Intramuscular Midazolam for Status Epilepticus
Intramuscular Midazolam for Status Epilepticus
Initial treatment typically consists of benzodiazepines followed by phenobarbital, phenytoin, valproate, or other antiepileptic drugs. In refractory cases, intubation and general anesthesia with midazolam, pentobarbital, propofol, or other drugs may be required.
One of the most important factors affecting treatment outcome is the duration of status epilepticus; longer episodes are associated with treatment resistance and higher morbidity and mortality.Consequently, there is a strong rationale for emergency medical personnel to initiate treatment in the field as soon as possible, rather than waiting for patients to arrive at the hospital.
In RAMPART, 893 persons who had convulsions lasting more than 5 minutes that were still ongoing when emergency medical personnel arrived were randomly assigned to receive either intramuscular midazolam plus intravenous placebo or intravenous lorazepam plus intramuscular placebo.Participants included 4313 paramedics, 33 emergency medical services agencies, and 79 receiving hospitals in the United States. Intramuscular midazolam was administered with an autoinjector.
Upon arrival in the emergency department, 329 (73.4%) of the 448 midazolam-treated patients vs 282 (63.4%) of the 445 lorazepam-treated patients were seizure-free, demonstrating both the noninferiority and superiority of midazolam (P < .001). In addition, the proportion of patients who required hospital admission was significantly lower in the midazolam group than the lorazepam group (57.6% vs 65.6%; P = .01). Adverse event rates were similar in both groups.
The results emphasize the importance of rapid administration of an active drug in treating status epilepticus. Median times to treatment were 4 times longer with intravenous lorazepam (4.8 minutes) vs intramuscular midazolam (1.2 minutes). The ease of administration of midazolam more than made up for the fact that it was slower-acting (3.3 minutes) than lorazepam (1.6 minutes). Consequently, the median time to seizure control was slightly longer with lorazepam (4.8 + 1.6 = 6.4 minutes) than with midazolam (1.2 + 3.3 = 4.5 minutes) (P value not significant).
Furthermore, 31 patients in the lorazepam group did not receive the active drug because of difficulty with intravenous access, whereas only 5 patients in the midazolam group did not receive drug owing to autoinjector failure. These results highlight the difficulty of establishing intravenous access in an actively convulsing patient.
Other routes of benzodiazepine administration, such as buccal, intranasal, and rectal, may also be effective in controlling seizures, but intramuscular administration by autoinjector offers more predictable dosing.
The benefit of intramuscular midazolam for status epilepticus demonstrated by the double-blind RAMPART study highlights the practical considerations of treating patients who are actively seizing. Although lorazepam had a faster onset of action, the fact that intramuscular midazolam could be administered more quickly resulted in similar times to effectiveness for the 2 drugs. More midazolam-treated patients were seizure-free upon hospital arrival (73.4% for midazolam vs. 63.4% for lorazepam) -- a difference of 10 percentage points, which demonstrated the noninferiority and superiority of midazolam.
Because prompt treatment of status epilepticus strongly influences morbidity and mortality, it is likely that the results of this study will translate into US Food and Drug Administration approval of intramuscular midazolam for status epilepticus in the near future.
Enter, Intramuscular Midazolam
Treatment Overview
Initial treatment typically consists of benzodiazepines followed by phenobarbital, phenytoin, valproate, or other antiepileptic drugs. In refractory cases, intubation and general anesthesia with midazolam, pentobarbital, propofol, or other drugs may be required.
One of the most important factors affecting treatment outcome is the duration of status epilepticus; longer episodes are associated with treatment resistance and higher morbidity and mortality.Consequently, there is a strong rationale for emergency medical personnel to initiate treatment in the field as soon as possible, rather than waiting for patients to arrive at the hospital.
Intramuscular Midazolam vs Intravenous Lorazepam
In RAMPART, 893 persons who had convulsions lasting more than 5 minutes that were still ongoing when emergency medical personnel arrived were randomly assigned to receive either intramuscular midazolam plus intravenous placebo or intravenous lorazepam plus intramuscular placebo.Participants included 4313 paramedics, 33 emergency medical services agencies, and 79 receiving hospitals in the United States. Intramuscular midazolam was administered with an autoinjector.
Upon arrival in the emergency department, 329 (73.4%) of the 448 midazolam-treated patients vs 282 (63.4%) of the 445 lorazepam-treated patients were seizure-free, demonstrating both the noninferiority and superiority of midazolam (P < .001). In addition, the proportion of patients who required hospital admission was significantly lower in the midazolam group than the lorazepam group (57.6% vs 65.6%; P = .01). Adverse event rates were similar in both groups.
Analysis of Results
The results emphasize the importance of rapid administration of an active drug in treating status epilepticus. Median times to treatment were 4 times longer with intravenous lorazepam (4.8 minutes) vs intramuscular midazolam (1.2 minutes). The ease of administration of midazolam more than made up for the fact that it was slower-acting (3.3 minutes) than lorazepam (1.6 minutes). Consequently, the median time to seizure control was slightly longer with lorazepam (4.8 + 1.6 = 6.4 minutes) than with midazolam (1.2 + 3.3 = 4.5 minutes) (P value not significant).
Furthermore, 31 patients in the lorazepam group did not receive the active drug because of difficulty with intravenous access, whereas only 5 patients in the midazolam group did not receive drug owing to autoinjector failure. These results highlight the difficulty of establishing intravenous access in an actively convulsing patient.
Other routes of benzodiazepine administration, such as buccal, intranasal, and rectal, may also be effective in controlling seizures, but intramuscular administration by autoinjector offers more predictable dosing.
Conclusions
The benefit of intramuscular midazolam for status epilepticus demonstrated by the double-blind RAMPART study highlights the practical considerations of treating patients who are actively seizing. Although lorazepam had a faster onset of action, the fact that intramuscular midazolam could be administered more quickly resulted in similar times to effectiveness for the 2 drugs. More midazolam-treated patients were seizure-free upon hospital arrival (73.4% for midazolam vs. 63.4% for lorazepam) -- a difference of 10 percentage points, which demonstrated the noninferiority and superiority of midazolam.
Because prompt treatment of status epilepticus strongly influences morbidity and mortality, it is likely that the results of this study will translate into US Food and Drug Administration approval of intramuscular midazolam for status epilepticus in the near future.
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