ORIGINAL STUDIES
Comparison of Propofol and Propofol/Ketamine Anesthesia for Evaluation of Laryngeal Function in Healthy Dogs Kelci L. McKeirnan, DVM*y, Marjorie E. Gross, DVM, MS, DACVA, Mark Rochat, DVM, MS, DACVS, Mark Payton, PhD
ABSTRACT Thiopental is an excellent choice for evaluation of laryngeal function. Unfortunately, thiopental is no longer manufactured. In its absence, the ideal anesthetic protocol for laryngoscopy has not been determined. Propofol and propofol/ketamine were compared for the evaluation of laryngeal function in 48 healthy dogs. Laryngeal exposure was moderate to excellent in all dogs and not significantly different between protocols. Saturation of peripheral O2 (SPO2) readings were decreased in the propofol/ ketamine group, and deeper respirations were more likely to correlate with normal laryngeal function regardless of treatment group. Doxapram was administered to apneic patients to stimulate respiration and allow for evaluation of laryngeal function. No significant difference in frequency of doxapram administration between groups was noted. Doxapram resulted in higher respiratory scores and significantly increased the ability to determine normal laryngeal function. Ketamine did not allow for a reduction in propofol dose and caused increased respiratory depression, making ketamine a poor addition to propofol for laryngeal function examination. Regardless of the protocol used, laryngeal function should be determined in conjunction with the respiratory phase and depth of respirations. Patients with either absent or shallow respirations should receive doxapram for accurate evaluation of laryngeal function. (J Am Anim Hosp Assoc 2014; 50:19–26. DOI 10.5326/JAAHA-MS-5959)
Introduction
Echolarynography and transnasal laryngoscopy have been
Laryngeal paralysis is a common acquired disease of older, large-
reported for laryngeal function evaluation; however, diagnosis of
breed dogs.1,2 Congenital and acquired forms can occur, with
laryngeal paralysis is most commonly made using direct oral
1–3
idiopathic acquired being the most common presentation.
laryngoscopy under a light plane of anesthesia.4 The ideal anes-
Arytenoid paralysis results in partial to complete loss of laryngeal
thetic protocol for accurate laryngeal examination results in
function, resulting in variable degrees of upper airway obstruc-
a light anesthetic plane with decreased jaw tone, intact laryngeal
tion. Affected dogs present with clinical signs ranging from mild
reflexes, and minimal respiratory depression. Doxapram has been
exercise intolerance to life-threatening respiratory distress. Dis-
added to variable anesthetic protocols to stimulate respirations in
ease severity is directly correlated with the degree of laryngeal
apneic patients and can increase intrinsic laryngeal motion, fa-
dysfunction, with clinical signs occurring most frequently with
cilitating laryngeal function examination in dogs.3
bilateral disease. Regardless of the underlying etiology, accurate
Thiopental, propofol, diazepam/ketamine, and gas anesthesia
observation of arytenoid function is critical to determine if la-
have all been used to provide anesthesia for laryngeal function
ryngeal paralysis is present.
examination.5–7 Thiopental has been found to be the best
From the Department of Veterinary Clinical Sciences (K.M., M.G., M.R.) and Department of Statistics, Oklahoma State University, Stillwater, OK (M.P.).
SPO2 saturation of peripheral O2
Correspondence: [email protected] (K.M.)
*K. McKeirnan’s updated credentials since article acceptance are DVM, MS, DACVS-SA. †
K. McKeirnan’s present affiliation is Animal Emergency and Specialty,
Kirkland, WA.
ª 2014 by American Animal Hospital Association
JAAHA.ORG
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injectable anesthetic for evaluating laryngeal function.5,6 Unfor-
were administered IV for anesthetic induction until the mouth
tunately, thiopental is no longer commercially available. In the
could easily be opened for examination. Propofol was adminis-
absence of thiopental, the ideal anesthetic protocol for the eval-
tered slowly over 1 min to effect in both protocols. The amount of
uation of laryngeal function has yet to be determined. Studies
propofol required to achieve adequate anesthesia for laryngeal
evaluating propofol for laryngeal examination have revealed ad-
examination was recorded. The percent of the propofol dose
equate laryngeal exposure with weaker laryngeal motion com-
administered was calculated to normalize dose for body weight
pared with thiopental.
5,6
Unfortunately, significant respiratory
and allow dose comparisons between groups. Ketamine was given
depression often occurs with propofol, with apnea related to dose,
as a calculated bolus followed by propofol to effect. The anes-
speed of injection, and concurrent premedications, complicating
thesiologist administered all anesthetic agents with the exception
laryngeal evaluation.8 Ketamine has been shown to preserve the
of the intramuscular premedications, which were given by fourth
laryngeal reflex to a greater degree than thiopental in people, al-
year veterinary students under direct supervision. Laryngeal
though the anesthetic plane may be inadequate for veterinary
function observers were blinded to the administered protocol by
5,6,9
Ketamine, in conjunction with
giving an equal volume of normal saline in lieu of ketamine to
propofol, may hypothetically provide an additive effect on relax-
patients in the propofol only group. Following anesthetic induc-
ation and laryngeal exposure, while minimizing respiratory de-
tion, dogs were placed in sternal recumbency with the head ele-
pression. The objective of this study was to compare the effects of
vated to the level of normal carriage. Laryngeal assessment was
propofol to propofol/ketamine anesthesia on laryngeal visualiza-
performed as soon as the mouth could be opened, and the larynx
tion and function in healthy dogs. The study authors hypothesized
was visualized by the same two individuals in succession (K.M.,
that propofol/ketamine would provide an adequate plane of an-
M.R.). Laryngeal examination began within 30 min of premed-
esthesia with decreased respiratory depression for laryngeal ex-
ication. Interobserver experience (between a third year resident
amination in dogs.
and a board-certified surgeon with w 20 yr of experience) was
patients given previous studies.
normalized by alternating who first evaluated each patient. The
Materials and Methods
evaluations were defined as early if they were the first evaluator
Animals
and late if they were the second evaluator. All evaluations were
Twenty-four male and 24 female healthy dogs, ranging from ap-
completed within 4 min of induction. A similar protocol for la-
proximately 6 mo to 5 yr, presented from surrounding animal
ryngeal examination described by Gross et al. (2002) was used.5
shelters for elective sterilization were studied. Age was estimated
Breathing score was defined as the score of the breath when la-
based on physical appearance and dentition. Each dog received
ryngeal function determination was made and was assigned by the
a thorough physical examination prior to entering the study, and
laryngeal observers. Parameters were outlined as described in
dogs were excluded if evidence of respiratory, cardiovascular, or
Table 1. Swallowing and laryngospasm were graded together as
systemic disease was present. Dogs weighed 15–35 kg and were
either present or absent. Laryngeal function was characterized as
randomly assigned by lottery to one of two anesthetic protocols,
normal (arytenoid cartilages abduct during inspiration), weak
providing an even distribution of males and females in each
(arytenoid cartilages abduct but poorly), or abnormal (one or
group. All protocols were approved by the University Animal Care
more arytenoid cartilages do not abduct during inspiration). The
and Use Committee and permission was obtained from each
observer’s ability to assess the co-ordination between respirations
participating shelter.
and arytenoid abduction was facilitated by a technician verbalizing the onset of inspiration. Overall respiratory score was
Experimental Protocol
characterized by the anesthesiologist following drug adminis-
Each dog was anesthetized once for elective sterilization with one
tration using the scale described in Table 2 and was a determi-
of two randomly assigned anesthetic protocols (i.e., propofola,
nation of how well the dogs breathed during the entire laryngeal
propofol/ketamineb). Dogs were premedicated with butorphanolc
examination.
d
(0.5 mg/kg) and glycopyrrolate (0.01 mg/kg) injected intra-
Anesthetic monitoring, including heart rate, respiratory rate,
muscularly 20 min prior to anesthetic induction. An IV catheter
and saturation of peripheral O2 (SPO2) measured by pulse oxi-
was placed approximately 15 min after premedication followed by
metry were performed during anesthetic induction and laryngeal
5 min of flow-by O2 prior to anesthetic induction.
examination. If a patient failed to abduct the arytenoid cartilages,
Depending on the patient’s assigned protocol, either propofol
a cotton tipped applicator was used to gently stimulate respiration
(6 mg/kg) or ketamine (2 mg/kg) followed by propofol (2–4 mg/kg)
by direct application of pressure to one arytenoid. If the patient
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Evaluation of Laryngeal Function Using Various Anesthetics
calculated. If the categorical variables were nominal, Fisher exact
TABLE 1
tests were conducted due to the small samples involved in the
Definitions of Laryngeal Examination Responses
creation of the tables. To assess the effect of treatment over time
Response
Definition
Breathing score 0
No spontaneous respiration
1
Shallow respirations, slow respiratory rate, weak attempt
2
Moderate respirations, respiratory rate, and attempt
The relationship between individual respiratory variables was
3
Deep respirations, normal rate, strong attempt
evaluated with linear correlation coefficients. Statistical signifi-
on the respiratory data, repeated measures analyses of variance assuming an autoregressive period one covariance structure were used. The simple effects of treatment given time were computed.
cance was set at the 0.05 level.
Jaw tone score 0
No jaw tone, easy to open
1
Slight jaw tone, easy to open
Results
2 3
Moderate jaw tone, some difficulty opening Excessive jaw tone, difficult to open
Forty-eight primarily mixed-breed dogs undergoing elective sterilization procedures were included in this study. The mean
Exposure score
body weight 6 standard deviation was 23.1 kg 6 5.1 kg in the
Excellent
Mouth easily opened, arytenoid cartilages easily visible, no swallowing or tongue movement
Moderate
Some jaw tone when opening mouth, good visibility, some swallowing or tongue movement
group and was not statistically different between groups.
Poor
Mouth difficult to open with poor visualization of the larynx due to swallowing or tongue movement
tered in the propofol and propofol/ketamine group were 64.2% 6
propofol group and 22.5 kg 6 5.8 kg in the propofol/ketamine The mean percentage of total calculated propofol adminis20.3% (3.8 mg/kg 6 1.2 mg/kg) and 60.1% 6 18.5% (2.4 mg/kg 6
became apneic (no spontaneous respirations $ 60 sec) and res-
0.7 mg/kg), respectively, and were not significantly different between the two groups (two tailed t test, P ¼ 0.464).
pirations could not be manually stimulated, a single dose of doxaprame (1 mg/kg IV) was administered and laryngeal function
The summary of the laryngeal examinations between the two observers were presented in Tables 3 and 4. The first evaluator’s
was subsequently evaluated. Doxapram administration, as well as whether it was administered early or late in the examination, was recorded. Following laryngeal examination, patients were intu-
TABLE 3
bated and isoflurane in O2 administered in preparation for elec-
Summary of Early Subjective Scoring of Laryngeal Examinations Between Protocols
tive sterilization.
Response
Statistical Analysis
Propofol (no. of dogs)
Propofol/ketamine (no. of dogs)
All statistical analyses were conducted with a commercial software
Breathing score* 0
0
1
systemf. The effect of treatment on the percentage of drug ad-
1
4
6
ministered was assessed with a t test. Any relationships of cate-
2
12
7
gorical variables were investigated with the use of contingency
3
8
10
tables. If the categorical variables were ordinal, g statistics were
Swallowing/laryngospasm
TABLE 2 Overall Respiratory Function Evaluation Response
Propofol (no. of dogs)
Propofol/ketamine (no. of dogs)
Present
7
11
Absent
17
13
Jaw tone scorey 0
12
15
1
10
8
2
2
1
3
0
0
Overall respiratory score* 0
3
9
Excellent
23
20
1
4
1
Moderate
1
4
2
9
10
Poor
0
0
3
8
4
Exposure score
* 0 ¼ no spontaneous respirations; 1 ¼ shallow respirations, slow respiratory rate, weak attempt; 2 ¼ moderate respirations, respiratory rate, and attempt; 3 ¼ deep respirations, normal respiratory rate, strong attempt
* 0 ¼ no spontaneous respirations; 1 ¼ shallow respirations, slow respiratory rate, weak attempt; 2 ¼ moderate respirations, respiratory rate, and attempt; 3 ¼ deep respirations, normal respiratory rate, strong attempt y 0 ¼ absent; 1 ¼ slight; 2 ¼ moderate; 3 ¼ strong
JAAHA.ORG
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propofol group and 16 breaths/min in the propofol/ketamine
TABLE 4 Summary of Late Subjective Scoring of Laryngeal Examinations Between Protocols Propofol (no. of dogs)
Response
Propofol/ketamine (no. of dogs)
group; P ¼ 0.0518). Mean SPO2 values were significantly higher in the propofol group than the dogs receiving propofol/ketamine (94% in the propofol group and 87% in the propofol/ketamine group 1 min following drug administration; P ¼ 0.0008). The breathing score was significantly related to the potential
Breathing score* 0
0
1
for a patient to have a normal laryngeal function examination. The
1
6
4
breathing score and laryngeal function were taken from each
2 3
10 8
11 8
evaluator to give a total of 96 data points for analysis. A significant
11
9
laryngeal function when a higher breathing score (i.e., deeper
13
15
breath) was used to make that determination compared with lower
0
12
18
The two evaluators disagreed in the evaluation of laryngeal
1
7
5
2 3
5 0
1 0
function determination 58.3% of the time. When selecting the
Swallowing/laryngospasm Present Absent y
difference was found in the likelihood of a patient having normal
breathing scores (g statistic, 0.7610; P , 0.0001).
Jaw tone score
result (i.e., either early or late) with a higher breathing score, that value decreased to 20.8%, with 80% of the discrepancies existing
Exposure score Excellent
20
19
being between weak and normal laryngeal function determi-
Moderate
4
5
nations. Weak laryngeal examinations were classified as normal for
Poor
0
0
statistical analysis because laryngeal abduction was present. Two
* 0 ¼ no spontaneous respirations; 1 ¼ shallow respirations, slow respiratory rate, weak attempt; 2 ¼ moderate respirations, respiratory rate, and attempt; 3 ¼ deep respirations, normal respiratory rate, strong attempt y 0 ¼ absent; 1 ¼ slight; 2 ¼ moderate; 3 ¼ strong
dogs were classified as abnormal by one evaluator and normal by the other despite equal breathing scores at the time of evaluation. One dog was determined to have an abnormal laryngeal evaluation by both evaluators due to failure of the right arytenoid to abduct.
results were designated as early and the second evaluator results as
Six dogs (12.5%) would have been classified as abnormal based on
late. No significant difference was identified in breathing scores in
examination and a low breathing score, but were evaluated as
regards to either treatment group or time of evaluation (g sta-
normal by the second observer based on a higher breathing score
tistic, 20.0309 and P ¼ 0.8955 for early evaluation; g statistic,
during their evaluation.
0.0265 and P ¼ 0.9112 for late evaluation). Evaluation of jaw tone
Doxapram was administered to 6 of 24 dogs in the propofol
score by the early evaluator was not significantly different between
group and 10 of 24 dogs in the propofol/ketamine group. The need
the two treatment groups (g statistic 20.2484; P ¼ 0.3351). A
for doxapram was not statistically different between the two groups
significant difference was noted when evaluating jaw tone score
(two sided t test, P ¼ 0.3587). Doxapram administration early
between the two groups late, with dogs in the propofol/ketamine
tended to result in higher breathing scores (g statistic 20.6279;
group having statistically significant lower jaw tone scores than
P ¼ 0.0373) and increased the likelihood of normal laryngeal
the propofol group (g statistic 20.5063; P¼0.0178). Laryngeal
function determination (g statistic 20.8125; P ¼ 0.0002).
exposure scores were not significantly different between either time of evaluation or treatment received, with all dogs having
Discussion
moderate to excellent exposure. No significant difference was
Laryngeal paralysis is a commonly diagnosed acquired disease of
noted in the prevalence of swallowing/laryngospasm with regards
older, large-breed dogs.1,2 Diagnosis is most commonly based on
to treatment group or time of evaluation (Fisher exact test, P ¼
oral laryngoscopy under a light plane of anesthesia in combina-
0.3715 for early evaluation and P ¼ 0.7702 for late evaluation).
tion with historical and physical examination data. Ideal anes-
Overall respiratory scores between the two treatment groups
thetic protocols allow adequate depth of anesthesia for laryngeal
have been summarized in Table 2, with no significant difference
visualization (while protecting the examiner/equipment), cause
identified (g statistic, 20.3522; P ¼ 0.0759). Higher mean re-
minimal respiratory suppression, and maintain the laryngeal re-
spiratory rates were noted in the propofol group than the
flex. The laryngeal reflex is defined as adduction of the arytenoid
propofol/ketamine group, which were not statistically significant
cartilages following exhalation and stimulation of the epiglottis.5,10
at 1 min following drug administration (28 breaths/min in the
The reflex is a protective mechanism against aspiration. That
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Evaluation of Laryngeal Function Using Various Anesthetics
reflex, combined with the observer’s ability to safely and ade-
evaluated to determine whether ketamine resulted in propofol-
quately observe the reflex, is typically used as an end point for
sparing effects on the amount required to facilitate laryngeal ex-
determining whether an adequate depth of anesthesia has been
amination. Ketamine did not reduce the propofol requirement for
obtained, while maintaining laryngeal function. The patient is
laryngeal examination. That was similar to findings described by
considered too deep for accurate evaluation of laryngeal function
Mair et al. (2009) evaluating the propofol-sparing effects of ke-
once that reflex is lost, increasing the risk of falsely diagnosing
tamine in coinduction of anesthesia in dogs, where ketamine did
laryngeal paralysis.
not change the blood propofol targets required for endotracheal
Historically, thiopental has been the drug of choice for lar-
intubation.15
yngoscopy in most practices. Thiopental is an ultrashort-acting
Evaluation of laryngeal function requires adequate laryngeal
injectable barbiturate that has been used for anesthetic induc-
exposure, which has been a disadvantage of many anesthetic
tion in dogs. Thiopental was shown to have the least suppressive
protocols. In this study, no significant difference in the prevalence
effect on arytenoid motion prior to anesthetic recovery and
of either swallowing or laryngospasm was observed in either
allowed accurate determination of laryngeal function in dogs and
treatment group. Jaw tone score was significantly decreased during
people.6,11 Unfortunately, thiopental has become unavailable and
the late observer’s evaluation in patients who received ketamine.
the need for alternate protocols has arisen. Previous studies have
That was likely due to the continued action of the ketamine fol-
evaluated propofol, ketamine/diazepam, acepromazine/propofol,
lowing rapid redistribution of the propofol, which was in contrast
and gas anesthesia independently for laryngeal function exami-
to another study that found increased laryngospasm and jaw tone
nations with variable success.5–7 Ketamine/diazepam studies have
in patients receiving diazepam/ketamine.5 The additive effects of
resulted in decreased laryngeal exposure due to excessive jaw tone
the propofol may have resulted in enough sedation to overcome
as well as decreased arytenoid movement.2,5,6 Propofol has been
the poor muscle relaxation achieved with ketamine alone,
associated with apnea and weak arytenoid motion when used
resulting in better laryngeal exposure scores in the current study.
either alone or in combination with acepromazine.6
The study authors evaluated each patient at two separate time
Propofol is a highly lipid soluble alkylphenol derivative that
points to determine if the ability to evaluate the larynx changed
has been used for sedation, anesthetic induction, and maintenance
as the patients neared recovery compared with initial induction
12
of anesthesia. It provides a rapid and smooth induction of an-
(i.e., late versus early time points). No significant difference was
esthesia by enhancing the effects of g-aminobutyric acid.12–14
present in laryngeal exposure scores between the two time points
Although propofol provides excellent muscle relaxation, pro-
and no difference between treatment groups was noted, indicating
pofol can result in apnea and significant respiratory depression
that both anesthetic protocols provided prolonged and adequate
following bolus administration, making laryngeal examination
exposure for evaluation. Clinically, that translates to being able to
difficult.
evaluate those patients through several respirations, with final
Ketamine is a phencyclidine derivative that acts as a dissociative anesthetic through noncompetitive binding of the N-methyl-
evaluation made just prior to recovery if function is unclear. Overall respiratory scores during the examination were not
receptor causing depressed thalamocortical and limbic
statistically different between the two groups. Patients in the
system activity.12–14 A dose-related effect is seen on the respiratory
propofol/ketamine group had lower overall respiratory scores
system with minimal depression at lower dosages, although ad-
compared with the propofol only group, although that difference
ditive effects have been reported when ketamine is combined with
did not reach statistical significance. That is likely due to inade-
D-aspartate
13–15
Although ketamine
quate patient numbers. Clinically, decreased respiratory rates
is more apt to maintain normal airway reflexes and respiratory
translated to statistically significant decreases in SPO2 readings in
drive, muscle relaxation is poor. In this study, the authors com-
dogs receiving propofol/ketamine. That was supported by previ-
other central nervous system depressants.
pared propofol to propofol/ketamine anesthesia with the hope
ous studies with variable ketamine doses (0.5–2 mg/kg) where
that the combination protocol would accentuate the favorable
increased respiratory depression was observed with propofol/
effects of both drugs (i.e., better muscle relaxation with the
ketamine compared with propofol alone.13–15 The true impact of
propofol and using ketamine to reduce the dose of propofol re-
the propofol/ketamine combination was difficult to ascertain in
quired for anesthesia, thereby causing less respiratory depression
those studies due to confounding factors such as premedication
and maintaining airway reflexes).
with acepromazine and morphine, acepromazine and meperidine,
The percentage of total calculated propofol administered was
and medetomidine, all of which have the potential for significant
not significantly different between the two groups. That was
additive respiratory suppression.13–15 In this study, the authors
JAAHA.ORG
23
elected to use butorphanol due to its very mild sedative and re-
Electromyography could have been considered for those dogs to
spiratory depressive effects. Given the finding of decreased SPO2
ensure normal arytenoid function; however, that is rarely available
readings in patients receiving propofol/ketamine despite the light
clinically and would have added to the invasiveness of this study.
premedication, it appears that ketamine may exacerbate the re-
Two dogs were classified as abnormal by one evaluator and
spiratory depressant effects of propofol in dogs. Although in-
normal by the other with equal breathing scores (scores of 1 and 2,
creased relaxation may occur with the propofol/ketamine
respectively). The true status of those dogs is unknown but believed
combination, respiratory depression limits its use in laryngeal
to be normal given the young age and abduction seen by one
function examination.
observer. That variability was likely due to the depth of breath in
In addition to adequate laryngeal exposure, inspiratory depth
the first dog (the breathing score was low) as well as effects of
and phase of respiration at laryngeal evaluation are important.
anesthesia and variable anesthetic depths at evaluations between
Paradoxical laryngeal motion with paralyzed arytenoid cartilages
the two observers. Observer experience level may also have played
being passively abducted upon exhalation can be mistaken for
a role, with the more experienced observer labeling both of those
normal arytenoid abduction if the phase of the respiratory cycle is
dogs as abnormal. Clinically, the findings would be taken in
not recognized. This was addressed in the current study by having
conjunction with historical and physical examination findings
an assistant verbally identify each inspiratory phase. Shallow
(normal in both dogs with no historical respiratory disease) when
inspirations can also make evaluation difficult with weak inspi-
determining therapeutic interventions required. One dog was
ration resulting in weak arytenoid abduction, and an increased
considered abnormal by both observers, with the right arytenoid
potential to falsely diagnose laryngeal paralysis. Final determina-
failing to abduct for either observer. That finding was believed to be
tion of laryngeal function should always be made during the
truly abnormal, giving either an incidence of 2% for laryngeal
deepest inspirations possible, as found in this study. Accordingly,
paralysis in this population or an incidence of 6% if the other two
because observing arytenoid function, depth, and timing of in-
dogs above were included, compared with a 25% prevalence of
spiration simultaneously is difficult, if not impossible, for a single
laryngeal paralysis in a group of dogs undergoing general anes-
observer, an assistant should be present to assist with those
thesia.16 While the number of affected dogs in the current study
determinations during laryngeal examination. Patients with
was much less than previously reported, direct comparisons are
a higher breathing score at final laryngeal function evaluation were
difficult as the population of dogs in the aforementioned study
significantly more likely to be considered normal. That conclusion
were significantly older than the study population included in this
was strengthened when looking at overall laryngeal function. The
study. An increased prevalence of laryngeal disease would be ex-
majority (58.3%) of the laryngeal function determinations between
pected in the older population.
the first and second observer were in overall disagreement. When
The lack of spontaneous respirations can be a tremendous
considering the breathing score during arytenoid evaluation, and
problem clinically in the diagnosis of laryngeal paralysis. Either
removing the patients with low scores (i.e., shallow breaths) at both
direct stimulation of the arytenoids or administration of a respi-
evaluation periods, only 20.8% of the patients had differences in
ratory stimulant have been proposed as corrective measures.3–7
their final function evaluation between the two observers, 80% of
Doxapram is a respiratory stimulant that acts through direct
which were between weak and normal determinations. The dif-
stimulation of the medullary respiratory centers as well as the
ference between weak and normal determinations of laryngeal
carotid body chemoreceptors.12,17 Its effects (increased respiratory
function between observers could have been because of the sub-
effort and intrinsic laryngeal motion) are transient, with the
jective nature of the assessment and was clinically unlikely to be
primary clinical application for doxapram being for patients at an
significant as most clinicians would classify those together as
excessively deep plane of anesthesia and for differentiating dogs
normal. The clinical significance of weak laryngeal abduction is
with normal laryngeal function.3,7 Doxapram was used in this
unknown and must be considered in light of clinical signs. Those
study as a rescue protocol for dogs that would not breathe
patients may either have early laryngeal dysfunction or weak ab-
spontaneously, even with direct stimulation of the arytenoids.
duction may be a product of the anesthetic protocol. While the true
One-third of the patients in this study required doxapram for
laryngeal function status in those dogs was unknown, given the
laryngeal function evaluation, with no difference between treat-
lack of respiratory signs and young age of the dogs evaluated in this
ment groups. Laryngeal examination would not have been pos-
study, weak arytenoid abduction in this population of dogs was
sible in those patients without doxapram. Doxapram resulted in
most likely a function of the anesthetic protocol, depth of in-
subjectively higher breathing scores for evaluation of laryngeal
spiration at evaluation, and subjectivity of the evaluator.
function and significantly increased the likelihood of a declaration
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Evaluation of Laryngeal Function Using Various Anesthetics
of normal laryngeal function. Doxapram is considered to be
a dose-sparing effect on propofol and resulted in increased re-
generally safe and was well tolerated in the young, healthy pop-
spiratory depression evidenced by reduced SPO2 values making
ulation of dogs included in this study, with no adverse effects
propofol/ketamine a poor choice for the evaluation of laryngeal
identified. Reported side effects include tachycardia, arrhythmias,
function in dogs. It is critical that the clinician evaluate laryngeal
muscle rigidity, seizures, hyperthermia, hypertension, and hyp-
function in conjunction with depth of inspiration to avoid a false
oxia.7 Given the low dose administered, the authors felt additive
diagnosis of laryngeal paralysis when drug-related apnea results in
cardiovascular or seizure activity was unlikely in patients receiving
poor arytenoid function. Doxapram can facilitate deeper inspi-
ketamine concurrently. Caution should be used in patients with
ration aiding proper laryngeal function examination and should
laryngeal paralysis as significant paradoxical movement and pos-
always be administered when arytenoid abduction is not observed
sible upper airway obstruction can result, necessitating rapid
under propofol anesthesia to eliminate the possibility of a false
endotracheal intubation.
7
positive diagnosis.
Limitations of this study included the lack of a control group, the inability to compare the study results to laryngoscopy using
The authors would like to thank Patti Anderson, Dr. Lesa Staubus,
thiopental, and the subjectivity of laryngeal assessment with dif-
Dr. Kimberly Carter, and the Junior Surgery technical staff for their
ferent breaths used for laryngeal evaluation by each observer. The
assistance with data collection. The authors would also like to ac-
lack of a control group (i.e., each dog receiving each treatment with
knowledge Dr. John Dodam for his assistance in study design.
an appropriate washout period) was addressed by having larger numbers of dogs in each treatment group and by evaluating a population expected to have normal laryngeal function. The study authors attempted to locate thiopental for comparison in this study without success because it is not currently manufactured. By using the same premedication and similar laryngeal assessment criteria as Gross et al. (2002), the authors felt that some com-
FOOTNOTES a PropoFlo; Abbott Laboratories, North Chicago, IL b Ketathesia; Butler Animal Health Supply, Dublin, OH c Torbugesic; Fort Dodge, Fort Dodge, IA d Glycopyrrolate; Baxter Healthcare Corp., Deerfield, IL e Doxapram; Bedford Laboratories, Bedford, OH f SAS version 9.2; SAS Institute, Cary, NC
parisons could be made between the two studies.5 The subjectivity of the laryngeal assessment between observers was considered to be a minor concern in this study and similar to that which faces clinicians on a daily basis in the diagnosis of this disease. Although more objective criteria such as electromyography and rima glottis area measurements have been evaluated for the diagnosis of laryngeal paralysis, the diagnosis in the clinical arena remains primarily based on subjective laryngoscopic evaluation coupled with additional clinical and historical information.3,18 The study authors believe that this study closely mirrored the realities of clinical practice, which was the authors’ intent. Endoscopic videography would have enabled each observer to evaluate the same breath for laryngeal function examination and could have eliminated some of the effect of respiratory character on laryngeal function determination. Although that approach would have allowed more conclusions regarding the effects of interobserver experience on characterization of laryngeal function, the authors’ approach did demonstrate the critical nature of evaluating laryngeal function in conjunction with phase and depth of respiration.
Conclusion Propofol and propofol/ketamine provided adequate visualization of the larynx in all dogs. Propofol/ketamine failed to have
REFERENCES 1. Burbidge HM. A review of laryngeal paralysis in dogs. Br Vet J 1995; 151(1):71–82. 2. Monnet E, Tobias KM. Larynx. In: Tobias KM, Johnston SA, eds. Veterinary surgery small animal. 1st ed. St. Louis (MO): Elsevier Saunders; 2012:1718–31. 3. Miller CJ, McKiernan BC, Pace J, et al. The effects of doxapram hydrochloride (dopram-V) on laryngeal function in healthy dogs. J Vet Intern Med 2002;16(5):524–8. 4. Radlinsky MG, Williams J, Frank PM, et al. Comparison of three clinical techniques for the diagnosis of laryngeal paralysis in dogs. Vet Surg 2009;38(4):434–8. 5. Gross ME, Dodam JR, Pope ER, et al. A comparison of thiopental, propofol, and diazepam-ketamine anesthesia for evaluation of laryngeal function in dogs premedicated with butorphanol-glycopyrrolate. J Am Anim Hosp Assoc 2002;38(6): 503–6. 6. Jackson AM, Tobias K, Long C, et al. Effects of various anesthetic agents on laryngeal motion during laryngoscopy in normal dogs. Vet Surg 2004;33(2):102–6. 7. Tobias KM, Jackson AM, Harvey RC. Effects of doxapram HCl on laryngeal function of normal dogs and dogs with naturally occurring laryngeal paralysis. Vet Anaesth Analg 2004;31(4):258–63. 8. Smith JA, Gaynor JS, Bednarski RM, et al. Adverse effects of administration of propofol with various preanesthetic regimens in dogs. J Am Vet Med Assoc 1993;202(7):1111–5. 9. Carson IW, Moore J, Balmer JP, et al. Laryngeal competence with ketamine and other drugs. Anesthesiology 1973;38(2):128–33.
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10. Turner DM, Ilkiw JE. Potency of rapidly acting barbiturates in dogs, using inhibition of the laryngeal reflex as the end point. Am J Vet Res 1990;51(4):595–7. 11. Barker P, Langton JA, Wilson IG, et al. Movements of the vocal cords on induction of anaesthesia with thiopentone or propofol. Br J Anaesth 1992;69(1):23–5. 12. Riviere JE, Papich MG, ed. Veterinary pharmacology and therapeutics. 9th ed. Ames (IA): Blackwell Publishing; 2009:275– 84,1309. 13. Lerche P, Nolan AM, Reid J. Comparative study of propofol or propofol and ketamine for the induction of anaesthesia in dogs. Vet Rec 2000;146(20):571–4. 14. Seliskar A, Nemec A, Roskar T, et al. Total intravenous anaesthesia with propofol or propofol/ketamine in spontaneously breathing
26
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15.
16.
17.
18.
dogs premedicated with medetomidine. Vet Rec 2007;160(3): 85–91. Mair AR, Pawson P, Courcier E, et al. A comparison of the effects of two different doses of ketamine used for co-induction of anaesthesia with a target-controlled infusion of propofol in dogs. Vet Anaesth Analg 2009;36(6):532–8. Broome C, Burbidge HM, Pfeiffer DU. Prevalence of laryngeal paresis in dogs undergoing general anaesthesia. Aust Vet J 2000;78(11): 769–72. Brunton LL, ed. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw Hill Companies; 2011: 536–9, 1058. Venker-van Haagen AJ. Diseases of the larynx. Vet Clin North Am Small Anim Pract 1992;22(5):1155–72.
Comparison of Propofol and Propofol/Ketamine Anesthesia for Evaluation of Laryngeal Function in Healthy Dogs Kelci L. McKeirnan, DVM*y, Marjorie E. Gross, DVM, MS, DACVA, Mark Rochat, DVM, MS, DACVS, Mark Payton, PhD
ABSTRACT Thiopental is an excellent choice for evaluation of laryngeal function. Unfortunately, thiopental is no longer manufactured. In its absence, the ideal anesthetic protocol for laryngoscopy has not been determined. Propofol and propofol/ketamine were compared for the evaluation of laryngeal function in 48 healthy dogs. Laryngeal exposure was moderate to excellent in all dogs and not significantly different between protocols. Saturation of peripheral O2 (SPO2) readings were decreased in the propofol/ ketamine group, and deeper respirations were more likely to correlate with normal laryngeal function regardless of treatment group. Doxapram was administered to apneic patients to stimulate respiration and allow for evaluation of laryngeal function. No significant difference in frequency of doxapram administration between groups was noted. Doxapram resulted in higher respiratory scores and significantly increased the ability to determine normal laryngeal function. Ketamine did not allow for a reduction in propofol dose and caused increased respiratory depression, making ketamine a poor addition to propofol for laryngeal function examination. Regardless of the protocol used, laryngeal function should be determined in conjunction with the respiratory phase and depth of respirations. Patients with either absent or shallow respirations should receive doxapram for accurate evaluation of laryngeal function. (J Am Anim Hosp Assoc 2014; 50:19–26. DOI 10.5326/JAAHA-MS-5959)
Introduction
Echolarynography and transnasal laryngoscopy have been
Laryngeal paralysis is a common acquired disease of older, large-
reported for laryngeal function evaluation; however, diagnosis of
breed dogs.1,2 Congenital and acquired forms can occur, with
laryngeal paralysis is most commonly made using direct oral
1–3
idiopathic acquired being the most common presentation.
laryngoscopy under a light plane of anesthesia.4 The ideal anes-
Arytenoid paralysis results in partial to complete loss of laryngeal
thetic protocol for accurate laryngeal examination results in
function, resulting in variable degrees of upper airway obstruc-
a light anesthetic plane with decreased jaw tone, intact laryngeal
tion. Affected dogs present with clinical signs ranging from mild
reflexes, and minimal respiratory depression. Doxapram has been
exercise intolerance to life-threatening respiratory distress. Dis-
added to variable anesthetic protocols to stimulate respirations in
ease severity is directly correlated with the degree of laryngeal
apneic patients and can increase intrinsic laryngeal motion, fa-
dysfunction, with clinical signs occurring most frequently with
cilitating laryngeal function examination in dogs.3
bilateral disease. Regardless of the underlying etiology, accurate
Thiopental, propofol, diazepam/ketamine, and gas anesthesia
observation of arytenoid function is critical to determine if la-
have all been used to provide anesthesia for laryngeal function
ryngeal paralysis is present.
examination.5–7 Thiopental has been found to be the best
From the Department of Veterinary Clinical Sciences (K.M., M.G., M.R.) and Department of Statistics, Oklahoma State University, Stillwater, OK (M.P.).
SPO2 saturation of peripheral O2
Correspondence: [email protected] (K.M.)
*K. McKeirnan’s updated credentials since article acceptance are DVM, MS, DACVS-SA. †
K. McKeirnan’s present affiliation is Animal Emergency and Specialty,
Kirkland, WA.
ª 2014 by American Animal Hospital Association
JAAHA.ORG
19
injectable anesthetic for evaluating laryngeal function.5,6 Unfor-
were administered IV for anesthetic induction until the mouth
tunately, thiopental is no longer commercially available. In the
could easily be opened for examination. Propofol was adminis-
absence of thiopental, the ideal anesthetic protocol for the eval-
tered slowly over 1 min to effect in both protocols. The amount of
uation of laryngeal function has yet to be determined. Studies
propofol required to achieve adequate anesthesia for laryngeal
evaluating propofol for laryngeal examination have revealed ad-
examination was recorded. The percent of the propofol dose
equate laryngeal exposure with weaker laryngeal motion com-
administered was calculated to normalize dose for body weight
pared with thiopental.
5,6
Unfortunately, significant respiratory
and allow dose comparisons between groups. Ketamine was given
depression often occurs with propofol, with apnea related to dose,
as a calculated bolus followed by propofol to effect. The anes-
speed of injection, and concurrent premedications, complicating
thesiologist administered all anesthetic agents with the exception
laryngeal evaluation.8 Ketamine has been shown to preserve the
of the intramuscular premedications, which were given by fourth
laryngeal reflex to a greater degree than thiopental in people, al-
year veterinary students under direct supervision. Laryngeal
though the anesthetic plane may be inadequate for veterinary
function observers were blinded to the administered protocol by
5,6,9
Ketamine, in conjunction with
giving an equal volume of normal saline in lieu of ketamine to
propofol, may hypothetically provide an additive effect on relax-
patients in the propofol only group. Following anesthetic induc-
ation and laryngeal exposure, while minimizing respiratory de-
tion, dogs were placed in sternal recumbency with the head ele-
pression. The objective of this study was to compare the effects of
vated to the level of normal carriage. Laryngeal assessment was
propofol to propofol/ketamine anesthesia on laryngeal visualiza-
performed as soon as the mouth could be opened, and the larynx
tion and function in healthy dogs. The study authors hypothesized
was visualized by the same two individuals in succession (K.M.,
that propofol/ketamine would provide an adequate plane of an-
M.R.). Laryngeal examination began within 30 min of premed-
esthesia with decreased respiratory depression for laryngeal ex-
ication. Interobserver experience (between a third year resident
amination in dogs.
and a board-certified surgeon with w 20 yr of experience) was
patients given previous studies.
normalized by alternating who first evaluated each patient. The
Materials and Methods
evaluations were defined as early if they were the first evaluator
Animals
and late if they were the second evaluator. All evaluations were
Twenty-four male and 24 female healthy dogs, ranging from ap-
completed within 4 min of induction. A similar protocol for la-
proximately 6 mo to 5 yr, presented from surrounding animal
ryngeal examination described by Gross et al. (2002) was used.5
shelters for elective sterilization were studied. Age was estimated
Breathing score was defined as the score of the breath when la-
based on physical appearance and dentition. Each dog received
ryngeal function determination was made and was assigned by the
a thorough physical examination prior to entering the study, and
laryngeal observers. Parameters were outlined as described in
dogs were excluded if evidence of respiratory, cardiovascular, or
Table 1. Swallowing and laryngospasm were graded together as
systemic disease was present. Dogs weighed 15–35 kg and were
either present or absent. Laryngeal function was characterized as
randomly assigned by lottery to one of two anesthetic protocols,
normal (arytenoid cartilages abduct during inspiration), weak
providing an even distribution of males and females in each
(arytenoid cartilages abduct but poorly), or abnormal (one or
group. All protocols were approved by the University Animal Care
more arytenoid cartilages do not abduct during inspiration). The
and Use Committee and permission was obtained from each
observer’s ability to assess the co-ordination between respirations
participating shelter.
and arytenoid abduction was facilitated by a technician verbalizing the onset of inspiration. Overall respiratory score was
Experimental Protocol
characterized by the anesthesiologist following drug adminis-
Each dog was anesthetized once for elective sterilization with one
tration using the scale described in Table 2 and was a determi-
of two randomly assigned anesthetic protocols (i.e., propofola,
nation of how well the dogs breathed during the entire laryngeal
propofol/ketamineb). Dogs were premedicated with butorphanolc
examination.
d
(0.5 mg/kg) and glycopyrrolate (0.01 mg/kg) injected intra-
Anesthetic monitoring, including heart rate, respiratory rate,
muscularly 20 min prior to anesthetic induction. An IV catheter
and saturation of peripheral O2 (SPO2) measured by pulse oxi-
was placed approximately 15 min after premedication followed by
metry were performed during anesthetic induction and laryngeal
5 min of flow-by O2 prior to anesthetic induction.
examination. If a patient failed to abduct the arytenoid cartilages,
Depending on the patient’s assigned protocol, either propofol
a cotton tipped applicator was used to gently stimulate respiration
(6 mg/kg) or ketamine (2 mg/kg) followed by propofol (2–4 mg/kg)
by direct application of pressure to one arytenoid. If the patient
20
JAAHA |
50:1 Jan/Feb 2014
Evaluation of Laryngeal Function Using Various Anesthetics
calculated. If the categorical variables were nominal, Fisher exact
TABLE 1
tests were conducted due to the small samples involved in the
Definitions of Laryngeal Examination Responses
creation of the tables. To assess the effect of treatment over time
Response
Definition
Breathing score 0
No spontaneous respiration
1
Shallow respirations, slow respiratory rate, weak attempt
2
Moderate respirations, respiratory rate, and attempt
The relationship between individual respiratory variables was
3
Deep respirations, normal rate, strong attempt
evaluated with linear correlation coefficients. Statistical signifi-
on the respiratory data, repeated measures analyses of variance assuming an autoregressive period one covariance structure were used. The simple effects of treatment given time were computed.
cance was set at the 0.05 level.
Jaw tone score 0
No jaw tone, easy to open
1
Slight jaw tone, easy to open
Results
2 3
Moderate jaw tone, some difficulty opening Excessive jaw tone, difficult to open
Forty-eight primarily mixed-breed dogs undergoing elective sterilization procedures were included in this study. The mean
Exposure score
body weight 6 standard deviation was 23.1 kg 6 5.1 kg in the
Excellent
Mouth easily opened, arytenoid cartilages easily visible, no swallowing or tongue movement
Moderate
Some jaw tone when opening mouth, good visibility, some swallowing or tongue movement
group and was not statistically different between groups.
Poor
Mouth difficult to open with poor visualization of the larynx due to swallowing or tongue movement
tered in the propofol and propofol/ketamine group were 64.2% 6
propofol group and 22.5 kg 6 5.8 kg in the propofol/ketamine The mean percentage of total calculated propofol adminis20.3% (3.8 mg/kg 6 1.2 mg/kg) and 60.1% 6 18.5% (2.4 mg/kg 6
became apneic (no spontaneous respirations $ 60 sec) and res-
0.7 mg/kg), respectively, and were not significantly different between the two groups (two tailed t test, P ¼ 0.464).
pirations could not be manually stimulated, a single dose of doxaprame (1 mg/kg IV) was administered and laryngeal function
The summary of the laryngeal examinations between the two observers were presented in Tables 3 and 4. The first evaluator’s
was subsequently evaluated. Doxapram administration, as well as whether it was administered early or late in the examination, was recorded. Following laryngeal examination, patients were intu-
TABLE 3
bated and isoflurane in O2 administered in preparation for elec-
Summary of Early Subjective Scoring of Laryngeal Examinations Between Protocols
tive sterilization.
Response
Statistical Analysis
Propofol (no. of dogs)
Propofol/ketamine (no. of dogs)
All statistical analyses were conducted with a commercial software
Breathing score* 0
0
1
systemf. The effect of treatment on the percentage of drug ad-
1
4
6
ministered was assessed with a t test. Any relationships of cate-
2
12
7
gorical variables were investigated with the use of contingency
3
8
10
tables. If the categorical variables were ordinal, g statistics were
Swallowing/laryngospasm
TABLE 2 Overall Respiratory Function Evaluation Response
Propofol (no. of dogs)
Propofol/ketamine (no. of dogs)
Present
7
11
Absent
17
13
Jaw tone scorey 0
12
15
1
10
8
2
2
1
3
0
0
Overall respiratory score* 0
3
9
Excellent
23
20
1
4
1
Moderate
1
4
2
9
10
Poor
0
0
3
8
4
Exposure score
* 0 ¼ no spontaneous respirations; 1 ¼ shallow respirations, slow respiratory rate, weak attempt; 2 ¼ moderate respirations, respiratory rate, and attempt; 3 ¼ deep respirations, normal respiratory rate, strong attempt
* 0 ¼ no spontaneous respirations; 1 ¼ shallow respirations, slow respiratory rate, weak attempt; 2 ¼ moderate respirations, respiratory rate, and attempt; 3 ¼ deep respirations, normal respiratory rate, strong attempt y 0 ¼ absent; 1 ¼ slight; 2 ¼ moderate; 3 ¼ strong
JAAHA.ORG
21
propofol group and 16 breaths/min in the propofol/ketamine
TABLE 4 Summary of Late Subjective Scoring of Laryngeal Examinations Between Protocols Propofol (no. of dogs)
Response
Propofol/ketamine (no. of dogs)
group; P ¼ 0.0518). Mean SPO2 values were significantly higher in the propofol group than the dogs receiving propofol/ketamine (94% in the propofol group and 87% in the propofol/ketamine group 1 min following drug administration; P ¼ 0.0008). The breathing score was significantly related to the potential
Breathing score* 0
0
1
for a patient to have a normal laryngeal function examination. The
1
6
4
breathing score and laryngeal function were taken from each
2 3
10 8
11 8
evaluator to give a total of 96 data points for analysis. A significant
11
9
laryngeal function when a higher breathing score (i.e., deeper
13
15
breath) was used to make that determination compared with lower
0
12
18
The two evaluators disagreed in the evaluation of laryngeal
1
7
5
2 3
5 0
1 0
function determination 58.3% of the time. When selecting the
Swallowing/laryngospasm Present Absent y
difference was found in the likelihood of a patient having normal
breathing scores (g statistic, 0.7610; P , 0.0001).
Jaw tone score
result (i.e., either early or late) with a higher breathing score, that value decreased to 20.8%, with 80% of the discrepancies existing
Exposure score Excellent
20
19
being between weak and normal laryngeal function determi-
Moderate
4
5
nations. Weak laryngeal examinations were classified as normal for
Poor
0
0
statistical analysis because laryngeal abduction was present. Two
* 0 ¼ no spontaneous respirations; 1 ¼ shallow respirations, slow respiratory rate, weak attempt; 2 ¼ moderate respirations, respiratory rate, and attempt; 3 ¼ deep respirations, normal respiratory rate, strong attempt y 0 ¼ absent; 1 ¼ slight; 2 ¼ moderate; 3 ¼ strong
dogs were classified as abnormal by one evaluator and normal by the other despite equal breathing scores at the time of evaluation. One dog was determined to have an abnormal laryngeal evaluation by both evaluators due to failure of the right arytenoid to abduct.
results were designated as early and the second evaluator results as
Six dogs (12.5%) would have been classified as abnormal based on
late. No significant difference was identified in breathing scores in
examination and a low breathing score, but were evaluated as
regards to either treatment group or time of evaluation (g sta-
normal by the second observer based on a higher breathing score
tistic, 20.0309 and P ¼ 0.8955 for early evaluation; g statistic,
during their evaluation.
0.0265 and P ¼ 0.9112 for late evaluation). Evaluation of jaw tone
Doxapram was administered to 6 of 24 dogs in the propofol
score by the early evaluator was not significantly different between
group and 10 of 24 dogs in the propofol/ketamine group. The need
the two treatment groups (g statistic 20.2484; P ¼ 0.3351). A
for doxapram was not statistically different between the two groups
significant difference was noted when evaluating jaw tone score
(two sided t test, P ¼ 0.3587). Doxapram administration early
between the two groups late, with dogs in the propofol/ketamine
tended to result in higher breathing scores (g statistic 20.6279;
group having statistically significant lower jaw tone scores than
P ¼ 0.0373) and increased the likelihood of normal laryngeal
the propofol group (g statistic 20.5063; P¼0.0178). Laryngeal
function determination (g statistic 20.8125; P ¼ 0.0002).
exposure scores were not significantly different between either time of evaluation or treatment received, with all dogs having
Discussion
moderate to excellent exposure. No significant difference was
Laryngeal paralysis is a commonly diagnosed acquired disease of
noted in the prevalence of swallowing/laryngospasm with regards
older, large-breed dogs.1,2 Diagnosis is most commonly based on
to treatment group or time of evaluation (Fisher exact test, P ¼
oral laryngoscopy under a light plane of anesthesia in combina-
0.3715 for early evaluation and P ¼ 0.7702 for late evaluation).
tion with historical and physical examination data. Ideal anes-
Overall respiratory scores between the two treatment groups
thetic protocols allow adequate depth of anesthesia for laryngeal
have been summarized in Table 2, with no significant difference
visualization (while protecting the examiner/equipment), cause
identified (g statistic, 20.3522; P ¼ 0.0759). Higher mean re-
minimal respiratory suppression, and maintain the laryngeal re-
spiratory rates were noted in the propofol group than the
flex. The laryngeal reflex is defined as adduction of the arytenoid
propofol/ketamine group, which were not statistically significant
cartilages following exhalation and stimulation of the epiglottis.5,10
at 1 min following drug administration (28 breaths/min in the
The reflex is a protective mechanism against aspiration. That
22
JAAHA |
50:1 Jan/Feb 2014
Evaluation of Laryngeal Function Using Various Anesthetics
reflex, combined with the observer’s ability to safely and ade-
evaluated to determine whether ketamine resulted in propofol-
quately observe the reflex, is typically used as an end point for
sparing effects on the amount required to facilitate laryngeal ex-
determining whether an adequate depth of anesthesia has been
amination. Ketamine did not reduce the propofol requirement for
obtained, while maintaining laryngeal function. The patient is
laryngeal examination. That was similar to findings described by
considered too deep for accurate evaluation of laryngeal function
Mair et al. (2009) evaluating the propofol-sparing effects of ke-
once that reflex is lost, increasing the risk of falsely diagnosing
tamine in coinduction of anesthesia in dogs, where ketamine did
laryngeal paralysis.
not change the blood propofol targets required for endotracheal
Historically, thiopental has been the drug of choice for lar-
intubation.15
yngoscopy in most practices. Thiopental is an ultrashort-acting
Evaluation of laryngeal function requires adequate laryngeal
injectable barbiturate that has been used for anesthetic induc-
exposure, which has been a disadvantage of many anesthetic
tion in dogs. Thiopental was shown to have the least suppressive
protocols. In this study, no significant difference in the prevalence
effect on arytenoid motion prior to anesthetic recovery and
of either swallowing or laryngospasm was observed in either
allowed accurate determination of laryngeal function in dogs and
treatment group. Jaw tone score was significantly decreased during
people.6,11 Unfortunately, thiopental has become unavailable and
the late observer’s evaluation in patients who received ketamine.
the need for alternate protocols has arisen. Previous studies have
That was likely due to the continued action of the ketamine fol-
evaluated propofol, ketamine/diazepam, acepromazine/propofol,
lowing rapid redistribution of the propofol, which was in contrast
and gas anesthesia independently for laryngeal function exami-
to another study that found increased laryngospasm and jaw tone
nations with variable success.5–7 Ketamine/diazepam studies have
in patients receiving diazepam/ketamine.5 The additive effects of
resulted in decreased laryngeal exposure due to excessive jaw tone
the propofol may have resulted in enough sedation to overcome
as well as decreased arytenoid movement.2,5,6 Propofol has been
the poor muscle relaxation achieved with ketamine alone,
associated with apnea and weak arytenoid motion when used
resulting in better laryngeal exposure scores in the current study.
either alone or in combination with acepromazine.6
The study authors evaluated each patient at two separate time
Propofol is a highly lipid soluble alkylphenol derivative that
points to determine if the ability to evaluate the larynx changed
has been used for sedation, anesthetic induction, and maintenance
as the patients neared recovery compared with initial induction
12
of anesthesia. It provides a rapid and smooth induction of an-
(i.e., late versus early time points). No significant difference was
esthesia by enhancing the effects of g-aminobutyric acid.12–14
present in laryngeal exposure scores between the two time points
Although propofol provides excellent muscle relaxation, pro-
and no difference between treatment groups was noted, indicating
pofol can result in apnea and significant respiratory depression
that both anesthetic protocols provided prolonged and adequate
following bolus administration, making laryngeal examination
exposure for evaluation. Clinically, that translates to being able to
difficult.
evaluate those patients through several respirations, with final
Ketamine is a phencyclidine derivative that acts as a dissociative anesthetic through noncompetitive binding of the N-methyl-
evaluation made just prior to recovery if function is unclear. Overall respiratory scores during the examination were not
receptor causing depressed thalamocortical and limbic
statistically different between the two groups. Patients in the
system activity.12–14 A dose-related effect is seen on the respiratory
propofol/ketamine group had lower overall respiratory scores
system with minimal depression at lower dosages, although ad-
compared with the propofol only group, although that difference
ditive effects have been reported when ketamine is combined with
did not reach statistical significance. That is likely due to inade-
D-aspartate
13–15
Although ketamine
quate patient numbers. Clinically, decreased respiratory rates
is more apt to maintain normal airway reflexes and respiratory
translated to statistically significant decreases in SPO2 readings in
drive, muscle relaxation is poor. In this study, the authors com-
dogs receiving propofol/ketamine. That was supported by previ-
other central nervous system depressants.
pared propofol to propofol/ketamine anesthesia with the hope
ous studies with variable ketamine doses (0.5–2 mg/kg) where
that the combination protocol would accentuate the favorable
increased respiratory depression was observed with propofol/
effects of both drugs (i.e., better muscle relaxation with the
ketamine compared with propofol alone.13–15 The true impact of
propofol and using ketamine to reduce the dose of propofol re-
the propofol/ketamine combination was difficult to ascertain in
quired for anesthesia, thereby causing less respiratory depression
those studies due to confounding factors such as premedication
and maintaining airway reflexes).
with acepromazine and morphine, acepromazine and meperidine,
The percentage of total calculated propofol administered was
and medetomidine, all of which have the potential for significant
not significantly different between the two groups. That was
additive respiratory suppression.13–15 In this study, the authors
JAAHA.ORG
23
elected to use butorphanol due to its very mild sedative and re-
Electromyography could have been considered for those dogs to
spiratory depressive effects. Given the finding of decreased SPO2
ensure normal arytenoid function; however, that is rarely available
readings in patients receiving propofol/ketamine despite the light
clinically and would have added to the invasiveness of this study.
premedication, it appears that ketamine may exacerbate the re-
Two dogs were classified as abnormal by one evaluator and
spiratory depressant effects of propofol in dogs. Although in-
normal by the other with equal breathing scores (scores of 1 and 2,
creased relaxation may occur with the propofol/ketamine
respectively). The true status of those dogs is unknown but believed
combination, respiratory depression limits its use in laryngeal
to be normal given the young age and abduction seen by one
function examination.
observer. That variability was likely due to the depth of breath in
In addition to adequate laryngeal exposure, inspiratory depth
the first dog (the breathing score was low) as well as effects of
and phase of respiration at laryngeal evaluation are important.
anesthesia and variable anesthetic depths at evaluations between
Paradoxical laryngeal motion with paralyzed arytenoid cartilages
the two observers. Observer experience level may also have played
being passively abducted upon exhalation can be mistaken for
a role, with the more experienced observer labeling both of those
normal arytenoid abduction if the phase of the respiratory cycle is
dogs as abnormal. Clinically, the findings would be taken in
not recognized. This was addressed in the current study by having
conjunction with historical and physical examination findings
an assistant verbally identify each inspiratory phase. Shallow
(normal in both dogs with no historical respiratory disease) when
inspirations can also make evaluation difficult with weak inspi-
determining therapeutic interventions required. One dog was
ration resulting in weak arytenoid abduction, and an increased
considered abnormal by both observers, with the right arytenoid
potential to falsely diagnose laryngeal paralysis. Final determina-
failing to abduct for either observer. That finding was believed to be
tion of laryngeal function should always be made during the
truly abnormal, giving either an incidence of 2% for laryngeal
deepest inspirations possible, as found in this study. Accordingly,
paralysis in this population or an incidence of 6% if the other two
because observing arytenoid function, depth, and timing of in-
dogs above were included, compared with a 25% prevalence of
spiration simultaneously is difficult, if not impossible, for a single
laryngeal paralysis in a group of dogs undergoing general anes-
observer, an assistant should be present to assist with those
thesia.16 While the number of affected dogs in the current study
determinations during laryngeal examination. Patients with
was much less than previously reported, direct comparisons are
a higher breathing score at final laryngeal function evaluation were
difficult as the population of dogs in the aforementioned study
significantly more likely to be considered normal. That conclusion
were significantly older than the study population included in this
was strengthened when looking at overall laryngeal function. The
study. An increased prevalence of laryngeal disease would be ex-
majority (58.3%) of the laryngeal function determinations between
pected in the older population.
the first and second observer were in overall disagreement. When
The lack of spontaneous respirations can be a tremendous
considering the breathing score during arytenoid evaluation, and
problem clinically in the diagnosis of laryngeal paralysis. Either
removing the patients with low scores (i.e., shallow breaths) at both
direct stimulation of the arytenoids or administration of a respi-
evaluation periods, only 20.8% of the patients had differences in
ratory stimulant have been proposed as corrective measures.3–7
their final function evaluation between the two observers, 80% of
Doxapram is a respiratory stimulant that acts through direct
which were between weak and normal determinations. The dif-
stimulation of the medullary respiratory centers as well as the
ference between weak and normal determinations of laryngeal
carotid body chemoreceptors.12,17 Its effects (increased respiratory
function between observers could have been because of the sub-
effort and intrinsic laryngeal motion) are transient, with the
jective nature of the assessment and was clinically unlikely to be
primary clinical application for doxapram being for patients at an
significant as most clinicians would classify those together as
excessively deep plane of anesthesia and for differentiating dogs
normal. The clinical significance of weak laryngeal abduction is
with normal laryngeal function.3,7 Doxapram was used in this
unknown and must be considered in light of clinical signs. Those
study as a rescue protocol for dogs that would not breathe
patients may either have early laryngeal dysfunction or weak ab-
spontaneously, even with direct stimulation of the arytenoids.
duction may be a product of the anesthetic protocol. While the true
One-third of the patients in this study required doxapram for
laryngeal function status in those dogs was unknown, given the
laryngeal function evaluation, with no difference between treat-
lack of respiratory signs and young age of the dogs evaluated in this
ment groups. Laryngeal examination would not have been pos-
study, weak arytenoid abduction in this population of dogs was
sible in those patients without doxapram. Doxapram resulted in
most likely a function of the anesthetic protocol, depth of in-
subjectively higher breathing scores for evaluation of laryngeal
spiration at evaluation, and subjectivity of the evaluator.
function and significantly increased the likelihood of a declaration
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JAAHA |
50:1 Jan/Feb 2014
Evaluation of Laryngeal Function Using Various Anesthetics
of normal laryngeal function. Doxapram is considered to be
a dose-sparing effect on propofol and resulted in increased re-
generally safe and was well tolerated in the young, healthy pop-
spiratory depression evidenced by reduced SPO2 values making
ulation of dogs included in this study, with no adverse effects
propofol/ketamine a poor choice for the evaluation of laryngeal
identified. Reported side effects include tachycardia, arrhythmias,
function in dogs. It is critical that the clinician evaluate laryngeal
muscle rigidity, seizures, hyperthermia, hypertension, and hyp-
function in conjunction with depth of inspiration to avoid a false
oxia.7 Given the low dose administered, the authors felt additive
diagnosis of laryngeal paralysis when drug-related apnea results in
cardiovascular or seizure activity was unlikely in patients receiving
poor arytenoid function. Doxapram can facilitate deeper inspi-
ketamine concurrently. Caution should be used in patients with
ration aiding proper laryngeal function examination and should
laryngeal paralysis as significant paradoxical movement and pos-
always be administered when arytenoid abduction is not observed
sible upper airway obstruction can result, necessitating rapid
under propofol anesthesia to eliminate the possibility of a false
endotracheal intubation.
7
positive diagnosis.
Limitations of this study included the lack of a control group, the inability to compare the study results to laryngoscopy using
The authors would like to thank Patti Anderson, Dr. Lesa Staubus,
thiopental, and the subjectivity of laryngeal assessment with dif-
Dr. Kimberly Carter, and the Junior Surgery technical staff for their
ferent breaths used for laryngeal evaluation by each observer. The
assistance with data collection. The authors would also like to ac-
lack of a control group (i.e., each dog receiving each treatment with
knowledge Dr. John Dodam for his assistance in study design.
an appropriate washout period) was addressed by having larger numbers of dogs in each treatment group and by evaluating a population expected to have normal laryngeal function. The study authors attempted to locate thiopental for comparison in this study without success because it is not currently manufactured. By using the same premedication and similar laryngeal assessment criteria as Gross et al. (2002), the authors felt that some com-
FOOTNOTES a PropoFlo; Abbott Laboratories, North Chicago, IL b Ketathesia; Butler Animal Health Supply, Dublin, OH c Torbugesic; Fort Dodge, Fort Dodge, IA d Glycopyrrolate; Baxter Healthcare Corp., Deerfield, IL e Doxapram; Bedford Laboratories, Bedford, OH f SAS version 9.2; SAS Institute, Cary, NC
parisons could be made between the two studies.5 The subjectivity of the laryngeal assessment between observers was considered to be a minor concern in this study and similar to that which faces clinicians on a daily basis in the diagnosis of this disease. Although more objective criteria such as electromyography and rima glottis area measurements have been evaluated for the diagnosis of laryngeal paralysis, the diagnosis in the clinical arena remains primarily based on subjective laryngoscopic evaluation coupled with additional clinical and historical information.3,18 The study authors believe that this study closely mirrored the realities of clinical practice, which was the authors’ intent. Endoscopic videography would have enabled each observer to evaluate the same breath for laryngeal function examination and could have eliminated some of the effect of respiratory character on laryngeal function determination. Although that approach would have allowed more conclusions regarding the effects of interobserver experience on characterization of laryngeal function, the authors’ approach did demonstrate the critical nature of evaluating laryngeal function in conjunction with phase and depth of respiration.
Conclusion Propofol and propofol/ketamine provided adequate visualization of the larynx in all dogs. Propofol/ketamine failed to have
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