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An Exploratory Pilot Study of Changes in Global DNA Methylation in Patients Undergoing Major Breast Surgery Under Opioid-Based General Anesthesia.

ABSTRACT: This study aimed to investigate DNA methylation levels in patients undergoing major breast surgery under opioid-based general anesthesia. Blood samples were collected from eleven enrolled patients, before, during and after anesthesia. PBMC were isolated and global DNA methylation levels as well as DNA methyltransferase (DNMT) and cytokine gene expression were assessed. DNA methylation levels significantly declined by 26%, reversing the direction after the end of surgery. Likewise, DNMT1a mRNA expression was significantly reduced at all time points, with lowest level of -68%. DNMT3a and DNMT3b decreased by 65 and 71%, respectively. Inflammatory cytokines IL6 and TNFα mRNA levels showed a trend for increased expression at early time-points to end with a significant decrease at 48 h after surgery. This exploratory study revealed for the first time intraoperative global DNA hypomethylation in patients undergoing major breast surgery under general anesthesia with fentanyl. The alterations of global DNA methylation here observed seem to be in agreement with DNMTs gene expression changes. Furthermore, based on perioperative variations of IL6 and TNFα gene expression, we hypothesize that DNA hypomethylation may occur as a response to surgical stress rather than to opiate exposure.

SUBMITTER: Caputi FF

PROVIDER: S-EPMC8491974 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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An Exploratory Pilot Study of Changes in Global DNA Methylation in Patients Undergoing Major Breast Surgery Under Opioid-Based General Anesthesia.

Caputi Francesca Felicia FF Carboni Lucia L Rullo Laura L Alessandrini Irene I Balzani Eleonora E Melotti Rita Maria RM Romualdi Patrizia P Candeletti Sanzio S Fanelli Andrea A

Frontiers in pharmacology 20210921

This study aimed to investigate DNA methylation levels in patients undergoing major breast surgery under opioid-based general anesthesia. Blood samples were collected from eleven enrolled patients, before, during and after anesthesia. PBMC were isolated and global DNA methylation levels as well as DNA methyltransferase (DNMT) and cytokine gene expression were assessed. DNA methylation levels significantly declined by 26%, reversing the direction after the end of surgery. Likewise, DNMT1a mRNA ex ...[more]

PMID: 34621169

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Project description:BackgroundReducing intra-operative opioid consumption benefits patients by decreasing postoperative opioid-related adverse events. We assessed whether opioid-free anesthesia would provide effective analgesia-antinociception monitored by analgesia index in video-assisted thoracoscopic surgery.MethodsPatients (ASA Ⅰ-Ⅱ, 18-65 years old, BMI <30 kg m-2) scheduled to undergo video-assisted thoracoscopic surgery under general anesthesia were randomly allocated into two groups to receive opioid-free anesthesia (group OFA) with dexmedetomidine, sevoflurane plus thoracic paravertebral blockade or opioid-based anesthesia (group OA) with remifentanil, sevoflurane, and thoracic paravertebral blockade. The primary outcome variable was pain intensity during the operation, assessed by the depth of analgesia using the pain threshold index with the multifunction combination monitor HXD‑I. Secondary outcomes included depth of sedation monitoring by wavelet index and blood glucose concentration achieved from blood gas.ResultsOne hundred patients were randomized; 3 patients were excluded due to discontinued intervention and 97 included in the final analysis. Intraoperative pain threshold index readings were not significantly different between group OFA and group OA from arriving operation room to extubation (P = 0.86), while the brain wavelet index readings in group OFA were notably lower than those in group OA from before general anesthesia induction to recovery of double lungs ventilation (P <0.001). After beginning of operation, the blood glucose levels in group OFA increased compared with baseline blood glucose values (P < 0.001). The recovery time and extubation time in group OFA were significantly longer than those in group OA (P <0.007).ConclusionsThis study suggested that our OFA regimen achieved equally effective intraoperative pain threshold index compared to OA in video-assisted thoracoscopic surgery. Depth of sedation was significantly deeper and blood glucose levels were higher with OFA. Study's limitations and strict inclusion criteria may limit the external validity of the study, suggesting the need of further randomized trials on the topic. Trial registration: ChiCTR1800019479, Title: "Opioid-free anesthesia in video-assisted thoracoscopic surgery lobectomy".

Project description:BackgroundAbnormal cardiac repolarization, indicated by a prolongation of the QT interval, increases the risk for torsades de pointes, a potentially life-threatening arrhythmia. Many perioperatively administered drugs and conditions prolong the QT interval. Despite several reports of perioperative torsades de pointes, systematic evidence regarding perioperative QT interval prolongation is limited.MethodsSerial postoperative 12-lead electrocardiograms were obtained from 469 adult patients undergoing major noncardiac surgery under general anesthesia. Heart rate corrected QT-interval duration (Fridericia formula) was the primary outcome. All perioperatively administered drugs were recorded. Emphasis was placed on absolute QTc prolongation greater than 500 ms and relative increases of 30 and 60 ms.ResultsAt the end of surgery, 80% of the patients (345 of 429) experienced a significant QTc interval prolongation (ΔQTc 23 ± 26 ms (mean and SD), 95% CI 20-25 ms, P less than 0.001). Approximately 51% (219 of 429) had a QTc greater than 440 ms, and 4% (16 of 429) a QTc greater than 500 ms. In 39% (166 of 429), the ΔQTc was greater than 30 ms, in 8% (34 of 429) >60 ms, and in greater than 0.5% (2 of 429) >100 ms. No changes in ΔQTc occurred at subsequent time points. One patient developed torsades de pointes with a ΔQTc: 29 ms (0.4% incidence rate). Several drugs had a large effect on ΔQTc: isoflurane, methadone, ketorolac, cefoxitin, zosyn, unasyn, epinephrine, ephedrine, and calcium. Postoperative body temperature had a weak negative correlation with ΔQTc (r = -0.15, P = 0.02); serum magnesium, potassium, and calcium concentrations were not correlated.ConclusionPostoperative QT-interval prolongation is common. Several perioperatively administered drugs are associated with a substantial QT-interval prolongation. The exact cause and its clinical relevance are, however, unclear. Nevertheless, an association between postoperative QT prolongation and risk for torsades de pointes is likely.

Project description:IntroductionThere is scarce data on the safety and efficacy of opioid-free anesthesia (OFA), in resource-limited settings due to the non-availability of dexmedetomidine, the reference OFA agent. We aimed to demonstrate the feasibility, efficacy and safety of a practical OFA protocol not containing dexmedetomidine, adapted for low-resource environments in very painful surgeries like gynecological surgery.MethodsWe conducted a randomized pilot study on ASA I and II women undergoing elective gynecological surgery at a tertiary care hospital in Cameroon. Patients were matched in a ratio of 1:1 into an OFA and a conventional general anesthesia (CGA) group. The OFA protocol entailed the intravenous (IV) magnesium sulfate, lidocaine, ketamine, dexamethasone, propofol, and rocuronium, followed by isoflurane and a continuous infusion of a calibrated mixture of magnesium sulfate, ketamine and clonidine. The CGA protocol was IV dexamethasone, diazepam, fentanyl, propofol, and rocuronium, followed by isoflurane and reinjections of fentanyl propofol and a continuous infusion of normal saline as placebo. The primary endpoints were the success rate of OFA, isoflurane consumption and intraoperative anesthetic complications. The secondary endpoints were postoperative pain intensity, postoperative complications, patient satisfaction assessed using the QoR-40 questionnaire and the financial cost of anesthesia.ResultsWe enrolled a total of 36 women undergoing gynecological surgery; 18 in the OFA group and 18 in the CGA group. The success rate of OFA was 100% with significant lesser consumption of isoflurane in the OFA group, no significant intraoperative complication and better intraoperative hemodynamic stability in the OFA group. Postoperatively, compared to the CGA group, the OFA group had statistically significantly less pain during the first 24 h, no morphine consumption for pain relief, had less hypoxemia during the first six hours, less paralytic ileus, less nausea and vomiting, no pruritus and better satisfaction. The mean financial cost of this adapted OFA protocol was statistically significant lesser than that of CGA.ConclusionThis OFA regimen without dexmedetomidine for a low-resource setting has a promising success rate with few perioperative complications including mild intraoperative hemodynamic changes, decrease postoperative complications, pain, and opioid consumption in patients undergoing elective gynecology surgery.Trial registrationThis study was registered at clinicaltrials.gov on 03/02/2021 under the registration number NCT04737473.

Project description:IntroductionThe number of elderly patients undergoing major surgery is rapidly increasing. They are particularly at risk of developing postoperative neurocognitive disorders (NCD). Earlier studies suggested that processed electroencephalographic (EEG) monitors may reduce the incidence of postoperative NCD. However, none of these studies controlled for intraoperative nociception levels or personalized blood pressure targets. Their results remain unclear if the reduction in the incidence of postoperative NCD relates to avoidance of any electroencephalographic pattern suggesting excessive anesthesia depth.ObjectiveThe objective of this trial is to investigate-in patients ≥ 70 years old undergoing major non-cardiac surgery-the effect of EEG-guided anesthesia on postoperative NCD while controlling for intraoperative nociception, personalized blood pressure targets, and using detailed information provided by the EEG monitor (including burst suppression ratio, density spectral array, and raw EEG waveform).Material and methodsThis prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients ≥ 70 years old undergoing elective major non-cardiac surgery will be included in the trial. The administration of sevoflurane will be adjusted to maintain a BIS index value between 40 and 60, to keep a Suppression Ratio (SR) at 0%, to keep a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta, and delta frequencies in the EEG-guided group. In the control group, sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of [0.8-1.2]. In both groups, a nociception monitor will guide intraoperative opioid administration, individual blood pressure targets will be used, and cerebral oximetry used to tailor intraoperative hemodynamic management. The primary endpoint will be the incidence of NCD at postoperative day 1, as evaluated by the Montreal Cognitive Assessment (MoCA). Secondary endpoints will include the incidence of postoperative NCD at different time points and the evaluation of cognitive trajectories up to 90 days after surgery among EEG-guided and control groups.Study registrationNCT04825847 on ClinicalTrials.gov.

Project description:Objective Emergence from anesthesia starts from the limbic structures and then spreads outwards to brainstem, reticular activating systems, and then to the cortex. Epilepsy surgery often involves resection of limbic structures and hence may disrupt the pattern of emergence. The aim of this study was to explore the pattern of emergence from anesthesia following epilepsy surgery and to determine associated variables affecting the emergence pattern. Setting and Design Tertiary care center, prospective observational study. Materials and Methods We conducted a prospective observation pilot study on adult patients undergoing anterior temporal lobectomy and amygdalohippocampectomy for epilepsy. Anesthesia management was standardized in all patients, and they were allowed to wake up with "no touch" technique. Primary outcome of the study was the pattern of emergence (normal emergence, agitated emergence, or slow emergence) from anesthesia. Secondary outcomes were to explore the differences in preoperative neuropsychological profile and limbic structure volumes between the different patterns of emergence. Quantitative variables were analyzed using Student's t -test. Qualitative variables were analyzed using chi-square test. Results Twenty-nine patients completed the study: 9 patients (31%) had agitated emergence, and 20 patients had normal emergence. Among the agitated emergence, 2 patients had Riker scale of 7 indicating violent emergence. Patient demographics, anesthetic used, neuropsychological profile, and limbic structure volumes were similar between normal emergence and agitated emergence groups. However, two patients who had severe agitation (Riker scale of 7) had the lowest intelligence quotient. Conclusion Our pilot study showed that emergence agitation is not uncommon in patients undergoing epilepsy surgery. However, due to smaller sample size, the role of preoperative neuropsychologic profile and hippocampal volumes in predicting the pattern of emergence is inconclusive.

Dataset Information

An Exploratory Pilot Study of Changes in Global DNA Methylation in Patients Undergoing Major Breast Surgery Under Opioid-Based General Anesthesia.

Publications

An Exploratory Pilot Study of Changes in Global DNA Methylation in Patients Undergoing Major Breast Surgery Under Opioid-Based General Anesthesia.

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