Effect of end-inspiratory pause duration on respiratory system compliance calculation in mechanically ventilated dogs with healthy lungs.

OBJECTIVE: To compare respiratory system compliance (CRS), expressed per kilogram of bodyweight (CRSBW), calculated without end-inspiratory pause (EIP) and after three EIP times (0.2, 0.5 and 1 seconds) with that after 3 second EIP (considered the reference EIP for static CRS) and to determine the EIP times that provided CRSBW values in acceptable agreement with static CRSBW during controlled mechanical ventilation (CMV) in anaesthetized dogs. STUDY DESIGN: Prospective, randomized, nonblinded, crossover clinical study. ANIMALS: A group of 24 client-owned dogs with healthy lungs undergoing surgery in lateral recumbency. METHODS: During CMV in dogs undergoing general anaesthesia, five EIPs [0 (no EIP), 0.2, 0.5, 1 and 3 seconds] were consecutively applied in random order. Tidal volume (Vt) was set at 10 mL kg-1 and positive end-expiratory pressure (PEEP) was not applied. Respiratory rate and inspiratory time were established according to each EIP time, setting EIP between 0 and 50% of the inspiratory time. The CRSBW was calculated as [expired Vt/(plateau pressure - PEEP)]/bodyweight and recorded every 15 seconds for 2 minutes after a 5 minute equilibration period with each EIP. One-way anova for repeated measures and the Bland-Altman analysis were used to compare CRSBW and evaluate agreement between EIP times, respectively. RESULTS: The CRSBW was significantly greater as the EIP time increased up to 1 second (p < 0.05). In the Bland-Altman analysis, none of the tested EIPs (0, 0.2, 0.5 and 1 seconds) provided 95% confidence intervals for limits of agreement within the maximum allowed difference considered for acceptable agreement with 3 second EIP. CONCLUSIONS: and clinical relevance An EIP ≤ to 1 second does not provide a CRSBW value in acceptable agreement with static CRSBW in healthy dogs. Besides, the application of an EIP ≤ to 0.5 seconds underestimates the static CRSBW to an increasing extent as the EIP time decreases.

Comparison of the sedative effects of intranasal or intramuscular dexmedetomidine at low doses in healthy dogs: a randomized clinical trial.

OBJECTIVE: To compare the sedative effects of dexmedetomidine administered either intranasally or intramuscularly to healthy dogs. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 16 client-owned healthy dogs. METHODS: Dogs were randomly allocated to one of two groups that were administered dexmedetomidine 5 µg kg-1 via either the intranasal route (INDex), through a mucosal atomization device in one nostril, or the intramuscular route (IMDex), into the epaxial muscles. Ease of intranasal administration, sedation score, onset of sedation, cardiopulmonary variables, mechanical nociceptive thresholds (MNTs) and response to venous catheterization were recorded at 0 (baseline), 5, 10, 15, 20, 25, 30, 35, 40 and 45 minutes, following drug administration. Data were compared with the one-way anova, Mann-Whitney U test, and chi-square test, where appropriate. RESULTS: Groups were not different for age, sex, weight, body condition score or temperament. Sedation scores, MNTs and response to intravenous catheter placement were not different when dexmedetomidine was administered by either route (p = 0.691; p = 0.630 and p = 0.435, respectively). Onset of sedation was not different between groups INDex and IMDex reaching a score of 4.2 ± 0.9 and 5.5 ± 1.2 at 9 ± 5 and 8 ± 4 minutes, respectively (p = 0.467). The highest sedation score was achieved at 30 and 35 minutes and sedation scores were 9.7 ± 2.0 and 9.5 ± 2.3 in groups INDex and IMDex, respectively (p = 0.799). Respiratory rate was higher in group INDex (p = 0.014), while there were no differences between routes in heart rate (p = 0.275), systolic (p = 0.957), diastolic (p = 0.837) or mean arterial pressure (p = 0.921). CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal administration of dexmedetomidine at 5 µg kg-1 provides effective sedation in healthy dogs.

Sedative and analgesic effects of two subanaesthetic doses of ketamine in combination with methadone and a low dose of dexmedetomidine in healthy dogs.

OBJECTIVE: To evaluate the sedative, analgesic and recovery characteristics of two subanaesthetic ketamine doses in combination with dexmedetomidine and methadone for intramuscular sedation in healthy Beagles. STUDY DESIGN: Randomized, blinded, crossover, experimental study. ANIMALS: Six healthy adult Beagles. METHODS: Dogs were randomly given three treatments: dexmedetomidine (3 µg kg-1) and methadone (0.3 mg kg-1) combined with ketamine at 1 and 2 mg kg-1 (K1 and K2, respectively) or saline (K0), intramuscularly. Sedation score, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35, and 45 minutes posttreatment. Pulse rate (PR), respiratory rate, oxygen haemoglobin saturation and noninvasive blood pressure were also recorded at baseline and every 5 minutes until 45 minutes posttreatment. Onset and duration of recumbency, response to venous catheterization and recovery quality were also assessed. Sedation and physiological variables were compared between treatments and within treatments compared to baseline (analysis of variance). Nonparametric data were analysed with the Friedman and Cochran's Q tests; p < 0.050. RESULTS: Increased sedation was found at 15 (K0 and K1), 25 (all treatments) and 35 (K1) minutes compared with baseline. Sedation score, onset (3-12 minutes) and duration of recumbency (29-51 minutes) were similar between treatments. Recovery quality was considered acceptable in all cases. Response to tail clamping was inconsistent within treatments with no differences between them. None of the dogs responded to venous catheterization. There were no differences between treatments in physiological variables, except for PR which was higher in K2 than in K0. Oxygen supplementation was required in five and three dogs administered saline and ketamine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of 1 or 2 mg kg-1 of ketamine to methadone and dexmedetomidine combination did not enhance sedation or antinociception in healthy dogs. Recovery quality was unaffected.

Individualized positive end-expiratory pressure following alveolar recruitment manoeuvres in lung-healthy anaesthetized dogs: a randomized clinical trial on early postoperative arterial oxygenation.

OBJECTIVE: To assess and compare the effect of intraoperative stepwise alveolar recruitment manoeuvres (ARMs), followed by individualized positive end-expiratory pressure (PEEP), defined as PEEP at maximal respiratory system compliance + 2 cmH2O (PEEPmaxCrs+2), with that of spontaneous ventilation (SV) and controlled mechanical ventilation (CMV) without ARM or PEEP on early postoperative arterial oxygenation in anaesthetized healthy dogs. STUDY DESIGN: Prospective, randomized, nonblinded clinical study. ANIMALS: A total of 32 healthy client-owned dogs undergoing surgery in dorsal recumbency. METHODS: Dogs were ventilated intraoperatively (inspired oxygen fraction: 0.5) with one of the following strategies: SV, CMV alone, and CMV with PEEPmaxCrs+2 following a single ARM (ARM1) or two ARMs (ARM2, the second ARM at the end of surgery). Arterial blood gas analyses were performed before starting the ventilatory strategy, at the end of surgery, and at 5, 10, 15, 30 and 60 minutes after extubation while breathing room air. Data were analysed using Kruskal-Wallis and Friedman tests (p < 0.050). RESULTS: At any time point after extubation, PaO2 was not significantly different between groups. At 5 minutes after extubation, PaO2 was 95.1 (78.1-104.0), 93.8 (88.3-104.0), 96.9 (86.6-115.0) and 89.1 (87.6-102.0) mmHg in the SV, CMV, ARM1 and ARM2 groups, respectively. PaO2 decreased at 30 minutes after extubation in the CMV, ARM1 and ARM2 groups (p < 0.050), but it did not decrease after 30 minutes in the SV group. Moderate hypoxaemia (PaO2, 60-80 mmHg) was observed in one dog in the ARM1 group and two dogs each in the SV and ARM2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Intraoperative ARMs, followed by PEEPmaxCrs+2, did not improve early postoperative arterial oxygenation compared with SV or CMV alone in healthy anaesthetized dogs. Therefore, this ventilatory strategy might not be clinically advantageous for improving postoperative arterial oxygenation in healthy dogs undergoing surgery when positioned in dorsal recumbency.

Attitudes of Spanish-speaking veterinarians interested in anaesthesia towards use of total intravenous anaesthesia in dogs: a survey study.

OBJECTIVES: To describe Spanish-speaking veterinary anaesthetists' attitudes towards use of total intravenous anaesthesia (TIVA) in dogs. STUDY DESIGN: Prospective online voluntary survey. POPULATION: Data from 300 answered surveys. METHODS: An anonymous questionnaire was sent via e-mail to representatives of the four largest Spanish-speaking veterinary anaesthesia and analgesia associations. It was distributed through mailing lists (Spain, Argentina, Mexico) or social media (Spain, Chile) to gather information on the use, opinions and perceived advantages of TIVA, as well as on preferred alternatives to isoflurane for providing general anaesthesia. Logistic regression was used to test for response associations. RESULTS: A total of 275 (92%) respondents had used TIVA (24% rarely, 36% sometimes, 40% very often or always). There was an association between a higher rate of TIVA usage and a low specialization level, less clinical experience and unavailability of anaesthetic gas scavenging systems. The main reasons for not using TIVA were lack of familiarity with the technique (92%), unavailability of infusion pumps (32%), established institutional anaesthetic protocol (32%), and technical difficulty (20%). Among frequent TIVA users, a higher proportion reported the greater ease of TIVA use (52%) compared to those that did not perceive such benefit (17%) [odds ratio (OR) = 5.2; 95% confidence interval (CI95), 1.7-16.6; p = 0.004). More respondents did not consider TIVA more expensive (60%) (OR = 2.1; CI95, 1.0-4.3; p = 0.034), more difficult to perform (59%) (OR = 2.5; CI95, 1.3-4.9; p = 0.006) or to manage the equipment (53%) (OR = 3.3; CI95, 1.4-7.8; p = 0.008), than inhalational anaesthetics. During isoflurane shortages, respondents reportedly preferred using an alternative inhalational agent (59%) rather than TIVA (47%). CONCLUSIONS AND CLINICAL RELEVANCE: TIVA use is widespread among veterinarians within the surveyed associations. Frequent TIVA users reported greater perceived advantages. In situations of isoflurane shortage, an alternative inhalational anaesthetic was preferred over TIVA.

Effects of ketamine or midazolam continuous rate infusions on alfaxalone total intravenous anaesthesia requirements and recovery quality in healthy dogs: a randomized clinical trial.

OBJECTIVE: To determine the alfaxalone dose reduction during total intravenous anaesthesia (TIVA) when combined with ketamine or midazolam constant rate infusions and to assess recovery quality in healthy dogs. STUDY DESIGN: Prospective, blinded clinical study. ANIMALS: A group of 33 healthy, client-owned dogs subjected to dental procedures. METHODS: After premedication with intramuscular acepromazine 0.05 mg kg-1 and methadone 0.3 mg kg-1, anaesthetic induction started with intravenous alfaxalone 0.5 mg kg-1 followed by either lactated Ringer's solution (0.04 mL kg-1, group A), ketamine (2 mg kg-1, group AK) or midazolam (0.2 mg kg-1, group AM) and completed with alfaxalone until endotracheal intubation was achieved. Anaesthesia was maintained with alfaxalone (6 mg kg-1 hour-1), adjusted (±20%) every 5 minutes to maintain a suitable level of anaesthesia. Ketamine (0.6 mg kg-1 hour-1) or midazolam (0.4 mg kg-1 hour-1) were employed for anaesthetic maintenance in groups AK and AM, respectively. Physiological variables were monitored during anaesthesia. Times from alfaxalone discontinuation to extubation, sternal recumbency and standing position were calculated. Recovery quality and incidence of adverse events were recorded. Groups were compared using parametric analysis of variance and nonparametric (Kruskal-Wallis, Chi-square, Fisher's exact) tests as appropriate, p < 0.05. RESULTS: Midazolam significantly reduced alfaxalone induction and maintenance doses (46%; p = 0.034 and 32%, p = 0.012, respectively), whereas ketamine only reduced the alfaxalone induction dose (30%; p = 0.010). Recovery quality was unacceptable in nine dogs in group A, three dogs in group AK and three dogs in group AM. CONCLUSIONS AND CLINICAL RELEVANCE: Midazolam, but not ketamine, reduced the alfaxalone infusion rate, and both co-adjuvant drugs reduced the alfaxalone induction dose. Alfaxalone TIVA allowed anaesthetic maintenance for dental procedures in dogs, but the quality of anaesthetic recovery remained unacceptable irrespective of its combination with ketamine or midazolam.

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

OBJECTIVE: To 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 DESIGN: Prospective experimental study. ANIMALS: A group of nine (seven male and two female) adult Beagle dogs weighing 13.4 ± 1.5 kg (mean ± standard deviation). METHODS: Anaesthesia 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. RESULTS: Immediate 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 RELEVANCE: The 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.

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles.

OBJECTIVE: To evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles. STUDY DESIGN: Randomized, blinded, crossover, experimental study. ANIMALS: A group of six adult Beagles. METHODS: Dogs were sedated on three different occasions with IM dexmedetomidine (3 µg kg-1) and methadone (0.3 mg kg-1) combined with two doses of alfaxalone (0.5 and 1 mg kg-1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO2) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran's Q tests. Significance was p < 0.05. RESULTS: Sedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum-maximum), 43 (35-54) versus 30 (20-47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO2. CONCLUSIONS AND CLINICAL RELEVANCE: Adding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.

Toll-like receptor 4 deficient mice do not develop remifentanil-induced mechanical hyperalgesia: An experimental randomised animal study.

BACKGROUND: Drugs with antagonistic actions on the Toll-like receptor 4 (Tlr4), such as naloxone at ultra low doses, have been used to inhibit opioid-induced hyperalgesia in rodents suggesting the involvement of this receptor and pathway on opioid-induced hyperalgesia. OBJECTIVE: The aim of this study was to determine whether mice without the Tlr4 gene (Tlr4) would not develop remifentanil-induced hyperalgesia. DESIGN: An experimental randomised animal study. SETTING: Experimental Unit, Complutense University of Madrid, Madrid, Spain. ANIMALS: Twelve adult female wild-type mice and 12 adult Tlr4 mice. INTERVENTIONS: Under sevoflurane anaesthesia, a 1-h, constant rate subcutaneous infusion of remifentanil (4 µg kg min) or 0.9% saline. MAIN OUTCOME MEASURES: Mechanical nociceptive thresholds were evaluated using a von Frey hair test before (baseline) and on days 5, 6 and 7 after treatment. Hyperalgesia was considered to be a decrease in the mechanical nociceptive threshold. Changes in mechanical nociceptive thresholds in the different groups were compared with one-sided paired t tests. RESULTS: Baseline mechanical nociceptive thresholds were similar in all groups (2.2 ±â€Š0.1 g). Remifentanil produced a 24% decrease in mechanical nociceptive thresholds in the wild-type mice (1.7 ±â€Š0.0 g, averaged over 3 days, P = 0.00021), whereas the nociceptive thresholds were not changed in Tlr4 mice (2.2 ±â€Š0.1 g, P = 0.857) or in mice receiving 0.9% saline (Tlr4, 2.2 ±â€Š0.1 g, P = 0.807; wild-type, 2.2 ±â€Š0.1 g, P = 0.962). CONCLUSION: Tlr4 receptor involvement is suggested in the development of remifentanil-induced hyperalgesia in mice. TRIAL REGISTRATION: CEA-UCM 107/2012.

Comparison of the postoperative analgesic effects of cimicoxib, buprenorphine and their combination in healthy dogs undergoing ovariohysterectomy.

OBJECTIVE: To determine the noninferior postoperative analgesic efficacy of cimicoxib compared to buprenorphine following elective ovariohysterectomy in healthy bitches. STUDY DESIGN: Prospective, randomized, blinded, controlled clinical trial. ANIMALS: A total of 63 healthy dogs. METHODS: To provide perioperative analgesia, cimicoxib 2 mg kg-1 (orally), buprenorphine 0.02 mg kg-1 (two doses, intramuscularly), or both drugs combined, were administered. Dogs were sedated with acepromazine and anaesthetized with propofol and isoflurane. Pain was assessed with the short form of the Glasgow Composite Pain Scale (GCPS), a pain numerical rating scale (NRS) and mechanical nociceptive thresholds (MNT), preoperatively and at 1, 2, 4, 6, 20 and 23 hours after extubation. Sedation was also scored at the same time points. A noninferiority approach was employed to determine the efficacy of cimicoxib compared to buprenorphine. Treatment groups were compared with parametric [analysis of variance (anova), t test] and nonparametric test as appropriate (Kruskal-Wallis, chi-square). RESULTS: The GCPS, pain NRS and MNT tests demonstrated noninferiority of cimicoxib compared to buprenorphine (rejection of inferiority: p < 0.001, all). Furthermore, cimicoxib provided better analgesia compared to buprenorphine alone according to the GCPS (p < 0.01) and NRS (p < 0.05), but not the MNT. Conversely, an increase in the analgesic effect when cimicoxib was combined with buprenorphine was only observed with the MNT (p < 0.01). There were no differences in rescue analgesia requirements both intra- and postoperatively between treatments. Gastrointestinal side effects were increased in dogs administered cimicoxib, whereas dogs treated with buprenorphine had higher sedation scores 1-hour postoperatively and required lower doses of propofol for the induction of anaesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Cimicoxib has noninferior postoperative analgesic efficacy compared to buprenorphine, and both drugs have comparable analgesic effects for the control of postoperative pain in bitches undergoing ovariohysterectomy.

The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats.

BACKGROUND: Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil. METHODS: Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C). RESULTS: A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone. CONCLUSIONS: Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil.

Isoflurane MAC determination in dogs using three intensities of constant-current electrical stimulation.

OBJECTIVES: To compare isoflurane minimum alveolar concentrations (MACs) in dogs determined using three intensities of constant-current electrical stimulation applied at the tail, and thoracic and pelvic limbs, and to compare isoflurane MACs obtained with all combinations of electrical stimulation and anatomic site with those obtained using the tail clamp as the noxious stimulus. STUDY DESIGN: Randomized trial. ANIMALS: Six mixed-breed, adult female dogs aged 1-2 years and weighing 11.1 ± 4.4 kg. METHODS: In each dog, MAC was determined by the bracketing method with the tail clamp (MACTAILCLAMP ), and three electrical currents (10 mA, 30 mA, 50 mA) at three anatomic sites (thoracic limb, pelvic limb, tail). Each MAC achieved with electrical stimulation was compared with MACTAILCLAMP using a mixed-model anova and Dunnett's procedure for multiple comparisons. The effects of current intensity and anatomic site on isoflurane MAC were tested using a mixed-model anova followed by Tukey's test for multiple comparisons (p < 0.05). RESULTS: Mean MACTAILCLAMP was 1.69%. MACs achieved with currents of 30 mA and 50 mA did not differ independently of anatomic site. When currents of 10 mA were applied to the tail and thoracic limb, resulting MACs were lower than those obtained using currents of 30 mA and 50 mA. Currents of 30 mA and 50 mA provided MACs that did not differ from those of MACTAILCLAMP , whereas a current of 10 mA achieved the same result only for the pelvic limb. CONCLUSIONS AND CLINICAL RELEVANCE: Isoflurane MAC is affected by current intensity and anatomic site. Current intensities of 30 mA and 50 mA provided consistent results when applied to the tail, and thoracic and pelvic limbs that did not differ from those obtained using the tail clamp. Consequently, they can be used in place of the tail clamp in MAC studies in dogs.

Tramadol-induced hyperalgesia and its prevention by ketamine in rats: A randomised experimental study.

BACKGROUND: Opioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics. OBJECTIVES: The objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes. DESIGN: A randomised, experimental study. SETTING: Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Thirty-nine adult male Wistar rats. INTERVENTIONS: Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg) with or without ketamine (10 mg kg), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments. MAIN OUTCOME MEASURES: The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT. RESULTS: Tramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P < 0.05; day 7). Ketamine administration prevented both the reduction in MNT and the increase in MAC (P > 0.05). CONCLUSION: Tramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.

Amitriptyline, minocycline and maropitant reduce the sevoflurane minimum alveolar concentration and potentiate remifentanil but do not prevent acute opioid tolerance and hyperalgesia in the rat: a randomised laboratory study.

BACKGROUND: The antidepressant amitriptyline, the inhibitor of microglia activation minocycline, and the neurokinin-1 antagonist maropitant have all been used to prevent or treat hyperalgesia and opioid tolerance. OBJECTIVES: To determine the effect of amitriptyline, minocycline, maropitant, independently or with remifentanil, on the sevoflurane minimum alveolar concentration in rats and whether these drugs may block opioid-induced hyperalgesia and acute opioid tolerance under inhalational anaesthesia. DESIGN: A randomised, laboratory study. SETTING: Experimental Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: One hundred and fourteen adult male Wistar rats. INTERVENTIONS: Intraperitoneal administration of amitriptyline (10 and 50  mg  kg-1), minocycline (30 and 100  mg  kg-1), maropitant (10 and 30 mg  kg-1) or isotonic saline, combined with a constant rate intravenous infusion of remifentanil (240 µg  kg-1  h-1) or saline. MAIN OUTCOME MEASURES: Sevoflurane minimum alveolar concentration was determined before and after administration of the drugs; acute opioid tolerance was defined as a decreased ability of remifentanil to reduce the minimum alveolar concentration in the short term. In addition, mechanical nociceptive thresholds were determined before and after these treatments. Opioid-induced hyperalgesia was defined as an increase in mechanical nociceptive thresholds after opioid administration. RESULTS: Amitriptyline, minocycline and maropitant reduced minimum alveolar concentration up to 24 (8)%, 23 (6)% and 15 (5)%, respectively (P <0.001). Remifentanil alone reduced minimum alveolar concentration by 36 (6)% (P <0.001), and in combination with amitriptyline, minocycline and maropitant, the reduction was 76 (9)%, 75 (16)% and 59 (5)%, respectively (P <0.001). An acute tolerance effect (P < 0.01) and a decrease in the mechanical nociceptive thresholds were observed with remifentanil in all groups. CONCLUSION: Amitriptyline, minocycline and maropitant reduced the minimum alveolar concentration and potentiated the remifentanil minimum alveolar concentration reduction but failed to block opioid-induced hyperalgesia and acute opioid tolerance.

The sedative effects of intramuscular low-dose medetomidine in combination with butorphanol or methadone in dogs.

OBJECTIVE: To compare the sedative effects of an intramuscular (IM) low dose of medetomidine in combination with butorphanol or methadone in dogs. STUDY DESIGN: Prospective, blinded, randomized clinical trial. ANIMALS: Forty-eight healthy adult dogs that required sedation for diagnostic or surgical elective procedures. METHODS: Dogs were sedated IM with medetomidine (2.5 µg kg(-1)) and either butorphanol (0.4 mg kg(-1)) or methadone (0.4 mg kg(-1)). The degree of sedation was assessed every 10 minutes, for 30 minutes, using a numeric descriptive scale. Data on heart rate (HR), respiratory rate, capillary refill time, temperature and response to a toe pinch were recorded. The response to venous catheterization at minute 30 was also evaluated. RESULTS: Both combinations produced moderate to deep sedation with a maximal effect at 20-30 minutes without significant differences in the degree of sedation between the treatments at any studied time-point. HR decreased from minute 10 to minute 30 with both opioid combinations (p<0.05); this reduction did not differ between groups (p>0.05). No differences between groups were detected in any of the other variables. CONCLUSIONS AND CLINICAL RELEVANCE: Combinations of a low dose of medetomidine with butorphanol or methadone, respectively, provide similar degrees of sedation.

Comparison of isoflurane and alfaxalone (Alfaxan) for the induction of anesthesia in flamingos (Phoenicopterus roseus) undergoing orthopedic surgery.

Used since the 1970s as an avian anesthetic, the neurosteroid alfaxalone has been reformulated to avoid side effects from its castor oil excipient. This case report describes the clinical use of a new alfaxalone formulation (Alfaxan) as an intravenous anesthetic induction agent in wild isoflurane-anesthetized rose flamingos (Phoenicopterus roseus). Twenty-five male and female rose flamingos underwent orthopedic surgery using isoflurane anesthesia. The animals were induced following one of two protocols: inhaled isoflurane by facemask (ISO; n = 9) or intravenous alfaxalone (2 mg/kg; ALF; n = 16). The time and quality of anesthetic induction (until first signs of muscle relaxation) and the time and quality of recovery (sternal recumbency) were recorded using a scoring system. Mild sedation was first observed at 18.4 +/- 3.8 min and 1.7 +/- 0.3 min, following isoflurane and alfaxalone administration, respectively (P < 0.001). Alfaxalone induction time was significantly shorter and induction quality was considered smoother than in the ISO group. Flamingos given alfaxalone induction required lower isoflurane concentrations for maintenance anesthesia than did flamingos induced with mask isoflurane (1.5-2 % vol vs. 4-5 % vol for ALF vs. ISO, respectively). Alfaxalone produced moderate cardiorespiratory effects not seen in the isoflurane induction group. Recovery times were similar with both protocols without significant differences in quality and length. The new alfaxalone formulation produces a safe and effective anesthetic induction in rose flamingos and has significant isoflurane-sparing effects during anesthesia.

Translation and linguistic validation into Spanish of the Owner-Reported Outcome Measure "Liverpool Osteoarthritis in Dogs".

Introduction: Assessing chronic pain in dogs has been greatly favoured by the development of Owner-Reported Outcome Measures. Among them, the Liverpool Osteoarthritis in Dogs (LOAD) has been widely used for this purpose. Most of these tools have been written in English and its use by non English natives requires not only translation but also linguistic validation for use by veterinarians and owners. For its use, the LOAD has not undergone translation into Spanish and the objective was to generate a linguistically validated Spanish translation of the LOAD. Methods: Following the World Health Organisation and the International Society for Pharmacoeconomics and Outcomes Research published guidelines, the original LOAD English version underwent analysis and translation by two native linguists proficient in the target language. Both translations were then reviewed by a third native linguist to identify potential disparities and establish a cohesive translation (reconciliation). Subsequently, an independent linguist, fluent in both English and the target language, conducted the back translation. Finally, the research team compared the original and back translated versions to pinpoint and resolve any significant differences. Following the creation of the translated version, a cognitive debriefing was conducted to assess the questionnaire within the target population. Results: A total of 89 surveys were distributed to dog owners of varying ages, genders, and socioeconomic backgrounds. Although there were some suggestions and comments, and some adjustments were made, all respondents found the survey to be clear, achieving a linguistic validation of the Spanish LOAD.

Effects of naloxone on opioid-induced hyperalgesia and tolerance to remifentanil under sevoflurane anesthesia in rats.

BACKGROUND: Opioid antagonists at ultra-low doses have been used with opioid agonists to prevent or limit opioid tolerance. The aim of this study was to evaluate whether an ultra-low dose of naloxone combined with remifentanil could block opioid-induced hyperalgesia and tolerance under sevoflurane anesthesia in rats. METHODS: Male adult Wistar rats were allocated into one of four treatment groups (n = 7), receiving remifentanil (4 µg·kg·min) combined with naloxone (0.17 ng·kg·min), remifentanil alone, naloxone alone, or saline. Animals were evaluated for mechanical nociceptive thresholds (von Frey) and subsequently anesthetized with sevoflurane to determine the baseline minimum alveolar concentration (MAC). Next, treatments were administered, and the MAC was redetermined twice during the infusion. The experiment was performed three times on nonconsecutive days (0, 2, and 4). Hyperalgesia was considered to be a decrease in mechanical thresholds, whereas opioid tolerance was considered to be a decrease in sevoflurane MAC reduction by remifentanil. RESULTS: Remifentanil produced a significant decrease in mechanical thresholds compared with baseline values at days 2 and 4 (mean ± SD, 30.7 ± 5.5, 22.1 ± 6.4, and 20.7 ± 3.7g at days 0, 2, and 4, respectively) and an increase in MAC baseline values (2.5 ± 0.3, 3.0 ± 0.3, and 3.1 ± 0.3 vol% at days 0, 2, and 4, respectively). Both effects were blocked by naloxone coadministration. However, both remifentanil-treated groups (with or without naloxone) developed opioid tolerance determined by their decrease in MAC reduction. CONCLUSIONS: An ultra-low dose of naloxone blocked remifentanil-induced hyperalgesia but did not change opioid tolerance under inhalant anesthesia. Moreover, the MAC increase associated with hyperalgesia was also blocked by naloxone.

Attitudes to acute pain and the use of pain assessment scales among Spanish small animal veterinarians.

Evaluation of acute pain in dogs and cats is the basis for an appropriate treatment and improved well-being. The difficulties involved in pain assessment pose a challenge for veterinarians, and recent findings indicate that the most effective tools available-validated pain assessment scales-may not be widely utilized. Objectives: This study aimed to characterize the level of concern among Spanish veterinarians regarding acute pain in companion animals. Additionally, it sought to determine whether this concern correlates with the utilization of optimal assessment tools. Methods: A survey was conducted to explore Spanish veterinarians' attitudes toward pain and its assessment. The survey was distributed through two most prominent small animal veterinary associations, the Spanish association for veterinary anesthesia and analgesia, as well as key industry players committed to proactive pain management. Descriptive analysis of the collected data was performed using Excel and SPSS. Results: A total of 292 veterinarians participated in the study. A high level of concern regarding pain in dogs and cats was determined where 44% of surveyed veterinarians assessed pain in all patients. Despite an awareness of validated pain scales, only 28% used them. The preferred scales were the Glasgow CMPS for dogs (94%) and the Feline Grimace Scale for cats (93%). Among respondents who do not use these validated tools, there was a considerable interest in incorporating these scales into practice (85%) and considered lack of training was the most relevant issue (32%). Other challenges to scale utilization were identified, including constraints related to time, staffing, and the need to establish a habit. Conclusions and relevance: Spanish small animal veterinarians demonstrated a strong awareness to pain in their patients and employed various methods for pain assessment. However, a limited use of validated tools was identified and likely attributed to challenges such as a lack of established routine, time constraints, insufficient personnel, and, notably, a knowledge gap among veterinarians who do not employ pain assessment scales. The most commonly used scales were the Glasgow CMPS for dogs and the FGS for cats. Overall, these results suggest a window of opportunity for the implementation of training programs in small animal pain assessment at a national level.