Compatibility and stability of ketamine and dexamethasone in continuous subcutaneous infusions
Following discussions between palliative care pharmacists in Scotland and the Royal Pharmaceutical Society's fellow in pharmaceutics, Colin Cable, it became clear that compatibility and stability information to support the clinical use of injection admixtures containing ketamine and dexamethasone was lacking. Outlined below is the background
to the problem and a brief description of stability work that has
been carried out. Further information on this and other pharmaceutics
topics can be obtained from Dr Cable (tel 020 7572 2302;
e-mail colin.cable@rpsgb.org).
Ketamine hydrochloride has been available as an anaesthetic agent for
around 40 years. More recently, it has been used at subanaesthetic doses
as an adjuvant analgesic where it acts as a non-competitive N-methyl-D-aspartate
receptor antagonist in the dorsal horn.1 Following continuous subcutaneous
infusion, ketamine has been useful in treating patients with neuropathic
pain that is poorly responsive to opioids. However, when ketamine is
administered by this route, there is often erythema and pain at the injection
site. It has been shown that the addition of 1 mg of dexamethasone sodium
phosphate to injections in syringe drivers improves the longevity of
subcutaneous cannulation sites in patients receiving palliative care.2 When injection admixtures containing ketamine and dexamethasone were
first used in clinical practice, there were no published studies in which
the physical compatibility and chemical stability of the combined injection
had been examined.
In 2005, Watson et al3 investigated the stability of ketamine hydrochloride
injections (50mg and 600mg) and dexamethasone sodium phosphate (1mg)
injection when mixed with sodium chloride injection (to 14ml). The infusions
were stored in polypropylene syringes at 4C, 23C and 37C under normal
fluorescent light conditions. Samples were removed over 192 hours (eight
days) for high performance liquid chromatography analysis, pH measurement
and an examination of colour and visible particles. All samples retained
at least 98 per cent of the initial concentration of each drug and no
degradation products were detected. The solutions remained clear and
colourless and pH varied by only 0.05 units over the duration of the
study.
It was concluded that, at the concentrations studied, ketamine hydrochloride
and dexamethasone sodium phosphate in sodium chloride 0.9 per cent injection
were physically compatible and chemically stable for at least eight days
when stored in polypropylene syringes.
References
1. Meller ST. Ketamine: Relief from chronic pain through actions at
NMDA receptor. Pain 1996;68:435–6.
2. Reymond L, Charles MA, Bowman J, Treston P. The effect of dexamethasone
on the longevity of syringe driver subcutaneous sites in palliative care.
MJA 2003;178:486–9.
3. Watson DG, Lin M, Morton A, Cable CG, McArthur DA. Compatibility and
stability of dexamethasone sodium phosphate and ketamine hydrochloride
subcutaneous infusions in polypropylene syringes. Journal of Pain and
Symptom Management 2005:30:80–6. |
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Pharmaceutical Journal