First Evaluation of Morphine Hydrochloride by Nebulisation in Healthy Volunteers
Status:
Completed
Trial end date:
2018-05-02
Target enrollment:
Participant gender:
Summary
Acute pain relief in emergency setting is still a public health priority. Pain is the primary
reason for emergency room use, but the situation of "oligo-analgesia" persists in all
countries. Intravenous morphine titration has become the standard method for severe acute
pain management in the emergency department, but it is still insufficiently implemented.
Deviations from the recommended protocol are common: initial additional loading doses,
unusually extended intervals between bolus, premature discontinuation. Several factors
contribute to these difficulties: heaviness of its setting up, especially in overcrowding
case, procedure rigidity, high consumption of nursing time. This method requires a systematic
intravenously route, which has several inconvenients: algogenic procedures, coupled initial
diagnostic venous sampling (delay for analgesia), excessive "medicalization" of ambulatory
patients (risk of infection and less mobility in the emergency department). An alternative to
reduce the analgesic latency in emergency department, without losing the benefits of
tolerance and safety should be welcome. The inhaled route looks promising, but has yet not
been enough evaluated in adults, and even less in the emergency room. Aerosol techniques
change from one study to another (molecules, materials, doses, painful intensities included,
judgment criteria and assessment times). A morphine titration by aerosol therapy could be an
interesting alternative to the standard method disadvantages, using faster, painless and
easier procedures, leading to "demedicalization".
To the need for stronger fundamentals, an additional study was designed in healthy
volunteers. The objective is to compare the titration of intravenous morphine titration
aerosol in moderate acute pain caused by electrostimulation.
To purchase this aim, we first need to determine accurately the smallest dose of effective
and well tolerated inhaled morphine, to provide the "bolus" dose we have to repeat by
titration, which is still currently unknown. This dose is called ED50, it's the effective
dose for at least 50% of healthy volunteers relieved. ED50 for intravenous morphine is also
needed to be established, unknown in this indication. The determination of these two parallel
ED50 would allow a reliable conversion factor between the two routes of administration for
morphine "bolus", which can then be tested in comparative titrations. To validate our induced
pain model in healthy volunteers, we also have chosen to fix in these conditions the ED50 of
fentanyl that the effective dose by nebulization is better known. This study would also
describe the pharmacokinetics of inhaled morphine and its derivatives after a single spray.