Evaluation of cardiovascular effects of total intravenous anesthesia with propofol or a combination of ketamine-medetomidine-propofol in horses

Mohammed A. Umar Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.

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Kazuto Yamashita Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.

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Tokiko Kushiro Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.

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William W. Muir III Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Abstract

Objective—To evaluate the cardiovascular effects of total IV anesthesia with propofol (P-TIVA) or ketamine-medetomidine-propofol (KMP-TIVA) in horses.

Animals—5 Thoroughbreds.

Procedures—Horses were anesthetized twice for 4 hours, once with P-TIVA and once with KMP-TIVA. Horses were medicated with medetomidine (0.005 mg/kg, IV) and anesthetized with ketamine (2.5 mg/kg, IV) and midazolam (0.04 mg/kg, IV). After receiving a loading dose of propofol (0.5 mg/kg, IV), anesthesia was maintained with a constant rate infusion of propofol (0.22 mg/kg/min) for P-TIVA or with a constant rate infusion of propofol (0.14 mg/kg/min), ketamine (1 mg/kg/h), and medetomidine (0.00125 mg/kg/h) for KMP-TIVA. Ventilation was artificially controlled throughout anesthesia. Cardiovascular measurements were determined before medication and every 30 minutes during anesthesia, and recovery from anesthesia was scored.

Results—Cardiovascular function was maintained within acceptable limits during P-TIVA and KMP-TIVA. Heart rate ranged from 30 to 40 beats/min, and mean arterial blood pressure was > 90 mm Hg in all horses during anesthesia. Heart rate was lower in horses anesthetized with KMP-TIVA, compared with P-TIVA. Cardiac index decreased significantly, reaching minimum values (65% of baseline values) at 90 minutes during KMP-TIVA, whereas cardiac index was maintained between 80% and 90% of baseline values during P-TIVA. Stroke volume and systemic vascular resistance were similarly maintained during both methods of anesthesia. With P-TIVA, some spontaneous limb movements occurred, whereas with KMP-TIVA, no movements were observed.

Conclusions and Clinical Relevance—Cardiovascular measurements remained within acceptable values in artificially ventilated horses during P-TIVA or KMP-TIVA. Decreased cardiac output associated with KMP-TIVA was primarily the result of decreases in heart rate.

Abstract

Objective—To evaluate the cardiovascular effects of total IV anesthesia with propofol (P-TIVA) or ketamine-medetomidine-propofol (KMP-TIVA) in horses.

Animals—5 Thoroughbreds.

Procedures—Horses were anesthetized twice for 4 hours, once with P-TIVA and once with KMP-TIVA. Horses were medicated with medetomidine (0.005 mg/kg, IV) and anesthetized with ketamine (2.5 mg/kg, IV) and midazolam (0.04 mg/kg, IV). After receiving a loading dose of propofol (0.5 mg/kg, IV), anesthesia was maintained with a constant rate infusion of propofol (0.22 mg/kg/min) for P-TIVA or with a constant rate infusion of propofol (0.14 mg/kg/min), ketamine (1 mg/kg/h), and medetomidine (0.00125 mg/kg/h) for KMP-TIVA. Ventilation was artificially controlled throughout anesthesia. Cardiovascular measurements were determined before medication and every 30 minutes during anesthesia, and recovery from anesthesia was scored.

Results—Cardiovascular function was maintained within acceptable limits during P-TIVA and KMP-TIVA. Heart rate ranged from 30 to 40 beats/min, and mean arterial blood pressure was > 90 mm Hg in all horses during anesthesia. Heart rate was lower in horses anesthetized with KMP-TIVA, compared with P-TIVA. Cardiac index decreased significantly, reaching minimum values (65% of baseline values) at 90 minutes during KMP-TIVA, whereas cardiac index was maintained between 80% and 90% of baseline values during P-TIVA. Stroke volume and systemic vascular resistance were similarly maintained during both methods of anesthesia. With P-TIVA, some spontaneous limb movements occurred, whereas with KMP-TIVA, no movements were observed.

Conclusions and Clinical Relevance—Cardiovascular measurements remained within acceptable values in artificially ventilated horses during P-TIVA or KMP-TIVA. Decreased cardiac output associated with KMP-TIVA was primarily the result of decreases in heart rate.

Prolonged general anesthesia in horses is generally accomplished by administering inhalation anesthetics. The concentration of inhalation anesthetics required to provide a surgical plane of anesthesia frequently contributes to the intraoperative development of hypotension and hypoventilation.1 On the other hand, findings during the infusion of injectable anesthetic drug combinations to horses suggests that cardiopulmonary parameters are better maintained during TIVA, compared with inhalation anesthesia.2-4 A variety of TIVA techniques have been investigated during short surgical procedures in horses.5 The use of TIVA for longer surgical procedures has been limited to combinations of muscle relaxants or α2-adrenoceptor agonists or both with ketamine4,6,7 and medetomidine-propofol combination.8

Propofol is a rapid-acting, short-duration, relatively noncumulative anesthetic for IV administration that could be useful for providing short-term or extended (infusion) TIVA in horses.9 Propofol has been used for induction and maintenance of anesthesia in horses, providing safe anesthesia with rapid and uneventful recovery even when used as a continuous infusion.10,11 The principal disadvantages of propofol are that it is a poor analgesic and causes substantial respiratory depression.9 Propofol is currently considered to be unsatisfactory as the sole anesthetic for horses because the volume of drug required is too large to enable rapid injection, the quality of anesthetic induction is unpredictable, and respiratory depression is common following IV bolus administration.12

The combination of propofol with analgesic agents could provide an alternative method for improving the quality and safety of anesthesia achieved in horses with propofol (ie, more-effective analgesia) and decreasing the total dose of drug required.10,13,14 Although propofol has been used for TIVA in horses, adequate anesthesia enabling surgical procedures and acceptable cardiovascular function was only achieved when propofol was administered with an infusion of ketamine, medetomidine, or both.8,14,15

We previously reported that the combination of ketamine-medetomidine-propofol for TIVA provided better maintenance of surgical anesthesia for carotid artery translocation and decreased the requirement of propofol, compared with propofol infusion alone, in horses.15 In that study, heart rate and MAP were adequately maintained during surgery; however, detailed measurement of cardiovascular function was not attempted. The purpose of the study reported here was to evaluate the cardiovascular effects of the combination of ketamine-medetomidine-propofol for TIVA and to compare these effects with those of propofol alone for TIVA in horses premedicated with medetomidine and induced for anesthesia with ketamine and midazolam.

Materials and Methods

Animals—Five healthy Thoroughbred mares weighing (mean ± SD) 501 ± 44 kg (range, 451 to 580 kg) and aged 12.8 ± 4.4 years (range, 5 to 18 years) were used for this study. Right carotid arteries of these horses had been relocated to a subcutaneous position at least 1 month prior to study. Each horse had been anesthetized for 4 hours on 2 occasions as follows: once with P-TIVA and once with KMP-TIVA. The protocol used was randomly chosen. There was a minimum of 28 days between treatments. Food but not water was withheld from horses for 12 hours before anesthesia. Horses were cared for according to the principles of the Guide for the Care and Use of Laboratory Animals prepared by Rakuno Gakuen University. The Animal Care and Use Committee of Rakuno Gakuen University approved this study.

Instrumentation—Horses were restrained in a wooden stockade to facilitate placement of vascular catheters and measurement of baseline hemodynamic data. Areas over the relocated right carotid artery and right and left jugular furrows were clipped and prepared aseptically, and approximately 1 mL of 2% lidocaine was injected SC at each introducer site. A 14-gauge, 13.3-cm jugular venous cathetera was placed percutaneously in the left jugular vein. An 18-gauge, 2.5-cm catheterb was placed in the repositioned right carotid artery. An 8-F introducerc was placed in the right jugular vein, and a 9-F introducerd was also placed in the right jugular vein 30 cm proximal to the 8-F introducer. A triplelumen, 7-F, 100-cm, Swan-Ganz, ballooned-tipped thermistor cathetere was placed in the pulmonary artery via the 8-F introducer by advancing it along the jugular vein and into the pulmonary artery. The position was confirmed by the characteristic pressure wave. An 8-F, 100-cm catheterf was placed in the right atrium via the 9-F introducer. The distance between the tip of the Swan-Ganz catheter and the 8-F catheter was adjusted to 40 to 50 cm. Ends of the Swan-Ganz, right atrial, and carotid arterial catheters were connected through saline (0.9% NaCl) solution–filled lines to pressure transducersg and a hemodynamic monitor.h Transducers were placed at the level of the shoulder for standing horses and the sternum for anesthetized horses.

Anesthesia—Each horse was premedicated with medetomidinei (0.005 mg/kg, IV) via the 14-gauge, 13.3-cm catheter placed in the left jugular vein. Five minutes later, anesthesia was induced by administering midazolamj (0.04 mg/kg, IV) and ketaminek (2.5 mg/kg, IV). All horses were orotracheally intubated and positioned in left lateral recumbency on an inflated airbed surgical table. The endotracheal tube was connected to a large animal circle systeml that incorporated a ventilatorm and delivered 100% oxygen (5 L/min). A loading dose of propofoln (0.5 mg/kg, IV) was administered to all horses in both groups, and a constant rate infusion of propofol alone at 0.22 mg/kg/min (P-TIVA group) or propofol (0.14 mg/kg/min) and a ketamine-medetomidine drug combination (ketamine at 1 mg/kg/h and medetomidine at 0.00125 mg/kg/h; KMP-TIVA group) was started and maintained for 4 hours. The ketaminemedetomidine drug combination was administered with a syringe infusion pump,o and propofol was administered with an infusion pump.p Rates of propofol and ketamine-medetomidine infusions were chosen on the basis of findings in a previous study.15

On the basis of the results of our previous report,15 breathing was controlled with IPPV initiated when apnea of > 60 seconds occurred and continued to the end of anesthesia in the present study. All horses were ventilated with IPPV; respiratory rate was set at 6 breaths/min and 20 to 25 cm H2O peak airway pressure to maintain a PaCO2 of 40 to 50 mm Hg. During anesthesia, lactated Ringer's solutionq was administered IV at 10 mL/kg/h to all horses. The urinary bladder was catheterized to maintain an empty bladder during anesthesia.

The monitoring equipment and catheters were disconnected at the end of 4 hours, and the infusion of the ketamine-medetomidine drug combination and propofol was discontinued. Horses were transported to a 3.5 X 3.5-m padded recovery stall. All horses were recovered with assistance by use of head and tail ropes.

Measurements—Hemodynamic and arterial bloodgas tension data were recorded before premedication administration (baseline values) and every 30 minutes during 4 hours of anesthesia. Baseline hemodynamic and arterial blood-gas tension data were obtained in all horses while horses stood in a stockade. Heart rate (beats/min), ECG (base-apex lead), MAP (mm Hg), MPAP (mm Hg), and mean right atrial pressure (mm Hg) were determined. Cardiac output (L/min) was measured by a thermodilution technique16 with 40 mL of a 5% dextrose solution at 0°C that was injected manually for approximately 2 seconds through the 8-F catheter placed in the right atrium. Fluctuation in temperature was detected with the Swan-Ganz catheter placed in the pulmonary artery. Cardiac output was measured at least 3 times, and the mean value was calculated. Cardiac index (mL/kg/min), stroke volume (mL/beat), and SVR (dynes/s/cm5) were calculated with standard formulas.17 Arterial blood samples were collected from the translocated carotid artery anaerobically into heparinized syringes for immediate blood-gas tension and pH analyses by use of a bloodgas analyzer.r

Quality of recovery—The quality of recovery was categorized by use of a scoring system. Recovery was considered to begin after the cessation of the drug infusion. Times to extubation, first movement, sternal positioning, and standing after the cessation of anesthesia were recorded. Recovery scores were assigned as follows: 0 = unable to stand (horse cannot stand for > 2 hours after multiple attempts to stand, excitement is evident, injury or high risk of injury), 1 = poor (multiple attempts to stand, excitement is evident, high risk of injury), 2 = fair (multiple attempts to stand, substantial ataxia), 3 = satisfactory (horse stands after 1 to 3 attempts, prolonged ataxia but no excitement), 4 = good (horse stands after 1 or 2 attempts; mild, short-term ataxia), and 5 = excellent (horse stands on first attempt, minimal or no ataxia).18 Observers were aware of the group allocation of each horse.

Statistical analysis—Data were recorded as mean ± SD. A repeated-measures ANOVA was used to analyze changes in hemodynamic and respiratory data. When appropriate, a Student paired t test was used to determine differences between time points and to compare characteristics of recovery from anesthesia between groups. The quality of recovery from anesthesia for P-TIVA and KMP-TIVA was analyzed with the Mann-Whitney U test. Values of P < 0.05 were considered significant.

Results

Cardiovascular effects—The heart rate remained between 30 and 40 beats/min during P-TIVA and KMP-TIVA. The MAP was maintained at > 90 mm Hg throughout 4 hours of anesthesia in both groups. The MPAP was significantly lower during KMP-TIVA than during P-TIVA from 120 to 240 minutes of anesthesia. Cardiac index was significantly lower during KMPTIVA than during P-TIVA from 60 to 150 minutes of anesthesia. Cardiac index was maintained between approximately 80% and 90% of baseline values in the P-TIVA group. Cardiac index reached a minimum value (about 65% of baseline value) at 90 minutes of anesthesia during KMP-TIVA, then recovered to approximately 70% of baseline value. Similarly, heart rate was lower in the KMP-TIVA group. Stroke volume was maintained between approximately 70% to 84% of the baseline value in the KMP-TIVA group and 82% to 90% of the baseline value in the P-TIVA group, respectively. The SVR remained between approximately 80% to 125% of the baseline value in both groups (Table 1).

Table 1—

Mean ± SD cardiovascular values during 4 hours of KMP-TIVA or P-TIVA in 5 horses.

VariableMinutes after induction of anesthesia
Baseline*306090120150180210240
HR (beats/min)
 KMP-TIVA38 ± 534 ± 234 ± 335 ± 534 ± 434 ± 433 ± 333 ± 331 ± 3
 P-TIVA39 ± 440 ± 539 ± 441 ± 740 ± 440 ± 639 ± 539 ± 539 ± 5
MAP (mm Hg)
 KMP-TIVA129 ± 698 ± 11110 ± 15121 ± 8121 ± 12122 ± 11122 ± 14121 ± 10119 ± 14
 P-TIVA128 ± 494 ± 9107 ± 12126 ± 15131 ± 6140 ± 11136 ± 12138 ± 14136 ± 18
MPAP (mm Hg)
 KMP-TIVA21 ± 718 ± 418 ± 318 ± 218 ± 318 ± 220 ± 418 ± 318 ± 3
 P-TIVA21 ± 418 ± 320 ± 322 ± 327 ± 226 ± 226 ± 226 ± 326 ± 3
MRAP (mm Hg)
 KMP-TIVA8 ± 310 ± 312 ± 211 ± 211 ± 211 ± 112 ± 111 ± 211 ± 2
 P-TIVA8 ± 310 ± 412 ± 414 ± 316 ± 415 ± 316 ± 415 ± 417 ± 4
Cardiac index (mL/kg/min)
 KMP-TIVA73 ± 556 ± 451 ± 447 ± 549 ± 548 ± 551 ± 1151 ± 851 ± 10
 P-TIVA72 ± 462 ± 664 ± 665 ± 564 ± 463 ± 559 ± 661 ± 962 ± 8
Stroke volume (mL/beat)
 KMP-TIVA982 ± 124823 ± 95760 ± 73685 ± 98730 ± 108718 ± 106774 ± 178793 ± 137825 ± 181
 P-TIVA922 ± 93802 ± 153833 ± 94800 ± 71808 ± 94795 ± 159755 ± 112798 ± 166812 ± 152
SVR (dynes/s/cm5)
 KMP-TIVA267 ± 17229 ± 46264 ± 45326 ± 77317 ± 66326 ± 77334 ± 91325 ± 87319 ± 79
 P-TIVA266 ± 8218 ± 21238 ± 24274 ± 27290 ± 35324 ± 44331 ± 51333 ± 65314 ± 70

Baseline values were measured before any medications were administered.

Values for KMP-TIVA group significantly (P = 0.01) lower than P-TIVA group.

Values for KMP-TIVA group significantly (P < 0.05) lower than P-TIVA group.

MRAP = Mean right atrial pressure. HR =Heart rate.

Respiratory rate and arterial blood-gas tensions—Respiratory rate decreased within 2 minutes of the start of propofol infusion; apnea occurred in all horses in both groups. Mean time after induction of anesthesia to the start of IPPV was 14.0 ± 1.6 minutes and 15.8 ± 2.9 minutes in horses anesthetized with KMP-TIVA and P-TIVA, respectively. Hypercarbia and hypoxemia were treated by IPPV in both groups of horses (Table 2).

Table 2—

Mean ± SD respiratory rate and arterial blood-gas tension values during 4 hours of KMP-TIVA or P-TIVA in 5 horses on IPPV.

VariableMinutes after induction of anesthesia
Baseline*306090120150180210240
RR (breaths/min)
 KMP-TIVA14 ± 36 ± 06 ± 06 ± 06 ± 06 ± 06 ± 06 ± 06 ± 0
 P-TIVA11 ± 16 ± 06 ± 06 ± 06 ± 06 ± 06 ± 06 ± 0 
pHa
 KMP-TIVA7.47 ± 0.027.38 ± 0.077.47 ± 0.047.49 ± 0.037.48 ± 0.027.49 ± 0.027.49 ± 0.017.50 ± 0.027.48 ± 0.02
 P-TIVA7.46 ± 0.017.43 ± 0.047.48 ± 0.047.48 ± 0.037.49 ± 0.017.48 ± 0.037.49 ± 0.037.49 ± 0.037.50 ± 0.04
PaCO2 (mm Hg)
 KMP-TIVA42 ± 358 ± 1643 ± 542 ± 342 ± 440 ± 440 ± 440 ± 542 ± 3
 P-TIVA44 ± 348 ± 542 ± 644 ± 342 ± 244 ± 343 ± 343 ± 342 ± 4
PaO2 (mm Hg)
 KMP-TIVA108 ± 10302 ± 89427 ± 72471 ± 71476 ± 89501 ± 99465 ± 52451 ± 59494 ± 81
 P-TIVA96 ± 4351 ± 33420 ± 17469 ± 49460 ± 62455 ± 63464 ± 74420 ± 73429 ± 52

RR = Respiratory rate. pHa = Arterial blood pH.

See Table 1 for remainder of key.

Qualities of anesthesia and recovery—The induction of anesthesia was smooth and excitement free with adequate muscle relaxation in all horses. It took horses 1 to 2 minutes from the time of injection of ketaminemidazolam to attain recumbency and no limb movements or head shaking occurred after becoming recumbent. The transition to infusions of propofol with or without the ketamine-medetomidine drug combination was uneventful in all horses. During maintenance of anesthesia, no movement was observed in all 5 horses that received KMP-TIVA or in 3 horses that received P-TIVA. The 2 remaining horses that received P-TIVA required 2 IV bolus injections (1 horse) and 3 IV bolus injections (1 horse) of propofol (200 mg/injection, IV bolus given with each movement) to control spontaneous limb movements during anesthesia.

Times to extubation, first movement, sternal recumbency, and the number of attempts to stand were not significantly different between groups. However, time to standing after the cessation of anesthesia was significantly longer in horses that received P-TIVA than in horses that received KMP-TIVA (Table 3). Quality of recovery from anesthesia was judged to be good after KMP-TIVA and good or satisfactory after P-TIVA. All 5 horses had a recovery score of 4 (good) after KMP-TIVA, whereas 3 horses had a recovery score of 4 (good) and 2 horses had a recovery score of 3 (satisfactory) after P-TIVA.

Table 3—

Mean ± SD recovery values after cessation of 4 hours of KMP-TIVA and P-TIVA in 5 horses.

VariableAnesthesia protocol
KMP-TIVAP-TIVA
Recovery times in minutes (range)*
   Extubation28 ± 9 (20–43)24 ± 11 (11–41)
   First movement31 ± 12 (20–52)21 ± 11 (11–36)
   Sternal recumbency75 ± 16 (52–93)114 ± 31 (71–155)
   Standing98 ± 21 (62–125)132 ± 31 (92–180)
No. of attempts to stand2.0 ± 1.1 (1–3)2.6 ± 1.6 (1–5)
Recovery score4 (n = 5)4 (n = 3); 3 (n = 2)

Times were recorded from the time propofol infusion was discontinued.

Significant (P < 0.05) difference between groups.

Discussion

Our data suggest that cardiovascular function is maintained within acceptable limits for horses anesthetized with KMP-TIVA or P-TIVA.2-4,13,19-21 During inhalation anesthesia in horses, as reported by Grosenbaugh and Muir,19 the calculated cardiac index during 90 minutes of halothane, isoflurane, and sevoflurane anesthesia was 46.1 to 55.4 mL/kg/min, 68.5 to 75.9 mL/kg/min, and 55.8 to 68.3 mL/kg/min, respectively. However, Mizuno et al20 reported a cardiac index of 35 to 55 mL/kg/min by use of thermodilution during 2 hours of halothane anesthesia; also in another study by Young et al,21 the calculated mean cardiac index value was 49 mL/kg/min by thermodilution during halothane anesthesia. Similarly, during 60 minutes of xylazine and ketamine anesthesia for TIVA in horses,4 the cardiac index ranged from 37.1 ± 9.6 mL/kg/min to 80.0 ± 17.3 mL/kg/min. In addition, Mama et al13 reported a cardiac index of 30 ± 6 mL/kg/min to 35 ± 10 mL/kg/min during 1 hour of ketamine TIVA and a cardiac index of 35 ± 8 mL/kg/min to 62 ± 15 mL/kg/min during 1 hour of propofol TIVA in horses. In a similar study2 that maintained anesthesia for 4 hours with propofol-medetomidine infusion in ponies, cardiac index ranged from 31.1 ± 7.7 mL/kg/min to 51.7 ± 9.8 mL/kg/min. In our study, cardiac index ranged from 47 ± 5 mL/kg/min to 56 ± 4 mL/kg/min during KMP-TIVA and from 59 ± 6 mL/kg/min to 65 ± 5 mL/kg/min during P-TIVA. These values were similar to, and in some cases higher than, those reported for horses.2-4,13,19-21 An MAP in excess of 70 mm Hg during anesthesia is important for preventing postoperative myopathy in horses.8,17 Primary factors affecting MAP are cardiac output and SVR. Results of previous studies2,4,7 of TIVA in horses or ponies indicate that cardiopulmonary parameters are better maintained during TIVA, compared with inhalation anesthesia. The MAP in our study ranged from 98 to 122 mm Hg during KMP-TIVA and 94 to 140 mm Hg during P-TIVA; these values were similar to, or higher than, MAP during halothane, isoflurane, or sevoflurane anesthesia.1,19,20 The MPAP was significantly lower during KMP-TIVA than during P-TIVA from 120 to 240 minutes of anesthesia. Changes in PAP were within normal ranges of 17 to 36 mm Hg for horses in both groups.17 Cardiac index was maintained at 65% to 70% and 80% to 90% of baseline values during KMP-TIVA and P-TIVA, respectively, whereas SVR varied from 80% to 125% of the baseline value. On the basis of our data, we conclude that KMPTIVA and P-TIVA provided prolonged general anesthesia and minimal changes in cardiovascular function in horses.

Significant differences were detected in cardiac index and MPAP between KMP-TIVA and P-TIVA. Compared with P-TIVA, these parameters were significantly lower in horses anesthetized with KMP-TIVA. Heart rate also was lower during KMP-TIVA. On the other hand, no significant difference was found in stroke volume, SVR, and mean right atrial pressure between groups. These findings indicate that the decreases in cardiac index during KMP-TIVA were mainly caused by a decrease in heart rate and reflected a decrease in MPAP. Medetomidine, which was included in the ketaminemedetomidine drug combination, causes dose-dependent cardiovascular depression resulting in decreases in heart rate and increases in SVR (ie, peripheral vasoconstriction) in horses.22,23 Several investigators have suggested that a low-dose infusion of medetomidine may produce minimum or no cardiovascular effects.24,25 Propofol decreases cardiac index and blood pressure by direct vasodilation.26 It has also been suggested that propofol may be associated with increased sympathetic tone12 and that the sympathomimetic action of ketamine27 minimizes the bradycardia and hypotensive effects associated with drugs used as sedatives.28 We used low doses of medetomidine, similar to those reported to produce minimal or no cardiovascular effects, and observed that cardiac index remained at approximately 50 mL/kg/min during KMP-TIVA, although the infusion of ketamine-medetomidine drug combination produced significant decreases (about 30%) in cardiac output and cardiac index. The decrease in cardiac index by approximately 30% during KMP-TIVA is minimal, compared with 50% depression reported during halothane anesthesia for horses20 and also with a 33% to 44% decrease in cardiac output with halothane.19 The decrease is comparable to a 24% to 38% decrease in cardiac output reported for sevoflurane19; however, it is more than the decrease in cardiac output (12% to 20%) reported for isoflurane.19 Cardiac index in standing unsedated horses ranges from 60 to 80 mL/kg/min.6,29-31 To our knowledge, 1 other study2 evaluated cardiopulmonary effects of 4 hours of TIVA and reported a mean cardiac index range of 31.1 to 51.7 mL/kg/min, representing a reduction from typical values of approximately 30% to 50%, with the lowest values occurring during the last hour of anesthesia. These changes are comparable to or slightly more profound than those of our study. We conclude, therefore, that cardiac index was well maintained within clinically acceptable values during KMPTIVA in our study and that the ketamine-medetomidine drug infusion produces minimal cardiovascular depression in horses.

Results of our previous report15 suggested that KMP-TIVA and P-TIVA induced respiratory depression and apnea and that IPPV is required to successfully treat these adverse effects. Others have reported similar results (respiratory depression and apnea) during TIVA with propofol in horses.8,13,32 Artificial ventilation was needed to maintain respiratory rate during either KMPTIVA or P-TIVA in our study reported here. Dobutamine and dopamine are often administered to counteract the cardiovascular depression induced by inhalant anesthetic drugs and IPPV.33 In our current study, cardiovascular parameters including cardiac index, stroke volume, and MAP were well maintained in all horses anesthetized with KMP-TIVA and P-TIVA without administering sympathomimetic drugs and despite applying IPPV. This finding has important implications and suggests that the development of TIVA techniques for use in horses should be continued given that the maintenance of cardiac output and MAP are key factors in maintaining adequate muscle perfusion.17,33

We did not apply painful stimuli to horses, and 2 horses anesthetized with P-TIVA required additional propofol injections to prevent limb movement; this might be attributable to the dose of propofol, when used alone, being inadequate to maintain anesthesia in all of the horses. However, the dose rates of propofol during both forms of TIVA in our study were chosen on the basis of results of a previous study15 during which the same dose rates were adequate to maintain anesthesia for surgical relocation of the right carotid arteries of horses. Probably individual variation in anesthetic demand induced the differences. As only horses with just propofol infusion had movement, it is likely that the dose rates for KMP-TIVA induced a deeper state of anesthesia and thus are more likely to be sufficient for clinical use. Inadequate depth of anesthesia was similarly reported in our earlier report,15 and during medetomidine and propofol anesthesia in horses,8 for certain major stimuli, anesthesia had to be deepened with ketamine and thiopental in horses that moved. Transition to infusion of KMP-TIVA or P-TIVA was smooth and uneventful. Maintenance of anesthesia with KMP-TIVA was considered more satisfactory than that achieved with P-TIVA.

Prompt and controlled recovery from anesthesia in horses is important if nerve or muscle damage attributable to prolonged recovery34 and poor-quality recoveries are to be avoided. Recovery from injectable anesthesia are dependent upon context-sensitive half-life. The context-sensitive half-life is reported to be quite short for propofol in horses following propofol infusions of 1 to 2 hours.35 In our study with P-TIVA, recovery duration was extended in comparison to recovery from KMP-TIVA or inhalation anesthesia. Probably also in horses, context-sensitive half-life of propofol increases with duration of infusion. It is possible that a dose regimen of dose administration to effect rather than a constant rate infusion could prevent such long recoveries. However, results of our study suggest that recovery from P-TIVA is slower than from KMP-TIVA. Reports2,10 that used propofol at infusion rates ranging from 0.06 to 0.11 mg/kg/min recorded fast recoveries of between 20 and 39 minutes after 4 hours of anesthesia, unlike horses in our study that had higher propofol infusion rates and required approximately 130 minutes to stand after 4 hours anesthesia with P-TIVA. Recovery from anesthesia was also prolonged after P-TIVA (time to standing of 87 ± 36 minutes) after approximately 2 hours of anesthesia in our previous study.15 The recoveries from P-TIVA were slower, compared with previous reports in which anesthesia was maintained by only propofol administration at 0.18 ± 0.04 mg/kg/min, with time to standing of 67 ± 29 minutes after 61 ± 19 minutes anesthesia32 and by only propofol administration at 0.25 mg/kg/min, with time to standing of 80.3 ± 32.8 minutes after 73 ± 1 minutes anesthesia.13 Unlike inhalation anesthetics that result in rapid recovery (mean times to standing were 30, 24, and 27 minutes with halothane, isoflurane, and sevoflurane,19 respectively, after 90 minutes of anesthesia), the main disadvantage of TIVA has been the potential accumulation of drugs and metabolites that might unsatisfactorily prolong recovery.5 The high infusion rate of propofol used for P-TIVA with a zero-order infusion for long periods could result in delayed recoveries from anesthesia because of propofol accumulation.36 Most studies2,3,10-12 investigating TIVA with propofol in horses have not subjected horses to surgical stimulation. We designed and administered a propofol anesthetic protocol and infusion rate on the basis of our previous study15 in which the right carotid artery of horses was translocated to a subcutaneous position. On the basis of results from that study, we assumed that the propofol infusion rate used in our current study would provide a suitable depth of anesthesia for surgery. Lower or higher infusion rates of propofol in KMP-TIVA might be required depending upon the degree of surgical stimulation, thereby providing smaller or larger degrees of accumulation of propofol in tissues and influencing recovery rates.

In conclusion, both regimens provided anesthesia, but the dose rate of propofol was insufficient for individual horses during P-TIVA. Some depression of cardiovascular function occurred with both regimens but was more pronounced with KMP-TIVA. Prolonged recoveries in both groups were probably caused by accumulation of propofol, and IPPV was required to maintain respiratory rate during both TIVA protocols.

ABBREVIATIONS

TIVA

Total IV anesthesia

MAP

Mean arterial blood pressure

P-TIVA

TIVA with propofol

KMP-TIVA

TIVA with ketamine-medetomidine-propofol

IPPV

Intermittent positive-pressure ventilation

MPAP

Mean pulmonary artery pressure

SVR

Systemic vascular resistance

a.

BD Angiocath, Becton-Dickinson, Sandy, Utah.

b.

Supercath, Medikit Co, Tokyo, Japan.

c.

Exacta percutaneous sheath introducer, 8F Ohmeda, Swindon, UK.

d.

Exacta percutaneous sheath introducer, 9F Ohmeda, Swindon, UK.

e.

Criti-Cath SP-5107, Ohmeda, Swindon, UK.

f.

Intervec super guiding catheter, Fuji Systems Co, Tokyo, Japan.

g.

CDX-A90, Cobe Laboratories, Tokyo, Japan.

h.

DS-5300, Fukuda Denshi, Tokyo, Japan.

i.

Domitor, Meiji Seika Co, Tokyo, Japan.

j.

Dormicum, Yamanouchi Pharmatheutical Co, Tokyo, Japan.

k.

Ketalar 100, Sankyo Co, Tokyo, Japan.

l.

Mallard Medical, Mallard Medical Inc, Redding, Calif.

m.

Mallard Medical ventilator Rachel Model 2800 L.A.A.V, Mallard Medical Inc, Redding, Calif.

n.

Rapinovet, provided by Takeda Schering-Plough Animal Health Co, Tokyo, Japan.

o.

STC-521, Terumo, Tokyo, Japan.

p.

Subratek 3030, JMS, Hiroshima, Japan.

q.

Solulact, Terumo Kabushiki Co, Tokyo, Japan.

r.

Rapidlab 348, Bayer Medical Co, Tokyo, Japan.

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