EditorialUpdates in Neurocritical Care

Christos Lazaridis,1 Laith Altaweel,2 and Dimitrios Karakitsos 3,4

1Division of Neurocritical Care, Departments of Neurology and Neurosurgery, University of Chicago, Chicago, IL, USA2Department of Medicine, Inova Fairfax Hospital, Falls Church, VA 22042, USA3Department of Critical Care, Keck Medical School, USC, Los Angeles, CA, USA4Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia

Correspondence should be addressed to Dimitrios Karakitsos; karakitsosdimitrios@gmail.com

Received 9 July 2018; Accepted 10 July 2018; Published 1 August 2018

Copyright © 2018 Christos Lazaridis et al. &is is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Caring for acutely and critically ill neurological and neu-rosurgical patients comprises the focus of the specialty ofneurocritical care. It should be recognized that in reality, thecare of such patients requires the expertise and involvementof a number of specialists including intensivists, neurolo-gists, neurosurgeons, anesthesiologists, and specializednurses. Although it is not only about “saving brain,” ad-mittedly successful neurocritical care is care that salvagesinjured brain tissue and enhances the prospects of neuro-logic recovery. Hereby, we briefly mention recent clinicalupdates in neurocritical care; several of them are further andthoroughly discussed in the manuscript collection of thisvolume. &e areas to be selectively highlighted in thisshort piece include the following: (a) management of largevessel occlusion (LVO) ischemic stroke, (b) global strategiesfor brain monitoring and protection after cardiac arrestand during extracorporeal cardiorespiratory support, (c)the approach towards monitoring and managing severetraumatic brain injury, and (d) minimally invasive neu-rosurgical approaches for intracerebral and ventricularhemorrhages.

Until recently, intravenous tPA was the only evidence-based treatment for acute ischemic stroke. More recentlyhowever, a number of high-quality multinational random-ized controlled trials (RCTs) have proven that for selectedpatients presenting with LVO up to 24 hours from symptomonset, endovascular recanalization improves functionalneurologic outcome, when compared to medical therapy. SixRCTs have independently demonstrated clinical benefit ofstent-retriever thrombectomy when performed within 6 hours

from stroke onset (REVASCAT, SWIFT PRIME, EXTEND-IA, ESCAPE, THRACE, andMR CLEAN). THRACE andMRCLEAN independently demonstrated benefit based solely onnoncontrast CT and demonstration of LVO; consequently,these are the recommended imaging eligibility criteria. Twoother trials have provided evidence for extending the windoweven further based on additional perfusion imaging anddemonstration of a favorable ratio between salvageable brainand infarcted core (DEFUSE 3: 6–16 hours; DAWN: 6–24hours) [1]. Based on the aforementioned literature, there isa clear imperative evaluating patients presenting with anNIHSS >5 for LVO, and depending on timing size of ischemicinfarct core, and penumbra. Challenges that remain relate tothe availability of experts and organization of care towardscenters that can offer expedited, specialized clinical and ra-diographic assessment followed by prompt intervention foreligible patients. Additional questions for future research in-clude extending the time window further, or abandoning alltogether “time from onset” as an eligibility criterion andreplacing it with imaging eligibility criteria.

Outcomes of patients who survive cardiac arrest arecritically dependent on the degree of global brain injurysustained. &e earlier days of enthusiastic endorsement oftherapeutic hypothermia with the goal of 32–34°C, based onthe 2002 RCTs by Bernard et al. and the HACA study group,have been tempered by the more recent, and larger, Nielsenet al.’s study [2–4].&e latter study found that 33 versus 36°Cwere equivalent targets in terms of mortality and neurologicoutcomes for patients with out-of-hospital cardiac arrest.A detailed comparison of these studies is out of scope, but it

HindawiCritical Care Research and PracticeVolume 2018, Article ID 1617359, 3 pageshttps://doi.org/10.1155/2018/1617359

is worth noting that the Nielsen study had a remarkably highrate of expedient bystander application of CPR (an un-realistic situation in most parts outside of Scandinavia) andthat what Nielsen et al. compared were two differentstrategies of targeted temperature management (TTM)rather than what the earlier RCTs tested, mild hypothermiaversus no temperature control. As a result, there is ongoingdebate on what the most appropriate target may be withinthe 32–36°C, and if there are patient characteristics ormonitoring modalities (or biomarkers) that could providepatient-specific targets. Nevertheless, what should be un-controversial is that TTM is the indicated brain protectivestrategy for 24–48 hours after cardiac arrest and that tem-peratures above 36–37°C are to be prevented with mainte-nance of normothermia thereafter. Global anoxic-ischemicbrain injury in addition to more focal ischemic and hem-orrhagic strokes has been observed, in nontrivial rates, inpatients subjected to extracorporeal membrane oxygenation(ECMO). In view of the increasing use of ECMO modalitiesfor the management of various causes of respiratory and/orcardiac failure, it is important that we consider methods toprevent, monitor, and potentially ameliorate brain injury inthis setting. Unfortunately, current tools for noninvasivemonitoring of cerebral blood flow (CBF), brain oxygenation,and energy dynamics are not advanced enough to be in-formative in optimizing patient-specific brain physiology.More study is clearly required while use of transcranialDoppler (TCD) and near-infrared spectroscopy (NIRS) hasbeen reported with interest. Interestingly, the ability tomonitor the status of CBF autoregulation after cardiac arrestand during ECMO may shed light to pathophysiologicmechanisms.

&e value of invasive, multimodality monitoring isanother passionately debated topic when it comes tomanaging patients with severe traumatic brain injury. Itseems that there are two camps of thought; one sees greatpotential in obtaining compartmental pressures, tissueoxygenation, and metabolic data with a goal of tailoringinterventions to the individual patient and according tophysiologic principles of oxygen delivery, demand, andutilization. &e second camp maintains skepticism to-wards the aforementioned approach arguing on the basisof a lack of hard data for improved patient outcomesin the face of potential adverse effects, resource utiliza-tion, and cost. &is debate has not been helped by recentRCTs addressing specific interventions against refrac-tory intracranial hypertension. &e Eurotherm 32-35 trialestablished that hypothermia should not be used early(i.e., before other stage 2 treatments such as osmother-apy) in patients with diffuse TBI, despite beneficial effectson intracranial pressure (ICP) control [5]. &e clinicaloutcomes of patients in the intervention arm of this studywere worse than those of control patients. More recently,the RESCUEicp trial sought to establish the role ofdecompressive craniectomy (DC) for treating refractoryICP [6]. &is trial took about 10 years to complete, in-volving 52 centers in 20 countries to recruit 408 patients.While there was a substantial mortality benefit withsurgical decompression (for every 100 patients treated

surgically versus medically there were 22 more survivors), itcame at the expense of increased rates of moderate and severedisability when compared to themedical management cohort.Such results require careful, engaged, and transparent con-versations with families during shared decision-making toavoid cognitive biases that may derive goals of care towardseither an overly pessimistic or nihilistic stance or, on thecontrary, be influenced by unrealistic optimistic biases. Fi-nally, a promising step was made in favor of the monitoringcamp by the completion of the BOOST phase II trial dem-onstrating that adding brain tissue oxygenation (PbtO2)monitoring to standard ICP/CPP resulted to less cerebralhypoxia [7]. &e forthcoming phase III trial will determinewhether PbtO2-targeted therapy will improve long-termneurologic outcomes.

Ischemic stroke, traumatic brain injury, neuro-monitoring, and global cerebral protection are among theconditions that the field can claim some developments andsuccesses. &e same cannot be said for nontraumatic, non-coagulopathy-related intracerebral and/or intraventricularhemorrhages (ICH/IVH). &ese types of hemorrhages re-main the most debilitating type of stroke with no specifictreatments that can alter their course for the better. &epromise of finding the optimal blood pressure target remainselusive with more aggressive control to possibly confermodest benefits in terms of hematoma expansion but noproof that it improves patient outcomes. Surgery trials havealso failed in this regard with the possible exception ofsuperficial lobar hemorrhage cases. Hope has been placed onminimally invasive approaches where a less morbid way ofevacuating intraparenchymal or clearing intraventricularblood may eventually confer either clinical outcome benefitsor secondary benefits such as faster resolution of hydro-cephalus or a decreased need for shunt placement. &erelevant studies are the recently completed CLEAR IVH IIIand the ongoing MISTIE-III and ENRICH trials. CLEAR-IIItested patients with ICH <30 cc and large IVH causinghydrocephalus for improved clinical outcomes when givenlow-dose rtPA via an external ventricular drain versusplacebo. Despite a reduction in mortality, no functionaloutcome benefit was seen in the intervention arm [8].MISTIE-III seeks to demonstrate that minimally invasivesurgery (MIS) plus rtPA for intraparenchymal hematomaevacuation, and for three days, improves functional outcomeby a 12% increase in the modified Rankin Scale (mRS) score0–3 compared to medically treated subjects assessed at 180days; it is underway involving 90 centers in the US, Europe,Israel, China, and Australia (ClinicalTrials.gov Identifier:NCT01827046). Finally, ENRICH is a multicenter, ran-domized, adaptive clinical trial comparing standard medicalmanagement to early surgical hematoma evacuation (lessthan 24 hours) using minimally invasive parafascicularsurgery (MIPS) in the treatment of intracerebral hemor-rhage (ClinicalTrials.gov Identifier: NCT02880878).

&e science and clinical medicine of “saving brain” arestill at an early stage. Notwithstanding, there have recentlybeen significant developments for a number of conditions.We have highlighted a few of these without an intention tobe exhaustive; the manuscripts in this special issue on

2 Critical Care Research and Practice

updates in neurocritical care cover some of these and otherrelevant topics in depth.

Christos LazaridisLaith Altaweel

Dimitrios Karakitsos

References

[1] W. J. Powers, A. A. Rabinstein, T. Ackerson et al., “2018guidelines for the early management of patients with acuteischemic stroke: a guideline for healthcare professionals fromthe American Heart Association/American Stroke Associa-tion,” Stroke, vol. 49, no. 3, pp. e46–e110, 2018.

[2] S. A. Bernard, T. W. Gray, M. D. Buist et al., “Treatment ofcomatose survivors of out-of hospital cardiac arrest with in-duced hypothermia,” New England Journal of Medicine,vol. 346, no. 8, pp. 557–563, 2002.

[3] &e Hypothermia after Cardiac Arrest Study Group, “Mildtherapeutic hypothermia to improve the neurologic outcomeafter cardiac arrest,”New England Journal of Medicine, vol. 346,pp. 549–556, 2002.

[4] N. Nielsen, J. Wetterslev, T. Cronberg et al., “Targeted tem-perature management at 33 versus 36°C after cardiac arrest,”New England Journal of Medicine, vol. 369, no. 23, pp. 2197–2206, 2013.

[5] P. J. D. Andrews, H. L. Sinclair, A. Rodriguez et al., “Hypo-thermia for intracranial hypertension after traumatic braininjury,” New England Journal of Medicine, vol. 373, no. 25,pp. 2403–2412, 2015.

[6] P. J. Hutchinson, A. G. Kolias, I. S. Timofeev et al., “Trial ofdecompressive craniectomy for intracranial hypertension,”New England Journal of Medicine, vol. 375, no. 12, pp. 1119–1130, 2016.

[7] D. O. Okonkwo, L. A. Shutter, C. Moore et al., “Brain oxygenoptimization in severe traumatic brain injury phase-II: a phaseII randomized trial,” Critical Care Medicine, vol. 45, no. 11,pp. 1907–1914, 2017.

[8] D. F. Hanley, K. Lane, N. McBee et al., “&rombolytic removalof intraventricular haemorrhage in treatment of severe stroke:results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial,” /e Lancet, vol. 389, no. 10069,pp. 603–611, 2017.

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