Intravenous (IV) fluids are given to replenish substantial deficits or continuing losses from the body, or to maintain normal fluid and electrolyte requirements. The fluids used in clinical practice can be classified into colloids, crystalloids and blood products.
Colloids, such as albumin, gelatin and starch remain in the intravascular compartment and expand the intravascular volume by drawing fluid from extravascular spaces due to their higher oncotic pressure1. On the other hand, crystalloids contain small molecules that can flow across cell membranes, which allows for transfer from bloodstream into the cells and body tissues1. Crystalloids can be subdivided into isotonic, hypotonic and hypertonic fluid1. The tonicity of fluid is influenced by solutes that cannot cross a semipermeable membrane.
Background of Safety Issue
The NPRA received an update from the European Medicines Agency (EMA) on the risk of hyponatraemia with the administration of IV fluids containing electrolytes and/or carbohydrates, particularly physiologically hypotonic fluids2.
Six (6) cases of hyponatraemia due to IV fluids containing electrolytes and/or carbohydrates had been detected as a signal based on the Danish Medicines Agency (DKMA) database3. In addition to that, a review by the UK Medicines and Healthcare products Regulatory Agency (MHRA) revealed more than 50 reported cases worldwide of permanent neurological injuries or deaths in children due to iatrogenic hyponatraemia, associated with the use of hypotonic intravenous fluids4.
The risk of hyponatraemia is prominent especially in patients with increased non-osmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients co-medicated with vasopressin agonists2. Hence, fluid balance, serum glucose, serum sodium and other electrolytes need to be monitored before and during administration, especially for physiologically hypotonic fluids2.
Acute hyponatraemia can lead to acute hyponatraemic encephalopathy. Patients with cerebral oedema are at risk of severe, irreversible and life-threatening brain injury2. Children, women of child-bearing age and patients with cerebral problems are at higher risk of severe and life-threatening brain swelling caused by acute hyponatraemia2.
Adverse Drug Reaction Reports
The NPRA has received a total of 363 reports of hyponatraemia related to various products. However, none of the reports related to IV fluids containing electrolytes and/or carbohydrates. To date, no report has been received on hyponatraemia syndrome nor hyponatraemia encephalopathy.
Advice for Healthcare Professionals
- Monitor patient’s fluid balance, serum glucose/sodium and other electrolytes when IV fluids containing electrolytes and/or carbohydrates are used, particularly physiologically hypotonic fluids.
- Beware that children, women of child-bearing age and patients with cerebral problems are at particular risk of the severe and life-threatening hyponatraemic encephalopathy.
- Please report all adverse events suspected to be related to the use of IV fluids to the NPRA.
- Dr. Ahmed Kholeif. Intravenous Fluid Therapy (Jan 2013).
- EMA (2017). PRAC Recommendations on Signals. EMA/PRAC/406987/2017.
- EMA (2017). Minutes of the PRAC Meeting on 14-17 March 2016. EMA/PRAC/259752/2016.
- MHRA (2012). Drug Safety Update: Intravenous 0.18% Saline/ 4% Glucose Solution (Hypotonic Saline) in Children: Reports of Fatal Hyponatraemia.
This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.