-
Alternative Therapies in Health and... Jun 2024This study aimed to compare the direct medication costs and clinical effectiveness of using remimazolam versus midazolam for goal-guided sedation therapy in the ICU...
OBJECTIVE
This study aimed to compare the direct medication costs and clinical effectiveness of using remimazolam versus midazolam for goal-guided sedation therapy in the ICU patients.
METHODS
This randomized controlled study was conducted in the ICU of People's Hospital Affiliated to Shandong First Medical University. Eighty adult patients admitted to the ICU and requiring sedation were enrolled and randomly assigned in a 1:1 ratio to receive either remimazolam-based sedation (study group, n=40) or midazolam-based sedation (control group, n=40). The inclusion criteria for patient selection were age 18-80 years, requirement for mechanical ventilation, and an expected ICU stay of at least 24 hours. Patients with significant liver or kidney dysfunction, neurological disorders, or contraindications to the study drugs were excluded. The target sedation depth for both groups was a Ramsay Sedation Scale score of 3-4, which was maintained by titrating the infusion rates of remimazolam or midazolam as needed. Vital signs, sedation scores, and respiratory parameters were closely monitored throughout the sedation period.
RESULTS
The time to onset of sedation, time to reach the target sedation depth, time to awakening, and length of ICU stay were all significantly shorter in the remimazolam group compared to the midazolam group (P < .05 for all). The remimazolam group had a mean time to onset of 5.2 ± 1.8 minutes versus 8.9 ± 2.4 minutes in the midazolam group. The mean time to reach the target Ramsay Sedation Scale score of 3-4 was 12.6 ± 3.1 minutes in the remimazolam group compared to 18.4 ± 4.2 minutes in the midazolam group. The mean time to awakening was 10.2 ± 2.7 minutes in the remimazolam group versus 16.5 ± 3.9 minutes in the midazolam group. The remimazolam group also had a significantly shorter mean ICU length of stay of 5.1 ± 1.3 days compared to 7.8 ± 2.1 days in the midazolam group (P < .01). The remimazolam group had a significantly higher metabolic clearance rate compared to the midazolam group (P < .001). The Ramsay sedation scores and Wong-Baker FACES pain scores were also significantly lower in the remimazolam group throughout the sedation period (P < .01). There were no significant differences in heart rate between the two groups at any timepoint. However, the overall incidence of adverse events was significantly lower in the remimazolam group compared to the midazolam group (P < .05).
CONCLUSION
This study demonstrated that the use of remimazolam-based goal-directed sedation in the ICU setting resulted in significantly faster onset of action, quicker achievement of the target sedation depth, shorter time to awakening, and shorter ICU length of stay compared to midazolam-based sedation. The remimazolam group also had a higher metabolic clearance rate, lower sedation and pain scores, and a lower incidence of adverse events.These findings suggest that remimazolam may provide advantages over midazolam for ICU sedation, potentially leading to improved patient comfort, more efficient utilization of ICU resources, and potentially better clinical outcomes. The rapid onset, titratability, and favorable safety profile of remimazolam make it a promising sedative agent that could help optimize sedation practices in the critical care setting. Further research is warranted to fully evaluate the impact of remimazolam on long-term patient-centered outcomes and overall healthcare costs in the ICU.
PubMed: 38843423
DOI: No ID Found -
Open Medicine (Warsaw, Poland) 2024Understanding the intricate relationship between cancer clinicopathological features and anesthetics dosage is crucial for optimizing patient outcomes and safety during...
Understanding the intricate relationship between cancer clinicopathological features and anesthetics dosage is crucial for optimizing patient outcomes and safety during surgery. This retrospective study investigates this relationship in patients with non-small cell lung cancer (NSCLC) undergoing video-assisted thoracic surgery (VATS). A comprehensive analysis of medical records was undertaken for NSCLC patients who underwent VATS with intravenous compound inhalation general anesthesia. Patients were categorized based on histological, chemotherapy, radiotherapy, and epidural anesthesia factors. Statistical analysis was performed to compare the differences between the groups. The results revealed compelling insights. Specifically, patients with lung adenocarcinoma (LUAD) undergoing VATS exhibited higher dosages of rocuronium bromide and midazolam during general anesthesia, coupled with a shorter post-anesthesia care unit (PACU) stay compared to those with squamous cell carcinoma (sqCL). Furthermore, chemotherapy patients undergoing VATS demonstrated diminished requirements for phenylephrine and remifentanil in contrast to their non-chemotherapy counterparts. Similarly, radiotherapy patients undergoing VATS demonstrated a decreased necessity for rocuronium bromide compared to non-radiotherapy patients. Notably, patients who received epidural anesthesia in combination with general anesthesia manifested reduced hydromorphone requirements and prolonged hospital stays compared to those subjected to general anesthesia alone. In conclusion, the findings from this study indicate several important observations in diverse patient groups undergoing VATS. The higher dosages of rocuronium bromide and midazolam in LUAD patients point to potential differences in drug requirements among varying lung cancer types. Additionally, the observed shorter PACU stay in LUAD patients suggests a potentially expedited recovery process. The reduced anesthetic requirements of phenylephrine and remifentanilin chemotherapy patients indicate distinct responses to anesthesia and pain management. Radiotherapy patients requiring lower doses of rocuronium bromide imply a potential impact of prior radiotherapy on muscle relaxation. Finally, the combination of epidural anesthesia with general anesthesia resulted in reduced hydromorphone requirements and longer hospital stays, suggesting the potential benefits of this combined approach in terms of pain management and postoperative recovery. These findings highlight the importance of tailoring anesthesia strategies for specific patient populations to optimize outcomes in VATS procedures.
PubMed: 38841176
DOI: 10.1515/med-2024-0961 -
Journal of Dental Anesthesia and Pain... Jun 2024Patients with autism spectrum disorder (ASD) present challenges in dental treatment cooperation owing to deficits in communication skills and social interaction....
BACKGROUND
Patients with autism spectrum disorder (ASD) present challenges in dental treatment cooperation owing to deficits in communication skills and social interaction. Behavioral guidance, sedation, and general anesthesia may be employed to ensure the quality of dental care for individuals with ASD. This study aimed to examine the trends in dental treatment for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital, an oral health center for the disabled in the Gyeonggi region, over the past 10 years.
METHODS
This study utilized the order communication system to gather data on sex, age, cooperation level, number of quadrants treated, and administration of sedation or general anesthesia for patients with ASD who visited the Department of Pediatric Dentistry at Dankook University Jukjeon Dental Hospital between January 2013 and December 2022.
RESULTS
The total number of patients with ASD increased annually, possibly due to an increase in ASD prevalence and the hospital's designation as a center for disabled oral health. General anesthesia was predominant before 2017, with a shift towards NO-O sedation. The most common age group for sedation or general anesthesia was 6-9 years, with a higher prevalence in males than in females. Notably, NO-O and midazolam sedation resulted in better cooperation and fewer treated teeth than general anesthesia.
CONCLUSION
This study highlights the evolving trends in dental treatment for individuals with ASD, indicating a shift towards outpatient methods, particularly NO-O sedation. The sex distribution aligns with national statistics, emphasizing a higher prevalence of ASD in males than in females. These findings underscore the need for further research to establish evidence-based guidelines for optimal dental care strategies tailored to the unique needs of individuals with ASD.
PubMed: 38840652
DOI: 10.17245/jdapm.2024.24.3.187 -
Journal of Dental Anesthesia and Pain... Jun 2024Excessive fear of dental procedures leads to disruptive behavior during dental examinations and treatments. Dental examinations and treatments of these patients usually...
BACKGROUND
Excessive fear of dental procedures leads to disruptive behavior during dental examinations and treatments. Dental examinations and treatments of these patients usually require additional techniques, such as sedation. The most commonly used techniques are inhalation of nitrous oxide, infusion of propofol with fentanyl, and premedication and infusion of midazolam.
METHODS
A prospective observational epidemiological study was conducted on patients who required sedoanalgesia techniques for dental exploration and procedures. The reasons for the inability of patients to cooperate (excessive fear or intellectual disability), age, sex, weight, systemic pathology, oral pathology, treatment performed, time of intervention, anesthetic technique performed, and occurrence of complications were recorded.
RESULTS
In total, 218 patients were studied. Sixty-five patients came for fear of dental treatment and 153 for presenting with a diagnosis of intellectual disability and not collaborating in the treatment with local anesthesia. The average age of all patients was 30.54 ± 17.30 years. The most frequent oral pathologies found in patients with excessive fear were tartar (6.8%) and wisdom teeth (6.4%), followed by missing teeth (5%). In patients with disabilities, a combination of tartar and cavities appeared most frequently (41.3%), followed by cavities (15.6%). The most frequently used sedoanalgesia technique was the infusion of propofol with fentanyl in both groups of patients, followed by nitrous oxide.
CONCLUSION
The combination of propofol and fentanyl was the most frequently used alternative in patients who were unable to collaborate because of intellectual disability or carry out longer or more complex treatments. Inhaled nitrous oxide and midazolam were the sedative techniques of choice for simpler oral treatments, such as tartrectomies, shallow obturations, and shorter interventions, or in younger patients.
PubMed: 38840648
DOI: 10.17245/jdapm.2024.24.3.173 -
Acta Medica Philippina 2024Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy...
Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy (EBBT) has been shown to provide palliative therapy. It is the insertion of a radioactive material near the mass to reduce tumor size, thereby improving airway obstruction. This is the first case of EBBT done in our institution during the COVID-19 pandemic. A 53-year-old male, 60 kg, ASA Physical Status 2 for hypertension, smoker, malignancy, and previous pulmonary tuberculosis patient, presented with a cough and dyspnea. An endobronchial mass almost obstructing the right mainstem bronchus was seen on a computed tomography (CT) scan. He was diagnosed with squamous cell carcinoma of the lung and underwent radiotherapy and erlotinib chemotherapy. On repeat CT scan, there was no noted decrease in the size of the mass. EBBT was suggested, and a multi-disciplinary team was formed for the planned procedure. Pulmonology, radiation oncology, and anesthesiology teams were identified, and thorough planning was done prior to the actual procedure. Three fractions of EBBT were done under sedation using midazolam, fentanyl, and dexmedetomidine infusion. Lidocaine spray and transtracheal block were also performed as adjuncts prior to sedation. The procedure went as planned, and points for improvement were discussed for subsequent fractions. Due to persistent cough and discomfort from the catheter, additional ipratropium nebulization for minimization of secretions, and oral dextromethorphan for cough suppression were incorporated. After each fraction, the patient was monitored post-procedure for any side effects both from the radiotherapy and anesthetic technique. Qualitative reduction in mass size was noted in subsequent fractions. The patient was able to complete 3 fractions and was advised to follow-up after a month. EBBT is an emerging palliative and treatment modality for lung cancer, especially for intraluminal masses. Anesthetic considerations will depend on each case's characteristics such as airway anatomy, patient comfort and capacity, and procedural requirements. Conscious sedation with topical anesthesia is an adequate and appropriate anesthetic option, especially in cases where severe airway obstruction may compromise ventilation if airway reflexes are blunted. A multidisciplinary approach with different services and stakeholders is important for the proper planning, execution, and management of such patients.
PubMed: 38836083
DOI: 10.47895/amp.v58i9.8839 -
Palliative Medicine Jun 2024Tracheostomy ventilation in motor neurone disease is an uncommon life-sustaining treatment. Best practice is having a plan for ventilation withdrawal, but the literature...
BACKGROUND
Tracheostomy ventilation in motor neurone disease is an uncommon life-sustaining treatment. Best practice is having a plan for ventilation withdrawal, but the literature to guide practice is limited. Case reports have documented standard doses of opioids and benzodiazepines used for sedation in such cases.
CASE
A 49-year-old man was diagnosed with motor neurone disease in 2016. He commenced tracheostomy ventilation in 2018. In 2022 and 2023, planning was undertaken, at the patient's request, for withdrawal of tracheostomy ventilation at home, when he was no longer able to communicate with technology.
CASE PLANNING
Planning included Bispectral Index monitoring prior to cessation of ventilation, ensuring this only occurred when deep sedation was achieved. After ventilation withdrawal in 2023, a retrospective review of medications given and his level of sedation on monitoring was undertaken, with family consent.
OUTCOME
Ventilation withdrawal was initiated after deep sedation was achieved, 6 h after commencing subcutaneous infusions of morphine, midazolam, clonazepam and phenobarbital.
LESSONS
Doses required to achieve acceptable sedation exceeded literature reports. Achieving deep sedation was a longer than expected process.
CONCLUSION
More research using an objective measure of sedation is required, as clinical assessment of sedation in this context is compromised.
PubMed: 38835175
DOI: 10.1177/02692163241257580 -
CPT: Pharmacometrics & Systems... Jun 2024Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC-1 study. Cytokines, especially interleukin (IL)-6, are known...
Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC-1 study. Cytokines, especially interleukin (IL)-6, are known suppressors of cytochrome P450 (CYP) enzymes' activity. A physiologically based pharmacokinetic model evaluated the impact of IL-6 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5). Two IL-6 kinetics profiles were assessed, the mean IL-6 profile with a maximum concentration (C) of IL-6 (21 pg/mL) and the IL-6 profile of the patient presenting the highest IL-6 C (288 pg/mL) among patients receiving the recommended phase II dose of teclistamab in MajesTEC-1. For the mean IL-6 kinetics profile, teclistamab was predicted to result in a limited change in exposure of CYP substrates (area under the curve [AUC] mean ratio 0.87-1.20). For the maximum IL-6 kinetics profile, the impact on omeprazole, simvastatin, midazolam, and cyclosporine exposure was weak to moderate (mean AUC ratios 1.90-2.23), and minimal for caffeine and s-warfarin (mean AUC ratios 0.82-1.25). Maximum change in exposure for these substrates occurred 3-4 days after step-up dosing in cycle 1. These results suggest that after cycle 1, drug interaction from IL-6 effect has no meaningful impact on CYP activities, with minimal or moderate impact on CYP substrates. The highest risk of drug interaction is expected to occur during step-up dosing up to 7 days after the first treatment dose (1.5 mg/kg subcutaneously) and during and after CRS.
PubMed: 38831634
DOI: 10.1002/psp4.13144 -
British Journal of Clinical Pharmacology Jun 2024Early clinical studies have indicated that the pharmacokinetics of Atuliflapon (AZD5718) are time and dose dependent. The reason(s) for these findings is(are) not fully...
A drug-drug interaction study and physiologically based pharmacokinetic modelling to assess the effect of an oral 5-lipoxygenase activating protein inhibitor on the pharmacokinetics of oral midazolam.
AIMS
Early clinical studies have indicated that the pharmacokinetics of Atuliflapon (AZD5718) are time and dose dependent. The reason(s) for these findings is(are) not fully understood, but pre-clinical profiling suggests that time-dependent CYP3A4 inhibition cannot be excluded. In clinical practice, Atuliflapon will be co-administered with CYP3A4 substrates; thus, it is important to determine the impact of Atuliflapon on the pharmacokinetics (PK) of CYP3A4 substrates. The aim of this study was to evaluate the effect of Atuliflapon on the pharmacokinetics of a sensitive CYP3A4 substrate, midazolam, and to explore if the time-/dose-dependent effect seen after repeated dosing could be an effect of change in CYP3A4 activity.
METHODS
Open-label, fixed-sequence study in healthy volunteers to assess the PK of midazolam alone and in combination with Atuliflapon. Fourteen healthy male subjects received single oral dose of midazolam 2 mg on days 1 and 7 and single oral doses of Atuliflapon (125 mg) from days 2 to 7. A physiologically based pharmacokinetic (PBPK) model was developed to assess this drug-drug interaction.
RESULTS
Mean midazolam values of maximum plasma concentration (C) and area under the curve (AUC) to infinity were increased by 39% and 56%, respectively, when co-administered with Atuliflapon vs. midazolam alone. The PBPK model predicted a 27% and 44% increase in AUC and a 23% and 35% increase in C of midazolam following its co-administrations with two predicted therapeutically relevant doses of Atuliflapon.
CONCLUSIONS
Atuliflapon is a weak inhibitor of CYP3A4; this was confirmed by the validated PBPK model. This weak inhibition is predicted to have a minor PK effect on CYP3A4 metabolized drugs.
PubMed: 38830622
DOI: 10.1111/bcp.16131 -
Emergency Medicine Australasia : EMA Jun 2024Out-of-hospital seizures demand rapid management. Midazolam plays a key role in stopping seizures. At times the first dose of midazolam proves insufficient,...
OBJECTIVE
Out-of-hospital seizures demand rapid management. Midazolam plays a key role in stopping seizures. At times the first dose of midazolam proves insufficient, necessitating additional doses. Within the New South Wales Ambulance (NSWA) service, the upper limit for midazolam administration is set at 15 mg. However, the outcomes and safety of using midazolam at this maximum dosage have not been thoroughly investigated.
METHODS
A retrospective analysis of out of hospital electronic health records from New South Wales, Australia, over the year 2022, was conducted. The study manually reviewed cases where adult patients received the maximum dose of midazolam for seizure management by paramedics. It focused on seizure cessation success rates and the incidence of adverse effects to evaluate the clinical implications of high-dose midazolam administration.
RESULTS
Of 818 790 individual attendances by NSWA clinicians, a total of 11 392 (1.4%) adults had seizures noted, of which midazolam was administered in 2565 (22.5%). An algorithm shows that in 2352 (91.7%) instances the midazolam was associated with the apparent termination of seizures. Analysis revealed that 176 (1.5%) proportion of all adult's seizure patients required the maximum dose of midazolam for seizure control. These higher doses successfully terminate seizures in about half of the instances. AEs following the maximum dose of midazolam included hypoxia in 26.7% of patients and respiratory depression in 9.7%, indicating significant side effects at higher dosages.
CONCLUSION
In New South Wales, Australia, administering the maximum dose of midazolam to seizure patients is rare but proves effective in approximately half of the refractory seizure cases. Therefore, assessing the potential for additional doses of midazolam or the use of a second-line agent is advisable.
PubMed: 38828557
DOI: 10.1111/1742-6723.14432 -
Clinical Neurology and Neurosurgery Jul 2024Cerebellar mutism syndrome (CMS) is a serious complication of posterior fossa surgeries affecting mainly pediatric age group. The pathophysiology is still not fully... (Review)
Review
INTRODUCTION
Cerebellar mutism syndrome (CMS) is a serious complication of posterior fossa surgeries affecting mainly pediatric age group. The pathophysiology is still not fully understood. It adversely affects the recovery of patients. There is no definitive and standardized management for CMS. However pharmacological therapy has been used in reported cases with variable effectiveness. We aim through this review to summarize the available evidence on pharmacological agents used to treat CMS.
METHOD
A thorough systematic review until December 2022, was conducted using PubMed Central, Embase, and Web of Science, databases to identify case reports and case series of CMS patients who underwent posterior fossa surgery and received pharmacological treatment. Patients with pathologies other than posterior fossa lesions were excluded from the study.
RESULTS
Of 592 initial studies, 8 studies met our eligibility criteria for inclusion, with 3 more studies were added through manual search; reporting on 13 patients. The median age of 13 years (Standard deviation SD=10.60). The most frequent agent used was Bromocriptine. Other agents were fluoxetine, midazolam, zolpidem, and arpiprazole. Most patients recovered within 48 hours of initiating medical therapy. The median follow-up period was 4 months (SD=13.8). All patients showed complete recovery at the end of follow-up period.
CONCLUSION
Cerebellar mutism syndrome is reported after posterior fossa surgeries, despite attempts to identify risk factors, pathophysiology, and management of CMS, it remains a challenging condition with significant morbidity. Different Pharmacological treatments have been proposed with promising results. Further studies and formalized clinical trials are needed to evaluate available options and their effectiveness.
Topics: Humans; Mutism; Neurosurgical Procedures; Postoperative Complications; Cranial Fossa, Posterior; Cerebellar Diseases; Child; Adolescent
PubMed: 38823197
DOI: 10.1016/j.clineuro.2024.108352