Midazolam: effects on epilepsy, how to use it?

Definition: what is midazolam?

Midazolam is a psycholeptic molecule, that is to say a sedative psychotropic, belonging to the class of benzodiazepines. Most of the specialties that contain it are intended for hospital use. Some are available in town pharmacies on presentation of a secure prescription (Buccolam® and solutions for injection of midazolam dosed at 1 mg/mL and 5 mg/mL). Midazolam has anticonvulsant (against epilepsy), sedative, anxiolytic and muscle relaxant properties (induces muscle relaxation).

Indications: when to use midazolam?

Depending on the specialty prescribed, midazolam in drinkable solution has a different indication:
► To Bucolam®: treatment of acute seizures in infants and children with epilepsy aged 3 months to under 18 years. In infants from 3 to 6 months, the treatment must necessarily be administered in the hospital so that monitoring can be set up.
► To Ozaline®: induction of a sedation in infants and children 6 months to 17 years old upstream of a medical intervention (for curative or diagnostic purposes) or anesthesia to reduce anxiety and agitation.
Midazolam for injectable and rectal routes is indicated in the following cases:

• in awake sedation : administration of several consecutive doses before or during a therapeutic or diagnostic intervention to reduce anxiety, without resorting to general anesthesia
• to induce sedation in certain hospitalized patients in intensive care unit or intensive care unit
• as part of a anesthesia : in premedication or associated with other anesthetics to induce anesthesia
• as part of palliative care : to obtain a proportionate sedation (intensity and duration adapted to the relief of the patient) or a deep and continuous sedation

► Buccolam® is the only medicine based on midazolam that can be administered by someone other than a doctor. Administration to a child older than 6 months can be carried out by a parent or third party when epilepsy was diagnosed. Faced with the occurrence of convulsions in the child, the adult present must administer a single dose. If the symptoms persist after 10 minutes, the accompanying person must then call 15 (Samu) as soon as possible. The solution must be given to the child using the syringe provided. The other midazolam-based specialties must be administered by a doctor.

► For Ozalin®, the dosage is determined according to body weight of the child and administered using a graduated applicator. The recommended doses for midazolam in solution for injection are defined according to several criteria: indication, administration schedule, adult or child, presence of a chronic disease, etc. In palliative care, the doses are gradually increased and reassessed according to the clinical situation.

What is the trade name of midazolam?

Commercial specialties containing midazolam are Buccolam® and Ozalin® (in drinkable solutions). Additionally, the drug Midaject® (solution for injection imported from Turkey) is temporarily available in France. Several generics of Hypnovel® (injection solution withdrawn from the market) are also marketed.

What are the side effects of midazolam?

The most common side effects are nausea and vomiting, respiratory depression and drowsiness. Midazolam is associated with a level 3 pictogram, thus driving a vehicle or using a machine is to be avoided in treated patients. In addition, headaches, restlessness and hallucinations can occur. More rarely, midazolam can cause an allergic reaction and skin disorders such as hives and itching. Similarly, addiction and cardiovascular disorders such as low blood pressure, slow heart rate or even cardiac arrest can be observed. Deaths resulting from respiratory depression have also been reported, mainly in patients with cardiac or respiratory failure. Note that some side effects are not identifiable in patients immersed in deep sedation due to lack of reaction.

Midazolam and end of life: how long?

In palliative care, midazolam is used as sedative to alter the patient’s consciousness and thus provide relief of an unbearable situation. Doses are increased gradually and reassessed regularly. Sedation can be transient or maintained until the patient’s death. Its duration varies according to the clinical situation, the patient’s tolerance and the doses administered. Unlike euthanasia, the time to death is not predictable.

What are the contraindications of midazolam?

Regardless of its pharmaceutical form, midazolam is contraindicated in patients allergic to benzodiazepines, to any of the components of the drug and in those with a severe respiratory failure. More specifically, the Buccolam® and Ozalin® specialties should not be administered in the event of myasthenia gravis (rare disease that weakens the muscles), sleep apnea and severe impairment of liver function. Ozalin® should be excluded in case of lung disease or airway malformation. The contraindications of injectable midazolam used in palliative care are different. In this context, it is contraindicated in case of acute respiratory depression and must be administered by an experienced physician (just like Ozalin®). Its administration in certain fragile patients requires a reduction in dosage and the establishment of medical supervision. This concerns patients over the age of 60 and those with a chronic disease such as severe myasthenia, malnutrition, dehydration, impaired renal, hepatic or cardiac functions. This vigilance also concerns children. It should be noted that injectable midazolam can only be administered to children under 6 months of age in the context of sedation carried out in intensive care. Midazolam is not contraindicated during pregnancy, but as a precautionary measure it is only used when absolutely necessary. In breastfeeding women, discontinuation of breast-feeding is strongly recommended within 24 hours of drug administration.

Sources:
– Public drug database, ANSM
– The vademecum on the use of Midazolam for sedative purposes, November 2021, French Society for Support and Palliative Care (SFAP)
– Analgesia for stubborn pain and sedative practices in adults: drug management in palliative situations until the end of life, January 2020, HAS