Evaluation of the averaged parasympathetic tone activity and its dynamic variation to assess intraoperative nociception in relation to hemodynamic changes in dogs.

This study aimed to determine the performance of the averaged parasympathetic tone activity (PTAm) and its dynamic variation (ΔPTA) to assess intraoperative nociception in relation to heart rate (HR) and direct mean arterial pressure (MAP) in dogs undergoing laparoscopic ovariectomy. This prospective, observational, clinical study included 32 bitches. The PTAm, HR, MAP, and bispectral index (BIS) were assessed before (pre-stimulus), as well as 1 min and 2 min after, four surgical stimuli: insufflation, introduction of trocars, and removal of the left and right ovaries. A two-way ANOVA was performed to compare PTAm, HR, MAP, and BIS data across surgical stimuli. A ≥ 20% drop in PTAm or a ≥ 20% increase in HR and/or MAP regarding the pre-stimulus values was considered a PTAm-drop and/or a hemodynamic response, respectively. The performance of PTAm pre-stimulus, PTAm 1 min, and ΔPTA in predicting the hemodynamic response was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. At insufflation, PTAm decreased after 1 (p = 0.010) and 2 (p = 0.045)min, and ΔPTA was different (p = 0.005) between dogs that presented hemodynamic response and dogs that did not. At PTAm-drop, MAP increased after 1 min (p = 0.001) and 2 min (p = 0.001) with respect to pre-stimulus value, whereas HR and BIS did not change. ROC curves showed a threshold value of PTAm pre-stimulus ≤51 to detect hemodynamic response (sensitivity 69%, specificity 52%). The PTAm and ΔPTA only assessed intraoperative nociception during insufflation. The PTAm pre-stimulus association to the hemodynamic response in anaesthetized dogs showed poor sensitivity and no specificity.

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.

Parasympathetic Tone Changes in Anesthetized Horses after Surgical Stimulation, and Morphine, Ketamine, and Dobutamine Administration.

Autonomic nervous system (ANS) activity can modify cardiovascular parameters in response to nociceptive stimuli or drugs in anesthetized animals. The aim of this study was to determine if a surgical nociceptive stimulus and morphine, ketamine, and dobutamine administration would modify ANS activity observed as a change in the mean parasympathetic tone activity (PTAm) in anesthetized horses. In 20 anesthetized horses, heart rate (HR), mean arterial pressure (MAP), and PTAm were monitored before and 1, 3, and 5 min after surgical incision, and before and 10 min after the administration of morphine (0.2 mg/kg IV). If nystagmus or spontaneous ventilation was observed, ketamine (0.5 mg/kg IV) was given, and the three variables were registered before and 3 and 5 min afterward. If MAP reached ≤62 mmHg, a dobutamine infusion was administered, and the three variables were recorded before and 5 min after starting/increasing the infusion (0.25 µg/kg/min IV every 5 min). The three variables were registered before and 1, 3, and 5 min after a PTAm decrease of ≥20%, HR increase of ≥10%, or MAP increase of ≥20%. The PTAm decreased 3 min after the administration of ketamine and 1 min after a PTA event. The surgical incision, dobutamine, and morphine did not modify PTAm. The absence of changes in ANS activity after the nociceptive stimulus and lack of correlation between PTAm and HR or MAP suggest that PTAm is a poor indicator of sympathetic activation under the study conditions. Ketamine seems to affect ANS activity by decreasing PTAm.

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.

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.

Systemic and local effects of lidocaine or mepivacaine when used for intravenous regional anaesthesia of the distal limb in standing sedated horses.

BACKGROUND: Local anaesthetics are being combined clinically with amikacin in intravenous regional limb perfusion (IVRLP), with limited knowledge on the analgesia provided and its onset and duration of action after tourniquet application and release. OBJECTIVE: To evaluate the systemic clinical effect, limb withdrawal to nociceptive stimulation, and plasma and synovial fluid concentrations after IVRLP with lidocaine or mepivacaine in standing sedated horses. STUDY DESIGN: Prospective, controlled, randomised, cross-over study. METHODS: Six healthy adult horses were sedated and received IVRLP with lidocaine, mepivacaine or saline (negative control), or perineural anaesthesia of the medial and lateral palmar and palmar metacarpal nerves (positive control) in one forelimb with a 3-week washout period between trials. Electrical and mechanical stimuli were used to test nociceptive threshold of the limb before and after IVRLP/perineural anaesthesia. For lidocaine and mepivacaine trials, blood was collected from the jugular vein and synovial fluid from the radiocarpal joint before, during and out to 24 hours after IVRLP. Drug concentrations were measured using high-performance liquid chromatography. RESULTS: Nociceptive thresholds for lidocaine, mepivacaine and perineural anaesthesia trials were significantly increased compared with saline and baseline values at 10, 20 and 30 minutes, with no differences between anaesthetic trials. During this time, horses had lower heart rates than IVRLP with saline. After tourniquet release at 30 minutes, nociceptive thresholds for lidocaine and mepivacaine trials gradually returned to baselines, whereas perineural anaesthesia trial remained unchanged out to an hour. Plasma lidocaine and mepivacaine concentrations were ≤50 ng/mL while the tourniquet was in place, significantly increasing 10 minutes after tourniquet release. Maximal lidocaine and mepivacaine concentrations in synovial fluid were reached 25 minutes after IVRLP injection. MAIN LIMITATIONS: Amikacin was not included in the perfusate. CONCLUSION: Similar to perineural anaesthesia, IVRLP with lidocaine or mepivacaine provides anti-nociception to the distal limb in standing sedated horses while a tourniquet is applied with concentrations remaining below toxic levels in plasma and synovial fluid.

Comparison of bispectral index and spectral entropy during isoflurane and medetomidine general anaesthesia in horses.

BACKGROUND: The bispectral index (BIS) has been evaluated as an indicator of central nervous system (CNS) depression in horses during general anaesthesia. The spectral entropy is another electroencephalographic device and it has not been evaluated yet in horses. OBJECTIVES: To determine if spectral entropy can assess anaesthetic depth during the different phases of anaesthesia, define the value of state and response entropy during surgical plane of anaesthesia and compare them with BIS. STUDY DESIGN: Clinical, prospective, non-blinded observational study. METHODS: Thirty-five horses ASA I or II undergoing scheduled surgical procedure were used. BIS and electromyography (EMG) with a BIS monitor and state and response entropy with a spectral entropy monitor were recorded at baseline after receiving 5 µg/kg bwt i.v. of medetomidine (sedation period), during the anaesthetic maintenance with isoflurane and medetomidine (intraoperative period) and once the trachea was extubated (recovery period). A general linear model for repeated measurements was employed. Correlation and agreement between methods were also assessed. Data are presented as mean ± SD. RESULTS: State entropy, response entropy and EMG showed significant differences according to the anaesthetic period (P < .001). There was no significant difference in BIS between baseline and sedation period, but there were differences between the remainder of the periods (P < .001). BIS (53.4 ± 11.2) was significantly higher (P < .001) than response entropy (35.1 ± 7.1) and state entropy (27.4 ± 4.8) during surgical plane of anaesthesia. The ICC between BIS and response entropy was 0.56 and between BIS and state entropy was 0.43, without agreement between them. MAIN LIMITATIONS: The need to shave the skin in contact with the sensors and the difficulty in taking measurements during recovery period. CONCLUSIONS: Spectral entropy can be used to detect the different periods of an anaesthetic protocol, with the lowest values during the intraoperative period. A low correlation and no concordance were observed between both methods.

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.

Comparison of central corneal thickness in dogs measured by ultrasound pachymetry and ultrasound biomicroscopy.

Ultrasound pachymetry (UP) is currently the most common technique used to evaluate central corneal thickness (CCT). New devices which allow assessment of CCT without corneal contact have been compared, but there are discrepancies among instruments. The aim of this study was to compare CCT measurements obtained by UP and ultrasound biomicroscopy (UBM) in 28 eyes of 14 healthy Beagles dogs. Mean CCT±standard deviation (SD) were 552±63µm for UP and 551±55µm for UBM. UBM showed both a fixed and proportional bias when compared to ultrasound pachymetry, but this was not considered to be clinically important. Measured CCT did not differ between UP and UBM (P=0.796). The intra-class correlation coefficient indicated a strong agreement between methods (0.990). The CCT measurements between left (548±61µm) and right (555±59µm) eyes did not differ (P=0.760). Male dogs had higher CCT measurements than female dogs (P=0.038).

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.

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.

Romifidine and low doses of tiletamine-zolazepam in dogs.

OBJECTIVE: To evaluate clinical effects of romifidine and low doses of tiletamine-zolazepam (TZ) in dogs. STUDY DESIGN: Randomized "blinded" cross-over study. ANIMALS: Six healthy beagle dogs (two males, four females). METHODS: In separate preliminary experiments dogs received intravenous (IV) tiletamine-zolazepam (TZ) at 1 and 2 mg kg(-1). For the main trial, dogs received romifidine (R) followed 5 minutes later by IV at six dose regimens: R40TZ1, R60TZ1, R80TZ1 (Romifidine at 40, 60, 80 µg kg(-1) and TZ at 1 mg kg(-1)), R40TZ2, R60TZ2 and R80TZ2 (Romifidine at 40, 60, 80 µg kg(-1) and TZ at 2 mg kg(-1)). Dogs underwent endotracheal intubation, but breathed room air. Cardiorespiratory variables were measured and arterial blood analyzed. Quality of sedation, duration of anaesthesia and time to recovery (TR) were recorded. Data were analysed by anova or Friedman test as relevant. RESULTS: Endotracheal intubation was possible with all romifidine/TZ combinations but not with TZ alone. Mean times (minutes) from TZ injection to return of pedal reflex were 1-3 minutes for TZ alone, and 9-17 minutes for romifidine combinations. In the main trial (romifidine combinations) mean time (minutes) to standing increased with increasing dosage (R40TZ1 13; R80TZ2 32). Five minutes after TZ administration, when compared with baseline arterial blood pressures and arterial carbon dioxide had increased, and respiratory rate, pH and arterial oxygen tensions decreased, these changes becoming statistically significant with the higher dose rates. One dog in R60TZ2 and three dogs in R80TZ2 became hypoxaemic. CONCLUSIONS AND CLINICAL RELEVANCE: Romifidine improves the quality and lengthens the duration of anaesthesia induced by TZ. The combination provides a suitable protocol for induction of or short-term anaesthesia in healthy dogs. However, the higher doses cause cardiovascular stimulation and respiratory depression, and precautions should be taken accordingly.

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.

Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant.

BACKGROUND: Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. MATERIALS AND METHODS: We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. RESULTS: Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1ß and TNF-α expression together with IL-6 upregulation in liver tissue. CONCLUSIONS: The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.

A comparison of the effect of convection against diffusion in hemodynamics and cytokines clearance in an experimental model of septic shock.

BACKGROUND: Replacement therapies based on the use of convection have value for the removal of inflammatory mediators. Such therapies have been proposed for the management of septic shock, but diffusion has not proved useful in this scenario, unless high-flow membranes are used. The exact role of diffusion in these cases remains to be clarified because continuous replacement therapies are usually delivered with low-flow membranes and mixed convection-diffusion modalities. However, studies specifically addressing this problem have not been performed. Our aim was to define the efficacy of hemofiltration (convection) and hemodialysis (diffusion) in cytokine clearance and hemodynamic improvement in an experimental model of septic shock. METHODS: Shock was induced in 15 beagle dogs (weight 10-15 kg) by infusion of 1 mg/kg of ultrapure Escherichia coli lipopolysaccharide diluted in 20 mL saline for 10 minutes. Five animals were followed without interventions (controls), five animals were treated with convection (100 mL kg h) for 6 hours, and five animals were treated with diffusion (100 mL kg h) for 6 hours. RESULTS: All subjects in the control group died during the study, whereas all treated subjects survived. Mean arterial pressure, cardiac output, systolic variability volume, systemic vascular resistances, dPMax, and pulmonary compliance improved in treated subjects. However, the differences in mean arterial pressure and cardiac output were significant only in the convection group and not in the diffusion-treated group.Tumor necrosis factor α rose equally in all groups and decreased only in treated subjects. Interleukin 6 rose in the three groups but decreased only in the convection group and remained unchanged in the control and diffusion groups. CONCLUSION: Convection and diffusion improved survival and hemodynamic parameters in a septic shock model. Improvement was more pronounced with convection, a difference that may be explained by convective clearance of cytokines.

Bladder mucosal CO2 compared with gastric mucosal CO2 as a marker for low perfusion states in septic shock.

Recent reports indicate the possible role of bladder CO(2) as a marker of low perfusion states. To test this hypothesis, shock was induced in six beagle dogs with 1 mg/kg of E. coli lipopolysaccharide, gastric CO(2) (CO(2)-G) was measured with a continuous monitor, and a pulmonary catheter was inserted in the bladder to measure CO(2) (CO(2)-B). Levels of CO(2)-B were found to be lower than those of CO(2)-G, with a mean difference of 36.8 mmHg (P < 0.001), and correlation between both measurements was poor (r(2) = 0.16). Even when the correlation between CO(2)-G and ΔCO(2)-G was narrow (r(2) = 0.86), this was not the case for the relationship between CO(2)-B and ΔCO(2)-B (r(2) = 0.29). Finally, the correlation between CO(2)-G and base deficit was good (r(2) = 0.45), which was not the case with the CO(2)-B correlation (r(2) = 0.03). In our experience, bladder CO(2) does not correlate to hemodynamic parameters and does not substitute gastric CO(2) for detection of low perfusion states.