Intra-articular Saline Research Articles

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular joint. Part II: mandibular growth

BackgroundTemporomandibular joint (TMJ) arthritis in children causes alterations in the craniomandibular growth. Resultant abnormalities include; condylar erosions, a posterior mandibular rotation pattern, micrognathia, malocclusion with an anterior open bite, altered joint and muscular function occasionally associated with pain. These alterations may be prevented by early aggressive anti-inflammatory intervention. Previously, we have shown that intra-articular (IA) corticosteroid reduces TMJ inflammation but causes additional mandibular growth inhibition in young rabbits. Local blockage of TNF-α may be an alternative treatment approach against TMJ involvement in juvenile idiopathic arthritis (JIA). We evaluated the anti-inflammatory effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in young rabbits in terms of mandibular growth. This article (Part II) presents the data and discussion on the effects on facial growth. In Part I the anti-inflammatory effects of systemic and IA etanercept administration are discussed.MethodsArthritis was induced and maintained in the TMJs of 10-week old pre-sensitized rabbits (n = 42) by four repeated IA TMJ injections with ovalbumin, over a 12-week period. One group was treated weekly with systemic etanercept (0.8 mg/kg) (n = 14), another group (n = 14) received IA etanercept (0.1 mg/kg) bilaterally one week after induction of arthritis and one group (n = 14) served as an untreated arthritis group receiving IA TMJ saline injections. Head computerized tomographic scans were done before arthritis was induced and at the end of the study. Three small tantalum implants were inserted into the mandible, serving as stable landmarks for the super-impositions. Nineteen variables were evaluated in a mandibular growth analysis for inter-group differences. All data was evaluated blindedly. ANOVA and T-tests were applied for statistical evaluation using p < 0.05 as significance level.ResultsSignificant larger mandibular growth disturbances were observed in the group receiving IA saline injections compared with the systemic etanercept group. The most pronounced unfavourable posterior mandibular rotation pattern was observed in the group receiving IA saline injections.ConclusionIntervention with systemic etanercept monotherapy equivalent to the recommended human dose allows a mandibular growth towards an original morphology in experimental TMJ arthritis. Systemic administrations of etanercept are superior to IA TMJ administration of etanercept in maintaining mandibular vertical growth.

Detection of Traumatic Arthrotomy of the Knee Using the Saline Solution Load Test

The saline solution load test helps to determine if a wound extends into the knee joint. Little is known about the volume of injected intra-articular saline solution that is needed to effectively rule in or rule out a traumatic arthrotomy of the knee. The purpose of the present study was to determine the appropriate volume and needle location for the diagnosis of a traumatic knee arthrotomy and to assess the effect of associated variables, including knee circumference, body mass index, and sex. Fifty-six consecutive patients scheduled for knee arthroscopy were enrolled. A standard inferolateral arthroscopic portal was made with a single stab incision with use of a number-11 blade. Injection sites were randomized to either a superomedial or inferomedial location. The injection of normal saline solution at a rate of 5 mL/sec through an 18-gauge needle was continued while the knee was moved through a range of motion until fluid extravasated from the iatrogenic laceration. The volume of injected fluid was recorded. The study group included thirty-one female patients and twenty-five male patients with a combined average age of fifty years and an average body mass index of 30.9. In order to effectively diagnose 50% of the arthrotomies, 75 mL of injected fluid was needed; the volumes that were needed in order to effectively diagnose 75%, 90%, 95%, and 99% of the arthrotomies were 110, 145, 155, and 175 mL, respectively. The mean volumes of injected fluid needed for a positive result at the inferomedial and superomedial needle locations were 64.0 and 95.2 mL, respectively; this difference was significant (p = 0.01). There was no correlation between necessary injection volume and sex, body mass index, or knee circumference. In order to detect 95% of 1-cm inferolateral arthrotomies of the knee with use of the saline solution load test, 155 mL must be injected. An inferomedial injection location requires significantly less fluid than a superomedial injection location does for the diagnosis of inferolateral arthrotomies of the knee.

Changes in gait after bilateral meniscectomy in sheep: effect of two hyaluronan preparations

BackgroundThis study examined the effect of bilateral meniscectomy on ground reaction forces (GRFs) in sheep, and the therapeutic effect of two hyaluronan (HA) preparations. MethodsEighteen sheep were subjected to bilateral lateral meniscectomy and were treated from 16 to 20 weeks post-operatively with intraarticular Hyalgan (Fidia Farmaceutici), HYADD4-G (a novel amide derivative; Fidia Farmaceutici), or saline placebo (n = 6 per group). GRFs were assessed at baseline and 6, 12, 16, 22, and 26 weeks postoperatively. Rheological parameters and HA content of synovial fluid samples were assessed using micro-Fourier rheometry. ResultsMeniscectomy significantly reduced GRF and abolished the normal two-peak vector. GRF deficits were partially ameliorated by both HA preparations: Hyalgan increased peak vertical forces at 6 weeks post-treatment (week 22), while HYADD4-G increased vertical impulse post-treatment. Both HA treatments, but not saline placebo, restored a two-peak composite force vector at 6 weeks post-treatment. Neither HA preparation significantly modulated osteoarthritis (OA) severity, or synovial fluid parameters. ConclusionsThis study showed that GRF responses to bilateral meniscectomy in sheep mimic available data for human meniscectomy and OA patients. However, this time course suggests that gait deficits are temporally unrelated to observed cartilage or synovial fluid changes. The bilateral ovine meniscectomy model demonstrates modest but quantifiable changes in GRF that mimic human OA and are amenable to modification by known OA therapies such as HA.

Effect of intra-articular dexmedetomidine on postoperative analgesia after arthroscopic knee surgery

BackgroundAlpha-2-adrenergic agonists have peripheral analgesic effects. We have assessed the potential analgesic effect of dexmedetomidine after intra-articular administration in arthroscopic knee surgery. MethodsSixty patients undergoing arthroscopic knee surgery were randomly assigned into three groups in a double-blind placebo controlled study. The control group received i.v. and intra-articular saline, the intra-articular group received i.v. saline and intra-articular dexmedetomidine, and the i.v. group received i.v. dexmedetomidine and intra-articular saline. Haemodynamic changes, pain visual analogue scale (VAS), sedation score, the time to first postoperative analgesic request, and the total postoperative analgesic use during the first 24 h were evaluated. ResultsDexmedetomidine administration resulted in a significant reduction in pain scores for 6 h after operation in the intra-articular group but only for 1 h in the i.v. group. The time to first postoperative analgesic request was longer in the intra-articular group [312.0 (sd 120.7) min] compared with the control group [71.0 (50.1) min] and the i.v. group [102.1 (54.4) min] (P<0.001). Total diclofenac requirement was significantly lower in the intra-articular group [90.0 (46.2) mg] than in the control group [165.0 (52.2) mg] and in the i.v. group [129.3 (54.3) mg] (P<0.05). ConclusionsIntra-articular dexmedetomidine enhanced postoperative analgesia after arthroscopic knee surgery, with an increased time to first analgesic request and a decreased need for postoperative analgesia.

Ultrasonographic examination of the synovial fold of the radiohumeral joint

This report describes the anatomy of the synovial fold of the radiohumeral joint and assesses its visibility by ultrasonography. Forty-nine fresh cadaver radiohumeral joints were examined by ultrasonography before and after intraarticular saline injection and then dissected. Digital photos were taken before and after the joint capsule was excised. The relative coverage of the radial head by the fold was calculated. Synovial folds were observed in all specimens. Forty-three had anterior and posterior lobes. The synovial fold covered an average of 28% of the radiocapitellar joint surface of the radial head. The sensitivity of the ultrasonography was 81%, 46%, and 85% from the anterior, lateral, and posterior aspects of the radiohumeral joint, respectively. Intraarticular saline injection improved the sensitivity to 96%, 67%, and 94%, respectively. The synovial fold is a consistent anatomic structure, and ultrasonography can be a useful preoperative diagnostic tool.

Intra-articular anesthesia and knee muscle response

Many receptors located within the intra-articular knee structures contribute to the neuromuscular responses of the knee. The purpose was to compare the automatic postural response induced by a perturbation at the foot before and after an intra-articular injection of a local anesthetic (bupivicaine), after a saline (sham) injection, and after no intra-articular injection (control) in the knee. Muscle onset latencies and automatic response magnitudes for the vastus medialis, vastus lateralis, biceps femoris, medial hamstrings, tibialis anterior, and gastrocnemius were measured using electromyography (EMG) when anteriorly directed perturbations were applied to the feet of 30 subjects. All subjects then received a lidocaine skin injection followed by: an intra-articular bupivicaine injection (treatment group); an intra-articular saline injection (sham group); or no injection (control group), depending on their randomized group assignment. The perturbation tests were then repeated. Muscle onset latencies and automatic response magnitudes did not change as a result of the intra-articular injections. Latencies were significantly greater for the vastus medialis and vastus lateralis when compared to the medial hamstrings, biceps femoris and tibialis anterior (P<0.001). Automatic response magnitudes for the tibialis anterior were significantly greater than those of the hamstrings, which were greater than those of the quadriceps (P<0.001). There were no differences in muscle response when anteriorly directed perturbations were applied to the foot with or without an injection of local anesthetic in the knee. Intra-articular receptors were either unaffected by the anesthetic or the extra-articular receptors or receptors of the other joints were able to compensate for their loss.

The Effect of Intra-articular Injection of Ultracain in the Temporomandibular Joint in Patients With Preauricular Pain

To evaluate the distinguishing ability of intra-articular anesthesia from placebo in orofacial pain patients with pain located in the temporomandibular joint (TMJ) region, aiming at a validation of intra-articular anesthesia injection as a diagnostic test of pain in the TMJ region. A randomized prospective double-blind, placebo-controlled crossover study was conducted among 19 patients (18 females, 1 male) with pain in the TMJ region. The short-term effects of intra-articular ultracain and saline injections on pain and maximum mouth opening were measured and analyzed. Compared with placebo injections, a statistically significant difference in pain scores was found after intra-articular injection of a local anesthetic on Visual Analog Scale values. The maximum mouth opening scores did, however, not differ between the 2 groups. TMJ injection with local anesthesia leads to the decrease of pain in patients with preauricular pain. To establish the source of pain, injection of a local anesthetic in the TMJ may be used as a diagnostic tool. However, the results of diagnostic injections should still be interpreted cautiously.

The efficacy of intra-articular bupivacaine for relief of pain following arthroscopy of the ankle

The intra-articular injection of local anaesthetic is frequently used for pain relief after arthroscopy. There is, however, no published evidence of the analgesic effect of bupivacaine in the ankle. In a randomised, double-blind study, 35 patients undergoing arthroscopy of the ankle were allocated to receive intra-articular saline or bupivacaine. Pain was assessed using pain scores and additional analgesic requirements. Intra-articular bupivacaine had a significant analgesic effect in the immediate post-operative period, reducing pain scores and the need for additional analgesics. We recommend the use of intra-articular bupivacaine for post-operative analgesia in ankle surgery.

PR_053: Functional Outcomes Improve With Hylan G-F 20 in Patients With Knee Osteoarthritis

Objective: To determine whether hylan G-F 20 (Synvisc) improves function when used to treat osteoarthritis (OA) knee pain. Design: Review of randomized, controlled, prospective clinical studies (with n>100 patients) that measured functional outcomes. Setting: Orthopedic clinics. Participants: Patients with knee OA. Interventions: Hylan G-F 20, intra-articular placebo, intra-articular corticosteroid, appropriate or conventional care, progressive knee exercises, and nonsteroidal anti-inflammatory drugs (NSAIDs). Main Outcome Measures: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) domain C (physical function), 36-Item Short-Form Health Survey (SF-36) physical component, and extent of patient’s activity loss with difficult tasks, activity restriction, walking distance, and range of motion (ROM). Results: In 8 prospective, randomized, controlled trials (1675 total patients), hylan G-F 20 improved function in patients with knee OA. WOMAC domain C and SF-36 physical component were significantly better with hylan G-F 20 than appropriate care at 12 months (P<.000). WOMAC domain C was also significantly better with hylan G-F 20 than conventional treatment at 9 months (P=.000) or intra-articular triamcinolone hexacetonide at 12 and 26 weeks after treatment (P≤.001). In 1 study, WOMAC domain C was similar between hylan G-F 20, sodium hyaluronate, and placebo. In another study, however, the extent of the patient’s activity loss with difficult daily tasks was significantly better with hylan G-F 20 than with intra-articular saline from weeks 1 to 26 (P range, .004−.000). Finally, hylan G-F 20 improved similarly from baseline for WOMAC domain C compared with diclofenac, for walking distance and ROM versus progressive knee exercises, and in activity restriction compared with NSAIDs or hylan G-F 20+NSAIDs. Conclusions: Patients experience improvements in functional outcomes when given hylan G-F 20 for the treatment of OA knee pain.

Intra-Articular Morphine 5 mg After Knee Arthroscopy Does Not Produce Significant Pain Relief When Administered to Patients With Moderate to Severe Pain via an Intra-Articular Catheter

Intra-articular (IA) morphine for postoperative analgesia after knee arthroscopy is controversial. The IA catheter technique for test drug administration allows baseline pain assessment before inclusion. Results from one such randomized controlled trial (RCT) in patients with moderate to severe pain have shown equal effects of IA saline with or without morphine 2 mg. However, the IA catheter technique may have an unintended placebo effect. The aims of this placebo-controlled RCT were (1) to compare the analgesic effect of IA saline 1 mL (placebo) with morphine 5 mg given through an IA catheter and (2) to analyze the impact on pain of immediate or delayed removal of the IA catheter. Sixty patients operated under general anesthesia had an IA catheter inserted at the end of arthroscopy. Patients who reported moderate or severe postoperative pain during the following hour were randomized to IA saline 1 mL (placebo) or IA morphine 5 mg and to immediate or delayed removal of IA catheter. Forty of 60 patients (67%) developed moderate to severe pain within 1 hour. In addition, 5 patients experienced intolerable pain and were excluded. Significantly more women (24/26) than men (26/39) reported at least moderate pain (P = .018) during the first hour after surgery. There were no differences between IA morphine 5 mg and placebo in pain intensity or pain relief at any time during the 48-hour observation period. There was no detectable effect on pain intensity of early compared with late removal of the IA catheter. IA morphine 5 mg does not produce clinically significant pain relief in patients with moderate or severe pain after knee arthroscopy.

THE EFFECT OF PROTEOLYTIC ENZYME SERRATIOPEPTIDASE IN THE TREATMENT OF EXPERIMENTAL IMPLANT-RELATED INFECTION

Background: Infection around an implanted orthopaedic device is a devastating complication, and the treatment of infections involving slime-forming bacteria is especially difficult. The purpose of the present study was to evaluate the effectiveness of a proteolytic enzyme, serratiopeptidase, in the eradication of a periprosthetic infection in an in vivo animal model. Methods: In sixty Sprague-Dawley rats, the medullary canal of the right femur was drilled through the intercondylar notch and was inoculated with a Staphylococcus epidermidis strain (ATCC 35984) with a high slime-producing capacity. The cavity was filled with polymethylmethacrylate cement, and a Kirschner wire that had contact with the knee joint was inserted. None of the animals received any treatment for two weeks. Twenty rats were killed at two weeks after the inoculation in order to determine if the infection had become established. The remaining forty rats were randomized into two groups. One group received serratiopeptidase enzyme injections into the knee joint in addition to antibiotic therapy for four weeks, and the other group received intra-articular saline solution injections together with the same antibiotic therapy. The animals from both groups were killed two weeks after the end of therapy (on Day 56). The knee specimens were evaluated bacteriologically and histologically to determine the prevalence of persistent infection and the effects of the enzyme on local tissue. Results: At two weeks, inoculated bacteria grew on culture of specimens from twelve (63.2%) of nineteen animals in the no-treatment group. Microbiological testing suggested that infection persisted in only one (5.6%) of eighteen animals in the serratiopeptidase-and-antibiotic group, whereas it was present in six (37.5%) of sixteen animals in the antibiotic-only group (p = 0.001). Histological evaluation showed similar results (kappa = 0.92). Conclusions: Serratiopeptidase was effective for eradicating infection caused by biofilm-forming bacteria in this experimental animal model. The antibiofilm property of the enzyme may enhance antibiotic efficacy in the treatment of staphylococcal infections.

The Effect of Proteolytic Enzyme Serratiopeptidase in the Treatment of Experimental Implant-Related Infection

Infection around an implanted orthopaedic device is a devastating complication, and the treatment of infections involving slime-forming bacteria is especially difficult. The purpose of the present study was to evaluate the effectiveness of a proteolytic enzyme, serratiopeptidase, in the eradication of a periprosthetic infection in an in vivo animal model. In sixty Sprague-Dawley rats, the medullary canal of the right femur was drilled through the intercondylar notch and was inoculated with a Staphylococcus epidermidis strain (ATCC 35984) with a high slime-producing capacity. The cavity was filled with polymethylmethacrylate cement, and a Kirschner wire that had contact with the knee joint was inserted. None of the animals received any treatment for two weeks. Twenty rats were killed at two weeks after the inoculation in order to determine if the infection had become established. The remaining forty rats were randomized into two groups. One group received serratiopeptidase enzyme injections into the knee joint in addition to antibiotic therapy for four weeks, and the other group received intra-articular saline solution injections together with the same antibiotic therapy. The animals from both groups were killed two weeks after the end of therapy (on Day 56). The knee specimens were evaluated bacteriologically and histologically to determine the prevalence of persistent infection and the effects of the enzyme on local tissue. At two weeks, inoculated bacteria grew on culture of specimens from twelve (63.2%) of nineteen animals in the no-treatment group. Microbiological testing suggested that infection persisted in only one (5.6%) of eighteen animals in the serratiopeptidase-and-antibiotic group, whereas it was present in six (37.5%) of sixteen animals in the antibiotic-only group (p = 0.001). Histological evaluation showed similar results (kappa = 0.92). Serratiopeptidase was effective for eradicating infection caused by biofilm-forming bacteria in this experimental animal model. The antibiofilm property of the enzyme may enhance antibiotic efficacy in the treatment of staphylococcal infections.

ULTRASONOGRAPHIC EVALUATION OF CRANIAL CRUCIATE LIGAMENT RUPTURE VIA DYNAMIC INTRA‐ARTICULAR SALINE INJECTION

Ultrasonographic examination of both stifle joints of five clinically and radiographically normal adult dogs was performed before and after surgical transection of the cranial cruciate ligament (CrCL). At pre- and postsurgery, the hyperechoic patellar ligament and the infrapatellar fat interfered with sonographic visualization of the CrCL. When the stifle joint, however, was imaged via dynamic intra-articular saline injection, the hyperechoic ligament was visualized because of the separation of the infrapatellar fat and the CrCL and the contrasting effect of anechoic saline. When the stifle joint was imaged by real-time scanning after the transection of the CrCL, flutter of the ligament and an anechoic area between the bone and the CrCL were identified. The increased diameter of the ligament and the increased thickness of the joint space were identified as well. Ultrasonographic examination via dynamic saline injection into the joint space has potential as a diagnostic tool for assessing CrCL rupture.

Pain relief following arthroscopy — A comparative study of intra-articular bupivacaine, morphine and neostigmine

Pain after arthroscopy is quite distressing. Intra-articular bupivacaine produces transient analgesia and reports of analgesia using intra-articular opioids have produced conflicting results. Recently, spinal administration of neostigmine was shown to produce dose-dependant analgesia. However, this was limited by adverse effects. The purpose of this study was to compare the effects on intra-articular neostigmine, bupivacaine and morphine. 75 patients were randomized to receive intra-articular saline, bupivacaine, morphine, neostigmine and bupivacaine-neostigmine after arthroscopic surgery under spinal anaesthesia. Visual analog pain scores (VAS), duration of analgesia as defined as time for first demand for parenteral opioids and the total subsequent consumption of morphine was evaluated. Intra-articular bupivacaine resulted in significant VAS reduction at one and four hours as compared to those receiving intra-articular saline and morphine. Analgesia lasted longer after 500ugm intra-articular neostigmine as compared with bupivacaine, morphine or saline. The need for supplementary analgesia was lowest in the neostigmine group as compared to the other groups. No significant difference was found if bupivacaine was added to neostigmine. Among all the groups, no significant side-effects were observed.

Intra-articular sufentanil for pain relief after knee arthroscopy

AbstractWe studied the effect of intra-articular saline or sufentanil after diagnostic knee arthroscopy. In a double-blind randomized study, 30 patients undergoing diagnostic knee arthroscopy without a therapeutic procedure were randomly allocated to two groups receiving intraarticular saline or intra-articular sufentanil (10 μg) at the end of arthroscopy during general anesthesia. Postoperatively and the day after surgery, pain levels at rest and during movement (i.e. active flexion of the knee), measured by a visual analogue scale, were significantly lower in the sufentanil group than in the control group. Moreover, intra-articular sufentanil significantly reduced the postoperative consumption of analgesics.

MR arthrography of postoperative knee: for which patients is it useful?

To assess which postoperative patients benefit most from MR arthrography of the knee. One hundred consecutive MR arthrograms obtained in patients who had previous knee surgery underwent retrospective review in consensus by three radiologists after prospective reading by one of the three radiologists. Criterion on MR arthrograms for a retear was abnormal tracking of an intraarticular dilute gadolinium-based contrast material and saline mixture into the substance of a meniscus. Patients were separated into three groups: those with more than 25% meniscal resection, those with less than 25% meniscal resection, and those with meniscal repair. All 100 patients had preoperative MR images to review directly in conjunction with the postoperative MR images. Fifty-seven of these 100 patients underwent second-look arthroscopy. Nine patients had MR findings consistent with avascular necrosis. Nineteen patients had marked degenerative arthrosis in the area of previous surgery. Seven patients had chondral defects or injuries. Twenty-nine patients had clear MR evidence of a meniscal retear without any contrast material injected into the joint. In 32 of the 100 patients, intraarticular contrast material was useful in demonstrating a retear. Of these 32 patients, 22 had MR arthrographic evidence of a retear, while 10 had no clear MR arthrographic finding to explain postoperative pain. Four additional patients had no clear MR imaging or MR arthrographic abnormality. All patients with meniscal repair (n = 16) needed MR arthrography to diagnose a residual or recurrent meniscal tear. No patient with less than 25% meniscal resection (n = 23) needed MR arthrography to demonstrate a residual or recurrent meniscal tear. Sixteen of 61 patients with more than 25% meniscal resection needed MR arthrography to demonstrate a residual or recurrent meniscal tear. All patients with meniscal repair required MR arthrography. All patients with meniscal resection of more than 25%, who did not have severe degenerative arthrosis, chondral injuries, or avascular necrosis required MR arthrography. Patients with less than 25% meniscal resection did not need MR arthrography.

Non-linear dependence of interstitial fluid pressure on joint cavity pressure and implications for interstitial resistance in rabbit knee.

Synovium retains lubricating fluid in the joint cavity. Synovial outflow resistance estimated as dPj/dQs (Pj, joint fluid pressure and Qs trans-synovial flow) is greater, however, than expected from interstitial glycosaminoglycan concentration. This study investigates whether subsynovial fluid pressure increases with intra-articular pressure, as this would reduce the estimated resistance estimate. Interstitial fluid pressure (Pif) was measured as a function of distance from the joint cavity in knees of anaesthetized rabbits, using servo-null pressure-measuring micropipettes and using an external 'window'. Joint fluid pressure Pj was either endogenous (-2.4 +/- 0.4 cmH2O, mean +/- SEM) or held at approximately 4, 8 or 15.0 cmH2O by a continuous intra-articular saline infusion that matched the trans-synovial interstitial drainage rate. At endogenous Pj the peri-articular Pif was subatmospheric (-1.9 +/- 0.3 cmH2O, n = 19). At raised Pj the Pif values became positive. Gradient dPif /dx was approximately 20 times steeper across synovium than subsynovium. Pif close to the synovium-subsynovium border (Pif*) increased as a non-linear function of Pj to 1.4 +/- 0.2 cmH2O (n = 23) at Pj = 4.3 +/- 0.1 cmH2O : 2.3 +/- 0.2 cmH2O (n = 17) at Pj = 7.6 +/- 0.2 cmH2O: and 3.0 +/- 0.4 cmH2O (n = 26) at Pj = 15 +/- 0.2 cmH2O (P = 0.03, anova). Synovial resistivity is approximately 20x subsynovial resistivity. The increase in Pif*with Pj means that true synovial resistance d(Pj-Pif*)/dQs is overestimated 1.5x by dPj/dQs. This narrows but does not eliminate the gap between analysed glycosaminoglycan concentration, 4 mg ml(-1), and the net interstitial biopolymer concentration of 11.5 mg ml(-1) needed to generate the resistance.

Intra-articular (IA) catheter administration of postoperative analgesics. A new trial design allows evaluation of baseline pain, demonstrates large variation in need of analgesics, and finds no analgesic effect of IA ketamine compared with IA saline

All previous studies of intra-articular (IA) analgesic drugs for postarthroscopy pain have administered test-drugs at the end of the arthroscopic procedure, before any baseline pain could be assessed. Assay sensitivity has often not been documented or has been assumed to be present if a placebo control group had significant pain during the observation period. We present an improved study design employing an IA catheter for test-drug administration only in patients with moderate-to-severe baseline pain within 2 h postoperatively. Using this technique we explored the incidence of moderate-to-severe pain and possible predisposing factors for pain through a close follow-up of all patients. The study incorporated an explanatory study of IA ketamine. A double-blind, double-dummy technique was used. Summed pain intensity differences 0–120 min after test medication was the primary outcome variable. Of 77 patients assessed for inclusion, only 45 had mderate or severe pain. Significantly more women (78%) than men (45%) had moderate-to-severe pain ( P<0.005). Those not included continued to have no or mild pain and consumed less rescue analgesics than those who had high baseline pain. Mean baseline pain in the patient group with moderate or severe pain was 50 mm on a 0–100 m visual analogue scale (VAS) (SD=15.1)( n=45). Mean VAS in the patient group with no or mild pain was 7.5 mm (SD=8.7)( n=32). The new method for IA analgesic trials solves the problem with undesirable inclusion of patients with no or mild pain. We observed rapid onset and significant pain relief after IA injection of 10 ml saline with or without ketamine 10 mg, but no difference between these two test medications. Intra-muscular ketamine 10 mg showed significantly better early pain relief, global evaluation, and longer time to rescue analgesic, compared with IA ketamine 10 mg.

Postoperative analgesia by intraarticular clonidine and neostigmine in patients undergoing knee arthroscopy

Background and Objective: Clonidine and neostigmine have a central mechanism of analgesic action and are synergistic when given intrathecally. Both drugs also have a peripheral analgesic effect. The purpose of this study was to compare the analgesic effect of intraarticular clonidine and neostigmine, used separately and in combination, in patients undergoing knee arthroscopy. Methods: Eighty-four American Society of Anesthesiologists (ASA) I and II patients scheduled for meniscus repair under arthroscopy were allocated randomly in 6 groups to receive in a double-blind manner at the end of surgery 150 μg of intraarticular clonidine with subcutaneous saline, 500 μg of intraarticular neostigmine with subcutaneous saline, an intraarticular combination of 150 μg of clonidine and 500 μg of neostigmine with subcutaneous saline, 150 μg of intraarticular clonidine with 500 μg of subcutaneous neostigmine, 500 μg of intraarticular neostigmine with 150 μg of subcutaneous clonidine, or intraarticular and subcutaneous isotonic saline. Postoperative pain scores were measured on a visual analog scale (VAS) at rest and on mobilization. Paracetamol (1 g) was given as a rescue medication when pain score was greater than 40. Results: VAS scores at rest and on mobilization were lower in the first 5 groups compared with the intraarticular saline group (P < .05), but no significant difference was documented between the treated groups. The time to the first paracetamol administration was shorter in the saline group compared with the other groups, and the paracetamol demand was also higher in this group. Forty-five percent of the patients who had received clonidine had at least 1 episode of hypotension versus 4% of those who did not (P < .01). The incidence of bradycardia was 20% and 0%, respectively (P = .01). The incidence of nausea was not statistically different in patients who did and did not receive neostigmine (43% v 36%, respectively). Conclusion: Intraarticular administration of 150 μg of clonidine, 500 μg of neostigmine, or both produce postoperative analgesia, and the combination is not more effective. Reg Anesth Pain Med 2001:26:342-347.

Postoperative analgesia by intraarticular and epidural neostigmine following knee surgery

Study Objectives: To define the analgesic efficacy, and to identify a possible site of action, of epidural and intraarticular neostigmine. Design: Randomized, double-blind study. Setting: Postoperative analgesia, teaching hospital. Patients: 58 ASA physical status I and II patients undergoing knee surgery. Interventions: All patients were premedicated with 0.05 to 0.1 mg/kg intravenous midazolam and received combined epidural/intrathecal technique. Intrathecal anesthesia consisted of 20 mg bupivacaine. A 10 mL epidural and intraarticular injection was administered to all patients; this consisted of either the study drug or normal saline. Postoperatively, pain was assessed using the 10 cm Visual Analog Scale (VAS), and intramuscular (IM) 75 mg diclofenac was available at patient request. The control group (CG) received both epidural and intraarticular saline. The 1 μg/kg epidural group (1 μg/kg EG) received epidural neostigmine and intraarticular saline. The 1 μg/kg intraarticular group (1 μg/kg AG) received epidural saline and intraarticular neostigmine. Finally, the 500 μg intraarticular group (500 μg AG) received epidural saline and intraarticular neostigmine. Measurements and Main Results: 56 patients were evaluated. Groups were demographically the same and did not differ in intraoperative characteristics. The VAS score at first rescue analgesic and the incidence of adverse effects were similar among groups ( p < 0.05). The time (min) to first rescue analgesic was shorter for both the CG (228 ± 54) and 1 μg/kg AG (251 ± 87) groups compared to the 1 μg/kg EG (333 ± 78) and 500 μg AG (335 ± 111) groups ( p < 0.05). The analgesic consumption (number of IM diclofenac injections (mean [25 th–75 th percentile]) in 24 hours was higher in the CG group than both the 1 μg/kg EG and 500 μg AG groups ( p < 0.05). The overall 24-hour pain VAS score (cm) was higher in the CG group than in the 1 μg/kg EG ( p < 0.05) group. Conclusion: Although peripheral neostigmine 1 μg/kg did not result in postoperative analgesia, the same dose applied epidurally resulted in over 5 hours of analgesia, similar to a fivefold dose applied peripherally. The results suggest that epidural neostigmine has a greater analgesic efficacy than peripherally applied neostigmine.