Gait analysis: An effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applications.

INTRODUCTION: Tissue engineering has emerged as an innovative approach to treat critical-size bone defects using biocompatible scaffolds, thus avoiding complex distraction surgeries or limited stock grafts. Continuous regeneration monitoring is essential in critical-size cases due to the frequent appearance of non-unions. This work evaluates the potential clinical use of gait analysis for the mechanical assessment of a tissue engineering regeneration as an alternative to the traditional and hardly conclusive manual or radiological follow-up. MATERIALS AND METHODS: The 15-mm metatarsal fragment of eight female merino sheep was surgically replaced by a bioceramic scaffold stabilized with an external fixator. Gait tests were performed weekly by making the sheep walk on an instrumented gangway. The evolution of different kinematic and dynamic parameters was analyzed for all the animal's limbs, as well as asymmetries between limbs. Finally, potential correlation in the recovery of the gait parameters was evaluated through the linear regression models. RESULTS: After surgery, the operated limb has an altered way of carrying body weight while walking. Its loading capacity was significantly reduced as the stance phases were shorter and less impulsive. The non-operated limbs compensated for this mobility deficit. All parameters were normalizing during the consolidation phase while the bone callus was simultaneously mineralizing. The results also showed high levels of asymmetry between the operated limb and its contralateral, which exceeded 150% when analyzing the impulse after surgery. Gait recovery significantly correlated between symmetrical limbs. CONCLUSIONS: Gait analysis was presented as an effective, low-cost tool capable of mechanically predicting the regeneration of critical-size defects treated by tissue engineering, as comparing regeneration processes or novel scaffolds. Despite the progressive normalization as the callus mineralized, the bearing capacity reduction and the asymmetry of the operated limb were more significant than in other orthopedic alternatives.

Comparison of the efficacy of two alveolar recruitment manoeuvres in improving the lung mechanics and the degree of atelectasis in anaesthetized healthy sheep.

The aim of the present study was to evaluate whether the application of two types of alveolar recruitment manoeuvres (ARMs) followed by a positive end-expiratory pressure (PEEP) improved lung mechanics and the degree of atelectasis caused by general anaesthesia. Twenty-one female Merino sheep were divided into three groups: sustained inflation ARM (ARMsust), stepwise ARM (AMRstep), and control (without ARM). Sheep received detomidine-morphine for premedication, propofol for induction, and isoflurane during general anaesthesia in a volume-controlled mode with 100% oxygen during the first 15 min of anaesthesia and 40% the rest of the study. The right jugular vein and metacarpal artery were catheterised for mixed venous and arterial blood sample collection, respectively. The quasistatic compliance (Cqst), oxygenation parameters, and shunt fraction (Qs/Qt) were monitored before ARM application (TpreARM), and at 10 (T10) and 60 min (T60) after ARM application. A pulmonary histopathological study was conducted on five animals from each group. A significant increase in Cqst was observed in both ARM groups at T10 compared to TpreARM (ARMsust: P = 0.001; ARMstep: P = 0.002), although only the ARMsust group showed significant differences compared to the control group. The ARMstep group presented a significant improvement in oxygenation parameters and Qs/Qt fraction (T10: 4.84 (3.26-16.48)%, P = 0.048; T60: 4.40 (4.31-14.16)%, P = 0.004) compared with TpreARM (21.48 (20.61-28.32)%). The ARMstep group had the highest percentage of alveolar area and the most homogeneous values. In conclusion, the application of a stepwise ARM followed by PEEP improved atelectasis caused by isoflurane anaesthesia in healthy sheep.

Intraoperative nociception-antinociception monitors: A review from the veterinary perspective.

OBJECTIVE: To review monitors currently available for the assessment of nociception-antinociception in veterinary medicine. DATABASES USED: PubMed, Web of Science and Google Scholar. The results were initially filtered manually based on the title and the abstract. CONCLUSIONS: The provision of adequate antinociception is difficult to achieve in veterinary anaesthesia. Currently, heart rate and arterial blood pressure are used to monitor the response to a noxious stimulus during anaesthesia, with minimum alveolar concentration-sparing effect and stress-related hormones used for this purpose in research studies. However, since none of these variables truly assess intraoperative nociception, several alternative monitoring devices have been developed for use in humans. These nociceptive-antinociceptive monitoring systems derive information from variables, such as electroencephalography, parasympathetic nervous system (PNS) response, sympathetic nervous system response and electromyography. Several of these monitoring systems have been investigated in veterinary medicine, although few have been used to assess intraoperative nociception in animals. There is controversy regarding their effectiveness and clinical use in animals. A nociceptive-antinociceptive monitoring system based on the PNS response has been developed for use in cats, dogs and horses. It uses the parasympathetic tone activity index, which is believed to detect inadequate intraoperative nociception-antinociception balance in veterinary anaesthesia. Nonetheless, there are limited published studies to date, and cardiovascular variables remain the gold standard. Consequently, further studies in this area are warranted.

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.

Comparative pharmacokinetics and a clinical laboratory evaluation of intravenous acetaminophen in Beagle and Galgo Español dogs.

OBJECTIVE: To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Español (GE) dogs. STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: A total of 20 healthy dogs - 10 Beagles and 10 GE (six males and four females in both groups). METHODS: Acetaminophen (10 and 20 mg kg-1) was administered intravenously (IV) to the dogs on two different occasions. Plasma concentrations were analysed by high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling with ADAPT 5 software. Simulations after multiple IV doses were investigated. Clinical laboratory values such as red blood cell (RBC) count, haemoglobin (Hb), haematocrit (Ht), white blood cell (WBC) count, platelet count, total proteins, alanine aminotransferase (ALT), aspartate aminotransferase, urea and creatinine were measured before and 24 hours after acetaminophen administration in combination with clinical examination to assess side effects resulting from the drug. RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. PK parameters were different as a result of a breed effect. For doses of 10 and 20 mg kg-1, respectively, clearance values were 1.70 (1.15-2.27) and 1.62 (1.06-2.86) L kg-1 hour-1 for Beagles and 1.18 (0.70-1.39) and 1.08 (0.67-1.35) L kg-1 hour-1 for GE; elimination half-life values were 2.64 (0.52-4.46) and 2.86 (0.87-4.63) hours for Beagles and 3.49 (1.89-7.80) and 4.57 (2.08-8.90) hours for GE. Significant differences were also found between GE and Beagles in the RBC count, Ht, Hb, WBC count and serum ALT before drug administration, and these differences were maintained 24 hours later, independent of the dosage used. For each breed, no side effects resulting from IV acetaminophen administration were observed at doses of either 10 or 20 mg kg-1. CONCLUSIONS AND CLINICAL RELEVANCE: IV PK of acetaminophen was different between Beagles and GE dogs. Side effects were not detected. Further studies are necessary to evaluate the PK in a clinical context.

Evaluation and comparison of postoperative analgesic effects of dexketoprofen and methadone in dogs.

OBJECTIVE: To evaluate and compare the analgesic efficacy and adverse effects of dexketoprofen and methadone using a noninferiority trial, during the first 24 postoperative hours in dogs undergoing orthopaedic surgery. STUDY DESIGN: Randomized, blinded clinical study. ANIMALS: A total of 38 healthy dogs undergoing orthopaedic surgery. METHODS: Dogs were premedicated with dexmedetomidine [1 µg kg-1 intravenously (IV)] followed by dexketoprofen (1 mg kg-1 IV; group DK) or methadone (0.2 mg kg-1 IV; group M). Anaesthesia was induced with propofol and maintained with isoflurane in 60% oxygen. Postoperatively, dexketoprofen was administered every 8 hours (group DK) and methadone every 4 hours (group M). Analgesia was assessed at baseline and at 1, 2, 4, 6, 18 and 24 hours after extubation using a dynamic and interactive visual analogue scale (DIVAS), the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF), mechanical wound thresholds (MWTs) and plasma cortisol levels. If CMPS-SF score was ≥5, rescue analgesia was administered. Data were analysed using a general linear mixed model, Mann-Whitney U test and chi-squared test as appropriate; a p value <0.05 was considered significant. RESULTS: The CMPS-SF and DIVAS scores were significantly higher in group M compared with group DK and remained higher for a longer period in group M, although the differences were not clinically significant. No significant differences were found in MWT assessment between groups. Plasma cortisol level significantly increased 2 hours after extubation, without significant differences between treatments. Rescue analgesia was administered to three animals (one in group DK; two in group M). CONCLUSION AND CLINICAL RELEVANCE: We conclude that 1 mg kg-1 IV dexketoprofen administered every 8 hours during the first 24 hours postoperatively is noninferior to methadone in controlling pain after orthopaedic surgery in dog, although frequent pain assessments are recommended to adjust the analgesia plan.

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.

Anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in isoflurane-anaesthetized sheep.

OBJECTIVE: To determine the anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in sheep anaesthetized with isoflurane and undergoing orthopaedic surgery. STUDY DESIGN: Prospective, randomised, 'blinded' controlled study. ANIMALS: Twenty healthy sheep (weight mean 41.1 ± SD 4.5 kg). METHODS: Sheep were sedated with intravenous (IV) dexmedetomidine (4 µg kg(-1) ) and morphine (0.2 mg kg(-1) ). Anaesthesia was induced with propofol (1 mg kg(-1)  minute(-1) to effect IV) and maintained with isoflurane in oxygen and a continuous rate infusion (CRI) of fentanyl 10 µg kg(-1)  hour(-1) (group F) or saline (group P) for 100 minutes. The anaesthetic induction dose of propofol, isoflurane expiratory fraction (Fe'iso) required for maintenance and cardiorespiratory measurements were recorded and blood gases analyzed at predetermined intervals. The quality of recovery was assessed. Results were compared between groups using t-tests or Mann-Whitney as relevant. RESULTS: The propofol induction dose was 4.7 ± 2.4 mg kg(-1) . Fe'iso was significantly lower (by 22.6%) in group F sheep than group P (p = 0). Cardiac index (mean ± SD mL kg(-1)  minute(-1) ) was significantly (p = 0.012) lower in group F (90 ± 15) than group P (102 ± 35). Other measured cardiorespiratory parameters did not differ statistically significantly between groups. Recovery times and recovery quality were statistically similar in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl reduced isoflurane requirements without clinically affecting the cardiorespiratory stability or post-operative recovery in anaesthetized sheep undergoing orthopaedic surgery.

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.

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

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

Evaluation of spectral entropy to measure anaesthetic depth and antinociception in sevoflurane-anaesthetised Beagle dogs.

The use of spectral entropy to determine anaesthetic depth and antinociception was evaluated in sevoflurane-anaesthetised Beagle dogs. Dogs were anaesthetised at each of five multiples of their individual minimum alveolar concentrations (MAC; 0.75, 1, 1.25, 1.5 and 1.75 MAC), and response entropy (RE), state entropy (SE), RE-SE difference, burst suppression rate (BSR) and cardiorespiratory parameters were recorded before and after a painful stimulus. RE, SE and RE-SE difference did not change significantly after the stimuli. The correlation between MAC-entropy parameters was weak, but these values increased when 1.75 MAC results were excluded from the analysis. BSR was different to zero at 1.5 and 1.75 MAC. It was concluded that RE and RE-SE differences were not adequate indicators of antinociception and SE and RE were unable to detect deep planes of anaesthesia in dogs, although they both distinguished the awake and unconscious states.