Presentation on theme: "Lecture outline Why use intranasal medications?"— Presentation transcript:
1Intranasal Drug Delivery – Clinical Implications for Emergency Medicine and EMS
2Lecture outline Why use intranasal medications? Intranasal drug delivery: General conceptsIntranasal drugs indications with clinical cases and personal insights:• Pain Control • Opiate overdose• Sedation • Epistaxis• Seizures • Nasopharyngeal proceduresDrug dosesResources
3Advantages of Nasal drugs Ease of use and convenienceSaves time / reduces resource utilizationRapidly effective - onset within 2-10 minutesSafe – No high peak serum levels yet rapidly therapeuticNo special training is required to deliver the medicationNo shots are neededPainlessNo needle stick riskExtensive literature supportPatients (& Parents & clinicians) really like this approachFaster care and discharge3
4Understanding IN delivery: General principles First pass metabolismNose brain pathwayBioavailabilitySafety vs IV drugs
5First pass metabolism Nasal Mucosa: No first pass metabolism Gut mucosa: Subject to first pass metabolism5
6Nose brain pathway Olfactory mucosa, nerve The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF.Medications absorbed across the olfactory mucosa directly enter the CSF.This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain.BrainCSFHighly vascular nasal mucosa6
8BioavailabilityHow much of the administered medication actually ends up in the blood stream.Examples:IV medications are 100% bioavailable by definition.Most oral medications are about 5%-10% bioavailable due to destruction in the gut and liver.Nasal medications vary depending on molecule, pH, etcMidazolam 75+%Fentanyl and Sufentanil 80+%Naloxone 90+%Lorazepam, ketamine, Romazicon, etc
9Optimizing Bioavailability of IN drugs CriticalConceptMinimize volume - Maximize concentration0.2 to 0.3 ml per nostril ideal, 1 ml is maximumMost potent (highly concentrated) drug should be usedMaximize total absorptive mucosal surface areaUse BOTH nostrils (doubles your absorptive surface area)Use a delivery system that maximizes mucosal coverage and minimizes run-off.Atomized particles across broad surface area9
10Dropper vs Atomizer Absorption Usability / acceptance Drops = runs down to pharynx and swallowedAtomizer = sticks to broad mucosal surface and absorbsUsability / acceptanceDrops = Minutes to give, cooperative patient, head position requiredAtomizer = seconds to deliver, better accepted
17Case: Pediatric Hand burn A 5 year old burned her hand on the stoveClinical Needs: Pain control, debride and clean wound.Treatment: 2.0 mcg/kg of intranasal fentanyl (40 mcg – 0.8 ml of generic “IV” fentanyl)Within 3-5 minutes her pain is improved15 minutes later the patient easily tolerates cleansing of the burn and dressing application.She is discharged with an oral pain killer one hour post triage.17
18Case: Injured ankleA 25 year old injured his ankle and has significant ankle swelling, bruising and pain.Clinical Needs: Pain control, x-ray, splint.Treatment: 0.5 mcg/kg of intranasal sufentanil (45 mcg – 0.9 ml of generic “IV” sufentanil)5-10 minutes later the pain is gone and he is calmHe is taken off to x-ray for diagnostic evaluation of his ankle, followed by a splint and referral to an orthopedist.
19Case: MVC pinned in carA 35 year old male pinned in a car following an MVC. Bilateral upper arm fractures, femur fracture, likely other injuries. Screaming in pain.Clinical Needs: Pain control, sedation, rapid extraction, then IV access (cannot do so now).Treatment: 1.5 mcg/kg of intranasal fentanyl plus 5 mg IN midazolamIn 7 minutes his pain is much better controlled and he is calmerExtraction requires 20 minutes, then full trauma assessment and care proceeds.19
20Literature to support this case - pediatrics NasalIntravenousBorland, Ann Emerg Med 200720
21Literature to support this case - adults Steenblik, Am J Emerg Med 201221
22Intranasal Ketamine for pain ?: Literature support US Army IN ketamine dataCompared IN ketamine to IV morphine for severe painIN ketamine (50 mg) as fast and as good as IV morphine (7.5 mg) w/o side effects.
23NasalThe Doubters: Surely IN drugs can’t be as good as an injection for pain control!IntravenousACTUALLY – They are equivalent or better (in these settings)Borland 2007 – IN fentanyl onset of action and quality of pain control was identical to IV morphine in patients with broken legs and armsBorland 2008, Holdgate 2010, Crellin time to delivery of IN opiates was half that of IV and more patients get treatedKendal 2001 – IN opiate superior to IM opiate for pain controlConclusionsIN opiates are just as good as IVIN opiates are delivered in half the waiting time as IVIN opiate are preferred by patients, providers and parents over injections23
24Pain control – Literature support Over a decade of prehospital and ER literature exists for burn, orthopedic trauma and visceral pain in both adults and children showing the following:Faster drug delivery (no IV start needed) so faster onsetEquivalent to IV morphineSuperior to IM morphineCare givers are more likely to treat pediatric severe painHighly satisfied patients and providersSafe
25IN opiates for Pain control – My insights This is the most common use of IN drugs in my practice - daily.Generic concentrations available in U.S. work fine and areinexpensive ($1-4/vial)Great patient and parent satisfier: Rapid pain resolution with noneed for a painful injection.Efficacy: Very effective – and it can be titrated.Use a pulse oximeter with sufentanil:Sufentanil is especially potent and must be treated withrespect.Fentanyl seems fine and can safely be given with minimalriskGive an oral pain killer as well: It kicks in as IN drug wears off
27Case: CT scan childA 5-year old boy requires a CT scan (computed tomography) of his head due to head injury.He does not have an IV in place and mildly agitated.He will not remain still enough to obtain quality images.The clinician administers topical lidocaine followed by 0.5 mg/kg of IN midazolam (or 2 ug/kg dexmedetomidine if longer duration of sedation is needed for MRI) and 10 minutes later he is dozing off and remains calm and still for the ct scan.27
28Case: Abscess Drainage A 40 year old male complains of redness, swelling and pain on his thigh. Exam reveals a large pus filled abscess.Clinical Needs: Pain control, sedation, incision and drainage of the abscessTreatment:40 mcg of IN sufentanil then 10 mg intranasal midazolam15 minutes later he is asleep, mildly sedatedThe abscess is injected with lidocaine, incised, drained and packed and patient is discharged when awake.
29Case: Excited Delirium A 27-year old male is apprehended by police and paramedics for extremely violent, out of control behavior following use of crystal meth.He is at significant risk of injuring himself and others.It is too dangerous (needle stick risk) to give him an injection of sedatives.The paramedic administers 10 mg of IN midazolam and 7 minutes later he is calm and can be transported safely to the hospital.29
30Literature to support this case - pediatrics Klein, Ann Emerg Med 201130
31Sedation – Literature support Hundreds of articles dating back into the 1980’s. Most used midazolam.Effective only if adequate dose is given (0.4 to 0.5 mg/kg)Burns upon application – pretreat with lignocaineEffective in children and adults (even exited delirium in EMS)Safe – no reports of respiratory depression
32IN Benzos for sedation – my insights Nasal Midazolam burns on application: Pretreat with lignocaine, warn the parents, this lasts seconds then dissipatesTiming: Children become sedated at about 5-10 minutes, maximal at and starts to wear off at so be ready to do prep and suture or do procedure in this time frame.Efficacy: Sedation is not deep. OK for minor procedures, CT, ?MRI, not good enough for complex face laceration. More data needs to be obtained for lorazepam.32
34Case: Seizing childThe ambulance is transporting a 13 y.o. girl suffering a grand mal seizure.Despite trying, no IV can be successfully established.Rectal diazepam is unsuccessful at controlling the seizure.IV attempts in the clinic / hospital 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.34
35Seizure Therapy - Literature support Lahat 2000; Fisgin 2002; Holsti 2006; Ahmad 2006; Arya 2011; Holsti 2011; Javadzadeh 2012; Thakker 2012:IN midazolam is superior to rectal diazepam for seizure control and is preferred by care giversIN midazolam is superior to intramuscular injection of paraldehydeIN midazolam/lorazepam is equivalent to intravenous delivery for stopping seizures, much faster at stopping them due to no IV start needed and it leads to less respiratory depressionIN midazolam can be delivered by family at home safely and effectively
36Onset of nasal vs buccal seizure drugs (Time of onset matters) Anderson 2011: IN vs buccal lorazepam
37The Doubters: Surely IN drugs can’t be as good as IV for seizures! ACTUALLY – They are equivalent or better (in these settings)Lahat 00, Mahmoudian 04, Arya 11, Thakker 12, Javadzadeh 12 – IV and IN are equivalent for stopping seizures rapidly, but IN works faster due to no delaysHolsti 2007, Fisgin 2002 – IN is superior to rectalHolsti 2011 – IN is safe at home with immediate resultsConclusionsIN seizure medication are just as good as IV, better than rectalIN seizure medication are delivered much more rapidly so seizure stops sooner.Anyone (Parents, care givers, nursing home staff, ambulance driver, etc.) can administer the medication so seizure length is shorter.37
38IN benzodiazepines for seizures – My insights Very effective, very fast: Rapid seizure resolution without IV access.Should be first line therapy in ALL prolonged acute seizures while IV access is being established (if at all)Effective and safe at home, in EMS setting, in hospitalMore effective, less expensive and preferred by providers when compared to alternative (rectal diazepam).
40Case: Heroin OverdoseThe ambulance responds to an unconscious, barely breathing patient with obvious intravenous drug needle marks on both arms – consistent with heroin overdoseAfter an IV is established, naloxone (Narcan) is administered and the patient is successfully resuscitated.Unfortunately, the medic 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 in the ED (i.e.- no need for an IV) and is discharged.
41Case: Heroin Overdose The medic now needs treatment - HIV prophylaxis The next few months will be difficult for him:Side effects that accompany HIV medicationsPersonal life is in turmoil due to issues of safe sex with his spouseMental anguish of waiting to see if he develops HIV or hepatitis C.He wonders why his system is not using LMA-MAD nasal to deliver naloxone on all these patients.
42Opiate overdose – Literature support Intranasal naloxone literatureBarton 02, 05; Kelly 05; Robertson 09; Kerr 09; Merlin 2010; Doe Simkins 09; Walley 12:IN naloxone is at least 80-90% effective at reversing opiate overdoseWhen compared directly it is equivalent in efficacy to IV or IM therapy.IN naloxone results in less agitation upon arousalIN naloxone is lay person approved in many places. It safe and has saved many lives.
43IN naloxone for opiate overdose – my insights Why not? Is there a downside?High risk population for HIV, HCV, HBVDifficult IV to establish due to scarring of veinsElimination of needle eliminates needle stick riskThey awaken more gently than with IV naloxoneNew epidemiology shows prescription drugs (methadone, etc) are causing many deaths that naloxone at home could reverse.Simple enough that lay public can administer and not even call ambulanceEvery ambulance system, police agency and many clinics and families with high risk patients should be utilizing this approach.
45Case: Epistaxis (Bloody nose) An elderly male arrives at the emergency room with profuse epistaxis from his anterior left nares.Treatment: Atomized oxymetazoline (Afrin) plus 4% lidocaine into the nostril, and insertion of an oxymetazoline soaked cotton pledget.15 minutes later his nasal mucosa is dry due to oxymetazoline induced vasoconstriction.One large vessel is cauterized (he is numb from the lidocaine).He is discharged with instructions to use oxymetazoline for 3 days, and to self treat in the future if possible.No packing is needed, no expensive clotting factors are required
46Nasopharyngeal procedures and epistaxis – Literature support Extensive literature in the past 40 years documents efficacy of topical anesthesiaWolfe 00 (MAD): IN lidocaine markedly reduces pain during nasogastric tube placement. Many similar studies since.National Center for patient safety 06: Online PDF review of the literature – recommends nasal/oral lidocaineKremple 95, Doo 99: IN oxymetazoline excellent single therapy for epistaxis (bloody nose).
47IN anesthetics and vasoconstrictors – my insights Nasal instrumentation: Do it every timeProven by multiple studies to improve procedural comfort.Epistaxis: Very effective, very simpleInexpensive and easy
48Drug doses Scenario Drug and Dose Important Reminders Pain Control Fentanyl: 2 mcg/kgSufentanil: 0.5 mcg/kgKetamine 1 mg/kg?Titration is possibleSufentanil – use pulse oxHalf up each nostrilSedationMidazolam: 0.5 mg/kg(combination w/ pain)Use lidocaine to prevent burningUse concentrated formulaSeizuresMidazolam: 0.2 mg/kgLorazepam 0.1 mg/kgSupport breathing while waitingOpiate OverdoseNaloxone: 2 mgSupport breathing while awaiting onsetEpistaxisOxymetazoline orPhenylephrine +LidocaineBlow nose prior to applicationSpray, then apply soaked cotton ballPinch nose for 10 minutesNasal ProceduresWait 3 full minutes for anesthetic effect
49Intranasal medications summary Another tool for drug delivery to supplement standard IV, IM, PO–very useful when appropriateSupported by extensive literatureInexpensiveSpeeds up care in many situationsSafe