Advanced Monitoring of Systemic Hemodynamics in Critically Ill Patients with Acute Brain Injury

Abstract

Hemodynamic monitoring is widely used in critical care; however, the impact of such intervention in patients with acute brain injury (ABI) remains unclear. Using PubMed, a systematic review was performed (1966–August 2013), and 118 studies were included. Data were extracted using the PICO approach. The evidence was classified, and recommendations were developed according to the GRADE system. Electrocardiography and invasive monitoring of arterial blood pressure should be the minimal hemodynamic monitoring required in unstable or at-risk patients in the intensive care unit. Advanced hemodynamic monitoring (i.e., assessment of preload, afterload, cardiac output, and global systemic perfusion) could help establish goals that take into account cerebral blood flow and oxygenation, which vary depending on diagnosis and disease stage. Choice of techniques for assessing preload, afterload, cardiac output, and global systemic perfusion should be guided by specific evidence and local expertise. Hemodynamic monitoring is important and has specific indications among ABI patients. Further data are necessary to understand its potential for therapeutic interventions and prognostication.

Introduction

The management of patients with acute brain injury (ABI) includes the diagnosis and management of several medical disorders and complications [1]. Cardiovascular impairment is frequent, e.g., after subarachnoid hemorrhage (SAH), and is associated with increased morbidity and mortality [2, 3]. The complex pathophysiology of these cardiovascular alterations has been directly linked to the neurological injury, with data suggesting involvement of hypothalamic stimulation and/or failure of the autonomic system [4–6]. Different therapeutic interventions to improve cerebral perfusion pressure (CPP), such as hypervolemia or induced hypertension, also can result in cardiac arrhythmias, pulmonary edema, or left ventricular dysfunction [7, 8], which may exacerbate brain injury. In this setting, monitoring systemic hemodynamics can play an important role in avoiding such complications and optimizing cerebral blood flow (CBF) and oxygen delivery [9, 10].

Methods

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [11].

Search Criteria

Studies were considered eligible based on the PICO approach, which includes (a) Patient population, i.e., critically ill patients with at least one of the following ABI: traumatic brain injury (TBI), SAH, intracranial hemorrhage (ICH), ischemic stroke, coma after cardiac arrest (CA), central nervous system infection, encephalitis, seizures; neurosurgery; (b) Intervention provided, i.e., monitoring of systemic hemodynamics; (c) Controls, i.e., patients with ABI without hemodynamic monitoring or patients without ABI but undergoing hemodynamic monitoring or patients with ABI monitored with two different devices; (d) Outcome endpoints, i.e., mortality, survival with intact neurological function, complications (cardiac, pulmonary, infection), or modification in therapy (including intensity or drug choice). For this review, arterial and central venous lines were considered the minimal monitoring needed in patients with ABI, and mean arterial pressure (MAP) and central venous pressure (CVP) monitoring were used as the “control” group when compared to more advanced monitoring. “Systemic hemodynamic” parameters were divided into the following categories: (a) assessment of systolic and diastolic function [left ventricular ejection fraction (LVEF); rate of rise of left ventricular pressure (dP/dt); continuous ejection fraction; global ejection fraction on trans-pulmonary thermodilution (GEF); esophageal Doppler]; (b) measurement of cardiac output (CO) [i.e., PAC; trans-pulmonary thermodilution (TT); pulse wave contour analysis (PWCA); echocardiography, bioimpedence, etc.]; (c) assessment of preload (pulmonary artery occlusion pressure (PAOP); extravascular lung water (EVLW); global end-diastolic volume (GEV); esophageal flow time corrected (FTC-Doppler)]; (d) assessment of afterload [(systemic vascular resistances (SVR); arterial elastance (Ea)]; (e) assessment of fluid responsiveness [systolic pressure variation (SPV); pulse pressure variation (∆PP); stroke volume variation (SVV); passive leg raising (PLR); pleth variability index)]; (f) adequacy of global perfusion [lactate levels; mixed or central venous saturation; venous-arterial difference in carbon dioxide (∆CO₂)]. Evaluation of heart-rate variability or other parameters of autonomic function, and studies using echocardiography to diagnose the etiology of ischemic stroke if no specific hemodynamic parameters were reported were not included in this review.

Information Sources and Search Strategy

Using PubMed, a systematic review of English articles was performed from 1966 through August 15, 2013. The search strategy included the terms “brain injury,” “traumatic brain injury,” “subarachnoid hemorrhage,” “stroke,” “intracranial hemorrhage,” “cardiac arrest,” “seizures,” “epilepsy,” “neurosurgery,” “encephalitis,” “meningitis”—used with one of the following: “hemodynamics,” “hemodynamic monitoring,” “cardiac output,” “ventricular function,” “ejection fraction,” “preload,” “extravascular lung water,” “end-diastolic volume,” “filling pressure,” “venous saturation,” “mixed venous saturation,” “central venous saturation,” “venous-arterial carbon dioxide,” “arterio-venous carbon dioxide difference,” “delta CO₂,” “CO₂ gap,” “venous CO₂,” “lactate,” “fluid responsiveness,” “stroke volume variation,” “systolic pressure variation,” “pulse pressure variation,” “passive leg raising,” “pleth variability index,” “afterload,” “vascular resistances,” and “elastance.” Additional references for relevant studies were also searched from review articles (i.e., defined as “other sources”).

Study Selection and Data Collection

One author independently reviewed all citations, abstracts, and full-text articles to select eligible studies. Excluded were (a) review articles; (b) case reports or case-series with ≤5 patients; (c) experimental studies; (d) studies on pediatric ICU populations (<18 years); (e) studies that were not conducted on ICU patients; (f) studies dealing with brain dead patients. Data were abstracted using a predefined abstraction spreadsheet, according to the PICO system. No attempt was made to re-analyze the data and no meta-analysis was performed since there are insufficient randomized (RCT) or case–control studies.

Review End-Points

The end-points of this review (in patients with ABI) were to answer the following questions:

• 1. What is the proportion of patients who have altered systemic hemodynamics and how many will develop circulatory failure, inadequate perfusion or organ dysfunction?

• 2. Can monitoring of systemic hemodynamics help understand the mechanisms of circulatory failure, inadequate perfusion, or organ dysfunction?

• 3. Does hemodynamic monitoring have a specific role in optimizing brain perfusion and oxygenation or brain-specific therapy?

• 4. What is the impact of systemic hemodynamic monitoring and related therapies on morbidity, mortality, and neurological outcome?

• 5. How can fluid responsiveness be assessed in ABI patients?

• 6. What hemodynamic monitoring is indicated in ABI patients, in particular to diagnose and support the management of unstable or at-risk patients?

Grading of Evidence

The quality of evidence was judged based on the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system approach [12].

Literature Summary

The search retrieved a total of 25,801 citations (Fig. 1), and 118 article met inclusion criteria. The numbers of articles for each disease were 68 for SAH, 12 for TBI, 8 for stroke or ICH, 23 for CA, and 7 for neurosurgery. The search found 4 randomized clinical trials (RCTs), 5 case-controlled studies (all “before-after” studies), 81 prospective/observational studies, and 28 retrospective studies.

Fig. 1

Flow-chart of the research process according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement

Forty-six studies (n = 5,022) included data on cardiac function. Most (38/46) were prospective and focused on SAH; all except three used echocardiography (Table 1). Forty-two studies (n = 4,224) reported data on CO. Most (28/42) were prospective and 27/42 focused on SAH; 3 studies were RCTs (Table 2). Twelve studies (n = 969) reported data on preload assessment. Most were performed in SAH patients (11/12; Tables 3, 4). Five studies (n = 198) reported data on afterload. All evaluated SVR and were mostly performed in SAH patients (4/5). No study evaluated arterial elastance (Table 5). Six studies (n = 250) reported data on fluid responsiveness (Table 6). Twenty studies (n = 3,870) reported data on the adequacy of global perfusion; 3 used ScvO₂, 16 measured lactate levels, and only 1 focused on ∆CO₂. Most of studies were retrospective (11/20) and evaluated patients after CA (12/20) (Table 6).

Table 1 Studies that evaluate cardiac function in acute brain injury patients

Table 2 Studies evaluating cardiac output (CO) in acute brain injury patients

Table 3 Studies evaluating preload in acute brain injury patients

Table 4 Studies evaluating afterload in acute brain injury patients

Table 5 Studies evaluating fluid responsiveness (FR) in acute brain injury patients

Table 6 Studies evaluating parameters of global perfusion in acute brain injury patients

What is the Proportion of Patients Who Have Altered Systemic Hemodynamics and How Many Will Develop Circulatory Failure, Inadequate Perfusion or Organ Dysfunction?

Several studies reported altered LVEF after SAH in 2–15 % of patients. [13–15] Similarly, regional wall motion abnormalities (RWMA) were described in 5–45 % of patients [16–19], although RWMA may be present together with normal LVEF [20]. Diastolic dysfunction occurred in 46–89 % patients after SAH [21–23]. Few studies evaluated the incidence of altered CO in patients with ABI. In SAH patients, high CI values were present on admission and progressively diminished on day 5 (from 5.3 ± 0.4 to 3.5 ± 0.2 L/min/m²); higher CI and EVLWI were found in those patients admitted with a poor neurological status (WFNS 4-5) [24]. After ischemic stroke, similar CI values were reported when compared to matched-control subjects; however, patients admitted with poor neurological status had higher CI than others [25]. Finally, low CI was common in the early phase after CA and progressively normalized over time, except in those patients who eventually died in cardiogenic shock [26]. Hypovolemia, suggested by low GEDVI on admission, is frequent after SAH, especially in those patients admitted with a poor neurological status [24].

Can Monitoring of Systemic Hemodynamics Help Understand the Mechanisms of Circulatory Failure, Inadequate Perfusion, or Organ Dysfunction?

Cardiac Function

Among several hypotheses, the main mechanism of cardiac injury following SAH is thought to be associated with sympathetic stimulation and catecholamine release. In one study in 48 SAH patients [27], those with RWMA had significantly higher plasma norepinephrine levels than did those with normal echocardiography (2,098 ± 1,773 vs. 963 ± 839 pg/mL, p = 0.02). Plasma norepinephrine levels also were inversely correlated with LVEF. Multivariate logistic regression analysis revealed that increased plasma norepinephrine levels were predictive of RWMA. Similarly, Sugimoto et al. [28] showed those patients with RWMA on admission had decreased estradiol and elevated norepinephrine levels, and the combination of both significantly increased the risk for RWMA development.

Another important issue was the concomitant presence of altered cardiac function and altered ECG or increased markers of heart injury. SAH patients with cTnI ≥0.3 ng/mL had significantly lower LVEF (52 vs. 63 %, p < 0.001) than others [29]. In addition, 44 % of them had LVEF <50 vs. 5 % in others (p < 0.001). A higher incidence of RWMA among patients with cTnI ≥0.3 ng/mL was found in both early and late phases after SAH [30, 31]. Patients with high cTnI levels also had a higher incidence of diastolic dysfunction [22]. These alterations were associated with normal myocardial perfusion but altered sympathetic innervation [6, 32].

Since pulmonary complications are frequent after ABI, the role of altered cardiac function was evaluated in several studies. Patients who developed pulmonary edema (PE) after SAH had lower global ejection fraction (GEF) than did others [33]. Also, a higher incidence of systolic and diastolic dysfunction was found in patients with PE compared to others after SAH [22, 23]. Naidech et al. [34] reported no association between LV dysfunction and the occurrence of PE, while Junttila et al. [35] showed that the proportion of patients with LVEF <50 % was similar in patients developing neurogenic pulmonary edema (NPE) and those who did not (26 vs. 18 %, p = 0.6). Although patients with NPE often had more a restrictive profile on echography when compared to others (21 vs. 5 %, p = 0.03), filling pressures were similar between groups. Moreover, echocardiographic abnormalities could not predict development of NPE.

Cardiac Output

In patients with SAH, lower CI was reported in patients developing PE compared to others; [36] however, variable hemodynamics, including even high CI after SAH, were found in patients with PE in other studies [37–39].Three studies evaluated changes in CI during the use of therapeutic hypothermia (TH). Cooling resulted in lower heart rate, filling pressure, and CI without deleterious effects on global perfusion in OHCA [40]. TH improved systemic hemodynamics in CA survivors suffering from cardiogenic shock [41]. The use of hypothermia in patients with SAH decreased CI and increased artero-venous jugular difference in oxygen, suggesting a potential role for brain hypoperfusion in this setting [42].

Preload

In three studies, patients with PE or poor oxygenation had a higher ELWI than others [33, 36, 43]. Moreover, PE was associated with higher GEDVI after SAH in another study [33]. However, two other studies reported a poor predictive value of PAOP for PE development [37, 44].

Adequacy of Global Perfusion

Admission lactate levels were significantly higher in patients with shock after CA than the others and were an independent predictor of ICU mortality [45].

Does Hemodynamic Monitoring Have a Specific Role in Optimizing Brain Perfusion and Oxygenation or Brain-Specific Therapy?

Cardiac Output and Preload

Several studies have shown a relationship between the development of DCI and low CI in SAH patients [33, 44, 46], and different therapeutic interventions have been performed using systemic hemodynamic monitoring in these patients to optimize brain perfusion. Since CBF values are associated with CI [47], the use of a “hyperdynamic” approach (i.e., increase CI optimizing preload and inotropes to increase CBF, Fig. 2) has been observed to be associated with neurological improvement [48–52]. Alternatively, the more traditional “hypertensive” approach (i.e., increase MAP to increase CBF) is used to increase CPP in symptomatic vasospasm after SAH and can improve CBF and brain oxygenation in this setting [53]. Importantly, a “hyperdynamic” approach may still improve neurological status when patients with vasospasm fail to respond to norepinephrine [54].

Fig. 2

Optimization of systemic hemodynamics in high-risk patients after subarachnoid hemorrhage (SAH). Adapted from [34, 35]

Afterload

Hadeishi et al. [48] reported that in 8 SAH patients, in whom a PAC was used to optimize therapy for cerebral vasospasm, fluids, and inotropic agents induced an increase of CI (from 3.4 to 4.9 L/min m²) with stable PAOP, while SVR decreased. Patients who develop DCI or symptomatic vasospasm have higher SVRI than others [33, 44]. Finally, the prophylactic use of IABP after SAH was associated with higher SVR than patients treated with a conventional approach but did not affect neurological outcome in this setting [55].

What is the Impact of Systemic Hemodynamic Monitoring and Related Therapies on Morbidity, Mortality, and Neurological Outcome?

Cardiac Function

Several studies have evaluated the impact of hemodynamic alterations on the morbidity and mortality after ABI. Patients with reduced LVEF are more likely to develop ventricular arrhythmias than others (29 vs. 13 %, p = 0.12) [56]. However, there is conflicting data exist on the association between LV dysfunction and survival or neurological outcome after SAH or CA [3, 14, 57–62].

Cardiac Output and Preload

Using a hemodynamic-guided therapy in out-of-hospital cardiac arrest (OHCA), Tagami et al. showed a significant increase of favorable neurological outcome from 0.5 to 3.0 % when compared to an historical cohort, even after adjustment for confounders [63]. The use of such intervention to improve patients’ management was an independent predictor of good outcome. In the sub-group of patients with witnessed ventricular fibrillation, the proportion of patients with good neurological outcome also significantly improved from 7.9 to 26.2 %. In SAH patients, “hyperdynamic” therapy does not always reduce the incidence of TCD-vasospasm or DCI, when compared to norepinephrine [64]. However, the duration of mechanical ventilation (median 8 vs. 19 days, p = 0.01) and ICU stay (11 vs. 21 days, p = 0.01) was less when using dobutamine than norepinephrine. ICU mortality was 18 % for dobutamine and 6 % for norepinephrine (p = 0.33). Kim et al. [65] showed that the occurrence of vasospasm, myocardial infarction, ARDS, and renal failure was similar when using invasive hemodynamic monitoring with PAC in SAH patients compared to non-monitored patients. However, the use of PAC was associated with a reduced incidence of pulmonary edema (6 vs. 14 %, p = 0.003) and sepsis (3 vs. 11 %, p < 0.001). Reduced 6-month mortality was observed using PAC (34 vs. 29 % p = 0.04). Others have observed that the use of TT was associated with significantly less TCD-vasospasm (50 vs. 66 %, p = 0.03), delayed neurological deficit (32 vs. 48 %, p = 0.03), and vasospasm-related infarctions (6 vs. 14 %, p = 0.049) than conventional therapy after SAH [66]. The use of TT also was associated with a reduced number of cardiopulmonary complications (from 12 to 2 %, p = 0.01) and reduced maximal daily fluid intake. Others have observed that the prophylactic use of hypertensive therapy does not reduce the incidence of delayed neurological deficit; instead it increases the occurrence of PE [67].

Adequacy of Global Perfusion

In TBI patients, ScvO₂ values are lower in non-survivors (n = 22; 67 ± 12 %) than in survivors (n = 99; 70 ± 9 %, p = 0.04). ScvO₂ ≤65 % had a relative risk for increased mortality of 2.3 (95 % CI 1.1–4.8); however, ScvO₂ was not an independent predictor of mortality [68]. Gaieski et al. [69] showed that early goal-directed hemodynamic optimization (EGHO) of patients after CA using a target ScvO₂ of ≥65 % (Fig. 3) was associated with reduced mortality when compared with historical controls (10/20, 50 % vs.14/18, 78 %; p = 0.15). Similarly, Walters et al. [70] showed better neurological outcome in patients treated with EGHO and TH when compared to historical controls (31 vs. 12 %, p = 0.08).

Fig. 3

Optimization of systemic hemodynamics in comatose patients after cardiac arrest. Adapted from [81]

Several studies have described lactate levels in CA patients with varied results. Starodub et al. [71] observed that initial serum lactate (divided in three groups; <5 mmol/L; 5–10 mmol/L; >10 mmol/L) was not associated with mortality. An association with serial lactate levels or lactate clearance and outcome is observed. For example, Kliegel et al. observed that lactate levels were significantly higher in non-survivors than survivors on admission, at 24 and 48 h in patients surviving OHCA [72]. However, lactate levels returned within normal ranges within 24 h in most of patients. A higher proportion of non-survivors had hyperlactatemia (defined as lactate >2 mmol/L) at 48 h than survivors (31 vs. 14 %, p < 0.001), and lactate levels at 48 h were independently associated with mortality. In the same study, similar results were reported when patients were categorized as good (n = 161) or poor (n = 233) neurological outcome. Some studies have shown that, rather than measuring admission lactate levels, the rate of decline in lactate concentration, the so-called “lactate clearance” reflects the improvement of global perfusion during therapy. A higher lactate clearance is independently associated with good outcome in this setting [73].

How Can Fluid Responsiveness be Assessed in ABI Patients?

Berkenstadt et al. [20] studied stroke volume variation in 15 patients undergoing elective neurosurgery; 140 fluid loadings were performed. Half of them were associated with fluid responsiveness (FR). Li et al. [74] examined FR in 48 patients undergoing brain surgery, and SVV was the best predictor of FR (defined as an increase of stroke volume >10 %), while other common hemodynamic variables, including MAP, CVP, and CO, did not discriminate between fluid responders and non-responders. Moretti et al. [75] showed that the inferior vena cava distensibility (dIVC) assessed on echocardiography was a strong predictor of FR in patients with SAH, with an AUC of 0.902 (95 % CI 0.73–0.98). A dIVC >16 % yielded a sensitivity of 71 % and a specificity of 100 % to predict FR. After SAH, changes in GEDVI after fluid loading are associated with changes in SV, while changes in PAOP and CVP were not [66]. The GEDVI had an AUC of 0.73 to predict FR (defined as an increase of stroke volume >10 %) in this setting.

What Hemodynamic Monitoring is Indicated in ABI Patients, in Particular to Diagnose and Support the Management of Unstable or At-Risk Patients?

Eight studies (n = 458) reported data on a specific technique/device to monitor CO and 3 (n = 71) to monitor FR in ABI patients. No study compared different parameters of preload, afterload, or global perfusion in patients with ABI. The main advantages and disadvantages of different monitoring devices are listed in Table 7.

Table 7 Available techniques used for hemodynamic monitoring in patients with acute brain injury and their potential advantages and disadvantages

In SAH patients receiving hyperdynamic therapy, the PCWA technique has good accuracy to measure CI when TT was used as reference; [76] the coefficient of agreement was 0.77, and the bias was 0.33 L/min m² with a percentage of error of 15 %. The incidence of side effects, cerebral infarction, maximal dobutamine doses, and neurological outcome was similar when patients were managed with one of the two techniques. In patients with SAH treated with a hyperdynamic approach, CI measured by TT showed a good correlation (r ² = 0.78) [66] with the PAC measurements, with a bias 0.05 L/min m², a precision of 0.11 L/min m² and a percentage of error of 14 %. In SAH patients undergoing brain surgery, PCWA-measured CI showed a good correlation with TT (r = 0.82); The percentage of error was higher when measurements were collected during mechanical ventilation than on spontaneous breathing [77]. In patients undergoing brain surgery, an important bias on CO measurement was reported (1.7 L/min), with limits of agreement of −2.4 to 5.4 L/min when a PCWA was compared to TT [78]. The percentage of error was 45 %. The bias was larger in those patients receiving norepinephrine and nimodipine, but not in those receiving dobutamine (Table 8). There was a significant negative correlation between SVR and bias. Others have observed a poor agreement between echocardiography, and PAC was reported to measure CO in SAH patients receiving aggressive fluid therapy [79]. After CA, TT, and not PCWA devices, appears to be a reliable technique to assess CO during TH [80, 81]. Finally other studies show that ΔPP or SVV was equivalent to assess FR in ABI patients [75, 82].

Table 8 Differences among different monitoring techniques for cardiac output (CO) in acute brain injury patients

Appendix: Participants in the International Multi-disciplinary Consensus Conference on Multimodality Monitoring

Peter Le Roux, MD, FACS

Brain and Spine Center,

Suite 370, Medical Science Building,

Lankenau Medical Center,

100 East Lancaster Avenue, Wynnewood, PA 19096, USA.

Tel: +1 610 642 3005;

Fax: 610 642 3057

email: lerouxp@mlhs.org

David K Menon MD, PhD, FRCP, FRCA, FFICM, FMedSci

Head, Division of Anaesthesia, University of Cambridge,

Consultant, Neurosciences Critical Care Unit,

Box 93, Addenbrooke’s Hospital,

Cambridge CB2 2QQ, UK

email: dkm13@wbic.cam.ac.uk

Paul Vespa, MD, FCCM, FAAN, FNCS

Professor of Neurology and Neurosurgery,

Director of Neurocritical Care,

David Geffen School of Medicine at UCLA

Los Angeles, CA 90095 USA

email: PVespa@mednet.ucla.edu

Giuseppe Citerio,

Director NeuroIntensive Care Unit,

Department of Anesthesia and Critical Care,

Ospedale San Gerardo, Monza.

Via Pergolesi 33, Monza 20900, Italy

email: g.citerio@hsgerardo.org

Mary Kay Bader RN, MSN, CCNS, FAHA, FNCS

Neuro/Critical Care CNS,

Mission Hospital,

Mission Viejo, CA 92691, USA

email: Marykay.Bader@stjoe.org

Gretchen M. Brophy, PharmD, BCPS, FCCP, FCCM

Professor of Pharmacotherapy & Outcomes Science and Neurosurgery,

Virginia Commonwealth University,

Medical College of Virginia Campus,

410 N. 12th Street,

Richmond, VA 23298-0533, USA

email: gbrophy@vcu.edu

Michael N. Diringer, MD

Professor of Neurology, Neurosurgery & Anesthesiology,

Chief, Neurocritical Care Section,

Washington University,

Department of Neurology, Campus Box 8111,

660 S Euclid Ave,

St Louis, MO 63110, USA

email: diringerm@neuro.wustl.edu

Nino Stocchetti, MD

Professor of Anesthesia and Intensive Care,

Department of physiopathology and transplant,

Milan University,

Director Neuro ICU,

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico,

Via F Sforza, 35 20122 Milan, Italy

e-mail: stocchet@policlinico.mi.it

Walter Videtta, MD

ICU Neurocritical Care,

Hospital Nacional ‘Prof. a. Posadas’,

El Palomar - Pcia. de Buenos Aires,

Argentina

email: wvidetta@ar.inter.net

Rocco Armonda, MD

Department of Neurosurgery,

MedStar Georgetown University Hospital,

Medstar Health, 3800 Reservoir Road NW,

Washington, DC 20007, USA

email: Rocco.Armonda@gmail.com

Neeraj Badjatia, MD

Department of Neurology,

University of Maryland Medical Center,

22 S Greene St,

Baltimore, MD 21201, USA

email: nbadjatia@umm.edu

Julian Boesel, MD

Department of Neurology,

Ruprect-Karls University,

Hospital Heidelberg, Im Neuenheimer Feld 400,

D-69120 Heidelberg, Germany

email: Julian.Boesel@med.uni-heidelberg.de

Randal Chesnut, MD, FCCM, FACS

Harborview Medical Center,

University of Washington Mailstop 359766,

325 Ninth Ave,

Seattle, WA 98104-2499, USA

email: chesnutr@u.washington.edu

Sherry Chou, MD, MMSc

Department of Neurology,

Brigham and Women’s Hospital,

75 Francis Street,

Boston, MA 02115, USA

email: schou1@partners.org

Jan Claassen, MD, PhD, FNCS

Assistant Professor of Neurology and Neurosurgery,

Head of Neurocritical Care and Medical Director of the Neurological Intensive Care Unit,

Columbia University College of Physicians & Surgeons,

177 Fort Washington Avenue, Milstein 8 Center room 300,

New York, NY 10032, USA

email: jc1439@cumc.columbia.edu

Marek Czosnyka, PhD

Department of Neurosurgery,

University of Cambridge,

Addenbrooke’s Hospital, Box 167,

Cambridge, CB20QQ, UK

email: mc141@medschl.cam.ac.uk

Michael De Georgia, MD

Professor of Neurology,

Director, Neurocritical Care Center,

Co-Director, Cerebrovascular Center,

University Hospital Case Medical Center,

Case Western Reserve University School of Medicine,

11100 Euclid Avenue,

Cleveland, OH 44106, USA

email: michael.degeorgia@uhhospitals.org

Anthony Figaji, MD, PhD

Head of Pediatric Neurosurgery,

University of Cape Town,

617 Institute for Child Health,

Red Cross Children’s Hospital,

Rondebosch, 7700 Cape Town, South Africa

email: anthony.figaji@uct.ac.za

Jennifer Fugate, DO

Department of Neurology,

Mayo Clinic,

200 First Street SW,

Rochester, MN 55905, USA

email: Fugate.Jennifer@mayo.edu

Raimund Helbok, MD

Department of Neurology, Neurocritical Care Unit,

Innsbruck Medical University,

Anichstr.35, 6020,

Innsbruck, Austria

email: raimund.helbok@uki.at

David Horowitz, MD

Associate Chief Medical Officer,

University of Pennsylvania Health System,

3701 Market Street,

Philadelphia, PA 19104, USA

email: david.horowitz@uphs.upenn.edu

Peter Hutchinson, MD

Professor of Neurosurgery,

NIHR Research Professor,

Department of Clinical Neurosciences,

University of Cambridge,

Box 167 Addenbrooke’s Hospital,

Cambridge, CB2 2QQ, UK

email: pjah2@cam.ac.uk

Monisha Kumar, MD

Department of Neurology,

Perelman School of Medicine, University of Pennsylvania,

3 West Gates,

3400 Spruce Street,

Philadelphia, PA 19104, USA

email: monisha.kumar@uphs.upenn.edu

Molly McNett, RN, PhD

Director, Nursing Research,

The MetroHealth System,

2500 MetroHealth Drive,

Cleveland, OH 44109, USA

email: mmcnett@metrohealth.org

Chad Miller, MD

Division of Cerebrovascular Diseases and Neurocritical Care,

The Ohio State University,

395 W. 12th Ave, 7th Floor,

Columbus, OH 43210, USA

email: ChadM.Miller@osumc.edu

Andrew Naidech, MD, MSPH

Department of Neurology,

Northwestern University Feinberg SOM 710,

N Lake Shore Drive, 11th floor,

Chicago, IL 60611, USA

email: ANaidech@nmff.org

Mauro Oddo, MD

Department of Intensive Care Medicine,

CHUV University Hospital, BH 08-623,

Faculty of Biology and Medicine, University of Lausanne,

1011 Lausanne, Switzerland

email: Mauro.Oddo@chuv.ch

DaiWai Olson, RN, PhD

Associate Professor of Neurology, Neurotherapeutics and Neurosurgery,

University of Texas Southwestern,

5323 Harry Hines Blvd.,

Dallas, TX 75390-8897, USA

email: daiwai.olson@utsouthwestern.edu

Kristine O’Phelan, MD

Director of Neurocritical Care,

Associate Professor, Department of Neurology,

University of Miami, Miller School of Medicine,

JMH, 1611 NW 12th Ave, Suite 405,

Miami, FL 33136, USA

email: kophelan@med.miami.edu

Javier Provencio, MD

Associate Professor of Medicine,

Cerebrovascular Center and Neuroinflammation Research Center,

Lerner College of Medicine,

Cleveland Clinic,

9500 Euclid Ave, NC30,

Cleveland, OH 44195, USA

email: provenj@ccf.org

Corina Puppo, MD

Assistant Professor, Intensive Care Unit,

Hospital de Clinicas, Universidad de la República,

Montevideo,

Uruguay

email: coripuppo@gmail.com

Richard Riker, MD

Critical Care Medicine,

Maine Medical Center,

22 Bramhall Street,

Portland, ME 04102-3175, USA

email: RRiker@cmamaine.com

Claudia Robertson, MD

Department of Neurosurgery,

Medical Director of Center for Neurosurgical Intensive Care,

Ben Taub Hospital,

Baylor College of Medicine,

1504 Taub Loop, Houston, TX 77030, USA

email: claudiar@bcm.tmc.edu

J. Michael Schmidt, PhD, MSc

Director of Neuro-ICU Monitoring and Informatics,

Columbia University College of Physicians and Surgeons,

Milstein Hospital 8 Garden South, Suite 331,

177 Fort Washington Avenue,

New York, NY 10032, USA

email: mjs2134@columbia.edu

Fabio Taccone, MD

Department of Intensive Care, Laboratoire de Recherche Experimentale,

Erasme Hospital,

Route de Lennik, 808,

1070 Brussels, Belgium

email: ftaccone@ulb.ac.be