Clopidogrel, an ADP-P2Y12 Receptor Antagonist, Can Prevent Severe Postoperative Pain: A Retrospective Chart Review.

Rikuhei Tsuchida,Masae Ando,Kohshi Hattori,Kazuhito Mietani,Kanji Uchida,Reo Inoue,Kosuke Saita,Masahiko Sumitani,Hiroaki Abe

doi:10.3390/life10060092

Abstract

The purinergic P2Y12 receptor regulates microglial activation, resulting in persistence and aggravation of pain in neuropathic and nociceptive pain models. We conducted a retrospective chart review to explore the analgesic potency of the P2Y12 receptor-specific antagonist, clopidogrel, for clinical management of postoperative pain in patients who underwent abdominal surgery. Twenty-seven patients with cardiovascular comorbidities, who underwent laparoscopic abdominal surgery and had ceased aspirin (ASP, n = 17) or clopidogrel (CLP, n = 10) for 14 days pre-operatively, were enrolled retrospectively. In both groups, the number of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) consumed for managing postoperative pain was compared using the chi-square test and Mann–Whitney test. Our results showed that from postoperative day (POD) 0 to POD 3, the average numerical rating reflecting the postoperative pain was comparable between the two groups (CLP: 4.0 ± 1.4 vs. ASP: 3.7 ± 0.8, P-value = 0.56). However, at POD 7, opioid consumption in the CLP-treated group (fentanyl-equivalent dose: 0.49 ± 0.56 mg) was significantly lower than that in the ASP-treated group (1.48 ± 1.35 mg, P-value = 0.037). After reaching a stable state by repeated systemic administration, clopidogrel sustained the analgesic efficacy for a certain period. In conclusion, microglial P2Y12 receptors may mediate signal transduction of postoperative nociceptive pain and enhance clinical opioid analgesia.

Highlights

Pain is one of the most frequent symptoms observed in postoperative patients
We retrospectively reviewed the pharmacy and medical records of 27 patients with a history of cardiovascular diseases, who underwent laparoscopic abdominal surgery and were prescribed antiplatelet drugs
Postoperative pain was treated with a continuous epidural infusion of local anaesthetics and intravenous fentanyl

Summary

Introduction

Pain is one of the most frequent symptoms observed in postoperative patients. Postoperative pain causes distress and interferes with cough, breathing depth, and expectoration during the acute postoperative period and can be followed by atelectasis, pneumonia, and hypoxia [1].postoperative pain can trigger the development of delirium and an associated increased mortality and morbidity [2]. Pain is one of the most frequent symptoms observed in postoperative patients. Postoperative pain causes distress and interferes with cough, breathing depth, and expectoration during the acute postoperative period and can be followed by atelectasis, pneumonia, and hypoxia [1]. Postoperative pain can trigger the development of delirium and an associated increased mortality and morbidity [2]. A multimodal analgesic strategy is recommended to control postoperative pain, opioids still hold a prominent position. A valid concern is that along with the favourable positive effects of opioids (i.e., analgesia), the diverse negative side effects (e.g., nausea and vomiting, respiratory depression, and opioid-induced delirium) may be triggered. It has been reported that opioids prescribed during acute postoperative periods could trigger misuse

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