Summer is finally here! 24’C outside and the hospital radiators in my office are still on! I’m hot, thirsty and so are my patients on the ward. In the news, unbelievably there are still recurring headlines of patients dying from thirst in UK hospitals and care homes.1 Why is it so hard to ensure patients are getting enough to drink? Why is this still happening?
If a patient in hospital cannot drink for themselves or is too unwell, intravenous (IV) fluids are often needed… but which IV fluid?
The choice of IV fluid can influence EVERYTHING, with many patient outcomes being affected by prescribing choice and delivery – it’s not all about AKI! 2, 3 Fluid prescribers need to think outside the box! Too little fluid, for example, causes dehydration, confusion, increase in venous thromboembolism (VTE) events, poor wound healing, pressure sores, longer length of hospital stay, increased risk of death and…. AKI! Too much fluid is also harmful, with fluid overload increasing risk of cardiorespiratory compromise, increased risk of falls with leg oedema and again increased hospital stay and risk of death. Patients with AKI who are fluid overloaded, particularly in critical care, have much worse outcomes.4 Too much of high chloride containing fluids or ‘unbalanced’ solutions such as 0.9% saline, are associated with increased AKI development.
The right fluid, type, volume and rate must be just right for the patient and just right for the clinical situation at hand! This ‘goldilocks’ approach to fluid therapy makes sense with a similar strategy being recommended by NICE (see 5R’s of fluid therapy).2 Unfortunately, although fluid therapy sounds simple, it is much more difficult to get right in practice, particularly in complex medical patients. It is concerning, as I am sure many hospital fluid audits would show, that most IV fluid prescribed on the wards is by the most junior members of the medical team, who have often had little or no training throughout university on what best fluid for a given situation to prescribe. Even when in foundation or core training roles, fluid therapy doesn’t seem to get the same respect as drug prescribing and often lacks senior (registrar/consultant) oversight. Many junior prescribers do not know what is contained in one litre of plasmalyte or a litre of 0.9% saline, yet they collectively prescribe many thousands of litres every day! The potential for patient harm, too little or too much, with fluid prescription is immense.
Any type of IV fluid has the potential for harm, yet there is, unfortunately, no ‘universal’ fluid that is suited to every clinical situation and patient. At best, it is worth thinking about what clinical situation the patient is in e.g. resuscitation, routine maintenance, replacement and to tailor fluid therapy accordingly; taking into account patient needs and best practice.
Crystalloids are currently the first-line IV fluids of choice with colloid use falling significantly out of favour following large randomised controlled trials (RCTs) showing increased AKI rates, particularly in septic patients, with starch-based colloids (e.g. HES) and worse patient outcomes.4 Amongst crystalloids, the question of which type to give, has been debated extensively for many years with little consensus or evidence. Unbalanced solutions such as 0.9% saline contain a higher amount of sodium (Na+ 154mmol/l) and chloride (Cl- 154mmol/l) compared to balanced solutions such as plasmalyte-148 (Na+ 140mmol/L, Cl- 98mmol/L) or Hartmann’s (Na+131mmol/L, Cl-111mmol/L).5 The daily requirement of sodium and chloride is about 1-2mmol/kg/day (about 70-140mmol/day for average 70kg person) and water 30ml/kg/day (about 2.1 litres, 70kg patient).2 It is quite easy to see how over-use of fluids can occur and how 0.9% saline use, in particular, can result in exceeding routine sodium and chloride requirements. For example, if a 70kg patient were to receive 3 litres of 0.9% saline over a day for maintenance, they would receive about 462mmol of Na+ and Cl, which is 4-6x their daily requirement. This sodium and chloride excess is thought to be associated with water retention, oedema development, metabolic acidosis and AKI.5
But is there any actual evidence that such excesses are bad or is it just theory?
The answer is Yes… or maybe!
In 2012, Yunos et al. found that in critically ill patients who were treated with a chloride-restrictive strategy (e.g. plasmalyte, Hartmans’, chloride poor 20% albumin) versus a chloride liberal approach (e.g. 0.9% saline, 4% gelatin, 4% albumin) had reduced AKI incidence and need for renal replacement therapy.6 However, it was not until recently that some convincing evidence to support balanced solutions over unbalanced ones has arisen.
The SPLIT trial in 2015, randomised over 2000 critically ill patients to receive either 0.9% saline or plasmalyte.7 No difference in outcomes was found including the risk of AKI development. However, patients in this study only received about 1 to 2 litres of either fluid, making it unclear whether larger volumes of 0.9% saline, which is often seen in practice, would influence patient outcomes.
Recently, the SALT-EM trial compared balanced solutions (mainly Hartmann’s) to 0.9% saline in non-critically ill patients.8 This study was large, enrolling over 13,000 adult patients in a single centre in the United States. 1 litre of crystalloid was received by the median with over 2 litres of crystalloid being received in a third of patients. This study found that in non-critically ill patients who were admitted from the emergency department to hospital, there was no difference in hospital-free days between patients who received balanced solutions compared to 0.9% saline. However, the study did find as a secondary outcome, that patients who received balanced solutions demonstrated a statistically significant decrease in Major Adverse Kidney Events at 30 days (MAKE30). MAKE30 is a composite measure of death from any cause, new renal-replacement therapy or persistent renal dysfunction. Patients in this study who received 0.9% saline were more likely to have AKI, a doubling of their creatinine, but not mortality or need for dialysis. Patients’ with a baseline creatinine of >132µmol/L or serum chloride >110mmol/L were seen to have the largest benefit of avoiding AKI with balanced crystalloid use. In another trial, The SMART study compared balanced crystalloids versus 0.9% saline in 15,802 critically ill adults.9 This study found that balanced crystalloid use resulted in a lower rate of any MAKE30 outcomes compared to 0.9% saline. Both the SALT-EM and SMART studies provide evidence of benefit with the use of balanced IV fluids. However, the differences found between balanced solutions and 0.9% saline was small and further larger RCTs, such as the PLUS trial, are needed.10
Confused?… So which fluid?!
Ensuring that a patient is drinking enough and that they are making urine seems so simple but requires a whole system and cultural change, both in the hospital and the community. Better attention to these ‘simple’ details is likely to bring about much wider patient benefits than any IV fluid used. However, if a patient cannot drink for themselves or their clinical situation warrants IV fluid use, current evidence would suggest that best practice, until proven otherwise, is to use balanced solutions (such as plasmalyte and other lower chloride containing crystalloids), as these solutions are unlikely to be harmful and may be beneficial when compared to 0.9% saline. However, it is important to remember that no one IV fluid is completely safe and that the ‘goldilocks’ principle needs to be thought about every time a fluid is being prescribed and that it needs to be ‘just right’ for the patient and the clinical situation faced. IV fluid therapy needs to command the same respect from prescribers as any medication.
Right, time for a drink…!
- Mail Online. Headline: At least two elderly patients are dying each week of hunger and thirst in British hospitals and care homes amid fears of neglect. 28th October 2017. http://www.dailymail.co.uk/news/article-5025851/Two-elderly-patients-week-die-hunger-UK-hospitals.html
- National Institute for Health and Care Excellence (NICE). Intravenous fluid therapy in adults in hospital. Clinical guideline [CG174] Published date: December 2013 https://www.nice.org.uk/guidance/cg174/resources/intravenous-fluid-therapy-in-adults-in-hospital-pdf-35109752233669
- National Institute for Health and Care Excellence (NICE). Acute kidney injury: prevention, detection and management. Clinical guideline [CG169] Published date: August 2013. https://www.nice.org.uk/guidance/cg169
- Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Medicine (2018). https://link.springer.com/article/10.1007/s00134-018-5085-0
- Royal College of Physicians. Acute care toolkit 12. Acute Kidney Injury and intravenous fluid therapy. September 2015. https://www.rcplondon.ac.uk/guidelines-policy/acute-care-toolkit-12-acute-kidney-injury-and-intravenous-fluid-therapy
- Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults. JAMA. 2012;308(15):1566–1572. doi:10.1001/jama.2012.13356
- Young P, Bailey M, Beasley R, et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit. The SPLIT Randomized Clinical Trial. JAMA. 2015;314(16):1701–1710. doi:10.1001/jama.2015.12334
- Self WH, Semler MW, Wanderer JP, et al. Balanced crystalloids versus saline in non-critically ill adults. The SALT-EM Study. NEJM. 2018;378:819-828. doi:10.1056/NEJMoa1711586
- Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. NEJM. 2018; 378:829-839. doi:10.1056/NEJMoa1711584
- Plasma-Lyte 148 versUs Saline Study (PLUS) https://clinicaltrials.gov/ct2/show/NCT02721654