Intranasal Medications in Hospice A Novel method of pain, dyspnea, seizure and anxiety control.
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Transcript of Intranasal Medications in Hospice A Novel method of pain, dyspnea, seizure and anxiety control.
Intranasal Medications in Hospice
A Novel method of pain, dyspnea, seizure and anxiety
control.
Disclosures
Off Label Medications will be discussed(all the indications are “on label” but the delivery
method is “off label”)
IN medications and off-label use
What is “off-label” use Use other than FDA approved specific indications in
specific subpopulations by specific route of delivery Is it OK to use drugs “off-label”
Yes – in fact is is expected this will occur and this actually helps advance medical care – supported by FDA, supreme court, standards of care practice, etc
We all do it and its not only legal, it is expected to occur. In fact – about 80% of critically ill children and 40% of
adults are treated with “off label” medications (Hospice?) Failure to provide off label can result in malpractice
Example - N-acetylcysteine for Tylenol overdose
Case 1: Patient with bony metastasis with breakthrough
pain
A 65 year old female with metastatic breast CA to her spine
Every time she gets up to use the toilet, she suffers severe pain. She also has spontaneous spells of severe pain even at rest (despite baseline opiate therapy).
Solution: Prior to movement and/or during spontaneous breakthrough pain she self administers 30 mcg of intranasal sufentanil (30 mcg – 0.6 ml of generic IV sufentanil) Within 5 minutes her pain is improved At 15 minutes the patient easily tolerates movement to go
to the toilet or conduct other activities.
Case 2: Episodic breathlessness
A 73 y.o. man with metastatic carcinoma to lungs complains of severe dyspnea and cough. RR = 30, O2 saturation 62%, air hunger. Solution: You administer 50 to 150 mcg of intranasal fentanyl –
(Fentanyl compounded to 500mcg/ml). In 3 minutes he has improved symptomatically At 7 minutes his RR = 12, O2 saturation = 94%. He self delivers 100 mcg IN fentanyl on an as needed basis for
the remainder of his care – using it about 7 times/day He dies comfortably within one week, having no further severe
dyspnea/air hunger issues.
Case 3: Neuropathic pain
A 59 y.o. man with ALS who suffers extreme neuropathic pain with any contact to his skin.
Is already on high doses of opiates to point of sedation and inability to interact with family
Family cannot touch him due to exacerbation of his pain Solution: You administer 50 mg of intranasal ketamine – (100
mg/ml – 0.5 ml total). In 10 minutes he can be touched He is able to back off the opiates and be somewhat more alert
so he can interact more and touch his loved ones for the last weeks of his life
Case 4: Dementia with spells of severe agitation
An 86-year old man with dementia, end stage cardiovascular disease suffers intermittent spells of agitation and violent behavior not amendable to pain medication. He is agitated, powerful and dangerous to home
assistants and to himself. Solution: You administer 5-10 mg of IN
midazolam (titrate) and 10 minutes later he is calm.
Last case: Seizing patient
55 y.o. with metastatic melanoma – has brain metastasis and seizures.
Suffers from recurrent seizures that often progress to status epilepticus.
Has been transported to ER multiple times simply to control seizures
Rectal diazepam is unsuccessful at controlling the seizure. Solution: Intranasal midazolam is given and within 3
minutes of drug delivery he stops seizing. This is implemented as home therapy and his EMS/ER trips drop off 80%.
Advantages of IN medications in Hospice
Ease of use and convenience Rapidly effective - onset within 3-10 minutes Short acting – no long side effects from drug No special training is required to deliver the medication No shots are needed – Totally Painless No needle stick risk, no infection risk Patients (and family) really like this approach Works even if patient cannot swallow or has N/V Socially acceptable (no rectal drugs) Better than sublingual (faster onset, higher drug levels) Titratable to effect – can re-dose every 5-15 minutes Inexpensive –use generic or compounded drug
Understanding IN delivery: Key concepts
First pass metabolism
Nose brain pathway
Bioavailability
First pass metabolism
Nasal Mucosa: No first pass metabolism
Gut mucosa: Subject to first pass metabolism
Nose brain pathway
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.
Olfactory mucosa, nerve
BrainCSF
Highly vascular nasal mucosa
Bioavailability
How much of the administered medication actually ends up in the blood stream. Examples:
IV medications are 100% bioavailable. Most oral medications are about 5%-10% bioavailable due to
destruction in the gut and liver. Nasal medications vary:
Midazolam 75+% Fentanyl and Sufentanil 80+% Naloxone 90+% Lorazepam, ketamine, Romazicon, etc, etc
Optimizing Bioavailability of IN drugs
Minimize volume - Maximize concentration 0.2 to 0.4 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
Beware of abnormal nasal mucosal characteristics Mucous, blood and vasoconstrictors reduce absorption Suction nose or consider alternate delivery route if present
Critical Concept
Potential indications for intranasal medications in Hospice:
Breakthrough pain control – Opiates, ketamineThis will be the main focus
Episodic breathlessness – OpiatesMinor comments
Sedation- Benzodiazepines, ketamine, dexmedetomidineMinor comments
Seizure Therapy – BenzodiazepinesMinor comments
Intranasal Opiates for pain: Literature support
Mercadante, Current Med Res Opinion 2009 Compared IN Fentanyl (compounded) to OTFC
(Actiq) for cancer breakthrough pain Prospective, Randomized, crossover trial Results: (see next slide)
IN fentanyl worked faster More patients achieved meaningful pain control 77% preferred nasal to Actiq lollipops
Mercadante 2009
Intranasal vs buccal: Meaningful pain
reduction 11 minutes vs 16 minutes
Preferred by 77% Much faster onset of
pain control on VAS for 33% and 50% drop in pain scores
33% pain reduction
50% pain reduction
Intranasal Opiates for pain : Literature support
Kress, Clinical Therapeutics 2009 Compared IN Fentanyl (compounded) to placebo
plus standard therapy for cancer breakthrough pain Prospective, Blinded, Randomized, crossover trial Results: (see next slide)
IN fentanyl showed significant pain reduction by 5 minutes
More INF patients achieved meaningful pain control Only 14% of INF used rescue drug, while 45% of control
group used rescue drug
Kress, 2009
Intranasal Fentanyl vs standard therapy: Much faster onset of pain control on VAS
Well tolerated
Impression of pain control “good to very good” in 75% vs 31%
Intranasal Opiates for pain : Literature support
Good, Palliative Med 2009 Investigated efficacy of generic IN sufentanil
for cancer breakthrough pain(Sufentanil is 10 times as potent as fentanyl)
Prospective trial Results: (see next slide)
IN sufentanil worked fast and was safe at home 94% preferred IN sufentanil to prior methods
Good 2009
Dose Titration of opiates
Intranasal Opiates for dyspnea: Literature support
Sitte, Intranasal fentanyl for episodic breathlessness, J Pain & Symptom Management 2008
Case series describing their experience with IN fentanyl for breathlessness
Their pharmacy compounds the drug for them Have used in over 200 patients successfully Have not seen patients overuse or significant side
effects
Intranasal Ketamine for pain:
Why ketamine? NMDA receptor blocker – different site than
opiates Doses 10-15 times less than anesthetic dose are all
that is needed for pain control (analgesia) Side effects are dose dependent – so rare side
effects Alternative option to opiates, ideal for neuropathic
pain (common in cancer, radiation injury to nerves, MS, ALS, etc)
Intranasal Ketamine for pain: Literature support
Carr, Pain 2004 Compared IN Ketamine (generic 100 mg/ml) to
placebo for breakthrough pain Prospective, Randomized, crossover trial 1 atomized spray (10 mg) q 90 sec to 5 doses max Results: (see next slide)
VAS drop in pain 26.5 mm vs 8 mm Onset of pain relief 10 minutes No side effects at this dose
Intranasal Ketamine:
Meaningful pain reduction in 10 minutes
Low dose No side effects Alternative
therapy when opiate failing
Carr 2004
Intranasal Ketamine for pain: Literature support
US Army IN ketamine data
Compared IN ketamine to IV morphine for severe pain
IN ketamine (50 mg) as fast and as good as IV morphine (7.5 mg) w/o side effects.
IN Midazolam for adult sedation
Hundreds of articles showing efficacy in sedation in children and in some adult studies outside the hospice setting.
No actual published literature in hospice Many discussions demonstrating sublingual
benzodiazepines work – so nasal should work as well or better (see www.palliativedrugs.com)
IN Midazolam for adult sedation
Hollenhorst, AJR 2001: IN midazolam for MR imaging in adults Resulted in “sizable reduction in MR imaging related
anxiety and improved MR image quality”
Tschirch,Eur Radiology 2007: IN midazolam prior to MRI in adults 97% success rate in anxiolysis
Manley, Brit Dental 2008: IN midazolam prior to dental therapy in agitated, mentally disabled adults 93% success rate in sedation prior to oral procedures
IN Midazolam for adult seizures
Scheepers, Seizure 2000: Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy? 84 adult seizures treated, 79 successfully Much preferred to rectal and more effective
Other: Numerous studies demonstrate successful, safe home, EMS and ER therapy for seizures. This is now standard of care in Australia/NZ and becoming
very common in USA
Contact and Educational Information
Educational web site(s) with extensive literature on this topic:
www.intranasal.net http://palliative.info/IncidentPain.htm www.palliativedrugs.com