Single dose oral naproxen for acute postoperative pain
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
1. To determine the efficacy of a single dose of oral naproxen in treating acute, postoperative pain in adults, compared with placebo.
2. To examine the quality and quantity of data in included studies relating to adverse events.
3. To examine, where possible, evidence for the duration of action of naproxen.
Background
The postoperative period is often dominated by the need to find effective ways of blocking both the inflammatory reaction to surgery and relieving acute pain (Salvato 1992). If managed incorrectly, acute postoperative pain can result in unnecessary chronic pain. In addition, poor postoperative pain management can lead to considerable patient stress and distress. A study by Warfield found that postsurgical pain was the leading cause of concern in 57% of patients before surgery (Warfield 1995).
Non‐steroidal anti‐inflammatory drugs (NSAIDs) demonstrate both analgesic and anti‐inflammatory effects and are therefore commonly used for the relief of postoperative pain. In general, the analgesic effect of NSAIDs comes on quickly and goes away within a few hours; in contrast, the anti‐inflammatory effect comes on over a few days and requires regular, repeated administration. The anti‐inflammatory effect of NSAIDs is thought to result from the inhibition of prostaglandin synthesis and, as the anti‐inflammatory response comes under control, there is a reduction in pain, stiffness, tenderness and swelling (Grahame‐Smith 2002). However, the inhibition of prostaglandin release can also cause damage to the gastrointestinal mucosa, and long‐term use can lead to the development of peptic erosions and ulcers, and gastrointestinal bleeding. In addition, NSAIDs have been associated with acute liver injury, acute renal injury, heart failure, and adverse reproductive outcomes (Hernandez‐Diaz 2001). Although these complications are more likely to occur in patients who take NSAIDs over a long period for the relief of chronic pain, and these drugs generally present fewer risks if used over a short time period (Rapoport 1999), it is important that adverse effects are considered when NSAIDs are used for acute pain management. NSAIDs should be used with caution in the elderly, in pregnant women and in those with renal impairment.
There are many NSAIDs currently in production and use, for example, diclofenac, indomethacin, ibuprofen, ketoprofen and mefenamic acid. The differences between them in terms of efficacy may be small but there is considerable variation in individual patient tolerance, and in the incidence and type of side effects (BNF 2002). This systematic review will assess evidence for the effectiveness of one NSAID, naproxen, and its derivative, naproxen sodium, for the relief of acute postoperative pain. Naproxen and naproxen sodium are commonly prescribed for acute pain (Fricke 1993). Naproxen sodium differs from naproxen in being more soluble and more readily absorbed, thus having a faster analgesic effect. Studies demonstrate that both naproxen and naproxen sodium can be clinically effective in patients with postoperative pain (Rasmussen 1993). In addition, naproxen has the advantage of requiring only one or two doses (the recommended daily dosage being 500‐1000 mg) within a 24‐hour period (BNF 2002).
Objectives
1. To determine the efficacy of a single dose of oral naproxen in treating acute, postoperative pain in adults, compared with placebo.
2. To examine the quality and quantity of data in included studies relating to adverse events.
3. To examine, where possible, evidence for the duration of action of naproxen.
Methods
Criteria for considering studies for this review
Types of studies
Studies will only be included if they meet all of the following criteria:
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randomised, double blind trial to receive either naproxen or a matched placebo
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contain extractable single dose data for the first treatment given
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pain intensity recorded at 4 to 6 hours following initial administration of study treatment using standard pain assessment scales
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minimum of 10 patients randomly assigned to a treatment group.
Abstracts, review articles, case reports and clinical observations will only be included if they contain evaluable data.
Types of participants
Adults (age 15+) experiencing moderate to severe pain following a surgical procedure, carried out in either a day surgery or in‐patients setting.
Types of interventions
Postoperative, oral administration of a single dose of naproxen or naproxen sodium (500‐1000 mg) or a matched placebo.
Types of outcome measures
Primary outcome measures will be patient reported pain relief and pain intensity measured using validated pain scales, ie,
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a five‐point pain relief (PR) scale with standard or comparable wording or
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a four‐point pain intensity (PI) scale or
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a 10 cm visual analogue scale (VAS) for pain relief or pain intensity
Global evaluations of pain relief over 4‐6 hours will also be accepted, if measured on a standard five‐point scale as reported by the patient. The data will be extracted as dichotomous information.
Secondary outcome measures will be:
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duration of action of treatment
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number of patients remedicating following the initial dose and the mean or median time to remedication
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reports of any adverse event experience and reports of particular adverse events such as headache or vomiting
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reasons for patient discontinuation or withdrawal
Search methods for identification of studies
Relevant studies will be sought regardless of language, publication type or publication status.
ELECTRONIC DATABASES
The following electronic databases searched:
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The Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 4 2002)
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MEDLINE and PreMedline 1966 to December 2002
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EMBASE 1980 to December 2002
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PubMed 1966 to December 2002
An in‐house, randomised controlled trials database (1954 to 1995) at the Pain Research Unit, Oxford, will also be searched. No additional hand searching will be conducted for this review.
SEARCH TERMS
The following search strategy will be used for searching MEDLINE and PubMed, and adapted for other databases:
The following free text terms, naproxen and naproxen sodium, together with their registered brand names, will be used.
Naproxen OR " Naproxen sodium" OR Acusprain OR Aleve OR Alganil OR Aliviomas OR Alpoxen OR Alprofen OR Anaprox OR Antalgin OR Aperdan OR Apo‐Napro‐Na OR Apranax OR Arthrosin OR Arthroxen OR Artroxen OR Axer OR Clinosyn OR Continus OR Denaxpren OR Diparene OR Dysmenalgit OR Femex OR Floginax OR Flogogin OR Floxalin OR Genoxen OR Gibinap OR Gibixen OR Gynestral OR Ilagane OR Inza OR Laraflex OR Laser OR Ledox OR Leniatril OR Lundiran OR Madaprox OR Miranax OR Miranax OR Nafasol OR Naparatec OR Napflam OR Napmel OR Naprel OR Napren OR Naprex OR Naprium OR Naprius OR Naprobene OR Naprocoat OR Naprodol OR Napro‐Dorsch OR Naprogesic OR Naprokes OR Naprorex OR Naproscript OR Naprosyn OR Naprosyne OR Naproval OR Naprovite OR Natrioxen OR Naxen OR Naxen OR Nitens OR Novo‐Naprox OR Numidan OR Numide OR Nu‐Naprox OR Nycopren OR Piproxen OR Pranoxen OR Praxenol OR Prexan OR Primeral OR Pronaxen OR Prosaid OR Proxen OR Proxine OR Rheuflex OR Rimoxyn OR Rofanten OR Sobronil OR Synalgo OR Synflex OR Ticoflex OR Timpron OR Traumox OR Valrox OR Xenar OR Xenopan
AND
Randomised control trial (MeSH term) OR Random* OR blind OR double‐blind OR double‐masked OR masked OR trial
AND
Postoperative pain (MeSH term) OR Pain* OR Analgesi*
AND
operat* OR postoperat* OR post‐operat* OR post‐surg* OR surgery OR surgical OR dental OR molar OR extraction OR hernia OR thoracotomy OR urological OR orthop?edic OR post‐orthop?edic OR postorthop?edic OR hysterectomy OR tonsillectomy OR C?esarean OR episiotomy OR laparoscop* OR cholecystectomy
Data collection and analysis
SELECTION OF STUDIES
Studies will be selected on the basis that they meet the selection criteria. This will be independently assessed by at least two reviewers by reading the abstracts of studies found in the search. If insufficient information is given to determine if a trial should be included, or the abstract is not present, a full paper copy will be obtained for assessment. Discrepancies as to whether a trial meets the selection criteria will be settled by discussion. Reasons for excluding trials from the review will be given.
DATA EXTRACTION
From each included study we will extract:
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number of patients treated
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patient characteristics (sex, age, weight)
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baseline pain intensity
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mean total pain relief (TOTPAR) and/or mean summed pain intensity difference (SPID)
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study duration
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treatment dose
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information on adverse events
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number of patients remedicating and time to remedication
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reasons for patient withdrawal and number of withdrawals
DATA SYNTHESIS
Mean TOTPAR or SPID over 4 to 6 hours will be extracted and converted into %maxTOTPAR and/or %maxSPID using verified equations (Moore 1997a; Moore 1997b; Moore 1996, Cooper 1991). These data can then be used to calculate the number of patients with at least 50% pain relief for both naproxen and placebo. The number‐needed‐to‐treat (NNT) and the number‐needed‐to‐harm (NNH) will be calculated, with 95% confidence intervals (Cook 1995). (The confidence interval includes no benefit of one treatment over the other when the upper limit is represented as infinity.)
Meta‐view 4.1 in Review Manager (version 4.1) will be used to calculate relative risk (RR) estimates with 95% confidence intervals, calculated using the fixed effect model (Morris 1995). A statistically significant benefit of the active treatment over placebo will be assumed when the lower limit of the 95% confidence interval (CI) of the relative benefit is more than one (unity). A statistically significant benefit of placebo over the active treatment will be assumed when the upper limit of the 95% CI of the relative benefit is less than one.
The number of patients remedicating and mean time to first remedication (weighted by N) will also be calculated.
Statistical homogeneity of studies used will be assumed when p > 0.01.
Sensitivity analysis for naproxen versus naproxen sodium will only be performed if there are sufficient data.
QUALITY ASSESSMENT
For each study a quality assessment form will be used. This employs a three‐item scale with a maximum quality score of five (Jadad 1996) shown below. A minimum of two points (for randomisation and double blinding) are required for a study to be included in the review.
1) Is the study randomised? If yes, add one point.
Is the randomisation procedure appropriate and reported in the study?
If yes, add one point. If reported but inappropriate, deduct one point.
2) Is the study double blind? If yes, add one point.
Is the double blinding method appropriate and reported in the study?
If yes, add one point. If reported but inappropriate, deduct one point.
3) Are the reasons for patient withdrawals and dropouts described?
If yes, add one point.
