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a cause of medication errors
Underdosage happens when patients do not receive the full dose of their prescribed drug. It is an often overlooked and underappreciated cause of medication errors. One cause of underdosage is the issue of the so-called dead volume. This describes a sometimes substantial amount of a prescribed intravenous drug remaining in the infusion set after the infusion, and thus never reaching the patient. Underdosage can lead to a decreased treatment response or treatment failure and may even contribute to the growing problem of resistances against antibiotic or anti-cancer treatment.
On average, a patient receives ten medications per day and will be subject to at least one medication error per day.1, 2 Studies investigating underdosing have shown even more worrying results:
Underdosing may arise due to errors in calculation or preparation of the drug.6 One often overlooked cause however is what literature refers to as either “dead volume” or “residual volume”. These terms actually mean the same thing, namely the (variable) volume of a prescribed drug that remains in the infusion system after the infusion has ended. Without taking measures to ensure that this volume is infused as well, the patients will not receive their full prescribed medication dose – with potentially adverse consequences such as inefficacy or resistance.7
Dead volume may vary greatly depending on the type of infusion system used, the length and diameters of the infusion tubing and the application of distributors (e.g. Y-connectors), which may also cause significant delays in drug administration, especially in small volumes and when using slow, concentrated infusions.8
Underdosing can result in therapy failure in general.7
Poor response to / failure of therapy: Calculations performed at Hull University showed that of an antibiotic regime prescribed for 12 weeks, an underdosage of 16ml per infusion set resulted in the equivalent of 12 missed doses, with “major concern of the impact this could potentially have on clinical outcomes, such as driving antibiotic resistance and undertreating infections”.12
And of course, underdosing is a Medication Error, and these are associated with life-threatening complications and death.16
It seems fair to assume that the health consequences mentioned will inevitably be associated with longer patient recovery, more drugs needed, a waste of staff time and a waste of money spent on non-effective equipment and drugs.4 Studies confirm this assumption: Researchers at Hull University Teaching Hospital (UK) estimated that the unintentional underdosing of intravenous antibiotics led to a waste of £ 9.09 per set (appr. 1,500 antibiotic doses per year), amounting to a drug wastage level calculated at close to £ 14,000 per year.12
Educate staff/raise awareness about the problem of underdosage: In one study, oncology was the only area where flushing was standard practice, in other areas it was optional.17
Use microbore administration sets to minimize dead volume.18
Flushing: Intravenous infusion sets should be routinely flushed with an adequate set to ensure the application of the full drug amount.19
- Caution: Volume used for flushing should be minimized in fluid-restricted patients.
- Caution: Flush with a compatible fluid (NIVAS Guidelines on in-line flushing).
Use sets whose inherent design ensures that the residual volume is reduced to an absolute minimum.
(last access June 2021)
 Toh MR et al, Prev Med Reports 2014;1:43-473. Plagge H et al, EJHPScience 2010;16:31-37
 Hughes RG et al, Evidence-based Handbook for Nurses 2008; US Dept of Health and Human Services
 Plagge H et al, EJHPSCience 2010;16:31-37
. Cousins D et al, Clinical Pharmacist 2018;10(12):356-357
 Patient Safety Observer, 2007
 Cooper DM et al, Bri J Nurs 2018;27:2-6
 Gregerson BG et al, Proc Bayl Univ Med Cent 2018;31(2):168-170
 Chan YK et al, CMBES Proc., vol 36, no1, May 2013
 Letter by Cousins D in the Clinical Pharmacist & Cooper et al
 MacLachlan L et al, Antimicrobial Stewardship – Ensuring full prescribed Dose Delivery of IV Antibiotics in OPAT, Hull University Teaching Hospitals, NHS Trust
 Fish and Ohlinger, 2006
 CDC 2015, https://www.cdc.gov/drugresistance/biggest-threats.html
 Gurney H et al, Bri J Cancer 2002;86:1297-1302
 Bowman S et al, Anaesthesia 2013;68:557-561
 Cooper DM et al, BJON 2018;27:14(suppl_000
 Peyko, V., An unrecognized Problem in Optimizing Antimicrobial Therapy: Significant Residual Volume Remaining in Intravenous Tubing With Extended-Infusion Piperacillin-Tazobactam, 2021 Journal of Pharmacy Practice Vol. 0.0 1-4