Determination of acute tolerance and hyperalgesia to remifentanil constant rate infusion in dogs undergoing sevoflurane anaesthesia.

OBJECTIVE: To determine if acute opioid tolerance (AOT) or opioid-induced hyperalgesia (OIH) could develop and limit the remifentanil-induced reduction in the sevoflurane minimum alveolar concentration (MAC). The response to mechanical nociceptive threshold (MNT) was evaluated and related to OIH. STUDY DESIGN: A crossover, randomized, experimental animal study. ANIMALS: A total of nine Beagle dogs. METHODS: The dogs were anaesthetized with sevoflurane in 50% oxygen. Baseline sevoflurane MAC was measured (MACb1). Remifentanil (0.3 µg kg-1 minute-1) or 0.9% saline constant rate infusion (CRI) was administered intravenously (IV). Sevoflurane MAC was determined 20 minutes after CRI was initiated (MACpostdrug1), 30 minutes after MACpostdrug1 determination (MACpostdrug2) and after 1 week (MACb2). The MNT was determined at baseline (before anaesthesia), 3 and 7 days after anaesthesia. An increase of MACpostdrug2 ≥0.25% compared to MACpostdrug1 was considered evidence of AOT. A decrease in MNT at 3 and 7 days or an increase in MACb2 or both with respect to MACb1 were considered evidence of OIH. RESULTS: Remifentanil CRI reduced sevoflurane MACpostdrug1 by 43.7% with respect to MACb1. MACpostdrug2 was no different from MACpostdrug1 with the saline (p = 0.62) or remifentanil (p = 0.78) treatments. No significant differences were observed in the saline (p = 0.99) or remifentanil (p = 0.99) treatments between MACb1 and MACb2, or for MNT values between baseline, 3 and 7 days. CONCLUSION AND CLINICAL RELEVANCE: In dogs, under the study conditions, remifentanil efficacy in reducing sevoflurane MAC did not diminish in the short term, suggesting remifentanil did not induce AOT. Hyperalgesia was not detected 3 or 7 days after the administration of remifentanil. Contrary to data from humans and rodents, development of AOT or OIH in dogs is not supported by the findings of this study.

Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study.

BACKGROUND: Intestinal ischemia-reperfusion (IR) is an important clinical occurrence seen in common diseases, such as gastric dilatation-volvulus in dogs or colic in horses. Limited data is available on the use of methylene blue in veterinary medicine for intestinal ischemia-reperfusion. The present study aimed to compare the hemodynamic, histopathological, and immunohistochemical effects of two doses of methylene blue in two rabbit model groups In one group, 5 mg/kg IV was administered, and in another, 20 mg/kg IV was administered following a constant rate infusion (CRI) of 2 mg/kg/h that lasted 6 h. All the groups, including a control group had intestinal ischemia-reperfusion. Immunohistochemical analysis was performed using caspase-3. RESULTS: During ischemia, hemodynamic depression with reduced perfusion and elevated lactate were observed. During reperfusion, methylene blue (MB) infusion generated an increase in cardiac output due to a positive chronotropic effect, an elevation of preload, and an intense positive inotropic effect. The changes in heart rate and blood pressure were significantly greater in the group in which methylene blue 5 mg/kg IV was administered (MB5) than in the group in which methylene blue 20 mg/kg IV dose was administered (MB20). In addition, lactate and stroke volume variations were significantly reduced, and vascular resistance was significantly elevated in the MB5 group compared with the control group and MB20 group. The MB5 group showed a significant decrease in the intensity of histopathological lesion scores in the intestines and a decrease in caspase-3 areas, in comparison with other groups. CONCLUSIONS: MB infusion produced improvements in hemodynamic parameters in rabbits subjected to intestinal IR, with increased cardiac output and blood pressure. An MB dosage of 5 mg/kg IV administered at a CRI of 2 mg/kg/h exhibited the most protective effect against histopathological damage caused by intestinal ischemia-reperfusion. Further studies with MB in clinical veterinary pathologies are recommended to fully evaluate these findings.

Evaluation of gastric and bladder tonometry as indicators of tissue perfusion in induced hypotension in dogs.

OBJECTIVE: To evaluate the use of gastric (PgCO2 ) and bladder (PbCO2 ) tonometry for assessing tissue hypoperfusion in dogs during sevoflurane-induced hypotension, and to compare these measurements with delivery of oxygen, arterial oxygen content, and plasma lactate concentration. DESIGN: Prospective experimental trial. SETTING: University veterinary teaching hospital. ANIMALS: Fourteen adult Beagle dogs. INTERVENTIONS: Anesthetic induction was performed by mask with sevoflurane and oxygen. Heart rate, direct arterial pressures, respiratory rate, and end-tidal carbon dioxide were recorded; arterial blood samples were taken to measure blood gases, and venous samples were sampled to measure plasma lactate. A tonometric catheter was introduced into the stomach to measure PgCO2 . Samples of saline from the balloon of a Foley catheter placed in the bladder were collected every 10 minutes and used to measure PbCO2 by gas analysis. Tonometry measurements, plasma lactate, and oxygen delivery and consumption were compared at 3 time points: at baseline, during hypotension, and during treatment periods. A hypotensive period (mean arterial pressure (MAP) < 60 mm Hg) of 15 minutes was induced by an overdose of sevoflurane, whereas during the treatment period, a constant-rate infusion of dopamine (10 µg/kg/min) was administered intravenously for 40 minutes. MEASUREMENTS AND MAIN RESULTS: Values for PgCO2 and PbCO2 increased significantly during the hypotensive period, and correlations were found between these values and the delivery of oxygen. Gastric tonometry values had stronger correlations compared with bladder tonometry values. CONCLUSIONS: Gastric and bladder tonometry can be used to detect hypoperfusion. Further studies are warranted to determine the potential use of gastric and bladder tonometry in assessing dogs in clinical situations.

A comparison of cardiopulmonary effects and anaesthetic requirements of two dexmedetomidine continuous rate infusions in alfaxalone-anaesthetized Greyhounds.

OBJECTIVE: To determine the effects of two dexmedetomidine continuous rate infusions on the minimum infusion rate of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent haemodynamic and recovery effects in Greyhounds undergoing laparoscopic ovariohysterectomy. STUDY DESIGN: Prospective, randomized and blinded clinical study. ANIMALS: Twenty-four female Greyhounds. METHODS: Dogs were premedicated with dexmedetomidine 3 µg kg-1 and methadone 0.3 mg kg-1 intramuscularly. Anaesthesia was induced with IV alfaxalone to effect and maintained with a TIVA mixture of alfaxalone in combination with two different doses of dexmedetomidine (0.5 µg kg-1 hour-1 or 1 µg kg-1 hour-1; groups DEX0.5 and DEX1, respectively). The alfaxalone starting dose rate was 0.07 mg kg-1 minute-1 and was adjusted (± 0.02 mg kg-1 minute-1) every 5 minutes to maintain a suitable depth of anaesthesia. A rescue alfaxalone bolus (0.5 mg kg-1 IV) was administered if dogs moved or swallowed. The number of rescue boluses was recorded. Heart rate, arterial blood pressure and arterial blood gas were monitored. Qualities of sedation, induction and recovery were scored. Differences between groups were tested for statistical significance using a Student's t test or Mann-Whitney U test as appropriate. RESULTS: There were no differences between groups in sedation, induction and recovery quality, the median (range) induction dose of alfaxalone [DEX0.5: 2.2 (1.9-2.5) mg kg-1; DEX1: 1.8 (1.2-2.9) mg kg-1], total dose of alfaxalone rescue boluses [DEX0.5: 21.0 (12.5-38.8) mg; DEX1: 22.5 (15.5-30.6) mg] or rate of alfaxalone (DEX0.5: 0.12±0.04 mg kg-1 minute-1; DEX1: 0.12±0.03 mg kg-1 minute-1). CONCLUSIONS AND CLINICAL RELEVANCE: Co-administration of dexmedetomidine 1 µg kg-1 hour-1 failed to reduce the dose rate of alfaxalone compared with dexmedetomidine 0.5 µg kg-1 hour-1 in Greyhounds undergoing laparoscopic ovariohysterectomy. The authors recommend an alfaxalone starting dose rate of 0.1 mg kg-1 minute-1. Recovery quality was good in the majority of dogs.

Effect of dexmedetomidine constant rate infusion on the bispectral index during alfaxalone anaesthesia in dogs.

OBJECTIVE: To assess the effect of two rates of infusion of dexmedetomidine on the bispectral index (BIS) in dogs anaesthetized with alfaxalone constant rate infusion (CRI). STUDY DESIGN: Prospective, randomized, 'blinded' experimental study. ANIMALS: Six healthy Beagles (three females and three males). METHODS: Dogs received as premedication saline (group D0), 1 µg kg(-1) (group D1) or 2 µg kg(-1) (group D2) dexmedetomidine, intravenously (IV). Anaesthesia was induced with alfaxalone (6 mg kg(-1) to effect IV) and maintained with alfaxalone at 0.07 mg kg(-1)  minute(-1) and a CRI of saline (D0) or dexmedetomidine 0.5 µg kg(-1)  hour(-1) (D1) or 1 µg kg(-1)  hour(-1) (D2) for 90 minutes. BIS, electromyography (EMG), signal quality index (SQI) and suppression ratio (SR) were measured at 10 minute intervals and the median values were calculated. Nociceptive stimuli were applied every 30 minutes and BIS and cardiorespiratory values were compared before and after stimuli. Cardiorespiratory parameters were recorded throughout the study. RESULTS: BIS and EMG values differed significantly among groups, being lower in D2 (71 ± 8) than in D0 (85 ± 10) and D1 (84 ± 9). SQI was always over 90% and SR was zero throughout all the treatments. There were no significant differences between pre- and post-stimulus values of BIS, EMG and SQI for any treatment, although in D0 and D1, heart rate, respiratory rate and arterial pressures increased significantly after the nociceptive stimulus. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of dexmedetomidine (2 µg kg(-1)  + CRI 1 µg kg(-1)  hour(-1) ) decreases the BIS values and avoids the autonomic responses of a nociceptive stimulus during alfaxalone anaesthesia at 0.07 mg kg(-1)  minute(-1) in dogs. However, further studies are needed to verify whether this combination produces an adequate degree of hypnosis under surgical situations.

Effectiveness of pre-peritoneal continuous wound infusion with lidocaine for pain control following ovariohysterectomy in dogs.

This study compared the post-operative analgesic efficacy of continuous lidocaine administration with that of intramuscular (IM) methadone in dogs undergoing ovariohysterectomy. Thirty-eight dogs were divided randomly into two groups. Following surgery, the lidocaine group (L) received a continuous lidocaine infusion (2 mg/kg/h) through a wound catheter inserted in the pre-peritoneal space; the control group (C) received methadone (0.2 mg/kg IM). A dynamic and interactive visual analogue scale (DIVAS), the Scale-Form Glasgow Composite Measure Scale (CMPS-SF), mechanical wound thresholds, heart rate, respiratory rate and blood pressure were assessed pre-operatively and 2, 4, 6, 18, and 24 h after surgery. The presence of the wound catheter prevented the evaluator from remaining blinded to group allocations. Plasma lidocaine and cortisol levels were measured 2, 6, 18, and 24 h after surgery. There were no intergroup differences in any pain assessment scale scores at any time point. Stable intravenous lidocaine levels were observed. Four animals in the control group but none in the lidocaine group required rescue analgesia. There were no differences in complication rates between groups. Continuous locoregional lidocaine delivered via a wound catheter between the parietal peritoneum and abdominal muscle offers effective analgesia in dogs during ovariohysterectomy and appears to be a promising analgesic option in veterinary surgery.

Comparison of thermodilution, lithium dilution, and pulse contour analysis for the measurement of cardiac output in 3 different hemodynamic states in dogs.

OBJECTIVE: To (1) evaluate lithium dilution (LiDCO) and transpulmonary thermodilution (PiCCOTD ) in relation to traditional thermodilution (PAC-TD) for determining cardiac output (CO) in 3 different hemodynamic states in dogs and to (2) compare the continuous CO values obtained using power analysis (PulseCO) with continuous PiCCO (PiCCOc). DESIGN: Prospective randomized study. SETTING: University research laboratory. ANIMALS: Fourteen healthy Beagles. INTERVENTIONS: CO was measured using PAC-TD, LiDCO, and PiCCOTD in 3 different hemodynamic states induced in random order and defined on the basis of the mean arterial pressure (MAP). Normodynamic state was defined as the baseline MAP and 1 MAC sevoflurane. The hypodynamic state was induced with a deep level of sevoflurane anesthesia. The hyperdynamic state was induced with noradrenaline. After these measurements were obtained in each hemodynamic state, CO was monitored continuously for 30 min using PulseCO and PiCCOc. Agreement was assessed using Bland-Altman analysis and intraclass correlation coefficients, and a trend score was determined for the continuous CO measurements. MEASUREMENTS AND MAIN RESULTS: There was good agreement among the 3 modalities of CO measurement in each hemodynamic state. The mean CIPAC-TD /CIPICCOTD bias was -0.04 ± 1.19 L/min/m(2) (limits of agreement, -2.37/1.93 L/min/m(2) ), and the mean CIPAC-TD /CILiDCO bias was -0.11 ± 1.55 L/min/m(2) (limits of agreement, -3.04/2.93 L/min/m(2) ). The mean CIPulseCO -CIPiCCOc bias was -0.04 ± 1.91 L/min/m(2) (limits of agreement, -1.95/1.87 L/min/m(2) ), which suggested good agreement. The CIPulseCO -CIPiCCOc trend score, calculated from 252 paired comparisons, was 93.3% positive after zone exclusion (∆CI < 15%). CONCLUSIONS: Both LiDCO and PiCCOTD agreed well with PAC-TD for the measurement of CO under different hemodynamic conditions. Moreover, PiCCOc appears to be an accurate method for monitoring continuous CO in dogs as its performance for measurement was similar to that of PulseCO.

Histological study of the influence of plasma rich in growth factors (PRGF) on the healing of divided Achilles tendons in sheep.

BACKGROUND: The use of plasma rich in growth factors (PRGF) has been proposed to improve the healing of Achilles tendon injuries, but there is debate about the effectiveness of this therapy. The objective of the present study was to evaluate the histological effects of PRGF, which is a type of leukocyte-poor platelet-rich plasma, on tendon healing. METHODS: The Achilles tendons of twenty-eight sheep were divided surgically. The animals were randomly divided into four groups of seven animals each. The repaired tendons in two groups received an infiltration of PRGF intraoperatively and every week for the following three weeks under ultrasound guidance. The tendons in the other two groups received injections with saline solution. The animals in one PRGF group and one saline solution group were killed at four weeks, and the animals in the remaining two groups were killed at eight weeks. The Achilles tendons were examined histologically, and the morphometry of fibroblast nuclei was calculated. RESULTS: The fibroblast nuclei of the PRGF-treated tendons were more elongated and more parallel to the tendon axis than the fibroblast nuclei of the tendons in the saline solution group at eight weeks. PRGF-treated tendons showed more packed and better oriented collagen bundles at both four and eight weeks. In addition to increased maturation of the collagen structure, fibroblast density was significantly lower in PRGF-infiltrated tendons. PRGF-treated tendons exhibited faster vascular regression than tendons in the control groups, as demonstrated by a lower vascular density at eight weeks. CONCLUSIONS: PRGF was associated with histological changes consistent with an accelerated early healing process in repaired Achilles tendons in sheep after experimental surgical disruption. PRGF-treated tendons showed improvements in the morphometric features of fibroblast nuclei, suggesting a more advanced stage of healing. At eight weeks, histological examination revealed more mature organization of collagen bundles, lower vascular densities, and decreased fibroblast densities in PRGF-treated tendons than in tendons infiltrated with saline solution. These findings were consistent with a more advanced stage of the healing process. CLINICAL IMPLICATIONS: Based on the findings in this animal model, PRGF infiltration may improve the early healing process of surgically repaired Achilles tendons.

Liver stiffness using transient elastography is applicable to canines for hepatic disease models.

BACKGROUND: The objectives of this study were to evaluate the best position and best exploration probe for determining liver stiffness (LS) in dogs using transient liver elastography (TE). Thirteen dogs were used in the study. METHODOLOGY/PRINCIPAL FINDINGS: Morphometric measurements taken were thoracic circumference, weight and height. Elastographic measurements were taken in 4 anatomical positions using two different probes: medium (M) and small (S). The exploration was considered correct when the success rate was above 60% and the interquartile range of the measurements did not exceed 30%. The best measurements were obtained in the middle of the 6th-9th intercostal spaces, with the dog in the left lateral position and using probe M for preference in adults and probe S mandatory for animals <2 years. The correlation between probes was 99%. Intra-observer variability showed an intra-class correlation of 97.6%. CONCLUSIONS/SIGNIFICANCE: TE is a technique that is reproducible in dogs.

Comparison of the cardiopulmonary parameters after induction of anaesthesia with alphaxalone or etomidate in dogs.

OBJECTIVE: To compare the cardiorespiratory effects and quality of induction of and recovery from anaesthesia following etomidate or alphaxalone-HPCD IV. STUDY DESIGN: Randomized 'blinded' cross-over study. Twenty-four hours was allowed between phases. ANIMALS: Eight healthy adult Beagles (four male, four female). METHODS: Dogs were anaesthetized with sevoflurane for instrumentation, then allowed to awake. They then received etomidate (treatment E) or alphaxalone-HPCD (treatment A) intravenously to effect. Heart rate (HR), body temperature, invasive arterial pressures (AP), systemic vascular resistance index (SVRI), stroke volume index, cardiac index (CI), contractility, respiratory rate, central venous pressure, and capnometry were obtained before anaesthetic induction (baseline), 30 seconds and 1 minute after induction, after intubation, one minute after intubation, and for every 5 minutes afterwards until the dog began to swallow and the trachea was extubated. Arterial bloods were taken for analyses before induction, after intubation and every 10 minutes thereafter. The dogs breathed room air. The quality of induction of and recovery from anaesthesia were scored categorically. Statistical analyses used anova for repeated measures, paired t-tests or Wilcoxon signed rank-test as relevant. Significance was set at p < 0.05. RESULTS: The induction doses required were (mean ± SD) 2.91 ± 0.41 mg kg(-1) and 4.15 ± 0.7 mg kg(-1) for treatment E and A respectively. No significant changes in cardiovascular parameters were observed with treatment E. Treatment A resulted in statistically significant increases in HR and CI and reductions of APs and SVRI. Time to extubation was longer with treatment A (25 ± 7 minutes) than with treatment E (17 ± 4 minutes). Dogs became hypoxic with both treatments. The quality of induction and recovery were excellent with treatment A, but significantly less satisfactory with treatment E (recovery score, treatment E median 1, range 0-2; treatment A median 0, range 0-1). CONCLUSIONS AND CLINICAL RELEVANCE: Alphaxalone-HPCD caused significant tachycardia and increase in CI, and statistically (but not clinically) significant decreases in APs and SVRI. Etomidate caused no statistically significant cardiovascular changes. Quality of recovery was better with alfaxalone-HPCD. Both agents caused short-lived hypoxia, and oxygen supplementation is advisable.