A Comparison of Thiopental, Propofol, and Diazepam-Ketamine Anesthesia for Evaluation of Laryngeal Function in Dogs Premedicated With Butorphanol-Glycopyrrolate
Thiopental, propofol, and diazepam-ketamine were compared for evaluation of laryngeal function in dogs. There was no significant difference among the three protocols in time to observation of normal function after drug administration or in the occurrence of swallowing, laryngospasm, or breathing. Jaw tone was significantly greater with diazepam-ketamine. Exposure of the larynx was excellent in five dogs and moderate in three dogs, each receiving thiopental or propofol. Exposure was excellent in one dog, moderate in six dogs, and poor in one dog receiving diazepam-ketamine. Exposure of the larynx for laryngeal function evaluation is more readily accomplished with thiopental or propofol than with diazepam-ketamine.
Introduction
In a dog with normal laryngeal function, the arytenoid cartilages of the larynx abduct during inhalation and passively relax during exhalation. Laryngeal paralysis results in arytenoid cartilages that are displaced medially and ventrally, remaining in a paramedian location during inhalation. Laryngeal paralysis usually manifests as inspiratory stridor, respiratory distress, or exercise intolerance. Clinical diagnosis of laryngeal paralysis in dogs is usually made by evaluating arytenoid cartilage abduction during inhalation using laryngoscopy under light anesthesia.1–3 Deeper levels of anesthesia will result in a loss of the laryngeal reflex4 and will make the larynx appear to be paralyzed,12 so an anesthetic protocol that allows easy visualization while preserving the laryngeal reflex is essential.
Thiopental,125 propofol,2 and diazepam-ketamine have been used to provide light anesthesia for evaluation of laryngeal function. The objective of this study was to compare these three anesthetic protocols to determine which would be most appropriate for assessing laryngeal function.
Materials and Methods
Animals
Eight healthy, female dogs between 2 and 6 years of age were studied. Prior to assignment to this study, the dogs received a physical examination, were treated for internal and external parasites, were vaccinated, checked for heartworms, and received permanent identification markings (ear tattoo). Dogs weighed an average of 18.4 kg (range, 15.3 to 20.9 kg). Food was withheld for 12 hours prior to the study.
Experimental Protocol
Each dog was anesthetized once with each of three anesthetic protocols (thiopental,a propofol,b diazepam-ketaminec), with a 24-hour period between each anesthetic administration. The order of drug administration was determined by random assignment to one of six schedules: thiopental, propofol, diazepam-ketamine; thiopental, diazepam-ketamine, propofol; propofol, thiopental, diazepam-ketamine; diazepam-ketamine, propofol, thiopental; diazepam-ketamine, thiopental, propofol; and propofol, diazepam-ketamine, thiopental.
After intravenous (IV) catheter placement, butorphanol (0.5 mg/kg body weight) and glycopyrrolate (0.01 mg/kg body weight) were administered IV 5 minutes prior to administration of the designated anesthetic protocol. Thiopental (20 mg/kg body weight, calculated dose), propofol (6 mg/kg body weight, calculated dose), or diazepam (0.5 mg/kg body weight, calculated dose) and ketamine (10 mg/kg body weight, calculated dose) were administered IV until the mouth could be gently pulled open for examination (“to effect”). Anesthetic drug doses were selected based on doses commonly administered to induce anesthesia in clinical patients at the University of Missouri Veterinary Medical Teaching Hospital. Thiopental was administered as a bolus for the first 50% of the volume, and the remainder titrated to effect. Propofol was administered slowly over 1 minute to effect. Diazepam and ketamine were mixed in the same syringe and administered slowly over 1 minute to effect. The same individual administered anesthesia for all dogs and anesthetic protocols. The amount of drug administered for adequate laryngeal exposure was recorded. Dogs were placed in sternal recumbency with the head elevated to the level of normal carriage. The mouth was held open by grasping the upper jaw in one hand and pulling the tongue forward and down between the lower canine teeth using the other hand. The blade of the laryngoscope was directed into the oropharynx, with the tip of the blade positioned under the tip of the epiglottis and angled ventrally to expose the arytenoid cartilages. Assessment of laryngeal function was made as soon after the mouth was opened and visualization of the larynx was possible, and it was performed for all dogs by the same individual, who was blinded to the anesthetic protocol. Time in seconds from drug administration to observation of arytenoid abduction was recorded. Jaw tone was graded from 0 (no jaw tone, easy to open) to 3 (excessive jaw tone, difficult to open). Breathing, swallowing, and laryngospasm were graded as present (score of 1) or absent (score of 0). Overall exposure of the larynx for observation of function was graded as excellent (i.e., mouth easily opened, arytenoid cartilages readily visualized with no swallowing or tongue movement), moderate (i.e., some jaw tone present when opening mouth, some swallowing or tongue movement during visualization of arytenoid cartilages), or poor (i.e., mouth difficult to open, arytenoid cartilages difficult to visualize due to swallowing or tongue movement). Laryngeal function was designated as normal (i.e., abduction during inhalation) or abnormal (i.e., no abduction during inhalation).
Statistical Analysis
A two-way analysis of variance (ANOVA) was used in the analysis of time to normal function (i.e., abduction). Variability between animals was accounted for as a blocking variable. Cochran’s Q test was used to test for differences in the proportion of positive responses for breathing, swallowing, and laryngospasm with each drug protocol. Friedman’s test was used to evaluate differences in jaw tone. A P value of <0.05 was considered significant for all of the above analyses.
Results
Normal laryngeal function was observed in all dogs. Mean time in seconds from drug administration to observation of normal function (i.e., arytenoid abduction) was 51.9±36.3 seconds (mean±standard deviation [SD]) for thiopental, 37.8±24.0 seconds for propofol, and 26.3±7.9 seconds for diazepam-ketamine, and did not differ significantly among the three protocols. Mean percentage of total calculated drug administered was 51.9±5.3% (10.4±1.1 mg/kg body weight) for thiopental; 60.1±13.2% (3.6±0.8 mg/kg body weight) for propofol; and 55.9±10.9% (0.3±0.1 and 5.6±1.1 mg/kg body weight, respectively) for diazepam-ketamine.
One dog experienced apnea after both the thiopental and propofol injections and would breathe only when the arytenoids were stimulated with a cotton-tipped swab. Swallowing occurred in two dogs receiving thiopental, one dog receiving propofol, and five dogs receiving diazepam-ketamine. Laryngospasm occurred in one dog receiving propofol and one dog receiving diazepam-ketamine [see Table]. No significant differences occurred among the three drug protocols for the occurrence of swallowing, laryngospasm, or breathing.
Jaw tone was absent in five dogs receiving thiopental, seven dogs receiving propofol, and one dog receiving diazepam-ketamine; slight in two dogs receiving thiopental; moderate in one dog receiving thiopental, one dog receiving propofol, and six dogs receiving diazepam-ketamine; and strong in one dog receiving diazepam-ketamine [see Table]. There was no significant difference between thiopental and propofol in the amount of jaw tone present after injection. However, the amount of jaw tone present after diazepam-ketamine injection was significantly increased when compared with both thiopental and propofol. Exposure of the larynx was graded as excellent in five dogs receiving thiopental (62.5%), in five dogs receiving propofol (62.5%), and in one dog receiving diazepam-ketamine (12.5%). Exposure was graded as moderate in three dogs receiving thiopental (37.5%), in three dogs receiving propofol (37.5%), and in six dogs receiving diazepam-ketamine (75%). One dog receiving diazepam-ketamine (12.5%) was scored as having poor exposure of the larynx [see Table].
Discussion
Disease or injury involving the caudal laryngeal or recurrent laryngeal nerves or the cricoarytenoideus dorsalis muscle could result in laryngeal paralysis. Laryngeal paralysis may be congenital67 or more commonly may be acquired. Acquired idiopathic laryngeal paralysis usually occurs in older, large-breed dogs, but may be observed in a variety of sizes and breeds of dogs.5 Laryngeal paralysis may be partial or complete, and unilateral or bilateral, with the severity of clinical signs directly related to degree of paralysis. Consequently, dogs with unilateral laryngeal paralysis may have no clinical signs unless they are working or extremely athletic dogs.89 Laryngeal paralysis may be the earliest evidence of a generalized neuropathy or myopathy,9–12 and possible association with hypothyroidism has been suggested.13 The larynx is in a relatively protected position in the dog, but laryngeal paralysis may be trauma induced, may occur as a postsurgical complication, or may be the result of pressure from space-occupying lesions, such as abscesses or tumors.15
Adduction of the arytenoid cartilages after exhalation when the epiglottis has been stimulated is referred to as the laryngeal reflex.4 The laryngeal reflex serves as an endpoint when assessing the level of anesthesia for evaluation of laryngeal function. Deeper levels of anesthesia, such as used to facilitate intubation, will result in loss of this reflex and will make the larynx appear to be paralyzed. To avoid inappropriate diagnosis of laryngeal paralysis, an anesthetic protocol that allows visualization while preserving the laryngeal reflex is essential. The three protocols investigated in this study have the benefit of being administered by titrating “to effect,” which may allow greater control over depth of anesthesia and make them uniquely suitable for assessing laryngeal function.
Before attempting to evaluate laryngeal function, the evaluator should become familiar not only with the anatomy and function of the larynx, but also with the drugs used to provide anesthesia for exposure of the arytenoid cartilages. Thiopental,125 propofol,12 and diazepam-ketamine are anesthetic protocols that have been commonly used to provide light anesthesia for evaluation of laryngeal function. Thiopental is an ultrashort-acting thiobarbiturate that is widely used for induction of anesthesia in dogs. It is typically titrated IV to effect,14 which allows some control over the level of anesthesia that is achieved. Consciousness is regained primarily due to rapid redistribution of the drug. Propofol is an alkyl phenol in an emulsion formulation that is used for induction and maintenance of anesthesia in dogs. It is administered slowly to effect IV. Recovery from propofol is due to rapid redistribution as well as to rapid metabolism, with both hepatic and extrahepatic metabolism occurring.15 Diazepam is a benzodiazepine sedative-hypnotic that has muscle relaxant and anticonvulsant properties. It is commonly combined with ketamine, a dissociative anesthetic, to relieve muscle rigidity and prevent seizure-like activity associated with dissociatives in dogs.16 Ketamine and diazepam are metabolized by the liver, although a percentage of ketamine is excreted unchanged in urine, and some metabolites of diazepam may be active. Some pharyngeal reflexes are preserved with this combination, which may make visualization of the larynx difficult.
The time from initial drug administration to observation of normal function was not significantly different among the three drug protocols in this study. However, laryngospasm occurred more frequently, and jaw tone was significantly increased with the diazepam-ketamine protocol. Consequently, overall exposure was more readily accomplished with thiopental or propofol when compared with diazepam-ketamine.
Deep inspiration is essential for accurate evaluation of laryngeal function. In this study, spontaneous breathing was preserved in all but one dog. Arytenoid activity can be very difficult to evaluate during shallow breathing or apnea and should be correlated with the phase of the respiratory cycle. Paralyzed arytenoid cartilages may actually be pushed outward during exhalation and give the appearance of abduction, or they may paradoxically be sucked inward due to the negative pressure generated during inhalation, giving the impression of adduction.2 This emphasizes the need for as light an anesthetic level as possible while still allowing exposure for evaluation. In a preliminary study, it was determined that light anesthesia was difficult to achieve and maintain without premedication.d However, because many of the patients undergoing laryngeal examination are also in some degree of respiratory distress, a very mild sedative with minimal respiratory depression would be desirable. In the present study, premedication with butorphanol was selected based on its mild sedative effects and minimal depression of respiration. Certainly, the doses of anesthetic drugs and the character of the laryngeal examination may differ if butorphanol were omitted from the protocol.
In this study, laryngeal function in normal dogs was determined while comparing three different anesthetic protocols. It may be convenient to infer from this study that anesthetic protocols that facilitate recognition of the presence or absence of normal arytenoid function would also be appropriate for evaluation of subtle changes in function. However, determining the appropriateness of these protocols for evaluating subtle changes in arytenoid function is beyond the intent and scope of this study.
Conclusion
Normal laryngeal function was observable with the three protocols investigated in this study. However, the overall exposure score indicates that visualization of the larynx in dogs premedicated with butorphanol is more readily accomplished with thiopental (10.4±1.1 mg/kg body weight) or propofol (3.6±0.8 mg/kg body weight) when compared with diazepam-ketamine (0.3±0.1 mg/kg body weight and 5.6±1.1 mg/kg body weight, respectively).
Pentothal; Abbott Laboratories, North Chicago, IL
Rapinovet; Schering-Plough Animal Health Corp., Union, NJ
Abbott Laboratories, North Chicago, IL Ketaject; Phoenix Pharmaceutical, Inc., St. Joseph, MO
Gross ME, Dodam JR. Personal communication.
Acknowledgment
The authors acknowledge the generosity of Mallinckrodt-Shering (presently Shering-Plough) in donating propofol for this study.
