1 Medical Department, IdeaPharma Ltd, Cranfield, UK. 2 Section for Surgical Pathophysiology, The Juliane Marie Centre, Copenhagen, Denmark. 3 Service Anesthesie Reanimation, Hôpital Tenon, Paris, France. 4 Department of Anaesthesia and Intensive Care, University Hospital, Örebro, Sweden
* Corresponding author: Section for Surgical Pathophysiology, The Juliane Marie Centre 4074, Rigshospitalet Blegdamsvej 9, 2100 Copenhagen, Denmark. E-mail: henrik.kehlet{at}rh.dk
Accepted for publication November 16, 2004.
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Abstract |
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Keywords: analgesia, postoperative ; analgesics, non-opioid, acetaminophen ; pain, postoperative ; pharmacology, acetaminophen ; potency, analgesic
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Introduction |
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League tables have been constructed to provide clinicians with an overview of comparative analgesic efficacy and harm, assisting in the planning of postoperative pain management protocols. However, they have a significant limitation: available NNT data have not identified statistically significant differences between analgesics with efficacies as disparate as those of acetaminophen and morphine,2 which is not clinically intuitive. This raises the fundamental question of whether pooling data of analgesic effects from different procedures and in different patient groups limits their interpretability, by creating an average value with a wide margin of error that lacks applicability to particular clinical scenarios.
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Are NNT values for analgesics applicable to specific surgical procedures? |
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A systematic review of the efficacy of acetaminophen, NSAIDs and their combination in postoperative pain was also able to examine relative effects in different pain models.4 Although the reviewers were unable to draw firm conclusions because of methodological problems in some of the individual studies examined, they found evidence that acetaminophen and NSAIDs had equivalent efficacy in major surgery, but that in dental pain NSAIDs had an advantage over acetaminophen for pain scores. This issue has been re-examined recently using data for aspirin, acetaminophen and ibuprofen, with pooled data from two groups of studies: dental extraction and postoperative pain.5 Using 50%maxTOTPAR to calculate NNT values, the authors observed that the relative benefit of these agents did not differ significantly between the two pain models examined. However, in common with the observations of Cooper, the efficacy of placebo and active agents differed, albeit not to the point of statistical significance, between the postoperative and dental pain settings. The relative benefits of aspirin, acetaminophen and ibuprofen were consistently lower in the postoperative than in the dental pain setting (Table 2). Furthermore, as with the analysis of Cooper, the range of benefits within the postoperative group was wider than in the dental group, a finding that again suggests differences between the procedures pooled in the postoperative group.
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Are NNT values for analgesics interpretable for clinical practice? |
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However, the shape of the analgesic benefit curve, not merely the area beneath it, can provide clinically important information. For example, similar AUCs may be achieved with agents with different times of onset, peak analgesic efficacy and duration of action. However, these specific details have significant implications for clinical practice. Furthermore, a 50% maximal pain response may not provide clinically relevant information. Guidelines suggest that a visual analogue scale (VAS) score of <30/100 mm is an appropriate target for analgesia, and a minimum clinically relevant drop in pain intensity has been considered to be 13 mm.12 It is also likely that, in order to achieve a clinically relevant drop in pain intensity, a larger decrease is required in patients with an initially higher pain intensity than in those with a lower pain intensity.13
NNT values based on a 50% response do not therefore provide information on whether the change was from high- or low-intensity pain (for example, from a VAS score of 90 to 45 or from 40 to 20). Additionally, they provide no information on reduction in time or overall need for supplementary analgesia. An analgesic intervention may provide little additional benefit in VAS scores, but may decrease supplementary opioid use; this is an important finding that cannot be contained within an NNT value. Thus, NNT values derived using this method may eliminate the details of analgesic benefits that are important for clinicians in making prescribing decisions.
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How can we optimize postoperative analgesia prescribing decisions? |
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In conclusion, using calculated outcome measures may not provide the most useful or reliable information on analgesic efficacy for clinical practice. It may be that the impact of analgesics vs placebo on pain intensity scores at multiple time pointsone of the most basic measures of efficacystill provides the most useful marker for clinicians. This needs to be supplemented by data on the effects on reducing supplementary analgesic consumption, an important endpoint that has utility in aiding clinicians to reduce postoperative opioid consumption. However efficacy information are presented, it is clear that average values derived by pooling data from different procedures can provide misleading information to clinicians. This reinforces the need to examine procedure-specific outcomes wherever possible, to ensure that postoperative pain management protocols are optimized, although further work is needed to define the boundaries of procedure-specificity.
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Footnotes |
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References |
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