Success or failure of some ophthalmic surgical procedures may depend in part on the ability to prevent or reduce intraocular hypertension. During open ophthalmic procedures or in patients with deep corneal ulcers or penetrating eye wounds, it is extremely important to maintain a low (but within reference range) IOP because decompression of a hypertensive eye may cause serious damage, including iris or lens prolapse, vitreous loss or expulsive choroidal hemorrhage, and possibly loss of vision.1,2
Most of the drugs commonly used for induction and maintenance of anesthesia will decrease IOP. The mechanism of action involves direct effects through action on central diencephalic control centers, inhibition of production of aqueous humor, increase in drainage of aqueous humor, and relaxation of extraocular muscles or indirect effects through cardiovascular and respiratory systems.2–5 Thiopental sodium and propofol are consistently associated with a significant decrease in IOP in humans,4,6–8 and these agents have been considered suitable for induction of anesthesia of patients undergoing open ophthalmic procedures or repair of penetrating eye injuries. On the other hand, thiopental induces a nonsignificant transient increase in IOP9 and propofol has been associated with no change10 or an increase in IOP in dogs.9,11,12 Species-specific differences in responses to these drugs (including effects on extraocular muscle tone, scleral rigidity, and aqueous humor production or drainage) might explain these conflicting results.9,11
In children, ketamine hydrochloride typically increases IOP13–15; however, this effect seems to be attenuated by low doses of ketamine.14 In dogs, ketamine has been associated with mild and nonsignificant increases in IOP.16,17 However, other studies18–20 in dogs, cats, and rabbits have revealed significant increases in IOP following ketamine administration. The postulated mechanisms for the increase in IOP associated with ketamine involve an increase in choroidal blood flow as a result of an increase in blood pressure and also an increase in extraocular muscle tone.13
Xylazine hydrochloride is an α2-adrenoreceptor agonist commonly used in horses for sedation and muscle relaxation. In horses, xylazine also significantly decreases IOP,21,22 although 1 study23 revealed a small effect of xylazine treatment in horses with no further change in IOP following subsequent administration of ketamine for induction of anesthesia. To our knowledge, the effects of thiopental or propofol on IOP in horses have not been reported. However, induction of anesthesia with propofol in horses has the potential to cause severe excitement and paddling,24–26 which can be a risk to the safety of a treated animal and attending personnel and might potentially increase the patient's extraocular muscle tone and consequently increase the IOP. However, prior administration of guaifenesin, a centrally acting skeletal muscle relaxant, prevents propofol-induced paddling in horses27; thus, this protocol might be a suitable anesthetic technique for horses in which intraocular hypertension is contraindicated.
In horses, cardiorespiratory function is maintained when ketamine is used,28,29 whereas propofol or thiopental administration is commonly associated with cardiorespiratory depression.29 Additionally, propofol has pharmacokinetic characteristics that would allow rapid recovery,29 and use of this drug is commonly associated with a good to excellent quality of recovery from anesthesia with minimal ataxia in horses.24,25,29,30 However, direct comparisons between single induction doses of all 3 agents under identical experimental conditions appear to be currently lacking.
The objective of the study reported here was to assess the effects of ketamine hydrochloride, propofol, or compounded thiopental sodium administration (each in combination with guaifenesin) on IOP in horses pretreated with xylazine. Additionally, the intent was to evaluate drug effects on commonly monitored cardiorespiratory responses and to assess qualities and times of induction of and recovery from anesthesia. We hypothesized that IOP would be higher following ketamine administration than values following either thiopental or propofol administration. We also hypothesized that for the 3 drug treatments, recovery time would be shortest and recovery quality would be greatest following propofol administration and that cardiorespiratory function would be least adversely affected by ketamine administration.
Materials and Methods
Animals—Six healthy horses that had no cardiovascular or respiratory tract abnormalities detectable via physical examination were studied prospectively. For each horse, a veterinary ophthalmology resident (SBM) performed a general ophthalmic examination, including full anterior segment and dilated fundic examinations, to verify that no ocular abnormalities were present. Among the horses, there were 2 mares and 4 geldings (5 Thoroughbred and 1 Quarter Horse); mean ± SD age was 16 ± 6 years, and mean weight was 559 ± 47 kg. Horses had access to grass hay and water at all times. The Institutional Animal Care and Use Committee at the University of California-Davis approved the study.
Experimental protocol—A Latin-square design was used to determine the order of drug administration. Three induction protocols were used in each horse at ≥ 1-week intervals. All protocols included 5% guaifenesina (glyceryl guaiacolate), which was administered over a 3-minute period via a 14-gauge IV catheter with a pressure bag (300 mm Hg), to induce profound ataxia and muscle weakness. Immediately after the administration of guaifenesin, 1 of the 3 induction drugs was administered IV: 10% ketamine hydrochlorideb (2 mg/kg), 1% propofolc (3 mg/kg), or 10% compounded thiopental sodiumd (4 mg/kg). Because it is no longer commercially available in the United States, thiopental was freshly prepared prior to each study by mixing > 99.5% chemical-grade powder in a volume of sterile 90mM sodium hydroxide sufficient to yield a 10% thiopental solution with a pH between 11 and 12. The thiopental solution was passed through a sterile 0.2-μm filter, and the final pH was verified by use of indicator paper.
Within 1 hour prior to induction of anesthesia, a venous blood sample (2 mL) for blood gas analysis was obtained directly from a jugular vein of each horse. A 14-gauge cathetere was placed percutaneously in a jugular vein, and heart rate, respiratory rate, and rectal temperature were recorded. An auriculopalpebral nerve block was performed with 2 to 3 mL of 2% lidocainef to provide eyelid akinesia of the right eye. The IOP of the right eye was then measured while the horse's head was physically restrained in a lowered position such that the right eye was approximately positioned at the level at which the jugular vein enters the thoracic inlet (equivalent to the level of the right atrium and a resulting in a zero heart-to-eye hydrostatic gradient). Because head position can affect IOP, all pressure measurements were obtained with this same zero heart-to-eye hydrostatic gradient.31 Each horse was walked into a padded recovery stall, and xylazineg (0.5 mg/kg) was then administered I V. Three minutes later, the horse's head was held up so that the right eye was level with the intersection of the jugular vein and thoracic inlet, and IOP was measured, another venous blood sample (2 mL) was collected, and facial artery pulse rate and respiratory rate were recorded; these values were considered as baseline values.
Next, guaifenesin was administered IV via a pressure bag (300 mm Hg) for 3 minutes followed by an IV bolus of the anesthetic induction agent (ketamine, propofol, or thiopental). Following induction, each horse was positioned in left lateral recumbency, and an IOP measurement was immediately (ie, approx 2 minutes after induction agent administration) recorded. The IOP, respiratory rate, rectal temperature, indirect systolic and mean and diastolic arterial blood pressure measurements (displayed by an automated oscillometric sphygmomanometerh with a tail cuff [width equal to 40% of the tail diameter]), heart rate, and arterial oxygen saturation (displayed by a pulse oximeteri with a tongue clip) were recorded, and a venous blood sample (2 mL) was collected every 3 minutes from the time that induction drugs were administered until the time that spontaneous ear movement, swallowing, or other spontaneous movements were observed. Respiratory rate was measured by counting the number of thoracic excursions in a 15-second period. Before induction of anesthesia, heart rate was calculated via palpation of facial artery pulses or determined via heart auscultation during a 15-second period. After induction of anesthesia, heart rate and arterial oxygen saturation were estimated by use of a pulse oximeter.
Each horse recovered from anesthesia without assistance in the same padded recovery stall. Through direct observation, time from administration of the induction drug to attainment of lateral recumbency, time from administration of the induction drug to first movement, time from administration of the induction drug to sternal recumbency, and time from administration of the induction drug to standing were determined.
For each experiment, the induction of and recovery from anesthesia was video recorded. The videos were edited to remove any indication of the induction agent administered to allow observational blinding of 2 anesthesia specialists (THF and YSB). To evaluate the quality of induction and recovery, a subjective score for induction of anesthesia and for recovery from anesthesia was assigned by each specialist by use of a VAS. The VAS was a horizontal 100-mm line, on which 0 mm corresponded to a catastrophic induction or recovery and 100 mm corresponded to an excellent or perfect induction or recovery.32
After xylazine administration, the horse's head was raised without touching the neck so that the eye was approximately at the level of the right atrium. Proparacaine hydrochloride (0.5%)j was applied topically to the right eye, and a single handheld applanation tonometerk was used by a veterinary ophthalmologist (SRH) for all IOP measurements. Only IOP readings within a 95% instrument-calculated confidence interval were considered acceptable, and 3 such readings were recorded and used to calculate a mean value for the right eye at each measurement time. The following time points were studied: before xylazine administration, after xylazine administration (defined as baseline), after induction of anesthesia at the time of attainment of left lateral recumbency (approx 2 minutes after induction agent administration), and at 3 and 6 minutes after induction agent administration. The 3 IOPs recorded after induction of anesthesia were compared with the IOP measured after xylazine administration because excitement and resistance in some unsedated horses may have adversely affected the accuracy of these measurements.
Data analysis—Data were summarized as mean ± SD and analyzed by use of commercial software.l Normality of response distributions was tested with Shapiro-Wilk tests and by subjective evaluation of normal probability plots. The effects of treatment and time on IOP were analyzed by repeated-measures ANOVA with Holm-Ŝidak post hoc comparisons.
A Pearson product moment test was used to confirm good VAS score correlation between the 2 evaluators. Values of the second evaluator were then transformed to the scale of the first evaluator by use of Passing-Bablok regression.33 Finally, these VAS scores were then averaged and analyzed with a repeated-measures ANOVA. Differences were considered significant at a value of P < 0.05.
Results
In each experiment, the first measurement of IOP after induction was obtained immediately after the horse attained left lateral recumbency. The mean ± SD time from induction drug administration to attainment of lateral recumbency was 75 ± 16 seconds, 93 ± 37 seconds, and 127 ± 38 seconds for thiopental, propofol, and ketamine, respectively (range, 60 to 150 seconds). With regard to guaifenesin administration, mean dose was 54 ± 9.6 mg/kg, 53 ± 11.8 mg/kg, and 58 ± 13.1 mg/kg, and mean total amount was 30 ± 5.0 g, 30 ± 5.8 g, and 32 ± 6.6 g for thiopental, propofol, and ketamine, respectively.
Mean IOPs before and after xylazine administration were significantly (P < 0.01) different (21 ± 3 mm Hg and 17 ± 3 mm Hg, respectively). Some horses appeared stressed when presedation measurements were obtained and resisted head restraint. Compared with measurements obtained after xylazine administration (baseline values), thiopental decreased IOP by 4 ± 23% at the time of attainment of lateral recumbency, whereas propofol and ketamine increased IOP by 8 ± 11% and 37 ± 16%, respectively, at that same time point. Only the ketamine anesthetic protocol resulted in a significant (P < 0.005) increase in IOP at the time of attainment of lateral recumbency, compared with baseline values (Figure 1); IOPs following propofol or thiopental were not significantly different from baseline value at any time point.
Mean ± SD IOP (mm Hg) of the right eye of 6 horses after administration of xylazine (0.5 mg/kg, IV; baseline) and at 2, 3, and 6 minutes after IV administration of ketamine hydrochloride (2 mg/kg; triangles), propofol (3 mg/kg; circles), or compounded thiopental sodium (4 mg/kg; squares) in a Latin-square crossover study with ≥ 1 week between treatments. After administration of xylazine in each experiment, each horse received 5% guaifenesin IV. Baseline IOP was measured 3 minutes after xylazine administration and immediately before guaifenesin administration. *At this time point, value is significantly (P < 0.05) different from that following ketamine treatment. †At this time point, value is significantly (P < 0.05) different from the respective baseline value.
Citation: American Journal of Veterinary Research 74, 8; 10.2460/ajvr.74.8.1070
When compared with the effect of ketamine, propofol or thiopental administration resulted in significantly (P < 0.05) lower IOP at the time of attainment of lateral recumbency (Figure 1) only. At 3 minutes after induction drug administration, mean IOP following ketamine administration was 21 ± 19% higher than the baseline value; however, there was no significant difference in IOP among the 3 treatments. At 6 minutes after induction drug administration, mean IOP following propofol or thiopental administration had returned to baseline value, but mean IOP following ketamine administration was 7 ± 25% higher than the baseline value.
With regard to venous blood-gas values or the physiologic variables evaluated, there was no significant difference among treatments, except that heart rate at 3 minutes after administration of thiopental or propofol was significantly (P < 0.05) higher than that following ketamine administration (Table 1). Rectal temperature ranged from 36.4° to 38.3°C.
Mean ± SD values of physiologic variables (heart rate, respiratory rate, mean arterial blood pressure, and arterial oxygen saturation [as measured by pulse oximetry]), partial pressure of carbon dioxide in venous blood (Pvco2), and venous blood pH in 6 healthy horses after IV administration of xylazine (0.5 mg/kg; baseline) and at 3 and 6 minutes after IV administration of compounded thiopental sodium (4 mg/kg), propofol (3 mg/kg), or ketamine hydrochloride (2 mg/kg) in a Latin-square crossover study with ≥ 1 week between treatments.
| Treatment | ||||
|---|---|---|---|---|
| Variable | Time point | Thiopental | Propofol | Ketamine |
| Heart rate (beats/min) | Baseline | 26 ± 3 | 27 ± 3 | 28 ± 3 |
| 3 min | 46 ± 4a | 44 ± 4a | 40 ± 3b | |
| 6 min | 43 ± 4 | 42 ± 4 | 40 ± 3 | |
| Respiratory rate (respirations/min) | Baseline | 11 ± 2 | 10 ± 2 | 10 ± 2 |
| 3 min | 7 ± 3 | 7 ± 5 | 11 ± 4 | |
| 6 min | 9 ± 2 | 7 ± 2 | 10 ± 4 | |
| Mean arterial blood pressure (mm Hg) | Baseline | NA | NA | NA |
| 3 min | 82 ± 9 | 80 ± 9 | 86 ± 12 | |
| 6 min | 82 ± 8 | 81 ± 9 | 80 ± 11 | |
| Arterial oxygen saturation (%) | Baseline | NA | NA | NA |
| 3 min | 89 ± 1 | 89 ± 5 | 88 ± 3 | |
| 6 min | 89 ± 2 | 91 ± 3 | 89 ± 3 | |
| Pvco2 (mm Hg) | Baseline | 49.3 ± 4.6 | 49.5 ± 4.6 | 48.9 ± 2.1 |
| 3 min | 49.4 ± 4.3 | 50.1 ± 2.6 | 50.6 ± 4.0 | |
| 6 min | 50.9 ± 3.8 | 49.7 ± 2.0 | 50.2 ± 3.4 | |
| Venous blood pH | Baseline | 7.38 ± 0.01 | 7.40 ± 0.03 | 7.38 ± 0.03 |
| 3 min | 7.38 ± 0.01 | 7.38 ± 0.02 | 7.36 ± 0.03 | |
| 6 min | 7.37 ± 0.01 | 7.39 ± 0.02 | 7.36 ± 0.03 | |
After administration of xylazine in each experiment, each horse received 5% guaifenesin IV. Baseline values were measured 3 minutes after xylazine administration and immediately before guaifenesin administration.
Within a row, values with different superscript letters are significantly (P < 0.05) different from each other.
NA = Not applicable.
Induction of anesthesia with thiopental, propofol, or ketamine and the respective recoveries from anesthesia occurred without complications. On the basis of the subjective VAS scores, the qualities of induction of and recovery from anesthesia for the 3 treatments were statistically indistinguishable. For the thiopental, propofol, and ketamine treatments, induction scores were 93 ± 5 mm, 86 ± 19 mm, and 96 ± 2 mm, respectively, and recovery scores were 72 ± 26 mm, 78 ± 25 mm, and 60 ± 22 mm, respectively. Subjective VAS scores were well correlated between evaluators for assessment of both induction quality (r = 0.91) and recovery quality (r = 0.97). There were also no significant differences in recovery times (Table 2) among treatments.
Mean ± SD times from IV administration of a bolus of thiopental (4 mg/kg), propofol (3 mg/kg), or ketamine (2 mg/kg) to first movement, attainment of sternal recumbency, and standing in the 6 horses (pretreated with xylazine and guaifenesin) in Table 1.
| Variable | Thiopental | Propofol | Ketamine |
|---|---|---|---|
| Time to first movement (min) | 15 ± 4 | 17 ± 6 | 15 ± 3 |
| Time to sternal recumbency (min) | 22 ± 9 | 28 ± 13 | 19 ± 5 |
| Time to standing (min) | 30 ± 12 | 35 ± 15 | 22 ± 7 |
Discussion
In the horses of the present study, the mean IOP before sedation with xylazine was 21 ± 3.4 mm Hg, which is within the range of values (17 to 24 mm Hg) for horses determined in most studies,22,23,34–38 although higher values have also been reported.21,35 Intravenous administration of xylazine significantly decreased IOP in the present study and in previous investigations21,22 (by 23% and 27%)21,22 in horses. Possible mechanisms for this xylazine-induced change include hemodynamic drug effects, relaxation of extraocular muscles, and altered rates of aqueous humor formation and outflow.21 In the present study, horses had variable degrees of resistance to head height manipulation prior to sedation, and general muscle tone or systemic hypertension associated with stress may have accounted for some of the IOP-lowering effect observed following xylazine administration by artificially increasing presedation values.
Because of the potential confounding effects of temperament on IOP measurements in unsedated horses, the IOP measurements obtained after administration of xylazine were considered the baseline values in the present study, and all the measurements obtained after administration of the induction drugs were compared with the respective baseline value. Additionally, because most horses are sedated with α2-adrenoceptor agonists prior to induction of anesthesia in clinical settings, use of xylazine as a premedication increases the clinical relevancy of the present study findings.
In the horses of the present study, induction of anesthesia with ketamine caused a significant increase in IOP (37%) from baseline value, compared with the change in IOP from baseline following administration of propofol (8%) or thiopental; the latter actually decreased IOP by 4%. There are many conflicting reports on the effects of ketamine on IOP within and between species. For instance, in humans (studies mainly performed in children), significant increases, no change, or decreases in IOP as a result of ketamine treatment have been reported13–15,39–41; the observed effect appears to be directly related to the drug dose.14 Although there are reports of mild and nonsignificant IOP increases as a result of ketamine treatment in some veterinary species,16,17 the drug typically causes significant increases in IOP in dogs (38%), cats (10%), and rabbits (198%).18–20 Failure of the xylazine-guaifenesin protocol to prevent ketamine-induced increases in IOP further suggests that it may not be possible to prevent ketamine-induced extraocular muscle contraction in horses even following administration of xylazine and high doses of guaifenesin known to cause muscle relaxation.
Differences in drug effects and in the magnitude of IOP effects between and within species may be attributed to the use of different drug doses and different anesthetic protocols—such as use of premedication (opioids or benzodiazepines, or no premedication)—or use of benzodiazepines in conjunction with ketamine. Additionally, ketamine is often administered IM in children, whereas ketamine is more commonly administered IV in veterinary species; route-dependent differences in plasma drug concentrations might also account for some effect differences between humans and other animals.
In 1 study23 in horses, there was no significant change in IOP following ketamine administration. However, unlike conditions of the present study, the anesthetic technique in that other study23 involved use of a higher dose of xylazine and no guaifenesin, and IOP was measured after induction of anesthesia when the horses were in sternal recumbency, which could have caused underestimation of IOP even though their muzzles were touching the floor. The use of different tonometers might also affect comparisons of data between studies.42 Additionally, the IOP in unsedated horses might be influenced by their temperament, which in turn could influence study outcomes if those values (as opposed to IOPs measured after sedation) are used for baseline comparisons.
Administration of thiopental or propofol is associated with significant decreases in IOP in humans.6–8 In a study8 in humans that received midazolam as a premedication followed by propofol administration and concurrent use of remifentanil, IOP decreased by as much as 65%, which was more pronounced than the decrease of up to 52% associated with sevoflurane anesthesia. In another study6 in humans, the decrease in IOP was slightly more pronounced following propofol administration (approx 40%), compared with findings following thiopental administration (31%). Although the human medical literature consistently reports that IOP decreases following administration of thiopental or propofol, thiopental in dogs can induce a nonsignificant transient increase with a later decrease in IOP,9 and propofol has been associated with no change10 or an increase in IOP.9,11,12 It was speculated that the opposite effects of propofol and thiopental on IOP in dogs (increase) versus those in humans (decrease) might be attributable to comparatively greater extraocular muscle tone, greater scleral rigidity, greater aqueous humor production, or less aqueous humor drainage in dogs.9,11
To our knowledge, this is the first study to evaluate the effects of propofol or thiopental on IOP in horses. Neither drug caused a significant change in IOP, although propofol slightly increased IOP and thiopental slightly decreased IOP. Species-related differences in ocular anatomic features may explain species differences in drug effects. The elastic properties of horses' eyes are different from those of many other animals' eyes.38 In horses, aqueous humor drainage via the suprachoroidal space (uveoscleral and uveovortex pathway)43 is more extensive than in other species, which may allow better homeostatic maintenance of IOP and explain why IOP does not change in response to other stimuli (eg, hypercapnia) that typically affect eye pressures in other species.34,44,45
Although there was a significant increase in IOP after ketamine administration (37% increase from baseline value) in the horses of the present study, the absolute calculated increase was, on average, 6 mm Hg, compared with the baseline value (ie, after xylazine administration), and only 2 mm Hg, compared with the value before xylazine administration. This might seem to be of little clinical relevance because the mean IOP after ketamine treatment remained within the reference range for IOP in horses (17 to 24 mm Hg)22,23,34–38 and the change was transient (almost returning to baseline value at 6 minutes after induction drug administration). However, there are a few points that should be taken into consideration. First, the IOP measurement was obtained as soon as possible after horses became laterally recumbent, which occurred approximately 2 minutes after induction drug administration; the mean time from induction drug administration to lateral recumbency was longest for ketamine (127 seconds). Intraocular pressure might have been even higher between the time of induction drug administration and the 2-minute time point. Second, although the increase in IOP following a single induction dose of ketamine was transient, we speculate that these changes would have been sustained if multiple ketamine doses had been administered, as is commonly done in clinical situations. Third, after induction of anesthesia, most horses are intubated. We do not know the effect of intubation on IOP in horses, but in humans, intubation significantly increases IOP,46 which in combination with ketamine administration could further compromise the integrity of an abnormal eye (eg, an eye with a deep corneal ulcer or descemetocele). Fourth, we do not know the effect of these drugs in horses with ocular diseases (eg, glaucoma) in which ocular elastance may be reduced,19 but suspect that such conditions may augment drug-induced increases in IOP. Therefore, for patients in which intraocular hypertension is contraindicated, further increases in IOP should be prevented or minimized.
The doses of ketamine and thiopental used in the present study were selected on the basis of doses used in horses in clinical settings.28 Dose-dependent anesthetic effects of propofol have been observed in horses.24,47 Brosnan et al27 found that the doses of guaifenesin and propofol necessary to induce anesthesia in 99% of the horses in their study were estimated to be 92 and 2.5 mg/kg, respectively. Thus, they suggested that the administration of 90 mg of guaifenesin/kg followed by 3 mg of propofol/kg would be sufficient to induce anesthesia in > 99% of healthy unsedated horses.27 Although it is not possible to confirm whether the doses of thiopental, propofol, and ketamine used in the present study are exactly equipotent, these doses are used to achieve the same anesthetic endpoint (centrally mediated immobility) in similar populations (> 99% of healthy adult horses) and are, on the basis of the available literature,29 clinical experience, and common equine anesthetic practice, approximately equipotent.
A rapid and smooth induction is advisable in patients with eye problems because struggling and rough handling can predispose them to damage of the affected eye.48 The use of propofol for induction of anesthesia in horses has been associated with increased incidence of excitement and paddling,24–26 which can be prevented with the use of guaifenesin.27 In the present study, no excitement or paddling was observed during induction of anesthesia with propofol or any other protocol, and no significant difference in quality of induction was found among treatments.
As with induction of anesthesia, a smooth recovery from anesthesia after an ophthalmologic procedure is also important. In the present study, it was hypothesized that the quality of recovery from anesthesia after administration of propofol would be better than that after administration of the other 2 drugs, as suggested by results of some studies.25,49,50 We also hypothesized that propofol administration would be associated with a shorter recovery time because of its pharmacokinetic profile.51 However, no significant difference in recovery quality or recovery time was evident among the 3 drug treatments. The influence of the other drugs (xylazine and guaifenesin) used in the study could have contributed to the lack of differences because both of those drugs have low clearances and cause more prolonged muscle relaxation, sedation, and ataxia that probably obscured differences among the propofol, thiopental, and ketamine treatments.
For most cardiorespiratory variables, there were no differences among treatments in the present study. Results of previous studies have suggested that ketamine causes minimal cardiovascular depression,52,53 in contrast to the effect of either thiopental54–56 or propofol.24,26,50,57–60 The finding of the present study may have been due to increased sympathetic tone caused by decreased arterial oxygen saturation61–66 in the horses, because supplemental oxygen was not administered and ventilation-perfusion inequality commonly causes venous admixture in anesthetized and recumbent horses.67 Increases in sympathetic tone, in turn, may have increased blood pressure during treatments with thiopental or propofol, thereby making the effects of these drugs appear similar to findings in ketamine-treated animals. Similarly, hypoxemia may have stimulated ventilation following thiopental or propofol administration, which would reduce Paco2 and mask the central respiratory depressant effects of these drugs. Similar heart rates and blood pressure values might also be related to the administration of xylazine, which increases blood pressure as a result of an increase in total peripheral resistance.68 Additionally, the induction drugs used in the present study have short durations of action; thus, their cardiovascular effects were evaluated as plasma concentrations were rapidly decreasing. As a result, the apparent lack of differences in cardiovascular variables in the present study may underestimate the effects observed if deeper anesthetic planes were maintained by repeated bolus administrations or infusions, as might be used clinically.
Establishment of alternative anesthetic protocols for horses with ophthalmic problems to improve anesthetic management for these patients and to increase the chances of a successful ophthalmologic repair is important. In the present study, satisfactory induction of and recovery from anesthesia were achieved after administration of a single bolus dose of thiopental, propofol, or ketamine in horses sedated with xylazine and treated with guaifenesin. However, one should keep in mind that recovery from anesthesia especially might be different in horses with painful conditions or different temperaments and in those undergoing surgical procedures. Ketamine caused a transient but significant increase in IOP from baseline value; it also caused a significant increase in IOP, compared with findings following thiopental or propofol treatment. The findings of the present study support the use of thiopental or propofol in preference to ketamine for horses in which increased IOP should be minimized.
ABBREVIATIONS
| IOP | Intraocular pressure |
| VAS | Visual analogue scale |
US Compounding Veterinary Pharmacy, Conway, Ark.
KetaVed, Vedco Inc, St Joseph, Mo.
APP Pharmaceuticals LLC, Schaumburg, Ill.
CGeneTech Inc, Indianapolis, Ind.
Abbocath-T, Hospira Inc, Lake Forest, Ill.
Hospira Inc, Lake Forest, Ill.
Anased, Akorn Inc, Decatur, Ill.
Cardell Veterinary Monitor 9401 B P, CAS Medical Systems Inc, Branford, Conn.
N-20PA, Nellcor Inc, Pleasanton, Calif.
Falcon Pharmaceuticals, Fort Worth, Tex.
Tono-Pen Avia Vet veterinary tonometer, Reichert Technologies, Westerville, Ohio.
Stata, version 12, StataCorp, College Station, Tex.
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