Morphine Sulfate Group Research Articles

Pharmacoeconomic analysis of the application of strong opioids for the treatment of chronic pain syndrome in patients with pancreatic cancer

Objective: to evaluate the clinical and economic feasibility of opioid therapy based on the analysis of its cost and effectiveness in patients with chronic pain syndrome in pancreatic cancer.Material and methods. An observational prospective study in parallel groups of patients with chronic pain syndrome associated with pancreatic cancer was carried out. The analysis of cost minimization and cost-effectiveness was applied, as well as pharmacoeconomic modeling, which included the construction of a decision tree in patients receiving morphine sulfate (n=45) and fentanyl TTS (n=45) for pain relief. The sensitivity of the obtained data was assessed using one-way analysis.Results. It was shown that the treatment of chronic pain syndrome in patients with pancreatic cancer with opioid analgesics as part of combined treatment is the least expensive in the morphine sulfate group (incremental cost-effectiveness ratio 144.93). Based on the results of modeling, the prognostic factors of influence on the cost of analgesic therapy were determined: the cost of combined analgesic therapy, the cost of treatment of adverse reactions, and the cost-effectiveness ratio.Conclusion. Analgesic therapy of chronic pain syndrome with morphine sulfate in patients with pancreatic cancer is pharmacoeconomically feasible.

Risk assessment of using off-label morphine sulfate in a population-based retrospective cohort of opioid-dependent patients.

Several addictovigilance studies have described the off-label use of morphine sulfate (MS) for nonchronic pain in opioid use disorder (OUD) patients as an alternative to conventional opioid substitution treatments (OSTs). This study primarily sought to compare the incidence of unintentional opioid-related overdose in the year following the prescription initiation in off-label MS users, compared to OST-maintained patients. Sequential cohorts of OUD patients who were regularly dispensed MS, buprenorphine, or methadone, between 1 April 2012 and 31 December 2014, were retrospectively identified using the French nationwide healthcare data system. The incidence of overdoses, deaths, doctor shopping, and complications of a viral, bacterial or thrombotic nature, was compared using the Cox regression method. Overall, 1075, 20834 and 9778 OUD patients without chronic-pain were included in the MS, buprenorphine, and methadone cohorts, respectively. Overdose incidence was 3.8 (P<.01 [95% confidence interval (CI): 2.1-6.8]) and 2.0 (P=.02 [95%CI: 1.1-3.6]) higher in the MS cohort vs buprenorphine and methadone, respectively. Death incidence was 9.1 (P < .01 [95%CI: 3.2-25.9]) and 3.9 (P < .01 [95%CI: 1.4-10.7]) higher in the MS cohort vs buprenorphine and methadone, respectively. The incidences of other associated risks were significantly higher in the MS group vs OSTs, except for hepatitis C viral infection and thrombotic complications. This first French comprehensive nationwide study reveals increasing overdose, death, bacterial infection, abuse and diversion risks when off-label MS is initiated as alternative to OST. These results question the relevance of prescribing MS as a safe opioid maintenance treatment, considering its health risk profile.

Oral Oxycodone Compared With Intravenous Morphine Sulfate for Pain Management of Isolated Limb Trauma; a Randomized Clinical Trial.

Appropriate pain relief enhances patient satisfaction and reduces patient anxiety. This study aimed to compare oral oxycodone with intravenous (IV) morphine sulfate (MS) in pain management of acute limb trauma. In this randomized double-blind clinical trial, patients over 14 years old, with acute isolated limb trauma were randomized to receive either 5mg IV MS or 5 mg oral oxycodone. Pain intensity and adverse effects of medications were recorded 0, 30 and 60 minutes after drug administration and compared between the groups. 58 patients were studied. Pain intensity was similar between the two studied groups at 30 minutes (P = 0.834) and 60 minutes (P = 0.880) after drug administration. Furthermore, there was no significant difference between the two groups regarding decrease in pain within the defined time interval. Drowsiness was reported more frequently in MS group after 30 minutes (p = 0.006). Patients in MS group asked for more rescue analgesia. Other adverse effects were similar in both groups. Oral oxycodone is as effective as IV morphine sulfate in treatment of acute musculoskeletal pain following blunt limb trauma.

Intravenous Acetaminophen Versus Intravenous Morphine Sulfate for Isolated Diaphyseal Long Bone Fractures: A Randomized Clinical Trial

Objectives: Pain management is an important issue in traumatic patients. The aim of this randomized clinical trial was to compare the analgesic effect of intravenous acetaminophen with intravenous morphine sulfate in patients with traumatic diaphyseal long bone fracture. Methods: This double-blind randomized clinical trial was carried out in an academic trauma center in Mashhad, Iran, from February to October 2013. After primary modalities like limb elevation, ice and limb splinting, patients were allocated to receive either acetaminophen 15 mg/kg or morphine sulfate 0.1 mg/kg randomly. The pain severity was measured using a visual analogue scale before drug administration and 5 and 30 minutes after drug administration. Then, the results were compared. Results: Of the 50 patients recruited over 9 months 26 patients received intravenous morphine sulfate and 24 patients received intravenous acetaminophen. A significant difference was observed between the two groups at 5 minutes after drug administration; the morphine sulfate group showed more reduction in pain severity after 5 minutes (P < 0.0001). However, there was no significant difference in pain severity at 30 minutes after drug administration between the two groups (P = 0.85). Conclusions: It seems that after 30 minutes, intravenous acetaminophen is as effective as intravenous morphine sulfate in pain management of isolated diaphyseal long bone fracture. However, it should be noted that the analgesic effect of acetaminophen begins with a delay. Thus, we suggest using intravenous acetaminophen when morphine administration is contraindicated.

Intravenous Lidocaine versus Morphine Sulfate in Pain Management for Extremity Fractures; a Clinical Trial.

Considering the existing contradictions regarding effectiveness of intravenous (IV) lidocaine, especially in emergency department (ED), the present study was designed to compare the analgesic effect of IV lidocaine and morphine sulfate in pain management for extremity bone fractures. In this triple blind clinical trial, 15 to 65 year-old patients with extremity fractures and in need of pain management were randomly allocated to either IV lidocaine or morphine sulfate group and were compared regarding severity of pain 5, 10, 15, 20, 25, and 30 minutes after infusion via intention to treat analysis. The absolute risk reduction, number needed to treat and relative risk of IV lidocaine after 30 minutes were 0.40 (95%CI: 0.25 - 0.64), 7 (95%CI: 3.7 - 23.1), and 20.71 (95%CI: 10.91 - 30.51), respectively. 280 patients with the mean age of 32.50 ± 12.77 years were randomly divided into 2 equal groups of 140 (73.9% male). The 2 groups had similar baseline characteristics. 15 minutes after injection success rate was 49.28% in lidocaine and 33.57% in morphine sulfate group (p = 0.011), and after 30 minutes it reached 85.71% and 65.00%, respectively (p < 0.001). Based on the results of the present study, IV lidocaine could be considered as a reasonable alternative choice for pain management in ED.

Oral oxycodone plus intravenous acetaminophen versus intravenous morphine sulfate in acute bone fracture pain control: a double-blind placebo-controlled randomized clinical trial

Bone fracture is a common cause of acute pain in emergency and orthopedics departments. Targeting the multifaceted mechanisms of pain with combinations of multiple analgesics (multimodal analgesia) can increase the pain control efforts efficacy and decrease the adverse effects of each medication. One hundred and fifty-three patients with acute bone fracture were randomly allocated to two groups receiving intravenous morphine sulfate (74 patients) or oral oxycodone plus intravenous acetaminophen (79 patients). Pain scores and drugs' adverse effects were assessed 10, 30 and 60 min after treatment. Pain scores were similar between groups before, 30 and 60 min after medication but patients in morphine sulfate group experienced less pain 10 min after medication. Eight (10.8%) patients in morphine sulfate group and 26 (32.9%) patients in acetaminophen/oxycodone group experienced nausea that was statistically significant higher (P value = 0.001). Itching was seen in 12 (15.1%) patients of acetaminophen/oxycodone group and three (4.0%) patients of patients in morphine sulfate group (P value = 0.02). Intravenous acetaminophen plus oral oxycodone is as effective as intravenous morphine sulfate in acute pain control in emergency department but with a less desirable safety profile.

A Randomized Controlled Trial Comparing a Fascia Iliaca Compartment Nerve Block to a Traditional Systemic Analgesic for Femur Fractures in a Pediatric Emergency Department

We determine whether a fascia iliaca compartment nerve block can provide superior pain management compared with intravenous morphine sulfate for the initial pain management of femur fracture patients presenting to a pediatric emergency department. The primary outcome measured is pain scores; a difference of 15% in scores assessed at 30 minutes from the study's baseline pain management is considered clinically meaningful. Secondary outcomes include the duration of analgesia, the need for additional medications, adverse events, nerve block complications, and satisfaction scores. This was a prospective, randomized, unblinded, controlled trial conducted on children aged 15 months to 18 years with acute femur fractures, presenting to a free-standing, tertiary care children's hospital. Patients were randomized to receive intravenous morphine sulfate or a fascia iliaca compartment nerve block using ropivacaine (Naropin). Pain scores (Children's Hospital of Eastern Ontario Pain Scale [CHEOPS]; Face, Legs, Activity, Cry and Consolability Pain Scale; Faces Pain Scale) were recorded at initial analgesic administration (baseline), at 5, 10, 15, 30, and 60 minutes, and then hourly up to 6 hours from baseline by trained nursing observers and research assistants. Fifty-five patients, 26 in the fascia iliaca compartment nerve block group and 29 in the morphine sulfate group, ranged in age from 16 months to 15 years (median 5.7 years). Baseline mean CHEOPS scores were similar: 9.4 fascia iliaca compartment nerve block and 9.5 morphine sulfate. Mean CHEOPS scores at 30 minutes after initial treatment were 5.87 for fascia iliaca compartment nerve block and 7.54 for morphine sulfate, with a difference of 1.67, which corresponds to an 18% (95% confidence interval [CI] 8% to 27%) difference in pain reduction between the 2 groups, according to the average baseline score of 9.45. Similar lower pain scores were observed in the fascia iliaca compartment nerve block group as early as 10 minutes from baseline and throughout the 6-hour duration of the study. In comparing the entire 6-hour CHEOPS pain scores, patients who received a fascia iliaca compartment nerve block showed lower scores by approximately 15% (95% CI 6% to 24%) compared to patients who received morphine sulfate. Median duration of analgesia was longer in the fascia iliaca compartment nerve block group compared with that in the morphine sulfate group (313 minutes [95% CI 154 to 360 minutes] versus 60 minutes [95% CI 10 to 255 minutes]). Fewer additional medications were given to patients who received the fascia iliaca compartment nerve block. No complications from the nerve block occurred. Satisfaction scores were higher with the fascia iliaca compartment nerve block among the medical staff. Fascia iliaca compartment nerve block provided clinically superior pain management compared with intravenous morphine sulfate at 30 minutes from baseline and throughout the initial 6 hours of medical treatment of children 16 months to 15 years who had isolated acute femur fractures. The results of this study, however, may be inflated by the nonblinding of the pain observers. Despite this potential bias, the fascia iliaca compartment nerve block should be considered as a valuable procedure in managing the pain commonly observed in these injured children.

A Comparison of Depodur???, a Novel, Single-Dose Extended-Release Epidural Morphine, with Standard Epidural Morphine for Pain Relief After Lower Abdominal Surgery

In this randomized, controlled, dose-ranging study, we evaluated the analgesic efficacy of a novel single-dose extended-release epidural morphine (Depodur) in patients undergoing lower abdominal surgery. Five-hundred-forty-one patients were randomly assigned to one of six epidural treatments administered approximately 30 min before surgery. The 6 treatments were 5 mg of standard epidural morphine sulfate (MS) (active comparator); 5 mg of single-dose extended-release epidural morphine (EREM) (dose control); and 10, 15, 20, and 25 mg of single-dose EREM. The main study objective was to assess the efficacy of single-dose EREM 10, 15, 20, or 25 mg versus single-dose EREM 5 mg for the management of postoperative pain. This was done by plotting a linear dose-response relationship to assess postoperative IV patient-controlled analgesia (PCA) fentanyl consumption for breakthrough pain for 48 h after surgery. Secondary safety and efficacy analyses compared the 10-, 15-, 20-, and 25-mg single-dose EREM groups with the 5-mg single-dose EREM group and compared each single-dose EREM group with 5 mg of MS. As shown by the dose-response relationship, there was a dose-related reduction in the use of postoperative IV fentanyl through 48 h (estimated slope, -22.2; P = 0.0002). Patients treated with 10, 20, and 25 mg of single-dose EREM used significantly less IV fentanyl (mean +/- sd: 995 +/- 987 microg, P = 0.0446; 972 +/- 982 microg, P = 0.0221; and 683 +/- 620 microg, P < 0.0001, respectively) through 48 h after surgery compared with the 5-mg single-dose EREM group (1218 +/- 894 microg). At 48 h postdose, significantly more single-dose EREM patients (13%) than MS patients (2%) had required no IV fentanyl (P < 0.01). Although all treatment groups had access to PCA fentanyl and there was more frequent PCA fentanyl use in the MS group, patients in the single-dose EREM 15, 20, and 25 mg groups reported significantly lower pain-intensity scores and greater satisfaction with their pain relief. Overall, single-dose EREM was well tolerated, with 97% of adverse events rated as mild to moderate. As expected, the adverse events reported were consistent with those of other epidural opioids (i.e., nausea, vomiting, pruritus, and hypotension). In conclusion, this controlled study demonstrated that single-dose EREM can provide up to 48 h of postoperative analgesia, but supplementation for breakthrough pain is still required in most patients. Within the context of this study, the side effect profile of single-dose EREM was acceptable and predictable.

MorphiDex ® (MS:DM) Double-Blind, Multiple-Dose Studies In Chronic Pain Patients

Preclinical and double-blind single-dose placebo-controlled studies demonstrated that MorphiDex ® (MS:DM), a 1:1 ratio of morphine sulfate (MS) to dextromethorphan hydrobromide (DM), provides significantly greater analgesia than an equal dose of immediate release MS, with a faster onset, and a duration of ≥8 h. The analgesic effect of MS:DM compared to MS was evaluated in 2 double-blind, multiple-dose studies in 321 patients with cancer and other chronic pain: a crossover study that consisted of two 2-wk periods and a 4-wk parallel study. As specified in the study protocols, patients took sufficient MS or MS:DM to achieve satisfactory pain control. In the crossover study, the MS:DM group required half as much morphine as the MS group to achieve satisfactory pain control (80 mg and 162 mg, respectively). The interval between doses and the time from the last dose of the day to the first dose of the next day were significantly longer for MS:DM compared to MS. In the parallel study, MS:DM also provided pain control at a significantly lower dose. After four weeks of treatment, the mean daily dose of MS increased, while there was little change in the MS:DM mean daily dose ( P = 0.025) to maintain satisfactory pain control. More patients preferred MS:DM to run-in MS than preferred MS to run-in MS ( P = 0.026). The addition of DM to MS did not increase the incidence of adverse events, which were those commonly associated with opioid use. These studies confirm that MS:DM provides satisfactory pain relief but at a significantly lower morphine daily dose.

Effects of morphine anesthesia on myocardial contractility, blood flow, and metabolism

Morphine sulfate is an anesthetic that is frequently used in cardiac operations. Because the knowledge regarding the effects of this drug on the hemodynamic status and myocardium is yet to be defined, we undertook a study in which the effects of morphine sulfate and saline (control group) were compared. Fifteen dogs were anesthetized with chloralose and underwent median sternotomy. A 2 mg/kg dose of morphine sulfate was administered intravenously three times—each time at a 30-min interval (morphine group, eight dogs). In the remaining seven dogs, an equal amount of saline was administered intravenously. The following parameters were measured 10 min after each injection: arterial, central venous, left atrial, and left ventricular pressures, arterial and coronary sinus blood gases and lactates, cardiac output, myocardial blood flow (microsphere technique), and myocardial ATP, glycogen and lactate. Cardiac output, mean arterial pressure, left ventricular dp/dt, myocardial blood flow, myocardial lactate, and lactate extraction did not change significantly in the control group. However, in the morphine group, cardiac output decreased from 103 ± 11 ml/kg/min to 43 ± 6 ( P < 0.005), mean arterial blood pressure decreased from 121 ± 7 mm Hg to 76 ± 10 ( P < 0.05), left ventricular dp/dt decreased from 3134 ± 439 mm Hg/sec to 1548 ± 305 ( P < 0.05), and myocardial blood flow fell from 63 ± 5 ml/min/100 g to 47 ± 4 ( P < 0.05), in spite of a reduction in coronary vascular resistance from 1.66 ± 0.14 mm Hg/ml/100 g/min to 0.74 ± 0.17 ( P < 0.01). Myocardial lactate increased in the morphine sulfate group from 3.04 ± 0.50 μmoles/g to 4.80 ± 0.71 ( P < 0.05), and lactate extraction decreased from 0.23 ± 0.06 μmoles/ml to -0.07 ± 0.13 ( P < 0.05). In chloralose-anesthetized animals, anesthetic doses of morphine sulfate decreased left ventricular contractility, cardiac output, and myocardial blood flow, and increased production of lactate by the myocardium. Our study indicates that morphine sulfate is not as safe a cardiac anesthetic as commonly thought.