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A Clinical Comparative Study of Propofol Total<br />
Intravenous Anesthesia in Dogs<br />
Yi-Chin Tsai, DVM MS; Liang-Yi Wang, PhD; Lih-Seng Yeh, DVM PhD<br />
Propofol total intravenous anesthesia (TIVA) was compared with a well established propofol induced,<br />
isoflurane maintained anesthesia in 271 client-owned canine patients of variable anesthetic<br />
risks. Dogs anesthetized with propofol TIVA showed generally higher values of heart rate<br />
and systemic blood pressure, especially in patients with greater anesthetic risks. Propofol TIVA<br />
appeared to offer lighter level of anesthesia which precludes its application in procedures eliciting<br />
nasal passage stimulation. The time to first regain spontaneous breathing after induction<br />
was significantly longer in dogs maintained with propofol. Uncommon seizure-like tremor episodes<br />
during propofol infusion were also observed in the study.<br />
Key Words: Propofol, total intravenous anesthesia, dogs<br />
Introduction<br />
D<br />
espite the wide adoption of inhalant<br />
anesthesia in veterinary practice,<br />
there are still occasions that a reliable injectable<br />
anesthesia is favorable. Inhalant<br />
anesthesia requires more expensive<br />
equipments and is unsuitable for animals<br />
with conditions such as malignant hyperpyrexia<br />
or in need of particular procedures<br />
such as magnetic resonance imaging<br />
(MRI). Total intravenous anesthesia<br />
(TIVA), which is the induction and maintenance<br />
of anesthesia with intravenous<br />
agents, bears potential advantages for<br />
small animal practitioners, especially when<br />
working in an understaffed and underequipped<br />
environment. TIVA also avoids<br />
some drawbacks of inhalant anesthesia, including<br />
operating room pollution and the<br />
cumbersome anesthetic equipments.<br />
Propofol is an injectable, short-acting,<br />
and rapidly metabolized agent chemically<br />
unrelated to barbiturates or other anesthetic<br />
agents. Propofol anesthesia in dogs<br />
is characterized by its rapid onset, short<br />
duration, rapid metabolism, lack of accumulation<br />
on rapid administration, some<br />
degrees of respiratory depression, and a<br />
From the Department of Veterinary Medicine, College of<br />
Bio-Resources and Agriculture, National Taiwan University,<br />
Taipei 106, Taiwan (Tsai, Yeh); the Graduate Institute<br />
of Epidemiology, College of Public Health, National Taiwan<br />
University, Taipei 106, Taiwan (Wang).<br />
Correspondence: Dr. Lih-Seng Yeh<br />
E-Mail: lsyeh@ntu.edu.tw<br />
rapid smooth recovery from anesthesia. 1,2<br />
The use of propofol for inducing and<br />
maintaining short period of anesthesia has<br />
gained increasing popularity in small animal<br />
practice.<br />
Propofol TIVA has become a widely<br />
adopted technique in human day-case anesthesia<br />
because of the advantages it offers.<br />
In humans, recovery from propofol infusion<br />
is reported to be as rapid as, or even<br />
faster than isoflurane or sevoflurane anesthesia,<br />
and with low incidence of postopertative<br />
nausea and vomiting (PONV). 3<br />
However, large scale systemic study of the<br />
merits of propofol TIVA in canine clinical<br />
anesthesia is not available.<br />
In this study, propofol TIVA was<br />
compared with a well established propofol<br />
induced and isoflurane maintained anesthesia<br />
in canine patients of different status.<br />
The objective of the study was to evaluate<br />
the clinical feasibility and limitations of<br />
propofol TIVA.<br />
Materials and Methods<br />
A total of 271 clients-owned dogs requiring<br />
general anesthesia for surgical or diagnostic<br />
procedures were included in this<br />
study. Dogs were randomly assigned to<br />
two groups of different anesthetic maintenance<br />
protocols. Group-one (Iso group)<br />
dogs received propofol a induction and<br />
52 JVCS, Vol. 1, No. 2, April, 2008
isoflurane b in oxygen maintenance anesthesia.<br />
Group-two (TIVA group) dogs received<br />
propofol total intravenous anesthesia<br />
with oxygen.<br />
Dogs were categorized by the American<br />
Society of Anesthesiologist (ASA)<br />
classification system as ASA 1, 2 or 3, according<br />
to their physical status and hematology<br />
laboratory results. Their breeds, age,<br />
sex, body weight, rectal temperature, heart<br />
rate, co-existing diseases and the nature of<br />
the procedures were recorded before premedication.<br />
A cephalic or lateral<br />
saphenous vein was cannulated for the<br />
administration of propofol. Suitable crystalloid<br />
solutions were also given at the rate<br />
of 10ml/kg/hr during anesthesia.<br />
Acepromazine c (0.05mg/kg of body<br />
weight, IV, with the maximal dose of 3mg)<br />
or diazepam d (0.3mg/kg of body weight,<br />
IV) was given as sedative agent according<br />
to the patients’ behavior and hemodynamic<br />
conditions. Ketoprofen e (1mg/kg of body<br />
weight, IM) was administered in orthropedic<br />
patients preoperatively or intraoperatively<br />
as analgesics. Opioids were not routinely<br />
given as premedication in this study.<br />
It was only given as a rescue remedy as<br />
needed postoperatively.<br />
Dogs were induced with propofol at<br />
an initial intravenous bolus dosage of 1.5-2<br />
mg/kg in about three seconds, and then incremental<br />
doses were administered intermittently<br />
until intubation of the trachea<br />
was possible. Any adverse effect during<br />
induction was recorded, which included<br />
and not limited to cyanosis, neurologic<br />
signs (padding, muscle tremor/twitching,<br />
opisthotnos, vocalization), vomiting and<br />
salivation.<br />
If dogs did not breathe within 30<br />
seconds after intubation, ventilation was<br />
assisted manually and maintained at 3-6<br />
ventilations/min under an appropriate airway<br />
pressure until spontaneous breathing<br />
resumed. The time of onset of spontaneous<br />
breathing was recorded.<br />
Anesthesia was maintained with<br />
isoflurane in oxygen (Iso group) or with<br />
intravenous infusion of propofol using a<br />
syringe pump (TIVA group). Vaporizer<br />
Tsai et al<br />
settings or propofol infusion rates were adjusted<br />
to the lowest by the judgment of<br />
anesthetists to maintain required anesthesia<br />
depth which providing adequate analgesia<br />
and muscle relaxation for the procedure<br />
designated. All dogs were connected<br />
to a semi-closed circle rebreathing anesthetic<br />
machine to provide pure oxygen<br />
with or without isoflurane. Heart rate (HR),<br />
systolic blood pressure (SBP), percent<br />
oxygen saturation, body temperature, capillary<br />
refill time, ventilation rate, vaporizer<br />
setting / propofol infusion rate were recorded<br />
immediately after induction and<br />
every 5 minutes for the duration of anesthesia.<br />
The SBP was obtained by an ultrasonic<br />
Doppler or oscillometric unit. If any<br />
abnormal condition would contribute to<br />
unstable anesthesia or interfered with the<br />
surgical procedures during maintenance,<br />
the case will be recorded and excluded<br />
from the statistical analysis.<br />
Descriptive (categorical) variables<br />
and the incidence of apnea after induction<br />
were analyzed using a chi-square test. Age,<br />
weight, rectal temperature, baseline heart<br />
rates, induction dosage of propofol and<br />
time of regaining spontaneous breathing in<br />
each group were calculated and compared<br />
using two-sample t-test. Paired t-test was<br />
used to compare baseline and postinduction<br />
HR within groups. Continuous<br />
variables (HR, SBP) were analyzed using<br />
two-sample t-test between groups and<br />
were further analyzed according to the<br />
dog’s ASA status, using two-sample t-test<br />
between groups. The data are presented as<br />
mean (SD, standard deviation), and differences<br />
are considered to be statistically significant<br />
at P
eventfully and didn’t show any complication<br />
related to the episode. None of the<br />
dogs had a history of neurological disorders.<br />
A total of three dogs were anesthetized<br />
with propofol TIVA for diagnostic<br />
nasal flushing and rhinoscopy. All of them<br />
attempted to lift the heads during anesthesia.<br />
Even with an increased propofol infusion<br />
rate, the attempt to overcome the irritating<br />
sensation of nasal mucus membrane<br />
was unsuccessful during the procedure.<br />
The condition prevented the diagnostic<br />
procedures from being carried out and the<br />
anesthetist had to shift to isoflurane for a<br />
smoother maintenance. None of the five<br />
dogs underwent diagnostic nasal flushing<br />
and rhinoscopy in the Iso group developed<br />
the same condition.<br />
The hemodynamic data of the eight<br />
cases above mentioned could no longer<br />
represent the exact manifestation in their<br />
group. They were excluded in the statistical<br />
analysis. A total of 263 dogs were included<br />
in the statistical analysis of the<br />
study.<br />
Descriptive variables were tested to<br />
ensure the validity of database and the results<br />
are shown in Table 1. There are no<br />
Table 1. Description of two groups.*<br />
Propofol TIVA in Dogs<br />
Variables Iso group(n=162) TIVA group(n=101)<br />
Gender (male / female) 80 / 82 42 / 59<br />
Surgical procedures ( A / B / C / D) 21 / 104 / 21 /16 11 / 76 / 12 / 2<br />
Abdominal cavity opened / non-opened 58 / 104 40 / 61<br />
Tranquilizers (Acp / Dia) 63 / 99 39 / 62<br />
ASA status ( 1 / 2 / 3 ) 54 / 83 / 25 35 / 50 / 16<br />
Surgical procedures A= Orthopedic, B= Soft tissue, C= Oral, D= others<br />
Tranquilizers Acp= Acepromazine, Dia= Diazepam.<br />
*Statistically significant differences were not found.<br />
Table 2. Age, weight, rectal temperature, baseline heart rate and induction dosage of<br />
propofol, expressed as mean (SD).<br />
Variables Iso group(n=162) TIVA group(n=101)<br />
Age (years) 7.5 (4.3) 7.7 (4.0)<br />
Weight (Kg) 11.3 (9.0)* 7.8 (6.0)*<br />
Rectal temperature (℃) 38.8 (0.6) 38.8 (0.6)<br />
Baseline heart rate (beats/min) 125.0 (27.8) 125.0 (25.0)<br />
Induction dosage of propofol (mg/kg) 5.0 (1.5) 5.3 (3.6)<br />
*Significant difference between groups (p< 0.05)<br />
statistically significant differences between<br />
the two groups with respect to gender distribution,<br />
categorized surgical procedures,<br />
whether the abdominal cavity had been<br />
opened, patient’s ASA status, and the<br />
tranquilizers (acepromazine or diazepam)<br />
given.<br />
Mean age, mean body weight, mean<br />
baseline rectal temperature, mean baseline<br />
HR and mean propofol induction dosages<br />
(mg/kg) in each group are shown in Table<br />
2. No statistically significant differences<br />
were found between the groups except the<br />
mean body weight.<br />
During propofol induction, adverse<br />
effects were observed in a total of 53 dogs<br />
(20%). Which included neurological signs<br />
(padding, muscle tremor/twitching…),<br />
cyanosis and other adverse effects (vomiting<br />
or salivation) in 37 (14%), 13 (5%) and<br />
3 (1%) of dogs, respectively. The 13 dogs<br />
developed cyanosis before intubation were<br />
all with concurrent cardiovascular and/or<br />
pulmonary disorders. After propofol induction,<br />
the incidence of apnea was 67%<br />
in the Iso group and 73% in the TIVA<br />
group, with no statistically difference.<br />
However, animals in the Iso group regained<br />
spontaneous breathing significantly<br />
54 JVCS, Vol. 1, No. 2, April, 2008
earlier than the TIVA group. [4.5(5.4)<br />
minutes versus 7.8(11.3) minutes, respectively;<br />
P< 0.05]<br />
Statistical evaluation of HR and SBP<br />
were carried out for the first 90 minutes of<br />
the anesthesia. Beyond which point the<br />
small data number collected was no longer<br />
feasible for statistical analysis (sample<br />
numbers
Propofol TIVA in Dogs<br />
Figure 2A to 2C-Changes in HR<br />
(mean ± SD) over a 90 minutes period<br />
in two anesthetic groups with different<br />
ASA status.<br />
#: significantly different between two<br />
groups, Post-ind: right after induction.<br />
56 JVCS, Vol. 1, No. 2, April, 2008<br />
A<br />
B<br />
C
apnea, and endotracheal intubation should<br />
be routinely performed for ventilation support.<br />
Neurological adverse effects during<br />
propofol administration were widely documented<br />
and with variable incidence in<br />
researches. 11 In a previous study, muscle<br />
tremor was developed in as high as 50% of<br />
dogs at 20-30 minutes after propofol infusion.<br />
12 However, most neurological complications<br />
were documented during induction<br />
or recovery phases of anesthesia. 11,12<br />
In this study, neurological signs usually<br />
appeared only for a short period of time<br />
and would not interfere with the diagnostic<br />
or surgical procedures. The incidence of<br />
neurological signs during propofol induction<br />
was 14% (37/263), including paddling,<br />
muscle tremor/twitching, opisthotnos and<br />
vocalization.<br />
Seizure-like phenomenon (SLP) related<br />
to propofol was discussed in a number<br />
of human case reports and may develop<br />
in patients with or without epilepsy history.<br />
13 However, the SLP with propofol infusion<br />
has not been systemically studied<br />
and was only documented in uncontrolled<br />
observations in human studies. During<br />
anesthetic maintenance of the present<br />
study, seizure-like generalized tremor was<br />
observed in five of 109 dogs in the TIVA<br />
group and none in the Iso group. The five<br />
cases were without any neurological medical<br />
history. The seizure was discontinued<br />
immediately after changing propofol infusion<br />
into isoflurane maintenance. This<br />
Tsai et al<br />
phenomenon indicated a disrupted central<br />
nervous system and prevented the procedures<br />
from being carried on. Though the<br />
incidence of generalized tremor in our<br />
TIVA group had been low (< 5 %), practitioners<br />
should still be aware of the symptom.<br />
If the condition is uncontrollable, the<br />
switch to inhalant maintenance is recommended.<br />
Propofol induction associated cyanosis<br />
was observed in 13 dogs (5%), which<br />
were all with co-existing cardio/pulmonary<br />
diseases. Though the incidence was low<br />
and the cyanosis was readily resolved once<br />
endotracheal tube was placed and manually<br />
ventilated, we believe that a preoxygenation<br />
before propofol induction may be<br />
beneficial for patients with cardio/pulmonary<br />
diseases.<br />
Propofol causes a fall in arterial pressure,<br />
but due to its central effects and baroreflex<br />
sensitization, it also causes a reduction<br />
in the heart rate, which is normally<br />
compensatedly increased associated with<br />
hypotension. 14,15 In the present study, the<br />
first detected HR after propofol induction<br />
was significantly lower in the TIVA group.<br />
This can be explained by the effect of continuing<br />
propofol infusion. The HR was<br />
gradually returned to baseline value and<br />
was elevated at surgical stimulations. Although<br />
the falling in heart rate after induction<br />
didn’t require medical intervention,<br />
anesthetists are advised to closely and continuously<br />
monitor post-induction HR during<br />
propofol TIVA.<br />
Figure 3-Changes in SBP (mean ±<br />
SD) over a 90 minutes period in two<br />
anesthetic groups.<br />
#: significantly different between two<br />
groups, Post-ind: right after induction.<br />
JVCS, Vol. 1, No. 2, April, 2008 57
Propofol TIVA in Dogs<br />
Figure 4A to 4C-Changes in SBP<br />
(mean ± SD) over a 90 minutes period<br />
in two anesthetic groups according<br />
to different ASA status.<br />
#: significantly different between two<br />
groups, Post-ind: right after induction.<br />
58 JVCS, Vol. 1, No. 2, April, 2008<br />
A<br />
B<br />
C
The hemodynamic effects of an anesthetic<br />
agent play an important role in patients’<br />
physical condition during and after<br />
anesthesia. In animals with severe systemic<br />
diseases, even the lightest levels of<br />
anesthesia may be stressful to the cardiovascular<br />
system, and will be associated<br />
with increased morbidity and mortality.<br />
Isoflurane provides progressive depression<br />
of the central nervous system, as well as<br />
inducing cardiovascular and respiratory<br />
depression in a dose-dependent fashion. 16<br />
Propofol had been reported to maintain<br />
better arterial blood pressure than isoflurane<br />
with a similar or lower HR. 17,18 In the<br />
present study, propofol TIVA did produced<br />
higher SBP throughout the anesthesia.<br />
And it also maintained equal or higher<br />
HR during the whole length of procedures<br />
compared with propofol induced, isoflurane<br />
maintained anesthesia, which is different<br />
from previous literatures. In dogs<br />
with higher anesthetic risk (ASA 2 and<br />
ASA 3), propofol TIVA produced even<br />
higher SBP during maintenance. We suggest<br />
that it would be more appropriate to<br />
consider propofol TIVA over propofolisoflurane<br />
anesthesia in patients with moderate<br />
to severe systemic disease for less<br />
compromised hemodynamic performance.<br />
Conculsion<br />
Both the propofol induced, isoflurane<br />
maintained anesthesia and the propofol<br />
References<br />
1. Buchanan JW. Watkins SB, Hall LW, et al. Propofol<br />
as an intravenous anaesthetic agent in dogs. Vet<br />
Rec 1987; 120: 326-329.<br />
2. Sebel PS, Lowdon JD. Propofol: a new intravenous<br />
anesthetic. Anesthesiology. 1989; 71: 260-77.<br />
3. Ozkose Z, Ercan B, Unal Y, et al. Inhalation versus<br />
total intravenous anesthesia for lumbar disc herniation:<br />
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characteristics, and cost. J Neurosurg Anesthesiol<br />
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4. Kuusela E, Vainio O, Short CE, et al. A comparison<br />
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5. Doust R, Sullivan M. Rhinoscopy and sampling<br />
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TIVA protocols offered clinical feasibility.<br />
Propofol TIVA provided adequate anesthesia<br />
for most surgical procedures with<br />
less compromised hemodynamic system. It<br />
is recommended as a safe and valid general<br />
anesthesia protocol for dogs regardless<br />
of anesthetic risk factors. However, propofol<br />
TIVA may not be suitable for diagnostic<br />
procedure involving nasal cavity passage<br />
and is with more respiratory depression<br />
during maintenance compared with<br />
propofol induced, isoflurane maintained<br />
anesthesia. Practitioners should also be<br />
alert of the uncommon seizure-like tremor<br />
episodes during propofol infusion. If the<br />
condition persists, a shift to inhalation<br />
anesthesia is recommended.<br />
Acknowledgement<br />
The authors acknowledge the anesthetists<br />
who involved in the study for their love<br />
and care for dogs and the record of data<br />
during anesthesia.<br />
Footnotes<br />
a propofol®, Lipuro, B Braun, Melsungen, AG<br />
b<br />
isoflurane®, Forane, Abbott Ltd, Queenborough, Kent,<br />
England<br />
c<br />
acepromazine®, Acepromazine Maleate, Veclco inc, St.<br />
Joseph, MO<br />
d<br />
diazepam®, Diazepam, Tai Yu Ltd, Taipei, Taiwan<br />
e<br />
ketoprofen®, Febin, Tai Yu Ltd, Taipei, Taiwan<br />
respiratory disease in dogs and cats. Saunders, 2004:<br />
100.<br />
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or thiopentone on post-intubation apnoea in the dog.<br />
J Small Anim Pract 2001; 42: 71-74.<br />
8. Sano T, Nishimura R, Mochizuki M, et al. Clinical<br />
usefulness of propofol as an anesthetic induction<br />
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641-643.<br />
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effects of administration of propofol with various<br />
preanesthetic regimens in dogs. J Am Vet Med Assoc<br />
1993; 202: 1111-1115.<br />
JVCS, Vol. 1, No. 2, April, 2008 59
10. Muir WW 3rd, Gadawski JE. Respiratory depression<br />
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Vet Res 1998; 59: 157-161.<br />
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North Am Small Anim Pract. 1999; 29: 759.<br />
12. Robertson SA, Johnston S, Beemsterboer J. Cardiopulmonary,<br />
anesthetic, and postanesthetic effects<br />
of intravenous infusions of propofol in greyhounds<br />
and non-greyhounds. Am J Vet Res 1992; 53: 1027-<br />
1032.<br />
13. Walder B, Tramer MR, Seeck M. Seizure-like phenomena<br />
and propofol: a systematic review. Neurology<br />
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14. Cullen PM, Turtle M, Prys-Roberts C, et al. Effect<br />
of propofol anesthesia on baroreflex activity in hu-<br />
Propofol TIVA in dogs<br />
mans. Anesth Analg 1987; 66:1115-1120.<br />
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375.<br />
16. Steffey EP, Howland D Jr. Isoflurane potency in the<br />
dog and cat. Am J Vet Res 1977; 38:1833-1836.<br />
17. Keegan RD, Greene SA. Cardiovascular effects of a<br />
continuous two-hour propofol infusion in dogs.<br />
Comparison with isoflurane anesthesia. Vet Surg<br />
1993; 22: 537-43.<br />
18. Deryck YL, Brimioulle S, Maggiorini M, et al. Systemic<br />
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