St Emlyn's in Brum #ICSSOA – Day 3

The final day is upon us. Some tired eyes and aching feet, no doubt fresh from the #party. Despite this, my first session was in a fully packed room. Well done all – cardiogenic shock clearly gets people out of bed.

A large panel from various backgrounds took us through an interesting morning; first of all Alasdair Proudfoot accused us of running an NHS system entirely dependent on luck – postcode lotteries, disparate teams, limited resource and subjective decision making all feed in to the 40-50% mortality outcome from cardiogenic shock. We are beginning to develop a common language about these patients, through SCAI and INTERMACS classification systems. We also have lots of available rescue strategies these days. But how can we ensure these resources are delivered consistently, to the right patient, at the right time?

Rapid action teams may be the right approach. But they need to be multi-disciplinary and have senior clinical leadership. Arise the cardiogenic shock team, a similar model to the now fairly well established Pulmonary Embolism Response Team (PERT). The MDT includes not just ECMO enthusiasts, but sonography experts, cardiologists, perfusionists and many others. Alasdair argued that this team provides equity of access, supportive decision making and robust governance/learning.

We then discussed how this team could help address the age old arguments via serial cases and panel discussion – load and go or stay and play? How to get an expert team to a critically ill patient quickly (land/air)? When does someone definitely need mechanical support for cardiogenic shock? Are there any absolute contra-indications to mechanical support? What about the health economics? Interesting to hear that ECMO as an intervention may not be quite as costly as we all imagine.

Onwards to coffee and then the unplugging of sepsis. I think after 2 days of skirting the issue, the audience was just about ready to take on vitamin C….

The Marik study was of course aired, but without the usual bashing (Francois is a polite Canadian after all..). Reference was made to a subsequent  recent systematic review highlighting similar clinical improvements in other studies and the audience was asked to look on the bright side. Maybe this stuff does work? Wouldn’t that be nice, if it did?

But how exactly does this miracle cure work? Several ways apparently, mainly through antioxidant action, improved immunity and use as a co-factor for catecholamine synthesis. This all sounds complex and we have seen cytokine pictures before and been told that the magic bullet exists, only to find out later that it does not. No wonder we are sceptical. But do we care how it works, if it helps patients? Recent results from some larger studies have been encouraging. Although mortality was not the primary outcome in CITRIS –ALI, the Kaplin Meier curves are hard to ignore. What about harm though? No intervention is without harm, even if this is through opportunity cost or rare events compromising routine care. And we still don’t have enough data to be sure that such high doses of vitamin C are harmless.

The jury remains out. Further work is clearly in the pipeline, via VITAMINS, ACTS, VICTAS, LOVIT and I am sure others. Watch this space.

Next up we heard about survivors of sepsis, and the challenges with methodology in this space.  Does sepsis carry a future mortality risk following the acute episode, and if so which risk factors contribute? Tricky to work out with the data we have at present. We also heard about very high rates of rehospitalisation following sepsis and saw data to suggest often these returns (and sometimes deaths) cannot be explained by pre-event comorbidities. It appears that the sepsis episode itself drives further complications.  What can we do about this? Quite a lot, it appears. A focus on early review following discharge, intervention for those conditions that place patients at risk, medication adjustment and appropriate referral, or transfer to palliation if needed. Just good primary care then? Tricky, with the current state of the NHS. Could we focus on a higher risk group to target a bit more aggressively? Perhaps, using this novel work and looking hard at the follow up for those patients with 2-3 organ failure, or those with a higher APACHE2  score. 

Of course, no sepsis session would be complete without Mervyn, who gave a talk to support his recent letter on the dangers of hype in regard to sepsis. The subsequent discussion on social media, in journals and no doubt hospital corridors, was widespread and lively. We heard direct from the horse’s mouth about the reasons for this letter and an explanation of data supporting the worries. In addition, we heard some concerning anecdotes about junior clinicians feeling forced to prescribe antibiotics (even when they did not feel infection was a concern). Have we really got to this stage? Really? Without doubt a huge concern for critical care. If you’ve not read the letter already, I would urge you to read and think about it very carefully.  

Loads of other great stuff going on this morning. I was particularly sad to miss the no place like work session. Sara Gray and Chris Turner are both ace and I would strongly suggest everyone listen to their various talks on self compassion and civility. The art and science of conversation also sounded brilliant. Good stuff.

The last plenary session was single track. Congratulations to all the prize winners including Neil Roberts (best eposter presentation), Guy Parsons (The Cauldron), Clare Leon-Villapalos (best oral presentation), Abbigail Beane (Gold medal) and lastly David Antcliffe and Mansoor Bangash (winners of the research prioritisation exercise).

Then, straight onto hot topics. First up, we heard more about molecular diagnostics through a recent project delivered by the defence science and technology lab. An interesting presentation of results followed (unfortunately embargoed),  looking at individual gene expression prior to and immediately following a diagnosis of sepsis. Case matching with controls and SIRS patients allowed comparison. Could we look at gene expression in patients and predict who may develop sepsis whilst in hospital? Minority report medicine? The paper is out next year.

More sepsis next and a study on a question I’ve always wondered about. Do you really need to take the cultures prior to antibiotics? Or can you do them within a couple of hours? This was Canadian work published this year as the FABLED study in the Annals of Internal Medicine. The authors worked hard to screen over 3000 patients. Unfortunately, only just over 300 patients were recruited with positive blood cultures seen in around 30%. And more unfortunately, the sensitivity of post antimicrobial blood cultures in all participants was only just over 50%. Looks like we actually do need to do those cultures quickly, and prior to abx, if we want to know what we are treating.

Hyperoxia next. Is it bad? We think so and have even been known to comment on this in the literature.  Ed Palmer presented interesting work from his PhD which has been recently published in the Blue Journal, which seems to agree overall. This was a clever study looking at hyperoxaemia as a daily dose window, which has often been the issue with other trials (looking only at isolated PaO2 readings). Turning hyperoxaemia into a dose allows an interesting interpretation of adverse impact on outcome; the results from this study suggest that an increasing dose does not result in an increasing mortality. This potentially raises some questions about causation. A nice analogy followed from Ed, who asked us to think in terms of a smoking study – it would appear smoking 20 cigarettes per day correlates with increased mortality, but the authors can’t tell us if smoking 40 cigarettes per day makes things any worse. More to follow on this topic of course, including a study with perhaps the best name for the last decade?? We await #MegaRox with great interest.

Tony Gordon last talking about the future approach to trials in sepsis. This was essentially a summary of a recent platform grant application, talking about key ongoing areas of interest and presenting a design for the next big UK sepsis study. A large group of very experienced collaborators have worked up a 2 by 2 factorial design RCT looking to recruit sepsis patients in order to address 4 big questions:

  1. Can early and rapid molecular diagnostics / procalcitonin improve antimicrobial stewardship and clinical outcomes?
  2. Do restrictive fluid strategies improve clinical outcomes?
  3. Does GM-CSF supplementation offer any benefits in sepsis?
  4. How cost effective are all these interventions?

Certainly big and ambitious, but actually this is only 60 centres at 2 patients/month over 3 years. Very doable. They are looking for sites in the summer, so keep your eyes and ears open and contact Tony if you want to get involved [email protected].

The final session of the conference was a top 4 papers, or editor’s picks. These sessions are always gold, and cleverly placed by the conference team in order to get people to stay. On with the countdown!

First up was the best from Thorax via Nicholas Hart – he wanted to talk about Greet Hermans paper on long term outcomes following brief or prolonged ICU stay. We always think long term outcomes are most affected by individual and disease characteristics, such as age or comorbidity. But does the actual duration of critical care stay in itself, impact on this? This paper suggests it may, as does the accompanying editorial. Propensity score matching was noted (some explanatory notes here), but the audience was also reminded about the observational methodology. Association or causation? Have a read and decide.

Next, the best of the Critical Care via Steve Brett. I almost got excited when he put up the European guideline on major bleeding in trauma, but it turns out he actually wanted to talk about this cohort study on the association between autoimmune disease and 30 day mortality in sepsis patients. Turns out it might be lower if you have autoimmune disease. Who would have thought? Steve discussed the retrospective nature of the study through database analysis and the potential exposure here to unmeasured and unreported confounding variables. Lots of other smaller issues as well. By no means perfect. But a fascinating hypothesis and a paper raising an eyebrow at current thinking and gently suggesting we might want to look again at this issue again.

Hannah Wunsch then on the best of the blue and she went for the previously mentioned CENSER trial. A single centre blinded RCT comparing early noradrenaline in septic shock or standard care in the Emergency Department. A positive outcome, with clear improvement in shock resolution within patients receiving noradrenaline. Very interesting stuff, as the method of administration was peripheral in many patients I think and a lot were managed in an essentially level 1 care environment (Although Hannah did point out that nursing ward ratios in Thailand approach 3:1 in some areas). Just as interesting, was the lower adverse event rate in the intervention arm; no significant increase in gut ischaemia, skin necrosis or any other AEs. Certainly makes the case well for a larger study.

Last up to close was Anders Perner as deputy editor for Intensive Care Medicine. His favourite? A cohort study on the benefits of influenza vaccination in a large cohort of just under 90,000 Danish ICU survivors. Apparently this helps. All well and good, and for strange benefits – reduction in the risks of stroke, for example. The conclusion from the authors was that vaccination should continue for the over 65’s but the panel took a swipe at some of the stats and the underlying issues with an uncontrolled intervention – maybe the hard to reach groups who do not get vaccinated have other confounding variables? Tricky. But definitely interesting.

And with that, we draw to a close. A great three days of content, networking, tips, tricks and hands on experimentation. Hats off to the conference organisers and all involved in this impressive meeting, which seems to grow in strength and quality every year.

Now I’m off to sleep on the train, all the way home. No one mention Coyote Ugly.

See you next time

Dan



Cite this article as: Dan Horner, "St Emlyn's in Brum #ICSSOA – Day 3," in St.Emlyn's, December 12, 2019, https://www.stemlynsblog.org/st-emlyns-in-brum-icssoa-day-3/.

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Posted by Dan Horner

Dr Daniel Horner BA MBBS MD PgCert MRCP (UK) FRCEM FFICM is an editorial board member on the St Emlyn’s blog and podcast. He is Professor of Emergency Medicine of the Royal College of Emergency Medicine. He is a consultant in Emergency Medicine and Intensive Care at Salford Royal NHS Foundation Trust. He is chair of the national exemplar centre Thrombosis Committee and Regional lead for Injuries and Emergencies on the NIHR Clinical Research Network. He is a Senior clinical lecturer at the University of Manchester and collaborator with the University of Sheffield. You can find him on twitter as @RCEMProf

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