opinion
Thinking the unthinkable
Poisoning with nerve agents and mustard gas are unthinkable horrors but particulate contamination of
intravenous fluids can also present insidious dangers, according to speakers at the 2018 GERPAC conference
Measures to treat the immediate
and long-term effects of
chemical warfare agents are still
important today, because chemical
attacks represent excellent value for
money for terrorist groups, according
to Colonel Dr Christophe Piérard,
a pharmacist who works in the French
military biomedical research institute.
Accidental exposure to sulphur
mustard (mustard gas) still occurs
occasionally due to release from gas
shells left over from the First World
War. It has also been used more
recently in conflicts in Iraq and Syria.
During the First World War casualties
were numerous and there was no
treatment other than supportive
measures, but now understanding has
advanced and new treatments are
emerging. Today, decontamination
using Fuller’s earth (or flour or talc)
and copious quantities of water
remains the most critical measure,
but it can be a slow process.
Sulphur mustard is odourless and
colourless and rapidly penetrates
the human body through skin and
mucous membranes causing blistering
and irritation. Its parent compound
forms highly reactive episulphonium
ions that alkylate nucleic acids and
proteins causing cell death. Although
the mortality is estimated to be about
2%, there is often long-term damage
to the eyes, skin and lungs and
psychological damage.
Neurotoxic organophosphorus
agents such as sarin, VX and Novichok
are irreversible cholinesterase
inhibitors. Exposure results in
widespread cholinergic effects
including miosis, rhinorrhoea, and
nausea and vomiting. Emergency
treatment for combatants involves
the use of an autoinjector to deliver
atropine and pralidoxime (to
reactivate cholinesterases). The needle
should be held in for ten seconds to
deliver effective doses but a common
reaction is to pull it out quickly
because of the pain of injection.
Furthermore, pralidoxime penetrates
the blood–brain barrier poorly and so
damage to the central nervous system
8 | Issue 90 | 2018 | hospitalpharmacyeurope.com
Christine Clark
PhD FRPharmS FCPP(Hon)
can be a serious complication.
Better cholinesterase reactivators
and bio-scavenger enzymes to
capture nerve agents are needed.
New approaches to sulphur mustard
poisoning include local cooling to
reduce the vesicant effects and give
time for repair enzymes to take effect.
Another approach is the use of anti-
connexin-43 because down-regulation
of connexin-43 favours wound healing.
The risk of military use of chemical
agents is moderate but the terrorist
threat is high, according to experts.
“Prepare for the unthinkable”, was
Dr Piérard’s message.
Particulate contamination
Particulate contamination of
injectable drugs is probably a more
common problem than many
people realise. Injected particles are
associated with clinical complications
that can include phlebitis, granuloma
formation, arterial embolism,
immune modulation, impaired
microcirculation, and even death.
Paediatric patients receiving multiple
intravenous doses are at particular risk
because of the small volumes in which
they have to be administered.
Commercially manufactured
injectable medicines have low particle
counts but the way that they are
handled can lead to considerable
contamination, explained Pascal Odou,
a pharmaceutical scientist at the
University of Lille, France.
Types of containers and devices,
speed of administration, chemical
incompatibilities and ambient
temperature can all contribute to
particle formation. For example, an
administration manifold with three–
four taps at 90 degrees to the direction
of flow results in considerable flow
disruption when doses are injected.
Furthermore, simply adding an
extension line to an intravenous
administration set greatly increases
the particle count.
Glass ampoules present the biggest
risk – producing particles of up to
400 micrometres, 83% of which can
be removed by using an in-line filter.
Syringes and administration tubing
can also be sources of particles.
There are numerous chemical
incompatibilities that can result in
precipitation of particles and although
filtration will remove many of them,
there can be appreciable particulate
contamination before it is visible
to the human eye. Multichannel
administration devices can reduce
particulate contamination. For
example, studies in children receiving
stem cell allografts showed a large
reduction in the number of particles
administered when a multichannel
device was used instead of the
traditional system. Such devices
should be positioned as near to
the patient as possible to minimise
the time available for potentially
incompatible drugs to mix before
entering the bloodstream.
Particulate contamination of
injectable drug solutions remains
a real problem in the care of seriously
ill patients. Measures to minimise
the number of particles in injected
fluids include the avoidance of known
incompatibilities and careful choice of
administration devices and protocols.
However, all of these require an
understanding of the problems in
the first place and for pharmacists,
this should go hand in hand with
knowledge of the pharmacology of
the drugs.