Effects of carprofen on renal function during medetomidine-propofol-isoflurane anesthesia in dogs

OBJECTIVE: To investigate effects of carprofen on indices of renal function and results of serum bio-chemical analyses and effects on cardiovascular variables during medetomidine-propofol-isoflurane anesthesia in dogs. ANIMALS: 8 healthy male Beagles. PROCEDURES: A randomized crossover study was conducted with treatments including saline (0.9% NaCl) solution (0.08 mL/kg) and carprofen (4 mg/kg) administered IV. Saline solution or carprofen was administered 30 minutes before induction of anesthesia and immediately before administration of medetomidine (20 microg/kg, IM). Anesthesia was induced with propofol and maintained with inspired isoflurane in oxygen. Blood gas concentrations and ventilation were measured. Cardiovascular variables were continuously monitored via pulse contour cardiac output (CO) measurement. Renal function was assessed via glomerular filtration rate (GFR), renal blood flow (RBF), scintigraphy, serum biochemical analyses, urinalysis, and continuous CO measurements. Hematologic analysis was performed. RESULTS: Values did not differ significantly between the carprofen and saline solution groups. For both treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses; a transient, significant increase in urine alkaline phosphatase activity; and blood flow diversion to the kidneys. The GFR increased significantly in both groups despite decreased CO, mean arterial pressure, and absolute RBF variables during anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen administered IV before anesthesia did not cause detectable, significant adverse effects on renal function during medetomidine-propofol-isoflurane anesthesia in healthy Beagles.     

Effects of acepromazine on renal function in anesthetized dogs

OBJECTIVE: To investigate the effects of IM administration of acepromazine on indices of relative renal blood flow and glomerular filtration rate (GFR) by means of scintigraphy, as well as the effects on physiologic, hematologic, and serum biochemical variables in anesthetized dogs, compared with effects of administration of saline. ANIMAL: 6 healthy Beagles. PROCEDURE: Acepromazine (0.1 mg/kg) or physiologic saline (0.9 NaCI) solution was administered IM 30 minutes prior to induction of anesthesia with thiopentone; anesthesia was maintained with inspired isoflurane for 2.25 hours. Blood gases and circulatory and ventilatory variables were monitored. Renal function was evaluated by scintigraphic measurements of GFR and relative renal blood flow and analyses of serum and urine. Statistical analyses used ANOVA or Friedman ANOVA. RESULTS: Values of relative renal blood flow and GFR remained high despite low blood pressures. After administration of acepromazine, mean +/- SD arterial blood pressure was 66 +/- 8 mm Hg during anesthesia; this value was below the threshold (80 mm Hg) for renal autoregulation of GFR. In comparison, mean arterial blood pressure after administration of saline was significantly higher (87 +/- 13 mm Hg). However, between treatments, there were no significant differences in GFR, relative renal blood flow, or other indices of renal function. CONCLUSIONS AND CLINICAL RELEVANCE: Measurements of renal function and blood flow in dogs during anesthesia with thiopentone and isoflurane did not differ significantly between treatments, which suggested that acepromazine protects renal function despite inducing reduction in blood pressure, compared with effects of administration of saline.     

Effect of meloxicam and carprofen on renal function when administered to healthy dogs prior to anesthesia and painful stimulation

OBJECTIVE: To determine whether administration of the nonsteroidal anti-inflammatory drugs meloxicam or carprofen to healthy dogs that were subsequently anesthetized and subjected to painful electrical stimulation has adverse effects on renal function as measured by glomerular filtration rate (GFR) and evaluation of serum concentrations of urea and creatinine. ANIMALS: 6 male and 6 female healthy young-adult Beagles. PROCEDURE: A study was conducted in accordance with a randomized crossover Latin-square design. One of 3 treatments (saline [0.9% NaCl] solution, 0.2 mg of meloxicam/kg, or 4.0 mg of carprofen/kg) was administered i.v. 1 hour before anesthesia was induced by use of drugs in accordance with a standard anesthetic protocol (butorphanol tartrate and acepromazine maleate as preanesthetic medications, ketamine hydrochloride and diazepam for induction, and maintenance with isoflurane). Anesthetized dogs were subjected to intermittent electrical stimulation for 30 minutes. Direct, mean arterial blood pressure; heart rate; and respiratory rate were monitored. End-tidal isoflurane concentration was maintained at 1.5 times the minimum alveolar concentration. The GFR, as measured by plasma clearance of 99mTc-diethylenetriaminepentaacetic acid, and serum concentrations of serum and creatinine were determined 24 hours after induction of anesthesia. RESULTS: Neither meloxicam nor carprofen significantly affected GFR or serum concentrations of urea and creatinine, compared with values for the saline treatment. CONCLUSIONS AND CLINICAL RELEVANCE: When administered 1 hour before onset of anesthesia and painful electrical stimulation, meloxicam or carprofen did not cause clinically important alterations of renal function in young healthy dogs.     

Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane

OBJECTIVE: To evaluate renal effects of carprofen in healthy dogs following general anesthesia. DESIGN: Randomized clinical trial. ANIMALS: 10 English hound dogs (6 females and 4 males). PROCEDURE: Dogs were randomly assigned to control (n = 5) or carprofen (5) groups. Anesthesia was induced with propofol (6 to 8 mg/kg [2.7 to 3.6 mg/lb] of body weight, i.v.) and maintained with isoflurane (end-tidal concentration, 2.0%). Each dog underwent two 60-minute anesthetic episodes with 1 week between episodes, and mean arterial blood pressure was maintained between 60 and 90 mm Hg during each episode. Dogs in the carprofen group received carprofen (2.2 mg/kg [1 mg/lb], p.o.) at 9:00 AM and 6:00 PM the day before and at 7:00 AM the day of the second anesthetic episode. Glomerular filtration rates (GFR) were determined during each anesthetic episode by use of renal scintigraphy. Serum creatinine and BUN concentrations and the urine gamma-glutamyltransferase-to-creatinine concentration (urine GGT:creatinine) ratio were determined daily for 2 days before and 5 days after general anesthesia. RESULTS: Significant differences were not detected in BUN and serum creatinine concentrations, urine GGT:creatinine ratio, and GFR either between or within treatment groups over time. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not significantly alter renal function in healthy dogs anesthetized with propofol and isoflurane. These results suggest that carprofen may be safe to use for preemptive perioperative analgesia, provided that normal cardiorespiratory function is maintained.     

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis

OBJECTIVE: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. RESULTS: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.     

Influence of three anesthetic protocols on glomerular filtration rate in dogs

OBJECTIVE: To investigate renal function in clinically normal dogs when awake and during anesthesia with medetomidine; xylazine, ketamine, and halothane (XKH) combination; or propofol. ANIMALS: 10 adult female Beagles. PROCEDURES: At intervals of 15 days, dogs were administered medetomidine (0.05 mg/kg, IV); XKH combination (xylazine [1 mg/kg, IV], ketamine [5 mg/kg, IV], and halothane [1% end-tidal concentration]); or propofol (6 mg/kg, IV) to induce anesthesia or no treatment. Glomerular filtration rate was assessed on the basis of renal uptake (RU; determined via renal scintigraphy) and plasma clearance (CL) of technetium 99m-labeled diethylenetriamine pentaacetic acid ((99m)Tc-DTPA). RESULTS: In awake dogs, mean +/- SEM RU was 9.7 +/- 0.4% and CL was 3.86 +/- 0.23 mL/min/ kg. Renal uptake and CL of (99m)Tc-DTPA were not significantly modified by administration of XKH (RU, 11.4 +/- 0.9%; CL, 4.6 +/- 0.32 mL/min/kg) or propofol (RU, 9.7 +/- 0.3%; CL, 3.78 +/- 0.37 mL/min/kg). Half-life elimination time of plasma (99m)Tc-DTPA decreased significantly in XKH-anesthetized dogs, compared with the value in awake dogs (14.4 minutes and 28.9 minutes, respectively). However, glomerular filtration rate was significantly decreased by administration of medetomidine (RU, 3.9 +/- 0.1%), and the time to maximum kidney activity was significantly increased (867 +/- 56 seconds vs 181 +/- 11 seconds without anesthesia). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that anesthesia with propofol or an XKH combination did not alter renal function in healthy Beagles, but anesthesia with medetomidine decreased early RU of (99m)Tc-DTPA.     

Effects of urine alkalization and activated charcoal on the pharmacokinetics of orally administered carprofen in dogs

OBJECTIVE: To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs. ANIMALS: 6 neutered male Beagles. PROCEDURES: Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test. RESULTS: Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean +/- SD maximum concentration was 85.9 +/- 11.9 mg/L and 58.1 +/- 17.6 mg/L, and area under the time-concentration curve was 960 +/- 233 mg/L x h and 373 +/- 133 mg/L x h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.     

Effect of short-term sequential administration of nonsteroidal anti-inflammatory drugs on the stomach and proximal portion of the duodenum in healthy dogs

OBJECTIVE: To evaluate effects of injection with a nonsteroidal anti-inflammatory drug (NSAID) followed by oral administration of an NSAID on the gastrointestinal tract (GIT) of healthy dogs. ANIMALS: 6 healthy Walker Hounds. PROCEDURES: In a randomized, crossover design, dogs were administered 4 treatments consisting of an SC injection of an NSAID or control solution (day 0), followed by oral administration of an NSAID or inert substance for 4 days (days 1 through 4). Treatment regimens included carprofen (4 mg/kg) followed by inert substance; saline (0.9% NaCl) solution followed by deracoxib (4 mg/kg); carprofen (4 mg/kg) followed by carprofen (4 mg/kg); and carprofen (4 mg/kg) followed by deracoxib (4 mg/kg). Hematologic, serum biochemical, and fecal evaluations were conducted weekly, and clinical scores were obtained daily. Endoscopy of the GIT was performed before and on days 1, 2, and 5 for each treatment. Lesions were scored by use of a 6-point scale. RESULTS: No significant differences existed for clinical data, clinicopathologic data, or lesion scores in the esophagus, cardia, or duodenum. For the gastric fundus, antrum, and lesser curvature, an effect of time was observed for all treatments, with lesions worsening from before to day 2 of treatments but improving by day 5. CONCLUSIONS AND CLINICAL RELEVANCE: Sequential administration of NSAIDs in this experiment did not result in clinically important gastroduodenal ulcers. A larger study to investigate the effect of sequential administration of NSAIDs for longer durations and in dogs with signs of acute and chronic pain is essential to substantiate these findings.     

Effect of general anesthesia and minor surgical trauma on urine and serum measurements in horses

OBJECTIVE: To characterize the effect of general anesthesia and minor surgery on renal function in horses. ANIMALS: 9 mares with a mean (+/- SE) age and body weight of 9+/-2 years and 492+/-17 kg, respectively. PROCEDURE: The day before anesthesia, urine was collected (catheterization) for 3 hours to quantitate baseline values, and serum biochemical analysis was performed. The following day, xylazine (1.1 mg/kg, IV) was administered, and general anesthesia was induced 5 minutes later with diazepam (0.04 mg/kg, IV) and ketamine (2.2 mg/kg, IV). During 2 hours of anesthesia with isoflurane, Paco2 was maintained between 48 and 52 mm Hg, and mean arterial blood pressure was between 70 and 80 mm Hg. Blood and urine were collected at 30, 60, and 120 minutes during and at 1 hour after anesthesia. RESULTS: Baseline urine flow was 0.92+/-0.17 ml/kg/h and significantly increased at 30 and 60 minutes after xylazine administration (2.14+/-0.59 and 2.86+/-0.97 ml/kg/h respectively) but returned to baseline values by the end of anesthesia. Serum glucose concentration increased from 12+/-4 to 167+/-8 mg/dl at 30 minutes. Glucosuria was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Transient hyperglycemia and an increase in rine production accompanies a commonly used anesthetic technique for horses. The increase in urine flow is not trivial and should be considered in anesthetic management decisions. With the exception of serum glucose concentration and urine production, the effect of general anesthesia on indices of renal function in clinically normal horses is likely of little consequence in most horses admitted for elective surgical procedures.     

Effect of marbofloxacin on cardiovascular variables in healthy isoflurane-anesthetized dogs

OBJECTIVE: To study the hemodynamic effects of marbofloxacin (MBF) in isoflurane-anesthetized dogs. ANIMALS: 6 healthy 8-month-old Beagles. PROCEDURE: Anesthesia was induced with sodium thiopental and maintained with isoflurane. Cardiovascular variables were monitored throughout anesthesia. Marbofloxacin was administered by an IV bolus at 2 mg/kg, followed 10 minutes later by an infusion at a rate of 40 mg/kg/h for 30 minutes (total dose, 20 mg/kg). Plasma MBF concentrations were measured by high-performance liquid chromatography. RESULTS: The mean peak concentration during MBF infusion was 34.2 +/- 6.4 microg/mL. The IV administration of the MBF bolus did not alter any cardiovascular variable in isoflurane-anesthetized dogs. Significant changes were found during infusion when a cumulative dose of 12 mg/kg had been given. The maximal decreases observed at the end of the infusion were 16% in heart rate, 26% in systolic left ventricular pressure, 33% in systolic aortic pressure, 38% in diastolic aortic pressure, 29% in cardiac output, and 12% in QT interval. All dogs recovered rapidly from anesthesia at the end of the experiment. CONCLUSIONS AND CLINICAL RELEVANCE: MBF may safely be used at 2 mg/kg IV in isoflurane-anesthetized dogs, and significant adverse cardiovascular effects are found only when 6 to 8 times the recommended dose is given.     

Effects of intravenous administration of dimethyl sulfoxide on cardiopulmonary and clinicopathologic variables in awake or halothane-anesthetized horses

OBJECTIVE: To evaluate the cardiopulmonary and clinicopathologic effects of rapid IV administration of dimethyl sulfoxide (DMSO) in awake and halothane-anesthetized horses. DESIGN: Prospective study. ANIMALS: 6 adult horses. PROCEDURES: Horses received IV infusion of 5 L of a balanced electrolyte solution with and without 1 g/kg (0.45 g/lb) of 10% DMSO solution when they were awake and anesthetized with halothane (4 treatments/horse). Arterial and venous blood samples were collected immediately before and at intervals during or after fluid administration and analyzed for blood gases and hematologic and serum biochemical variables, respectively. Heart rate, respiratory rate, and arterial blood pressure variables were recorded prior to, during, and after fluid administration. RESULTS: After administration of fluid with or without DMSO, changes in measured variables were detected immediately, but most variables returned to baseline values within 4 hours. One awake control horse had signs of anxiety; agitation and tachycardia were detected in 2 awake horses administered DMSO. These clinical signs disappeared when the rate of infusion was reduced. In anesthetized horses, increased concentrations of WBCs and plasma fibrinogen and serum creatine kinase activity persisted for 24 hours, which was related to the stress of anesthesia more than the effects of fluid administration. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of 5 L of balanced electrolyte solution with or without 10% DMSO induced minimal changes in cardiopulmonary function and clinicopathologic variables in either awake or halothane-anesthetized horses. Stress associated with anesthesia and recovery had a greater influence on measured variables in anesthetized horses than fluid administration.     

Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs

OBJECTIVE: To evaluate the effects of butorphanol and carprofen, alone and in combination, on the minimal alveolar concentration (MAC) of isoflurane in dogs. DESIGN: Randomized complete-block crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: Minimal alveolar concentration of isoflurane was determined following administration of carprofen alone, butorphanol alone, carprofen and butorphanol, and neither drug (control). Anesthesia was induced with isoflurane in oxygen, and MAC was determined by use of a tail clamp method. Three hours prior to induction of anesthesia, dogs were fed a small amount of canned food without any drugs (control) or with carprofen (2.2 mg/kg of body weight [1 mg/lb]). Following initial determination of MAC, butorphanol (0.4 mg/kg [0.18 mg/lb], i.v.) was administered, and MAC was determined again. Heart rate, respiratory rate, indirect arterial blood pressure, endtidal partial pressure of CO2, and saturation of hemoglobin with oxygen were recorded at the time MAC was determined. RESULTS: Mean +/- SD MAC of isoflurane following administration of butorphanol alone (1.03 +/- 0.22%) or carprofen and butorphanol (0.90 +/- 0.21%) were significantly less than the control MAC (1.28 +/- 0.14%), but MAC after administration of carprofen alone (1.20 +/- 0.13%) was not significantly different from the control value. The effects of carprofen and butorphanol on the MAC of isoflurane were additive. There were not any significant differences among treatments in regard to cardiorespiratory data. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of butorphanol alone or in combination with carprofen significantly reduces the MAC of isoflurane in dogs; however, the effects of butorphanol and carprofen are additive, not synergistic.     

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair

Objective— To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. Study Design— Blind, randomized clinical study. Animals— Dogs with femoral (n=18) or pelvic (27) fractures. Methods— Dogs were grouped by restricted randomization into 4 groups: group 1=carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2=carprofen immediately after extubation, no epidural anesthesia; group 3=carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4=mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. Results— Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. Conclusions— Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. Clinical Relevance— Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.     

Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs

OBJECTIVE: To compare systemic bioavailability and duration for therapeutic plasma concentrations and cardiovascular, respiratory, and analgesic effects of morphine administered per rectum, compared with IV and IM administration in dogs. ANIMALS: 6 healthy Beagles. PROCEDURE: In a randomized study, each dog received the following: morphine IV (0.5 mg/kg of body weight), morphine per rectum (1, 2, and 5 mg/kg as a suppository and 2 mg/kg as a solution), and a control treatment. Intramuscular administration of morphine (1 mg/kg) was evaluated separately. Heart and respiratory rates, systolic, diastolic, and mean blood pressures, adverse effects, and plasma morphine concentrations were measured. Analgesia was defined as an increase in response threshold, compared with baseline values, to applications of noxious mechanical (pressure) and thermal (heat) stimuli. Data were evaluated, using Friedman repeated-measures ANOVA on ranks and Student-Newman-Keuls post-hoc t-tests. RESULTS: Significant differences were not found in cardiovascular, respiratory, or analgesia values between control and morphine groups. Overall systemic bioavailability of morphine administered per rectum was 19.6%. Plasma morphine concentration after administration of the highest dose (5 mg/kg) as a suppository was significantly higher than concentrations 60 and 360 minutes after IV and IM administration, respectively. A single route of administration did not consistently fulfill our criteria for providing analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Rectal administration of morphine did not increase bioavailability above that reported for oral administration of morphine in dogs. Low bioavailability and plasma concentrations limit the clinical usefulness of morphine administered per rectum in dogs.     

Comparison of high (5%) and low (1%) concentrations of micellar microemulsion propofol formulations with a standard (1%) lipid emulsion in horses

OBJECTIVE: To compare anesthesia-related events associated with IV administration of 2 novel micellar microemulsion preparations (1% and 5%) and a commercially available formulation (1%) of propofol in horses. Animals-9 healthy horses. PROCEDURES: On 3 occasions, each horse was anesthetized with 1 of the 3 propofol formulations (1% or 5% microemulsion or 1% commercial preparation). All horses received xylazine (1 mg/kg, IV), and anesthesia was induced with propofol (2 mg/kg, IV). Induction and recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and at intervals following anesthesia for quantification of clinicopathologic variables. RESULTS: Compared with the commercial formulation, the quality of anesthesia induction in horses was slightly better with the micellar microemulsion formulas. In contrast, recovery characteristics were qualitatively and quantitatively indistinguishable among treatment groups (eg, time to stand after anesthesia was 34.3 +/- 7.3 minutes, 34.1 +/- 8.8 minutes, and 39.0 +/- 7.6 minutes in horses treated with the commercial formulation, 1% microemulsion, and 5% microemulsion, respectively). During recovery from anesthesia, all horses stood on the first attempt and walked within 5 minutes of standing. No clinically relevant changes in hematologic and serum biochemical analytes were detected during a 3-day period following anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the micellar microemulsion preparation of propofol (1% or 5%) has similar anesthetic effects in horses, compared with the commercially available lipid propofol formulation. Additionally, the micellar microemulsion preparation is anticipated to have comparatively low production costs and can be manufactured in various concentrations.     

Influence of preinduction methoxamine, lactated Ringer solution, or hypertonic saline solution infusion or postinduction dobutamine infusion on anesthetic-induced hypotension in horses

A controlled study of the cardiovascular responses in horses anesthetized with acepromazine (0.05 mg/kg of body weight, IV), guaifenesin (100 mg/kg, IV), thiamylal (5.0 mg/kg, IV), and halothane in O2 (1.2 to 1.4% end-expired concentration) was performed to determine whether hypotension could be prevented by use of various treatments. Six horses were given 5 treatments in a randomized sequence: no treatment (control), methoxamine (0.04 mg/kg, IV), lactated Ringer solution (20.0 ml/kg, IV), 7.5% hypertonic saline solution (4.0 ml/kg, IV), or constant infusion of dobutamine (5.0 mg/kg/min, IV) during anesthesia. Heart rate, ECG, blood pressure, central venous pressure, cardiac output, blood gas analysis, PVC, and plasma total protein concentration were measured during the study. Compared with the control value, an increase in blood pressure during halothane administration was observed after administration of lactated Ringer solution, hypertonic saline solution, or dobutamine (P less than 0.05). The improved blood pressure response to hypertonic saline solution and dobutamine was related to an increase in cardiac output, which was statistically significant (P less than 0.05). Other statistically significant differences in cardiopulmonary responses among treatments were not observed during anesthesia. The PCV was increased in response to dobutamine infusion, and plasma total protein concentration was reduced in response to administration of hypertonic saline or lactated Ringer solution.     

Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair

OBJECTIVE: To evaluate effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing general anesthesia for fracture repair. ANIMALS: 26 client-owned dogs. PROCEDURE: Anesthesia was induced with levomethadone, diazepam, and propofol and maintained by administration of isoflurane in oxygen-nitrous oxide. Carprofen (4 mg/kg, SC) was administered 1 hour before induction to 13 dogs (group 1) and after extubation to the other 13 dogs (group 2). All dogs also received carprofen (4 mg/kg, SC, q 24 h) for the first 4 days after surgery. Renal function (glomerular filtration rate [GFR], urinary protein-to-urinary creatinine ratio [UP:UC], and results of urinalysis and biochemical analysis of plasma), hemostatic variables (bleeding time, platelet aggregation, prothrombin time [PT], activated partial thromboplastin time [APTT], and platelet count), and Hct were assessed before and at various time points after surgery. RESULTS: Analysis of results for renal function tests, most of the hemostatic and plasma biochemical variables, and Hct did not reveal significant differences between treatment groups. Values for GFR, UP:UC, PT, APTT, and platelet aggregation were outside reference ranges in many dogs before surgery and during the first 6 hours after surgery. In most dogs, these trauma-induced pathologic changes returned to within reference ranges during the 4-day period after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not cause clinically relevant adverse effects in dogs anesthetized for fracture repair after 5 days of treatment, even when it was administered before surgery or given to patients with trauma-induced alterations in renal function or hemostasis.     

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

OBJECTIVE: To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. ANIMALS: 36 adult dogs. PROCEDURES: Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. RESULTS: For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.     

Xylazine and tiletamine-zolazepam anesthesia in horses

The cardiopulmonary and anesthetic effects of xylazine in combination with a 1:1 mixture of tiletamine and zolazepam were determined in 6 horses. Each horse was given xylazine IV or IM, as well as tiletamine-zolazepam IV on 4 randomized occasions. Anesthetics were administered at the rate of 1.1 mg of xylazine/kg of body weight, IV, 1.1 mg of tiletamine-zolazepam/kg, IV (treatment 1); 1.1 mg of xylazine/kg, IV, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 2); 1.1 mg of xylazine/kg, IV, 2.2 mg of tiletamine-zolazepam/kg, IV (treatment 3); and 2.2 mg of xylazine/kg, IM, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 4). Tiletamine-zolazepam doses were the sum of tiletamine plus zolazepam. Xylazine, when given IV, was given 5 minutes before tiletamine-zolazepam. Xylazine, when given IM, was given 10 minutes before tiletamine-zolazepam. Tiletamine-zolazepam induced recumbency in all horses. Duration of recumbency in group 1 was 31.9 +/- 7.2 (mean +/- 1 SD) minutes. Increasing the dosage of tiletamine-zolazepam (treatments 2 and 3) significantly (P less than 0.05) increased the duration of recumbency. Xylazine caused significant (P less than 0.05) decreases in heart rate and cardiac output and significant (P less than 0.05) increases in central venous pressure and mean pulmonary artery pressure 5 minutes after administration. Respiratory rate was decreased. Arterial blood pressures increased significantly (P less than 0.05) after xylazine was administered IV in treatments 1 and 3, but the increases were not significant in treatment 2. Xylazine administered IM caused significant (P less than 0.05) increases in central venous pressure and significant (P less than 0.05) decreases in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of administration of nonsteroidal anti-inflammatory drugs before surgery on renal function in clinically normal dogs

OBJECTIVES: To investigate renal function in clinically normal dogs undergoing general anesthesia for ovariohysterectomies that received nonsteriodal antiinflammatory drugs (NSAID) before surgery. ANIMALS: 40 clinically normal dogs. PROCEDURE: After induction of anesthesia, dogs were given an analgesic. Renal function was assessed before surgery and 24 and 48 hours after surgery by means of serum urea and creatinine concentrations, fractional clearance of sodium (FC(Na)), urine gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) activities, and urine analysis. Ten dogs in each of 4 groups received ketorolac tromethamine (0.5 mg/kg of body weight), ketoprofen (1 mg/kg), carprofen (4 mg/kg), or morphine (0.1 mg/kg; control group). RESULTS: Duration of general anesthesia ranged from 1.75 to 5 hours, with a mean of 3 hours. Two ketorolac- and 2 ketoprofen-treated dogs had transient azotemia. A significant decrease in the FC(Na) between before surgery and 24 hours after surgery, and between before surgery and 48 hours after surgery, was found in ketoprofen- and carprofen-treated dogs. Ketorolac-, ketoprofen-, and morphine-treated dogs had a decrease in urine specific gravity. Two ketorolac, 1 ketoprofen-, 1 carprofen-, and 4 morphine-treated dogs had increases in renal tubular epithelial cells on urine sediment examination 24 hours after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: In clinically normal dogs undergoing general anesthesia and elective surgery, the use of NSAID as analgesics is not contraindicated. Compared with ketorolac or ketoprofen, carprofen had the least effect on renal function and integrity.