Fluid resuscitation: evidence-based solutions?

In a blog for health professionals, Kinseng Tong looks at the latest Cochrane evidenceCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. on intravenous fluid resuscitation.

Page last checked 21 April 2023

Take-home points

• Colloids are probably no better than crystalloids for fluid resuscitation.
• Buffered solutions make no difference to overall mortalitydeath and may make little or no difference to kidney function, compared with 0.9% saline.
• More research is needed to determine whether buffered solutions have a significant impact on electrolyte levels and the need for blood transfusions.

Intravenous fluid prescribing

Intravenous (IV) fluid prescribing is one of the commonest tasks carried out by junior doctors.  I still remember around this time last year when I was fresh out of medical school and had just been let loose on the wards, I was asked by a nurse to prescribe a bag of maintenance fluids for a young surgical patient with no significant comorbidities.  Being the clueless junior doctor that I was, I replied that I needed to examine the patient first and would get back to her, to which in return I saw the nurse’s expression change from one of bewilderment to that of amusement, as she walked away with a chuckle.

While I don’t necessarily examine all my patients before prescribing routine fluids now (nurses are your trusted friend), it is still a good idea to at least have a think about the patient’s fluid balance, especially in those who are at riskA way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of fluid overload.  To put things into perspective, the 1999 National Confidential Enquiry into Perioperative Deaths (NCEPOD) found that 1 in 5 patients suffered complications relating to inadequate IV fluid prescribing; a further report in 2011 showed that poor fluid management is associated with a significantly higher 30-day mortality^1,2.

The main indications for IV fluids are resuscitation (in acutely unwell patients having dangerously low blood pressures), routine maintenance (to meet daily fluid and electrolyte requirements), and replacement (of additional fluid and electrolyte losses).  There are comprehensive guidelines by the National Institute of Clinical Excellence (NICE) on IV fluid therapy^3,4.  The focus of this blog is on IV fluid resuscitation.

What we already know: colloids versus crystalloids

There are different types of IV fluid preparations, which can be classified as colloids and crystalloids.  Colloids contain large particles with limited ability to cross the endothelium, whereas particles in crystalloids can freely move across the endothelium.  It was once thought that colloids were better for fluid resuscitation as they had been shown in experimental models to be able to keep more fluid within blood vessels, meaning that there would be a greater volume in the bloodstream to support the blood pressure.  This observation is governed by a phenomenon known as Starling’s Law, which states that the greater the number of large particles in a capillary (which are unable to cross the endothelium), the more fluid that is retained within the capillary (or drawn from surrounding soft tissues by osmosis).

However, this theoretical advantage of colloids did not translate into clinical benefit in human trialsClinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known..  Several Cochrane ReviewsCochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. have found that colloids probably make little or no difference to overall mortality^5,6, and in fact, some types of colloids (those that contain starches) probably increase the need for blood transfusion and renal replacement therapy (filtering the blood, with or without dialysis machines, if kidneys fail)^5,7.  These studies have effectively abolished the favourable position for colloids in critical care medicine.

What does the new Cochrane evidence add?

Buffered solutions versus 0.9% saline

Another key topic of debate is whether there is any difference in outcomesOutcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’. among different crystalloid solutions.  0.9% saline is one of the most widely used (and very cheap) crystalloids but other ‘buffered’ solutions are available, such as Hartmann’s solution and Plasma-Lyte.  The ‘buffered’ solutions are so named because they have specific electrolyte compositions that provide a degree of buffering from factors that may alter the pH of the solutions.  On the other hand, 0.9% saline contains a much higher amount of chloride than is present in human blood, and in the absence of a buffer, the excess chloride may make the blood slightly more acidic than it should be (a phenomenon known as ‘hyperchloraemic acidosis’).

There is a narrow window of pH which is considered ‘normal’ for human blood (pH 7.35 – 7.45).  Patients who are critically ill tend to have a build-up of toxins in their bloodstream, and some of these are acidic.  The presence of an acidic environment can affect the function of vital organs such as the kidneys and brain.  Because of the potential risk of exacerbating blood acidity, some clinicians avoid using 0.9% saline and prefer buffered solutions in these patients. This practice is especially prevalent in the surgical realm and is endorsed by national guidelines⁸.

The latest Cochrane Review comparing buffered solutions with 0.9% saline for resuscitation in critically ill adults and children included 21 studies involving 20213 participants (adult and children included)⁹.  The authors included studies on patients with critical illness (including trauma and burns) and those undergoing emergency surgery during critical illness. Patients undergoing elective surgery were excluded.  The authors analysed in-hospital mortality rateThe speed or frequency of occurrence of an event, usually expressed with respect to time. For instance, a mortality rate might be the number of deaths per year, per 100,000 people., the incidenceThe number of new occurrences of something in a population over a particular period of time, e.g. the number of cases of a disease in a country over one year. of organ dysfunction (kidney, lungs, liver and brain), electrolyte levels in the blood, and the need to receive blood transfusions.  They found that:

1. buffered solutions made no difference to overall mortality (high-certainty evidence);
2. buffered solutions may make no difference in reducing the number of patients with worsening kidney function (low-certainty evidence); and
3. it was uncertain whether buffered solutions reduce impairment of other organs or electrolyte imbalances, or whether they affect the need to receive blood transfusions (very low-certainty evidence).

Where does this leave us?

The latest Cochrane Review provides strong evidence that 0.9% saline is comparable to buffered solutions in mortality outcomes when used for fluid resuscitation.  This is of interest not just because of cost differences (Hartmann’s solution is marginally more expensive, Plasma-Lyte much more so), but also in light of the recent temporary shortage of buffered solutions in certain regions of the UK¹⁰.

The effect of buffered solutions on kidney function is less certain, and it is even more difficult to draw conclusions on other-organ dysfunction, electrolyte imbalances and the need to receive blood transfusions due to the very low quality of evidenceThe certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty.  Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach.  It is hoped that future studies will shed more light on these remaining issues.

Join in the conversation on Twitter with @KinsengT @CochraneUK @Cochrane_ACE or leave a comment on the blog.

References (pdf)

Kinseng Tong has nothing to disclose.