Ramirez L, Cros J, Marin B, Boulogne P, Bergeron A, de Lafont G E, Renon-Carron F, de Vinzelles M-A, Guigonis V, Nathan N, Beaulieu P
Department of Anaesthesia, CHU Limoges, France.
Eur J Pain. 2015 May;19(5):661-8. doi: 10.1002/ejp.587. Epub 2014 Sep 2.
The mechanism of action of acetaminophen remains unclear. One hypothesis involves an interaction with the serotoninergic system. Antagonists to serotonin (5-HT)3 receptors (setrons) have antiemetic properties. Therefore, co-administration of acetaminophen and a setron could lead to a decrease or a loss of acetaminophen analgesic effects. The aim of this study was to demonstrate such an interaction.
Paratron is a prospective, randomized, controlled, double-blind, parallel group trial. All children aged 2-7 years (n = 69) scheduled for a tonsillectomy ± adenoidectomy received intraoperative acetaminophen with ondansetron or droperidol. Pain scores [Children's Hospital of Eastern Ontario Pain Scale (CHEOPS)], morphine consumption and the incidence of post-operative nausea and vomiting (PONV) were measured for 24 h following surgery.
Pain scores were not different at all times between the groups but median morphine consumption (μg) in recovery was 322.5 [interquartile range (IQR) 0.0-500.0] and 0 (IQR 0-0) in the ondansetron (n = 35) and droperidol (n = 34) groups, respectively (p = 0.004). The percentages of patients who received morphine titration were 57.1% and 20.6% in the ondansetron and droperidol groups, respectively (p = 0.008). No significant difference was found for PONV.
An interaction between acetaminophen and ondansetron is suggested, with children receiving three times more morphine during pain titration in the recovery room. More studies are necessary to evaluate whether this finding is clinically relevant enough to preclude the simultaneous perioperative administration of both drugs in the future.
对乙酰氨基酚的作用机制仍不清楚。一种假说涉及与5-羟色胺能系统的相互作用。5-羟色胺（5-HT）3受体拮抗剂（司琼类）具有止吐特性。因此，对乙酰氨基酚与一种司琼类药物联合使用可能会导致对乙酰氨基酚的镇痛效果降低或丧失。本研究的目的是证实这种相互作用。
Paratron是一项前瞻性、随机、对照、双盲、平行组试验。所有计划接受扁桃体切除术±腺样体切除术的2至7岁儿童（n = 69）在术中接受对乙酰氨基酚与昂丹司琼或氟哌利多联合使用。在术后24小时测量疼痛评分[东安大略儿童医院疼痛量表（CHEOPS）]、吗啡消耗量以及术后恶心呕吐（PONV）的发生率。
两组之间在所有时间点的疼痛评分均无差异，但在恢复过程中，昂丹司琼组（n = 35）和氟哌利多组（n = 34）的吗啡消耗量中位数（μg）分别为322.5[四分位间距（IQR）0.0 - 500.0]和0（IQR 0 - 0）（p = 0.004）。在昂丹司琼组和氟哌利多组中，接受吗啡滴定的患者百分比分别为57.1%和20.6%（p = 0.008）。PONV方面未发现显著差异。
提示对乙酰氨基酚与昂丹司琼之间存在相互作用，在恢复室进行疼痛滴定期间，接受昂丹司琼的儿童使用的吗啡量是接受氟哌利多儿童的三倍。需要更多研究来评估这一发现是否在临床上具有足够的相关性，从而在未来排除围手术期同时使用这两种药物的情况。
