STH Journal Club

STH Journal Club

An excellent new resource from our colleagues in Sheffield has arrived! They are now publishing short summaries of their “live” journal club on a blog (link above) and on a twitter stream (@sthjournalclub). We are planning to collaborate in the future, and I’d encourage all followers of Critical Insight to check them out and join in the discussions! In fact this resource is so good its rather put our recent output (zero) to shame…..I will put this right over the coming couple of months! 

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A Black Water Day ?

Mortality after Fluid Bolus in African Children with Severe Infection. Maitland, K et al. New England Journal of Medicine, May 26th 2011 (epub ahead of print) (DOI: 10.1056/NEJMe1105490)
An interesting paper published in this weeks NEJM will cause substantial comment and concern after it’s headline result showed increased mortality with rapid fluid resuscitation in paediatric sepsis. This surprising result is potentially extremely important as, if verified, undermines much of peadiatric (and adult)emergency care.

Before examining the paper in detail it’s worth making a few comments on what we think we know already….

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The Pinocchio Effect

An interesting editorial published a couple of months ago in Anaesthesia by Neil Soni. It adds to the growing disquiet that our understanding of disease, and attempts to find effective remedies, are being hampered by the tendency to treat all organ failures equally. I agree that there seems little reason to believe that meningococal sepsis in an 18 year old will behave the same as peritonitis in an 80 year old, nor that ARDS following pancreatitis is the same as that following FFP. However, these syndromes were designed partly to make research into rare presentations possible. If we define patients according to causative factor and co-morbidity how are we ever to recruit enough to power even the most basic trial ?

ARDS, acronyms and the Pinocchio effect. Soni N.Anaesthesia. 2010 Oct;65(10):976-9. doi: 10.1111/j.1365-2044.2010.06508.x.PMID: 21198467

NMB in Early ARDS.

A fascinating study from the NEJM.

Neuromuscular Blockers in Early ARDS. Papazian, L et al. NEJM. Vol 6, 12, 2010.

This RCT gave a 48 hr infusion of cis-atricurium to early (<24hrs) ARDS patients. It is the first study to show a mortality difference in this condition since ARDSnet a decade ago (although caution is required as it was underpowered). Whilst it is likely that a large proportion of the population included in this study (early, severe ARDS) will already be on NMB to aid ventilation, there has up until now been an assumption that this therapy was a necessary harm (due to the risk of critical illness polyneuropathy and subsequent slow weaning). This study questions that wisdom, showing both a reduction in adjusted mortality at 90 days (although not at 28) and no increase in the risk of CIPN. The results need to be taken with caution, but are certainly interesting and if confirmed may offer an important advance. There is further detailed analysis of the paper in the presentation ‘Atricurium ARDS’ in the blue box. Remember that restrictions on comments have been lifted on Critical Insight, no sign in required – so let us know your opinions.

Oxygen – too much of a good thing ?

We’ve known for sometime that high inspired oxygen fractions (>0.8) are associated with atelechasis (and decruitment / shunt) and lung injury and suspected that hyperoxia also leads to the generation of toxic oxygen free radicals, which may have deleterious effects in other pathologies. A recent paper adds to this story;

Association between arterial hypoxia following resuscitation from cardiac arrest and In Hopsital mortality. Hope, J et al. JAMA. 2010;303(21):2165-2171 (doi:10.1001/jama.2010.707).

This paper has been appraised by a colleague, Paul Townsley, and you can download his presentation from the blue box on the right. Although the methodology has some potential flaws (which is probably inevitable), the paper provides evidence of definite harm of hyperoxia in ischemic brain injury.

Of course, there is an alternative weight of evidence of the harm associated with even short periods of desaturation in traumatic brain injury (and presumably also brain injury from poor perfusion). How to square this circle? The devil as always is in the detail. Controlling hyperoxia is probably important, but whether the benefits of avoiding hyperoxia outweigh the additional risk of periods of desaturation, or how often those periods occur within patient populations, is unknown. There is sufficient evidence to warrant a carefully designed RCT in the post resuscitation phase, (and maybe also in ARDS while we’re at it).

Post Publication Peer Review

First an apology, there’s been quite a gap since my last post. I will be trying my best to increase the frequency of appraisals on Critical Insight, especially since Schringer & Altman’s editorial in this week’s BMJ. They comment that the “lack of post-publication review of medical research is a sign of an unhealthy research environment in clinical medicine”, and that “we need a change in culture to value public discussion”, I couldn’t agree more.
The major journals have a vested interest in suppressing critical appraisal of published papers as this tends to undermine their pre-publication peer review, a process that has failed to prevent publication of flawed research and in any case adds little to clinicians ability to apply that research. Letters to the editor are limited, screened by the same process that published the original research and significantly delayed. Apart from the BMJ other major journals have not embraced post publication discussion, although there are other sites that are filling the gap, for instance F1000 (conflict of interest – I have also published appraisals for this site).

Critical Insight was started to help fill this post publication review gap, and your help in the form of comments and posts is always welcome. To that end I’ve removed the need to be signed in to comment, if you can see the site you should be able to post a comment.

SOAP II – That’s cleaned that up then.

Dopamine has been the vasopressor of choice in septic patients in continental europe historically, although this may be changing. Dopamine has theoretically beneficial effects in maintaining splancnic and renal perfusion although in the SOAP trial (observational) suggested that there was an excess of mortality of dopamine treated patients. The old story of “renal dose dopamine” having an additional effect over and above the improvement in perfusing pressure has been discredited, but this result suggests a harmful signal over and above noradrenaline (the preferred agent in the UK).

Comparison of dopamine and norepinephrine in the treatment of shock. De Backer DN, et al. N Engl J Med. 2010 Mar 4;362(9):779-89.
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BIS – magic prediction post arrest ?

A fascinating paper very well reviewed by Dr. James Dawson at the QMC journal club;

The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest Intensive Care Med. 2010 Feb;36(2):281-8. Epub 2009 Oct 22. Read more »

Renal Intensity – How High ?

The ANZICS group appear to have done it again; that is taken a single centre trial done in Europe, repeated it in a sensible and pragmatic way but in a much larger, adequately powered multi centre setting and determined an evidence based outcome. It’s something of a shame that again the evidence based outcome doesn’t support the optimism of the initial trial.
This time the therapy in question is the ‘dose’ of RRT (renal replacement therapy). A previous trial by influential group led by Ronco suggested a survival benefit of 35mls/kg/hr effluent flow rate as opposed to 20ml/kg/hr. A major US study (the Veterans/NIH study) showed no difference in mortality but was limited in its application is the UK because of the relatively large proportion of patients who received intermittent heamodialysis, and the slightly complicated rationale for choosing which patients received which therapy. Most UK ICUs would provide only CVVH (or variants) to ICU patients.
Intensity of Renal Replacement Therapy in Critically Ill Patients. RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S.   N Engl J Med.   2009 Oct 22;361(17):1627-3.

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Medpedia & Twitter

Critical Insight has been included as a founding member of Medpedia’s News & Analysis website. Medpedia is an exciting project to build a first class medical resource on the internet using world wide wiki collaboration in association with major US universities, you can find more details here. Critical Insight was started to try and encourage similar professional collaboration and discussion, and I hope that international visitors will find Critical Insight useful.

If you struggle to visit Critical Insight frequently why not be notified of new posts ? It’s been possible to receive email notifications and RSS feeds for some time, and you now have a third option – following Critical Insight on Twitter! Click the buttons on the right and follow the instructions.