Intranasal opiate delivery offers one of the most interesting and perhaps broadly useful indications for intranasal medication delivery. Acute pain is an extremely common problem in the outpatient setting (over 40 million emergency room visits in the United States per year for acute pain),[1] as well as in the hospice setting where patients often have acute episodes of breakthrough pain despite long acting opioid use. Due to the sheer volume and variety of patients a large number of treatment options are necessary to meet each patients individual needs.

Intranasal opiates are simply one of many treatment options that may be useful in selected patients. For selected opiate medications, intranasal delivery can result in rapid medication absorption with serum and cerebral spinal fluid (CSF) levels approaching those comparable to intravenous (IV) administration.

This delivery method is effective because the enormous surface area (180 cm2) and blood supply of the mucosa allows small molecules to be rapidly transported into the blood stream.[2] For example, dipping a cotton swab tip into sufentanil and applying it to the nasal mucosa of the ferret produces an effect within seconds.[2] Recognition of this rapid opiate analgesic effect has resulted in numerous research publications confirming its effectiveness. Studies investigating treatment of acute pain via opiate delivery across the nasal mucosa note equivalent or superior pain control to IV, IM and subcutaneous delivery methods.[3-6] In the post-operative setting, patient controlled intranasal analgesia (PCINA) systems used to deliver intranasal fentanyl or sufentanil result in equivalent pain control as IV PCA devices and superior pain control to customary ward-delivered pain medication.[7-11] Oncologists are beginning to recognize the advantage of this delivery site and have posted a web site protocol for intranasal fentanyl and sufentanil directed to patients suffering breakthrough cancer pain that is resistant to standard therapy.[7] (click here for link) The U.S. military is even investigating intranasal analgesics (ketamine) as an option for their soldiers to self treat the pain associated with battlefield injuries and possibly self-extract themselves from the situation.[12](click here for slides)

Literature overview and discussion

Myringotomy:

An additional group of studies have specifically investigated the efficacy of intra-nasal fentanyl to improve emergence characteristic of patients following myringotomy (a procedure commonly done without an IV in place).[29, 30] Both Finkel et al and Galinkin et al found that intraoperative treatment with intra-nasal fentanyl reduced post-operative agitation. Galinken also noted a reduction in tachycardia, nausea, vomiting and recovery room length of stay in-patient treated with IN fentany while Finkel found a slight increase in PONV.  Perhaps as important, these two authors as well as a third (Voronov et al) find that in children undergoing myringotomy (no IV at all) they were able to easily control pain at the end of the case with intranasal fentanyl. [29, 30, 61] In a more recent study Rampersad found IN fentanyl equivalent fro controlling post-operative myringotomy pain to other non-opioid medications, however these authors used a dose (1 mcg/kg) that is probably barely effective when given intranasally so one would not expect much effect on pain.[77] Pestieau compared IN fentanyl to IN dexmedetomidine and placebo for post-operative myringotomy pain and agitation. Both fentanyl and dexmedetomidine resulted in better pain control than placebo. However, the study had to be stopped early due to overly long sedation in the high dose dexmedetomidine group.[81] This is not entirely surprising since the length of action of IN dexmedetomidine is around 60-100 minutes. The authors conclude that IN fentanyl or rectal acetaminophen are very effective and therefore the longer length of time in recovery for IN dexmedetomidine cannot be clinically justified in short operative cases such as myringotomy where the drug effect is so prolonged. Hippard conducted a randomized double blind trial comparing nasal fentanyl to intravenous morphine and intramuscular morphine to assess the immediate postoperative analgesia can behavioral effects of these three routes of administration. They found them all to be equivalent in terms of efficacy and minimal side effects and conclude that establishing an IV in this setting is unnecessary.[83]

Post-operative abdominal pain:

Heshmati et al found intranasal sufentanil (0.7 mcg/kg) effectively treated the pain of lower abdominal surgery within 10 minutes time in thirty children.[48] They noted only two episodes of nausea and no respiratory compromise, excess sedation, hemodynamic effects or desaturation. They conclude that intranasal sufentanil in this dose range is rapidly effective and safe and suggest that it be considered not only in post-operative care but also as a triage initiated pain medication in the emergency department. Additional investigations note IN opiates are appropriate alternatives for pain treatment in the post-operative pediatric patient.[31, 32]

In a recent review of the drug Sufentanil, Lundeberg and Roelofse tout their experience with over 1000 uses of intranasal sufentanil in pediatric anesthesia practice.[74] Here is what they say:

Different devices could be used for creating an aerosol but we favor ...atomization devices, for simplicity and accuracy of dosing. The onset of sufentanil aerosol is about 5–10 min with a maximum sedative and analgesic effect at about 20– 25 min. Depending on the dose used, the effect wears off at about 60 min. Doses used for procedural pain are usually 0.7–1 ug/kg) and very occasionally over 1.5 ug/kg). These doses (<1.5 ug/kg) very seldom give adverse effects like nausea ⁄ vomiting and ventilatory depression. Lower doses of intranasal sufentanil can be used when combined with other drugs such as intranasal s-ketamine or dexmedetomidine."

Striebel is the thought leader in adult post-operative pain therapy using intranasal opiates. He and his colleagues have published multiple studies investigating both nurse administered as well as patient administered intranasal fentanyl or intranasal meperidine (pethidine) in patients following surgical procedures.[3, 4, 8-10, 33, 34] These investigators used non-concentrated IV formulations of the opiate medication and overcame the volume issue by administering multiple small doses in a titrated fashion. In all of this groups published data the intranasal formulation was equivalent in onset of action and quality of pain control to the IV delivery route. Furthermore, when the patient was given control of dosing using a patient-controlled intranasal analgesia pump (PCINA) there was improved satisfaction and improved pain control due to the lack of need for a health care worker to respond to the patients pain needs.

Christrup et al confirmed Striebel’s data in a double blind, crossover trail in patients undergoing multiple molar extractions. They found the IN and IV fentanyl were equivalent in quality of pain control and in duration of effect.[35] Other authors have found similar results using various different opiate formulations.[36-39]

Hallett et al noted that intranasal diamorphine (heroin) provided good to complete post-operative pain relief in the majority of patients studied, but the delivery system they used suffered some technical problems, leading the authors to conclude that the concept is valid but the delivery system needed improvement.[40]

Abboud et al noted that intranasal butorphanol was superior to placebo, but of slower onset than IV butorphanol in treating post-cesarean section pain.[41]

Cannon found adequate pain relief with IN butorphanol in about 70% of his post-op head and neck outpatients.[42] A review of additional data on intranasal butorphanol can be found in an article by Gillis and a review by Dale.[18, 43]

Several well designed randomized controlled trials exist that demonstrate intranasal opiates are clinically equivalent to intravenous morphine and superior to intramuscular morphine for the management of acutely painful conditions in children.

Saunders et al conducted a similar trial assessing the efficacy of 2 mcg/kg of IN generic fentanyl (50 mcg/ml) in pain reductions for pediatric orthopedic trauma. They found effective control and high satisfaction scores using this treatment method.[44]

Kendall et al conducted a randomized controlled trail comparing intranasal diamorphine to intramuscular morphine in 404 children and teenagers with extremity fractures.[6] Intranasal therapy provided superior pain control at 5, 10 and 20 minutes while pain control was similar for both study groups by 30 minutes. Treatment acceptability as judged by nurses and parents was 98% and 97% for intranasal therapy versus 32% and 72% for intramuscular therapy (see diagram above demonstrating patients reactions to each type of therapy). The authors conclude: "Nasal diamorphine spray should be the preferred method of pain relief in children and teenagers presenting to emergency departments in acute pain with clinical fractures. The diamorphine spray should be used in place of intramuscular morphine."

Cole investigated the efficacy of intranasal fentanyl (50 mcg/ml) in children ages 12 to 36 months who were suffering painful injuries in need of more than an oral medication.[62] In a prospective sample of 57 patients these authors found a mean initial pain score of 8/10 with pain reduction to a mean of 2/10 by 10 minutes (93% had control of their pain) and to a mean of 0/10 by 30 minutes (98% had control of their pain). There were no complications and the delivery was well tolerated (nasal fentanyl does not burn nor taste bad). They conclude this is an effective, safe, well-tolerated method of pain control for moderate to severe pain.

Holdgate evaluated the time it took to treat children (ages 1-15 years) with acute pain when IV morphine was the standard, compared to after the introduction of intranasal fentanyl.[63] The study occurred in a mixed setting ED (adult and pediatric emergency department). In the 7 months before study implementation they administered opiates (IV morphine) to 63 children. In the 7 months after study implementation they provided opiates to twice as many children (118 patients). 81 children received intranasal fentanyl while 37 received IV morphine. The median time for delivery of pain control was 32 minutes for nasal fentanyl and 63 minutes for IV morphine. Furthermore, there was a clear trend to provide opiates via the nasal route to younger children (who might otherwise NOT get pain medicine due to the need for an IV). Median age for IN fentanyl was 8.5 years while it was 12 years for IV morphine.  The authors conclude - "This study demonstrates that children treated with IN fentanyl received analgesic medication faster than those treated with IV morphine in a mixed ED. Younger children were more likely to receive opioid analgesia following the introduction of fentanyl."

Crellin et al evaluated the efficacy of generic IV fentanyl (50 mcg/ml) for treating orthopedic pain in children 5-15 years of age.[64] They found it very effective with pain score reductions from 7 at onset to 5 in 5 minutes and 2 at 30 minutes (see above figure). Mean time from triage to drug delivery was only 20 minutes. They titrated to effect with multiple doses as needed. It was well tolerated and very inexpensive. The authors conclude that generic 50 mcg/ml fentanyl is very effective, well tolerated and inexpensive method for treating painful injuries in children.

Regan found intranasal diamorphine to be equivalent to intravenous morphine in terms of time to administration of the drug in children in his A&E department.[84] However, there was less frequent need for further analgesia using the nasal medication. They conclude that nasal diamorphine remains a preferred agent and note that it has been adopted in 60% of U.K. emergency departments.

Harlos et al have even used nasal fentanyl in newborn babies who are suffering from terminal illnesses in an effort to reduce their pain and suffering.[86] They demonstrated safety and efficacy (as well as possible in this unique setting) and felt this was more compassionate than an injection. Prior to this publication the youngest reported age of nasal atomized fentanyl was 3 months old.

 A nice review of most of these pediatric articles was published in September 2011.[80] The conclusions are that IN fentanyl is equivalent or superior to morphine administered IV, IM or orally and that it is much faster in onset. Furthermore it is safe and does not require compounding (generic 50 ug/ml is fine for children). Given this efficacy, safety and low cost it offers an approach to improve care, improve satisfaction and reduce resource utilization.

Click here for a table from the article that summarizes all the articles.

Intranasal opiates for acute pain in adults

Most of the emergency medicine literature relating to intranasal opiates focuses on pediatric cases due to the desire to limit further pain from starting an IV or giving an intramuscular injection. However, intranasal opiates are also very useful in the adult patient (see the EMS and Burn sections below). Many adults with minor acute burns, orthopedic trauma and other painful conditions often get an IV line for  pain control (no resuscitation needed). In this setting nasal opiates are very effective, save nursing time and are well accepted by the patients.

Steenblik published a series of 40 patients with acute orthopedic trauma who were cared for in a ski clinic that confirms the above statement.[82  ] In this non-blinded clinical trial the investigators entered patients that they cared for in a ski clinic who were suffering from moderate to severe pain related to orthopedic trauma. The mean pain score on study entry was 9 (on a 10 point scale). Patient all were administered intranasal sufentanil (chosen rather than fentanyl due to higher potency and smaller weight based volume) at a does of 0.5 mcg/kg.

This treatment was successful in 95% f patients with a mean reduction in pain from 9 to 4.3 at 10 minutes and 3.3 at 20 minutes – a highly clinically significant reduction in pain.  On a 5 point satisfaction scoring they found that “very satisfied” answer in 78% of patients, 83% of nurses and 87% of physicians. There were minimal side effects – dizziness being the most frequently reported. One patient dropped their saturations to less than 92% after a second dose of nasal sufentanil was given due to inadequate pain control. The authors conclude that intranasal sufentanil provides rapid and adequate pain control in austere conditions and can be easily administered with no pain to the patient.

Stephen investigated the efficacy, safety and satisfaction scores when IN sufentanil was used in adults with acute orthopedic trauma.[85] Using a dose of 0.5 micrograms per kg they found pain scores dropped from 7.8 to 3.5 within 30 minutes, that of the 15 patients studies only one had a reduction in their pulse oximetry below 90% (88%) but 46% had some sensation of feeling whoozy. Satisfaction scores for patients, nurses and physicians (5 Point Likert score with 5 being the best) were 4.5, 4.0 and 4.2 respectively.

The authors conclude this is an effective, safe method to treat acute pain in adults and sufentanil offers many highly desirable features (volume of administration, potency, therapeutic index, cost) for use in the emergency setting.

Intranasal opiates for ambulance patients:

Rickard et al conducted a randomized controlled trial comparing intranasal fentanyl to intravenous morphine in a pre-hospital ambulance setting.[16] 227 adult patients with severe pain (mean VAS score 8/10) were randomized to treatment, with pain scores repeated upon hospital arrival. Both methods were clinically equivalent with mean pain scores dropping to 4/10 by hospital arrival. The authors conclude that IN fentanyl is an effective alternate to IV morphine and is particularity valuable in situations where IV cannulation is difficult, unwanted or unnecessary. Other studies comparing intranasal opiates to alternate therapies for acute pain, have routinely found IN therapy to be an effective and acceptable route in the right clinical situation.[5, 14, 20, 21, 44]

McLean studied IN fentanyl (50 mcg/ml) in adult trauma patients seen at a ski clinic.[65] They treated 46 patients, using a mean does of 1.4 mcg/kg and found clinically significant decreases in pain scores by 2 minutes (14 mm VAS decrease), 5 minutes (28 mm VAS decrease) and 10 minutes (28 mm VAS decrease). they conclude this is an effective analgesic in acutely injured adults in whom immediate IV access is complicated by scenario or resource limitations. and feel its potential in search-and-rescue and other austere medical situations is widespread. (Web site Editors note - this is a relatively low dose of medication using a fairly dilute form for adults - yet it was still fairly effective and very inexpensive and safe.) (click here for abstract)

Johnston studied the efficacy of intranasal fentanyl given to over 500 adult ambulance patients for the treatment of non-orthopedic visceral pain (i.e. chest and abdominal pain). They found it effective with a mean pain score reduction of 32 mm on visual analog score.[67]

Middleton did a retrospective analysis of several thousand uses of intranasal fentanyl for acute pain in an ambulance setting.[75] They found it was about 80% effective at reducing pain by >30% during transport – perhaps very slightly less effective than IV morphine (81.8% effective) but that that benefit was likely offset by the need for an IV to deliver the morphine.

Bendall published another article of many noting that IN fentanyl is just as good as IV morphine for controlling acute pain in children.[76] The authors were allowed to titrate IV and IN drugs to effect allowing customization to the patients needs. The unique feature of this article is the clinical setting of EMS where IV lines in children are even more difficult and time consuming due to a variety of factors. The authors appropriately conclude that in light of the non-invasive route of administration and equivalence to IV morphine, IN fentanyl is the most suitable analgesic agent for managing pediatric patients with moderate to severe pain in the EMS setting.

Another promising concept for prehospital pain control is intranasal ketamine. Ketamine in sub-anesthetic doses (about 10-15 times less than doses used for deep sedation) is an excellent pain killer, yet does not cause dysphoria nor respiratory depression (see details below and in the hospice section). This lack of respiratory depression may make this drug an attractive acute pain treatment modality for both ALS and BLS providers (it is already being used by lay people in the military and hospice setting). Reid et al have published the first report of such use in the EMS setting.[78] They treated a 9 y.o. child who was burned with 0.5 mg/kg (or less due to dead space losses) and within 3 minutes the child's pain and anxiety resolved, he was able to assist in his transfer and he was not sedated. This case report points towards another area of EMS research that is wide open - IN ketamine for acute pain - what is the right dose and is this safe enough for BLS delivery?

Intranasal opiates (diamorphine) for sickle cell crisis

The management of sickle cell crisis is dependent on immediate pain control, often requiring injectable opiates to achieve success. Unfortunately, sickle cell patients present to the emergency room so often in crisis that their veins are often damaged and it is very difficult to obtain rapid IV access - leading to delays in treatment and excessive nursing resources to gain IV access.  An obvious solution given the information presented at this web site is intranasal opiates titrated to effect. Telfer et al report their findings from an observational trial comparing intranasal diamorphine plus IV morphine in 9 patients to intranasal diamorphine plus oral morphine in 13 patients.[49]  By 15 minutes, adequate pain control was achieved in 89% of the IN plus IV group versus 70% of the IN plus oral group. At 30 minutes it was 100% vs. 89% and at 120 minutes it was 89% versus 100%.  Based on this initial trial, this emergency room has instituted immediate intranasal opiate delivery to all patients presenting in sickle cell crisis, followed by oral  opiate medications for longer efficacy.  They report high patient and caregiver satisfaction using this protocol.  While diamorphine is not available in many countries, fentanyl and sufentanil are often readily available and there is little reason to suspect it would not be just as effective as diamorphine,.  Instituting a protocol similar to Telfer's, with the added caveat of allowing titration of repeated IN opiates every 15-20 minutes as needed would greatly reduce suffering, expedite patient care and reduced nursing resource utilization.

Currently there is an ongoing clinical trial comparing IV morphine to IN fentanyl. These results should prove interesting:

A randomised controlled double-blind  trial of intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children.

Kulbe found low dose intranasal ketamine to be very effective for treating pain associated with burn dressing changes.[59]  Since the dose necessary for pain control is about 10 to 15 times less than that needed for sedation, ketamine is often an appropriate drug in situations where opiates are not effective or their side effects cannot be tolerated.

Intranasal ketorolac is also quite effective for treating painful conditions (and recently gained FDA approval). Initial studies showed peak levels around 30-45 minutes with half life of 5-6 hours and bioavailability over 70%.(68, 69) In postoperative patients, 30 mg of intranasal ketorolac  results in marked decreases in pain scores and over 30% reduction in opiate use.(70-72) Similar findings occur in patients using intranasal ketorolac for post-dental extraction pain.(73)

Ketamine is labeled as a general anesthetic drug and in anesthetic doses causes a dissociated catatonic state where patients stare into space – seemingly awake, breathing – but they do not react to painful stimuli.  In these doses it can be used for very painful procedures such as joint and bone reduction and other orthopedic and plastic surgical interventions.  However, ketamine is also an analgesic drug and demonstrates analgesic properties at doses 10-15 times less that that required for anesthesia.  Because of this analgesic effect at low doses, patients often remain completely awake and alert while obtaining substantial relief of their pain.  Several studies now confirm the analgesic effect of ketamine in low doses when used to treat painful conditions as well as during dressing changes.[57, 59, 60, 87-91]

The following text reviews currently available literature on this topic:

Kulbe 1996: This short article is really a case report confirming that intranasal ketamine spray can be effective for acute pain control during burn dressing changes. [59] It is interesting but offers little in terms of dosing  - only suggesting this is an area that deserves further research.

Kaube 2000: Kaube tested 25 mg of intranasal ketamine in 11 patients with severe disabling neurologic deficits due to migraine aura finding that about half the time the nasal ketamine was effective in reducing both severity and duration of the symptoms.[87] 

Editorial comment -  Other migraine researchers have found intranasal lidocaine occasionally effective for aborting migraines  – perhaps a combination of lidocaine with ketamine (I suggest 50 mg ketamine) might be an effective first step therapy to abort a migraine patient visiting the emergency room. If this fails, progression to more time consuming and complex therapies can then proceed.

Carr 2004: Carr found doses of up to 50 mg of IN ketamine were effective in many patients with difficult to control breakthrough pain (mean pain score reductions of about 23 mm on a 100 mm VAS).[60] There was some mild dizziness and feeling of unreality. They conclude that IN ketamine is safe and effective for augmenting pain control in this population but that further investigation is necessary.

Christensen 2007: Christensen investigated intranasal ketamine for treating post-operative pain following wisdom tooth removal. [88] Adult patients were randomized to placebo and doses of 10, 30 or 50 mg of intranasal ketamine. They found that “meaningful pain relief was achieved by 14 minutes in 70% of patients receiving the 50 mg dose of IN ketamine.  Peak analgesic effect (44 mm drop on VAS) was at 30 minutes.

Figure demonstrating rapid reduction in pain scores using 50 mg of IN ketamine in adults.

There was some feeling of unreality and or visual changes side effects noted in about 50% of patients who received the 50 mg dose which tended to resolve within an hour. The authors report prior data showing Ketamine bioavailability of their formulation (0.1 ml = 10 mg) of about 33%.

Huge 2009: This was a small study investigating the pharmacokinetics of low doses of intranasal ketamine as well as its impact on pain control and the resulting side effects.[57] The authors studies 16 patients with chronic neuropathic pain, randomizing them to either 0.2 mg/kg or 0.4 mg/kg of a dilute form of ketamine (25 mg/ml). Measured serum levels of ketamine peaked at 15 minutes indicating rapid absorption. Although the doses were low, a measurable impact on pain control occurred within 15 minutes and peaked at 60 minutes, lasting several hours. Mild to moderate dose dependent side effects were common, consisting of vertigo, concentration difficulty, blurred vision and some sedation, though measured cognitive ability was never impacted.

Reid 2011:  Reid et al report the successful use in intranasal ketamine in a prehospital setting to treat severe pain in a child with a 3% scald burn.[89] They used low dose ketamine (between 0.25 and 0.5 mg/kg) and noted onset within 3 minutes. There was minimal side effects (no dysphoria, some swimmy feeling). They conclude that more investigation is necessary for this promising intervention.

Goudas 2002 abstract: In this RCT patients received either IN ketamine (10 mg per spray up to 50 mg maximum per event) or placebo for breakthrough pain.[90] The group using ketamine had markedly better control of pain within 5 minutes and never needed rescue analgesia. There were no serious side effects though 20% of the ketamine cases reported feelings of unreality.

Kronenburg 2002:  This study is a review of ketamine in a variety of administrative formulations (including nasal) demonstrating that subanesthetic doses result in good pain control without significant side effects. [91] It is a bit dated now but contains a fair amount of interesting data.

Abdel-Ghaffar 2012:  This RCT comparing IN ketamine (1.5 mg/kg) vs. IN fentanyl (1.5 mcg/kg) for controlling postoperative pain following FESS sinus surgery showed equivalent pain control (much better than placebo) with a slight increase in dissociative side effects in the Ketamine group.[93]

Full article here (click)

Afridi 2013: RCT on IN ketamine (25 mg) vs. IN midazolam (2 mg) for migraines showed reduced severity of migraine in the ketamine group.[92]

The U.S. military may be the group most interested in intranasal ketamine for treating acute pain. This group is looking for a pain medication that can be self administered and relieve a soldiers acute pain related to war injury, yet let him/her still function at a high level and either be able to extricate himself or finish the mission (often saving his/her life and others by being a functional asset rather than a detriment). To date they have funded and conducted numerous studies to find the right dose of IN intranasal ketamine while determining the incidence of side effects.  Looking at the material posted on the internet, they have studied at least 117 subjects with doses ranging from 10 to 50 mg of ketamine finding no serious effects and adequate pain control.  The graph above notes their results in terms of dosing equivalency – finding 50 mg of nasal ketamine as effective or more effective than 7.5 mg of IV morphine without the loss of function seen with morphine. Look for more literature on this topic in the near future. (click here for military report from the internet in 2005)

Click here for a 2009 review of combat pain control

Click here for a slide set 2010 review of ketamine

Summary: While dissociative sedation with Ketamine requires fairly high doses of drug (10 mg/kg to be reliable - see sedation section) it appears that about  1 mg/kg of nasal ketamine (or simply 50 mg in an adult) is quite effective for pain control without substantial sedation. Many patients do feel a bit dysphoric, but their cognitive functions remain intact.  Using the generic formulation of ketamine at 100mg/ml would make nasal volumes ideal for atomization at this dose. It will be interesting to see if further research in the acute setting such as remote clinics, prehospital  setting (where generic fentanyl is a bit dilute for adult pain control), battle field setting and emergency room validate this concept. Especially interesting to those of us in the hospital will be for use in conditions such as migraines and chronic pain situations where treatment with an opiate has significant clinical downsides.

See separate extensive Hospice section as well (click here)

Link to 2011 study abstract by Dr. Crocker showing a comprehensive pain management strategy (including IN fentanyl if appropriate) reduces the childs recollection of pain at ED discharge.

Treatment protocol

1. Adult and pediatric minor painful injuries or procedures:
   • Orthopedic trauma not requiring an IV (or prior to starting an IV)
   • Anytime pain control is needed but oral medication is too slow
   • Burn dressing changes
   • Re-packing wounds such as abscesses
   • Any time you consider an IM shot for pain control (IN works as well or better with faster onset and no pain on delivery)
   • Titration of opiates is often needed - repeat another half to full dose every 15 minutes to until desired effect is obtained
   • The single biggest reason for failure of intranasal opiates is the clinician gives an in-appropriate dose (too low) similar to an IV dose which will simply fail in most situations.

1. Fentanyl, sufentanil or diamorphine are most appropriate for IN delivery to treat pain
   1. Reasonable IN starting dose for painful procedures:
      1. Fentanyl: 2 ug/kg (comes in 50 ug/ml, you can ask your pharmacy to concentrate the solution or use sufentanil in larger patients).
      2. Sufentanil: 0.5 to 0.7 ug/kg (0.5 for elderly, 0.7 for young)
      3. Diamorphine 0.1 mg/kg (not available in USA)
   2. Administer half the dose into each nostril
   3. 1/3 to ½ ml per nostril is ideal but can push up to 1 ml per nostril though some will run off. If you need more than 2 ml total, consider titration with second dose in 5 minutes or use sufentanil. If you have diamorphine you can simply solubilize it within the appropriate volume of liquid so you deliver 1/3 ml per nostril.
   4. Be Wary of respiratory depression with sufentanil – monitor patients with pulse oximetry and close observation whenever using this powerful opiate.
   5. Titration to pain is often necessary – repeat dosing (1/2 to full dose) every 15 minutes until desired effect is achieved.

Strongly consider administering an oral pain medication at the same time as the nasal medication. This way as the effect of the nasal drug wanes, the effect of the oral medication begins to have an effect.

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4. Striebel, H.W., et al., Self-administered intranasal meperidine for postoperative pain management. Can J Anaesth, 1995. 42(4): p. 287-91.

5. Wilson, J.A., J.M. Kendall, and P. Cornelius, Intranasal diamorphine for paediatric analgesia: assessment of safety and efficacy. J Accid Emerg Med, 1997. 14(2): p. 70-2.

6. Kendall, J.M., B.C. Reeves, and V.S. Latter, Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures. Bmj, 2001. 322(7281): p. 261-5.

7. Jackson, K., M. Ashby, and J. Keech, Pilot dose finding study of intranasal sufentanil for breakthrough and incident cancer-associated pain. J Pain Symptom Manage, 2002. 23(6): p. 450-2.

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12. PharmacologyFocusTeam, Battlefield pain control: Intranasal ketamine. Cognitive Performance Workshop. 19-25 July 2005: p. https://www.momrp.org/CognitivePerformance/Pharmos/PO5.pdf.

13. Borland, M., et al., A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med, 2007. 49(3): p. 335-40.

14. Borland, M.L., I. Jacobs, and G. Geelhoed, Intranasal fentanyl reduces acute pain in children in the emergency department: a safety and efficacy study. Emerg Med (Fremantle), 2002. 14(3): p. 275-80.

15. Moksnes, K., et al., Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference? Eur J Clin Pharmacol, 2008.

16. Rickard, C., et al., A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. Am J Emerg Med, 2007. 25(8): p. 911-7.

17. Zeppetella, G., An assessment of the safety, eff icacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain. A pilot study. J Pain Symptom Manage, 2000. 20(4): p. 253-8.

18. Dale, O., R. Hjortkjaer, and E.D. Kharasch, Nasal administration of opioids for pain management in adults. Acta Anaesthesiol Scand, 2002. 46(7): p. 759-70.

19. Takala, A., et al., Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone. Acta Anaesthesiol Scand, 1997. 41(2): p. 309-12.

20. Wolfe, T., Intranasal fentanyl for acute pain: techniques to enhance efficacy. Ann Emerg Med, 2007. 49(5): p. 721-2.

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