All posts by Jamie Strachan

Immunotherapies for cancer in the ICU

The first lecture of the day was given by the expert in the area Elie Azoulay.  He talked through immune therapies that are being used in cancer.

Immune therapy “boosts” the immune system and restores its ability to eradicate cancer cells.  There are loads of different types of immune therapy – but Azoulay focussed on the ones that are of relevance to intensivists – Adoptive Cell Transfer, encapsulating “CAR T-cells” and “checkpoint inhibitors”.

Cancer cells normally find ways to act on checkpoints (molecules on T Cells) to avoid being attacked by the immune system.  Checkpoint inhibitors, drugs like pembrolizumab and vivolumab [act on PD-1] or atezolizumab [acts on PD-L1] activate the immune system to get to work on tumours.  BUT the usual safeguards against autoimmunity within the body are also affected.  Other drugs that target CTLA-4 (such as ipilimumab used in melanoma)  act as a type of “off switch” on T Cells.  And they work in solid organ tumours – particularly in combination the oncology trial results are impressive… This paper is an overview of the field from a couple of years ago as quoted below:

There are lots of these drugs – how might you identify if your patient has received one? Well hopefully it will be abundantly clear from their treatment or oncologist – but they are all monclonal antibodies of course so end in -mab.  Heres a list:

The other type of treatment in this category then is Chimeric Antigen Receptor T Cells (CAR-T cells).  These are the patient’s own T Cells, apheresed, stimulated and expanded and then re-infused.

The treatments and trials of note are Tisagenlecuecel in the ELIANA trial for young people with refectory B Cell ALL and JULIET trial for high grade B Cell lymphoma and Axicabtagene cioleucel for relapsed B Cell lymphoma in the ZUMA-I trial.

The reason these second or third line cancer treatment matters for intensive care though is because of the serious adverse event rate.  All this immune system jiggery pokery comes at the cost of upsetting normal function and some 30 to 40% of patients will get some sort of complication:

So what will we need to do on ICU?

The lists of critical care support is quite long as theses patients can get multi organ failure requiring support! They range from ruling out infection (e.g. LP in neurotoxicity – is it CAR-T related or CNS infection/sepsis?) and admiting for close observation/monitoring, good symptom control/IV fluids through to oxygenation and ventilation for acute respiratory failure, vasopressors and shock treatment and even renal and cardiac support and monitoring.  There are specific treatments – steroids are the mainstay but blocking the cytokines responsible for the cytokine storm (for example with IL6 antagonists /  tacilizumab) and other rescue strategies.

Some of the complications are still not fully understood – for example neurotoxicity might be related to the parenchyma effect of CAR-T cells or might be a break down of the blood brain barrier, and earlier onset cytokine storm seems to lead to worse neurotoxicity – prompting some people to think there is a link.  But its still an area of research…

The current reality in many units is that CART therapy is bringing patients to ICU for reversible pathology, and because CAR T therapy is an exciting area, perhaps perhaps it will expand beyond its current remit in cancer to other conditions… So we need to be ready!

My favourite bit of Azoulays talk today was his patient information leaflet – enjoy!

Jamie

The PARTNER trial

The PARTNER trial was presented today (published over the summer in NEJM) which is the latest in the critical care community’s attempt to support families with loved ones in ICU.

We know that its a stressful time for families (and of course patients) and we think we could do better in communication with them, and support.

The family members who are involved in the discussion around care and end of life and limitation of treatment often suffer psychological morbidity

Could these outcomes for families be improved by “reengineering” the ICU team and up-skilling them? And interestingly, might that even extend to less burden of treatment for patients?

Thats what the partner trial set out to discover and Derek Angus presented the results this morning in Paris

At its heart PARTNER was a nurse driven emotional support and relationship building intervention

The key thrust of the intervention was around 3 things

  1. Protocolled pathway of family support
  2. Advanced communication skills training for staff
  3. Intensive implementation support of the pathway

It was a stepped wedge cluster RCT in 5 different ICUs  of differing sizes and case mix.

It didn’t show a difference in its primary outcome (HADS score) but it did improve how people felt – families AND nurses! Which is promising – but the real win was reduced length of stay for me, a relatively cheap intervention that saves money, sounds good huh!

Of note there was an apparent increase in ICU mortality, as some patients had treatment limited earlier – but that disappeared at later follow up.

If you are interested in the field its worth reading this study from Curtis et al which was similar but did show a difference in depressive symptoms in families later on… Why? not sure – perhaps just the play of chance??? Perhaps difference in the way the intervention was blanket applied?

Your roving reporter, JS

ESICM opening ceremony #LIVES2017

The ESICM meeting traditionally opens on the Sunday evening, with a plenary speech and ceremony.  This year was in Vienna so clearly classical music was going to be involved- A quartet of violins wading through the audience, with drum beats behind! (see this short periscope clip!)

There was a great talk on psychological safety from Amy Edmondson (her TED talk is viewable here) and Peter Suter the first ever president explained the history of ESICM (“ESICM 1982-2017: From pampers to maturity and excellence”).  Members can view these opening ceremony talks in full here.

All the past presidents of ESICM were present as to celebrates 35 years of the society.  They did a special jigsaw on the stage to celebrate!

 

Changing models of care in ICM? #LIVES2017

I am still not sure what the question is (?!), but this poll at the start of this session looked like tele-ICU didn’t answer it….

The first speaker was Charlie Corke from Australia, who talked about what it meant to him – “Failure to rescue in the wards: human factors and technology”.  He talked through the 2004 ACADEMIA study – this was a collaboration and comparison between the Intensive Care Society and Australia’s ANZICS group that showed “bad things happen before Intensive Care admission”.  The following year the (in)famous study of rapid response MET teams (the MERIT study) was published, which failed to find any effect on cardiac arrest, unplanned ICU admission or unexpected death from the activation of these teams.

He then seemed to be making a call to arms for remote monitoring, but didn’t seem to know of many of the recent advances is the field!  The audience helped him out – there are a lot of remote monitoring and tele-medicine advances in monitoring respiratory rate, but none quite at full clinical roll out stage yet… (for example http://www.oxehealth.com/ or even http://www.acupebble.com/)

Then Richard Beale took to the stage – High cost or cost saving? was the topic.  He recommended this JAMA paper.  It defines the tele-intensive care unit nicely as:

A tele-intensive care unit (ICU) is a promising technological approach designed to systematically alter processes of care that affect outcomes. Tele-ICU can be defined as the provision of care to critically ill patients by health care professionals located remotely. Tele-ICU clinicians use audio, video, and electronic links to assist bedside caregivers in monitoring patients, to oversee best practice adherence, and to help create and execute care plans. Tele-ICU programs have the potential to target processes that are associated with better outcomes, including shorter response times to alarms4 and abnormal laboratory values,5 more rapid initiation of life-saving therapies,6,7 and higher rates of adherence to critical care best practices.8

These systems seem to save money… So they are probably coming to a (large?!) unit near you soon.

Then my favourite talk of the session was from Marius Terblanche (follow him on twitter) who had spent a lot of his early consultant life implementing a tele-medicine system in Guys and St Thomas’s hospital in London.  He gave a refreshingly honest account of this, and recounted the problems he faced as he went along.

He ran through all the lessons he had learned, including simple things like the need to consider the “estate” – he found that background noise was a problem for cameras and microphones.  But the biggest problem the implementation faced was convincing people to change -disruption to job plans, ways of working etc.! Trying to create and convey a “sense of urgency” and need was tricky, he found that without an influential “guiding coalition” it was hard to move forward (not necessarily just powerful – an interesting distinction).  He admitted that without a clear vision to communicate, it is hard to convince people to undergo such big change and that he felt that he could have done that better.  He also thought that it was/would have been important to create short term wins with such a project, and also not to announce success too early.

Are you trying to do something similar and want to know more?  Well his recommended reading was not about tele-medicine or technology, but change management – and John Kotters 8 steps.

Overall an inspiring talk and a great debate at the end with audience pitching in.  Prof Bion raised the major challenge with tele-ICU – and our challenge to avoid as these systems become more widespread: