Cardiovascular depression, hypoxemia, and hypoventilation are common problems associated with the use of inhalant anesthetics in horses. Cardiac output, stroke volume, and left ventricular work all decrease during anesthesia and dorsal recumbency in horses.1 Positioning and anesthetic drugs contribute to impaired oxygen exchange,2 increased ventilation-perfusion mismatch,3–6 and atelectasis.7 Hypoventilation is common if horses are not mechanically ventilated, in part because of positioning and in part because of the decrease in minute ventilation caused by inhalant anesthetics.6,8,9 Mild to moderate hypercapnia (Paco2 > 50 to 65 mm Hg) may improve cardiac output through sympathetic stimulation. However, severe hypercapnia and respiratory acidosis decrease cardiac contractility and increase the frequency of arrhythmias.6,10 Hypoxemia (Pao2 < 60 mm Hg) is a common complication during general anesthesia and recumbency in horses.6,7 Although a high inspired concentration of oxygen can improve arterial oxygenation during dissociative anesthesia in horses, it also increases intrapulmonary shunting and impairs pulmonary function.11 Intermittent positive-pressure ventilation can also improve arterial oxygenation, but venous return, cardiac output, and arterial blood pressure decrease.1
The α2-adrenergic receptor agonists are commonly used in conjunction with inhalant anesthetics in horses. Historically, xylazine has been used for premedication and is often administered again prior to recovery. Medetomidine, a more selective α2-adrenergic receptor agonist, has recently been evaluated in anesthetized horses.12 The short half-life of medetomidine in horses (51 minutes)13 and its selectivity and potency14 make it suitable for administration as a CRI to reduce the concentration of isoflurane required to maintain anesthesia.a,12 Medetomidine administered IV at a rate of 0.0035 mg/kg/h (0.0016 mg/lb/h) decreases the MAC of isoflurane by 20%.a The addition of MCRI to isoflurane during anesthesia may result in improved cardiopulmonary function, analgesia, and muscle relaxation and reduced movement in response to surgical stimulation.12,15 The sedative effects of medetomidine at 0.004 mg/kg (0.0018 mg/lb) are comparable to those of xylazine at 0.4 mg/kg (0.18 mg/lb).16
Traditionally, depth of anesthesia in horses has been evaluated by use of eye signs, such as spontaneous palpebral reflex and nystagmus, and movement. However, administration of medetomidine as a CRI preserves more brisk eye reflexes when horses are maintained at a 20% to 30% lower inhalant anesthetic concentration, and only nystagmus or movement are reliable indicators of insufficient depth of anesthesia.a,12,17
Bispectral index is a number ranging from 0 (an isoelectric electroencephalogram) to 100 (an electroencephalogram indicative of being awake and alert).18,19 Although BIS has not been validated in horses, there has been considerable recent investigation into its use. It has not been seen as a reliable indicator of background anesthetic depth, but it has been useful in predicting awakening.20,21 In humans, BIS reflects CNS depression, with a BIS value of 40 to 50 representing a surgical plane of anesthesia. Electromyographic activity is also measured by the BIS monitor. The BIS monitor displays EMG power in the frequency range from 70 to 110 Hz, which can overlap the BIS power spectra.22 Substantial EMG activity can falsely elevate BIS readings through this band overlap.
The purpose of the study reported here was to compare the effects of administration of a single IV bolus of xylazine at the end of anesthesia with that of MCRI throughout anesthesia on cardiopulmonary function and depth of anesthesia in horses, without the confounding effects of surgery or the variability inherent in clinical trials. We hypothesized that MCRI would be associated with better cardiovascular performance, improved ventilation, and a more stable plane of anesthesia, compared with xylazine bolus administration.
Materials and Methods
Animals—This study was approved by the university's animal care committee and was conducted in compliance with published standards of animal care. Ten Standardbreds (5 mares, 4 geldings, and 1 stallion) were studied. Horses were owned by the Atlantic Veterinary College. The same horses were included simultaneously in a similar study23 in which different variables were measured in response to the same protocol. Power analysis done before the present study was begun revealed that 10 horses used in a crossover design had a power of > 0.8 to detect a 10% change in physiologic and biochemical values. Horses ranged in age from 3 to 7 years (mean ± SD, 3.8 ± 1.3 years) and weighed 400 to 560 kg (880 to 1,232 lb; mean ± SD, 450.3 ± 47.1 kg [990.7 ± 103.6 lb]). Prior to inclusion in the study, horses were determined to be healthy on the basis of a physical examination, CBC, serum biochemical analysis, and arterial blood gas analysis. Food but not water was withheld for 12 hours prior to anesthesia.
Experimental design—Horses were randomly assigned to 1 of 2 treatment protocols; a statistical table of random digits was used.24 Each horse received both protocols, with a minimum of 10 days between trials. On the morning of each treatment, baseline heart rate was recorded. A 14-gauge catheter was placed in the left jugular vein. Horses were premedicated with either xylazine hydrochloride (0.7 mg/kg [0.32 mg/lb], IV) or medetomidine hydrochloride (0.007 mg/kg [0.0032 mg/lb], IV). Ten minutes later, anesthesia was induced with diazepam (0.05 mg/kg [0.023 mg/lb], IV) and ketamine hydrochloride (2.5 mg/kg [1.14 mg/lb], IV). Horses were orotracheally intubated with a cuffed endotracheal tube (internal diameter, 26 mm) and positioned in dorsal recumbency on a padded surgery table. Horses were connected to a large animal anesthetic circuitb that provided isoflurane in oxygen. Connection to the breathing circuit was designated as time 0. Horses breathed spontaneously throughout each treatment. Oxygen flow was 10 L/min for the first 10 minutes and 6 L/min thereafter.25 The isoflurane vaporizer was set to maintain an end-tidal concentration of 1.7% (1.2 MAC isoflurane) during xylazine treatment and 1.4% (1.0 MAC isoflurane) during MCRI treatment. During MCRI treatment, horses were given medetomidine at a rate of 0.005 mg/kg/h (0.0023 mg/lb/h), by use of a syringe pump.c This reduction in isoflurane concentration and this infusion rate were selected on the basis of a previous study14 and our experience with clinical cases over the last 3 years. The infusion was started 10 minutes after induction of anesthesia and stopped when isoflurane was discontinued. Horses were given an isotonic crystalloid solution (lactated Ringer's solution) at a rate of 10 mL/kg/h (4.5 mL/lb/h) throughout each treatment. Horses that moved during the maintenance phase of anesthesia were given ketamine (0.5 mg/kg [0.23 mg/lb], IV). Anesthesia was maintained for 150 minutes. At the end of xylazine treatment, horses were given xylazine (0.2 mg/kg [0.09 mg/lb], IV) immediately before disconnection from the anesthetic machine. During recovery, oxygen was supplemented at 15 L/min by insufflation into the endotracheal tube until extubation, then nasally until the horse rolled into sternal recumbency. Endotracheal tubes were removed after horses regained their swallowing reflex. Horses were allowed to recover without assistance.
Monitoring—A 1.1 × 48-mm, 20-gauge catheter was placed in the facial artery after the horse was connected to the anesthetic machine. A disposable pressure transducerd was zeroed at the level of the point of the shoulder for measurement of invasive blood pressure. Arterial blood gas samples were collected anaerobically by use of a vented syringe.e Heart rate was measured by thoracic auscultation for 1 minute, and respiratory rate was manually counted for 1 minute. Continuous monitoring of ECG and invasive blood pressure was done by use of a calibrated monitor.f Continuous monitoring of inspired and expired isoflurane and end-tidal partial pressure of CO2 was done by use of a calibrated airway gas monitor.g
Subdermal electrodes were placed for BIS monitoringh in each horse, on the basis of a previously described method.20,21 The BIS sensor was modified to be used with subdermal electrodes.i Conductive gel and foam patches were removed, and silver conductive epoxyj was used to bond the subdermal electrodes to the BIS sensor. The first subdermal electrode was placed midline at a point connecting the zygomatic processes of the frontal bones (the caudal margin of the orbit). The second electrode was placed near the temporal margin of the frontal bone, halfway between the first electrode and the dorsal aspect of the zygomatic arch. The third electrode was placed over the dorsal aspect of the zygomatic arch. The fourth electrode was placed rostral to the tragus of the right ear. A smoothing rate of 30 seconds was selected, and BIS was continuously monitored and recorded every 10 minutes throughout each treatment. Traditional signs of anesthetic depth were continuously monitored, and the presence or absence of a spontaneous palpebral reflex as well as tearing, nystagmus, and movement was recorded every 10 minutes throughout each treatment.
All physiologic parameters, except rectal temperature, were continuously monitored and recorded every 10 minutes throughout each treatment. Rectal temperature was measured and recorded every 10 minutes. Ten minutes after isoflurane administration was discontinued, heart rate, respiratory rate, and arterial blood pressure were measured and recorded in the recovery stall. Blood was collected for immediate analysis of arterial blood gas parametersk at 30, 60, 90, and 150 minutes after isoflurane administration began and 10 minutes after isoflurane administration was discontinued when the horse was recovering in lateral recumbency.
Statistical analysis—Data analysis was performed by use of a commercially available software package.l Data were recorded at 10-minute intervals, and all data were included in the statistical analysis. The data (from 20, 30, 40, 50, 60, 90, and 150 minutes after isoflurane administration began and 10 minutes after isoflurane administration was discontinued) were summarized. Continuous cardiopulmonary data are reported as mean ± SD. Binomial data for eye reflexes, movement, and ketamine administration are reported as percentages. Continuous data were analyzed by use of 2-way repeated-measures ANOVA. When a significant treatment-time interaction was found, Holm-Sidak multiple comparisons tests were used to compare differences between treatments over time. Significant P values for treatment-time interactions are reported for continuous data. Dichotomous data (spontaneous palpebral reflex, tearing, nystagmus, and movement) were compared by use of the McNemar test, which is a contingency table analysis for paired data.26 The number of horses that were given ketamine and the amount of ketamine given to each horse were compared by use of paired t tests. A post hoc analysis compared BIS values during treatments with and without horse movement by use of 2-way repeated-measures ANOVA with Holm-Sidak multiple comparisons tests. For all tests, values of P ≤ 0.05 were considered significant.
Results
Cardiovascular data were summarized (Table 1). Mean baseline heart rates did not differ between treatments. Heart rate was significantly (P < 0.001) lower with MCRI treatment, compared with xylazine treatment, from 40 through 150 minutes of anesthesia. Arterial blood pressure decreased significantly (P < 0.001) immediately after induction of anesthesia with both treatments; however, this decrease was less profound with MCRI treatment. Values for SAP and MAP were significantly (P < 0.001) greater with MCRI treatment, compared with xylazine treatment, from 20 through 40 minutes of anesthesia. Values for DAP were significantly (P < 0.001) greater with MCRI treatment, compared with xylazine treatment, from induction through 30 minutes of anesthesia. Arterial blood pressures increased significantly (P < 0.001) with both treatments from 60 minutes after connection to the breathing circuit through 10 minutes after disconnection from the breathing circuit; however, this increase was less profound with MCRI treatment. Values for SAP and MAP were significantly (P < 0.001) lower with MCRI treatment, compared with xylazine treatment, from 70 through 150 minutes after connection to the breathing circuit and 10 minutes after disconnection from the breathing circuit. Values for DAP were significantly (P < 0.001) lower with MCRI treatment, compared with xylazine treatment, from 80 through 150 minutes after connection to the breathing circuit and 10 minutes after disconnection from the breathing circuit.
Mean ± SD values of cardiovascular parameters in 10 healthy adult isoflurane-anesthetized Standardbreds that received a single IV bolus of xylazine at the end of anesthesia or MCRI throughout anesthesia in a crossover study design.
| Time after connection to breathing circuit (min) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Variable | Treatment | 20 | 30 | 40 | 50 | 60 | 90 | 150 | 10 minutes after disconnection |
| HR (beats/min) | XYL | 38 ± 4 | 39 ± 5 | 41 ± 3 | 42 ± 4 | 41 ± 4 | 38 ± 5 | 42 ± 5 | 36 ± 7 |
| MED | 34 ± 4 | 35 ± 4 | 35 ± 6* | 35 ± 5* | 32 ± 4* | 32 ± 4* | 32 ± 5* | 35 ± 6 | |
| SAP (mm Hg) | XYL | 83 ± 9 | 78 ± 12 | 83 ± 14 | 92 ± 17 | 104 ± 14 | 116 ± 10 | 122 ± 14 | 141 ± 20 |
| MED | 93 ± 12* | 92 ± 11* | 94 ± 12* | 96 ± 12 | 98 ± 13 | 100 ± 11* | 101 ± 8* | 127 ± 12* | |
| DAP (mm Hg) | XYL | 49 ± 8 | 46 ± 10 | 52 ± 14 | 62 ± 17 | 71 ± 16 | 84 ± 10 | 94 ± 12 | 114 ± 15 |
| MED | 61 ± 9* | 59 ± 10* | 59 ± 10 | 59 ± 12 | 64 ± 15 | 76 ± 11* | 78 ± 10* | 104 ± 8* | |
| MAP (mm Hg) | XYL | 62 ± 9 | 58 ± 11 | 64 ± 14 | 74 ± 17 | 84 ± 15 | 97 ± 10 | 106 ± 11 | 123 ± 16 |
| MED | 74 ± 11* | 74 ± 11* | 72 ± 11* | 72 ± 14 | 76 ± 15 | 87 ± 10* | 87 ± 9* | 113 ± 8* | |
Mean ± SD baseline HR for the xylazine trial was 33 ± 5 beats/min and for the MCRI trial was 33 ± 7 beats/min.
Significantly (P ≤ 0.05) different from xylazine treatment.
HR = Heart rate. MED = Medetomidine. XYL = Xylazine.
Respiratory rate and rectal temperature were summarized (Table 2). Respiratory rate did not change significantly over time with xylazine treatment, but it increased significantly with MCRI treatment from 60 through 140 minutes of anesthesia. Respiratory rate was significantly (P < 0.001) greater with MCRI treatment, compared with xylazine treatment, at 60, 70, 100, and 140 minutes of anesthesia. End-tidal partial pressure of CO2 was significantly (P = 0.003) greater with MCRI treatment, compared with xylazine treatment, at 20 minutes and from 70 through 150 minutes of anesthesia. Rectal temperature decreased over time with both treatments and was significantly (P < 0.001) greater with MCRI treatment, compared with xylazine treatment, from 90 through 150 minutes of anesthesia. Arterial pH, Pao2, and Paco2 were not significantly different between treatments.
Mean ± SD values of respiratory parameters and rectal temperature in 10 healthy adult isoflurane-anesthetized Standardbreds that received a single IV bolus of xylazine at the end of anesthesia or MCRI throughout anesthesia in a crossover study design.
| Time after connection to breathing circuit (min) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Variable | Treatment | 20 | 30 | 40 | 50 | 60 | 90 | 150 | 10 minutes after disconnection |
| RR (breaths/min) | XYL | 5 ± 2 | 6 ± 3 | 5 ± 2 | 6 ± 3 | 5 ± 2 | 5 ± 2 | 6 ± 3 | 10 ± 3 |
| MED | 6 ± 3 | 6 ± 4 | 6 ± 2 | 7 ± 5 | 8 ± 7* | 8 ± 5 | 8 ± 4 | 12 ± 3 | |
| Petco2 (mm Hg) | XYL | 49 ± 5 | 50 ± 5 | 51 ± 4 | 50 ± 4 | 50 ± 4 | 47 ± 5 | 44 ± 7 | — |
| MED | 56 ± 7* | 54 ± 4 | 53 ± 5 | 53 ± 5 | 52 ± 7 | 52 ± 7* | 50 ± 8* | — | |
| pH | XYL | — | 7.324 ± 0.037 | — | — | 7.332 ± 0.041 | 7.324 ± 0.050 | 7.341 ± 0.039 | 7.425 ± 0.056 |
| MED | — | 7.320 ± 0.054 | — | — | 7.332 ± 0.030 | 7.324 ± 0.044 | 7.344 ± 0.038 | 7.441 ± 0.040 | |
| Paco2 (mm Hg) | XYL | — | 65.8 ± 8 | — | — | 67.8 ± 8.7 | 67.8 ± 11.5 | 65.6 ± 9 | 52.1 ± 11.5 |
| MED | — | 68.9 ± 12.3 | — | — | 68.1 ± 7.7 | 71.5 ± 10.8 | 70.1 ± 10.5 | 53.2 ± 6.4 | |
| Pao2 (mm Hg) | XYL | — | 126.3 ± 53.8 | — | — | 108.6 ± 40.4 | 75.5 ± 19.7 | 62.6 ± 14.9 | 53.2 ± 11.2 |
| MED | — | 127.1 ± 59.5 | — | — | 116.9 ± 41.8 | 80.2 ± 19.8 | 61.8 ± 13.8 | 54.3 ± 8.1 | |
| RT (°C) | XYL | 37.3 ± 0.3 | 36.9 ± 0.2 | 36.7 ± 0.4 | 36.7 ± 0.4 | 36.3 ± 0.5 | 36 ± 0.6 | 35.6 ± 0.7 | — |
| MED | 37.5 ± 0.3 | 37.1 ± 0.5 | 36.9 ± 0.5 | 36.9 ± 0.4 | 36.7 ± 0.6 | 36.7 ± 0.5* | 36.4 ± 0.6* | — | |
— = Not measured. Petco2 = End-tidal partial pressure of carbon dioxide. RR = Respiratory rate. RT = Rectal temperature.
See Table 1 for remainder of key.
Bispectral index, EMG, and eye reflex data were summarized (Table 3). Values for BIS were significantly (P = 0.002) lower with MCRI treatment, compared with xylazine treatment, from 80 through 150 minutes of anesthesia. Values for EMG were significantly (P < 0.001) lower with MCRI treatment, compared with xylazine treatment, from 30 through 150 minutes of anesthesia.
Mean ± SD values indicating depth of anesthesia in 10 healthy adult isoflurane-anesthetized Standardbreds that received a single IV bolus of xylazine at the end of anesthesia or MCRI throughout anesthesia in a crossover study design.
| Time after connection to breathing circuit (min) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Variable | Treatment | 20 | 30 | 40 | 50 | 60 | 90 | 150 |
| BIS | XYL | 54 ± 7 | 52 ± 11 | 53 ± 12 | 53 ± 10 | 54 ± 9 | 53 ± 6 | 55 ± 7 |
| MED | 48 ± 6 | 49 ± 8 | 49 ± 9 | 49 ± 11 | 49 ± 11 | 45 ± 9* | 45 ± 11* | |
| EMG | XYL | 36 ± 2 | 37 ± 2 | 40 ± 7 | 40 ± 3 | 40 ± 3 | 39 ± 3 | 39 ± 4 |
| MED | 34 ± 2 | 34 ± 3* | 33 ± 3* | 33 ± 2* | 33 ± 2* | 32 ± 2* | 31 ± 3* | |
| Spontaneous palpebral reflex (%) | XYL | 30 | 10 | 20 | 10 | 10 | 0 | 0 |
| MED | 40 | 30* | 20* | 20* | 30* | 10* | 10* | |
| Tearing (%) | XYL | 20 | 10 | 0 | 0 | 0 | 0 | 0 |
| MED | 10 | 0 | 10 | 0 | 10 | 10 | 0 | |
| Nystagmus (%) | XYL | 0 | 0 | 0 | 0 | 0 | 10 | 20 |
| MED | 0 | 0 | 0 | 0 | 0 | 0 | 10 | |
| Movement (%) | XYL | 20 | 10 | 20 | 10 | 10 | 10 | 0 |
| MED | 10 | 0 | 10 | 0 | 0 | 0 | 0 | |
See Table 1 for remainder of key.
There was no significant difference between treatments for spontaneous palpebral reflex from 0 to 30 minutes of anesthesia, although horses had more spontaneous palpebral reflex responses with MCRI treatment (Table 3). From 30 through 150 minutes of anesthesia, significantly (P = 0.001) more horses had a spontaneous palpebral reflex with MCRI treatment, compared with xylazine treatment. Ketamine was given if the horses moved during anesthesia. The number of horses given ketamine and the number of boluses given did not differ significantly between treatments. With MCRI treatment, 2 of 10 horses moved and the number of supplemental ketamine doses given to each horse ranged from 0 to 5. With xylazine treatment, 6 of 10 horses moved and the number of supplemental ketamine doses given to each horse ranged from 0 to 5. No horses were given ketamine during the last 30 minutes of anesthesia. A post hoc analysis showed that BIS values during treatments where horses moved were significantly (P = 0.003) greater than during treatments where horses did not move at every time point from 10 through 150 minutes of anesthesia except at 90 minutes (Table 4).
Mean ± SD values of BIS during trials with and without movement in 10 healthy adult isoflurane-anesthetized Standardbreds that received a single IV bolus of xylazine at the end of anesthesia or MCRI throughout anesthesia in a crossover study design.
| Time after connection to breathing circuit (min) | Movement | No movement |
|---|---|---|
| 20 | 53 ± 6* | 45 ± 4 |
| 30 | 57 ± 9* | 46 ± 7 |
| 40 | 59 ± 8* | 46 ± 6 |
| 50 | 58 ± 10* | 47 ± 8 |
| 60 | 59 ± 8* | 47 ± 9 |
| 90 | 53 ± 6 | 47 ± 10 |
| 150 | 56 ± 8* | 46 ± 10 |
Significantly (P ≤ 0.05) different from trials with no movement.
See Table 1 for remainder of key.
Discussion
Reflex bradycardia is an expected response to IV administration of α2-adrenergic receptor agonists,27,28 due to the initial increase in arterial blood pressure induced by these agents. Heart rate was lower with MCRI treatment, compared with xylazine treatment, but this decrease represented only a 10% change from baseline in these horses. Although all α2-adrenergic receptor agonists produce bradycardia, the lower heart rates seen with MCRI treatment are likely a result of the greater total cumulative dose of medetomidine, compared with xylazine.
After IV administration, α2-adrenergic receptor agonists cause an initial period of hypertension and bradycardia, followed by a longer period of hypotension and reduced cardiac output.29 These changes are due to inhibition of CNS sympathetic tone and norepinephrine release, increased vagal tone, and increased acetylcholine release from cardiac parasympathetic nerves.30 Arterial blood pressure was higher with MCRI treatment in the period shortly after induction, compared with xylazine treatment. This is an important finding because hypotension early in anesthesia may be a contributing factor in postanesthetic morbidity and death.6,31,32 Mean MAP with MCRI treatment was not < 72 mm Hg at any time point, but those with xylazine treatment were < 70 mm Hg, the clinically accepted value,33 from 20 to 50 minutes after induction of anesthesia. Clinicians should also remember that arterial blood pressure alone is not an accurate reflection of cardiac output and tissue perfusion. Isoflurane induces relaxation of vascular smooth muscle and a reduction in arterial blood pressure.26 In spontaneously breathing horses, moderate respiratory acidosis leads to activation of the sympathetic nervous system and an increase in arterial blood pressure over time.34 The α2-adrenergic receptor agonists potently decrease sympathoadrenal outflow and therefore the sympathetic response,30 and this may explain why MAP in the MCRI trials was significantly less than that in the xylazine trials late in anesthesia despite the high Paco2 in both trials.
Mature horses are particularly vulnerable to respiratory depression during inhalation of anesthetics.4,5,31,35 There is considerable variation in the respiratory response to administration of α2-adrenergic receptor agonists in anesthetized horses.29 Respiratory rate was higher with MCRI treatment, compared with xylazine treatment late in anesthesia. It may be that the lower concentration of isoflurane with MCRI treatment allowed horses to respond to the increased dead space ventilation that accompanies anesthesia, although horses were unable to respond with xylazine treatment.
Arterial partial pressure of CO2 was moderately high with both treatments, with no significant differences between treatments. This was an expected finding in spontaneously breathing, dorsally recumbent horses and contributes to sympathetic stimulation and an improvement in cardiac output6,10 and blood pressure.5 In horses, end-tidal partial pressure of CO2 is not an accurate reflection of Paco2, particularly late in anesthesia.36 With MCRI treatment, end-tidal partial pressure of CO2 was greater with MCRI treatment, compared with xylazine treatment late in anesthesia. It is possible that horses developed a greater increase in ventilation-perfusion mismatch with xylazine treatment, and this is reflected by the lower end-tidal partial pressure of CO2 and comparable Paco2 measured with xylazine treatment. Cardiac output was not measured in the present study because the hemodynamic effects of medetomidine and dexmedetomidine have been reported previously.37,38
All horses had low Pao2 with both treatments, which is an expected finding in dorsally recumbent, spontaneously breathing horses.2 To ensure normal lung function in each horse prior to inclusion in the study, a physical examination was performed, and an arterial blood sample was obtained. All horses had Pao2 > 88.8 mm Hg while breathing room air.36 The low Pao2 values during anesthesia suggest that these horses all developed atelectic areas of lung during the early maintenance phase of anesthesia, resulting in poor oxygenation. Horses and ponies develop atelectic areas in dependent lung regions within 20 minutes after being positioned in dorsal recumbency, and impairment in gas exchange is proportional to the atelectasis.2 The equine hemoglobin dissociation curve is shifted to the left, compared with other species, and horses can maintain 90% saturation at a Pao2 of 54 mm Hg.31 As such, it is unlikely that hypoxemia influenced the results. However, mechanical ventilation is recommended for most clinical patients positioned in dorsal recumbency to prevent progressive atelectasis and the development of hypoxemia.
Core body temperature steadily decreases over time in anesthetized adult horses.39 Temperature was measured rectally in the present study, which accurately reflects core temperature in anesthetized adult horses.40 Rectal temperature was better maintained with MCRI treatment, compared with xylazine treatment; this may reflect less vasodilation with MCRI treatment due to the lower isoflurane concentration and the medetomidine infusion.
Although it remains to be validated in horses, this study found BIS to be a predictor of background anesthetic depth and awakening. Mean BIS values were lower with MCRI treatment, with significant differences seen late in anesthesia. A post hoc analysis showed that mean BIS values were greater during treatments with movement, compared with treatments with no movement. The higher BIS values correlate well with traditional signs of inadequate depth such as nystagmus and movement. Perhaps with the changing levels of surgical stimulation found in clinical cases, BIS would not be as useful as a measure of anesthetic depth. However, in horses not subjected to surgical stimulation, BIS was a reliable measure of background anesthetic depth. The EMG values were lower with MCRI treatment. This increase in muscle relaxation is an expected result and is consistent with the data from chronically instrumented cats given dexmedetomidine.41
A spontaneous palpebral reflex, generally an indicator of a light plane of anesthesia, was observed more frequently with MCRI treatment during the maintenance phase of anesthesia. No significant difference was seen between treatments for nystagmus or for ketamine administration, indicating that the horses were at a similar plane of anesthesia during both treatments.
We intended to maintain the end-tidal isoflurane concentration at 1.3% (0.9 MAC isoflurane) during MCRI treatment, but the mean end-tidal isoflurane concentration for these treatments was 1.4% (1.0 MAC isoflurane). This resulted in an increased depth of anesthesia with MCRI treatment and may have been a confounding factor in the present study. In light of the higher BIS values measured in the xylazine treatment, a higher concentration of isoflurane may have induced an increase in anesthetic depth and more comparable BIS values. We also used a methane-sensitive airway gas analyzer. At the oxygen flow rates used in this study, end-tidal isoflurane concentrations are approximately 0.3% lower than those reported during the maintenance phase of anesthesia.25 However, this measurement error is the same for both trials and does not affect the analysis of the data. Observer bias is also a potential limitation of this study. However, cardiopulmonary measurements are objective and therefore less subject to observer bias. Horses were maintained at a light plane of anesthesia during both treatments. Consequently, there were safety concerns for both the staff and the horses, and the veterinarian managing the cases needed to be aware of the treatment to respond appropriately to changes in anesthetic depth.
In horses anesthetized with isoflurane, premedication with and administration of medetomidine as a CRI resulted in better maintenance of arterial blood pressure in the period immediately following induction of anesthesia, compared with xylazine bolus administration. The BIS correlated well with traditional signs of anesthetic depth. Despite more active eye signs, horses had lower BIS and EMG values with MCRI treatment. Further work in carefully controlled clinical trials is needed to fully evaluate the use of MCRI during inhalant anesthesia in equine patients undergoing surgery.
ABBREVIATIONS
| BIS | Bispectral index |
| CRI | Constant rate infusion |
| DAP | Diastolic arterial blood pressure |
| EMG | Electromyography |
| MAC | Minimum alveolar concentration |
| MAP | Mean arterial blood pressure |
| MCRI | Medetomidine constant rate infusion |
| SAP | Systolic arterial blood pressure |
Neges K, Bettschart-Wolfensberger R, Muller J, et al. The isoflurane sparing effect of a medetomidine constant rate infusion in horses (abstr), in Proceedings. Assoc Vet Anaesth Autumn Meet 2002;92–93.
LDS 3000 Anesthesia Machine, Surgivet Anesco, Waukesha, Wis.
Medfusion 3500, Smiths Medical MD Inc, Saint Paul, Minn.
PX272 Pressure monitoring kit with TruWave disposable pressure transducer, Edwards Lifesciences Canada Inc, Mississauga, ON, Canada.
Quik ABG, Vital Signs Colorado Inc, Englewood, Colo.
Dash 2000, GE Medical Systems, Milwaukee, Wis.
Capnomac Ultima, Datex-Ohmeda Division, Instrumentarium Corp, Helsinki, Finland.
A2000, software revision 3.21, Aspect Medical Systems Inc, Leiden, The Netherlands.
60-cm platinum subdermal needle electrode, Grass Instrument Division, Astro-Med Inc, West Warwick, RI.
MG Chemicals, Markham, ON, Canada.
Irma TruPoint Blood Analysis System, ITC, Edison, NJ.
Sigma Stat, version 3.0, SPSS Inc, Chicago, Ill.
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