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Frontiers in Medicine 2023Patients with Parkinson's disease (PD), often elderly with various comorbidities, may require a continuous intestinal infusion of carbidopa/levodopa gel by the placement...
Effectiveness and safety of an atropine/midazolam and target controlled infusion propofol-based moderate sedation protocol during percutaneous endoscopic transgastric jejunostomy procedures in Parkinson's disease: a real-life retrospective observational study.
Patients with Parkinson's disease (PD), often elderly with various comorbidities, may require a continuous intestinal infusion of carbidopa/levodopa gel by the placement of a percutaneous endoscopic gastrostomy (PEG) with a jejunal tube (PEG-J) to improve their motor outcome and quality of life. However, it is unclear what is the best procedural sedation protocol for PEG-J procedures. Fifty patients with PD and indication for PEG-J procedure (implantation, replacement, removal) underwent, from 2017 to 2022, a sedation protocol characterized by premedication with atropine (0.01 mg/Kg ), midazolam (0.015-0.03 mg/Kg ) and induction with bolus propofol (0.5-1 mg/Kg ) as well as, finally, sedation with continuous infusion propofol (2-5 mg/Kg/h ) by Target Controlled Infusion (TCI) technique. Ninety-eight per cent of patients experienced no intraprocedural or peri-procedural adverse events. All the procedures were technically successful. A good discharge time was recorded. The vital parameters recorded during the procedure did not vary significantly. A PEG-J procedure conducted within 30 min showed a significant advantage over end-tidal carbon dioxide (EtCO). Indeed, the latter showed some predictive behavior (OR: 1.318, 95% CI 1.075-1.615, = 0.008). In the real world, this sedation protocol showed a good safety and effectiveness profile, even with reduced doses of midazolam and a TCI propofol technique in moderate sedation.
PubMed: 37771983
DOI: 10.3389/fmed.2023.1233575 -
Molecular Autism Aug 2023Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic-like behaviors and is...
BACKGROUND
Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic-like behaviors and is primarily caused by haploinsufficiency of SHANK3 gene. Currently, there is no specific treatment for PMS, highlighting the need for a better understanding of SHANK3 functions and the underlying pathophysiological mechanisms in the brain. We hypothesize that SHANK3 haploinsufficiency may lead to alterations in the inhibitory system, which could be linked to the excitatory/inhibitory imbalance observed in models of autism spectrum disorder (ASD). Investigation of these neuropathological features may shed light on the pathogenesis of PMS and potential therapeutic interventions.
METHODS
We recorded local field potentials and visual evoked responses in the visual cortex of Shank3∆11 mice. Then, to understand the impact of Shank3 in inhibitory neurons, we generated Pv-cre Shank3 conditional mice, in which Shank3 was deleted in parvalbumin-positive neurons. We characterized the phenotype of this murine model and we compared this phenotype before and after ganaxolone administration.
RESULTS
We found, in the primary visual cortex, an alteration of the gain control of Shank3 KO compared with Wt mice, indicating a deficit of inhibition on pyramidal neurons. This alteration was rescued after the potentiation of GABA receptor activity by Midazolam. Behavioral analysis showed an impairment in grooming, memory, and motor coordination of Pv-cre Shank3 compared with Pv-cre Shank3 mice. These deficits were rescued with ganaxolone, a positive modulator of GABA receptors. Furthermore, we demonstrated that treatment with ganaxolone also ameliorated evocative memory deficits and repetitive behavior of Shank3 KO mice.
LIMITATIONS
Despite the significant findings of our study, some limitations remain. Firstly, the neurobiological mechanisms underlying the link between Shank3 deletion in PV neurons and behavioral alterations need further investigation. Additionally, the impact of Shank3 on other classes of inhibitory neurons requires further exploration. Finally, the pharmacological activity of ganaxolone needs further characterization to improve our understanding of its potential therapeutic effects.
CONCLUSIONS
Our study provides evidence that Shank3 deletion leads to an alteration in inhibitory feedback on cortical pyramidal neurons, resulting in cortical hyperexcitability and ASD-like behavioral problems. Specifically, cell type-specific deletion of Shank3 in PV neurons was associated with these behavioral deficits. Our findings suggest that ganaxolone may be a potential pharmacological approach for treating PMS, as it was able to rescue the behavioral deficits in Shank3 KO mice. Overall, our study highlights the importance of investigating the role of inhibitory neurons and potential therapeutic interventions in neurodevelopmental disorders such as PMS.
Topics: Mice; Animals; Autism Spectrum Disorder; Problem Behavior; Nerve Tissue Proteins; Neurons; Microfilament Proteins
PubMed: 37528484
DOI: 10.1186/s13229-023-00557-2 -
Scientific Reports Feb 2024Administration of sedatives for post-resuscitation care can complicate the determination of the optimal timing to avoid inappropriate, pessimistic prognostications. This... (Observational Study)
Observational Study
Administration of sedatives for post-resuscitation care can complicate the determination of the optimal timing to avoid inappropriate, pessimistic prognostications. This prospective study aimed to investigate the distribution and elimination kinetics of midazolam (MDZ) and its metabolites, and their association with awakening time. The concentrations of MDZ and its seven metabolites were measured immediately and at 4, 8, 12, and 24 h after the discontinuation of MDZ infusion, using liquid chromatography-tandem mass spectrometry. The area under the time-plasma concentration curve from 0 to 24 h after MDZ discontinuation (AUC) was calculated based on the trapezoidal rule. Of the 15 enrolled patients, seven awakened after the discontinuation of MDZ infusion. MDZ and three of its metabolites were major compounds and their elimination kinetics followed a first-order elimination profile. In the multivariable analysis, only MDZ was associated with awakening time (AUC: R = 0.59, p = 0.03; AUC: R = 0.96, p < 0.001). Specifically, a 0.001% increase in MDZ AUC was associated with a 1% increase in awakening time. In the individual regression analysis between MDZ concentration and awakening time, the mean MDZ concentration at awakening time was 16.8 ng/mL. The AUC of MDZ is the only significant factor associated with the awakening time.
Topics: Humans; Midazolam; Prospective Studies; Hypnotics and Sedatives; Chromatography, Liquid
PubMed: 38403792
DOI: 10.1038/s41598-024-54968-z -
Journal of Clinical Medicine Mar 2024Precise assessment of hypnotic depth in children during procedural sedation with preserved spontaneous breathing is challenging. The Narcotrendindex (NI) offers...
Precise assessment of hypnotic depth in children during procedural sedation with preserved spontaneous breathing is challenging. The Narcotrendindex (NI) offers uninterrupted information by continuous electrocortical monitoring without the need to apply a stimulus with the risk of assessment-induced arousal. This study aimed to explore the correlation between NI and the Comfort Scale (CS) during procedural sedation with midazolam and propofol and to identify an NI target range for deep sedation. A prospective observational study was conducted on 176 children (6 months to 17.9 years) undergoing procedural sedation with midazolam premedication and continuous propofol infusion. Statistical analyses included Pearson correlation of NI and CS values, logistic regression, and receiver operating curves. Median NI values varied with CS and age. The correlation coefficient between CS and NI was 0.50 and slightly higher in procedure-specific subgroup analyses. The optimal NI cut-off for deep sedation was between 50 and 60 depending on the analyzed subgroup and displayed high positive predictive values for sufficient sedation throughout. Our study found a moderate correlation between NI and CS, demonstrating reliable identification of adequately sedated patients.
PubMed: 38592307
DOI: 10.3390/jcm13051483 -
Patient Preference and Adherence 2024In the US, 3 rescue treatment options are approved for patients with seizure clusters (ie, acute repetitive seizures), which are intermittent increases of seizure... (Review)
Review
In the US, 3 rescue treatment options are approved for patients with seizure clusters (ie, acute repetitive seizures), which are intermittent increases of seizure activity. This narrative PubMed review of these 3 treatments examines newer intranasal options that are well suited for adolescent and adult patients who may desire a transition from rectal treatment. Diazepam rectal gel is indicated for patients ≥2 years, diazepam nasal spray for those ≥6 years, and midazolam nasal spray for those ≥12 years. Approvals for diazepam rectal gel and midazolam nasal spray were based on safety and efficacy comparisons with placebo. Approval for diazepam nasal spray was based on results from long-term safety and tolerability studies in addition to its comparable bioavailability to diazepam rectal gel, while also showing less interpatient variability. The safety profiles of diazepam rectal gel and nasal spray are similar, and the medications share safety, warning, and precaution labeling. Thus, patients ≥6 years could be introduced to intranasal diazepam, allowing for continuity of familiar treatment while improving access and comfort. Intranasal midazolam also has a well-characterized safety profile. A proxy for effectiveness is the number of seizure clusters that were treated with a single dose, and these differed in separate, noncomparative studies. The safety and effectiveness of diazepam nasal spray have been examined in multiple subpopulations, whereas patient/caregiver experiences with both approved intranasal formulations have been characterized. Users may prefer nasal administration because it is noninvasive and effective, and provides social advantages, comfort, ease of use, and less variability compared with rectal gel. Nasal sprays are portable and convenient for use in the community (school, work, travel), and self-administration was reported in one study, with patients as young as 11 years old self-administering diazepam nasal spray. These newer, intranasal rescue treatments for seizure clusters provide an alternative to the rectal route.
PubMed: 38344151
DOI: 10.2147/PPA.S447028 -
Medicina (Kaunas, Lithuania) Oct 2023: Remimazolam besylate, a newly developed drug, is linked to various anaphylaxis cases. We present a case of remimazolam anaphylaxis confirmed using a provocation test.... (Review)
Review
: Remimazolam besylate, a newly developed drug, is linked to various anaphylaxis cases. We present a case of remimazolam anaphylaxis confirmed using a provocation test. : A 51-year-old female patient was scheduled for humeral pinning. General anesthesia was induced using remimazolam, rocuronium, and remifentanil. After tracheal intubation, the patient experienced decreased blood pressure, increased heart rate, and a systemic rash. Epinephrine was administered repeatedly, and the patient's vital signs stabilized. Acute phase tryptase levels were within normal limits. After four weeks, intradermal test results were negative. When remimazolam was administered intravenously for the provocation test, facial swelling, flushing, and coughing occurred, which improved with epinephrine. The culprit drug was identified as remimazolam using a provocation test. : When anaphylaxis occurs during anesthesia induction, remimazolam should not be ruled out as the causative drug. If the skin test result for remimazolam is negative, a provocation test should be considered. The provocation test should be initiated cautiously at a low dose under careful patient monitoring.
Topics: Female; Humans; Middle Aged; Anaphylaxis; Anesthesia, General; Benzodiazepines; Epinephrine
PubMed: 38003965
DOI: 10.3390/medicina59111915 -
European Journal of Medical Research Oct 2023This study compared remimazolam tosylate with propofol or midazolam to assess its safety and effectiveness for long-term sedation of intensive care unit (ICU) patients... (Observational Study)
Observational Study
OBJECTIVE
This study compared remimazolam tosylate with propofol or midazolam to assess its safety and effectiveness for long-term sedation of intensive care unit (ICU) patients requiring mechanical ventilation.
METHODS
Adult patients in the ICU receiving sedation and mechanical ventilation for longer than 24 h were included in this single-center, prospective, observational study. Depending on the sedatives they were given, they were split into two groups (midazolam or propofol group; remimazolam group). ICU mortality was the main result. Laboratory tests, adverse events, and the length of ICU stay were considered secondary outcomes.
RESULTS
A total of 106 patients were involved (46 received propofol or midazolam versus 60 received remimazolam). Age (P = 0.182), gender (P = 0.325), and the amount of time between being admitted to the ICU and receiving medication infusion (P = 0.770) did not substantially differ between the two groups. Multivariate analysis revealed no statistically significant difference in ICU mortality between the two groups. The remimazolam group showed less variability in heart rate (P = 0.0021), pH (P = 0.048), bicarbonate (P = 0.0133), lactate (P = 0.0002), arterial blood gas analyses, liver, and kidney function. The Richmond Agitation and Sedation Scale scores, length of ICU stay, and occurrence of adverse events did not exhibit significant differences between the two groups.
CONCLUSION
Remimazolam tosylate did not increase the total inpatient cost, the incidence of adverse events, and ICU mortality in patients with mechanical ventilation. These findings suggest that remimazolam may represent a promising alternative for sedation in the ICU setting.
Topics: Adult; Humans; Hypnotics and Sedatives; Propofol; Respiration, Artificial; Midazolam; Prospective Studies; Intensive Care Units
PubMed: 37865799
DOI: 10.1186/s40001-023-01440-9 -
Indian Journal of Anaesthesia Mar 2024Thoracic continuous spinal anaesthesia (TCSA) is emerging as the sole anaesthetic for major abdominal surgery due to its better perioperative outcomes. This study was...
Comparison of block characteristics and outcomes in opioid-free and opioid-based thoracic continuous spinal anaesthesia in patients undergoing major abdominal surgery: A double-blinded randomised controlled trial.
BACKGROUND AND AIMS
Thoracic continuous spinal anaesthesia (TCSA) is emerging as the sole anaesthetic for major abdominal surgery due to its better perioperative outcomes. This study was designed to evaluate block characteristics and outcomes in 'opioid-free' and 'opioid-based' TCSA.
METHODS
After ethical approval, trial registration and written informed consent, 50 adult patients undergoing major abdominal surgery were randomised into 'opioid-free' (bupivacaine alone) and 'opioid-based' (bupivacaine with fentanyl) groups. After confirmation of T4-L1 dermatome level of spinal anaesthesia, sedation by intravenous (IV) midazolam (0.02-0.05 mg/kg), ketamine (0.25 mg/kg) and dexmedetomidine (bolus dose of 1 µg/kg IV over 10 min followed by 0.2-0.7 µg/kg/h infusion) were started. The primary outcome measured was postoperative pain scores for 72 h in both groups. The secondary objectives were rescue opioid requirement, and the dose of bupivacaine required to achieve T4 level. Data were compared using the two-sided Student -test, Mann-Whitney and Fisher's exact tests.
RESULTS
The 'opioid-based' group performed significantly better compared with the 'opioid-free' group concerning pain scores at rest at 0 h ( = 0.023), 18 h ( = 0.023) and 24 h ( = 0.016) postoperatively, decreased intrathecal bupivacaine requirement [(induction ( = 0.012) and maintenance ( = 0.031)], postoperative rescue fentanyl requirement ( = 0.018) and patient satisfaction ( = 0.032) at the cost of increased postoperative nausea and vomiting ( = 0.049).
CONCLUSION
The 'opioid-based' TCSA provided better postoperative analgesia with significantly lesser postoperative pain scores when compared to the 'opioid-free' group in patients undergoing major abdominal surgery.
PubMed: 38476549
DOI: 10.4103/ija.ija_729_23 -
Pain Research & Management 2023Pediatric dentists often find it challenging to handle pediatric patients due to their fear, unease, and anxiety toward dental procedures. To address this, sedation... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pediatric dentists often find it challenging to handle pediatric patients due to their fear, unease, and anxiety toward dental procedures. To address this, sedation agents such as intranasal midazolam and nitrous oxide are commonly used as pharmacological behavior management methods. A child's temperament affects their behavior in unfamiliar settings.
AIM
To study the effect of child temperament on the acceptance of the nasal mask and intranasal drug administration in children undergoing dental treatment.
METHODS
Thirty-two anxious children aged three to five were randomly assigned to two groups. During the first visit, one group received intranasal midazolam sedation, while the other group received nitrous oxide administered through a mask. On the subsequent visit, the groups crossed over. The parent assessed the child's temperament, and the acceptance of the sedation methods was recorded. The Ohio State University Behavioral Rating Scale (OSUBRS) was employed to assess behavior during the administration of local anesthesia. Statistical analysis was carried out using the chi-square test and Mann-Whitney test ( value <0.05).
RESULTS
Children exhibited greater acceptance of the nasal mask compared to using the intranasal route for delivering midazolam during the induction process. A significant statistical influence of temperament was observed on the acceptance of the nasal mask and the intranasal atomisation device ( value <0.05). The mean OSUBRS scores did not show any statistically significant differences between the sedation groups ( = 0.14).
CONCLUSION
Most children demonstrated a more favorable acceptance of the nasal mask during the induction process; however, intranasal midazolam can serve as an effective alternative for anxious patients who struggle to keep the nitrous oxide mask on during the dental procedure. The adoption of these methods is influenced directly by the child's temperament.
Topics: Humans; Child; Child, Preschool; Midazolam; Conscious Sedation; Cross-Over Studies; Nitrous Oxide; Temperament
PubMed: 37649959
DOI: 10.1155/2023/6655628 -
Europace : European Pacing,... Aug 2023A standardized sedation protocol for pulsed-field ablation (PFA) of atrial fibrillation (AF) through irreversible cellular electroporation has not been well established.... (Clinical Trial)
Clinical Trial
AIMS
A standardized sedation protocol for pulsed-field ablation (PFA) of atrial fibrillation (AF) through irreversible cellular electroporation has not been well established. We report our experience of a protocol for deep sedation with ketamine in spontaneous respiration during the PFA of AF.
METHODS AND RESULTS
All consecutive patients undergoing PFA for AF at our center were included. Our sedation protocol involves the intravenous administration of fentanyl (1.5 mcg/kg) and midazolam (2 mg) at low doses before local anesthesia with lidocaine. A ketamine adjunct (1 mg/kg) was injected about 5 minutes before the first PFA delivery. We enrolled 66 patients (age = 59 ± 9 years, 78.8% males, body mass index = 28.8 ± 5 kg/m2, fluoroscopy time = 21[15-30] min, skin-to-skin time = 75[60-100] min and PFA LA dwell time = 25[22-28] min). By the end of the procedure, PVI had been achieved in all patients by means of PFA alone. The mean time under sedation was 56.4 ± 6 min, with 50 (76%) patients being sedated for less than 1 hour. A satisfactory Ramsey Sedation Scale level before ketamine infusion was achieved in all patients except one (78.8% of the patients with rank 3; 19.7% with rank 2). In all procedures, the satisfaction level was found to be acceptable by both the patient and the primary operator (Score = 0 in 98.5% of cases). All patients reported none or mild pain. No major procedure or anesthesia-related complications were reported.
CONCLUSION
Our standardized sedation protocol with the administration of drugs with rapid onset and pharmacological offset at low doses was safe and effective, with an optimal degree of patient and operator satisfaction.
CLINICAL TRIAL REGISTRATION
Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice (ATHENA). URL: http://clinicaltrials.gov/Identifier: NCT05617456.
Topics: Aged; Female; Humans; Male; Middle Aged; Administration, Intravenous; Anesthesia; Atrial Fibrillation; Catheter Ablation; Deep Sedation; Ketamine; Respiration; Treatment Outcome
PubMed: 37494101
DOI: 10.1093/europace/euad230