1) Effectiveness of miscellaneous analgesics with emphasis on dipyrone in the post-operative period of tonsillectomy in children:
Dipyrone has an efficacy, measured by the number of patients needed to treat to achieve a 50% reduction in postoperative pain in 4 to 6 hours, that is lower than potassium diclofenac and etoricoxib, but greater than several NSAIDs (paracetamol, naproxen, ibuprofen, celecoxib, aspirin and sodium diclofenac). Unfortunately, all these estimates are for adults, and there are no similar studies in children34. There is one systematic review specifically evaluating the efficacy of dipyrone in postoperative pain in children35. Ten systematic reviews were identified regarding postoperative analgesia in tonsillectomy performed in children. The first studied the use of systemic paracetamol, NSAIDs and opioids. However, it did not comment on dipyrone36. Two analysed the effect of ketamine via peritonsillar or systemic injection37,38, two studied the effect of corticosteroids39,40, one focused on the effect of bupivacaine41 and the other on dexmedetomidine compared to morphine or fentanyl42. A Cochrane systematic review analysed the form of analgesic prescription (different analgesics, but never dipyrone), if required or fixed43. Finally, there was another review that was restricted to the use of oral rinses and sprays to improve recovery followed by tonsillectomy44. An overview of all these systematic reviews was given in the recent work by Boric et al., 20173.
As demonstrated in the present review, there are only two randomised clinical trials that have evaluated the analgesic effect of dipyrone in the postoperative period of tonsillectomy in children6,7. Unfortunately, it was not possible to perform a meta-analysis, as one study included isolated tonsillectomy7 and the other allowed associated adenoidectomy and / or ventilation tubes6, which can lead to different levels of pain, due to the greater manipulation of the patients. In addition, one study evaluated preemptive6and the other postoperative analgesia7. Finally, the study of pre-emptive analgesia gave a single dose of dipyrone or placebo right after introduction of the anaesthetic6, while the other study evaluated analgesia initiated in the postoperative period through the use of PCA7. The limitation is that PCA is not available in most hospitals and requires the understanding and collaboration of the patient, thus being ineffective for young children.
Both studies demonstrated adequate methodological care, with sample size calculations, and with randomisation performed through the website randomization.com. Moreover, hypotheses were established a priori, with the use of a placebo with the same characteristics as the active medication, with adequate blinding of both patients and examiners, and with effective and validated outcome measures, in addition to a careful choice of the statistical tests used. Together with another study dealing with abdominal surgery5, they comprise the 3 clinical trials with the best level of evidence of all studies commented here, according to the Oxford classification, the GRADE system or the Jadad scores.
However, the studies have short follow-up times (maximum 24 hours). It would be preferable to have a longer follow-up time to monitor the effect of dipyrone, as the pain after tonsillectomy persists for at least 7 days. Another limitation of the results is that, in addition to being developed by the same group of researchers and not being able to be combined for a meta-analysis for the reasons already specified, the data have never been replicated elsewhere by different researchers, which can limit the extrapolation of data to populations other than Turkish patients.