Evaluation of intra-articular and subcutaneous administration of meloxicam for postoperative analgesia following stifle surgery in dogs.

The objective of this study was to compare the efficacy of meloxicam when given by intra-articular (IA) and subcutaneous (SC) routes of administration for postoperative analgesia versus a placebo for dogs undergoing stifle surgery. Twenty-five dogs with cranial cruciate ligament rupture (CCLR) were randomly assigned to one of three treatment groups, each with nine dogs, before surgical repair of twenty-seven stifles using a modified lateral retinacular imbrication technique. Group 1 dogs received IA administration of meloxicam and SC placebo. Group 2 dogs received IA placebo and SC meloxicam. Group 3 dogs received IA and SC administration of placebo. Dogs were assessed for pain by blinded observers using a visual analog scale (VAS), a numerical pain scoring system (NPS), and measurement of pain threshold using an algometer applied to the affected stifle. Assessments were made prior to pre-medication, postoperatively at the time of extubation, and at 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 hours following extubation. The results did not identify any significant effect of treatment between groups on the VAS data, algometer readings, or NPS data. Significantly increased VAS scores and decreased algometer readings were noted from preoperative to postoperative times. No differences were noted in early postoperative pain between dogs treated with IA meloxicam, SC meloxicam, or placebo. While intra-articular non-steroidal anti- inflammatory drug administration has shown efficacy in joint surgery for people, we did not find any evidence to support its use in dogs undergoing repair of CCLR.

Pharmacokinetics and toxic effects of lithium chloride after intravenous adminstration in conscious horses.

OBJECTIVE: To determine the pharmacokinetics and toxic effects associated with IV administration of lithium chloride (LiCl) to conscious healthy horses. ANIMALS: 6 healthy Standardbred horses. PROCEDURE: Twenty 3-mmol boluses of LiCl (0.15 mmol/L) were injected IV at 3-minute intervals (total dose, 60 mmol) during a 1-hour period. Blood samples for measurement of serum lithium concentrations were collected before injection and up to 24 hours after injection. Behavioral and systemic toxic effects of LiCl were also assessed. RESULTS: Lithium elimination could best be described by a 3-compartment model for 5 of the 6 horses. Mean peak serum concentration was 0.561 mmol/L (range, 0.529 to 0.613 mmol/L), with actual measured mean serum value of 0.575 mmol/L (range, 0.52 to 0.67 mmol/L) at 2.5 minutes after administration of the last bolus. Half-life was 43.5 hours (range, 32 to 84 hours), and after 24 hours, mean serum lithium concentration was 0.13+/-0.05 mmol/L (range, 0.07 to 0.21 mmol/L). The 60-mmol dose of LiCl did not produce significant differences in any measured hematologic or biochemical variables, gastrointestinal motility, or ECG variables evaluated during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of lithium best fit a 3-compartment model, and clearance of the electrolyte was slow. Healthy horses remained unaffected by LiCl at doses that exceeded those required for determination of cardiac output. Peak serum concentrations were less than steady-state serum concentrations that reportedly cause toxic effects in other species.

Local and regional anesthesia.

Local anesthetics have the unique ability to produce complete blockade of sensory nerve fibers and prevent or pre-empt the development of secondary (central) sensitization to pain. For this reason, local and regional anesthetic techniques are often used with opioids, alpha 2-receptor agonists, dissociatives, and anti-inflammatory drugs as part of a multimodal strategy to manage pain. Lidocaine and bupivacaine are the local anesthetics used most commonly in dogs and cats. Lidocaine has a fast onset (10-15 min) and an intermediate duration of action (60-120 min), and is used for short diagnostic and surgical procedures. Bupivacaine has a slow onset (20-30 min) and a long duration of action (240-360 min), and is used to control pain both preoperatively and postoperatively. Local anesthetics are relatively safe if they are administered correctly. Administration of an excessive dose and accidental intravenous administration are probably the most common causes of systemic toxicity in small animals. Doses of local anesthetics, especially those for cats and small dogs, should always be calculated carefully. In many animals, the most simple and elegant way to control pain perioperatively is to perform a local or regional anesthetic block. Veterinarians should not hesitate to incorporate local and regional anesthetic techniques into their pain management strategies for dogs and cats.

Sedative effects of intramuscular administration of a low dose of romifidine in dogs.

OBJECTIVE: To evaluate sedative effects of IM administration of a low dose of romifidine in dogs. ANIMALS: 13 healthy adult Beagles. PROCEDURE: Physiologic saline solution (0.2 ml), 0.1 % romifidine (10, 20, or 40 microg/kg), or 10% xylazine (1 mg/kg) was given IM in a crossover study design. Heart rate, respiratory rate, rectal temperature, hemoglobin saturation, and scores for sedation, muscle relaxation, posture, auditory response, and positioning response were recorded before and at regular intervals for up to 240 minutes after drug administration. RESULTS: Scores for sedation, muscle relaxation, posture, auditory response, and positioning response increased in a dose-dependent manner after romifidine administration. Sedation induced by the highest dose of romifidine (40 microg/kg) was comparable to that induced by xylazine (1 mg/kg). Heart rate, respiratory rate, and rectal temperature decreased in a dose-dependent manner after romifidine administration, but hemoglobin saturation did not change. CONCLUSIONS AND CLINICAL IMPLICATIONS: Romifidine (10, 20, or 40 microg/kg, IM) is an effective sedative in dogs, but causes a decrease in heart rate, respiratory rate, and rectal temperature.

Effects of medetomidine on serum osmolality; urine volume, osmolality and pH; free water clearance; and fractional clearance of sodium, chloride, potassium, and glucose in dogs.

OBJECTIVE: To determine effects of i.v. medetomidine administration on selected clinicopathologic variables in dogs. ANIMALS: 6 healthy adult Beagles. PROCEDURE: Dogs were randomly assigned to each of 3 treatments in a crossover study design. Serum osmolality, urine osmolality, urine pH, and fractional clearances of sodium, chloride, potassium, and glucose were determined before and 20, 40, 60, 120, 180, 240, 300, 360, 420, and 480 minutes after i.v. administration of 0.9% NaCl (saline) solution (control) or medetomidine (10 or 20 micrograms/kg of body weight). The urinary bladder was emptied prior to saline or medetomidine administration, and urine volume was determined at the same posttreatment times as those described previously. Free water clearance was calculated for all posttreatment times. RESULTS: After medetomidine administration, serum osmolality, urine volume, free water clearance, and fractional clearance of potassium and glucose increased; urine osmolality decreased. Initially, urine pH and fractional clearance of chloride decreased, then subsequently increased. Fractional clearance of sodium did not change. CONCLUSIONS AND CLINICAL RELEVANCE: Because i.v. administration of medetomidine to dogs at dosages of 10 and 20 micrograms/kg induces a diuretic effect that lasts up to 4 hours, the drug should be used with discretion in hypovolemic or dehydrated dogs, and its use should be avoided in those with urinary tract obstruction.

Effects of medetomidine on serum insulin and plasma glucose concentrations in clinically normal dogs.

OBJECTIVE: To determine the effects of medetomidine, administered i.v., on serum insulin and plasma glucose concentrations in clinically normal dogs. ANIMALS: 6 healthy adult Beagles. PROCEDURE: Dogs were randomly assigned to each of 3 treatments in a prospective cross-over study design. Serum insulin and plasma glucose concentrations were determined before and 20, 40, 60, 120, 180, 240, 300, 360, 420, and 480 minutes after i.v. administration of 0.9% NaCl solution (control) or medetomidine (10 or 20 micrograms/kg of body weight). RESULTS: Mean serum insulin concentration decreased after medetomidine administration and was significantly (P < or = 0.05) lower than control values 20, 40, 60, and 120 minutes after drug administration. Mean plasma glucose concentration tended to increase after medetomidine administration, but did not differ significantly from control values. CONCLUSIONS: In dogs, i.v. administration of medetomidine at dosages of 10 and 20 micrograms/kg transiently decreases serum insulin concentration, but plasma glucose concentration remains within the normal physiologic range. CLINICAL RELEVANCE: Medetomidine can be given at low, preanesthetic dosages without significantly altering plasma glucose concentration in clinically normal dogs.

Ability of flumazenil, butorphanol, and naloxone to reverse the anesthetic effects of oxymorphone-diazepam in dogs.

OBJECTIVE: To evaluate the ability of flumazenil (FLU), butorphanol (BUT), and naloxone (NAL) to reverse the anesthetic effects of oxymorphone-diazepam in dogs. ANIMALS: 6 healthy adult mixed-bread dogs. PROCEDURE: Dogs were randomly assigned to each of 6 reversal treatment groups. In each experiment, oxymorphone (0.22 mg/kg of body weight, i.v.) and diazepam (0.22 mg/kg. i.v.) were given sequentially 15 minutes after glycopyrrolate (0.01 mg/kg, i.v.) administration. Physiologic saline solution (SAL; 1 ml), FLU (0.01 mg/kg), BUT (0.44 mg/kg), or NAL (0.06 mg/kg) alone, or FLU-BUT or FLU-NAL (same dosages) was given i.v. as a reversal treatment 15 minutes after oxymorphone-diazepam administration. An individual unaware of the treatment protocol recorded time to extubation, sternal recumbency, and walking. RESULTS: Time to extubation was significantly (P < 0.05) less with BUT, NAL, FLU-BUT, or FLU-NAL treatment, compared with that for SAL treatment. Time to sternal recumbency was less with BUT, NAL, FLU-BUT, or FLU-NAL treatment, compared with that for SAL treatment. Time to walking was less with FLU-BUT or FLU-NAL treatment, compared with that for SAL treatment. CLINICAL IMPLICATIONS: Flumazenil, in combination with BUT or NAL, can be used to reverse the anesthetic effects of oxymorphone-diazepam in dogs.

Influence of cholinergic blockade on the development of epinephrine-induced ventricular arrhythmias in halothane- and isoflurane-anesthetized dogs.

The arrhythmogenic effects of anesthetic drugs are assessed using the arrhythmogenic dose of epinephrine (ADE) model. The purpose of this study was to determine the influence of cholinergic blockade (CB) produced by glycopyrrolate (G) on ADE in 1.5 minimum alveolar concentration (MAC) halothane (H)- and isoflurane (I)-anesthetized dogs. Eight dogs (weighing between 12.5 and 21.5 kg) were randomly assigned to four treatment groups (H, HG, I, and IG) and each treatment was replicated three times. Anesthesia was induced and maintained with H (1.31%, end-tidal [ET]) or I (1.95%, ET) in oxygen. Ventilation was controlled (carbon dioxide [PCO2] 35 to 40 mmHg, ET). G was administered 10 minutes before ADE determination at a dose of 22 microgram/kg (11 microgram/kg, intravenous [IV] and 11 micrograms/kg, intramuscular [IM]). The ADE was determined by IV infusion of epinephrine at sequentially increasing rates of 1.0, 2.5, and 5.0 micrograms/kg/min; and defined as the total dose of epinephrine producing at least four ectopic ventricular contractions (EVCs) within 15 seconds during a 3-minute infusion and up to 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Data were analyzed using a randomized complete block analysis of variance. When significant (P < .05) F values were found a least significant difference test was used to compare group means. Values are reported as means +/- standard error. The ADE (micrograms/kg) for H, HG, I, and IG were 1.53 +/- 0.08, 3.37 +/- 0.46, 1.61 +/- 0.21, and > 15.00, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in halothane-anesthetized dogs.

Eight dogs (12.5 to 21.5 kg) were assigned at random to each of 3 groups that were not given glycopyrrolate (HS, HX, HM) and to each of 3 groups that were given glycopyrrolate (HGS, HGX, HGM). Dogs were anesthetized with halothane (1.31% end-tidal concentration), and ventilation was controlled (PCO2 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered IV and IM at a dosage of 11 micrograms/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, IM), or medetomidine (15 micrograms/kg, IM) was administered 10 minutes after baseline arrhythmogenic dose of epinephrine (ADE) determination. Redetermination of the ADE at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0 and 2.5 micrograms/kg/min. The ADE was defined as the total dose of epinephrine inducing at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline ADE and posttreatment ADE for groups HS, HX, and HM was performed by use of one-way ANOVA.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in isoflurane-anesthetized dogs.

Eight dogs (body weight, 12.5 to 21.5 kg) were assigned at random to each of 3 treatment groups (IS, IX, IM) that were not given glycopyrrolate and to each of 3 groups that were given glycopyrrolate (IGS, IGX, IGM). Dogs were anesthetized with isoflurane (1.95% end-tidal concentration), and ventilation was controlled (PCO2, 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered IV and IM at a dosage of 11 micrograms/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, IM), or medetomidine (15 micrograms/kg, IM) was administered 10 minutes after baseline ADE determination. Redetermination of the ADE at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. The ADE was defined as the total dose of epinephrine that induced at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion, or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline and treatment ADE values was performed by use of one-way ANOVA. Mean +/- SEM baseline ADE values for groups IS, IX, and IM were 1.55 +/- 0.23, 1.61 +/- 0.28, and 1.95 +/- 0.65 micrograms/kg, respectively. Differences for groups IS, IX, and IM were -0.12 +/- 0.05, -0.31 +/- 0.40, and -0.17 +/- 0.26, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of atropine and glycopyrrolate in isoflurane-xylazine-anesthetized dogs.

Alterations in parasympathetic tone are partially responsible for xylazine's hemodynamic effects. The purpose of this study was to evaluate and compare the hemodynamic changes caused by the administration of intravenous (IV) atropine or glycopyrrolate after IV xylazine in isoflurane-anesthetized dogs. Six healthy beagles (8.2 to 10.7 kg) were used in two trials separated by 7 days. Anesthesia was induced and maintained with isoflurane in 100% oxygen with controlled ventilation. Once constant end-tidal isoflurane (1.8%) and arterial partial pressure of carbon dioxide (35 to 45 mm Hg) values were reached, baseline data were recorded and xylazine (0.5 mg/kg, i.v.) was given. In trial 1 atropine (0.1 mg/kg, i.v.) was given 5 minutes after xylazine, and in trial 2 glycopyrrolate (0.025, mg/kg, i.v.), was given 5 minutes after xylazine. Hemodynamic variables were recorded 3 minutes after xylazine and 3 minutes after anticholinergic administration. In trial 2, bilateral vagotomies were performed 10 minutes after glycopyrrolate, and hemodynamic variables were recorded 3 minutes later. Heart rate, cardiac index, and stroke index decreased; arterial pressure and systemic vascular resistance increased after xylazine. Heart rate, cardiac index, and rate pressure product increased after anticholinergic administration. Significant differences between atropine and glycopyrrolate were not observed in any of the hemodynamic parameters. Similarly, significant differences between glycopyrrolate and bilateral vagotomy were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)