Wednesday, August 11, 2010

Intranasal Medication Delivery for Children Reviewed

From Medscape Medical News

Laurie Barclay, MD

August 9, 2010 — The most frequent pediatric indications for intranasal medication delivery are pain control, anxiolysis, and seizure control, according to a review published online August 9 in Pediatrics. Other potential indications for intranasal medication delivery not reviewed in this article include the treatment of epistaxis, pretreatment before nasogastric tube insertion, and administration of naloxone for reversal of narcotic overdose.

"Intranasal delivery offers unique advantages that may allow more efficient use of resources, more rapid patient care, and higher patient and provider satisfaction," write Timothy R. Wolfe, MD, from University of Utah School of Medicine in Salt Lake City, and Darren A. Braude, MD, from the University of New Mexico School of Medicine in Albuquerque. "The highly vascularized nasal mucosa and the olfactory tissue in direct contact with the central nervous system allow nasally administered drugs to be rapidly transported into the bloodstream and brain, with onsets of action approaching that of intravenous therapy. First-pass drug metabolism via the liver is also avoided, resulting in high bioavailability of many medications."

Except for orally and intranasally administered medications, most formulations require a needle injection, which may be painful, anxiety-provoking, and time-consuming for staff, who must be trained in proper injection technique and who are exposed to the risks for needle stick injury. In comparison, intranasal delivery of medication is relatively painless, inexpensive, and easy to administer with minimal training.

Specific uses of intranasally delivered medications include the following:

•For pain control, fentanyl 1.5 to 2.0 μg/kg. This may be titrated every 15 minutes as needed. Patients should be monitored for respiratory depression. It may be appropriate to administer oral medications concurrently so that they take effect as the intranasal fentanyl effect wears off.
•For anxiolysis, midazolam 0.4 to 0.5 mg/kg. The concentrated form (5 mg/mL) should be used, because other concentrations may be ineffective when administered intranasally. The patient and family should be advised that a burning sensation may last for 30 seconds.
•For seizures, midazolam 0.2 mg/kg. As for anxiolysis, the concentrated form (5 mg/mL) should be used for intranasal delivery.
Intranasal opiates may be especially useful for minor fractures, large abrasions, burns, wound-dressing changes, extremity fractures, and other acutely painful conditions in children. For treatment of acute pain, intranasal opiates have been shown to be as effective as intravenous morphine and faster than intramuscular morphine.

Procedures in which light procedural sedation and anxiolysis may be achieved with intranasal medications include laceration repair, magnetic resonance imaging and computed tomography scans, burn-dressing changes, dental extractions, endoscopies, and central venous port access. Although intranasal midazolam is the most commonly studied drug in these settings, other options may include intranasal fentanyl, ketamine, sufentanil, dexmedetomidine, and combinations of these drugs.

Intranasal midazolam is effective for prolonged seizures because it easily and rapidly crosses the nasal mucosa and the blood-brain barrier, with similar efficacy to intravenous diazepam but faster onset because of the lack of need to start an intravenous line. Intranasal midazolam and lorazepam are also safe for treating seizures outside of the hospital setting, and intranasal midazolam may be a useful option for treating status epilepticus when intravenous access is not immediately available.

Specific considerations for administering intranasally delivered medications include the following:

•Deliver immediately to allow absorption while the airway is being supported.
•The nostril should be inspected for significant amounts of blood or mucous discharge that could limit absorption of a nasal medication. When these are present, alternative delivery options should be considered, or it may be appropriate to suction the nasal passage before medication delivery.
•Deliver half of the medication dose up each nostril, which doubles the available mucosal surface area (vs a single nostril) for drug absorption and increases the rate and amount of absorption.
•The most concentrated form available of the medication should be used, because dilute forms are less effective for intranasal delivery.
•The ideal volume for intranasal medication delivery is 0.2 to 0.3 mL of medication per nostril, and volume per nostril should not exceed 0.5 to 1.0 mL. Two separate doses may be used when a higher volume is needed, with a few minutes between doses to allow the first dose to absorb.
Adverse effects of nasal medications seldom occur. The most common adverse effect is transient nasal burning and irritation with midazolam. Except with high doses of intranasal sufentanil for induction during surgery, oversedation has not been reported for intranasal medications, including fentanyl or midazolam.

"Intranasal medication delivery is an effective method of delivering analgesia, anxiolysis, and anticonvulsants to pediatric patients," the review authors conclude. "In the properly selected patient, nasal administration can reduce time to medication delivery and onset, reduce medical staff resource use, eliminate needle-stick exposure risk, and eliminate pain from the injection, thereby leading to improved patient and parent satisfaction. Pediatricians, pediatric emergency physicians, and emergency medical services medical directors should consider adopting this delivery method for medications and indications that are appropriate to their practice setting."

Dr. Wolfe is affiliated with Wolfe Tory Medical, Inc, the maker of the MAD nasal drug delivery device. Dr. Braude has disclosed no relevant financial relationships.

Pediatrics. Published online August 9, 2010.

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