Postsurgical Pain Relief Research Articles

Determination of ED50 of hydromorphone for postoperative analgesia following cesarean delivery

BackgroundMorphine is the most common opioid injected into the intrathecal space for postoperative analgesia following cesarean delivery, but ongoing medication shortages have resulted in limited availability. One proposed morphine alternative is hydromorphone. Studies investigating its use in post-cesarean analgesia are limited. This study was conducted to determine the median effective dose of intrathecal hydromorphone 12h postpartum. MethodsTwenty healthy women undergoing elective cesarean delivery were recruited into this study. Hydromorphone doses were determined using the up-down sequential method. The study dose of hydromorphone started at 6μg and was raised or lowered by 2μg depending on the 12-h efficacy of the preceding participant’s dose. Pain scores of <3/10 were considered successful and the subsequent patient received a lower dose. Participants received 0.5% bupivacaine 12.5mg, fentanyl 25μg, and the study dose of hydromorphone as a single intrathecal injection. ResultsTen of 20 participants reported an effective hydromorphone dosage 12h post-injection. The median effective hydromorphone dosage was 4.6μg (95% CI 3.72 to 5.48μg) based on participants’ reported visual analog pain scores of <3/10. No significant side effects or adverse outcomes were observed. ConclusionIntrathecal hydromorphone may be an effective alternative to morphine for post-cesarean pain management. The amount of intrathecal hydromorphone necessary to provide analgesia at 12h postoperatively may be significantly lower than doses currently in use. Further research should be performed to identify the optimal dose of intrathecal hydromorphone for post-surgical pain relief.

Chronic postsurgical pain and persistent opioid use following surgery: the need for a transitional pain service.

To identify the 3-month incidence of chronic postsurgical pain and long-term opioid use in patients at the Toronto General Hospital. 200 consecutive patients presenting for elective major surgery completed standardized questionnaires by telephone at 3 months after surgery. 51 patients reported a preoperative chronic pain condition, with 12 taking opioids preoperatively. 3 months after surgery 35% of patients reported having surgical site pain and 13.5% continued to use opioids for postsurgical pain relief. Postoperative opioid use was associated with interference with walking and work, and lower mood. Chronic postsurgical pain and ongoing opioid use are concerns that warrant the implementation of a Transitional Pain Service to modify the pain trajectories and enable effective opioid weaning following major surgery.

Injectable thermosensitive gelling delivery system for the sustained release of lidocaine.

Patients undergoing arthroplasty require appropriate postsurgical pain relief. Analgesia is typically achieved through bolus doses of short-acting local anesthetics and with oral analgesics such as opiates, which are associated with systemic side effects. By formulating an injectable thermosensitive gelling system containing lidocaine, sustained and local delivery can be achieved following a single administration. Poloxamer-based thermosensitive gelling formulations were prepared. Altering the weight ratios of poloxamers affected the sol-to-gel transition temperature, mechanical and rheological properties and in vitro drug release. Desirable formulations gelled between 28 and 33°C providing sustained release of lidocaine over 48 h. Thermosensitive gelling systems are promising for sustained drug release following patient administration and may be beneficial in addressing postoperative pain.

Effects of Tourniquet in Total Knee Arthroplasty

Tourniquet has long been used in TKA (Total Knee Arthroplasty) as the other orthopedic procedures for decreasing operation time and blood loss, providing better visualization of anatomic structures. While having much more advantages, these devices have a potential of serious complications, so they must be used with adequate knowledge and attention. Paralysis, compression neuropathy, compartment syndrome, prolonged period of rehabilitation, edema, pain, skin problems, nerve damage and systemic problems are the some complications seen. Selections of appropriate blood pressure, cuff selection, tourniquet timing are the essential points of tourniquet use. Through these increasing complication rates and improvements in the surgical and anesthesia methods contrary to old beliefs, surgery has been preferred without tourniquet in the patients who have no cardiovascular problems and morbidity. In the patients who have any contraindicated situations as stated above, TKA must be performed with tourniquet, with proper control of the amount of pressure and the duration of application, the risk of complications decrease, in the other situations TKA can be performed without tourniquet with the aims for fast-recovery, postsurgical pain relief and better muscle activity. The objective of this paper is to describe current perspectives of tourniquet use in total knee arthroplasty.

Do Physical Symptoms Predict the Outcome of Surgical Fusion in Patients with Discogenic Low Back Pain?

Study DesignRetrospective case series.PurposeTo determine whether symptoms predict surgical outcomes for patients with discogenic low back pain (DLBP).Overview of LiteratureSpecific diagnosis of DLBP remains difficult. Worsening of pain on flexion is a reported symptom of DLBP. This study sought to determine whether symptoms predict surgical outcomes for patients with DLBP.MethodsWe investigated 127 patients with low back pain (LBP) and no dominant radicular pain. Magnetic resonance imaging was used to select patients with disc degeneration at only one level. If pain was provoked during discography, we performed fusion surgery (87 patients). Visual analogue scale score and responses to a questionnaire regarding symptoms including worsening of pain on flexion or extension were assessed. Symptom sites before surgery were categorized into LBP alone, or LBP plus referred inguinal or leg pain. We followed 77 patients (average 3.0 years) and compared symptoms before surgery with surgical outcome.ResultsSixty-three patients with a good outcome showed postsurgical pain relief (≥60% pain relief) and 14 patients with a poor outcome did not (<60% pain relief). In patients with good outcomes, worsening of LBP was evident in 65% of cases on flexion and in 35% on extension. However, these findings were not significantly different from those in patients with poor outcomes. The percentage of patients with LBP alone was significantly lower and the percentage of patients with LBP plus referred inguinal or leg pain was significantly higher in the group with good surgical outcome compared with patients in the group with poor surgical outcome (p<0.05).ConclusionsWorsening of pain on extension may be a symptom of DLBP. Surgical outcomes were superior in patients with both LBP and either referred inguinal or leg pain compared with those having LBP alone.

A Systematic Review of the Classification, Diagnosis, Treatment and Outcome of Osteonecrosis of the Hips in Sickle Cell Disease

Background: Osteonecrosis (ON) is a prevalent (30-50% by age 30) yet underdiagnosed complication in patients with sickle cell disease (SCD), commonly affecting the femoral and humeral head. SCD ON is progressive resulting in chronic intractable pain and disability. Various imaging modalities are available for the diagnosis of ON and a number of staging methods have been proposed to classify its severity. Numerous surgical and non-surgical treatments exist for different stages of ON. There is a lack of consensus on how to best investigate, classify and treat patients with SCD ON. A previous systematic review included only 1 randomized controlled trial (RCT) but the majority of the literature are non-randomized studies.Objectives: To systematically review and summarize the available evidence from randomized and non-randomized studies with regard to the classification, diagnosis, treatment options and outcome of ON of the hips in SCD adults.Methods: Searches were conducted using the following search concepts: (sickle cell disease OR sickle cell anemia OR hemoglobin SC disease) AND (osteonecrosis OR avascular necrosis OR bone and joint complications) NOT Bisphosphonate-Associated Osteonecrosis of the Jaw. Related terms were also searched in order to maximize sensitivity. MEDLINE, Embase, CINAHL, Current Controlled Trials, and Cochrane Central Register of Controlled Trials were queried. Two independent reviewers (DM-A and AP) excluded abstracts based on pre-defined criteria. A third reviewer (KK) resolved all conflicts. Full-text of included abstracts were translated to English as needed, extracted by DM-A, AP, KK and YP and screened based on the inclusion/exclusion criteria. Two assessors (DM-A and KK) independently assessed trial quality of extracted data. Study limitations (risk of bias) and confidence in effect estimates (quality of evidence) were assessed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies.Results and Discussion: 25 studies (1 RCT, 1 case-control, 10 prospective and 13 retrospective studies) were included from 544 unique citations (kappa=0.82). A total of 2,640 participants (median number of patients/study 34, range 10-1,031) with mean age of participants in each study between 19 and 40 years. Majority were HbSS (n=1,888), followed by 302 HbSC, 98 HbS/thalassemia, 27 sickle cell trait, 22 unspecified SCD genotype and 1 HbS/hereditary persistence of fetal hemoglobin. The male to female distribution was equal. Mean duration of follow-up was between 3 and 19 years. Majority (n=12) of the studies included symptomatic patients only. Nine studies used x-rays only to identify ON and 9 used x-ray with CT and/or MRI. Classification of ON between studies was heterogeneous (Ficat and Arlet: 3, Steinberg: 4, Ficat: 4, Mitchell 1987: 1, Arlet: 1, no classification scheme: 12). Treatment modalities used were extremely diverse. Of the 22 studies that described an intervention: 11 used hip arthroplasty only, 1 with cement injection only, 1 with core decompression only, and 9 used a combination of surgical and non-surgical interventions. There was also tremendous heterogeneity with the outcomes reported which precluded the conduct of any meta-analysis. The revision rate after hip arthroplasty, cement injection, and core decompression were 21% (range 3-40%), 13%, and 12% respectively. Median difference in Harris Hip Score post-hip arthroplasty was 52 (range 44-58), and 25 post-cement injection. The median rate of prosthesis infection post-hip arthroplasty was 5.5% (range 2-34%). Summary statistics were not possible on other outcome measurements since they were used in single study. Risk of bias in all the studies was moderate to high.Conclusion: The heterogeneity in diagnosing, classifying and treating ON makes the development of a consensus guideline difficult. Ficat and Arlet, Steinberg, and Ficat were the most common method in ON staging. Hip arthroplasty alone or in combination with non-surgical interventions were the most commonly used treatment options. Although hip arthroplasty offers post-surgical pain relief, it is associated with high rates of revision. The paucity of RCT and the high risk of bias with the existing non-randomized studies highlight the importance of developing prospective controlled studies examining existing and novel therapies using a unified approach in determining the severity of ON and outcome measures. DisclosuresKuo:Novartis Canada: Honoraria, Other: Advisory Board; Alexion Pharmaceuticals: Honoraria, Other: Advisory Board.

Liposome Bupivacaine for Postsurgical Analgesia in Patients Undergoing Robotically Assisted Cardiac Surgery.

Despite the advantages of robotically assisted cardiac surgery over conventional open sternotomy, robotically assisted surgery may be associated with substantial postsurgical pain arising from multiple incisions and access ports. This single-site, retrospective chart review evaluated the impact of liposome bupivacaine compared with bupivacaine HCl on postsurgical pain management in patients undergoing robotically assisted endoscopic cardiac surgery. Sequential patient cohorts undergoing robotically assisted cardiac surgery received either 0.25% bupivacaine HCl (100 mg in 40 mL, n = 30) or liposome bupivacaine (266 mg in 20 mL, expanded to 40 mL with 0.9% sterile normal saline, n = 30) intraoperatively via equal-volume infiltration across port sites. Outcome measures, collected from the day of surgery through postoperative day 3, were daily and total use of opioid analgesics (converted to morphine equivalents), pain intensity (11-point numeric rating scale), and incidence of postoperative nausea and vomiting. Median length of hospital stay was 4 days in the liposome bupivacaine group and 3 days in the bupivacaine HCl group. Patients receiving liposome bupivacaine had numerically lower mean pain scores (at six of seven time points), reduced mean opioid consumption, and a reduced incidence of postoperative nausea and vomiting compared with those receiving bupivacaine HCl, although none of the differences reached statistical significance. Results from this small retrospective, observational study suggest that liposome bupivacaine may improve postsurgical pain relief and reduce postsurgical opioid consumption, in comparison with bupivacaine HCl, in patients undergoing robotically assisted cardiac surgery. Larger prospective studies of liposome bupivacaine in this setting are warranted.

Sustained release of bupivacaine for post-surgical pain relief using core-shell microspheres.

Core-shell polymer microspheres with poly(d,l-lactic-co-glycolic acid) (PLGA) core and poly(l-lactic acid) (PLLA) shell were developed for sustained release of bupivacaine for postoperative pain relief after knee surgery. The PLLA-rich shell acted as a diffusion barrier, allowing linear release of bupivacaine in a goat model over an extended period of 2 weeks post-surgery. In vivo bupivacaine concentrations in the goat synovial fluid remained within therapeutic levels for the 2 weeks, whereas bupivacaine concentrations in the blood plasma remained safely below toxic levels. All animals survived until the end of the 28 day study, with no inflammation, infection or reduced mobility. Explantation at day 28 revealed some soft microsphere remnants in the para-patellar space of the knee joint. However, there was no damage to the articular surfaces, or interference with joint motion. Histological analysis of each knee compartment did not reveal any signs of osteoarthrosis or degeneration within the joints, and safranin-O staining showed intact cartilage surfaces with well-preserved proteoglycan content.

Bupivacaine liposome injectable suspension: A new treatment option for posturgical pain

A multivesicular liposomal formulation of bupivacaine which can provide prolonged postsurgical pain relief has been developed. Two pivotal placebo-controlled phase III trials, one in hemorrhoidectomy and one in bunionectomy procedures, showed that wound infiltration of the suspension at the end of surgery could provide analgesia for up to 72 hours, reduce the amount of opiate rescue medications, the time to their first use and increase patient satisfaction. Liposomal bupivacaine was generally well tolerated, with no signal of QTc prolongation or evidence of impaired wound healing. A small open U.S. health economic study showed benefits (versus patient-controlled analgesia) for the preparation in decreasing total opioid use, length of hospital stay and total hospital costs. Further larger studies are warranted, in particular using bupivacaine hydrochloride as the comparator.

Challenges in the Management of Acute Postsurgical Pain

The majority of patients who undergo surgery will require drug therapy for the management of acute postsurgical pain. Effective control of acute postsurgical pain is essential for the patient not only in the short term but also in the long term to prevent the development of chronic pain, which can occur if early acute pain is prolonged. Currently, opioid analgesics are widely used for the management of acute postsurgical pain. Although opioids provide effective postsurgical pain relief, their use is associated with a number of risks, including the development of opioid-related adverse drug events (ORADEs). This review investigates the prevalence of opioid use in the postsurgical setting, the incidence of ORADEs, and the impact of these ORADEs on patient outcomes, length of stay, and costs after common surgeries. According to a national analysis of ORADE incidence, almost 20% of patients treated with opioids experienced an ORADE, with the most common being gastrointestinal effects, central nervous system effects, pruritus, or urinary retention. Studies show that the risk of developing an ORADE is higher in patients receiving higher doses of opioids and in patients undergoing orthopedic or gynecologic surgery compared with patients undergoing general surgery. Elderly patients and those with comorbidities (e.g., obesity, sleep apnea, respiratory disease, urinary disorders) may be particularly vulnerable to ORADE development. Both hospital costs and length of stay are increased in patients with an ORADE versus those without an ORADE. Strategies to reduce the use of opioids after surgery are likely to result in positive outcomes by reducing the incidence of ORADEs and, as a result, reducing treatment costs associated with surgery and improving patient care.

P02.189. GOALS: bundled services to reduce the length of hospital stay in women undergoing gynecology oncology surgery

Purpose To examine if a multi-modal integrative intervention (education, early feeding/activity, epidural, integrative therapies) impacts length of hospital stay (LOS) compared to historical controls in women undergoing surgery for known or suspected endometrial, ovarian, or cervical cancer. Methods The multi-modal intervention combines various therapies into a cohesive program. Prior to surgery, participants receive explicit patient education, acupuncture and mind/body therapies to assist with physical and mental preparation for surgery. On the day of surgery, an epidural is placed prior to general anesthesia administration to manage post-operative pain. Patients undergo standard of care surgery. The evening after surgery, patients eat a high protein “surgical soft” dinner and nurses assist patients in walking down the hospital halls. Acupuncture is provided on post-operative days one and two for postsurgical pain relief, nausea control and for stimulation of bowel function. Patients’ electronic medical records are reviewed to obtain intra-operative and post-operative details including amount of medications administered, length of surgery, time of admission to post-anesthesia care unit, time of first ambulation out of the room, percent of diet eaten first 24 hours, nausea/pain level, discharge date/time/disposition, and patient satisfaction scores. The primary endpoint is the difference in patient LOS following surgery relative to a historical control. Secondary endpoints include FACT-G, State-Trait Anxiety Inventory, Patient Activated Measure before admission and roughly six months after discharge from the hospital. Results

Peripheral neurectomies: A treatment option for trigeminal neuralgia in rural practice

Background:Trigeminal neuralgia is a commonly diagnosed neurosensory disease of head, neck and face region, involving 5th cranial nerve. Carbamazepine is the first line drug if there is decrease in efficacy or tolerability of medication, surgery needs to be considered. Factors such as pain relief, recurrence rates, morbidity and mortality rates should be taken in to account while considering which technique to use. Peripheral neurectomy is a safe and effective procedure for elderly patients and in rural and remote centers where neurosurgical facilities are not available. It is also effective in those patients who are reluctant for major neurosurgical procedures. Although loss of sensation along the branches of trigeminal nerve and recurrence rate are associated with peripheral neurectomy, we consider it as the safe and effective procedure in rural practice, which can be done under local anesthesia.Aims:The aim of this prospective study is to evaluate the long term efficacy of peripheral neurectomy with and without the placement of stainless steel screws in the foramina and to calculate the mean remission period after peripheral neurectomies for different branches of trigeminal nerve.Setting and Design:The sample was divided into 2 groups by selecting randomly the patients, satisfying inclusion criteria. Both groups were operated under local anesthesia by regional nerve blocks. In one group of patients after peripheral neurectomy, the proximal nerve stump was left alone in the foramina, and in another group of patients, obturation of foramina was done with stainless steel screws after peripheral neurectomy.Materials and Methods:Peripheral neurectomy was done on the terminal branches of trigeminal nerve in 14 patients. We selected only those cases that were experiencing pain after Carbamazepine therapy, all our patients were from rural and remote areas where facilities to neurosurgical centers are limited. Elderly patients who were unfit for surgical procedures and those patients who were reluctant for major neurosurgical treatments were considered for the study.Results:Post-surgical pain relief varied from 15 months to 24 months in cases where neurectomy was done without placing stainless steel screws in the foramina. Those cases where peripheral neurectomy was done along with the placement of stainless steel screws in the foramina, none of the patient had painful symptoms even after minimum 2 years of follow-up. Student's `t`-test of 2 groups showed the remission period to be statistically highly significant in patients with stainless steel screw obturation, having P-value <0.0005.Obturating the foramen with stainless steel screws can prevent nerve regeneration. Thus, remission of pain can be prolonged.Conclusion:Peripheral neurectomy is thus a safe and effective procedure for elderly patients, for those patients living in remote and rural places that cannot avail major neurosurgical facilities, and for those patients who are reluctant for major neurosurgical procedures.

Efficacy and Safety of Dual-Opioid Therapy in Acute Pain

Although opioids are widely accepted as standard therapy for treating acute postoperative pain, the frequent occurrence of adverse events (AEs) and the substantial burden on the patient and the costs of care are a barrier to optimal dosing and adherence to prescribed treatment. Coadministration of two opioids is not often recommended as a multimodal treatment option for moderate to severe acute pain because of lack of knowledge about the potential benefit of such combinations and due to potential concerns about side effects and doubts about the added benefits. Study results on the coadministration of two or more opioids demonstrate synergistic analgesia with a similar or lower incidence of opioid-related AEs. One such combination is morphine and oxycodone. Moxduo® (morphine/oxycodone 3/2) is a dual-opioid combination of morphine and oxycodone used to treat acute pain. Independent controlled studies of the coadministration of morphine plus oxycodone demonstrate excellent analgesia with a lower incidence or less-intense AEs, especially nausea and vomiting, compared with equianalgesic doses of individual opioids. Controlled trials with morphine/oxycodone 3/2 have enrolled approximately 1,500 subjects with moderate to severe post-surgical pain who received multiple doses of morphine/oxycodone 3/2 or single-entity opioids for a maximum of 23 days. These phase 2 and phase 3 clinical studies demonstrate analgesic efficacy that is at least comparable to the individual components and showing a 50-75% reduction in moderate to severe AEs, especially nausea and vomiting. Thus, the dual-opioid combination product, morphine/oxycodone 3/2, compared with equianalgesic monotherapy doses of oxycodone or morphine may provide effective relief of moderate or severe post-surgical pain, while reducing the impact of AEs on patients and prescribers.

Palliative Care Pharmacotherapy Literature Summaries and Analyses

Timely and important studies are reviewed and commentaries provided by leading palliative care clinicians. Symptoms, interventions, and treatment-related adverse events addressed in this issue are antidepressants, postsurgical neuropathic pain, endogenous opioids and dyspnea relief, cancer cachexia, and atypical antipsychotics.

Post-tonsillectomy pain management in children: Can we do better?

The search for an effective post-tonsillectomy analgesic has been disappointing. This study tests the hypothesis that rofecoxib improves pain scores in children for 72 hours post-tonsillectomy when compared to hydrocodone with acetaminophen elixir. Prospective, randomized, double-blind, active comparison of postoperatively administered rofecoxib or hydrocodone with acetaminophen in 60 healthy children scheduled for elective tonsillectomy. Sixty ASA I and II children scheduled for elective tonsillectomy were enrolled to receive either rofecoxib or hydrocodone with acetaminophen, commencing at discharge from day surgery. Active and passive pain scores and side effects were assessed for 3 days. Rofecoxib significantly reduced active pain scores at all time intervals after 6 hours following surgery when compared to hydrocodone with acetaminophen without detectable differences in adverse effects. This difference was not apparent in passive pain scores. A review of analgesic strategies is presented. Study results and review of the literature support the development of pediatric formulations of NSAIDs with greater COX-2 selectivity to improve postsurgical pain relief for children.

(894): Assessing post-surgical pain and pain relief by measuring skin potential assymmetry in a non-verbal (equine) population

(894): Assessing post-surgical pain and pain relief by measuring skin potential assymmetry in a non-verbal (equine) population

Prospective, randomized, open-label, pilot clinical trial comparing the effects of dexamethasone coadministered with diclofenac potassium or acetaminophen and diclofenac potassium monotherapy after third-molar extraction in adults

Background: Patients who experience pain, swelling, and trismus after third-molar extraction are reported to experience a 3-fold higher rate of adverse effects (AEs) on quality of life compared with those who are asymptomatic after this surgery. Therefore, investigators emphasize the necessity for better control of this triad of sequelae. Steroids can reduce the risk for physiologic processes of inflammation, thereby suppressing the development of inflammation. Objective: The aim of this study was to compare the effects of dexamethasone 8 mg IM and diclofenac potassium (K) 50 mg PO, dexamethasone 8 mg IM and acetaminophen 1000 mg PO, and monotherapy with diclofenac K 50 mg PO on postoperative pain, swelling, and trismus after surgical removal of third molars. Methods: This prospective, randomized, open-label pilot study was conducted at the Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Lagos, Nigeria. Patients were randomly allocated to 1 of 3 treatment groups: concomitant treatment with dexamethasone 8 mg IM and diclofenac K 50 mg PO or acetaminophen 1000 mg PO, or monotherapy with diclofenac K 50 mg PO. Overall analgesic efficacy of the drug combinations was assessed for 7 days postoperatively using a 4-point categorical pain-intensity rating scale (0 = no pain; 1 = mild pain; 2 = moderate pain; and 3 = severe pain). Facial swelling was measured in 1 dimension on days 1, 2, and 7 after surgery using a tape measure placed from the tip of the tragus, to gonion, to the tip of the contralateral tragus, and trismus was assessed using interincisal mouth-opening ability, measured using a vernier-calibrated caliper on postoperative days 1, 2, and 7. Tolerability was assessed using direct questioning of the patients at follow-up visits. Results: A total of 150 patients (50 per treatment group) were included in the analysis (76 women, 74 men; mean [SD] age, 26.8 [5.04] years [range, 18–45 years]; 100% Nigerian). The proportion of patients reporting no pain on the pain-intensity rating scale was significantly higher in the group receiving dexamethasone and diclofenac K compared with that in the groups receiving dexamethasone and acetaminophen or diclofenac K monotherapy (44% vs 22% and 24%, respectively; both, P < 0.05). Facial swelling was significantly less with dexamethasone and diclofenac K or dexamethasone and acetaminophen compared with diclofenac K alone (day 1: P = 0.013 and P = 0.011, respectively; day 2: P = 0.002 and P = 0.004, respectively). However, trismus relief was statistically similar between the 3 treatment groups on postoperative days 1 and 2. No AEs or complications were recorded. Conclusion: In this open-label pilot study, concomitant treatment with dexamethasone and diclofenac K provided significant relief of postsurgical pain and swelling compared with dexamethasone and acetaminophen or monotherapy with diclofenac K after third-molar extraction in these patients.

Research &amp; commentary Post-surgical pain relief

Research &amp; commentary Post-surgical pain relief

Liposome-encapsulated oxymorphone provides prolonged relief of post-surgical visceral pain in rats

A delayed-release formulation of liposome-encapsulated oxymorphone was produced using a novel dehydration-rehydration technique. The purpose of this study was to (i) compare the analgesic properties of this preparation with those of repeated injections of standard oxymorphone in rats with post-operative visceral pain and (ii) determine whether liposome-encapsulated oxymorphone differed from standard oxymorphone in duration of the effect.

Evaluation of intravenous parecoxib for the relief of acute post-surgical pain

Parecoxib is a prodrug of valdecoxib, which is a potent and selective inhibitor of COX-2. Intravenous preparation of parecoxib is in Phase III clinical trials for the management of acute and severe post-surgical pain. It is the only COX-2 inhibitor that is available in a parenteral formulation. Clinical results compare parecoxib with ketorolac, a NSAID, which is the only non-narcotic analgesic available in parenteral formulation that can be administered for the relief of moderate to severe acute pain. Pharmacokinetic studies have shown that parecoxib is converted to valdecoxib within a short time following administration by im. or iv. injection. In clinical trials, parecoxib compares favourably with ketorolac and produces less gastric or duodenal ulcers, the predominant adverse effect, than ketorolac. Parecoxib, thus, fulfils some of the desirable characteristics of an ideal non-narcotic analgesic for severe post-surgical pain and has application in other acutely painful conditions. Parecoxib is expected to be filed for approval before the end of 2000 and is expected to be introduced in the market in 2001. It has favourable prospects for a fair share of the post-surgical pain relief market which is valued at approximately US$ 1 billion for the year 2000.