◊ BACKGROUND:
Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma. We studied 6-7-year-old children from Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme to investigate the association between paracetamol consumption and asthma.
◊ METHODS:
As part of Phase Three of ISAAC, parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors, including the use of paracetamol for fever in the child's first year of life and the frequency of paracetamol use in the past 12 months. The primary outcome variable was the odds ratio (OR) of asthma symptoms in these children associated with the use of paracetamol for fever in the first year of life, as calculated by logistic regression.
◊ RESULTS:
205 487 children aged 6-7 years from 73 centres in 31 countries were included in the analysis. In the multivariate analyses, use of paracetamol for fever in the first year of life was associated with an increased risk of asthma symptoms when aged 6-7 years (OR 1.46 [95% CI 1.36-1.56]). Current use of paracetamol was associated with a dose-dependent increased risk of asthma symptoms (1.61 [1.46-1.77] and 3.23 [2.91-3.60] for medium and high use vs no use, respectively). Use of paracetamol was similarly associated with the risk of severe asthma symptoms, with population-attributable risks between 22% and 38%. Paracetamol use, both in the first year of life and in children aged 6-7 years, was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema.
◊ CONCLUSIONS:
Use of paracetamol in the first year of life and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood.
◊ Reviewed by Christopher Wu, MD,
Professor of Anesthesiology and Critical Care Medicine,
The Johns Hopkins School of Medicine,
Baltimore, Maryland, USA. chwu@jhmi.edu
The increasing interest and use of a multimodal approach to postoperative analgesia has in part led to investigation of analgesic agents that may not have been clinically used on a widespread basis. One promising agent is magnesium which when administered intravenously has been shown to reduce postoperative analgesic requirements in some clinical trials [1,2]. One of the appeals of magnesium is that it is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Since the NMDA receptor is widely recognized to be important in mediating central sensitization with subsequent development of chronic postsurgical pain, one hypothetical benefit of magnesium would be the reduction in the incidence or severity of chronic postsurgical pain.
One of the interesting and unique aspects of this study is that magnesium was added as an adjuvant to ropivacaine for wound infiltration in patients undergoing radical prostatectomy. It is unclear as to why magnesium administered in this fashion would exhibit an apparently superior analgesic effect compared to that given intravenously. The authors provide several possibilities including inhibition of peripheral NMDA receptors, a direct action by magnesium on the nerve, and a vasodilatory effect (mediated by endothelium nitric oxide) which may attenuate ischemia and pain.
Despite the authors’ findings in this study, overall the benefits of magnesium in postoperative analgesia are uncertain. Two earlier systematic reviews [3,4] examining intravenous magnesium did not indicate any benefit in reduction of postoperative pain. The earlier systematic review [3] examined 4 randomized controlled trials for magnesium and found that none of them demonstrated preventive analgesia. The second review [4] examined 14 randomized trials (778 patients, 404 of whom received magnesium) and noted that postoperative pain intensity was significantly decreased in only 4 trials but did also state that magnesium-treated patients had less postoperative shivering (relative risk = 0.38, 95% confidence interval: 0.17-0.88, number-needed-to-treat = 14). The authors of this systematic review concluded that the available data does not provide convincing evidence that perioperative magnesium may have favorable effects on postoperative pain intensity and analgesic requirements; however, they also mentioned that it may be worthwhile to further study the role of magnesium as a supplement to postoperative analgesia, due to the favorable side-effect profile, cost, and available data elucidating the biological basis for potential antinociceptive effects. Finally, at least one double-blind, placebo-controlled trial also suggests a lack of benefit of intravenous magnesium in reducing long-term chronic pain after surgery (i.e., Cesarean section) [5].
In some ways, this study raises more questions regarding the role of magnesium in postoperative analgesia. Although the analgesic efficacy of intravenous magnesium is uncertain at this time, the infiltration of magnesium may hold more promise. Further investigation in this area should be directed at elucidating the mechanism of analgesia for magnesium administered in this fashion, examining the analgesic effects of wound infusions of regimens containing magnesium, and determining whether this mode of administration of magnesium would result in a decreased incidence or severity of chronic postsurgical pain.
◊ References
1. Kara H, Sahin N, Ulusan V, Aydogdu T.
Magnesium infusion reduces perioperative pain. Eur J Anaesthesiol 2002 Jan;19(1):52-6.
2. Koinig H, Wallner T, Marhofer P, Andel H, Hörauf K, Mayer N.
Magnesium sulfate reduces intra- and postoperative analgesic requirements. Anesth Analg 1998 Jul;87(1):206-10.
3. McCartney CJ, Sinha A, Katz J.
A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg 2004 May;98(5):1385-400.
4. Lysakowski C, Dumont L, Czarnetzki C, Tramèr MR.
Magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials. Anesth Analg 2007 Jun;104(6):1532-9.
5. Paech MJ, Magann EF, Doherty DA, Verity LJ, Newnham JP.
Does magnesium sulfate reduce the short- and long-term requirements for pain relief after caesarean delivery? A double-blind placebo-controlled trial. Am J Obstet Gynecol 2006 Jun;194(6):1596-602.
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