Expression of matrix metalloproteinases, type IV collagen, and interleukin-10 in rabbits treated with morphine after lamellar keratectomy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of analgesia provided by lidocaine, lidocaine-morphine or lidocaine-tramadol delivered epidurally in dogs following orchiectomy

ObjectiveTo evaluate and compare the postoperative analgesia provided by epidural lidocaine, lidocaine/morphine or lidocaine/tramadol in dogs following elective orchiectomy.Study designProspective experimental trial.AnimalsThirty-six mongrel dogs aged 2-8 years old, weighing 6.6-22 kg.MethodsThe dogs received 6.0 mg kg-1 of lidocaine combined with 1.0 mg kg-1 of tramadol, 0.1 mg kg-1 of morphine or 0.01 mL kg-1 of 0.9% NaCl epidurally. Analgesia was assessed at 4, 8, 12, 18 and 24 hours (T4, T8, T12 and T24) after the offset of lidocaine using a scale composed of physiologic and behavioral parameters. Rescue analgesia with morphine (0.2 mg kg-1, IM) was performed if the evaluation score exceeded 10 during the postoperative period. The scores over time were analyzed using the Friedman's two-way analysis of variance and the comparison between groups was made by the Kruskal-Wallis test with statistical significances accepted if p < 0.05.ResultsThere were no differences in the pain scores between the morphine and tramadol groups over time and no rescue analgesia was administered. In the NaCl group, rescue analgesia was needed at T4, T8 and T12. Within this group, the final evaluation times (T18 and T24) had lower pain scores than at T4, T8 and T12.Conclusions and clinical relevanceEpidural lidocaine/tramadol provided an analgesic effect comparable to that of epidural lidocaine/morphine during the first 12 hours after surgical castration without substantial side effects, suggesting that tramadol may be an effective postoperative analgesic in dogs submitted to this surgical procedure.

Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in ovariohysterectomized dogs

Objective-To evaluate analgesic effects of epidurally administered neostigmine alone or in combination with morphine in dogs after ovariohysterectomy.Animals-40 healthy bitches.Procedures-After acepromazine premedication, anesthesia was induced. Dogs randomly received 1 of the following 4 epidural treatments 30 minutes before ovariohysterectomy (n = 10/group): saline (0.9% NaCl) solution (control), morphine (0.1 mg/kg), neostigmine (10 pg/kg), or morphine-neostigmine (0.1 mg/kg and 10 pg/kg, respectively). Analgesia was assessed for 24 hours after surgery by use of a visual analogue.scale (VAS; scale of 0 to 10) or numeric descriptive scale (NDS; scale of 0 to 24) and by the need for supplemental analgesia (morphine [0.5 mg/kg, IM] administered when VAS was >= 4 or NDS was >= 8).Results-Significantly more control dogs (n = 8) received supplemental analgesia, compared with the number of neostigmine-treated dogs (1); no dogs in the remaining groups received supplemental analgesia. Compared with values for the control dogs, the NDS scores were lower for morphine-neostigmine-treated dogs (from 2 to 6 hours and at 12 hours) and for morphine-treated dogs (all time points). The NDS scores were lower for morphine-treated dogs at 3, 12, and 24 hours, compared with values for neostigmine-treated dogs. The VAS was less sensitive than the NDS for detecting differences among groups.Conclusions and Clinical Relevance-Epidurally administered neostigmine reduced the use of supplemental analgesia after ovariohysterectorny in dogs. However, analgesic effects were less pronounced than for epidurally administered morphine or morphine-neostigmine. Adding neostigmine to epidurally administered morphine did not potentiate opioid-induced analgesia.

Effect of intravenous alizapride on spinal morphine-induced pruritus

Background. This double-blind study was undertaken to determine whether alizapride inhibits spinal morphine-induced pruritus.Methods. Eighty-four patients undergoing Caesarean section under spinal anaesthesia (100 mg of hyperbaric lidocaine 5% plus morphine 0.2 mg) were randomly allocated to one of two groups. just after birth, alizapride-50 mg (alizapride group) or metoclopramide 10 mg (metoclopramide group) were injected i.v. Patients were assessed after surgery for pruritus (absent, mild, moderate or severe) or other untoward symptoms.Results. In the metoclopramide group, pruritus was absent in 5 (12%) patients, mild in 23 (55%), moderate in 11 (26%), and severe in 3 (7%), while in the alizapride group, these incidences were, respectively, 5 (12%), 33 (79%), 4 (10%), and 0 (P=0.045, chi(2)-test). There was no difference in the incidence of side-effects, which were all minor.Conclusions. Alizapride reduced the severity of morphine-induced pruritus.

Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by ANOVA (P < 0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8 +/- 3 degrees C), 1-3 h after methadone (maximum 3.4 +/- 1.9 degrees C) and 45 min to 1 h (maximum 3.4 +/- 2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238 +/- 206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255 +/- 232 mmHg) and 45-60 min and 3-6 h (maximum 255 +/- 232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes.

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

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.Prospective randomized, blinded, experimental trial.Six adult mixed-breed male dogs weighing 12.0 +/- 4.3 kg.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.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.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.

Comparison of the cardio-respiratory effects of methadone and morphine in conscious dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of ropivacaine combined with morphine at 0.15 and 0.2 mg kg-1 in bitches undergoing epidural anesthesia

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effects of the morphine-lidocaine-ketamine combination on cardiopulmonary function and isoflurane sparing in sheep

The aims of this study were to evaluate the isoflurane sparing and clinical effects of a constant rate infusion of morphine - lidocaine - ketamine (MLK) in healthy sheep undergoing experimental gastrointestinal surgery. Twelve adult female sheep (Texel breed) were used, weighing 36.5 +/- 8.1 kg. The sheep were anesthetized for the implantation of duodenal cannulas. The sheep were premedicated with 0.3 mg kg(-1) intramuscular (IM) morphine and 20 mu g kg(-1) intravenous (IV) detomidine. After premedication, anesthesia was induced using 5 mg kg(-1) ketamine and 0.5 mg kg(-1) diazepam IV and maintained using isoflurane in 100% oxygen. After the induction of anesthesia, the animals were allocated into two groups (each n=6); the GMLK (MLK group - 10 mg morphine, 150 mg lidocaine, 30 mg de ketamine were added in 500 mL saline) received a 10 mL kg(-1)h(-1) MLK infusion during the maintenance of anesthesia, and GCON (control group) received 10 mL kg(-1)h(-1) of 0.9% sodium chloride. The animals were mechanically ventilated. Cardiopulmonary variables and end-tidal isoflurane concentration (FE'Iso) were measured at baseline (immediately before the surgery) and 15, 30 and 45 minutes after initiation of surgery. In GMLK, there was a decrease in the FE 'Iso at 15, 30 and 45 minutes, a reduction of up to 75.6% during the surgery. The HR was lower in GMLK compared with GCON at 30 minutes, and the MAP was at during baseline in GCON compared with GMLK. The standing time was less in GMLK than in GCON. The use of intravenous MLK was demonstrated to offer great efficiency as part of a balanced anesthesia protocol in sheep, with a 75.6% reduction in the need for isoflurane, providing stability of the cardiovascular parameters and blood gases with a shortened recovery period.

Comparison of droperidol and ondansetron prophylactic effect on subarachnoid morphine-induced pruritus

The prophylactic effect of ondansetron on subarachnoid morphine-induced pruritus is controversial, while evidence suggests that droperidol prevents pruritus. The aim of this study is to compare the effects of droperidol and ondansetron on subarachnoid morphine-induced pruritus. 180 ASA I or II patients scheduled to undergo cesarean sections under subarachnoid anesthesia combined with morphine 0.2mg were randomized to receive, after the child's birth, metoclopramide 10mg (Group I - control), droperidol 2.5mg (Group II) or ondansetron 8mg (Group III). Postoperatively, the patients were assessed for pruritus (absent, mild, moderate or severe) or other side effects by blinded investigators. Patients were also blinded to their group allocation. The tendency to present more severe forms of pruritus was compared between groups. NNT was also determined. Patients assigned to receive droperidol [Proportional odds ratio: 0.45 (95% confidence interval 0.23-0.88)] reported less pruritus than those who received metoclopramide. Ondansetron effect was similar to metoclopramide [Proportional odds ratio: 0.95 (95% confidence interval 0.49-1.83)]. The NNT for droperidol and ondansetron was 4.0 and 14.7, respectively. Ondansetron does not inhibit subarachnoid morphine-induced pruritus.

Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Postoperative pain control in cats: clinical trials with pre-emptive lidocaine epidural co-administered with morphine or methadone

To evaluate the effectiveness of epidural lidocaine in combination with either methadone or morphine for postoperative analgesia in cats undergoing ovariohysterectomy. Under general anesthesia, 24 cats that underwent ovariohysterectomy were randomly allocated into three treatments groups of eight each. Treatment 1 included 2% lidocaine (4.0 mg/kg); treatment 2 included lidocaine and methadone (4.0 mg/kg and 0.3 mg/kg, respectively); and treatment 3 included lidocaine and morphine (4.0 mg/kg and 0.1 mg/kg, respectively). All drugs were injected in a total volume of 0.25 ml/kg via the lumbosacral route in all cats. During the anesthetic and surgical periods, the physiological variables (respiratory and heart rate, arterial blood pressure and rectal temperature) were measured at intervals of time zero, 10 mins, 20 mins, 30 mins, 60 mins and 120 mins. After cats had recovered from anesthesia, a multidimensional composite pain scale was used to assess postoperative analgesia at 2, 4, 8, 12, 18, and 24 h after epidural. The time to first rescue analgesic was significantly (P <0.05) prolonged in cats that received both lidocaine and methadone or lidocaine and morphine treatments compared with those that received the lidocaine treatment. All cats that received lidocaine treatment alone required rescue analgesic within 2 h of epidural injections. All treatments had significant cardiovascular and respiratory changes but they were within acceptable range for healthy animals during the surgical period. The two combinations administered via epidural allowed ovariohysterectomy with sufficient analgesia in cats, and both induced prolonged postoperative analgesia.

Efeitos comportamental, clínico e analgésico promovidos pela injeção epidural preventiva de morfina, xilazina ou clonidina, em equinos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Uso de morfina, xilazina e meloxicam para o controle da dor pós-operatória em cadelas submetidas à ovariossalpingo-histerectomia

Foram realizados estudos empregando-se analgésicos por via epidural e subcutânea em cadelas de diferentes raças e idades, submetidas à castração mediante celiotomia. Vinte animais foram tranquilizados e anestesiados com tiletamina-zolazepam, e aleatoriamente distribuídos em quatro grupos (n=5), de acordo com o fármaco e a via de administração. Os do grupo morfina (GM) foram submetidos à anestesia epidural no espaço lombossacro, com morfina (0,1mg/kg) associada ao cloreto de sódio a 0,9%. Aos do grupo xilazina (GX), foram administrados xilazina (0,2mg/kg) e cloreto de sódio a 0,9%. Os do grupo meloxicam (GME) receberam 0,2mg/kg do anti-inflamatório meloxicam associado ao cloreto de sódio a 0,9%, injetado pela via subcutânea. Os do grupo-controle (CG) receberam apenas cloreto de sódio a 0,9%. O volume final para as injeções epidurais foi padronizado para 0,3mL/kg. A mensuração inicial da concentração de cortisol plasmático, do ritmo cardíaco, da frequência respiratória e os parâmetros comportamentais foram registrados imediatamente antes do procedimento cirúrgico (M1). Registros adicionais foram apresentados às 2, 6, 12 e 24 horas após o procedimento cirúrgico (M2, M3, M4 e M5, respectivamente). As variáveis comportamentais foram avaliadas por meio de sinais clínicos e seus respectivos escores. em GX foram observadas depressão respiratória, bradicardia e concentração de cortisol mais alta do que o registrado no GM. A analgesia obtida pelo meloxicam foi considerada ineficiente. É possível concluir que a morfina, via epidural, promoveu menor incidência de efeitos colaterais e melhor analgesia e bem-estar animal.

Postoperative renal function evaluation, through RIFLE criteria, of elderly patients who underwent femur fracture surgery under spinal anesthesia

Introduction. The postoperative acute renal failure (ARF) incidence in different kinds of surgery has rarely been studied. Age, cardiac dysfunction, previous renal dysfunction, intraoperative hypoperfusion, and use of nephrotoxic medications are mentioned as risk factors for ARF at the postoperative period. The postoperative ARF definition was based on the creatinine increase by the RIFLE classification (R = risk, I = injury, F = failure, L = loss, E = end stage), which corresponds to a 1.5 creatinine increase, two to three times, respectively, above the basal value. This study aimed to evaluate the postoperative ARF incidence in elderly patients who underwent femur fracture surgery under subarachnoid anesthesia and stratify it by the RIFLE criteria. Methods. Ninety patients older than 65 years under spinal anesthesia with fixed dosage of 15 mg of 0.5% isobaric bupivacaine associated with morphine 50 g were studied. Immediate postoperative creatinine was considered basal and compared with maximal creatinine evaluated at 24, 48, and 72 postoperative hours. Results. The mean age of the patients was 80.27 years. ARF incidence was 24.44% and stratified this way: R = 21.11% and I = 3.33%. Conclusions. In conclusion, the postoperative ARF incidence after femur fracture surgery in patients over 65 years was 24.44%. By analyzing the stratification based on the RIFLE classification, the incidence was categorized as Risk (R) = 21.11% and Injury (I) = 3.33%.