Evaluation of histamine release during constant rate infusion of morphine in dogs

OBJECTIVE: To evaluate histamine release and selected physiologic variables during constant rate infusion (CRI) of morphine in dogs. ANIMALS: Five healthy, conscious, intact female dogs. MATERIAL AND METHODS: Using a Latin square, repeated-measures design, dogs were randomly assigned to three treatment groups to receive a 4-hour CRI of saline (SAL), or a loading dose of morphine at 0.3 mg kg(-1) (LM), or 0.6 mg kg(-1) (HM), followed by an infusion of 0.17 mg kg(-1) hour(-1) (LM) and 0.34 mg kg(-1) hour(-1) (HM) respectively. Dogs received each of the three treatments at intervals of at least 7 days. Plasma histamine concentration, skin flushing, edema and wheals, heart rate and rhythm and non-invasive arterial blood pressure were measured before the loading dose and at 1, 2, 5, 15, 30, 60, 120, 180 and 240 minutes during the CRI, or at the time of occurrence. RESULTS: The loading dose induced the highest histamine release in the HM group being statistically higher than the SAL group. The histamine release obtained in the LM group after the loading dose did not differ from SAL. During the infusion, plasma histamine levels were numerically higher in the LM group. Besides one dog that developed hypotension for 2 minutes after the loading dose in the HM group and one dog that showed occasional ventricular premature contractions during both morphine infusions, cardiovascular variables were similar among the three treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Both doses of morphine induced variable histamine release with minimal adverse cardiovascular effects in these conscious, healthy dogs. The plasma histamine levels obtained may be associated with significant hemodynamic changes in patients with limited cardiovascular reserve and sympathetic nervous tone.     

Evaluation of a local anesthetic delivery system for the postoperative analgesic management of canine total ear canal ablation--a randomized, controlled, double-blinded study

OBJECTIVE: To determine if a constant rate local anesthetic delivery system is more effective than continuous intravenous (IV) morphine infusion for postoperative analgesia. ANIMALS: Twenty client-owned dogs undergoing total ear canal ablation. METHODS: Dogs were randomly assigned to the lidocaine group (LID) or the morphine group (MOR). The LID group received a constant rate infusion of lidocaine locally and a continuous IV infusion of saline, while the MOR group received a constant rate infusion of saline locally and a continuous IV infusion of morphine. The primary investigator evaluated each patient and determined a hospital behavior score, anesthesia recovery score, preoperative pain score, and serial postoperative pain and sedation scores over 38 hours. Pain and sedation observations were videotaped and scored by three additional evaluators. Evaluators were blinded to treatment assignments. RESULTS: There were no significant differences in age, weight, hospital behavior scores or anesthesia recovery scores. The primary investigator's pain scores were not significantly different, but sedation scores were significantly lower for the LID group. Sedation and pain scores by the video evaluators were not significantly different between groups. Kappa agreement between observers was poor, but better agreement was noted between sedation scores than pain scores. Drug-related complications were significantly lower in the LID group (n = 0) compared with the MOR group (n = 5). Wound complications were not significantly different (LID = 4, MOR = 4). Intravenous delivery complications occurred in 12 (60%) patients. Local delivery complications occurred in five (25%) dogs. Delivery complications were not significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous incisional lidocaine delivery was an equipotent and viable method of providing postoperative analgesia compared with IV morphine. Lidocaine delivery resulted in a trend toward lower pain scores, significantly lower sedation scores, and no dogs requiring analgesic rescue. Wound complications secondary to local infusion were minor and self-limiting. Drug-related complications occurred only in the MOR group.     

Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs

Objective  To compare the effects of morphine (MOR), methadone (MET), butorphanol (BUT) and tramadol (TRA), in combination with acepromazine, on sedation, cardiorespiratory variables, body temperature and incidence of emesis in dogs.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Six adult mixed-breed male dogs weighing 12.0 ± 4.3 kg.
Methods  Dogs received intravenous administration (IV) of acepromazine (0.05 mg kg⁻¹) and 15 minutes later, one of four opioids was randomly administered IV in a cross-over design, with at least 1-week intervals. Dogs then received MOR 0.5 mg kg⁻¹; MET 0.5 mg kg⁻¹; BUT 0.15 mg kg⁻¹; or TRA 2.0 mg kg⁻¹. Indirect systolic arterial pressure (SAP), heart rate (HR), respiratory rate ( f _R), rectal temperature, pedal withdrawal reflex and sedation were evaluated at regular intervals for 90 minutes.
Results  Acepromazine administration decreased SAP, HR and temperature and produced mild sedation. All opioids further decreased temperature and MOR, BUT and TRA were associated with further decreases in HR. Tramadol decreased SAP whereas BUT decreased f _R compared with values before opioid administration. Retching was observed in five of six dogs and vomiting occurred in one dog in MOR, but not in any dog in the remaining treatments. Sedation scores were greater in MET followed by MOR and BUT. Tramadol was associated with minor changes in sedation produced by acepromazine alone.
Conclusions and clinical relevance  When used with acepromazine, MET appears to provide better sedation than MOR, BUT and TRA. If vomiting is to be avoided, MET, BUT and TRA may be better options than MOR.     

Laparoscopic ovariectomy using the endo-GIA stapling device and endo-catch pouches and evaluation of analgesic efficacy of epidural morphine sulfate in 10 mares

OBJECTIVE: To evaluate use of ENDO-GIA staples and ENDO-Catch pouches for ovariectomy in mares and to evaluate the efficacy of epidural morphine analgesia. STUDY DESIGN: Randomized clinical trial. ANIMALS: Mares (n = 10) with normal ovaries. METHODS: An Endo-GIA II stapler (United States Surgical Corp., Norwalk, CT) was used to amputate the ovaries bilaterally, in standing mares, and Endo-Catch II pouches (United States Surgical Corp.) were used for retrieval. Epidural morphine was used in 5 mares, and procedure duration, volume of lidocaine required to desensitize the ovarian pedicle, and sedation were compared with horses not administered epidural morphine. RESULTS: Use of the Endo-GIA II stapling device was an easy and an efficient method of ovariectomy, which was facilitated by use of epidural morphine. For the epidural group, the mean (+/-SD) surgical time was 69.2 +/- 10.2 minutes compared with 124.4 +/- 21.2 minutes for mares not administered morphine. Less systemic sedation was required for mares administered epidural morphine. CONCLUSIONS: Minimal ovarian manipulation was required to apply the stapler, hemorrhage was slight, and none of the mares had complications. Epidural morphine provided effective analgesia, improving patient comfort, and reduced the sedation needed to perform ovariectomy. CLINICAL RELEVANCE: Endo-GIA II staples are an efficient method for ovariectomy in normal mares. Epidural morphine should be considered to facilitate ovariectomy because less sedation and local anesthetic administration is required.     

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.     

Thoracic epidural analgesia via the lumbosacral approach using multiport catheters with a low concentration of bupivacaine and morphine in sheep

ObjectiveTo determine the analgesic and systemic effects of thoracic epidural administration of bupivacaine (BP) and morphine (MP) in conscious sheep.Study designRandomized, crossover, experimental study.AnimalsSix healthy castrated sheep weighing between 40 and 50 kg.MethodsEach sheep received, via the lumbosacral approach, BP (0.5 mg kg^?1), MP (0.1 mg kg^?1), and BP plus MP (BPMP; 0.25 mg kg^?1 + 0.05 mg kg^?1) in a randomized order. Heart rate, blood pressure, respiratory rate, blood gas analysis, skin temperature, rectal temperature, analgesia, sedation, and motor blockade were determined before treatment and at predetermined intervals until analgesia had disappeared.ResultsThe main areas of complete analgesia for the BP and BPMP treatments were the thorax and forelimb bilaterally. The median duration of analgesia was shorter with MP treatment (45 minutes; score 2) than with BP treatment (70 minutes) and BPMP treatment (140 minutes; p < 0.05). The BP and BPMP treatments caused motor block, and MP and BPMP treatments showed mild sedation. Significant decreases in systolic and diastolic arterial blood pressures were observed only with the BP treatment (p < 0.05). Epidural MP combined with the BP local anesthetic depressed ventilation but within acceptable limits in these clinically healthy sheep.ConclusionsThoracic epidural administration of BPMP to sheep resulted in longer duration of analgesia of the thorax and forelimbs bilaterally in conscious sheep than the administration of MP or BP alone. The incidence of complications was low, but side-effects such as depressed ventilation and muscle paralysis occurred and require appropriate management.Clinical relevanceThis technique should be considered as another method for the relief of postoperative pain after thoracic surgery in sheep.     

Hypotension and pruritus induced by neuraxial anaesthesia in a cat

Although preventive epidural morphine administration with bupivacaine is effective in producing long‐lasting analgesia, neuraxial anaesthesia can cause cardiovascular depression and pruritus. This report presents the development and treatment of hypotension and pruritus after intrathecal morphine and bupivacaine administration in a 3‐year‐old female spayed Domestic Short‐hair cat presented for surgical repair of a torn right cranial cruciate ligament. Opioid‐induced pruritus is not usually considered a frequently occurring complication, but may be easily misinterpreted as being dysphoria in recovery. It can be treated by administration of ondansetron, with human patients usually responding within 30 min after treatment.     

Inhibition of motility in isolated horse small intestine is mediated by κ but not µ opioid receptors

The effects of preferential μ (morphine), selective μ (fentanyl), selective κ (compound U69593) opioid receptor agonists, and nonselective (naloxone) and selective μ (naloxonazine) antagonists on equine small intestinal motility were evaluated in vitro. Samples of circular muscle from equine jejunum were placed in isolated organ baths and drug-induced modifications of both spontaneous and electrically evoked contractile activity were measured. None of the opioid agonists induced a significant change in spontaneous contractions. Fentanyl and U69593 reduced electrically induced contractions, whereas morphine reduced them only slightly. Naloxone competitively antagonised U69593, but both naloxone and naloxonazine were unable to counteract the inhibition of contractions induced by fentanyl. The inhibition of contractions shown by fentanyl is therefore probably not mediated by opioid receptors, but due to an anticholinergic activity of this drug. In summary, these data showed an inhibitory effect exerted by κ receptors on equine small intestinal motility, whereas the role of μ receptors seemed marginal and would need further characterisation.     

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.     

Effects of morphine and fentanyl constant rate infusion on urine output in healthy and traumatized dogs

ObjectiveTo determine whether healthy and traumatized dogs receiving a constant rate infusion (CRI) of either morphine or fentanyl have decreased urine production.Study designProspective randomized controlled study.Animal populationEighteen privately owned previously healthy dogs that had undergone trauma were included. Twenty-three privately owned healthy dogs were used as the controls.MethodsTraumatized dogs were randomized into one of two groups. Group Tmorphine received a CRI of morphine (0.12 mg kg⁻¹ hour⁻¹) and group Tfentanyl received a CRI of fentanyl (3 μg kg⁻¹ hour⁻¹) both administered in lactated Ringer’s solution (LRS) at a rate of 60 mL kg⁻¹ day⁻¹. Control healthy dogs were randomized into one of three groups. The LRS control group (CLRS) (n = 8) received LRS at a rate of 60 mL kg⁻¹ day⁻¹. Group Cmorphine (n = 8) and group Cfentanyl (n = 7) received the same infusions as Tmorphine and Tfentanyl, respectively. Collected data were identical for all groups and consisted of measuring total fluid administered, urine output, and urine specific gravity (USG) for a 24-hour period. An analysis of variance (anova) was used for statistical analysis and a p < 0.05 was considered statistically significant.ResultsUrine output was significantly decreased (p < 0.05) in all groups compared with the LRS control group. The end mean USG was significantly lower (p = 0.003) in the LRS control group compared with all other groups.ConclusionsThere was a decrease in urine output with a CRI of morphine or fentanyl in both healthy and traumatized dogs.Clinical relevanceDecreased urine output caused by an opioid effect might lead to improper assessments of renal function and urine production.