Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs

This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg⁻¹ bolus and at a dose rate of 10 μg kg⁻¹ min⁻¹) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography.Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog.     

Noninvasive assessment of the facilitation of the nociceptive withdrawal reflex by repeated electrical stimulations in conscious dogs

OBJECTIVE: To investigate the facilitation of the nociceptive withdrawal reflex (NWR) by repeated electrical stimuli and the associated behavioral response scores in conscious, nonmedicated dogs as a measure of temporal summation and analyze the influence of stimulus intensity and frequency on temporal summation responses. ANIMALS: 8 adult Beagles. PROCEDURES: Surface electromyographic responses evoked by transcutaneous constant-current electrical stimulation of ulnaris and digital plantar nerves were recorded from the deltoideus, cleidobrachialis, biceps femoris, and cranial tibial muscles. A repeated stimulus was given at 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, and 1.1 x I(t) (the individual NWR threshold intensity) at 2, 5, and 20 Hz. Threshold intensity and relative amplitude and latency of the reflex were analyzed for each stimulus configuration. Behavioral reactions were subjectively scored. RESULTS: Repeated sub-I(t) stimuli summated and facilitated the NWR. To elicit temporal summation, significantly lower intensities were needed for the hind limb, compared with the forelimb. Stimulus frequency did not influence temporal summation, whereas increasing intensity resulted in significantly stronger electromyographic responses and nociception (determined via behavioral response scoring) among the dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, it is possible to elicit nociceptive temporal summation that correlates with behavioral reactions. These data suggest that this experimental technique can be used to evaluate nociceptive system excitability and efficacy of analgesics in canids.     

The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

ObjectiveTo examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia.Study designProspective experimental blinded cross-over study.AnimalsEight healthy mixed breed dogs, body weight Mean ± SD 26.5 ± 8.4 kg and age 25 ± 16 months.MethodsAnaesthesia was induced with propofol and maintained with isoflurane (Fe′ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 μg kg^?1 IV) followed by a continuous rate infusion (1 μg kg^?1 hour^?1) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data.ResultsThe AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0.ConclusionsDuring isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation.Clinical relevanceThis experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.     

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

ObjectiveTo evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses.Study designProspective, blinded, randomized cross-over study.AnimalsTen healthy adult horses weighing 527–645 kg and aged 11–21 years old.MethodsElectrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg^?1, romifidine 0.08 mg kg^?1, or xylazine, 1 mg kg^?1, was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation.ResultsThe administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively.Conclusions and clinical relevanceDetomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.     

Effect of romifidine on the nociceptive withdrawal reflex and temporal summation in conscious horses

OBJECTIVE: To investigate the action of a single IV administration of romifidine on the thresholds of the nociceptive withdrawal reflex (NWR) and temporal summation in conscious horses. ANIMALS: 10 adult horses. PROCEDURE: Single electrical stimulations were applied on the digital nerves to evoke NWR from the left forelimb and hind limb. Repeated electrical stimulations (10 stimuli, 5 Hz) were given to obtain temporal summation. Surface electromyographic reflex activity was recorded from the common digital extensor and cranial tibial muscles. After baseline assessment of NWR and temporal summation thresholds, romifidine (80 microg x kg(-1), IV) was administered. Successive determinations of NWR and temporal summation thresholds were performed 5, 25, and 55 minutes after administration. RESULTS: Romifidine significantly increased the current intensities necessary to evoke NWR and temporal summation in forelimbs and hind limbs of horses. Values were significantly higher than baseline values 55 minutes after romifidine administration. After administration of romifidine, a facilitation of reflex components of tactile origin was observed when repeated stimulations were applied. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm antinociceptive activity of romifidine and may represent an objective demonstration of the well-known hypersensitivity to tactile stimuli observed in horses receiving alpha2-adrenoreceptor agonists in clinical practice. Romifidine can be included in analgesic and anesthetic protocols to provide additional analgesia in horses.     

Quantitative assessment of nociception in horses by use of the nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation

OBJECTIVES: To evoke and measure the nociceptive withdrawal reflex (NWR) by use of electromyographic recordings and to score the behavioral nociceptive responses to electrical pulses in standing nonsedated horses. ANIMALS: 10 adult horses. PROCEDURE: The lateral palmar digital nerve of the forelimb was transcutaneously stimulated, and surface electromyographic responses were recorded from the ulnaris lateralis, extensor carpi radialis, and common digital extensor muscles. Stimuli consisted of a 25-millisecond train of 5 constant-current pulses delivered by a computer-controlled stimulator. The 80- to 250-milliseconds poststimulation interval was analyzed to detect the NWR. The current intensity was increased in steps of 0.5 mA until the NWR threshold intensity (lt) was reached. The stimulus at It was repeated twice. Latency and amplitude of the NWR, together with the behavioral reaction of horses, were analyzed. The latter was scored according to a scale from 0 (no reaction) to 5 (vigorous reaction). Finally, 3 suprathreshold stimuli at 1.2 X It were analyzed. RESULTS: The median It to elicit NWR was 2.5 mA. Median onset latency of the NWR was 96.0 milliseconds at It and 89.6 milliseconds for suprathreshold stimuli. The amplitude of the reflexes was higher for suprathreshold stimulations, and behavioral reactions were slightly stronger when stimulus intensity increased. CONCLUSIONS AND CLINICAL RELEVANCE: Results of our study indicate that it is possible to record NWR in conscious standing horses, to define a reflex threshold, and to measure reflexes in response to increasing stimulus intensity.     

Quantitative assessment of nociceptive processes in conscious dogs by use of the nociceptive withdrawal reflex

OBJECTIVE: To investigate the feasibility of evoking the nociceptive withdrawal reflex (NWR) from fore and hind limbs in conscious dogs, score stimulus-associated behavioral responses, and assess the canine NWR response to suprathreshold stimulations. ANIMALS: 8 adult Beagles. PROCEDURE: Surface electromyograms evoked by transcutaneous electrical stimulation of ulnaris and digital plantar nerves were recorded from the deltoideus, cleidobrachialis, biceps femoris, and tibialis cranialis muscles. Train-of-five pulses (stimulus(train)) were used; reflex threshold (I(t train)) was determined, and recruitment curves were obtained at 1.2, 1.5, and 2 x I(t train). Additionally, a single pulse (stimulus(single)) was given at 1, 1.2, 1.5, 2, and 3 x I(t train). Latency and amplitude of NWRs were analyzed. Severity of behavioral reactions was subjectively scored. RESULTS: Fore- and hind limb I(t train) values (median; 25% to 75% interquartile range) were 2.5 mA (2.0 to 3.6 mA) and 2.1 mA (1.7 to 2.9 mA), respectively. At I(t train), NWR latencies in the deltoideus, cleidobrachialis, biceps femoris, and cranial tibialis muscles were not significantly different (19.6 milliseconds [17.1 to 20.5 milliseconds], 19.5 milliseconds [18.1 to 20.7 milliseconds], 20.5 milliseconds [14.7 to 26.4 milliseconds], and 24.4 milliseconds [17.1 to 40.5 milliseconds], respectively). Latencies obtained with stimulus(train) and stimulus(single) were similar. With increasing stimulation intensities, NWR amplitude increased and correlated positively with behavioral scores. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, the NWR can be evoked from limbs and correlates with behavioral reactions. Results suggest that NWR evaluation may enable quantification of nociceptive system excitability and efficacy of analgesics in individual dogs.     

Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies

ObjectiveTo investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies.Study designProspective, blinded, cross-over study.AnimalsSix healthy 5-year-old Shetland ponies.MethodsPonies received either 0.6 mg kg⁻¹ racemic ketamine (group RS) or 0.3 mg kg⁻¹ S-ketamine (group S) intravenously (IV), followed by a CRI of 20 μg kg⁻¹minute⁻¹ racemic ketamine (group RS) or 10 μg kg⁻¹minute⁻¹ S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate.ResultsThe NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL⁻¹ of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9–15 ng mL⁻¹) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5–10 minutes after bolus drug administration in both groups.ConclusionAntinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary.     

Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals

ObjectiveTo elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated.Study designProspective, experimental cross-over trial.AnimalsNine Norwegian Fjord research foals.MethodsBuprenorphine, 10 μg kg⁻¹ was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration.ResultsWe were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p < 0.001) in both age groups, and increased the NWR threshold following single electrical stimulation in 2 day old foals (p = 0.0012). Repeated electrical stimulation at 2 Hz was more effective to elicit temporal summation compared to 5 Hz (p < 0.001). No effect of age upon the NWR threshold was found (p = 0.34). Sedation when left undisturbed (11 occasions), increased locomotor activity when handled (9 occasions) and tachypnea (13 occasions) were common side-effects of buprenorphine.Conclusion and clinical relevanceThese findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals.     

Effects of meperidine or saline on thermal, mechanical and electrical nociceptive thresholds in cats

ObjectiveTo measure cutaneous electrical nociceptive thresholds in relation to known thermal and mechanical stimulation for nociceptive threshold detection in cats.Study designProspective, blinded, randomized cross-over study with 1-week washout interval.AnimalsEight adult cats [bodyweight 5.1 ± 1.8 kg (mean + SD)].MethodsMechanical nociceptive thresholds were tested using a step-wise manual inflation of a modified blood pressure bladder attached to the cat’s thoracic limb. Thermal nociceptive thresholds were measured by increasing the temperature of a probe placed on the thorax. The electrical nociceptive threshold was tested using an escalating current from a constant current generator passed between electrodes placed on the thoracic region. A positive response (threshold) was recorded when cats displayed any or all of the following behaviors: leg shake, head turn, avoidance, or vocalization. Four baseline readings were performed before intramuscular injection of meperidine (5 mg kg⁻¹) or an equal volume of saline. Threshold recordings with each modality were made at 15, 30, 45, 60, 90, and 120 minutes post-injection. Data were analyzed using anova and paired t-tests (significance at p < 0.05).ResultsThere were no significant changes in thermal, mechanical, or electrical thresholds after saline. Thermal thresholds increased at 15–60 minutes (p < 0.01) and mechanical threshold increased at 30 and 45 minutes after meperidine (p < 0.05). Maximum thermal threshold was +4.1 ± 0.3 °C above baseline at 15 minutes while maximum mechanical threshold was 296 ± 265 mmHg above baseline at 30 minutes after meperidine. Electrical thresholds following meperidine were not significantly different than baseline (p > 0.05). Thermal and electrical thresholds after meperidine were significantly higher than saline at 30 and 45 minutes (p < 0.05), and at 120 minutes (p < 0.05), respectively. Mechanical thresholds were significantly higher than saline treatment at 30 minutes (p ≤ 0.05).Conclusion and clinical relevanceElectrical stimulation did not detect meperidine analgesia whereas both thermal and mechanical thresholds changed after meperidine administration in cats.     

The post-tetanic count during vecuronium-induced neuromuscular blockade in halothane-anaesthetized dogs

ObjectiveTo evaluate the post‐tetanic count (PTC) for predicting the return of reversible neuromuscular blockade at the n. facialis–m. nasolabialis (nF–mNL) and n. ulnaris–mm. carpi flexorii (nU–mCF) nerve‐muscle units (NMUs) during profound vecuronium neuromuscular blockade in halothane‐anaesthetized dogs.Study designRandomized, prospective, experimental study.AnimalsTwenty‐five dogs (seven male 18 female) undergoing surgery; mean age: 4.8 years; mean body weight 22 kg.MethodsThirty minutes after acepromazine (0.05 mg kg^?1) and morphine (0.5 mg kg^?1) pre‐medication, anaesthesia was induced with intravenous (IV) thiopental and maintained with halothane, N₂O and O₂. The lungs were mechanically ventilated and end‐tidal halothane concentration (Fe′_HAL) maintained at 1.04%. Neuromuscular transmission was monitored using the train‐of‐four count (TOFC) at one nF–mNL and both nU–mCF units. Vecuronium (50 µg kg^?1 IV) was injected after 15 minutes constant Fe′_HAL. When the first twitch (T1) at both nU–mCF units had disappeared (t = 0) one (randomly allocated) ulnar nerve was stimulated every 5 minutes using PTC; TOF stimulation continued at the other sites. The PTC was plotted against the interval between recording time and T1's reappearance at the other NMUs.ResultsAt t = 0, the mean PTC in the contralateral nU–mCF unit was 18 (range 0–20). Mean PTC was a minimum at t = 5, rising to the maximum (20) at 25 minutes. Six dogs were vecuronium‐resistant as monitored by PTC. Excluding data from these revealed a strong negative relationship between ulnar PTC and the time taken for T1's return at the facial (r = ?0.7018; p < 0.00001) and contralateral ulnar (r = ?0.8409; p < 0.00001) NMUs.Conclusion and clinical relevancePost‐tetanic count monitoring beginning >5 minutes after the TOFC at nU–mCF = 0 provided a reliable estimate of T1's return at ulnar and facial NMUs.     

Investigation of the facilitation of the nociceptive withdrawal reflex evoked by repeated transcutaneous electrical stimulations as a measure of temporal summation in conscious horses

OBJECTIVE: To investigate whether facilitation of the nociceptive withdrawal reflex (NWR) can be evoked and quantified as a measure of temporal summation from the distal aspect of the left forelimb and hind limb in standing nonsedated horses via repeated stimulations of various subthreshold intensities and frequencies. ANIMALS: 10 adult horses. PROCEDURE: Surface electromyographic activity evoked by stimulation of the digital palmar and plantar nerves was recorded from the common digital extensor and cranial tibial muscles. For each horse, the NWR threshold intensity to a single stimulus was determined for the forelimb and hind limb. Repeated stimulations were performed at subthreshold intensities and at frequencies of 2, 5, and 10 Hz. The reflex amplitude was quantified, and the behavioral responses accompanying the stimulations were scored. RESULTS: Repeated stimulations at subthreshold intensities were able to summate and facilitate the NWR in conscious horses. The reflex facilitation was significantly related to the intensity of the repeated stimuli, whereas no effect of stimulation frequency was found. Reaction scores increased significantly for increasing stimulation intensities. CONCLUSIONS AND CLINICAL RELEVANCE: Temporal summation obtained by repeated stimulations of subthreshold intensity appears to represent a new tool for investigating nociceptive pathophysiologic processes in horses; this experimental model may be useful to examine the mode of action and efficacy of analgesic and anesthetic interventions and possibly to assess sensory dysfunction in clinical settings.     

Effect of intravenous propofol and remifentanil on heart rate, blood pressure and nociceptive response in acepromazine premedicated dogs

ObjectiveTo investigate the cardiorespiratory, nociceptive and endocrine effects of the combination of propofol and remifentanil, in dogs sedated with acepromazine.Study designProspective randomized, blinded, cross-over experimental trial.AnimalsTwelve healthy adult female cross-breed dogs, mean weight 18.4 ± 2.3 kg.MethodsDogs were sedated with intravenous (IV) acepromazine (0.05 mg kg^?1) followed by induction of anesthesia with IV propofol (5 mg kg^?1). Anesthesia was maintained with IV propofol (0.2 mg kg^?1 minute^?1) and remifentanil, infused as follows: R1, 0.125 μg kg^?1 minute^?1; R2, 0.25 μg kg^?1 minute^?1; and R3, 0.5 μg kg^?1 minute^?1. The same dogs were administered each dose of remifentanil at 1-week intervals. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (f_R), end tidal CO₂ (Pe′CO₂), arterial hemoglobin O₂ saturation, blood gases, and rectal temperature were measured before induction, and 5, 15, 30, 45, 60, 75, 90, and 120 minutes after beginning the infusion. Nociceptive response was investigated by electrical stimulus (50 V, 5 Hz and 10 ms). Blood samples were collected for plasma cortisol measurements. Statistical analysis was performed by anova (p < 0.05).ResultsIn all treatments, HR decreased during anesthesia with increasing doses of remifentanil, and increased significantly immediately after the end of infusion. MAP remained stable during anesthesia (72–98 mmHg). Antinociception was proportional to the remifentanil infusion dose, and was considered satisfactory only with R2 and R3. Plasma cortisol concentration decreased during anesthesia in all treatments. Recovery was smooth and fast in all dogs.Conclusions and clinical relevanceInfusion of 0.25–0.5 μg kg^?1 minute^?1 remifentanil combined with 0.2 mg kg^?1 minute^?1 propofol produced little effect on arterial blood pressure and led to a good recovery. The analgesia produced was sufficient to control the nociceptive response applied by electrical stimulation, suggesting that it may be appropriate for performing surgery.     

Thermal and mechanical nociceptive threshold testing in pregnant sheep

ObjectiveAnalgesic regimes were compared in pregnant ewes after laparotomy by measuring thermal (TT) and mechanical (MT) nociceptive thresholds.Study designProspective randomised experimental study.AnimalsPregnant ewes at 121 days gestation underwent laparotomy as part of another research project.MethodsThermal and mechanical thresholds were measured before, and 2, 6, 24 and 48 hours after surgery. Thermal stimuli were delivered to the lateral aspect of the metatarsus via a skin-mounted probe, and mechanical stimuli to the contralateral site via a pneumatically driven 1.5 mm diameter pin. Each test was performed five times, alternating thermal and mechanical stimuli, with ten minutes between thermal stimuli. At the end of surgery ewes received either: 75 μg hour^?1 transdermal fentanyl patch (medial thigh) (group FP) (n = 8), or 3 μg kg^?1hour^?1 intra-peritoneal medetomidine via an osmotic pump (group IPM) (n = 8) inserted immediately prior to closure. Data were analysed using the Kruskal–Wallis RS Test (p < 0.05). Once a significant effect was identified, pairwise comparisons were performed using paired Wilcoxon RS tests. To compensate for multiple hypotheses testing, p < 0.005 was considered significant.ResultsPrior to surgery mean ± SD TT was 56.1 ± 5.0 °C (FP) and 55.6 ± 5.0 °C (IPM); MT was 5.3 ± 2.6 N (FP) and 8.0 ± 5.0 N (IPM). In FP there was no significant change in either TT or MT over time. In IPM there was no significant change in MT over time but TT increased at two hours to 59.2 ± 3.0 °C (p = 0.003). Skin temperature (ST) ranged from 33.0 to 34.7 °C and did not change over time. There were no significant differences between groups in TT, MT or ST.Conclusions and clinical relevanceAdministration of intra-peritoneal medetomidine (3 μg kg^?1hour^?1) by an osmotic pump increases the thermal nociceptive threshold in the immediate post operative period in pregnant sheep, suggesting that this agent may have a role in providing post-operative analgesia.     

Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine

ObjectiveTo describe alfaxalone total intravenous anaesthesia (TIVA) following premedication with buprenorphine and either acepromazine (ACP) or dexmedetomidine (DEX) in bitches undergoing ovariohysterectomy.Study designProspective, randomised, clinical study.AnimalsThirty-eight healthy female dogs.MethodsFollowing intramuscular buprenorphine (20 μg kg^?1) and acepromazine (0.05 mg kg^?1) or dexmedetomidine (approximately 10 μg kg^?1, adjusted for body surface area), anaesthesia was induced and maintained with intravenous alfaxalone. Oxygen was administered via a suitable anaesthetic circuit. Alfaxalone infusion rate (initially 0.07 mg kg^?1 minute^?1) was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Alfaxalone boluses were given if required. Ventilation was assisted if necessary. Alfaxalone dose and physiologic parameters were recorded every 5 minutes. Depth of sedation after premedication, induction quality and recovery duration and quality were scored. A Student's t-test, Mann–Whitney U and Chi-squared tests determined the significance of differences between groups. Data are presented as mean ± SD or median (range). Significance was defined as p < 0.05.ResultsThere were no differences between groups in demographics; induction quality; induction (1.5 ± 0.57 mg kg^?1) and total bolus doses [1.2 (0 – 6.3) mg kg^?1] of alfaxalone; anaesthesia duration (131 ± 18 minutes); or time to extubation [16.6 (3–50) minutes]. DEX dogs were more sedated than ACP dogs. Alfaxalone infusion rate was significantly lower in DEX [0.08 (0.06–0.19) mg kg^?1 minute^?1] than ACP dogs [0.11 (0.07–0.33) mg kg^?1 minute^?1]. Cardiovascular variables increased significantly during ovarian and cervical ligation and wound closure compared to baseline values in both groups. Apnoea and hypoventilation were common and not significantly different between groups. Arterial haemoglobin oxygen saturation remained above 95% in all animals. Recovery quality scores were significantly poorer for DEX than for ACP dogs.Conclusions and clinical relevanceAlfaxalone TIVA is an effective anaesthetic for surgical procedures but, in the protocol of this study, causes respiratory depression at infusion rates required for surgery.     

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.     

Comparison of nociceptive withdrawal reflexes and recruitment curves between the forelimbs and hind limbs in conscious horses

OBJECTIVE: To compare nociceptive withdrawal reflexes (NWRs) evoked from the distal aspect of the left forelimb and hind limb in conscious standing horses and to investigate NWR recruitment for graded electrical stimulation intensities. ANIMALS: 20 adult horses. PROCEDURE: Surface electromyographic (EMG) activity evoked by transcutaneous electrical stimulation of the digital palmar (or plantar) nerve was recorded from the common digital extensor and cranial tibial muscles. Stimuli consisted of 25-millisecond train-of-5 constant current pulses. Current intensity was gradually increased until NWR threshold intensity was reached. The EMG signal was analyzed for quantification of the NWR. Behavioral responses accompanying the reflex were scored (scale, 0 to 5). The NWR recruitment curves were determined at 0.9, 1.1, 1.2, and 1.3 times the NWR threshold intensity. RESULTS: The NWR threshold was significantly higher for the hind limb (median value, 6.6 mA; range, 3 to 10 mA) than the forelimb (median, 3 mA; range, 1.7 to 5.5 mA). The NWR of the hind limb had a significantly longer latency (median, 122.8 milliseconds; range, 106 to 172 milliseconds), compared with the forelimb (median, 98 milliseconds; range, 86 to 137 milliseconds), and it was associated with significantly stronger behavioral reactions. Gradual increase of NWR amplitude was evident at increasing stimulation intensities and supported by the behavioral observations. CONCLUSIONS AND CLINICAL RELEVANCE: We documented NWRs evoked from the forelimb and hind limb and their recruitment with stimuli of increasing intensity in horses. These results provide a basis for use of NWRs in studies on nociceptive modulation in horses.     

Efficacy of the Parasympathetic Tone Activity monitor to assess nociception in healthy dogs anaesthetized with propofol and sevoflurane

ObjectiveTo compare a Parasympathetic Tone Activity (PTA) monitor with cardiovascular changes in invasive mean arterial pressure (IMAP) and heart rate (HR) when evaluating the response to nociceptive stimuli in anaesthetized dogs.Study designProspective experimental study.AnimalsA group of nine (seven male and two female) adult Beagle dogs weighing 13.4 ± 1.5 kg (mean ± standard deviation).MethodsAnaesthesia was induced with propofol and maintained with sevoflurane in oxygen. Electrical stimuli of different nociceptive intensities were applied for 30 seconds. Stimuli were classified in each patient according to the response obtained (relevant change ≥ 20%) as low (no response), medium (PTA only) or high (PTA and IMAP/HR). Immediate and averaged values of PTA, IMAP and HR were recorded every second from 60 seconds before to 120 seconds after application of the nociceptive stimulus. Time to nociceptive response and peak response were evaluated with analysis of variance and t test.ResultsImmediate PTA baseline values did not differ significantly before application of the low, medium and high stimuli (73 ± 15, p = 0.966). Immediate PTA response was observed with the medium stimulus at 33 ± 7 seconds with a maximum decrease of 57 ± 13% at 69 ± 5 seconds. With the high stimulus, the immediate PTA response was of a similar magnitude to the medium stimulus with a response at 28 ± 7 seconds (p = 0.221) and a maximum decrease of 68 ± 15% (p = 0.115) at 72 ± 7 seconds (p = 0.436). The cardiovascular change occurred (22 ± 8 seconds) prior to the immediate PTA response (p = 0.032).Conclusions and clinical relevanceThe PTA monitor detected nociceptive stimuli at lower intensities than those eliciting cardiovascular changes. However, nociceptive stimuli of higher intensities provoked cardiovascular changes that occurred before a PTA response was observed.     

The effect of volatile anaesthetics on the relative sensitivity of facial and distal thoracic limb muscles to vecuronium in dogs

ObjectiveTo compare n. facialis-m. nasolabialis (nF-mNL) and n. ulnar-mm. carpi flexorii (nU-mCF) sensitivity to vecuronium during halothane or isoflurane anaesthesia.Study designRandomized, prospective, experimental study.AnimalsForty-four client-owned dogs (19 male, 25 female) undergoing surgery; mean age: 5.0 years; mean body mass: 24.7 kg.MethodsThirty minutes after acepromazine (0.05 mg kg^?1) and morphine (0.5 mg kg^?1), anaesthesia was induced with intravenous (IV) thiopental and maintained with either halothane (n = 22) or isoflurane (randomly allocated) in oxygen. The lungs were mechanically ventilated and end-tidal inhaled anaesthetic (Fe’_IAA) maintained at 1.2 × MAC values. Neuromuscular transmission at nF-uNL and nU-mCF was monitored using the train of four count. Vecuronium (50 μg kg^?1 IV) was injected (t = 0) after 15 trains, 50-60 minutes after inhalational anaesthesia began, when Fe’_IAA had been constant for >15 minutes. Times of the disappearance (-) and reappearance (+) of the fourth (T4) and first twitch (T1) were recorded allowing the calculation of: latent (t = 0 to T4-) and manifest onset times (t = 0 to T1-) duration of blockade (T1- to T1+) and drug effect (T4- to T4+) and recovery time (T1+-T4+). Student’s paired t-test was used to compare simultaneous responses at nF-uNL and nU-mCF. An unpaired t-test was used to compare anaesthetic effects.ResultsLatent and manifest onset times were significantly (p < 0.05) briefer, blockade and drug effects were significantly longer and recovery from blockade were significantly slower in the nF-mNL unit in both halothane and isoflurane recipients. Profound block duration and drug action were significantly longer and recovery from blockade were significantly slower in halothane recipients at both nerve-muscle units.Conclusion and clinical relevanceThe nF-mNL was more sensitive than nU-mCF to vecuronium, particularly in halothane-anaesthetized dogs.