Objectives: This review of systematic reviews evaluated the effectiveness and safety of the preemptive use of anti-inflammatory and analgesic drugs in the management of postoperative pain, edema, and trismus in oral surgery. Materials and methods: The databases searched included the Cochrane Library, MEDLINE, EMBASE, Epistemonikos, Scopus, Web of Science, and Virtual Health Library, up to March 2023. Pairs of reviewers independently selected the studies, extracted the data, and rated their methodological quality using the AMSTAR-2 tool. Results: All of the 19 studies reviewed had at least two critical methodological flaws. Third molar surgery was the most common procedure (n = 15) and the oral route the most frequent approach (n = 14). The use of betamethasone (10, 20, and 60 mg), dexamethasone (4 and 8 mg), methylprednisolone (16, 20, 40, 60, 80, and 125 mg), and prednisolone (10 and 20 mg) by different routes and likewise of celecoxib (200 mg), diclofenac (25, 30, 50, 75, and 100 mg), etoricoxib (120 mg), ibuprofen (400 and 600 mg), ketorolac (30 mg), meloxicam (7.5, 10, and 15 mg), nimesulide (100 mg), and rofecoxib (50 mg) administered by oral, intramuscular, and intravenous routes were found to reduce pain, edema, and trismus in patients undergoing third molar surgery. Data on adverse effects were poorly reported. Conclusion: Further randomized clinical trials should be conducted to confirm these findings, given the wide variety of drugs, doses, and routes of administration used.
Pain is one of the most frequent and relevant symptoms in cancer patients. The World Health Organization's analgesic ladder proposes the use of strong opioids associated with adjuvants such as acetaminophen or nonsteroidal anti-inflammatory drugs in step III. However, it is unclear whether adding acetaminophen to an analgesic regimen based on strong opioids has any benefit in cancer patients with moderate to severe pain. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified two systematic reviews including five randomized trials overall. We extracted data and generated a summary of findings table using the GRADE approach. We concluded that adding acetaminophen to strong opioids might make little or no difference in improving pain management in cancer patients.
DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on noninvasive treatment of low back pain.
METHODS: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials and systematic reviews published through April 2015 on noninvasive pharmacologic and nonpharmacologic treatments for low back pain. Updated searches were performed through November 2016. Clinical outcomes evaluated included reduction or elimination of low back pain, improvement in back-specific and overall function, improvement in health-related quality of life, reduction in work disability and return to work, global improvement, number of back pain episodes or time between episodes, patient satisfaction, and adverse effects.
TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute, subacute, or chronic low back pain.
RECOMMENDATION 1: Given that most patients with acute or subacute low back pain improve over time regardless of treatment, clinicians and patients should select nonpharmacologic treatment with superficial heat (moderate-quality evidence), massage, acupuncture, or spinal manipulation (low-quality evidence). If pharmacologic treatment is desired, clinicians and patients should select nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants (moderate-quality evidence). (Grade: strong recommendation).
RECOMMENDATION 2: For patients with chronic low back pain, clinicians and patients should initially select nonpharmacologic treatment with exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (moderate-quality evidence), tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation (low-quality evidence). (Grade: strong recommendation).
RECOMMENDATION 3: In patients with chronic low back pain who have had an inadequate response to nonpharmacologic therapy, clinicians and patients should consider pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy, or tramadol or duloxetine as second-line therapy. Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. (Grade: weak recommendation, moderate-quality evidence).
RESULTS: Of the 2,545 citations identified at the title and abstract level, a total of 156 publications were included. Most trials enrolled patients with pain symptoms of at least moderate intensity (e.g., >5 on a 0- to 10-point numeric rating scale for pain). Across interventions, pain intensity was the most commonly reported outcome, followed by back-specific function. When present, observed benefits for pain were generally in the small (5 to 10 points on a 0- to 100-point visual analog scale or 0.5 to 1.0 points on a 0- to 10-point numeric rating scale) to moderate (10 to 20 points) range. Effects on function were generally smaller than effects on pain; in some cases, there were positive effects on pain but no effects on function, and fewer studies measured function than pain. Benefits were mostly measured at short-term followup. For acute low back pain, evidence suggested that NSAIDs (strength of evidence [SOE]: low to moderate), skeletal muscle relaxants (SOE; moderate), opioids (SOE; low), exercise (SOE; low), and superficial heat (SOE; moderate) are more effective than placebo, no intervention, or usual care, and that acetaminophen (SOE; low) and systemic corticosteroids (SOE; low) are no more effective than placebo. For chronic low back pain, effective therapies versus placebo, sham, no treatment, usual care, or wait list are NSAIDs, opioids, tramadol, duloxetine, multidisciplinary rehabilitation, acupuncture, and exercise (SOE; moderate) and benzodiazepines, psychological therapies, massage, yoga, tai chi, and low-level laser therapy (SOE; low); spinal manipulation was as effective as other active interventions (SOE; moderate). Few trials evaluated the effectiveness of treatments for radicular low back pain, but the available evidence found that benzodiazepines, corticosteroids, traction, and spinal manipulation were not effective or were associated with small effects (SOE; low). Relatively few trials directly compared the effectiveness of different medications or different nonpharmacological therapies, or compared pharmacological versus nonpharmacological therapies, and they generally found no clear differences in effects. Pharmacological therapies were associated with increased risk of adverse events versus placebo (SOE; low to moderate). Trials were not designed or powered to detect serious harms from pharmacological therapies. Although rates appeared to be low and there was not an increased risk of serious harms versus placebo, this does not rule out significant risk from some treatments. For nonpharmacological therapies, assessment of harms was suboptimal, but serious harms appeared to be rare (SOE; low).
BACKGROUND: Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain.
OBJECTIVES: To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain.
METHODS: We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions. We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo.
MAIN RESULTS: We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations. The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo.
AUTHORS' CONCLUSIONS: There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.
BACKGROUND: This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data.
OBJECTIVES: To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic.
METHODS: We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable.
MAIN RESULTS: The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence).
AUTHORS' CONCLUSIONS: There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.
Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
BACKGROUND: This article is the first in a series presenting the strongest published evidence for physical and rehabilitation medicine (PRM) to date coming from the Cochrane Collaboration. The intent of the series is to stimulate ideas for reviews and research in neglected areas of PRM.
AIM: To systematically review the rehabilitation contents of the Cochrane Collaboration on disabilities due to spinal disorders or pain syndromes in adults.
METHODS: The Cochrane Database of Systematic Reviews was searched at the end of June 2013 for articles relevant for PRM about disabilities resulting from spinal disorders or pain syndromes in adults. Retrieved papers were classified according to the PRM approach: active therapies, which require active participation by patients to achieve treatment goals, and passive treatments, which rely on the application of external forces. The quality of the reviews was checked against the AMSTAR checklist.
RESULTS: Reviews on spinal disorders or pain syndromes were found in the Cochrane Back Group (CBG) and in the Pain, Palliative and Supportive Care Group (CPPSCG). Thirty-eight (42.8%) of 89 Cochrane reviews in the CBG and 7 (2.4%) of 293 Cochrane reviews in the CPPSCG were included. All were of high quality (range, 8-11 points out of 11 on the AMSTAR checklist). The contents of the reviews are given in detail.
CONCLUSION: This review presents an overview of the current evidence for PRM in the treatment of disabilities due to spinal disorders or pain syndromes in adults. Within PRM there is ample space for research in the Cochrane Collaboration and for producing original studies (randomized controlled trials [RCTs]).
CLINICAL REHABILITATION IMPACT: To apply evidence-based clinical practice, clinicians must be familiar with the current best evidence.
BACKGROUND: Medications are the most frequently prescribed therapy for low back pain. A challenge in choosing pharmacologic therapy is that each class of medication is associated with a unique balance of risks and benefits. PURPOSE: To assess benefits and harms of acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, benzodiazepines, antiepileptic drugs, skeletal muscle relaxants, opioid analgesics, tramadol, and systemic corticosteroids for acute or chronic low back pain (with or without leg pain). DATA SOURCES: English-language studies were identified through searches of MEDLINE (through November 2006) and the Cochrane Database of Systematic Reviews (2006, Issue 4). These electronic searches were supplemented by hand searching reference lists and additional citations suggested by experts. STUDY SELECTION: Systematic reviews and randomized trials of dual therapy or monotherapy with 1 or more of the preceding medications for acute or chronic low back pain that reported pain outcomes, back-specific function, general health status, work disability, or patient satisfaction. DATA EXTRACTION: We abstracted information about study design, population characteristics, interventions, outcomes, and adverse events. To grade methodological quality, we used the Oxman criteria for systematic reviews and the Cochrane Back Review Group criteria for individual trials. DATA SYNTHESIS: We found good evidence that NSAIDs, acetaminophen, skeletal muscle relaxants (for acute low back pain), and tricyclic antidepressants (for chronic low back pain) are effective for pain relief. The magnitude of benefit was moderate (effect size of 0.5 to 0.8, improvement of 10 to 20 points on a 100-point visual analogue pain scale, or relative risk of 1.25 to 2.00 for the proportion of patients experiencing clinically significant pain relief), except in the case of tricyclic antidepressants (for which the benefit was small to moderate). We also found fair evidence that opioids, tramadol, benzodiazepines, and gabapentin (for radiculopathy) are effective for pain relief. We found good evidence that systemic corticosteroids are ineffective. Adverse events, such as sedation, varied by medication, although reliable data on serious and long-term harms are sparse. Most trials were short term (< or =4 weeks). Few data address efficacy of dual-medication therapy compared with monotherapy, or beneficial effects on functional outcomes. LIMITATIONS: Our primary source of data was systematic reviews. We included non-English-language trials only if they were included in English-language systematic reviews. CONCLUSIONS: Medications with good evidence of short-term effectiveness for low back pain are NSAIDs, acetaminophen, skeletal muscle relaxants (for acute low back pain), and tricyclic antidepressants (for chronic low back pain). Evidence is insufficient to identify one medication as offering a clear overall net advantage because of complex tradeoffs between benefits and harms. Individual patients are likely to differ in how they weigh potential benefits, harms, and costs of various medications.
Objectives: This review of systematic reviews evaluated the effectiveness and safety of the preemptive use of anti-inflammatory and analgesic drugs in the management of postoperative pain, edema, and trismus in oral surgery. Materials and methods: The databases searched included the Cochrane Library, MEDLINE, EMBASE, Epistemonikos, Scopus, Web of Science, and Virtual Health Library, up to March 2023. Pairs of reviewers independently selected the studies, extracted the data, and rated their methodological quality using the AMSTAR-2 tool. Results: All of the 19 studies reviewed had at least two critical methodological flaws. Third molar surgery was the most common procedure (n = 15) and the oral route the most frequent approach (n = 14). The use of betamethasone (10, 20, and 60 mg), dexamethasone (4 and 8 mg), methylprednisolone (16, 20, 40, 60, 80, and 125 mg), and prednisolone (10 and 20 mg) by different routes and likewise of celecoxib (200 mg), diclofenac (25, 30, 50, 75, and 100 mg), etoricoxib (120 mg), ibuprofen (400 and 600 mg), ketorolac (30 mg), meloxicam (7.5, 10, and 15 mg), nimesulide (100 mg), and rofecoxib (50 mg) administered by oral, intramuscular, and intravenous routes were found to reduce pain, edema, and trismus in patients undergoing third molar surgery. Data on adverse effects were poorly reported. Conclusion: Further randomized clinical trials should be conducted to confirm these findings, given the wide variety of drugs, doses, and routes of administration used.
