A controlled evaluation of orally administered aspirin,dipyrone and placebo in patients with post-operative pain

Summary

A double-blind controlled trial was carried out in 267 patients with inoderate to severe pain following episiotomy to compare the pain relief provided over a 6-hour period by a single oral close of 500?mg dipyrone, 500?mg aspirin or placebo. The results showed that dipyrone and aspirin were both significantly superior to placebo. Pain relief with dipyrone was already apparent at 30 minutes after drug intake, and was of significantly longer duration than that of aspirin. No side-effects were reported.     

Analgesia following oral surgery for day patients a clinical comparison of two analgesics

Summary

A single-blind, between-patient study was carried out in 167 patients following oral surgery to compare the effectiveness and tolerance of two combination analgesic preparations/pentazocine (15?mg) plus paracetamol (500?mg) and dextropropoxyphene hydrochloride (32.5?mg) plus paracetamol (325?mg). Assessments of pain and pain relief were made over two periods, initially over the 90 minute period following administration of either preparation and secondly, over the subsequent 3 days following discharge. At the hospital, those patients receiving pentazocine plus paracetamol achieved a greater relief of pain than those receiving dextropropoxyphene plus paracetamol, though the differences did not reach statistical significance. At home,pain relief was very similar for both groups of patients, both preparations being effective and well tolerated.     

Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain

OBJECTIVE: The objective of this single-center, single-dose, double-blind randomized parallel group study was to evaluate the analgesic efficacy of a new liquid formulation of ketoprofen at two dose levels (25 mg or 50 mg) compared to a commercially available liquid form of dipyrone 500 mg and placebo with all treatments administered as drops to patients with severe postepisiotomy pain. METHODS: The study was designed with a sample size of 69 patients per treatment for a total of 276 patients. However, due to administrative changes at the site, the study was prematurely terminated; thus only 108 patients (26 to 28 patients per treatment), 18 years or older, with severe postepisiotomy pain were randomized to one of the four treatments. Treatments were assessed over a 6-hour period using standard scales for pain intensity and pain relief and a number of derived variables based on these data. Since the study medications were not identical in appearance, the preparation and administration of the study medication, and the observation of the patient, were carried out by two different individuals to maintain double-blind conditions. RESULTS: All active treatments were significantly superior to placebo for several measures of analgesia including 4-hour and 6-hour SPID and TOTPAR scores. The global rating was assessed as "good" or "excellent" by over 75% of the patients in the active treatment groups compared to 7.4% of the patients in the placebo group. Reduction in pain intensity was very similar for the two-dose levels of ketoprofen and the comparator dipyrone 500 mg. CONCLUSION: Ketoprofen 25 mg or 50 mg, and dipyrone 500 mg seem to be equally suited for use as pain relief medication after minor surgery, as well as episiotomy. This study did not demonstrate a need for more than 25 mg of ketoprofen in postepisiotomy pain. All treatments were well tolerated. No adverse events were reported.     

The use of diflunisal in post-operative pain: a report of double-blind Comparative trials in patients after meniscectomy

Summary

A series of double-blind randomized trials was carried out in patients suffering from moderate to severe pain after meniscectomy to assess the analgesic effectiveness of diflunisal. In a single-dose study, 150 patients received either diflunisal (125?mg, 250?mg or 500?mg), aspirin (600?mg), or placebo, and hourly assessments were made of pain severity over an 8-hour period. The results showed that 500?mg diflunisal produced comparable relief to aspirin within 3 to 4 hours, but the analgesic effect continued for longer and was still very marked after 8 hours. A multi-dose study in 120 patients receiving doses of diflunisal (375?mg or 500?mg) or placebo confirmed the overall effectiveness of twice daily treatment with diflunisal. In a comparative study against oxyphenbutazone (200?mg t.i.d.), hourly pain scores made on the first postoperative day showed that a single dose of 500?mg diflunisal produced comparable relief over a 12-hour period to that with 2 doses of 200?mg oxyphenbutazone. Overall response to multiple doses was assessed as excellent or good by all the patients receiving diflunisal. Preliminary results are reported on the use of diflunisal in other painful conditions.     

Efficacy of a paracetamol–pseudoephedrine combination for treatment of nasal congestion and pain-related symptoms in upper respiratory tract infection

ABSTRACT

Objective: This study compared the efficacy of 1000?mg of paracetamol combined with 60?mg of pseudoephedrine, with that of either paracetamol or pseudoephedrine alone and placebo for the treatment of symptomatic URTI.

Research design and methods: A double‐blind, parallel group study was performed on 305 patients with URTI (nasal airflow resistance [NAR] of > 0.25 Pa cm³ s and a global pain score of at least moderate intensity). NAR and pain relief/intensity scores were measured over 4?h after initial dose. Patients then dosed up to three times daily for 3 days and recorded nasal congestion and pain intensity scores.

Main outcome measures: Nasal airflow conductance (NAC) and pain relief after the initial dose were primary objectives. NAC was calculated from NAR. Pain relief was measured on a 5‐point verbal rating scale (VRS) and pain intensity and nasal congestion on a 4‐point VRS. Data were analysed using analysis of covariance. Safety was assessed by adverse events.

Results: A single dose of the combination was superior to paracetamol and placebo for NAC (?p = 0.0001) and was superior to pseudoephedrine and placebo for pain relief (?p ≤ 0.048). Multiple doses of the combination were also superior to paracetamol and placebo for decongestion (?p ≤ 0.021) and were superior to pseudoephedrine and placebo for pain reduction (?p ≤ 0.0057). All treatments were well tolerated.

Conclusions: The combination treatment provided a greater decongestant effect than either paracetamol or placebo and better pain relief than either pseudoephedrine or placebo. The additive effect of the combination was apparent for both single and multiple doses.     

Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative analgesia after surgery for breast cancer

ABSTRACT

Objective: To assess clinical efficacy of IV paracetamol 1?g and IV dipyrone 1?g on a 24.h dosing schedule in this randomised, double-blinded study of 40 ASA I–III (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer.

Research design and methods: General anaesthesia using remifentanil and propofol was performed for surgery. The patients were randomly allocated to two groups, receiving infusions of paracetamol 1?g/100?mL (Para Group) or of dipyrone 1?g/100?mL (Dipy Group) 30?min before arrival in the recovery area and every 6?h up to 24?h postoperatively. All patients had unrestricted access to opioid rescue medication via an IV patient-controlled analgesia (PCA) device.

Main outcome measures: The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 30?h postoperatively. The equivalence margin was determined as ±10?mm on the visual analogue scale (VAS).

Results: Regarding pain scores at rest, the 90% CI of the mean differences between the treatment groups over 30?h postoperatively was found to be within the predefined equivalence margin [+7.5/–6.2], and the CI values for pain scores on coughing [+7.3/–9.0] were similar. The two groups did not differ in cumulative opioid rescue consumption (Dipy-Group 14.8 ± 17.7?mg vs. Para Group 12.1 ± 8.8?mg, p = 0.54) nor in piritramide loading dose (Dipy Group 0.95 ± 2.8?mg vs. Para Group 1.3 ± 2.8?mg, p = 0.545). Five patients in the Dipy Group experienced hypotension in contrast to none in the Para Group (?p = 0.047). There were no significant between-treatment differences for other adverse events, patient satisfaction scores (?p = 0.4) or quality of recovery scores (?p = 0.3).

Conclusion: IV paracetamol 1?g is clinically equivalent to IV dipyrone 1?g for postoperative analgesia after surgery for breast cancer.     

A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy

Summary

A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125?mg, 250?mg, or 500?mg), aspirin (600?mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500?mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.     

The Onset of Action and the Analgesic Efficacy of Saridon®* (a Propyphenazone/Paracetamol/Caffeine Combination) in Comparison with Paracetamol,Ibuprofen, Aspirin and Placebo (Pooled Statistical Analysis)

Summary

The objective was to evaluate the onset of action, analgesic efficacy and tolerability of Saridon, a propyphenazone 150?mg/paracetamol 250?mg/caffeine 50?mg combination, in comparison with paracetamol 500?mg, aspirin 500?mg, ibuprofen 200?mg and placebo, by a pooled statistical analysis of eight studies. Out of 500 generally healthy patients (55.2% men, 44.8% women), average age 43.5 years, 329 (65.8%) had moderate and 171 (34.2%) severe acute dentoalveolar pain. More Saridon-treated patients reported ‘pain gone/partly gone’ and less ‘pain unchanged or worse’ compared with paracetamol, aspirin and placebo 30?min (p?=?0.009, p?<?0.001, p?=?0.001, respectively) and 60?min after dosing (p?<?0.0001 for all). The difference with ibuprofen was observed 60?min after dosing (p?<?0.01). Pain intensity differences 30?min and 60?min after dosing infer that Saridon has a faster onset of action than all of the other medications that it was compared with (ibuprofen at only 60?min after dosing). Total pain relief scores four hours after dosing were higher in the Saridon group compared with the paracetamol, ibuprofen, placebo (p?<?0.0001 for all) and aspirin groups (p?<?0.01). At the end of the study, patients assessed Saridon as more efficacious than the other study medications (p?<?0.0001 for all). No serious adverse events were observed with any of the drugs studied. All medications were well tolerated. Twenty patients (4.0%) reported adverse events with no significant differences between groups. The most common adverse events were gastrointestinal disorders, followed by nervous system, skin, subcutaneous tissue, respiratory, cardiac and general disorders. Saridon is an effective analgesic that combines the advantage of fast onset and effective analgesia as compared with paracetamol alone, ibuprofen, aspirin or placebo. The results of this pooled analysis of eight studies should be confirmed in a double-blind study, since seven of the studies included in this analysis were single blind.     

Comparison of intravenous dexketoprofen and dipyrone in acute renal colic

Objective

The aim of this study was to assess the efficacy and safety of a single intravenous (i.v.) bolus of dexketoprofen trometamol compared with an i.v. infusion of dipyrone in patients with moderate to severe pain due to renal colic.

Methods

A total of 308 patients with renal colic and visual analog scale (VAS) score ≥40 mm participated in a multicenter, randomized, double blind, double-dummy, parallel, and active-controlled study and were randomized to dexketoprofen 25 mg (n?=?101), dexketoprofen 50 mg (n?=?104), and dipyrone 2 g (n?=?103).

Results

Mean [± standard deviation (SD)] total pain relief (TOTPAR) scores were similar in the dexketoprofen 50 mg (15.3?±?8.6) and dipyrone (15.5?±?8.6) and slighly higher than in dexketoprofen 25 mg (13.5?±?8.6), although significant differences were not achieved. In the same way, patients in the dexketoprofen 50 mg and dipyrone groups showed higher scores in the sum of pain intensity differences (SPID) and the sum of analogue pain intensity differences (SAPID) than patients in the dexketoprofen 25 mg group, reaching statistical significance in comparison with dexketoprofen 25 mg and dipyrone for SPID and SAPID (p?p?Conclusions Dexketoprofen 50 mg administered as a single i.v. bolus was effective for the relief of moderate to severe pain in patients with renal colic, with a good safety profile and efficacy similar to i.v. dipyrone 2 g. Dexketoprofen produced analgesia that was faster in onset.     

Diflunisal in the management of sprains

Summary

A double-blind randomized trial was carried out in 31 patients suffering from acute, minor ligamentous injuries to compare the efficacy of diflunisal in the relief of pain with that of oxyphenbutazone. Patients received either 500?mg diflunisal twice daily or 200?mg oxyphenbutazone 3-times daily for 3 days. The results of subjective assessments showed that by Day 3 spontaneous pain had either completely resolved or markedly improved in all patients, and that diflunisal was significantly better than oxyphenbutazone on Days 1 and 3 in relieving pain on movement of the joint.     

Radiotherapy plus either transdermal fentanyl or paracetamol and codeine for painful bone metastases: a randomised study of pain relief and quality of life

SUMMARY

Objective: To compare the effects of providing analgesia with either transdermal fentanyl (TTS-fentanyl) or paracetamol and codeine (P/C) in addition to radiotherapy in patients with metastatic bone pain.

Methods: In a prospective study, 26 patients with radiologically confirmed bony metastases received radiotherapy (R/T). They were randomised to receive either 500?mg paracetamol and 30?mg codeine four times per day (P/C group), or transdermal fentanyl patches delivering 25|ig fentanyl/h (TTS-fentanyl group). Pain was assessed using visual analogue pain ratings (VAS) and the Greek Brief Pain Inventory (G-BPI) questionnaire administered before R/T and after 3 months.

Results: Data were available from 24 eligible patients. Use of TTS-fentanyl was associated with significantly superior pain relief. Mean VAS fell from 7.0 to 1.1 with TTS-fentanyl and from 8.3 to 4.3 with P/C, p?<?0.01. The TTS-fentanyl group also showed significantly greater improvements of important G-BPI domains including global quality of life, pain, and physical, cognitive, and role functioning, than the P/C group (p?<?0.01). Four patients receiving TTS-fentanyl and three receiving P/C reported severe nausea/vomiting.

Conclusions: Transdermal fentanyl combined with R/T was more effective in reducing metastatic bone pain and resulted in greater improvements in quality of life than paracetamol and codeine.     

Efficacy of a paracetamol and caffeine combination in the treatment of the key symptoms of primary dysmenorrhoea

ABSTRACT

Objective: Primary dysmenorrhoea is characterised by pain, cramping and backache at the time of menses. Despite the high prevalence of dysmenorrhoea, few sufficiently powered, placebo-controlled studies have examined the efficacy of over the counter analgesics in this condition. Furthermore, even fewer studies have directly examined the efficacy of analgesics on specific dysmenorrhoea symptoms.

Research design and main outcome measures: This was a single-dose, placebo-controlled, double blind, crossover study carried out in 320 women with moderate-to-severe dysmenorrhoea pain. At 2?h following dosing, 1?g paracetamol plus 130?mg caffeine led to significantly greater pain relief compared to 1?g paracetamol alone (?p < 0.05), 130?mg caffeine alone (?p < 0.01) or placebo (?p < 0.01). The combination was also significantly more effective in relieving abdominal cramping and backache compared to the other treatment arms. No major treatment related adverse events were reported during this study.

Conclusions: When taken at recommended doses, both paracetamol and the combination of paracetamol and caffeine are safe and effective treatments for primary dysmenorrhoea. Consistent with results from other acute pain states, caffeine acts as an analgesic adjuvant and enhances the efficacy of paracetamol.     

Tramadol/paracetamol

The orally administered fixed combination tablet of tramadol (centrally-acting opiate) plus paracetamol (acetaminophen; nonopiate, nonsalicylate analgesic) [37.5/325 mg] provides effective analgesia in patients with moderate to severe acute pain and those with chronic painful conditions characterised by intermittent exacerbations of pain. Two tramadol/paracetamol 37.5/325 mg tablets provided greater relief of dental pain over an 8-hour period than either agent alone, with a faster onset of action than tramadol alone and a longer duration of action than either agent as monotherapy. In patients with postoperative dental pain, two tramadol/paracetamol tablets (37.5/325 mg) provided similar analgesia to hydrocodone/paracetamol 10/650 mg over an 8-hour period. The addition of one or two tramadol/paracetamol 37.5/32 5mg tablets (up to four times daily) for 5 days to existing NSAID or cyclo-oxygenase-2 inhibitor analgesic therapy provided effective pain relief in patients with osteoarthritis flare pain. Tramadol/paracetamol 37.5/325 mg provided similar efficacy to that of codeine/paracetamol 30/300 mg in patients with chronic back pain in a 4-week, randomised, double-blind trial (a maximum of 10 tablets or capsules per day of the active drug).     

The efficacy of ketoprofen and paracetamol (acetaminophen) in postoperative pain after third molar surgery

1 A placebo-controlled, double-blind, randomized trial was carried out to evaluate the efficacy of single doses of racemic ketoprofen 12.5 and 25  mg and paracetamol 500 and 1000  mg in patients with post-operative pain after third molar surgery over a 6  h investigation period.
2 Outcome variables included overall pain scores (AUC(0,360  min), maximum pain relief, pain relief at 1  h after dosage and the number of patients taking escape analgesics.
3 Overall pain scores (AUC(0,360  min) were significantly lower for all active treatments when compared to placebo ( P <0.01).
4 Both ketoprofen treatments and patients treated with paracetamol 1000  mg reported significantly greater pain relief ( P <0.01) and a later time to taking escape analgesics ( P <0.01) than patients medicated with placebo.
5 At 1  h after dosage, pain scores were significantly less ( P <0.01) after both doses of ketoprofen when compared with placebo.
6 Single doses of ketoprofen 12.5 and 25  mg, together with paracetamol 1000  mg are effective analgesics for treating post-operative pain after third molar surgery. These treatments provide up to 4  h of pain relief after this surgical procedure.     

Effect of a combination of orphenadrine/paracetamol tablets (‘Norgesic’) on myalgia: A double-blind comparison with placebo in general practice

Summary

The clinical efficacy and tolerability of a combination preparation (‘Norgesic’) of 35?mg orphenadrine plus 450?mg paracetamol was compared with that of placebo in a controlled double-blind, parallel group, 7-day study comprising 44 patients suffering from pain due to tension of the cervical and upper thoracic musculature. The patients were allocated at random into two homogenous groups, stratified by sex and initial pain intensity. One group received the combination, the other placebo. The dosage used was 1 tablet 3-times daily. The effect of treatment of pain was assessed daily using a visual analogue scale. Despite the low dosage used, orphenadrine/paracetamol produced statistically significant pain relief from initial levels by and from the second day of the study. Comparison between the groups showed that the analgesic efficacy of the combination was significantly superior to that of placebo from the third day of treatment. These results confirm the efficacy of a combination of orphenadrine/paracetamol in patients suffering from myalgia nuchae.     

Single-dose dextropropoxyphene in post-operative pain: a quantitative systematic review

Objective: To determine the analgesic efficacy and adverse effects of single-dose oral dextropropoxyphene alone and in combination with paracetamol for moderate to severe post-operative pain. Methods: Published reports were identified from a variety of electronic databases including MEDLINE, Biological Abstracts, EMBASE, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat for one patient to achieve at least 50% pain relief. Six reports (440 patients) compared dextropropoxyphene with placebo and five (963 patients) compared dextropropoxyphene plus paracetamol 650 mg with placebo. Results: For a single dose of dextropropoxyphene 65 mg in post-operative pain the number-needed-to-treat for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22) when compared with placebo over 4–6 h. For the equivalent dose of dextropropoxyphene in combination with paracetamol 650 mg the number-needed-to-treat was 4.4 (3.5 to 5.6) when compared with placebo. Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol when compared with placebo. A rank order of single-dose analgesic effectiveness in post-operative pain of moderate to severe intensity obtained from similar systematic reviews is presented. Conclusion: Dextropropoxyphene 65 mg plus paracetamol 650 mg has a similar analgesic efficacy to that of tramadol 100 mg but with a lower incidence of adverse effects. Ibuprofen 400 mg has a lower (better) number-needed-to-treat than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg. Received: 2 June 1997 / Accepted in revised form: 11 November 1997     

Analgesia following oral surgery for day patients: a clincial comparison of two analgesics.

A single-blind, between-patient study was carried out in 167 patients following oral surgery to compare the effectiveness and tolerance of two combination analgesic preparations; pentazocine (15 mg) plus paracetamol (500 mg) and dextropropoxyphene hydrochloride (32.5 mg) plus paracetamol (325 mg). Assessments of pain and pain relief were made over two periods, initially over the 90 minute period following administration of either preparation and secondly, over the subsequent 3 days following discharge. At the hospital, those patients receiving pentazocine plus paracetamol achieved a greater relief of pain than those receiving dextropropoxyphene plus paracetamol, though the differences did not reach statistical significance. At home, pain relief was very similar for both groups of patients, both preparations being effective and well tolerated.     

A double-blind comparison of meptazinol versus paracetamol and placebo in acute and chronic painful conditions presenting to the general practitioner

Summary

A double-blind study was carried out in 90 patients with acute or chronic painful musculoskeletal conditions of at least moderate severity to compare the efyectiveness over a 72-hour period of oral treatment, 3 to 6 hourly, with 200 rng meptazinol, 1?g paracetamol and placebo. Assessments of pain by physicians and patients indicated that both active treatments produced effective analgesia compared with placebo. No significant dgferences were observed between meptazinol and paracetamol. The frequency of adverse effects reported was low and similar in all three treatment groups.     

A controlled study of diflunisal in Sprains and Strains

Summary

A preliminary double-blind, randomized trial was carried out in general practice to compare the efficacy of treatment with diflunisal (500?mg) twice daily and a combination of dextropropoxyphene (65?mg) plus paracetamol (650?mg) 3-times daily for 3 days in relieving pain associated with strains and sprains. Analysis of the results from 51 patients showed that both treatments were equally effective in relieving spontaneous pain and pain on movement after 1 and 3 days, and there were no differences between the two groups in patients' overall evaluation of treatment or physicians' assessment of therapeutic response. Both treatments were well tolerated during the short-term period of the trial.