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Impact of CYP3A4*1G Polymorphism on Fentanyl Analgesia Assessed by Analgesia Nociception Index in Chinese Patients Undergoing Hysteroscopy.

ABSTRACT: Background:The clinical efficacy of fentanyl for pain control differs greatly across individuals. The purpose of this study was to investigate the impact of CYP3A4*1G polymorphism including wild-type homozygote (CYP3A4*1/*1, GG), mutant heterozygote (CYP3A4*1/*1G, GA), and mutant homozygote (CYP3A4*1G/*1G, AA) on fentanyl analgesia in Chinese patients undergoing hysteroscopy by the assessment of analgesia nociception index (ANI). Methods:A total of 200 gynecologic patients scheduled for elective hysteroscopy under general anesthesia at Peking University People's Hospital from May to December in 2017 were enrolled in this study. Venous blood was withdrawn for genotyping of CYP3A4*1G before operation. Fentanyl 1 ?g/kg was administered preoperatively followed by target-controlled infusion of propofol for induction and maintenance. Intraoperative analgesic efficacy of fentanyl was assessed by ANI monitoring at T0 (entering room), T1 (cervical dilation), T2 (start of cervical aspiration), and T3 (end of cervical aspiration) time points. The duration of propofol infusion and total dosage of propofol were recorded as well. Results:The patients were divided into three groups according to CYP3A4*1G polymorphism, including 143 in GG group, 47 in GA group, and 10 in AA group. There was no significant difference in clinical demographics among three groups. The frequency of CYP3A4*1G variant alleles accounted for 16.8% and the distribution of variant alleles was consistent with Hardy-Weinberg equilibrium. Using a multilevel model, ANI values at T1 (63.81 ± 19.61), T2 (63.63 ± 17.82), and T3 (65.68 ± 17.79) were significantly lower than that at T0 (77.16 ± 12.93) in the study population (F = 23.50, P < 0.001), suggesting that higher levels of pain at T1, T2, and T3 than T0. Patients with GG genotype showed significantly lower ANI than those with GA or AA genotypes during hysteroscopy under the same dose of fentanyl. Conclusion:CYP3A4*1G polymorphism associated with the analgesic efficacy of intraoperative fentanyl in the patients undergoing hysteroscopy under general anesthesia.

SUBMITTER: Yan Q

PROVIDER: S-EPMC6247602 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Impact of CYP3A4*1G Polymorphism on Fentanyl Analgesia Assessed by Analgesia Nociception Index in Chinese Patients Undergoing Hysteroscopy.

Yan Qi Q Su Yi Y Gao Lan L Ding Nan N Zhang Hong-Ying HY E Wen W Wang Yue Y Feng Yi Y An Hai-Yan HY

Chinese medical journal 20181101 22

<h4>Background</h4>The clinical efficacy of fentanyl for pain control differs greatly across individuals. The purpose of this study was to investigate the impact of CYP3A4*1G polymorphism including wild-type homozygote (CYP3A4*1/*1, GG), mutant heterozygote (CYP3A4*1/*1G, GA), and mutant homozygote (CYP3A4*1G/*1G, AA) on fentanyl analgesia in Chinese patients undergoing hysteroscopy by the assessment of analgesia nociception index (ANI).<h4>Methods</h4>A total of 200 gynecologic patients schedul ...[more]

PMID: 30381583

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Project description:Background: The PMD100™ (Medasense Biometrics Ltd., Ramat Yishai, Israel) is a novel non-invasive nociception monitor that integrates physiological parameters to compute a real-time nociception level index (NOL) in the anesthetized patients. Thoracic epidural analgesia provides effective analgesia and improves surgical outcomes. Side effects include sympathectomy, hypotension, changes in skin temperature and a decreased cardiac accelerator fiber tone. The purpose of this pilot study was to evaluate changes in NOL values after incision in patients with and without epidural analgesia. Methods: Half of the patients scheduled for Video-Assisted Thoracoscopic Surgery (VATS) received a thoracic epidural catheter, placed and tested 2h before surgery and activated prior to incision. The other half of the patients received i.v. fentanyl (1 mcg/kg) five minutes before incision. Anesthesia and analgesia were maintained in a standardized manner. NOL and heart rate (HR) were compared before and after the nociceptive stimuli intubation and skin incision. Results: NOL significantly increased in all patients after intubation by 10.2 points (CI: 4.5-16.0; p=0.002) as well as HR by 9 beats per minute after intubation in all patients (CI: 3.3-15.6; p=0.01). After incision, in patients without epidural analgesia the NOL increased by 13.9 points (CI: 7.4-20.3; p=0.0001), compared to 5.4 points (CI: -6.3-17.1; p=0.29) in patients with epidural analgesia. HR did not significantly vary after incision in both groups. The area under the curve of delta NOL and delta HR variations after incision were significantly different (p<0.05) between groups and delta NOL variations were significantly different from baseline values but not the delta HR variations. Conclusions: This pilot study suggests that the PMD100™ Monitor may be a useful tool to evaluate the efficacy of an intraoperative thoracic epidural analgesia. Clinical Trial Registry Number: ClinicalTrials.gov record ID: NCT01978379 registered 10/25/2014.

Project description:There are many surgical operations performed daily in operation rooms worldwide. Adequate anesthesia is needed during an operation. Besides hypnosis, adequate analgesia is critical to prevent autonomic reactions. Clinical experience and vital signs are usually used to adjust the dosage of analgesics. Analgesia nociception index (ANI), which ranges from 0 to 100, is derived from heart rate variability (HRV) via electrocardiogram (ECG) signals, for pain evaluation in a non-invasive manner. It represents parasympathetic activity. In this study, we compared the performance of multilayer perceptron (MLP) and long short-term memory (LSTM) algorithms in predicting expert assessment of pain score (EAPS) based on patient's HRV during surgery. The objective of this study was to analyze how deep learning models differed from the medical doctors' predictions of EAPS. As the input and output features of the deep learning models, the opposites of ANI and EAPS were used. This study included 80 patients who underwent operations at National Taiwan University Hospital. Using MLP and LSTM, a holdout method was first applied to 60 training patients, 10 validation patients, and 10 testing patients. As compared to the LSTM model, which had a testing mean absolute error (MAE) of 2.633 ± 0.542, the MLP model had a testing MAE of 2.490 ± 0.522, with a more appropriate shape of its prediction curves. The model based on MLP was selected as the best. Using MLP, a seven-fold cross validation method was then applied. The first fold had the lowest testing MAE of 2.460 ± 0.634, while the overall MAE for the seven-fold cross validation method was 2.848 ± 0.308. In conclusion, HRV analysis using MLP algorithm had a good correlation with EAPS; therefore, it can play role as a continuous monitor to predict intraoperative pain levels, to assist physicians in adjusting analgesic agent dosage. Further studies may consider obtaining more input features, such as photoplethysmography (PPG) and other kinds of continuous variable, to improve the prediction performance.

Dataset Information

Impact of CYP3A4*1G Polymorphism on Fentanyl Analgesia Assessed by Analgesia Nociception Index in Chinese Patients Undergoing Hysteroscopy.

Publications

Impact of CYP3A4*1G Polymorphism on Fentanyl Analgesia Assessed by Analgesia Nociception Index in Chinese Patients Undergoing Hysteroscopy.

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