The concept of the modern anaesthesiological technique partial intravenous anaesthesia (PIVA) is by means of infusion of different pharmacological agents as a supplement to inhalation anaesthetics to reduce the concentration of volatile agents maintaining surgical anaesthesia and to decrease their noxious side effects mainly on cardiovascular and respiratory systems. Alpha-2 agonists are agents with frequent use in equine practice either as sedatives or in general anaesthesia PIVA protocols. The most selective amongst them, dexmedetomidine, is characterized by fewer side effects, lower doses, and fast elimination which make it appropriate for application as a continuous rate infusion (CRI). The purpose of this study was to trace out the effects of dexmedetomidine continuous rate infusion (CRI) as part of PIVA using isoflurane on volatile agent requirements, cardiovascular function, respiration and coagulation parameters, and recovery in healthy horses. Six healthy horses with average age 9.0 ± 5.1 year and mean body weight 247.7 ± 71.4 kg were subjected to either 3-hour lasting isoflurane or isoflurane-dexmedetomidine anaesthesia two weeks apart. The main clinical and anaesthesiological parameters were monitored in 10 minutes intervals. Electrolytes, acid-base, blood gases, and coagulation parameters were measured at the beginning and at the end of each anaesthesia. Recovery times and qualities were also recorded. The results showed that, the addition of dexmedetomidine by CRI at 1.75 μg·kg -1·hour -1 to isoflurane anaesthesia slightly reduced isoflurane requirement for maintenance of surgical anaesthesia but had negligible effects on the recovery time and quality. PIVA using dexmedetomidine and isoflurane produced respiratory acidosis similar to isoflurane anaesthesia alone but with significantly more pronounced hypoxaemia and hyperlactaemia. Both investigated anaesthesia protocols did not influence significantly haemocoagulation parameters.
Anaesthesia related mortality in horses is much higher than other species [
Inhalation agents provide deep and long enough anaesthesia for surgical procedures but on the price of pronounced cardiorespiratory depression [
Alpha 2-adrenoceptor agonists are widely used in equine anaesthesia including as a part of PIVA. They are potent sedatives with good analgesic properties and also have side effects after bolus administration such as bradycardia, arrhythmias, decreases in cardiac output, and increases in systemic vascular resistance, respiratory depression, decreasing intestinal motility, and ataxia. The use of IV alpha-2 agonists in balanced anaesthetic techniques has become more and more popular, mainly to reduce MAC of volatile agents and to improve recovery during the perioperative period without significant cardiorespiratory effects.
Xylazine, the least selective alpha-2 agonist (selectivity ratio α2:α1 = 160:1) has been shown to reduce MAC of isoflurane by 25% and 34% following IV administration of 0.5 and 1 mg∙kg−1 respectively [
A CRI of detomidine (α2:α1 = 260:1) at 5 µg∙kg−1∙hour−1 after bolus of 10 µg∙kg−1 administered in isoflurane anesthetized horses undergoing to elective surgeries demonstrated typical cardiovascular effects without any beneficial influence on isoflurane requirements, recovery duration and quality [
The use of romifidine (α2:α1 = 340:1) as a CRI in isoflurane anesthetized horses submitted to elective surgeries was also described with contradictory results. According to Kuhn et al. [
Medetomidine is an extremely selective alpha-2 agonist (α2:α1 = 1620:1) and lower side effects could be assumed. PIVA using isoflurane and CRI of medetomidine has been studied widely in the equine anaesthesia. The application of 7 µg∙kg−1 IV followed by a CRI at 3.5 µg∙kg−1∙hour−1 in addition to isoflurane anaesthesia during orthopaedicsurgeries was found to reduce EtIso by 20% with lower dobutamine requirements to maintain arterial blood pressure and no differences in respiratory parameters comparatively to volatile anaesthetic alone [
Dexmedetomidine, the active enantiomer of medetomidine, is the most selective alpha-2 agonist (α2:α1 = 3240:1). It possesses beneficial pharmacokinetic properties such as short half-life and rapid distribution which render its use as a CRI very appropriate [
In the present study, we tested the effects of dexmedetomidine CRI on isoflurane requirements for maintenance of surgical anaesthesia as well as its influence on cardiopulmonary function, haemocoagulation and recovery in clinically healthy horses.
The study was approved by the Ethical Committee of the Faculty of Veterinary Medicine at Trakia University in Stara Zagora.
Six healthy horses from local primitive Karakachan breed with average age 9.0 ± 5.1 year and mean (± SD) body weight 247.7 ± 71.4 kg were included in the trial. Animals were bought from owners who intended to send them to slaughter house. They were kept in identical living and feeding conditions for a month before starting the experiment in order to eliminate the effect of environmental stress on the invest had variables. During this period a routine anthelmintic treatment was given using fenbendazole (Panacur®, Intervet) at a dose of 7.5 mg∙kg−1 PO or mebendazol (Telmin®, Janssen Pharmaceutical, Belgium) at the same dose. Clinical and laboratory investigations were also preliminarily performed and all animals were allocated in ASA grade I or II thereafter. Horses were assigned first to control/saline (ISO) group and next (two weeks apart) to experimental/dexmedetomidine (ISOD) group in order to produce cross-over design. Food but not water was deprived 12 hours before general anaesthesia.
Experimental design was similar to our previously accomplished experiment using PIVA with halothane and dexmedetomidine CRI in horses [
Acepromazine maleate (Neurotranq®, Alfasan International, Holland) was given IV at dose 0.03 mg∙kg−1 as a premedication agent in the two groups. Xylazine hydrochloride (Alfasan International, Holland) 0.8 mg∙kg−1 was administered IV thirty minutes later through one of the two 14―gauge 2.1 × 50 mm catheters (Venocan plus®, Kruuse, Denmark) placed in both jugular veins.
Anaesthesia was induced five to ten minutes after xylazine injection by mixture of ketamine hydrochloride (Anaket®, Richter Pharma, Austria) 2.2 mg∙kg−1 with diazepam (Diazepam, Sopharma, Bulgaria) 0.05 mg∙kg−1 injected intravenously in the two protocols. Trachea was intubated with 20 - 22 mm OD tracheal tube (Cook) and the horses were moved to operation theatre where were placed on a padded surgical table in dorsal recumbency.
Anaesthesia was maintained for 3 hours with isoflurane (Foran®, Abbot labretories, Switzerland) in oxygen 100% through closed circuit system of a large animal anaesthesia machine LDS 300 (Surgivet, USA) equipped with large animal ventilator DHV 1000 (Surgivet, USA) and out―of―circuit isoflurane vaporizer (Penion Limited Abington, Oxon, Ox 143 PH, UK). As soon as the vaporizer was switched on, group ISOD received a CRI of dexmedetomidine hydrochloride (Dexdomitor®, Orion Pharma, Finland) 1.75 µg∙kg−1∙hour−1 diluted with saline to a concentration of 0.01 mg∙ml−1, while group ISO received a CRI of equivalent volume of saline solution administered by means of microinfusion pump WZ―50C6 (All Pro, China) until the end of anaesthesia. Syringes were prepared in advance so as the anaesthetist was unaware of medications given.
Monitoring was performed throughout anaesthesia using a patient monitor PM―9000Vet (Mindray, China). The main clinical parameters heart rate (HR), electrocardiogram (ECG), haemoglobine oxygen saturation (Sat), respiratory rate (RR), inspired (FiIso) and expired (EtIso) fractions of isoflurane, inspired and expired fractions of CO2 (FiCO2, EtCO2), of O2 (FiO2, EtO2), and minimal alveolar concentration (MAC) of isoflurane were recorded every five minutes. For ECG recording II lead was used derived from sternal―wither configuration. Saturation probe was placed on the tongue.
Systolic (SYS), diastolic (DIA), and mean (MEAN) arterial blood pressures were measured invasively after can- nulation of left or right facial artery using 22―gauge 0.9 × 25 mm catheter (Venocan plus®, Kruuse, Denmark). Arterial blood samples were collected immediately after catheter placement and before the end of anaesthesia for blood gases, electrolytes and acid―base status measurement. Repiratory/blood gases VetStat® cassettes and VetStat® electrolyte and blood gas analyzer (IDEXX Laboratories, Inc., USA) were used for that purpose. Arterial lactate levels were measured by colorimetric method using enzymatic Roche/Hitachi lactate reagent (Roche Diagnostica, Germany).
Venous blood samples were taken at the beginning and at the end of anaesthesia in vials containing sodium citrate for measurement of some parameters of coagulation system such as fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) using coagulometer Amelung KC1A (Germany) and tests of Human Diagnostica (Germany). Blood D-dimer was measured by means of quantitative latex―aglu- tination method (Spinreact, Spain).
Second venous catheter was used for administration of Ringer’s solution (Actavis, Bulgaria) at a minimal rate of 10 ml∙kg−1∙hour−1 with some corrections throughout the anaesthesia. The rate was adjusted to maintain mean arterial pressure above 60 mmHg. Nevertheless, if blood pressure continued to drop, dopamine hydrochloride (Warsaw Pharmaseutical Works Polfa SA, Poland) was infused starting with a rate of 0.5 µg∙kg−1∙minute−1 and adjusted as required.
The animals were allowed to breathe spontaneously. If the arterial partial pressure of CO2 (PaCO2) increased above 60 mmHg, the arterial partial pressure of O2 (PaO2) decreased bellow 100 mmHg, or RR was lower than 4 breaths minute−1 for more than 3 minute an intermittent positive pressure ventilation (IPPV) was provided. Tidal volume of 20 ml∙kg−1, peak inspiratory pressure (PIP) no more 30 cm H2O, RR 8 breaths minute−1, and inspiratory time 2.5 seconds were set in an assisted-controlled mode of respiration. Urinary catheter was placed as well.
Deep surgical plane of anaesthesia was maintained by altering the vaporizer setting and thus inspired isoflurane concentrations. The depth of anaesthesia was assessed observing RR, HR, blood pressures, ocular position, movements, reflexes and moisture. Moreover, nociceptive electrical stimulation was given 30 minutes after induction of anaesthesia and every 30 minutes thereafter. For that purpose two surface electrodes were applied to the shaved and moistured skin over the lateral palmar digital nerve between the coronary band and the fetlock joint of the right hind limb, 1 cm apart and secured with elastic bandage. A constant current (CC) electrical stimulation was delivered [
Three hours after tracheal intubation, the vaporizer was switched off and the animals allowed to recover in a quiet padded box. Horses were extubated as soon as they were able to swallow. No any assistance, oxygen supp- lementation, or additional sedation was applied during this period. The quality of recovery was evaluated by recording extubation time, time to sternal and time to standing positions, and observing the number of attempts to stand, the presence of violence, ataxia, or injury. The quality of recovery was scored from 1 to 5 grades (
Data were analyzed by means of a commercially available software package (Statistica® 6-0 version, StatSoft Inc. USA). The distribution of continuous data was tested using the Kolmogorov-Smirnov test. Analysis of variance (ANOVA) for repeated measurements was used to detect the influence of time and treatment upon each anaesthesiological or clinical variable. Factorial ANOVA was used to test the alterations in blood gases, electrolytes, and haemocoagulation parameters. Fisher LSD post-hoc analysis was performed in order to determine the probability value. Recovery durations were compared between two anaesthetic protocols using one-way ANOVA and post-hoc Fisher test. Recovery scores were compared in the Wilcoxon signed rank test. The minimal level of statistical significance was set at 0.05 for all analyses.
HR, RR, Sat, SYS, MEAN, and DIA remained unchanged throughout isoflurane anaesthesia alone, whereas RR and Sat decreased over time in ISOD group with statistically significant alterations at 150 and 180 minutes comparatively to the initial period. Comparative analysis between groups showed several periods with lower HR, higher RR, SYS and MEAN values in horses anesthetized with PIVA using dexmedetomidine and isoflurane in relation to isoflurane anaesthesia alone (
The inspired and expired fractions of oxygen remained high during the whole anaesthesia in two groups (
| Description | Points |
|---|---|
| Getting up after one attempt, without ataxia | 1 |
| Getting up after one or two attempts, mild ataxia | 2 |
| More than two attempts to get up, but quiet | 3 |
| More than two attempts to get up, agitation | 4 |
| Significant violence, self-injury | 5 |