BackgroundThe 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.MethodsParatron is a prospective, randomized, controlled, double-blind, parallel group trial. All children aged 2-7years (n=69) scheduled for a tonsillectomyadenoidectomy 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 24h following surgery.ResultsPain scores were not different at all times between the groups but median morphine consumption (g) 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.ConclusionsAn 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.

Ramirez, L.; Cros, J.; Boulogne, P.; Bergeron, A.; Nathan-Denizot, N.; Beaulieu, P.Author Information

Although some studies have shown the essential role of descending serotonergic pathways and spinal 5-HT1A, 5-HT2A, or 5-HT3 receptors in the antinociceptive effects of paracetamol, other studies have presented conflicting results, and the particular subtype of spinal 5-HT receptors involved in paracetamol-induced analgesia remains to be clarified. Recent studies have demonstrated the importance of spinal 5-HT7 receptors in descending serotonergic pain inhibitory pathways. In this study, we investigated the role of descending serotonergic pathways and spinal 5-HT7 receptors compared with 5-HT3 and 5-HT2A receptors in the antinociceptive and antihyperalgesic effects of paracetamol. Tail-flick, hot plate and plantar incision tests were used to determine nociception in male BALB/c mice. Lesion of serotonergic bulbospinal pathways was performed by intrathecal (i.th.) injection of 5,7-dihydroxytryptamine (5,7-DHT), and spinal 5-HT levels were measured by HPLC. To evaluate the particular subtypes of the spinal 5-HT receptors, the selective 5-HT7, 5-HT3 and 5-HT2A receptor antagonists SB 269970, ondansetron and ketanserin, respectively, were given i.th. after oral administration of paracetamol. Oral paracetamol (200, 400 and 600 mg/kg) elicits dose-dependent antinociceptive and antihyperalgesic effects. I.th. pretreatment with 5,7-DHT (50 μg) sharply reduced 5-HT levels in the spinal cord. Depletion of spinal 5-HT totally abolished the antinociceptive and antihyperalgesic effects of paracetamol. I.th. injection of SB 2669970 (10 μg) blocked the antinociceptive and antihyperalgesic effects of paracetamol, but ondansetron and ketanserin (10 μg) did not. Our findings suggest that systemic administration of paracetamol may activate descending serotonergic pathways and spinal 5-HT7 receptors to produce a central antinociceptive and antihyperalgesic effects.

The authors report the first case of gas embolism arising during an upper gastrointestinal endoscopy to a patient carrier of a biliary drain placed by radiological way. The hypothesis of a biliary-vascular fistula with abnormal connection between the biliary tree and the hepatic vascular system and finally an arteriovenous intrapulmonary shunt was retained to explain the physiopathology. The immediate stop of the endoscopic procedure and the implementation of symptomatic treatment allowed a favorable neurological outcome without sequelas. The realization of an upper gastrointestinal endoscopy to a patient carrier of a biliary drain has to lead the anaesthesiologists and the gastroenterologists to take care given the incurred risk of gas embolism.