Tailored nutrition in and beyond the ICU T - intensive.org · post-ICU is an important focus as...

The future of critical care . . . . . . . . . . . . . . . . 5

AKI: is it inevitable? . . . . . . . . . . . . . 9

Vasospasm a “silent menace” . . . . . . . . . . . . . 10

Should everyone be in a trial? . . . . . . . . . . . . . . 18

Tailored nutrition in and beyond the ICU

T hroughout medicine, “one size does not fit all”, thus why should the same nutrition be given at all

stages of the continuum of critical illness? This will be the message of Paul Wischmeyer (Department of

Anesthesiology and Surgery, Duke Clinical Research Institute, Duke Uni-versity School of Medicine, Durham, NC, USA), who will take to the stage today to argue that we must tailor nu-trition during illness and recovery.

Professor Wischmeyer will spend a

significant amount of time discussing the Minnesota Starvation Study, a daring and pioneering exploration of the physiological and psychological impact of a calorie restricted diet.1 The study, led by Dr Ansel Keys and col-leagues at the University of Minneso-

ta, USA, restricted the diet of healthy individuals for an initial six-month period (1,800 kcal/day and ~0.8 g/kg/day of protein), before trialing what level of nutrition was needed to bring them back to a healthy weight.

Wednesday 21 March 2018 Day 2The official daily newsletter of the 38th ISICEM

Continued on page 2

Delegates of ISICEM 2018 fill the Henry Le Bœuf

auditorium during Tuesday’s opening session.

2 ISICEM News Wednesday 21 March 2018 Issue 2

Remarkably, it was determined that around 4,000 calories a day (at least) would be needed to rebuild the bodies of these “starved” men, which was a striking lesson to learn.2 Even more striking was that the study was actually undertaken more than 70 years ago, in 1945.

The study was born in the wake of World War II, during which time a new threat to the lives of the many was being realized: a lack of food.2 With the USA and other nations desperate to know just how much nu-trition would be needed to recover its inhabitants from a state of starvation, the Minnesota study’s outcomes were groundbreaking. Indeed, the men included in the study, 36 in total, took an average of six months to two years to regain a normal weight, and many reported having an unquenchable hunger for months after the trial end-ed, no matter how much they ate.2 Even worse, some men were driven to states of severe mental distress.2

Importantly, after rehabilitation was complete, no appreciable long-term effects were noted.

Crucially, the lessons learned from the Minnesota study are very

applicable to the nutritional climate of today’s ICUs. “I think one key finding was that these men had lost similar weight to that of many of our ICU patients,” Professor Wischmeyer told ISICEM News, adding: “ICU patient data has shown that caloric need later in critical illness (after the acute phase), during and after the second week post-injury, is an average of ≈4120 kcal/day or 59 kcal/kg/day, nearly identical to the 4000 kcal/day Dr Keys demonstrated to be required to recover from starvation in the young subjects in Minnesota.

“This demonstrates that in the later recovery phase of critical illness, the body experiences a massive increase in metabolic needs, with TEE [total energy expenditure] increas-ing as much as ≈1.7-fold above REE [resting energy expenditure]. With the onset of early ICU mobility pro-grams, this may increase further as activity increases.”

Bearing this in mind, Professor Wischmeyer was keen to stress that calories and protein in many present-day ICUs are actually fall-ing short of the starvation study. “This must be improved!”

Indeed, he relayed that the International Nutrition Survey, conducted regularly by the Cana-dian Critical Care Nutrition Group (www.criticalcarenutrition.com), has revealed that the average calories delivered in an ICU over the first 12 days is 1,034 kcals, along with 47 g of protein. This is a period far longer than the first 1-3 days of the acute phase, where hypocaloric feeding (with adequate protein) may make physiologic sense.2

As Professor Wischmeyer wrote in his recent paper on tailored nutrition in critical illness,2 such data confirm that ICU patients worldwide average far less energy and protein than in the Minnesota study – an investigation that would likely be never repeated today due to ethical reasons.

Could this be partly to blame for increasing numbers of ICU survivors who ultimately become “victims” of post-ICU syndrome (PICS)? “We must ask: are we creating survivors, or are we creating victims from the starva-tion we allow to occur daily in our ICUs?” he said.

Indeed, the topic of nutrition post-ICU is an important focus as well, continued Professor Wischmeyer. “This is a period we must [encourage]

much more research and clinical fo-cus,” he said. “How we feed post-ICU is just as important as how we feed in the ICU. Plus, catabolism, hyperme-tabolism, and anabolic resistance is known to persist for months to years after the ICU, and so we should real-ize that recovery and nutrition must continue for months to years.

“We actually are finding there are some similarities in later recovery between healthy starvation survivors’ caloric needs, as discussed above, and ICU patients’ caloric needs. This increased protein need and kcal need likely persists as in the Minne-sota [study].”

Tailoring nutrition“I think we do need to have a ‘personalized-medicine’ approach to

our feeding strategy,” noted Profes-sor Wischmeyer, before diving into the specifics of tailored nutrition. Malnourished patients, he said, are at much greater risk for mortality, or at least poor functional recovery from critical illness. Indeed, every unit decrease in BMI of patients in the ICU is associated with a 7% decrease in the likelihood of functional recovery, he added.

“To illustrate the magnitude of this effect, a woman who is 5’4” and 130 pounds (BMI=22.0) would have ~60% reduced likelihood of post-ICU functional recovery versus a woman of same height who weighs 175 pounds (BMI=30.0),” said Professor Wischmeyer. “Our recent TOP-UP pilot trial of early nutrition delivery to higher nutrition-risk [groups] (BMI<25 or >35) … showed a strong trend for early nutrition delivery via supplemen-tal parenteral nutrition (SPN) added to enteral nutrition (EN), improving hospital discharge functional Quality of life status measured via the Barthel Index (BI) versus EN alone (p<0.08).

“Observed overall improvement in BI (14.6) was greater than established clinically important difference for BI (10 points). Signal of benefit on func-tional outcome by BI was much larger in patients with a BMI<25 (+18.5) versus BMI>35 subjects (+11), with a

Individualized nutrition 100 Hall Wednesday 13:45

ISICEM NewsPublishing and ProductionMediFore Limited

Symposium ChairmanJean-Louis Vincent

Editor-in-ChiefPeter Stevenson

EditorsRysia BurmiczTatum AndersonBecky McCallJo Waters

DesignPeter Williams

Industry Liaison ManagerLorraine Tighe

Head Office51 Fox Hill, London, SE19 2XEUnited KingdomTelephone: +44 (0) 20 8771 [email protected] © 2018: Université Libre de Bruxelles. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, transmitted in any form or by any other means, electronic, mechanical, photocopying, recording or otherwise without prior permission in writing of ISICEM. The content of ISICEM News does not necessarily reflect the opinion of the ISICEM 2018 Symposium Chairman, the ISICEM Scientific Advisors or Collaborators.

Continued on page 4

“In the later recovery phase of critical illness, the body experiences a massive increase in metabolic needs, with total energy expenditure increasing as much as ≈1.7-fold above resting energy expenditure.”Paul Wischmeyer

Tailored nutrition in and beyond the ICUContinued from page 1


signal of improved hospital mortality only observed in BMI<25 group.”

Putting forward some rough numbers as to what might be an appropriate caloric/protein intake in the different phases of critical illness, Professor Wischmeyer commented: “Data is beginning to show in well-nourished patients that keeping protein at 0.8-1.0 g/kg/day up to day three may be reasonable, and then increasing to 1.5-2.0 g/kg/day after day three.”

He added that feeding at <18 kcal/kg/day for day 1-4 in well-nourished patients seems rational, increasing to 20-25 kcal/kg/day during day 4-7, and >25 kcal/kg/day after day seven.

Personal experienceDuring his presentation, Professor Wischmeyer will also convey personal experiences, having been admitted to the ICU several times throughout his life. “I have found it takes around two years to meaningfully recover from a major illness or ICU stay,” he said, adding the perspectives he gleaned from a patient, who said that “dis-charge is a bit like going off a cliff, in terms of support and guidance.”

Professor Wischmeyer now takes more than 10 supplements every day to recover from his last ICU stay (now over two years ago), and prepares for the “inevitable” next surgery and ICU stay. This ‘Wischmeyer ICU nutrition recovery list’ (Figure) has gathered much interest: “I am asked for this many times a year by physicians and patients,” he said, adding: “It includes eating right every day and exercising 4-5 days a week – who will teach our

patients to do that?”Turning to the future, Professor

Wischmeyer touched on several fac-tors that might be pivotal in improving tailored nutrition for critically-ill patients. First, he said, would be more studies of personalized nutrition targeted to malnour-ished patients: “We have proposed a follow-up to TOP-UP, named SPiNER, to look at this,” he said. “We also need com-bined nutrition and exercise trials (like Dr Heyland’s NEXIS trial, which is ongoing), and definitive trials of protein dosing of course. Finally, post-ICU discharge trials are needed too.”

Tools for better assessment of nu-tritional demand, and receipt, are also particularly intriguing. For example, new user-friendly metabolic carts that

can actually be used in ICUs worldwide, as well as new technolo-gies such as muscle glycogen ultrasound, which could predict the transition from the acute phase to the chronic/recovery phase. “Furthermore, exhaled C12/C13 breath testing at the bedside is showing promise to measure over-/under-feeding, and determine if the

nutrients delivered are being utilized,” said Professor Wischmeyer.

Finally, nutritional agents should

also be under more investigation, he added: “Agents I think we need more studies of include betablockers and testosterone, to reduce persistent catabolism and hypermetabolism (like the burn world uses).

“Large trials of Vitamin D to re-duce mortality are ongoing, to further support the mortality reductions seen from Dr Amrein’s paper in JAMA – showing Vitamin D can reduce mortality in severely deficient patients. Finally, with a large paper in Nature having showed that a symbiotic (pre-/probiotic combination) approach can reduce sepsis and infection in >4000 term infants in India, there is great promise for microbiome-guided probi-otic therapy to improve outcomes. My lab is working on this now.”

References1. Keys A, Brozek J, Henschel A, Mickelsen O,

Taylor HL. The Biology of Human Starvation. Vols I–II. Minneapolis: University of Minnesota Press; 1950.

2. Wischmeyer PE. Tailoring nutrition therapy to illness and recovery. Critical Care 2017, 21(Suppl 3):316

Individualized nutrition 100 Hall Wednesday 13:45

“I have found it takes around two years to meaningfully recover from a major illness or ICU stay.”Paul Wischmeyer

Tailored nutrition in and beyond the ICUContinued from page 2

“We must ask: are we creating survivors, or are we creating victims from the starvation we allow to occur daily in our ICUs?”Paul Wischmeyer

Issue 2 Wednesday 21 March 2018 ISICEM News 5

The future of critical care

C raig M Coopersmith is Director of the Sur-gical/Transplant ICU and Professor of Sur-gery at Emory University, Atlanta, GA, USA.

He will be giving a plenary lecture this afternoon on the future of critical care, focusing on the near-, medium- and long-term advancements that may find their way into practice in the coming years.

In conversation with ISICEM News, he noted that in the next one to five years, existing ideas that should gain traction include the better imple-mentation of existing data, early mobilization, decreased burnout, novel trial designs, and the use of nurse practitioners (NPs) and physician assistants (PAs) in the ICU.

First touching upon NPs and PAs, Professor Cooper added: “In the United States, utiliza-tion of advance practice practitioners (APPs; nurse practitioners and physician assistants) in the ICU is now widespread. I will be giving a talk on this, and including our local experi-ence, where we have 140 APPs in the ICU at Emory, and every single ICU has [year-round] coverage. APPs practicing to the full extent of their license can provide the highest possible care for patients, and are associated with very posi-tive outcomes.”

Turning to novel trial designs, Professor Coop-ersmith stressed that for a long time now, we have relied on the two-armed prospective randomized trial as a gold standard. Assuredly, this study design maintains significant utility, he said, but moving forward, adaptive trials represent a more efficient way of testing multiple interventions simultane-ously. “Furthermore, they have the advantage that treatments that appear efficacious can be acceler-ated, while study arms that appear ineffective can be stopped earlier,” he said.

In addition, telemedicine is also taking shape. “Telemedicine is now used in 16% of ICUs in the United States, and that percentage grows annu-ally,” he said. “Increasing evidence demonstrates better outcomes with telemedicine, and I believe this is a key solution moving towards addressing physician shortages.

“I believe the Emory ‘night into day’ pilot, where we provide telemedicine services from Australia (12 hours away, so ICU providers are working in the daytime when it is night in Atlanta) is an excit-ing vision of what the future might look like, and removes a key disincentive of working in the ICU: nighttime hours.”

There are challenges to telemedicine, however: “A lack of reimbursement is still an important issue,” continued Professor Coopersmith. “How-ever, a strong business case is being developed for telemedicine reimbursement in light of data show-ing it improves outcomes. I am hopeful that as the concept of telemedicine – both inside and outside the ICU – is shown to be effective clinically and cost-wise, that it will eventually be reimbursed.”

Other short-term goals include wider adop-tion of the Surviving Sepsis Campaign (SSC). As Professor Coopersmith relayed, higher compliance with the SSC bundles in aggregate is associated with improved survival. In addition, as the SSC

guidelines are a compendium of evidence-based recommendations for sepsis – with proven benefits for outcomes – following them should also lead to improved outcomes.

Moving on to the potential of early mobilization, he continued: “I believe that early mobilization will be proven to be of significant importance. While the evidence behind its efficacy on long-term out-comes is still emerging, I do believe that, in time, we will ultimately have a robust literature support-ing the usage of early mobilization. Despite this, many (perhaps most) centers still have concerns about early mobilization, and adoption is moving slower than one might hope.”

Professor Coopersmith then shared his projec-tions for the next 5-15 years, focusing on aspects that are plausible, but not-yet realized in the current ICU climate. These include personalized medicine, endotyping, immunotherapy, as well as and restora-tion of diversity (and prevention of virulence) in the microbiome.

Exploring personal-ized medicine in more detail, he commented: “Although we try to individualize elements of care as much as practi-cable, we currently treat patients very similarly even if their underly-ing host response and pathophysiology is quite different. As we under-stand more on a mechanistic level, and can rapidly determine how an individual patient will respond (and even predict that they will decompensate before it happens), we will be able to tailor therapy to the individual patient to give the treatment that is maximally efficacious to them.”

During his plenary lecture, Professor Cooper-smith will delve deeper into several fascinating therapeutic horizons, including the role of T-cell signaling and co-inhibitory receptor blockade in

sepsis. Delegates will have to attend to learn more, but he did share some other intriguing concepts with ISICEM News. For instance, the microbiome is a particularly burgeoning area of study. “There has been an explosion of data on the microbiome recently,” said Professor Coopersmith.

“It stands to reason that if we have 40-trillion microbes living within our body (the same number as our own cells) then, evolutionarily, they must play a critical role. The literature is now replete with associative studies suggesting the importance of the microbiome and how it is profoundly altered to turn into the pathobiome in critical illness. While our understanding of how to manipulate the mi-crobiome is still relatively nascent, preliminary data suggest this may be a key target for therapy in the future in the ICU.”

In the longer-term, say 15-30 years in the future, Professor Coopersmith foresees a number of ad-vancements that would offer a real boon for critical care. These could include the ability to regenerate or reanimate failing or hibernating organs, achieve

instantaneous assess-ment of the immune system, microbiome or other compartments, and finally, predict decompensation before it starts.

Offering some conclusions, he said: “The future of critical care is incredibly bright.

Someone working in the ICU 30 years ago would not be able to recognize today’s ICU. Many of us now take for granted that we have continuous renal replacement, that we have medical records available to us at the touch of the button, that we have access to the entire literature on demand with us on rounds, etc. All of these were Science fiction when I did my critical care fellowship. As technol-ogy catches up with the human imagination, the advances we will see in critical care will be nothing short of extraordinary.”

The future of critical care Silver Hall Wednesday 17:35

“Telemedicine is now used in 16% of ICUs in the United States, and that percentage grows annually.”Craig M Coopersmith

“As technology catches up with the human imagination, the advances we will see in critical care will be nothing short of extraordinary.”Craig M Coopersmith


Do new attending physicians present an increased mortality risk?

T he impact of visiting consultants on an ICU team will be covered on Thursday morn-ing by Tony Whitehouse, a consultant in

intensive care at the Queen Elizabeth Hospital in Birmingham, the largest intensive care department in the UK.

Dr Whitehouse will be discussing the results of a paper that may have implications for ICU teams worldwide1. His team looked at what would hap-pen if their own highly-trained consultants visited different ICU specialties to update themselves, as part of a hospital reorganization. “We started writ-ing the rotas so that two of those consultants in a given specialty moved out to another area,” he told ISICEM News. “So, we’d have a home team who would normally work in one intensive care, with a couple of visitors who had come from another intensive care.

When they looked at the results after five years, they discovered something rather surprising. “Being a visitor made a difference,” he said. “We demonstrated that in intensive care, there is a net increase in mortality when a visiting consultant cov-ers the ICU.”

How to account for the rise may be less obvious, but Dr Whitehouse has a theory: “I generally don’t think that it’s about the doctor who stands at the end of the bed. Their knowledge base, in general, is usually very, very good.”

He added: “However, the reason I think that the mortality was higher was that visiting consultants were ad-mitting sicker patients some of whom had no chance of survival anyway. So, the death appears on our ICU ‘books’, rather than staying on the ward.”

Dr Whitehouse, whose sub-specialty is in liver transplantation, stressed that venturing into another specialty ICU can also present challenges: “When I go to the neuro-intensive care I don’t nec-essarily know who those staff are,” he said. “So, if I am invited to see a patient on the ward who is sick,

and I don’t normally do that specialty, I don’t have that dialogue with the referring clinicians.” In other words, he may not be able to take advantage of the network to assess the likelihood that a patient is suitable for the ICU.

“Somebody who is more familiar with the situation may have a dialogue with the referrers and discuss whether you should be admitting the

patient,” he continued. “The fact that they haven’t built a relationship up and know their colleagues, is nothing to do with their knowledge, and nothing to do with their abilities.”

The ramifications of taking on a visiting consult-ant are far-reaching, Dr Whitehouse underlined: “When I work with nurses and trainee doctors on a fairly regular basis, I probably use a form of shorthand to relay exactly how I want things done. A visitor may have to give more precise instructions to get the same thing across.”

He added that the team may also feel more comfortable challenging decisions with someone they are more familiar with. “I think that the dialogue with the nurses means that if I wanted to do something they consider to be not routine, they would be empowered to say, ‘do you really want to do that?’. If I can then say ‘Yes, I think you should do that because of a particular reason’, we have entered into a dialogue that results in them being comfortable in delivering care. It’s also empower-ing for me: if I miss something or get something wrong, hopefully I’m approachable enough for them to say so.”

Crucially, this may not be the case with a new consultant. “If I’m visiting somewhere else, the staff might be more likely to think, ‘Well, if that’s what Dr Whitehouse thinks is right, we had better do it,’ and they follow the instructions, come what may.”

But, he added, these kinds of issues will fade with time, as new ICU staff settle in, and relation-ships improve. “Clearly there comes a point where you have to be an independent practitioner on an intensive care and build those relationships as you see fit,” said Dr Whitehouse.

A solution may involve more oversight from experienced consultants, he continued: “That has a resource implication, I guess, but the most obvi-ous thing you can do is to implement this, and see whether it makes a difference.”

References1. Whitehouse T, et al. The Association Between Visiting Intensivists

and ICU Outcomes. Crit Care Med. 2017;45(6):949-955.

Making a better ICU team 400 Hall Thursday 08:00

“We demonstrated that in intensive care, there is a net increase in mortality when a visiting consultant covers the ICU.”Tony Whitehouse


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As the 2018 edition of the International

Symposium on Intensive Care and Emer-

gency Medicine opens its doors, its with

great pleasure that we welcome you to

our 38th year.

We hope to see you all in the sprawling Henry

Le Bœuf auditorium this morning to witness the

opening session: a dazzling display of topics that

will set the tone for the rest of the four-day pro-

gram. It begins with a report from the Round Table

conference on metabolic care, delivered by Kenneth

Christopher and Jan Wernerman, before Kevin

Dhaliwal takes to the podium to show us amazing

and surprising pictures of the lung at the bedside.

We will also hear about the contributions from

military medicine, by Michael Reade. A lot to learn!

This year, Tom van der Poll will be invited to deliver

the Max Harry Weil lecture, a hotly anticipated ex-

ploration of the future of sepsis therapies, particu-

larly the targeting of selected patient populations.

Other “hot topics” include clinical trials on

interferon-beta in ARDS, selepressin in septic shock,

inhaled antibiotics in severe lung infections, alkaline

phosphatase in sepsis, a re-exploration of bicarbo-

nate administration in metabolic acidosis, the use of

pupillometry, and the long-term administration of

albumin, just to name a few. And of course, there will

be debates about fluid requirements, types of intrave-

nous fluids, corticosteroids in septic shock, and so on.

What’s then still to come is too much to even

begin to describe, but rest assured that over four

days, 12 rooms and hundreds of individual sessions,

there will be plenty to choose from. Round tables,

tutorials, workshops, pro-con debates, meet the ex-

perts sessions and clinical vignettes all sit alongside

a roster of standard presentations, and of course

our selection of esteemed plenary lectures.

As always, industry is a main driver of how this

meeting is possible, and I would like to sincerely

thank our sponsors for their continued support,

especially in this new regulatory era.

I wish you a truly enlightening ISICEM 2018, and

an enjoyable stay in the great city of Brussels. Don’t

forget to join us at the end of the sessions this even-

ing for the poster discussion, with hors d’oeuvres

and drinks, held in the scientific exhibition area.

See you next year!Jean-Louis Vincent

ISICEM Chairman;

Professor of Intensive Care Medicine, Université

Libre de Bruxelles;

Dept of Intensive Care, Erasme University Hospital

Tuesday 20 March 2018 Day 1

The official daily newsletter of the 38th ISICEM

Experience from the 2016 Nice attack . . . . . . . 5

The future of hemodynamic monitoring . . . . 8

Who should staff the ICU at night? . . . . . . 10

“Close the lungs

and keep them rested!” . . . . . . . 14

Welcome to Brussels!

The future of critical care . . . . . . . . . . . . . . . . 5

AKI: is it inevitable? . . . . . . . . . . . . . 9

Vasospasm a “silent menace” . . . . . . . . . . . . . 10

Should everyone be in a trial? . . . . . . . . . . . . . . 18

Tailored nutrition in and beyond the ICU

T hroughout medicine, “one

size does not fit all”, thus

why should the same

nutrition be given at all

stages of the continuum of critical

illness? This will be the message of

Paul Wischmeyer (Department of

Anesthesiology and Surgery, Duke

Clinical Research Institute, Duke Uni-

versity School of Medicine, Durham,

NC, USA), who will take to the stage

today to argue that we must tailor nu-

trition during illness and recovery.

Professor Wischmeyer will spend a

significant amount of time discussing

the Minnesota Starvation Study, a

daring and pioneering exploration of

the physiological and psychological

impact of a calorie restricted diet.1 The

study, led by Dr Ansel Keys and col-

leagues at the University of Minneso-

ta, USA, restricted the diet of healthy

individuals for an initial six-month

period (1,800 kcal/day and ~0.8 g/kg/

day of protein), before trialing what

level of nutrition was needed to bring

them back to a healthy weight.

Wednesday 21 March 2018 Day 2The official daily newsletter of the 38th ISICEM

Continued on page 2

Delegates of ISICEM 2018

fill the Henry Le Bœuf

auditorium during Tuesday’s

opening session.


Preventing renal failure Tent Wednesday 13:45

Acute kidney injury. Not an inevitability?

A cute kidney injury (AKI) con-tinues to challenge physicians, researchers and patients,

and to date, there is no efficient treatment, delegates will hear from John Kellum, Professor of Critical Care Medicine at the University of Pittsburgh, PA, USA during a session dedicated to preventing renal failure this afternoon.

Professor Kellum will speak about the potential that lies in upcoming studies of patients at high risk for AKI1: “A new study might just change the way we approach this seemingly intractable problem,” he said in con-versation with ISICEM News.

Possibly the most cutting-edge study2 to date evaluates the efficacy of Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers. “This study shows that a biomarker-guided personalized-medicine approach to preventing AKI is feasible,” said Professor Kellum. “The use of biomarkers to identify patients who are at highest risk, and selecting them for interventions, is far more likely to be effective.”

Professor Kellum will also look at the use of computer decision sup-port systems for AKI3.

Importantly, he will also discuss a pair of studies just published in NEJM, comparing balanced crystalloids and saline in critically ill4 and noncritically ill patients5 cared for outside the ICU. While both are used for intravenous fluid administration in critically ill adults, it is not known which results in better clinical outcomes. “These studies represent the opposite para-

digm (not personalized) but an effect seen across the entire population,” explained Professor Kellum.

“The traditional approach has been to use fluid resuscitation and give them more fluid when kidney function falters – when in fact the opposite may be what’s needed,” he said. “Restricting the use of nephro-

toxins and using more careful titration of hemodynamics in this group may be of particular interest.”

Until now, there have been signifi-cant challenges in the treatment of patients at risk of acute kidney injury, said Professor Kellum. “There has

been a lack of precision in defining AKI subtypes because AKI is not a single disease but a collection of syn-dromes,” he explained. In addition, those patients at highest risk haven’t always been selected. “And there has been a failure to move past the traditional ‘renal blood flow’ concept of AKI mechanisms,” he said. “Fortu-nately, all of these are giving way.”

Professor Kellum said he’d like to see a whole range of studies to look at the prevention of AKI including the use of biomarkers to identify high-risk patients to increase effect sizes and a focus on specific types of AKI (sepsis, surgery, drugs) for prevention protocols. “Otherwise they must be very large studies to tease out small effect sizes (like the studies in NEJM),” he concluded.

References

1. Kellum, J. A. Acute kidney injury: AKI: the myth of inevitability is finally shattered. Nat Rev Nephrol 2017, 13(3), 140–141.

2. Meersch, M et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identi-fied by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Medicine, 2017; 43: 1551

3. Al-Jaghbeer, M et al. Clinical Decision Sup-port for In-Hospital AKI. J Am Soc Nephrol. 2018 Feb;29(2):654-660.

4. Semler, MW et al. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med 2018; 378:829-839

5. Self WH, Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med 2018; 378:819-828

“The traditional approach has been to use fluid resuscitation and give them more fluid when kidney function falters – when in fact the opposite may be what’s needed.”John Kellum

“The use of biomarkers to identify patients who are at highest risk, and selecting them for interventions, is far more likely to be effective.”John Kellum


Tackling the silent menace of vasospasm

N ino Stocchetti is Professor of Anesthesia and Intensive Care at the Department of Physi-

opathology and Transplant at Milan University, Italy. He has spent the last 40 years dealing with brain damage, and during this morning’s symposium on intracerebral bleeding, he will be bringing his considerable expertise on the threat of vasospasm.

ISICEM News caught up with Pro-fessor Stocchetti to find out more.

How has the treatment of intracerebral bleeding changed since you began practicing?In the beginning, the whole field was managed by neurosurgeons: they could save lives by promptly diagnosing and removing intracranial bleedings. Very often, neurosurgeons took responsibility not just for doing surgery: they also quickly cannulated arteries for performing angiography, read and interpreted the results, and so on. In many institutions, especially in the USA, they also managed their patients in the newly-created Intensive Care Units.

Decades later, it became evident that high-quality monitoring and specialized care of critically injured patients was necessary. This required competences not directly part of surgical or anesthesiology training, thus a whole new body of knowledge accumulated, and doctors specialized in intensive care took direct respon-sibility in the acute management of severe cases.

Somehow neuro-intensive care has been built around the challenges of traumatic lesions to the brain. Then the lessons we have learned have been applied to other pathologies, like subarachnoid hemorrhage (SAH).

What will you be covering in your talk?Vasospasm after SAH remains a heavy burden. Can we detect it more quickly and efficient-ly? And can we use more effective treatments (such as continuous intra-arterial vasodilator infusion or me-chanical dilation of the ves-sel’s lumen)? It’s important to say that I am proposing questions rather than announcing miraculous weapons and strategies. In fact, I believe we are making progress towards earlier vasospasm diagnosis, and perhaps potential new therapies. Everything, however, requires a lot

of research and confirmation. In other words, if we have to fight (and we must) against vasospasm, we are very far from winning.

Tell us more about subarachnoid hemorrhageSAH, usually due to the rupture of an intracranial vascular malformation (i.e. an aneurysm) is a life-threatening event. It is estimated that up to one third of cases fail to reach the hospital

alive. The aneurysm can re-bleed, and kill the patient, if it is not quickly identified and repaired. Therefore, the immediate goals for patients suffering from SAH are: to keep them alive, to diagnose the aneurysm (where it is

located in the brain, how it is shaped) and to fix it, by endovascular proce-dures or by neurosurgical clipping.

All these goals require a well-coordinated team, including skilled anesthesiologists/intensivists, accurate imaging specialists, skilled inter-ventional neuro-radiologists and

extremely specialized neuro-surgeons.

What are the drivers of vasospasm?Unfortunately, even in cases successfully treated, the problems are not over once the aneurysm has been

closed. Days after the initial bleeding, a new enemy may appear: vasospasm. Vasospasm is an inflammatory disease of the intracranial vessels which reduces the caliber of major intrac-ranial vessels, and therefore lowers

the amount of blood flowing into the brain vasculature. If vasospasm is severe, the vessels become so small that a decent circulation can’t be guaranteed, and parts of the brain do not receive the necessary delivery of oxygen and substrates.

This brain ischemia may irrevers-ibly damage substantial regions of the brain, causing permanent deficits in survivors, but even killing the most severe cases.

An especially unpleasant feature of vasospasm is that it is a late compli-cation: once the patient and his/her family are relaxing because the aneu-rysm has been closed, and everything seems going in the right direction, then a new disaster may materialize, and all progress could be jeopardized.

What other issues should be addressed with regards to vasospasm?More effective methods for early diagnosis and more effective therapies would be, of course, very welcome. Unfortunately, we are, at the mo-ment, not adequately equipped for restoring normal brain circulation when vasospasm is particularly ag-gressive, as in the case with diffuse and persistent narrowing. Efforts are

mainly focused on early vasospasm recognition.

Do you perceive any risks?There is another side of the coin. The risk of over-diagnosis and over-treatment is particularly

insidious. Vasospasm is very frequent after SAH, in the order of two pa-tients for every three. In half of these cases, fortunately, it doesn’t affect brain integrity. As such it is a threat worth monitoring, but it doesn’t require aggressive treatment. On the contrary, patients with impending brain ischemia do require all our effort for preserving vital brain tissue.

How should the risks be mitigated?Missing a severe vasospasm may induce devastating ischemic damage. Therefore we need a careful iden-tification of vasospam and prompt interventions. A broader identification of cases with vasospasm should distin-guish who requires active interven-tions, and who do not. Otherwise we may end-up with unnecessary therapies and unjustified side effects.

Intracerebral bleeding Tent Wednesday 08:00

“Vasospasm after SAH remains a heavy burden. Can we detect it more quickly and efficiently??”Nino Stocchetti

“… if we have to fight (and we must) against vasospasm, we are very far from winning.”Nino Stocchetti



or intensive

Ultra-short-acting beta blockers could play important role in minimizing decatecholaminization

During yesterday’s Amomed-sponsored symposium ‘Decatecholaminization

What’s new?’, Matthias Heringlake, Professor of Anesthesiology at the University of Lübeck, Germany and Johann Knotzer, Head of the Department of Anesthesiology at Hospital Wels-Grieskirchen, Aus-tria, spoke about the role of ultra-short-acting beta blockers in sepsis, and after cardiac surgery.

Managing septic shock remains a significant therapeutic challenge. Ultra-short-acting beta blockers can effectively control the heart rate and may have other significant non-cardiac benefits, the ISICEM audience heard.

Introducing the sym-posium was session chair, Mervyn Singer, Professor of Intensive Care Medicine at University College London, UK. Professor Singer noted that although norepinephrine is the standard treatment for low blood pressure in septic shock, it is associated with multiple negative effects too. These include tachyar-rhythmias, digital ischemia, immunosuppression, stimula-tion of bacterial growth and virulence, and increases in myocardial stress, oxygen consumption and damage. Mortal-ity rises with norepinephrine dose and this may not be simply related to illness severity.

Professor Singer said: “I’m a believer – and there is quite a lot of pre-clinical and some clinical

evidence that perhaps we need a little bit of sympathetic stimula-tion in our lives, but too much of a good thing becomes bad, and unfortunately once a patient becomes ill we then ply them with even more stimulation in the form of catecholamines.”

“Alternatives include vasopres-sin, but the clinical trials conducted so far have not shown any differ-ence in outcomes, although a recent post-hoc analysis of the VASST trial1 in Canada did suggest benefits in hypotensive patients not meeting the Sepsis-3 shock criteria,” said Professor Singer.

“The challenge is to find a bio-

logical phenotype that can identify those patients who will benefit from the drug. When it comes to using beta-blockers for these patients, the single-center trial from Morelli et al. in patients with resistant septic shock showed that esmolol was effective in reducing heart rate to target levels without an increase in adverse outcomes compared to standard treatment, and that out-comes, including time on vasopres-sors and mortality, were improved.2

“As a consequence, the UK Department of Health has funded a multicenter study called STRESS-L, using landiolol to treat patients in septic shock, which is now starting

to recruit,” said Profes-sor Singer. “Alternatives include vasopressin, but the clinical trials conducted so far have not shown any difference in outcomes, although the recent VANCS trial3 in Canada did find some benefits in a subgroup of patients.” This trial was discussed in greater detail by Dr Knotzer during the session.

Dr Knotzer addressed the audience about catecholamine toxicity, ex-plaining that, to avoid this, norepinephrine shouldn’t

be given at high doses, nor for long periods of time.

Speaking to ISICEM News ahead of the session, Dr Knotzer said the severity and duration of hypotension in cardiac anesthesia is associated with a negative outcome:

“Catecholaminergic vasopressors may induce adverse cardiac events. We need to think about the nega-tive side effects when using catecho-lamines and consider alternatives – one possibility being vasopressin.”

Vasopressin works in the endothelium mainly through VI: “Relative vasopressin deficiency backs up the rationale for early-phase combinations of vasopres-sin and norepinephrine in cardiac surgery patients,” said Dr Knotzer. “In the presence of constant mean arterial pressure, norepinephrine doses may be minimized.”

The VANCS trial3, published in 2017, investigated early applica-tion of vasopressin in hypotensive cardiac surgery patients. This was a randomized double-blind controlled trial with 330 patients present-ing hypotension following heart surgery. Severe hypotension was defined as mean arterial pressure <65 mmHg and a cardiac index of >2.2 l/min/m2. Half of the patients were randomly assigned to receive either first-line vasopressin (0.01 to 0.06 IU/min), and the other half first-line norepinephrine (10 to 60 μg/min). The primary endpoint was a combination of mortality and severe complications.

“The study showed that acute kidney failure and atrial fibrillation occur significantly more often in norepinephrine patients than vaso-pressin patients (49% vs 32% [p = 0.0014]),” Dr Knotzer explained. VANCS also found a significantly lower rate of atrial fibrillation in the vasopressin group

“Despite [the fact that] we don’t have the data yet for landiolol’s effectiveness in sepsis patients, it is not unlikely that it will be even more effective than esmolol since it has less negative effect on blood pressure.”Matthias Heringlake


(63.8% vs 82.1%; p = 0.0004) and shorter mean length of hospital stay (10 vs 13 days; p=0.0016).

“The VANCS trial is a promis-ing and very interesting trial, with good results,” said Dr Knotzer. “We know that vasopressin has a positive effect in cardiac surgery patients according to a decrease in atrial fibrillation and in renal replacement therapy. Furthermore, in the VANCS trial, vasopres-sin was tested as a verum against norepinephrine, and not on top of norepinephrine. However, no ben-efit in outcome was detected. The door is open for a large randomized controlled trial to show a mortal-ity benefit.”

To sum up, he said severity and duration of hypotension is associated with a negative outcome, and catecholaminergic drugs may induce cardiac events. Vasopressin is an alternative vasopressor, but there are still open questions on mortality, benefit, dosage, time point and the right patients.

In his talk, Professor Heringlake focused on lan-diolol, which acts as a highly cardio-selective ultra-short-acting beta blocker. Used as an anti-arrhythmic agent, it has shown it can achieve rapid and reversible heart rate reduction with minor effects on blood pressure.

Landiolol has been available in Europe since July 2017 but has been used in Japan for 15 years in the prevention and treatment of 3.5-million atrial fibrillation patients following cardiac surgery or intensive care. Postoperative atrial fibrillation develops in 30 to 50% of cardiac patients following coronary

artery bypass grafting, valvular surgery or other interventions and is associated with a significant increase in post-operative morbidity and mortality.

“Landiolol is particularly effec-tive for this treatment, as pointed out by several recent meta-analyses; a feature possibly related to its high β-1 cardioselectivity,” said Profes-sor Heringlake.

He added that one of the main

advantages of using landiolol is that it has only minimal effects on blood pressure, even in patients who are hemodynamically compromised, and can be used to titrate the heart rate and optimize stroke volume – an important physiological regulator.

“Despite [the fact that] we don’t have the data yet for landiolol’s effectiveness in sepsis patients, it is not unlikely that it will be even more effective than esmolol since it has less negative effect on blood pressure,” he said. “Additionally, based on the experience in patients undergoing cardiac surgery, and in patients with heart failure, landiolol may be used to prevent atrial fibrillation also in patients presenting with sepsis. This, however, also needs to be shown in future trials.”

Professor Heringlake summed up his talk by relaying that septic shock leads to vascular hyper responsiveness and myocardial dysfunction and said that increased sympathetic tone and high doses of catecholamines may perpetuate sys-temic inflammation and increases mortality. He said vasopressin used in septic shock restores vascular tone, avoids catecholamine toxicity, ameliorates AKI and may be associ-ated with reduced mortality.

“Beta-blocking agents (and avoidance of classical catechola-mines) may be useful in septic cir-culatory failure – beyond prevention of atrial fibrillation,“ said Profes-sor Heringlake.

“Stroke volume optimization improves visceral perfusion, and other benefits include re-duced inflammation, and improved hemodynam-ics and outcomes during septic shock.”

References

1. Russell JA, Lee T, Singer J, et al. Vasopressin and Septic Shock Trial (VASST) Group. The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience. Crit Care Med. 2017;45:940–8.

2. Morelli A, Ertmer C and Westphal M. Effect of heart rate control with esmolol in hemo-dynamic and clinical outcome in patients with septic shock. A randomised Controlled trial. JAMA.2013;310(16):1683-1691.

3. Hajjar L, Vincent J, Galas F, et al. Vasopres-sion versus Norepinephrine in Patients with Vasoplegic Shock After Cardiac Surgery; The VANCS Randomized Controlled Trial. Anesthesiology 1 2017, Vol.126, 85-93.

Additional information• Tamura T, Yokoyama M. ‘Prevention of atrial

fibrillation after cardiac surgery using low dose landiolol. A systematic review and meta-analysis. J. Clinical Anesth 2017 Nov: 42:1-6.

• Nagai R, Kinugawa K, Inoue H, Atarashi H, Seino Y, Yamashita T. Urgent management of rapid heart rate in patients with atrial fibrilla-tion/ flutter and left ventricular dysfunction: comparison of the ultra-short-acting landiolol with digoxin (J-Land Study). Circ J. 2013; 77 (4):908-16.

“The challenge overall is finding a biological phenotype to identify those patients who may benefit from the drug.”Mervyn Singer

“We need to think about the negative side effects when using catecholamines and consider alternatives – one possibility being vasopressin.”Johann Knotzer


Anxiety in the ICU: sometimes it serves a purpose

D uring this afternoon’s session on analgo-sedation, Tarek Shar-

shar (Pasteur Institute, Paris, France) presents data from a recently-completed observa-tional, multicenter study to determine the relationship between the intensity and object of a patient’s anxiety and their deterioration over the first seven days after ICU admission.

The study is unique, explained Dr Sharshar to ISICEM News, because anxi-ety was assessed qualitatively as well as quantitatively. The importance of this is rooted in the notion that anxiety is a complex phenomenon with, consequentially, unclear therapeutic implications.

“A long time ago it was stated that sedation should be used to alleviate anxiety of the patient,” said Dr Sharshar. “Now, it is not considered that sedation should be used in this way. We should use other drugs, such as anxiolytics, or may be dexmedetomidine, for example, but also non-phar-macological approach – such as hypnotism, musicotherapy, for instance – if we want to target anxiety. Using sedative agents like midazolam, benzo-diazepine or propofol, is not considered a good recommen-dation for this purpose.”

As a consequence of lighter sedation, patients may be more anxious as a result of increased discomfort, as a result of pain, mechanical ventilation, delusion, and the general theme of the ICU ex-perience1. “On the one hand, we should not deeply sedate the patient, and we should even avoid sedation because we know it is bad,” said Dr Sharshar. “On the other hand, maybe the patient will have to then cope with many anxi-ogenic discomforts.”

Anxiety does not always conclude when the anxiogenic stimuli are removed, either. Some patients go on to experi-ence post-traumatic stress syn-dromes (PTSS) following ICU illness, as recently reviewed by Bienvenu and Gerstenblith2.

Returning to the definition of anxiety, Dr Sharshar stressed that it is distinct from fear (the latter defined as an short-lived, appropriate and focused cognitive and emotional response to a particular threat) and involves physiological as well as psychologi-cal components. “Like pain, it is an accessory that protects you,” said Dr Shar-shar, expanding the analogy: “You do not need to let the patient have pain, but pain is a physiological response that is necessary for protecting the body. Pain can be too strong, or not intense enough.

“Anxiety can be looked at in the same way. Anxiety is a way to perceive and react to danger, but it can be bad when it is too high, or too low. When too high – hyper-anxiety – you may have too much of a bodily response and psychological burden. When too low, you may not be able to cope with the danger, be-cause you will not be able to mobilise all of your bodily and psychological resources to face the danger. So dealing with anxiety is more complicated than saying, ‘anxiety is bad’, or that it is too high, repre-sents discomfort, or that it is a psychological burden.”

In terms of neural cor-

relates, anxiety (as well as depression and PTSS) is associated with the limbic system, with increased amyg-dala activation in response to emotional stimuli indicative of impaired emotional regula-tion. This provides a bridge between the psychological and physiological, explained Dr Sharshar: “We also know that the amygdala is highly connected to autonomic systems and neuroendocrine systems. It can integrate all of the stress signals coming from the body, from outside, and it also controls the autonomic response in terms of heart rate, blood pressure, etc. It controls the neuroendocrine system, especially the hypo-thalamic–pituitary–adrenal (HPA) axis and the secretion of cortisol, which is a major hormone for stress.”

The issue, summarized Dr Sharshar, is in determining whether an individual patient’s response is adapted or

maladapted. He first explored this question in a study of individuals with Guillain-Barré syndrome (GBS), published in 20123. Between 2006 and 2010, 110 hospitalized adult GBS patients were assessed for anxiety associated with the possibility of subse-quent intubation, in order to determine the prognostic significance of this phenome-non. “Intensity of anxiety was associated with subsequent deterioration and the need for mechanical ventilation,” said Dr Sharshar of the study. “We also found that patients who were anxious, because of an uncertainty about what

will happen later, will more frequently require mechanical ventilation. This was the first step in our Task Force on ICU admission. We realized that it is not only a ques-tion of intensity, but how the situation is perceived by the patient.”3

In the study he will present in Brussels today, Dr Sharshar and colleagues found that, following ICU admission,

45% of patients subsequently deteriorate, experiencing prolonged organ failure or developing new organ failure within the first seven days.

Anxiety was measured using the State-Trait Anxiety Inventory score (STAI), which measures via self-report the presence and severity of current symptoms of anxiety and a generalized propen-sity to be anxious. Thus, a comprehensive snapshot of individual patients’ trait anxi-ety (relatively stable aspects of anxiety-proneness, including general states of calmness, confidence, and security) and state anxiety (how respond-ents feel in the moment by way of feelings of apprehen-sion, tension, nervousness, worry, and activation/arousal of the autonomic nervous system) is achieved. The score ranges between 20 and 80.4

Interestingly, Dr Sharshar and colleagues found STAI scores above 40/80 to be

associated with subsequent deterioration – the intensity of anxiety seeming to be predic-tive of subsequent deteriora-tion in this population. Fur-thermore, the absence of fear of dying was also associated with subsequent deterioration. In addition, more than 60% of patients felt vulnerable to being or possibly being in a serious condition; these two responses were also associated with subsequent deteriora-tion in multivariate analysis. Patients also had a fear of being intubated.

“What is highly interest-ing in this study is that you have to look not only at the intensity of anxiety, but you also have to know what the patient is anxious about, or what they are not anxious about. This seems to have a prognostic value, a clinical sig-nificance. This is the first time we have asked ICU patients how they feel and what they are anxious about.”

Exploring the possible explanation for the associa-tion between the absence of fear of death and subsequent deterioration, he went on: “There are different expla-nations, and I don’t know which one is the best. Our explanation is that the patient can feel that something is not going well, so there is a diffuse anxiety. But the patient is not able to perceive the severity of his condition, so he is not able to integrate the danger in order to mobilize his resources. But there are many different explanations.”

This study opens many doors for future investiga-tion, explained Dr Sharshar in his concluding remarks. For example, a patient’s trait anxiety is fed by genetic predispositions as well as sociocultural factors that may influence the likelihood of anxiety and subsequent PTSS. As his work demonstrates, such study would incorporate the physiological aspects of the relationship between anxi-ety and autonomic activation, neuroendocrine activation, and so on. “These two direc-

Analgo-sedation 400 Hall Wednesday 13:45

“This is the first time we have asked ICU patients how they feel and what they are anxious about.”Tarek Sharshar


tions are not contradictory,” he said.

“But the most difficult aspect will be the sociocultural one. For example, people al-ways ask me, are the patients who have less fear of death more religious? We have not asked this question. We know that, to deal with this issue it will be more complicated than asking the patient whether he believes in God or not, because there are so many ways of believing in God. It is not so simple.

“The way of living, and how aware the patient is of his condition, will have a dramatic impact on the occurrence of post-ICU psychological dis-orders. When I discussed the phenomenon of being anxious without fear of dying with psychiatrists, they told me that it is a sort of dissociation behavior. We know that these dissociation patterns can favor the outcome of PTSS. For the moment, I do not know if this was the case in this popula-tion, but it would be interest-

ing to find out.”Anxiety in the ICU context

is more about how the danger is perceived rather than its ob-jective severity, summarized Dr Sharshar. The phenomenon’s complexity demands caution in interpretation of results, he added. The only way to determine causality would be to conducted randomized controlled study of outcomes when anxiety is modulated at ICU admission.

Yet, still, a therapeutic hy-pothesis is lacking, he noted,

until anxiety is better under-stood on an individual basis: “If we say that anxiety can be adapted or maladapted, should we be reducing intense anxiety if it is adaptive? If the absence of fear to die is bad, do we think the patient should have a fear to die? I don’t know. I don’t think that the therapeutic goal should be over-simplified.”

Dr Sharshar speaks during the session, ‘Analgo-sedation’ tak-ing place in 400 Hall from 14:00.

References1. Berntzen H, Bjørk IT, Wøien H. “Pain

relieved, but still struggling”—Criti-cally ill patients experiences of pain and other discomforts during analgosedation. J Clin Nurs. 2018 Jan;27(1-2):e223-e234.

2. Bienvenu OJ, Gerstenblith TA. Posttraumatic Stress Disorder Phenomena After Critical Illness. Crit Care Clin. 2017 Jul;33(3):649-658.

3. Sharshar T, Polito A, Porcher R. Rel-evance of anxiety in clinical practice of Guillain-Barré syndrome: a cohort study. BMJ Open. 2012 Aug 24;2(4). pii: e000893.

4. Julian L J. Measures of anxiety: State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S467-72.

New Study Investigates the Clinical Utility of ORi,™ Masimo Oxygen Reserve Index™

In a study presented at the recent International Anesthesia Research Society (IARS) An-

nual Meeting in Washington, DC, researchers at the UC Davis School of Medicine evaluated the potential clinical utility of Masimo Oxygen Reserve Index™ (ORi™) as an early warning of arterial hemoglobin de-saturation in critically ill patients.1

ORi is a relative indicator of the partial pressure of oxygen in arterial blood (PaO2) in the range of 100 to 200 mmHg. ORi is in-tended to supplement, not replace, oxygen saturation (SpO2) monitor-ing and PaO2 measurements. As an “index” parameter with a unit-less scale between 0 and 1, ORi can be trended and has optional alarms to notify clinicians of changes in a patient’s oxygen reserve.

In the prospective, collaborative, observational study, Dr. Leonard Lee and colleagues enrolled 40 adult critically ill patients who were scheduled for elective surgical procedures requiring endotracheal intubation and planned arterial pressure monitoring catheter placement prior to induction of general anesthesia. The patients’ ORi values were measured using a Masimo Radical-7® Pulse CO-Ox-imeter®. The researchers recorded the time elapsed from the start of ORi alarming (triggered by decrease in the absolute value and rate of change in ORi) to 94% oxygen saturation, as well as the time

elapsed from 98% to 94% satura-tion. The average time interval between the start of ORi alarming and 98% saturation was considered to be the average increase in warn-ing time provided by ORi.

The researchers found that among the patients, the average time from the start of ORi alarm-ing to 94% oxygen saturation was 80±38 seconds (ranging from 29 to 227 seconds). The average time from 98% to 94% saturation was 46±23 seconds (ranging from 12 to

108) seconds. Therefore, the aver-age increase in warning time pro-vided by ORi was 34±23 seconds (ranging from 4 to 119) seconds. On a percentage basis, the increase provided by ORi was 96%±92% (ranging from 5% to 479%).

The researchers concluded that the study “demonstrates the poten-tial utility of ORi as an advanced warning of arterial desaturation and as an adjunct to SpO2. This additional warning time can poten-tially translate to improved patient

safety by allowing earlier calls for help, assistance from a more ex-perienced person, or modification of airway management. For this analysis we defined the advance warning to end at 98% SpO2. In clinical situations this SpO2 might not be considered to be critical. Using a lower SpO2 as the alarm level would increase the advance warning provided by ORi. Further analysis of the correlation of ORi and PaO2, the use of ORi as a guide to pre-oxygenation, and its utility in the morbidly obese are areas for future study.”

In another recent study, researchers at Children’s Medical Center in Dallas, Texas concluded that ORi could provide clinicians with a median of 31.5 seconds advanced warning of impending desaturation in pediatric patients with induced apnea after pre-oxygenation.2

ORi has not received 510(k) clearance and is not available for sale in the United States.

References

1. Lee L, Singh A, Applegate R, and Fleming N.

Oxygen Reserve Index: An early warning for

desaturation in critically ill patients. Proceed-

ings from the 2017 IARS Annual Meeting,

Washington, DC. Abstract #A1406.

2. Szmuk P et al. Oxygen Reserve Index A

Novel Noninvasive Measure of Oxygen

Reserve – A Pilot Study. Anesthesiology.

4 2016, Vol. 124, 779-784. doi:10.1097/

ALN.0000000000001009.


Tackling the remaining controversies in CPR

J erry Nolan is a consultant in anaesthesia and intensive care medicine at the Royal United Hospital, Bath, UK and Honorary Professor

of Resuscitation Medicine at Bristol University, UK. He will be speaking today on several controversial topics in the CPR world: oxygen, adrenaline, airway management, extracorporeal CPR, and when to stop CPR.

In conversation with ISICEM News, Professor Nolan gave a glimpse of some of the key messages he will be sharing with the audience.

What will this session address?I’ll look at the remaining controversial topics; the role of compression-only CPR, public access defibril-lation (PAD), the use of drones to deliver AEDs, dou-ble sequential defibrillation, antiarrhythmic drugs, cooling pre-ROSC, and mechanical CPR.

What is controversial about compression-only CPR?There has been a long-standing debate on whether compression-only CPR results in similar or even better outcomes than the combination of chest compressions and rescue breathing. Data from Japan as well as many other countries indicate that implementation of compression-only CPR, particu-

larly when this is part of a telephone-CPR strategy, is associated with substantial increases in rates of bystander CPR and survival.

How might rates of bystander CPR be improved?There has been a considerable increase in PAD schemes, but many registries have documented low rates of bystander defibrillation (around 2%). Public AEDs need to be made more accessible and their location should be logged with local emergency medical services (EMS). Placement of AEDs in well-known businesses such as coffee shops may make them more accessible. In remote locations, the use of drones may enable an AED to be delivered to the site of a cardiac arrest more rapidly than the EMS.

What’s important to discuss regarding double sequential defibrillation?Using two manual defibrillators simultaneously, to provide dual sequential defibrillation in cases of shock refractory VF/VT, has been adopted by EMS services in several countries. To date, there are only observational studies on this practice and those provide less than convincing evidence of benefit. Defibrillator manufacturers have warned of the risk

of serious damage to the defibrillator with this practice and this is supported by at least one case report.

Why are you looking at amiodarone, in particular?Amiodarone has been included in international guidelines for the treatment of shock-refractory VF/VT since 2000 and this was supported at the time by a randomized controlled trial showing increased survival to hospital admission with amiodarone compared with placebo. However, the placebo in this study was polysorbate 80 (the diluent used for amiodarone) and this is known to cause hypoten-sion. A more recent study has showed no difference in survival to hospital discharge with either ami-odarone or lidocaine in comparison with placebo. However, the formulation of amiodarone used in this study (Nexterone) is not used in clinical practice, which it makes it difficult to generalize the study’s findings. Although current guidelines recommend

amiodarone instead of lidocaine there is a strong rationale for reconsidering a more prominent role for lidocaine.

Are there any other issues to be addressed?Two studies have shown that prehospital infusion of ice-cold crystalloid during cardiac arrest or immedi-ately after return of spontaneous circulation appears to be harmful and is no longer recommended in current guidelines. The use of mechanical CPR de-vices has been the subject of long-standing debate. Although several RCTs have failed to show a benefit for these devices in unselected out-of-hospital cardiac arrests, they are still advocated for transport-ing patients in cardiac arrest and for use in cardiac catheterization laboratories.

CPR Silver Hall Wednesday 13:45

“In remote locations, the use of drones may enable an AED to be delivered to the site of a cardiac arrest more rapidly than the EMS.”Jerry Nolan

“Although current guidelines recommend amiodarone instead of lidocaine there is a strong rationale for reconsidering a more prominent role for lidocaine.”Jerry Nolan


Shouldn’t everybody be in a clinical trial?

S imon Finfer is a Professorial Fellow in the Critical Care and Trauma Division at The

George Institute for Global Health in Sydney, Australia as well as Director of Intensive Care at the Sydney Adventist Hospital, the largest not-for-profit hospital in New South Wales.

Tomorrow afternoon at ISICEM, he will be arguing that every patient should be involved in a clinical trial. In an interview with ISICEM News, he shared the logic behind his viewpoint, as well as the benefits and likely chal-lenges important to discuss.

Tell us about your expertise in clinical trialsI run large clinical trials in critically-ill patients, including the SAFE study, which was the first full ICU mega-trial, recruiting 7,000 patients. Prior to that, the majority of trials were less than a hundred patients, while others were around a thousand patients, which isn’t really large enough to demonstrate the sorts of realistic treatment effects that we might see from ICU treatments.

So, with our clinical trials group, we’ve developed expertise to run these large trials, and now work with

a number of like-minded tri-als groups around the world.

Given the trials you have conducted, what’s your opinion on ICU evaluations to date?Unlike the process to author-ize a medicine, very few procedures we do routinely in intensive care units have been subjected to that sort of rigorous evaluation. When we as a community have rigorously evaluated treatments that, on face value, appeared to be sensible, ben-eficial and not harmful, like early decompressive craniec-tomy, we have often found out

that they harm our patients.

So, why should every patient be in a clinical trial?Firstly, patients are often being subjected to untested treatments, cer-tainly treatments that are random and different. We know there are huge practice variations between intensive care units and even between doctors who work in the same intensive care unit. Patients are

being subjected, at random, to differ-ent treatments depending on which day of the week they happen to be admitted, and who is on duty.

That sort of random practice does not inform us about what is best for people. A clinical trial does. We could do better if we replaced random treatments with rand-omized treatments.

Are there other reasons?Patients who enter clinical trials

are persistently being shown to have better outlooks for recovery than if they are not

in a clinical trial. When you run a clinical trial in an intensive care unit, regard-less of the treatment the patient is allocated to, compared with normal

treatments, they do better. Why that’s the case is un-

clear, but it’s probably because a lot of

treatment

within the clinical trial is protocolized, i.e. patients get more attention, addi-tional investigations are carried out as part of the clinical trial, there is closer observation, and more protocol-ized management.

So, there is a good reason to argue that if you enter a hospital and are asked to be in a clinical trial, you should say yes. The evidence is that it improves your outcomes.

Is there a knock-on effect for healthcare providers as well?Hospitals that conduct research have also been convincingly demonstrated to perform better than hospitals that don’t. There are nationwide clinical trial groups in Australia and New Zealand, Canada and increasingly in Europe that show when you change the culture of an intensive care unit into a research culture, people look at their own work more critically.

Would there not be tremendous expense in running so many clinical trials?Obviously, the complexity of running clinical trials means more staff, and there is an operating cost associ-ated with running a trial. Some people may think that affects care, or diverts resources, but it doesn’t really because at the end of the day, you are responsible for doing the best for your patients.

And the apparent cost and complexity of these trials is actu-ally rewarded six-fold – according to the research that’s been done in our country by the Australian Commission on Safety and Quality in Health Care, an independent body. Every dollar spent on research saves the health-care system six dollars each year. This pays back.

What’s your final say on the matter?In the end, if it means that a patient is getting the best treatment that they can get, I don’t know why anyone would argue against doing more clini-cal trials.

We have so many negative clinical trials Lippens Room (kbr) Thursday 13:30

“We could do better if we replaced random treatments with randomized treatments.”Simon Finfer

“… if you enter a hospital and are asked to be in a clinical trial, you should say yes. The evidence is that it improves your outcomes.”Simon Finfer

Date post:	06-Mar-2019
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Tailored nutrition in and beyond the ICU T - intensive.org · post-ICU is an important focus as...

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