Presentation on theme: "Intranasal Drug Delivery – Advantages of use in Rural and Remote practice."— Presentation transcript:
Intranasal Drug Delivery – Advantages of use in Rural and Remote practice
Lecture outline Why use intranasal medications? Intranasal drugs indications with clinical cases and personal insights: Pain Control Sedation Seizures Opiate overdose Drug doses and optimizing absorption Resources
Why nasal drugs in rural practice? Ease of use and convenience Saves time / reduces human resource utilization Rapidly effective - onset within 2-10 minutes Safe – No high peak serum levels yet rapidly therapeutic No special training is required to deliver the medication No injection is needed Painless No needle stick risk Extensive literature support Patients (& Parents & clinicians) really like this approach Faster care and discharge
Intranasal Medication Cases Pain Control
Case: Pediatric Hand burn A 5 year old burned her hand with boiling water Clinical Needs: Pain control, debride, clean and dress the 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 improved 15 minutes later the patient easily tolerates cleansing of the burn and dressing application. She is discharged with an oral pain killer less than one hour after arrival.
Case: Injured ankle A 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 calm He is taken off to x-ray for diagnostic evaluation of his ankle, followed by a splint, crutches and referral to followup. He leaves with very little pain, pleased with the timely care
Literature to support these cases – long bone fractures in pediatrics Nasal Intravenous Borland, Ann Emerg Med 2007
Literature to support these cases – extremity trauma in adults Steenblik, Am J Emerg Med 2012
But - are nasal drugs safe?
Over a decade of EMS 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 onset min vs minutes to drug delivered Equivalency to IV morphine (even if they have an IV) Superior to IM morphine Care givers are more likely to treat pediatric severe pain Highly satisfied patients and providers Safe Pain control – Literature support
IN 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 are inexpensive ($1-4/vial) Great patient and parent satisfier: Rapid pain resolution with no need 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 with respect. Fentanyl seems fine and can safely be given with minimal risk Give an oral pain killer as well: It kicks in as IN drug wears off
The Doubters: Surely IN drugs cant be as good as an injection for pain control! ACTUALLY – 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 arms Borland 2008, Holdgate 2010, Crellin time to delivery of IN opiates was half that of IV and more patients get treated Kendal 2001 – IN opiate superior to IM opiate for pain control Conclusions IN opiates are just as good as IV IN opiates are delivered in half the waiting time as IV IN opiate are preferred by patients, providers and parents over injections Nasal Intravenous
Intranasal Medication Cases Sedation
Case: CT scan child A 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 is 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.
Case: Abscess Drainage A 21 year old autistic male complains of redness, swelling and pain on his thigh. Exam reveals a large pus filled abscess, terrified patient. Clinical Needs: Pain control, sedation, incision and drainage of the abscess Treatment: 40 mcg of IN sufentanil then 5 mg intranasal midazolam 15 minutes later he is asleep, mildly sedated The abscess is incised, drained and patient is discharged when awake.
Literature to support these cases - pediatrics Klein, Ann Emerg Med 2011
Sedation – Literature support Hundreds of articles dating back into the 1980s. Most used midazolam. Effective only if adequate dose is given (0.4 to 0.5 mg/kg) Burns upon application – pretreat with lignocaine Effective in children and adults (even exited delirium in EMS) Safe – no reports of respiratory depression
Intranasal Medication Cases Seizure Control
Case: Seizing child The ambulance is transporting a 4 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 0.2 mg/kg of nasal midazolam (Versed, Dormicum) is given and within 3 minutes of drug delivery the child stops seizing.
Seizure 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 givers IN midazolam is superior to intramuscular injection of paraldehyde IN 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 depression IN midazolam can be delivered by family at home safely and effectively
Nasal vs buccal Anderson 2011: IN vs buccal lorazepam
The Doubters: Surely IN drugs cant 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 delays Holsti 2007, Fisgin 2002 – IN is superior to rectal Holsti 2011 – IN is safe at home with immediate results Conclusions IN seizure medication are just as good as IV, better than rectal IN 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.
IN 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 hospital More effective, less expensive and preferred by providers when compared to alternative (rectal diazepam).
Intranasal Medication Cases Opiate Overdose
Case: Methadone induced coma A mother enters her daughters room to find her unconscious, barely breathing, blue color. Since her daughter is on methadone maintenance, the family was trained to deliver rescue naloxone (see photo of kit above). The mother quickly delivers the naloxone intranasally. She provides 2-3 minutes of rescue breathing until her daughter begins to arouse. She gradually awakens over 10 minutes. The patient is transferred to the hospital for observation due to the long half life of methadone, but makes an uneventful recovery.
Opiate overdose – Literature support Intranasal naloxone literature Barton 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 overdose When compared directly it is equivalent in efficacy to IV or IM therapy. IN naloxone results in less agitation upon arousal IN naloxone is lay person approved in many places. It safe and has saved many lives.
IN naloxone for opiate overdose – my insights Why not? Is there a downside? High risk population for HIV, HCV, HBV Difficult IV to establish due to scarring of veins Elimination of needle eliminates needle stick risk They awaken more gently than with IV naloxone New epidemiology shows prescription drugs (methadone, etc) are causing many deaths that naloxone at home could reverse. Simple enough that lay public can administer Every ambulance system, police agency and many clinics and families with high risk patients should be utilizing this approach.
Drug doses ScenarioDrug and DoseImportant Reminders Pain ControlFentanyl: 2 mcg/kg Sufentanil: 0.5 mcg/kg Titration is possible Sufentanil – use pulse ox Half up each nostril SedationMidazolam: 0.5 mg/kg (combination w/ pain) Use lidocaine to prevent burning Use concentrated formula SeizuresMidazolam: 0.2 mg/kg Lorazepam 0.1 mg/kg Support breathing while waiting Use concentrated formula Opiate OverdoseNaloxone: 2 mg Support breathing while awaiting onset EpistaxisOxymetazoline or Phenylephrine + Lidocaine Blow nose prior to application Spray, then apply soaked cotton ball Pinch nose for 10 minutes Nasal ProceduresOxymetazoline or Phenylephrine + Lidocaine Wait 3 full minutes for anesthetic effect
Optimizing absorption of IN drugs Minimize volume - Maximize concentration 0.2 to 0.3 ml per nostril ideal, 1 ml is maximum Most potent (highly concentrated) drug should be used Maximize total absorptive mucosal surface area Use BOTH nostrils (doubles your absorptive surface area) Use a delivery system that maximizes mucosal coverage and minimizes run-off. Atomized particles across broad surface area Critical Concept
Dropper vs Atomizer Absorption Drops = Oral drug via the nasal passage Atomizer = nasal mist onto broad mucosal surface Usability / acceptance Drops = Minutes to give, cooperative patient, head position critical Atomizer = seconds to deliver, better accepted
Dropper vs Atomizer Merkus 2006
Intranasal medications summary Another tool for drug delivery to supplement standard IV, IM, PO–very useful when appropriate Supported by extensive literature Inexpensive Speeds up care in many situations Safe
Questions? Educational Web site:
IN Benzos for sedation – my insights Nasal Midazolam burns on application: Pretreat with lignocaine, warn the parents, this lasts seconds then dissipates Timing: 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, calming an agitated patient, CT/ MRI. It is not good enough for complex face laceration repair.