Recovery characteristics of dogs following anesthesia induced with tiletamine-zolazepam, alfaxalone, ketamine-diazepam, or propofol and maintained with isoflurane

Chiara E. Hampton 1Department of Clinical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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Thomas W. Riebold 1Department of Clinical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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Ronald E. Mandsager 1Department of Clinical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.
1Department of Clinical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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Abstract

OBJECTIVE To compare characteristics of recovery from isoflurane anesthesia in healthy nonpremedicated dogs after anesthetic induction by IV administration of tiletamine-zolazepam with those observed after induction by IV administration of alfaxalone, ketamine-diazepam, or propofol.

DESIGN Prospective, randomized crossover study.

ANIMALS 6 healthy adult hounds.

PROCEDURES Each dog underwent the 4 treatments in random order with a ≥ 7-day washout period between anesthetic episodes. Anesthesia was induced by IV administration of the assigned induction drug or combination (each to effect in 25% increments of calculated dose) and maintained with isoflurane in oxygen for 60 minutes. Cardiorespiratory variables and end-tidal isoflurane concentration (ETISO) were measured just before isoflurane administration was discontinued. Dogs were observed and video recorded during recovery. Recovery characteristics were retrospectively scored from recordings by 3 raters. Interrater and intrarater reliability of scoring was assessed by intraclass correlation coefficient calculation. Linear and mixed ANOVAs were used to compare extubation times, recovery scores, and body temperature among treatments.

RESULTS Most cardiorespiratory variables, body temperature, ETISO, and time to extubation did not differ between tiletamine-zolazepam and other induction treatments. Recovery scores were lower (indicating better recovery characteristics) with propofol or alfaxalone than with tiletamine-zolazepam but did not differ between tiletamine-zolazepam and ketamine-diazepam treatments. Anesthetic episode number and ETISO had no effect on extubation time or recovery score. Intrarater and interrater correlations for recovery scores were excellent.

CONCLUSIONS AND CLINICAL RELEVANCE Recovery of healthy dogs from anesthesia with isoflurane after induction with tiletamine-zolazepam was uncomplicated and had characteristics comparable to those observed following induction with ketamine-diazepam. However, recovery characteristics were improved when anesthesia was induced with propofol or alfaxalone.

Abstract

OBJECTIVE To compare characteristics of recovery from isoflurane anesthesia in healthy nonpremedicated dogs after anesthetic induction by IV administration of tiletamine-zolazepam with those observed after induction by IV administration of alfaxalone, ketamine-diazepam, or propofol.

DESIGN Prospective, randomized crossover study.

ANIMALS 6 healthy adult hounds.

PROCEDURES Each dog underwent the 4 treatments in random order with a ≥ 7-day washout period between anesthetic episodes. Anesthesia was induced by IV administration of the assigned induction drug or combination (each to effect in 25% increments of calculated dose) and maintained with isoflurane in oxygen for 60 minutes. Cardiorespiratory variables and end-tidal isoflurane concentration (ETISO) were measured just before isoflurane administration was discontinued. Dogs were observed and video recorded during recovery. Recovery characteristics were retrospectively scored from recordings by 3 raters. Interrater and intrarater reliability of scoring was assessed by intraclass correlation coefficient calculation. Linear and mixed ANOVAs were used to compare extubation times, recovery scores, and body temperature among treatments.

RESULTS Most cardiorespiratory variables, body temperature, ETISO, and time to extubation did not differ between tiletamine-zolazepam and other induction treatments. Recovery scores were lower (indicating better recovery characteristics) with propofol or alfaxalone than with tiletamine-zolazepam but did not differ between tiletamine-zolazepam and ketamine-diazepam treatments. Anesthetic episode number and ETISO had no effect on extubation time or recovery score. Intrarater and interrater correlations for recovery scores were excellent.

CONCLUSIONS AND CLINICAL RELEVANCE Recovery of healthy dogs from anesthesia with isoflurane after induction with tiletamine-zolazepam was uncomplicated and had characteristics comparable to those observed following induction with ketamine-diazepam. However, recovery characteristics were improved when anesthesia was induced with propofol or alfaxalone.

In veterinary patients, a good quality of recovery from general anesthesia is characterized by quiet, coordinated movements with sternal recumbency and standing achieved in single attempts. Excitement upon recovery results in increased circulating concentrations of catecholamines and greater oxygen consumption, which can be harmful for patients with cardiovascular, respiratory, and metabolic compromise.1 Poor recoveries are characterized by vocalization, lack of coordination, thrashing of limbs, paddling, excitement, disorientation, lacrimation, and salivation.2–5 A search of the current literature found a lack of studies that compared recovery quality following induction of anesthesia by IV administration of tiletamine-zolazepam with that following induction with alfaxalone, ketamine-diazepam, or propofol in dogs.

The purpose of the study reported here was to assess recovery characteristics in healthy adult dogs after anesthetic induction by IV administration of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, or propofol and maintenance with isoflurane in oxygen. We hypothesized that, in nonpremedicated dogs, there would be no difference in extubation time and recovery quality after induction with tiletamine-zolazepam, compared with results of the other treatments.

Materials and Methods

Dogs

Six healthy adult hound-type dogs owned by Oregon State University were enrolled in the study. The sample size was chosen on the basis of previous prospective studies6,7 that evaluated the effects of anesthetic agents and found that a sample size of 6 animals produced valid results. The study population included 3 sexually intact males and 3 sexually intact females; the mean ± SD body weight and age were 22.1 ± 2.6 kg (48.6 ± 5.7 lb) and 14.6 ± 3 months, respectively. All dogs were considered healthy (American Society of Anesthesiologists health status I) on the basis of results of a physical examination, CBC, and serum biochemical analysis.

Dogs were acclimated to the housing facility for 1 week prior to the start of the study. Food but not water was withheld for 12 hours before each anesthetic episode. Ethical approval for the study was obtained from the Oregon State University Institutional Animal Care and Use Committee (No. 4504).

Procedures

The study was designed as a prospective, blinded, randomized, crossover study. Induction protocol and monitoring procedures were previously described for a concurrently performed study.8 A commercially available randomization toola was used to randomize dog selection and treatment order in a manner that ensured each dog would undergo each of 4 induction treatments (tiletamine-zolazepam,b alfaxalone,c ketamined-diazepam,e or propofolf) once. Induction was followed by inhalation anesthesia with isoflurane and monitoring through recovery. A washout period of ≥ 7 days was provided between anesthetic episodes. Although administration of sedative and tranquillizing agents prior to induction of anesthesia is advised as part of a balanced anesthetic protocol, premedicants were not administered to avoid the presence of confounding factors.

For each induction treatment, an 18-gauge IV catheterg was placed in the right saphenous vein with an aseptic technique. The assigned induction drug or combination was administered IV in 25% increments of the total estimated dose over 10 seconds, with a 15-second pause between increments, until tracheal intubation could be performed. All intubations were performed by 1 individual. Criteria for attempting intubation were lack of spontaneous movement of the head when opening of the mouth was attempted and lack of voluntary tongue retraction. Lack of jaw tone, palpebral reflex, or swallowing movements were not adopted for this purpose because the criteria were not considered useful owing to the nature of some tested induction drugs; these features are known to be maintained in patients that receive dissociative agents, even if anesthetized, but they are lost after induction with alfaxalone and propofol.9 An additional dose consisting of 25% of the calculated induction dose of the same assigned treatment was available if intubation conditions were not deemed adequate after administration of the full calculated dose. The calculated doses were as follows: tiletamine-zolazepam, 5 mg/kg (2.27 mg/lb); alfaxalone, 4 mg/kg (1.81 mg/lb); ketamine, 7 mg/kg (3.18 mg/lb), and diazepam, 0.3 mg/kg (0.14 mg/lb); and propofol, 6 mg/kg (2.73 mg/lb). The doses of induction agents used were consistent with doses for tiletamine-zolazepam,10 alfaxalone,11,12 ketamine-diazepam,13 and propofol11,12,14 available in the literature for nonsedated dogs.

Anesthesia was maintained with isofluraneh in oxygen (40 mL/kg/min [18.2 mL/lb/min], titrated to achieve absence of palpebral reflex and ventromedial position of the eye globe). A circle systemi and a precision vaporizer were used to deliver the anesthetic gas mixture. A multiparameter monitorj was used to monitor heart rate and hemoglobin oxygen saturation via pulse oximetry, cardiac rhythm via electrocardiography, and mean arterial pressure measured with a direct technique. A 20-gauge, 40-mm catheterg was placed in the right dorsal pedal artery and connected via noncompliant tubing to a mercury column–calibrated blood pressure transducerk leveled at the height of the manubrium and zeroed at atmospheric pressure. Cardiac output was measured with a Swan-Ganz catheterl and thermodilutionm technique, and oxygen delivery and stroke volume were calculated. Respiratory rate, end-tidal concentration of carbon dioxide, and anesthetic concentrations were monitored with a gas analyzern and sidestream technique, and Pao2 and Paco2 were measured with a blood gas analyzer.o The gas analyzer was calibrated with a mixturep of oxygen, desflurane, and carbon dioxide according to the manufacturer's recommendations 60 minutes prior to induction of anesthesia. Cardiorespiratory variables and blood gases were measured at regular intervals for the concurrent study8 throughout the anesthetic episode (60 minutes). Body temperature was continuously monitored via esophageal probe placed at the level of the tenth intercostal space, with placement confirmed by fluoroscopy. Lactated Ringer solutionq was administered via IV catheter at a rate of 5 mL/kg/h. Active heating was provided during each anesthetic episode by means of a warm-air blowing devicer and blankets with the goal of maintaining body temperature between 37.8° and 39°C (100.04° and 102.2°F).

Dogs were allowed to recover in kennels to which they had previously been acclimated. Prior to disconnection from the anesthetic breathing system, the ETISO was recorded. Dogs were disconnected from the breathing circuit without prior alteration in oxygen flow rate and were allowed to breathe room air during recovery. Criteria for extubation were presence of strong palpebral reflexes and 2 consecutive swallowing movements within a 10-second period. One investigator (CEH) monitored the dogs during recovery. The investigator who visually monitored dogs during recovery was unaware of the induction treatment used. A dose of dexmedetomidinet (1μg/kg [0.45 μg/lb], IV) was available as a rescue drug if deemed necessary (eg, if flailing occurred for > 2 minutes or other excitement with the potential to cause direct injury to the dog was observed). Extubation time was defined as the time from the end of isoflurane administration to when extubation criteria were met, and it was recorded at the time of the anesthetic episode.

A video camerau was positioned to record recovery periods (30 min/episode) starting when isoflurane administration was discontinued and the dog was placed in a recovery kennel. Twenty-four videos (1/dog/treatment) were recorded, and each was reviewed by 3 raters (CEH, TWR, and REM) on 2 occasions (sets 1 and 2) 30 days apart. The raters were blinded to the induction treatment at the time of scoring for each video set. For each set of recordings, videos were randomized for sequence of evaluation with a randomizing sequence tool.v To help ensure assessments were performed in a blinded manner, videos were scored 6 months after the anesthesia experiments ended. The scoring system for recovery from anesthesia was modified from scales described in the literature.12,15 Factors assessed during scoring were struggling and excitement, paddling and flailing, vocalization, and administration of rescue drugs (performed if struggling, excitement, or paddling and flailing were prolonged and endangered the safety of the dog). Each set of clinical signs was assigned a score from 0 to 3 (0 = none; 1 = transient, easily calmed by the investigator's voice; 2 = prolonged [> 1 minute]; and 3 = persistent [or requiring restraint]). Rescue drug administration was assigned a score of 0 (not given) or 3 (given). The range of possible scores was 0 to 12, with lower scores indicative of better recovery quality. The mean of recovery scores for set 1 from the 3 raters was used in the statistical analysis model for comparison of recovery quality among treatments.

Statistical analysis

Distribution of data was assessed with a Shapiro-Wilk test. Data were parametric and are presented as mean ± SD. Data from cardiorespiratory and blood gas analysis variables were tested with repeated-measures ANOVA for differences among time points (ie, prior to induction, immediately after induction, and at 10, 20, 40, and 60 minutes after induction) and among treatments. If a significant difference was detected among induction regimens at the 60-minute time point, a post hoc Student t test was used to compare tiletamine-zolazepam with the other induction regimens. A Bonferroni correction was then applied (with values of P < 0.017 deemed significant). A mixed ANOVA was used to test the linearity of body temperature. Slope for the interaction was calculated and tested to detect differences among induction regimens. A multifactor ANOVA that accounted for induction agent (fixed factor), anesthetic episode (fixed factor), dog (fixed factor), final concentration of ETISO (continuous factor), and final body temperature (continuous factor) was used to test for differences in mean extubation times and recovery scores. An ANOVA used to evaluate recovery scores was modeled to include the mean of scores for the 3 raters and individual rater scores from set 1 video recordings. If a significant difference was found, a post hoc Tukey test was used for pairwise comparisons. Results for comparisons of extubation time and recovery scores are reported as the difference from a referent category for each of the categorical variables (treatment [tiletamine-zolazepam], anesthetic episode [episode 1], dog [dog 1], and rater [rater 1]). Therefore, the generated coefficients represented differences in time (seconds) or scores as applicable from results for these referents. Data for the 2 linear models for extubation time and mean recovery scores were entered in a scatterplot to verify their relationship. Intrarater and interrater reliability for recovery score assignment was tested by calculation of 2-way random effect model ICCs with 95% confidence intervals. The ICCs were classified as follows: < 0.4 = poor; 0.4 to 0.59 = fair; 0.6 to 0.74 = good; and 0.75 to 1 = excellent.16 A paired t test was used to compare recovery scores for set 1 and set 2 for each rater. A mixed repeated-measures ANOVA that accounted for induction agent (fixed factor), dog (random factor), anesthetic episode (fixed factor), and time point (ie, prior to induction, immediately after induction, and at 10, 20, 40, and 60 minutes after induction; fixed factor) was used to test for the difference in body temperature between time points and among treatments. Residuals of the mixed ANOVA models were normally distributed. Values of P < 0.05 were considered significant except as noted for Bonferroni correction. An open-access statistical software programw was used.

Results

Delivered IV drug doses for anesthetic induction and cardiorespiratory variables were previously reported.8 Doses were as follows: tiletamine-zolazepam, 3.8 ± 0.8 mg/kg (1.7 ± 0.4 mg/lb); alfaxalone, 2.8 ± 0.3 mg/kg (1.3 ± 0.1 mg/lb); ketamine-diazepam, 6.1 ± 0.9 mg of ketamine/kg (2.8 ± 0.4 mg/lb) plus 0.26 ± 0.04 mg of diazepam/kg (0.1 ± 0.02 mg/lb); and propofol, 5.4 ± 1.1 mg/kg (2.5 ± 0.5 mg/lb). Intubation was quickly and smoothly performed, except for 1 occasion in which an additional dose of propofol was necessary to allow intubation of 1 dog. Most cardiorespiratory variables measured just prior to discontinuation of isoflurane (heart rate [P = 0.086], mean arterial pressure [P = 0.134], cardiac output [P = 0.178], oxygen delivery [P = 0.071], respiratory rate [P = 0.598], end-tidal CO2 concentration [P = 0.942], ETISO [P = 0.569], Paco2 [P = 0.075], and Pao2 [P = 0.987]) did not differ among treatments. Before discontinuation of isoflurane, ETISO was 1.2 ± 0.1%, 1.3 ± 0.1%, 1.3 ± 0.1%, and 1.2 ± 0.1% for dogs that received tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol, respectively, for induction of anesthesia.8 Stroke volume was significantly (P = 0.04) lower after tiletamine-zolazepam treatment (30.5 ± 4.1 mL) than after propofol administration (37.4 ± 3.7 mL) but did not differ significantly from that after alfaxalone (33 ± 5 mL; P = 0.156) or ketamine-diazepam (32 ± 3 mL; P = 0.923) treatment.8 Mean body temperature for all treatments was 37.2 ± 0.4°C (98.9 ± 0.9°F) before discontinuation of anesthesia and did not differ among treatment groups; body temperature decreased linearly (slope, 0.27°C/60 minutes; P < 0.001), and this variable was independent of the induction regimen used.8

All dogs recovered from anesthesia in each episode without complications; none required the rescue treatment, and all were returned to their routine housing ≤ 2 hours after isoflurane administration was discontinued. One video recording (after ketamine-diazepam treatment) was excluded from analysis because of technical difficulties during recording. Therefore, 23 video recordings were analyzed. All dogs had recovery scores of 0 for 2 of the 4 rated factors (vocalization and administration of rescue drugs). No dogs had a score of 3 for struggling and excitement or paddling and flailing.

After accounting for the factors included in the ANOVA model, extubation times did not differ significantly (P = 0.368) for propofol, alfaxalone, or ketamine-diazepam treatments, compared with tiletamine-zolazepam treatment (Table 1). Body temperature (P = 0.169) and final ETISO (P = 0.2) had no effect on recovery time. Dog 5 consistently had longer extubation time (a difference of 7.8 minutes; P = 0.04), compared with dog 3, independent of induction treatment.

Table 1—

Comparison of extubation times and recovery scores for 6 healthy nonpremedicated adult dogs in a randomized crossover-design study to compare characteristics of recovery from isoflurane anesthesia after induction with tiletamine-zolazepam with those observed after induction with alfaxalone, ketamine-diazepam, or propofol (each given IV to effect in 25% increments of the calculated dose).

VariableExtubation time (min)P valueRecovery scoreP value
Induction treatment
 Tiletamine-zolazepam12.7 ± 5.31.4 ± 1.4
 Alfaxalone11.5 ± 40.9980.8 ± 1.20.008
 Ketamine-diazepam11.3 ± 4.30.9691.9 ± 1.20.078
 Propofol9.3 ± 3.80.570.5 ± 0.8< 0.001
Anesthetic episode
 110.3 ± 6.10.7 ± 1.2
 212 ± 5.50.9511.3 ± 1.30.881
 311.5 ± 2.90.8471.2 ± 1.40.521
 411 ± 2.40.9971.5 ± 1.10.237
Dog
 110.7 ± 2.21.2 ± 1.1
 213.7 ± 2.90.9980.9 ± 1.20.405
 36.75 ± 2.20.9682.3 ± 1.10.004
 47.7 ± 4.20.9991.3 ± 1.40.655
 515.5 ± 3.40.4300.58 ± 1.10.066
 612.7 ± 3.60.9471.3 ± 1.20.655
Rater
 12.3 ± 1.4
 20.7 ± 1< 0.001
 30.7 ± 0.7< 0.001

Results are reported as mean ± SD. Extubation time was measured from the time that administration of isoflurane in oxygen was discontinued. Recovery was video recorded and retrospectively scored (range of possible scores, 0 [best quality] to 12 [worst quality]) on 2 occasions by 3 raters who were unaware of the anesthetic induction treatment given; results for the first set of video recordings were used for analysis.

The P values are shown for the reported difference from the referent category (treatment = tiletamine-zolazepam, dog = dog 1, anesthetic episode = epsiode 1, and rater = rater 1). Values of P < 0.05 were considered significant.

— = Not applicable.

Analysis of recording set 1 revealed that, after controlling for the effects included in the linear model, mean recovery scores from all raters were significantly lower for dogs that received propofol (P < 0.001) or alfaxalone (P = 0.008), but not ketamine-diazepam (P = 0.078), compared with dogs that received tiletamine-zolazepam (Table 1). Dog 3 consistently had higher recovery scores (P = 0.004), compared with the referent (dog 1), independent of induction treatment. Visual analysis of the scatterplot for extubation time versus recovery score revealed a cluster of recovery scores ≤ 1 for dogs extubated between 10 and 16 minutes after isoflurane administration was discontinued (Figure 1). Agents highly represented in this area were propofol and alfaxalone.

Figure 1—
Figure 1—

Scatterplot of extubation time versus recovery score (mean values) for 6 healthy nonpremedicated dogs in a randomized crossover-design study to compare characteristics of recovery from isoflurane anesthesia after induction with tiletamine-zolazepam (squares) with those observed after induction with alfaxalone (black triangles), ketamine-diazepam (circles), or propofol (white triangles). Dose was calculated for the assigned induction drugs, and each was given IV to effect in 25% increments. The maintenance period for isoflurane in oxygen was 60 minutes; extubation time was measured from the end of isoflurane delivery. Recovery was video recorded and retrospectively scored on 2 occasions by 3 raters who were unaware of the anesthetic induction treatment given; mean results for the first set of video recordings were used for analysis. The range of possible scores was 0 to 12, with lower scores indicative of better recovery quality. The circle depicts a cluster of recovery scores ≤ 1.0.

Citation: Journal of the American Veterinary Medical Association 254, 12; 10.2460/javma.254.12.1421

The total recovery scores (from set 1 video recordings) assigned by raters 2 and 3 were lower than those assigned by rater 1 (Table 1). Rater 1 consistently scored recovery in set 2 recordings lower than in set 1 (P < 0.001). Intrarater reliability of scores between set 1 and set 2 recordings (rater 1 ICC, 0.86 [95% CI, 0.68 to 0.94]; rater 2 ICC, 0.76 [95% CI, 0.45 to 0.9]; and rater 3 ICC, 0.77 [95% CI, 0.45 to 0.9]), and interrater reliability (ICC, 0.91 [95% CI, 0.82 to 0.96]) of scores for duplicate recovery evaluations were excellent.

Discussion

In the present study, there was no difference in extubation time after isoflurane anesthesia among healthy dogs that underwent anesthetic induction with tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol. A brief period of emergence delirium manifesting as a hyperactive motor behavior in the immediate postanesthetic period was occasionally observed as paddling, flailing of short duration, and brief excitement with all tested treatments. However, all dogs recovered without complications and were returned to their routine housing facility ≤ 2 hours after the end of each anesthetic episode. The lack of difference in ETISO just prior to the end of inhalation anesthesia among dogs that received the 4 induction treatments was interpreted as indicating a similar anesthetic depth at the start of recovery. Analysis of cardiorespiratory and metabolic variables at the same time provided further evidence to support that all dogs had similar cardiovascular and respiratory performance at a similar anesthetic plane. Stroke volume was the only cardiovascular variable that differed significantly among treatments (lower after tiletamine-zolazepam treatment than after propofol treatment). This hemodynamic difference could potentially have delayed inhalation anesthetic elimination and prolonged recovery (as evidenced by extubation time), although oxygen delivery and cardiac output did not differ among treatments. Administration of various premedications, anesthetic induction agents, and anesthetic maintenance drugs as well as body temperature have been reported to affect recovery quality and extubation time in dogs.17 In the present study, administration of different induction agents was found to have an effect on recovery quality but not on extubation time.

Drug doses used in the present study were slightly lower than those in other investigations that included nonpremedicated dogs,10,18–21 and this factor may have contributed to the short extubation times in our study. Recovery scores after tiletamine-zolazepam treatment were higher (indicating poorer recovery quality) than those after propofol or alfaxalone treatment but were similar to those assigned after ketamine-diazepam treatment. Pablo and Bailey18 suggested that maintenance of anesthesia with inhalation agents (halothane and isoflurane) markedly improves recovery quality after induction with tiletamine-zolazepam in dogs, especially after long anesthetic episodes, implying that maintenance with isoflurane could ameliorate the excitatory effects of tiletamine in this species.

One dog in the study cohort had a significantly longer extubation time than another, irrespective of induction treatment, and this was not accompanied by a worsening in recovery scores. Further diagnostic testing to investigate this phenomenon was not carried out because the dog had already been discharged from the study at the time of statistical analysis. One other dog had significantly worse recovery scores than the referent dog, and this appeared to be associated with the shortest extubation time, although the latter finding was nonsignificant. On the basis of visual analysis of the scatterplot for the relationship between extubation time and recovery scores, we defined a time window of approximately 6 minutes, starting 10 minutes after isoflurane administration was discontinued, in which high-quality recoveries occurred, primarily in dogs that received alfaxalone or propofol. This finding represents an important clinical consideration for veterinary practitioners because it provides new information on predictability (between 10 and 16 minutes) and quality of recovery (score < 1) for healthy unpremedicated dogs that could potentially be used to define an optimal recovery. Furthermore, the results suggested that a clinician could choose to use an IV induction with alfaxalone or propofol (vs a dissociative agent) before maintenance of anesthesia with isoflurane for procedures not requiring administration of sedative or analgesic agents in healthy dogs for which a smooth and predictable extubation time is desirable.

Limitations of the present study included the short duration (30 minutes) of recordings used to score recovery for all dogs and the inability to use one of the video recordings for recovery evaluations. Furthermore, these results were obtained for recoveries of healthy dogs that were not premedicated with injectable sedative or analgesic agents, and the use of premedicants would likely change the recovery window of time as well as recovery quality. The small sample size of dogs enrolled in this study likely increased the potential for type II errors, and it is possible that we erroneously failed to reject the null hypothesis that extubation time of dogs would not differ between tiletamine-zolazepam and other treatments. However, on the basis of the study results, we did reject the null hypothesis that recovery quality of dogs would not differ between tiletamine-zolazepam and other treatments. Induction of anesthesia with tiletamine-zolazepam and recovery following maintenance with isoflurane in oxygen for 60 minutes were uncomplicated and comparable to results achieved with ketamine-diazepam in this group of healthy adult dogs. Although these dissociative drug combinations are commonly and safely used in clinical practice, induction with propofol or alfaxalone provided a more predictable alternative in terms of extubation time and quality of recovery in this study.

Acknowledgments

This manuscript represents a portion of a thesis submitted by Dr. Hampton to the Oregon State University Department of Clinical Sciences as partial fulfillment of the requirements for a Master of Science degree.

Funded in part by Zoetis Inc. Funding sources did not have any involvement in the study design, data analysis and interpretation, or writing and publication of the manuscript.

The authors thank Darci Palmer and April Simons for technical assistance during the study and Dr. Chin Chi Liu for assistance with statistical analysis.

ABBREVIATIONS

ETISO

End-tidal isoflurane concentration

ICC

Intraclass correlation coefficient

Footnotes

a.

Microsoft Excel 2014, Microsoft Corp, Redmond, Wash.

b.

Zoetis Inc, Kalamazoo, Mich.

c.

Alfaxan, Jurox Inc, Kansas City, Mo.

d.

Zetamine, VetOne, Boise, Idaho.

e.

Hospira, Lake Forest, Ill.

f.

PropoFlo, Abbott, North Chicago, Ill.

g.

BD, Franklin Lakes, NJ.

h.

Isoflo, Abbott Animal Health, Abbott Park, Ill.

i.

Excel 210 MRI Compatible, Ohmeda, Madison, Wis.

j.

Spectrum, Datascope Corp, Mahawah, NJ.

k.

DTXPlus, BD Medical Systems, Sandy, Utah.

l.

Edwards Lifescience, Irvine, Calif.

m.

Mac-Lab TRAM 451 Marquette, GE Medical Systems, Chicago, Ill.

n.

Gas Module GE, Datascope Corp, Mahawah, NJ.

o.

RAPIDlab 1200 system, Siemens, Munich, Germany.

p.

Airgas Specialty Gases Inc, Lenexa, Kan.

q.

Hospira, Lake Forest, Ill.

r.

Bair Hugger, Arizant Inc, Eden Prairie, Minn.

s.

Jorgensen Laboratories Inc, Loveland, Colo.

t.

Dexdomitor, Zoetis, Kalamazoo, Mich.

u.

GoPro, San Mateo, Calif.

v.

RANDOM.ORG true random number generator. Available at: www.random.org. Accessed Jan 2, 2015.

w.

R: a language and environment for statistical computing, version 3.0, R Foundation for Statistical Computing, Vienna, Austria.

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