Mazzotta Elvio, Villalobos-Hernandez Egina Criseida, Fiorda-Diaz Juan, Harzman Alan, Christofi Fievos L
Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Front Pharmacol. 2020 Nov 24;11:583422. doi: 10.3389/fphar.2020.583422. eCollection 2020.
Postoperative ileus (POI) and postoperative gastrointestinal tract dysfunction (POGD) are well-known complications affecting patients undergoing intestinal surgery. GI symptoms include nausea, vomiting, pain, abdominal distention, bloating, and constipation. These iatrogenic disorders are associated with extended hospitalizations, increased morbidity, and health care costs into the billions and current therapeutic strategies are limited. This is a narrative review focused on recent concepts in the pathogenesis of POI and POGD, pipeline drugs or approaches to treatment. Mechanisms, cellular targets and pathways implicated in the pathogenesis include gut surgical manipulation and surgical trauma, neuroinflammation, reactive enteric glia, macrophages, mast cells, monocytes, neutrophils and ICC's. The precise interactions between immune, inflammatory, neural and glial cells are not well understood. Reactive enteric glial cells are an emerging therapeutic target that is under intense investigation for enteric neuropathies, GI dysmotility and POI. Our review emphasizes current therapeutic strategies, starting with the implementation of colorectal enhanced recovery after surgery protocols to protect against POI and POGD. However, despite colorectal enhanced recovery after surgery, it remains a significant medical problem and burden on the healthcare system. Over 100 pipeline drugs or treatments are listed in Clin.Trials.gov. These include 5HTR agonists (Prucalopride and TAK 954), vagus nerve stimulation of the ENS-macrophage nAChR cholinergic pathway, acupuncture, herbal medications, peripheral acting opioid antagonists (Alvimopen, Methlnaltexone, Naldemedine), anti-bloating/flatulence drugs (Simethiocone), a ghreline prokinetic agonist (Ulimovelin), drinking coffee, and nicotine chewing gum. A better understanding of the pathogenic mechanisms for short and long-term outcomes is necessary before we can develop better prophylactic and treatment strategies.
术后肠梗阻（POI）和术后胃肠道功能障碍（POGD）是肠道手术患者中众所周知的并发症。胃肠道症状包括恶心、呕吐、疼痛、腹胀、肠胃气胀和便秘。这些医源性疾病与住院时间延长、发病率增加以及高达数十亿美元的医疗费用相关，而目前的治疗策略有限。这是一篇叙述性综述，重点关注POI和POGD发病机制的最新概念、在研药物或治疗方法。发病机制中涉及的机制、细胞靶点和途径包括肠道手术操作和手术创伤、神经炎症、反应性肠神经胶质细胞、巨噬细胞、肥大细胞、单核细胞、中性粒细胞和肠间质细胞。免疫、炎症、神经和神经胶质细胞之间的确切相互作用尚不清楚。反应性肠神经胶质细胞是一个新兴的治疗靶点，目前正针对肠神经病变、胃肠动力障碍和POI进行深入研究。我们的综述强调了当前的治疗策略，首先是实施结直肠术后加速康复方案以预防POI和POGD。然而，尽管有结直肠术后加速康复方案，它仍然是一个重大的医学问题和医疗系统的负担。超过100种在研药物或治疗方法列于美国国立医学图书馆临床试验数据库（Clin.Trials.gov）。这些包括5-羟色胺受体激动剂（普芦卡必利和TAK 954）、迷走神经刺激ENS-巨噬细胞烟碱型乙酰胆碱受体胆碱能途径、针灸、草药、外周作用的阿片类拮抗剂（阿维莫潘、甲基纳曲酮、纳洛酮）、抗腹胀/肠胃气胀药物（西甲硅油）、一种胃饥饿素促动力激动剂（乌利莫林）、喝咖啡和尼古丁口香糖。在我们能够制定更好的预防和治疗策略之前，有必要更好地了解短期和长期结果的致病机制。
