The official daily newsletter of the 32nd ISICEM Friday 23 ... 12_FINAL.pdf · Dr Malbrain will...

Issue 4 Friday 23 March 2012 ISICEM News 1

Friday 23 March 2012 Day 4The official daily newsletter of the 32nd ISICEM

W elcome to the fourth and final day of ISICEM 2011. We are proud to announce that there have been over 6000 attendees at this year’s meeting, from a multitude of countries and a huge number of different centers and intensive care specialties.

Over the last three days, ISICEM 2012 has featured a wide-ranging and extensive program of sessions that has explored intensive care medicine to the fullest. We hope that all of you have been able to stay for the last day to witness the interesting and comprehensive symposia dedicated to the most interesting and hotly debated aspects of the field.

Key topics that will be covered to-day include adjuncts in sepsis, antibiotic strategies, multi-resistant organisms, delirium, non-invasive ventilation, con-troversies in acute respiratory distress syndrome and life in the emergency room. In addition, sessions on tempera-ture control, neuromonitoring, manag-ing the neurologic patient and what we learned from H1N1 are just some of the remaining topics that will be covered.

Friday’s program will also play host to a large number of tutorials, which provide an avenue of expert-driven learning for all attendees. Some of the vast number of topics that be

will touched upon include: seda-tion; pulmonary embolism; antibiotic choices; how to arrange a MET team; optimizing oxygen delivery; optimizing cardiac output; and fluid responsive-

ness. There will also be a Round Table discussion on how to prepare for the next pandemics.

The final issue of ISICEM News brings you even more inside looks,

news, commentaries and interviews related to the conference as a whole. We hope you have thoroughly enjoyed ISICEM 2012 and we hope to see you next year at ISICEM 2013.

Delegates packed into the Tent

Today at ISICEM: Friday

A comprehensive look at abdominal problems . . . . . . . . . . . 4

Optimizing blood pressure in brain injury . . . . . . . . 8

New strategies offer breath of fresh air in ARDS . . . . . . . . . . . . 12

The final word: Jean-Louis Vincent . . . . 14

A packed audience attended the an-nouncement of the Poster Awards on Thursday morning in the Tent, when four outstanding examples of research were recognized at ISICEM 2012.

Handing out the awards, Paolo Pelosi (University of Genoa, Italy) explained that all of the submitted posters were evaluated, and it was decided that four were worthy winners this year, three of which were related to clinical issues and

one related to pathophysiol-ogy and laboratory studies.

Beginning with the basic science poster, Dr Pelosi an-nounced that the winner was Jan Gunst and colleagues from Katholieke Universiteit

Paolo Pelosi with representatives of the winning posters

Reaping the benefits of innovative researchThe Poster Awards at ISICEM 2012

Live from ISICEM 2012

Continued on page 2

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2 ISICEM News Friday 23 March 2012 Issue 4

ISICEM NewsPublishing and Production MediFore LimitedSymposium Chairman Jean-Louis VincentEditor in Chief Liam DavenportEditor Peter StevensonDesign Peter WilliamsIndustry Liaison Manager Cheryl CagiolaHead Office Woodside Villa, 11 Sydenham Hill London SE26 6SHTelephone: +44 (0) 208 244 0583 [email protected] www.medifore.co.ukCopyright © 2012: 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 2012 Symposium Chairman, the ISICEM Scientific Advisors or Collaborators.

Leuven Belgium, whose work demonstrated that insufficient autophagy con-tributes to mitochondrial dysfunction, organ failure and adverse outcome in critical illness. The research, Dr Pelosi said, offered evi-dence on “the importance of the relationship of au-tophagy and mitochondrial dysfunction, and opened up possible new developments for treatments related to increased autophagy”.

Moving on to the patient clinical studies, Dr Pelosi said that the second poster award was, again, for research originating from Katholieke Universiteit Leuven, with a team led by Eva Boonen. The topic was the contention that reduced cortisol metabolism drives

hypercortisolism in critical care and, as Dr Pelosi ex-plained: “This is, of course, an endocrinological study, which new gives insights in the interaction of cortisol metabolism.”

The next award was for a “more clinical study”, Dr Pelosi said. Describing the announcement as “a great pleasure” he revealed that the award was for a team outside Europe, led by Yuda Sutherasan, from Mahidol University, Bangkok, Thai-land. The focus of the study was the use of portable ICU ultrasound to predict post-extubation failure. Dr Pelosi commented: “This was a really nice study about the use of ultrasound in critically ill patients, which is gaining more and more in popularity.”

The last study to be awarded was for a prospec-tive, randomized controlled trial in pediatric patients. “So, you see, we tried to have a different topics awarded this year,” Dr Pelosi said. The study, led by F Galas, from the Heart Institute in Sao Paolo, Brazil, working with partners in King’s College School of Medicine in London, UK, was a randomized compari-son of fibrinogen concen-

trate versus cryoprecipitate for bleeding control in pediatric cardiac surgery. In closing, Dr Pelosi said: “This is, again, a very interesting clinical study in the pediatric population.”

All of the winning post-ers can be viewed in the main entrance to ISICEM 2012, while the poster sessions continue in the Copper Foyer, the Cube and at the entrance to the Silver Foyer.

Reaping the benefits of innovative researchThe Poster Awards at ISICEM 2012


Continued from page 1

Awaiting the results of the Poster Awards

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T he clinical aspects of renal disease took centre stage on Thursday morning in a comprehensive four-hour session that covered many different aspects of the syndrome.

One topic that was given particular attention was GFR (glomerular filtra-tion rate) monitoring, something which has been identified as a power-ful tool in dose calculation, and other aspects of managing acute kidney failure. However, there are many pitfalls of the existing technology, especially in sheer size and expense of the monitoring devices.

To that end, Bruce A Molitoris (Indiana Center for Biological Micros-copy, Indianapolis, USA) presented his ‘adventures’ in the development of a new bedside GFR monitoring device. He began by discussing acute kidney injury (AKI) therapies in the current time. “Why a lack of therapy in AKI therapies?” he said. “We think there’s a diagnostic dilemma, the absence of a sensitive and timely information that allows one to make a diagnosis early enough to apply secondary therapy.

“There’s an inability to determine the severity of injury, poor staging of

our patients until we do it retrospec-tively, and therefore the thought of us-ing therapy has to be to a very broad base of patients, and very expensive studies. Third, we’re unable to trans-late effective therapies from animals to humans because we can’t make this diagnosis in stage 2 [AKI] patients in a reasonable fashion.”

He continued to explain the genesis of the GFR bedside technol-ogy. “So why are we interested in having GFR at the bedside?” he said. “Well, number one, the severity of injury is measured by maximum serum creatinine concentration by the RIFLE technique, or AKIN correlates with mortality. We know that from a number of studies. GFR is a proven measure of global kidney function.

“The termination of GFR would allow for a more rapid, sensitive diagnosis of AKI, with stratification by severity of injury, and we could follow the level of injury over time. It would allow for the rapid determination of response to therapy. For example, in differentiating PreRenal Azotemia and ATN [acute tubular necrosis], you can measure prior to and following the fluid bolus, and know pretty much

precisely what you’re dealing with.“It can be used to determine use

and discontinuation of renal replace-ment therapy, i.e. in the patient who is relatively anuric or oliguric, you could measure the GFR, and if it’s below 5, for instance, or below 10, you might want to start your renal replacement therapy, and as they come off renal replacement therapy, you could, for a short period of time, actually determine their GFR. Serum creatinine biomarkers cannot provide this infor-mation, especially the quantitative nature of the severity of injury.”

Dr Molitoris said that other current sampling techniques – e.g. inulin, iohexol – all require approximately six hours in which to draw meaningful samples. He added that the measure-ment of GFR has not found a popular following, as more centralized GFR monitoring devices are expensive, con-sisting of approximately US$750,000 microscopes, amongst other items.

Explaining the design of the bedside GFR monitor, Dr Molitoris outlined that it relies on the injection of two different dextrans (safe, high solubility, easily tagged with fluores-cent markers etc), one labeled with

a red marker, and other one labeled with a green marker.

“The red dextran is maintained in the plasma, and therefore measures volume of the plasma by dilution,” he said. “The green marker is re-filtered across the glomerulus, and is lost in the plasma, and we’re measuring then the quantitative loss of this green marker over time.”

Instead of a microscope, the bedside system uses an LED light source and CCD (charge-coupled device) camera, which are both off the shelf and inexpensive. “Instead of an expensive microscope lens we use an optical catheter,” he added. Results have been impressive, with good correlation to standard, more time consuming techniques. In tests with rats, the bedside monitor has been able to measure GFR in less than 10 minutes. “We now believe that we have a device, and a technique, that measures both plasma volume and GFR,” said Dr Molitoris.

He added: “We believe this will al-low early diagnosis of AKI; allows the real time staging of kidney injury by severity; assists in determining initia-tion titration and cessation of thera-pies; assesses response to therapy by measuring changes in GFR; allows titration of IV fluids and actual plasma volume status; and [will] be able to allow proper drug dosing.

Novel bedside monitor offers effective, affordable GFR measurement


A bdominal problems will be the focus of attention on Friday morning, when leading European experts will explore a range of issues and novel approaches to management in this challenging area.

To discuss the wide-ranging pres-entations and offer some personal in-sights into abdominal problems, Mark Coburn (University Hospital, Aachen, Germany), who will be chairing the session alongside John Devlin (North-eastern University, Boston, Massachu-setts, USA), spoke to ISICEM News.

He said: “First of all, for the ses-sion, we have really very well chosen speakers. They are key experts in their field, especially in intra-abdominal pressure [IAP]. Both Jan De Waele [Ghent Medical School and University Hospital, Belgium] and Manu Malbrain [ZNA Stuivenberg, Antwerp, Belgium] are [Executive Committee mem-bers] from the World Society of the Abdominal Compartment Syndrome [WSACS]. So they really are the key experts in the field. It is very interesting and important to have their opin-ion.”

Dr Malbrain will focus on what is new in abdominal pressure measure-ment. He will ar-gue that IAP needs to be measured in order to make a proper diagnosis of abdominal hyper-tension or abdomi-nal compartment syndrome. It can be measured directly via needle puncture connected to a water column or pressure transducer, which is the principle that is used during laparoscopy while the insuffla-tor pressure is limited to 24 mmHg. However, in clinical practice and at the bedside, indirect techniques are more often used, Dr Malbrain will say.

In addition to setting out the WSACS guideline definitions, he will look at commercial techniques for IAP measurement. For example, one technique uses the patient’s own urine as a transmitting medium by looking at the height of the urine column in cm H2O or mmHg, while another technique combines a one-way valve with a pressure transducer.

He will suggest that continuous

monitoring of IAP via a balloon-tipped catheter is an elegant option for monitoring IAP continuously together with the abdominal perfusion pressure (APP), using the equation APP = MAP – IAP, where MAP is mean arterial pressure. He will say that this is a better resuscitation target than MAP

alone.Among others,

new techniques, Dr Malbrain will say, include special probes allow-ing gastric IAP measurement with postpyloric feeding and the combina-tion of esopha-geal and gastric pressure measure-ment, which offers the possibility of estimating trans-diaphragmatic pressures that are related to breath-ing work and failure to wean. He

will argue that, in the future, these continuous techniques will allow us to understand better the interactions between the different compartments.

Jan De Waele will give a pres-entation on leaving the abdomen open, during which he will say that the prevention of intra-abdominal hypertension/compartment syndrome is the main indication for open abdo-men treatment. Importantly, this is no longer what he will describe as a nursing nightmare, in addition to which temporary abdominal closure techniques have evolved. In terms of intervention, Dr De Waele will say that the peritoneal cavity is a target, with decreasing inflammation and the facilitation of early abdominal

wall closure important aspects of this treatment.

Dr Coburn commented: “Jan De Waele will point out the necessity of having this treatment, especially for patients with abdominal hypertension or abdominal compartment syndrome. It is an opportunity to show to the audience the advantages of this treat-ment.”

There will also be two presen-tations on abdominal infections. Dylan de Lange (Universitair Medisch Centrum Utrecht, The Netherlands) will examine severe intra-abdominal infection, noting that complicated intra-abdominal infections confer high mortality, and will talk about pathogens in abdominal sepsis. He will question the appropriateness of empirical antibiotics, and ask whether enterococci and yeast, especially Candida spp, need to be covered. He will also examine the ideal duration of antibiotics in complicated intra-abdominal infections.

Reflecting on the areas that Dr de Lange will cover, Dr Coburn said that abdominal infections are “a severe problem”. He added: “The mortality rate is quite high, and it has a huge range of causes. [Dr de Lange] will focus specifically on peritonitis due to perforation of suture leakage, not bacterial infection, such as clostridium infections, which will be covered by different talks at ISICEM.

“He will discuss different approaches for antibiotic treat-ment and which bacteria have to be treated or not, and will cover how long antibiotics should be given, especially for severe or long, complicated treat-ment.”

Rounding off the session will be Matteo Bas-setti (Santa Maria della Misericordia University Hospital, Udine, Italy), who will give a presenta-tion on antifungal prophylaxis. Not all

patients are at the same risk of fungal infections, he will say, with some patients at high risk. But what is the definition of risk? The overall risk of candidiasis in ICU surgical patients is approximately 2%, he will explain, while high risk would be over 10%.

Dr Bassetti will argue that only in high risk patients is antifungal prophylaxis justified, because then the benefits are greater than the risks and costs. Although the risk factors have been recognized, the next step – to identify and validate a prediction model – is still needed in order to be able to select high-risk patients. The choice of antifungals at present, he will say, is likely to be fluconazole or echinocandins, while, in the future, polymerase chain reaction testing is likely to play a large part in diagnosis and management.

Other speakers during the ses-sion will look at pancreatitis and the complications of inflammatory bowel disease.

The session ‘Abdominal problems’ will take place at 13:30 on Friday 23 March in 400 Hall .

A comprehensive look at abdominal problems

Abdominal problems 400 Hall Friday 23 March 13:30–15:30

“For the session, we have really very well chosen speakers…They really are the key experts in the field. It is very interesting and important to have their opinion.”

Mark Coburn (University

Hospital, Aachen, Germany)

Mark Coburn

Manu Malbrain


Dear valued ISICEM delegates, With great pleasure we announce that our new Pump Assisted Lung Protection (PALP) system, powered by CARDIOHELP, will be presented for the first time at this year’s ISICEM in Brussels.

MAQUET has developed CARDIOHELP for three major important growing markets: Firstly for the ventricular assist (VAD) market, secondly for the fast growing ECMO and ECLS market and thirdly for the pump assisted lung protection (PALP) market. It is the PALP market where MAQUET sees the highest potential and this market can now be addressed with this special extracorporeal low flow system.

Today, all the known and well established therapies for preventing or slowing down the course of ALI and ARDS are limited by hypercap-nia. What if the guidelines for ARDS with low tidal ventilation, pressure limitation or permis-sive hypercapnia could be followed safely and effectively with the support and backup of an ex-tracorporeal low flow CO2 removal system? With PALP powered by CARDIOHELP, such a support system for pump assisted lung protection is finally available and when initiated at an early stage on offers a chance to break through the vicious circle of ALI, ARDS and COPD.

The most frequent reason for exacerbation of COPD is CO2 retention, which often results from non-invasive (NIV) or mechanical ventilation. CO2 removal with PALP powered by CARDIO-HELP opens up a whole new era where long term invasive ventilation can be avoided and/or time is provided for the save initiation of NIV. Shorten-ing the intubation time and/or perhaps avoiding intubation altogether will have a big impact on the

quality of patients’ lives, the length of hospitaliza-tion and conceivably patient mortality.

Furthermore, weaning patients from ventila-tor therapy seems to be one of the most difficult and staff demanding propositions in the ICU. PALP with CARDIOHELP is an excellent choice for extracorporeal low flow CO2 removal and even offers the possibility for combined airway therapy to train patients with high-end ventila-tor devices like the SERVO-i with NAVA and pump assisted lung protection.

We believe that the market for such a system is as big as the market for mechani-cal ventilation today, which we estimate at 900,000 patients yearly worldwide. There are an estimated one million patients yearly worldwide with end-stage COPD that could potentially benefit from an extracorporeal support system. The restricting factors and main reasons for the limited adoption of such systems in the ICU,

are the high blood flows that such systems require and the complications which are associ-ated with this high flow. With the new Pump Assisted Lung Protection system, MAQUET has overcome these limitations and is offering a system which effectively reduces CO2 levels with very low extracorporeal blood flow. Much smaller cannulae also enable easier cannulation techniques to be used. With ‘ICU-like’ products MAQUET puts CO2 removal in line with other ICU therapies such as CRRT. With our experi-ence of more than 25 years in designing and manufacturing gas exchange devices, we offer high quality membranes for long-term use, ide-ally suited for the new PALP product which will be approved for a 30 day application. Marcus FelsteadDirector Global Marketing Dr. Tilmann Schwab Medical Director Advanced Therapies

Tilmann Schwab Marcus Felstead

Exploring new ideas in pulmonary embolism management

T he management of pulmonary embolism was explored from all angles in a special session in 400 Hall on Thursday morning. Along-side new concepts in diagnosis and management, Giorgio Berlot (Cattinara Hospital, Trieste, Italy) asked whether pulmonary embolism is still a problem, while Andrew Shorr (Washington Hospital Center, Washington DC, USA) answered the question as to when one can send emergency room patients home. Giorgio Berlot speaking to attendees at the Pulmonary Embolism session

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In the emergency room Tent Friday 23 March 08:00

T he use of non-invasive hemodynamic moni-toring in the emergency room (ER) could improve the predictive power for overall pa-tient outcome, delegates will hear this morning in a session dedicated to patient management in the ER.

“It’s very difficult and it’s very inaccurate to clinically estimate both the cardiac output and the systemic vascular resistance,” Richard M Nowak (Henry Ford Medical Center, Detroit, USA) told ISICEM News. “You just can’t do it clinically, because blood pres-sure and pulse don’t correlate to those parameters.”

To that end, Dr Nowak is now involved in a study that is investigating the use of continuous non-invasive hemody-namic monitoring in the emergency room. The largest of its type, the PREMIUM Registry has enrolled a large number of patients with acute congestive heart failure, acute systemic infection or acute stroke.1

“What we’re doing is just monitoring their non-invasive hemodynamics over four hours and looking at the profiles to try and determine whether or not the profiles in the ER actually predict outcome, both in terms of hospital length of stay, death in 30 days or emergency revisits to the institution or elsewhere in 30 days,” said Dr Nowak.

“And, to me, this concept of taking new technologies and applying them to the ER, but in particular looking at hemodynamic variables of hemodynamic profiling, is very, very exciting. I can tell you that in all those three diseases, the profiles are wildly different. What that all means I don’t know, but the fact that you can talk about a het-erogeneity of hemodynamic profiles in emergency department patients who are labeled with the same disease is pretty interesting.”

The device used within the trial is the Nexfin (BMEYE, The Netherlands), a non-invasive finger cuff hemodynamic monitor that provides real-time continuous information on cardiac output, stroke volume blood pressure and other hemodynamic

parameters.2 With no need for invasive measures such as an arterial line or oximetry catheter,

Dr Nowak said he has been very pleased with the simplicity of the device thus far.

“We’re using it because it’s the easiest to use, and I think it gives you the best data,” he said. “We’ve played with some of these other impedance devices, that you put a bunch of electrodes on the chest for, but they’re not nearly as friendly to apply, and I’m not sure the data is as accurate.

“So we’ve been enthralled with this because it’s easier to apply, it gives you continuous monitoring, you can apply it to anybody and you don’t have to stick an arterial line in or anything.” In fact, the

Nexfin’s ease of use has not just made an impres-sion on Dr Nowak. The device has now found its way into space, monitoring astronauts working on the International Space Station.

In his presentation at ISICEM, Dr Nowak will share some initial data analysis from the PREMIUM registry, example case studies, and his overall impressions as to how the study is progressing. Ultimately, he said, it is hoped that better hemody-namic profiling in an ER setting would in turn help intensivists better predict patient outcomes further

down the line.

Dr Nowak will give his presentation ‘Non-invasive hemo-dynamic monitoring in the ER’ during the session ‘In the emer-gency room’; 08:00, Friday 23 March in the Tent .

References1) clinicaltrials.gov. PRE-

MIUM Registry: PRognostic HEModynamIc Profiling in the AcUtely Ill EMergency Department Patient. http://clinicaltrials.gov/ct2/show/NCT01208077; (Accessed March 2012)

2) BMEYE. Nexfin. http://www.bmeye.com/products-nexfin; (Accessed March 2012)

“This concept of taking new technologies and applying them to the ER, but in particular looking at hemodynamic variables of hemodynamic profiling, is very, very exciting.”

Richard M Nowak (Henry Ford Medical Center, Detroit, USA)

Hemodynamic profiling in the emergency department

“We’re using [the Nexfin hemodynamic monitor] because it’s the easiest to use, and I think it gives you the best data. We’ve played with some of these other impedance devices, that you put a bunch of electrodes on the chest for, but they’re not nearly as friendly to apply, and I’m not sure the data is as accurate.”

Richard M Nowak (Henry Ford Medical Center,

Detroit, USA)

Richard Nowak


T he problem of delirium during and after admission to the intensive care unit (ICU) will be examined from all angles on Friday, when a dedicated session will look at the causes, assessment, prevention and treatment of this potentially fatal complication of critical illness.

The session, which will be chaired by Peter Kruger (University of Queens-land, Brisbane St Lucia, Australia) and Giovanni Landoni (Milan, Italy) will focus on the risk factors for delirium, how it should be recognized, both nonpharmacologic and pharmacologic prevention strategies as well as its long-term consequences.

John Devlin (Northeastern Uni-versity, Boston, Massachusetts, USA), who is giving the final presentation during the session spoke to ISICEM News, explaining the importance of delirium in the ICU and outlining the presentations that will be given.

He said: “Delirium occurs in up to 80% of critically ill patients and is associated with higher mortality, a longer duration of mechanical ventilation and compromised post-ICU functionality and psy-chological health. Furthermore, the greater costs associated with delirium are a major healthcare issue.”

He added: “While

delirium is a clinical diagnosis that only psychiatrists and neurologists are qualified to make, ICU guidelines recommend that patients be routinely screened for delirium by non-psychi-atric personnel using psychometrically validated tools such as the Confusion Assessment Method for the ICU (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC).1,2

“Both the CAM-ICU and the ICD-

SC, when used by trained non-psychi-atric personnel, have been shown to identify delirium as well as psychia-trists’ using DSM-IV criteria. These tools are also highly reliable, and have been translated and adopted for use in ICUs around the world.”

However, Dr Devlin notes: “Despite the explosion of ICU delirium-related research over the past decade, a host of ques-tions in this field remain unanswered.”

He continued: “At the ISICEM congress, a panel

of ICU delirium experts

has been convened who will review a number of important issues in this area and provide ‘state of the art’ guidance to the bedside ICU clini-cian on how ICU delirium should be prevented, identified and treated.”

Dr Devlin explained: “Dr Theodore Iwashyna [University of Michigan Health System, Ann Arbor, USA] will highlight the long term consequence of delirium in the critically ill, while Dr Jesse Hall [The University of Chicago Medi-cine, Illinois, USA] will review the current role of delirium screening tools in the ICU and discuss newer

strategies for delirium assessment in this population.

“Realizing that prevention of delirium in the ICU is the key, Dr Wes Ely [Vanderbilt University Medical Center, Nashville, Tennes-see, USA] will review the causes for delirium and Dr Eddy Fan [University of Toronto, Ontario, Canada] will discuss the impor-tant relationship between the

quality of care we provide to our critically ill patients and their risk for developing delirium. In addi-tion, Dr Mark Coburn [Universität-sklinikum Aachen, Germany] will discuss the role of inhaled xenon as a strategy to prevent delirium.”

Finally, Dr Devlin will examine the current published evidence to review the role for pharmacologic interven-tions in both the prevention and treat-ment delirium in the ICU setting.”

The session ‘Delirium’ will take place at 11:15 on Friday 23 March in Copper Hall .

References

1. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001;29(7):1370-1379.

2. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med 2001;27(5):859-864.

Delirium Copper Hall Friday 23 March 11:15–13:00

Bringing clarity to the management and prevention of delirium in the ICU

“Delirium occurs in up to 80% of critically ill patients and…Despite the explosion of ICU delirium-related research over the past decade, a host of questions in this field remain unanswered.”

John Devlin (Northeastern University, Boston,

Massachusetts, USA)


M aintenance of safe blood pressure lev-els in brain injured patients with auto-regulatory impairment is an essential step in preventing further injury, delegates will hear in a ses-sion dedicated to neurological management this afternoon.

“Blood pressure is a really critical parameter in brain-injured patients,” Kees Polder-man (University of Pittsburgh School of Medicine, USA) told ISICEM News ahead of his presentation in the session.

Dr Polderman stressed that the main concern in such cases is the risk of blood pressures that are either excessively hypertensive or hy-potensive, both of which are extremely dangerous for the patient. “The best example is ischemic stroke,” he said. “If

you have a low blood pressure you can imagine that there is an area that has too low oxygen, and then getting too little perfusion, which then becomes ischemic and necrotic, so the stroke gets bigger.

“But if you have too high blood pressure, you get hyper-perfusion, and you can actually also get injury to the cells, although low blood pressure is [still] worse than high blood pressure.”

He continued: “A lot of the ischemic stroke trials show a bimodal curve, with increas-ing mortality and morbidity at very high blood pressures and very low blood pressures. And

that concept applies to other types of brain injury as well.”

In a healthy person, the brain will auto-regulate to stay in a safe zone between these

two extremes, as Dr Polder-man explained: “The brain protects itself from higher or lower blood pressure by dilat-

ing or contracting the vessels that lead to it. So the brain is always perfused exactly the same. You have a very wide margin – a very good toler-ance, especially when you’re young – for both low and high blood pressure.”

Dr Polderman stressed that the ‘viscous cycle’ for patients with brain injury is that the

injury itself can cause swings in blood pressure, which in turn can cause further injury. “In various types of brain

injury, you can lose that cerebral auto-regulation, and that means that every change in blood pressure immediately translates into more or less perfusion of the brain,” said Dr Polderman. “And you can imagine that, when that happens, the brain is far less susceptible to changes in blood pressure.”

He continued: “When your blood pressure gets really, really low, then your brain gets hypo-per-fused and you lose consciousness. But it happens very late.” Conversely, he said, when blood pressure elevates very high, a patient runs the risk of hypertensive en-cephalopathy, which can then cause all manner of neurologi-

cal symptoms.“Probably about half of

patients with severe acute brain injury lose the ability

“The brain protects itself from higher or lower blood pressure by dilating or contracting the vessels that lead to it…In various types of brain injury, you can lose that cerebral auto-regulation, and that means that every change in blood pressure immediately translates into more or less perfusion of the brain.”

Kees Polderman (University of Pittsburgh School of Medicine, USA)

Managing the neurologic patient Silver Hall Friday 23 March 13:30

Optimizing blood pressure in brain injury


to auto-regulate,” said Dr Polderman. “It can also vary over time. In those patients, it is more important to get the number for that patient exactly right so you get good perfusion of the brain. Not too much, not too little.”

To that end, within his presentation Dr Polderman will focus on some of the ways that a clinician can determine the optimal blood pressure for each patient, in-cluding those situations where auto-regulation is no longer functioning.

Adding his thoughts to the discussion of optimal blood pressure for patients with brain injury, session co-chair

Richard M Nowak (Henry Ford Medical Center, De-troit, USA) warned that we mustn’t lose focus on other additional criteria that could help manage these sorts of patients: “Does it matter if they have a high cardiac output, low cardiac output? High systemic vascular resistance, low systemic vas-cular resistance?” he said.

He added that one aspect that is fundamentally lost in such cases is determi-nation of forward flow: “If you have two people with an equal blood pressure and very different underlying hemodynamic profiles in terms of forward flow, what

does that mean in terms of the disease and outcome?” he said.

“I think it’s going to mean something, but I think we need to move to these sorts of discussions rather than something as simplistic as blood pressure.”

‘Managing the neurologic pa-tient’, 13:30, Friday 23 March, Silver Hall . In addition to Dr Polderman’s presentation on optimal blood pressure, other topics that will be addressed in the session include: ventila-tor management (including closed-loop); meningitis; HIV; thrombotic microangiopathies and status epilepticus .

Managing the neurologic patient Silver Hall Friday 23 March 13:30

A rguments for and against the pharmaco-logical value of com-mon nutritional substances were presented on Wednesday morning in a special session that took a frank and open look at pharmaconutrition.

As session co-chair, Jukka Takala (University Hospital Bern, Switzerland) offered his thoughts on pharmaco-nutrition as a whole. “It’s been around for about two decades, and there have been various, let’s say, fashions in that area,” he told ISICEM News. “It all started with the concept of enteral nutrition having benefits beyond its direct metabolic impact, with the concept of gut and bowel protection.

“Then it went on to progress towards the ideas of having specific nutrients which would have actual pharmaco-logical effects, i.e. going be-yond their direction metabolic or nutritional impact.”

He added that there have also been a number of products in the marketplace based on different ‘cocktails’ of nutrients, thought to have mostly immunomonitory ef-fects. “[It] is actually a fairly controversial situation where, let’s say, the proponents firmly

believe on the positive phar-macological impacts of certain nutrients, whereas those who are not the believers argue that even if such effects would be present, they should be assessed formally like drugs are being assessed,” said Professor Takala.

“In a way, it’s a slightly bi-zarre situation, because if you think about the introductions of new drugs or new medica-

tions, they go through a very strict evaluation process, whereas nutritional products which are believed to have pharmacological effects do not necessitate the same procedure.

“So I think that’s part of the controversy – part of the debate – that we are repeat-edly confronted with. It’s, in fact, the situation that if there are indeed some pharmacolog-

ical effects of these nutrients, they should be evaluated for efficacy and safety, and that’s not the case until now.”

One of the roadblocks to actually achieving this evalua-tion, however, is the difficulty in setting up trials to test each nutrient. “The problem is, of course, once investigators start doing such trials, which would have the same quality as in the assessment of drugs,

those trials are very expensive to do, and if we are talking about established nutrients, then the industry is unlikely to be willing to invest in them,” said Professor Takala.

He continued: “[That] would really necessitate investigator-initiated trials on a large scale, and running such trials with the qualitative documentation that would be needed for any medication is very expensive. It’s therefore unlikely to happen in the near future, unless there is really strong evidence that it would have a major benefit.”

“Therefore the efficacy of these nutrients remains debatable and what I think is even more concerning and frustrating is that if one believes efficacy, one should also assess safety.”

As such, is it fair to say that people are too compla-cent that these nutritional substances will not cause harm to the patient?

“Exactly,” said Professor Takala. “We’re talking about patient groups who have an inherently high risk of mortal-ity, and therefore any interven-tions which we believe they might have benefit, they also have the potential of causing harm. And therefore their ap-plication in these patient popu-lations should really be studied first, with safety in mind.”


Feeding the debate in pharmaconutrition

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Snapshots from ISICEM 2012

C ontroversial issues in renal failure will be offered up for debate this morning during a session that will put the classifica-tion, origins and mortality rates of this lethal disease on trial.

“People who develop acute renal failure in the ICU have an extraordi-narily high mortality: between 50 and 75% of those people will die,” session co-chair Jonathan Sevransky (Emory University School of Medicine, Atlanta, USA) told ISICEM News.

“And so we have a tremendous number of controversies in terms of both what is the syndrome – what is acute renal failure – and what causes acute renal failure?”

Discussing the presentations due to be featured in the session, Dr Sevransky gave an overview of what he thought was likely to be addressed: “The first three speakers are going to concentrate on whether or not organ ischemia is the major cause of acute renal failure, taking a ‘yes’, ‘no’ and ‘maybe’ approach, since there’s data supporting each of those potential options,” he said. “[I.e.] whether or

not treating ischemia by volume or giving an inotrope or vasopressor may help treat patients with acute renal failure, and improve mortality in this syndrome.”

Dr Sevransky continued by adding that one of the main controversies in renal failure was the identifica-tion of the cause and effect within the disease: “I guess that one of the other controversies is whether acute renal failure is by itself dangerous, or whether it’s just a marker for severity of illness,” he said.

He added: “The next topic of discussion is whether it makes a dif-ference, so whether in fact people die with acute renal failure rather than of acute renal failure.”

In order to classify renal failure, the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria is a commonly used measurement, but it does have its naysayers: “A lot of peo-ple use the RIFLE criteria now, which has benefits and downsides,” said Dr Sevransky.

However, this classification is still key, thus the session will include pres-

entations that focus on this concept: “The final talk is whether or not this is in fact one syndrome, or whether it’s a constellation of syndromes,” said Dr Sevransky.

“Since we don’t have a good biomarker for renal failure, there’s a possibility that we are confusing several syndromes, in that we may want to treat people with one of the syndromes caused by, say, organ

hypoperfusion differently than some-body who has a different cause for renal failure.”

“It may be us lumping things together, [when] maybe we ought to be splitting them into different categories.”

Referring again to the use of bio-markers, Dr Sevransky stressed that, at the current time, biomarkers have only been truly established as functional indicators, thus there is a great deal of personal interpretation as to their efficacy in identifying kidney injury.

“I think if you put 10 experts into a room together, you’d get 10 different opinions as to what the best biomarker of acute kidney injury or of acute kidney failure is,” said Dr Sevransky. “And I think we will hear some of those differences during the presentations.”

“There are a number of potential items on the horizon, but I don’t think any of them have been validated in patients,” he added in closing.

More detail on these, and other, con-cepts in renal disease will be addressed in the session ‘Controversies in renal failure’; 08:00, Friday 23 March in the Lippens Room National Library .

Contention reigns in renal disease

Controversies in renal failure Lippens Room National Library Friday 23 March 08:00–09:50

Jonathan Sevransky


A session that explored new therapeutic options in the treatment of acute respira-tory syndrome (ARDS) took place on Thursday afternoon, with invited experts presenting a range of con-cepts hoped to revolutionize future treatment strategies.

“The session is very important because ARDS still has a high mor-tality,” session co-chair Nicolas Nin (Hospital Universitario de Getafe, Madrid, Spain) told ISICEM News. “It’s decreasing but it’s still around 30-35%, so it’s very important to have new therapeutic options for the future.”

He added: “There is still a big field for this because now there are very few clinical assays that are studying ARDS. It’s very important to start thinking what to do in the future.”

The session presented concepts in gene activation, antiplatelet agents, cell therapy, TAT protein and delta-PKC inhibition, purine metabolism alterations with CD 73 and interferon. In addition, older anti-inflammatory concepts will be given a fresh update.

Discussing the current status of cell therapy, Dr Nin said that there is experimental ev-idence established in cell therapy, but not in the case of ARDS. However, he added that there are several new publications that are hoped to increase the use of cells therapies, and extend into clinical ARDS use.

“I think in per-haps in five to ten years it could be translated to the patients, but, yes, we have started to use cells in acute lung injury,” said Dr Nin. “It’s still very experimen-tal.”

Gene therapy is very much the same, he said, but, again, an ‘explosion’ of ex-perimental models in the field of gene therapy is hoped to be part of a very bright future.

Anti-inflammatory agents may not be as new a concept, but revisiting their use, and dangers, in the session

was an important component, as Dr Nin explained: “There are some more experi-mental models that are trying to recover the use of the old anti-inflammatory agents,” he said.

He continued: “They may be harmful, because they have lots of reactions: vascular reactions, not only pulmonary…There are some experimental models and some clinical assays that were done about 20 years ago that don’t [cause] any kind of increased survival for the patients.”

As a gen-eral note, Dr Nin stressed that to advance forward more effectively in ARDS treat-

ment, more thought regarding thera-peutic pathways and mechanisms

is required. “I think there are a lot of people who are using [classes of]

specific proteins, and in experiential models they see some increase in some of the physiological param-eters of animals, and it would work to start thinking about pathways,” he said.

“When you start to experiment with proteins and pathways, the thing is to have an answer, and start thinking about what pathway we can explore in the future. So a lot of people who are doing experiments have started to think of mechanisms, and it’s very important.”

Despite this array of novel thera-peutics, Dr Nin emphasized what he thought the most crucial next steps for ARDS therapy would be: “The most important is to do a good diag-nostic,” he said.

“We even now don’t have any kind of biomarker that is specific for ARDS, so we are at the beginning. The future will be to discover metabolic, proteomic and genetic pathways, and the biology system of this disease. But the first important thing is to have a biomarker-specific to do a very quick diagnosis of this entity.”

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“We even now don’t have any kind of biomarker that is specific for ARDS, so we are at the beginning. The future will be to discover metabolic, proteomic and genetic pathways, and the biology system of this disease. But the first important thing is to have a biomarker-specific to do a very quick diagnosis of this entity.”

Nicolas Nin (Hospital

Universitario de Getafe,

Madrid, Spain)


New strategies offer breath of fresh air in ARDS

Nicolas Nin


P rofessor Vincent has authored more than 600 original articles, more than 257 book chapters and review articles, and 680 original abstracts. He has published over 85 books, including more than 60 in his own series “Update in Intensive Care and Emergency Medicine” and “Yearbook in Intensive Care and Emergency Medicine”, published by Springer-Verlag (Heidelberg, Berlin, New York). He has also written a French Manual of Intensive Care and Emergency Medicine (Springer, France).

He took time out from his busy schedule to speak to ISICEM News on how he feels the meeting has gone so far, some of the areas of debate in managing the critically ill pa-tient that have been discussed, and the importance of a meet-ing such as ISICEM 2012.

Good afternoon Professor . How do you feel the con-ference has gone so far? Has anything stood out for you, perhaps, from what we have seen and heard over the last three days?It has gone very, very well. The echoes we have got are all very positive. Obviously, in terms of participants, we have about the same number as last year, despite difficul-ties, especially in the south of Europe. We have had 6000 participants all together, and they are all very, very happy. They are also very happy about the weather, of course! Clearly, all the rooms are full, with standing room only, and the quality of the program is just outstanding. We are really grateful to our speakers and faculty members.

There were lots of good discussions about different topics. It is difficult to name them all, but we had a lot on types of IV fluids, as it was the topic for our Round Table conference, and lots of

discussions about the possible toxicity of some of these fluids, including perhaps some colloid solutions, some saline solutions, and we don’t know very much about what we call balanced solutions, includ-ing other electrolytes. So, that raises a lot of very active discussions.

We also had many discus-sions about optimal nutrition-al support. Should we start early? Should we wait a little bit? Should we use special-ized solutions, maybe with glutamine, with arginine, with omega-3 or other particular constituents? This is still very controversial, and we had the best experts in the world here, who could really argue about that.

Close to that subject is that of glucose control, not only the exact level at which we should keep blood sugar, but how we could avoid vari-ability, because we know that going from a rather low value to a high value and back to a low value could result in more damage than staying relatively stable at any level. There is a lot of interest from the industry side to develop better tools to monitor blood sugar at most continuously. We also have another Round Table conference on Thursday afternoon and Friday morn-ing, with about 20 experts who will address these issues and really evaluate the various systems that are out there to control blood sugar more ac-curately. There are at least 10 companies interested in this. It’s really moving very fast, and I think in a very interest-ing direction.

We had a lot on neuro-monitoring as well. On how we could better monitor the brain in severe trauma, head trauma or in severe cerebro-vascular accidents, and how we could better monitor the brain either with systems to evaluate the circulation using

infra-red spectroscopy or with actual probes that we could insert into the brain to monitor the oxygen tension of the brain in order to look at local lactate levels, and other metabolites. These are some important tools that we may have to better evaluate brain function and better adjust our therapies to that.

Of course, the amount of fluids to be given is still an im-portant issue. It is interesting to hear that there is a pendu-lum, as in everything, and the pendulum now goes towards less fluids to be administered

in critically ill patients. We are concerned about excessive edema formation and possible fluid overload when we are perhaps a bit too dynamic with our fluid regimen. So now the tendency is to try to limit it a little more than a few years ago.

In terms of the pendulum of medicine, clearly we have been disappointed in recent trials in sepsis and clearly the studies have been negative, one after another. We need to revisit our strategies a little here. Not necessarily revisit the concept of sepsis – sepsis

is there and will remain – but how we tackle it. How we address this type of problem is perhaps changing now, as we think that perhaps it is not so necessary to concentrate on patients with documented infections, but that we should try to find a proper biomarker that could better identify the patient populations who may benefit from this or that intervention. So our approach has changed somewhat, and it was inter-esting to hear that at various sessions, to see how people have somewhat changed their minds about these new therapeutic interventions.

There has been such a fast pace of learning in intensive care medicine, whether it be in terms of diagnosis and management or simply our understand-ing of the physiology . Does it makes a meeting like this all the more important for people to be able get this latest update?I think you can learn a num-ber things from the internet, and now the publication of data is more rapid than be-fore. So, you can have access to the latest information just by going on PubMed or even on Google Scholar, but when you go to a meeting, you can really feel the pulse. You can really learn from discus-sions at question times, from discussions in the hallways or in the bar, and you can pick up some new concepts and see in which direction we are going. It’s more than just data presentation, it is the overall approach to the critically ill patient that is better defined when you go to a big meet-ing like this one.

Perhaps also it is about giv-ing context, because data on it’s own is just that: data .Exactly. We need to interpret data and see how people interpret them. At this meet-ing we like also interaction, so that’s why we organize Pro and Con debates or Round Ta-ble discussions, and we leave ample time for discussions. A lot of interesting information comes out of that.

The final word: Jean-Louis VincentISICEM Chairman Jean-Louis Vincent (Erasme University Hospital, Université Libre de Bruxelles and Secretary General of the World Federation of Societies of Intensive and Critical Care Medicine) is a world-renowned expert in intensive care and emergency medicine. His main fields of investigation are severe sepsis, acute circulatory failure (circulatory shock) and its treatment, oxygen, hemodynamics and vital emergencies.

Jean-Louis Vincent

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