Therapeutic
Intranasal Drug DeliveryFeatured new articles related to intranasal drug delivery
January-September 2016:
Smith, D., H. Cheek, et al. (2016). "Lidocaine Pretreatment Reduces the
Discomfort of Intranasal Midazolam Administration: A randomized,
double-blind, placebo-controlled trial." Acad Emerg Med.
Abstract:
OBJECTIVE: Intranasal (IN) midazolam is a commonly prescribed medication
for pediatric sedation and anxiolysis. One of its most
frequently-encountered adverse effects is discomfort with
administration. While it has been proposed that premedicating with
lidocaine reduces this undesirable consequence, this combination has not
been thoroughly researched. The objective of our study was to assess
whether topical lidocaine lessens the discomfort associated with IN
midazolam administration. METHODS: This was a double-blinded,
randomized, placebo-controlled trial performed in an urban, academic
pediatric emergency department. Children 6-12 years of age who were
receiving IN midazolam for procedural sedation received either 4%
lidocaine or 0.9% saline (placebo) via mucosal atomizer. Subjects were
subsequently given IN midazolam in a similar fashion, and then rated
their discomfort using the Wong-Baker FACES Pain Rating Scale (WBS). The
primary endpoint of WBS score was analyzed with a two-tailed
Mann-Whitney U test, with P < 0.05 considered statistically significant.
RESULTS: Seventy-seven patients were enrolled over a consecutive 8-month
period. One child was excluded from analysis due to a discrepancy in
recording the drug identification number. Study groups were similar in
regards to demographic information and indication for sedation. Subjects
who received IN lidocaine reported less discomfort with IN midazolam
administration (median WBS 3, interquartile range [IQR] 0-6) than those
who received placebo (median WBS 8, IQR 2-9) (P=0.006). CONCLUSIONS:
Premedication with topical lidocaine reduces the discomfort associated
with administration of IN midazolam. (ClinicalTrials. gov, NCT02396537).
This article is protected by copyright. All rights reserved.
Web site Editorial comments:
Several articles this year ( Smith, Peerbhay) have discussed
pretreatment with IN lidocaine prior to administration of IN midazolam.
This is by far the best designed of these recent trials – double blind,
RCT. The bottom line – pre-treatment with 4% lidocaine markedly reduces
discomfort (nasal burning) experienced by children who are treated with
nasal midazolam. If you have not done so already here is the definative
evidence suggesting this should be added to your protocol.
(Chiaretti showed this years ago, we have been doing
this for over a decade and suggested it here on this web site from the
outset).
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Crawford, D. (2016). "Implementation of Intranasal Midazolam for
Prolonged Seizures in a Child Neurology Practice." J Neurosci Nurs.
Abstract:
Currently, evidence supports the use of intranasal midazolam as an
effective, and in many cases, preferable treatment option for prolonged
seizures in children. Despite this knowledge, intranasal midazolam is
not routinely found as a standard of care. The goal of this project was
to implement the use of intranasal midazolam as a rescue medication for
prolonged seizures within a child neurology practice and, in doing so,
create a model for implementation that would be replicable for other
practice sites. This project focused on the development of a process to
make intranasal midazolam available as a treatment option and then the
creation of an educational intervention for providers within a child
neurology practice. Provider surveys analyzed provider attitudes toward
intranasal midazolam and its frequency of use. Because of this project,
a dramatic increase in the prescribing of intranasal midazolam was
observed within a child neurology practice.
Web site Editorial comments:
This article is packed full of data that essentially mirrors what is
stated in this web site: When comparing IN midazolam to rectal diazepam
for outpatient treatment of status epilepticus the IN route is more
effective, costs much less, results in better outcomes (shorter seizure
time, less admission to hospital), has less of a social stigma and is
markedly preferred by families of the epileptic patient. Based on this
information the authors attempted to change practice in their medical
community and transition their neurologic practice over to prescribing
IN midazolam as the preferred outpatient rescue medication and make it
avialable from local pharmacies. They note very rapid adoption in the
practice after presenting detailed information and setting up local
pharmacies with delivery devices and appropriate drugs. Further
challenges involved school nurse education when children showed up with
a new drug delivery system. This paper addresses this and many
challenges and should be read by any clinician who anticipates adopting
IN benzodiazepine use in their community.
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Cozzi, G., S. Lega, et al. (2016). "Intranasal Dexmedetomidine Sedation
as Adjuvant Therapy in Acute Asthma Exacerbation With Marked Anxiety and
Agitation." Ann Emerg Med.
Abstract:
We describe 2 patients with acute asthma exacerbation who were admitted to the emergency department (ED) with severe agitation and restlessness as a prominent finding, for which bedside asthma treatment sedation with intranasal dexmedetomidine was performed. In both cases, dexmedetomidine allowed the patients to rest and improved tolerance to treatment. Dexmedetomidine is a unique sedative with an excellent safety profile and minimal effect on respiratory function. These properties render it particularly promising for the management of severe agitation in children admitted to the ED with acute asthma exacerbation.
Web site Editorial comments:
Here is an ideal that deserves more research – sedation with IN
dexmedetomidine in pediatric respiratory crisis to relax the child
(without further exacerbating their problem by starting an IV). This is
only a case report but suggests potential for further investigation.
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Fenster, D. B., P. S. Dayan, et al. (2016). "Randomized Trial of
Intranasal Fentanyl Versus Intravenous Morphine for Abscess Incision and
Drainage." Pediatr Emerg Care.
Abstract:
OBJECTIVES: Abscess incision and drainage (I&D) are painful and distressing
procedures in children. Intranasal (IN) fentanyl is an effective
analgesic for reducing symptomatic pain associated with fractures and
burns but has not been studied for reducing procedural pain during
abscess I&D. Our objective was to compare the analgesic efficacy of IN
fentanyl with intravenous (IV) morphine for abscess I&D in children.
METHODS: We performed a randomized noninferiority trial in children aged
4 to 18 years undergoing abscess I&D in a pediatric emergency
department. Patients received IN fentanyl (2 mug/kg; maximum, 100 mug)
or IV morphine (0.1 mg/kg; maximum, 8 mg). The primary outcome,
determined independently by blinded assessors, was the Observational
Scale of Behavioral Distress-Revised (OSBD-R). The prestated margin of
noninferiority (Delta) was 1.80. Secondary outcomes included
self-reported pain, treatment failure, and patient and parental
satisfaction. RESULTS: We enrolled 20 children (median age, 15.4 years),
10 in each group. The difference between total OSBD-R scores was -13.45
(95% confidence interval, -24.24 to -2.67), favoring IN fentanyl. There
was less self-reported pain in patients who received IN fentanyl
immediately after the procedure. Four patients (40%) receiving IV
morphine had treatment failures and required moderate sedation or had
the procedure terminated. More patients who received IN fentanyl were
satisfied with the analgesic administered compared with those who
received IV morphine. CONCLUSIONS: In a small sample of children aged 4
to 18 years undergoing abscess I&D, IN fentanyl was noninferior, and
potentially superior, to IV morphine for reducing procedural pain and
distress.
Web site Editorial comments:
Here is an article once again showing IN fentanyl is as effective (in
this case more effective) than IV morphine for acute pain control. The
twist here is that it was used to control pain for a procedural
intervention – Abscess incision and drainage. I use IN fentanyl (kids)
and IN sufentanil (adults) often for non-invasive pain control prior to
abscess I&D as it is very effective, markedly reduces nursing time (no
IV needed) and allows me to rapidly and compassionately treat the
patient but also get them back to their lives and out of the busy
emergency department in a time efficient fashion.
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Kurien, T., K. R. Price,
et al. (2016). "Manipulation and reduction of paediatric fractures of
the distal radius and forearm using intranasal diamorphine and 50%
oxygen and nitrous oxide in the emergency department: a 2.5-year study."
Bone Joint J 98-B(1): 131-136.
Abstract:
A retrospective study was performed in 100 children aged between two and 16
years, with a dorsally angulated stable fracture of the distal radius or
forearm, who were treated with manipulation in the emergency department
(ED) using intranasal diamorphine and 50% oxygen and nitrous oxide. Pre-
and post-manipulation radiographs, the final radiographs and the
clinical notes were reviewed. A successful reduction was achieved in 90
fractures (90%) and only three children (3%) required remanipulation and
Kirschner wire fixation or internal fixation. The use of Entonox and
intranasal diamorphine is safe and effective for the closed reduction of
a stable paediatric fracture of the distal radius and forearm in the ED.
By facilitating discharge on the same day, there is a substantial cost
benefit to families and the NHS and we recommend this method. TAKE HOME
MESSAGE: Simple easily reducible fractures of the distal radius and
forearm in children can be successfully and safely treated in the ED
using this approach, thus avoiding theatre admission and costly hospital
stay.
Web site Editorial comments:
Yet another study to support IN opiates for painful procedures – this
time fracture reduction. Both this study and the other recently
presented study by Fenster (I&D abscesses- see above) note reduced
resource utilization during painful procedures using IN opiates.
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Murphy, A. P., M. Hughes, et al. (2016). "Intranasal fentanyl for the
prehospital management of acute pain in children." Eur J Emerg Med.
Abstract:
INTRODUCTION: Acute pain is the most common symptom in the
emergency setting and its optimal management continues to challenge
prehospital emergency care practitioners, particularly in the paediatric
population. Difficulty in establishing vascular access and fear of
opiate administration to small children are recognized reasons for
oligoanalgesia. Intranasal fentanyl (INF) has been shown to be as safe
and effective as intravenous morphine in the treatment of severe pain in
children in the Emergency Department setting. AIM: This study aimed to
describe the clinical efficacy and safety of INF when administered by
advanced paramedics in the prehospital treatment of acute severe pain in
children. METHODS: A 1-year prospective cross-sectional study was
carried out of children (>1 year, <16 years) who received INF as part of
the prehospital treatment of acute pain by the statutory national
emergency medical services in Ireland. RESULTS: Ninety-four children
were included in the final analysis [median age 11 years (interquartile
range 7-13)]; 53% were males and trauma was implicated in 86% of cases.
A clinically effective reduction in the pain score was found in 78
children [83% (95% confidence interval: 74-89%)]. The median initial
pain rating score was 10. Pain assessment at 10 min after INF
administration indicated a median pain rating of 5 (interquartile range
2-7). No patient developed an adverse event as a result of INF.
DISCUSSION: INF at a dose of 1.5 microg/kg appears to be a safe and
effective analgesic in the prehospital management of acute severe pain
in children and may be an attractive alternative to both oral and
intravenous opiates.
Web site Editorial comments:
Here is another EMS study noting IN fentanyl efficacy for pain control
in children suffering from severe pain. If you look at other EMS studies
you will discover that the majority of children in severe pain get NO
treatment what-so-ever in the EMS phase – for a variety of reasons but
the primary reason being the need to start and IV and the desire to
cause no further pain to an already suffering child. Here is the
solution – a huge reduction in median pain scores (dropped pain in half
from score of 10 to score of 5) within 10 minutes and no adverse events.
If you work with an EMS agency that has not introduced this intervention
for children it is time to revisit and reassess what you are doing and
why you have not adopted this concept.
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Fisher, R., D. O'Donnell,
et al. (2016). "Police Officers Can Safely and Effectively Administer
Intranasal Naloxone." Prehosp Emerg Care: 1-6.
Abstract:
INTRODUCTION: Opioid overdose rates continue to rise at an
alarming rate. One method used to combat this epidemic is the
administration of naloxone by law enforcement. Many cities have
implemented police naloxone administration programs, but there is a
minimal amount of research examining this policy. The following study
examines data over 18 months, after implementation of a police naloxone
program in an urban setting. We describe the most common indications and
outcomes of naloxone administration as well as examine the incidence of
arrest, immediate detention, or voluntary transport to the hospital. In
doing so, this study seeks to describe the clinical factors surrounding
police use of naloxone, and the effects of police administration.
METHODS: All police officer administrations were queried from April 2014
through September 2015 (n = 126). For each incident we collected the
indication, response, and disposition of the patient that was recorded
on a "sick-injured civilian" report that officers were required to
complete after administration of naloxone. All of the relevant
information was abstracted from this report into an electronic data
collection form that was then input into SPSS for analysis. RESULTS: The
most common indication for administration was unconscious/unresponsive
(n = 117; 92.9%) followed by slowed breathing (n = 72; 57.1%), appeared
blue (n = 63; 50.0%) and not breathing (n = 41; 32.5%). After
administration of naloxone the majority of patients regained
consciousness (n = 82; 65.1%) followed by began to breath (n = 71;
56.3%). However, in 17.5% (n = 22) of the cases "Nothing" happened when
naloxone was administered. The majority of patients were transported
voluntarily to the hospital (n = 122; 96.8%). Lastly, there was only one
report where the patient became combative. CONCLUSION: Our study shows
that police officers trained in naloxone administration can correctly
recognize symptoms of opioid overdose, and can appropriately administer
naloxone without significant adverse effects or outcomes. Furthermore,
the administration of police naloxone does not result in a significant
incidence of combativeness or need for scene escalations such as
immediate detention. Further research is needed to investigate the
impact of police naloxone; specifically, comparing outcomes of police
delivery to EMS alone, as well as the impact on rural opioid overdoses.
Web site Editorial comments:
This paper demonstrates that non-medical first responders (police) are
fully capable or delivering IN naloxone to appropriate candidates. The
data is essentially identical to EMS data
- noting over 80% effective response to the drug
(breathing). Only one case (out of 126 patients) led to combativeness –
also confirming the low incidence of agitation following IN naloxone
delivery.
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Baier, N. M., S. S.
Mendez, et al. (2016). "Intranasal dexmedetomidine: an effective
sedative agent for electroencephalogram and auditory brain response
testing." Paediatr Anaesth 26(3): 280-285.
Abstract:
OBJECTIVE: Dexmedetomidine is an alpha2 agonist with sedative,
anxiolytic, and analgesic properties. The intranasal (IN) route avoids
the pain of intravenous (i.v.) catheter placement but limited literature
exists on the use of IN dexmedetomidine. This study examines the
effectiveness and safety of IN dexmedetomidine for sedation of patients
undergoing electroencephalogram (EEG) and auditory brain response (ABR)
testing. STUDY DESIGN: This was a review of all outpatients sedated with
IN dexmedetomidine for EEG or ABR between October 1, 2012 and October 1,
2014. An initial dose of 2.5-3 mug . kg(-1) IN dexmedetomidine was given
with a repeat dose of 1-1.5 mug . kg(-1) IN if needed 30 min later.
Prospectively entered patient information was extracted from a quality
assurance database and additional information gathered via retrospective
chart review. RESULTS: Intranasal dexmedetomidine was used in 169
patients (EEG = 117, ABR = 52). First-dose success rates were 90.4% for
ABR and 87.2% for EEG. Total success rates (with one or two doses of IN
dexmedetomidine) were 100% for ABR and 99.1% for EEG. The median time to
onset of sleep was 25 min (IQR, 20-32 min). The median duration of
sedation was 107 min (IQR, 90-131 min). Adverse events included: 18
patients (10.7%) with hypotension which resolved without intervention,
six patients with oxygen desaturation <90%, two of whom received
supplemental oxygen, and one patient with an underlying upper airway
abnormality who was treated with continuous positive airway pressure.
CONCLUSIONS: IN dexmedetomidine is an effective and noninvasive method
of sedating children for EEG and ABR.
Web site Editorial comments:
This is an interesting sedation study because they used a high dose of
dexmedetomidine initially (2.5- 3mcg/kg) and allowed a second dose of 1
to 1.5 mcg/kg to be administered if adequate sedation was not achieved.
By allowing titration they achieved essentially 99.1% success at
sedation with minor side effects treatable with oxygen or minor airway
support. Sedation onset was 25 minutes and duration just under 2 hours
so this should not be used for any brief rapid sedation setting. Again,
in contrast to many IN sedation studies – if you use a proper dose and
you titrate, you can achieve non-invasive sedation effectively with a
very high degree of success. As with any sedation you need to be
cognizant of the airway and oxygenation.
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