Clinical efficacy of dexmedetomidine combined with lidocaine for femoral and sciatic nerve blocks in dogs undergoing stifle surgery.

OBJECTIVE: To evaluate the effects of dexmedetomidine administered perineurally or intramuscularly (IM) on sensory, motor function and postoperative analgesia produced by lidocaine for sciatic and femoral nerve blocks in dogs undergoing unilateral tibial tuberosity advancement surgery. STUDY DESIGN: Prospective, blinded, clinical study. ANIMALS: A group of 30 dogs. METHODS: Dogs were anaesthetized with acepromazine, propofol and isoflurane in oxygen/air. Electrolocation-guided femoral and sciatic nerve blocks were performed: group L, 0.15 mL kg-1 2% lidocaine (n = 10); group LDloc, lidocaine and 0.15 µg kg-1 dexmedetomidine perineurally (n = 10); group LDsys, lidocaine and 0.3 µg kg-1 dexmedetomidine IM (n = 10). After anaesthesia, sensory blockade was evaluated by response to forceps pinch on skin innervated by the saphenous/femoral, common fibular and tibial nerves. Motor blockade was evaluated by observing the ability to walk and proprioception. Analgesia was monitored with Short Form of Glasgow Composite Pain Scale for up to 4 hours after extubation. Methadone IM was administered as rescue analgesia. Data were analysed by linear mixed effect models and Kaplan-Meier test (p < 0.05). RESULTS: Median duration of the sensory blockade for all nerves was longer (p < 0.001) for group LDloc than for groups L and LDsys and was longer (p = 0.0011) for group LDsys than for group L. Proprioception returned later (p < 0.001) for group LDloc [285 (221-328) minutes] compared with group L [160 (134-179) minutes] or LDsys [195 (162-257) minutes]. Return of the ability to walk was similar among all groups. Dogs in group LDloc required postoperative rescue analgesia later (p = 0.001) than dogs in groups LDsys and L. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine administered perineurally with lidocaine prolonged sensory blockade and analgesia during the immediate postoperative period. Systemic dexmedetomidine also prolonged the sensory blockade of perineural lidocaine.

An alveolar recruitment maneuver followed by positive end-expiratory pressure improves lung function in healthy dogs undergoing laparoscopy.

OBJECTIVE: To evaluate the effects of an alveolar recruitment maneuver (ARM) followed by 5 cmH2O positive end-expiratory pressure (PEEP) in dogs undergoing laparoscopy. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: A group of 20 dogs undergoing laparoscopic ovariectomy. METHODS: Dogs were sedated with acepromazine and methadone intramuscularly; anesthesia was induced with propofol intravenously and maintained with inhaled isoflurane. The following baseline ventilatory setting (BVS) was administered: tidal volume of 12 mL kg-1, inspiratory to expiratory ratio of 1:2, inspiratory pause 25% of inspiratory time, no PEEP and a respiratory rate to maintain end-tidal carbon dioxide tension between 5.3 and 7.3 kPa. Then, 10 minutes after the pneumoperitoneum, 10 dogs (RM) underwent a sustained inflation ARM followed by BVS plus 5 cmH2O PEEP, while 10 dogs (NO-RM) were left with BVS throughout the procedure. Gas exchange and respiratory system mechanics were evaluated before the pneumoperitoneum (PPpre), before ARM (PP10), 30 minutes later (PP30) and 20 minutes after pneumoperitoneum discontinuation (PPpost20). Data were analyzed using anova (p < 0.05). RESULTS: The Fshunt at PP30 and PPpost20 was lower (p < 0.001) in the RM (2.3 ± 2.2 and 4.7 ± 3.7%) than in the NO-RM (5.2 ± 2.1 and 11.1 ± 5.2%), and PaO2 at PP30 and PPpost20 was higher (p < 0.001) in the RM (67.3 ± 4.2 and 60.1 ± 9.4 kPa) than in the NO-RM (50.2 ± 7.4 and 45.5 ± 11.1 kPa). Static compliance of the respiratory system at PP30 and PPpost20 was greater (p < 0.001) in the RM (2.4 ± 0.2 and 2.1 ± 0.4 mL cmH2O-1 kg-1) than in the NO-RM (0.9 ± 0.4 and 1.2 ± 0.2 mL cmH2O-1 kg-1). CONCLUSIONS AND CLINICAL RELEVANCE: In dogs undergoing laparoscopy, ARM followed by 5 cmH2O PEEP improves gas exchange and respiratory system mechanics.

Perioperative analgesic effects of an ultrasound-guided transversus abdominis plane block with a mixture of bupivacaine and lidocaine in cats undergoing ovariectomy.

OBJECTIVE: To evaluate the perioperative analgesic effects of a transversus abdominis plane (TAP) block with a mixture of lidocaine and bupivacaine administered to cats undergoing ovariectomy. STUDY DESIGN: Controlled, randomized, prospective, blinded clinical study. ANIMALS: A group of 20 healthy cats. METHODS: Robenacoxib (2 mg kg-1) was administered subcutaneously 0.5 hour before intramuscular (IM) administration of ketamine (5 mg kg-1), methadone (0.1 mg kg-1) and dexmedetomidine (0.01 mg kg-1). General anesthesia was induced with intravenous (IV) propofol and maintained with isoflurane. An ultrasound-guided TAP block was performed by injecting 0.5% bupivacaine (0.2 mL kg-1) diluted in a total volume of 1.5 mL 2% lidocaine bilaterally (TAP group, n = 10) or the same volume of saline solution bilaterally in controls (CTR group, n = 10). During surgery, a 20% increase in heart rate and respiratory frequency was treated with IV fentanyl (0.001 mg kg-1). Before premedication and at 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 hours after extubation, pain was assessed with a simple descriptive pain scale, that ranged from 0 (no pain) to 4 (intense pain). For pain scores ≥3, IM methadone (0.1 mg kg-1) was administered. Data were analyzed with the Friedman or the analysis of variance (anova) test, and p < 0.05 was considered statistically significant. RESULTS: Only two cats in the CTR group were administered one dose of fentanyl during surgery. At 2, 6, 8, 12, 16, 20 and 24 hours after surgery, the pain score was higher in the CTR group. A mean dose of 0.5 ± 0.2 mg kg-1 methadone was administered to all cats in the CTR groups within 24 hours. Methadone was not administered to the TAP group (pain score < 3). CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound-guided TAP block can be a reliable adjunctive technique, providing analgesia for up to 24 hours in cats undergoing ovariectomy.

A preliminary study evaluating cardiac output measurement using Pressure Recording Analytical Method (PRAM) in anaesthetized dogs.

BACKGROUND: Haemodynamic variations normally occur in anaesthetized animals, in relation to the animal status, administered drugs, sympathetic and parasympathetic tone, fluid therapy and surgical stimulus. The possibility to measure some cardiovascular parameters, such as cardiac output (CO), during anaesthesia would be beneficial for both the anaesthesia management and its outcome. New techniques for the monitoring of CO are aimed at finding methods which are non invasive, accurate and with good trending ability, which can be used in a clinical setting. The aim of this study was to compare the Pressure Recording Analytical Method (PRAM) with the pulmonary artery thermodilution (TD) for the measurement of cardiac output in 6 anaesthetized critically ill dogs. RESULTS: Fifty-four pairs of CO measurements were obtained with a median (range) of 3.33 L/min (0.81-7.21) for PRAM-CO and 3.48 L/min (1.41-6.56) for TD-CO. The Bland-Altman analysis showed a mean bias of 0.17 L/min with limits of agreement (LoA) of - 0.46 to 0.81 L/min. The percentage error resulted 18.2%. The 4-quadrant plot analysis showed an acceptable concordance (93%) between the 2 methods. The polar plot showed a good trending ability with the mean angular bias of 3.9° and radial LoA ± 12.1°. CONCLUSIONS: The PRAM resulted in good precision, acceptable concordance and good trending ability for the measure of CO in the anaesthetized dog, representing a promising alternative to thermodilution for the measurement of CO. Among all the pulse contour methods available on the market it is the only one that does not require any calibration or adjustment of the measurement. Further studies are required to verify the ability of this method to accurately measure cardiac output even during unstable hemodynamic conditions.

Noninvasive continuous positive airway pressure delivered using a pediatric helmet in dogs recovering from general anesthesia.

OBJECTIVE: To evaluate the feasibility and efficacy of noninvasive continuous positive airway pressure (CPAP) administered with a pediatric helmet in healthy dogs recovering from general anesthesia. DESIGN: Randomized, cross-over, clinical study. SETTING: University teaching hospital. ANIMALS: Fifteen healthy female, client-owned dogs recovering from general anesthesia following elective ovariohysterectomy. INTERVENTIONS: All dogs received the same standardized anesthetic protocol (acepromazine, morphine, propofol, and isoflurane in oxygen). After extubation, a pediatric helmet was placed on all dogs and connected to a venturi valve supplied with medical air. In all patients, the gas flow was set to 50 L/minute and the FiO2 to 0.21. Dogs received the following sequence of treatments, each lasting 20 minutes: 0 CPAP (pre-CPAP), CPAP of 5 cm H2 O (CPAP), and again 0 CPAP (post-CPAP). MEASUREMENTS AND MAIN RESULTS: During the entire study, the following data were collected: pressure and FiO2 inside the helmet, mean arterial pressure, respiratory rate, heart rate, sedation score (0 = awake, 10 = deep sedation), and tolerance to the helmet (0 = excellent, 4 = poor). At the end of each phase, an arterial blood sample was sampled. As compared with the pre-CPAP and the post-CPAP periods, during the CPAP period, the PaCO2 , alveolar-arterial oxygen gradient (P[A-a]O2 ), and respiratory rate significantly decreased. The PaO2 was higher at CPAP (105.6 ± 4.0 mm Hg) compared with pre-CPAP (80.6 ± 6.9 mm Hg) and post-CPAP (86.7 ± 5.8 mm Hg). Tolerance and sedation scores during the CPAP period were not different from those in the pre-CPAP and post-CPAP periods. CONCLUSIONS: Noninvasive CPAP applied through a helmet is a feasible and effective supportive technique in dogs recovering from general anesthesia.

Low respiratory rate plus minimally invasive extracorporeal Co2 removal decreases systemic and pulmonary inflammatory mediators in experimental Acute Respiratory Distress Syndrome.

OBJECTIVE: The Acute Respiratory Distress Syndrome Network protocol recommends limiting tidal volume and plateau pressure; it also recommends increasing respiratory rate to prevent hypercapnia. We tested a strategy that combines the low tidal volume with lower respiratory rates and minimally invasive CO2 removal. SUBJECTS: Ten lung-damaged pigs (instilled hydrochloride). INTERVENTIONS: Two conditions randomly applied in a crossover fashion: the Acute Respiratory Distress Syndrome Network protocol and the Acute Respiratory Distress Syndrome Network protocol plus lower respiratory rate plus minimally invasive Co2 removal. A similar arterial Co2 partial pressure was targeted in the two conditions. MEASUREMENTS AND MAIN RESULTS: Physiological parameters, computed tomography scans, plasma and bronchoalveolar lavage concentrations of interleukin-1ß, interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-α. During the lower respiratory rate condition, respiratory rate was reduced from 30.5 ± 3.8 to 14.2 ± 3.5 (p < 0.01) breaths/min and minute ventilation from 10.4 ± 1.6 to 4.9 ± 1.7 L/min (p < 0.01). The extracorporeal device removed 38.9% ± 6.1% (79.9 ± 18.4 mL/min) of CO2 production. During the lower respiratory rate condition, interleukin-6, interleukin-8, and tumor necrosis factor-α concentrations were significantly lower in plasma; interleukin-6 and tumor necrosis factor-α concentrations were lower in bronchoalveolar lavage, whereas the concentrations of the other cytokines remained unchanged. CONCLUSION: The strategy of lower respiratory rate plus minimally invasive extracorporeal CO2 removal was feasible and safe and, as compared with the Acute Respiratory Distress Syndrome Network protocol, reduced the concentrations of some, but not all, of the tested cytokines without affecting respiratory mechanics, gas exchange, and hemodynamics.

Adenosine deaminase, a key enzyme in DNA precursors control, is a new p73 target.

The discovery of the p73 and p63 genes, homologous to p53 tumor suppressor has uncovered a family of transcription factors and widened the scenario of cell cycle control and apoptosis. We have identified a putative p53-responsive element in the human adenosine deaminase (ADA) gene, an important enzyme involved in nucleotide metabolism, the deficit of which causes the inhibition of DNA synthesis and repair. Here, we demonstrate that the ectopic expression of p73 isoforms leads to the ADA gene upregulation, showing for the first time a correlation between p73 and ADA. We found that p73 promotes ADA gene expression following a dNTP unbalance generated by ADA enzyme deficiency and 2'deoxyadenosine accumulation. The abrogation of p73 transcriptional activity by the specific dominant-negative p73DD abolishes ADA induction. By contrast, the ADA gene does not appear to be a functional p53 target in the physiological conditions we tested. On the whole, our results contribute to the emerging picture that p73 could play a different role from p53 in normal growth and development by inducing alternative target genes, which are not shared by p53.