A Comparison of Epidural Saline, Morphine, and Bupivacaine for Pain Relief After Abdominal Surgery in Goats

The purpose of this study was to determine the analgesic efficacy of bupivacaine, morphine, or saline (control) when injected epidurally into the lumbosacral epidural space in goats after abdominal surgery. Goats received either bupivacaine (0.5%; 1.5 mg/kg in 0.9% sodium chloride solution), 0.9% sodium chloride solution (0.2 mL/kg), or preservative-free morphine (0.1 mg/kg). Total volume injected into the epidural space was 0.2 mL/kg for all groups. The variables evaluated were times to extubation, sternal recumbency, standing, and eating; heart and respiratory rates; and pain score. Only two of the goats in the bupivacaine group were able to stand on their hindlimbs before 6 hours. Time to eating was shorter for the saline group when compared with the bupivacaine group. Heart rate over all time in the saline group (137 ± 4 beats/min, mean ± SEM) was higher than the morphine (125 ± 3 beats/min) and bupivacaine groups (121 ± 3 beats/min). Respiratory rate over all time was increased in the saline group (26 ± 1 breaths/min) compared with the bupivacaine (24 ± 1 breaths/min) or morphine (24 ± 1 breaths/min) groups. At 50 minutes, the pain score for the saline group was higher than the morphine group. Pain score over all time in the saline group (1.5 ± 0.10) was higher than the morphine (1.2 ± 0.07) and bupivacaine (1.2 ± 0.04) groups. One goat in the saline group required two intravenous injections of flunixin meglumine for pain.     

Comparison of Intra-articular and Epidural Morphine for Analgesia Following Stifle Arthrotomy in Dogs

We prospectively studied 18 dogs that presented for exploratory stifle arthrotomy, with or without meniscectomy, and lateral extracapsular stabilization as a result of cranial cruciate ligament rupture. Dogs were premedicated with acepromazine, induced with thiopental, and maintained with halothane in oxygen. Preoperatively, dogs were assigned to one of three groups. Group 1 (n = 6) received intra-articular morphine (0.1 mg/kg diluted in 1 mL/10 kg body weight of saline) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 2 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 3 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural morphine (0.1 mg/kg of morphine diluted in 1 mL/5 kg body weight saline). The efficacy of each analgesia regimen was evaluated for 6 hours postoperatively with a pain score based on subjective and objective variables. Serum Cortisol and blood glucose concentrations were measured. Butorphanol was used to provide analgesia as needed based on a predetermined maximum pain score. Supplemental analgesics were required postoperatively every 2 to 3 hours for 6 hours in all dogs that did not initially receive analgesics (group 2). Pain scores were significantly lower in dogs administered morphine intra-articularly (group 1) and epidurally (group 3) at 30 minutes and 30, 120, and 360 minutes, respectively, compared with dogs that did not initially receive analgesics (group 2). One dog in group 1 and one dog in group 3 required supplemental analgesia with butorphanol. There was no difference between analgesia produced by intra-articular morphine compared with that of epidural morphine. Side effects after intra-articular or epidural morphine were not observed. Intra-articular administration of morphine can produce effective analgesia in dogs comparable with that produced by epidural administration of morphine.     

Postoperative Analgesia for Stifle Surgery: A Comparison of Intra-articular Bupivacaine, Morphine, or Saline

A prospective study was undertaken to compare the analgesic effect of intra-articular bupivacaine, morphine, or saline in the 24-hour period following cranial cruciate ligament repair in dogs. Thirty-six clinical patients with ruptured cranial cruciate ligaments were randomly assigned to one of three groups. After surgical stabilization, and before skin closure, an intra-articular injection was given; group one (n = 12) received 0.5% bupivacaine HCl at 0.5 mL/kg, group two (n = 12) received morphine at 0.1 mg/kg diluted with saline to a volume of 0.5 mL/kg, and group three (n = 12) received saline at 0.5 mL/kg. Heart rate, respiratory rate, mean arterial blood pressure, cumulative pain score, visual analog pain score, and pain threshold test on both stifles were recorded preoperatively and at 0 to 6 and 24 hours postoperatively. Surgeons and pain scoring investigators were unaware of the intra-articular medication given. Supplemental analgesia, if needed, was provided in the postoperative period according to subjective assessment of patient discomfort. Postoperative pain scores were lowest in the bupivacaine group and highest in the saline group. Pain threshold, measured by applying calibrated loads to the knee, was higher postoperatively in the bupivacaine group than in the saline group. Dogs in the morphine and bupivacaine groups required less supplemental analgesia than dogs in the saline group. The local provision of analgesia reduces the need for systemic drugs with potential side effects. Both intra-articular morphine and intra-articular bupivacaine provided better postoperative analgesia than intra-articular saline, with intra-articular bupivacaine showing the greatest effect.     

Effects of epidurally administered morphine or buprenorphine on the thermal threshold in cats

Objective: To determine the antinociceptive effects of epidural administration of morphine or buprenorphine in cats by use of a thermal threshold model. ANIMALS: 6 healthy adult cats. PROCEDURES: Baseline thermal threshold was determined in duplicate. Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a total volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a total volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. Thermal threshold was determined at various times up to 24 hours after epidural injection. RESULTS: Epidural administration of saline solution did not affect thermal threshold. Thermal threshold was significantly higher after epidural administration of morphine and buprenorphine, compared with the effect of saline solution, from 1 to 16 hours and 1 to 10 hours, respectively. Maximum (cutout) temperature was reached without the cat reacting in 0, 74, and 11 occasions in the saline solution, morphine, and buprenorphine groups, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of morphine and buprenorphine induced thermal antinociception in cats. At the doses used in this study, the effect of morphine lasted longer and was more intense than that of buprenorphine.     

Effects of extradural morphine on end-tidal isoflurane concentration and physiological variables in pigs undergoing abdominal surgery: a clinical study

OBJECTIVE: To evaluate the effects of preoperative extradural morphine on the end-tidal isoflurane (Fe'ISO) concentration and on physiological variables in pigs undergoing abdominal surgery. STUDY DESIGN: Prospective, randomized, blinded study. ANIMALS: Fourteen healthy pigs (20 +/- 4 kg) undergoing intestinal cannulation. MATERIALS AND METHODS: Anaesthesia was induced with a combination of medetomidine (50 microg kg(-1)) and tiletamine-zolazepam (2.5 mg kg(-1)) injected intramuscularly, and was maintained with isoflurane in air and oxygen (FiO(2) = 50% O(2)). In the first group, morphine (0.1 mg kg(-1)) was administered extradurally before surgery. The second group received an equivalent volume of extradural saline as control. During the experiment, heart and respiratory rates, mean arterial blood pressure, tidal volume and minute ventilation were recorded every 10 minutes. The concentration of Fe'ISO was adjusted, according to the depth of anaesthesia, by an experienced animal nurse. Within treatment groups, time-related changes in Fe'ISO and physiological variables were analysed using a repeated measurement anova. Differences in data between treatment groups were analysed at specific time points using a Mann-Whitney U-test. Results are presented as mean +/- SD; p < 0.05 was considered as significant. RESULTS: After the onset of action of the morphine, the Fe'ISO required to maintain anaesthesia was significantly lower in the extradural morphine group compared with control. During the expected maximal effect of the drug, Fe'ISO was significantly lower in the morphine group (0.6 +/- 0.2%) than in the control group (0.9 +/- 0.2%). The decrease in Fe'ISO indicated that the onset of action of morphine was approximately 30 minutes after injection. No significant differences in other clinical variables were found between the groups. CONCLUSION: Pigs that received extradural morphine before abdominal surgery achieved surgical anaesthetic depth at a lower Fe'ISO concentration. CLINICAL RELEVANCE: Extradural morphine allows abdominal surgery to be performed at a lower Fe'ISO concentrations.     

The cardiorespiratory effects of morphine and butorphanol in horses anaesthetised under clinical conditions

Twenty-five horses admitted for minor orthopaedic or soft tissue surgery were anaesthetised with detomidine, ketamine and halothane. Heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, blood gases and occlusion pressures were measured before and for 30 mins after intravenous (iv) injection of saline, butorphanol 0.05 mg/kg bodyweight (bwt) or morphine 0.02 or 0.05 mg/kg bwt. Drug or saline treatment induced no significant changes from pre-treatment values within a group for arterial blood pressure, heart rate, respiratory rate, arterial carbon dioxide tension, arterial oxygen tension and occlusion pressure. In conclusion, both morphine and butorphanol at the stated doses cause no adverse effects on the cardiovascular and respiratory systems of anaesthetised horses.     

The Effects of Atropine and Glycopyrrolate on Heart Rates in Conscious Mature Goats

The effects of intravenously administered atropine (0.2 mg/kg) and glycopyrrolate (0.01 mg/kg) on heart rate were studied in 10 conscious mature goats. In a drug cross-over fashion, either atropine, glycopyrrolate, or 0.9% saline solution was administered using the same volume (0.05 mL/kg). Atropine and glycopyrrolate caused a significant increase in heart rate ( P <.05), whereas saline solution (0.09%) did not. The mean percent changes in heart rate from baseline were similar for atropine and glycopyrrolate up to 14 minutes after administration. Thereafter, glycopyrrolate had a significantly greater mean change in heart rate than atropine, ie, up to 29 minutes ( P <.05). Within the atropine group, the mean percentage changes in heart rate became significantly lower compared with the initial increase (1 minute) starting at 11 minutes. For the glycopyrrolate group, the mean percent changes became significantly lower starting at 27 minutes. Glycopyrrolate and atropine had a mean percentage change in heart rate of greater than 1.0%, up to 31 and 22 minutes, respectively. At the doses used, glycopyrrolate had longer duration of action than atropine but the magnitude of increase was similar.     

Effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats. Animals-6 healthy adult domestic shorthair cats. PROCEDURES: Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. The minimum alveolar concentration (MAC) of isoflurane was measured in triplicate by use of the tail clamp technique. At least 1 week was allowed between successive experiments. RESULTS: The MAC of isoflurane was 2.00 +/- 0.18%, 2.13 +/- 0.11%, and 2.03 +/- 0.09% in the morphine, buprenorphine, and saline solution groups, respectively. No significant difference in MAC was detected among treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: A significant effect of epidural administration of morphine or buprenorphine on the MAC of isoflurane in cats could not be detected. Further studies are needed to establish whether epidural opioid administration has other benefits when administered as a component of general anesthesia in cats.     

内毒素血症山羊体征变化及氨基胍对其影响

将22只山羊随机分为5组，即对照组、内毒素血症模型组（内毒素LPS1800EU／kg）、内毒素血症氨基胍组（AG25mg／kg）、大剂量内毒素血症模型组（内毒素LPS5400EU／kg）和大剂量内毒素血症氨基胍组。肉眼观察动物精神状态和粪便的变化；用体温计检测直肠体温；用听诊器记录呼吸频率。结果表明：实验后1～9h，大、小剂量的内毒素（LPS）均使山羊表现出不同程度的精神不振、腹泻、食欲废绝。体温显著升高（P〈0．05），24h后体温恢复正常（P〉0．05）；但氨基胍对内毒素血症时体温的变化无调理作用（P〉0．05）。小剂量LPS和氨基胍对呼吸频率无影响（P〉0．05）；大剂量LPS却显著增加了山羊呼吸频率（P〈0．05），同时氨基胍也显著阻止了呼吸频率的升高（P〈0．05）。揭示体温、呼吸与内毒素剂量存在依赖关系；小剂量的氨基胍（25mg／kg）对内毒素血症时体温变化没有影响，但可明显减少呼吸频率。     

Analgesic and cardiopulmonary effects of intrathecally administered romifidine or romifidine and ketamine in goats (Capra hircus)

The study was conducted to evaluate the effects of romifidine alone (50 microg/kg) and a combination of romifidine (50 microg/kg) and ketamine (2.5 mg/kg) after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II). The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 +/- 6.25 s) compared to that of group I (5.2 +/- 0.54 min). Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I) and respiratory rate (more pronounced in group II), and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electrocardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.     

Pulmonary function in dogs after intercostal thoracotomy: comparison of morphine, oxymorphone, and selective intercostal nerve block

A thoracotomy was performed at the left 5th intercostal space in 24 dogs. Dogs were assigned to 4 groups of 6 dogs each. Postoperative analgesia was administered as follows: group 1--control, no analgesia; group II--morphine (0.5 mg/kg of body weight); group III--oxymorphone (0.1 mg/kg); group IV--selective intercostal nerve block with bupivacaine HC1. Respiratory rate, minute volume (VE), and arterial blood gases were measured during the recovery period. Ventilation-perfusion mismatch was estimated by calculation of the alveolar-arterial oxygen tension difference. Arterial carbon dioxide tension (Paco2) in the control and selective intercostal nerve block groups remained within the normal range and did not differ significantly (P less than 0.05) between groups. During the first 60 to 90 minutes after surgery, Paco2 tension was increased significantly (P less than 0.05) in the groups given morphine and oxymorphone. Hypoventilation in the groups given narcotics resulted from significant reductions (P less than 0.05) in the respiratory rate and VE and produced significant (P less than 0.05) respiratory acidosis and hypoxemia. Three dogs in the groups given narcotics had a panting response that resulted in increased respiratory rates and VE. This response did not improve alveolar ventilation in these dogs, which was evidenced by increased Paco2 values. Hypoventilation, respiratory acidosis, and hypoxemia in the groups given narcotics improved significantly with time, presumably because of drug clearance. Values for alveolar-arterial oxygen tension difference indicated moderate ventilation-perfusion mismatch secondary to anesthesia in all groups; however, significant differences (P less than 0.05) between the groups were not observed.     

Comparison of morphine and butorphanol as pre-anaesthetic agents in combination with romifidine for field castration in ponies

OBJECTIVE: The aim of this study was to compare two different alpha2 agonist-opioid combinations in ponies undergoing field castration. STUDY DESIGN: Prospective double-blind randomized clinical trial. ANIMAL POPULATION: Fifty-four ponies undergoing field castration. MATERIALS AND METHODS: The ponies were randomly allocated to receive one of three different pre-anaesthetic medications [intravenous (IV) romifidine 100 microg kg(-1) and butorphanol 50 micro kg(-1); romifidine 100 microg kg(-1) and morphine 0.1 mg kg(-1) IV, or romifidine 100 microg kg(-1) and saline IV] before induction of anaesthesia with ketamine 2.2 mg kg(-1) IV. Further doses of romifidine (25 microg kg(-1)) and ketamine (0.5 mg kg(-1)) were given when required to maintain anaesthesia. Quality of sedation, induction of anaesthesia, maintenance of anaesthesia, recovery, and surgical condition were assessed using a visual analogue scale scoring system and compared. The effects of the different drug combinations on heart and respiratory rate were evaluated and the recovery time was recorded. RESULTS: Anaesthesia was considered adequate for surgery in all ponies. No anaesthetic complications were observed. Quality of sedation was significantly better in the butorphanol group compared with the control group (p = 0.0428). Overall quality of anaesthesia was better in the butorphanol group compared with morphine (p = 0.0157) and control (p < 0.05) groups. Quality of induction of anaesthesia and recovery were not significantly different between groups, nor were the surgical conditions, recovery time and the number of repeated anaesthetic doses required during the procedure. Muscle twitches were observed in both the control and morphine groups. Maintenance of anaesthesia was judged to be smoother in the butorphanol group compared with the morphine and control groups (p = 0.006). Heart rate decreased significantly (p < 0.01) in all groups after administration of sedatives but did not differ significantly between groups at any time point. CONCLUSION: The combination of butorphanol and romifidine was found to provide better sedation compared with the other drug combinations. CLINICAL RELEVANCE: The combination of butorphanol and romifidine provided better sedation, but morphine was found to be a suitable alternative to butorphanol. Use of morphine and butorphanol in combination with alpha2 agonists should be further investigated to assess their analgesic effects.     

Effect of morphine and flunixin meglumine on isoflurane minimum alveolar concentration in goats

OBJECTIVE: To determine the effect of morphine and flunixin meglumine on isoflurane (ISO) minimum alveolar concentration (MAC) in goats. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: Five adult, wether goats from 1 to 3 years in age, and weighing 24-65 kg. METHODS: Anesthesia was induced using ISO, which was delivered via a mask. Goats were intubated and ventilated to maintain an end-tidal carbon dioxide concentration between 25 and 30 mm Hg (3.3-4 kPa). End-tidal ISO concentration was measured using an infrared analyzer. The baseline ISO MAC that prevented purposeful movement in response to clamping a claw was determined. Following baseline MAC determination, each goat received one of the following four treatments intravenously (IV): morphine (2 mg kg(-1)), flunixin (1.5 mg kg(-1)), flunixin (1.5 mg kg(-1)) plus morphine (2 mg kg(-1)) or saline, and the MAC was re-determined. Goats were studied at weekly intervals, and each goat received each treatment in a randomized fashion. RESULTS: The baseline ISO MAC for the control treatment was 1.43%. Morphine reduced the MAC by 29.7%. Flunixin did not significantly decrease the MAC nor did it potentiate the effect of morphine on MAC. The quality of recovery was good in all cases. CONCLUSIONS: Morphine (2 mg kg(-1), IV) significantly reduced the ISO MAC in goats and did not adversely affect the quality of recovery. CLINICAL RELEVANCE: The use of morphine, at the dose studied, in association with ISO anesthesia, will allow a clinically significant reduction in the concentration of ISO required to maintain general anesthesia in goats.     

Cardiorespiratory effects and efficacy of morphine sulfate in winter flounder (Pseudopleuronectes americanus)

OBJECTIVE: To assess the cardiorespiratory effects of morphine sulfate and evaluate whether morphine blocks cardiac responses to a noxious stimulus in winter flounder. ANIMALS: 42 winter flounder (Pseudopleuronectes americanus) that were acclimated at 10 degrees C. PROCEDURES: Each fish was fitted with a Doppler flow probe around the ventral aorta; cannulae were placed for injection of drug or saline (0.9% NaCl) solution and assessments of respiration. Selected cardiorespiratory variables were measured in morphine-injected (40 mg/kg, IP [n = 18] or 17 mg/kg, IV [2]) or saline solution-injected (1.6 mL [22]) fish at various intervals. Heart rate and cardiac output (CO) were also measured in flounder that were injected with saline solution (n = 19) or morphine (10) and received a noxious or innocuous stimulus (injection of 5% acetic acid or saline solution SC into a cheek) 50 minutes later. RESULTS: Morphine administration promptly induced marked bradycardia (and a concomitant reduction in CO), followed by prolonged (> 48 hours) increases in CO and heart rate. Morphine injection only transiently affected respiratory rate. Application of a noxious stimulus to control flounder resulted in a significant (10%) but transient (< 5 minutes' duration) increase in CO, which was completely blocked by prior administration of morphine. CONCLUSIONS AND CLINICAL RELEVANCE: Although morphine blocked the response to a noxious stimulus in fish, its cardiovascular effects might preclude its use in many research situations. Investigation of the dose dependency of these cardiovascular effects and their interspecific variation is required to determine the applicability of morphine for use in fish.     

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.     

ACE inhibition in goats under fixed‐time artificial insemination protocol increases the pregnancy rate and twin births

To assess the effect of the angiotensin‐converting enzyme (ACE) inhibition on the efficiency of the fixed‐time artificial insemination (TAI), 69 goats were divided randomly into two groups: enalapril (n = 35) and control (n = 34). In the experiment, all animals underwent the protocol of fixed‐time artificial insemination for 12 days. Enalapril group received enalapril maleate dissolved in saline (Enalapril, Lab Teuto Ltda) subcutaneously at the following doses: 0.2 mg/kg/day in D0‐D2; 0.3 mg/kg/day in D3‐D6 and 0.4 mg/kg/day in D7‐D11. The control group received the corresponding volume of 0.9% saline solution. We performed a single insemination 36 hr after sponge removal using frozen semen from two adult male goats with recognized fertility. The ultrasound pregnancy diagnosis was 30 days after the artificial insemination (AI). There was significant increase in pregnancy rates and twinning as well as a decrease in foetal loss in animals receiving enalapril (p < .01). The use of ACE inhibitors during the TAI protocol was shown to be a promising alternative to increase the efficiency of such reproductive biotechnology.     

Comparison of the hemodynamic effects of halothane alone and halothane combined with epidurally administered morphine for anesthesia in ventilated dogs

The hemodynamic effects of 1.5 minimal alveolar concentration of halothane alone (1.6% end-tidal) and 1.5 minimal alveolar concentration of halothane (1.1% end-tidal concentration) combined with epidurally administered morphine were compared during controlled ventilation in 10 dogs used on 2 occasions and randomly allocated to 2 groups. Arterial blood pressure, cardiac index, stroke volume, left ventricular work, and pulmonary arterial pressure were significantly (P less than 0.05) higher in dogs of the morphine-treated group before administration of morphine. After epidural administration of morphine (0.1 mg/kg of body weight diluted in 0.26 ml of saline solution/kg), hemodynamic changes were not observed, and the aforementioned variables remained significantly (P less than 0.05) higher than values in dogs of the halothane only group. Compared with halothane (1.6%) alone, the reduction in halothane end-tidal concentration (1.1%) associated with epidurally administered morphine is beneficial in maintaining hemodynamic function.     

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.