Introduction
Seizures in children usually cease spontaneously within 5-10 minutes and are rarely associated with significant sequelae. The chance of a seizure stopping spontaneously decreases significantly after 10-15 minutes. Similarly, the efficacy of anticonvulsant medication decreases after 10-15 minutes of fitting and the risk of adverse effects increases.1 Convulsive seizures lasting longer than 30 minutes constitute status epilepticus and may be complicated by cardio respiratory depression and brain injury. Diazepam or clonazepam, given intravenously, is generally the drug of choice for the emergency treatment of convulsive status epilepticus. Intravenous diazepam may be difficult to administer to the young convulsing child and, because of the need for intravenous access, is not ideal for rapid treatment in the community by non-medical carers.
Pharmacokinetics
The lipid solubility of diazepam allows it to enter the brain readily and terminate seizures quickly. Unfortunately, this pharmacokinetic profile means diazepam is quickly redistributed to other fatty tissues. The concentrations in the brain and serum fall rapidly.
The absorption of oral diazepam is slow (1-2 hours) and variable. Intramuscular diazepam has similar absorption problems, is painful and may cause muscle necrosis. Suppositories have slow and variable absorption rates and are not recommended in an emergency. Rectal administration of the intravenous form of diazepam has been used successfully for hospital and home treatment of prolonged seizures.1
Indications
Rectal diazepam can be given by a treating doctor when intravenous access cannot readily be obtained, as is often the case in infants and toddlers. In the emergency department of the Royal Children's Hospital, Melbourne, rectal diazepam is often given instead of intravenous diazepam for prolonged convulsions when intravenous access cannot be obtained. Guidelines and indications for the home use of rectal diazepam in children by non-medical people are listed in Table 1.
Efficacy
Experience suggests that rectal diazepam is rapidly effective in children, but efficacy has not been well studied in adults. Diazepam given rectally appears to be as effective as intravenous diazepam in terminating seizures. It may have
| Table 1 Guidelines for home use of rectal diazepam in children* The recommended dose for children is 0.5 mg/kg up to 10 mg. Intravenous preparations are used. It is reasonable to consider prescribing rectal diazepam for home use in the following situations. - Patient has a pattern of prolonged seizures (>10 minutes) which have previously responded to intravenous or rectal diazepam. If there is no response within 10 minutes of administration, the child should be urgently transported to hospital.
- Patient tends to have `clusters' of seizures and oral therapy is not appropriate. Rectal diazepam may abort the cluster.
- Patient has a history of spontaneous status epilepticus and diazepam has been shown to be effective in previous episodes. Rectal diazepam may be given at home before transport to hospital. (Rectal diazepam is not an ideal means of treating status epilepticus out of hospital and parents/carers should be discouraged from giving repeated doses at short intervals, which will increase the possibility of life-threatening respiratory depression).
- Patient has a history of severe epilepsy and is remote from any form of emergency services.
Rectal diazepam need not be considered in the management of patients with well-controlled epilepsy. * Somerville E, Antony J. Position statement on the use of rectal diazepam. Med J Aust 1995;163:268-9. ©Copyright 1995. The Medical Journal of Australia - reproduced with permission. |
advantages, including more prolonged action (20-30 minutes compared to 10-20 minutes), less respiratory depression, less drowsiness and little effect on blood pressure.2 Intravenous and rectal diazepam both stop seizures in more than 80% of cases within 10-15 minutes.1
Time to peak plasma levels after rectal administration (about 5-10 minutes) is longer than after intravenous injection (1-3 minutes). This time difference may be important in status epilepticus where rapid seizure termination is necessary. It also possibly explains the lower incidence of respiratory depression experienced with rectal administration. The prolonged action after rectal administration may prevent seizure recurrence and allow more time to seek medical assistance. Despite the potential for faeces to affect absorption, faecal evacuation before giving diazepam is not recommended.
Formulations
Most studies have used injectable diazepam. The breaking of ampoules (10 mg/2 mL) and the use of needles by non-medical carers can be difficult and dangerous. If it is necessary to dilute diazepam, it is important to dilute it correctly as certain volumes of normal saline or dextrose can result in the precipitation of diazepam. Some institutions like the Royal Children's Hospital in Melbourne prepare 25 mL bottles of a rectal solution (1 mg/mL) using 50% propylene glycol in water. This is easy to use and does not expire for one year.3 Diazepam adsorbs to plastic and thus needs to be stored in glass. There are anecdotal reports of using diazepam oral mixture rectally, but its efficacy is not proven and thus cannot be recommended. Oil in water emulsions of injectable diazepam (e.g. Diazemuls) are slowly absorbed rectally and thus are inappropriate to use.
Dosage
Most studies describe effective treatment and few adverse effects with rectal doses of 0.2-0.5 mg/kg with 0.5 mg/kg being the most common.1,2 Patients taking phenobarbitone or patients who have major co-morbidities should possibly receive a lower dose e.g. 0.25 mg/kg. Conversely, patients on maintenance benzodiazepines may be tolerant and require a larger dose. The commonly accepted maximum dose for rectal administration is 10 mg. The comparable intravenous dose is 0.1-0.3 mg/kg (maximum 10 mg). If the seizures persist after rectal diazepam, intravenous diazepam should be considered at a dose of 0.1 mg/kg.
Administration
The time to give rectal diazepam should be individualised for each child. In general, diazepam is given if the seizure does not cease spontaneously within 5-10 minutes. Some carers may be instructed to give rectal diazepam at the start of a seizure or when a seizure changes in a certain way, if the history suggests that these situations usually proceed to status epilepticus or other complications.
First-aid management to prevent injury and protect the child's airway during and following the seizure should not be forgotten.
In addition, it is advisable for carers who will be giving rectal diazepam to be trained in basic paediatric cardiopulmonary resuscitation. Some parents or carers prefer to give rectal diazepam for the first time under supervision e.g. when the ambulance arrives, during a hospital admission or in the emergency department. Carers and parents are generally advised to call for an ambulance and then administer rectal diazepam.
The delivery technique varies from using a tuberculin syringe (without a needle) to a syringe with a rectal tube. If using a rectal tube, it is important to draw up the dose with the rectal tube already fitted to the syringe to fill the dead space in the tube and thus ensure correct dosing. A lubricated and suitably soft rectal tube is necessary as there are reports of hard plastic nozzles damaging the rectum. It is recommended that the tube or syringe is introduced only 4-5 cm into the rectum. Theoretically, administration of drugs higher into the rectum may result in greater first-pass metabolism, but clinically this is of minimal importance with rectal diazepam.
If possible, infants and toddlers should be placed prone for rectal diazepam to be administered. Older children should be positioned on their side, in the recovery position. After administration, keep the child in the same position and hold the buttocks together for a few minutes to limit leakage from the rectum.
Conclusion
The rectal use of diazepam is not licensed in Australia, but its use in general and paediatric practice has become commonplace. Rectal diazepam is widely used by carers to terminate prolonged convulsive seizures and clusters of repeated seizures in children with febrile convulsions and epilepsy. A position statement on the use of rectal diazepam in epilepsy, written on behalf of the Epilepsy Society of Australia, the Child Neurology Study Group, the Australian Association of Neurologists and the National Epilepsy Association of Australia, has outlined accepted indications4 (Table 1).
