Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: a single-dose, randomized, placebo-controlled, and double-blind study

Purpose Effect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg, and placebo were investigated to establish the multidimensional pharmacodynamic profiles of each drug on acute pain with calculated effect size estimates. Methods A randomized, double-blind, single-dose, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 350 patients (mean age 25 year, range 18 to 30 years) of homogenous ethnicity after third molar surgery. Primary outcome was sum pain intensity over 6 h. Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference, maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat values, adverse effects, overall drug assessment as patient-reported outcome measure (PROM), and the effect size estimates NNT and NNTp. Results Ibuprofen doses above 400 mg do not significantly increase analgesic effect. Paracetamol has a very flat analgesic dose–response profile. Paracetamol 1000/codeine 60 mg gives similar analgesia as ibuprofen from 400 mg, but has a shorter time to analgesic onset. Active drugs show no significant difference in maximal analgesic effect. Other secondary outcomes support these findings. The frequencies of adverse effects were low, mild to moderate in all active groups. NNT and NTTp values did not coincide well with PROMs. Conclusion Ibuprofen doses above 400 mg for acute pain offer limited analgesic gain. Paracetamol 1000 mg/codeine 60 mg is comparable to ibuprofen doses from 400 mg. Calculated effect size estimates and PROM in our study seem not to relate well as clinical analgesic efficacy estimators. Trial registration NCT00699114.

Efficacy and safety of sufentanil sublingual tablet system in postoperative pain management: a systematic review and meta-analysis

BackgroundSufentanil sublingual tablet system (SSTS) is a recently approved formulation for postoperative pain management that has become popular due to its pharmacokinetic properties such as good bioavailability, rapid attainment of equilibrium and elimination without any metabolites, along with its pharmacodynamic properties such as rapid onset and effective pain reduction. It is also relatively well tolerated by patients.ObjectiveThis is a quantitative analysis of the efficacy and safety of SSTS in patients with moderate to severe postoperative pain.DesignThis is a systematic review and meta-analysis. Databases such as Cochrane Library, MEDLINE and EMBASE were searched for eligible articles.SettingsRandomised controlled trials published after 2000 in English language and which assessed at least one of the outcome measures of interest with pain intensity difference between 12 hours and a maximum of 96 hours.ParticipantsAdults with moderate to severe postoperative pain and taking SSTS for pain management.MethodsData were analysed using Review Manager (RevMan) V.5.3. Risk of bias (RoB) assessment was done using RoB-2 scale, and overall grading of evidence of each outcome was done using GRADEpro Guideline Development Tool.ResultsAnalysis of SSTS versus control indicates a statistically significant reduction in summed pain intensity difference at 12 hours (mean difference (MD)=−12.33 (95% CI −15.5 to −9.17), p<0.00001), summed pain intensity difference at 48 hours (MD=−43.57 (95% CI −58.65 to −28.48), p<0.00001), time-weighted total pain relief over 12 hours (MD=−4.77 (95% CI −6.28 to −3.27), p<0.00001) and pain intensity difference (MD=–0.73 (95% CI −1.00 to −0.46), p<0.00001) with SSTS, alongside high quality of evidence. Success of treatment as assessed by Patient Global Assessment (OR=4.01 (95% CI 2.74 to 5.89), p<0.00001) and Healthcare Professional Global Assessment (OR=4.46 (95% CI 3.03 to 6.56), p<0.00001) scoring at 72 hours was observed in a significantly high number of individuals using SSTS, with high quality of evidence. There was no difference in adverse events except for dizziness (RR=1.90, 95% CI 1.02 to 3.52). There was a significantly higher number of total adverse events in orthopaedic surgery in the SSTS group than in the comparator.ConclusionSSTS is effective in postoperative pain management in patients with moderate to severe pain. It also has good tolerability and high patient satisfaction.PROSPERO registration numberCRD42018115458.

Evaluation of topical morphine for treatment of oral mucositis in cancer patients

Introduction: Oral mucositis is a painful side effect to chemotherapy. Orally applied opioids may offer analgesia with fewer side effects than systemic opioids. Methods: A randomized trial comparing the analgesic effect of a morphine oromucosal solution (OM) to placebo and a positive control group receiving intravenous (IV) morphine as an add-on treatment to morphine patient-controlled analgesia (PCA) in a mixed population of paediatric and adult haematology patients. All patients in the study were equipped with a morphine PCA pump and the participating patients were instructed to use this pump as an escape. Primary outcome was morphine consumption (mg/kg/hour) on the PCA pump. Secondary outcomes included pain intensity difference at rest and when performing oral hygiene, time to first PCA bolus, nutrition intake and adverse events. Findings: A total of 60 patients (38 children <18 years) were randomized. Thirty patients were allocated to morphine OM/placebo IV (group MO), 15 patients to placebo OM/morphine IV (group MI) and 15 patients to placebo OM/placebo IV (group P). The median morphine consumption in the MO group (22.7 mcg/kg/hour 95% confidence interval (CI) 19.4–29.4 mcg/kg/hour, p = 0.38) was not significantly different from the placebo group (24.6 mcg/kg/hour 95% CI 16.8–34.4 mcg/kg/hour, p = 0.44) or the MI group (13.7 mcg/kg/hour 95% CI 9.7–37.8 mcg/kg/hour). For the secondary outcomes, the analysis of summed pain intensity difference after the first, third and fourth administrations of study medication indicated a reduction in pain for the MI group compared to the P and MO groups. No serious adverse events were reported. Conclusion: The findings indicate that the analgesic effect of peripherally applied morphine is not significantly different from placebo, and parenteral opioids should continue to be the standard of care.

Efficacy of non-opioid analgesics to control postoperative pain: a network meta-analysis

Background The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. Methods We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000–2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in R to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 h postoperatively (sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish treatments on the basis of their outcomes such that higher SUCRA values indicate better outcomes. The study protocol was prospectively registered with by PROSPERO (CRD42019117360). Results Out of 2313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). MIV was associated with significantly less MME utilization versus all comparators for abdominal procedures, hysterectomy, and versus acetaminophen in orthopedic procedures. Elsewhere MME utilization outcomes for MIV were largely equivalent or nominally better than other comparators. Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). Conclusions MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results as all comparisons involving MIV were indirect.

Efficacy of non-opioid analgesics to control postoperative pain: A network meta-analysis

BACKGROUND The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000-2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in STATA (v15.0) to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 hours postoperatively (Sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish each treatment by efficacy and safety where higher SUCRA values indicated better outcomes. Treatments were also compared by frequency of opioid-related adverse events (ORADEs) including gastrointestinal and respiratory and reduction in morphine milligram equivalents (MME). The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS Out of 2,313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). Significantly lower MME was associated with MIV for abdominal (vs acetaminophen, ibuprofen and ketorolac), bunionectomy (vs acetaminophen), hysterectomy (vs acetaminophen and ketorolac) and orthopedic procedures (vs acetaminophen and ibuprofen). Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS MIV 30mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results, as all comparisons involving MIV were indirect.

Efficacy of non-opioid analgesics to control postoperative pain: A network meta-analysis

BACKGROUND The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000–2019, adult human subjects) of IV nonopioids (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in STATA (v13.0) to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 hours postoperatively (Sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish each treatment by efficacy and safety where higher SUCRA values indicated better outcomes. Treatments were also compared by frequency of opioid-related adverse events (ORADEs) including gastrointestinal and respiratory and reduction in morphine milligram equivalents (MME). The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS Out of 2,313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). Significantly lower MME was associated with MIV for abdominal (vs acetaminophen, ibuprofen and ketorolac), bunionectomy (vs acetaminophen), hysterectomy (vs acetaminophen and ketorolac) and orthopedic procedures (vs acetaminophen and ibuprofen). Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results, as all comparisons involving MIV were indirect.

The Effect of Giving Cold Therapy to Decreased Pain Sprain Ankle Basket Ball Players

Sprain, is an injury to a joint that results in a torn ligament that functions as a binding between bones and as a stabilizer for the joint that occurs due to excessive pressure and sudden movements repeatedly. It is estimated that nearly 1,6 million injuries occur in connection with basketball in Indonesia. The epidemiology of injuries to male basketball players during training is 4,3 per 1000 while the competition is 9,9 per 1000. This study is an experimental study with a Two Group Pre-Test and Post-Test Design. The research subjects were 30 permanent members of the Bangau Basketball Club which were divided into 2 groups: O1 group was a group that was given cold therapy before training alone, O2 group was a group that was given cold therapy after exercise alone. The study was conducted in October-November 2018. There was a difference between pain intensity and the degree of ankle sprain O1 group before and after exercise with the pain intensity difference test value of 0,000 and the value of the ankle sprain degree difference test result of 0,029 (p <0,05). There was a difference between the intensity of pain and the degree of ankle sprain in the O2 group before and after exercise with the test value of the pain intensity difference of 0,024 and the value of the test result of the degree of ankle sprain difference of 0,047 (p <0,05). Wilcoxon test results showed that there was an effect of cold therapy to reduce ankle sprain pain with p <0,05.

The Complex Balance between Analgesic Efficacy, Change of Dose and Safety Profile Over Time, in Cancer Patients Treated with Opioids: Providing the Clinicians with an Evaluation Tool

Background: Scanty data exist on the integration between the analgesic effect of opioids, dose changes, and adverse events in cancer patients. Methods: To provide further information on this issue, we analysed data on 498 advanced-stage cancer patients treated with strong opioids. At baseline and three visits (at days 7, 14, and 21), pain intensity, oral morphine-equivalent daily dose, and the prevalence of major adverse events were measured. The proportion of responders (pain intensity decrease ≥30% from baseline) and non-responders, as well as of patients with low or high dose escalation, was calculated. Results: Pain intensity strongly decreased from baseline (pain intensity difference −4.0 at day 7 and −4.2 at day 21) in responders, while it was quite stable in non-responders (pain intensity difference −0.8 at day 7 and −0.9 at day 21). In low dose escalation patients (82.4% at final visit), daily dose changed from 52.3 to 65.3 mg; in high dose escalation patients (17.6%), it varied from 94.1 to 146.7 mg. Among responders, high dose escalation patients experienced significantly more frequent adverse events compared to low or high dose escalation patients, while no differences were observed in non-responders. Conclusions: The response to opioids results from the combination of three clinical aspects, which are strongly interrelated. These results provide some thoughts to help clinical evaluations and therapeutic decisions regarding opioid use.

Analgesic Efficacy and Tolerability of Tramadol Versus Low Dose Tramadol-Paracetamol in Patients with Gastro Intestinal Surgery

INTRODUCTION: Analgesic regimens with an improved efficacy and tolerability balance have potential to improve acute pain management, and thus reduce the progression into chronic pain. Hence, an opportunity was gained to compare analgesic efficacy and tolerability of Tramadol (T) 1.5 mg/kg versus low dose Tramadol 1mg/kg-Paracetamol 1000mg (T-P) in patient with Gastro Intestinal (GI) surgery. MATERIAL AND METHODS: The study was a hospital based prospective, observational study conducted in sixty post-operative GI surgery patient at Universal College of Medical Sciences-Teaching Hospital, Ranigaon, Bhairahawa, Nepal. One group received Tramadol 1.5mg/kg (n=30) while the other group received Tramadol 1mg/kg with Paracetamol 1000 mg (n=30). The primary efficacy outcome measures were pain intensity difference (PID) and sum of pain intensity difference (SPID) whereas secondary efficacy measures included number of patient who require rescue medication, haemodynamic parameter, their quality of sleep in the night and satisfaction with their medication. For tolerability, adverse effect was noted that occurred during study time intervals. RESULTS: Mean pain intensity differences assessed on Numerical Rating Scores (NRS) were significantly better for Group T-P compared to Group T at all the points except 0.5, 1 and 6 hrs. The sum of pain intensity difference over 8, 16, 24, 48 hrs for Group T-P was significantly superior to Group T. Two patients in Tramadol group required rescue medication. Satisfaction to the pain medication was comparatively higher for Tramadol-Paracetamol group. CONCLUSION :- Tramadol-Paracetamol had more pronounced analgesic effect with lower incidence of side effect than Tramadol alone. Thus, low dose Tramadol-Paracetamol is better option for management of post-operative pain in patient with GI surgery.

Intravenous Lidocaine: Old-School Drug, New Purpose—Reduction of Intractable Pain in Patients with Chemotherapy Induced Peripheral Neuropathy

Background. Treatment of intractable pain due to chemotherapy induced peripheral neuropathy (CIPN) is a challenge. Intravenous (iv) lidocaine has shown to be a treatment option for neuropathic pain of different etiologies. Methods. Lidocaine (1.5 mg/kg in 10 minutes followed by 1.5 mg/kg/h over 5 hours) was administered in nine patients with CIPN, and analgesic effect was evaluated during infusion and after discharge. The immediate effect of lidocaine on pressure pain thresholds (PPT) and the extent of the stocking and glove distribution of sensory abnormalities (cold and pinprick) were assessed. Results. Lidocaine had a significant direct analgesic effect in 8 out of 9 patients (P=0.01) with a pain intensity difference of >30%. Pain reduction persisted in 5 patients for an average of 23 days. Lidocaine did not influence mean PPT, but there was a tendency that the extent of sensory abnormalities decreased after lidocaine. Conclusion. Iv lidocaine has direct analgesic effect in CIPN with a moderate long-term effect and seems to influence the area of cold and pinprick perception. Additional research is needed, using a control group and larger sample sizes to confirm these results.