Analgesic Effects Of Intra-articular Morphine Research Articles

Single dose intra-articular morphine for pain control after knee arthroscopy.

Knee arthroscopy is a common procedure and is associated with postoperative pain. Intra-articular (IA) injection of morphine for pain control has been widely studied, but its analgesic effect after knee arthroscopy is uncertain. To evaluate the relative effects on pain relief and adverse events of IA morphine given for pain control after knee arthroscopy compared with placebo, other analgesics (local anaesthetics, non-steroidal anti-inflammatory drugs (NSAIDs), other opioids) and other routes of morphine administration. We searched CENTRAL (The Cochrane Library Issue 4, 2015), MEDLINE via Ovid (January 1966 to May 2015), EMBASE via Ovid (January 1988 to May 2015), and the reference lists of included articles. We also searched the metaRegister of controlled trials, clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials. We identified all the randomised, double-blind controlled trials that compared single dose IA morphine with other interventions for the treatment of postoperative pain after knee arthroscopy. We excluded studies with fewer than 10 participants in each group, using spinal or epidural anaesthesia, or assessing the analgesic effect of IA morphine on chronic pain. Two authors independently assessed the quality of each trial and extracted information on pain intensity, supplementary analgesics consumption and adverse events. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. We included 28 small, low quality studies (29 reports) involving 2564 participants. Of 20 studies (21 reports) comparing morphine with placebo, nine studies with adequate data were included in the meta-analysis. Overall, the risk of bias was unclear. Overall, the quality of the evidence assessed using GRADE was low to very low, downgraded primarily due to risk of bias, small study size, and imprecision.No statistical difference was found between 1 mg IA morphine and placebo in pain intensity (visual analogue scale (VAS)) at early phase (zero to two hours) (mean difference (MD) -0.50, 95% CI -1.15 to 0.14; participants = 297; studies = 7; low quality evidence), medium phase (two to six hours) (MD -0.47, 95% CI -1.09 to 0.14; participants = 297; studies = 7; low quality evidence) and late phase (six to 30 hours) (MD -0.88, 95% CI -1.81 to 0.04; participants = 297; studies = 7; low quality evidence). No significant difference was found between 1 mg and 2 mg morphine for pain intensity at early phase (MD -0.56, 95% CI -1.93 to 0.81; participants = 105; studies = 2; low quality evidence), while 4 mg/5 mg morphine provided better analgesia than 1 mg morphine at late phase (MD 0.67, 95% CI 0.08 to 1.25; participants = 97; studies = 3; low quality evidence). IA morphine was not better than local anaesthetic agents at early phase (MD 1.43, 95% CI 0.49 to 2.37; participants = 248; studies = 5; low quality evidence), NSAIDs at early phase (MD 0.95, 95% CI -0.95 to 2.85; participants = 80; studies = 2; very low quality evidence), sufentanil, fentanyl or pethidine for pain intensity. IA morphine was similar to intramuscular (IM) morphine for pain intensity at early phase (MD 0.21, 95% CI -0.48 to 0.90; participants = 72; studies = 2; very low quality evidence).Meta-analysis indicated that there was no difference between IA morphine and placebo or bupivacaine in time to first analgesic request. Eleven out of 20 studies comparing morphine with placebo reported adverse events and no statistical difference was obtained regarding the incidence of adverse events (risk ratio (RR) 1.09, 95% CI 0.51 to 2.36; participants = 314; studies = 8; low quality evidence). Seven of 28 studies reported participants' withdrawal. There were not enough data for withdrawals to be able to perform meta-analysis. We have not found high quality evidence that 1 mg IA morphine is better than placebo at reducing pain intensity at early, medium or late phases. No statistical difference was reported between IA morphine and placebo regarding the incidence of adverse events. The relative effects of 1 mg morphine when compared with IA bupivacaine, NSAIDs, sufentanil, fentanyl and pethidine are uncertain. The quality of the evidence is limited by high risk of bias and small size of the included studies, which might bias the results. More high quality studies are needed to get more conclusive results.

Analgesic efficacy of intra-articular morphine in experimentally induced radiocarpal synovitis in horses

ObjectiveTo compare the analgesic effect of intra-articular (IA) and intravenous (IV) morphine in horses with experimentally induced synovitis. AnimalsEight adult horses. Study designRandomized, observer blinded, double dummy trial with sequential crossover design. MethodsRadiocarpal synovitis was induced by IA injection of lipopolysaccharide on two occasions separated by a 3-week washout period. In one study period horses received treatment IA; morphine IA (0.05 mg kg−1) plus saline IV and in the other study period they received treatment IV; saline IA plus morphine IV (0.05 mg kg−1). Lameness and pain were evaluated repeatedly by two observers throughout each of the two 168-hour study periods. Pain was evaluated by use of a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS). Comparison of treatments was performed by analysis of variance with repeated measurements. Significance level was set to p ≤ 0.05. Inter-observer agreement and agreement between the VAS and CMPS was assessed by use of the Bland–Altman method. ResultsIntra-articular injection of LPS elicited a marked synovitis resulting in lameness and pain. IA morphine resulted in significantly less lameness than IV morphine (p = 0.03). CMPS (p = 0.09) and VAS (p = 0.10) pain scores did not differ significantly between treatments. Inter-observer agreement of the CMPS was classified as good, but only fair for the VAS. Agreement between the two pain scales was considered fair. Conclusions and clinical relevanceAn analgesic effect of IA morphine was demonstrated by significantly reduced lameness scores. The results support the common practice of including IA morphine in a multimodal analgesic protocol after arthroscopic surgery, although further studies in clinical cases are needed. The employed CMPS had good reproducibility, and was easy to use, but may have limited sensitivity at mild intensity pain.

(227) Comparative Study of Intra-Articular Morphine, Fentanyl or Bupivacaine for Knee Surgery

Introduction: After identification of peripheral receptors, a possibility was open to apply peripheral opioids in an attempt to use the strong analgesic effects of such drugs and, at the same time, avoid undesirable side effects. The aim of this study was to evaluate the analgesic effect of intra-articular morphine, fentanyl and bupivacaine in knee surgeries. Methods: Forty patients physical status ASA I or II scheduled for arthroscopic knee surgery were randomized to one of four groups. GI (10 patients) received 10 ml of 0.9% saline; GII (10 patients) received 10 ml of 0.25% bupivacaine with epinephrine; GIII received 2 mg of morphine diluted in 0.9% saline to 10 ml; GIV (10 patients) received 100 mcg of fentanyl diluted to 10 ml with saline. All patients were submitted to spinal anesthesia with 15 mg of 0.5% hyperbaric bupivacaine and at the end of the surgery received analgesic solutions. Pain intensity was evaluated through analogical visual scale at 0, 6, 12, 18 and 24 hours. T0 was considered the time when the patient entered the post-anesthetic care unit. Results: There were no pain intensity differences during different periods (Table 1). No side effects were observed. Conclusions: Morphine was similar to bupivacaine but needed more additional analgesics. All groups showed effective analgesia during 24 hours. Table 1. Pain intensity in different periods Groups Periods T0 T6 T12 T18 T24 G I saline 0 ± 0 1.6 ± 2.3 3.0 ± 2.5 2.3 ± 1.2 2.2 ± 1.3 GII bupivacaine 0.5 ± 1.1 2.1 ± 1.8 1.6 ± 0.9 1.7 ± 1.4 1.6 ± 1.2 G III morphine 0.2 ± 0.8 2.2 ± 1.8 2.2 ± 1.5 2.0 ± 1.7 1.5 ± 1.2 G IV fentanyl 0.2 ± 0.6 0.5 ± 0.4 1.1 ± 1.1 1.1 ± 0.9 1.4 ± 0.9

Intraarticular Morphine after Knee Arthroscopy. A Prospective, Randomized and Double-blind Study

Knee arthroscopy is a usual procedure in orthopedic surgery, which currently tends to be performed on an ambulatory basis. This underscores the need to provide the patient with efficient and safe analgesia. To assess the analgesic effect of intraarticular morphine after knee arthroscopy, as well as whether this effect is dose-dependent or whether, on the contrary, it is influenced by the patient's body mass index (BMI) or the duration of the procedure. The study analyzed 45 patients subjected to a knee arthroscopy at the Castelló General Hospital. They were randomly distributed across 3 groups (saline solution, 1 mg morphine chloride, 4 mg morphine chloride). For pain control, the visual analog scale (VAS) and the demand of rescue analgesia (metamizole 2 gr i.v.).In addition, a note was made of the time at which side effects occurred that could be attributed to the morphine chloride. Significant differences were found between the two morphine chloride groups and the control group regarding VAS scores at 24 hours. There were no significant differences in the remaining AVS measurements or in the demand of rescue analgesia. We did not observe a dose-dependent effect. There were no side effects that could be attributed to the intraarticular morphine chloride. The use of morphine chloride as an analgesic for patients undergoing knee arthroscopy is an effective and safe method. Larger study groups are necessary to find other statistically significant differences. La artroscopia de rodilla es una intervención frecuente en cirugía ortopédica, y últimamente se realiza sin ingreso, debiéndose proporcionar una analgesia eficaz y segura. Valorar el efecto analgésico de la morfina intraarticular tras artroscopia de rodilla, así como si este efecto es dosis dependiente o está influenciado por el índice de masa corporal del paciente o por la duración de la intervención. Se han incluido 45 pacientes intervenidos por artroscopia de rodilla en un hospital general. Se distribuyeron aleatoriamente en 3 grupos (suero fisiológico, 1 mg de cloruro mórfico, 4 mg de cloruro mórfico). Para el control del dolor se empleó la escala visual analógica (EVA) y la demanda de analgesia de rescate (metamizol 2 g intravenosos). También se recogió la hora a la que se presentaron efectos secundarios que podrían deberse al cloruro mórfico. Se encontraron diferencias significativas entre los dos grupos con cloruro mórfico respecto al grupo control en las puntuaciones de la EVA a las 24 horas. No se apreciaron diferencias significativas en el resto de las mediciones de la EVA ni en la demanda de analgesia de rescate. No observamos efecto dosis dependiente. No aparecieron efectos secundarios que puedan asociarse al cloruro mórfico intraarticular. El uso del cloruro mórfico como analgesia en pacientes sometidos a artroscopia de rodilla es un método eficaz y seguro. Hacen falta grupos de estudio más numerosos para encontrar otras diferencias estadísticas.

A systematic review of the peripheral analgesic effects of intraarticular morphine.

The analgesic effects of intraarticular morphine are controversial. To systematically evaluate the effects, we performed a review of the literature and a metaanalysis of the peripheral effects of morphine injected intraarticularly. Research databases were searched to identify articles in which peripheral analgesic effects of morphine were studied in patients undergoing arthroscopic knee procedures under local, regional, or general anesthesia. The review was performed on three issues: does morphine injected intraarticularly produce analgesia, is it a dose-dependent effect, and, if so, is the effect systemic or mediated via peripheral opioid receptors? Visual analog score (VAS) and analgesic consumption were studied during the early phase (0-2 h), intermediate phase (2-6 h), and late phase (6-24 h) postoperatively after injection of morphine intraarticularly. Metaanalysis of these effect variables was performed by the weighted-analysis technique, and the essential homogeneity assumption was tested by the chi(2) test. Forty-five articles could be identified in which the effects of morphine were studied in a prospective, randomized manner, and 32 of these studies included a placebo control. Pooled analyses of data from 19 studies suitable for metaanalysis showed an improvement in analgesia after morphine compared with placebo in the order of 12-17 mm on the VAS during all three phases of treatment. Studies with high quality scores showed somewhat smaller improvements. Total analgesic consumption could not be analyzed statistically, but the number of studies showing decreased analgesic consumption or no differences between groups was identical (six and six). No clear dose-response effect was seen when VAS was used as a measure of pain, but it was seen when area under the curve was used as a measure of pain. A systemic effect of peripherally-injected morphine was not possible to exclude because of the very limited data available. We conclude from this metaanalysis that intraarticularly administered morphine has a definite but mild analgesic effect. It may be dose dependent, and a systemic effect cannot be completely excluded.

Use of intra-articular morphine for postoperative analgesia following TMJ arthroscopy

Recent studies have suggested that giving opioids locally into inflamed tissue may cause analgesia. This antinociceptive effect has been attributed to the interaction of the drug with opioid receptors upregulated by inflammation in the peripheral tissues. We have compared the analgesic effect of intra-articular morphine with that of normal saline and a combination of morphine and its antagonist naloxone after arthroscopy of the temporomandibular joint (TMJ). Twenty-one patients took part in a randomized controlled double-blind trial and received one of these three solutions at the end of operation.The pain scores, time to the first request for analgesia, and the analgesic consumption of the patients in the three groups did not differ significantly at any time during the study period.

Dose-dependency of intra-articular morphine analgesia

We have examined if the analgesic effects of intra-articular morphine are dose-dependent in patients undergoing elective arthroscopic knee surgery. At the end of surgery, patients were allocated randomly to one of four groups to receive intra-articular saline (n = 22), or morphine 1 mg (n = 24), 2 mg (n = 21) or 4 mg (n = 19). After operation, patients remained in hospital overnight and pain intensity was assessed using a visual analogue scale at 1, 2, 3, 6, 9, 12, 18 and 24 h after intra-articular injection. Patients requesting additional analgesia received a loading dose of piritramide 0.1 mg kg-1 i.v. and were connected to a PCA device using the same drug. Increasing doses of intra-articular morphine were associated with greater analgesic effects and less supplementary analgesic requirements.

Analgesic effect of intra-articular morphine after arthroscopic knee surgery

Objectives: To assess the analgesic effect of intra-articular morphine. To establish the optimal dose of morphine as well as the best volume of solution to obtain an adequate analgesic effect. Patients and methods: Prospective, randomized, double blind study of 120 patients undergoing elective arthroscopic meniscectomy. Patients were randomly allocated to one of the following five groups: In group A1 ( n=28) and B1 ( n=20) patients received 1 and 5 mg of intra-articular morphine, respectively; in both groups morphine was diluted in 20 ml of saline. Another two groups, groups A2 ( n=22) and B2 ( n=26) received 1 and 5 mg of intra-articular morphine, respectively, that was diluted in 40 ml of saline. Finally, the control group, group C ( n=26), received 20 ml of saline without morphine. The intensity of the pain was evaluated by visual analog scale of 1 to 10 points at 30 min and at 1, 2, 3, 6, 12 and 24 h after arthroscopic surgery. Needs for complementary analgesia and side effects related to morphine were also recorded. Results: With respect to the control group there was a significant improvement in pain scores in those patients that were treated with morphine ( p<0.05). The best morphine dose to improve pain was 5 mg. The amount of analgesic therapy required by the patients within the first 24 h after surgery was lower in groups B1 and B2. No important side effects or complications of therapy were seen in any of the groups. Conclusions: Intra-articular morphine is effective in the postoperative period after arthroscopic meniscectomy. This method of administration provides a safe way to control the postoperative pain after arthroscopic ambulatory surgery of knee. In our experience a morphine dose of 5 mg disolved in 20 ml of saline constitutes the best therapeutic approach to reduce postoperative pain after arthroscopic meniscectomy.

Analgesic effects of intra-articular morphine during and after knee arthroscopy: a comparison of two methods

The objective of this study was to compare the analgesic effects of intra-articularly administered bupivacaine with bupivacaine/morphine during and after therapeutic knee arthroscopy. In a prospective, randomized study, 50 patients with clinical signs of medial meniscal injury were allocated to two groups, A and B. The patients in group A received 40 mL of 0.25% bupivacaine while the same dose of bupivacaine combined with 1 mg of morphine sulphate was administered in group B. Pain was estimated using the visual analogue scale (VAS) during surgery and at 2, 4, 6, and 24 hours after the operation was completed. Supplementary analgesic requirements were also registered, as well as the patients' overall rating of the entire procedure. The pain scores were significantly lower in Group B throughout the whole postoperative observation period. However, no significant differences were found between the two groups in terms of intraoperative pain scores, supplementary analgesic requirements, or the overall rating of the procedure. This study provides evidence that arthroscopic surgery can be performed in a safe manner after intra-articularly administered bupivacaine with or without low-dose morphine. The combination of low- dose morphine and bupivacaine did, however, produce a superior postoperative analgesic effect during the 24 hours following knee arthroscopy compared with bupivacaine alone. Arthroscopy 1998 Mar;14(2):192-6

No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia.

Pain treatment with centrally acting opiates is limited by tolerance. Tolerance is a decreasing effect of a drug with prolonged administration of that drug or of a related (e.g., endogenous) compound acting at the same receptor. This is often associated with a downregulation of receptors. In peripheral inflamed tissue, both locally expressed opioid peptides and morphine can produce powerful analgesia mediated by similar populations of opioid receptors. We hypothesized that the chronic presence of endogenous opioids in inflamed joints might convey downregulation of peripheral opioid receptors and tolerance to the analgesic effects of intraarticular morphine. We assessed these effects after arthroscopic surgery in patients with and without histologically verified synovial cellular infiltration, and we examined synovial opioid peptides and opioid receptors by immunocytochemistry and autoradiography, respectively. We found that, despite an abundance of opioid-containing cells in pronounced synovitis, morphine is at least as effective as in patients without such cellular infiltrations, and there is no major downregulation of peripheral opioid receptors. Thus, opioids expressed in inflamed tissue do not produce tolerance to peripheral morphine analgesia. Tolerance may be less pronounced for peripherally than for centrally acting opioids, which provides a promising perspective for the treatment of chronic pain in arthritis and other inflammatory conditions.

Intraarticular Morphine for Pain Relief after Knee Arthroscopy Performed under Regional Anaesthesia

Comment: Previous studies have demonstrated that the primary analgesic effects of intra-articular morphine are delayed in action (about 3–4 hr) but provide satisfactory analgesia for up to 48 hr. The combination of intra-articular bupivacaine and morphine provides a faster onset, with long lasting analgesia after general anesthesia. This study further demonstrates the potentially important role of intraarticular morphine in postoperative pain management in knee arthroscopy patients after local anesthesia. It is unclear why the intra-articular morphine had no effect in patients who had bupivacaine spinal anesthesia, because the analgesic effects from intraarticular morphine should have outlasted the bupivacaine. Recent evidence suggests that intra-articular morphine is only effective in inflammatory disease states.

Analgesic effect of intra‐articular morphine after arthroscopic meniscectomy

A study was performed to assess the analgesic effect of intra-articular morphine 2 mg in 33 patients undergoing elective arthroscopic meniscectomy. Patients were randomly allocated to receive either 2 mg of morphine hydrochloride in 40 ml of normal saline intra-articularly and 1 ml of normal saline intramuscularly (n = 18), or 40 ml of normal saline intra-articularly and 2 mg of morphine hydrochloride intramuscularly (n = 15). The latter group was to act as a control for any potential systemic effects of the morphine. All patients received an identical general anaesthesia consisting of propofol, alfentanil, enflurane and nitrous oxide/oxygen. No significant differences between the groups were found in pain scores at rest or during active flexion of the knee at 1-6 h postoperatively, or during walking at 6 h postoperatively (p > 0.05). Six and two patients in the intra-articular and intramuscular morphine group, respectively, requested supplemental morphine given intravenously (p > 0.05). In conclusion, no significant differences in pain scores or in requirements for supplemental morphine were observed between patients receiving intra-articular versus intramuscular morphine 2 mg after elective arthroscopic meniscectomy and consequently no specific local analgesic effect of intra-articular morphine could be demonstrated.