The official daily newsletter of the 35th ISICEM Thursday 19 March 2015 Day 3 Outcomes from the 2015 Round Table on sepsis

uring the opening session on Tues- day morning, Simon Finfer (Royal North Shore Hospital of Sydney and Sydney Adventist Hospital, Sydney, Australia) was joined by Steven DOpal (Memorial Hospital of Rhode Island, RI, USA) to summarize the major outcomes of the two-day Round Table discussion “This will be a on sepsis. This was a joint conference significant part of our conducted between ISICEM and the Inter- national Sepsis Forum, with representa- research agenda in the tives from every continent highlighting the future – making sure global nature of the problem. Beginning by addressing the current that our patients are state of knowledge in the epidemiology of doing well after they sepsis, Professor Finfer noted that we know leave the hospital.” surprising little, but that obtaining this data will be crucial if any meaningful strategy is Steven Opal to be developed: “To some degree we have data from developed countries, possibly far less than you would expect or think,” he said. “But there are certainly places in, notably, Africa, where we are completely devoid of data.” The reasons for this lack of data can in part be understood by an appreciation of how patient data are currently characterized and treated, with the Global Burden of Disease Project emerging as a central player in generating evidence and guiding is surprising because we believe that sepsis kills one comes into your ICU with community-acquired global health policy. more people than prostate cancer, breast cancer, pneumonia, you treat the pneumonia; maybe they “The only reference to sepsis in these sta- and many other high profile diseases. The reason are an elderly person with a lot of comorbidities; tistics is to neonatal sepsis,” noted Professor for that is that the Global Burden of Disease only they have sepsis, but the sepsis goes unresolved Finfer. “There is nothing else about sepsis, which counts the underlying cause of death. So if some- Continued on page 19

The protective role of Intensive “No shortcuts” Massive exercise in critical illness careers: Providing with process measures bleeding: support for our ICU staff lessons from the military ...... 2 ...... 5 ...... 10 ...... 14 2 ISICEM News Thursday 19 March 2015 Issue 3

Plenary lecture: Critical illness is top sport Arc Room Tuesday 17:30 The protective role of exercise for critical illness regular and consistent exercise regime prior to critical illness is a significant boon for Aoutcomes, offering a protective effect that means patients can expect to re- cover quicker, and have an improved quality of life. So was the message of Can Ince (Erasmus Medical Center, Erasmus University of Rotterdam, the Netherlands) who shared his perspec- tives, as a physiologist, on the role of exercise in critical illness during his plenary lecture on Tuesday. “I have been involved in critical care medicine as my main topic of interest for more than 30 years,” he told ISICEM News. “I have been interested in physiological function, the function of organs, and specifi- cally how the cardiovascular system functions in states of critical illness, and how to improve it – especially in terms of transport and the microcirculation.” During his lecture, Professor Ince relayed his experience from decades of work, paying particular attention

ISICEM News Publishing and Production “When you are sick, what is MediFore Limited particularly debilitating is the Symposium Chairman to a project in the last 5-10 “What is very interesting Jean-Louis Vincent feeling of helplessness … it is years which has focused on from an academic view I think Editor-in-Chief extreme physiology. “How do important to get across the is how much emphasis there Peter Stevenson you react, when healthy, to ex- message that you might end is on drug-related interven- Editors treme conditions?” he said. “I tions to health and disease, Rysia Burmicz am talking about low oxygen, up in intensive care, but you and that exercise is a relative Becky McCall high , strenuous exer- can already start working on side-show when it comes to Additional content cise, dehydration, extreme cold making sure you have a good the big journals of critical Aisling Koning etc. That has been an interest illness and perioperative Design of mine, because it is amazing chance of surviving.” medicine,” he said. Peter Williams what the can “If you look how you can Can Ince Industry Liaison Manager endure, but with critical illness, actually influence physiology Bethan Coulbeck the smallest glitch happens while exercising, one of the and then the alarms go off.” big problems in this area is Head Office 19 Jasper Road, Crystal Palace As part of this burgeoning work, department of surgery at the Eras- actually getting people to do it in the London SE19 1ST, UK Professor Ince has been involved in mus Medical Center, at which they first place, because for true benefit Telephone: +44 (0) 20 8761 2790 Xtreme Everest – a unique research are thinking of how to improve the you have to do it for a lengthy period [email protected] project at which outcomes of their patients by preop- of time, and it has to be done consist- www.medifore.co.uk has been exploring the response of erative exercise,” said Professor Ince. ently.” Copyright © 2015: Université Libre de the body to oxygen-thin air at high “There is this whole of idea of how Specifically, Professor Ince spoke Bruxelles. All rights reserved. No part of this .1 In fact, oxygen levels in is fitness related to outcomes, and of a ‘sweet-spot’ of around 200 publication may be reproduced, stored in a the infamous ‘Death Zone’ were so whether you can you do something minutes of exercise per week to see etrieval system, transmitted in any form or by any other means, electronic, mechanical, low they were barely able to sustain preoperatively to influence it.” substantial benefit, which in practice photocopying, recording or otherwise without human life, thus providing enlighten- The third piece of the puzzle that can be difficult for busy individuals prior permission in writing of ISICEM. The ing data as to the conditions faced by Professor Ince is concentrating on is to do. Furthermore, this must be content of ISICEM News does not necessarily reflect the opinion of the ISICEM 2015 intensive care patients. how the body actually responds to ex- moderately intense exercise, not just Symposium Chairman, the ISICEM Scientific “The second area of interest ercise, exploring its beneficial effects a walk in the park: “This is cycling Advisors or Collaborators. concerns my involvement in the from a physiological perspective. Continued on page 4

4 ISICEM News Thursday 19 March 2015 Issue 3

Plenary lecture: Critical illness is top sport Arc Room Tuesday 17:30 The protective role of exercise for critical illness

Continued from page 2 in abdominal surgery, for example. “So when I look at it from my point and proactively work for better out- or running where your heart beat This is one of our main interests. of view in physiology, I see a cluster comes. “When you are sick, what is is going high,” he said. “Or playing “From my physiological perspec- of lots of different little contributors, particularly debilitating is the feeling tennis, swimming etc. tive, I think you have to look at a like the ‘Butterfly Effect’ – i.e. they all of helplessness, and I think that from “200 minutes is quite a lot actual- bigger picture, as looking at gross can contribute to an adverse outcome, that point of view, it is important to ly, if you try and do it, but neverthe- get across the message that you less if you do that for a consistent might end up in intensive care, period of time, you do notice your “Now people are much more interested in quality of but you can already start working gait is better, your general feeling life: can you think, can you walk, can you do simple on making sure you have a good is better, and people who have chance of surviving,” said Professor previously not done it, but start to – things, are you enjoying the fact you are alive, and Ince. “Popping pills is not the way… and keep it up for a period of time have survived critical illness? And from this point of but exercise is something that you – will certainly notice a difference in view you need all of the help you can get.” can already start investing in.“ their general wellbeing.” Indeed, in the United States, Getting into the meat of the Can Ince there is already a public program data, and looking at how we encouraging exercise, called ‘Ex- can assess the positive influence ercise is Medicine’, which acts to of exercise for critically ill patients, clinical outcome parameters is the and that itself is also a fuzzy concept. boost awareness and take-up of a Professor Ince commented: “It is dif- way to go. If you have a serious Obviously being alive or dead is the good exercise regime. ficult because you have to objectively disease, and it can be anything from ultimate outcome parameter, but now For Professor Ince, his take-home measure parameters of fitness, which renal transplantation to cancer, etc., people are much more interested in message was clear: exercise is a pow- is a whole murky area of trying to there are a number of clusters of quality of life: can you think, can you erful way to improve the chance of find out if someone is fit or not.” pathogenic issues that will contrib- walk, can you do simple things, are superior outcomes in many diseases, He added: “But the British Medi- ute to the ultimate outcome of that you enjoying the fact you are alive, including critical illness. “It certainly cal Journal has announced a relatively patient. And it is not only whether and have survived critical illness? And is an important contributing factor in large trial in which they are going to cancer will come back, whether from this point of view you need all of ensuring that you have a good qual- do this. I think the clearest evidence there will be a massive hemorrhage, the help you can get.” ity of life. Whether you will actually is in cardiac surgery, where if you whether they will be able to have One vital component in the survive or not is dependent on a lot go on to an exercise machine about cognitive function once discharged argument for exercise as a protec- more factors,” he said in closing. three months before you go to sur- from the hospital, or suffer sepsis etc. tive measure in critical illness is the References gery, your outcome is much better. All of these issues are bits and pieces power it gives the patient to take 1. Xtreme Everest (Available at: The question is how much it can help of the puzzle. their health into their own hands, http://www.xtreme-everest.co.uk/) Issue 3 Thursday 19 March 2015 ISICEM News 5

ICU organization Lippens Room National Library Wednesday 08:00 Intensive by name, intensive by nature for ICU docs

xtreme stress, burnout, health I think we always assume the doctors will issues, drop-outs and even heal themselves, but they don’t. We do suicide are worryingly-common lose doctors from burnout, from substance Eoutcomes affecting ICU doctors, abuse, from suicide, from depression. Their nurses and other allied healthcare staff home lives can get really hurt unless we in centers the world over. This turbu- look after them, and look for early warning lence is further compounded by the signs that they need a break, and need presence of elevated infection risks, support.” meaning that mental and physical Turning to the risk of infection, Dr strain are part-and-parcel of the daily Ramsay spoke of his personal experience in life of ICU staff. Dallas, which suffered an Ebola outbreak With this is mind, it is not sur- in 2014. Several nurses were infected in prising that mounting emphasis is the outbreak, despite them following what being placed on protecting our ICU were supposedly up-to-date guidelines professionals, reaching out wherever for protection, as Dr Ramsay explained: possible to make sure that those most “When you saw what was happening on vulnerable to the maelstrom of every- TV, when they were shipping the doctors day ICU practice are given the physical back, they had hazmat suits on, with no and psychological care they need. exposed skin at all, so there was clearly “I think that emergency medicine information about how to protect and critical care medicine are two yourself out there, but the CDC of the highest-stress specialities in “We do lose doctors from hadn’t picked it up and spread medicine,” Michael Ramsay (Baylor burnout, from substance it to the rest of the healthcare Health Care System, Dallas, TX, USA) systems in the United States. That who delivered a lecture on the topic abuse, from suicide, was the problem in Dallas where of ‘Keeping the ICU doctor happy’ on from depression. Their those two nurses got caught with Wednesday, told ISICEM News. “So what do we do junior staff. They have home lives can get really it: we just weren’t prepared.” to stop burnout? What do we do to keep our doc- the experience, and In fact, Dr Ramsay under- tors functioning well, keep them on top of their they have the know- hurt unless we look after lined that the quest to improve game? I don’t think we do much to keep a check how of what they them, and look for early protection for infectious diseases on making sure they are not getting burnt out, or have been through, has been a continual journey for stressed out.” and they need to be warning signs that they doctors, beginning with inventions For Dr Ramsay, we are still failing to effectively looking for warn- need a break, and need such as René Laennec’s stethoscope and consistently teach ICU doctors on how to ing signs from their (itself purported to have been protect themselves from infection, and the same colleagues who support.” designed to avoid listening close is true in terms of reaching-out to discuss mat- didn’t make it. Who Michael Ramsay to the chest, and therefore risking ters of their job, their life etc, in order to identify dropped out and why infection), all the way up to mod- those at risk of burnout, or worse. “If they are not did they drop out? ern epidemics such as Ebola, or the healthy, they are not functioning properly, and Then they can try and intervene early, so we don’t SARS outbreak in Hong Kong in the early 2000s. that stretches to mental health as well as physical lose any more people from what is really a very Offering a snapshot of how we can improve the health,” he said. If you don’t put in a good support valuable clinical care resource.” care of our doctors overall, whether that is imple- programme, your turnover of staff, and absentee- “As administrators we have to be very watchful mentation of better infection control, or psycho- ism of staff, is incredible.” that we are looking after the staff, nurses and logical and physical support, Dr Ramsay concluded: He added: “I think the senior doctors are the physicians. Nurses I think we do focus on a lot, “Some of it has got to be education, but a lot of it ‘survivors’, and they need to be looking after the but we don’t focus on the physicians enough, as is communication.” 6 ISICEM News Thursday 19 March 2015 Issue 3

ARDS: Prevention rather than cure Salle M (Bozar) Thursday 10:45 Perioperative prev ention of ARDS

ocus will be shifted from cure patients that we know are at risk simply to prevention today in an based on the type of surgery they are ARDS-centric session that will having,” said Dr Blum. Fsee a number of experts present their “The other aspect that we know perspectives on the strategies, consid- that predisposes people to ARDS are erations and outlook for the disease. patients that are undergoing emer- Tackling the prevention of perioperative gency surgery, or those with additional ARDS will be the James Blum (Emory comorbidities that are undergoing sur- University Hospital, Atlanta, GA, USA), gery. And there is a classification system who will explore some of the risks, for the level of organ dysfunction that frequencies and predictive aspects of people have, or the chronic comorbidi- ARDS occurrence. ties that they may have, defined by the Dr Blum spoke to ISICEM News to American Society of Anaesthesiologists first offer his perspectives on those who [ASA].” might be most at risk of ARDS, splitting The ASA classification ranges from 1 the major con- to 6, increasing in severity as the number “I’m hopeful that aspirin siderations into increases. ASA 1 refers to a normal two patient cat- healthy patient; 2 = those with mild will actually be a modality egories. “The systemic disease; 3 = chronic conditions that we can use to help first of which suboptimally managed; 4 = ongoing is patients who medical conditions that are a constant prevent ARDS.” are undergoing threat to life; 5 = those expected to die procedures that within 24-hours, without an operation; 6 James Blum are known to = patient who has been declared brain- be high-risk for dead and is awaiting organ donation. ARDS – things like major aortic surgery, “What we’ve found is that patients cardiac surgery, trauma. Those are who are ASA 3,4,5 are generally at Issue 3 Thursday 19 March 2015 ISICEM News 7

ARDS: Prevention rather than cure Salle M (Bozar) Thursday 10:45 Perioperative prev ention of ARDS

higher risk for the development of maybe 300 patients with ‘real’ ARDS, While he commented that He went on: “Now on the flip postoperative ARDS,” said Dr Blum. or even less than that, at the end of the jury was “still out” on other side I think that in the operat- “In addition, if they have emergency the year. The incidence of substantial potential ARDS-preventative agents, ing room, anaesthesiologists have surgery, those people have increased ARDS is probably about 0.2 to 0.5% and technologies such as stem cells, been doing a terrible job managing risk. So that knowledge is what the of cases, so enrolling patients into Dr Blum noted that there really are ventilators, despite the fact they anesthesiologists and the intensiv- a single canter study is a challenge, some exciting methods of interest on mechanically ventilate more people ists are left with before they head and then since we know that than anyone else on the into the operating room with the the patients with the highest planet, on a daily basis. surgeon. risk for this are actually sick “If my feedback signal is that every For the most part they do “I think the question is then what patients that are undergoing 200-500 cases I wind up with one not intelligently set their can we do perioperatively to try to emergency surgery, it gets ventilator settings. So I prevent ARDS? There is not a lot of difficult to enroll them in any patient that develops postoperative do think that, periop- great data on this, but some that type of trial with consent.” ARDS, well it is very difficult for me eratively, there is the op- does exist suggests that we can actu- Looking to the role of portunity for us to impact ally potentially impact the likelihood various new therapies or as a practitioner to say I am going development of ARDS of development of postoperative techniques that may show to change my behaviour.” using the ventilator. But I ARDS. The way we do that is most promise in preventing ARDS, don’t think it is a case of likely by changing our ventilator Dr Blum continued: “Surpris- James Blum doing anything innovative settings to be less injurious. This is in ingly there are some data – it is just applying the addition to reducing the amount of that just aspirin may actually things we already know: fluid we give patients in an attempt be productive. There is a study ongo- the horizon. providing a sufficient amount of to reduce the amount of blood we ing right now that will be hopefully Conversely, the ventilator may PEEP, reducing which by need to give them as well. All those published within the year… it doesn’t have reached its potential: “I think definition should reduce your drive things seem to predispose to the risk focus exclusively on perioperative we have done pretty much every- pressure.” of development of ARDS.” patients, but it does look at the thing we can in terms of the ventila- Dr Blum underlined that, like most Dr Blum went on to note that idea of patients that are high risk tor,” he said, adding that recent pub- situations found in anaesthesiology, there is difficulty in setting up trials of injury receiving aspirin, in a lished work by both his center and patients that present for surgery are, to better assess the others has suggested most of the time, fairly robust. “We statistical significance that the one thing that cannot be perfect in the anaesthetic of ARDS risk. For one, “Perioperatively, there is the opportunity hasn’t received enough we give them, yet the vast majority almost half of the for us to impact development of ARDS focus is the drive pres- of time they will do just fine,” he patients undergo- using the ventilator. But I don’t think it is sure. “That we found, said. “It is in the rare cases, those 0.2 ing cardiac surgery, in our own work, to to 0.5% of cases, where they will for example, show a case of doing anything innovative – it be the most sugges- develop postoperative ARDS. Then signs of postopera- is just applying the things we already tive to development of what we do may actually really mat- tive ARDS after their postoperative ARDS,” ter. So if my feedback signal is that surgery, but are then know.” he said. every 200-500 cases I wind up with “But I really think one patient that develops postop- clear the day after. James Blum “Those patients that that the next big jump erative ARDS, well it is very difficult develop severe ARDS in ARDS survival is for me as a practitioner to say I am postoperatively are rare,” he said. randomized controlled fashion. I’m going to be either early institution of going to change my behaviour on a “In a large university hospital, you hopeful that aspirin will actually be ECMO or it is going to be a biologic. daily basis, and that I am to prevent may do up to 50,000 anesthetics a modality that we can use to help I don’t think we are going to make something that happens every 1/200 a year, and you will wind up with prevent ARDS.” the next big jump with a ventilator.” to 1/500 times.” 8 ISICEM News Thursday 19 March 2015 Issue 3

Diagnosing pneumonia: is pneumonia present, and if so, which bugs are causing it?

ot least among the challenges presented by critically ill patients is which antibiotics they have received,” said Dr. Sánchez García. Nthe question of confirming the diagnosis of a patient with suspected Relatively non-specific criteria exist to aid diagnosis, alongside scoring pneumonia. Miguel Sánchez García (Head of Critical Care, Hospital systems. Invasive techniques can be used to sample the lung with bron- Clínico San Carlos, Madrid, Spain) addressed this challenge in his talk choalveolar lavage, and ultrasound might also be performed. “Ultrasound during the session ‘Challenges in pneumonia man- experts say that they can distinguish different types agement of critically ill patients’, held on Wednesday “For accurate diagnosis of infiltrate and identify a pneumonia from other at ISICEM 2015. types of infiltrates.” Currently, no gold standard exists to diagnose the you need experience, Dr. Sánchez García explained that of the diag- disease, so Dr. Sánchez García emphasized that cli- recognition of several nostic protocols that do exist, none are sufficiently nicians needed to explore two key aspects when ap- sensitive and specific: “Clinicians need to take a proaching the diagnosis of such a patient. Firstly, it signs and all together protected specimen, not contaminated with upper is necessary to determine whether the patient really you arrive at, or reject airway bugs, to confirm that an infection is present. has pneumonia. “For accurate diagnosis you need ex- Most patients with negative protected specimens perience, recognition of several signs and all together the diagnosis.” should not be treated.” you arrive at, or reject the diagnosis. This is the first Miguel Sánchez García However, he added that false negatives are not difficulty because unlike other infections that are unusual and if this is found then a second sample more visible, with pneumonia it is more difficult – might help clarify the situation: “Antibiotics might for example, infiltrate on X-ray might be due to other phenomena.” be given for a few days and then the patient is re-sampled.” Secondly, accurate identification of the infectious micro-organism is Turning to the second aspect of diagnosis, concerning the identification important to help determine which antibiotic is needed for treatment. of the infecting microbes, Dr. Sánchez García pointed out that an inves- “This is a whole universe and a difficult question to tackle. It is related tigation into the immediate prior history of the patient would be the first to where that patient has come from, what they have been treated with, approach. “Watch out for more resistant microorganisms which might Issue 3 Thursday 19 March 2015 ISICEM News 9

be involved if the patient has already been hospitalized for several days or available to treat these bacteria are few, leading to an increased selec- weeks and has previously received antibiotics,” he said. “There might be tion pressure related to using the same drugs and the threat of increased micro-organisms resistant to prior antibiotic therapy which is one of the resistance.” key risk factors for the presence of multi-drug resistant micro-organisms.” Over the last decade, many studies have emphasized the need for Whilst determining whether the patient’s infection is a resistant form an adequate treatment of all the cultured organisms found, because an of bacteria, one major issue is that the report on the microbe’s suscepti- inadequate therapy that fails to target all bacteria is associated with bility is not returned for 3-4 days after sampling, and delaying therapy is increased mortality and morbidity rates. “In addition, this treatment directly related to mortality. should be provided as an emergency, as soon However, Dr. Sánchez García pointed out as the diagnosis has been made and pulmonary that certain rapid tests are being developed than “Infections can be acquired samples collected.” can deliver a result in a few hours like, for exam- outside the ICU or in Dr. Montravers noted that the usual approach ple, those based on polymerase chain reaction to overcome issues related to full coverage of all (PCR). Some rapid tests are already available and the ICU setting in non- isolates is based on combination therapy, which are proving to be very sensitive and specific, but ventilated patients leading extends the range of bacteria targeted. He added further data are required on morbidity and mor- to the common name that despite several sets of guidelines having been tality before conclusions can be drawn. “Most formulated, the most recent ones do not add are specific for a particular organism, and do not of hospital acquired anything particularly different compared to those exclude the presence of other, potentially multi- pneumonia (HAP).” published ten years ago. “These recommenda- drug resistant bacteria.” tions are the reflection of the national or interna- Looking ahead to the future of diagnostic Philippe Montravers tional ecological and microbiological concerns of tests, Dr. Sánchez García anticipates that tests their authors, and might not always be relevant will, most likely, be able to determine that firstly to the prescribers and readers,” he said. a pneumonia is present and identify the causative microbe, although he In essence, Dr. Montravers concluded that in this respect, “the best added that a combination of diagnostic resources is likely to be required. option should be to know your own ecology to better tailor the treatment Also speaking at the same session was Dr. Philippe Montravers, of your patients.” (Department of Anesthesia, Hospital Bichat Claude Bernard, Paris, He also highlighted data that suggested that ceftobiprole represents a France) who discussed nosocomial pneumonia, which, he pointed out, new option approved for community-acquired pneumonia and HAP that remained the first site of infection in ICU patients and one of the first further extends the range of drugs in the armamentarium. causes of admission in the ICU. Ceftobiprole, a fifth-generation cephalosporin antibiotic has dem- “These infections can be acquired outside the ICU or in the ICU set- onstrated good efficacy against Gram-positive cocci, especially against ting in non-ventilated patients leading to the common name of hospital methicillin-resistant Staphylococcus aureus. Its efficacy against the acquired pneumonia (HAP),” said Dr. Montravers. Gram-negative organisms is also of interest, he remarked. Echoing Dr. Sánchez García’s talk, Dr. Montravers highlighted that “Overall, the drug has been compared in a double blind randomized making the correct diagnosis was a significant difficulty, especially if trial against a combination of ceftazidime and linezolide and has dem- not based on invasive techniques such as bronchoscopy. Furthermore, onstrated a non-inferiority in clinical cure. The non-inferiority was not determining which microorganisms to target with treatment was another achieved in a sub-group of patients with ventilator associated pneumo- challenge. “Many microorganisms cultured from patients with HAP are nia, but this goal was not the primary endpoint of the trial.” difficult to treat, such as staphylococci, pseudomonas and enterobacte- As a consequence, the indication of ceftobiprole for the moment is riaceae. We frequently face multi-drug-resistant pathogens, and the drugs limited to HAP. 10 ISICEM News Thursday 19 March 2015 Issue 3

How to improve ICU quality Studio (Bozar) Thursday 13:45 “No shortcuts” with process measures

session dedicated to improve- That makes good clinical sense. But ments in ICU quality will take what is hidden beneath this is two place this afternoon, with potential sources of error: one, how Avarious speakers sharing the latest in do you account for patients with quality understanding and delivery. missing information? Do you simply During the proceedings, Michael exclude these from the equation? Klompas (Harvard Medical School, That doesn’t make sense, because Boston, USA) will be taking a look these are arguably the people that at how process measures could be you most want to know about, be- put to better use relative to the cur- cause maybe they are the ones that rent reality, asking: are we fooling aren’t getting any of these practices ourselves? at all. Dr Klompas will primarily speak “Two, how do you actually decide about process measures pertaining to for whom the measure is indicated or the care of ventilated patients, as he not? There are listed indications and explained to ISICEM News. A number contraindications for these tests, but of bundles have been proposed for if you drill down, there is variability the care of ventilated patients, each from hospital to hospital. In many of which put together a collection of cases it turns out to be that there is best practices, such as elevating the a fair bit of subjectivity as to when head of the bed, use of chlorhex- something is indicated or contrain- idine, spontaneous awakening trials, dicated.” spontaneous trials, stress What emerges from these two ulcer prophylaxis and deprophylaxis. factors is that a hospital might, on “What is good about these is the face of it, demonstrate high that, if these are our best practices, it rates of compliance in those patients makes sense that we should be doing with unambiguous indications, while them for every patient every day,” missing another swathe of more said Dr Klompas. “It is a very acces- complicated patients, either through sible way to measure the quality of missing information or erroneously care that is being delivered.” assigned contraindication. But there are shortfalls to this: Asked how, given these issues, “There is some debate as to what any of the analyses derived from actually constitutes best practices process measures can be of any use, for ventilated patients,” said Dr Dr Klompas replied: “That is the Klompas. Hence, whether or not the million-dollar question. The bottom components that make line is that they are only valuable if up bundles of care are you have rigorously thought through the fit for the task is a and defined these problems, if you matter of contention. “If you were to survey hospitals that look ous awakening trial, have a well-defined protocol for “The second line of after ventilated patients, they will all you turn down the what constitutes an indication or not thought is that when it sedation or you turn an indication, you have addressed comes down to actually tell you that they have a bundle, and off the sedation. Turn- the problem of missing data, and you measuring these things, they will all tell you that they have ing the patient back define what constitutes the right way the nitty-gritty details outstanding bundle adherence.” up to the same level of to react to the measure – and you of how to do it are sedation as before de- measure all of these variables.” complicated, and there Michael Klompas spite the spontaneous Such an endeavor requires buy-in is no consensus as to awakening trial might from all parties involved in the com- how to do it. actually affect their plex care environment, which could “As an example, if outcome. Likewise, if be a challenge to obtain. But, said Dr the measure is elevating the head they remain tools by which we can the patient passes the spontaneous Klompas, there is no substitute for it of the bed, how do you make that assess whether or not it is safe to (in breathing trial but you don’t actually if quality of care is the goal. observation? How many times a day the case of spontaneous awakening) extubate, the spontaneous breathing “I think if you were to survey do you make it? Is it sufficient for reduce sedation, and to reduce it to trial hasn’t actually changed anything hospitals that look after ventilated a nurse to simply eyeball it in the the minimum level that is neverthe- for the patient at the bedside level.” patients, they will all tell you that morning as a one-shot assessment? less deemed to be safe. Similarly, As well as an appreciation of the they have a bundle, and they will all Does that inform us of what is hap- the spontaneous breathing trial is value and importance of such practic- tell you that they have outstanding pening to the patient throughout the a prompt to inform the practitioner es for optimal outcomes, compliance bundle adherence,” said Dr Klompas. other 23 hours and 59 minutes of whether or not a patient is ready for on the whole is essential. But how But a more detailed look would the day?” extubation. can this be measured in a meaningful reveal another story – that perhaps This is not to overlook the actual “Of course, these things only way? Dr Klompas explained, “The all patients do not receive the highest goal of practices such as spontane- work if you react to the information classic way to do this is to measure standard of care all the time. ous awakening and spontaneous from these trials in the express fash- the proportion of patients who get That being said, he concluded, breathing trials, which process ion,” said Dr Klompas. “This means this practice divided by the number this is precisely what proper use of measures are intended to ensure: that if the patient passes spontane- of patients for whom it is indicated. process measures is intended to Issue 3 Thursday 19 March 2015 ISICEM News 11

How to improve ICU quality Studio (Bozar) Thursday 13:45

“What is hidden beneath this is two potential capture. Perhaps, if we captured with complex patients, and they have such information more accurately, we to therefore be dealt with using the sources of error: one, how do you account for would find better ways of improving appropriate level of complexity.” patients with missing information?...Two, how this care: “The disparity between do you actually decide for whom the measure measured adherence and reality Dr Klompas will be speaking on ‘Pro- questions the capacity of these pro- cessing process measures’ during the is indicated or not?” cesses to positively impact care. The session ‘How to improve ICU quality,’ answer is that there is no shortcut. taking place this afternoon from 13:45 Michael Klompas This is a complex care environment, in the Studio (Bozar). 12 ISICEM News Thursday 19 March 2015 Issue 3

Therapeutic 400 Hall Thursday 10:30 Cold, cold heart: targeted temperature control

complications – in using the 36°C discuss some of the finer details of approach.” the practicalities and logistics around The International Liaison Commit- TTM, which revealed yet more tee on Resuscitation (ILCOR) will be unanswered questions as to how it publishing a systematic review and can best be achieved with minimal treatment recommendations on this risk to the patient; questions such as, topic in the next few weeks, he said. when should we start temperature “The message coming from this is management? “It has generally been that, regardless of target tempera- believed that the earlier we introduce ture, the really important thing is that temperature control the better, what- we do control temperature in some ever the target temperature might way, whether it is at 33°C or 36°C. be,” said Dr Nolan. We still believe that it is very, very “There has been important important to prevent research on the use of prehospital (pyrexia) in these patients. cooling or temperature control. One Dr Nolan then moved on to of the important studies looked at starting cooling as soon as possible after the return of “Many clinicians would argue that spontaneous circulation versus if there is no apparent advantage delaying it until the patient in using the lower temperature, had arrived in the hospital.”6 Although prehospital there may be practical advantages – cooling reduced patients’ potentially in reduced complications core temperatures before they reached the hospital, – in using the 36°C approach.” thereby reducing the time Jerry Nolan interval between cardiac arrest and target temperature, no

session dedicated to the topic brought to the fore by the targeted of therapeutic hypothermia temperature management (TTM) takes place this morning in trial, which was published in 2013.4 A400 Hall, with a detailed look at This was a RCT comparing two dif- cooling strategies and temperature ferent temperatures, 33°C and 36°C, management, and their places in in patients who have had an out- traumatic brain injury, severe hemor- of-hospital cardiac arrest from any rhage, and after cardiac arrest. rhythm. Both of those groups were Covering the latter will be Jerry Nolan controlled at these temperatures for (Royal United Hospital, Bath, UK), 24 hours.” who spoke to ISICEM News to discuss The trial showed no difference the latest understanding in the field. in the primary outcome of all-cause Therapeutic hypothermia is in- mortality through the end of the duced in patients who have sustained trial period, a minimum of 180 days an hypoxic-ischemic injury following following the enrollment of the last cardiac arrest, with evidence suggest- patient. Importantly, a secondary ing that this improves survival and analysis from the same study, recently brain function.1 Its broad adoption published in Circulation, has shown followed two randomized controlled no difference in cognitive outcome trials (RCT) in 2002, which dem- between those that were controlled onstrated improved survival after at 33°C versus 36°C, in a subgroup out-of-hospital cardiac arrest with of survivors from the 2013 TTM trial.5 induced mild hypothermia of 32°C to This presents a dilemma for 34°C for up to 24 hours.2-3 clinicians who will want to know Since then, explained Dr Nolan, whether this is sufficient evidence most of the controversy has centered to adopt (what is now called) TTM, around the question of whether or and whether they should be doing not this therapy benefits patients so at 36°C or the ‘classic’ 33°C. Dr who have had a cardiac arrest from Nolan explained: “Many clinicians non-shockable rhythms as well as would argue that if there is no ap- shockable rhythms – the original parent advantage in using the lower focus of the two 2002 RCTs. temperature, there may be practical “The controversy has been advantages – potentially in reduced Issue 3 Thursday 19 March 2015 ISICEM News 13

Therapeutic hypothermia 400 Hall Thursday 10:30

Cold, cold heart: targeted temperature control “In terms of other controversies, how long should they be improvement was found in temperature managed for? What ture. RCTs provide the only “Although the evidence is quite survival or neurological sta- means of addressing such scant, we still believe that tempera- tus in these patients.6 “Im- do we do at the end of the 24-hour confounds identified from ture control is important in those portantly there appeared to temperature managed period?” observational studies. patients that remain comatose, at be some disadvantages of Until then, faith ought least to prevent fever, for up 72 starting temperature con- Jerry Nolan to be put in expert opin- hours. And many clinicians will elect trol pre-hospital,” said Dr ion, said Dr Nolan: “Most to leave their temperature manage- Nolan, “At least in the way experts in the field believe ment in place for 72 hours, not just that it was done in the study, which improves outcome, especially given that it is better to use some form of for 24 hours.” was to use up to two liters of ice-cold that so many studies are observation- temperature management technique References fluid to reduce temperature. al rather than randomized-controlled. that involves continuous monitoring 1 Arrich J et al. Hypothermia for neuroprotec- tion in adults after cardiopulmonary resuscita- “Two elements of potential Patients who spontaneously cool the and automatic feedback of tem- tion. Cochrane Database Syst Rev. 2012 Sep harm were shown in the group that most rapidly tend to have worse out- perature, than standard manual tech- 12;9:CD004128. received prehospital ice-cold fluid. comes. However, rapid cooling could niques such as ice. So some form of 2 Bernard SA, Gray TW, Buist MD, et al. Treat- ment of comatose survivors of out-of-hospital They had an increased incidence of be a signal that the body has lost the either temperature control blankets, cardiac arrest with induced hypothermia. N re-arrest during transport to hospital. ability to regulate its temperature, or temperature control vascular de- EnglJ Med 2002;346:557-563. vice with an automatic system which 3 The Hypothermia after Cardiac Arrest Study They also showed an increased inci- implying that it accompanies more Group. Mild Therapeutic Hypothermia to Im- dence of pulmonary edema on the serious brain injuries. sets the desired temperature seems to prove the Neurologic Outcome after Cardiac first chest x-ray that was taken upon To further complicate the matter, be easier to use and easier to main- Arrest. N Engl J Med 2002; 346:549-556. 4 Nielsen N et al. Targeted Temperature Man- arrival. So it is generally thought that external temperatures must be fac- tain a constant body temperature.” agement at 33°C versus 36°C after Cardiac we should not be using cold IV fluid tored in to such studies: patients ar- He concluded the interview with Arrest. N Engl J Med 2013; 369:2197-2206. pre-hospital to induce hypothermia, riving at hospital with lower tempera- a run-through of the many open 5 Lilja G et al. Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After Target but whether or not we should still ture have shown poorer outcomes in questions begging formal study: “In Temperature Management at 33ºC Versus use it under more controlled circum- cold climates, with the inverse being terms of other controversies, how 36ºC. Circulation. 2015 Feb 13. pii: CIRCULA- TIONAHA.114.014414. [Epub ahead of print] long should they be temperature stances in hospital remains to be true in hotter climates where warmer 6 Kim F et al. Effect of prehospital induction of determined.” patients tend to fare worse – both, managed for? What do we do at mild hypothermia on survival and neurologi- Dr Nolan noted the difficultly in however, indicating that the body has the end of the 24-hour temperature cal status among adults with cardiac arrest: a randomized clinical trial. JAMA. 2014 Jan trying to prove that earlier cooling lost its ability to control its tempera- managed period? 1;311(1):45-52. 14 ISICEM News Thursday 19 March 2015 Issue 3

Massive bleeding Lippens Room National Library Thursday 10:05 Lessons from the military: massive bleeding

he tragic levels of bloodshed in conflict In 2009, Dr Reade was deployed with the Aus- moglobin; they weren’t having a lot of hemolysis zones over the past decade have provided tralian Defence Force to a Dutch-run NATO hospi- (as demonstrated by absence of bilirubin and renal valuable logistical lessons in getting large tal in Tarin Kot, Afghanistan, where cryopreserva- failure afterwards). Tvolumes of blood to those who need it fast – les- tion was the preferred method of supplying blood “In particular, we were seeing what we felt was sons that will surely save many lives in the future, products. Cryopreserved red cells and cryopre- even a greater hemostatic effect than what we in civilian and military trauma centers alike. served deep-frozen plasma had a shelf life of 10 would have expected just based on our experi- Michael Reade (University of Queensland and years; cryopreserved platelets, a newer technology, ence with conventional blood products in civilian Royal Brisbane and Women’s Hospital, Australia), had a shelf life of possibly two years. hospitals. We attributed that to the cryopreserved a lieutenant colonel at the Royal Australian Army “We gave a number of patients massive trans- platelets.” Medical Corps as well as an intensivist, has worked fusions using those blood products,” explained Dr The technology of cryopreservation was in both of these settings. He will be presenting his Reade. “Despite the fact that some of those units originally developed by the US military, after which experiences of managing massive bleeding and were years old, we were seeing a good result. it was modified by the Dutch forces. “The US critical hemorrhage during his two deployments to People were having good increments in their he- have deployed cryopreserved red cells elsewhere Afghanistan in 2009 and 2013 as part of a session in Afghanistan,” noted Dr Reade. “When I was dedicated to massive bleeding taking place this in Kandahar at the Role 3 – a larger hospital – in morning in the Lippens Room. 2013, we had such a high but predictable usage Describing his experiences of deployment to requirement for red cells and plasma, and the facil- ISICEM News, he said: “The intensity and extent ity had been there long enough to develop some of the wounds of individual patients has been very infrastructure around blood banking, that we were much greater than anything I have seen in civilian bringing in fresh red cells and fresh frozen plasma practice. A higher proportion of those patients from the US. So the red cells had the conventional have what is conventionally defined as a massive shelf life of 42 days.” transfusion – 10 units in 24 hours, or five units in Because of the transit time, the median age of the first six to 12 hours. Certainly that is a feature storage of these fresh products at transfusion was of the pattern and the mechanisms of wounding in averaging 20 days, which is perhaps slightly longer Afghanistan at those times.” than would be expected within the civilian hospital In addition to sheer volume demands, Dr environment. Even so, Dr Reade saw no evidence Reade’s location presented additional logistical that any harm was being done to patient because problems that would not tend to occur in a civilian of this, relative to those receiving fresher blood in hospital. “Not that these problems are insubstan- a civilian hospital. tial in a civilian hospital,” he added. “Especially in Interestingly, Dr Reade noted a very good but a non-trauma setting, to have to produce 20 to transient blood pressure response from these aged 50 units of cross-matched blood, red blood cells red blood cells, an hour or two after the transfu- or fresh frozen plasma quickly, is very challenging. sion, after which the patient’s hemodynamics dete- The blood bank staff have to either work excep- riorated again. While this may have been because tionally hard or find extra people to come and help of the continual bleeding, inflammation and the them to meet that requirement. multiple effects of trauma, Dr Reade “In a sense, we had an advantage over nevertheless came civilian blood banks in that we were up with a staffed and equipped to be able hypothesis to provide that much blood regarding that quickly. So at a local lev- its tran- el, you might even say that sient we were better prepared. nature We were able to provide that those blood products more might readily than I am used to in war- a civilian hospital.” The disadvantages lie “The intensity and extent of within being placed so remotely from poten- the wounds of individual tial blood donor pools, patients has been very much which impacts upon the availability and the type greater than anything I have of blood products on seen in civilian practice.” offer. On top of this, the nature of the military ex- Michael Reade perience means that dif- ferent sets of challenges will present themselves to military doctors depending on where they are deployed to and what infrastruc- ture exists there. Issue 3 Thursday 19 March 2015 ISICEM News 15

Massive bleeding Lippens Room National Library Thursday 10:05

Lessons from the military: massive bleeding “In a sense, we had an advantage over civilian blood banks in that rant further, more formal investigations: “You more than 6,000 we were staffed and equipped Reade, when logistical would expect there to be more free units transfused, to be able to provide that much restraints, rather than in an aged unit of red cells. Hemoglobin is a that the hemostatic patient benefit, dictated sequestrator of nitrous oxide, which is a vasodila- and cardiovascular blood that quickly.” practice. “You just can- tor, so it would not have been surprising if this was efficacy of fresh not do that these days,” Michael Reade the cause of the transient improvement of blood whole blood ap- he explained. “There are pressure that isn’t really reflective of the improved pears superior to a whole lot of research hemodynamic status of the patient. We observed component product. questions or technological questions around some that in many patients and to my knowledge, “That has never been subjected to a convincing of these issues, where things can’t simply be this has not been previously described, so that is RCT, largely because providing fresh whole blood in introduced into the blood system just because they ‘Reade’s hypothesis’!” a civilian context is difficult. The point that I am keen seem like a good idea. The Role 3 hospital had been established long to make here is that the key word is ‘fresh’ – they “We are interested in looking at RCTs that enough as to have a platelet apheresis program, were transfusing the blood in less than 12 or 24 investigate the effect of length of storage dura- and Dr Reade’s team hours after it had been tion. We are interested in looking at cryopreserved brought donors in “We are interested in looking at donated. This would platelets. Although a military-specific priority has from the local military be almost impos- led to them being introduced in a very limited community on the RCTs that investigate the effect sible to do in a civilian clinical practice, we – the military and people who airbase to donate of length of storage duration. context, given the way do trauma medicine – accept that before they were platelets, which that blood transfusion introduced to the general blood supply you would would then be stored We are interested in looking at services are organ- need to do a proper clinical trial.” for the conventional cryopreserved platelets.” ized: the idea that “The effects of blood transfusion are not all shelf life of five days. you would put out a immediately apparent, which has become clear The addition of a Michael Reade call to the community just from the study of component therapy over the recall register meant and have donors turn past twenty years. There are subtle complications that the hospital was always well-stocked. up on the doorstep of a blood transfusion center or that we know are very common in critical illness Describing a further solution to bolstering blood hospital just seems impractical. People do talk about like acute respiratory distress syndrome and really supply, Dr Reade continued: “Although I have whole blood transfusion, but they generally are refer- without a proper RCT comparing two strategies never done this in my personal practice, I know ring to stored whole blood transfusion, and it is not you are not going to be able to identify differences that in the early phases of the military conflicts at all clear that you would achieve the same result.” in those kinds of endpoints. This will bring transfu- in both Afghanistan and Iraq the US extensively Today, the methods by which blood are pro- sion medicine in line with the rest of medicine, used fresh whole blood by way of a walking blood vided increasingly rely on evidence to support their relying on evidence rather than another factor such bank. There are anecdotal impressions, based on use. This lies in contrast to fifty years ago, noted Dr as logistics, in the case of blood.” 16 ISICEM News Thursday 19 March 2015 Issue 3

How much oxygen? Copper Hall Thursday 11:30 Breathing in the facts for optimal oxygenation

his morning will feature a session that genation as part of care in the ICU? poses the question of just how much is primarily on the avoidance of . Indeed oxygen should be given to ICU patients? we want to avoid hypoxia, but the exact threshold TWithin the session, toxicity, hypoxia, mechanical for hypoxia tolerance is not well established. With ventilation, atelectasis, trial data and the effects of respect to the brain, avoidance of brain hypoxia oxygenation levels on the brain, neuropsychologi- is crucial, and monitors for brain tissue oxygena- cal sequellae and sepsis will all be explored in great tion and protocols to avoid hypoxia have been detail. proposed. Ahead of the session, ISICEM News spoke to Brain hypoxia may be multifactorial and its presenter Mauro Oddo (CHUV-University Hospital, treatment can be challenging. Having said that, I Lausanne, Switzerland) for a brief glimpse of his believe there is a lack of emphasis in avoiding sus- talk on how much oxygen is sufficient to protect tained hyperoxia. Things may change in the future the brain. given recent studies, but we should reinforce the message that prolonged hyperoxia ma be detri- What is lacking in terms of how we monitor mental and should be avoided. While we always oxygenation of the brain (use of technology, set low limits for oxygenation, in clinical practice I protocols)? believe we rarely set the “high” limits. While monitors (invasive and non-invasive) are available, they may not always appropriately reflect What should be our emphasis moving forward tissue oxygenation (particularly for non-invasive non-randomized observational studies found an – what’s your take-home message? tools). What is especially lacking are protocols with association between hyperoxia and increased rate Management of hypoxia is the goal of critical specific thresholds/targets for optimal PaO2, that of mortality and poor neurological outcomes. How- care – hyperoxia may be detrimental and should avoid high FiO2/PaO2 ever this was not found by all studies, and we need be limited. Moving forward, a strategy of con- a randomized control trial to examine whether trolled oxygenation (aiming to avoid hypoxia and What do you see in clinical practice in terms of hyperoxia versus controlled oxygenation (aiming to hyperoxia) is recommended. To that end, additional mortality/morbidity due to hyperoxia (such as avoid hypoxia) is associated with worse outcomes. studies should focus on better defining the exact worsened outcomes for stroke, COPD, MI etc)? thresholds for controlled oxygenation and the Regarding patients with acute brain injury, several Is there a lack of emphasis in accurate oxy- individual lowest levels of hypoxia tolerance. Issue 3 Thursday 19 March 2015 ISICEM News 17

™ Masimo Announces CE Marking of O3 Regional Oximetry asimo returned to ISICEM with another Mbreakthrough technology – O3™ regional oximetry for the Root™ patient monitoring and connectivity platform. O3 regional oximetry is a new technology developed by Masimo and uses near-infrared spectroscopy (NIRS) in Masimo Open Connect (MOC-9TM) modules and up to four sensors, each with four light-emitting diodes (LEDs) and two detectors, to continuously measure both tissue (rSO2) and arterial blood oxygenation (SpO2) on Root.TM NIRS can monitor tissue oxygenation in unstable patients, and may provide early indication of deterioration in circulatory function.1 Some evidence suggests NIRS can be used to guide treatment in patients with brain injuries, se- vere anemia, as well as cardiac surgery patients and preterm newborns.2-9 O3 will allow clinicians to detect regional that pulse oximetry alone can miss. In addition, the onboard pulse oximeter on the O3 sensor means that clinicians can readily calculate the difference between central and regional oxygen saturation. O3 monitoring is as simple as applying two O3 regional oximetry sensors to each side of the forehead and connecting the O3 MOC-9 module to any Root™ through one of its three MOC-9™ ports. Root™ offers unprecedented, high-impact innovations including: Masimo O3™ regional oximetry MOC-9 module for the Root™ patient monitoring and connectivity platform. n Radical-7® with Masimo’s breakthrough rainbow® and SET® measurements n Instantly interpretable, high visibility, intui- 45, which suggests clinicians are more likely to References tive navigation touchscreen display get accurate measurements with O3 than other 1 Scheeren TW, Schober P, Schwarte LA: Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background n MOC-9™ flexible measurement expansion regional oximeters. and current applications. J Clin Monit Comput 2012, 26:279- ® with SedLine EEG brain function monitor- In addition to O3’s regional oximetry abso- 287. ing and Phasein™ capnography, in addition lute accuracy, O3 also provides the ability for 2 Beynon C, Kiening KL, Orakcioglu B, Unterberg AW, Sakowitz OW: Brain tissue oxygen monitoring and hyperoxic treatment to O3 regional, including cerebral, oximetry clinicians to measure pulse oximetry simul- in patients with traumatic brain injury. Journal of neuro- and future measurements taneously from the same sensor, which can trauma 2012, 29:2109-2123. n Iris™ for built-in connectivity gateway automate the differential analysis of regional to 3 Zheng F, Sheinberg R, Yee MS, Ono M, Zheng Y, Hogue CW: for standalone devices such as IV pumps, central oxygen saturation monitoring. Cerebral near-infrared spectroscopy monitoring and neuro- logic outcomes in adult cardiac surgery patients: a systematic ventilators, hospital beds, and other patient review. Anesth Analg 2013, 116:663-676. monitors 4 Mittnacht AJ: Near infrared spectroscopy in children at high n MyView™ for automatic display of param- risk of low . Curr Opin Anaesthesiol 2010, 23:342- eters, waveforms, and viewing configuration 347. 5 Bronicki RA, Chang AC: Management of the postopera- based on the clinician’s presence tive pediatric cardiac surgical patient. Crit Care Med 2011, In an abstract presented at the Society for 39:1974-1984. Technology in Anesthesia 2014 Annual Meet- 6 Bellapart J, Boots R, Fraser J: Physiopathology of anemia and transfusion thresholds in isolated head injury. The journal of ing in Orlando, Fla., Dr. Daniel Redford from trauma and acute care surgery 2012, 73:997-1005. the University of Arizona evaluated cerebral 7 Cerbo RM, Cabano R, Di Comite A, Longo S, Maragliano oxygen saturation on 23 subjects and 202 R, Stronati M: Cerebral and somatic rSO2 in sick preterm paired measurements of rSO from O regional infants. The journal of maternal-fetal & neonatal medicine : 3 the official journal of the European Association of Perinatal oximetry and reference arterial and venous Medicine, the Federation of Asia and Oceania Perinatal Socie- 10 blood samples (SavO ). Reference blood sam- ties, the International Society of Perinatal Obstet 2012, 25 ples were taken from both an arterial cannula Suppl 4:97-100. 8 Seidel D, Blaser A, Gebauer C, Pulzer F, Thome U, Knupfer M: placed in the radial artery and a catheter placed Changes in regional tissue oxygenation saturation and de- in the internal jugular bulb vein, obtained saturations after transfusion in preterm infants. at baseline and after a series of increasingly Journal of perinatology : official journal of the California Perinatal Association 2013, 33:282-287. hypoxic states induced by altering the inspired 9 Hanson SJ, Berens RJ, Havens PL, Kim MK, Hoffman GM: oxygen concentration while maintaining a Effect of volume resuscitation on regional perfusion in dehydrated pediatric patients as measured by two-site near- normocapnic arterial pressure of carbon dioxide Masimo O3 sensors enable simultaneous infrared spectroscopy. Pediatr Emerg Care 2009, 25:150-153. (PaCO ) level. measurement of regional oxygen saturation (rSO ) 2 10 Redford D, Paidy S, Kashif F, STA 2014; 46 (abstract). In this study, PaCO ranged between 30 to and arterial oxygen saturation (SpO2). 18 ISICEM News Thursday 19 March 2015 Issue 3

Massive bleeding complications with new anticoagulants Lippens Room National Library Friday 09:40 “My perspective” on NOACs: Hematology

n this new era of novel oral rivaroxaban, apixaban and edoxaban) anticoagulation (NOAC) therapy, appears to be reversed by using PCC. the emergence of cutting-edge Dabigatran seems less reversible from agentsI has brought with it a number the limited literature but its antidote of potential benefits, as well as a is being pushed through clinical trials good proportion of questions as well. very quickly. To that end, ISICEM 2015 will stage a Many of us are very excited about dedicated session on Friday morning the antidote for the anti-Xa agents: it that will explore the hematological, is in fact a modified activated Factor anesthesiological and intensivistic X molecule, without hemostatic ac- perspectives on NOACs, with particu- tivity and therefore would be able to lar focus on bleeding complications. reverse the effects of low molecular Offering her hematological weight heparin and fondaparinux perspective during the session will be too. Beverley Hunt (Guy’s & St Thomas’ NHS Foundation Trust, London, UK), What particular perspectives from who spoke to ISICEM News to share the point of view of a hematolo- some of the talking points she will be gist would you like to communi- touching upon. cate during the session? Of course most of the audience only The novel anticoagulants are a see major bleeding due to NOACs hot topic in bleeding. How have and may be a little cynical. But I you seen a change in your prac- want to persuade them that there is tice? Does warfarin take a “back a charm and ease for the patients, seat” now? and doctors, when using a NOAC in Forty percent of patients clinical practice, compared with the starting oral antico- “Women who have switched tortuous bridging and monitoring agulation are now being from warfarin to rivaroxaban protocols of the vitamin K antago- given NOACs instead nists. of warfarin in North state that bleeding is worse America and much of than on warfarin. But despite Is the lack of reversal agents the What do you see for the (near) mainland Europe, and thorny issue here? future with regards to novel in the UK it is only 6% this problem, not one woman It is not for most hematologists! We anticoagulant use? What has to with widespread regional wanted to go back to are used to non-reversible, short- be done now? variation – so we have a warfarin!” acting anticoagulants such as the The NOACs are being trialed in many long way to go! low molecular weight heparins and areas at the moment and I suspect Warfarin is definitively Beverley Hunt fondaparinux. will be highly successful. For me the not taking a backseat However because the medical most exciting application is for those because there are many community has been dependent on with venous thromboembolism and groups not suitable for NOACs due and I need not remind readers that oral anticoagulants such as warfarin, cancer, as 10% of cancer patients to the lack of trials, or adverse results an intracranial bleed on warfarin is with high bleeding risks, unpredict- have a venous thromboembolic event from trials e.g. those with mechanical very bad news, even with use of PCC able pharmacokinetic profiles and during the course of their illness. heart valves. And then many centers (prothrombin complex concentrate). long half-lives of 60 years, there is a International recommendations are are slow to switch from warfarin for We have been using rivaroxaban mindset that “all anticoagulants must to use a daily subcutaneous injection licensed indications due to lack of in my center for the of low molecular weight heparin for clinical leadership and misinformation treatment of venous six months, and it would be lovely to about the need for an antidote and thromboembolism for “NOACs of course do have have a reliable and safe oral agent. how much they cost. several years now, and side effects, like any drug. But Comparative trials of NOACs versus have found that fertile overall if used in the current LMWH are under way in this arena. How common, and how severe, women often experience Furthermore, we have just are bleeding complications in menorrhagia, which has licensed indications they are finished a trial of rivaroxaban in your experience? Are they linked been poorly reported efficacious and also safer that patients with antiphospholipid to one or more drugs in particu- before. Those women syndrome (RAPS) and will report on lar, or in certain situations? who have switched from the vitamin K antagonists.” this in June. Major bleeding is very rare on warfarin to rivaroxaban Beverley Hunt NOACs, despite the flurry of publica- state that bleeding is What you think is an important tions in medical journals, no doubt worse than on warfa- take-home message? accepted because of the novelty of rin. But despite this problem, not be monitored and need an antidote”. NOACs of course do have side the drugs. The FDA have gathered one woman wanted to go back to So yes it is a thorny issue for many effects, like any drug. But overall a lot of data showing reassuringly warfarin! We successfully managed medic, but we need to keep giving if used in the current licensed indica- that the “real life” experience of menorrhagia associated with rivar- out the message that with NOACs, tions they are efficacious and also NOACs is the same as in the trials, oxaban with dose reduction and/or one, major bleeds are rare, and two, safer that the vitamin K antagonists. i.e. overall there is a lower risk of the use of tranexamic acid tablets (1 the short half-life means the effect And of course the patients love intracranial bleeding. Bleeding on g three times a day) and/or use of will wear off quickly. the convenience and freedom that warfarin is much, much commoner, the MIRENA coil. The effect of anti-Xa agents (for NOACs bring. Issue 3 Thursday 19 March 2015 ISICEM News 19

Opening HLB Room Tuesday 8:30 Outcomes from the 2015 Round Table on sepsis

Continued from page 1 and they eventually die of multi-organ failure.” Deaths such as these would be chalked up as pneumonia. As such, establishing the role of sepsis in disease demands a closer interaction between health leaders and those involved in the Global Burden of Disease Project – and these channels of communications are now open, said Professor Finfer: “This is one of the major positive things to emerge out of the Round Table. There will be an ongoing dialogue led by Derek [Angus] and oth- ers, to make sure we work towards getting sepsis recognized. “There will be multiple flow-on effects of that. But one of the issues that you and I can all ad- dress is that of documentation and coding. I have spoken to the Australian Global Burden of Disease Program, and they have told me that if I write in a patient’s chart, ‘query sepsis’, they ignore it. It is ignored in coding. You actually have to write ‘diagnosis = sepsis’ and then it will be counted. These are not very exciting things, but they will have major positive effects for the management of obtaining resources.” The burden of sepsis on children, which Niran- jan (Tex) Kissoon (BC Children’s Hospital and Sunny Hill Health Centre, BC, Canada) spoke of during the Round Table discussion, is another important element of the puzzle. Speaking of the sobering statistics that Dr Kissoon raised, Professor Finfer said: “Many people in the US may be economically devastated by chronic illness and hospitalizations, but particularly in low-income countries one hos- pitalization can be economically devastating for an entire family. “Another statistic that really hits home is that, in many African “By preventing the countries, if a mother dies and mother having sepsis they have a neonatal child, that there are many negatives ered from sepsis. “We tend to think of sepsis as an neonate has an 80% chance of – or treating the in poor housing, over- acute, severe illness that resolves after a week or being dead within a year. So by mother – we have a crowding, poor hygiene, et two if we do a good job,” said Dr Opal. “But there preventing the mother having cetera.” is an increasing recognition that those patients sepsis – or treating the mother chance to improve Outlining the mission that survive sepsis don’t necessarily always do – we have a chance to improve mortality by 200%.” and key goals to have that well and may be left with significant physical mortality by 200%. If it is an older emerged from the Round and psychological disability that may last for long child, there is a 50% chance of dy- Simon Finfer Table, Dr Opal began by periods of time. ing within a year. Those of us that explaining how previously- “What if we are just substituting death with work in the developed world do implemented public health significant morbidity? That might not be so good, not face those issues.” campaigns have driven improvements in outcomes or might not really be helping at all. Of course, we The evolving world is bringing about environ- across societies and the wider world. He noted that are all hoping that we are decreasing morbidity as mental changes that also have knock-on effects early HIV campaigns brought down rates of transmis- well as mortality; this will be a significant part of upon disease patterns and distributions, which sion dramatically, and that the same should be done our research agenda in the future – making sure must be understood in order to deal with health to make people aware of the problem of sepsis. that our patients are doing well after they leave the crises on the horizon. This is exacerbated by anti- Another successful campaign was the promo- hospital.” biotic resistance, explained Professor Finfer, which tion of hand-washing in the clinical environment. Along with improving epidemiology, increasing has been recognized by the WHO and many politi- The success of this campaign, explained Dr Opal, awareness and patient advocacy, and improving cal leaders as a pressing health issue. was precisely because of the broad involvement sepsis care, Dr Opal concluded by reiterating that “We have aging populations,” he continued. of multiple stakeholders, including everyone from prevention, early recognition, improved diagnostics “And not only does the incidence of sepsis rise patients to policy-makers, as well as public spokes- and precision medicine are also major priorities. dramatically with age but so does the mortality persons to act as figureheads for the cause. Such This will all be facilitated by further research, which rate. Populations are on the move between coun- promotion must also be accompanied by adequate it is hoped will yield new treatments in the form of tries and within countries; this means that disease and early diagnosis and treatment, and patient antibiotics and vaccines, incorporating the growing is more transmissible. There is global urbanization advocacy. disciplines of genomics and epigenomics to im- occurring. If people are moving to cities they are Another emerging area of concern involves prove prediction of the individual patient’s disease closer to health services, which is a positive; but what happens to patients once they have recov- course and response to particular therapies.