www.mcpcil.org.uk

A continuous subcutaneous infusion (CSCI) is considered fundamental for continued symptom management in palliative care1. The National Patient Safety Agency (NPSA) issued a patient safety alert in 2007 promoting the safer use of injectable medicines. In order to reduce risks, the NPSA produced guidance which included the recommendation that healthcare staff must have full technical information about the stability in solution and compatibility of commonly used drug combinations2.

Many combinations have been used successfully in clinical practice despite the paucity of supporting laboratory stability data3. Both visual compatibility and a clinical assessment have generally been used to determine whether or not a particular combination is suitable for administration by CSCI. An observable change on mixing of drugs is a simple way of identifying an incompatibility or instability4. Such problems can, however, occur without a visual change and these are of the greatest concern. It is possible that unidentified incompatibilities or instabilities could compromise symptom management in patients receiving treatment by a CSCI.

BACKGROUND

AIMS

REFERENCES

METHODS

Analysis of the Chemical Compatibility and Stability of Drug Combinations used in Continuous Subcutaneous Infusions.

Andrew Dickman1,2, Stephen Mason1, John Ellershaw1,3, Phil Weir4, Ellen Roberts4, Richard Jackson5, Matt Bickerstaff5, James Baker1,3

1. Marie Curie Palliative Care Institute, University of Liverpool, 2. Blackpool Teaching Hospitals NHS Foundation Trust, 3. Royal Liverpool and Broadgreen University Hospitals NHS Trust, 4. Quality Control North-West, Stockport NHS Foundation Trust, 5. Liverpool Clinical Trials Unit, University of Liverpool

1. National Patient Safety Agency. 2007. Promoting safer use of injectable medicines. Available from: http://www.nrls.npsa.nhs.uk/ resources/?entryid45=59812 (accessed 4th March 2016).

2. Graham F, Clark D. The syringe driver and the subcutaneous route in palliative care: the inventor, the history and the implications. J Pain Symptom Manage. 2005; 29(1):32-40.

3. Wilcock A, Jacob JK, Charlesworth S, Harris E et al. Drugs given by a syringe driver: a prospective multicentre survey of palliative care services in the UK. Palliat Med. 2006; 20(7):661-664.

4. Dickman A, Schneider J. Continuous Subcutaneous Infusions in Palliative Care 3rd Edition. Oxford University Press. 2011.

5. Dickman A. Continuous Subcutaneous Infusions – Analysis of National Practice. Poster presented at: 8th World Research Congress of the European Association for Palliative Care; 5-7 June 2014; Lleida.

RESULTS

To establish the compatibility and stability of drug combinations administered by CSCI, particularly those combinations most commonly prescribed.

Syringes of 30 Drug combinations identified from previous work5

(tables 1-4) were prepared as close to clinical practice as possible and underwent simulated infusion using a T34 syringe pump (CME Medical) and Saf-T-Intima administration set (BD). Samples taken from the administration line were tested for chemical compatibility and stability using pH, visual inspection and high performance liquid chromatography diode array detection (HPLC-DAD).

Table 4 – Combinations analysed comprising alfentanil hydrochloride

CONCLUSION

The combinations analysed in this study were shown to be chemically compatible and stable. Collectively, these findings form the basis of authoritative advice, as recommended by the NPSA and CHM. In UK clinical practice there are at least 3000 possible combinations leaving scope for further analysis of other commonly used combinations.

The results demonstrated that all thirty combinations tested are chemically compatible and stable over an infusion period of 24 hours. However, nine combinations containing midazolam and two combinations containing octreotide showed adsorption to a clinically insignificant extent (<10% of drug loss).

Figure 1 – CME Medical T34 Syringe Pump

Alfentanil & Cyclizine

Diamorphine, Haloperidol & Midazolam

Morphine & CyclizineMorphine & Haloperidol

Alfentanil & Haloperidol

Diamorphine, Levomepromazine & Midazolam

Morphine & Hyoscine butylbromide

Alfentanil & Metoclopramide

Morphine & Metoclopramide

Alfentanil & Midazolam

Morphine, Dexamethasone & Ranitidine

Alfentanil, Hyoscine butylbromide & Levomepromazine

Morphine, Glycopyrronium & Midazolam

Alfentanil, Hyoscine butylbromide & Octreotide

Morphine, Haliperidol & Hyoscine butylbromide

Alfentanil, Levomepromazine & & Midazolam

Morphine, Haliperidol & Midazolam

Alfentanil, Metoclopramide & & Midazolam

Morphine, Hyoscine butylbromide & Midazolam

Alfentanil, Hyoscine butylbromide, Levomepromazine & & Midazolam

Morphine, Levomepromazine & MidazolamMorphine, Metolclopramide & Midazolam

Table 1 – Combinations analysed comprising morphine sulphate

Table 3 – Combinations analysed comprising diamorphine hydrochloride

Oxycodone, Glycopyrronium & MidazolamOxycodone, Haloperidol & Hyoscine butylbromideOxycodone, Haloperidol & MidazolamOxycodone, Hyoscine butylbromide & MidazolamOxycodone, Hyoscine butylbromide & OctreotideOxycodone, Ketamine & LevomepromazineOxycodone, Levomepromazine & MidazolamOxycodone, Metolclopramide & Midazolam

Table 2 – Combinations analysed comprising oxycodone hydrochloride