Intranasal Drug Delivery: An Alternative to Intravenous Administration in Selected Emergency Cases

Factors affecting nasal drug absorption 

The percentage of medication that ends up in the bloodstream after administration is termed “bioavailability.” Intravenous medication is 100% bioavailable after administration. Oral medications are about 5% to 10% bioavailable because of gastrointestinal and hepatic destruction. Intranasal medication bioavailability varies from negligible to almost 100%.

If a drug molecule can cross the nasal mucosa, the primary factors influencing bioavailability are medication concentration and volume, delivery method, and nasal mucosal health.1 The most concentrated form of the medication available should be used, because large volumes (more than .5 to 1 mL per nostril) will run out of the nose, reducing total absorption. If volumes greater than 1 mL are required, they should be applied as divided doses, allowing a few minutes for the first dose to absorb. On the other hand, if small volume doses are used, be aware that delivery devices have a “dead space” in the applicator tip where some medication will remain. This should be kept in mind when calculating the volume of medication to be administered.

To optimize drug absorption, the delivery system must allow maximal surface area coverage with a thin layer of drug.1 The easiest method is to deliver half the dose into each nostril, doubling the absorptive surface area. Atomized drug delivery systems result in superior surface area coverage compared with drops or spray methods and will improve medication bioavailability3 (Table 1; FIGURE 1, FIGURE 2, FIGURE 3). Nasal mucosal destruction and copious mucous or blood secretions inhibit medication absorption. With a quick look into the nostril, the nurse can notice mucosal abnormalities and predict in advance whether nasal drug absorption will be less effective.

TABLE 1. Nasal medication delivery device options

	Device type	Advantages	Disadvantages	Per patient cost
	Cotton swabs	Inexpensive	Unmeasured dose (swab)	Pennies
	Syringe droppers	Measured dose (syringe)	No atomization
			Uncomfortable (swab)
			Bioavailability problem: limited area of mucosal contact
	Single use syringe-driven devices	Improved bioavailability: atomized drug delivery	More expensive than dripping in with a syringe or using a cotton swab	$2.45*
	MAD Nasal (Figure 1)	Measured dose
	Positive displacement pump atomizers	Improved bioavailability: atomized drug delivery	More expensive than dripping in with a syringe or using a cotton swab	MADomizer tip: $0.84*
	MADomizer*(Figure 2)	Measured dose		Go Medical Nasal
	Go Medical†	Inexpensive		PCA costs approximately $10 US; eEntire pump is disposable†
	Nasal Inhaler (Figure 3)	(MADomizer)
	Venturi Atomizer	Improved bioavailability: atomized drug delivery	Expensive, unmeasured dose; potentially substantial medication wasting; resterilization prior to reuse§	Cleaning, sterilization, replacement parts and reassembly costs§
	De Vilbiss‡			Capital expenditure§

Therefore, per patient costs include labor involved in disassembly, cleaning/sterilization, and reassembly. capital expenditure may include autoclave, air compressor, and atomizer cart purchase and upkeep, compressed air hosing routed to every location, and device purchase.

* Manufacturer: Wolfe Tory Medical, Inc, Salt Lake City, Utah. † Manufacturer: Go Medical, Subiaco, Western Australia. § Venturi devices pose infectious risk unless cleaned between each patient. ‡ Manufacturer: De Vilbiss Atomizers, Sunrise Medical, Carlsbad, Calif.

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FIGURE 1. The MAD 100 single-use, syringe-driven atomizer allows the administration of a measured dose of intranasal medication. (Photo courtesy of Wolfe Tory Medical, Inc.)

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FIGURE 2. A positive displacement pump atomizer, the MADomizer, is an inexpensive system for administering medications across the nasal mucosa. (Photo courtesy of Wolfe Tory Medical, Inc.)

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FIGURE 3. The Go Medical Nasal Inhaler is a disposable pump atomizer for delivering intranasal medications. It costs approximately US $10. (Photo courtesy of Go Medical.)

Intranasal medication delivery in the emergency department 

A number of commonly used ED medications are effective when delivered intranasally. These medications include the synthetic opiates fentanyl and sufentanil for the treatment of acute pain; midazolam, for procedural sedation and for the treatment of seizures; naloxone, for opiate overdose; and topical anesthetics/vasoconstrictors for use prior to nasal intubation or nasogastric tube (NGT) placement or for the treatment of epistaxis (Table 2).

TABLE 2. Intranasal medications and doses for treatment of emergency conditions

	Clinical scenario	Intranasal medication and dose	Important reminders
	Pain control	Sufentanil 0.2 to 1.0 μg/kg	Always monitor for respiratory depression
		Fentanyl 1.5 to 3.0 μg/kg	Only use a device that can deliver an exact dose of medication
			Titration is possible
	Sedation	Midazolam 0.5 mg/kg	Always monitor for respiratory depression
		Sufentanil 0.2 to 1.0 μg/kg	Combination therapy probably more affective than single drug therapy
		Ketamine 6–8 mg/kg	Titration is possible
	Seizures	Midazolam 0.2 to 0.3 mg/kg (Use 10 mg in teenagers and adults)	ALWAYS use the concentrated form of midazolam: 5 mg/ml
			Deliver immediately to allow absorption to occur while you support the airway
	Opiate overdose	Naloxone 2 mg (2 mL)	ALWAYS use the concentrated form of naloxone: 1 mg/mL
			Deliver immediately to allow absorption to occur while you support the airway
	Epistaxis	Oxymetazoline 0.5-1.0 mL to affected nostril (2 squeezes) of bottle or measure it and deliver with atomizer)	Have patient blow nose to remove all clots from nostril prior to delivery of the medication
		Add 1.5 mL lidocaine 4% if cautery will be performed	Spray 0.5-1.0 mL of medication up affected nostril(s)
			Soak a cotton swab with additional oxymetazoline and insert into nose
			Pinch nose for 5–10 minutes then re-examine and cauterize, if necessary
			Have patient purchase oxymetazoline over the counter and use at home
	Nasal procedures (nasogastric tube, fiberoptics, nasopharyngeal airway, nasal intubation)	Lidocaine 4% (plus oxymetazoline 0.5 mL)	Spray both the nose (1.5 mL lidocaine and the throat (3 mL lidocaine)
			Wait 3 minutes for full anesthetic effect before doing the procedure; repeat half the dose, if necessary

Pain control: intranasal opiates 

Many patients who visit the emergency department fail to obtain adequate pain relief.4 One reason is the lack of a rapid, effective, painless method for pain control. Nasal opiates offer an effective, inexpensive solution. The synthetic opiates fentanyl and sufentanil are uniquely suited for transmucosal delivery because of their high lipid solubility and their high potency (100 to 1000 times more potent than morphine).2., 5., 6., 7. Sufentanil is probably the best opiate medication currently available for intranasal drug delivery because of its high concentration, rapid mucosal absorption, and large therapeutic index.2 Dipping a cotton swab tip into sufentanil and applying it to the nasal mucosa produces an effect within seconds.2 In addition, it produces longer lasting analgesia with less persistent respiratory depression than does fentanyl.2 Situations in which intranasal opiates may be particularly useful are for minor fractures and contusions, wound dressing changes, and in children with acutely painful conditions.6., 7. Most of these patients never get an intravenous line, and intramuscular injections or oral medications are too painful or too slow to allow timely interventions. Spraying atomized fentanyl or sufentanil intranasally will result in rapid pain control and allow the nurse to proceed with care.

[Intranasal medication administration] is painless and needleless, which eliminates the risk of needle-stick injuries and reduces patient discomfort.

Procedural sedation: intranasal opiates, benzodiazepines, and ketamine 

Procedural sedation also can be achieved using intranasal medications.5., 7., 8. Midazolam is the most commonly studied medication for this indication, although data on fentanyl, ketamine, sufentanil, and combinations of these drugs are available.5 The data allow a few generalizations. First, intranasal medications are effective for mild to moderate sedation but not for deep sedation. Second, benzodiazepines and opiates produce varying levels of patient sedation, regardless of the route of delivery. For this reason, a combination of medications and the ability to titrate their effect is attractive. Third, respiratory depression is still a risk, especially when potent opiates are used. Therefore, staff must monitor the patient closely. Finally, adverse effects, such as nasal burning, are common with nasal midazolam.8 Nevertheless, in the pediatric setting, where mild sedation is often enough to relieve the anxiety of the parents as well as the child, intranasal medications are effective sedatives.

Many medications delivered intranasally achieve absorption rates and plasma concentrations comparable with that obtained by intravenous administration.

Seizure control: intranasal benzodiazepines 

In situations where an intravenous line is not available, intranasally administered benzodiazepines offer a rapid, effective method to treat an acutely seizing patient. Fisgin et al9 found that intranasally administered midazolam was effective in 87% of patients with prolonged seizures, whereas rectally administered diazepam was only effective 60% of the time (P < 0.05). The authors concluded that intranasal midazolam is more effective, socially acceptable, and convenient than rectally administered diazepam. A similar study compared intranasal midazolam to intravenous diazepam.10 These authors found that nasally administered midazolam stopped 88% of seizures, whereas 92% were controlled with intravenously administered diazepam (P = NS). Although similarly effective, intranasally administered midazolam worked more rapidly: The mean time to seizure cessation was 6.1 minutes with midazolam and 8.0 minutes with diazepam. The single study that has investigated intranasal lorazepam absorption suggests that it should be effective for seizure control.11 However, its use remains investigative. Based on these studies, many EMS agencies have adopted intranasal midazolam as the first-line therapy for treating seizures in the field.12

Nasopharyngeal procedures: nasal and oral 4% lidocaine 

Nasogastric tube placement is a very painful procedure. Nevertheless, it is routinely performed with little or no analgesia.13 A number of prospective studies demonstrate that topical 4% lidocaine applied to both the nose and the throat results in dramatic reduction in pain compared with lidocaine jelly alone.13., 14. The addition of a topical vasoconstrictor also appears beneficial because of nasal mucosal shrinkage and the prevention of epistaxis. These data strongly suggest that topical nasal and oral anesthetics/vasoconstrictors should be considered for all conscious patients before NGT placement. Be aware that vasoconstrictors can be absorbed and cause hypertension problems, especially in patients taking ∃-blockers who receive phenylephrine (Neosynephrine).15 Although oxymetazoline (Afrin) has milder cardiovascular effects than does phenylephrine, care should be taken when administering vasoconstrictors to patients with significant cardiovascular disease or hypertension.

Epistaxis: nasal oxymetazoline and 4% lidocaine 

Epistaxis is a common and messy problem, and its treatment can require substantial time and resources. Interestingly, otolaryngologists note that most epistaxis is easily controlled with intranasal oxymetazoline.16., 17. This method eliminates suction, cautery, and nasal packing, and the patient can continue topical oxymetazoline treatment at home. Triage nurses can start the treatment (in patients without significant cardiovascular disease), often resulting in bleeding cessation before the physician sees the patient. Pretreatment with intranasal 4% lidocaine and oxymetazoline also is useful in preventing pain and epistaxis before nasal procedures such as intubation, nasopharyngeal airway placement, and NGT placement.18

The most concentrated form of the medication available should be used, because large volumes (more than .5 to 1 mL per nostril) will run out of the nose, reducing total absorption.

Opiate overdose treatment: intranasal naloxone 

Intravenous drug abusers requiring injectable naloxone place the emergency nurse at an especially high risk for bloodborne pathogen exposure.19 Because these patients rarely need an intravenous line for any reason beyond the administration of naloxone, it would be helpful to have a needleless method for administering the medication.20 Fortunately, naloxone is a small molecule that easily crosses the nasal mucosal membranes. Intranasal naloxone exhibits opiate antagonist effects almost as rapidly as does intravenous naloxone, with bioavailability approaching 100%.21 The Denver Health Paramedic system investigated the use of intranasal naloxone in heroin overdose patients and found it to be 83% effective at awakening patients.22 Awakening times were comparable with those in previous studies investigating intravenously administered naloxone and faster than when naloxone was administered subcutaneously.23 Treatment “failures” occurred in 2 situations: either intravenous naloxone was given so rapidly that the intranasal naloxone did not have time to be effective, or the treated patient had significant bloody or mucosal nasal discharge, making absorption inadequate. The authors concluded that intranasal naloxone can be effective in the field, acts rapidly, and reduces the risk of needle-stick injury.

Atomized drug delivery systems result in superior surface area coverage compared to drops or spray methods and will improve medication bioavailability.

Conclusion 

Although the intranasal route is a rapid and convenient way to deliver medications in the emergency department, it will not replace the need for injections. However, awareness of its limitations combined with the correct equipment and medication concentrations will allow emergency nurses to bypass the need for intravenous lines in certain cases. This improves the safety of the work environment and eliminates the professional, personal, and family turmoil that may occur when a medical worker incurs a needle-stick injury.