754425

research-article2018
JFM0010.1177/1098612X18754425Journal of Feline Medicine and SurgerySakai et al

Original Article

Journal of Feline Medicine and Surgery

Intravenous rocuronium 0.3 mg/kg 1­–6

© The Author(s) 2018
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DOI: 10.1177/1098612X18754425
https://doi.org/10.1177/1098612X18754425

intubation in cats: a randomized, journals.sagepub.com/home/jfms

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placebo-controlled trial by the American Editorial Office (AAFP)

for publication in JFMS

Daniel M Sakai1, Kailee Anne Zornow1, Luis Campoy1,

Christina Cable2, Leslie D Appel2, Holly J Putnam2
and Manuel Martin-Flores1

Abstract
Objectives We evaluated the use of rocuronium 0.3 mg/kg intravenously (IV) to facilitate tracheal intubation in cats
anesthetized for elective ovariohysterectomy.
Methods Thirty female cats were randomly allocated to receive rocuronium 0.3 mg/kg IV or an equal volume of
normal saline, following induction of anesthesia with ketamine and midazolam. Thirty seconds after induction, a
single investigator, unaware of treatment allocation, attempted tracheal intubation. The number of attempts and the
time to complete intubation were measured. Intubating conditions were assessed as acceptable or unacceptable
based on a composite score consisting of five different components. Duration of apnea after induction was measured
and cases of hemoglobin desaturation (SpO2 <90%) were identified.
Results Intubation was completed faster (rocuronium 12 s [range 8–75 s]; saline 60 s [range 9–120 s]) and with
fewer attempts (rocuronium 1 [range 1–2]; saline 2 [range 1–3], both P = 0.006) in cats receiving rocuronium.
Unacceptable intubating conditions on the first attempt occurred in 3/15 cats with rocuronium and in 10/15 with
saline (P = 0.01). Apnea lasted 4 ± 1.6 mins with rocuronium and 2.3 ± 0.5 mins with saline (P = 0.0007). No cases
of desaturation were observed.
Conclusions and relevance Rocuronium 0.3 mg/kg IV improves intubating conditions compared with saline and
reduces the time and number of attempts to intubate with only a short period of apnea in cats.

Accepted: 19 December 2017

Introduction
Neuromuscular blocking agents (NMBAs) are com-
monly used to facilitate tracheal intubation in people; it
is well established that the inclusion of NMBAs during
the induction of anesthesia in humans improves the
quality of intubation and reduces the incidence of
trauma.1,2 The use of NMBAs during intubation has also
been evaluated in cats, showing that placement of the
tracheal tube is facilitated with these agents.3–5 However,
non-depolarizing NMBAs at the doses commonly used
almost invariable result in apnea of long duration, which
reducing the dose of this agent from 0.6 to 0.3 mg/kg
intravenously (IV) can significantly limit the time of
apnea while preserving the ability to blunt laryngo-
spasm in response to laryngeal stimulation.6 However,
to our knowledge, whether the technique improves
1Department of Clinical Sciences, College of Veterinary Medicine,
Cornell University, Ithaca, NY, USA
2Shelter Outreach Services, Ithaca, NY, USA

may increase the risk of hemoglobin desaturation during

induction and require the institution of positive pressure
ventilation for prolonged periods.4
A recent dose-finding study in a laboratory setting
evaluating the NMBA rocuronium in cats showed that
Corresponding author:
Manuel Martin-Flores DVM, DACVAA, Department of Clinical
Sciences, College of Veterinary Medicine, Cornell University,
930 Campus Rd, Ithaca, NY 14853, USA
Email: martinflores@cornell.edu
2 Journal of Feline Medicine and Surgery
Table 1 Composite score of intubating conditions for cats (modified from Fuchs-Buder et al7)
Excellent
Visualization
Laryngoscopy Easy
Arytenoid/vocal cords position Abducted
Response to intubation
Laryngeal response None
Limbs response None
Cough None
Intubating conditions are considered ‘unacceptable’ if a score of ‘poor’ is assigned to any category
tracheal intubation in a clinical setting has not yet been
evaluated.
In the current study we evaluated the use of a low
dose of rocuronium to facilitate tracheal intubation in
cats anesthetized for elective ovariohysterectomy (OHE).
We hypothesized that administration of rocuronium 0.3
mg/kg IV after induction of anesthesia with ketamine
and midazolam: (1) improves the quality of intubation;
(2) reduces the time and number of attempts to intubate;
and (3) causes no significant difference in the duration of
apnea after induction of anesthesia compared with cats
not receiving rocuronium.
Materials and methods
This study was approved by the Institutional Animal
Care and Use Committee of Cornell University. Thirty
female cats scheduled for OHE were included. Cats were
classified as American Society of Anesthesiologists (ASA)
status 1–2, based on clinical examination. Any cat classi-
fied as ASA status >2, weighing <2 kg or with orofacial
masses or malformations that may interfere with direct
laryngoscopy was excluded. Cats were fasted from solid
food for at least 12 h; water was not withheld.
Each cat received dexmedetomidine 5 μg/kg (Dex­
domitor; Zoetis) and butorphanol 0.2 mg/kg intramus-
cularly (Torbugesic-SA; Zoetis) prior to anesthesia. At
least 20 mins later, a catheter was placed in a cephalic
vein and 100% oxygen (2 l/min) was supplemented
through a tight-fitting facemask for 2 mins. General
anesthesia was induced with ketamine 5 mg/kg and
midazolam 0.2 mg/kg administered IV as a single bolus
in the same syringe. Immediately after administration
of the induction agents, either rocuronium 0.3 mg/kg IV
(rocuronium bromide; X-Gen Pharmaceuticals) or an
equal volume or saline was administered IV and
flushed with 1 ml saline. Treatment allocation was
selected at random by removing labels from an opaque
envelope (starting with 15 labels for each group) prior
to induction of anesthesia. Thirty seconds after injec-
tion of rocuronium or saline, the cat’s mouth was held
Intubating conditions
Good Poor
Fair Difficult
Neutral Closed
Movement Closure
Slight Vigorous
Diaphragmatic movement Vigorous
open and direct laryngoscopy was performed using a
Miller blade #1 by an experienced veterinary anesthesi-
ologist (DMS) unaware of treatment allocation.
Intubating conditions were assessed based on a com-
posite score modified from Fuchs-Buder et al,7 consist-
ing of five categories, which included ease of
laryngoscopy, arytenoid/vocal cord position, and three
categories describing reaction to intubation: movement
of vocal cords, coughing and movement of the limbs
(Table 1). The investigator scored the quality of laryn-
goscopy as ‘easy’, ‘fair’ or ‘difficult’ based on absence
or presence of muscular tone and/or swallowing;
scored the position of the arytenoid cartilages and vocal
cords as ‘abducted’, ‘neutral’ or ‘closed’, as observed on
initial visualization; and scored the coughing reflex
during intubation as ‘absent’, ‘diaphragmatic move-
ment’ and ‘vigorous’. The score was modified by add-
ing two categories for response to intubation: laryngeal
movement and movement of limbs. Intubating condi-
tions were scored as ‘acceptable’ if all components were
‘excellent’ or ‘good’, or ‘unacceptable’ if at least one
component was scored as ‘poor’. Tracheal intubation
with a 3–3.5 mm ID polyvinylchloride cuffed tube
without the use of a stylet, and lubricated with a
­
water-soluble gel, was performed. If intubating
­
­conditions were deemed as ‘unacceptable’ based on the
composite score, then one actuation of lidocaine 1%
(approximately 0.1 ml) was sprayed with an atomizer
on the laryngeal mucosa and intubation attempted
again 30 s later. Desensitization with additional topical
lidocaine could be repeated after another 30 s if intuba-
tion was still unsuccessful. The number of attempts and
the time to complete intubation was measured.
Upon placement of the tracheal tube, a mainstream
capnograph (Cardell Touch; Midmark) was attached and
the capnographic waveform was observed for spontane-
ous breaths. If no spontaneous breath was observed
within 30 s, positive pressure ventilation (PPV) was insti-
tuted manually at a rate of 2 breaths/min until spontane-
ous ventilation (breathing interval <30 s) resumed with a
Sakai et al
Table 2 Median (range) number of attempts to intubate and time required to intubate the trachea of 30 cats anesthetized
with midazolam and ketamine, and receiving either rocuronium 0.3 mg/kg intravenously (IV) or normal saline IV
Rocuronium
Attempts to intubate (n) 1 (1–2)
Time to intubate (s) 12 (8–75)
normal capnographic waveform. The incidence and
duration of PPV were measured. The SpO2 (Cardell
Touch; Midmark) was placed on the tongue as soon as
possible after intubation and observed continuously; if
hemoglobin desaturation (SpO2 <90%) was observed,
PPV would be instituted immediately until the SpO2
increased above 90%. After restoration of spontaneous
ventilation, edrophonium 0.5 mg/kg (Enlon; Mylan) and
atropine 0.02 mg/kg (Atroject SA; Henry Schein Animal
Health) were administered IV to reverse potential resid-
ual block. Meloxicam (0.1 mg/kg SC) was administered.
Cats were moved onto the surgical table; the anesthetic
monitoring thereafter was performed as routinely by the
local personnel.
The train-of-four (TOF; 2 Hz, 200 ms, 40 mA) ratio
was measured with an accelerometer placed over the
dorsal aspect of the metatarsus (Stimpod; Xavant
Technology) with the electrodes (subcutaneous needles)
placed over the lateral aspect of the stifle to stimulate the
peroneal nerve once the surgical procedure was com-
pleted, and prior to extubation in order to detect any
potential residual neuromuscular block.
Data analysis
Distribution of all results was evaluated with the
Shapiro–Wilk test. The significance of differences in age,
weight, number of attempts to intubate, time to intubate
and time of PPV was evaluated with unpaired t-tests or
Mann–Whitney tests, for parametric and non-parametric
results, respectively.
The scores for each component of the composite score
for intubating conditions and the overall score for intu-
bating conditions (acceptable vs unacceptable) was com-
pared between groups with one-tailed Fisher’s exact
tests or χ2 tests. Differences were considered significant
when P <0.05. Results are summarized as mean ± SD
for parametric and median (range) for non-parametric
results.
Results
All cats completed the study. There was no significant
difference in weight between groups (rocuronium 3.0 ±
0.4 kg vs saline 3.2 ± 0.6 kg; P = 0.2); however, age was dif-
ferent between groups (rocuronium 1.5 years [range 0.5–3
years] vs saline 1.0 years [range 0.3–2.0 years]; P = 0.01).
The number of attempts to intubate and the time to
intubate were significantly less in cats receiving
3
Saline P value
2 (1–3) 0.006
60 (9–120) 0.006
rocuronium (Table 2). There were no differences
between groups for individual components of the intu-
bating conditions score (all P ⩾0.07; Figure 1); however,
intubating conditions were unacceptable in more cats
receiving saline (10/15) than in those receiving rocuro-
nium (3/15; P = 0.01). Conditions were deemed unac-
ceptable in cats receiving saline due to closed arytenoid/
vocal cords observed during direct laryngoscopy (n = 3)
or closure of the larynx during intubation (n = 9).
Conditions were unacceptable in the three cats receiv-
ing rocuronium due to closed arytenoid/vocal cords
observed at laryngoscopy. Three of the 10 cats receiving
lidocaine in the saline group, but none in the rocuro-
nium group, required a second dose of topical lidocaine
before intubation was possible.
PPV was administered for 4 ± 1.6 mins to cats receiv-
ing rocuronium and 2.3 ± 0.5 mins to those receiving
saline (P = 0.0007). PPV was required for all 15 cats
receiving rocuronium and seven cats receiving saline
(P = 0.0022). No cases of hemoglobin desaturation (SpO2
<90%) was observed.
Surgery was completed within 15–20 mins in all cats.
The TOF ratio was not measured in the first three cats
receiving rocuronium. No cases of residual neuromuscu-
lar block (TOF ratio <90%) were observed in the remain-
ing 12 cats; TOF ratio was 120 ± 13% prior to extubation.
Discussion
The main findings of this work are that administration of
rocuronium 0.3 mg/kg IV after induction of anesthesia
improved the quality of intubation when compared with
no treatment, and decreased the number of attempts and
time required to place the tracheal tube. The duration of
PPV after induction of general anesthesia was also pro-
longed by administration of rocuronium.
Despite the many benefits of tracheal intubation, this
procedure is not without risks. There are abundant
reports of injuries resulting from intubation in this spe-
cies.8–10 Moreover, it has been reported that tracheal intu-
bation in cats is an independent factor associated with
increased risk of death.11 Difficulties during tracheal intu-
bation in cats may stem from vigorous laryngospasm
triggered during direct laryngoscopy or placement of the
tube. Many techniques have been adopted to facilitate
intubation. Bougies, or guidewires, have been used either
to guide the endotracheal tube into the larynx or to add
rigidity to the tracheal tube; rigid guidewires have been
4 Journal of Feline Medicine and Surgery

Figure 1 Number of cats assigned each score for every category of the intubating conditions composite score at the first
attempt. (a) Quality of larygoscopy: ‘easy’, ‘fair’ or ‘difficult’ based on muscular tone and/or swallowing. (b) Position of
the vocal cords and arytenoids during laryngoscopy: ‘abducted’, ‘neutral’ or ‘closed’. (c) Movement of the larynx during
intubation attempt: ‘none’, ‘movement’ or ‘closure’. (d) Movement of limbs during intubation attempt: ‘none’, ‘slight’ or
‘vigorous’. (e) Presence of coughing during intubation attempt: ‘absent’, ‘diaphragmatic movement’ or ‘vigorous’. The first two
classifications of each category were considered ‘acceptable’ and the last classification was considered ‘unacceptable’ and
lidocaine was sprayed over the laryngeal mucosa before second attempt of intubation

implicated in trauma of the trachea during intubation.8
Topical desensitization of the laryngeal mucosa is also
commonly used to prevent laryngospasm and aid intu-
bation. While this technique has shown to facilitate intu-
bation, a long onset time (up to 1.5 mins) is required
before desensitization is fully effective.12,13 It is possible
that the topical lidocaine applied in some cats in this
study did not reach peak effect. We attempted intubation
30 s after application in an attempt to expedite placement
of the tracheal tube. Laryngeal mucosa desensitization
also relies, at least in part, on a uniform application of the
drug over the mucosal area. Regardless of specific advan-
tages and disadvantages of each technique, the present
association between intubation and increased risk of
mortality,11 or the occurrence of tracheal and laryngeal
lesions following intubations in this species,8–10 suggest
that neither method has completely resolved the issue.
To assess the effect of rocuronium on intubation we
used different variables. The number of attempts
required to intubate and the time to complete intubation
were measured. To decrease variability, all intubation
attempts were made by a single investigator. In addition,
intubating conditions were assessed using a composite
score consisting of five categories, which was modified
from a score previously used in people.7 We modified
the score by adding two categories: laryngeal and limb
movements in response to intubation. We did not find
statistical differences between groups when individual
categories of the score were compared; however, the
composite score reflecting whether intubating condi-
tions were deemed acceptable or unacceptable were dif-
ferent in favor of those cats receiving the NMBA.
One disadvantage associated with the use of NMBAs
is that they almost invariably result in apnea, which may
increase the risks of hemoglobin desaturation and
require PPV. When 0.6 mg/kg rocuronium was adminis-
tered to cats to facilitate intubation, PPV was required
for approximately 30 mins.4 The current investigation
confirmed the findings of a laboratory study that showed
that a lower dose of rocuronium-blunted laryngospasm
while substantially reducing the duration of apnea.
Duration of apnea with the current method was reduced
to an average of 4 mins. Apnea in cats receiving saline
was shorter; however, it was still present and averaged
2.3 mins. These findings underscore the importance of
pre-oxygenation, even when NMBAs are not included
during induction, and highlight the potential apneic
effects produced by the combination of midazolam and
ketamine.
Neuromuscular block was reversed once spontane-
ous ventilation had returned. Thereafter, PPV ceased;
that is, cats breathed spontaneously for the duration of
surgery. In dogs, return of ventilation parameters to pre-
blockade levels does not ensure recovery of neuromus-
cular function for the entire skeletal musculature.14
Therefore, we decided to systematically reverse the
Sakai et al
neuromuscular block with edrophonium. Edrophonium
is an inhibitor of acetylcholinesterase in the neuromus-
cular junction. This class of pharmacological agents pro-
motes an increase in the concentration of acetylcholine
and hastens the recovery in the neuromuscular func-
tion.15 This approach decreases the occurrence of resid-
ual muscular weakness during emergence from general
anesthesia. In concordance with the previous statement,
no cases of residual neuromuscular block were identi-
fied upon recovery from surgery; the TOF ratio after sur-
gery was 120%. TOF ratio values >90% are associated
with fewer complications in the postoperative period.16
The short duration of apnea after induction, and the
complete recovery of the TOF ratio (albeit, enhanced by
the use of edrophonium), in these cats suggest that this
technique is suitable even for short procedures. In com-
parison, the effects of spraying 2% lidocaine over the
laryngeal mucosa lasted between 17 and 100 mins,13
blunting the protective reflexes of the larynx beyond the
time the trachea is extubated.
Rocuronium was selected for this study as it has a
quick onset time in cats.17 While the onset of action was
not measured in the current study, the improved intubat-
ing conditions 30 s after the injection of rocuronium sug-
gest that this period of time was sufficient for most cats.
Such a short onset time represents an advantage over
topical laryngeal anesthesia, which might have a slower
onset of action.12,13 Other NMBAs might provide similar
benefits. In the past, the depolarizing agent succinylcho-
line has been used successfully to intubate cats.5
Succinylcholine is also characterized by quick onset and
short duration of action;18 however, its use is associated
with several side effects, including muscular fascicula-
tions,19 arterial hypotension and,20 in some cases, hyper-
kalemia;21 no such associations exist for rocuronium.
Gantacurium is a novel, ultra-short-acting non-depolar-
izing NMBA. In cats it produces a fast onset of paralysis,
blunts laryngospasm and has a short duration of action.22
However, at the time this manuscript was prepared, gan-
tacurium was not commercially available.
In this study, no cases of hemoglobin desaturation
<90% were observed, despite periods of apnea. However,
it should not be assumed that hypoxemia may not occur
with this technique. First, PPV was applied during peri-
ods of apnea, albeit at a low rate. Second, cats were deni-
trogenized for 2 mins with oxygen using a tight-fitting
facemask. Denitrogenation increases the amount of oxy-
gen available in the functional residual capacity during
periods of apnea and extends the time to desaturation in
dogs.23 If pre-oxygenation is not performed, it is possible
that hypoxemia may ensue.
There are some limitations to consider. First, pulse
oximetry was not measured before or during intubation
while the mouth was held open. While we cannot com-
ment on the SpO2 levels during that short period, no
5
cases of hypoxemia were observed when the pulse
oximeter was applied, immediately after intubation.
­
Second, spontaneous ventilation was assessed with
ETCO2. Further information such as tidal volume would
improve the analysis of the ventilatory effects of rocuro-
nium. Third, we evaluated the effects of rocuronium in
cats receiving ketamine/midazolam. It is possible that
the results would vary if other induction agents are used.
Lastly, the quality of intubating conditions was assessed
with a subjective score. This score is commonly used to
assess intubation in people. To reduce variability, only
one investigator, unaware of treatment allocation, scored
the larynx. In addition, we added other measurable out-
comes such as time to intubation and number of attempts
to increase the validity of our observations.
Conclusions
Rocuronium 0.3 mg/kg IV improves intubating condi-
tions and reduces the time and number of attempts to intu-
bate when compared with no treatment, with only a short
period of apnea. Apnea requiring PPV may occur during
induction of anesthesia even if rocuronium is omitted.
Acknowledgments The authors thank Midmark Animal
Health for generously providing monitoring equipment for this
project, and the Chemung County Humane Society and SPCA
for consenting to the use of its facilities and animals.
Conflict of interest The authors declared no potential con-
flicts of interest with respect to the research, authorship, and/
or publication of this article.
Funding This work was funded by the Clinical Fellowship
Program, College of Veterinary Medicine, Cornell University.
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