Intranasal Medications in the Prehospital Setting : Intranasal Medications in the Prehospital Setting Scenario 1: Broken arm : Scenario 1: Broken arm A 12 year old fell off his bicycle and fractured his distal arm.
He is in significant pain.
EMS protocols call for IN administration of fentanyl (2 mcg/kg).
10 minutes later the child’s pain is improved but still substantial.
After a second ½ dose of IN fentanyl he is comfortable. Scenario 2: Seizing child : Scenario 2: Seizing child You respond to the home of a 3 y.o. girl suffering a grand mal seizure for at least 15 minutes.
Rectal diazepam (Valium) administered by the mother is unsuccessful at controlling the seizure.
However, on arrival you administer a dose of nasal midazolam (Versed) and the child stops seizing 5 minutes later.
No IV can be established. Scenario 3: Heroin Overdose : Scenario 3: Heroin Overdose You respond to an unconscious male. 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 and taken to the ED.
Unfortunately, you suffer 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 in the ED with no further therapy (i.e.- no need for an IV) and is discharged. Scenario 3: Heroin Overdose : Scenario 3: Heroin Overdose You are given your first dose of HIV prophylactic medications. No treatment for hep C prophylaxis exists.
The next few months will be difficult: You face the substantial side effects that accompany HIV medications and your personal life is in turmoil due to issues of safe sex with your spouse and the mental anguish of waiting to see if you will contract HIV or hepatitis C.
A friend informs you that new evidence suggests that naloxone is effective at reversing heroin overdose if it is given intranasally – with no risk of a needle stick. The problem! NEEDLESTICKS : The problem! NEEDLESTICKS Nasal drug delivery is attractive not because it is BETTER than injectable therapy……
…Because it is SAFER!
..No needle NO needle stick risk! The problem! NEEDLESTICKS : The problem! NEEDLESTICKS The CDC estimates:
600,000 percutaneous injuries each year involving contaminated sharps in the U.S. A..
Technological developments can increase protection. …in the field! Very high risk : …in the field! Very high risk High risk patients
HIV+ patients = 4.1-8.3/100 transports
Marcus et al, Ann Em Med, 1995
High risk environments
Altered patients, combative
Scene control issues
Moving ambulance Intranasal Medication Administration : Intranasal Medication Administration Intranasal Medication administration offers a truly “Needleless” solution to drug delivery.
The remainder of this slide show will surround the topic of intranasal drug delivery issues. Intranasal Medication Administration: Basic Concepts : Intranasal Medication Administration: Basic Concepts 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 than the arm, especially in winter)
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 you, the medical provider Understanding IN delivery: Definitions : Understanding IN delivery: Definitions First pass metabolism
Nose brain pathway
Bioavailability These have already been reviewed in part 1 – please refer to that broad cast for overview details Nasal Drug Delivery in EMS: What Medications? : Nasal Drug Delivery in EMS: What Medications? Drugs of interest to EMS systems:
Intranasal naloxone (Narcan)
Intranasal midazolam (Versed)
Others Intranasal (IN) Naloxone : Intranasal (IN) Naloxone Background
Absorption of IN naloxone almost as fast as IV in both animal and human models
Hussain et al, Int J Pharm, 1984
Loimer et al, Int J Addict, 1994
Loimer et al, J Psychiatr Res, 1992
Atomized spray of medications show much better absorption via the IN route
Bryant et al, Nucl Med Comm, 1999
Daley-Yates et al, Br J Clin Pharm 2001
Henry et al, Ped Dent 1998 “Intranasal Administration of Naloxone by Paramedics” : “Intranasal Administration of Naloxone by Paramedics” Prospective clinical trial
Preliminary study February, 2001
Barton et al, Prehosp Emer Care 2002
Final study completed
Barton et al, J Emerg Med 2005
Kelly et al, Med J Aust 2005 (a study in Australia)
Required all patients to get an IV and IV naloxone (standard care) – however nasal naloxone was administered first and if the patient awoke prior to IV therapy they could stop. IN Naloxone by Paramedics : IN Naloxone by Paramedics Prehospital IN Naloxone : Prehospital IN Naloxone Results
43/52 (83%) = “IN Naloxone Responders.”
Median time to awaken from drug delivery = 3 min.
Median time from first contact = 8 min.
9/52 (17%) = “IN Non-responders.”
4 patients noted to have “epistaxis,” “trauma,” or “septal abnormality.”
Note – no one waited for them to respond, once IV started they got IV naloxone so some cases were given IV naloxone before the nasal drug could absorb. Prehospital IN Naloxone : Prehospital IN Naloxone Conclusions
IN naloxone is effective
83% response in the field
Potentially higher if one waits a few minutes for its effect prior to giving IV naloxone.
Syringe driven atomizer (about $3 for the device)
May decrease prehospital blood exposures
29% no IV in the field (woke up before one could be started.) Potential for at least 83% with no IV. Prehospital IN Naloxone : Prehospital IN Naloxone 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 Other Naloxone Studies… : Other Naloxone Studies… IV vs. SQ Naloxone:
Wanger et al, Acad Emer Med, 1998.
196 patients in Vancouver, BC.
IV naloxone (0.4mg) vs. SQ (0.8mg).
Response time = crew arrival to RR > 10.
Median response time IV = 9.3 min.
Median response time SQ = 9.6 min.
Conclusions = No significant difference.
Delay in SQ response offset by time for IV insertion.
*Median response time IN naloxone = 8.0 min.
Point: IN responses from time of arrival to RR > 10 are same as those for IV and SQ. Prehospital IN Naloxone : Prehospital IN Naloxone Take away lessons for nasal naloxone:
Dose and volume – higher concentration preferred so use 1mg/ml IV solution. More concentrated drug would be better
Delivery – immediately on decision to treat inject naloxone into nose with atomizer, then begin standard care.
Successful awakening eliminates the need for any IV or further ALS care.
Awakening is gradual-patient doesn’t jump off the bed, but adequate respiratory efforts occur as fast or faster than IV naloxone due to no delays with IV start.
Not 100% effective so failures with IN naloxone need to be followed with IV naloxone. What if intranasal naloxone does not work? : What if intranasal naloxone does not work? 1st - Continue ABC’s to support breathing and circulation.
2nd – Administer Naloxone IM or IV.
3rd - Consider other causes for coma:
Is there anything you can do for these processes? Protocol: Dosing for IN naloxone : Protocol: Dosing for IN naloxone Inspect nostrils for mucus, blood or other problems which might inhibit absorption.
(If these are present, consider suction of nostrils or consider other routes and be aware of increased risk of failure.)
Draw 2mg of 1mg/ml solution for delivery by atomizer device.
Give ½ of volume in each nostril.
Support ventilations for 4 to 5 minutes, if no response proceed to IM/IV therapy and consider other causes for coma. Midazolam : Midazolam What is it?
Benzodiazepine related to Valium (diazepam)
Benzodiazepines act on the GABA receptor to stabilize neural membrane and reduce neuronal irritation.
Water soluble, pH 3.5 (Valium thick, alkalotic)
Amnesia Prehospital IN Midazolam : Prehospital IN Midazolam Why intranasal midazolam in the EMS setting?
No needles, no need for an IV in a seizing patient.
Rapid delivery – No delays in IV attempts.
Socially acceptable: No need for rectal drug administration.
As effective as IV therapy, more effective than rectal therapy, faster onset than either.
Agitation/combative patient IN Midazolam : IN Midazolam Supporting data:
Nasal midazolam has been extensively studied for over a decade with hundreds of studies published regarding its effectiveness for sedation children.
Very effective for treating acute seizures and status epilepsy. IN Midazolam : IN Midazolam Seizures.
Lahat et al, 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. IN Midazolam : IN Midazolam Lahat et al, BMJ, 2000 (cont):
IV diazepam and IN midazolam have similar efficacy at controlling prolonged seizures in children.
IN midazolam controls seizures more rapidly because there is no delay in establishing an IV. IN Midazolam : IN Midazolam Sheepers et al, 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. IN Midazolam : IN Midazolam Fisgin, J Child Neur, 2002.
IN midazolam versus rectal diazepam for treatment of pediatric seizure. Prospective trial
IN midazolam effective in 87% of seizures.
Rectal diazepam effective in 60%
IN midazolam is more effective for controlling seizures than rectal diazepam.
IN midazolam will be “very useful” in the emergency setting IN Midazolam : IN Midazolam Holsti, Pediatr Emerg Care, 2007.
IN midazolam versus rectal diazepam (PR) for treatment of pediatric seizure in EMS setting - before an after trial
IN midazolam - 19 minutes less seizure activity on average (11 min IN vs 30 min PR)
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) IN Midazolam : IN Midazolam Take away lessons for nasal midazolam:
Dose and volume: Higher concentration required - use 5mg/ml IV solution.
Dosing calculations are difficult: Use a predefined age or weight based table to determine dose.
Deliver immediately on decision to treat: Spray into nose with atomizer, then begin standard care.
Efficacy: Not quite 100% effective so failures with nasal may need follow-up with IV therapy. IN Midazolam Dosing chart : IN Midazolam Dosing chart Fentanyl : Fentanyl What is it?
Synthetic opiate pain killer
Fentanyl is 50 to 100 times more potent than morphine
It is 1/2 to 1/3 as long lasting as morphine
Amnesia Prehospital IN Fentanyl : Prehospital IN Fentanyl Why intranasal fentanyl in the EMS setting?
No needles, no need for an IV
Rapid delivery – No delays in IV attempts.
As effective as IV morphine in children & adults
Allows adequate pain control without need to establish an IV in patients that likely do not need IV access (minor orthopedic trauma and burns) IN Fentanyl : IN Fentanyl Borland, Ann Emerg Med, 2007.
IN fentanyl versus IV morphine for treatment of pediatric orthopedic fractures - Randomized, double blind, placebo controlled trial
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 IN Fentanyl : IN Fentanyl 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
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 IN Fentanyl : IN Fentanyl 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 (I use 2 mcg/kg) and to possibly titrate dose. IN Fentanyl : IN Fentanyl Take away lessons for IN fentanyl:
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.
Dosing calculations are easy: Use 2 mcg/kg for first dose, 1 mcg/kg if inadequate pain control in 15 minutes.
Use a pulse oximeter: It is a potent drug, play it safe and monitor the patients mental status and oxygenation. Other IN Medications : Other IN Medications ALS Drugs
This is being used in several U.S. EMS systems – I would like them to collect and publish their data to share with all of us.
?Hydroxycobalamine for cyanide exposure (i.e. smoke inhalation arrests during fires)
??others Photo guide for IN drug delivery : Photo guide for IN drug delivery Collect supplies:
Proper drug in correct concentration
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 Conclusions : Conclusions Multiple drugs can be given IN
Can be given to almost anyone
Exception = Nasal mucosal abnormalities.
Delivery method and drugs (generic) are inexpensive Conclusions : Conclusions Intranasal drug delivery is a true “needleless” system!
Reduce blood borne exposure risks
Hepatitis B, C
Decrease IV placements in the field
Improve care in situations where an IV cannot be established.
Equivalent results to IV in many cases, superior to rectal