129 6 98 11 110 15 121 8
121 12 122 11 122 14 121 10 119 14 P-TIVA 128
4 94 9 107 12 126 15 131 6 140 11 136 12
138 14 136 18
MPAP (mm Hg) KMP-TIVA 21 7 18 4 18 3 18 2 18
3† 18 2‡ 20 4‡ 18 3‡ 18 3‡ P-TIVA 21 4 18 3
minutes of anesthesia. Cardiac index was maintained
between ap-proximately 80% and 90% of baseline
values in the P-TIVA group. Cardiac index reached a
minimum value (about 65% of baseline value) at 90
minutes of anesthe-sia during KMP-TIVA, then
recovered to approximately 70% of baseline value.
Similarly, heart rate was lower in the KMP-TIVA group.
Stroke volume was maintained between approximately
70% to 84% of the baseline value in the KMP-TIVA
group and 82% to 90% of the baseline value in the
P-TIVA group, respectively. The SVR remained
between approximately 80% to 125% of the baseline
value in both groups (Table 1).
Respiratory rate and arterial blood-gas
tensions⎯Respiratory rate decreased within 2 min-utes
of the start of propofol infusion; apnea occurred in all
horses in both groups. Mean time after induc-tion of
anesthesia to the start of IPPV was 14.0 ± 1.6 minutes
and 15.8 ± 2.9 minutes in horses anesthetized with
KMP-TIVA and P-TIVA, respectively. Hypercarbia and
hypoxemia were treated by IPPV in both groups of
horses (Table 2).
Qualities of anesthesia and recovery⎯The
induc-tion of anesthesia was smooth and excitement free
with
20 3 22 3 27 2 26 2 26 2 26 3 26 3
MRAP (mm Hg) KMP-TIVA 8 3 10 3 12 2 11 2 11
2 11 1 12 1 11 2 11 2 P-TIVA 8 3 10 4 12 4
14 3 16 4 15 3 16 4 15 4 17 4
Cardiac index (mL/kg/min) KMP-TIVA 73 5 56 4 51 4†
47 5† 49 5† 48 5† 51 11 51 8 51 10 P-TIVA 72
4 62 6 64 6 65 5 64 4 63 5 59 6 61 9 62 8
Stroke volume (mL/beat) KMP-TIVA 982 124 823 95 760
73 685 98 730 108 718 106 774 178 793 137
825 181 P-TIVA 922 93 802 153 833 94 800 71
808 94 795 159 755 112 798 166 812 152
SVR (dynes/s/cm ) KMP-TIVA 267 17 229 46 264 45
326 77 317 66 326 77 334 91 325 87 319 79
P-TIVA 266 8 218 21 238 24 274 27 290 35 324
44 331 51 333 65 314 70
5
*Baseline values were measured before any medications
were administered. †,‡Values for KMP-TIVA group significantly
(P = 0.01 and P 0.05, respectively) lower than P-TIVA group.
=Heart rate.
MRAP = Mean right atrial pressure. HR
Table 2⎯Mean ± SD respiratory rate and arterial blood-gas
tension values during 4 hours of KMP-TIVA or P-TIVA in 5
horses on IPPV.
Minutes after
Variable
60
Baseline*
90
180
inductionof
anesthesia
30
120
210
150
240
RR (breaths/min) KMP-TIVA 14 36 06 06 06 06
06 06 06 0 P-TIVA 11 16 06 06 06 06 06
RR = Respiratory rate. pHa = Arterial
blood pH.See Table 1 for remainder of
key.
Variable
KMP-TIVA
P-TIVA
Recovery times in
06 06 0
pHa KMP-TIVA 7.47 0.02 7.38 0.07 7.47 0.04 7.49
0.03 7.48 0.02 7.49 0.02 7.49 0.01 7.50 0.02 7.48
0.02 P-TIVA 7.46 0.01 7.43 0.04 7.48 0.04 7.48 0.03
7.49 0.01 7.48 0.03 7.49 0.03 7.49 0.03 7.50 0.04
Paco2 (mm Hg) KMP-TIVA 42 3 58 16 43 5 42 3 42
4 40 4 40 4 40 5 42 3 P-TIVA 44 3 48 5 42 6
44 3 42 2 44 3 43 3 43 3 42 4
Pao2 (mm Hg) KMP-TIVA 108 10 302 89 427 72 471
71 476 89 501 99 465 52 451 59 494 81 P-TIVA
96 4 351 33 420 17 469 49 460 62 455 63 464
74 420 73 429 52
Table 3⎯Mean ±SD recovery values after
cessation of 4 hours of KMP-TIVA and
P-TIVA in 5 horses.
Anesthesia protocol
minutes (range)* Extubation 28 9 (20–43) 24 11 (11–41)
First movement 31 12 (20–52) 21 11 (11–36)Sternal
recumbency 75 16 (52–93) 114 31 (71–155) Standing 98
21 (62–125) 132 31 (92–180)†
No. of attempts to stand 2.0 1.1 (1–3) 2.6 1.6
(1–5)Recovery score 4 (n = 5) 4 (n = 3); 3 (n = 2)
*Times were recorded from the time propofol infusion was
discontinued. †Significant (P
0.05) difference between
groups.
adequate muscle relaxation in all horses. It took horses 1
to 2 minutes from the time of injection of
ketamine-midazolam to attain recumbency and no limb
move-ments or head shaking occurred after becoming
recum-bent. The transition to infusions of propofol with
or
without
the
ketamine-medetomidine
drug
combination was uneventful in all horses. During
maintenance of anesthesia, no movement was observed
in all 5 horses that received KMP-TIVA or in 3 horses
that received P-TIVA. The 2 remaining horses that
received P-TIVA required 2 IV bolus injections (1
horse) and 3 IV bolus injections (1 horse) of propofol
(200 mg/injection, IV bolus given with each movement)
to control spontane-ous limb movements during
anesthesia.
Times to extubation, first movement, sternal
re-cumbency, and the number of attempts to stand were
not significantly different between groups. However,
time to standing after the cessation of anesthesia was
significantly longer in horses that received P-TIVA than
in horses that received KMP-TIVA (Table 3). Quality
of recovery from anesthesia was judged to be good
af-ter KMP-TIVA and good or satisfactory after
P-TIVA. All 5 horses had a recovery score of 4 (good)
after KMP-TIVA, whereas 3 horses had a recovery
score of 4 (good) and 2 horses had a recovery score of 3
(satisfac-tory) after P-TIVA.
Discussion
Our data suggest that cardiovascular function is
maintained within acceptable limits for horses
anesthetized with KMP-TIVA or P-TIVA.
During
inhalation anesthesia in horses, as reported by
Grosen-baugh and Muir, the calculated cardiac index during 90 minutes of
2-4,13,19-21
19
halothane, isoflurane, and sevoflurane anesthesia was 46.1 to 55.4 mL/kg/min, 68.5 to 75.9
20
mL/kg/min, and 55.8 to 68.3 mL/kg/min, respectively. However, Mizuno et al reported a cardiac
index of 35 to 55 mL/kg/min by use of thermodilution during 2 hours of halothane anesthesia; also in
21
another study by Young et al, the calculated mean cardiac index value was 49 mL/kg/min by
thermodilution during halothane anesthesia. Similarly, during 60 minutes of xylazine and ketamine
4
the cardiac in-dex ranged from 37.1 ±
9.6 mL/kg/min to 80.0 ± 17.3 mL/kg/min. In addition,
Mama et al reported a cardiac index of 30 ± 6
mL/kg/min to 35 ± 10 mL/kg/min dur-ing 1 hour of
ketamine TIVA and a cardiac index of 35 ± 8
mL/kg/min to 62 ± 15 mL/kg/min during 1 hour of
propofol TIVA in horses. In a similar study that
main-tained
anesthesia
for
4
hours
with
propofol-medetomi-dine infusion in ponies, cardiac
index ranged from 31.1 ± 7.7 mL/kg/min to 51.7 ± 9.8
mL/kg/min. In our study, cardiac index ranged from 47
± 5 mL/kg/min to 56 ± 4 mL/kg/min during KMP-TIVA
and from 59 ± 6 mL/kg/ min to 65 ± 5 mL/kg/min
during P-TIVA. These values were similar to, and in
some cases higher than, those reported for horses.
An
anesthesia for TIVA in horses,
13
2
2-4,13,19-21
MAP in excess of 70 mm Hg during anesthesia is important for preventing postoperative myopathy in
8,17
horses.
2,4,7
Primary factors affecting MAP are cardiac output and SVR. Results of previous studies
of TIVA in horses or ponies indicate that
cardiopulmonary parameters are better maintained
during TIVA, compared with inhalation anesthesia. The
MAP in our study ranged from 98 to 122 mm Hg during
KMP-TIVA and 94 to 140 mm Hg during P-TIVA;
these values were similar to, or higher than, MAP during
hal-othane, isoflurane, or sevoflurane anesthesia. The
1,19,20
MPAP was significantly lower during KMP-TIVA than during P-TIVA from 120 to 240 minutes of
17
anesthesia. Changes in PAP were within normal ranges of 17 to 36 mm Hg for horses in both groups.
Cardiac index was maintained at 65% to 70% and 80%
to 90% of base-line values during KMP-TIVA and
P-TIVA, respectively, whereas SVR varied from 80% to
125% of the baseline value. On the basis of our data, we
conclude that KMP-TIVA and P-TIVA provided
prolonged general anesthe-sia and minimal changes in
cardiovascular function in horses.
Significant differences were detected in cardiac
in-dex and MPAP between KMP-TIVA and P-TIVA.
Com-pared with P-TIVA, these parameters were
significantly lower in horses anesthetized with
KMP-TIVA. Heart rate also was lower during
KMP-TIVA. On the other hand, no significant
difference was found in stroke volume, SVR, and mean
right atrial pressure between groups. These findings
indicate that the decreases in cardiac index during
KMP-TIVA were mainly caused by a de-crease in heart
rate and reflected a decrease in MPAP. Medetomidine,
which was included in the ketamine-medetomidine drug
combination, causes dose-depen-dent cardiovascular
depression resulting in decreases in heart rate and
increases in SVR (ie, peripheral va-soconstriction) in
horses. Several investigators have suggested that a
low-dose infusion of medetomidine may produce
minimum or no cardiovascular effects. Propofol
decreases cardiac index and blood pressure by direct
vasodilation. It has also been suggested that propofol
may be associated with increased sympathetic tone and
that the sympathomimetic action of ketamine minimizes
the bradycardia and hypotensive ef-fects associated with
drugs used as sedatives. We used low doses of
medetomidine, similar to those reported to produce
minimal or no cardiovascular effects, and ob-served that
cardiac index remained at approximately 50 mL/kg/min
during KMP-TIVA, although the infusion of
ketamine-medetomidine drug combination produced
significant decreases (about 30%) in cardiac output and
cardiac index. The decrease in cardiac index by
ap-proximately 30% during KMP-TIVA is minimal,
com-pared with 50% depression reported during
halothane anesthesia for horses and also with a 33% to
44% de-crease in cardiac output with halothane. The
decrease is comparable to a 24% to 38% decrease in
cardiac out-put reported for sevoflurane ; however, it is
more than the decrease in cardiac output (12% to 20%)
reported for isoflurane. Cardiac index in standing
unsedated horses ranges from 60 to 80 mL/kg/min. To
our
knowledge,
1
other
study
evaluated
cardiopulmonary effects of 4 hours of TIVA and
reported a mean cardiac index range of 31.1 to 51.7
mL/kg/min, representing a reduction from typical values
of approximately 30% to 50%, with the lowest values
occurring during the last hour of anesthesia. These
changes are comparable to or slightly more profound
than those of our study. We conclude, therefore, that
cardiac index was well main-tained within clinically
acceptable values during KMP-TIVA in our study and
that the ketamine-medetomidine drug infusion produces
minimal cardiovascular depres-sion in horses.
22,23
24,25
26
12
27
28
20
19
19
19
6,29-31
2
15
Results of our previous report suggested that
KMP-TIVA and P-TIVA induced respiratory depression
and apnea and that IPPV is required to successfully treat
these adverse effects. Others have reported similar
results (respiratory depression and apnea) during TIVA
with propofol in horses. Artificial ventilation was
needed to maintain respiratory rate during either
KMP-TIVA or P-TIVA in our study reported here.
8,13,32
Dobuta-mine and dopamine are often administered to
counter-act the cardiovascular depression induced by
inhalant anesthetic drugs and IPPV. In our current
study, car-diovascular parameters including cardiac
index, stroke volume, and MAP were well maintained in
all horses anesthetized with KMP-TIVA and P-TIVA
without ad-ministering sympathomimetic drugs and
despite apply-ing IPPV. This finding has important
implications and suggests that the development of TIVA
techniques for use in horses should be continued given
that the main-tenance of cardiac output and MAP are
key factors in maintaining adequate muscle perfusion.
We did not apply painful stimuli to horses, and 2
horses anesthetized with P-TIVA required additional
propofol injections to prevent limb movement; this
might be attributable to the dose of propofol, when used
alone, being inadequate to maintain anesthesia in all of
the horses. However, the dose rates of propofol during
both forms of TIVA in our study were chosen on the
basis of results of a previous study during which the
same dose rates were adequate to maintain anesthe-sia
for surgical relocation of the right carotid arteries of
horses. Probably individual variation in anesthetic
demand induced the differences. As only horses with
just propofol infusion had movement, it is likely that the
dose rates for KMP-TIVA induced a deeper state of
anesthesia and thus are more likely to be sufficient for
clinical use. Inadequate depth of anesthesia was
similar-ly reported in our earlier report, and during
medeto-midine and propofol anesthesia in horses, for
certain major stimuli, anesthesia had to be deepened
with ket-amine and thiopental in horses that moved.
Transition to infusion of KMP-TIVA or P-TIVA was
smooth and uneventful. Maintenance of anesthesia with
KMP-TIVA was considered more satisfactory than that
achieved with P-TIVA.
Prompt and controlled recovery from anesthesia in
horses is important if nerve or muscle damage
attribut-able to prolonged recovery and poor-quality
recover-ies are to be avoided. Recovery from injectable
anes-thesia are dependent upon context-sensitive
half-life. The context-sensitive half-life is reported to be
quite short for propofol in horses following propofol
infu-sions of 1 to 2 hours. In our study with P-TIVA,
re-covery duration was extended in comparison to
recov-ery from KMP-TIVA or inhalation anesthesia.
Probably also in horses, context-sensitive half-life of
propofol increases with duration of infusion. It is
possible that a dose regimen of dose administration to
effect rather than a constant rate infusion could prevent
such long recoveries. However, results of our study
suggest that recovery from P-TIVA is slower than from
KMP-TIVA. Reports that used propofol at infusion
rates ranging from 0.06 to 0.11 mg/kg/min recorded fast
recoveries of between 20 and 39 minutes after 4 hours of
anesthesia, unlike horses in our study that had higher
propofol in-fusion rates and required approximately 130
minutes to stand after 4 hours anesthesia with P-TIVA.
Recovery from anesthesia was also prolonged after
P-TIVA (time to standing of 87 ± 36 minutes) after
approximately 2 hours of anesthesia in our previous
study. The recov-eries from P-TIVA were slower,
compared with previ-ous reports in which anesthesia
was maintained by only propofol administration at 0.18
± 0.04 mg/kg/min, with time to standing of 67 ± 29
minutes after 61 ± 19 min-utes anesthesia and by only
propofol administration at 0.25 mg/kg/min, with time to
standing of 80.3 ± 32.8 minutes after 73 ± 1 minutes
33
17,33
15
15
8
34
35
2,10
13
anesthesia. Unlike inha-lation anesthetics that result in
rapid recovery (mean times to standing were 30, 24, and
27 minutes with halothane, isoflurane, and sevoflurane,
respectively, after 90 minutes of anesthesia), the main
disadvantage of TIVA has been the potential
accumulation of drugs and metabolites that might
unsatisfactorily prolong re-covery. The high infusion
rate of propofol used for P-TIVA with a zero-order
infusion for long periods could result in delayed
recoveries from anesthesia because of propofol
accumulation. Most studies
investigat-ing TIVA with
propofol in horses have not subjected horses to surgical
stimulation. We designed and admin-istered a propofol
anesthetic protocol and infusion rate on the basis of our
previous study in which the right carotid artery of
horses was translocated to a subcuta-neous position. On
the basis of results from that study, we assumed that the
propofol infusion rate used in our current study would
provide a suitable depth of anes-thesia for surgery.
Lower or higher infusion rates of pro-pofol in
KMP-TIVA might be required depending upon the
degree of surgical stimulation, thereby providing smaller
or larger degrees of accumulation of propofol in tissues
and influencing recovery rates.
In conclusion, both regimens provided anesthe-sia,
but the dose rate of propofol was insufficient for
individual horses during P-TIVA. Some depres-sion of
cardiovascular function occurred with both regimens but
was more pronounced with KMP-TIVA. Prolonged
recoveries in both groups were probably caused by
accumulation of propofol, and IPPV was required to
maintain respiratory rate during both TIVA protocols.
19
5
36
2,3,10-12
15
a.
BD Angiocath, Becton-Dickinson, Sandy, Utah.
b.
Supercath, Medikit Co, Tokyo, Japan.
c.
Exacta percutaneous sheath introducer, 8F
Ohmeda, Swindon, UK.
d.
Exacta percutaneous sheath introducer, 9F
Ohmeda, Swindon, UK.
e.
Criti-Cath SP-5107, Ohmeda, Swindon, UK.
f.
Intervec super guiding catheter, Fuji Systems
Co, Tokyo, Japan.
g.
CDX-A90, Cobe Laboratories, Tokyo, Japan.
h.
DS-5300, Fukuda Denshi, Tokyo, Japan.
i.
Domitor, Meiji Seika Co, Tokyo, Japan.
j.
Dormicum, Yamanouchi Pharmatheutical Co,
Tokyo, Japan.
k.
Ketalar 100, Sankyo Co, Tokyo, Japan.
l.
Mallard Medical, Mallard Medical Inc,
Redding, Calif.
m.
Mallard Medical ventilator Rachel Model 2800
L.A.A.V, Mallard Medical Inc, Redding, Calif.
n.
Rapinovet, provided by Takeda
Schering-Plough Animal Health Co, Tokyo, Japan.
o.
STC-521, Terumo, Tokyo, Japan.
p.
Subratek 3030, JMS, Hiroshima, Japan.
q.
Solulact, Terumo Kabushiki Co, Tokyo, Japan.
r.
Rapidlab 348, Bayer Medical Co, Tokyo, Japan.
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