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    Wagner AE, Mama KR, Steffey EP, et al. A comparison of equine recovery characteristics after isoflurane or isoflurane followed by a xylazine-ketamine infusion. Vet Anaesth Analg 2008; 35:154160.

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Evaluation of infusions of xylazine with ketamine or propofol to modulate recovery following sevoflurane anesthesia in horses

Ann E. Wagner DVM, MS1, Khursheed R. Mama DVM2, Eugene P. Steffey VMD, PhD3, and Peter W. Hellyer DVM, MS4
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  • 1 Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523
  • | 3 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523

Abstract

Objective—To determine whether infusion of xylazine and ketamine or xylazine and propofol after sevoflurane administration in horses would improve the quality of recovery from anesthesia.

Animals—6 healthy adult horses.

Procedures—For each horse, anesthesia was induced by administration of xylazine, diazepam, and ketamine and maintained with sevoflurane for approximately 90 minutes (of which the last 60 minutes were under steady-state conditions) 3 times at 1-week intervals. For 1 anesthetic episode, each horse was allowed to recover from sevoflurane anesthesia; for the other 2 episodes, xylazine and ketamine or xylazine and propofol were infused for 30 or 15 minutes, respectively, after termination of sevoflurane administration. Selected cardiopulmonary variables were measured during anesthesia and recovery. Recovery events were monitored and subjectively scored.

Results—Cardiopulmonary variables differed minimally among treatments, although the xylazine-propofol infusion was associated with greater respiratory depression than was the xylazine-ketamine infusion. Interval from discontinuation of sevoflurane or infusion administration to standing did not differ significantly among treatments, but the number of attempts required to stand successfully was significantly lower after xylazine-propofol infusion, compared with the number of attempts after sevoflurane alone. Scores for recovery from anesthesia were significantly lower (ie, better recovery) after either infusion, compared with scores for sevoflurane administration alone.

Conclusions and Clinical Relevance—Xylazine-ketamine or xylazine-propofol infusion significantly improved quality of recovery from sevoflurane anesthesia in horses. Xylazine-ketamine or xylazine-propofol infusions may be of benefit during recovery from sevoflurane anesthesia in horses for which a smooth recovery is particularly critical. However, oxygenation and ventilation should be monitored carefully.

Abstract

Objective—To determine whether infusion of xylazine and ketamine or xylazine and propofol after sevoflurane administration in horses would improve the quality of recovery from anesthesia.

Animals—6 healthy adult horses.

Procedures—For each horse, anesthesia was induced by administration of xylazine, diazepam, and ketamine and maintained with sevoflurane for approximately 90 minutes (of which the last 60 minutes were under steady-state conditions) 3 times at 1-week intervals. For 1 anesthetic episode, each horse was allowed to recover from sevoflurane anesthesia; for the other 2 episodes, xylazine and ketamine or xylazine and propofol were infused for 30 or 15 minutes, respectively, after termination of sevoflurane administration. Selected cardiopulmonary variables were measured during anesthesia and recovery. Recovery events were monitored and subjectively scored.

Results—Cardiopulmonary variables differed minimally among treatments, although the xylazine-propofol infusion was associated with greater respiratory depression than was the xylazine-ketamine infusion. Interval from discontinuation of sevoflurane or infusion administration to standing did not differ significantly among treatments, but the number of attempts required to stand successfully was significantly lower after xylazine-propofol infusion, compared with the number of attempts after sevoflurane alone. Scores for recovery from anesthesia were significantly lower (ie, better recovery) after either infusion, compared with scores for sevoflurane administration alone.

Conclusions and Clinical Relevance—Xylazine-ketamine or xylazine-propofol infusion significantly improved quality of recovery from sevoflurane anesthesia in horses. Xylazine-ketamine or xylazine-propofol infusions may be of benefit during recovery from sevoflurane anesthesia in horses for which a smooth recovery is particularly critical. However, oxygenation and ventilation should be monitored carefully.

In the past 10 to 20 years, anesthetic management of horses undergoing surgery has improved greatly, particularly with regard to the monitoring of arterial blood pressure, treatment of hypotension, prevention of post-anesthetic myopathy, and provision of assisted ventilation. However, recovery from anesthesia still entails risk for both horses and personnel.

Traditionally, induction of anesthesia in horses has been performed by use of drugs administered IV, such as xylazine, guaifenesin or diazepam (or both), and ketamine; however, for maintenance of anesthesia for procedures > 60 minutes in duration, inhalation anesthetic agents such as isoflurane and sevoflurane are recommended.1 An advantage of maintenance with contemporary inhalation anesthetic agents is that they are eliminated from the body mainly through the respiratory tract and do not accumulate during long surgeries or require extensive metabolism for the termination of their effects. However, in horses, the recovery from inhalation anesthesia is often less than ideal and, occasionally, a poor recovery results in serious injuries. Reportedly, 0.2% to 1.6% of recoveries of horses from inhalation anesthesia result in serious or life-ending injuries, such as fractures.2–4 Although these data illustrate the severe consequences of a poor recovery from anesthesia in a few horses, they do not reflect the overall morbidity among horses during recovery in terms of nonterminal injuries such as lacerations, breakdown of surgical incisions, or destruction of bandages and do not account for the time spent by, or injuries incurred by, personnel who attempt to assist these horses.

One study5 conducted to compare sevoflurane and isoflurane anesthesia in horses revealed that sevoflurane resulted in faster and better quality recoveries, compared with recoveries from isoflurane anesthesia, but a more recent report6 indicated no difference in duration or quality of recovery from anesthesia. In recent years, there has been increasing interest in the use of injectable anesthetic agents, such as xylazine, ketamine, propofol, and guaifenesin, for maintenance of anesthesia in horses partly because of reports7,8 published during the 1990s that suggested superior quality of recoveries when injectable drugs were used for maintenance of anesthesia. In 1 study,9 the quality of recovery from anesthesia was considered excellent or good in 35 of 36 (97%) horses in which anesthesia was maintained for 1 hour by use of xylazine-ketamine infusions. However, because of possible prolonged or difficult recoveries associated with excessive accumulation of injectable drugs and the time required for drug metabolism, long-term maintenance of anesthesia with currently available injectable drugs is still not generally recommended.1

To promote improved recoveries following long anesthesia procedures, attempts have been made to combine the advantages of injectable and inhalation anesthetic agents. It was speculated that administration of injectable anesthetic agents for induction and inhalation anesthetic agents for maintenance, followed by administration of injectable drugs at the end of anesthesia could result in an improved quality of recovery from anesthesia. Investigators in 1 study10 evaluated the use of xylazine-ketamine infusions to modify recoveries from isoflurane anesthesia in horses, but only the duration of recovery, not the quality, was increased by a significant margin. Despite the failure of the combination of xylazine and ketamine to result in a clear improvement in recovery from isoflurane anesthesia in horses, the effect of a similar xylazine-ketamine infusion after sevoflurane anesthesia still warrants investigation. In addition, propofol, an injectable anesthetic agent that is associated with rapid, smooth recovery in several species, has been used for both induction and maintenance of anesthesia in horses.8,11–13 In horses, the use of the combination of xylazine and propofol to modify recovery from desflurane anesthesia has been reported to result in an improved quality of recovery but potentially detrimental respiratory depression.14,15

The primary hypothesis for the study reported here was that prolongation of sedation and recumbency by use of a xylazine-ketamine or xylazine-propofol infusion administered during the first 15 to 30 minutes after discontinuation of sevoflurane inhalation would result in an improved quality of recovery from anesthesia in horses, compared with the quality of recovery from sevoflurane anesthesia alone. It was also hypothesized that cardiopulmonary variables in horses would not be negatively impacted by the use of a xylazine-ketamine or xylazine-propofol infusion to modify recovery from sevoflurane anesthesia.

Materials and Methods

The study protocol was reviewed and approved by the Colorado State University Animal Care and Use Committee. Six adult horses (4 Quarter Horses and 2 Thoroughbreds; mean ± SD age, 11.4 ± 3.4 years; body weight, 540 ± 42 kg) were anesthetized 3 times, 1 week apart. Following the recording of baseline (rectal temperature, HR by auscultation, RR, and weight) measurements for each horse during each time, anesthesia was induced by administration of xylazine (1 mg/kg, IV), followed 5 minutes later by administration of diazepam (0.05 mg/kg, IV) and ketamine (2 mg/kg, IV) via a 14-gauge catheter in the right jugular vein. Each horse was positioned in left lateral recumbency on a 30-cm-thick foam pad in a padded recovery stall, with the left (dependent) forelimb advanced cranially and the right (nondependent) forelimb and hind limb elevated slightly to reduce risk of nerve and muscle damage. Anesthesia was maintained by inhalation of sevoflurane in oxygen, delivered via a standard large animal circle breathing system. The HR and heart rhythm were monitored continuously by use of a multichannel vital signs ECG monitor.a A 20-gauge catheter was placed in a transverse facial artery for continuous direct measurement of arterial blood pressureb and periodic measurement of PCV, serum total protein concentration, and pH and analysis of blood gases.c Blood gas values were corrected for each horse's body temperature, which was measured by use of a temperature probea placed in the nasopharynx. To determine the end-tidal sevoflurane concentration, samples of gas were collected continuously from the distal end of a catheter inserted into the endotracheal tube for analysis by use of a quartz crystal agent analyzer.d The agent analyzer was calibrated before and inspected during and after each experiment by use of 3 appropriate sevoflurane standardse and ambient air as a zero reference point. As soon as instrumentation was complete (generally within 10 minutes after intubation), ventilation was mechanically controlled to maintain mean ± SD Paco2 at 45 ± 10 mm Hg, and body temperature was maintained at 37 ± 0.5°C by the use of blankets and heat lamps. Following a 30-minute period for instrumentation and equilibration, each horse was maintained at 1.2 times the reported minimum alveolar concentration for sevoflurane for an additional 60 minutes.16 Mean arterial blood pressure was maintained ≥ 70 mm Hg by administration of dobutamine (1 to 2 μg/kg/min, IV), if necessary. A balanced electrolyte solution was administered IV at a rate of 5 to 7 mL/kg/h, and an indwelling urinary catheter was placed to evacuate the bladder.

After a period of 45 to 50 minutes at 1.2 times the minimum alveolar concentration for sevoflurane anesthesia, each horse was weaned from controlled ventilation to resume spontaneous breathing. Each horse was briefly hoisted so that the thick pad could be removed; each horse was then carefully lowered and repositioned in left lateral recumbency on the floor of the recovery stall, at which time videotape recording of the recovery from anesthesia commenced. At the end of the 60-minute maintenance period (ie, after a 90-minute period of sevoflurane anesthesia), each horse was randomly assigned in a Latin square design to be allowed to recover from sevoflurane anesthesia, receive a xylazine-ketamine infusion to maintain anesthesia for an additional 30 minutes, or receive a xylazine-propofol infusion to maintain anesthesia for an additional 15 minutes. The xylazine-ketamine treatment consisted of administration of a bolus of xylazine (0.15 mg/kg, IV) and ketamine (0.3 mg/kg, IV) at 5 minutes after discontinuation of sevoflurane inhalation, accompanied by the immediate initiation of IV infusion of xylazine (20 μg/kg/min) and ketamine (60 μg/kg/min). The infusion was continued for 30 minutes and resulted in a total duration of anesthesia of 125 minutes for the xylazine-ketamine treatment. The xylazine-propofol treatment did not include administration of a bolus of xylazine but consisted of a bolus of propofol (0.75 mg/kg, IV), delivered over 3 minutes, starting at 5 minutes after and ending 8 minutes after discontinuation of sevoflurane inhalation and accompanied by immediate initiation of IV infusion of xylazine (30 μg/kg/min) and propofol (125 μg/kg/min). The infusion was continued for 15 minutes, resulting in a total duration of anesthesia of 113 minutes for the xylazine-propofol treatment. The bolus and infusion doses and durations for xylazine, ketamine, and propofol were intended to achieve a light plane of anesthesia and were selected on the basis of the authors' experience with xylazine-ketamine and xylazine-propofol infusions in horses as well as information in published reports.10,14,15 After disconnection from the anesthetic breathing circuit, each horse received supplemental oxygen, insufflated at 15 L/min via the endotracheal tube, as long as it remained in lateral recumbency. Heart rate, RR, and MAP were continuously monitored until sevoflurane delivery was discontinued, and values were recorded immediately before administration of the xylazine-ketamine or propofol bolus (5 minutes after termination of sevoflurane administration) and every 5 minutes thereafter during administration of the xylazine-ketamine or xylazine-propofol infusions. Arterial blood gas analyses were performed at 15-minute intervals during the infusions and at the termination of each infusion but not during recovery from anesthesia with sevoflurane alone because it was considered unwise to risk stimulating any of the horses during recovery from sevoflurane anesthesia. Any horse that was apneic for ≥ 2 minutes was manually ventilated at a rate of 1 to 2 breaths/min by use of a demand valve supplying 100% oxygen.

Each horse was allowed to recover without assistance in the same 3.6-m2 padded recovery stall. Recovery was continuously observed through a window in the recovery stall door by 2 observers (one was aware of the treatment received and the other was unaware of the treatment received by the horse under observation), both of whom were experienced at assessing horses during recovery from anesthesia. The mean of the 2 observers' subjective scores for overall quality of recovery (1 = excellent, 2 = good, 3 = fair, 4 = poor, or 5 = unacceptably poor) was calculated to provide an overall recovery score. In addition to an overall recovery score, these observers also assigned scores to each horse, ranging from 1 to 7, specifically for the quality of the recovery to standing. This latter scale assigned numbers according to specific descriptors and events. For example, a score of 1 was assigned when a horse made 1 attempt to stand that was successful and without ataxia, a score of 4 was assigned when a horse made 2 or 3 attempts to stand before it was successful but had evidence of ataxia, and a score of 7 was assigned when a horse made multiple uncoordinated attempts to stand without success or that resulted in injury. Quantitative data, such as the interval from discontinuation of sevoflurane, xylazine-ketamine, or xylazine-propofol delivery to first movement, interval until sternal recumbency, and the number of attempts to achieve sternal recumbency and stand, were also recorded by the observers. The endotracheal tube was removed only after a horse was standing and had coordinated movements. For the xylazine-ketamine and xylazine-propofol treatments, a final arterial blood sample was collected for blood gas analysis within 5 minutes after each horse achieved a standing position.

Statistical analysis—A restricted maximum likelihood-based mixed-effects model for repeated-measures analysis17,f was used to determine the magnitude and significance of differences in mean steady-state and recovery variables and mean changes over time for the 3 treatments. Analyses included the categorical, fixed effects of treatment, time, sequence of treatment application, and treatment-by-time interaction. A first-degree autoregressive correlation structure was used to model the within-subject errors. Satterthwaite approximation was used to estimate denominator df.

The significance of changes in means over time for the additional recovery data obtained from horses receiving the xylazine-ketamine and xylazine-propofol treatments was assessed by use of a mixed-effects model for repeated-measures analysis17,f that included the categorical, fixed effect of time and a random effect of animal. Satterthwaite approximation was used to estimate denominator df. Values of P < 0.05 were considered significant for all analyses.

Results

We did not detect significant differences among treatments in terms of mean baseline body weight, HR, RR, or body temperature or in HR, RR, MAP, Petco2, or blood gas variables measured during steady-state anesthesia (Tables 1 and 2). All horses required dobutamine infusion to maintain MAP ≥ 70 mm Hg during steady-state sevoflurane anesthesia, and there was no difference in mean dobutamine dosage among treatments. During steady-state sevoflurane anesthesia, the mean MAP was significantly higher at the 60-minute time point in horses receiving sevoflurane alone, compared with the MAP in horses receiving the xylazine-ketamine or xylazine-propofol infusions.

Table 1—

Mean ± SD cardiovascular and end-tidal gas values in 6 healthy adult horses during steady-state sevoflurane anesthesia and after discontinuation of sevoflurane administration and subsequent administration of a xylazine-ketamine infusion or xylazine-propofol infusion.

 Steady-state anesthesia (min after initiation of sevoflurane administration)Infusion administration (min after discontinuation of sevoflurane administration)
Variable153045605101520
HR (beats/min)        
  Sevoflurane34 ± 536 ± 437 ± 645 ± 6
  Xylazine-ketamine35 ± 636 ± 639 ± 643 ± 740 ± 629 ± 3a31 ± 928 ± 4
  Xylazine-propofol33 ± 335 ± 435 ± 438 ± 237 ± 640 ± 10b33 ± 531 ± 6
RR (breaths/min)        
  Sevoflurane5 ± 15 ± 16 ± 12 ± 1
  Xylazine-ketamine4 ± 15 ± 15 ± 13 ± 26 ± 59 ± 38 ± 58 ± 4
  Xylazine-propofol5 ± 15 ± 15 ± 14 ± 36 ± 45 ± 74 ± 34 ± 3
MAP (mm Hg)        
  Sevoflurane75 ± 374 ± 277±6 683 ± 10a
  Xylazine-ketamine78 ± 478 ± 378 ± 474 ± 5b83 ± 6108 ± 9110 ± 11113 ± 10
  Xylazine-propofol78 ± 377 ± 577 ± 275 ± 8b84 ± 1197 ± 19107 ± 17107 ± 21
End-tidal sevoflurane concentration (%)        
    Sevoflurane4.29 ± 0.074.26 ± 0.124.27 ± 0.064.39 ± 0.18
    Xylazine-ketamine4.27 ± 0.114.25 ± 0.074.25 ± 0.084.34 ± 0.230.45 ± 0.210.37 ± 0.060.33 ± 0.130.31 ± 0.11
    Xylazine-propofol4.30 ± 0.074.23 ± 0.044.24 ± 0.044.25 ± 0.080.66 ± 0.410.47 ± 0.330.41 ± 0.260.41 ± 0.25
Petco2 (mm Hg)        
  Sevoflurane39 ±339 ± 438 ± 253 ± 10
  Xylazine-ketamine39 ± 340 ± 339 ± 254 ± 751 ± 348 ± 450 ± 447 ± 8
  Xylazine-propofol37 ± 537 ± 538 ± 454 ± 244 ± 741 ± 750 ± 1752 ± 21

Each horse was anesthetized 3 times (once with each treatment), 1 week apart, in a Latin square study design. Anesthesia was maintained with sevoflurane at a steady state for 60 minutes, after which administration of sevoflurane was discontinued and the horses were allowed to recover or were administered an infusion of xylazine (20 μg/kg/min) and ketamine (60 μg/kg/min) for 30 minutes or an infusion of xylazine (30 μg/kg/min) and propofol (125 μg/kg/min) for 15 minutes.

— = Not measured.

Within a variable and time point, values with different superscript letters are significantly (P < 0.05) different.

Table 2—

Mean ± SD blood gas values in 6 healthy adult horses during steady-state sevoflurane anesthesia and during xylazine-ketamine infusion or xylazine-propofol infusion after discontinuation of sevoflurane administration.

 Steady-state anesthesia min after initiation of sevoflurane administration)   
Variable306015 minutes after initiation of infusionEnd of infusionStanding
pH     
  Sevoflurane7.43 ± 0.037.26 ± 0.04
  Xylazine-ketamine7.42 ± 0.027.25 ± 0.037.39 ± 0.077.36 ± 0.047.39 ± 0.07
  Xylazine-propofol7.45 ± 0.047.27 ± 0.057.31 ± 0.107.29 ± 0.097.39 ± 0.04
Pao2 (mm Hg)     
  Sevoflurane360 ± 54179 ± 78
  Xylazine-ketamine374 ± 50193 ± 6580 ± 1583 ± 2974 ± 13
  Xylazine-propofol383 ± 47230 ± 72109 ± 61123 ± 6764 ± 8
Paco2 (mm Hg)     
  Sevoflurane44 ± 473 ± 5
  Xylazine-ketamine45 ± 276 ± 852 ± 1055 ± 5a47 ± 4
  Xylazine-propofol41 ± 670 ± 865 ± 1769 ± 17b53 ± 8
Bicarbonate (mEq/L)     
  Sevoflurane28.2 ± 1.331.7 ± 1.0
  Xylazine-ketamine29.0 ± 1.332.5 ± 1.830.7 ± 2.231.6 ± 1.928.5 ± 5.0
  Xylazine-propofol27.4 ± 2.131.2 ± 1.331.4 ± 2.131.8 ± 2.229.6 ± 4.1
Base excess (mEq/L)     
  Sevoflurane3.7 ± 1.22.3 ± 1.5
  Xylazine-ketamine4.1 ± 1.52.6 ± 1.25.0 ± 1.55.1 ± 1.72.9 ± 5.5
  Xylazine-propofol3.6 ± 1.72.2 ± 1.83.4 ± 2.53.2 ± 2.54.0 ± 4.0

See Table 1 for key.

During xylazine-ketamine and xylazine-propofol infusions, there were no significant differences in mean values of RR, MAP, end-tidal sevoflurane concentration, or Petco2 (Table 1). However, 1 horse was apneic when treated with the xylazine-propofol infusion and was manually ventilated by use of a demand valve at a rate of 2 breaths/min for 20 minutes during and after infusion. When treated with the xylazine-ketamine or xylazine-propofol infusion, horses breathed irregularly during the infusion, with long pauses between breaths, but this was more pronounced during the xylazine-pro-pofol treatment. Mean Paco2 was significantly higher during the xylazine-propofol treatment, compared with the value during the xylazine-ketamine treatment at the end of the respective infusion (Table 2). Mean HR was significantly lower in horses when they received the xylazine-ketamine treatment, compared with horses when they received the xylazine-propofol treatment, only at 10 minutes after initiation of the infusion. One horse developed evidence of second-degree AV block during xylazine-ketamine infusion.

Regarding recovery variables, the intervals from discontinuation of sevoflurane or infusion administration to first movement, first attempt to gain sternal recumbency, and first attempt to stand were significantly longer for horses when they received the xylazine-propofol infusion than those same intervals for horses when they received the xylazine-ketamine infusion (Table 3). The interval to first attempt to gain sternal recumbency and first attempt to stand were significantly longer for horses when they received the xylazine-propofol infusion than those same intervals for horses when they recovered from sevoflurane anesthesia alone. Although not significantly different, the mean number of attempts to achieve sternal recumbency appeared to be higher for horses when they received the xylazine-propofol treatment, compared with the number of attempts to achieve sternal recumbency for horses when they received the xylazine-ketamine treatment or sevoflurane anesthesia alone, but this was because 1 horse made 33 slow, controlled attempts before successfully achieving sternal recumbency after receiving the xylazine-pro-pofol treatment. The number of attempts required to stand successfully was significantly fewer following the xylazine-propofol treatment, compared with the number of attempts to stand successfully following sevoflurane anesthesia alone. However, the time required to achieve sternal recumbency or stand successfully did not differ significantly among treatments. Mean score for quality of standing was significantly lower following the xylazine-propofol treatment, compared with that following sevoflurane anesthesia alone. Mean overall recovery score was significantly lower (ie, better recovery) in horses when receiving the xylazine-ketamine or xylazine-propofol infusion, compared with the recovery score for horses when receiving sevoflurane alone.

Table 3—

Mean ± SD recovery variables in 6 healthy adult horses following steady-state sevoflurane anesthesia and following xylazine-ketamine infusion or xylazine-propofol infusion after discontinuation of sevoflurane administration.

VariableSevoflurane onlyXylazine-ketamine infusionXylazine-propofol infusion
Time to first movement (min)12 ± 6a,b7 ± 7a15 ± 8b
Time to first attempt to sternal recumbency (min)20 ± 10a22 ± 11a33 ± 12b
Time to successfully attain sternal recumbency (min)30 ± 2029 ± 2139 ± 14
No. of attempts to attain sternal recumbency2.7 ± 2.12.8 ± 1.97.9 ± 12.5
Time to first attempt to stand (min)28 ± 14a34 ± 19a47 ± 12b
Time to successfully stand (min)47 ± 3040 ± 1551 ± 7
No. of attempts to stand4.0 ± 1.6a3.3 ± 2.7a,b1.7 ± 0.5b
Score for quality of standing*†4.8 ± 1.1a3.7 ± 1.8a,b2.8 ± 0.7b
Score for overall quality of recovery*‡3.1 ± 0.7a2.5 ± 0.8b2.1 ± 0.2b

Scores are the means of the scores from 2 observers experienced at observing horses recover from anesthesia; 1 was aware of the treatment each horse received and 1 was unaware of the treatment. A lower score indicates a better quality recovery.

Scored on a scale 1 to 7 (1 = stood successfully on first attempt; 7 = multiple, uncoordinated attempts to stand without success or which resulted in injury).

Scored on a scale of 1 to 5 (1 = excellent; 5 = unacceptably poor).

Within a row, values with different superscripts are significantly (P < 0.05) different.

See Table 1 for remainder of key.

Discussion

In the present study, the quality of recovery from sevoflurane anesthesia was improved by the use of xylazine-ketamine or xylazine-propofol infusion after the discontinuation of sevoflurane administration in horses. Results of another study5 in horses indicated that xylazine prolonged the recovery from sevoflurane anesthesia but did not significantly alter the quality of the recovery. The infusion rates and durations for xylazine-ketamine and xylazine-propofol treatments in the present study were the same as those administered after isoflurane or desflurane anesthesia, respectively, in other studies.10,14 Scores for overall quality of the recovery in the present study were significantly lower (ie, better recovery) when horses received the xylazine-ketamine or xylazine-propofol treatment, compared with the scores when horses were anesthetized with sevoflurane alone. When horses received the xylazine-propofol infusion, they required significantly fewer attempts to stand successfully, compared with their attempts to stand following sevoflurane anesthesia alone. Although the times to first movement, first attempt to gain sternal recumbency, and first attempt to stand were significantly longer following the xylazine-propofol treatment, there was no significant difference in the time required to stand successfully among the 3 treatments. These results differ from those of a study10 in horses that were administered xylazine and ketamine after isoflurane anesthesia, in which the xylazine-ketamine treatment prolonged the time to first movement, first attempt to stand, and stand successfully but did not significantly improve the quality of the recovery.

Although the recovery data for the present study, which involved sevoflurane anesthesia, were not compared statistically with the recovery data from another study,10 which involved isoflurane anesthesia, the recoveries of horses when they received sevoflurane alone or a xylazine-ketamine infusion after sevoflurane anesthesia appeared to be no faster, and perhaps slightly slower, than the recoveries of horses that received isoflurane alone or xylazine-ketamine after isoflurane. For example, when horses were administered a xylazine-ketamine infusion after sevoflurane anesthesia, mean times to first movement, sternal recumbency, and successful standing were 7, 29, and 47 minutes, respectively; however, the corresponding times for horses when administered a xylazine-ketamine infusion after isoflurane were 11, 26, and 37 minutes, respectively.10 This was somewhat surprising because sevoflurane has lower blood gas solubility, compared with the blood gas solubility of isoflurane; therefore, sevoflurane should be associated with faster recoveries.18

It is possible that individual horse temperament had a role in recovery times, as has been reported else-where.19 The present study and the aforementioned isoflurane study10 involved 2 population samples of only 6 horses (4 Quarter Horses and 2 Thoroughbreds) and 7 horses (3 Quarter Horses, 3 Thoroughbreds, and 1 Quarter Horse crossbred), respectively. Larger sample sizes in both studies might have yielded different findings. The results of our study also differ from those of another investigation14 in horses in which xylazine and propofol were administered following desflurane anesthesia. In that study,14 the xylazine-propofol treatment significantly prolonged the times for all signs of recovery (nystagmus; movements of ear, limb, or head; swallowing; chewing; and standing). When horses were recovering from sevoflurane anesthesia alone in the present study, they required significantly more attempts to stand successfully than they did when recovering after receiving the xylazine-propofol infusion. Following sevoflurane anesthesia alone, it is probable they tried to stand while they were still uncoordinated, and the xylazine-propofol infusion was beneficial in delaying attempts at moving or standing until the horses were, as stated in 1 report,15 “more thoughtful.”

It is important to recognize that the use of propofol in horses is not necessarily associated with the rapid recoveries expected in humans or dogs. In the present study, mean times to first movement, first attempt to gain sternal recumbency, and first attempt to stand after the xylazine-propofol infusion were significantly longer than the times after the xylazine-ketamine infusion, even though each xylazine-propofol infusion was delivered for only 15 minutes and each xylazine-ketamine infusion was delivered for 30 minutes. Mean time to stand successfully was also longer after the xylazine-propofol infusion, although it was not significantly different from that associated with the xylazine-ketamine infusion.

Administration of xylazine-ketamine infusions without inhalation anesthesia in horses has generally been associated with good- to excellent-quality recoveries,9 which would be equivalent to a recovery score of 1 or 2 on the scale used in the present study. In the present study, administration of a xylazine-ketamine or xylazine-propofol infusion after a period of sevoflurane anesthesia resulted in an improved quality of recovery for horses, compared with the quality of recovery for horses when they were anesthetized with sevoflurane alone. However, the mean ± SD scores for overall recovery quality (2.5 ± 0.8 and 2.1 ± 0.2 for the xylazine-ketamine and xylazine-propofol infusions, respectively) were not quite as favorable as those in another study9 (recovery quality score range, 1.0 to 1.6) in which xylazine and ketamine were administered without inhalation anesthesia. When an infusion of xylazine and ketamine was used to modulate recovery from isoflu-rane anesthesia in horses,10 the overall mean score for recovery quality (2.0) was similar to that of the present study. Therefore, isoflurane and sevoflurane appear to negatively impact the likelihood for an excellent recovery, even when the inhalation agent is discontinued for 15 to 30 minutes before the horse is allowed to recover. The same may not be true for desflurane anesthesia followed by an infusion of xylazine-propofol, which was associated with a mean recovery quality score of 1.2 (ie, an almost excellent recovery).14

Although there were few significant differences in cardiopulmonary variables when the horses in the study reported here were treated with the xylazine-ketamine and xylazine-propofol infusions, caution is warranted when these infusions are used. Both sevoflurane16 and propofol8,11 are profound respiratory depressants. In the present study, xylazine-ketamine and xylazine-propofol infusions were associated with irregular respiratory patterns, such as cluster breathing, in which several rapid breaths were followed by a long pause. When horses were treated with xylazine and propofol, Paco2 was significantly higher at the end of the infusion, compared with the Paco2 when horses were treated with xylazine and ketamine, even though the duration of the xylazine-propofol infusion was shorter than that of the xylazine-ketamine infusion. One horse was apneic and required assisted ventilation for 20 minutes during and after the xylazine-propofol infusion. The highest Paco2 (96 mm Hg) was measured in a horse when it received xylazine and propofol. Other studies14,15 in horses have revealed that apnea was commonly associated with xylazine-propofol infusions following desflurane anesthesia. Respiratory depression associated with infusion of xylazine and propofol following sevoflurane anesthesia may be profound. Horses must be closely observed, supplemental oxygen should be administered, and a demand valve or other means to assist ventilation must be available to prevent or treat severe hypoventilation and hypoxemia during anesthesia.

At the typical ambient barometric pressure (640 mm Hg) in Fort Collins, Colo (elevation, approx 1,500 m), the mean reference Pao2 value for standing, unmedicated horses is 76 mm Hg.g The horses of the present study received oxygen insufflation at 15 L/min via an endotracheal tube during the infusions and early recovery period, and the mean Pao2 values ranged from 80 to 123 mm Hg (Table 2). Interestingly, despite more severe hypoventilation (higher Paco2) at the end of the xylazine-propofol infusions, Pao2 values associated with the xylazine-propofol infusion were generally slightly higher than those associated with the xylazine-ketamine infusion, which suggested that matching of ventilation and perfusion was better with the xylazine-propofol infusion than with the xylazine-ketamine infusion. However, it is also possible that mean Pao2 was skewed in the horses during xylazine-propofol treatment because 1 horse developed apnea and had to be ventilated by use of a demand valve, which likely provided a higher fraction of inspired oxygen than would have been provided by simple oxygen insufflation and resulted in an individual Pao2 of 205 mm Hg. Regardless, administration of supplemental oxygen is highly recommended to prevent clinically important hypoxemia when infusions of either xylazine and ketamine or xylazine and propofol are administered after discontinuation of sevoflurane anesthesia in horses.

In the present study, MAP was generally higher during xylazine-ketamine or xylazine-propofol infusion than during sevoflurane administration, which should alleviate concerns about hypotension associated with these infusion techniques. There are several possible explanations for higher MAP during the infusions. It is possible that the horses were at a lighter plane of anesthesia during the infusions than during sevoflurane administration; they were no longer being mechanically ventilated, and their Paco2 values were typically higher during the infusions. Any or all of these factors may contribute to increased blood pressure.20,21 However, blood pressure is influenced by vascular tone as well as cardiac output, and cardiac output was not measured in the present study. Xylazine causes vasoconstriction as a result of its peripheral α-adrenoceptor agonist effects.22 Therefore, it is also possible that MAP was higher during xylazine-ketamine and xylazine-propofol infusions because of increased vascular tone, and blood flow and perfusion of muscles may not have been any better during xylazine-ketamine or xylazine-propofol infusions than during sevoflurane administration when the MAP was lower.

Xylazine administration is often associated with bradycardia and second-degree AV block.22 In the horses of the present study, mean HR was significantly lower at 10 minutes during the xylazine-ketamine infusion, most likely because the start of the xylazine-ketamine infusion, in contrast to the start of the xylazine-propofol infusion, was accompanied by an additional bolus injection of xylazine given at 5 minutes. One horse developed second-degree AV block during the xylazine-ketamine infusion. However, neither bradycardia nor the AV block was profound enough to cause clinically apparent harm.

Analysis of results of the present study in horses indicated that infusions of xylazine and ketamine or xylazine and propofol administered after sevoflurane anesthesia significantly improved the quality of recovery, compared with the quality of recovery from sevoflurane anesthesia alone. These infusions may be useful to promote smooth recovery from anesthesia in horses in clinical settings, but careful attention and support related to oxygenation and ventilation is required. Further studies may help to refine infusion rates or timing to minimize respiratory depression and further enhance recovery quality.

ABBREVIATIONS

AV

Atrioventricular

HR

Heart rate

MAP

Mean arterial blood pressure

Petco2

End-tidal partial pressure of carbon dioxide

RR

Respiratory rate

a.

Escort II, MDE, Arleta, Calif.

b.

Cobe pressure transducer, Electricom, Denver, Colo.

c.

ABL505, Radiometer Medical A/S, Copenhagen, Denmark.

d.

Biochem 8100, Biochem International Inc, Waukesha, Wis.

e.

Scott Medical Products, Plumsteadville, Pa.

f.

. PROC MIXED, SAS, version 6.11, SAS Institute Inc, Cary, NC.

g.

Mama KR, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado: Unpublished data, 2005.

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Contributor Notes

Supported by a grant from the College Research Council, College of Veterinary Medicine and Biomedical Sciences, Colorado State University.

Presented as an oral abstract at the 8th World Congress of Veterinary Anesthesia, Knoxville, Tenn, September 2003.

The authors thank Tara Raske and Pamela Vogel for technical assistance and Lucien Brevard for assistance in evaluating recoveries.

Address correspondence to Dr. Wagner (aewagner@colostate.edu).