Xinmei Cai1, Bilian Li2, Wei Wei2, Yanping Guan1, Xue Bai2, Min Huang1, Yaying Huang2, Lili Rong3, Xingrong Song4, Guoping Zhong5. 1. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China. 2. Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China. 3. Department of Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China. 4. Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China. sxjess@126.com. 5. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China. zhonggp@mail.sysu.edu.cn.
Abstract
PURPOSE: The aim of this study was to investigate the expression levels of plasma miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p and their relationship to dexmedetomidine efficacy and adverse effects in pediatric patients. METHODS: The expression levels of miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p were measured by qRT-PCR in plasma of 133 pediatric patients receiving dexmedetomidine for preoperative sedation. We analyzed the relationship between miRNA abundance and dexmedetomidine response, including sedative effect and adverse effects, and assessed the predictive power of miRNAs for drug response. RESULTS: Among 133 pediatric patients, 111 patients were dexmedetomidine responders (UMSS ≥ 2) and 22 patients were non-responders (UMSS < 2). We observed higher expression levels of miR-101-3p and miR-140-3p in dexmedetomidine responders compared with non-responders (P < 0.05, P < 0.0001). In contrast, there was no significant difference in the expression levels of miR-30a-5p and miR-141-3p between responders and non-responders (P > 0.05). The plasma levels of miR-101-3p and miR-30a-5p were markedly downregulated in patients who experienced hypotension and bradycardia, respectively (P < 0.05). MiR-101-3p and miR-140-3p demonstrated a potential discriminatory ability between dexmedetomidine responders and non-responders, with AUC of 0.64 (P < 0.05) and 0.77 (P < 0.0001), respectively. The AUC of miR-101-3p in distinguishing patients without hypotension was 0.63 (P < 0.05). The AUC of miR-30a-5p in distinguishing patients without bradycardia was 0.74 (P < 0.05). CONCLUSION: Our study demonstrated that circulating miR-101-3p, miR-140-3p and miR-30a-5p might be used as a blood-based marker for dexmedetomidine efficacy and safety in pediatric patients.
PURPOSE: The aim of this study was to investigate the expression levels of plasma miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p and their relationship to dexmedetomidine efficacy and adverse effects in pediatric patients. METHODS: The expression levels of miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p were measured by qRT-PCR in plasma of 133 pediatric patients receiving dexmedetomidine for preoperative sedation. We analyzed the relationship between miRNA abundance and dexmedetomidine response, including sedative effect and adverse effects, and assessed the predictive power of miRNAs for drug response. RESULTS: Among 133 pediatric patients, 111 patients were dexmedetomidine responders (UMSS ≥ 2) and 22 patients were non-responders (UMSS < 2). We observed higher expression levels of miR-101-3p and miR-140-3p in dexmedetomidine responders compared with non-responders (P < 0.05, P < 0.0001). In contrast, there was no significant difference in the expression levels of miR-30a-5p and miR-141-3p between responders and non-responders (P > 0.05). The plasma levels of miR-101-3p and miR-30a-5p were markedly downregulated in patients who experienced hypotension and bradycardia, respectively (P < 0.05). MiR-101-3p and miR-140-3p demonstrated a potential discriminatory ability between dexmedetomidine responders and non-responders, with AUC of 0.64 (P < 0.05) and 0.77 (P < 0.0001), respectively. The AUC of miR-101-3p in distinguishing patients without hypotension was 0.63 (P < 0.05). The AUC of miR-30a-5p in distinguishing patients without bradycardia was 0.74 (P < 0.05). CONCLUSION: Our study demonstrated that circulating miR-101-3p, miR-140-3p and miR-30a-5p might be used as a blood-based marker for dexmedetomidine efficacy and safety in pediatric patients.
Authors: Stephan M Jakob; Esko Ruokonen; R Michael Grounds; Toni Sarapohja; Chris Garratt; Stuart J Pocock; J Raymond Bratty; Jukka Takala Journal: JAMA Date: 2012-03-21 Impact factor: 56.272