Comparative study of three intramuscular anaesthetic combinations (medetomidine/ketamine, medetomidine/fentanyl/midazolam and xylazine/ketamine) in rabbits

OBJECTIVE: To compare the quality of surgical anaesthesia and cardiorespiratory effects of three intramuscular (IM) anaesthetic combinations in rabbits. STUDY DESIGN: Prospective randomized cross-over experimental study. ANIMALS: Nineteen adult female chinchilla mixed-bred rabbits weighing 3.9 +/- 0.8 kg. METHODS: Rabbits were given one of three IM anaesthetic combinations: 0.25 mg kg(-1) medetomidine and 35.0 mg kg(-1) ketamine (M-K), 0.20 mg kg(-1) medetomidine and 0.02 mg kg(-1) fentanyl and 1.0 mg kg(-1) midazolam (M-F-Mz) and 4.0 mg kg(-1) xylazine and 50 mg kg(-1) ketamine (X-K). The effects of anaesthesia on nociceptive reflexes, circulatory and respiratory function were recorded. Statistical analyses involved repeated measures anova with paired Student's t-test applied post hoc. P-values <0.05 were considered as significant. RESULTS: Reflex loss was most rapid and complete in M-K recipients, whereas animals receiving M-F-Mz showed the longest tolerance of endotracheal intubation (78.1 +/- 36.5 minutes). Loss of righting reflex was significantly most rapid (p < 0.05) in the X-K group (114.7 +/- 24.0 minutes). Surgical anaesthesia was achieved in 16 of 19 animals receiving M-K, in 14 animals receiving M-F-Mz, and in seven animals with X-K, but only for a short period (7.1 +/- 11.6 minutes). This was significantly (p < 0.001) shorter than with M-K (38.7 +/- 30.0 minutes) and M-F-Mz (31.6 +/- 26.6 minutes). Heart rates were greatest in X-K recipients; lowest HR were seen in animals receiving M-F-Mz. Mean arterial blood pressure was significantly higher (about 88 mmHg) during the first hour in the M-K group. During recovery, the greatest hypotension was encountered in the X-K group; minimum values were 53 +/- 12 mmHg. Six of 19 animals in the M-F-Mz group showed a short period of apnoea (30 seconds) immediately after endotracheal intubation. Respiratory frequency was significantly lower in this group (p < 0.001). Highest values for arterial carbon dioxide partial pressures (PaCO(2)) (6.90 +/- 0.87 kPa; 52.5 +/- 6.5 mmHg) occurred after induction of anaesthesia in group M-F-Mz animals. There was a marked decrease in PaO(2) in all three groups (the minimum value 5.28 +/- 0.65 kPa [39.7 +/- 4.9 mmHg] was observed with M-K immediately after injection). Arterial PO(2) was between 26.0 and 43.0 kPa (196 and 324 mmHg) in all groups during O(2) delivery and decreased - but not <7.98 kPa - on its withdrawal. Immediately after drug injection, pH(a) values fell in all groups, with lowest values after 30 minutes (7.23 +/- 0.03 with M-K, 7.28 +/- 0.05 with M-F-Mz, and 7.36 +/- 0.04 with X-K). The X-K animals showed significantly (p < 0.001) higher pH values than medetomidine recipients. During 1 hour of anaesthesia pH values in the medetomidine groups remained below those of the X-K group. CONCLUSIONS: Surgical anaesthesia was induced in most animals receiving medetomidine-based combinations. Arterial blood pressure was maintained at baseline values for about 1 hour after M-K. Transient apnoea occurred with M-F-Mz and mandates respiratory function monitoring. Oxygen enrichment of inspired gases is necessary with all three combinations. Endotracheal intubation is essential in rabbits receiving M-F-Mz. CLINICAL RELEVANCE: The quality of surgical anaesthesia was greatest with M-K. All combinations allowed recoveries of similar duration. It is theoretically possible to antagonize each component of the M-F-Mz combination.     

A2-agonists in sheep: a review

OBJECTIVE: To review the use and adverse effects of alpha(2)-agonists in sheep. STUDY DESIGN: Literature review. MATERIAL AND METHODS: 'Pubmed' of the United States National Library of Medicine and 'Veterinary Science' of CAB International were searched for references relating sheep to alpha(2)-agonists. The bibliographies of retrieved articles were further scrutinized for pertinent references, and relevant articles were selected manually. RESULTS: Reports on the use of clonidine, xylazine, detomidine, romifidine, medetomidine and dexmedetomidine, MPV-2426 and ST-91 in sheep were found in the literature. Most of the studies described xylazine followed by medetomidine and clonidine. The literature on detomidine and romifidine in sheep was sparse. Reports included pharmacokinetic studies, evaluation of sedative, analgesic, and anaesthetic techniques with or without cardiovascular effects, and experimental investigations of adverse effects (mainly hypoxaemia) including the mechanisms of pulmonary oedema and impaired oxygenation after alpha(2)-agonist administration. CONCLUSIONS: A(2)-agonists are potent and effective analgesics in sheep. In combination with ketamine, they are frequently used for the induction and maintenance of anaesthesia, in this case analgesia is satisfactory. The degree of hypoxaemia which occurs with all commercially available alpha(2)-agonists is highly variable and depends on individual or breed-related factors; the most severe reactions occur after intravenous (IV) injection and during general anaesthesia. Clinical relevance Subclinical respiratory disease is common in sheep. Rapid IV injection of alpha(2)-agonists without supplementary oxygen should be avoided whenever hypoxaemia may be critical.     

A comparison of two different ketamine and diazepam combinations with an alphaxalone and medetomidine combination for induction of anaesthesia in sheep

Abstract

AIMS: To investigate the perceived adverse effects of a particular batch of ketamine during induction of anaesthesia in sheep and to assess if any adverse effects would make intubation more difficult for the veterinary students.

METHODS: Thirty adult sheep (mean bodyweight 74.5 (SD 9.4) kg) were randomly assigned to one of six groups of five sheep. Sheep in Groups A and B received I/V 0.5 mg/kg diazepam and 10 mg/kg ketamine (Ketamine Injection; Parnell Laboratories NZ Ltd, of the suspect batch); those in Groups C and D received I/V 0.5 mg/kg diazepam and 10 mg/kg ketamine (Ketalar; Hospira NZ Ltd.), and those in Groups E and F received I/V 2 μg/kg medetomidine and 2 mg/kg alphaxalone. In Groups A, C and E, intubation was by an experienced anaesthetist, and in Groups B, D and F intubation was by a veterinary student. Time from injection to successful intubation, the ease of intubation, saturation of haemoglobin with oxygen (SpO₂) and partial pressure of oxygen in arterial blood (PaO₂) were measured before the sheep were connected to an anaesthetic machine and allowed to breath oxygen. Times to extubation, holding its head up and standing, maximum and minimum heart rates, respiratory rates, maximal end tidal CO₂, and the quality of recovery were then recorded.

RESULTS: There were no measurable differences in outcomes between sheep in Groups A and B compared with C and D. Time to intubation was slightly shorter for the experienced anaesthetist than the student, but the difference was not significant. The sheep in Groups E and F took less time to recover than those in Groups A?D (p<0.05), but there were no significant differences between the groups in either the ease of induction or quality of recovery. Most sheep in Groups E and F showed minor excitatory effects, mainly at induction, which did not interfere with induction. Respiratory rates were lower in Groups E and F than Groups A?D (p<0.01), but SpO₂ was higher in Groups E and F than A and B (p<0.05).

CONCLUSIONS: The clinical impression that the batch of Parnell ketamine produced unexpected effects was shown to be incorrect. All the combinations produced anaesthesia that allowed intubation by the veterinary student.

CLINICAL RELEVANCE: All the drug combinations produced satisfactory anaesthesia in sheep, but the alphaxaloneand medetomidine combination resulted in faster recovery.     

Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog

Alpha(2)-adrenoreceptor agonists (alpha(2)-agonists) are commonly used in small animal anaesthesia for their potent sedative and analgesic properties, although concerns about their cardiovascular effects have prevented their full adoption into veterinary practice. Research into alpha(2) adrenoreceptor agonists and their clinical use is extensive, therefore this review focuses on the use of dexmedetomidine and medetomidine in dogs. Emphasis is given to the cardiovascular effects and antinociceptive action of these agents.     

The impact of MK‐467 on plasma drug concentrations,sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal

The effect of MK‐467, a peripheral α₂‐adrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2‐week washout periods. Medetomidine (MED) 30 μg/kg alone or combined in the same syringe with MK‐467 300 μg/kg (MMK) was injected intramuscular, followed by ATI 150 μg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30 min later. Plasma was analysed for drug concentrations, and sedation was subjectively assessed with a visual analogue scale. Systemic haemodynamics and blood gases were measured before treatments and at intervals thereafter. With MK‐467, medetomidine plasma concentrations were threefold higher prior to ATI, which was associated with more profound sedation and shorter onset. No significant differences were observed in early cardiopulmonary changes between treatments. Atipamezole reversed the medetomidine‐related cardiopulmonary changes after both treatments. Sedation scores decreased more rapidly when MK‐467 was included. In this study, MK‐467 appeared to have a pronounced effect on the plasma concentration and central effects of medetomidine, with minor cardiopulmonary improvement.     

The effects of medetomidine on the action of vecuronium in dogs anaesthetized with halothane and nitrous oxide

ObjectiveTo quantify the effects of medetomidine on the onset and duration of vecuronium-induced neuromuscular blockade in dogs.Study designRandomized, prospective clinical study.AnimalsTwenty-four, healthy, client-owned dogs of different breeds, aged between 6 months and 10 years and weighing between 5.0 and 40.0 kg undergoing elective surgery.MethodsDogs were randomly allocated to two groups. Pre-anaesthetic medication in group M+ was intramuscular acepromazine (ACP) 25 μg kg⁻¹, morphine 0.5 mg kg⁻¹ and medetomidine 5 μg kg⁻¹. Group M− received ACP and morphine only, at the same dose rate. After induction with thiopental, anaesthesia was maintained with halothane in oxygen and nitrous oxide. End-tidal halothane concentration was maintained at 1.1%. Neuromuscular blockade was produced with intravenous vecuronium (50 μg kg⁻¹) and monitored using a train of four stimulus applied at the ulnar nerve. The times taken for loss and reappearance of the four evoked responses (twitches [T]) were recorded. Normal and nonparametric data were analysed with an independent t-test and Mann-Whitney's U-test, respectively.ResultsThe fourth twitch (T4) disappeared at similar times in each group: 107 ± 19; [72–132] (mean ± SD; [range]) seconds in M+ and 98 ± 17 [72–120] seconds in M− dogs. The first twitch (T1) was lost at 116 ± 15; [96–132] seconds in group M+ and 109 ± 19; [72–132] seconds in M−. The fourth twitch returned significantly earlier in M+ dogs: 20.8 ± 3.8 [14–28] minutes compared with 23.8 ± 2.7 [20–27] minutes (p = 0.032). The duration of drug effect (T4 absent) was significantly shorter (p = 0.027) in M+ (18.9 ± 3.7 minutes) compared with M− dogs (22.2 ± 2.9 minutes). The recovery rate (interval between reappearance of T1 and T4) was significantly more rapid (p = 0.0003) in medetomidine recipients (3.0 ± 1.2 versus 5.2 ± 1.3 minutes).Conclusion and clinical relevance Medetomidine 5 μg kg⁻¹ as pre-anaesthetic medication shortened the duration of effect of vecuronium in halothane-anaesthetized dogs and accelerated recovery, but did not affect the onset time. These changes are of limited clinical significance.     

Sedative effects of three doses of romifidine in comparison with medetomidine in cats

ObjectiveTo compare the sedative effects of three doses of romifidine with one dose of medetomidine.Study designProspective blinded experimental cross-over.AnimalsFive adult Domestic Short Hair cats.MethodsCats were administered romifidine at 80, 120 and 160 μg kg^?1 or medetomidine at 20 μg kg^?1 (M20) intramuscularly (IM). Sedative effects were assessed for 3 hours by summing the scores given to posture, auditory response, resistance to positioning, muscular relaxation, and response to noxious stimuli, giving a total sedation score (TS). The area under the curve (AUC) of TS ≥7 (the score considered as clinically useful sedation) was calculated. Times to stages of sedation were determined. Some physiological parameters were measured. Data to compare treatments were analysed by anova or Kruskal–Wallis test as relevant.ResultsAll treatments gave a TS considered clinically useful. There were no significant differences between treatments for times to onset of sedation, maximum TS reached, or AUC. Differences between romifidine treatments for other sedation parameters were not significant but the time to maximum TS and to recovery was shortest in M20. Heart rate (HR) fell significantly with all treatments and, although with M20 it recovered at 65 minutes, it remained significantly depressed for 3 hours after all romifidine treatments. Most cats vomited, and/or hypersalivated after all treatments.ConclusionsDoses of 80, 120 and 160 μg kg^?1 romifidine IM produce sedation in cats which is similar to that following medetomidine 20 μg kg^?1. Recovery from sedation and of physiological parameters was quickest after M20.Clinical relevanceDoses of romifidine considerably lower than those investigated by previous authors give a clinically useful level of sedation, and their use might result in less side effects and a quicker recovery.     

Comparison of peripheral and core temperatures in anaesthetized hypovolaemic sheep

OBJECTIVE: To compare rectal (C(R) degrees ), coronary band (P(CB) degrees ) and ear base (P(E) degrees ) temperatures with pulmonary arterial temperature (C(PA) degrees ), and to investigate the relationship between core-peripheral temperature difference ([C - P]t degrees ) and cardiac output (Qt) in an acute ovine trauma model (PIL 60/9064). STUDY DESIGN: Observational study. ANIMALS: Thirteen mixed-breed male sheep, body mass (mean +/- SD) 45.50 +/- 4.21 kg, aged approximately 1 year. MATERIALS AND METHODS: Anaesthesia was induced with intravenous etomidate 0.5 mg kg(-1) and midazolam 0.5 mg kg(-1) and following endotracheal intubation maintained with halothane in a 2:1 N(2)O:O(2) mixture. The lungs were mechanically ventilated to maintain normocapnia. Core temperature was measured using a pulmonary arterial thermistor. Rectal temperature and peripheral temperatures at the thoracic limb coronary band and ear base were recorded using thermistor probes with a multi-channel recorder. Cardiac output was measured by continuous thermodilution. Recordings were taken hourly over a 24-hour period. After baseline data collection, hypovolaemia was induced by haemorrhage from bilateral femoral fractures. The development of hypovolaemic shock was confirmed by falling Qt, central venous pressure, mean arterial pressure and urine output. Resuscitation was attempted using intravenous fluids, inotropes and vasoconstrictors. Nine sheep received lumbosacral extradural bupivacaine. RESULTS: The rectal temperature correlated closely with pulmonary arterial temperature in all sheep (r(c) = 0.924). There was no consistent statistically significant relationship between Qt and [C - P]t degrees . CONCLUSIONS AND CLINICAL RELEVANCE: Rectal temperature accurately reflected core temperature in anaesthetized sheep but [C - P]t degrees was unrelated to Qt, under the conditions described in this study.     

Comparison of the efficacy of two ventilatory strategies in improving arterial oxygen tension and content in anaesthetized sheep

ObjectiveTo compare F-shunt and oxygen content indices in sheep ventilated with a positive end-expiratory pressure (PEEP) of 5 cmH₂O alone or preceded by a stepwise alveolar recruitment manoeuvre (ARM).Study designRandomized crossover design.AnimalsA total of six nonpregnant Brogna ewes weighing 34–47 kg, undergoing thoracolumbar magnetic resonance scan.MethodsIn medetomidine-sedated sheep, anaesthesia was induced with propofol and maintained with isoflurane 1.1% ± 0.1% and an inspired oxygen fraction (FiO₂) of 0.4. Animals were placed in left lateral recumbency and, after 10 minutes of spontaneous breathing, mechanically ventilated with 5 cmH₂O of PEEP with (group ARM) or without (group PEEP) a stepwise recruitment manoeuvre. Maintaining a fixed driving pressure of 15 cmH₂O, PEEP was increased from 0 to 20 cmH₂O every 3 minutes in 5 cmH₂O increments. In each sheep, arterial blood samples were collected to measure arterial gases and to calculate F-shunt, PaO₂/alveolar oxygen partial pressure (PAO₂) and PaO₂/FIO₂ during spontaneous breathing before mechanical ventilation (T₀), after 20 minutes of ventilation (T₂₀) and during spontaneous breathing at extubation (T_ext).ResultsBoth ventilatory strategies improved the arterial oxygen content although four animals in group PEEP showed oxygen content compatible with hypoxia compared with group ARM. F-shunt values were not statistically different at any time point in sheep that underwent only PEEP ventilation while they decreased at T₂₀ and T_ext compared with T₀ in group ARM. At extubation F-shunt was statistically lower in sheep that underwent an ARM. Mechanical ventilation improved PaO₂/PAO₂ and PaO₂/FIO₂ but they did not differ between groups.Conclusionsand clinical relevance The stepwise ARM evaluated in this study improved oxygenation indices and decreased F-shunt. This effect was maintained at extubation compared with sheep that were ventilated with only PEEP 5 cmH₂O.     

Cardiovascular and haemodynamic effects of intramuscular doses of xylazine in conscious sheep

OBJECTIVE: To determine if a commonly used analgesic dose of xylazine has detrimental cardiovascular or haemodynamic effects in sheep. DESIGN: A physiological study following intramuscular administration of xylazine. PROCEDURE: Xylazine (50 micrograms/kg) was injected intramuscularly into six healthy Merino ewes. For 60 min heart rate, mean arterial blood pressure and cardiac output were recorded; arterial blood samples for the measurement of blood gas tensions were also collected. RESULTS: There were no significant changes in heart rate, mean arterial blood pressure, cardiac output or arterial carbon dioxide tension. A slight degree of arterial hypoxaemia was noted with a 10% reduction in arterial oxygen tension values at 30 min. CONCLUSION: The minimal changes to cardiovascular and respiratory values in this study verify the safety of previously suggested analgesic dosing regimens for sheep. Previously reported hypoxaemic effects in sheep as a result of intravenous xylazine administration appear to be reduced as a result of intramuscular administration.     

A clinical comparison of two anaesthetic protocols using lidocaine or medetomidine in horses

OBJECTIVE: To compare the effects of two balanced anaesthetic protocols on end-tidal isoflurane (Fe'ISO), cardiopulmonary performance and quality of recovery in horses. DESIGN: Prospective blinded randomized clinical study. ANIMALS: Sixty-nine client-owned horses, American Society of Anesthesiologists category I and II, undergoing elective surgery. METHODS: The horses were premedicated with acepromazine (0.03 mg kg(-1)) IM 30-60 minutes before induction of anaesthesia and were randomly assigned to one of two treatments: in group L (37 horses) xylazine (1 mg kg(-1)) and in group M (31 horses) medetomidine (7 microg kg(-1)) was administered IV for sedation. Anaesthesia was induced 5 minutes later with ketamine (2.2 mg kg(-1)) and diazepam (0.02 mg kg(-1)) IV and maintained with isoflurane in oxygen/air (initial FIO2 0.40-0.50) and a constant rate infusion (CRI) of either lidocaine (2 mg kg(-1)/15 minutes loading dose followed by 50 microg kg(-1) minute(-1)) (group L) or medetomidine (3.5 microg kg(-1) hour(-1)) (group M). If horses showed movement or nystagmus, additional thiopental or ketamine was administered. Heart rate, mean arterial pressure (MAP), Fe'ISO and arterial blood gases were measured. Cardiac output was measured with the lithium dilution method in 10 (group L) and 11 (group M) horses every 45 minutes. Recovery was scored. RESULTS: Heart rate and the cardiac index (CI) were significantly higher in group L with changes over time. In group M, MAP was significantly higher during the first 50 minutes. Group L needed more additional ketamine and thiopental to maintain a surgical plane of anaesthesia and Fe'ISO was significantly higher from 70 minutes. Recovery was longer in group M and of better quality. The significance level was set at p < 0.05. CONCLUSIONS AND CLINICAL RELEVANCE: In group M, maintenance of stable anaesthetic depth was easier and lower Fe'ISO was required to maintain a surgical plane of anaesthesia. Recoveries were longer but of better quality. The CI was higher in group L but cardiovascular function was generally well maintained in both groups.     

Cardiac troponin I in dogs anaesthetized with propofol and sevoflurane: the influence of medetomidine premedication and inspired oxygen fraction

Objective

To investigate changes in serum cardiac troponin I (cTnI) concentrations in dogs in which medetomidine was used for sedation or for premedication prior to anaesthesia with propofol and sevoflurane.

Plasma concentration and cardiovascular effects of intramuscular medetomidine combined with three doses of the peripheral alpha2-antagonist MK-467 in dogs

Objective

We investigated the plasma concentrations and cardiovascular effects of intramuscularly (IM) administered medetomidine, administered alone or with three different doses of MK-467.

Perineal analgesic actions of epidural clonidine in cattle

Objective To determine the analgesic, sedative, motor, cardiac and respiratory effects of epidural clonidine in cattle. Study design Prospective randomized study. Animal population Six healthy male cattle weighing between 236 and 365 kg. Methods To investigate the effect of epidural clonidine, the animals received 2 and 3 µg kg^?1 of clonidine diluted to 8 mL with 0.9% saline. Two treatments were utilized as controls. The animals from the first control treatment received 2% lidocaine (0.4 mg kg^?1) and those from the second received an equal volume of 0.9% saline. Each animal received each treatment in random order. Evaluations of analgesia, sedation, muscle relaxation, heart rate, respiratory rate and rectal temperature were obtained at 0 (basal), 2, 5, 10, 15 and 30 minutes after epidural injection, and then at 30‐minute intervals until loss of analgesia occurred. All the animals received a standard noxious stimulus consisting of needle insertion into the skin and deep muscle; a 4‐point scale was used to score the response. A second scale was used to score sedation and a third for muscle relaxation. Results Both doses of clonidine were effective in producing analgesia of the tail, perineum, and upper hindlimb. Complete analgesia was present before (mean ± SE = 9 ± 4 vs. 19 ± 9 minutes) and lasted longer (311 ± 33 vs. 192 ± 27 minutes) for the 3 µg kg^?1versus the 2 µg kg^?1 dose, respectively. A dose‐dependent sedative effect of clonidine was also observed, with a peak effect between 60 and 180 minutes. No effects on heart or respiratory rates were observed with either dose of clonidine. Conclusions Epidural administration of 2 and 3 µg kg^?1 of clonidine in cattle in this study provided bilateral perineal analgesia/anesthesia with a dose‐dependent onset and duration of action. Clinical relevance Further studies are required to determine whether the analgesia is sufficient for surgery.     

Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse

ObjectiveTo describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse.Study designProspective experimental trial.AnimalsEight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg.MethodsMedetomidine (10 μg kg^?1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis.ResultsPharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL^?1) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg^?1 minute^?1 and a volume of distribution of 1854 ± 565 mL kg^?1. The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL^?1 approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.     

The hemodynamic effects of medetomidine continuous rate infusions in the dog

ObjectiveTo characterize the hemodynamic effects of continuous rate infusions (CRI) of medetomidine administered at doses ranging from 0 to 3 μg kg^?1 hour^?1.Study designProspective, blinded, randomized experimental trial.AnimalsSix adult purpose-bred mongrel dogs.MethodsAnesthesia was induced with sevoflurane for placement of arterial and venous catheters. Dogs recovered from anesthesia after which baseline hemodynamic measurements were obtained via lithium dilution cardiac output (CO) determination, with subsequent measurements via pulse power analysis to provide continuous CO determinations. Medetomidine, 1, 2, or 3 μg kg^?1 hour^?1 or a volume equivalent placebo, was administered via CRI for 60 minutes. Systolic, mean, and diastolic arterial pressure, heart rate (HR), CO and stroke volume were measured and stroke index (SI), cardiac index (CI), total peripheral resistance (TPR), and total peripheral resistance index (TPRI) were calculated at 3, 7, 10, 20, 30, 45, 60, 90, and 120 minutes from the start of the infusion.ResultsIncrease in dose decreased SI by 25%, 19%, and 30%, HR by 33%, 57%, and 60%, CI by 50%, 65%, 70% and increased TPRI by 109%, 235%, and 222% from baseline to the 60-minute measurement for the 1, 2, and 3 μg kg^?1 hour^?1 doses, respectively. HR, TPRI, and CI all showed significant differences over the duration of the study from the placebo treatment.ConclusionsMedetomidine CRI produces clinically relevant changes in CO, TPR, and HR. The demonstrated decrease in CO is largely because of bradycardia and the degree of cardiovascular depression appears to be dose-dependent. These findings are consistent with previously described hemodynamic changes with single bolus administration of medetomidine.Clinical relevanceLow-dose medetomidine CRIs produce clinically relevant hemodynamic depression at doses as low as 1 μg kg^?1 hour^?1 and should be used cautiously in dogs.