This website is intended for healthcare professionals only.

Hospital Pharmacy Europe     Newsletter          

Crystalloids: an overview

Education of the entire multi-disciplinary team regarding the appropriate use of crystalloids within a balanced fluid regimen is essential to ensure that practice is consistent and informed by consensus guidelines

Crystalloids are solutions made from low molecular weight salts or sugars that can pass between the intravascular and interstitial compartments. They are the most widely utilised intravenous solutions in hospitals, with the majority of surgical in-patients and many medical patients receiving at least one intravenous crystalloid infusion during their hospital admission. They were first used, in the form of intravenous salt solutions, in the early 19th century for the treatment of dehydration due to cholera, and were then first administered to surgical patients in the late 19th century.1 They are utilised for both fluid and electrolyte maintenance and replacement. Crystalloids are often perceived to be innocuous, low-risk intravenous solutions, with junior doctors often being responsible for their prescribing, despite them acknowledging a lack of expertise in fluid management.2 This lack of knowledge and training in fluid and electrolyte management was highlighted in the 1999 National Confidential Enquiry into Perioperative Deaths in the UK as contributing to perioperative morbidity and mortality.3 This led to the development of national consensus guidelines to facilitate a consistent, evidence-based approach to crystalloid prescribing as a component of effective fluid management.4

There is an ongoing debate regarding the comparative effectiveness and adverse effects of crystalloids versus colloids for specific clinical indications. This article will not examine these issues in great detail but instead aims to provide a brief overview of the main pros and cons of crystalloid solutions.



Crystalloid solutions have lower acquisition costs compared with colloids.5 In addition, a cost-effectiveness analysis performed in 1991 regarding the use of colloids and crystalloids in fluid resuscitation also illustrated that the cost of each life saved using crystalloids was $45.13 compared to $1493.60 with colloids.6

Easy to store and long shelf life

Crystalloid solutions are stable at room temperature, and so can easily be stored in a range of clinical settings, both in the hospital and in more challenging environments, such as field hospitals in combat settings, emergency ambulances or remote medical outposts. A long shelf life facilitates responsive stock management.

Readily available

Crystalloid solutions are readily obtained within clinical settings, with the majority of clinical areas within an acute care environment maintaining stock of a range of appropriate crystalloids.

Low incidence of adverse events

There is a low incidence of adverse reactions associated with crystalloid solutions. The main problems associated with the use of crystalloids are not immunologically-mediated reactions but are due to the prolonged administration of supraphysiological amounts of sodium and chloride, which can result in hyperchloraemic acidosis and a reduced glomerular filtration rate.7 Utilising a more physiologically balanced intravenous fluid regimen appropriate to the individual’s biochemistry and fluid balance can reduce the sodium and chloride load. A meta-analysis demonstrated that, compared with hydroxyethyl starches, patients who received crystalloids or albumin were less likely to require renal replacement therapies and transfusion with red blood cells and experienced fewer overall adverse events.8

Range of formulations and volumes

A range of different crystalloid solutions are available, mainly containing sodium chloride and/or dextrose in a range of different concentrations, the most commonly used solutions being detailed in Table 1.

Hartmann’s and Ringer’s lactate solutions are also available, both of which contain lactate as a bicarbonate precursor. These were developed to be more similar to plasma in their composition. Some solutions are also available with additional potassium, so that maintenance or replacement of potassium can also be achieved via the one infusion. Most solutions are also available in a range of different volumes, according to individual patient fluid requirements.

Wide compatibility

Most crystalloid solutions are compatible with a range of intravenous drugs and sodium chloride 0.9% and dextrose 5% are often used as diluents and carrier solutions for their administration. Individual compatibility details should always be confirmed before administration. However, it is not recommended to administer blood products via the same intravenous line as Hartmann’s or dextrose 5% due to concerns over clotting and haemolysis.9

No religious/moral objections to use

As crystalloids are not derived from either human or animal sources, there are no religious or moral objections associated with their use.

Can be used as replacement or maintenance fluids

Crystalloids can be used as both replacement and maintenance fluids. Meta-analyses and systematic reviews have shown that crystalloids are effective in fluid resuscitation in septic and critically ill patients.5,6,8 If used appropriately according to individual maintenance fluid requirements, crystalloid solutions can effectively maintain fluid and electrolyte balance.4
However, it should be noted that crystalloids are not indicated for volume replacement in all clinical settings. According to recommendations of the Surviving Sepsis Campaign Guidelines and the European Society of Intensive Care Medicine, the use of albumin is advocated for fluid resuscitation in patients with severe sepsis, particularly if they require large amounts of fluid.10,11

Similarly, crystalloids might not always be the best choice for volume resuscitation in cases of cardiac surgery due to the potential for fluid overload.


The comparative ‘cons’ of crystalloids are due to their inherent pharmacological properties. As long as crystalloids are used in a considered manner, alongside colloids (if appropriate), then these pharmacological properties can be exploited for their clinical utility.

Potential for fluid and electrolyte overload

Crystalloids pass rapidly and freely across capillary membranes and equilibrate within the entire extracellular fluid space. Therefore, retention of a crystalloid within the intravascular space is poor. To replace a given volume of blood loss requires at least three times more crystalloid volume. As 75–80% of the infused crystalloid volume will remain in the extravascular space,12 fluid replacement with crystalloids is associated with an increased level of tissue hydration and risk of oedema: specifically, increased extravascular lung water and peripheral tissue oedema. Peripheral tissue oedema can affect wound healing and is uncomfortable for the patient, potentially making mobilisation more difficult. Oedema adversely affects the transport of oxygen and nutrients to tissue cells, potentially impairing organ function. Fluid overload with crystalloids can result in an increase in the fluid content of vital organs, including a delay in the return of normal gastrointestinal motility. In elderly patients with reduced functional respiratory and cardiovascular function, this can also result in significant morbidity and mortality.3 In such situations, fluids with a high volume effect, such as albumin, should be considered instead for volume resuscitation.13

If large volumes of crystalloids with high chloride content, particularly sodium chloride 0.9%, are given in an attempt to restore the circulating volume, there is a risk of hypochloraemic acidosis. This, then, causes renal vasoconstriction and reduced glomerular filtration rate. In catabolic surgical patients, this is further compounded by increased urea production and the inflammatory response to surgery, resulting in a large proportion of sodium, chloride and water being retained within the interstitial space. Hence, there is a need for a balanced fluid replacement regimen, ensuring that an excessive quantity of neither fluid nor electrolytes are administered. Crystalloids are adequate for fluid resuscitation but lack additional beneficial properties provided by fluids such as albumin.

Potential for adverse respiratory effects

If an excessive amount of dextrose is administered, particularly in critically ill, ventilator-dependent patients, an enhanced production of carbon dioxide and lactate may result. In addition, dextrose should not be used in isolation to treat hypovolaemia, as it only provides free water and does not replace electrolytes.

Lack of additional biochemical properties

Crystalloids do not have any additional biochemical properties, with their action being only to provide fluid and, depending on the solution administered, electrolytes.


Crystalloids are inexpensive, readily available intravenous solutions for the replacement and maintenance of fluid requirements. However, they should be prescribed in a considered approach tailored to individual patients’ fluid requirements and clinical condition to avoid excessive fluid and electrolyte administration and subsequent effects on morbidity and mortality. A balanced fluid regimen should be administered incorporating a combination of different crystalloids and colloids, if indicated. Individual solution choices should reflect the current evidence-base. Education of the entire multi-disciplinary team regarding the appropriate use of crystalloids within a balanced fluid regimen is essential to ensure that practice is consistent and informed by consensus guidelines.


  1. Awad S, Allison SP, Lobo DN. The history of 0.9% saline. Clin Nutr 2008;27:179–88.
  2. Lobo DN et al. Problems with solutions: drowning in the brine of an inadequate knowledge base. Clin Nutr 2001;20:125–30.
  3. Callum KG et al. Extremes of Age: The 1999 Report of the National Confidential Enquiry into Perioperative Deaths: London: NCEPOD, 1999.
  4. Powell-Tuck J et al. British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients (GIFTASUP). BAPEN Medical, 2011. (accessed June 2019).
  5. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2013;2:CD000567. doi: 10.1002/14651858.CD000567.pub6.
  6. Bisonni RS et al. Colloids versus crystalloids in fluid resuscitation: an analysis of randomized controlled trials. J Fam Pract 1991;32:387–90.
  7. Skellett S et al. Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline. Arch Dis Child 2000;83:514–6.
  8. Haase N et al. Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 2013;346:f839
  9. McClelland DBM (ed). Handbook for Transfusion Medicine (4th edition). UK Blood Services, TSO Norwich, 2007.
  10. Rhodes A et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med 2017;43:304–77.
  11. Reinhart K et al. Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients. Intens Care Med 2012;38:368–83.
  12. Halijame H. Use of fluids in trauma. Int J Intens Care 1999;6:20.
  13. Jacob M et al. The intravascular effect of Ringer’s lactate is below 20%: a prospective study in humans. Crit Care 2012;16:R86.