Nasal De-Convulsant Relief: Intranasal Midazolam for Pediatric ...

CFD EMS OVERVIEW

CFD EMS OVERVIEW• All ALS EMS System• Two EMT-Ps on each Medic Vehicle (32)• At least one EMT-P on each engine (34)• Engine/medic stations• Seven EMS Officers

Do you know Columbus???§ What was the name of the vehicle thatColumbus Fire Department deployed in1969 to take care of cardiac patients?

IN Midazolam(Midazolam)for seizurecontrol§ There are an estimated 150,000 cases of statusepilepticus every year in the US.§ Morbidity and mortality are at least partiallydependent on the duration of seizure activity soseizures should be stopped as soon aspossible.§ IN delivery of benzodiazepines (midazolam orlorazepam) provides a very effective, safe andinexpensive means to rapidly achieve seizurecontrol.

Why Intranasal?

Which would YOU prefer?

Why Intranasal?The nose is a preferred access point formedication administration because:• Training is minimal• No shots are needed• It is virtually painless• It eliminates any risk of a needle stick

Nasal Mucosa§ The rich vascular plexus of the nasalcavity provides a direct route into theblood stream for medications that easilycross mucous membranes.

Nasal Mucosa§ The total surface area available in the nasal mucosa isestimated to be about 180 cm2 or (28 square inches)§ 10 cm2 is olfactory mucosa§ 170 cm2 is the richly vascularized respiratory mucosa.

Why Intranasal?§For many IN medications the rates of absorption and plasmaconcentrations are comparable to IV administration, and are typicallybetter than subcutaneous or intramuscular routes.

Nose brain pathway§ The olfactory mucosa is in direct contact withthe brain and CSF.§ Medications absorbed across the olfactorymucosa directly enter the brain.§ This area is termed the nose brain pathway andoffers a rapid, direct route for drug delivery tothe brain.

Tips on IN Administration§Always use amethod thatallows thedelivery of ameasured dose

Tips on IN Administration§ Use a method that fragments the medicationinto fine particles so the maximal nasalmucosal surface is covered and minimalvolume runs out the nose or into the throat

Tips on IN Administration§ Utilize both nostrils to double thesurface area for absorption and halvethe volume delivered per nostril

Tips on IN Administration§ Be knowledgeable of the “dead space”within the delivery device and accountfor this dead space when calculatingthe volume you will deliver to thepatient

KEY CONCEPTSMinimize volume, maximize concentration• 1/3 mL per nostril is ideal, 1 mL is maximum• Use the appropriately concentrated drug

KEY CONCEPTSBeware of abnormal mucosal characteristics• Mucous, blood and vasoconstrictors reduce absorption• Suction nostrils or consider alternate drug delivery method inthese situations

Mucosal Atomization Device(Nasal Device)§ Device designed to allowemergency personnel todelivery nasal medicationsas an atomized spray.§ Broad 30-micron sprayensure excellent mucosalcoverage.§ Cost: $3.32 apiece

DevicePediatric Nasal

Nasal Drug Delivery inEMS: What Medications?§ Drugs of interest to EMS systems:§ Intranasal naloxone (Naloxone)§ Intranasal midazolam (Midazolam)§ Intranasal Fentanyl§ Intranasal Glucagon§ Intranasal Ketamine§ Intranasal Epinephrine§ Others

How To Use the Nasal Device

Intranasal Midazolameffects in the field§ Why intranasal Midazolam for seizuresin 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.

But does intranasalMidazolam work inPediatric seizures?

§ Seizures.Intranasal MidazolamResearch Studies§ Lahat et al, BMJ, 2000.§ Prospective study: IN midazolam versus IV diazepamfor prolonged seizures (>10 minutes) in children.§ Similar efficacy in stopping seizures (app. 90%).§ Time to seizure cessation:§ IV Diazepam: 8.0 minutes.§ IN Midazolam: 6.1 minutes.

Intranasal MidazolamResearch Studies§ Seizures.§ Lahat et al, BMJ, 2000.§ Conclusions:§ IV diazepam and IN midazolam have similar efficacy atcontrolling prolonged seizures in children.§ IN midazolam controls seizures more rapidly becausethere is no delay in establishing an IV.

Pediatric NeurologyVolume 34, Issue 5 , Pages 355-359, May 2006

Intranasal MidazolamResearch Studies• Rectal diazepam fails to abort about 40 percent ofseizures in randomized controlled trials. • (Lancet 1999;353:623; J Pediatr 1999;135:398; J Child Neurol2002;17:123.) • Several randomized trials now demonstrate thattransmucosal intranasal midazolam is as effective asintravenous diazepam and more effective than rectaldiazepam in aborting prolonged seizures. • (J Child Neurol 2002;17:123; Brit Med J 2000;321:83; Epilepsy Behav2004;5:253.) • In addition, its preference over rectal diazepam bycaregivers and its safety as home therapy have beenestablished in multiple small studies. • (Arch Dis Child 2004;89:50; J Paediatr Child Health 2004;40:556; Eur J PaediatrNeurol 1999;3:73; Seizure 2000;9:417.)

BOTTOM LINE:IN Midazolam as good and probably betterthan PR Diazepam in pediatric seizures

CFD Intranasal Drugs Given800Intranasal Drugs Administered 700600Axis Title500400300NalozoneMidazolam20010002008 2009 2010

IN Midazolam Indications140120100806040200820092010200

Pediatric seizure patients given Intranasal MidazolamYearNumber treated2008 102009 212010 212011 252012 14 (as of 8/2012)

Conversion Rate of pediatric seizurepatients given Intranasal MidazolamYearConversion Rate2008 50%2009 80%2010 64%2011 75%2012 72%(as of 8/2012)

NO HEAD TO HEAD COMPARISONWITH INTRANASAL MIDAZOLAM

IN Midazolam for seizure control

CFD Implementation of IN Midazolam§ Analysis of product: Jan-May 2003§ Recommendations Nasal Device: June 2003§ Nasal Device arrives: September 2003§ Training/Protocol development: Oct 2003§ Training completed: December 2003§ Devices deployed: Feb 2004

CFD Protocol for IN Midazolam§ For treatment of persistent seizure activity§ Procedure:§ Assess ABC’s – Airway, Breathing, Circulation§ For pulseless patients, proceed to ACLSguidelines§ Apply 100% oxygen NRB mask to seizingpatient§ Use age based table to determine propervolume of Midazolam for atomization:

IN Midazolam Dosing Table

Take away lessons for nasal midazolam:§ Dose and volume: Higher concentration required - use 5mg/mlIV solution.§ Dosing calculations are difficult: Use a predefined age or weightbased table to determine dose.§ Deliver immediately on decision to treat: Atomize into nose withNasal Device, then begin standard care.§ Efficacy: No quite 100% effective so failures with nasal mayneed follow-up with IV therapy.

Survey on IN Midazolam use§ Distributed to all EMS personnel on medics§ 2 EMT-Ps/32 medics x 3 units = 192 total medicsreceived survey§ Two month response time given§ Oct-Dec 2007§ Responses returned to EMS education§ 149 responses back: 77% return rate

Conclusions from survey on INMidazolam§ IN Midazolam used most often for seizures (81%)§ IN Midazolam used 0 - 5 times per month (97%)§ 96% felt comfortable with education on CPAP§ 3% felt uncomfortable utilizing CPAP§ Patient remains unchanged or improves 99% of time§ 93% felt it somewhat or somewhat or greatly enhancedtheir practice

Naloxone

§ Questions??????????