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Veterinary Anaesthesia and Analgesia 2022, 49, 243e250 https://doi.org/10.1016/j.vaa.2021.07.

006

RESEARCH PAPER

Determining an optimum propofol infusion rate for


induction of anaesthesia in healthy dogs: a randomized
clinical trial

Kate Waltersa, Kristina Lehnusb, Nai-Chieh Liua & Sarah E Bigbyc


a
The Queen’s Veterinary School Hospital, University of Cambridge, Cambridge, UK
b
Hamilton Specialist Referral Unit 5 Halifax Road, Cressex Business Park, Buckinghamshire, UK
c
Veterinary Specialist Services, Carrara, Queensland, Australia

Correspondence: Kate Walters, The Queen’s Veterinary School Hospital, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK. E-mail:
katelwalters49@gmail.com

Abstract Conclusions and clinical relevance An infusion rate of 1.0


mg kge1 minutee1 (group B) appears to offer the optimal
Objective To determine an optimum infusion rate of pro-
compromise between speed of induction and duration of
pofol that permitted rapid tracheal intubation while mini-
postinduction apnoea.
mizing the duration of postinduction apnoea.
Study design Prospective, randomized, blinded clinical trial. Keywords dog, induction, infusion rate, intubation time,
Animals A total of 60 client-owned dogs presented for postinduction apnoea, propofol.
elective neutering and radiography.
Methods Dogs were randomly allocated to one of five Introduction
groups (groups AeE) to have propofol at an infusion rate
Propofol is an alkyl phenol used for rapid induction of general
of 0.5, 1, 2, 3, or 4 mg kge1 minutee1, respectively,
anaesthesia. A rapid recovery from anaesthesia then occurs
following intramuscular premedication with methadone
owing to redistribution (Goodman et al. 1987; Morgan &
0.5 mg kge1 and dexmedetomidine 5 mg kge1. Propofol
Legge 1989). It has market authorization for induction of
administration was stopped when adequate conditions for
anaesthesia at 1.0e4.0 mg kge1 in premedicated dogs, or 6.5
tracheal intubation were identified. Time to tracheal
mg kge1 in unpremedicated dogs (Morgan & Legge 1989;
intubation and duration of apnoea were recorded. If oxy-
Zoetis UK Limited, 2019). The current recommendation in the
gen haemoglobin saturation decreased to < 90%, manual
datasheet is to administer a calculated dose to effect over
ventilation was initiated. A one-way analysis of covariance
10e40 seconds (Zoetis UK Limited, 2019). In clinical practice,
was conducted to compare the effect of propofol infusion
incremental boluses of propofol are often administered,
rate on duration of apnoea and intubation time whilst
although little definitive guidance exists, and administration
controlling for covariates, followed by post hoc tests. The
techniques differ significantly between clinicians.
significance level was set at p < 0.05.
The optimum delivery of an induction agent (in terms of
Results Propofol infusion rate had a significant effect on administration technique, rate and dose) should result in rapid
duration of apnoea (p ¼ 0.004) and intubation time (p < loss of consciousness with no or minimal adverse effects. A time
0.001) after controlling for bodyweight and sedation delay between drug injection and loss of consciousness arises
scores, respectively. The adjusted means (± standard error) while the cardiovascular system transports the drug to the brain
of duration of apnoea were significantly shorter in groups where the clinical effect occurs. This delay often results in the
A and B (49 ± 39 and 67 ± 37 seconds, respectively) than delivered dose exceeding the minimum dose required to achieve
in groups C, D and E (207 ± 34, 192 ± 36 and 196 ± 34 loss of consciousness, as the drug continues to be injected until
seconds, respectively). Group B (115 ± 10 seconds) had a an adequate anaesthetic plane is reached (Kazama et al. 2000).
significantly shorter intubation time than group A (201 ± Adverse effects associated with propofol administration are
10 seconds, p < 0.001). dose dependent. Postinduction apnoea is the most common

243
Optimum propofol infusion rate for induction K Walters et al.

adverse event following propofol administration, occurring Lees 1989; Stokes & Hutton 1991). Currently, it is unknown
with an incidence of 85e100% in studies conducted in which infusion rate produces the most favourable combination
humans and dogs. Apnoea results from a reduction in central of induction speed while minimizing postinduction apnoea by
inspiratory drive and ventilatory responses to carbon dioxide dose reduction in healthy dogs.
(Goodman et al. 1987; Grounds et al. 1987; Smith et al. 1993; The aim of this study was to determine an optimum infusion
Muir & Gadawski 1998; Bigby et al. 2017a,b). However, rate of propofol that permitted rapid tracheal intubation while
postinduction apnoea rarely led to cyanosis if dogs were pro- minimizing the duration of postinduction apnoea in healthy
vided with supplemental oxygen at induction (Smith et al. dogs. We hypothesized that the optimum infusion rate would
1993; McNally et al. 2009). Another adverse effect associ- lie between the previously described 1 mg kge1 minutee1 and
ated with propofol administration is decreased mean arterial 4 mg kge1 minutee1 (Bigby et al. 2017b; Zoetis UK Limited,
blood pressure owing to a reduction in systemic vascular 2019).
resistance and a slight decrease in heart rate (HR) (Suarez et al.
2012; Henao-Guerrero & Ricco 2014). Materials and methods
The propofol infusion rate affects the dose required to induce
anaesthesia (Stokes & Hutton 1991; Bigby et al. 2017b), in- Animals
duction time (Rolly et al. 1985; Gillies & Lees 1989; Stokes & All American Society of Anesthesiologists (ASA) score I dogs
Hutton 1991) and the duration of apnoea (Gillies & Lees 1989; presenting for elective neutering or elective radiography for hip
Bigby et al. 2017b) in humans and animals. In humans, slower scoring at the Queen’s Veterinary School Hospital, UK, be-
administration was associated with a lower incidence of tween November 2017 and July 2019 were recruited.
apnoea, but longer induction times (Rolly et al. 1985; Gillies & Brachycephalic breeds, animals on concurrent medication or

Figure 1 CONSORT (CONsolidated Standards of Reporting Trials 2010) flow diagram outlining the progression of all animals in this randomized
controlled study to identify an optimum propofol infusion rate for the induction of anaesthesia in healthy dogs.

244 © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights
reserved., 49, 243e250
Optimum propofol infusion rate for induction K Walters et al.

with a history of regurgitation were excluded. Informed owner Intersurgical Inc, NY, USA) to a breathing system delivering
consent was obtained, and the project was approved by the oxygen at 2 L minutee1. The ETT cuff was inflated guided by
University of Cambridge Animal Welfare and Ethical Review pilot balloon palpation. No further manipulation of the animal
Body (AWERB), UK (ref CR 246). was permitted until spontaneous breathing occurred, at which
point an end-tidal carbon dioxide reading was recorded. Once
Study protocol spontaneous breathing occurred, a positive pressure leak test
guided further ETT cuff inflation and isoflurane (IsoFlo; Zoetis)
The progression of all animals included in this study are shown
delivery commenced.
in Fig. 1. Dogs were randomized to one of five groups using a
A second observer, also blinded to the propofol infusion rate,
random number generator (Excel 2010; Microsoft Corporation,
started a stopwatch (Adanac 3000; Marathon, UK) the
WA, USA). Each group was administered a different propofol
moment the syringe driver was activated. They recorded the
infusion rate for induction of anaesthesia: group A, 0.5 mg
time the infusion was stopped, tracheal intubation was ach-
kge1 minutee1; group B, 1.0 mg kge1 minutee1; group C, 2.0
ieved and the first spontaneous breath. The latter was defined
mg kge1 minutee1; group D, 3.0 mg kge1 minutee1; and group
as the first visible chest excursion.
E, 4.0 mg kge1 minutee1. Signalment and planned procedure
Throughout the induction of anaesthesia, HR and respira-
were recorded for each animal. An independent person
tory rates were monitored manually using a stethoscope.
calculated the propofol infusion rate (mL houre1) allocated to
Systolic, mean (MAP) and diastolic arterial blood pressure were
each dog and programmed the rate into the syringe driver
monitored using an oscillometric blood pressure cuff applied to
(Alaris GH; Cardinal Health, Switzerland) before obscuring the
the animal’s pelvic limb distal to the hock (PetMap Graphical
display from view. A total of 6 mg kge1 propofol (10 mg mLe1;
II; Ramsey Medical Inc and CardioCommand Inc., FL, USA). A
Propoflo Plus; Zoetis, UK) was drawn up and set up with an
pulse oximeter probe (Avante Waveline Nano-V2; DRE Vet-
extension set (V-green extension; Vygon, France).
erinary, KY, USA) was placed on the tongue to measure hae-
All animals underwent a physical examination before pre-
moglobin oxygen saturation (SpO2). Recordings were taken
medication with 0.5 mg kge1 methadone (Synthadon; Ani-
before premedication, at the end of preoxygenation (prein-
malcare, UK) and 5 mg kge1 dexmedetomidine (Dexdomitor;
duction), after tracheal intubation and immediately after the
Orion Pharma, UK) by deep intramuscular injection into the
first breath observed after completion of endotracheal intuba-
cervical muscles. An intravenous 22 or 20 gauge cephalic
tion. Animals with SpO2 < 90% received manual ventilation at
cannula (Jelco; Smiths Medical International, UK) with T-
4 breaths minutee1 to a pressure of 12e15 cmH2O until
connector (Bionector T-connector LL; Vygon) was inserted 15
saturation increased to 95% or spontaneous breathing
minutes after premedication. At 30 minutes after premed-
occurred.
ication, each animal was assigned a sedation score between
The total propofol dose administered was calculated by
0 (not sedated) and 21 (profound sedation) by the same
subtracting the residual volume in the syringe and 1.4 mL
observer (KW) familiar with the subjective scoring system
from the extension set, from the original volume drawn up.
assessment tool (Grint et al. 2009; Appendix SA). Oxygen was
The difference in MAP before induction and after tracheal
supplemented via face mask (Face mask clear with diaphragm;
intubation was also calculated. Intubation time was recorded
J.A.K Medical, UK) at 4 L minutee1 for 5 minutes before
as the time taken from starting the infusion to successful
starting the allocated propofol infusion.
tracheal intubation. Duration of apnoea was recorded as the
The same anaesthetist (KW), blinded to the assigned pro-
time from tracheal intubation to the first breath observed
pofol infusion rate, intubated the trachea of all animals using
after completion of endotracheal intubation. For any animals
an endotracheal tube (ETT) (Surgivet; Smiths Medical, UK)
that desaturated and required manual ventilation, duration of
appropriate to the animal’s size. Once the dog was unable to
apnoea was determined as the time taken from tracheal
support its own head and the palpebral reflex and jaw tone
intubation to initiation of manual ventilation; this is included
were absent, the propofol infusion was stopped. If there was no
in subsequent analysis. Any adverse event or intervention
resistance to gentle tongue traction, tracheal intubation was
was recorded.
attempted. In the event of unsuccessful tracheal intubation
(indicated by coughing or resistance to passage of the ETT), the
Statistical analysis
infusion was restarted until tongue retraction was possible and
a second attempt at tracheal intubation was made. Animals A sample size calculation based on a previous study comparing
were excluded from the study if two unsuccessful attempts propofol infusion rate and duration of apnoea (Bigby et al.
occurred. 2017b) was performed. When considering an effect size of
Once the trachea was intubated, the ETT was connected via 0.4 minutes for duration of apnoea, 12 dogs per group would
a capnograph adapter (Clear-therm HMEF with luer port; be required to achieve a power of 80% and an a of 0.05.

© 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights 245
reserved., 49, 243e250
Optimum propofol infusion rate for induction K Walters et al.

All statistical analyses were performed using the software R


version 4.0.2 for Mac (R Foundation for Statistical Computing,
Austria; http://www.r-project.org). The significance level was
set at p < 0.05. Distribution of data was assessed by Shapiro-
Wilk test for numeric variables within groups. Equality of
variance was tested using Levene’s test. Data are summarized
as mean ± standard deviation for normally distributed data or
median (range) for non-normally distributed data. Either one-
way analyses of variance or Kruskal-Wallis tests followed by
post hoc pairwise comparisons were used to assess differences
among groups in terms of the following variables: age, sedation
score, bodyweight, change in blood pressure and total dose of
propofol.
Outliers [above upper quartile þ 1.5*interquartile range
(IQR) or below lower quartile e 1.5*IQR] were identified for
duration of apnoea and intubation time by group. One-way
analyses of covariance were performed to determine the ef- Figure 2 Box and whisker plots showing the distribution of duration
fect of propofol infusion rate on duration of apnoea and intu- of apnoea and time to tracheal intubation for five different propofol
bation time after controlling for selected covariates and is infusion rates used for the induction of anaesthesia in 60 healthy dogs
following intramuscular premedication with methadone 0.5 mg kge1
presented as adjusted means ± standard error. Covariates were
and dexmedetomidine 5 mg kge1. There were 12 dogs per group:
selected based on linearity with the dependent variables with p group A, propofol infusion rate 0.5 mg kge1 minutee1; group B, 1 mg
< 0.05. Post hoc tests were then performed for pairwise com- kge1 minutee1; group C, 2 mg kge1 minutee1; group D, 3 mg kge1
parisons among groups with Bonferroni multiple testing minutee1; group E, 4 mg kge1 minutee1. The whiskers demonstrate
correction. the range; the boxes show the interquartile range; the line in the box
is the median. Outliers are marked as dots. Significance is set at p <
0.05. *Significantly different from groups CeE. ySignificantly different
Results
from groups BeE.
A total of 62 dogs were enrolled in the study, with a median
age of 22 (8e112) months and a median bodyweight of 11.5
(3e44.3) kg. Prior to induction of anaesthesia, one animal was mg kge1; p ¼ 0.003) and E (3.9 ± 1.3 mg kge1; p ¼ 0.004),
withdrawn owing to bradycardia (HR ¼ 27 beats minutee1, with no significant difference from group A (1.6 ± 0.8 mg
sinus rhythm) following premedication and the dog was given kge1; p ¼ 0.917).
atipamezole. Another was withdrawn owing to cannula failure Bodyweight (p ¼ 0.034) and sedation score (p ¼ 0.026)
during propofol administration (Fig. 1). Of the 60 animals that were identified as covariates for duration of apnoea and
completed the study, 21 presented for ovariohysterectomy, 21 intubation time, respectively. Propofol infusion rate had sig-
for laparoscopic ovariectomy, and 17 for castration and one for nificant effects on duration of apnoea [F (4,48) ¼ 4.403, p ¼
hip scoring. Each group contained 12 animals, and tracheal 0.004] and intubation time [F (4,48) ¼ 23.103, p < 0.001]
intubation was successful at the first attempt in all animals. after controlling for body weight and sedation score, respec-
Desaturation (SpO2 values of 84e87%) occurred in three dogs tively. Subsequent post hoc pairwise comparisons between the
(5%) in group D requiring manual ventilation at 96, 394 and adjusted means identified that groups A and B had a signifi-
404 seconds after tracheal intubation, respectively. cantly shorter duration of apnoea than groups CeE, with no
The mean dose of propofol, duration of apnoea and intuba- significant difference between groups A and B (Table 1).
tion time were significantly different among groups (p < 0.001, Intubation time was significantly shorter in group B than in
p ¼ 0.017 and p < 0.001, respectively), whereas age, body- group A, with no significant difference in groups CeE
weight, sedation score and blood pressure difference were not (Table 2).
(p ¼ 0.697, p ¼ 0.722, p ¼ 0.956, and p ¼ 0.456, respec-
tively). Distribution of results for duration of apnoea and Discussion
intubation time are shown in Fig. 2. There were six outliers A propofol infusion rate of 1.0 mg kge1 minutee1 is optimal for
identified: three in group A, two in group B and one in group D. the induction of general anaesthesia in healthy dogs sedated
The total dose of propofol administered to induce anaes- with methadone and dexmedetomidine. Both 0.5 and 1.0 mg
thesia was significantly less in group B (2.1 ± 0.5 mg kge1) kge1 minutee1 rates were associated with significantly
than in groups C (3.4 ± 0.9 mg kge1; p ¼ 0.037), D (3.8 ± 0.8 reduced propofol induction doses and shorter postinduction

246 © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights
reserved., 49, 243e250
Optimum propofol infusion rate for induction K Walters et al.

Table 1 Pairwise comparisons of duration of apnoea between five different propofol infusion rates. A total of 60 dogs were included, 12 in each
group. A one-way analysis of covariance was conducted with bodyweight identified as a covariate and is presented as adjusted mean ±
standard error. The significance identified by post hoc pairwise comparisons with Bonferroni multiple testing correction between groups are
shown. Propofol infusion rate: group A, 0.5 mg kge1 minutee1; group B, 1 mg kge1 minutee1; group C, 2 mg kge1 minutee1; group D, 3 mg
kge1 minutee1; group E, 4 mg kge1 minutee1

Group (p)

Group Duration of apnoea (seconds) A B C D E


A 49 ± 39 e 0.732 0.004* 0.010* 0.007*
B 67 ± 37 e e 0.008* 0.020* 0.015*
C 207 ± 34 e e e 0.760 0.808
D 192 ± 36 e e e e 0.946
E 196 ± 34 e e e e e

*
Significance level was set at p < 0.05.

apnoea than higher rates. However, 1 mg kge1 minutee1 This probably occurs as slow infusion rates are less likely to
resulted in a significantly shorter time to tracheal intubation overshoot the dose required, and therefore cause fewer dose-
than 0.5 mg kge1 minutee1. dependent adverse effects (Stokes & Hutton 1991; Ludbrook
Shorter tracheal intubation times were achieved with faster & Upton 1997; Ludbrook et al. 1998). The duration of post-
infusion rates in the present study, although no statistical induction apnoea reported by Bigby et al. (2017b) was shorter
difference was found between 1 mg kge1 minutee1 and higher for 1.0 mg kge1 minutee1 and longer for 4.0 mg kge1
rates. There appears, therefore, to be no benefit in adminis- minutee1 (10 ± 18 and 287 ± 125 seconds, respectively) than
tering propofol infusions at a rate greater than 1.0 mg kge1 in the present study. This could be related to individual
minutee1 to hasten tracheal intubation in healthy animals. anaesthetist variability, timing of tracheal intubation and
The more rapid onset of clinical effects can be explained by study design, such as criteria dictating when the propofol
higher infusion rates more rapidly achieving greater concen- infusion should cease. In the present study, the propofol infu-
tration gradients between the arterial blood and the central sion was stopped when the plane of anaesthesia was deemed
nervous system (CNS) than slower infusion rates (Stokes & adequate for tracheal intubation, while in the study reported
Hutton 1991). However, there is also a positive association by Bigby et al. (2017b) the infusion was continued until suc-
between the infusion rate and total propofol dose administered. cessful tracheal intubation was achieved. The decision to alter
In the present study, for the 1.0 and 4.0 mg kge1 minutee1 the protocol was taken to reflect clinical practice.
infusion rates, the total doses administered mirror those re- Covariance was identified between duration of apnoea and
ported by Bigby et al. (2017b) (1.8 ± 0.6 and 4.1 ± 0.7 mg bodyweight, as well as intubation time and sedation score.
kge1, respectively). The association between higher infusion Although no significant difference was identified between
rates and larger propofol doses suggests that the transfer of groups, there was variation within each group for these vari-
drug to the effect site (CNS) is not solely dependent on drug ables. In addition, although infusion rates are calculated based
concentration gradients, but also on rate-limiting kinetics on bodyweight, physiological processes including metabolic
described as the ‘biophase delay’ (Stokes & Hutton 1991; rate and drug metabolism are more closely correlated to body
Larrson & Wahlstrom 1994). The biophase delay arises as a surface area (El Edelbi et al. 2012; Nam et al. 2017). This may
result of a set transport time limiting the uptake to the effect account for the covariance identified in the present study.
site, permitting even slow infusion rates of propofol to achieve a The effect of propofol on blood pressure was minimal and not
sufficient and sustained concentration gradient. In addition, significantly different between groups. Significant decreases in
the effect site concentration for the clinical measures of drug arterial blood pressure and systemic vascular resistance have
effect is independent of the rate of increase of the effect site been reported in humans and veterinary species following
concentration (Doufas et al. 2004). Therefore, faster propofol propofol administration (Fairfield et al. 1991; Hug et al. 1993;
infusion rates result in plasma accumulation and a relative Smith et al. 1993; Zheng et al. 1998; Suarez et al. 2012;
overdose, prior to the onset of clinical signs. Henao-Guerrero & Ricco 2014; de Wit et al. 2016; Cattai et al.
The present study mirrors findings in humans and dogs, 2018). In sheep, Zheng et al. (1998) identified a correlation
where slower propofol infusion rates were associated with between propofol plasma concentration and the magnitude of
reduced incidences and durations of postinduction apnoea blood pressure decline, with the greatest reduction seen in
(Rolly et al. 1985; Goodman et al. 1987; Gillies & Lees 1989; cases receiving propofol at high injection speeds. Similarly, in
Berthoud et al. 1993; Bigby et al. 2017b). acepromazine-premedicated dogs, Cattai et al. (2018)
© 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights 247
reserved., 49, 243e250
Optimum propofol infusion rate for induction K Walters et al.
Table 2 Pairwise comparisons of intubation time between different propofol infusion rates. A total of 60 dogs were included, with 12 per
group. A one-way analysis of covariance was conducted with sedation score identified as a covariate and is presented as adjusted mean ±
standard error. The significance identified by post hoc pairwise comparisons with Bonferroni multiple testing correction between groups are
shown. Propofol infusion rate: group A, 0.5 mg kge1 minutee1; group B, 1 mg kge1 minutee1; group C, 2 mg kge1 minutee1; group D, 3 mg
kge1 minutee1; group E, 4 mg kge1 minutee1

Group (p)

Group Intubation time (seconds) A B C D E


A 201 ± 10 e < 0.0001* < 0.0001* < 0.0001* < 0.0001*
B 115 ± 10 e e 0.913 0.113 0.055
C 113 ± 9 e e e 0.121 0.053
D 93 ± 9 e e e e 0.204
E 76 ± 9 e e e e e

*
Significance level was set at p < 0.05.

identified maximal cardiovascular depression 50e60 seconds was no difference in weight among groups, the impact on the
after propofol administration, with the magnitude related to data should have been minimal. In future, the connector could
propofol plasma concentration. The fact that these effects were be primed with propofol in addition to the extension line, or the
not observed in the present study could be explained by the use timer only started when propofol visibly reached the animal.
of lower infusion rates than the 10 mg kge1 minutee1 reported Another limitation was the use of subjectively defined time
by Cattai et al. (2018). Furthermore, we did not administer points guiding decisions about when to stop propofol admin-
acepromazine, which may exacerbate hypotension by istration or determine what constituted a first breath. The first
contributing to vasodilation (Smith et al. 1993; Maddison et al. breath was recorded as the first visible chest excursion. During
2008). In addition, dexmedetomidine-mediated vasoconstric- the study, it became apparent not all animals continued to
tion may have helped to maintain vascular tone in animals in breathe once the first chest excursion had occurred, while
the present study (Robinson et al. 1997; Ohata et al. 1999). others initially breathed very shallowly. However, as the same
Effects of rate of administration on blood pressure may be more blinded observers determined what constituted the first breath
readily elucidated if potent vasoconstrictors such as a2-adre- and decided when the infusion should stop, the impact of
noceptor agonist drugs are not used prior to administration of subjective decisions was minimized. Another limitation of the
propofol. study design was the inclusion of animals requiring ventilation
In the present study, the mean duration of apnoea in dogs following desaturation. If this intervention had not been initi-
given 0.5 and 1.0 mg kge1 minutee1 propofol infusion rates ated, apnoea would have continued in these three animals.
was shorter than desaturation times (69.6 ± 10.6 seconds for Therefore, duration of apnoea would have been longer in their
dogs breathing room air and 297.8 ± 42.0 seconds for dogs respective groups if no intervention was made. Finally, physi-
receiving oxygen supplementation) reported by McNally et al. ological monitoring was noninvasive relying on oscillometric
(2009). This suggests that slower infusion rates would be blood pressure and SpO2 rather than direct arterial pressure
particularly beneficial in animals that do not tolerate preox- measurements or blood gas sampling. This type of monitoring
ygenation. In the present study, three animals desaturated and was most relevant to daily clinical practice for ASA I animals
required manual ventilation despite preoxygenation. All three undergoing neutering and imaging procedures.
animals received high doses of propofol at faster infusion rates. In conclusion, a 1.0 mg kge1 minutee1 infusion rate offers
Desaturation occurred early after induction in one dog, and the best compromise between speed of induction and duration
this may be linked to a sampling error, such as compression of of postinduction apnoea in healthy dogs. Differences in the
lingual vessels or ambient light interference; while two dogs distribution pharmacokinetics between propofol infusions
developed prolonged postinduction apnoea and probably and boluses are reported (Stokes & Hutton 1991). Therefore,
desaturated owing to hypoventilation. further studies should compare the optimum infusion rate
The present study has several limitations. The setup using a (1.0 mg kge1 minutee1) we identified with incremental low
T-connector as a cannula attachment was a limitation. dose (1e1.5 mg kge1) bolus administration of propofol to
Although the T-connector has a volume of 0.3 mL, this addi- facilitate tracheal intubation. This may identify whether the
tional volume introduced a delay between starting the infusion optimal induction dose of propofol is less using bolus admin-
and the drug reaching the animal. This is most relevant in istration as compared with the slow continuous administra-
smaller animals at slower infusion speeds. However, as there tion used in this study.

248 © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights
reserved., 49, 243e250
Optimum propofol infusion rate for induction K Walters et al.

Acknowledgements Grint NJ, Burford J, Dugdale AHA (2009) Does pethidine affect the
cardiovascular and sedative effects of dexmedetomidine in dogs?
Thank you to Jennifer E. Carter, University of Melbourne, J Small Anim Pract 50, 62e66.
Australia, for the original concept. This research did not Grounds RM, Maxwell DL, Taylor MB et al. (1987) Acute ventila-
receive any specific grant from funding agencies in the public, tory changes during IV induction of anaesthesia with thio-
commercial or not-for-profit sectors. pentone or propofol in man. Br J Anaesth 59, 1098e1102.
Henao-Guerrero N, Ricco CH (2014) Comparison of the cardiore-
Authors’ contributions spiratory effects of a combination of ketamine and propofol,
propofol alone, or a combination of ketamine and diazepam
KW: data collection, statistical analysis and interpretation of before and after induction of anaesthesia in dogs sedated with
the data, manuscript preparation. KL: experimental design, acepromazine and oxymorphone. Am J Vet Res 75, 231e239.
data collection, manuscript preparation. NCL: statistical anal- Hug CC Jr, McLeskey CH, Nahrwold ML et al. (1993) Hemodynamic
ysis and interpretation of the data, manuscript preparation. effects of propofol: data from over 25,000 patients. Anesth Analg
SEB: experimental design and manuscript preparation. 77, S21eS29.
Kazama T, Ikeda K, Morita K et al. (2000) Investigation of effective
Conflict of interest statement anesthesia induction doses using a wide range of infusion rates
with undiluted and diluted propofol. Anaesthesiology 92,
The authors declare no conflict of interest 1017e1028.
Larrson J, Wahlstrom G (1994) Optimum rate of administration of
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