Evaluation of cardiovascular effects of total intravenous anesthesia with propofol or a combination of ketamine-medetomidine-propofol in horses
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- Objective
- Conclusions and Clinical Relevance
- Materials and Methods Animals
- Results Cardiovascular effects
- (Table 1) . Respiratory rate and arterial blood-gas tensions
- (Table 2) . Qualities of anesthesia and recovery
- Minutes after induction of anesthesia Variable Baseline* 30 60 90 120 150 180 210 240
- Variable KMP-TIVA P-TIVA
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Evaluation of cardiovascular effects of total intravenous anesthesia with propofol or a combination of ketamine-medetomidine-propofol in horses Mohammed A. Umar, DVM, MVSc; Kazuto Yamashita, DVM, PhD; Tokiko Kushiro, DVM, PhD; William W. Muir III, DVM, PhD
Received May 17, 2006. Accepted September 14, 2006. From the Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan (Umar, Yamashita, Kushiro) and the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210 (Muir). Dr. Kushiro’s present address is Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610. Dr. Umar was supported by a study fellowship awarded by Monbukagakusho, Tokyo. Address correspondence to Dr. Umar.
surgical procedures in horses.5 The use of TIVA for lon-ger surgical procedures has been limited to combina-tions 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, relative-ly 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 de-pression.9 Propofol is currently considered to be unsat-isfactory as the sole anesthetic for horses because the volume of drug required is too large to enable rapid in-jection, the quality of anesthetic induction is unpredict-able, 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 cardiovas-cular function was only achieved when propofol was administered with an infusion of ketamine, medetomi-dine, 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 ade-quately maintained during surgery; however, detailed measurement of cardiovascular function was not at-tempted. 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 pre-pared by Rakuno Gakuen University. The Animal Care and Use Committee of Rakuno Gakuen University ap-proved 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 triple-lumen, 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 po-sitioned 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-medeto-midine 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 ketamine-medetomidine drug combination was administered with a syringe infusion pump,o and propofol was ad-ministered 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 ap-nea of > 60 seconds occurred and continued to the end of anesthesia in the present study. All horses were venti-lated 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 dis-connected at the end of 4 hours, and the infusion of the ketamine-medetomidine drug combination and propo-fol was discontinued. Horses were transported to a 3.5 X 3.5-m padded recovery stall. All horses were recov-ered with assistance by use of head and tail ropes. Measurements⎯Hemodynamic and arterial blood-gas 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 hors-es while horses stood in a stockade. Heart rate (beats/ min),ECG(base-apexlead),MAP(mmHg),MPAP(mm Hg), and mean right atrial pressure (mm Hg) were de-termined. Cardiac output (L/min) was measured by a thermodilution technique16 with 40 mL of a 5% dextrose solution at 0oC that was injected manually for approxi-mately 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 ar-tery anaerobically into heparinized syringes for immedi-ate blood-gas tension and pH analyses by use of a blood-gas 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 infu-sion. Times to extubation, first movement, sternal po-sitioning, and standing after the cessation of anesthesia were recorded. Recovery scores were assigned as fol-lows: 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 (mul-tiple attempts to stand, excitement is evident, high risk of injury), 2 = fair (multiple attempts to stand, substan-tial ataxia), 3 = satisfactory (horse stands after 1 to 3 at-tempts, 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 deter-mine 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 KMP-TIVA than during P-TIVA from 60 to 150 minutes of anesthesia. Cardiac index was maintained between ap-proximately 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 anesthe-sia 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). Respiratory rate and arterial blood-gas tensions⎯Respiratory rate decreased within 2 min-utes of the start of propofol infusion; apnea occurred in all horses in both groups. Mean time after induc-tion 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). Qualities of anesthesia and recovery⎯The induc-tion of anesthesia was smooth and excitement free with Table 1⎯Mean ±} SD cardiovascular values during 4 hours of KMP-TIVA or P-TIVA in 5 horses. Minutes after induction of anesthesia Variable Baseline* 30 60 90 120 150 180 210 240 HR (beats/min) KMP-TIVA 38 5 34 2 34 3 35 5 34 4 34 4 33 3 33 3 31 3 P-TIVA 39 4 40 5 39 4 41 7 40 4 40 6 39 5 39 5 39 5 MAP (mm Hg) KMP-TIVA 129 6 98 11 110 15 121 8 121 12 122 11 122 14 121 10 119 14 P-TIVA 128 4 94 9 107 12 126 15 131 6 140 11 136 12 138 14 136 18 MPAP (mm Hg) KMP-TIVA 21 7 18 4 18 3 18 2 18 3† 18 2‡ 20 4‡ 18 3‡ 18 3‡ P-TIVA 21 4 18 3 20 3 22 3 27 2 26 2 26 2 26 3 26 3 MRAP (mm Hg) KMP-TIVA 8 3 10 3 12 2 11 2 11 2 11 1 12 1 11 2 11 2 P-TIVA 8 3 10 4 12 4 14 3 16 4 15 3 16 4 15 4 17 4 Cardiac index (mL/kg/min) KMP-TIVA 73 5 56 4 51 4† 47 5† 49 5† 48 5† 51 11 51 8 51 10 P-TIVA 72 4 62 6 64 6 65 5 64 4 63 5 59 6 61 9 62 8 Stroke volume (mL/beat) KMP-TIVA 982 124 823 95 760 73 685 98 730 108 718 106 774 178 793 137 825 181 P-TIVA 922 93 802 153 833 94 800 71 808 94 795 159 755 112 798 166 812 152 SVR (dynes/s/cm5) KMP-TIVA 267 17 229 46 264 45 326 77 317 66 326 77 334 91 325 87 319 79 P-TIVA 266 8 218 21 238 24 274 27 290 35 324 44 331 51 333 65 314 70 *Baseline values were measured before any medications were administered. †,‡Values for KMP-TIVA group significantly (P = 0.01 and P 0.05, respectively) lower than P-TIVA group.
MRAP = Mean right atrial pressure. HR =Heart rate. 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. Minutes after induction of anesthesia
RR (breaths/min) KMP-TIVA 14 36 06 06 06 06 06 06 06 0 P-TIVA 11 16 06 06 06 06 06 06 06 0 pHa KMP-TIVA 7.47 0.02 7.38 0.07 7.47 0.04 7.49 0.03 7.48 0.02 7.49 0.02 7.49 0.01 7.50 0.02 7.48 0.02 P-TIVA 7.46 0.01 7.43 0.04 7.48 0.04 7.48 0.03 7.49 0.01 7.48 0.03 7.49 0.03 7.49 0.03 7.50 0.04 Paco2 (mm Hg) KMP-TIVA 42 3 58 16 43 5 42 3 42 4 40 4 40 4 40 5 42 3 P-TIVA 44 3 48 5 42 6 44 3 42 2 44 3 43 3 43 3 42 4 Pao2 (mm Hg) KMP-TIVA 108 10 302 89 427 72 471 71 476 89 501 99 465 52 451 59 494 81 P-TIVA 96 4 351 33 420 17 469 49 460 62 455 63 464 74 420 73 429 52
RR = Respiratory rate. pHa = Arterial blood pH.See Table 1 for remainder of key. Table 3⎯Mean ±}SD recovery values after cessation of 4 hours of KMP-TIVA and P-TIVA in 5 horses. Anesthesia protocol Variable KMP-TIVA P-TIVA Recovery times in minutes (range)* Extubation 28 9 (20–43) 24 11 (11–41) First movement 31 12 (20–52) 21 11 (11–36)Sternal recumbency 75 16 (52–93) 114 31 (71–155) Standing 98 21 (62–125) 132 31 (92–180)† No. of attempts to stand 2.0 1.1 (1–3) 2.6 1.6 (1–5)Recovery score 4 (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. adequate muscle relaxation in all horses. It took horses 1 to 2 minutes from the time of injection of ketamine-midazolam to attain recumbency and no limb move-ments or head shaking occurred after becoming recum-bent. 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 spontane-ous limb movements during anesthesia. Times to extubation, first movement, sternal re-cumbency, 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 af-ter 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 (satisfac-tory) after P-TIVA.
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 Grosen-baugh 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 in-dex 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 dur-ing 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 main-tained anesthesia for 4 hours with propofol-medetomi-dine 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 hal-othane, 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 base-line 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 KMP-TIVA and P-TIVA provided prolonged general anesthe-sia and minimal changes in cardiovascular function in horses. Significant differences were detected in cardiac in-dex and MPAP between KMP-TIVA and P-TIVA. Com-pared 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 de-crease in heart rate and reflected a decrease in MPAP. Medetomidine, which was included in the ketamine-medetomidine drug combination, causes dose-depen-dent cardiovascular depression resulting in decreases in heart rate and increases in SVR (ie, peripheral va-soconstriction) 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 ef-fects 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 ob-served 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 ap-proximately 30% during KMP-TIVA is minimal, com-pared with 50% depression reported during halothane anesthesia for horses20 and also with a 33% to 44% de-crease in cardiac output with halothane.19 The decrease is comparable to a 24% to 38% decrease in cardiac out-put 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 main-tained within clinically acceptable values during KMP-TIVA in our study and that the ketamine-medetomidine drug infusion produces minimal cardiovascular depres-sion 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 KMP-TIVA or P-TIVA in our study reported here. Dobuta-mine and dopamine are often administered to counter-act the cardiovascular depression induced by inhalant anesthetic drugs and IPPV.33 In our current study, car-diovascular parameters including cardiac index, stroke volume, and MAP were well maintained in all horses anesthetized with KMP-TIVA and P-TIVA without ad-ministering sympathomimetic drugs and despite apply-ing IPPV. This finding has important implications and suggests that the development of TIVA techniques for use in horses should be continued given that the main-tenance 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 anesthe-sia 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 similar-ly reported in our earlier report,15 and during medeto-midine and propofol anesthesia in horses,8 for certain major stimuli, anesthesia had to be deepened with ket-amine 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 attribut-able to prolonged recovery34 and poor-quality recover-ies are to be avoided. Recovery from injectable anes-thesia are dependent upon context-sensitive half-life. The context-sensitive half-life is reported to be quite short for propofol in horses following propofol infu-sions of 1 to 2 hours.35 In our study with P-TIVA, re-covery duration was extended in comparison to recov-ery 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 in-fusion 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 recov-eries from P-TIVA were slower, compared with previ-ous 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 min-utes 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 inha-lation 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 re-covery.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 investigat-ing TIVA with propofol in horses have not subjected horses to surgical stimulation. We designed and admin-istered 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 subcuta-neous 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 anes-thesia for surgery. Lower or higher infusion rates of pro-pofol 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 anesthe-sia, but the dose rate of propofol was insufficient for individual horses during P-TIVA. Some depres-sion 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.
References
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rolonged general anesthesia in horses is generally accomplished by administering inhalation anes-thetics. The concentration of inhalation anesthetics required to provide a surgical plane of anesthesia fre-quently contributes to the intraoperative development of hypotension and hypoventilation.1 On the other hand, findings during the infusion of injectable anes-thetic drug combinations to horses suggests that car-diopulmonary parameters are better maintained during TIVA, compared with inhalation anesthesia.2-4 A variety of TIVA techniques have been investigated during short