Department

Intensive Care

The mission from the Intensive Care is to improve the care of critically ill patients through translational and clinical research. We achieve this in close collaboration with (inter)national partners.

About our Department

Our research

Our research is initiated by principal investigators (PIs) who have completed a PhD and are staff members of our department. The PIs form a research group together with research nurses and young investigators. They meet monthly to discuss new research lines, which are then discussed with the department’s management team to evaluate adherence to research strategy and financial support. Upon approval, the clinical research coordinator and the clinical ethicist approve the necessary administrative procedures before admitting the study protocol to METC.

The daily coordination and organization of scientific research is performed by research nurses, one of which is the coordinator. The PIs and research nurses provide guidance and support to all researchers in conducting clinical research. The research nurses ensure that an investigator site file or trial master file is established for each research project.

Experimental research takes place in the Laboratory for Translational Intensive Care Medicine located in the medical faculty. It is coordinated by prof. Can Ince.

Our research focuses on four areas:

A) Shock, sepsis and microcirculation
B) Mechanical support of ventilation and circulation in the critically ill
C) Brain injury and brain dysfunction
D) Outcomes and ethics

Shock, sepsis and microcirculation

The cardiovascular system is the prime physiological compartment responsible for oxygen transport to the tissues to meet their metabolic demands in support of organ function. That is why its injury and failure form a life-threating event directly related to mortality and morbidity in intensive care. The cardiovascular system is especially compromised in states of shock (e.g. cardiogenic, obstructive, hemorrhagic and septic shock) which readily occurs during or prior to intensive care requiring resuscitation (e.g. fluid, vasoactive compounds and blood transfusion). It is especially complicated in states of inflammation and infection, the most severe form of which is sepsis. The treatment and containment of sepsis and septic shock form the largest challenge, and this is studied by our group. The treatment of infection through adequate antibiotic therapy and containment and modulation of the immune response to sepsis also forms another part of this research line. We will continue our investigations focused on metabolic (e.g. lactate) and tissue oxygenation, and we will monitor resuscitation with different approaches to improve outcomes in our ICU patients

Mechanical support of ventilation and circulation in the critically ill

Extracorporeal organ support (ECOS) includes both venous-arterial and venous-venous extracorporeal membrane oxygenation (vv- and va-ECMO), and mechanical ventilation forms a core clinical competency and expertise in our department. We have a long track record of research into the mechanical ventilation of lungs, introducing new concepts (e.g. the open lung concept) and technologies (electrical impedance tomography; EIT) to investigate and support the failing lung. Lung injury induced by mechanical ventilation and infection form the subject matter of this line of research. Our department is a national referral centre for ECMO and, together with the Departments of Neonatal and Pediatric ICU, form an ECMO Academic Center of Excellence (ACE) at the Erasmus MC. Our department has engaged this research line on the mechanical support of ventilation and circulation in the critically ill in support of these clinical activities. Oxygenation and decarboxylation can be changed extremely rapidly by the ECMO system, and we study ischemia-reperfusion injury, especially in out-of-hospital cardiac arrest patients. We will perform a nationwide study equipping all four Helicopter Emergency Medical Services (HEMS) with ECPR in a stepped-wedge design (On-Scene Study).

Brain injury and brain dysfunction

Our studies in neurocritical care have focused on traumatic brain injury and subarachnoid hemorrhage (SAH), both of which are expert areas at the Erasmus MC. We have been participating in the Collaborative European Neuro-Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective observational study on patients with traumatic brain injury (TBI). An important contribution of our group is the notion that high amounts of fluids administered by health care professionals in routine daily practice occur, and seem to constitute a hidden but preventable cause of harm to the brain. This topic is now included in the main research question of an international collaborative NIH (USA) grant proposal on SAH, that builds further on our experience with comparative effectiveness research in CENTER-TBI, to study effective treatment approaches for subarachnoid hemorrhage patients (with US partners). We are also interested in brain dysfunction due to delirium in non-neurologic ICU patients. Our group is running an RCT on haloperidol for ICU delirium (we have obtained ZonMW ‘large clinical trials’ funding) and we have established significant funding and collaboration with TU Delft to study the effects of smart alarm systems on patient comfort in the ICU, as well as delirium and sleep quality (the ‘silent ICU’ concept).

Outcomes and ethics

Our outcomes and ethics research includes expertise in informed consent in emergency and critical care medicine, studies into the disproportionate use of intensive care resources, and the identification of burnout and compassion fatigue among IC doctors and IC nurses. We recently started the COHESIS study examining the perceptions of health care providers on admitting cancer patients into the ICU. We are also interested in studying the perceptions of brain deaths and organ donation.

Topics such as creating a virtual reality environment for patients and cancelling the burden of noise in the ICU are lines of research that are expected to improve outcomes in critically ill patients. We are also studying the effect of music on sleep quality and opioid use.

Notable results

Research: scientific results during the past six years

In the past, our group has worked on the clinical parameters of hypo-perfusion in critically ill patients and how to use these in clinical practice. An extensively-studied parameter is the serum concentration of lactate. A large number of clinical experimental studies in healthy volunteers and studies in various subgroups of critically ill patients showed that the parameter of skin perfusion was strongly related to the development of circulatory dysfunction, lactate levels, organ perfusion and outcome [1]. The use of lactate can have major confounders, so the next element of this project was to compare the use of lactate versus the use of an indicator of tissue perfusion (capillary refill time - CRT) [2]. The ANDROMEDA-Shock study (a multicentre study in Latin America) showed that the use of CRT to resuscitate patients in the early phase of septic shock was most likely superior to the use of lactate levels to guide therapy [3].

Publications:
1. Brunauer, A., A. Kokofer, O. Bataar, I. Gradwohl-Matis, D. Dankl, J. Bakker and M. W. Dunser (2016). "Changes in peripheral perfusion relate to visceral organ perfusion in early septic shock: A pilot study." J Crit Care 35: 105-109.
2. Hernandez, G., R. Bellomo and J. Bakker (2018). "The ten pitfalls of lactate clearance in sepsis." Intensive Care Med 45(1): 82-85.
3. Hernandez, G., G. A. Ospina-Tascon, L. P. Damiani, E. Estenssoro, A. Dubin, J. Hurtado, G. Friedman, R. Castro, L. Alegria, J. L. Teboul, M. Cecconi, G. Ferri, M. Jibaja, R. Pairumani, P. Fernandez, D. Barahona, V. Granda-Luna, A. B. Cavalcanti, J. Bakker, A.-S. Investigators and N. the Latin America Intensive Care (2019). "Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients with Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial." JAMA 321(7): 654-664.

Prof. C. Ince joined our research group part-time in 2007. Since then, he has significantly contributed to the development and clinical introduction of hand-held video microscopes that allows us, for the first-time, to visualize and monitor microcirculation at the bedside during surgery, anesthesia and intensive care medicine. This gives us important insights into pathophysiology of disease and response to therapy. Our group conducted the first multicentre international study on the occurrence of microcirculatory alterations in intensive care medicine in 501 patients at 38 ICUs across the world [1]. We subsequently published international consensus guidelines (under the auspices of the ESICM and authored by 24 key opinion leaders in intensive care medicine) on the assessment of sublingual microcirculation using hand-held vital microscopes (HVM) in critically ill patients [2]. In addition, we developed an automatic analysis platform for the standardized analysis of the videos [3].

Publications:
1. Vellinga N, Boerma C, Koopmans M, Donati A Dubin A, Shapiro N, Pearse R, Machado F, Fries M, Tulin Akarsu-Ayazoglu T, Pranskunas A, Hollenberg S, Balestra G, van Iterson M, van der Voort P, Sadaka F, Minto G, Aypar U, Hurtado J, Martinelli G, Payen D, van Haren F Holley A, Pattnaik R, Gomez H, Mehta R, Rodriguez A, Ruiz C, Canales H, Duranteau J, Spronk, P Jhanji S, Hubble S, Chierego M, Jung C, Martin D, Sorbara C, Tijssen J, Bakker J, Ince C International study on Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP) Crit Care Med 2015 Jan;43(1):48-56
2. Ince C, Boerma EC, Cecconi M, De Backer D, Shapiro NI, Duranteau J, Pinsky MR, Artigas A, Teboul JL, Reiss IKM, Aldecoa C, Hutchings SD, Donati A, Maggiorini M, Taccone FS, Hernandez G, Payen D, Tibboel D, Martin DS, Zarbock A, Monnet X, Dubin A, Bakker J, Vincent JL, Scheeren TWL (2018) Second consensus on the assessment of sublingual microcirculation in critically ill patients. : Results from a task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2018;44(3):281-299. 15.
3. Hilty MP, Guerci P, Ince Y, Toraman F, Ince C. MicroTools enables automated quantification of capillary density and red blood cell velocity in handheld vital microscopy. Commun Biol. 2019 Jun 19;2:217. doi: 10.1038/s42003-019-0473-8.

The Erasmus MC’s ventilation research enjoys great national and international fame through the merits of Professor Burkhard Lachmann, the former Head of the Experimental Anesthesiology Department (1985-2007). He has shown experimentally that breathing according to the Open Lung Concept (OLC) is the superior type of ventilation in experimental settings. Since then, we have started translational research in which we have successfully applied OLC in cardio-surgical and ARDS patients [1]. We have cooperated with various companies to develop and test lung monitoring systems to optimize the effect of OLC [2]. Together with the use of vv-ECMO, this approach is important in our lung transplantation program with early mobilization. Our ECMO research also studied cost-effectiveness, the use of microcirculation during weaning from va-ECMO [3], and Extracorporeal Cardio-Pulmonary Resuscitation (ECPR). We performed a multicentre observational study investigating the efficacy of ECPR in patients with massive pulmonary embolism in cardiac arrest, and showed that survival increased from 5% to 26% using ECPR [4].

Publications:
1. van der Zee P, Dos Reis Miranda D, Meeder H, Endeman H, Gommers D. vvECMO can be avoided by a transpulmonary pressure guided open lung concept in patients with severe ARDS. Crit Care 2019; 23:133
2. Blankman P, Hasan P, Erik G, Gommers D. Detection of ‘best’ PEEP derived from EIT parameters during a decremental PEEP trial. Crit Care 2014; 18: R95.
3. Akin S, Reis Miranda dos D, Caliskan K, Soliman OI, Guven G, Struijs A, van Thiel RJ, Jewbali LS, Lima A, Gommers D, Zijlstra F, Ince C. Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock. Crit Care 2017; 21:265.
4. Mandigers L, Scholten E, Rietdijk WJR, den Uil CA, van Thiel RJ, Rigter S, Heijnen BGADH, Gommers D, Dos Reis Miranda D. Survival and neurological outcome with extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest caused by massive pulmonary embolism: A two centre observational study. Resuscitation 2019;136:8–13.

Our neuro-critical care group has studied patients with severe traumatic brain injuries and subarachnoid hemorrhage (SAH). We also studied brain dysfunction (delirium) in non-neurologic critically ill patients. Our group has gained important insights in this regard:

A) High amounts of fluids are administered by health care professionals in routine daily care to brain injured patients, and seem to constitute a hidden but preventable cause of harm to the brain [1,2].
B) Induced hypertension in patients with aneurysmal subarachnoid hemorrhage may be harmful if careful patient selection for this widely applied therapy is omitted [3].
C) Implementation of delirium guidelines in intensive care is cumbersome. It should be very focused and follow a step-by-step approach when resources are limited [4].

Further research on all three topics has already been established (a data analysis phase, CENTER-TBI [insight A]), or is under development for all three areas (partners: TU Delft, the Mayo Clinic [Rochester, USA], Johns Hopkins Hospital [USA]).

Publications:
1. Van der Jagt M. Fluid management of the neurological patient. Crit Care. 2016 May 31;20(1):126
2. Vergouw LJM, et al. High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output-Guided Fluid Restriction. J Intensive Care Med. 2017 Jan 1:885066617732747
3. Gathier CS, et al; HIMALAIA Study Group. Induced Hypertension for Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial. Stroke. 2018;49:76-83.
4. Zoran Trogrlić, et al. Improved Guideline Adherence and Reduced Brain Dysfunction after a Multicentre Multifaceted Implementation of ICU Delirium Guidelines in 3,930 Patients. Crit Care Med 2019;47:419-427.

We have also studied the ethical and social consequences of intensive care treatment for patients, including: decisions to withhold and withdraw life-sustaining measures; anticipating palliative care after the withdrawal of life-sustaining measures; death criteria and post-mortem organ donation; and the psycho-social implications for doctors and nurses of long-term care for seriously ill patients. We have had a longstanding and close collaboration with international experts in this field. In this context, we cooperate closely with the University of Antwerp (Prof. A.I.R. Maas) and the University of Cambridge (UK; Prof. D. Menon) regarding ethics and regulations within the prestigious CENTER-TBI study, and with the University Hospital Gent (Prof. dr. D. Benoit) for the DISPROPRICUS and COHESIS studies. In addition, the principal investigators are part of various (inter) national advisory committees for governments and scientific associations.

Publications:
1. Jeroen T.J.M. van Dijck, Roel P.J. van Wijk, Marjolein Timmers Valerie Legrand, Ernest van Veen, Andrew I.R. Maas, David K. Menon, Giuseppe Citerio, Nino Stocchetti, , Erwin J.O. Kompanje,. Informed Consent Procedures in acutely mentally incapacitated patients: policy and practice in the CENTER-TBI study. Intensiv Care Med 2019 (Submitted)
2. Benoit D.D., Jensen H.I., Malmgren J, Metaxa V, Reyners A.K., Darmon M, Rusinova K, Talmor D, Meert A.P., Cancelliere L., Zubek L, Maia P, Michalsen A, Vanheule S, Kompanje E.J.O., Decruyenaere J, Vandenberrghe S, Vansteelandt S, Gadeyne B, Van den Bulcke B, Azoulay E, Piers R.D., DISPROPRICUS study group of the Ethics Section of the European Society of Intensive Care Medicine. 2018. Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA. Intensiv Care Med 2018. Doi: 10.1007/s00134-018-5231-8
3. Van Veen E, Van der Jagt M., Cnossen M.C., Maas A.I.R., De Beaufort I.D., Menon D.K., Citerio G., Stocchetti N., Rietdijk W.J.R., Van Dijck J.T.J.M., Kompanje E.J.O. 2018. Brain death and post-mortem organ donation: report of a questionnaire from the CENTER-TBI study. Crit Care 2018; 22: 306.

Facilities

In September 2019, our department founded the Laboratory for Translational Intensive Care Medicine (prof. dr. C. Ince). This laboratory conducts fully instrumented in vivo physiological measurements in experimental animals focused on organ function, microcirculation, resuscitation and oxygenation in models of sepsis and shock. It supports clinical research through the measurement of innovative biomarkers and by performing and supporting clinical microcirculation measurements performed in various institutions.

Collaborations

Interdepartmental collaborations within the Erasmus MC

Anesthesiology
Cardiology
Pediatrics and Neonatal ICU
Surgery
Gastroenterology
Nephrology
Neurology/Neurosurgery
Pharmacology
Public Health
Emergency
Internal Medicine
Viroscience

Regional and national collaborations

This exist at several levels. We are currently conducting the following multicentre research:

ECMO, a haloperidol trial supported by ZON-MW.

A hypertension trial in SAB.
A delirium study (=DECISION study).
Antibiotic dosing in the ICU.
Microcirculation during burns and resuscitation (Maasstad Hospital, Department of ICU).
Microcirculation during abdominal surgery (St Antonius Hospital, Nieuwegein).
Microcirculation during mechanical support and cardiac surgery (Department of Cardiac Surgery, Amsterdam University Medical Center).
Microcirculation in critically ill patients (Department of Intensive Care, Leeuwarden Medical Centrum).

Our department has a structural collaboration with the Department of Industrial Design at TU Delft, from where we have recruited dr. E. Özcan into our department for research regarding alarming in the ICU. Our participation in the NICE (National ICU database) has resulted in studies on the incidence of AKI and resuscitation outcomes in the Netherlands. There has also been an ongoing collaboration with the Department of Translational Physiology Academic Medical Center with prof. C. Ince who was a part-time staff member since 2007 and now works at our institution full-time.

Our department participates in and has initiated several international collaborative relationships and studies related to our research themes. Examples include:

The Center of Traumatic Brain Injury (TBI): an EU-funded study on neurotrauma patients in 66 academic trauma centres across 28 EU countries, coordinated by the University of Antwerp.
The COHESIS and DISPROPRICUS study on the ethics of critical care (together with University Hospital Ghent, Belgium and academic centres in France).
The ECMO eCPR study, together with Universtätsklinikum Freiburg, Germany.
The National Institute of Neurological Disorders and Stroke (NINDS) INSIDER study and common data elements (CDE) for subarachnoid hemorrhage (worldwide partners, including the US/Canada), coordinated by Johns Hopkins, Baltimore.
The TRAIN study (transfusions in brain injury), coordinated by Erasme Hopital, Brussels; a European Society of Intensive Care medicine study.
A Haloperidol trial, in collaboration with the School of Pharmacy at Northwestern University, Boston.

Several structural collaborations with international research institutions have resulted in ongoing research projects related to our research themes. These include projects with Columbia University and New York University in New York (USA), and the Department of Intensive Care at the Catholic University of Chile in Santiago. A structural collaboration has also been established between our department and the University Hospital of Taiwan.