Single dose oral flurbiprofen for acute postoperative pain in adults

Nuffield Department of Anaesthetics, Oxford Radcliffe Hospitals NHS Trust, Headley Way, Oxford, UK, OX3 9DU.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 02/2009; DOI: 10.1002/14651858.CD007358.pub2
Source: PubMed

ABSTRACT Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain.
To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults.
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009.
Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain.
Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected.
Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions.The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25% and 16% of participants with flurbiprofen 50 mg and 100 mg over 6 hours, compared with almost 70% with placebo.Adverse events were uncommon, and not significantly different from placebo.
Flurbiprofen at doses of 50 mg and 100 mg is an effective analgesic in moderate to severe acute postoperative pain. The NNT for at least 50% pain relief is similar to that of commonly used NSAIDs such as ibuprofen and naproxen at usual doses. Use of rescue medication indicates a duration of action exceeding 6 hours.

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    ABSTRACT: BACKGROUND: Post-thymectomy pain in myasthenia gravis (MG) patients can inhibit breathing and coughing. Inappropriate usage of analgesics may exacerbate respiratory inhibition and even cause myasthenic crisis. Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used to control moderate postoperative pain and is not associated with respiratory inhibition. We hypothesized that flurbiprofen may provide post-thymectomy pain relief without increasing the risk of complications in MG patients. METHODS: Two hundred MG patients underwent extended thymectomy from March 2006 to December 2010 and were randomly allocated to a flurbiprofen group (110 patients, 50 mg intravenous flurbiprofen axetil) or a control group (90 patients, 100 mg intramuscular tramadol) as postoperative analgesia. Visual analog scale (VAS) pain score, heart rate, blood pressure, respiratory rate, pulse oximetry (SpO2), and adverse effects were recorded before and up to 24 h after drug administration. RESULTS: There were no significant differences in the preoperative clinical characteristics of the flurbiprofen and control (tramadol) groups. Both flurbiprofen and tramadol significantly alleviated post-thymectomy pain (p < 0.05 for both), but patients in flurbiprofen group had significantly lower VAS pain scores at 0.5 h, 2 h, 4 h, and 8 h after surgery (p < 0.05 for all times). There were no significant post-thymectomy changes of heart rate, respiratory rate, mean arterial blood pressure, or SpO2 in either group at all time points. CONCLUSIONS: Post-thymectomy intravenous administration of flurbiprofen axetil provides safe and effective analgesia for MG patients.
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    ABSTRACT: Chemistry Flurbiprofen, a non steroidal anti-inflammatory drug is a phenylalkanoic acid derivative (2-2-Fluoro-4-biphenyl 4-yl, propionic acid) having molecular weight 244.3 g/mol with molecular formula of C 15 H 13 FO 2 [1-3]. Flurbiprofen is commercially available as a racemate blend of (+) Sand (-) R-enantiomers. The enanteomeric form of the drug has potentially developing role in the treatment of Alzheimer's disease and metastatic prostate cancer with anti-inflammatory activity [4-5]. Davis et al in 2000 observed the significant stimulatory effects on intestinal permeability in rats followed single oral doses of Flurbiprofen as racemate and enantiomer [6] (Figure 1). Pharmacokinetics Flurbiprofen completely absorbed after oral administration [7] with peak plasma levels occurring at 1 hour Plasma concentration is related to dosage in the range 15 to 150 mg and peak plasma concentration is about 12μg/ml after a 100 mg dose and is usually attained 1.5 to 3 hours after ingestion [8,9]. Flurbiprofen is 99% bound to human serum albumin [10,11]. Flurbiprofen undergoes rapid oxidative metabolism and is excreted primarily in the urine as both glucuronide and sulphate conjugates and approx 20% of drug eliminated unchanged [10,11]. There are no known active metabolites in humans and there is no evidence of dose dependent alterations of pharmacokinetics or of drug accumulation in plasma after multiple dose administration. The elimination half-life is about 3.5 hours during repeated doses [12]. Gastric emptying rate is found notably higher in fed state [13]. Flurbiprofen is a CYP2C9 substrate and modification of the Dose adjustments are recommended when given with inhibitor of CYP2C9 agents [14]. Flurbiprofen gastrointestinal tolerance is considered better than other NSAIDs i.e. indomethacin and aspirin, and comparable to naproxen and ibuprofen. It has shown no problematic or irreversible hepatotoxic, carcinogenic or teratogenic effects. Hypertensive and renal effects are probably similar to other NSAIDs.
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    ABSTRACT: Background. Post-craniotomy intracranial haematoma is one of the most serious complications after neurosurgery. We examined whether post-craniotomy intracranial haematoma requiring surgery is associated with the non-steroidal anti-inflammatory drugs fiurbiprofen, hypertension, or hydroxyethyl starch (HES). Methods. A case-control study was conducted among 42 359 patients who underwent elective craniotomy procedures at Beijing Tiantan Hospital between January 2006 and December 2011. A one-to-one control group without post-craniotomy intracranial haematoma was selected matched by age, pathologic diagnosis, tumour location, and surgeon. Perioperative blood pressure records up to the diagnosis of haematoma, the use of flurbiprofen and HES were examined. The incidence of post-craniotomy intracranial haematoma and the odds ratios for the risk factors were determined. Results. A total of 202 patients suffered post-craniotomy intracranial haematoma during the study period, for an incidence of 0.48% (95% CI=0.41 -0.55). Haematoma requiring surgery was associated with an intraoperative systolic blood pressure of >160 mm Hg (OR=2.618, 95% CI=2.084-2.723, P=0.007), an intraoperative mean blood pressure of >110 mm Hg (OR=2.600, 95% CI=2.312-3.098, P=0.037), a postoperative systolic blood pressure of >160 mm Hg (OR=2.060, 95% CI=1.763-2.642, P=0.022), a postoperative mean blood pressure of >110 mm Hg (OR=3.600, 95% CI=3.226-4.057, P=0.001), and the use of fiurbiprofen during but not after the surgery (OR=2.256, 95% CI=2.004-2.598, P=0.005). The intraoperative infusion of HES showed no significant difference between patients who had a haematoma and those who did not. Conclusions. Intraoperative and postoperative hypertension and the use of fiurbiprofen during surgery are risk factors for post-craniotomy intracranial haematoma requiring surgery. The intraoperative infusion of HES was not associated with a higher incidence of haematonna.
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