Paracetamol for pain relief after surgical removal of lower wisdom teeth
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the beneficial and harmful effects of paracetamol for pain relief after surgical removal of lower wisdom teeth, compared to placebo, at different doses and administered preoperatively or postoperatively.
PRIMARY
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To test the null hypothesis of no difference in the beneficial and harmful effects between paracetamol and placebo for pain relief in patients requiring surgical removal of a lower wisdom tooth or teeth, against the alternative hypothesis of a difference.
SECONDARY
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To test the null hypothesis of no difference in the beneficial and harmful effects between different doses of paracetamol for pain relief in patients requiring surgical removal of a lower wisdom tooth or teeth, against the alternative hypothesis of a difference.
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To test the null hypothesis of no difference in the beneficial and harmful effects between different times of administration of paracetamol for pain relief in patients requiring surgical removal of a lower wisdom tooth or teeth, against the alternative hypothesis of a difference.
Background
The surgical removal of wisdom teeth is the most commonly performed surgical procedure undertaken in oral surgery practice. Postoperative complications may include swelling, bruising and limited mouth opening but patients are most often concerned about postoperative pain, which may be severe. The pain experienced after oral surgery is a validated and widely used pain model for the clinical evaluation of analgesic efficacy (Cooper 1976). Tissue damage produced during surgery releases chemicals that initiate inflammatory pain by activating and sensitising nerve fibre receptors (Loeser 1999). Chemicals include bradykinin, prostaglandins, serotonin and histamine (Dray 1997).
Paracetamol (acetaminophen) is a non‐opioid analgesic possessing antipyretic activity and is effective in relieving pain with a low incidence of adverse effects (Moore 1998). It is one of the most commonly used analgesics and is widely available without prescription around the world. Paracetamol is often grouped with the nonsteroidal anti‐inflammatory drug (NSAID) family, however, it is considered only to have relatively weak anti‐inflammatory activity (Rang 2003). NSAIDs are assumed largely to produce their analgesia as a result of the inhibition of prostaglandin production by the enzyme cyclo‐oxygenase (Malmberg 1992). Although the mechanism of action has not been fully understood for some time, it was recently reported paracetamol is a selective inhibitor of the newly described COX‐3 enzyme, a cyclo‐oxygenase‐1 variant, in the central nervous system. This inhibition could represent a primary central mechanism by which paracetamol decreases pain and possibly fever (Chandrasekharan 2002). It has been shown to be an effective analgesic in the control of postoperative dental pain in a number of clinical trials (Bentley 1987; Mehlisch 1990; Kiersch 1994). Pain intensity following third molar surgery has been suggested to reach its maximum between three to five hours following surgery (Seymour 1985; Fisher 1988) and therefore this pain model is used to test the efficacy of a single analgesic dose.
A recent systematic review (Moore 1998) has looked at the efficacy and safety of paracetamol for postoperative pain management and has included the findings of studies involving a wide variety of types of surgery such as gynaecology surgery, abdominal surgery, orthopaedic surgery amongst others including the removal of wisdom teeth. There is some debate as to whether dental pain is different from other pain. It has been suggested that the effect of some analgesics including tramadol were worse for dental pain than for other types of postsurgical pain (Moore 1997).
In this review we will be investigating the optimal dose of paracetamol and the optimal time for drug administration to provide pain relief, taking into account the side effects of different doses of the drug. This will inform dentists and their patients of the best strategy for best pain relief after the surgical removal of wisdom teeth.
Objectives
To assess the beneficial and harmful effects of paracetamol for pain relief after surgical removal of lower wisdom teeth, compared to placebo, at different doses and administered preoperatively or postoperatively.
PRIMARY
-
To test the null hypothesis of no difference in the beneficial and harmful effects between paracetamol and placebo for pain relief in patients requiring surgical removal of a lower wisdom tooth or teeth, against the alternative hypothesis of a difference.
SECONDARY
-
To test the null hypothesis of no difference in the beneficial and harmful effects between different doses of paracetamol for pain relief in patients requiring surgical removal of a lower wisdom tooth or teeth, against the alternative hypothesis of a difference.
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To test the null hypothesis of no difference in the beneficial and harmful effects between different times of administration of paracetamol for pain relief in patients requiring surgical removal of a lower wisdom tooth or teeth, against the alternative hypothesis of a difference.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled double blinded clinical trials.
Types of participants
Patients of all health states who require the surgical removal of a lower wisdom tooth or teeth that require(s) bone removal or at least having a baseline pain intensity of moderate to severe pain. Patients who also require removal of an additional tooth or teeth will also be included. Surgery may be undertaken under local anaesthesia, intravenous sedation or general anaesthesia. Patients taking concurrent analgesia will be excluded.
Types of interventions
EFFICACY
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Paracetamol given as a single dose by mouth in any dose and in any formulation (for example, immediate or slow release) regardless of when the single dose was given (for example, preoperatively or postoperatively).
SIDE EFFECTS
In order to investigate side effects more thoroughly, we will be including both single and multiple dose studies.
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Paracetamol given up to seven days by mouth in any dose and in any formulation (for example, immediate or slow release) regardless of when the first dose was given (for example, preoperatively or postoperatively).
CONTROL ‐ PLACEBO
Types of outcome measures
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Pain (visual analogue scale (VAS), categorical verbal rating, verbal numerical scale, global subjective efficacy ratings and other categorical rating scales).
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Pain relief (VAS, categorical verbal rating, verbal numerical scale, global subjective efficacy ratings and other categorical rating scales) and derived pain relief outcomes extracted will be total pain relief (TOTPAR), summed pain intensity difference (SPID) over four to six hours.
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Side effects (for example, hepatic and renal) (binary).
Search methods for identification of studies
To identify studies for inclusion or consideration in this review a detailed search strategy will be developed for each database searched. These will be based on the search strategy developed for MEDLINE but revised appropriately for each database. The search strategy will combine a sensitive search strategy for randomised controlled trials (RCTs) revised from phases one and two of the Cochrane Sensitive Search Strategy for RCTs (as published in Appendix 5b in the Cochrane Reviewers' Handbook). The subject search will use a combination of controlled vocabulary and free text terms based on the following search strategy for searching CENTRAL:
#1. MOLAR THIRD single term (MeSH)
#2. (wisdom next tooth)
#3. (wisdom next teeth)
#4. (third near molar*)
#5. (#1 or #2 or #3 or #4)
#6. TOOTH EXTRACTION single term (MeSH)
#7. (extract* near tooth)
#8. (extract* near teeth)
#9. (extract* near (third next molar*))
#10. (extract* near (third near molar*))
#11. (remov* near tooth)
#12. (remov* near teeth)
#13. (surgical* near remov*)
#14. (surgery near remov*)
#15. (surgical* near extract*)
#16. (surgery near extract*)
#17. (#6 or #7 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16)
#18. (#5 and #17)
DATABASES TO BE SEARCHED
The Cochrane Oral Health Group's Trials Register (most recent)
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library ‐ most recent)
Cochrane Pain Database (most recent)
Palliative Care and Supportive Care Review Group's Trials Register (most recent)
MEDLINE (1966 to most recent)
EMBASE (1980 to most recent)
Current Controlled Trials Register (www.controlled‐trials.com) (most recent)
The bibliographies of papers and review articles will be checked for studies outside the handsearched journals. Personal references will also be searched.
LANGUAGE
There will be no language restrictions and where necessary, translation into the English language of relevant studies will be conducted.
UNPUBLISHED STUDIES
Authors of RCTs identified will be written to in order to obtain further information about the trial and to attempt to identify unpublished or ongoing studies. We will also write to manufacturers of analgesic pharmaceuticals.
HANDSEARCHING
Several journals relevant to this review are being handsearched as part of the Oral Health Group's ongoing journal handsearching programme. The list of the dental journals handsearched by The Cochrane Collaboration can be found at http://www.cochrane‐oral.man.ac.uk.
Data collection and analysis
The titles and abstracts (when available) of all reports identified will be scanned independently and in duplicate by two reviewers. For studies appearing to meet the inclusion criteria, or for which there were insufficient data in the title and abstract to make a clear decision, the full report will be obtained and assessed independently and in duplicate by two reviewers to establish whether the studies meet the inclusion criteria or not. Disagreements will be resolved by discussion. Where resolution is not possible, a third reviewer will be consulted. All studies meeting the inclusion criteria will then undergo quality assessment and data extracted. Studies rejected at this or subsequent stages will be recorded in the table of excluded studies, and reasons for exclusion recorded.
QUALITY ASSESSMENT
The quality assessment of the included trials will be undertaken independently and in duplicate by two reviewers based on what is written in the articles.
Three main quality criteria will be examined:
(1) Randomisation and allocation concealment, recorded as:
(A) Adequate
(B) Unclear
(C) Inadequate
(D) Not used
(2) Completeness of follow up (is there a clear explanation for withdrawals and drop outs in each treatment group?) assessed as:
(A) Yes
(B) No
(3) Whether a sample size calculation was used, assessed as:
(A) Yes
(B) No.
The agreement for the quality criteria between assessors will be determined by Kappa statistics.
After taking into account the additional information provided by the authors of the trials, studies will be grouped into the following categories:
(A) Low risk of bias (plausible bias unlikely to seriously alter the results) if all criteria were met.
(B) Moderate risk of bias (plausible bias that raises some doubt about the results) if one or more criteria are partly met (for example, when authors respond that they had made some attempts to conceal the allocation of patients, to give an explanation for withdrawals, but these attempts were not judged to be ideal, these criteria will be categorised as 'partly').
(C) High risk of bias (plausible bias that seriously weakens confidence in the results) if one or more criteria are not met as described in the Cochrane Reviewers' Handbook 4.2.
We will also report whether the authors of included trials have conducted a sample size calculation.
DATA EXTRACTION
Data will be extracted by two reviewers independently and in duplicate using specially designed data extraction forms. Any disagreement will be discussed and a third reviewer consulted where necessary. Authors will be contacted for clarification of missing information. Data will be excluded until further clarification is available if agreement cannot be reached.
For each trial the following data will be recorded:
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Year of publication, country of origin, setting and source of study funding.
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Details of the participants including demographic characteristics and criteria for inclusion.
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Details on the study design (parallel group or crossover design).
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Details on the type of intervention.
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Details of the outcomes reported, including method of assessment and time intervals.
DATA SYNTHESIS
From the mean total pain relief (TOTPAR) or summed pain intensity difference (SPID) pain indices reported we will compute a dichotomous outcome variable for the number of patients with at least 50% pain relief according to the methods outlined in a Cochrane review (Collins 1998). For each of the three objectives we will examine the appropriateness of different continuous outcome measurements, and some may be meta‐analysed and reported in the final review.
For dichotomous outcomes, the estimate of an intervention will be expressed as relative risks together with 95% confidence intervals. For continuous outcomes, mean differences and 95% confidence intervals will be used to summarise the data for each trial.
Clinical heterogeneity will be assessed by examining the types of participants, interventions and outcomes in each study. Meta‐analysis will be conducted only with studies of similar comparisons reporting the same outcome measures. Relative risks will be used to combine dichotomous data, and weighted mean differences for continuous data, using random effects models. The significance of any discrepancies in the estimates of the treatment effects from the different trials will be assessed by means of Cochran's test for heterogeneity and any heterogeneity investigated.
Subgroup analysis
Subgroup analysis will be conducted for studies :
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Where patients have undergone surgery with local anaesthesia alone, local anaesthesia and intravenous sedation, general anaesthesia alone and general anaesthesia with local anaesthetic.
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Where patients have undergone surgery with bone removal and those who did not have bone removed.
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Where different types of formulation of paracetamol are used: for instance, immediate release versus slow release.
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Where time of administration of paracetamol differs: preoperative versus postoperative.
