Comparative evaluation of ciramadol (WY-15.705), morphine and placebo for treatment of postoperative pain

The efficacy and safety of intramuscular ciramadol to alleviate postoperative pain was compared to morphine in a double-blind placebo controlled study of 100 patients. Postoperative analgesia was assessed using a visual analog scale and two categorical measurements. Two dose levels of ciramadol (30 and 60 mg) were compared to morphine (5 and 10 mg). A valid dose-response curve was obtained for both drugs with no significant deviation from parallelism. Compared to morphine 10 mg, ciramadol 60 mg induced a faster onset of analgesia and showed a longer lasting effect as deduced from the pain intensity difference and pain analog intensity difference time-effect curves (P less than 0.01). All active therapy groups provided better analgesia than the placebo group. The estimated relative analgesic potency of ciramadol to morphine was 0.3 to 1. Some increase in sedation level was seen following therapy in each group with the largest increase in the ciramadol 60 mg group. There was no statistically meaningful among group differences in the adverse experience incidence rates. Postoperative respiratory function showed a significant decrease from the baseline respiration rate in the ciramadol 60 mg group, although respiration rate was notably reduced in each active therapy group more than in the placebo group. Blood pressure was not impaired following ciramadol whereas morphine 10 mg induced a significant decrease in diastolic blood pressure.     

A comparison of intramuscular and sublingual buprenorphine, intramuscular morphine and placebo as premedication

Buprenorphine premedication by two routes, 0.4 mg sublingual and 0.3 mg intramuscular was compared double-blind, double-dummy with intramuscular morphine 10 mg and placebo in 74 patients undergoing elective total hip replacement. Anxiety, depressive mood, sedation, vital signs and side-effects were measured before surgery. All patients then received a standardised general anaesthetic using a muscle relaxant and ventilation. The effects of the premedication on the anaesthetic were assessed by a scoring system. Intra- and postoperative blood gases, plasma cortisol and glucose were measured and the 1 hour postoperative pain intensity, side-effects and sedation were assessed. No differences between the premedications were seen on any of the pre-, intra- or postoperative measurements, suggesting that even with adequate measurement sensitivity it is difficult to distinguish opiate from placebo premedication.     

A comparison of regularly administered sustained release oral morphine with intramuscular morphine for control of postoperative pain

We studied the efficacy and side effect profile of regularly administered, oral sustained-release morphine sulfate tablets (MST) and IM morphine in patients undergoing total hip arthroplasty under lumbar spinal anesthesia. Patients in Group I received MST 20 mg 12 hourly and a placebo IM injection 6 hourly regularly. Group II patients received an oral placebo 12 hourly and morphine sulfate 10 mg IM 6 hourly regularly. Rescue analgesia was provided with regular diclofenac suppositories and patient-controlled analgesia. Pain scores assessed by using visual analog scale and verbal pain scoring at rest and with movement were low in both groups, with no statistical difference between groups. Mean patient-controlled analgesia morphine consumption during the 48-h study was 16.7 mg in the IM group and 25.9 mg in the MST group. The difference between the groups was significant at 36 h postoperatively (0.03). Side effects of sedation and respiratory depression were not problematic in either group, with a maximal sedation score of 2 occurring once in a patient in Group II. Nausea and vomiting occurred more often in Group II, but this was not statistically significant, with a mean nausea/vomiting score for Group II of 1.7. We conclude that oral, sustained-release morphine is an attractive alternative to IM opiates in patients undergoing body surface surgery under regional anesthesia. IMPLICATIONS: Each postoperative analgesic has its own limitations for route of administration, dosage, and potential side effects. Using the oral route for drug administration seems more attractive than other methods but may not be suitable in all postoperative patients. We studied the efficacy and side effect profile of sustained-release, oral morphine compared with standard IM morphine for the treatment of pain after hip replacement surgery. We concluded that use of the oral preparation is a suitable alternative to the IM route in this population undergoing surgery under spinal anesthesia.     

A double-blind comparison of the efficacy of methadone and morphine in postoperative pain control

This study reports the results of a double-blind, parallel-group comparison of intravenous methadone with morphine for the control of postoperative pain. Twenty patients (ASA Status 1 or 2) undergoing a surgical procedure involving an upper abdominal incision were randomly allocated to the methadone (n = 10) or morphine (n = 10) treatment groups. The patients were administered a 20-mg intraoperative opioid dose and 5-mg intravenous increments of opioid from precoded syringes in response to pain in the recovery and surgical wards. There was no significant difference between the mean +/- SD amount of supplementary methadone (8 +/- 6.3 mg) and morphine (9 +/- 9 mg) required in the recovery ward to provide initial pain control. The time from initial pain control to the first supplementary dose in the surgical ward was significantly different (P less than 0.01) in the methadone group (20.7 +/- 20.2 h) when compared to the morphine group (6.2 +/- 3.0 h). Further, patients required significantly less (P less than 0.001) methadone (11.5 +/- 8.5 mg) than morphine (41 +/- 14.1 mg) in the surgical ward to provide adequate pain relief throughout the duration of the study (i.e., 60 h). There was a significant difference in visual analogue pain scores between the methoadone and morphine groups on postoperative days 1 and 2, suggesting the quality of pain relief was similar for both treatment groups. Blood opioid-concentration monitoring indicated that there was a relationship between blood opioid concentration and pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blind comparison of intravenous doses of dezocine, butorphanol, and placebo for relief of postoperative pain

The safety and efficacy of intravenous doses of dezocine (5 or 10 mg), butorphanol (1 mg), and placebo were compared in a double-blind study in 160 patients with moderate to severe postoperative pain. Analgesic efficacy was assessed for 6 hours after each dose. Mean pain relief scores were consistently higher, indicating greater pain relief, for the three active treatment groups than for the placebo group. The 10-mg dezocine dose was the most effective treatment, and 5 mg of dezocine was comparable to 1 mg of butorphanol. In the 2 hours after the first dose, 32% of the 10-mg dezocine group, 53% of the 5-mg dezocine group, 65% of the butorphanol group, and 88% of the placebo group withdrew from the study because of unsatisfactory pain relief. The differences in these percentages were statistically significant (P less than 0.05) between each active therapy group and the placebo group, and between the 10-mg dezocine group and the butorphanol group. Changes in degree of sedation were similar in the three active therapy groups. Adverse reactions were rare, mild, and equally distributed among the four treatment groups. We conclude that 10 mg of dezocine is superior to 1 mg of butorphanol, and that 5 mg of dezocine is as effective as 1 mg of butorphanol for the relief of moderate to severe postoperative pain.     

A double-blind study of the speed of onset of analgesia following intramuscular administration of ketorolac tromethamine in comparison to intramuscular morphine and placebo

A double-blind, randomised, parallel group, placebo-controlled study was performed in 85 patients to compare the speed of onset of analgesia following the intramuscular administration of a single dose of 30 mg of ketorolac tromethamine, 10 mg of morphine or placebo. A new, sensitive, method was used to measure the latency of analgesia. The onset of analgesia was defined by the time taken for the pain intensity score to reach a specified percentage of the baseline value. Twenty-five percent of patients achieving a 50% reduction in baseline pain intensity score appears to be the most appropriate parameter to assess the speed of onset of analgesia of ketorolac and morphine in the postoperative setting. Paired comparison demonstrated that ketorolac had a significantly faster onset of analgesia (p = 0.03) when compared to placebo, whilst comparison of morphine to placebo analgesic latency (p = 0.06) just failed to reach significance. There was no significant difference between the analgesic onset time of ketorolac and morphine (p = 0.73). Intramuscular ketorolac and intramuscular morphine have comparable analgesic onset times in the postoperative pain context. However, the sensitive method of measuring onset of analgesia described, highlights the slow onset of analgesia when analgesics of known efficacy are given by the intramuscular route in the postoperative period. More attention should be given to the speed of onset of analgesia in future assessments of analgesics.     

A comparison of regularly dosed oral morphine and on-demand intramuscular morphine in the treatment of postsurgical pain

A randomized, placebo-controlled, double-blind clinical trial was conducted to compare the use of regularly dosed po morphine and on-demand im morphine in 47 patients undergoing total hip arthroplasty. Patients were randomized to receive either 20 mg (initial dose) of regularly dosed morphine (every four hours po) plus breakthrough pain medication on-demand consisting of both 10 mg morphine po and placebo im, or an equivalent regularly dosed oral placebo (every four hours) with breakthrough pain medication consisting of oral placebo and 5–10 mg morphine im. Subsequent to each request for break-through pain medication, the next regularly dosed oral solution was increased by 5 mg (or equivalent volume of placebo) to a maximum of 40 mg po Q4H. Time-averaged pain scores were lower on both postoperative day 1 and 2 in the group receiving regularly dosed morphine po (P < 0.05). Fewer patients requested breakthrough pain medication on both days in the oral morphine group. The incidences of nausea and vomiting, and of decreased respiratory rates were similar in both groups. Regularly dosed oral morphine is inexpensive and should be compared to other methods of opioid delivery.     

A comparison of intramuscular tenoxicam with intramuscular morphine for pain relief following tonsillectomy in children

A double blind trial was conducted to evaluate the analgesic efficacy of intramuscular tenoxicam for pain relief following tonsillectomy in children. Fifty children, aged 3–10 years, were randomly allocated to receive intramuscular tenoxicam 0.75 mg·kg^?1 or intramuscular morphine sulphate 0.2 mg·kg^?1 after induction of anaesthesia. Although the tenoxicam group required significantly more postoperative morphine (mean 57.8 μg·kg^?1 compared with 26.9 μg·kg^?1, P=0.025), the total morphine dose was significantly reduced after tenoxicam (57.8 μg·kg^?1 compared with 226.9 ug·kg^?1, P<0.0001). There was no difference between the quality of analgesia after discharge from recovery. The incidence of postoperative vomiting was significantly reduced after tenoxicam (20%) compared with morphine (71%).     

A double-blind comparison of codeine and morphine for postoperative analgesia following intracranial surgery

Codeine and morphine were compared in a double-blind study of postoperative analgesia in 40 patients after intracranial neurosurgery. Eighteen patients received codeine phosphate 60 mg and 18 morphine sulphate 10 mg, both by intramuscular injection; 4 patients (10%) required no analgesia. Both drugs provided analgesia within 20 min of injection but morphine was more effective than codeine beyond 60 min (p = 0.01). Fewer doses of morphine than codeine were required (p = 0.003). Nine patients requested one dose of morphine and 9 two doses. Seven patients required three doses of codeine and 1 patient required four doses. Neither drug caused respiratory depression, sedation, pupillary constriction or unwanted cardiovascular effects. We conclude that, in the doses used, morphine is a safe alternative to codeine for analgesia after neurosurgery and has a more persistent action.     

A double-blind, placebo controlled comparison of the morphine sparing effect of oral rofecoxib and diclofenac for acute renal colic

PURPOSE: We compared the morphine sparing effect of a single dose of 50 mg oral rofecoxib, 3, 8-hourly doses of 50 mg diclofenac and placebo for acute renal colic. MATERIALS AND METHODS: Patients who were 18 to 69 years old with clinically diagnosed acute renal colic and a visual analog scale (VAS) score of 40 mm or greater at hospital admission were randomized to receive 1 of the 3 treatment regimens, delivered in 3 identical encapsulated tablets. The primary end point was the mean total amount of intravenously administered morphine in the 24 hours following study medication dose 1. Secondary end points were mean VAS score and the number of treatment withdrawals due to pain. RESULTS: Of 400 patients admitted with acute flank pain 225 fulfilled the inclusion criteria, of whom 110 (49%) were eligible for evaluation and received rofecoxib (36), diclofenac (39) and placebo (35). Baseline characteristics in the 3 groups did not differ. Intent to treat analysis showed that mean morphine consumption was 13.6 mg in the rofecoxib group (95% CI 10.3 to 16.9), 10.2 mg in the diclofenac group (95% CI 7.7 to 12.7) and 11.5 mg in the placebo group (95% CI 8.8 to 14.3). The differences were not significant (p = 0.23). The same applied to mean VAS scores in the 3 groups (p = 0.22). There were no differences in the number of pain related treatment withdrawals (p = 0.64). CONCLUSIONS: No clinically relevant morphine sparing effect was seen in patients with renal colic treated with 50 mg oral diclofenac every 8 hours or a single dose of 50 mg rofecoxib as a representative of the specific inhibitors of cyclooxygenase-2.     

A comparison of rectal diclofenac with intramuscular papaveretum or placebo for pain relief following tonsillectomy

A controlled investigation was conducted to compare the effectiveness of diclofenac and papaveretum in the prevention of pain and restlessness after tonsillectomy in children. Sixty children between 3 and 13 years of age were randomly allocated to receive rectal diclofenac 2 mg/kg, intramuscular papaveretum 0.2 mg/kg or no medication immediately after induction of anaesthesia. Pain and appearance were assessed 1, 3 and 6 hours postoperatively, and the following morning. The assessments were double-blind and performed by the same observer. No significant differences in postoperative pain were found between the groups at any time. The use of diclofenac was associated with a significantly more rapid return to calm wakefulness and had significantly less effect upon respiratory rate. Consumption of paracetamol on the day of operation was significantly less in the diclofenac group. Diclofenac may offer advantages compared to papaveretum with regard to safety and convenience for use in the treatment of pain after tonsillectomy in children.     

Epidural ketamine for postoperative pain relief after gynecologic operations: a double-blind study and comparison with epidural morphine

This double-blind study evaluates whether ketamine given epidurally is effective for postoperative pain relief, and compares the effects of epidural ketamine with those of epidural morphine. Sixty-eight patients undergoing abdominal gynecologic surgery were randomly assigned into six groups (control; ketamine 4, 6, and 8 mg in saline; 6 mg in 10% glucose; morphine 3 mg). All patients were anesthetized with thiopental, nitrous oxide, and enflurane, and drugs were administered epidurally at the end of the operation. The duration of analgesia in the ketamine groups did not differ from that in control patients and the difference in diluent had no observable effects. Significantly, none of the patients in the morphine group needed additional analgesics within 24 hr, whereas 85% in the other five groups did. We conclude that ketamine administered epidurally is inadequate for postoperative pain relief after gynecologic operations.     

A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine.

This double-blind randomised study compared postoperative analgesia after a loading regimen of methadone or morphine in thirty women undergoing abdominal hysterectomy. Methadone or morphine, 0.25 mg.kg-1, was given intravenously at induction of anaesthesia with further increments in the recovery room for analgesia if required. The mean (SD) total doses of methadone and morphine required were 0.43 (0.13) mg.kg-1 and 0.45 (0.15) mg.kg-1 respectively. Patients in the methadone group had lower pain scores in the subsequent 48 hours (P less than 0.001) and required less supplementary intramuscular opioids (P less than 0.001). Ten patients in the methadone group did not request any further opioid analgesics while all patients in the morphine group made at least two requests for opioids. The overall postoperative course was remembered as less painful by patients in the methadone group (P less than 0.001). There was no significant respiratory depression or excessive sedation in either group.     

Patient-controlled antiemesis: a randomized, double-blind comparison of two doses of propofol versus placebo.

BACKGROUND: The role of propofol for the management of postoperative nausea and vomiting (PONV) is not well established. This study determines the efficacy of small doses of propofol administered by patient-controlled device for the treatment of PONV. METHODS: Patients presenting for ambulatory surgery received a standardized general anesthetic. Those who experienced significant nausea or emesis within 1 h of arrival in the recovery room were randomized to receive repeated doses of propofol 20 mg (P-20), propofol 40 mg (P-40), or intralipid (placebo) on demand. Study medications (in equal volumes) were administered with a patient-controlled delivery device for 2 h. A lockout interval of 5 min between doses was used. The following parameters were assessed: nausea, vomiting, rescue antiemetic use, recovery profile, study drug administration history, and satisfaction with treatment. RESULTS: Sixty-nine patients participated in the study. Patient demographics were similar. The average nausea score for a patient in the P-20 and P-40 groups was 25% and 29% less, respectively, compared with placebo during the study period (P < 0.05). This difference was apparent 15 min after initiation of therapy. More placebo patients vomited (P-20, 12%; P-40, 23%; placebo, 56%; P = 0.003) and needed rescue antiemetics (P-20, 17%; P-40, 23%; placebo, 70%; P = 0.001) compared with treatment groups. Sedation scores were similar between groups. Propofol-treated patients had shorter stays in the post-anesthesia care unit (PACU; P-20, 131+/-35 min [mean +/- SD]; P-40, 141+/-34 min; placebo, 191+/-92 min; P = 0.005) and higher satisfaction with their control of PONV than placebo (P < 0.01). CONCLUSIONS: Propofol is effective in managing PONV with shorter PACU stay and great degree of patient satisfaction. There were two episodes of oversedation in the P-40 group. Hence, propofol at a demand dose of 20 mg seems more appropriate.     

Treatment of postoperative nausea and vomiting with ondansetron: a randomized, double-blind comparison with placebo

Postoperative nausea and vomiting are common after recovery from general anesthesia. The antiemetic effect and safety of ondansetron, a selective serotonin type 3 (5-HT3) receptor antagonist, was determined in 36 patients suffering from nausea or vomiting during recovery from intravenous anesthesia by giving either a single intravenous dose of ondansetron (8 mg, n = 18) or placebo (n = 18) over 2-5 min in a randomized, double-blind manner. A "rescue" antiemetic was provided in case of continued vomiting or at the patient's request. Antiemetic efficacy was defined as no request for rescue antiemetic and/or no vomiting episode during the next 4 h. There was no significant difference in the demographic data between the groups. Administration of ondansetron or placebo had no significant effect on vital signs. Ondansetron was an effective antiemetic in 78% (14/18) and placebo was effective in 28% (5/18) of the patients. Laboratory studies 24 h later showed no signs of hematologic, hepatic, or renal alterations. Ondansetron at a dose of 8 mg administered intravenously over 2-5 min appears to be a safe and effective antiemetic for the treatment of nausea and/or vomiting after intravenous anesthesia.     

Epidural droperidol and morphine for postoperative pain

Epidural morphine is effective in the treatment of postoperative pain, but the incidence of associated side effects is high. To assess a potential reduction of opioid side effects by droperidol, 4 mg morphine with either placebo or 2.5 mg droperidol was injected epidurally in a double-blind, randomized, postoperative trial. Forty patients undergoing hip replacement surgery were studied. The overall incidence of side effects during the first 24 h in the group receiving droperidol and morphine was less than 50% of that in the group receiving placebo and morphine (P less than 0.008). Pruritus, emesis, nausea, urinary retention, and hypotension were diminished in the group with droperidol. No significant differences in duration or quality of analgesia were seen. Epidural injection of droperidol did not result in any local or systemic side effects.     

A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy

BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively. RESULTS: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P< 0.0001). Pain during movement was reduced from 41 (31-59) to 22 (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects. CONCLUSION: A single dose of 1,200 mg oral gabapentin resulted in a substantial reduction in postoperative morphine consumption and movement-related pain after radical mastectomy, without significant side effects. These promising results should be validated in other acute pain models involving central neuronal sensitization.     

The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief.

STUDY OBJECTIVE: To examine the efficacy of intramuscular (IM) ketorolac used in combination with intravenous (IV) patient-controlled analgesia (PCA) morphine for postoperative pain relief following intra-abdominal gynecologic surgery. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Patient care unit at a university medical center. PATIENTS: Thirty-five healthy women undergoing intra-abdominal gynecologic surgery who requested postoperative PCA. INTERVENTIONS: Postoperatively, all patients received IV PCA morphine, with the PCA device programmed to deliver a maximum of 1 mg every 6 minutes (maximum of 30 mg over 4 hours). In addition, patients received one of three regimens: (1) IM saline every 6 hours; (2) IM ketorolac 30 mg while in the postanesthesia care unit (PACU), followed by 15 mg every 6 hours; or (3) IM ketorolac 60 mg while in the PACU, followed by 30 mg every 6 hours. MEASUREMENTS AND MAIN RESULTS: Patients were assessed at regular intervals. Visual analog scale (VAS) scores were used to assess analgesia and patient satisfaction with therapy. Data on morphine usage were obtained from the PCA device, and the frequency and severity of adverse effects were assessed for the presence or absence of side effects. Cumulative morphine dosages were lower (p less than 0.05) in both ketorolac groups at 12, 18, and 24 hours. VAS scores and the frequency of side effects did not differ significantly among groups. CONCLUSIONS: IM ketorolac significantly decreased PCA morphine requirements. The analgesic effects of the two drugs appear to be additive.     

Epidural morphine prophylaxis of postoperative pain: report of a double-blind multicentre study

In a double-blind placebo-controlled trial, 154 subjects, having intraperitoneal surgery or Caesarean section, and 53 patients undergoing lower limb orthopaedic surgery, received epidural morphine, 5 mg in 10 ml 0.9 per cent NaCl, or placebo, 10 ml 0.9 per cent NaCl, intraoperatively to determine duration of action and efficacy in preventing postoperative pain. Epidural morphine gave significantly longer postoperative analgesia (greater than 11 h) than placebo (3-6 h) in both groups (p less than 0.05) and patients who received morphine required less postoperative analgesic. Obstetric subjects experienced longer pain relief (18.3 +/- 1.3 h) than patients undergoing non-obstetric intraperitoneal surgery (9.2 +/- 1.2 h) (p less than 0.001). Generally mild pruritus affected more than 40 per cent of those receiving morphine, but over 90 per cent of obstetric patients receiving morphine. Respiratory depression occurred in 2-7 per cent of subjects who received morphine; unpredictable in onset, it responded rapidly to naloxone. Epidural bupivacaine, if employed for the surgical procedure, appeared to prolong epidural morphine analgesia. We consider epidural morphine useful in preventing postoperative pain, but its use demands close observation of respiratory rate in a high density nursing area.