The end of the road for colloids in sepsis??? St.Emlyn’s

Basically the evidence from RCTs of colloids in sepsis suggests that there is no potential benefit and that we should abandon colloids as they are more expensive. They quote the data in the abstract as being definitive, but it’s a bit tricky to understand as there are no ‘real’ numbers presented. Instead, and as usual, the data is presented in the abstracts as a series of pooled relative risks which unless you are a total stats geek mean next to nothing to be honest. I am a stats geek/nerd/weirdo and I still hate them as they make it difficult for working clinicians to get a feel for the magnitude of effect. So let’s try a bit of translation and work out what the main findings mean in practice.

In the main paper this is analysis 1.1 They looked at 24 trials (all RCTs), these encompassed 9920 patients.

Overall 922/4951 (18.6%) patients died in the crystalloid group

Overall 914/4969 (18.3%) patients died in the albumin group

This was not statistically significant.

Now this is more like it, we have already looked at trials of hydroxyethylstarch on St.Emlyn’s and have declared that their days as ICU fluids for sepsis resuscitation are over. That was on the basis of the CRYSTMAS and the study by Perner comparing starch against Hartman’s. We came to a conclusion that the number needed to harm was really high – in the region of 13 if memory serves me right which was enough to abandon their use.

In the Cochrane review they have looked at a total of 25 trials.

• Overall they found a mortality of  1002/4615 (21.7%)( in the starch group
• Overall they found a mortality of 912/4521 (20.2%)

That’s a number needed to harm (by giving starch) of 66.6

11 trials to look at here

• Overall deaths were 13/224 (5.8%) in gelatin group
• Overall deaths were 15/282 (5.3%) in crystalloid group. (Ed – pretty low death rate for sepsis here hmmm)

A pretty low event rate to be honest and not much data here.

They also looked at Dextran, but since no-one I know uses it I’m not going to talk about it!

The bottom line in the paper is fair and goes like this…….

“Authors’ conclusions: There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. Furthermore, the use of hydroxyethyl starch might increase mortality. As colloids are not associated with an improvement in survival and are considerably more expensive than crystalloids, it is hard to see how their continued use in clinical practice can be justified.”

Now I am fairly happy with that as it does concur with my own feelings, but I am still left with a few questions about this kind of study when we look at the complexities of a condition such as sepsis.

Well, call me a party pooper, but I think it is vitally important that we critique meta-analysis just as we critique primary research papers. It is all too easy to assume that because the buzz words meta-analysis and systematic review appear in the title then it has to be of excellent quality.

This is not the case as it is quite possible to do a bad systematic review. So is that something that has been done here?

In general no. The work is explicit in its methods and the authors have clearly described how they have sought, analysed and transcribed their data. The analysis that I have simplified above is the correct model and with most Cochrane reviews it is well presented.

I do think that it is worth looking at the collation of trials in studies like this. In order for the pooling of data I believe that it is very important to look to see if the patient populations are similar. Whilst there are statistical methods to pool data from trials with different event rates it is never quite so pure as using data from trials with similar methods and patient groups. This may well account for the difference in the number needed to harm for starches we found previously (NNH – 13) as compared to the pooled data in the Cochrane review (NNH-66.6). If you download the full version of the paper then you will see that the event rate (death) varies widely betweem studies and this is usually a fair indicator that we are looking at different populations where the effect of colloids may subsequently also be different.

Let’s go for three.

1. Colloids do not appear to have any benefit in sepsis
2. Converting numbers reported in meta-analysis to NNH or NNT is SO much more intuitive
3. Look at the event rates for individual studies in the meta-analysis to get an idea about the variation in patient populations.

Obviously there is always more to talk about, but we are all busy people and I must pack to travel to the other side of the world at SMACC2013. Look out Sydney, here comes Virchester.