Analgesia in Dogs After Intercostal Thoracotomy: A Clinical Trial Comparing Intravenous Buprenorphine and Interpleural Bupivacaine

We prospectively studied 26 dogs that presented for intercostal thoracotomy. Dogs were pre-medicated with oxymorphone, induced with diazepam and etomidate, and anesthesia was maintained with isoflurane in oxygen. Preoperatively, animal patients were randomly assigned to one of two groups. Group 1 (n = 13) received buprenorphine (10 μg/kg intravenously [IV]) every 6 hours for 24 hours starting 10 minutes before tracheal extubation. Group 2 (n = 13) received 0.5% bupivacaine (1.5 mg/kg) administered interpleural (IP) by slow injection through a pediatric feeding tube fixed to the most dorsal aspect of the thoracotomy incision. Interpleural injections were administered with each dog placed in lateral recumbency with the incision positioned ventrally; IP injections were administered every 4 hours for 24 hours starting 10 minutes before tracheal extubation. All cases were monitored in the intensive care unit for 24 hours postoper-atively. The analgesic efficacy of each regimen was evaluated using a pain scoring system that included a subjective pain score, heart rate, and respiratory rate. Arterial blood pressure, arterial blood gases, oxygen saturation, body temperature, and changes in the electrocardiogram or neurological status were also noted. Significant increases in mean heart rate, respiratory rate, and total pain score occurred after surgery in dogs in the buprenorphine group. In contrast, dogs in the bupivacaine group had no significant changes when compared with their preoperative values. Dogs in the bupivacaine group had significantly decreased total pain scores and better PaO₂ and oxygen saturation values when compared with the dogs receiving buprenorphine. Hypoventilation did not occur in either group.     

Epidural anesthesia with bupivacaine, bupivacaine and fentanyl, or bupivacaine and sufentanil during intravenous administration of propofol for ovariohysterectomy in dogs

OBJECTIVE: To compare cardiovascular and systemic effects and analgesia during the postoperative period of epidural anesthesia performed with bupivacaine alone or with fentanyl or sufentanil in bitches maintained at a light plane of anesthesia with continuous infusion of propofol. STUDY DESIGN: Prospective randomized masked clinical trial. ANIMALS: 30 female dogs of various breeds. PROCEDURES: Dogs were allocated into 3 groups of 10 each. One group received fentanyl (2 microg/kg [0.91 microg/lb]) and bupivacaine (1 mg/kg [0.45 mg/lb]), 1 group received sufentanil (1 microg/kg) and bupivacaine (1 mg/kg), and 1 group received bupivacaine (1 mg/kg). All dogs received acepromazine (0.1 mg/kg [0.045 mg/lb]) and continuous infusion of propofol for sedation. The agents were administered into the lumbosacral space and diluted in saline (0.9% NaCl) solution to a total volume of 0.36 mL/kg (0.164 mL/lb). Cardiac and respiratory rates, arterial blood pressures, pH, and blood gases were evaluated. Analgesia, sedation level, serum cortisol concentrations, and plasma catecholamine concentrations were measured regularly for 6 hours. RESULTS: No important changes in cardiovascular, respiratory, or sedation variables were observed. Degree of analgesia in the postoperative period was higher in the sufentanil group, although use of fentanyl and bupivacaine also resulted in a sufficient level of analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the 3 anesthetic techniques permitted ovariohysterectomy with sufficient analgesia and acceptable neuroendocrine modulation of pain with minimal adverse effects.     

Hemodynamic effects of interpleural lidocaine and bupivacaine combination in anesthetized dogs with and without an open pericardium

OBJECTIVE: To identify dysrhythmias and hemodynamic changes after lidocaine and bupivacaine infusion into the interpleural space with an open pericardium. STUDY DESIGN: Experimental study. ANIMALS: Six adult dogs. METHODS: Systemic arterial pressure and electrocardiogram were recorded. A 7.5 Fr Swan-Ganz catheter was advanced to the level of the main pulmonary artery to record pulmonary arterial pressure. Cardiac output was measured by a thermodilution technique. A pericardial window (PW) was performed in 3 dogs using thoracoscopy. Hemodynamic variables were recorded before and 15 minutes after injection of lidocaine (1.5 mg/kg) and bupivacaine (1.5 mg/kg) into the pleural space in the control group and in the pericardial space for the PW group. A randomized-block ANOVA for repeated measures was used to evaluate the effect of local anesthetic administration on hemodynamic and electrophysiologic variables in dogs with a pericardectomy. RESULTS: Each dog maintained sinus rhythm. Infusion of local anesthetic induced a significant increase in right ventricular diastolic pressure (P = .002) and a significant decrease in stroke volume (P = .047) in both groups; however, the effects were not significantly different between groups. CONCLUSIONS: Infusion of lidocaine and bupivacaine, either intrapleural or in the pericardial space, had a mild detrimental effect on cardiac output. CLINICAL RELEVANCE: Intrapleural administration of lidocaine and bupivacaine at a therapeutic dose can be used safely in healthy dogs with a pericardectomy.     

Plasma concentrations of an angiotensin-converting enzyme inhibitor, benazepril, and its active metabolite, benazeprilat, after repeated administrations of benazepril in dogs with experimental kidney impairment

In order to examine the safety of an angiotensin-converting enzyme (ACE) inhibitor in dogs with impaired renal excretion route, benazepril was administered orally, and plasma concentrations of benazeprilat, the active metabolite of benazepril, were determined in dogs with renal mass reduction (1/4th kidney) created by right-side nephrectomy and ligation of branches of the left renal arteries. Five dogs were administered benazepril orally at a given dose (0.5 mg/kg body weight) and 4 other dogs received 20 times that dose (10 mg/kg body weight) once daily for 15 consecutive days before (intact kidney period) and after (1/4th kidney period) creation of kidney impairment. Six control dogs received surgical treatment, but no drug. After creating a 1/4th kidney, plasma urea nitrogen and creatinine concentrations increased to approximately 30 mg/dl and 2.0 mg/dl, respectively, and renal plasma flow and glomerular filtration rate decreased to 37% and 30% of pre-treatment values, respectively. However, these parameters did not change significantly during the 1/4th kidney period both in the 0.5 mg/kg and 10 mg/kg groups. In the 0.5 mg/kg group, plasma benazeprilat concentrations increased to approximately 20 ng/ml to 340 ng/ml 2 hr after each administration, and there were no significant differences between the plasma benazeprilat concentrations during the intact and 1/4th kidney periods. In the 10 mg/kg group, plasma benazeprilat concentrations varied in the individual dog, but did not increase with the days of administration, and were not significantly different on each administration day between the intact and 1/4th kidney periods in either dose group. The AUCs(0-24) of plasma benazeprilat concentrations determined on the 15th administration day were not different between the intact and 1/4th kidney periods in dogs of either dose group. Plasma ACE activities decreased after drug administration in dogs of both groups. Benazepril seemed to have a high safety, and the adjustment of dosage regimen might not be needed in dogs with mild to moderate renal function impairment because the drug was excreted both from the kidneys and liver.     

End tidal halothane concentration and postoperative analgesia requirements in dogs: a comparison between intravenous oxymorphone and epidural bupivacaine alone and in combination with oxymorphone.

The purpose of this study was to compare the effects of epidural bupivacaine (BUP) and oxymorphone/bupivacaine (O/B) and intravenous (i.v.) oxymorphone (IVO) on halothane requirements during hind end surgery and postoperative analgesia in 24 dogs. Dogs were randomly assigned to treatment groups: O/B--oxymorphone (0.1 mg/kg) in 0.75% bupivacaine (1 mg/kg for a total volume of 0.2 ml/kg); BUP--0.5% bupivacaine (1 mg/kg for a total volume of 0.2 ml/kg) with i.v. oxymorphone (0.05 mg/kg) postoperatively; and IVO--oxymorphone (0.05 mg/kg) pre- and postoperatively. Heart rate (HR), respiratory rate, arterial blood pressure, end-tidal carbon dioxide and halothane, and arterial blood gases were recorded prior to treatment and every 15 minutes thereafter. Once surgery had begun, end-tidal halothane concentrations were decreased as low as possible while still maintaining a stable anesthetic plane. Data were analyzed using ANOVA with P < 0.05 considered significant. End-tidal halothane requirements did not differ significantly among treatments. Respiratory depression was increased and HR was decreased in the O/B and IVO groups. Postoperative analgesic requirements were significantly less in dogs receiving O/B.     

Serum salicylate concentrations and endoscopic evaluation of the gastric mucosa in dogs after oral administration of aspirin-containing products

The serum salicylate concentration produced by oral administration of plain aspirin and several aspirin-containing products given at 8-hour intervals for 7 treatments was measured in 36 laboratory-conditioned adult dogs. The dogs were randomly allotted to 6 groups of 6 dogs each: group 1 was given plain aspirin at a dosage of 25 mg/kg of body weight: group 2 was given plain aspirin at a dosage of 10 mg/kg; group 3 was given buffered aspirin at a dosage of 25 mg/kg; group 4 was given enteric-coated aspirin at a dosage of 25 mg/kg; group 5 was given buffered aspirin at a dosage of 25 mg/kg; and, group 6 was given a placebo. Serum salicylate concentration was measured at 2-hour intervals for the first 8 hours, and then at 8-hour intervals for the next 40 hours. Following the last dosing, serum salicylate concentration was measured at 2-hour intervals until 56 hours; the final 2 samples were measured at 64 and 72 hours. The effect of aspirin on the gastric mucosa was studied in 12 dogs, 3 each randomly selected from groups 1, 3, 4, and 5. The gastric mucosa of each dog was examined with a fiberoptic gastroscope 3 days before the beginning of treatment; lesions were not seen. The drugs were administered as described and the gastric mucosa of each dog was reexamined at 72 hours. Administration of the aspirin-containing products at 8-hour intervals resulted in sustained therapeutic serum salicylate concentrations (greater than 5 mg/dl) in all dogs, except those of group 2. The greatest fluctuation in serum salicylate concentration was found in dogs of group 4. Gastric lesions were seen only in the 3 dogs of group 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication

OBJECTIVE: To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. ANIMALS: 42 client-owned dogs that underwent elective ovariohysterectomy. PROCEDURE: Each dog was randomly allocated to receive medetomidine and butorphanol tartrate (20 microgram/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanesthetic medication. Approximately 80 minutes later, anesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and beta-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored. RESULTS: Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of beta-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that for preanesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system.     

Use of a low dose synthetic ACTH challenge test in normal and prednisone-treated dogs

The utility of a low dose (1 microgram/kg) synthetic ACTH challenge test in detecting moderate reductions in adrenocortical sensitivity in dogs was examined. First, the adrenocortical responses to an intravenous bolus of either 1 microgram/kg or 0.25 mg per dog of synthetic ACTH were compared in two groups of normal dogs. While plasma cortisol concentrations were similar in both groups 60 minutes after ACTH injection, dogs given 0.25 mg ACTH showed continued elevations in plasma cortisol concentrations at 90 and 120 minutes after ACTH injection. Later, the dogs previously tested with the 1 microgram/kg ACTH challenge were given a single intramuscular dose of prednisone (2.2 mg/kg) and retested with 1 microgram/kg of ACTH one week later. Plasma cortisol levels were significantly reduced after ACTH injection in dogs previously given prednisone demonstrating that a single intramuscular prednisone dose causes detectable adrenocortical suppression one week after administration. The 1 microgram/kg synthetic ACTH challenge test provides a sensitive means for evaluating adrenocortical suppression in dogs.     

Effect of intraperitoneal or incisional bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs

ObjectiveTo compare the effect of intraperitoneal (IP) or incisional (INC) bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs.Study designProspective, randomized clinical study.AnimalsThirty female dogs undergoing ovariohysterectomy (OHE).MethodsDogs admitted for elective OHE were anesthetized with acepromazine, butorphanol, thiopental and halothane. Animals were randomly assigned to one of three groups (n = 10 per group). The treatments consisted of preincisional infiltration with saline solution (NaCl 0.9%) or bupivacaine with epinephrine and/or IP administration of the same solutions, as follows: INC and IP 0.9% NaCl (control group); INC 0.9% NaCl and IP bupivacaine (5 mg kg^?1, IP group); INC bupivacaine (1 mg kg^?1) and IP 0.9% NaCl (INC group). Postoperative pain was evaluated by a blinded observer for 24 hours after extubation by means of a visual analog scale (VAS) and a numeric rating scale (NRS). Rescue analgesia (morphine, 0.5 mg kg^?1, IM) was administered if the VAS was >5/10 or the NRS >10/29.ResultsAt 1 hour after anesthesia, VAS pain scores were [medians (interquartile range)]: 6.4 (3.1–7.9), 0.3 (0.0–2.6) and 0.0 (0.0–7.0) in control, IP and INC groups, respectively. VAS pain scores were lower in the IP compared to the control group. Over the first 24 hours, rescue analgesia was administered to 7/10, 5/10 and 3/10 dogs of the control, INC and IP groups, respectively. Total number of dogs given rescue analgesia over the first 24 hours did not differ significantly among groups.Conclusions and clinical relevanceIntraperitoneal bupivacaine resulted in lower pain scores during the first hour of the postoperative period and there was a trend towards a decreased need for rescue analgesia after OHE in dogs.     

Use of a continuous, local infusion of bupivacaine for postoperative analgesia in dogs undergoing total ear canal ablation

OBJECTIVE: To determine whether addition of a continuous, local infusion of bupivacaine would improve postoperative analgesia in dogs undergoing total ear canal ablation. DESIGN: Randomized controlled trial. ANIMALS: 16 dogs undergoing total ear canal ablation (12 unilaterally and 4 bilaterally with > 1 month between procedures). PROCEDURE: Dogs were randomly allocated to receive morphine (0.25 mg/kg [0.11 mg/lb]) at the end of the procedure (10 procedures) or morphine and a continuous, local infusion of bupivacaine (0.13 to 0.21 mg/kg/h [0.06 to 0.1 mg/lb/h]; 10 procedures). Dogs were observed for 48 hours after surgery. Additional doses of morphine were administered up to every 4 hours in dogs with signs of severe pain. RESULTS: Temperament, sedation, analgesia, and cumulative pain scores were not significantly different between groups any time after surgery. Recovery score was significantly higher for dogs that received bupivacaine than for control dogs 2 hours after extubation but not at any other time. Serum cortisol concentration was not significantly different between groups at any time but, in both groups, was significantly increased at the time of extubation, compared with all other observation times. Total number of additional doses of morphine administered was not significantly different between groups. Bupivacaine was not detected in the plasma of any of the dogs that received the local bupivacaine infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that addition of a continuous, local infusion of bupivacaine did not significantly increase the degree of postoperative analgesia in dogs that underwent total ear canal ablation and were given morphine at the end of surgery.     

Sprayed intraperitoneal bupivacaine reduces early postoperative pain behavior and biochemical stress response after laparoscopic ovariohysterectomy in dogs

This study investigated the use of sprayed intraperitoneal bupivacaine to relieve postoperative pain behavior and biochemical stress response after laparoscopic ovariohysterectomy (LOVH) in dogs. Sixteen sexually intact female dogs were randomly assigned to two groups. The sprayed intraperitoneal bupivacaine (SIB) group received 4.4 mg/kg of sprayed intraperitoneal bupivacaine diluted to 0.25% with an equivalent volume of saline after pneumoperitoneum. The control group received 1.76 mL/kg of saline in a similar fashion. Both groups received preoperative periportal 5% bupivacaine (1 mL) before incision. Postoperative pain was measured using the short form of the Glasgow composite measures pain scale (CMPS-SF, 0-24). Serum cortisol and glucose concentrations were measured preoperatively and 0.5, 1, 2, 4, 6, 12, and 24h postoperatively. The SIB group had significantly lower CMPS-SF compared to the control group 1, 2, 4, 6, and 12h after the operation. Cortisol concentrations were significantly increased from preoperative concentrations in the control group at 0.5, 1, 2, and 4h post operation and at 0.5 and 1h post operation in the SIB group. No significant differences were seen in serum glucose within each group. This report suggests that the use of sprayed intraperitoneal bupivacaine can be used as part of a multimodal approach for pain management after LOVH in dogs.     

Evaluation of intraperitoneal and incisional lidocaine or bupivacaine for analgesia following ovariohysterectomy in the dog

Objective To determine if intraperitoneal (IP) and incisional (SC) lidocaine or bupivacaine provide analgesia following ovariohysterectomy (OHE). Study Design Prospective, randomized, controlled, blinded clinical trial. Animals Thirty dogs presenting to the Veterinary Teaching Hospital for elective OHE. Methods Dogs were pre‐medicated with acepromazine and butorphanol, induced with thiopental and maintained with isoflurane. They were randomly assigned to three groups: 10 received 8.8 mg kg^?1 2% lidocaine with epinephrine IP (LID); 10 received 4.4 mg kg^?1 0.75% bupivacaine IP (BUP); and 10 received 0.9% saline IP (SAL) upon completion of OHE. All IP doses were standardized to 0.88 mL kg^?1 with saline. An additional 2 mL of undiluted solution was placed SC prior to incisional closure. Dogs were scored at 0.5, 1, 2, 3, 6, 8 and 18 hours post‐extubation by one observer. Dogs were evaluated using a visual analogue scale (VAS) for pain and sedation, and a composite pain scale (CPS) that included physiologic and behavioral variables. Dogs were treated with 0.22 mg kg^?1 butorphanol + acepromazine if their VAS (pain) score was >50. Parametric variables were analyzed using Student's t‐test or repeated measures anova as appropriate. Non‐parametric variables were analyzed by χ²‐test. Results There were no significant differences in age, weight, incision length, surgery time, anesthesia time, or total thiopental dose among groups. Peak post‐surgical pain scores for all groups occurred at 0.5 hours and returned to baseline by 18 hours. Dogs in the BUP group had significantly lower VAS‐pain scores overall than dogs in the SAL group. Seven out of 10 dogs in the SAL group, 4/10 in the LID group and 2/10 in the BUP group were treated with supplemental acepromazine and butorphanol. No differences between groups were detected with the CPS. No adverse side‐effects were observed. Conclusions and clinical relevance Our findings support the use of IP and SC bupivacaine for post‐operative analgesia following OHE in the dog.     

Plasma salicylate concentrations in immature dogs following aspirin administration: comparison with adult dogs

Aspirin disposition in immature and adult dogs, assessed by plasma salicylate concentrations following single doses of aspirin given orally (p.o.) and intravenously (i.v.), was compared. Using a cross-over design, four immature (12–16-weeks-old) and eight adult (1– 2-years-old) dogs were given a single dose of aspirin at 17.5 mg/kg body weight i.v. and a single dose of buffered aspirin at 35 mg/kg body weight p.o. Blood was collected from the jugular vein for 24 h following each dose. A fluorescence polarization immunoassay was used for determination of salicylate in plasma. Significant differences in aspirin disposition were identified between the two groups. Immature dogs had significantly shorter salicylate half-life, lower mean residence time, and more rapid salicylate clearance than adult dogs. The difference in volume of distribution between the two groups was not significantly different. Immature dogs had lower mean (± SD) peak plasma salicylate concentrations (64.5 ± 2.38 mg/L) than adult dogs (95.9 ± 12.2 mg/L) following a single oral dose of buffered aspirin at 35 mg/kg body weight. Predicted plasma salicylate concentration-time curves were constructed for various aspirin dosage regimens. This analysis showed that the previously recommended buffered aspirin dose for adult dogs of 25 mg/kg body weight p.o. every 8 h would be ineffective in maintaining plasma salicylate concentrations > 50 mg/L in immature dogs.     

Non-dexamethasone-suppressible, pituitary-dependent hyperadrenocorticism in a dog

A 5-year-old female dog with hyperadrenocorticism was determined to have pituitary-dependent hyperadrenocorticism even though plasma cortisol concentrations were not suppressed after high-dosage dexamethasone administration. The diagnosis was based on a supranormal response of plasma cortisol to ACTH administration and a lack of suppression of plasma cortisol concentration after administration of 0.1 mg of dexamethasone/kg. Although a higher dosage of dexamethasone (1 mg/kg) did not cause suppression of plasma cortisol, plasma ACTH concentrations in the dog were increased above those in clinically normal dogs, supporting a diagnosis of pituitary-dependent hyperadrenocorticism. During treatment with mitotane, the dog became unconscious and died. Necropsy revealed a pituitary tumor that had compressed and displaced the hypothalamus. Although high-dosage dexamethasone suppression tests often are useful in the differential diagnosis of hyperadrenocorticism, a lack of suppression of plasma cortisol does not necessarily exclude pituitary-dependent hyperadrenocorticism.     

Effects of moxifloxacin on QT interval in conscious dogs

Moxifloxacin has been shown to induce QT prolongation in both clinical and preclinical models. However, the ability to observe this effect at clinically relevant concentration in normal conscious dogs has not been reported. The purpose of this study was to investigate the effects of moxifloxacin on the QT interval in conscious, healthy dogs. Four male mongrel dogs were chronically instrumented for the measurement of arterial blood pressure, left ventricular blood pressure, cardiac output, electrocardiograms (ECGs), and body temperature. Animals were administered a 1-h i.v. infusion of moxifloxacin once per day via a catheter in the cephalic vein. Each dog received all doses (0, 1, 10, 25 and 50 mg/kg) in an escalating fashion. Moxifloxacin caused a statistically significant increase in arterial blood pressure at 50 mg/kg. A dose-response effect on QT and QTc prolongation was observed. A statistically significant prolongation in the QT interval was observed at 10, 25 and 50 mg/kg and a prolongation of QTc was observed at 25 and 50 mg/kg. These effects occurred at clinically relevant plasma concentrations. This study demonstrate that a study design with four dogs was sensitive enough to measure moxifloxacin-induced QT prolongation at clinically relevant plasma concentrations.     

Comparison of aqueous porcine ACTH with synthetic ACTH in adrenal stimulation tests of the female dog

The adrenocortical (plasma corticosteroid) responses in female dogs given porcine ACTH in gelatin (1-39 amino acid sequence) and synthetic ACTH (1-24 amino acid sequence) were compared. Sixteen dogs were used. Each dog underwent 4 different ACTH stimulation studies, these being done with a 4- to 8-week interval. The studies in each dog included injections of 2 doses of porcine ACTH--2.2 IU and 4.4 IU/kg of body weight--and of 2 doses of synthetic ACTH--0.25 mg/dog and 0.50 mg/dog. The dogs were arbitrarily allotted to 4 groups, each group being subjected to a given sequence of stimulation studies. The purpose in this project was to determine whether the established methods for synthetic and porcine ACTH stimulation tests had similar results. Statistical analysis of the 4 stimulation methods revealed no significance (P greater than 0.05) in the resting or poststimulation plasma corticosteroid concentrations. Thus, it was concluded that either recommended method using ACTH (porcine ACTH at 2.2 IU/kg or synthetic ACTH at 0.25 mg/dog) causes maximal secretion of adrenocortical reserve. Either ACTH preparation, using the established method, can be used interchangeably.     

Acute cardiovascular effects of diltiazem in anesthetized dogs with induced atrial fibrillation

Atrial fibrillation (AF) is one of the most important arrhythmias of dogs. In a previous study, we determined the dosage of intravenously administered diltiazem necessary to reduce ventricular response (VR), cardiac output (CO), and mean systemic arterial pressure (P(Ao)) to values similar to those observed during sinus rhythm (SR) before induction of AF. The present study was conducted to establish an acute, effective dosage of diltiazem given PO. AF was produced by rapid atrial pacing in healthy, anesthetized Beagle Hounds. Dogs were instrumented to record hemodynamic and electrophysiological parameters. Four dogs were given 2.5 mg/kg diltiazem, and another 4 dogs were given 5 mg/kg diltiazem by stomach tube, whereas 4 other dogs received vehicle in equivalent volumes. Plasma concentrations of diltiazem were measured at various intervals after dosing. A dosage of 5 mg/kg diltiazem produced plasma concentrations of 32-100 ng/mL 3 hours after administration, concentrations within the published effective range for dogs with naturally occurring AF. Between 2 and 3 hours after this dosage, the rate pressure product (RPP) and an index of left ventricular efficiency returned to values similar to those observed during SR. Thus, we believe that diltiazem at anorally administered dosages of 5 mg/kg should be considered to produce therapeutic blood concentrations and favorable hemodynamic effects in dogs with naturally occurring AF. These data must be extrapolated with caution to dogs with long-standing AF produced by natural causes.     

高乌甲素对犬术后血浆PGE_2含量的影响及其镇痛机理

选取18只健康杂交雌犬,随机分为A、B、C、D、E、F共6个组,每组3只。A、B、C、D、E组均实施子宫卵巢摘除术制作动物疼痛模型;F组不做手术作为对照组。A、B、C组分别一次性皮下注射高乌甲素0.2、0.4、0.8 mg/kg,D组口服卓比林（20 mg/kg）;E组不给与镇痛治疗。各组动物均在术前、术毕、术后2、6、12、24 h等时间点进行疼痛评分并采血测定血浆中前列腺素E2（PGE2）含量。结果显示：E组术后PGE2含量随时间增加而显著升高;高乌甲素能显著降低术后血浆PGE2含量（P〈0.05）,B组效果最佳;D组与B组无显著差异（P〉0.05）。术后各组的疼痛评分,D组与B组差异不显著（P〉0.05）。结果表明,高乌甲素的镇痛效果与卓比林相当,且其镇痛机理可能是通过抑制PGE2生成来实现的。     

A comparison of ketorolac with flunixin, butorphanol, and oxymorphone in controlling postoperative pain in dogs.

Ketorolac tromethamine, a nonsteroidal anti-inflammatory analgesic, was compared with flunixin and butorphanol for its analgesic efficacy and potential side effects after laparotomy or shoulder arthrotomy in dogs. Sixty-four dogs were randomly assigned to receive butorphanol 0.4 mg/kg body weight (BW) (n = 21), flunixin 1.0 mg/kg BW (n = 21), or ketorolac 0.5 mg/kg BW (n = 22), in a double blind fashion. The analgesic efficacy was rated from 1 to 4 (1 = inadequate, 4 = excellent) for each dog. The average scores after laparotomy were ketorolac, 3.4; flunixin, 2.7; and butorphanol, 1.6. After shoulder arthrotomy, the average scores were ketorolac, 3.5; flunixin, 3.0; and butorphanol, 1.4 (5/11 dogs). As butorphanol was unable to control pain after shoulder arthrotomy, oxymorphone, 0.05 mg/kg BW, replaced butorphanol in a subsequent group of dogs and had a score of 2.0 (6/11 dogs). Serum alanine aminotransferase and creatinine were significantly elevated above baseline at 24 hours postoperatively in dogs receiving flunixin. One dog in each group developed melena or hematochezia. One dog receiving ketorolac had histological evidence of gastric ulceration. We concluded that ketorolac is a good analgesic for postoperative pain in dogs.     

Estimated plasma bupivacaine concentration after single dose and eight-hour continuous intra-articular infusion of bupivacaine in normal dogs

Objective— To estimate maximum plasma concentration (C_max) and time to maximum plasma (t_max) bupivacaine concentration after intra‐articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Study Design— Cross‐over design with a 2‐week washout period. Animals— Healthy Coon Hound dogs (n=8). Methods— Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration–time curves and estimate C_max, T_max and other pharmacokinetic variables for comparison of SI and CI. Results— Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C_max, 1.33±0.954 μg/mL) occurred at 11.37±4.546 minutes. For CI, mean C_max (1.13±0.509 μg/mL) occurred at 10.37±4.109 minutes. The area under the concentration–time curve was smaller for SI (143.59±118.390 μg/mL × min) than for CI (626.502±423.653 μg/mL × min, P=.02) and half‐life was shorter for SI (61.33±77.706 minutes) than for CI (245.363±104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 μg/mL for SI and 2.3 μg/mL for CI. Conclusion— Intra‐articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C_max below that considered toxic and no systemic drug accumulation. Clinical Relevance— Intra‐articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra‐articular injection.