Genetic Susceptibility Toward Nausea and Vomiting in Surgical Patients.

Yvonne Gloor,Jules A Desmeules,Christoph Czarnetzki,Béatrice Gil-Wey,Martin R Tramèr,François Curtin

doi:10.3389/fgene.2021.816908

Abstract

Postoperative nausea and vomiting (PONV) are frequently occurring adverse effects following surgical procedures. Despite predictive risk scores and a pallet of prophylactic antiemetic treatments, it is still estimated to affect around 30% of the patients, reducing their well-being and increasing the burden of post-operative care. The aim of the current study was to characterize selected genetic risk factors of PONV to improve the identification of at risk patients. We genotyped 601 patients followed during the first 24 h after surgery for PONV symptoms in the absence of any antiemetic prophylaxis. These patients were recruited in the frame of a randomized, placebo controlled clinical study aiming to test the efficacy of dexamethasone as a treatment of established PONV. We examined the impact of selected single nucleotide polymorphisms (SNPs) located around 13 different genes and the predicted activity of 6 liver drug metabolizing enzymes from the cytochromes P450 family (CYP) on the occurrence and recurrence of PONV. Our genetic study confirms the importance of genetic variations in the type 3B serotonin receptor in the occurrence of PONV. Our modelling shows that integration of rs3782025 genotype in preoperative risk assessments may help improve the targeting of antiemetic prophylaxis towards patients at risk of PONV.

Highlights

Postoperative nausea and vomiting (PONV) are frequently occurring adverse effects following surgical procedures concerning about one third of patients, with a prevalence that can reach up to 70–80% in high risk populations (Amirshahi et al, 2020; Elvir-Lazo et al, 2020; Ziemann-Gimmel et al, 2020)
As serotonin is known to play an important role in emesis and as we were able to involve several single nucleotide polymorphisms (SNPs) related to type 3B serotonin receptors in the occurrence of PONV, we examined the effect of HTR3B genotype in patients having received tramadol as part of their postoperative analgesic treatment
The current genetic study first examined the impact of 28 individual single nucleotide polymorphisms (SNPs) located around 13 genes as well as the activity of six liver cytochromes (CYP) on the occurrence of PONV in a cohort of 601 patients without anti-emetic prophylaxis followed during the first 24 h after surgery

Summary

Introduction

Postoperative nausea and vomiting (PONV) are frequently occurring adverse effects following surgical procedures concerning about one third of patients, with a prevalence that can reach up to 70–80% in high risk populations (Amirshahi et al, 2020; Elvir-Lazo et al, 2020; Ziemann-Gimmel et al, 2020). The most effective and commonly used anti-emetic treatments consist of 5-HT3 and D2-and more recently NK-1 receptor antagonists [reviewed in (Elvir-Lazo et al, 2020; Gan et al, 2020)]. As systematic administration of antiemetic prophylaxis before surgery is neither safe nor cost-effective (Tramèr et al, 1999), it is important to identify patients with a high-risk profile. A number of patient characteristics, as well as anesthetic or surgical procedures have been identified as risk factors of PONV including, but not limited to: female gender, young age, non-smoking status, previous history

Objectives

Methods

Results

Conclusion