In addition to the presentation of the VITAMINS trial and the PEPTIC trial we also saw a number of other papers presented. These are listed below, but have not been fully critically appraised. We’ll leave that to you.
The ROSE study 1was an RCT of neuromuscular blockade (NMB) in ARDS. It’s an interesting study as it was stopped early owing to an interim analysis showing futility. Just over 1000 patients were recruited to either receive early NMB with deep sedation, or not, in severe ARDS by the Berlin definition. Patients were recruited in 48 US ICUs.
They used cis-atracurium for 48 hours as an intervention.
The primary outcome of death at 90 days showed no difference between the two strategies, (42.5% vs. 42.8%). Segun Olusanya on the Bottom Line website2 concludes that there is no benefit to NMB, but that there are other reasons why you might want to do this in practice (e.g. to achieve synchrony with the vent).
After the controversy of this mornings VITAMINS trial result it was good to review the CITRIS-ALI 4 study of vitamin C use in sepsis. This RCT looked at the effect of a 96 hour infusion of vitamin C on inflammatory markers and end organ damage, so not as hard a clinical outcome as we would want and arguably not that patient centred.
They recruited 170 patients across 7 US ICUs.
They found no difference in CRP, SOFA score or thrombomodulin concluding that there was no significant effect. There was a benefit in terms of mortality and this needs exploring further, but as a secondary outcome (one of many secondary analyses) this must be considered hypothesis generating rather than conclusive3. In the post presentation debate Andrew Althouse argues that not all secondary outcomes are the same and we should not be as dismissive of them as some have suggested. Of note Andrew was a bit of a star at #CCR20 I don’t agree with everything he says, but I learned a lot. You can follow him here.
The Early Spontaneous Breathing in Acute Respiratory Distress Syndrome (BiRDS) study looked at different ventilatory modes for ICU patients. Basically asking whether BIPAP-APRV modes improve gas exchange, improves haemodynamic tolerance of ventilation and/or reduces the need for sedative drugs.
The aim of this multicenter, prospective, randomized, controlled, open study is to compare the effects of two ventilatory strategies on the mortality of ARDS patients and placed under mechanical ventilation. The primary outcome was all cause mortality up to 60 days.
I can’t seem to find an abstract for this paper so I don’t think it’s published as yet so it’s tricky to critically appraise. The results presented today appear to show no difference in outcomes between the two strategies.
Amongst the audience there was some confusion about what exactly was delivered in the APRV group. Certainly manhy people in the audience do not use the strategy proposed by the author.
The Editor’s view
Howard Bauchner is the editor of JAMA, ex of Archives of Diseases of Childhood. He talks of the rise of digital technologies and the requirement to embrace the readership in the digital and social media spaces. We see this through better website design, digital summaries and infographics. The recognition that we need to think about how we get to readers and not just publish and forget that crucial step. Publication is about getting content to where it’s needed and not just producing a physical copy. Digital content is clearly something that modern journals need to embrace.
I’ve been an associate editor at EMJ for many years and it’s still a bit mysterious and controversial. Authors are often frustrated by the process but Howard, like all of us are there to promote good science and learning. That came across in his interview here.
JAMA has split into a range of sub-journals now, but arguably they are more than offsprings of the main journal. Some of them like JAMA Oncology have very high impact factors and are the journal of choice (beyond main JAMA) for speciality researchers.
For authors Howard recommends the basics and well trodden advice of all editors. Read the advice for authors, read the journal, submit the right type of paper to the right type of journal and be honest and balanced about what you’ve done.
Howard also addressed some of the ethical issues that all editors face, particularly around data sharing, which in principle is great, but ethically challenging at times. My view is that the data ultimately belongs to the patient and we should respect their sacrifice in producing it and share, but I also accept that this is rather simplistic and arguably naive. There are good arguments to say that the data belongs to the research group and it’s up to them who can use it. The bottom line is that someone paid to get the data, and simply offering that out for free and without the pain associated with acquiring it is complex6,7. JAMA will be asking all authors to make a declaration on data sharing from the beginning of 2020.
The issues of data fabrication and the Carlisle method discussion once again
raised concerns about the quality of submissions. Howard suggested that true
fraud is rare, but when they find it there is a process to investigate and it’s
not swept under the carpet.
Finally, the question of social media came up again. I’m not sure we need to
ask this now. Social media is not going away and can be used as a force for
good or bad. It’s up to us to make sure we use it well. As clinicians and
scientists we have a collective responsibility to use it wisely.
John Hinds Memorial Lecture.
Sadly the @stemlyns team had to jump on a plane back to Manchester a little earlier than planned so we missed this. A great shame as Kath Maitland is a deserving and wonderful choice to keep John at the forefront of our minds. It’s great to see his name and legacy celebrated once again.
Critical Care Reviews is a unique meeting in my experience. The combination of author presentation followed by an expert verbal editorial, followed by a panel discussion really allows the audience to understand not just what was done, but also why it was done and then what it means. This should happen at more scientific conferences in my opinion.
Beyond that, the CCR team really look after delegates and speakers. They’ve thought hard about how a conference can be designed to be academically rigorous and friendly and open. Again, I think there are lessons to be learned for other conference organisers here. They are also very fortunate to have such a wonderful setting to run the conference. The Titanic centre is stunning and worth a visit to Belfast on its own.
If you want to see how it’s done well, and if you have the time and funds to get to Belfast I thoroughly recommend you look out for tickets to the 2021 meeting. It’s really worth the trip and I’ll be back if I can next year.
- 1.Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. May 2019:1997-2008. doi:10.1056/nejmoa1901686
- 2.Olusanya S. ROSE study. The Bottom Line. https://www.thebottomline.org.uk/summaries/icm/rose/. Published 2019. Accessed 2020.
- 3.Olusanya S. CITRIS-ALI. The Bottom Line. https://www.thebottomline.org.uk/summaries/vitamin-c-sepsis/. Published 2019. Accessed 2020.
- 4.Fowler AA III, Truwit JD, Hite RD, et al. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure. JAMA. October 2019:1261. doi:10.1001/jama.2019.11825
- 5.Mercat A. Early Spontaneous Breathing in Acute Respiratory Distress Syndrome (BiRDS). Clinical Tials. https://clinicaltrials.gov/ct2/show/record/NCT01862016. Published 2017. Accessed 2020.
- 6.Bauchner H, Golub RM, Fontanarosa PB. Data Sharing. JAMA. March 2016:1238. doi:10.1001/jama.2016.2420
- 7.Bauchner H, Fontanarosa PB. The Challenges of Sharing Data in an Era of Politicized Science. JAMA. December 2019:2290. doi:10.1001/jama.2019.19786