June 2017 Journal Club

Hi Everyone

I know I don’t usually send out review articles in journal club but please indulge me this month as it’s a bit of a pet subject for me……

Have a read of this wonderful article (by 2 very big names in the global ICU community) here


It is deliberately provocative (and I think it’s meant to be) and does what all good science should do namely challenged received wisdom……

Hope you enjoy it!

X : “Great article Rob and very relevant to the current vogue of less is more. I guess its similar to the knee jerk response to WCC that use to characterise antibiotic prescribing. Clearly its also not as simple as lactate = hypoperfusion.

My only question is having accepted that lactate is a marker of severity of illness and degree of sympathetic stimulation, where do we go with the use of b-blockers.
Whilst i’m a keen adopter of these is certain patients, I’ve witnessed not too infrequently the rapid deterioration of patients given them at the wrong time. My concern is that promoting lactate = stress response may be as harmful as lactate = hypoperfusion. To me there is a more complex biochemical and physiological relationship with lactate production and clearance that requires a bit more teasing out, before deciding on how to respond or intervene. Does anyone else use b-blockers in these patients and when?”

“Hi all

Hope you enjoyed the paper (and saw past all the typo’s!).

As X has already alluded to this review article is part of the new wave of critical care that is rebelling against the previous “supersizing” generation who advocated an approach that focused upon achieving supranormal physiological values for things like cardiac index, Hb, PaO2, etc. in order to reverse end organ damage due to tissue hypoxia. In essence they felt “more was better”.

The only problem though is that the evidence just isn’t there to support the “more is better” approach ( see ARISE, ProCESS and ProMISe trials ) and as we have said in previous journal clubs (https://yorkshireicm.wordpress.com/2016/03/14/march-journal-club/) the benefits seen in early trials may actually have been due to their, at the time, truly pioneering approach of consultant delivered care….

So what this review article tries to do is suggest a reason as to why improving oxygen delivery above normal levels sadly just won’t translate into better outcomes. This can be summarised as follows:


The human body is really quite complex………


Lactate is a perfect example of this bleedingly obvious but commonly forgotten point. Hyperlactemia is associated with worse outcomes and a metabolic acidosis. However this is not the same as saying that hyperlactemia causes worse outcomes or an acidosis. Increased lactate production in a physiologically stressed individual is possibly even an adaptive, evolutional response that may even have some advantages (see this wonderful review article as well, if you can stomach it! https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664920/). Embarrassingly it seems that the physiologists have known this for some time…….

Unfortunately we (medical doctors) may have inadvertently  created a back story that wasn’t there when we assumed that tissue hypoxia caused hyperlactemia which then caused acidosis, cell death and generalised physiological Armageddon. And then for, good measure, created a treatment rationale (supranormal physiology) targeting improved cardiac outputs, PaO2’s, Hb’s etc. that although made perfect sense in that context turned out in fact to do more harm than good.

I suspect that the lactate molecule is actually a harmless intermediate energy substrate that the body turns to in times of dire need (hence it’s association with poor outcomes) but rather than being a participant in the physiological crime is more like an innocent bystander who’s been forced to take the blame for the real culprits (?unmeasured kreb cycle anions? see https://ccforum.biomedcentral.com/articles/10.1186/cc4954 ).

So what can we say for certain?

1) Don’t ever ignore raised lactate in a septic patient as it’s a sign of a stressed physiological system.

2) Give things that work (early antibiotics, noradrenaline, targeted FiO2 , enteral nutrition) and avoid things that don’t (excessive fluids, excessive FiO2, Excessive Hb, drugs that increase cardiac output).

3) Be humble in the face of the shear scale of stuff we don’t fully understand, but keep an open mind and keep asking questions.


What do you think?




PS in answer to X’s question re B Blockers I’d tentatively put them in the “don’t work” category as the data is just not there to support there wide scale use in septic patients yet but that’s only my view so please feel free to see here for a balanced discussion on it (https://yorkshireicm.wordpress.com/2017/04/10/beta-blockers-in-sepsis/)…..

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