Intranasal drugs in emergency medicine

Intranasal Medications in the Emergency Room : 

Intranasal Medications in the Emergency Room

Scenario 1: Broken arm : 

Scenario 1: Broken arm A 25 year old fell off her bicycle and fractured her distal arm. She is in significant pain. ED protocols call for IN administration of sufentanil (0.7 mcg/kg). (Fentanyl for children) 10 minutes later the patients pain gone and she is calm She is taken off to x-ray for diagnostic evaluation of her fracture

Scenario 2: Frightened child : 

Scenario 2: Frightened child A 5-year old boy requires head CT scan (or a number of other procedures). He does not have an IV in place and is terrified of needles. He will not relax and clings to his parent. You administer 0.5 mg/kg of IN midazolam and 10 minutes later he is dozing off and is easily separated from his parent and taken over for his testing.

Scenario 3: Seizing child : 

Scenario 3: Seizing child EMS is enroute with a 3 y.o. girl suffering a grand mal seizure for at least 15 minutes. No IV can be established. Rectal diazepam (Valium) is unsuccessful at controlling the seizure. IV attempts in the ED are also unsuccessful. However, on patient arrival a dose of nasal midazolam (Versed, Dormicum) is given and within 3 minutes of drug delivery the child stops seizing.

Scenario 4: Epistaxis : 

Scenario 4: Epistaxis An elderly male arrives at the emergency room with his third episode of epistaxis in 3 days. He was cauterized and packed in another ER the day prior, but started bleeding 5 hours after the packing was removed. You administer 1.5 ml of atomized oxymetazoline (Afrin) into the nostril, and insert an oxymetazoline soaked cotton pledget. 15 minutes later his nasal mucosa is dry. You discharge him with instructions to use oxymetazoline TID for 3 days, and to self treat in the future if possible. No packing is needed, no expensive clotting factors are required

Scenario 5: Heroin Overdose : 

Scenario 5: Heroin Overdose An unkempt male is dumped in your ambulance bay. He has slow respirations, pinpoint pupils, cool dusky skin and obvious intravenous drug abuse needle track marks on both arms. After an IV is established, naloxone (Narcan) is administered and the patient is successfully resuscitated. Unfortunately, the nurse suffers a contaminated needle stick while establishing the IV. The patient admits to being infected with both HIV and hepatitis C. He remains alert for 2 hours with no further therapy (i.e.- no need for an IV) and is discharged.

Scenario 5: Heroin Overdose : 

Scenario 5: Heroin Overdose The nurse is given his first dose of HIV prophylactic medications. No treatment for hep C prophylaxis exists. The next few months will be difficult: He faces the substantial side effects that accompany HIV medications and his personal life is in turmoil due to issues of safe sex with his wife and the mental anguish of waiting to see if he will contract HIV or hepatitis C. A friend informs him that new evidence suggests that naloxone is effective at reversing heroin overdose if it is given intranasally – with no risk of a needle stick.

Why IN medications? : 

Why IN medications? This delivery route has several advantages: Its easy and convenient Almost everyone has a nose The nose is a very easy access point for medication delivery - even easier to access than IM or IV sites No special training is required to deliver the medication No shots are needed It is painless It eliminates any risk of a needle stick to the medical provider

Understanding IN delivery: Definitions : 

Understanding IN delivery: Definitions First pass metabolism Nose brain pathway Lipophilicity Bioavailability These have already been reviewed in Part 1 – please refer to that broad cast for overview details

Nasal Drug Delivery: What Medications? : 

Nasal Drug Delivery: What Medications? Drugs of interest to Emergency Departments: Pain control - Opiates Sedation- Benzodiazepines, ketamine Seizure Therapy - Benzodiazepines Nasopharyngeal procedures and epistaxis- Anesthetics, vasoconstrictors Opiate overdose - Naloxone Other

Pain control : 

Pain control Nasal Pain Medications • Diamorphine • Fentanyl • Sufentanil • Meperidine – no ER data

Pain control : 

Pain control Kendall et al: Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures. BMJ, 2001. Randomized trial - 204 IN diamorphine, 200 IM morphine. Results: IN medication achieved superior pain control at 5, 10 and 20 minutes. Equal at 30 minutes. IN much better tolerated. IN better accepted by parents and staff. Conclusion: Nasal opiates should be the preferred method of pain relief in children with painful conditions presenting to the emergency department.

Pain control : 

Pain control Borland, Ann Emerg Med, 2007. IN fentanyl versus IV morphine for treatment of pediatric orthopedic fractures - Randomized, double blind, placebo controlled trial Results: Pain scores identical for IV morphine and IN fentanyl at 5, 10, 20 and 30 minutes Less time to delivery of medication via nasal route Conclusion: IN fentanyl is as effective as IV morphine for treating pain associated with broken extremities

IN Fentanyl : 

IN Fentanyl Borland, Ann Emerg Med, 2007

Pain control : 

Pain control Borland, Emerg Med Australasia, 2008. Comparison of use of IV morphine vs IN fentanyl for acute pain in a pediatric Emergency Department Looked at use of IN fentanyl following the completion of prior study: Time from arrival to delivery of pain medications (IN vs IV) 24 minutes for INF vs 53 minutes for IVM Established an IV for pain control (before vs after INF) 100% vs 42% Conclusion: Compared to IV morphine, IN fentanyl is faster to administer and results in dramatic reduction in the need for IV access in children with acute pain

Pain control : 

Pain control Rickard, Am J Emerg Med, 2007. IN fentanyl versus IV morphine for treatment of adult patients with non-cardiac pain in the prehospital setting - Randomized, open label trial Results: Pain scores identical for IV morphine and IN fentanyl by the time the hospital was reached Less time to delivery of medication via nasal route Conclusion: IN fentanyl is as effective as IV morphine for treating pain in adult EMS patients

Pain control : 

Pain control Heshmati, Ir J Pharm, 2006. Intranasal sufentanil for treatment of postoperative pain following abdominal surgery Dose – 0.7 mcg/kg Onset of good pain control within 10 minutes NO ER studies for pain control using sufentanil exist My colleagues and I are conducting one right now 0.7 mcg/kg works very well – be sure to use a pulse oximeter and use slightly lower dose in elderly

Pain control : 

Pain control Caveats: Borland and Rickard used concentrated fentanyl (150 to 300 mcg/ml) U.S. generic fentanyl comes in 50 mcg/ml concentrations This lower concentration requires slightly higher doses to be effective and to possibly titrate dose. I use 2 mcg/kg in kids and just use sufentanil in adults Sufentanil is more potent than fentanyl and is very effective in adults for controlling pain.

Pain control : 

Pain control Take away lessons for IN opiates: Great patient and parent satisfier: Rapid pain resolution with no need for shot. Efficacy: It is just as effective as IV morphine – and it can be titrated. Use a pulse oximeter: These are potent drugs, play it safe and monitor the patient’s mental status and oxygenation.

Photo guide for IN drug delivery : 

Photo guide for IN drug delivery Collect supplies: Proper drug in correct concentration Syringe Method to aspirate drug from vial Atomization delivery device

Photo guide for IN drug delivery : 

Photo guide for IN drug delivery Aspirate drug Connect atomizer

Photo guide for IN drug delivery : 

Photo guide for IN drug delivery Deliver drug: Place atomizer against nostril and briskly compress to deliver half the drug to one nostril Move atomizer to other nostril and repeat – delivering the remaining drug into that nostril

Sedation : 

Sedation Nasal Sedatives • Midazolam • Ketamine • Sufentanil

Sedation : 

Sedation Lane and Schunk: Atomized intranasal midazolam for minor pediatric procedures. Ped Emerg Care 2008 3 month review of IN midazolam use in their ED 205 uses in children less than 5 years age 89% of time for laceration repair 95 % effective – 5% required more sedative No adverse events Conclusion: IN midazolam is an effective and safe anxiolytic for minor procedures

Sedation : 

Sedation Tschirch et al: Intranasal vs Oral midazolam for MRI of claustrophobic patients. Eur Rad, 2007 97% effective sedation for IN route 50% effective sedation for oral route Conclusion: IN midazolam is an effective and patient friendly solution to overcoming anxiety and claustrophobia in patients undergoing MRI.

Sedation : 

Sedation Louon et al: Nasal midazolam and ketamine for paediatric sedation during computerized tomography. Acta Anaesthesiol Scand, 1994 30 children < 16 kg requiring CT Dose: Midazolam 0.6 mg/kg, Ketamine 5 mg/kg mixed Results: 83% effective sedation Rapid onset No complications or desaturations

Sedation : 

Sedation Bates et al: A comparison of intranasal sufentanil and midazolam to intramuscular meperidine, promethazine, and chlorpromazine for conscious sedation in children. Ann Emerg Med, 1994 Both methods equally effective in achieving sedation IN sufentanil and midazolam superior in: Better tolerated by the patients 13 minutes faster onset to time of laceration injection (20 vs 33 minutes) 27 minute faster discharge (54 vs 81 minutes)

Sedation : 

Sedation Take away lessons for IN sedatives: Right tool for the right case: Rapid onset with no need for shot. Not typically effective for more than minor sedation – unless you mix drugs Midazolam burns for 30 seconds – forewarn parents

Seizure Therapy : 

Seizure Therapy Anticonvulsants Midazolam Lorazepam?

Seizure Therapy : 

Seizure Therapy Fisgin et al:Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol, 2002 IN midazolam versus rectal diazepam for treatment of pediatric seizure. Prospective trial Results: IN midazolam effective in 87% of seizures. Rectal diazepam effective in 60% Conclusion: IN midazolam is more effective for controlling seizures than rectal diazepam and is more socially acceptable

Seizure Therapy : 

Seizure Therapy Scheepers et al: Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy? Seizure, 2000 IN midazolam for treatment of severe epilepsy in adults. Results: IN midazolam effective in 94% of seizures. Conclusion: IN midazolam an effective method for controlling seizures and is a “more acceptable and dignified route” than rectal diazepam.

Seizure Therapy : 

Seizure Therapy Lahat et al: Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ, 2000 Prospective study: IN midazolam versus IV diazepam for prolonged seizures (>10 minutes) in children. Similar efficacy in stopping seizures (app. 90%). Time to seizure cessation: IV Valium: 8.0 minutes. IN Versed: 6.1 minutes. Conclusions: IN midazolam controls seizures more rapidly because there is no delay in establishing an IV.

Seizure Therapy : 

Seizure Therapy Holsti, Pediatr Emerg Care, 2007. IN midazolam versus rectal diazepam (PR) for treatment of pediatric seizure in EMS setting - before an after trial Results: IN midazolam - 19 minutes less seizure activity on average (11 min IN vs 30 min PR) Rectal diazepam More likely to re-seize (O.R. 8.4) More likely to need intubation (O.R. 12.2) More likely to require admission to hospital (O.R. 29.3) More likely to require admission to ICU (O.R. 53.5)

Seizure Therapy : 

Seizure Therapy Wilson, M. et al: Nasal/buccal midazolam use in the community. Arch Dis Child 2004. Survey of families with epileptic patients who were prescribed IN midazolam. 83% “effective and easy to use.” 83% “preferred it to rectal diazepam.”

Seizure Therapy : 

Seizure Therapy Ahmad. et al: Seizure therapy - IN lorazepam vs IM paraldehyde in rural Africa. Lancet 2006. RCT of 160 children with status epilepticus. Mean seizure duration 128 minutes 75% controlled with single dose IN lorazepam 61% controlled with IM paraldehyde Conclusions: IN lorazepam is safe, non-invasive and effective in acute setting

Seizure Therapy : 

Seizure Therapy Cost (AWP 2006): Rectal diazepam (Diastat brand name) 10 mg: $117/dose IN midazolam 10 mg: $3.20 (plus a few dollars for applicator)

Seizure Therapy : 

Seizure Therapy Take away lessons for IN anticonvulsants: Very effective, very fast: Rapid seizure resolution without IV access. Should be first line therapy in all acute seizures while IV access is being established Effective and safe at home, in EMS setting, in hospital Drug concentration: Midazolam is barely potent enough at 5 mg/ml. Ideally a more potent form would be available either from a compounding pharmacy or from the pharma companies

Nasopharyngeal procedures and epistaxis : 

Nasopharyngeal procedures and epistaxis Topical anesthetics Topical vasoconstrictors • Lidocaine • Oxymetazoline • Benzocaine • Phenylephrine • Tetracaine • Cocaine • Cocaine • Etc.

Nasopharyngeal procedures and epistaxis : 

Nasopharyngeal procedures and epistaxis Singer et al:Comparison of topical anesthetics and vasoconstrictors vs lubricants prior to nasogastric intubation: a randomized, controlled trial. Acad Emerg Med, 1999 Topical nasal and oral anesthetics with nasal vasoconstrictors result in markedly reduced pain and gagging compared to placebo during NGT placement Pain VAS: 28.6 mm vs 57.5 mm Gagging VAS: 24.1 mm vs 50.9 mm

Nasopharyngeal procedures and epistaxis : 

Nasopharyngeal procedures and epistaxis Wolfe et al:Atomized lidocaine as topical anesthesia for nasogastric tube placement: A randomized, double-blind, placebo-controlled trial. Ann Emerg Med, 2000 Topical nasal and oral anesthetics result in markedly reduced pain compared to topical intranasal 2% lidocaine jelly alone during NGT placement. Pain VAS: 37.4 mm vs 64.5 mm

Nasopharyngeal procedures and epistaxis : 

Nasopharyngeal procedures and epistaxis Krempl et al: Use of oxymetazoline in the management of epistaxis. Ann Otol Rhinol Laryngol, 1995 Retrospective ED study 60 patients with epistaxis Results: 65% controlled with oxymetazoline alone 83% success with oxymetazoline plus silver nitrate Only 17% needed packing

Nasopharyngeal procedures and epistaxis : 

Nasopharyngeal procedures and epistaxis Doo et al: Oxymetazoline in the treatment of posterior epistaxis. Hawaii Med J, 1999 Retrospective study 36 patients with posterior epistaxis Results: 75% controlled with oxymetazoline alone Remaining 25% treated non-surgically with recurrent oxymetazoline therapy

Nasopharyngeal procedures and epistaxis : 

Nasopharyngeal procedures and epistaxis Katz et al: A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation. J Clin Anesth 1990 3 groups of 14 patients pretreated with the study drug Following NT intubation, amount of epistaxis scored Lidocaine with epi: No bleeding in 29% Cocaine: No bleeding in 57% Oxymetazoline: No bleeding in 86% Vitals: Slightly higher SBP with cocaine, o/w no changes

IN anesthetics and vasoconstrictors : 

IN anesthetics and vasoconstrictors Take away lessons: Nasal instrumentation: Do it every time Proven by multiple RCT’s to reduce pain and bleeding associated with nasal procedures such as NGT placement and nasal intubation. Epistaxis: Usually effective, very simple Nasal oxymetazoline for the treatment of epistaxis is easy to administer and works about 80% of the time. If it fails you can always move to more aggressive treatments.

Photo guide for epistaxis therapy : 

Photo guide for epistaxis therapy Collect supplies: Oxymetazoline (not phenylephrine) Medication cup Atomizer Cotton balls Collection basin Nose clamp Gloves and mask Tissue paper

Photo guide for epistaxis therapy : 

Photo guide for epistaxis therapy Prepare Drug for delivery: Squirt several ml of oxymetazoline into cup (Add 4% lidocaine to liquid in case you need to cauterize at some point) Aspirate 1.0 to 1.5 ml into the atomizer syringe Soak a cotton ball in the remaining solution

Photo guide for epistaxis therapy : 

Photo guide for epistaxis therapy Prepare patient: Have patient blow nose to remove all loose clot and blood from nasal cavity

Photo guide for epistaxis therapy : 

Photo guide for epistaxis therapy Administer medication: Immediately after blowing the nose: Briskly atomize the oxymetazoline into the affected side. Place the cotton ball into the affected side Clamp the nostril Wait 15 minutes

Photo guide for epistaxis therapy : 

Photo guide for epistaxis therapy Re-evaluate: Remove cotton Reassess Cautery if indicated Topical clotting factors plus oxymetazoline if indicated Discharge with bottle of oxymetazoline to use TID for 2-3 days

Treating Opiate overdose : 

Treating Opiate overdose The problem! NEEDLESTICKS Nasal drug delivery of naloxone for opiate overdose is attractive not because it is BETTER than injectable therapy…… BUT …Because it is SAFER! ..No needle NO needle stick risk!

Treating Opiate overdose : 

Treating Opiate overdose Barton et al: Intranasal administration of naloxone by paramedics. Prehosp Emerg Care, 2002 Prospective prehospital study investigating the efficacy of IN naloxone in treating opiate overdoses 100 patients entered, 52 determined to have opiate overdose Results: 43/52 (83%) = “IN Naloxone Responders.” Conclusions: IN naloxone is effective most of the time Routine use may reduce needle stick injuries

IN Naloxone by Paramedics : 

IN Naloxone by Paramedics

Treating Opiate overdose : 

Treating Opiate overdose Other IN naloxone studies Kelly et al 2005 and Kerr 2009 Have duplicated this original data in larger group of patients 75-80% response in the field Less agitated awakening than injectable naloxone – probably due to less rapid increase in blood naloxone and awakening. State of New Mexico home naloxone protocol High risk families of heroin addicts are taught to use intranasal naloxone for rescue therapy in case of overdose Other states are considering adoption of this idea

What if IN naloxone had been available here? : 

What if IN naloxone had been available here? Opiate is gas used at theater By Judith IngramASSOCIATED PRESS  MOSCOW — Russia's top health official said yesterday that the gas used in the storming of a Moscow theater held by Chechen gunmen was based on fentanyl, a fast-acting opiate with medical applications, Russian news agencies reported.

Treatment of opiate overdose with IN naloxone : 

Treatment of opiate overdose with IN naloxone Why not? High risk population for HIV, HCV, HBV Difficult IV to establish due to scarring of veins Elimination of needle reduces needle stick risk IV unnecessary for any other therapy in majority of cases IN works as fast or faster than IV naloxone If the treatment is unsuccessful, one can always proceed to injectable naloxone and no untoward effects should occur (may need 3 minutes of bag ventilation while waiting) Every EMS system should be utilizing this approach.

Other potential IN medications : 

Other potential IN medications IN glucagon for hypoglycemia IN lidocaine for cluster headaches IN saline for severe sinus congestion IN hydroxycobalamine for cyanide treatment? IN antiemetics for N/V, headaches?