Comparative study of intranasal midazolam and intravenous diazepam sedation for procedures and seizures

Mittal, Priya; Manohar, Ram; Rawat, Anurag

doi:10.1007/bf02758299

Cited by 35 publications

(42 citation statements)

References 7 publications

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“…Three articles of similar construct compared intranasal midazolam with intravenous diazepam for cessation of seizures rates and time to cessation. [37][38][39] Each research team reached the same conclusions: 1) midazolam injection administered nasally was equally effective as IV diazepam in seizure cessation, and 2) intranasal midazo- lam reduced time to cessation of seizures by eliminating the need to establish IV access. Bhattacharyya et al 40 conducted a controlled trial of intranasal midazolam to rectal diazepam in children.…”

Section: Experience With Intranasal Delivery Of Benzodiazepines For Tmentioning

confidence: 87%

Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures

Wermeling

2009

Neurotherapeutics

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Summary: Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are all deemed medical emergencies. Mortality and worse neurologic outcome are directly associated with the duration of seizure activity. A number of recent reviews have described consensus statements regarding the pharmacologic treatment protocols for seizures when patients are in pre-hospital, institutional, and home-bound settings. Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection.Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures in the pre-hospital setting, when actively seizing patients arrive in the emergency room, and at home where caregivers treat their dependents. This review summarizes factors to consider when choosing a benzodiazepine for intranasal administration, including formulation and device considerations, pharmacology and pharmacokinetic/pharmacodynamic profiles. A review of the most relevant clinical studies in epilepsy patients will provide context for the relative success of this technique with a number of benzodiazepines and relatively less sophisticated nasal preparations. Neuropeptides delivered intranasally, crossing the blood-brain barrier via the olfactory system, may increase the availability of medications for treatment of epilepsy. Consequently, there remains a significant unmet medical need to serve the pharamcotherapeutic requirements of epilepsy patients through commercial development and marketing of intranasal antiepileptic products.

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Section: Experience With Intranasal Delivery Of Benzodiazepines For Tmentioning

confidence: 87%

Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures

Wermeling

2009

Neurotherapeutics

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“…Clinical studies on the use of intranasal BDZs for the acute management of seizures are available for MDZ [13][14][15][16][17][18][19][20][21][22] and LZP [23,24] suggesting that, in both cases, the intranasal delivery is a potentially efficient alternative root of administration (Table 3) and ad hoc technologies are currently under investigation. In particular, there are two intranasal DZP formulations currently under development by Neurelis (10 mg) and Acorda Therapeutics (20 mg) and a MDZ intranasal formulation by Upsher-Smith Laboratories (2.5 mg, 5 mg, 7.5 mg) [10].…”

Section: Intranasal Deliverymentioning

confidence: 99%

“…A number of trials compared intranasal MDZ with either rectal DZP or intravenous DZP [13][14][15][16][17][18][19][20][21][22] (Table 3). Available data suggests that intranasal MDZ is effective, safe and more efficient that rectal DZP in controlling seizure activity [7] (Table 3).…”

Section: Intranasal Deliverymentioning

confidence: 99%

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

Mula

2016

CNS Drugs

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Benzodiazepines (BDZs) represent first line treatment for the acute management of epileptic seizures and status epilepticus. The emergency use of BDZs requires timely administration and considering that most seizures occur outside of the hospital, there is a significant need for easy to use delivery methods that can be given quickly and safely by nonclinical caregivers. In addition, the ideal route of administration should be reliable in terms of absorption. In the US, rectal diazepam is the only licensed formulation, while in the EU rectal diazepam and buccal midazolam are currently licensed. However, both the rectal and buccal administration are not ideal as the absorption can be sometimes unpredictable. Several alternative routes are being explored and are currently under investigation. This is a narrative review of available data about delivery methods for BDZs alternative to the intravenous and oral routes for the acute treatment of seizures. Unconventional delivery options such as the direct delivery in the central nervous system or inhalers are reported. Available data shows that intranasal diazepam or midazolam and the intramuscular auto-injector for midazolam are as effective as rectal or intravenous diazepam. Head to head comparisons with buccal midazolam are urgently needed. In addition, the majority of trials focused on children and adolescents and further trials in adults are warranted.

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“…13 Several authors have also assessed the time to seizure termination with IV vs. alternative routes of medication (intranasal (IN), IM, and buccal). 13,51,53,55,58,59 In general, investigators have shown that while benzodiazepines delivered via an IV have a more rapid onset of action from dose delivery to seizure cessation, a greater amount of time is required to place the IV than to deliver the therapy by non-IV routes. 13,55,59,60,61 Therefore, the total amount of time from the decision to treat with a benzodiazepine to seizure cessation is equivalent or less when alternative routes are used.…”

Section: Therapy: IV Vs Non-iv Treatmentmentioning

confidence: 99%

An Evidence-based Guideline for Pediatric Prehospital Seizure Management Using GRADE Methodology

Shah¹,

Macias²,

Dayan³

et al. 2013

Prehospital Emergency Care

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Objective. The objective of this guideline is to recommend evidence-based practices for timely prehospital pediatric seizure cessation while avoiding respiratory depression and seizure recurrence. Methods. A multidisciplinary panel was chosen based on expertise in pediatric emergency medicine, prehospital medicine, and/or evidence-based guideline development. The panel followed the National Prehospital EBG Model using the GRADE methodology to formulate questions, retrieve evidence, appraise the evidence, and formu- The panel finalized a draft of a patient care algorithm in 2012 that was presented to stakeholder organizations to gather feedback for necessary revisions. Results. Five strong and ten weak recommendations emerged from the process; all but one was supported by low or very low quality evidence. The panel sought to ensure that the recommendations promoted timely seizure cessation while avoiding respiratory depression and seizure recurrence. The panel recommended that all patients in an active seizure have capillary blood glucose checked and be treated with intravenous (IV) dextrose or intramuscular (IM) glucagon if <60 mg/dL (3 mmol/L). The panel also recommended that non-IV routes (buccal, IM, or intranasal) of benzodiazepines (0.2 mg/kg) be used as first-line therapy for status epilepticus, rather than the rectal route. Conclusions. Using GRADE methodology, we have developed a pediatric seizure guideline that emphasizes the role of capillary blood glucometry and the use of buccal, IM, or intranasal benzodiazepines over IV or rectal routes. Future research is needed to compare the effectiveness and safety of these medication routes.

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Comparative study of intranasal midazolam and intravenous diazepam sedation for procedures and seizures

Abstract: Midazolam by the intranasal route provides safe and equally effective non-invasive method of sedation for procedures and seizures.

Cited by 35 publications

References 7 publications

Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures

Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

An Evidence-based Guideline for Pediatric Prehospital Seizure Management Using GRADE Methodology

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