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Pharyngeal Trauma in the Horse
REFEREED
ORIGINAL RESEARCH
The Effects of Anesthesia on Laryngeal Function and Laryngeal/Pharyngeal Trauma in the Horse Leah A. Bradbury, BVSc (hons) CertVA,a Alexandra H.A. Dugdale, MA, VetMB, DVA, Dipl.ECVA, PGCert(LTHE), MRCVS,b Derek C. Knottenbelt, DVM&S, DipECEIM, MRCVS,b Shaun A. Mackane, BVSc, BSc(vet), PhD, DACVIM, DECEIM, MRCVS,b and J. Mark Senior, BVSc, Cert VA, DiplECVA, MRCVSb
ABSTRACT Laryngeal paralysis in horses has been reported after inhalational anesthesia and can result in significant morbidity/mortality. The cause of the condition is unclear. The objective of this study was to examine the effects of a standardized anesthetic protocol on laryngeal function and laryngeal/pharyngeal trauma in the peri-anesthetic period in a prospective study. A 30- to 60-second digitalized video clip of laryngeal movement from a standardized endoscopic view was recorded at five time points: before sedation, postsedation, post-induction, immediately after recovery to standing, and at 24 hours after recovery. A standardized anesthetic regimen was used in all cases. Video clips were randomized and evaluated by two blinded assessors. Each assessor scored each clip for laryngeal function and trauma using previously validated scoring systems. Agreement between assessors was calculated using the mean of the five time-specific weighted kappa statistics. Post-anesthesia laryngeal function and trauma scores were compared with initial scores using the Wilcoxon signed rank test with Bonferroni adjustment. Spearman’s rank coefficient was used to assess correlation between trauma and function scores and between anesthetic duration and laryngeal function and trauma scores. There was no significant effect of anesthesia on laryngeal function. Trauma scores were not significantly higher after tracheal intubation. The trauma scoring system requires further validation. There was no correlation between higher trauma scores and laryngeal function or duration and laryngeal function or trauma.
From Veterinary Clinic and Hospital, University of Melbourne, Werribee Victoria, Australiaa; and Philip Leverhulme Large Animal Hospital, University of Liverpool, Wirral, UK.b Reprint requests: Leah A. Bradbury, BVSc (hons) CertVA, c/o Veterinary Clinic and Hospital, University of Melbourne, 250 Princes Highway, Werribee VIC 3030, Australia. 0737-0806/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2008.07.006
Journal of Equine Veterinary Science Vol 28, No 8 (2008)
Further work is required to evaluate other variables that may affect laryngeal function after anesthesia, using a larger number of horses with varying degrees of laryngeal dysfunction. Keywords: Anesthesia; Equine; Larynx; Function; Trauma
INTRODUCTION It has been suggested that anesthesia in the horse can cause abnormalities in laryngeal function, such as unilateral and bilateral laryngeal paralysis, which can result in significant morbidity/mortality in the peri-anesthetic period.1-4 Laryngeal paralysis or paresis secondary to endotracheal intubation has been reported in humans.5-7 In horses, the cause of this condition is unclear. Anesthetic agents, trauma secondary to endotracheal intubation, or damage to the recurrent laryngeal nerve (RLN) through hypoxia, head positioning, or catheter placement may each play a role in the etiopathogenesis either by causing a primary problem or by exacerbating a subclinical/undiagnosed laryngeal hemiplegia.1-4 If damage to the peripheral pathway of the RLN is a contributing factor in bilateral laryngeal paresis/paralysis, there must be either a bilateral insult to the RLN or a proximal lesion.2 Abrahamsen et al1 suggested that stretching and increasing tension across the nerve may be involved, and Rooney and Delaney8 hypothesized that this may lead to a reduction in blood flow to the nerve. Abrahamsen et al1 and Dixon et al2 reported that both patients that developed bilateral laryngeal paralysis were positioned for general anesthesia with their head and neck in extension. Hypoxemia may contribute to ischemic necrosis of the RLN. One reported case1 had marked hypoxemia (partial pressure of oxygen of between 50 and 87 mmHg) during anesthesia. Cleaning products used to disinfect endotracheal tubes between patients have not been reported as a cause of laryngeal dysfunction; however, they may cause local irritation and a resultant laryngeal dysfunction if not adequately rinsed.
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Previous studies have demonstrated extensive local trauma to the larynx and trachea associated with orotracheal and nasotracheal intubation in the horse9,10; however, the degree of trauma has not yet been conclusively linked to laryngeal paralysis or dysfunction in horses. The aim of this study was to examine the effect of anesthesia on equine laryngeal function and to assess the degree of pharyngeal and laryngeal trauma that is associated with orotracheal intubation.
MATERIALS AND METHODS A pilot study was conducted before performing the main study to evaluate the endoscopic protocol and scoring systems. The study had institutional approval. Twenty horses (American Society of Anesthesiologists physical classification I or II) of varied breeds, age, sex, and weight presented for elective surgery were included in this study. Owner consent was obtained. Only horses that tolerated endoscopic examination without chemical restraint at the first time point were included in the study. All horses had no known history of laryngeal or respiratory dysfunction. No evidence of trauma (eg, epistaxis) caused by endoscopic examination of the larynx was detected at any time in any of the horses used during the study. Before sedation, a 12-gauge catheter (Intraflon 2 [polytetrafluoroethylene; PTFE]; Vygon UK Ltd, Bridge Rd, Cirencester, Gloucestershire, GL7 1PT, UK) was placed aseptically in the left jugular vein. Endoscopy was performed using a 1-meter videoendoscope (Olympus EVIS system, CV 240 video processor). During each endoscopic examination, the external nares were temporarily occluded to stimulate arytenoid movement.11 The first endoscopic examination was performed once the catheter had been placed. A 30- to 60-second clip was recorded at the following time points: (1) Before sedation (T1). This video clip was used as the control for each horse. (2) Five minutes after intravenous sedation with acepromazine and romifidine (T2). (3) Immediately after induction of anesthesia, before intubation (no twitch) (T3). (4) After the horse was standing and it was safe to enter the recovery box (T4). (5) Twenty-four hours after T4. A standardized anesthetic regimen was used in all cases. Acepromazine maleate (ACP; 10 mg/mL, C-Vet VP Leyland, Lancs., UK) 0.03 mg/kg, and romifidine (Sedivet Boehringer Ingelheim Limited, Ellesfield Avenue, Bracknell, Berkshire, UK) 80 mg/kg were administered intravenously before anesthesia. General anesthesia was induced with ketamine hydrochloride (Vetalar Pharmacia & Upjohn, Crawley, West
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Sussex, UK), 2.2 mg/kg, and diazepam (Hamelin Pharmaceuticals Ltd, Gloucester, UK) 0.05 mg/kg administered intravenously. Orotracheal intubation was then performed by a student closely observed by an anesthetist, and the cuff was inflated to form a seal when positive pressure was applied to the breathing system. Only three attempts at orotracheal intubation were allowed. Anesthesia was maintained with halothane (Merial Animal Health Ltd, Sandringham House, Harlow Business Park, Harlow, Essex, UK) in 100% oxygen delivered by a large animal circular rebreathing system (MDS Matrix VML LA Anesthetic machine, 145 Mid County Drive, Orchard Park, NY) under spontaneous ventilation. Analgesia (nonsteroidal anti-inflammatory) was administered at the discretion of the anesthetist in charge of the case. Pulse oximetry, capnography, and electrocardiography were used to aid monitoring of anesthesia. Blood gas analysis and direct arterial blood pressure monitoring were employed in cases of over 20 minutes’ anesthetic duration. Mean arterial blood pressure was maintained above 60 mmHg by adjustment of the vaporizer setting according to anesthetic depth, dobutamine hydrochloride (dobutamine concentrate, Hamelin Pharmaceuticals Ltd, Gloucester, UK) infusion, or phenylephrine infusion (Phenylephrine Injection BP, Sovereign Medical, Sovereign House, Miles Gray Rd, Basildon, Essex UK). All horses received intravenous fluids at a rate of 10 mL/kg/ hour (Isolec Combi [compound sodium lactate] IVEX Pharmaceuticals, Larne, UK) for the first hour, decreasing to 5 mL/kg/hour thereafter. Procedures were performed in dorsal or lateral recumbency, and overextension of the neck was avoided. Horses’ tracheas were extubated after swallowing was observed, and horses recovered from anesthesia with a nasopharyngeal tube in place. The one hundred video clips were digitally recorded and randomized. A previously validated grading system was amended and used to grade laryngeal function (Table 1).12 Laryngotracheal trauma was assessed using a previously devised scoring system (Table 2).9 The clips were assessed by two blinded assessors (assessor A and assessor B). Assessors were blinded to each other’s results, to the time point of each clip, and to the identity of the horse. Statistical Analysis Agreement between assessors for laryngeal function score was assessed using a linear weighted kappa statistic.13 A score of 0 or greater than 0 was used when estimating kappa for trauma scores. Kappas are reported as the mean of the five time-specific kappa statistics. The effect of general anesthesia on laryngeal function and trauma to the laryngeal/pharyngeal tissue was assessed using the Wilcoxon signed rank test comparing all other time points to time point 1. Wilcoxon signed rank tests were calculated using SPSS 15.0.1 (SPSS Inc, Chicago, IL) for Windows,
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Table 1. Grading system used for evaluation of laryngeal function Grade 1 Grade 2
Grade 3
Grade 4
Synchronous abduction and adduction of the left and right cartilages Asynchronous movement such as hesitation, flutters, adductor weakness of the arytenoids during inspiration or expiration or both, but full abduction induced by swallowing or nasal occlusion Asynchronous movement of the arytenoids during inspiration or expiration or both, but full abduction not induced or maintained by swallowing or nasal occlusion Significant asymmetry of the larynx at rest and lack of substantial movement of the arytenoids.
and 95% confidence intervals for the median of the differences between time points were calculated by the centile command of Stata 10.0 (StataCorp, College Station, TX). A P-value of .0125 was considered to be statistically significant when comparing time points, after adjusting for multiple comparisons by the Bonferroni method. Spearman’s rank correlation was used to assess the relationship between trauma and function scores at each time point, and between anesthetic duration and trauma and function scores at time points 4 and 5.
RESULTS Six mares and 14 geldings ranging in age from 1 to 14 years (mean, 7.5 years) were used. Horses were of varied breed; their weights ranged from 320 to 700 kg (mean, 506.6 kg) (Table 3). No difficult intubations were noted in any of the horses in this study. The agreement for laryngeal scores and trauma scores are shown in Tables 4 and 5, respectively. For laryngeal function scoring, there was an inter-assessor observed agreement of 73% (mean weighted kappa, 0.45). For laryngeal trauma scoring, there was an observed agreement of 88% (mean kappa, 0.64). Median laryngeal function scores and laryngeal trauma scores for each assessor A and B at each time point are shown in Table 6. The median laryngeal score for assessor A was 1 at each time point except T4 (once stood, after recovery from anesthesia), when it was 2. The median laryngeal score for assessor B was 1 at each time point. Median trauma scores for assessor A were between 0.5 and 0 for the first three time points, and 2 for time points 4 and 5. Median trauma scores for assessor B were 0 for time points 1 through 3 and 1 for time points 4 and 5. The Wilcoxon signed rank test with Bonferroni adjustment (P < .0125) was used to compare laryngeal and
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Table 2. Scoring system for laryngeal trauma None (grade 0) Mild (grade 1)—only mucous or slight erythema <10 cm square Moderate (grade 2)—erythema and mucous plaques 1020 cm square Severe (grade3)—definite erythema and multiple areas suggesting ulceration and diphtheritic membranous appearance trauma scores at T2 through T5, with the score at T1 for assessors A and B. The results are shown in Table 6. For laryngeal function scores for assessors A and B, there was no significant difference between time point 1 and time points 2 through 5. For trauma scores, there was a significant difference for assessor A comparing time point 1 with time point 2 (P ¼ .008) and for assessor B comparing time points 1 and 5 (P ¼ .005). For trauma scores, the median values are shown in Table 6. The median trauma score was numerically higher for time points 4 and 5 for both assessors when compared with time points 1 through 3. Correlation between trauma and function scores was assessed using the Spearman’s rank coefficient (rho); results are shown in Table 7. For both assessors at all time points, there was no significant correlation (absolute rho, <0.31) between trauma and function scores. Spearman’s rank correlation coefficients between anesthetic duration and laryngeal trauma and function scores at time points 4 and 5 were not significant. The correlation coefficients ranged from 0.37 (P ¼ .10) to 0.08 (P ¼ .74).
DISCUSSION The current study aimed to assess equine laryngeal function in the peri-anesthetic period to determine whether there was a detrimental effect of this standardized anesthetic protocol on laryngeal function. Because the incidence of bilateral laryngeal paralysis is very low, with no cases identified in a population of 479 horses,14 we did not anticipate detecting severe bilateral laryngeal dysfunction. We assessed laryngeal function 24 hours after anesthesia to determine whether there was a lasting effect on laryngeal function from anesthesia. Trauma scoring was used to assess whether orotracheal intubation was associated with trauma and whether more severe trauma scores were associated with worse scores for laryngeal function. Agreement for laryngeal function scores was moderate at 73% (weighted kappa ¼ 0.45).15 Previous studies have shown an interobserver agreement of between 70.4 and 80.6%16; however, these studies allowed for longer examination of the larynx. A study by Lindegaard et al17 demonstrated a significant effect of observer during a similar study using blinded assessors to evaluate the endoscopic effect of
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Table 3. List of horses including age in years, breed, weight in kilograms, ET (endotracheal tube) internal diameter size in millimeters, whether ionotropes or vasopressors were used in the management of the case, the procedure performed, and type of recumbency
Breed
Wt (kg)
Tube Size Ionotrope / (ID mm) Pressors
2 5 9 6 10 13 1 3 7 3 5 14 6
TB IDx IdxTB Idx TBx IdxTB TBx Ax TB Pony TBx WelshxTB X breed
435 557 615 637 636 525 320 525 540 365 642 527 437
25 25 30 30 30 30 25 30 25 20 30 30 25
DOB Nil DOB Phenyl Nil Nil DOB and NAD DOB & NAD Nil DOB NAD DOB DOB NAD DOB Phenyl Nil
14 15
14 6
TBx IDxTB
535 540
25 30
Nil DOB
16 17 18 19 20
10 7 4 6 7
TB Idx IdxTB Cob X Cob x
Est 400 585 475 466 700
25 30 30 30 30
Phenyl Nil DOB Nil Nil
Horse
Age (yr)
1 2 3 4 5 6 7 8 9 10 11 12 13
Surgery Type
Position
Duration (min)
Fetlock arthroscopy Tendon split—L patella Remove skin mass Keratoma drill Ring sarcoids Stifle arthroscopy R stifle arthroscopy Tenoscopy Sarcoid removal Debride wound Arthroscopy fetlock chip P1 fracture repair Annular ligament desmotomy Ring sarcoids Arthroscopy/annular ligament Stifle arthroscopy Hoof wall strip Stifle arthroscopy Malleolar chip removal Navicular bursa arthrocentesis
R lat R lat R lat R lat L lat Dorsal Dorsal L lat R lat R lat Dorsal L lat L lat
105 80 100 30 20 115 65 90 60 75 95 120 75
R lat & dorsal 20 L lat 75 Dorsal L lat Dorsal L lat R lat
110 55 140 60 130
A, Arabian; ID, Irish Draft; TB, Thoroughbred; DOB, dobutamine; NAD, noradrenaline; Phenyl, phenylephrine; R, right; L, left; Lat, lateral.
sedative agents on laryngeal function. Kappa was used to assess agreement because it takes into account agreement by chance. Weighted kappa allows a measure of agreement between rank-ordered variables. Both assessors used in this study were experienced clinicians, which should improve the accuracy and repeatability of the scores.18 A standardized endoscopic view of the larynx after insertion of the endoscope via the left nares was used at all time points, because it has been shown to improve inter-assessor agreement.19 Although all possible means of improving agreement between assessors were undertaken, agreement of function scores was still considered moderate, with an agreement of 73% and a mean weighted kappa of 0.45. The agreement was, however, similar to other similar studies in unanesthetized patients.16 There was substantial inter-observer agreement (88%) for trauma scoring with a weighted kappa of 0.64. Only horses that tolerated endoscopic examination without sedation were used in this study; the first and last time points required examination of the larynx without sedation, because sedation has been shown to affect laryngeal
movement.19 This limited the number of cases admitted to the study and may have led to bias because horses were selected based on temperament. The application of a twitch to the upper lip was used at all time points apart from time point 3; use of a twitch has been shown to not have a significant effect on laryngeal function.11 Examination of the larynges of the horses before sedation showed a median score of 1 (range, 12) for both assessors. The prevalence of pathologic change of the laryngeal muscles supplied by the left recurrent laryngeal nerve in clinically normal horses has been shown to be as high as 30%,20 whereas a study by Raphel14 reported a prevalence of idiopathic laryngeal hemiplegia of 3.3% in a population of 479 horses. Because all horses entered into the study had no history of respiratory noise indicating impaired laryngeal function, a low prevalence of hemiplegia would be expected, as is shown in the results. It is likely more horses would need to be included in the study to increase the likelihood of detecting previously undiagnosed hemiplegia. Horses with preexisting laryngeal dysfunction may be at increased risk of developing a disturbance in laryngeal
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Table 4. Agreement of laryngeal function scores for assessor A and B Assessor B Score Assessor A Score*
1
2
3
Total
1 2 3 Total
53 10 1 64
14 18 2 34
0 0 2 2
67 28 5 100
* Because there was no score of 4 for laryngeal function given by either assessor, it has been omitted from the table.
Table 5. Agreement of trauma scores for assessors A and B Assessor B Score Assessor A Score
0
>0
Total
0 >0 Total
42 8 50
4 46 50
46 54 100
function after anesthesia; however, none were included in this study. It has been suggested that sedation will reduce laryngeal function, resulting in decreased abduction of the arytenoid cartilages.11 Endoscopy was performed within 5 minutes of pre-anesthetic medication with acepromazine and romifidine when the horses showed clinical signs of sedation. Interestingly, there was no significant difference in laryngeal scores from T1 to T2 for either assessor (P ¼ 1.00 for both). The median score for each assessor at time point 2 was 1 (range, 13). This is in contrast to the study by Archer et al11 that demonstrated a significant reduction in vocal fold abduction after xylazine sedation11 and that of Lindegaard et al,17 who demonstrated a significant impairment to abduction of the left arytenoid cartilage after detomidine. However, romifidine was used in this study, and its effect on laryngeal function has not been reported. Sedation with a2 adrenoreceptor agonists is associated with a varying degree of muscle relaxation.21 The degree of muscle relaxation varies among the a2 adrenoreceptor agonists, with xylazine associated with greater muscle relaxation and ataxia than romifidine.22 The greater degree of muscle relaxation11 and local anesthetic effects23 associated with xylazine may explain the higher laryngeal function scores seen after xylazine sedation. There was no significant effect on laryngeal function when comparing T3 with T1 (P ¼ 1.00 assessor A, P ¼ 0.45 assessor B). If drugs associated with anesthesia had a detectable effect on laryngeal function, a higher comparative score at time point 3 would have been expected. Ketamine and diazepam were used for induction of
anesthesia. When ketamine is used alone in humans, pharyngeal and laryngeal reflexes remain active.24 However, when ketamine is used in combination with diazepam in dogs, there is a significant reduction in arytenoid motion in comparison with other agents.25 In the current study, there was no significant difference in laryngeal function scores after induction of anesthesia with ketamine and diazepam in this population of horses. Endoscopy performed at time point T4 was used to assess laryngeal function after a period of orotracheal intubation. Laryngeal function scores at T4 were not significantly higher than scores at T1 (P ¼ .03 assessor A and P ¼ .73 for assessor B). Median trauma scores were higher at T4 for both assessors A and B. However, when trauma scores at T4 were compared with T1, they were not significantly higher (P ¼ .03 for A and P ¼ .014 for B). This is in contrast to studies by Holland et al10 and Heath et al,9 in which traumatic lesions to the laryngeal/pharyngeal region were present in most cases 1 to 48 hours after extubation. Holland et al10 and Heath et al9 reported that endoscopy was performed before tracheal intubation; however, scores for this time point were not reported, so it is not possible to assess whether there were any high trauma scores reported before intubation, as was the case in the current study. Also, neither study stated whether assessors were blinded to whether the clips were pre-intubation or post-intubation, which may have led to bias in their trauma scores. In our study, some clips from horses taken before orotracheal intubation were assessed as having trauma scores of between 1 and 3, and scores at T1 had a significantly higher score (P ¼ .008) than T2 for assessor A. The number of ‘‘false’’ positive results would indicate that the trauma scoring system used in this study is not very specific. For horses to be classified as having a trauma score of 1 or 2, they had to have mucus and erythema of less than 10 cm2. The presence of abnormal mucus and erythema during endoscopy is subjective. Perhaps a better measure of trauma after intubation would be the presence/absence of hemorrhage or soft tissue swelling. The use of certain agents also may have influenced the trauma scores; for example, ketamine is known to increase pharyngeal secretions and mucus.26 We assessed whether there was any correlation between horses with higher trauma scores having higher laryngeal function scores using the Spearman rank correlation coefficient. All absolute rho values were less than 0.31 for assessor A and less than 0.18 for assessor B (>0.4 was considered clinically significant). Overall rho for each assessor was also low. These results suggest that there is no relationship between trauma scores and laryngeal function. At T5 (24 hours after recovery from anesthesia), there was no significant difference in laryngeal function when compared with T1 (P ¼ .73 for A, P ¼ .73 for B). The data suggest that median trauma scores were higher at T5 than at T1 through T3, which may become significant
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Table 6. Median and range of laryngeal function and trauma scores for assessor A and B at all time points Time
A Larynx
B Larynx
A Trauma
B Trauma
1 2 Median difference 95% CI P value 3 Median difference 95% CI P value 4 Median difference 95% CI P value 5 Median difference 95% CI P value
1 (12) 1 (13) 0 (0 to 0) 1.000 1 (13) 0 (0 to 0) 1.000 2 (13) 0.5 (0 to 1) .033 1 (12) 0 (0 to 0) .727
1 (12) 1 (13) 0 (0 to 0) 1.000 1 (12) 0 (0 to 0) .453 1 (13) 0 (0 to 0) .727 1 (12) 0 (0 to 0) .727
0.5 (02) 0 (01) 0.5 (2 to 0) .008 0 (02) 0 (1 to 0) .020 2 (03) 1 (0 to 1) .027 2 (03) 0.5 (0 to 2) .026
0 (02) 0 (02) 0 (1 to 0) .078 0 (02) 0 (0 to 0) .625 1 (03) 0.5 (0 to 1) .014 1 (02) 1 (0 to 1) .005
The median difference between the time point and time point 1. The 95% confidence intervals of the difference. P-values for Wilcoxon signed rank test for laryngeal function and trauma scores. Results compare whether there is a significant difference between time point 1 and time points 25 for assessors A and B. P-values <0.0125 were considered statistically significant after the Bonferroni adjustment for multiple comparisons was applied.
with a larger sample size (see Table 6). For assessor B, the trauma score was significantly higher at T5 when compared with T1 (P ¼ .005). Therefore, in this study, there was no lasting, subclinical laryngeal dysfunction at 24 hours after anesthesia. However, there was evidence of trauma to the laryngeal/pharyngeal tissue at this time. Our results did not detect a statistically significant effect of anesthesia and orotracheal intubation on laryngeal function during the peri-anesthetic period in the sample of horses studied. It is likely that more horses would be needed to be able to detect subtle changes in laryngeal function. To have achieved better inter-assessor agreement, longer video clips could have been taken, including more functional tests (eg, swallowing). However, this was not possible at all time points because the patient was anesthetized. Inter-assessor agreement was poor in the pilot study. This was improved by ensuring that the images included a central view of the larynx taken over two to three full respiratory cycles and included the time the nares were occluded. Trauma scores at each time point were consistently higher after intubation, as has been shown in previous studies.9,10 However, these scores were not correlated with worsening laryngeal function scores. Using the standard deviation of the differences of time point 4 versus time point 1 and time point 5 versus time point 1, with a type 1 error of 0.0125 and a 15% compensation for nonparametric testing, a sample size of 22 horses achieved 82% power to detect a difference of one score for
Table 7. Correlation between laryngeal function and trauma scores using Spearman’s rank correlation coefficient for assessors A and B Time Point
Assessor A rho
Assessor B rho
1 2 3 4 5 Overall
0.07 (P ¼ .78) 0.21 (P ¼ .38) 0.09 (P ¼ .70) 0.31 (P ¼ .18) 0.30 (P ¼ .20) 0.03 (P ¼ .77)
0.18 (P ¼ .45) 0.07 (P ¼ .78) 0.15 (P ¼ .53) 0.10 (P ¼ .66) 0.17 (P ¼ .46) 0.002 (P ¼ .99)
laryngeal scores, and a sample size of 11 horses achieved 82% power to detect a difference of one score for trauma scores.27 Laryngeal function as assessed by blinded assessors using a validated scoring system did not change significantly as a result of a standardized anesthetic protocol in 20 horses. Sedation with acepromazine and romifidine did not influence laryngeal function scores in this study. Laryngeal/ pharyngeal trauma also was assessed under the same conditions using a previously published scoring system; scores were higher after intubation but showed no correlation with laryngeal function. The laryngeal function scoring system used in this study was effective. However, the scoring system used to assess laryngeal trauma produced a number of ‘‘false positive’’ results, which brings the validity of this system into question. Further work is required to evaluate
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other variables that may affect laryngeal function after anesthesia, using a larger number of horses with varying degrees of laryngeal function.
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11. Archer RM, Lindsay WA, Duncan RD. A comparison of techniques to enhance the evaluation of equine laryngeal function. Equine Vet J 1991;23:104–107. 12. Ducharme NG, Hackett RP. The value of surgical treatment of laryn-
ACKNOWLEDGMENTS The authors thank The Horse Trust (The Home of Rest for Horses) for support of L. A. Bradbury in a Clinical Training Scholarship in Anesthesia, Analgesia, and Critical Care and all the staff and students at the Philip Leverhulme Equine Hospital, University of Liverpool, for their help and support, and Garry Anderson for his help with the statistics.
geal hemiplegia in horses. Comp Cont Educ Pract Vet 1991;13: 472–475. 13. Altman DG. Practical statistics for medical research. London: Chapman and Hall; 1991:403–407. 14. Raphel CF. Endoscopic findings in the upper respiratory tract of 479 horses. J Am Vet Med Assoc 1982;181:470–473. 15. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159–174. 16. Hackett RP, Ducharme NG, Fubini SL, Erb HN. The reliability of endoscopic examination in assessment of arytenoid cartilage move-
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and sedation. Vet Surg 1991;20:180–184. 20. Duncan ID, Griffiths IR, McQueen A, Baker GO. The pathology of equine laryngeal hemiplegia. Acta Neuropathol 1974;27:337–348. 21. Gross ME. Tranquilizers, a-adrenergic agonists and related agents. In: Adams HR, ed. Veterinary pharmacology and therapeutics, 8th ed. Ames, IA: Iowa State University Press; 2001:313. 22. England GC, Clarke KW, Goossens L. A comparison of the sedative effects of three alpha 2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse. J Vet Pharmacol Ther 1992;15: 194–201. 23. Aziz MA, Martin RJ. Alpha agonists and local anaesthetic properties of xylazine. Zentrablatt Vet Med 1978;25:180–188. 24. Lanning CF, Harmel MH. Ketamine anaesthesia. Ann Rev Med 1975;26:137–141. 25. Jackson AM, Tobias K, Long C, Bartges J, Harvey R. Effects of various anesthetic agents on laryngeal motion during laryngoscopy in normal dogs. Vet Surg 2004;33:102–106. 26. Branson KR. Injectable anesthetics. In: Adams HR, ed. Veterinary pharmacology and therapeutics, 8th ed. Ames, IA: Iowa State University Press; 2001:247. 27. Bradley JV. Distribution-free statistical tests. New Jersey: Prentice Hall Inc; 1968:60.
ORIGINAL RESEARCH
The Effects of Anesthesia on Laryngeal Function and Laryngeal/Pharyngeal Trauma in the Horse Leah A. Bradbury, BVSc (hons) CertVA,a Alexandra H.A. Dugdale, MA, VetMB, DVA, Dipl.ECVA, PGCert(LTHE), MRCVS,b Derek C. Knottenbelt, DVM&S, DipECEIM, MRCVS,b Shaun A. Mackane, BVSc, BSc(vet), PhD, DACVIM, DECEIM, MRCVS,b and J. Mark Senior, BVSc, Cert VA, DiplECVA, MRCVSb
ABSTRACT Laryngeal paralysis in horses has been reported after inhalational anesthesia and can result in significant morbidity/mortality. The cause of the condition is unclear. The objective of this study was to examine the effects of a standardized anesthetic protocol on laryngeal function and laryngeal/pharyngeal trauma in the peri-anesthetic period in a prospective study. A 30- to 60-second digitalized video clip of laryngeal movement from a standardized endoscopic view was recorded at five time points: before sedation, postsedation, post-induction, immediately after recovery to standing, and at 24 hours after recovery. A standardized anesthetic regimen was used in all cases. Video clips were randomized and evaluated by two blinded assessors. Each assessor scored each clip for laryngeal function and trauma using previously validated scoring systems. Agreement between assessors was calculated using the mean of the five time-specific weighted kappa statistics. Post-anesthesia laryngeal function and trauma scores were compared with initial scores using the Wilcoxon signed rank test with Bonferroni adjustment. Spearman’s rank coefficient was used to assess correlation between trauma and function scores and between anesthetic duration and laryngeal function and trauma scores. There was no significant effect of anesthesia on laryngeal function. Trauma scores were not significantly higher after tracheal intubation. The trauma scoring system requires further validation. There was no correlation between higher trauma scores and laryngeal function or duration and laryngeal function or trauma.
From Veterinary Clinic and Hospital, University of Melbourne, Werribee Victoria, Australiaa; and Philip Leverhulme Large Animal Hospital, University of Liverpool, Wirral, UK.b Reprint requests: Leah A. Bradbury, BVSc (hons) CertVA, c/o Veterinary Clinic and Hospital, University of Melbourne, 250 Princes Highway, Werribee VIC 3030, Australia. 0737-0806/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2008.07.006
Journal of Equine Veterinary Science Vol 28, No 8 (2008)
Further work is required to evaluate other variables that may affect laryngeal function after anesthesia, using a larger number of horses with varying degrees of laryngeal dysfunction. Keywords: Anesthesia; Equine; Larynx; Function; Trauma
INTRODUCTION It has been suggested that anesthesia in the horse can cause abnormalities in laryngeal function, such as unilateral and bilateral laryngeal paralysis, which can result in significant morbidity/mortality in the peri-anesthetic period.1-4 Laryngeal paralysis or paresis secondary to endotracheal intubation has been reported in humans.5-7 In horses, the cause of this condition is unclear. Anesthetic agents, trauma secondary to endotracheal intubation, or damage to the recurrent laryngeal nerve (RLN) through hypoxia, head positioning, or catheter placement may each play a role in the etiopathogenesis either by causing a primary problem or by exacerbating a subclinical/undiagnosed laryngeal hemiplegia.1-4 If damage to the peripheral pathway of the RLN is a contributing factor in bilateral laryngeal paresis/paralysis, there must be either a bilateral insult to the RLN or a proximal lesion.2 Abrahamsen et al1 suggested that stretching and increasing tension across the nerve may be involved, and Rooney and Delaney8 hypothesized that this may lead to a reduction in blood flow to the nerve. Abrahamsen et al1 and Dixon et al2 reported that both patients that developed bilateral laryngeal paralysis were positioned for general anesthesia with their head and neck in extension. Hypoxemia may contribute to ischemic necrosis of the RLN. One reported case1 had marked hypoxemia (partial pressure of oxygen of between 50 and 87 mmHg) during anesthesia. Cleaning products used to disinfect endotracheal tubes between patients have not been reported as a cause of laryngeal dysfunction; however, they may cause local irritation and a resultant laryngeal dysfunction if not adequately rinsed.
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Previous studies have demonstrated extensive local trauma to the larynx and trachea associated with orotracheal and nasotracheal intubation in the horse9,10; however, the degree of trauma has not yet been conclusively linked to laryngeal paralysis or dysfunction in horses. The aim of this study was to examine the effect of anesthesia on equine laryngeal function and to assess the degree of pharyngeal and laryngeal trauma that is associated with orotracheal intubation.
MATERIALS AND METHODS A pilot study was conducted before performing the main study to evaluate the endoscopic protocol and scoring systems. The study had institutional approval. Twenty horses (American Society of Anesthesiologists physical classification I or II) of varied breeds, age, sex, and weight presented for elective surgery were included in this study. Owner consent was obtained. Only horses that tolerated endoscopic examination without chemical restraint at the first time point were included in the study. All horses had no known history of laryngeal or respiratory dysfunction. No evidence of trauma (eg, epistaxis) caused by endoscopic examination of the larynx was detected at any time in any of the horses used during the study. Before sedation, a 12-gauge catheter (Intraflon 2 [polytetrafluoroethylene; PTFE]; Vygon UK Ltd, Bridge Rd, Cirencester, Gloucestershire, GL7 1PT, UK) was placed aseptically in the left jugular vein. Endoscopy was performed using a 1-meter videoendoscope (Olympus EVIS system, CV 240 video processor). During each endoscopic examination, the external nares were temporarily occluded to stimulate arytenoid movement.11 The first endoscopic examination was performed once the catheter had been placed. A 30- to 60-second clip was recorded at the following time points: (1) Before sedation (T1). This video clip was used as the control for each horse. (2) Five minutes after intravenous sedation with acepromazine and romifidine (T2). (3) Immediately after induction of anesthesia, before intubation (no twitch) (T3). (4) After the horse was standing and it was safe to enter the recovery box (T4). (5) Twenty-four hours after T4. A standardized anesthetic regimen was used in all cases. Acepromazine maleate (ACP; 10 mg/mL, C-Vet VP Leyland, Lancs., UK) 0.03 mg/kg, and romifidine (Sedivet Boehringer Ingelheim Limited, Ellesfield Avenue, Bracknell, Berkshire, UK) 80 mg/kg were administered intravenously before anesthesia. General anesthesia was induced with ketamine hydrochloride (Vetalar Pharmacia & Upjohn, Crawley, West
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Sussex, UK), 2.2 mg/kg, and diazepam (Hamelin Pharmaceuticals Ltd, Gloucester, UK) 0.05 mg/kg administered intravenously. Orotracheal intubation was then performed by a student closely observed by an anesthetist, and the cuff was inflated to form a seal when positive pressure was applied to the breathing system. Only three attempts at orotracheal intubation were allowed. Anesthesia was maintained with halothane (Merial Animal Health Ltd, Sandringham House, Harlow Business Park, Harlow, Essex, UK) in 100% oxygen delivered by a large animal circular rebreathing system (MDS Matrix VML LA Anesthetic machine, 145 Mid County Drive, Orchard Park, NY) under spontaneous ventilation. Analgesia (nonsteroidal anti-inflammatory) was administered at the discretion of the anesthetist in charge of the case. Pulse oximetry, capnography, and electrocardiography were used to aid monitoring of anesthesia. Blood gas analysis and direct arterial blood pressure monitoring were employed in cases of over 20 minutes’ anesthetic duration. Mean arterial blood pressure was maintained above 60 mmHg by adjustment of the vaporizer setting according to anesthetic depth, dobutamine hydrochloride (dobutamine concentrate, Hamelin Pharmaceuticals Ltd, Gloucester, UK) infusion, or phenylephrine infusion (Phenylephrine Injection BP, Sovereign Medical, Sovereign House, Miles Gray Rd, Basildon, Essex UK). All horses received intravenous fluids at a rate of 10 mL/kg/ hour (Isolec Combi [compound sodium lactate] IVEX Pharmaceuticals, Larne, UK) for the first hour, decreasing to 5 mL/kg/hour thereafter. Procedures were performed in dorsal or lateral recumbency, and overextension of the neck was avoided. Horses’ tracheas were extubated after swallowing was observed, and horses recovered from anesthesia with a nasopharyngeal tube in place. The one hundred video clips were digitally recorded and randomized. A previously validated grading system was amended and used to grade laryngeal function (Table 1).12 Laryngotracheal trauma was assessed using a previously devised scoring system (Table 2).9 The clips were assessed by two blinded assessors (assessor A and assessor B). Assessors were blinded to each other’s results, to the time point of each clip, and to the identity of the horse. Statistical Analysis Agreement between assessors for laryngeal function score was assessed using a linear weighted kappa statistic.13 A score of 0 or greater than 0 was used when estimating kappa for trauma scores. Kappas are reported as the mean of the five time-specific kappa statistics. The effect of general anesthesia on laryngeal function and trauma to the laryngeal/pharyngeal tissue was assessed using the Wilcoxon signed rank test comparing all other time points to time point 1. Wilcoxon signed rank tests were calculated using SPSS 15.0.1 (SPSS Inc, Chicago, IL) for Windows,
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Table 1. Grading system used for evaluation of laryngeal function Grade 1 Grade 2
Grade 3
Grade 4
Synchronous abduction and adduction of the left and right cartilages Asynchronous movement such as hesitation, flutters, adductor weakness of the arytenoids during inspiration or expiration or both, but full abduction induced by swallowing or nasal occlusion Asynchronous movement of the arytenoids during inspiration or expiration or both, but full abduction not induced or maintained by swallowing or nasal occlusion Significant asymmetry of the larynx at rest and lack of substantial movement of the arytenoids.
and 95% confidence intervals for the median of the differences between time points were calculated by the centile command of Stata 10.0 (StataCorp, College Station, TX). A P-value of .0125 was considered to be statistically significant when comparing time points, after adjusting for multiple comparisons by the Bonferroni method. Spearman’s rank correlation was used to assess the relationship between trauma and function scores at each time point, and between anesthetic duration and trauma and function scores at time points 4 and 5.
RESULTS Six mares and 14 geldings ranging in age from 1 to 14 years (mean, 7.5 years) were used. Horses were of varied breed; their weights ranged from 320 to 700 kg (mean, 506.6 kg) (Table 3). No difficult intubations were noted in any of the horses in this study. The agreement for laryngeal scores and trauma scores are shown in Tables 4 and 5, respectively. For laryngeal function scoring, there was an inter-assessor observed agreement of 73% (mean weighted kappa, 0.45). For laryngeal trauma scoring, there was an observed agreement of 88% (mean kappa, 0.64). Median laryngeal function scores and laryngeal trauma scores for each assessor A and B at each time point are shown in Table 6. The median laryngeal score for assessor A was 1 at each time point except T4 (once stood, after recovery from anesthesia), when it was 2. The median laryngeal score for assessor B was 1 at each time point. Median trauma scores for assessor A were between 0.5 and 0 for the first three time points, and 2 for time points 4 and 5. Median trauma scores for assessor B were 0 for time points 1 through 3 and 1 for time points 4 and 5. The Wilcoxon signed rank test with Bonferroni adjustment (P < .0125) was used to compare laryngeal and
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Table 2. Scoring system for laryngeal trauma None (grade 0) Mild (grade 1)—only mucous or slight erythema <10 cm square Moderate (grade 2)—erythema and mucous plaques 1020 cm square Severe (grade3)—definite erythema and multiple areas suggesting ulceration and diphtheritic membranous appearance trauma scores at T2 through T5, with the score at T1 for assessors A and B. The results are shown in Table 6. For laryngeal function scores for assessors A and B, there was no significant difference between time point 1 and time points 2 through 5. For trauma scores, there was a significant difference for assessor A comparing time point 1 with time point 2 (P ¼ .008) and for assessor B comparing time points 1 and 5 (P ¼ .005). For trauma scores, the median values are shown in Table 6. The median trauma score was numerically higher for time points 4 and 5 for both assessors when compared with time points 1 through 3. Correlation between trauma and function scores was assessed using the Spearman’s rank coefficient (rho); results are shown in Table 7. For both assessors at all time points, there was no significant correlation (absolute rho, <0.31) between trauma and function scores. Spearman’s rank correlation coefficients between anesthetic duration and laryngeal trauma and function scores at time points 4 and 5 were not significant. The correlation coefficients ranged from 0.37 (P ¼ .10) to 0.08 (P ¼ .74).
DISCUSSION The current study aimed to assess equine laryngeal function in the peri-anesthetic period to determine whether there was a detrimental effect of this standardized anesthetic protocol on laryngeal function. Because the incidence of bilateral laryngeal paralysis is very low, with no cases identified in a population of 479 horses,14 we did not anticipate detecting severe bilateral laryngeal dysfunction. We assessed laryngeal function 24 hours after anesthesia to determine whether there was a lasting effect on laryngeal function from anesthesia. Trauma scoring was used to assess whether orotracheal intubation was associated with trauma and whether more severe trauma scores were associated with worse scores for laryngeal function. Agreement for laryngeal function scores was moderate at 73% (weighted kappa ¼ 0.45).15 Previous studies have shown an interobserver agreement of between 70.4 and 80.6%16; however, these studies allowed for longer examination of the larynx. A study by Lindegaard et al17 demonstrated a significant effect of observer during a similar study using blinded assessors to evaluate the endoscopic effect of
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Table 3. List of horses including age in years, breed, weight in kilograms, ET (endotracheal tube) internal diameter size in millimeters, whether ionotropes or vasopressors were used in the management of the case, the procedure performed, and type of recumbency
Breed
Wt (kg)
Tube Size Ionotrope / (ID mm) Pressors
2 5 9 6 10 13 1 3 7 3 5 14 6
TB IDx IdxTB Idx TBx IdxTB TBx Ax TB Pony TBx WelshxTB X breed
435 557 615 637 636 525 320 525 540 365 642 527 437
25 25 30 30 30 30 25 30 25 20 30 30 25
DOB Nil DOB Phenyl Nil Nil DOB and NAD DOB & NAD Nil DOB NAD DOB DOB NAD DOB Phenyl Nil
14 15
14 6
TBx IDxTB
535 540
25 30
Nil DOB
16 17 18 19 20
10 7 4 6 7
TB Idx IdxTB Cob X Cob x
Est 400 585 475 466 700
25 30 30 30 30
Phenyl Nil DOB Nil Nil
Horse
Age (yr)
1 2 3 4 5 6 7 8 9 10 11 12 13
Surgery Type
Position
Duration (min)
Fetlock arthroscopy Tendon split—L patella Remove skin mass Keratoma drill Ring sarcoids Stifle arthroscopy R stifle arthroscopy Tenoscopy Sarcoid removal Debride wound Arthroscopy fetlock chip P1 fracture repair Annular ligament desmotomy Ring sarcoids Arthroscopy/annular ligament Stifle arthroscopy Hoof wall strip Stifle arthroscopy Malleolar chip removal Navicular bursa arthrocentesis
R lat R lat R lat R lat L lat Dorsal Dorsal L lat R lat R lat Dorsal L lat L lat
105 80 100 30 20 115 65 90 60 75 95 120 75
R lat & dorsal 20 L lat 75 Dorsal L lat Dorsal L lat R lat
110 55 140 60 130
A, Arabian; ID, Irish Draft; TB, Thoroughbred; DOB, dobutamine; NAD, noradrenaline; Phenyl, phenylephrine; R, right; L, left; Lat, lateral.
sedative agents on laryngeal function. Kappa was used to assess agreement because it takes into account agreement by chance. Weighted kappa allows a measure of agreement between rank-ordered variables. Both assessors used in this study were experienced clinicians, which should improve the accuracy and repeatability of the scores.18 A standardized endoscopic view of the larynx after insertion of the endoscope via the left nares was used at all time points, because it has been shown to improve inter-assessor agreement.19 Although all possible means of improving agreement between assessors were undertaken, agreement of function scores was still considered moderate, with an agreement of 73% and a mean weighted kappa of 0.45. The agreement was, however, similar to other similar studies in unanesthetized patients.16 There was substantial inter-observer agreement (88%) for trauma scoring with a weighted kappa of 0.64. Only horses that tolerated endoscopic examination without sedation were used in this study; the first and last time points required examination of the larynx without sedation, because sedation has been shown to affect laryngeal
movement.19 This limited the number of cases admitted to the study and may have led to bias because horses were selected based on temperament. The application of a twitch to the upper lip was used at all time points apart from time point 3; use of a twitch has been shown to not have a significant effect on laryngeal function.11 Examination of the larynges of the horses before sedation showed a median score of 1 (range, 12) for both assessors. The prevalence of pathologic change of the laryngeal muscles supplied by the left recurrent laryngeal nerve in clinically normal horses has been shown to be as high as 30%,20 whereas a study by Raphel14 reported a prevalence of idiopathic laryngeal hemiplegia of 3.3% in a population of 479 horses. Because all horses entered into the study had no history of respiratory noise indicating impaired laryngeal function, a low prevalence of hemiplegia would be expected, as is shown in the results. It is likely more horses would need to be included in the study to increase the likelihood of detecting previously undiagnosed hemiplegia. Horses with preexisting laryngeal dysfunction may be at increased risk of developing a disturbance in laryngeal
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Table 4. Agreement of laryngeal function scores for assessor A and B Assessor B Score Assessor A Score*
1
2
3
Total
1 2 3 Total
53 10 1 64
14 18 2 34
0 0 2 2
67 28 5 100
* Because there was no score of 4 for laryngeal function given by either assessor, it has been omitted from the table.
Table 5. Agreement of trauma scores for assessors A and B Assessor B Score Assessor A Score
0
>0
Total
0 >0 Total
42 8 50
4 46 50
46 54 100
function after anesthesia; however, none were included in this study. It has been suggested that sedation will reduce laryngeal function, resulting in decreased abduction of the arytenoid cartilages.11 Endoscopy was performed within 5 minutes of pre-anesthetic medication with acepromazine and romifidine when the horses showed clinical signs of sedation. Interestingly, there was no significant difference in laryngeal scores from T1 to T2 for either assessor (P ¼ 1.00 for both). The median score for each assessor at time point 2 was 1 (range, 13). This is in contrast to the study by Archer et al11 that demonstrated a significant reduction in vocal fold abduction after xylazine sedation11 and that of Lindegaard et al,17 who demonstrated a significant impairment to abduction of the left arytenoid cartilage after detomidine. However, romifidine was used in this study, and its effect on laryngeal function has not been reported. Sedation with a2 adrenoreceptor agonists is associated with a varying degree of muscle relaxation.21 The degree of muscle relaxation varies among the a2 adrenoreceptor agonists, with xylazine associated with greater muscle relaxation and ataxia than romifidine.22 The greater degree of muscle relaxation11 and local anesthetic effects23 associated with xylazine may explain the higher laryngeal function scores seen after xylazine sedation. There was no significant effect on laryngeal function when comparing T3 with T1 (P ¼ 1.00 assessor A, P ¼ 0.45 assessor B). If drugs associated with anesthesia had a detectable effect on laryngeal function, a higher comparative score at time point 3 would have been expected. Ketamine and diazepam were used for induction of
anesthesia. When ketamine is used alone in humans, pharyngeal and laryngeal reflexes remain active.24 However, when ketamine is used in combination with diazepam in dogs, there is a significant reduction in arytenoid motion in comparison with other agents.25 In the current study, there was no significant difference in laryngeal function scores after induction of anesthesia with ketamine and diazepam in this population of horses. Endoscopy performed at time point T4 was used to assess laryngeal function after a period of orotracheal intubation. Laryngeal function scores at T4 were not significantly higher than scores at T1 (P ¼ .03 assessor A and P ¼ .73 for assessor B). Median trauma scores were higher at T4 for both assessors A and B. However, when trauma scores at T4 were compared with T1, they were not significantly higher (P ¼ .03 for A and P ¼ .014 for B). This is in contrast to studies by Holland et al10 and Heath et al,9 in which traumatic lesions to the laryngeal/pharyngeal region were present in most cases 1 to 48 hours after extubation. Holland et al10 and Heath et al9 reported that endoscopy was performed before tracheal intubation; however, scores for this time point were not reported, so it is not possible to assess whether there were any high trauma scores reported before intubation, as was the case in the current study. Also, neither study stated whether assessors were blinded to whether the clips were pre-intubation or post-intubation, which may have led to bias in their trauma scores. In our study, some clips from horses taken before orotracheal intubation were assessed as having trauma scores of between 1 and 3, and scores at T1 had a significantly higher score (P ¼ .008) than T2 for assessor A. The number of ‘‘false’’ positive results would indicate that the trauma scoring system used in this study is not very specific. For horses to be classified as having a trauma score of 1 or 2, they had to have mucus and erythema of less than 10 cm2. The presence of abnormal mucus and erythema during endoscopy is subjective. Perhaps a better measure of trauma after intubation would be the presence/absence of hemorrhage or soft tissue swelling. The use of certain agents also may have influenced the trauma scores; for example, ketamine is known to increase pharyngeal secretions and mucus.26 We assessed whether there was any correlation between horses with higher trauma scores having higher laryngeal function scores using the Spearman rank correlation coefficient. All absolute rho values were less than 0.31 for assessor A and less than 0.18 for assessor B (>0.4 was considered clinically significant). Overall rho for each assessor was also low. These results suggest that there is no relationship between trauma scores and laryngeal function. At T5 (24 hours after recovery from anesthesia), there was no significant difference in laryngeal function when compared with T1 (P ¼ .73 for A, P ¼ .73 for B). The data suggest that median trauma scores were higher at T5 than at T1 through T3, which may become significant
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Table 6. Median and range of laryngeal function and trauma scores for assessor A and B at all time points Time
A Larynx
B Larynx
A Trauma
B Trauma
1 2 Median difference 95% CI P value 3 Median difference 95% CI P value 4 Median difference 95% CI P value 5 Median difference 95% CI P value
1 (12) 1 (13) 0 (0 to 0) 1.000 1 (13) 0 (0 to 0) 1.000 2 (13) 0.5 (0 to 1) .033 1 (12) 0 (0 to 0) .727
1 (12) 1 (13) 0 (0 to 0) 1.000 1 (12) 0 (0 to 0) .453 1 (13) 0 (0 to 0) .727 1 (12) 0 (0 to 0) .727
0.5 (02) 0 (01) 0.5 (2 to 0) .008 0 (02) 0 (1 to 0) .020 2 (03) 1 (0 to 1) .027 2 (03) 0.5 (0 to 2) .026
0 (02) 0 (02) 0 (1 to 0) .078 0 (02) 0 (0 to 0) .625 1 (03) 0.5 (0 to 1) .014 1 (02) 1 (0 to 1) .005
The median difference between the time point and time point 1. The 95% confidence intervals of the difference. P-values for Wilcoxon signed rank test for laryngeal function and trauma scores. Results compare whether there is a significant difference between time point 1 and time points 25 for assessors A and B. P-values <0.0125 were considered statistically significant after the Bonferroni adjustment for multiple comparisons was applied.
with a larger sample size (see Table 6). For assessor B, the trauma score was significantly higher at T5 when compared with T1 (P ¼ .005). Therefore, in this study, there was no lasting, subclinical laryngeal dysfunction at 24 hours after anesthesia. However, there was evidence of trauma to the laryngeal/pharyngeal tissue at this time. Our results did not detect a statistically significant effect of anesthesia and orotracheal intubation on laryngeal function during the peri-anesthetic period in the sample of horses studied. It is likely that more horses would be needed to be able to detect subtle changes in laryngeal function. To have achieved better inter-assessor agreement, longer video clips could have been taken, including more functional tests (eg, swallowing). However, this was not possible at all time points because the patient was anesthetized. Inter-assessor agreement was poor in the pilot study. This was improved by ensuring that the images included a central view of the larynx taken over two to three full respiratory cycles and included the time the nares were occluded. Trauma scores at each time point were consistently higher after intubation, as has been shown in previous studies.9,10 However, these scores were not correlated with worsening laryngeal function scores. Using the standard deviation of the differences of time point 4 versus time point 1 and time point 5 versus time point 1, with a type 1 error of 0.0125 and a 15% compensation for nonparametric testing, a sample size of 22 horses achieved 82% power to detect a difference of one score for
Table 7. Correlation between laryngeal function and trauma scores using Spearman’s rank correlation coefficient for assessors A and B Time Point
Assessor A rho
Assessor B rho
1 2 3 4 5 Overall
0.07 (P ¼ .78) 0.21 (P ¼ .38) 0.09 (P ¼ .70) 0.31 (P ¼ .18) 0.30 (P ¼ .20) 0.03 (P ¼ .77)
0.18 (P ¼ .45) 0.07 (P ¼ .78) 0.15 (P ¼ .53) 0.10 (P ¼ .66) 0.17 (P ¼ .46) 0.002 (P ¼ .99)
laryngeal scores, and a sample size of 11 horses achieved 82% power to detect a difference of one score for trauma scores.27 Laryngeal function as assessed by blinded assessors using a validated scoring system did not change significantly as a result of a standardized anesthetic protocol in 20 horses. Sedation with acepromazine and romifidine did not influence laryngeal function scores in this study. Laryngeal/ pharyngeal trauma also was assessed under the same conditions using a previously published scoring system; scores were higher after intubation but showed no correlation with laryngeal function. The laryngeal function scoring system used in this study was effective. However, the scoring system used to assess laryngeal trauma produced a number of ‘‘false positive’’ results, which brings the validity of this system into question. Further work is required to evaluate
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other variables that may affect laryngeal function after anesthesia, using a larger number of horses with varying degrees of laryngeal function.
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11. Archer RM, Lindsay WA, Duncan RD. A comparison of techniques to enhance the evaluation of equine laryngeal function. Equine Vet J 1991;23:104–107. 12. Ducharme NG, Hackett RP. The value of surgical treatment of laryn-
ACKNOWLEDGMENTS The authors thank The Horse Trust (The Home of Rest for Horses) for support of L. A. Bradbury in a Clinical Training Scholarship in Anesthesia, Analgesia, and Critical Care and all the staff and students at the Philip Leverhulme Equine Hospital, University of Liverpool, for their help and support, and Garry Anderson for his help with the statistics.
geal hemiplegia in horses. Comp Cont Educ Pract Vet 1991;13: 472–475. 13. Altman DG. Practical statistics for medical research. London: Chapman and Hall; 1991:403–407. 14. Raphel CF. Endoscopic findings in the upper respiratory tract of 479 horses. J Am Vet Med Assoc 1982;181:470–473. 15. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159–174. 16. Hackett RP, Ducharme NG, Fubini SL, Erb HN. The reliability of endoscopic examination in assessment of arytenoid cartilage move-
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