Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What are starch-based colloid fluids and how do they differ from saline-based crystalloid fluids?
Saline is just salty water, whereas colloids are solutions that have large molecules in them. In this case, the molecules are starch.
The idea is that because these molecules are big they don’t leak out of the circulation as much. Because they stay inside the circulation it expands the intravascular volume more than salty water.
How do the two different fluids differ in cost?
They differ massively. About 500ml of starch costs about £12; whereas 500ml of normal saline costs about £2. So there is at least £10 difference.
What is the reason for this difference?
Salty water is easy to make; whereas for colloids you have to do some chemical processing.
What type of intravenous (IV) fluids are used on the NHS and why?
Colloids are widely used in the NHS, much more than other national health services actually. For some reason, we have a predilection for starch use in the NHS.
I don’t think there is any good reason for it. It is about habit and marketing and reimbursement arrangements etc.
The fact that people get away without using them perfectly well in other parts of the world shows it is not necessary to use them.
Now evidence from randomised control trials shows that they do more harm than good – that the alternative saline is actually cheaper and safer.
How does the NHS’s use of IV fluids differ from their use in other countries?
We seem to be particularly enamoured with colloids in Europe. Australia also uses a lot of colloids.
France, Germany and New Zealand tend to use more crystalloid fluids. The USA also uses much more crystalloid fluids.
I think it is just marketing and habit. There is no good scientific reason for using colloids; it is more for historical reasons.
How did your research into IV fluids originate?
There’s been a long-standing debate over whether colloids are superior to crystalloids. Most of this debate is based on fancy theories about why they are better.
Doctors can always come up with fancy theories and you can generally always think of a theoretical advantage. But the way to find out whether something is better or worse is to forget about theory and try them out in a randomised control trial. Over the years there have been many trials now and what we have done is to add them up.
About 15-20 years ago we started looking at the evidence comparing colloids to crystalloids in randomised trials with an outcome that matters to patients like death. We find that there is no evidence that colloids are better than crystalloids whatsoever.
Recently, there have been several large, new, high-quality trials published and now the balance of evidence shifts even further against colloids. This one colloid – starch – has statistically significant increase in death rates.
What did your research involve?
Our research was about keeping up to date with the evidence from randomised control trials in systematic reviews.
Knowledge is always changing and it has to be updated on a regular basis. This process of updating knowledge as new knowledge accumulates is important.
There’s no point making a decision based on knowledge ten years ago and carrying on doing it.
When new knowledge comes along and tells you what you’re doing is wrong you’ve got to change course.
What did your research find and was this surprising?
We found that starch colloids increased the risk of death in comparison to normal saline.
This was reasonably surprising. I was sceptical that there would be any benefit from starch-based colloids. Lots of people had previously suggested that they can do more harm than good – I remember meeting an intensivist who said he wouldn’t give them to his dog!
Is anything known about the mechanism by which starch-based colloids can produce death?
There are different theories. They seem to cause more adverse events. They have various side effects like causing a lot of itching in people that survive.
There’s evidence that they can cause renal problems and renal problems can cause death.
They might be a bit better at expanding the circulation, but expanding the circulation might not always be the right thing to do. They might be harmful because they are more effective at doing something you shouldn’t do.
What impact do you think this research will have?
I don’t know. I’ve pointed it out to the Department of Health. The European Medicines Agency are conducting a review and they are going to report in some months’ time.
They’ll hopefully either send a warning out or withdraw them. I really hope this happens.
It is ridiculous at a time when health services all over the world are short of funds to use an expensive treatment that is more dangerous than a cheaper alternative.
The European Medicines Agency is conducting a review into the safety of hydroxyethyl starch in critically ill patients. How will this review differ from your research?
A review for them means more than just reviewing the evidence. They’ve got to think about what mechanisms they’ve got for taking action, of those mechanisms which is the most appropriate action.
They have to consider science and the law and other things.
Where can readers find more information?
They can read our paper on the Cochrane library: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000567.pub6/abstract
They can find more information about the London School of Hygiene & Tropical Medicine at: www.lshtm.ac.uk
About Dr Ian Roberts
Ian Roberts is Professor of Epidemiology & Public Health at the London School of Hygiene & Tropical Medicine. His main research interests are the prevention and treatment of trauma and the links between energy and health.
He trained as a paediatrician and then in epidemiology at the University of Auckland, New Zealand and at McGill University, Canada. He established and is co-ordinating editor of the Cochrane Injuries Group, an international network of individuals that prepares and maintains systematic reviews of the effectiveness of interventions in the prevention, treatment and rehabilitation of injury.
He is principal investigator of the CRASH trials, large international randomised controlled trials that seek better ways to treat seriously injured trauma patients. The MRC CRASH trial, which included 10,000 patients with head injury from around the world, showed that corticosteroids, which were widely used in the management of head injury, did not improve patient outcome after head injury but increased the risk of death. The CRASH-2 trial has shown that tranexamic acid, an inexpensive and widely practicable treatment, safely reduces mortality in bleeding trauma patients.
He is the author with Phil Edwards of The Energy Glut: the politics of fatness in an overheating world.