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Febrile seizures
Published in Samar Razaq, Difficult Cases in Primary Care, 2021
Immediate management to terminate the seizure is indicated if the seizure is prolonged. Treatment should be given if the seizure lasts longer than 5 minutes. Rectal diazepam or buccal midazolam at a dose of 0.5 mg/kg is effective at terminating seizures. Midazolam may also be given intranasally. They are the drugs of choice in the primary care setting because of the likelihood of not having intravenous access. In a study comparing the two benzodiazepines in children aged 6 months and older attending hospital, buccal midazolam was found to be more effective than rectal diazepam in terminating the seizure within 10 minutes for at least an hour (McIntyre, et al., 2005). If the seizure is not terminated within 10 minutes of delivery of the drug or the seizure recurs, then an ambulance should be called to organise hospital admission. Long-term management is centred on parent reassurance and explanation of the condition.
Critical care, neurology and analgesia
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Midazolam is a water-soluble benzodiazepine that produces effective sedation and reduces the recall of critically ill patients. Tolerance and withdrawal phenomena are the most frequently encountered problems with midazolam. The incidence of adverse events following midazolam discontinuation in critically ill children is quoted as between 17% and 30% and usually occurs within a few hours of stopping the drug. There may be central nervous system symptoms such as seizures, paradoxical agitation, hallucinations and psychotic reactions or somatic manifestations such as tachycardia, vomiting and fever.
Local Anesthesia for Children
Published in Marwali Harahap, Adel R. Abadir, Anesthesia and Analgesia in Dermatologic Surgery, 2019
Thierry Pirotte, Francis Veyckemans
The major concern with midazolam is respiratory depression, which may be life threatening, especially when used in association with other sedatives or with narcotics. Moreover, paradoxal reactions (agitation) are not uncommon as with any benzodiazepine (98).
The alteration of drug metabolism enzymes and pharmacokinetic parameters in nonalcoholic fatty liver disease: current animal models and clinical practice
Published in Drug Metabolism Reviews, 2023
Yan Zhu, Li Chen, Yuqi He, Lin Qin, Daopeng Tan, Zhaojun Bai, Yu Song, Yu-He Wang
Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions (Nielsen et al. 2016), and it is a selective probe of CYP2E1 activity in vivo. It was found that the metabolic clearance of chlorzoxazone was markedly elevated in obese subjects with NASH than those without NASH (Emery et al. 2003). Midazolam is a short-acting benzodiazepine that is widely used as a premedicant prior to surgery, for induction of anesthesia, and for conscious sedation (Rodolà 2006). The CYP3A4 protein expression levels were significantly lower in patients with NAFLD and NASH. Compared with control subjects, midazolam concentrations were significantly higher in human subjects with NASH (Woolsey et al. 2015; Jamwal et al. 2018). In the HFD-fed mice model, both mRNA and protein expression levels of Cyp3a11/CYP3A4 tended to decrease. What’s more, HFD mice had significantly prolonged sleeping times after midazolam (Cyp3a11/CYP3A4 substrate) (Ghose et al. 2011). The results led us to wonder whether current drug dosage recommendations may need to be reevaluated in the NAFLD population to ensure the premier clinical outcomes of these drug therapies.
The Effectiveness of Intranasal Midazolam for the Treatment of Prehospital Pediatric Seizures: A Non-inferiority Study
Published in Prehospital Emergency Care, 2022
Denise Whitfield, Nichole Bosson, Amy H. Kaji, Marianne Gausche-Hill
In our study cohort, redosing overwhelmingly occurred by the same route as initial midazolam administration, with patients more frequently requiring a second IN dose at 0.1 mg/kg in order to terminate seizure activity. A third dose was rarely required in both groups. Further, though not powered for this outcome, our study demonstrated no difference in need for bag-mask ventilation between study groups despite the higher need for redosing among patients treated with IN midazolam. In response to these results, the dose for IN midazolam is currently 0.2 mg/kg in LAC EMS protocols. Future studies should evaluate IN midazolam dosed at a minimum of 0.2 mg/kg as compared to IM and IV routes of administration. With higher dosing, one may risk greater chances for respiratory depression and airway complications. However, a prior evaluation from our system demonstrated that the greatest risk for apnea occurs when the seizure persists, rather than as the result of the midazolam administration (25). A tendency for EMS systems to underdose midazolam in treating status epilepticus has been noted in adult patients, even though those patients receiving higher doses of midazolam were less likely to need subsequent rescue therapy and had decreased need for respiratory support (26). One multicenter study demonstrated EMS underdosing in pediatric seizure management, where 36% of patients in that study received an incorrect first dose, with 72% of those misdosed receiving an underdose (27). Medication underdosing may be a correctable contributing factor to prolonged pediatric seizures in the field and warrants further study.
Induction and maintenance of procedural sedation in adults: focus on remimazolam injection
Published in Expert Review of Clinical Pharmacology, 2021
Weiyun Chen, Shaohui Chen, Yuguang Huang
Benzodiazepines are also commonly used for procedural sedation. As the shortest-acting benzodiazepine available for the past several decades, midazolam is the most frequently used benzodiazepine in clinical practice [5,28]. Midazolam shows rapid onset and offset comparable to propofol but has a longer half-life and longer duration of action [29,30]. Midazolam itself also has no analgesic effects and opioids are usually combined for procedural sedation [1]. Midazolam has a wide margin for safety, is less likely to cause respiratory depression and rarely associated with significant hemodynamic instability, making it a favorable choice for both anesthesiologists and non-anesthesiologists for procedural sedation [31]. However, alpha-hydroxy-midazolam, an active metabolite of midazolam, has potential sedative effects, which may put the patients at risk of repeat sedation [32,33]. Also, accumulation in peripheral tissues could occur when midazolam is administered with repeated boluses or prolonged infusion, causing over titration [29,32]. In addition, its duration of action increases in elderly patients and those with impaired liver and renal function as it relies on the liver enzyme cytochrome P450 3A4 for metabolism [34]. Moreover, midazolam has relatively large interindividual variability, with approximately 30% variability in clearance and 50% variability in half maximum effective concentration (EC50), making it not so well controllable [35]. Therefore, midazolam is mainly used for short procedures and should be administered with caution in patients with comorbidities, especially when repeated dosages are given.