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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 />

comparison of hemodynamic effects, recovery<br />

characteristics, and cost. J Neurosurg Anesthesiol<br />

2001; 13:296-302.<br />

4. Kuusela E, Vainio O, Short CE, et al. A comparison<br />

of propofol infusion and propofol/isoflurane anaesthesia<br />

in dexmedetomidine premedicated dogs. J<br />

Vet Pharmacol Ther 2003; 26:199-204.<br />

5. Doust R, Sullivan M. Rhinoscopy and sampling<br />

from the nasal cavity. In: King LG, ed. Textbook of<br />

Tsai et al<br />

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 />

6. Morgan DWJ, Legge K. Clinical evaluation of propofol<br />

as an intravenous anesthetic agent in cats and<br />

dogs. Vet Rec 1989; 124:31-33.<br />

7. Murison PJ. Effect of propofol at two injection rates<br />

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 />

agent in dogs and cats. J Vet Med Sci 2003; 65:<br />

641-643.<br />

9. Smith JA, Gaynor JS, Bednarski RM, et al. Adverse<br />

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 />

and apnea induced by propofol in dogs. Am J<br />

Vet Res 1998; 59: 157-161.<br />

11. Short CE, Bufalari A. Propofol anesthesia. Vet Clin<br />

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 />

2002; 58: 1327-1332.<br />

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 />

15. Ebert TJ, Muzi M. Propofol and autonomic reflex<br />

function in humans. Anesth Analg 1994; 78: 369-<br />

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 />

vascular effects of isoflurane versus propofol<br />

anesthesia in dogs. Anesth Analg 1996; 83: 958-964.<br />

60 JVCS, Vol. 1, No. 2, April, 2008

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