Differential depression of neuronal network activity by midazolam and its main metabolite 1-hydroxymidazolam in cultured neocortical slices

Balk, Monika; Hentschke, Harald; Rudolph, Uwe; Antkowiak, Bernd; Drexler, Berthold

doi:10.1038/s41598-017-03154-5

Cited by 20 publications

(11 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of antegrade amnesia, combined with opioids, etomidate, propofol drugs can produce synergistic or additive effects, resulting in analgesic effect. 27 , 28 Previous studies have found that midazolam could shorten sleep latency, reduce wakefulness frequency, improve objective sleep evaluation and reduce daytime sleepiness. 29 However, some scholars have also pointed out that long-term application of benzodiazepines could lead to an increase of shallow sleep and increased risk of adverse effects such as cognitive impairment and falling, especially in the elderly.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of Nomogram Prediction Model for Postoperative Sleep Disturbance in Patients Undergoing Non-Cardiac Surgery: A Prospective Cohort Study

Yang¹,

Zhang²,

Xu³

et al. 2021

NSS

View full text Add to dashboard Cite

Purpose To develop a risk prediction nomogram of postoperative sleep disturbance (PSD) in patients undergoing non-cardiac surgery. Patients and methods Data on 881 consecutive patients who underwent non-cardiac surgery at the Affiliated Hospital of Xuzhou Medical University between June 2020 and April 2021 were prospectively collected. Of these, we randomly divided 881 non-cardiac patients into two groups, training cohort (n = 617) and validation cohort (n = 264) at the ratio of 7:3. Characteristic variables were selected based on the data of training cohort through least absolute shrinkage and selection operator (LASSO) regression. Multivariate logistic regression was used to identify the independent risk factors associated with PSD that then were incorporated into the nomogram. The predictive performance of the nomogram was measured by concordance index (C index), receiver operating characteristic (ROC) curve, and calibration with 1000 bootstrap samples to decrease the over-fit bias. Results PSD was found in 443 of 617 patients (71.8%) and 190 of 264 patients (72.0%) in the training and validation cohorts, respectively. The perioperative risk factors associated with PSD were female sex, anxiety, dissatisfaction of ward environment, absence of combined regional nerve block, postoperative nausea and vomiting (PONV), the longer duration stayed in post anesthesia care unit (PACU), the higher dose of midazolam and sufentanil, the higher postoperative numeric rating score for pain (NRS) score. Incorporating these 9 factors, the nomogram achieved good concordance indexes of 0.82 (95% confidence interval [CI], 0.78–0.85) and 0.80 (95% CI, 0.74–0.85) in predicting PSD in the training and validation cohorts, respectively, and obtained well-fitted calibration curves. The sensitivity and specificity (95% CIs) of the nomogram were calculated, resulting in sensitivity of 74.0% (70.0–78.2%) and 75.3% (68.4–81.7%) and specificity of 79.3% (72.5–85.2%) and 70.3% (58.4–80.7%) for the training and validation cohorts, respectively. Patients who had a nomogram score of less than 262 or 262 or greater were considered to have low or high risks of PSD presence, respectively. Conclusion The proposed nomogram achieved an optimal prediction of PSD in patients undergoing non-cardiac surgery. The risks for an individual patient to harbor PSD can be determined by this model, which can lead to a reasonable preventive and treatment measures.

show abstract

Section: Discussionmentioning

confidence: 99%

Development and Validation of Nomogram Prediction Model for Postoperative Sleep Disturbance in Patients Undergoing Non-Cardiac Surgery: A Prospective Cohort Study

Yang¹,

Zhang²,

Xu³

et al. 2021

NSS

View full text Add to dashboard Cite

show abstract

“…The observed increase in exposure to the active metabolite 1′‐OH‐MDZ may therefore be due to CBD‐mediated inhibition of UGTs, in particular UGT2B7 22 . The increase in exposure to 1′‐OH‐MDZ with concomitant CBD could potentially increase the effects of MDZ in cases of impaired drug metabolism or when MDZ is administered at high doses 43 . The clinical relevance of the increase in exposure to 1′‐OH‐MDZ when MDZ is administered with CBD is unknown.…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of trials investigating drug‐drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs

et al. 2020

View full text Add to dashboard Cite

Highly purified cannabidiol (CBD) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome in randomized, double-blind, add-on, controlled phase 3 trials. It is important to consider the possibility of drug-drug interactions (DDIs). Here, we review six trials of CBD (Epidiolex/ Epidyolex; 100 mg/mL oral solution) in healthy volunteers or patients with epilepsy, which investigated potential interactions between CBD and enzymes involved in drug metabolism of common antiseizure drugs (ASDs). CBD did not affect CYP3A4 activity. Induction of CYP3A4 and CYP2C19 led to small reductions in exposure to CBD and its major metabolites. Inhibition of CYP3A4 activity did not affect CBD exposure and caused small increases in exposure to CBD metabolites. Inhibition of CYP2C19 activity led to a small increase in exposure to CBD and small decreases in exposure to CBD metabolites. One potentially clinically important DDI was identified: combination of CBD and clobazam (CLB) did not affect CBD or CLB exposure, but increased exposure to major metabolites of both compounds. Reduction of CLB dose may be considered if adverse reactions known to occur with CLB are experienced when it is coadministered with CBD. There was a small increase of exposure to stiripentol (STP) when coadministered with CBD. STP had no effect on CBD exposure but led to minor decreases in exposure to CBD metabolites. Combination of CBD and valproate (VPA) did not cause clinically important changes in the pharmacokinetics of either drug, or 2-propyl-4-pentenoic acid. Concomitant VPA caused small increases in exposure to CBD metabolites. Dose adjustments are not likely to be necessary when CBD is combined with STP or VPA. The safety results from these trials were consistent with the known safety profile of CBD. These trials indicate an overall low potential for DDIs between CBD and other ASDs, except for CLB.

show abstract

“…Because midazolam is a short-acting water-soluble benzodiazepine sedative, midazolam produces sedative, hypnotic, anticonvulsant, and anxiolytic effects by altering the configuration of the GABAA receptor complex and opening the chloride channel. The effect of antegrade amnesia, combined with opioids, etomidate, propofol drugs can produce synergistic or additive effects, resulting in analgesic effect (17). However, the use of midazolam can accumulate in patients with renal failure, and some patients may also develop drug resistance; while the excessive injection dose or use may cause blood pressure drop or respiratory depression in patients with hypovolemia (18).…”

Section: Discussionmentioning

confidence: 99%

Effect of dexmedetomidine anesthesia on perioperative levels of TNF-α and IL-6 in patients with ovarian cancer

Liu

Zhao

2019

Oncol Lett

View full text Add to dashboard Cite

Effect of continuous use of dexmedetomidine during general anesthesia on perioperative levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in patients undergoing radical resection of ovarian cancer was investigated. The initial treatment of ovarian cancer is mainly radical surgery. Most patients with ovarian cancer radical surgery can achieve good results, but the use of improper anesthetic drugs in radical surgery can easily lead to unstable patient vital signs. Therefore, the selection of appropriate anesthetic drugs has become the key to radical ovarian cancer surgery. There are few reports on the use of dexmedetomidine in anesthesia for ovarian cancer radical surgery. This study was performed to retrospectively analyze the case data of patients undergoing laparoscopic ovarian cancer radical surgery, and to compare the hemodynamics of dexmedetomidine anesthesia with midazolam anesthesia and the concentrations of TNF-α and IL-6, to provide reference for clinical implementation of ovarian cancer radical surgery. The hemodynamics of patients in the dexmedetomidine group were stable compared with the midazolam group. Serum TNF-α and IL-6 levels were significantly lower in the dexmedetomidine group than that in the midazolam group. If dexmedetomidine were continuously used during general anesthesia, the perioperative serum levels of TNF-α and IL-6 could be effectively reduced in patients undergoing radical resection of ovarian cancer, and the perioperative stress response was suppressed.

show abstract

Differential depression of neuronal network activity by midazolam and its main metabolite 1-hydroxymidazolam in cultured neocortical slices

Cited by 20 publications

References 45 publications

Development and Validation of Nomogram Prediction Model for Postoperative Sleep Disturbance in Patients Undergoing Non-Cardiac Surgery: A Prospective Cohort Study

Development and Validation of Nomogram Prediction Model for Postoperative Sleep Disturbance in Patients Undergoing Non-Cardiac Surgery: A Prospective Cohort Study

Clinical implications of trials investigating drug‐drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs

Effect of dexmedetomidine anesthesia on perioperative levels of TNF-α and IL-6 in patients with ovarian cancer

Contact Info

Product

Resources

About