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Lorazepam (Ativan) 0.1–0.15 mg/kg IV (4 mg max.) over 2 minutes or IM (repeat once if no response after 10 minutes – maximum dose 8 mg)

OR

Midazolam (Versed) 0.2 mg/kg IV or IM to maximum of 10 mg

OR

Diazepam (Valium) 0.2–0.3 mg/kg IV over 2–5 minutes (max. 10 mg) ‐OR‐ 0.5 mg/kg per rectum

Note: See text for details of alternative dosing regimens. Respiratory depression is the most serious side effect and is likely related to rate of administration.

Generally, IV administration of benzodiazepines has been the standard because of rapid therapeutic drug levels, but a variety of reports substantiates the effectiveness of intramuscular, rectal, nasal, and buccal administration of different agents. Benzodiazepines are well tolerated, with primary side effects of sedation and respiratory depression. The respiratory depression seems to be related to time to peak serum concentration. Somewhat paradoxically, the IV route may offer the quickest time to peak concentrations but at a risk of greater respiratory depression.

The use of alternative routes is particularly attractive in the pediatric population. Intraosseous administration should be an effective route of administration, but it has been little studied in seizure patients.

Rectal administration of benzodiazepines (particularly diazepam) for status epilepticus in children has been reported for years [33]. Studied dosages are 0.5 mg/kg administered using a syringe and a soft catheter. Correction should be made for the volume left in the catheter. A second dose of 0.25 mg/kg may be administered if needed. It is generally thought that rectal administration results in peak plasma levels within 10 minutes. A preparation approved by the US Food and Drug Administration, Diastat, is available [34].

Nasal administration of benzodiazepines (usually midazolam) has been reported in small case series [35]. Ease of use was the focus in studies comparing nasal midazolam with IV diazepam [36]. Time to seizure cessation was comparable. Another report compared intranasal administration of midazolam using an atomizer device with rectal diazepam and found better seizure control and fewer respiratory complications in the group treated with intranasal midazolam [37].

Buccal midazolam has been studied for seizure control in children in the ED, in comparison with rectal diazepam, and has been found to be as effective or more effective without increased risk of respiratory depression [38, 39]. Dosages administered were 0.25 mg/kg or 0.5 mg/kg with adjustments by age, and a 10 mg maximum dosage for children age 10 or older. As with many of the therapies discussed here, this is off‐label usage. Buccal midazolam is advocated by some as a choice for initial management of prolonged seizures in children, although issues of dosing remain and further study is desirable [40, 41].

Intramuscular (IM) administration of a benzodiazepine is possible with midazolam, which has solubility characteristics favorable for absorption [42]. IM administration is rapid and aspiration is not a concern. Increased use of IM midazolam has been noted in some systems [43]. In one small series of children with seizures, comparing treatment with IM midazolam with IV diazepam, the former was found to be an effective alternative. Part of the efficacy was thought to be from the rapid administration possible by the IM route without having to establish IV access [44]. The RAMPART study established the safety and efficacy of IM midazolam compared to IV lorazepam when administered for prehospital status epilepticus [45]. Paramedics in this large, randomized, double‐blind trial administered midazolam intramuscularly using preloaded auto‐injectors. Advantages of the intramuscular route included more rapid drug administration. Dosages of midazolam were 10 mg IM for adults and children estimated to weigh more than 40 kg and 5 mg IM for children estimated to weigh 13–40 kg. Adverse events were similar in both groups. However, IV midazolam was found to be more effective than IM administration in one prehospital study, with minimal risk of respiratory depression in both groups [46].