Paracetamol as a prophylactic analgesic for hysterosalpingography: a double blind randomized controlled trial. Efficacy of a paracetamol and caffeine combination in the treatment of the key symptoms of primary dysmenorrhoea. Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: a randomized, controlled trial. Comparison of postpartum pain treatments using a sequential trial design. I. Paracetamol versus placebo. Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain. The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea. Paracetamol 1 g given rectally at the end of minor gynaecological surgery is not efficacious in reducing postoperative pain. [Analgesic and opioid-sparing effects of intravenous paracetamol in the early period after aortocoronary bypass surgery]. Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery.
To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG).
                A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded.
                Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P = 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations.
                Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic analgesic is considered necessary for pain relief during HSG we recommend that a non-steroidal anti-inflammatory drug (NSAID) is used. 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.
                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. Intravenously administered paracetamol is an effective analgesic in postoperative pain management. However, there is a lack of data on the effect of intravenous (i.v.) paracetamol on pain following soft tissue surgery.
                Eighty-seven patients undergoing elective breast surgery with total i.v. anaesthesia (propofol/remifentanil) were randomized to three groups. Group para received 1 g i.v. paracetamol 20 min before and 4, 10 and 16 h after the end of the operation. Group meta and plac received 1 g i.v. metamizol or placebo, respectively, scheduled at the same time points. All patients had access to i.v. morphine on demand to achieve adequate pain relief.
                No significant difference in total morphine consumption between groups was detectable. The proportion of patients who did not receive any morphine in the postoperative period was significantly higher in group para (42%) than in group plac (4%). Ambulation was significantly (P < 0.05) earlier in group para (4.0 +/- 0.2 h) than in groups meta (4.6 +/- 0.2 h) and plac (5.5 +/- 1.0 h). No differences were observed between groups meta and plac. There were no differences between groups with regard to incidence of postoperative nausea and vomiting or changes in vigilance.
                Neither i.v. paracetamol nor i.v. metamizol provided a significant reduction in total postoperative morphine consumption compared with placebo in the management of postoperative pain after elective breast surgery. Administration of paracetamol resulted in a significant reduction in the number of patients needing opioid analgesics to achieve adequate postoperative pain relief. A new sequential test has been used to compare the effect of paracetamol and placebo on uterine cramping. Paracetamol was significantly superior to placebo at the 5% level. 75 patients were included in the trial, whereas in a fixed sample study 90 patients would have been required to obtain the same significance level and power. The magnitude of the difference in treatment effect was estimated following the sequential test. In addition to the effect on uterine pain, which was the primary variable, the effect on episiotomy pain was also estimated. Paracetamol was also superior to placebo against the episiotomy pain. Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied.
                Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data.
                One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L).
                We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested.
                Copyright Acta Anaesthesiologica Scandinavica 47 (2003) To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea.
                In this double-blind, prospective, multicentre, randomised, three-way, crossover study, women were randomly assigned to receive one of six treatment sequences, comprising single oral doses of aceclofenac 100 mg, naproxen 500 mg or placebo, when menstrual pain reached a predetermined level of severity. A single dose of the assigned study medication was taken on three menstrual periods; a different medication was taken on each treatment day. Analgesic efficacy was determined by self-reported analgesia scoring and participants' and investigators' global evaluation of treatment effectiveness. Measurements also included physical examination and adverse events.
                Total pain relief scores were not statistically significantly different for aceclofenac and naproxen, and both were statistically significantly more effective than placebo (p = 0.019 and 0.002, respectively). This finding was supported by secondary endpoints including sum of pain intensity differences (SPID/8), peak analgesia (peak pain intensity and peak pain relief), and participants' and investigators' overall evaluation of effectiveness. Both aceclofenac and naproxen were well tolerated.
                Aceclofenac (100 mg) and naproxen (500 mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria. We studied the analgesic effects of 1 g paracetamol given rectally at the end of surgery in a prospective, randomised, double-blind study.
                One hundred and forty ASA I-II women scheduled for elective termination of pregnancy under general anaesthesia were randomly allocated to receive paracetamol or placebo. All patients had standardised anaesthesia with propofol, fentanyl and oxygen in nitrous oxide. Postoperative pain was assessed by VAS score.
                We could find no difference regarding postoperative pain, need for analgesics or time to discharge between the groups.
                The routine use of 1 g paracetamol given rectally at the end of surgery after termination of pregnancy seems not to be justified. The study was to evaluate the analgesic and opioid-sparing effect of intravenous paracetamol injections in cardiosurgical patients in the early postoperative period. Adequate analgesia within the first 12-18 hours of the early postoperative period is very important for a good prognosis of the further course of pain syndrome and for the reduction of a risk for its progression to its chronic form. In early studies, propacetamol lowered morphine use after orthopedic and gynecological operations. The efficacy of paracetamol used in cardiac surgery has been little studied and the results of the studies are conflicting. The randomized, blind, placebo-controlled study included patients after aortocoronary bypass surgery, of them 22 patients received paracetamol and 23 had placebo. The test drug (perfalgan 100 ml or placebo) was intravenously injected 30 min before extubation and then every 6 hours within succeeding 18 hours. The intensity of the pain syndrome was rated by a 5-score verbal scale every 2 hours. With pain score of 2 or more, promedol was intramuscularly administered in a dose of 10 mg. Inspiratory volume was recorded before extubation and the first administration of a drug just after extubation and then every 2 hours. The baseline indices did not differ in both groups. Throughout the observation, the inspiratory volume was lower in the paracetamol group than in the placebo group; however, there was a statistically significant difference (p = 0.012) in the reduction in the manifestations of the pain syndrome (by 81%) only just after tracheal extubation. During this period, inspiratory volume values were higher in the paracetamol group; however, a statistically significant (39%) difference between the groups in the mean values was obtained only during and 2 hours after extubation. In the perfalgan group, the mean total use of promedol was 36% less than in the placebo-group, which was statistically significant (p = 0.019). The early postoperative use of paracetamol after myocardial revascularization reduces the intake of opioids and diminishes the intensity of the pain syndrome within the first hours after extubation, which promotes a higher thoracic excursion, as confirmed by a statistically significant increase in the maximum inspiratory capacity. The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2 g starting dose.
                A single-centre, randomised, double-blind, placebo-controlled, 3-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were performed before and 48 h after drug administration.
                Two hundred and ninety seven patients (132 = IV paracetamol 2g; 132 = IV paracetamol 1g; 33 = placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV paracetamol 1g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2g were significantly superior to IV paracetamol 1g and to placebo from T30' to T8h (p < 0.0001). Median duration of analgesia was significantly longer following IV paracetamol 2 g compared to IV paracetamol 1g and placebo (p < 0.0001). Adverse events occurred with the same frequency in the 3 treatment groups. No clinically significant changes from baseline were observed for vital signs or laboratory tests.
                The analgesic efficacy of a 2 g starting dose of IV paracetamol was superior over the recommended dose of 1g in terms of magnitude and duration of analgesic effect for postoperative pain following third molar surgery, with no significant difference between groups regarding safety.
More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.