Mixing critical care injectable medicines together in a syringe during COVID-19

John Minshull, Deputy Director, London Medicines Information Service, Specialist Pharmacy ServicePublished

Critical care patients will be receiving numerous injectable medicines during the pandemic, and mixing injectable medicines together in a syringe is likely to be more necessary than normal.

Our pages give direct advice on specific compatibility for medicines likely to be used together during the pandemic.  We also guide on what to do where combinations are suggested or required in practice that we don’t cover specifically.

Our advice is constantly reviewed as the pandemic situation evolves; if you spot anything that’s wrong report a concern to us.

Advice on individual medicines

Our individual medicines advice is available at the links below.  In addition, a compatibility summary table is attached to this page to adapt, print, laminate, and use in clinical areas.

Alfentanil hydrochloride
Fentanyl citrate
Midazolam hydrochloride
Morphine sulfate

Other medicines and combinations

Our advice on individual medicines should cover a number of combinations likely to be used.  However, other combinations or other medicines may also be necessary and syringe compatibility may need to be considered for these.

Combining medicines in a syringe creates an unlicensed product, and pharmacists and other healthcare professionals should consider compatibility as follows:

  • Consult specialist resources on compatibility

These should include:

Medicines Information departments can provide access to these resources where necessary.

  • Where compatibility information is absent, consider whether the medicines could be given differently  

Ask the following:

      • Are all the medicines essential? Could any be stopped?
      • Could some be administered as a bolus or via gravity? Refer to our summary
      • Could the time of administration for any of the medicines be changed to avoid the need for concurrent administration?
      • Is it possible to use an alternative product or method of administration (e.g. subcutaneous, rectal or sublingual)?
  • Where mixing medicines in a syringe is unavoidable, consider practice points and principles below 
      • Only mix injectable medicines which have a similar rate of administration
      • Minimise the number of medicines in one syringe; incompatibility risk increases with more medicines
      • Use a common diluent for each medicine where possible. Check national injectable medicines guide
      • If you have to mix a powder or emulsion with any other medicine, always check specialist advice since such products are inherently less stable
      • Injectable medicines prepared in a clinical area should:
        • normally be administered immediately
        • finish within 24 hours of preparation or within 12 hours for propofol
        • finish within the in-use stability time for a combination where shorter than 12 or 24 hours
      • Look for signs of physical incompatibility before administration (precipitate formation, haziness, or crystallisation), but note that physical incompatibility with propofol would not be visible since it is an emulsion
      • Never mix acids with bases; acid and base characteristics for a range of commonly used ITU medicines are presented in the table at the bottom of the page
  • If incompatibility occurs, act quickly and decisively 
      • Stop the infusion
      • Either switch drugs or split the combination into separate pumps
      • Report via usual incident reporting mechanism (e.g. Datix)

Table: Common ITU Medicines – pH and presentation

Medicine pH Presentation
Adrenaline hydrochloride Acid Solution for injection
Alfentanil hydrochloride Acid Solution for injection
Atracurium besilate Acid Solution for injection
Cisatracurium besilate Acid Solution for injection
Fentanyl citrate Varies from acid to base by product Solution for injection
Metaraminol tartrate Acid Solution for injection or infusion
Midazolam hydrochloride Acid Solution for injection or infusion
Morphine sulphate Acid Solution for injection
Noradrenaline tartrate Acid Concentrate for solution for infusion
Pancuronium bromide Acid Solution for injection
Propofol Varies from acid to base by product Aqueous isotonic oil-in-water emulsion
Rocuronium bromide Acid Solution for injection / infusion
Suxamethonium chloride Acid Solution for injection
Vasopressin Acid Solution for injection (Argipressin)