Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.

BACKGROUND: There has been a trend over recent years for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However, therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We evaluated the efficacy of the combination of paracetamol and an NSAID versus either drug alone in various acute pain models. METHODS: A systematic literature search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed covering the period from January 1988 to June 2009 was performed to identify randomized controlled trials in humans that specifically compared combinations of paracetamol with various NSAIDs versus at least 1 of these constituent drugs. Identified studies were stratified into 2 groups: paracetamol/NSAID combinations versus paracetamol or NSAIDs. We analyzed pain intensity scores and supplemental analgesic requirements as primary outcome measures. In addition, each study was graded for quality using a validated scale. RESULTS: Twenty-one human studies enrolling 1909 patients were analyzed. The NSAIDs used were ibuprofen (n = 6), diclofenac (n = 8), ketoprofen (n = 3), ketorolac (n = 1), aspirin (n = 1), tenoxicam (n = 1), and rofecoxib (n = 1). The combination of paracetamol and NSAID was more effective than paracetamol or NSAID alone in 85% and 64% of relevant studies, respectively. The pain intensity and analgesic supplementation was 35.0% +/- 10.9% and 38.8% +/- 13.1% lesser, respectively, in the positive studies for the combination versus paracetamol group, and 37.7% +/- 26.6% and 31.3% +/- 13.4% lesser, respectively, in the positive studies for the combination versus the NSAID group. No statistical difference in median quality scores was found between experimental groups. CONCLUSION: Current evidence suggests that a combination of paracetamol and an NSAID may offer superior analgesia compared with either drug alone.

The analgesic efficacy of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery.

PURPOSE: The aim of this study was to compare the analgesic efficacy of single-dose preoperative intravenous versus oral tramadol for preventing pain after third molar surgery. PATIENTS AND METHODS: Seventy-two patients undergoing elective third molar surgery were randomized to receive either intravenous (n = 36) or oral (n = 36) tramadol 50 mg. The intravenous group received an oral placebo capsule followed by intravenous tramadol 50 mg preoperatively. The oral tramadol group received a 50-mg oral tramadol capsule followed by intravenous placebo saline preoperatively. In both groups, a standard intravenous sedation technique was administered and the impacted third molars were removed under local anesthesia. The difference in postoperative pain was assessed by 4 primary end points: hourly pain intensity as measured by a 100-mm visual analog scale for 8 hours, time to rescue analgesic, postoperative acetaminophen consumption, and a 5-point global assessment scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent). RESULTS: Throughout the 8-hour investigation period, patients reported significantly lower pain intensity scores in the intravenous versus oral group (15.9 +/- 9.6 mm versus 36.9 +/- 17.2 mm, P = .03). Patients also reported significantly longer time to rescue analgesic (7.0 hours versus 3.5 hours, P = .00001), lesser postoperative acetaminophen consumption (1,823 +/- 1,266 mg versus 3,558 +/- 1,418 mg, P = .000006), and better global assessment (2.6 +/- 0.9 versus 1.1 +/- 0.8, P = .01) for the intravenous versus oral group. CONCLUSIONS: We conclude that preoperative intravenous tramadol is superior to oral tramadol for preventing postoperative pain following third molar surgery. However, it should be noted that there is a difference in the bioavailability between the 2 formulations of up to 30%, which may explain the findings.

The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis.

Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.

Sedation with midazolam leads to reduced pain after dental surgery.

UNLABELLED: Our principal objective in this study was to evaluate the potential pain reducing effect of i.v. midazolam in patients undergoing oral surgery. One-hundred-twenty-five patients with impacted mandibular third molars requiring removal under local anesthetic were randomized into 2 groups. The first group (n = 64) was administered i.v. midazolam by titration until a clinical end-point of conscious sedation followed by local anesthetic before surgery; the second group (n = 61) was the control and was administered only local anesthetic before surgery. The surgery was performed in a standardized manner in both groups by the same surgeon. Outcome measures were four primary end-points: pain intensity as assessed by a 100-mm visual analogue scale and a 4-point categorized scale hourly for 8 h, time to first analgesic, total analgesic (ibuprofen) consumption over the first 48 h, and a 5-point categorical patient global assessment scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent). Throughout the 8-h investigation period, patients in the midazolam group reported significantly lower pain intensity scores than those in the control group (19.0 +/- 13.2 mm versus 28.1 +/- 12.8 mm, P < 0.05). The patients in the midazolam group also reported significantly longer time to first analgesic (165.5 +/- 56.5 min versus 202.2 +/- 79.0 min, P < 0.05), less analgesic consumption (1275 +/- 364 mg versus 1688 +/- 407 mg, P < 0.001) and better patient global assessment (3.34 +/- 0.8 versus 2.4 +/- 0.9, P < 0.001). We conclude that systemically administered midazolam is effective in reducing postoperative pain after third molar surgery. IMPLICATIONS: In this observer blinded study, we found that i.v. midazolam treatment (0.09 mg/kg) has a pain-reducing effect after third molar surgery, thus improving postoperative pain management.

Pathogenesis of postoperative oral surgical pain.

Pain is a major postoperative symptom in many oral surgical procedures. It is a complex and variable phenomenon that can be influenced by many factors. Good management of oral surgical pain requires a detailed understanding of the pathogenesis of surgical pain. This article aims at reviewing postoperative pain from a broad perspective by looking into the nociception, neuroanatomy, neurophysiology, and neuropharmacology of pain. Therapeutic recommendations are made after reviewing the evidence from the literature for maximizing the efficacy of pain management techniques for oral surgical pain.