Pan European Networks - Horizon 2020 - page 192

O
pioid overdoses are a worldwide epidemic affecting
both users of illicit drugs and patients taking
prescribed opioid painkillers. An estimated 69,000
people die worldwide annually, among them about 250 untimely
deaths in Norway.
1
The Norwegian Government is currently
implementing a strategy for combatting this epidemic.
2
Among
the actions promoted in this strategy is the distribution of
naloxone for intranasal (IN) administration. This is currently being
implemented and tried out around the world, but very little has
been done to pharmacologically study this new route of
administration of this well-known drug, and only three open label
randomised controlled trials (RCT) have been conducted.
3-5
Off-label use
A recent guideline from the World Health Organization (WHO) on
community management of opioid overdoses reviews many of the
aspects we cover in our research regarding dosage, routes of
administration of naloxone, and care of these patients in the
prehospital setting.
6
The WHO also focuses on the problematic
current widespread off-label use of nasal naloxone and identifies
several research questions of critical importance and very low
evidence. Our research effort aims to answer several of these
questions, including the time to opioid reversal, and opioid
withdrawal reactions to naloxone. Our goal is that the IN
administration shall have similar regulatory and scientific support
as today’s intravenous (IV)/intramuscular (IM) treatment, in
contrast to the on-going administration of dilute formulations.
3,7-9
Safety for those that administer the drug by creating a needle-free
system will be an added spin-off.
Opioid overdose is suspected in a patient with reduced level of
consciousness, small pupils, and a respiratory rate below eight
breaths per minute or respiratory arrest. It must be emphasised
that the indication for administering naloxone by emergency
medical services (EMS) staff is respiratory depression or
respiratory arrest in an unconscious patient.Without airway
management, breathing support and naloxone, the patient will go
into cardiac arrest. Immediate treatment with a μ-opioid
antagonist such as naloxone is vital. Intravenous naloxone
reverses the respiratory depression rapidly with effect peak at five
to ten minutes,
10
a duration of action of approximately 90
minutes.
11
Elimination half-life is of about one hour (range 30-81
minutes).
12
Naloxone is usually administered IV and/or IM; the
former requires considerable skill, and the latter has a slower
onset of action.
Aims
The aim of naloxone administration in this setting is not to fully
antagonise and reverse the full opioid effect in the patient, but to
increase the level of consciousness enough for the patient to
maintain a free airway without assistance and increase rate of
respiration for adequate oxygenation. It would be unfavourable
and even dangerous for the patient to fully antagonise all the
opioids in his or her body, as this would precipitate a serious
withdrawal reaction.
Nasal naloxone has been suggested as an alternative for EMS
and possibly also for bystanders.
3,7,8
The justification for IN
administration is the elimination of the risk for needle stick
injuries and blood exposure from a population with high
prevalence of blood-borne viruses. Moreover, cannulation of the IV
drug users may be very challenging.
13
Finally, lay people with very
little training can perform nasal administration.
In Australia, the ambulance service in Victoria has conducted two
open label RCTs comparing IN and IM naloxone. Kelly, 2005,
compared 2mg naloxone (5ml 0.4mg/ml solution divided in both
nostrils) to 2mg naloxone IM.
4
Kerr, 2009, compared 2mg
naloxone in 1ml solution IN with 2mg naloxone IM.
3
A WHO meta-
analysis of these studies indicates no difference between the IN
and IM administrations.
6
Another study found that 0.4 mg
naloxone diluted to 2ml divided in both nostrils and 0.4mg
naloxone IV were equal.
5
Proper nasal naloxone may contribute to fewer deaths from opioid overdose
Reducing overdose fatalities?
192
I S S U E S I X
H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L
P R O F I L E
A D D I C T I O N
© Kaare Eidet; Oslo University Hospital
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