ESICM ESICM
A message from the Co-Chair Jean-Louis Vincent

The 28th annual European Society of Intensive Care Medicine (ESICM) LIVES 2015 Congress took place at the CityCube Exhibition Centre, in the historic capital Berlin, on the 3rd-7th October. The aim of the congress was to bring together intensive care and allied healthcare professionals from around the world in order to update them on the latest and most relevant advances in critical care and emergency medicine. This edition of the Society’s annual congress is unique in its representation of the breadth and depth of the intensive care medicine (ICM) community, including physicians, nurses, industry partners, and other allied healthcare professionals.

For me as Co-Chair, a major highlight of the ESICM Congress was the ‘Edwards Lunch Symposium’, which was held on Tuesday 6th October. Edwards Lifesciences organized the symposium, during which the latest research and current expert opinion on ‘the evolving future of hemodynamic monitoring in the intensive care unit (ICU)’ was presented by Kai Zacharowski, MD, PhD FRCA (Frankfurt, Germany), Maurizio Cecconi, MD FRCA, FFICM, MD(res) (London, UK) and Richard Beale, MB, BS FRCA (London, UK). Attendees had the opportunity to discuss and debate this hot topic in ICM, the highlights of which are presented in this report. In addition, question and answer style interviews for each of the ‘Edwards Lunch Symposium’ keynote speakers are provided towards the end of the report.

In summary, there were three key takeaways from the ESICM Congress and Edwards Symposium: (1) simple protocols do not work in the ICU – our therapeutic approach must integrate complex pathophysiological concepts; (2) we spend too much time on large clinical trials yielding negative results; and (3) personalized medicine is the future.

Patient-tailored risk prediction and treatment are applied routinely in the clinic in some areas of medicine, however in intensive care medicine more work is required to translate scientific advances into individualized treatment and personalized algorithms. This future therapeutic approach must integrate complex pathophysiological concepts. Indeed, a better integration of all the different variables would enable improved visualization of abnormalities, which in turn would help guide therapeutic interventions, and consequently improve patient outcomes.

The evolving future of hemodynamic monitoring in the ICU
CityCube Berlin, Germany©

Berlin, October 2015 − Hemodynamic monitoring is a broad term describing any technique used to monitor a patient’s hemodynamic status. Technologies that monitor hemodynamic status range from very invasive and mini-invasive to totally noninvasive. The main goals of hemodynamic monitoring are to alert the healthcare team to impending post-surgical complications such as cardiovascular crisis, to monitor the response to therapy and effectiveness of interventions, and to avoid progression to a decompensated shock state. Hemodynamic monitoring has become a central component of intensive care medicine, most commonly used to manage critically ill patients with any condition that reduces cardiac output or is associated with hypoperfusion. For example, goal-directed cardiac hemodynamic measurements are often employed in the intensive care setting to carefully manage fluid status in patients with acutely decompensated heart failure. A mounting body of evidence shows that goal-directed strategies coupled with appropriate therapy reduces post-surgical complications and mortality. Despite a general reluctance to this approach, hemodynamic fluid management has been successfully implemented in many hospitals in order to improve quality of care and patient outcomes, as well as decrease costs.

A significant number of patients undergoing surgery may experience a postoperative complication1. Complication rates as high as 30% have been reported in some patient groups2,3. Common general post-surgical complications include postoperative pneumonia, septic shock, deep wound infection, pulmonary embolism and deep vein thrombosis (DVT)1. In the short-term, postoperative complications potentially result in greater morbidity for patients, increased length of hospital stay, and higher hospital costs4,5. In a study of more than 7,000 patients that underwent non-cardiac surgery, postoperative pneumonia in 3% of patients was associated with a 55% increase in hospital costs and an 89% increase in length of stay6. Reducing postoperative complications may result in significant cost savings7,8. Numerous factors have been found to increase risk for postoperative complications, including preoperative patient risk, hospital factors and operative approach9. Also, long-term survival after major surgery is related to a number of factors, including patient age and avoidance of perioperative complications10. Independent of patient risk, the occurrence of a complication reduced median patient long-term survival by 69%10. Interestingly, reported overall mortality in postoperative patients ranges from 0.79% to 5.7%9; 80% of these deaths occur in only 12% of surgical patients at high-risk11.

In October 2015, Edwards Lifesciences organized a lunch symposium in Berlin as part of the ‘LIVES 2015’ ESICM Congress, during which the collective experience about the future of hemodynamic monitoring in critically ill patients was presented and discussed in interviews with Kai Zacharowski, MD, PhD FRCA (Frankfurt, Germany) and Maurizio Cecconi, MD FRCA, FFICM, MD (res) (London, UK).

Goal-directed strategy
“GDT is not a ‘magic bullet’, but it is a useful tool when integrated as part of high quality care.”
Dr Maurizio Cecconi

Goal-directed therapy (GDT) optimizes individual cardiac output and, thus, oxygen delivery (DO2) by targeted administration of intravenous fluids and vasoactive agents12. The morbidity and mortality benefits of perioperative GDT (PGDT) have been confirmed in high-risk patient groups (>5% mortality)12. In addition to the clinical benefits, implementation of GDT is also cost-effective, decreasing short-term costs by an estimated £2,632 per patient and by £2,135 per hospital survivor.8

Based on the results of a single-center randomized trial by Rivers et al. (2001)13, which used a protocol for resuscitation for critically ill patients with septic shock, early goal-directed therapy (EGDT) was recommended by international guidelines for this indication13,14. A recent systematic review of three large trials (ARISE, ProCESS and ProMISE trials) showed no effect of an EGDT protocol resulting in more fluids given to patients with septic shock14.

Hemodynamic needs vary from patient-to-patient and benefits of GDT are not always definitive. Other factors such as the patient risk group and surgical procedure effect outcome. Stroke optimization during elective major abdominal surgery in ‘aerobically fit’ patients showed no benefit15. In theory, colloid fluids should have greater fluid efficacy in expanding fluid volume and enhancing oxygen delivery during GDT regimens, however recent evidence has also shown detrimental outcomes of colloid-based GDT in ‘very fit’ patients having colorectal surgery16. Even in high-risk patients undergoing major gastrointestinal surgery, the benefits of a cardiac output-guided hemodynamic therapy algorithm compared with usual care were not obvious from the initial analysis17. It is however very clear that GDT using administration of fluid challenges and inotropes guided by haemodynamic monitoring is not harmful and does not result in an increased rate of complications, such as cardiac events, in high-risk patients18.

Fluid challenges
“To achieve optimal fluid balance, many patients should be allowed to eat and drink soon after an operation, if possible. Also, stopping maintenance fluids early should also be a consideration. Therefore, hemodynamic fluid management needs to be a team effort.”
Dr Maurizio Cecconi

Abnormalities of fluid and electrolyte balance may adversely affect organ function and surgical outcome in patients at risk of developing complications19,20. Notably, the relationship between the amount of fluid administered in the perioperative period and the postoperative morbidity rate has been historically defined as a U-shaped curve20. However, following organ failure the benefits of GDT are limited, therefore timing of hemodynamic intervention is important12.

Fluid challenges are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care medicine21. In patients at risk of developing complications, hemodynamic optimization with treatment protocols based on flow parameters (e.g. stroke volume, SV) and/or dynamic predictors of fluid responsiveness (e.g. stroke volume variation, SVV) are useful to decrease post-surgical morbidity. More than 30 randomized controlled trials and several meta-analyses have demonstrated the superiority of hemodynamic optimization over standard fluid management to decrease renal, gastrointestinal, respiratory and infectious complications, as well as the overall morbidity rate22-27. However, current practices and evaluation of fluid challenges in critically ill patients are highly variable21. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed fluid challenges is not always taken into account21.

The critical care team has the potential to improve its ability to adopt to hemodynamic optimization methodology in order to more effectively evaluate new monitoring systems and their impact on patient outcome.

PGDT treatment protocols

The use of a fluid therapy protocol combined with GDT may be associated with a significant change in morbidity, length of hospital stay, and mortality, compared to standard fluid therapy protocol28. The benefit of simple protocols however remains an issue of debate29. The results of the FENICE study indicate that there is a large gap between even the simple modelling of the effects of a fluid bolus and clinical practice.

It is clear that a multidisciplinary, comprehensive and timely patient assessment is of great importance. Different evaluation protocols have been proposed for GDT in the critical care setting. The RIVERS protocol13 is typically used for the management of the septic patient in the emergency department and in the intensive care unit, but the range of protocols available for the perioperative setting is much wider and depends mainly on the patient’s vascular access and the availability of specific monitors. There is at present no uniformly accepted or recommended practice, so a team initiative is required to change standard of care and select the most appropriate PGDT protocol for the surgical patient population (see Figure 1). Several evidence-based protocols have been shown to be effective: Benes30, Cecconi31, NHS-NICE/Kuper32,33, Ping34, Ramsingh35, Wang34, and Donati36. To ensure PGDT is implemented successfully, appropriate training is required for all healthcare professionals and compliance should be tracked.

Based on mounting evidence supporting PGDT, clinical societies have published guidelines for operative fluid management in Europe37, UK38,39, and France40. Because of the clear benefits of PGDT, an increasing number of centers are beginning to establish PGDT protocols for their patients.

Less invasive monitoring systems are now available for use in conjunction with a PGDT treatment protocol. Flow-based hemodynamic monitoring with a minimally invasive device, such as FloTrac (Figure 2), provides more reliable data than conventional measurements41-43. The FloTrac system provides real time data and reliably trends cardiac output (CO) values for estimation of patient hemodynamics. The monitoring system also produces reliable SVV (stroke volume variation) which is practical for assessing patients’ needs and responsiveness to fluid. The system automatically updates advanced parameters every 20 seconds, reflecting rapid physical changes in patients undergoing moderate to high-risk surgery.

The ClearSight product (Figure 3) is a noninvasive technology to continuously monitor key hemodynamic parameters. The ClearSight system uses an inflatable cutoff around the finger to give rapid and up-to-the-minute hemodynamic information for moderate to high-risk surgical patients44.

Figure 1. General Considerations when Choosing a PGDT Protocol
Figure 2. FloTrac System
Figure 3. ClearSight System

Cross-section of cuff application.
To accurately mirror arterial line output, real-time finger pressure measurement is performed 1000 times per second utilizing the volume clamp method.

Blood conservation in the critically ill patient
“Precision is required when prescribing blood products.”
Prof. Kai Zacharowski

Even mild preoperative anemia is associated with an increased morbidity and mortality across a wide range of surgical procedures and settings, irrespective of transfusion status, age or sex45. As a result, patient blood management clinics have been established e.g., to screen for anemia in patients scheduled for elective surgeries with a high transfusion probability. Patients admitted to ICUs are commonly affected by anemia, multifactorial and contributed to by iatrogenic blood loss from diagnostic testing46. Hospital-acquired anemia (HAA) in patients with acute myocardial infarction (AMI) is also associated with poor outcomes47. HAA develops in nearly 50% of AMI hospitalizations as a result of in-hospital treatments and processes of care47.

Blood loss through patient sampling can be considerable in critically ill patients and anemia is a common consequence48. Diagnostic phlebotomy in critical care can result in a mean loss of approximately 40 mL per patient per day49. Lower mean hemoglobin levels in ICU patients are associated with higher Sequential Organ Failure Assessment (SOFA) scores, longer lengths of stay, and higher mortality rates48. Treatment of anemia in these patients typically involves blood transfusions to help maintain adequate oxygen delivery, however there is evidence of an association between transfusion and diminished organ function as well as between mortality48, even when as little as 1 unit of packed blood cells has been given50.

How much blood should you take from a patient? This should be an important decision because bloodletting often leads to hospital-acquired anemia. Too often, members of the healthcare team are seldom aware of the frequency and volume of phlebotomy for laboratory testing51. Implementation of process improvement initiatives, such as restrictive blood loss and closed blood sampling, can potentially reduce phlebotomy volumes and resource utilization51.

Hemostatic therapy algorithms in conjunction with point-of-care (POC) testing can reduce the number of transfused units of packed erythrocytes compared with conventional laboratory coagulation testing52. There is also evidence that POC-guided therapy is associated with lower fresh frozen plasma (FFP) and pooled platelet concentrate (PC) usage, which can significantly improve costs as well as clinical outcome 52.

The role of innovation in products
“It is very difficult to foresee technological development beyond a certain point. Often, the innovation is as much by the users as the original developer.”
Dr Richard Beale

In recent years, many innovative hemodynamic technologies have been introduced for use in PGDT. Available technologies have limitations so new technologies and treatments are certainly needed, but, more importantly, a new model of care is needed. At present, health systems are slowly struggling towards this goal — it is a matter of culture and behavior as much as of structure and technology. Achieving the necessary change requires key members of the healthcare team to change practice, and education in the right direction is a key driver.

Standard invasive techniques are progressively being replaced in many patients by less invasive monitoring techniques, and continuous or semi-continuous data collection is becoming more realistic53-56. One example is the new calibrated pulse wave analysis method that has been developed to continuously monitor arterial pressure waveform for estimation of cardiac output (CO), replacing standard thermodilution techniques54. Perioperative hemodynamic management guided by minimally invasive or noninvasive cardiac output (CO) monitoring has been recently introduced to clinical practice57,58. A continuous CO monitor uses an inflatable finger cuff as the only interface to the patient57. Very recent technologies include detection of hypovolemia in postoperative patients using a discrete Fourier transform59, and measurement of cardiovascular state using reconstruction analysis.

For hemodynamic monitoring to evolve in the future, healthcare workers should first recognize the need for change, and focus on the problems that need to be urgently addressed. There also needs to be a focus on quality, reliability and productivity of the new monitoring technologies, as well as personalized medicine, all of which may require fundamental upheaval.

Further highlights of ESICM 2015

Despite extensive research, the debate continues as to the optimal way of guiding intraoperative and postoperative fluid therapy. Prof. Thomas Scheeren discussed the best ways to monitor fluid responsiveness in the operating room (OR). In summary, he listed several take-home messages: static variables fail at evaluating volume requirements; fluid challenge is more feasible than passive leg raising test in the OR; dynamic variables such as SW, PPV etc., may better predict volume responsiveness; and feasible alternatives include non-invasive hemodynamic monitoring (e.g. PVI, Nexfin, CNAP) of blood flow rather than pressure; and echocardiography in skilled hands!

Dr Michael Pinsky gave a presentation entitled: ‘How to guide fluid therapy in septic shock patients’. He explained that the goal of resuscitation in septic shock is to restore and maintain tissue wellness. Dr Pinsky summarized current recommendations for monitoring and managing septic shock: measure real performance variables, measure adequacy of blood flow and functional hemodynamic variables, manage fluids and vasopressors to keep MAP > 65 mmHg, choose the vasopressor norepinephrine, and consider increasing inotrophy if cardiac output remains low and not volume responsive, but not if hyperdynamic.

The recommendations of early goal directed therapy (EGDT) in septic shock and those of conservative fluid management in ARDS may be seen as potentially conflicting practices. Based on evidence from the literature, Prof. Azriel Perel recommended that in hemodynamically unstable patients with severe ARDS, consider the use of inotropes before normalizing preload parameters with fluids.

Dr Aarne Feldheiser provided an update of the Enhanced Recovery After Surgery (ERAS) program as well as the future of ERAS (i.e. in high-risk surgery or in emergency medicine). He also summarized the current consensus guidelines for perioperative care following different surgical procedures.

Prof. Robert Sladen highlighted the challenges of perioperative hemodynamic optimization, including the vicious cycle in left ventricular (LV) ischemia. In addition to focusing on RV and LV interdependence, he also presented hemodynamic algorithms for the LV and RV; the latter of which is a new concept in hemodynamic optimization.

Because anemia is often ‘accepted’ or ignored in critically ill patients, Patient Blood Management (PBM) is all the more important. Dr Aryeh Shander gave an eloquent talk about how best to manage anemia by PBM using evidence-based practices. He explained how PBM reduces the requirement for transfusions by addressing modifiable risk factors.

The question: “Perioperative Fluid Management in Major Colorectal Surgery: Do we comply with current guidance and what are the implications for our patients?” was discussed by Dr Laura Vincent. She presented the unpublished results of a retrospective analysis, which aimed to review local perioperative fluid management and assess the extent to which goal-directed fluid therapy influences outcome for major colorectal surgical patients. Based on the results of the study, the trial authors conclude that administration of higher volumes of intraoperative fluid does not translate into better postoperative outcomes. They also conclude that postoperative IV fluid is better controlled in higher dependency care areas.

An interview with Maurizio Cecconi
Consultant and Honorary Senior Lecturer in Anesthesia and Intensive Care at St George's Hospital, London

What are the risks of non-optimized fluid management in perioperative patients?
A restrictive or liberal approach to perioperative fluid management can have adverse consequences, especially for high-risk patients. Too little fluid can result in hypovolemia, dehydration, low output state etc., and ultimately organ failure. In contrast, too much given fluid may increase the risk of edema. Kidneys do not function well with excessive fluid and salts. Therefore, giving too much fluid is as dangerous as giving too little.

Which patients benefit from perioperative fluid management?
I think perioperative fluid management is beneficial for all patients. However, many patients are not high-risk and don’t necessarily need advanced monitoring for optimal fluid management. The current evidence base for what is considered to be goal-directed therapy i.e., flow monitors and protocols, is for higher-risk patient groups. Optimal fluid management with flow monitors to decrease complications and length of hospital stay is therefore recommended for patients with a mortality risk of more than 5%.

Who is involved in perioperative fluid management?
It is a team effort, both before and during surgery through to the postoperative period. To achieve good perioperative care each member of the healthcare team needs to be involved: nurses, anesthesiologists, surgeons and intensivists.

An interview with Kai Zacharowski
Professor and Director of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Germany

Edwards Products for Blood Management
The VAMP (Venous Arterial blood Management Protection) system is an evidence- based solution that combines the safety and simplicity of needleless blood sampling with a unique reservoir designed to conserve blood (Figure 4). Notably, the reservoir allows the clinician to re-infuse excess blood not needed for the sample. The VAMP system is a closed blood sampling system with published data demonstrating significantly reduced transfusion risk60-62, and contamination rates63,64 compared to conventional sampling. Moreover, the VAMP system is an essential component of perioperative blood conservation and infection control.

What methods of blood conservation are used in the ICU?
Proper planning and appropriate decision making are important initially. For elective procedures, patients may undergo preoperative measures prior to surgery. If a preoperative patient has anemia, you can diagnose and treat the anemia first to reduce complications in the ICU. But once a patient is in the ICU, other measures to treat anemia, for example, are required. One such measure is the important decision of how much blood to take from a patient. Is it really necessary to take blood ten times a day? Is it necessary to take 2 mL or just 1 mL for blood gas analysis? After two weeks in ICU, every patient will lose almost one liter of blood; each unit adds up, so careful planning is critical.

What are the benefits of Patient Blood Management (PBM) in an ICU?
One clear benefit is a reduction in the number of transfusions an ICU patient needs (e.g. by restricting blood sampling, preoperative anemia treatment etc.), which results in fewer side effects. In some situations blood products are safe and absolutely critical whereas in other situations they may have side effects. Importantly, blood products should be considered like other medications and used with caution. All the biological effects of blood and blood products have yet to be fully elucidated and many questions pertaining to increased inflammation, infections and unknown diseases remain unanswered; PBM can therefore help avoid some side effects.

What are the barriers to PBM implementation today?
Although implementation of PBM is improving, the most important barrier remaining is that doctors are still inadequately trained in the field of PBM. Secondly, doctors remain largely unaware of anemia as a disease, the severity of the condition in patients, as well as its global burden. Hospitals have no algorithms or standing operating procedures (SOPs) in place for doctors to overcome these issues. During a typical busy day in an ICU, doctors often fail to remember the benefits of PBM. Hospitals should take the lead in establishing a PBM program.

What would a possible PBM program look like?
I think the most important thing is for the hospital to be convinced that the PBM program is the right thing to do. The hospital should then share all their standard operating procedures and knowledge with other hospitals, as well as providing material on how they can implement the PBM measures. Not every hospital has to do the same thing. The exact PBM measures depends on which procedures the hospital performs, and what kind of patients they are treating; there are hundreds of different measures to implement, but hospitals don’t have to implement all of them.

More than 100 hospitals in Germany have now enrolled and are participating in the PBM program. However, implementation of the PBM program is still a work-in-progress because we lack data from a large clinical trial. Such a trial, with more than 100,000 patients, has just been completed and results will be published early next year. Evidence from the literature will then be available, which will increase the pressure for every hospital to follow the PBM program.

What is the role of closed blood sampling in PBM?
I believe this should be mandatory in the ICU – it is the primary goal which we should follow up. Using the reflux system maintains the patient’s own blood volume. I think it is a patient’s right to keep their own blood, and I can see no valid reason why closed blood sampling is not being implemented because the price is almost the same as the traditional system. The benefits for the patient, in terms of outcome but also fewer transfusions, are clear. I am certain that more evidence will be available next year confirming that closed blood sampling is now a mainstay measure in PBM.

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For professional use. See instructions for use for full prescribing information, including indications, contraindications, warnings, precautions and adverse events. Edwards Lifesciences devices placed on the European market, meet the essential requirements referred to in Article 3 of the Medical Device Directive 93/42/EEC, and bear the CE marking of conformity. Edwards, Edwards Lifesciences, the stylized E logo, ClearSight and FloTrac are trademarks of Edwards Lifesciences Corporation. All other trademarks are the property of their respective owners. © 2015 Edwards Lifesciences Corporation. All rights reserved. E5869/10-15/CC

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