Sedative and electrocardiographic effects of low dose dexmedetomidine in healthy cats / Efeitos sedativos e eletrocardiográficos da baixa dose de dexmedetomidina em gatos saudáveis

In feline veterinary practice sedation is often needed to perform diagnostic or minimally invasive procedures, minimize stress, and facilitate handling. The mortality rate of cats undergoing sedation is significantly higher than dogs, so it is fundamental that the sedatives provide good cardiovascular stability. Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist utilized in cats to provide sedation and analgesia, although studies have been utilized high doses, and markedly hemodynamic impairments were reported. The aim of this study was to prospectively investigate how the sedative and electrocardiographic effects of a low dose of DEX performing in cats. Eleven healthy cats were recruited; baseline sedative score, systolic arterial pressure, electrocardiography, and vasovagal tonus index (VVTI) were assessed, and repeated after ten minutes of DEX 5μg/kg intramuscularly (IM). A smooth sedation was noticed, and emesis and sialorrhea were common adverse effects, observed on average seven minutes after IM injection. Furthermore, electrocardiographic effects of a low dose of DEX mainly include decreases on heart rate, and increases on T-wave amplitude. The augmentation on VVTI and appearance of respiratory sinus arrhythmia, as well as sinus bradycardia in some cats, suggesting that DEX enhances parasympathetic tonus in healthy cats, and therefore will be best avoid in patients at risk for bradycardia.(AU)

Na rotina clínica da medicina veterinária felina a sedação é frequentemente requerida para realização de procedimentos diagnósticos ou minimamente invasivos, para minimizar o estresse e facilitar o manuseio dos pacientes. A taxa de mortalidade de gatos submetidos à sedação é mais elevada do que em cães, por esse motivo, é fundamental que os sedativos confiram estabilidade hemodinâmica. A dexmedetomidina (DEX) é um α2-agonista utilizado em felinos para promover sedação e analgesia, porém os estudos têm utilizado doses elevadas, e com isso prejuízos hemodinâmicos importantes foram relatados. O objetivo desta investigação foi avaliar os efeitos sedativos e eletrocardiográficos da baixa dose de DEX em gatos. Para tal, onze felinos saudáveis foram recrutados, foram obtidos valores basais para escore de sedação, pressão arterial sistólica e eletrocardiografia, além do índice de tônus vaso vagal (ITVV). Após dez minutos da aplicação intramuscular (IM) de DEX 5μg/kg todos os exames foram repetidos. Após a DEX, sedação suave foi detectada, e a êmese e sialorreia foram efeitos adversos comuns, observados em média 7 minutos após a injeção IM. Ademais, os principais efeitos eletrocardiográficos foram redução na frequência cardíaca e aumento na amplitude da onda T. O ITVV mais elevado e surgimento de arritmia sinusal respiratória, bem como bradicardia sinusal em alguns gatos, sugerem que a DEX eleva o tônus parassimpático, e por esse motivo deve ser utilizada com cautela em pacientes com predisposição à bradicardia.(AU)

Dexmedetomidine low dose followed by constant rate infusion and antagonism by atipamezole in isoflurane-anesthetized cats: an echocardiographic study.

OBJECTIVE: To investigate the effects of a low dose of dexmedetomidine (DEX) followed by constant rate infusion (CRI) and reversal with atipamezole on systolic and diastolic functions in isoflurane-anesthetized healthy cats. STUDY DESIGN: Prospective cohort study. ANIMALS: A group of 11 client-owned adult cats. METHODS: Baseline transthoracic echocardiography (TTE) was performed, followed by intramuscular (IM) administration of DEX (5 µg kg-1). After 10 minutes, sedation was scored, adverse effects were recorded and another TTE performed. Approximately 40 minutes after DEX administration, anesthesia was induced by isoflurane mask and maintained with 1.2% end-tidal isoflurane and DEX CRI (1 µg kg-1 hour-1) for 80 minutes. Physiological variables were recorded every 10 minutes, and TTE was repeated 10, 30 and 60 minutes after the start of anesthesia. CRI was stopped, atipamezole (30 µg kg-1) was administered IM and a final TTE was performed after 10 minutes. Repeated measures over time were submitted to one-way analysis of variance or Kruskal-Wallis test according to data distribution; significance was assumed at p < 0.05. RESULTS: After DEX premedication, mild sedation and a slight but significant increase in systolic arterial pressure occurred, and vomiting was a common adverse effect. The cardiac output (CO) and heart rate decreased during anesthesia, with no changes after administration of atipamezole. Trivial valvular insufficiencies were commonly seen after DEX premedication and during CRI. Myocardial radial and longitudinal systolic functions were not affected by sedation or by anesthesia. The late phase of diastole on both right and left ventricles was affected by isoflurane-DEX CRI. Global left ventricular myocardial performance was not impaired. CONCLUSIONS: and clinical relevance Decreased CO and late diastolic impairment were observed in healthy cats administered a low dose of DEX for premedication followed by anesthesia with isoflurane and DEX CRI.

Inconsistency of allometric scaling for dissociative anesthesia of wild felids.

OBJECTIVE: To evaluate allometric scaling for ketamine-xylazine (KX) anesthesia in wild felids using domestic cats for reference. STUDY DESIGN: Prospective single-phase non-blinded study. ANIMALS: Six domestic cats and 13 wild felids (five Leopardus pardalis, five Puma concolor, one Panthera onca and two Panthera leo). METHODS: Six domestic cats (4.1 ± 0.8 kg, REF1) were anesthetized by intramuscular administration of ketamine (15 mg kg(-1) ) and xylazine (1 mg kg(-1) ). Wild cats were divided into three groups based on body weight: 12.9 ± 2.4 kg (G1; n = 7), 43.0 ± 15.7 kg (G2; n = 4) and 126.0 ± 7.8 kg (G3; n = 2). Ketamine and xylazine doses were calculated based on allometric scaling of the basal metabolic rate (BMR = 70 × body mass(0.75) ). Afterwards, the six domestic cats were administered mean KX doses calculated for G1 and G2 (REF2). The heart rate, systolic arterial pressure, respiratory frequency, pH, the venous partial pressure of carbon dioxide, bicarbonate and lactate concentrations were recorded for up to 60 minutes. RESULTS: Additional doses were required in 12 out of the 13 wild cats. Anesthesia was not achieved in G3. Latency periods in wild felids were longer than REF1 and REF2. Anesthesia duration in REF1 was longer than that in the other groups. Recovery from anesthesia in REF1 and REF2 was longer than G1 and G2. Physiological variables remained within the range limits for the species. G1 baseline lactate concentration was higher than in the other groups. CONCLUSION AND CLINICAL RELEVANCE: KX anesthesia established by allometric scaling of BMR from doses administered to domestic cats did not predict reliable anesthetic doses for wild cats. Dose rates calculated with this method must not be applied to these species.

Physiological and analgesic effects of continuous-rate infusion of morphine, butorphanol, tramadol or methadone in horses with lipopolysaccharide (LPS)-induced carpal synovitis.

BACKGROUND: Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. RESULTS: Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throughout the CRI period. Morphine, butorphanol and methadone each caused a reduction in gut sounds, and this effect was greatest in animals that received morphine. Administration of morphine or methadone reduced the degree of lameness after the end of intravenous infusion. Administration of tramadol did not alter the degree of lameness in the animals. CONCLUSIONS: CRI of morphine or methadone, but not butorphanol or tramadol, provided analgesia in horses with carpal synovitis. All of these opioids increased cardiovascular and respiratory parameters and reduced gut sounds during CRI.

Effect of tepoxalin on renal function and hepatic enzymes in dogs exposed to hypotension with isoflurane.

OBJECTIVE: To evaluate the possible renal and hepatic toxicity of tepoxalin in dogs exposed to hypotension during isoflurane anesthesia. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: Twenty adult mixed-breed dogs, weighing 18.8 ± 2.8 kg. METHODS: The animals received 10 mg kg(-1) tepoxalin orally 2 hours before the anesthetic procedure (PRE; n = 6), or 30 minutes after anesthesia (POST; n = 6), along with a control group (CON; n = 8), which were only anesthetized. The PRE and POST groups also received the same dose of tepoxalin for 5 days post-procedure. All dogs were anesthetized with propofol and maintained with isoflurane and the end-tidal isoflurane (Fe'Iso) was increased until mean arterial pressure decreased to 50-60 mmHg. These pressures were maintained for 60 minutes. Heart rate, arterial pressures and Fe'Iso were recorded at 0, 10 and every 10 minutes up to 60 minutes of hypotension. Blood gases, pH, electrolytes and bleeding time were analyzed before and at 30 and 60 minutes of hypotension. Renal and hepatic changes were quantified by serum and urinary biochemistry and creatinine clearance. RESULTS: Serum concentrations of alanine amino transferase (ALT), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT), blood urea nitrogen (BUN) and creatinine (Cr), and urinary output, urinary Cr, Cr clearance, and GGT:Cr ratio remained stable throughout the evaluations. During the anesthetic procedure there were no important variations in the physiological parameters. No side effects were observed in any of the groups. CONCLUSIONS AND CLINICAL RELEVANCE: Tepoxalin did not cause significant effects on renal function or cause hepatic injury in healthy dogs exposed to hypotension with isoflurane, when administered pre- or postanesthetic and continued for five consecutive days.

Evaluation of analgesic and physiologic effects of epidural morphine administered at a thoracic or lumbar level in dogs undergoing thoracotomy.

OBJECTIVE: To evaluate the analgesic and physiological effects of epidural morphine administered at the sixth and seventh lumbar or the fifth and sixth thoracic vertebrae in dogs undergoing thoracotomy. STUDY DESIGN: Prospective, randomized, blinded trial. ANIMALS: Fourteen mixed-breed dogs, weighing 8.6 ± 1.4 kg. METHODS: The animals received acepromazine (0.1 mg kg⁻¹) IM and anesthesia was induced with propofol (4 mg kg)⁻¹ IV. The lumbosacral space was punctured and an epidural catheter was inserted up to the region between the sixth and seventh lumbar vertebrae (L, n = 6) or up to the fifth or sixth intercostal space (T, n = 8). The dogs were allowed to recover and after radiographic confirmation of correct catheter position, anesthesia was reinduced with propofol IV and maintained with 1.7% isoflurane. Following stabilization of monitored parameters, animals received morphine (0.1 mg kg⁻¹) diluted in 0.9% NaCl to a final volume of 0.25 mL kg⁻¹ via the epidural catheter, and after 40 minutes, thoracotomy was initiated. Heart rate and rhythm, systolic, mean and diastolic arterial pressures, respiratory rate, arterial hemoglobin oxygen saturation, partial pressure of expired CO2 and body temperature were measured immediately before the epidural administration of morphine (0 minute) and every 10 minutes during the anesthetic period. The Melbourne pain scale and the visual analog scale were used to assess postoperative pain. The evaluation began 3 hours after the epidural administration of morphine and occurred each hour until rescue analgesia. RESULTS: There were no important variations in the physiological parameters during the anesthetic period. The post-operative analgesic period differed between the groups, being longer in T (9.9 01.6 hours) compared with L (5.8 ± 0.8 hours). CONCLUSIONS: The use of morphine, at a volume of 0.25 mL kg 0.1, administered epidurally over the thoracic vertebrae provided longer lasting analgesia than when deposited over the lumbar vertebrae.

Acid-base and biochemical stabilization and quality of recovery in male cats with urethral obstruction and anesthetized with propofol or a combination of ketamine and diazepam.

This study compared acid-base and biochemical changes and quality of recovery in male cats with experimentally induced urethral obstruction and anesthetized with either propofol or a combination of ketamine and diazepam for urethral catheterization. Ten male cats with urethral obstruction were enrolled for urethral catheterization and anesthetized with either ketamine-diazepam (KD) or propofol (P). Lactated Ringer's solution was administered by intravenous (IV) beginning 15 min before and continuing for 48 h after relief of urethral obstruction. Quality of recovery and time to standing were evaluated. The urethral catheter was maintained to measure urinary output. Hematocrit (Hct), total plasma protein (TPP), albumin, total protein (TP), blood urea nitrogen (BUN), creatinine, pH, bicarbonate (HCO3-), chloride, base excess, anion gap, sodium, potassium, and partial pressure of carbon dioxide in mixed venous blood (pvCO2) were measured before urethral obstruction, at start of fluid therapy (0 h), and at subsequent intervals. The quality of recovery and time to standing were respectively 4 and 75 min in the KD group and 5 and 16 min in the P group. The blood urea nitrogen values were increased at 0, 2, and 8 h in both groups. Serum creatinine increased at 0 and 2 h in cats administered KD and at 0, 2, and 8 h in cats receiving P, although the values were above the reference range in both groups until 8 h. Acidosis occurred for up to 2 h in both groups. Acid-base and biochemical stabilization were similar in cats anesthetized with propofol or with ketamine-diazepam. Cats that received propofol recovered much faster, but the ketamine-diazepam combination was shown to be more advantageous when treating uncooperative cats as it can be administered by intramuscular (IM) injection.

Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis.

This study evaluated the analgesia effects of the epidural administration of 0.1 mg/kg bodyweight (BW) of morphine or 5 µg/kg BW of buprenorphine in ponies with radiocarpal joint synovitis. Six ponies were submitted to 3 epidural treatments: the control group (C) received 0.15 mL/kg BW of a 0.9% sodium chloride (NaCl) solution; group M was administered 0.1 mg/kg BW of morphine; and group B was administered 5 µg/kg BW of buprenorphine, both diluted in 0.9% NaCl to a total volume of 0.15 mL/kg BW administered epidurally at 10 s/mL. The synovitis model was induced by injecting 0.5 ng of lipopolysaccharide (LPS) in the left or right radiocarpal joint. An epidural catheter was later introduced in the lumbosacral space and advanced up to the thoracolumbar level. The treatment started 6 h after synovitis induction. Lameness, maximum angle of carpal flexion, heart rate, systolic arterial pressure, respiratory rate, temperature, and intestinal motility were evaluated before LPS injection (baseline), 6 h after LPS injection (time 0), and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after treatments. Although the model of synovitis produced clear clinical signs of inflammation, the lameness scores in group C were different from the baseline for only up to 12 h. Both morphine and buprenorphine showed a reduction in the degree of lameness starting at 0.5 and 6 h, respectively. Reduced intestinal motility was observed at 0.5 h in group M and at 0.5 to 1 h in group B. Epidural morphine was a more effective analgesic that lasted for more than 12 h and without side effects. It was concluded that morphine would be a valuable analgesic option to alleviate joint pain in the thoracic limbs in ponies.

Formulation and in vivo evaluation of sodium alendronate spray-dried microparticles intended for lung delivery.

Spray-dried powders for lung delivery of sodium alendronate (SA) were prepared from hydroalcoholic solutions. Formulations display geometric particle size below to 12 µm and spherical shape associated to a hollow structure. The addition of leucine and ammonium bicarbonate leads to porous particles with rough surfaces. The tapped density ranges from 0.016 to 0.062 g/cm(3), decreasing with the increase of the leucine concentration. For all formulations, the calculated aerodynamic diameters are lower than 5 µm. The in vitro aerodynamic evaluation shows that all powders present a high emitted fraction of 100%, a fine particle fraction ranging from 34.4% to 62.0% and an alveolar fraction ranging from to 23.7% to 42.6%. An optimized sample was evaluated regarding sodium alendronate acute pulmonary toxicity and lung bioavailability. The bronchoalveolar lavage study shows that the intratracheal administration of sodium alendronate dry powder and sodium alendronate aqueous solution do not induce significant increases of lung toxicity indicators as compared with the positive control. Moreover, the intratracheal administration of sodium alendronate dry powder results in a 6.23 ± 0.83% bioavailability, a 3.5-fold increase as compared to oral bioavailability. Finally, these results suggest that sodium alendronate pulmonary delivery could be a new and promising administration route.

Renal and cardiorespiratory effects of treatment with lactated Ringer's solution or physiologic saline (0.9% NaCl) solution in cats with experimentally induced urethral obstruction.

OBJECTIVE: To compare the renal and cardiorespiratory effects of IV treatment with lactated Ringer's solution (LRS) or physiologic saline (0.9% NaCl) solution (PSS) in severely decompensated cats with urethral obstruction (UO). ANIMALS: 14 cats (4 cats were used only to establish infusion rates). PROCEDURES: An occluded urethral catheter was used to induce UO in each cat. After development of severe metabolic acidosis, hyperkalemia, and postrenal azotemia, the obstruction was relieved (0 hours); LRS or PSS (5 cats/group) was administered IV (gradually decreasing rate) beginning 15 minutes before and continuing for 48 hours after UO relief. Ten minutes before urethral catheter placement (baseline), at start of fluid therapy (SFT), and at intervals during fluid administration, various physical and clinicopathologic evaluations were performed. RESULTS: Metabolic acidosis was detected in the PSS-treated group at SFT and 2 hours after relief of UO and in the LRS-treated group only at SFT The PSS-treated group had significantly lower blood pH and bicarbonate concentrations at 8 through 48 hours and lower base excess values at 2 through 48 hours, compared with the LRS-treated group. Hypocalcemia and hypernatremia were detected in the PSS-treated group at 2 and 12 hours, respectively. Absolute serum potassium and chloride concentrations did not differ significantly between groups at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with LRS or PSS appeared to be safe and effective in cats with experimentally induced UO; however, LRS was more efficient in restoring the acid-base and electrolyte balance in severely decompensated cats with UO.