- Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia. [Journal Article]Hum Brain Mapp 2019HB
- Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting-state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with th…
Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting-state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19-37 years) underwent a randomized, three-way, cross-over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long-distance (seed-based and dual-regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13 ± 0.28, p = 4.0 × 10-3 ), auditory network (d: 0.67 ± 0.26, p = .04) and default mode network (DMN, d: 0.63 ± 0.26, p = .05). Midazolam significantly reduced connectivity in the DMN (d: 0.77 ± 0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia-related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = -.17, p = .65). The subtraction of ketamine and midazolam patterns showed a significant positive correlation with the pattern of schizophrenia deficits (r = .68, p = .03). RsPhfMRI reliably detected the shared and divergent pharmacological actions of ketamine and midazolam on cerebral networks. The pattern of disconnectivity produced by ketamine was positively correlated with the pattern of connectivity deficits observed in schizophrenia, suggesting a brain functional basis for previously poorly understood effects of the drug.
- Maturation of midazolam clearance in critically ill children with severe bronchiolitis: a population pharmacokinetic analysis. [Journal Article]Eur J Pharm Sci 2019; :105095EJ
- CONCLUSIONS: The developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam.
- Validation of methods for determining pediatric midazolam using wet whole blood and volumetric absorptive microsampling. [Journal Article]Bioanalysis 2019B
- CONCLUSIONS: Validation data met internationally accepted guideline criteria. A strong correlation was observed in calculated concentrations between wet and dry test samples, indicating that VAMS is a suitable technique for use in pediatric clinical studies.
- Lack of recall after sedation for cataract surgery and its effect on validity of measuring patient satisfaction. [Journal Article]Korean J Anesthesiol 2019KJ
- CONCLUSIONS: Evaluating patient satisfaction with sedation shortly after admission to post-anesthesia care unit is invalid because of a lack of recall; the sedation/amnesia is ongoing. Patient comfort may be assessed, but comfort is not synonymous with satisfaction; "satisfaction" implies presence of recall. Because we studied sedation with low doses of midazolam and fentanyl, the same conclusion reliably would apply to larger doses of anxiolytics administered intraoperatively. The results match previous findings that when patients receive preoperative midazolam prior to meeting the anesthesiologist, even if the patient fully answers questions, they may have negligible recall of having met the anesthesiologist.
- Validation of a 3-h Sampling Interval to Assess Variability in Cytochrome P450 3A Phenotype and the Impact of Induction and Mechanism-Based Inhibition Using Midazolam as a Probe Substrate. [Journal Article]Front Pharmacol 2019; 10:1120FP
- CONCLUSIONS: On this basis, it is proposed that a 3-h assessment of midazolam AUC (AUC0-3) represents a viable strategy to reduce the logistical burden associated with the assessment of CYP3A phenotype.
- Postanaesthetic effects of ketamine-midazolam and ketamine-medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. [Journal Article]Vet Rec 2019VR
- CONCLUSIONS: Clinicians should therefore be aware of the potential gastrointestinal side effects of KMT-A, particularly in rabbits at risk for gastrointestinal stasis.
- Sedative depth on neurological outcomes in a juvenile rat model of cardiopulmonary resuscitation. [Journal Article]Med Hypotheses 2019; 132:109233MH
- The guidelines for cardiopulmonary resuscitation (CPR) in pediatric advanced life support suggest that midazolam is the preferred agent for sedation in patients with mild hypothermia, whereas children with cardiac arrest (CA) are at a crucial stage regarding their immature nervous system. Studies have shown that midazolam may have a detrimental effect on the developmental of the pediatric nervous…
The guidelines for cardiopulmonary resuscitation (CPR) in pediatric advanced life support suggest that midazolam is the preferred agent for sedation in patients with mild hypothermia, whereas children with cardiac arrest (CA) are at a crucial stage regarding their immature nervous system. Studies have shown that midazolam may have a detrimental effect on the developmental of the pediatric nervous system. Our previous study found that midazolam induced neuronal damage after CPR in young rats. It is speculated that: midazolam causes the potential injury of neurons by inhibiting mitochondrial autophagy expression and is an important factor for the poor prognosis in children after successful CPR. This project intends to adopt the modified asphyxiant CPR model in juvenile rats. Survival rate, neurological function and histopathological changes were evaluated to determine the protective effects of appropriate sedation depth on cerebral ischemia-reperfusion injury in juvenile rats after CPR. Combined with cell biology and molecular biology related technologies, the mechanism by which the mitochondrial pinkl-parkin signaling pathway induces autophagy to inhibit neuronal apoptosis may be key factor in the protective effects of sedation depth on the brain. The aim of this study is to provide experimental evidence and elucidate the mechanisms of improvement of cerebral ischemia-reperfusion injury by sedation depth in children after successful CPR and to lay a theoretical and experimental basis for clinical treatment.
- Sedation During Endoscopy in Patients with Cirrhosis: Safety and Predictors of Adverse Events. [Journal Article]Dig Dis Sci 2019DD
- CONCLUSIONS: Adverse events in cirrhotic patients undergoing endoscopy appeared to be similar with moderate sedation or MAC, and the frequency was the same for different types of procedures.
- A Comparative Study of Midazolam Alone or in Combination with Dexmedetomidine or Clonidine for Awake Fiberoptic Intubation. [Journal Article]Anesth Essays Res 2019 Jul-Sep; 13(3):539-546AE
- CONCLUSIONS: Patients who received α2 agonist were calmer and cooperative with less pain and discomfort than the patients who received midazolam. Dexmedetomidine allows better endurance, stable hemodynamics, and patent airway as compared to clonidine.
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- Efficacy of Adding Midazolam to Bupivacaine for Transversus Abdominis Plane Block on Postoperative Analgesia after Hysterectomy: A Randomized Controlled Study. [Journal Article]Anesth Essays Res 2019 Jul-Sep; 13(3):522-527AE
- CONCLUSIONS: Adding midazolam as a bupivacaine adjuvant for TAP block reduces the 24-h morphine consumption, extends the postoperative analgesia duration, and decreases the incidence of adverse effects following abdominal hysterectomy.