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. Author manuscript; available in PMC: 2018 Aug 12.
Published in final edited form as: Curr Treat Options Cardiovasc Med. 2017 Jun;19(6):41. doi: 10.1007/s11936-017-0542-6

Critical Care Management of Acute Ischemic Stroke

Matthew B Bevers 1, W Taylor Kimberly 2
PMCID: PMC6087663  NIHMSID: NIHMS983936  PMID: 28466119

Opinion Statement

Ischemic stroke accounts for approximately 85% of all strokes. Although severe strokes constitute a minority of cases, they are associated with a majority of the subsequent disability and death. Reperfusion therapy with intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy is a mainstay of acute stroke management. Intensive care management of stroke is focused on reducing complications of reperfusion such as hemorrhagic transformation, and minimizing secondary brain injury, including brain edema and progressive stroke. Additionally, severe stroke patients frequently need ventilatory or hemodynamic support provided in an intensive care unit (ICU) setting. Here, we discuss the current medical and surgical ICU management aspects of acute ischemic stroke, and identify areas where ongoing studies may reveal new treatments to improve neurological recovery.

Introduction

Ischemic stroke epidemiology

Stroke is the fifth leading cause of death and a leading cause of disability in the United States, with nearly 800,000 Americans experiencing new or recurrent stroke annually [1]. Globally, stroke is the second leading cause of death, with 11.6 million incident ischemic strokes each year. While these numbers remain high, there has in fact been much progress in reducing mortality from stroke. This has been due in part to a focus on providing care in specialized stroke units. Less widely understood is the role of intensive care in stroke management, which is the focus of this review.

There are number of types of ischemic stroke patients who may benefit from intensive care. The most obvious are those who qualify for an intensive care unit (ICU) setting based on respiratory or hemodynamic needs. In addition, specific stroke therapies place the patient at higher risk of complication in the immediate post intervention period. These include intravenous tissue plasminogen activator (tPA), which is used in 3.4–5.2% of ischemic strokes [2], and endovascular clot retrieval, which is increasing in use since the publication of multiple randomized trials demonstrating its efficacy [3–7]. These patients benefit from the close neurologic and hemodynamic monitoring provided in the ICU to minimize the risk of secondary injury, as discussed below. Separately, there is a subset of large hemispheric stroke patients who require close neuromonitoring in the ICU, in particular to watch for and intervene upon the development of malignant edema and hemorrhagic transformation.

Critical Care Neurology

Neuroscience-specific ICUs developed out of post-neurosurgical units and general intensive care units, with the first multidisciplinary unit established in the early 1980s, accompanied by publication of the first textbook of neurocritical care in 1983[8]. Since that time, neurointensive care has matured as a field, with establishment of the Neurocritical Care Society in 2002 and accreditation of neurocritical care fellowship programs starting in 2007. Conditions treated by neurointensivists include subarachnoid and other intracranial hemorrhages, head trauma, status epilepticus, severe neuromuscular and demyelinating disease, CNS infections as well as acute ischemic stroke. In addition to physicians with specialty training in neuroscience (neurology, neurosurgery, anesthesia) and intensive care, the neuro ICU is staffed by a team of neuroscience nurses, physical medicine and rehab physicians, occupational, physical, speech and respiratory therapists. There is evidence that care in a neuroscience-specific ICU leads to improved outcomes in TBI, intraparenchymal hemorrhage, and subarachnoid hemorrhage [9] and reduced cost of care for neurosurgical patients [10]. There is less direct evidence to support an outcome benefit of ICU care in ischemic stroke, but the association between care at a specialized stroke center and outcome is well established [11]. As this review will discuss, there is a significant subset of these ischemic stroke patients who are at risk for secondary brain injury (Table 1) and may benefit from critical care monitoring and interventions.

Table 1.

Types of secondary injury and treatment after ischemic stroke

ICU interventions References
Cerebral edema Osmotic therapy [41]
Surgical decompression [44-46]
Hemorrhagic transformation Continuous BP titration [22]
Reversal of coagulopathy [22]
Progressive stroke BP augmentation extrapolation from [58, 59]
Early antiplatelet therapy [66, 67]
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Treatment

Airway management/ventilatory support

Indications for Endotracheal Intubation

  • As with any critically ill patient, a failure in adequate oxygenation or ventilation is an indication for endotracheal intubation following acute ischemic stroke.

  • More commonly, stroke patients require intubation due to failure to protect the airway. Reduced level of consciousness (Glasgow coma scale < 8), either due to edema with resulting midline shift or due to thalamic or brainstem stroke, may also necessitate endotracheal tube placement. Other patients may have preserved consciousness, but have impaired oropharyngeal function due to the stroke injury itself. This is common with cerebellar, brainstem, and large hemispheric strokes. The need for intubation can at times be anticipated based on the location of the infarct, but more reliable are clinical indicators such as dysarthria and inability to manage secretions.

Management of Aspiration

  • Even those stroke patients without obvious difficulty protecting their airway may have more subtle oropharyngeal dysfunction and are at risk for aspiration. For this reason, it is imperative to keep all acute stroke patients strictly nothing-by-mouth until a swallow screening can be performed. Patients at risk for airway obstruction or aspiration should be maintained with the head of bed elevated 15–30 degrees.

  • Initial fever, leukocytosis, and chest x-ray findings after an aspiration can be due to a chemical pneumonitis rather than true pneumonia and can at times be managed conservatively. Persistent fever, sputum production, and increasing oxygen requirement are all suggestive of developing aspiration pneumonia and should prompt empiric treatment for community- or hospital-acquired organisms, as appropriate [12, 13].

Extubation vs. Tracheostomy Placement

  • Acute stroke patients typically require little in the way of mechanical ventilatory support, such that the limiting factor in extubation is oropharyngeal control and the timing and pace of neurologic recovery. In those patients with large hemispheric (middle cerebral artery or MCA) stroke, a GCS ≥ 8 was associated with successful extubation [14]. Similar results were seen in posterior fossa stroke, where GCS > 6 at the time of intubation combined mechanical ventilation time of less than 7 days were associated with success [15]. It is likely that more fined-grained examination can provide better predictive value, as evidenced by a study of a mixed group of neuro ICU patients (including ischemic stroke), showing that the ability to follow four separate commands was predictive of extubation success, more so than GCS alone [16].

  • In those patients who fail extubation, or who are not expected to recover oropharyngeal function for a prolonged period of time, tracheostomy surgery is an appropriate bridge to allow for rehabilitation. While the overall rate of tracheostomy following stroke is low, it can be required in up to a third of patients with large stroke who require hemicraniectomy [17]. Optimal timing of tracheostomy is not clear, and is the subject of ongoing studies [18, 19].

Blood pressure management

Autoregulation

  • Blood pressure is frequently elevated in the acute phase of ischemic stroke, with the intent to maximize perfusion of the ischemic tissue. There is evidence that lower blood pressure in the acute setting after stroke is associated with worsening of neurologic outcome [20, 21]. Similarly, highly elevated blood pressure is considered detrimental [22]. As a result, it is advisable to avoid extremes of blood pressure while allowing for autoregulation of systolic blood pressure (SBP) in the initial 24 hours after stroke onset. Current guidelines recommend a target SBP <220mmHg [22], but a lower goal is appropriate, particularly if there are signs of cardiac strain or if there are comorbid conditions such as acute myocardial infarction, heart failure or aortic dissection in which a lower blood pressure target would be clearly beneficial.

Induced hypertension

  • In the initial hours after onset of stroke, rare patients may show fluctuation in their exam associated with changes in blood pressure. These patients may benefit from ICU monitoring, and in some cases from induced hypertension. Case reports have shown that artificial augmentation of blood pressure can improve cerebral blood flow [23] and recruit collaterals [24]. It appears safe [25], but only small series have shown an associated improvement in neurological exam [26]. While larger trials are needed, induced hypertension may be appropriate in the right clinical scenario.

Special considerations in the post-thrombolysis/endovascular therapy patient

  • To be eligible for treatment with intravenous tissue plasminogen activator (tPA), patients must have a blood pressure less than 185/110 [27, 28]. This can be achieved by treatment with intravenous antihypertensives within the acute period. After administration of tPA, patients should be maintained below 180/105 to minimize the risk of hemorrhagic conversion. A similar approach is taken with patients following endovascular thrombectomy, many of whom will have also received IV tPA. There may be a role for further blood pressure decrease after clot retrieval, an an effort to limited potential reperfusion hyperemia, however this has not been systematically examined.

Management of Cerebral Edema

Overview and Risk Factors

  • Ischemic brain injury following stroke leads to an initial cytotoxic injury that can lead to the influx of water and development of tissue edema. While there is evidence that such swelling can impact outcome even in small infarcts [29], most concerning is the malignant edema that can occur following large hemispheric infarction. While this complication affects only an estimated 2–8% of ischemic stroke admissions annually, the mortality is high at 40–80% [30].

  • Clinical factors associated with development of ischemic cerebral edema include young age [31], NIHSS ≥ 20 for dominant or ≥ 15 for non-dominant lesions, nausea/vomiting within 24 hours, systolic BP > 180mmHg within 12 hours [32], and an early decrease in level of alertness [33].

  • Imaging can be helpful in predicting the risk of early cerebral edema. Head CT scanning within 6 hours that reveals hypodensity in >50% of the MCA territory or involvement of multiple vascular territories is associated with subsequent malignant edema [34]. The presence of a diffusion weighted imaging (DWI) lesion of >82 cm3 within 6 hours of symptom onset alongside known vessel occlusion is a specific, but not sensitive, marker for the prediction of malignant edema [35]. Sensitivity can be improved when a large early DWI lesion is combined with high NIHSS at 24 hours [36]. The degree of restriction on apparent diffusion coefficient (ADC) imaging, has been associated with edema [29] and outcome [37] after small stroke, but applicability to large stroke has not yet been reported.

Management and Monitoring of Elevated ICP

  • While invasive ICP monitoring has a role following traumatic brain injury and is used for subarachnoid and intraparenchymal/intraventricular hemorrhage [38], it is not typically used in ischemic stroke. There is evidence that ICP can be elevated following decompressive hemicraniectomy [39], however the effect of monitoring and treating that ICP on outcome is unknown. It is possible that use of invasive ICP monitors, particularly as part of a multimodal monitoring strategy including cerebral blood flow, tissue oxygen and other sensors may play a role in stroke management at some point in the future, but current data does not support the routine use of such monitors.

  • In addition to specific therapies for managing ICP, a number of conservative measures can be used to maximize cerebral venous outflow thereby minimizing the blood volume contribution to ICP. The head of bed should be elevated to at least 30 degrees with the head positioned midline to ensure patency of the internal jugular veins bilaterally. When central access is required, a subclavian site may avoid the potential risk of IJ thrombosis and occlusion, but is associated with higher rate of pneumothorax [40]. In ventilated patients, PEEP should be minimized to reduce intrathoracic pressure and improve venous return. Similarly, patients at risk for elevated ICP should be placed on a standing bowel regimen to avoid the increased abdominal (and therefore thoracic) pressure that can result from constipation.

Sodium management/Hyperosmolar therapy

  • Given the potential for low serum sodium to contribute to cerebral edema, we maintain eunatremia (135–145mmol/L) in patients at risk for swelling after ischemic stroke. While sustained hypernatremia through the use of continuous 3% saline infusion is sometimes employed as an anti-edema measure, evidence for its clinical efficacy is lacking [41]. There is some evidence, particularly in subarachnoid hemorrhage, that sustained hypernatremia is associated with adverse cardiac events and poor neurologic outcome [42], however the causality of this relationship has not been established. Sustained hypernatremia may also theoretically lessen the effect of bolus hyperosmolar therapy by reducing the gradient across which water can be pulled out of tissue.

  • Intermittent administration of hyperosmolar agents (such as 20% mannitol and 23.4% saline) is the mainstay of cerebral edema treatment in large ischemic stroke. A meta-analysis has shown a slight benefit for hypertonic saline in TBI patients [43], but the effect was modest and randomized trials do not yet exist. As a result, we tend to use mannitol and 23.4% saline interchangeably following ischemic stroke and choice of agent is driven by other patient factors. Mannitol is renally cleared and thus its use should be limited in those with acute or chronic kidney injury. Hypertonic saline requires central access for administration, and thus mannitol is often used as a first agent until such access can be established. Hypertonic saline also represents a greater volume challenge, and thus should be avoided in patients with congestive heart failure.

  • Mannitol is given as a 20% solution at a dose of 1g/kg body weight every six hours. Serum osmolarity, BUN, sodium and glucose are monitored to allow for calculation of the osmolal gap according to the formula: Osm gap = Measured osm – (1.86(Na + K [mmol/L]) + glucose[mg/dL]/18 + BUN[mg/dL]/2.8). Osm gap > 10 suggests that mannitol is no longer being adequately cleared, and therefore additional doses should be held until the osmolal gap has closed to < 10.

  • 23.4% saline is given as a bolus of 30mL every six hours. Serum sodium is monitored, and additional boluses are typically held if sodium is greater than 160mmol/L.

  • In cases of severe, refractory edema, mannitol and hypertonic saline can be given in an alternating regimen. This is done in a “2/2/2” scheme, whereby mannitol is given at hour 0, 23.4% saline at hour 2, and then labs are checked at hour 4 in preparation for repeating the cycle starting at 6 hours.

  • Patients receiving prolonged courses of hyperosmolar therapy will often “auto-taper” by missing doses due to exceeding laboratory parameters. In those that do not, we monitor for signs of clinical and radiographic improvement and then begin to taper treatment by spacing doses of hyperosmolar agents to every 8 or 12 hours before tapering off.

Decompressive Craniectomy

  • Multiple randomized trials have demonstrated the efficacy of hemicraniectomy in improving both survival and outcome following hemispheric MCA infarction with malignant edema in patients under the age of 60 [44–46]. A more recent trial in patients ages 60–82 showed improved survival, but at the expense of more severe disability [47]. Based on these trials, our practice is to recommend hemicraniectomy within 24–48 hours of presentation in patients up to age 60 with large (>2/3 of MCA territory) hemispheric infarction and a decreased level of consciousness. For patients between the ages of 60–80, hemicraniectomy remains a life-saving procedure, however it should only be pursued if the likelihood of living with severe disability is within the patient’s goals of care.

  • Similar trials have not been performed for posterior fossa stroke. However, given the potentially dire consequences of edema in this region, suboccipital craniectomy should be considered for any large cerebellar infarct. In particular, if brainstem compression is avoided through surgery, neurological outcome from the cerebellar infarction typically is good. Indicators for decompression have primarily been studied in cerebellar hemorrhage, but one can extrapolate from that data to consider craniectomy after cerebellar stroke in patients with development of new cranial nerve findings, reduced level of consciousness, evidence of brainstem compression, hydrocephalus, and/or with lesions > 3cm in diameter [48, 49].

Anti-edema pharmacotherapy

  • There is no currently approved treatment to prevent the development of ischemic cerebral edema. A randomized, double-blind phase II trial of intravenous glyburide for the prevention of malignant edema found the drug to be well tolerated, to limit the development of midline shift, and to reduce mortality. However, glyburide did not impact the primary outcome of mRS at 90 days without hemicraniectomy [50]. A phase III trial is planned.

Management of Hemorrhagic Transformation

Hemorrhage risk factors and classification

  • The most reliable predictor of hemorrhagic transformation is infarct size, with review of multiple studies showing that larger infarcts are associated with higher risk of transformation [51]. Level of matrix metalloproteinase 9 [52] has been associated with hemorrhagic transformation, particularly after tPA [53], but this marker is not sensitive or specific enough for routine clinical use.

  • Post-stroke hemorrhagic conversion is typically classified using the categories established by the European Cooperative Acute Stroke Study (ECASS) criteria (Table 2) [27]. Hemorrhagic Infarction (HI) is defined as punctate or variable CT hyperdensity within the infarct. It is further subdivided into HI1 (small petechiae) or HI2 (more confluent). Parenchymal hematoma (PH) is an organized clot with mass effect, with PH1 defined as occupying <30% of the infarct territory with mild mass effect while PH2 occupies >30% of the infarct and has significant mass effect. Classification of hemorrhage type is important because it make dictate further plan of care, with those larger or symptomatic bleeds requiring aggressive treatment of coagulopathy and blood pressure while petechial hemorrhage can often be observed.

Table 2.

Types of Hemorrhagic Transformation

Definition Clinical Significance
Hemorrhagic infarction 1 (HI1) Hemorrhagic infarction with small petechiae within the stroke Uncertain; may be a beneficial marker of reperfusion
Hemorrhagic infarction 2 (HI2) Hemorrhagic infarction with confluent petechiae within the stroke Uncertain
Parenchymal hematoma 1 (PH1) Parenchymal hematoma with an organized clot <30% of stroke and mild mass effect Often associated with neurological deterioration
Parenchymal hematoma 2 (PH2) Parenchymal hematoma with a large organized clot and significant mass effect Associated with neurological deterioration from mass effect
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Reversal of coagulopathy

  • Hemorrhage in the first 24 hours after receiving tPA can be reversed with administration of either cryoprecipitate or concentrated fibrinogen. Patient fibrinogen levels can be tracked to guide therapy, and if the fibrinogen level is < 100mg/dL, we typically give 0.15 units/kg of cryoprecipitate, which can be repeated an hour later if bleeding persists. Fibrinogen concentrate is known to be effective at achieving hemostasis in a number of settings, and may have a more favorable safety profile than cryoprecipitate [54]. Head-to-head trials against cryoprecipitate have not been reported.

  • Bleeding in the setting of elevated INR from warfarin can be reversed using either fresh frozen plasma, or one of several commercially available prothrombin complex concentrates (PCC). Dosing depends on the patient’s INR and the particular product used. There is evidence that four-factor PCC reverses INR more quickly [55] and its use is associated with improved outcome after primary ICH [56]. For this reason, PCC should be the first choice for INR reversal if available.

  • Newer oral anticoagulants, including the direct thrombin inhibitor dabigatran and factor Xa inhibitors abixaban, rivaroxaban and edoxaban, require different strategies for reversal. Coagulopathy due to dabigatran is treated with the specific reversal agent idarucizumab [57]. The factor Xa inhibitors can all be reversed using four factor prothrombin complex concentrate [58]. In all cases of severe bleeding, non-specific strategies can also be used to reduce the effect of drug. These include early administration of activated charcoal, hemodialysis (for dabigatran), or use of an anti-fibrinolytic agent such as tranexamic acid or aminocaproic acid.

Blood pressure management

  • There aren’t specific trials looking at blood pressure management after hemorrhagic transformation of an ischemic stroke, so BP targets are extrapolated from studies on primary intracerebral hemorrhage (ICH). Intensive (SBP < 140) BP control after ICH is achievable and safe [59] has been associated with less hematoma growth [60] compared to standard (SBP < 180) management. Given the preference to maintain adequate perfusion pressure immediately following ischemic stroke, it is reasonable to maintain SBP < 180 following hemorrhagic transformation, unless in cases of large or expanding hematoma where the balance of risk may favor a lower BP target.

Surgical clot evacuation

  • It is relatively uncommon to pursue surgical evacuation for hemorrhagic conversion of an ischemic stroke. As with blood pressure management, most data comes from trials of primary ICH. Two randomized trials found no benefit for surgical clot evacuation over medical therapy alone[61, 62]. However, both trials had high crossover rates from the medical to surgical arm, so the possibility remains for a benefit of surgery in selected circumstances.

  • Surgical evacuation of hemorrhage following ischemic stroke is not routinely recommended. However, there may be isolated cases where the volume of hematoma and resulting mass effect is enough to prompt surgery. Importantly, the current trials have not examined posterior fossa hemorrhage, and so hemorrhagic transformation of a cerebellar stroke with subsequent mass effect should be considered for decompressive suboccipital craniectomy with or without clot evacuation.

Prevention of Early Recurrent Stroke/Stroke Progression

Antiplatelet therapy

  • Aspirin is the mainstay of therapy immediately following acute stroke, having been shown in two large trials to reduce recurrent stroke and improve mortality [63, 64]. Aspirin should be started as soon as possible in all acute stroke patients that do not have a contraindication. Potential reasons to hold aspirin initially include treatment with tPA (hold aspirin for 24 hours after tPA), potential for needing surgery such as hemicraniecomty or early hemorrhagic conversion.

  • There is not clear evidence for changing antiplatelet agents for patients who present with stroke despite taking aspirin. While clopidogrel has shown benefit in treatment of cardiac and peripheral arterial disease, there is not a demonstrated benefit over aspirin when used as a single agent for stroke prevention [65]. A trial of the newer antiplatelet agent ticagrelor [66] also did not show any additional benefit over aspirin.

  • There is evidence for using dual antiplatelet therapy for a period of time in patients with small stroke or TIA [67]. Combined aspirin and clopidogrel is also often used in those with substantial intracranial arterial atherosclerosis, based on the medical arm of the SAMMPRIS trial of intracranial stenting [68].

Indications for acute anticoagulation

  • While acute anticoagulation with heparin has not shown a benefit over aspirin when considering all comers with acute stroke [64], or even those with known atrial fibrillation [69], there are isolated cases where anticoagulation is indicated. These patients may benefit from monitoring in the intensive care unit while anticoagulation is administered, particularly in cases of large stroke where the risk of hemorrhagic transformation is significant.

  • Patients who present with artery-to-artery embolus from carotid disease may benefit from acute anticoagulation [70] based on subgroup analysis from the TOAST trial. We often use anticoagulation as a bridge to carotid endarterectomy in patients where the stroke volume is low enough that there is minimal risk of reperfusion injury.

  • A recent randomized trial did not find any benefit of anticoagulation over antiplatelet for the prevention of recurrent stroke after carotid or vertebral dissection [71]. However, the rate of stroke in this trial was very low and a large proportion of patients did not have dissection radiographically confirmed by central readers. Given that anticoagulation can reduce embolization from dissection as measured by transcranial Doppler [72], there is likely still a role for anticoagulation in patients who are at high risk or who have proven ongoing embolization, but further studies are needed to appropriately select patients.

Delayed endovascular therapy

  • While a trial of intracranial stenting showed no benefit over medical therapy [68], patients with intracranial stenosis and recurrent stroke or blood pressure dependence may theoretically benefit from angioplasty [73]. Dual antiplatelet or anticoagulation is often tried as an initial strategy, and endovascular therapy pursued only if medical therapy fails.

  • Randomized trials of endovascular stroke therapy have focused on anterior circulation disease, and as a result little is known about the time window of intervention in the posterior circulation. However, clot retrieval is sometimes considered up to 24 hours after onset for basilar disease as well as delayed angioplasty in those with vertebrobasilar stenosis with recurrent infarct or fluctuating symptoms suggestive of hypoperfusion [74].

Other supportive care

Fever management

  • Hyperthermia following ischemic stroke is associated with increased mortality [75]. In addition to identifying potential infectious sources of fever, normothermia should be maintained through the use of antipyretic medications and mechanical cooling if necessary.

Glucose control

  • Hyperglycemia is correlated with poor outcome after ischemic stroke [76, 77], particularly in those patients without a history of DM [78–80]. Previous trials of tight glycemic control in stroke have thus far been inconclusive [81–83] and a large multi-center trial of glucose control is ongoing [84].

  • In the absence of clear stroke-specific data on glucose control, a target of <180mg/dL is suggested, as that level was associated with improved outcome in a mixed ICU population [85].

Conclusion

Severe ischemic stroke is often complicated by factors that require intensive care management. In additional to general ICU needs such as airway and ventilatory support and post-procedure or post-thrombolysis care, several complications of acute stroke present unique challenges best addressed in a neurocritical care setting. Monitoring and management of cerebral edema and elevated ICP, early recognition and management of hemorrhagic transformation, and prevention of recurrent and progressive ischemia are the primary goals of critical care management of acute stroke. Effective treatment requires careful clinical and physiologic monitoring to support application of both medical and surgical therapies.

Acknowledgments

Dr. Bevers has nothing to disclose. Dr. Kimberly reports grants from Remedy Pharmaceuticals, during the conduct of the study; grants from NINDS K23 NS076597, grants from NINDS R01 NS099209, grants from AHA 14GRNT19060044, outside the submitted work.

Footnotes

Disclosures

Dr. Bevers has nothing to disclose.

References

  • 1.Mozaffarian D, Benjamin EJ, Go AS, et al. (2016) Heart disease and stroke statistics-2016 update a report from the American Heart Association. Circulation. doi: 10.1161/CIR.0000000000000350 [DOI] [PubMed] [Google Scholar]
  • 2.Adeoye O, Hornung R, Khatri P, Kleindorfer D (2011) Recombinant tissue-type plasminogen activator use for ischemic stroke in the united states: A doubling of treatment rates over the course of 5 years. Stroke 42:1952–1955 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Saver JL, Goyal M, Bonafe A, et al. (2015) Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke. N Engl J Med 372:2285–2295 [DOI] [PubMed] [Google Scholar]
  • 4.Goyal M, Demchuk AM, Menon BK, et al. (2015) Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 372:1019–1030 [DOI] [PubMed] [Google Scholar]
  • 5.Campbell BC, Mitchell PJ, Kleinig TJ, et al. (2015) Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 372:1009–1018 [DOI] [PubMed] [Google Scholar]
  • 6.Jovin TG, Chamorro A, Cobo E, et al. (2015) Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 372:2296–306 [DOI] [PubMed] [Google Scholar]
  • 7.Berkhemer OA, Fransen PSS, Beumer D, et al. (2015) A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. New Engl J Med 372:11–20 [DOI] [PubMed] [Google Scholar]
  • 8.Ropper A, Kennedy S, Zervas N (1983) Neurological and neurosurgical intensive care. University Park Press, Baltimore, MD [Google Scholar]
  • 9.Kramer AH, Zygun DA (2011) Do neurocritical care units save lives? measuring the impact of specialized ICUs. Neurocrit Care 14:329–333 [DOI] [PubMed] [Google Scholar]
  • 10.Mirski M, Chang C, Cowan R (2001) Impact of a neuroscience intensive care unit on neurosurgical patient outcomes and cost of care: evidence-based support for an intensivist-directed specialty ICU model of care. J Neurosurg Anesthesiol 13:83–92 [DOI] [PubMed] [Google Scholar]
  • 11.Stroke Unit Trialists’ Collaboration (2013) Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev 2013–2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Kalil AC, Metersky ML, Klompas M, et al. (2016) Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 63:e61–e111 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Mandell LA, Wunderink RG, Anzueto A, et al. (2007) Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis 44:S27–S72 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Wendell LC, Raser J, Kasner S, Park S (2011) Predictors of extubation success in patients with middle cerebral artery acute ischemic stroke. Stroke Res Treat 2011:248789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Guru PK, Singh TD, Pedavally S, Rabinstein AA, Hocker S (2016) Predictors of Extubation Success in Patients with Posterior Fossa Strokes. Neurocrit Care 25:117–127 [DOI] [PubMed] [Google Scholar]
  • 16.Anderson CD, Bartscher JF, Scripko PD, Biffi A, Chase D, Guanci M, Greer DM (2011) Neurologic examination and extubation outcome in the neurocritical care unit. Neurocrit Care 15:490–497 [DOI] [PubMed] [Google Scholar]
  • 17.Walcott BP, Kamel H, Castro B, Kimberly WT, Sheth KN (2014) Tracheostomy after severe ischemic stroke: A population-based study. J Stroke Cerebrovasc Dis 23:1024–1029 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Bösel J, Schiller P, Hook Y, et al. (2013) Stroke-related early tracheostomy versus prolonged orotracheal intubation in neurocritical care trial (SETPOINT): A randomized pilot trial. Stroke 44:21–28 [DOI] [PubMed] [Google Scholar]
  • 19.Schönenberger S, Niesen W-D, Fuhrer H, Bauza C, Klose C, Kieser M, Suarez JI, Seder DB, Bösel J (2016) Early tracheostomy in ventilated stroke patients: Study protocol of the international multicentre randomized trial SETPOINT2 (Stroke-related Early Tracheostomy vs. Prolonged Orotracheal Intubation in Neurocritical care Trial 2). Int J Stroke 11:368–79 [DOI] [PubMed] [Google Scholar]
  • 20.Oliveira-Filho J, Silva S, Trabuco C, Pedreira B, Sousa E, Bacellar A (2003) Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology 61:1047–1051 [DOI] [PubMed] [Google Scholar]
  • 21.Castillo J, Leira R, García MM, Serena J, Blanco M, Dávalos A (2004) Blood Pressure Decrease during the Acute Phase of Ischemic Stroke Is Associated with Brain Injury and Poor Stroke Outcome. Stroke 35:520–527 [DOI] [PubMed] [Google Scholar]
  • 22.* Jauch EC, Saver JL, Adams HP, et al. (2013) Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44:870–947 * This publication enumerates the current guidelines from the American Stroke Association on the initial inpatient management of ischemic stroke.
  • 23.Chalela JA, Dunn B, Todd JW, Warach S (2005) Induced hypertension improves cerebral blood flow in acute ischemic stroke. Neurology 64:1979. [DOI] [PubMed] [Google Scholar]
  • 24.Georgiadis AL, Al-kawi A, Janjua N, Kirmani JF (2007) Cerebral Angiography Can Demonstrate Changes in Collateral Flow During Induced Hypertension. Radiol Case Reports 2:3–5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Koenig MA, Geocadin RG, de Grouchy M, Glasgow J, Vimal S, Restrepo L, Wityk RJ (2006) Safety of induced hypertension therapy in patients with acute ischemic stroke. Neurocrit Care 4:3–7 [DOI] [PubMed] [Google Scholar]
  • 26.Hillis AE, Ulatowski JA, Barker PB, Torbey M, Ziai W, Beauchamp NJ, Oh S, Wityk RJ (2003) A pilot randomized trial of induced blood pressure elevation: Effects on function and focal perfusion in acute and subacute stroke. Cerebrovasc Dis 16:236–246 [DOI] [PubMed] [Google Scholar]
  • 27.* Hacke W, Kaste M, Fieschi C, et al. (1995) Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 274:1017–1025 * This landmark trial demonstrated the efficacy of intravenous tPA in treating acute ischemic stroke.
  • 28.*The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581–1587* This landmark trial demonstrated the efficacy of intravenous tPA in treating acute ischemic stroke.
  • 29.Battey TW, Karki M, Singhal AB, Wu O, Sadaghiani S, Campbell BC, Davis SM, Donnan GA, Sheth KN, Kimberly WT (2014) Brain edema predicts outcome after nonlacunar ischemic stroke. Stroke 45:3643–3648 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.*Wijdicks EFM, Sheth KN, Carter BS, Greer DM, Kasner SE, Kimberly WT, Schwab S, Smith EE, Tamargo RJ, Wintermark M (2014) Recommendations for the management of cerebral and cerebellar infarction with swelling: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:1222–1238 * These are the guidelines from the American Stroke Association on the management of post-stroke cerebral edema, a common stroke complication managed in the ICU.
  • 31.Wijdicks EF, Diringer MN (1998) Middle cerebral artery territory infarction and early brain swelling: progression and effect of age on outcome. Mayo Clin Proc 73:829–836 [DOI] [PubMed] [Google Scholar]
  • 32.Krieger DW, Demchuk A, Kasner SE, Jauss M, Hantson L (1999) Early clinical and radiological predictors of fatal brain swelling in ischemic stroke. Stroke 30:287–292 [DOI] [PubMed] [Google Scholar]
  • 33.Cucchiara BL, Kasner SE, Wolk DA, Lyden PD, Knappertz VA, Ashwood T, Odergren T, Nordlund A (2004) Early impairment in consciousness predicts mortality after hemispheric ischemic stroke. Crit Care Med 32:241–245 [DOI] [PubMed] [Google Scholar]
  • 34.Kasner SE, Demchuk AM, Berrouschot J, et al. (2001) Predictors of fatal brain edema in massive hemispheric ischemic stroke. Stroke 32:2117–2123 [DOI] [PubMed] [Google Scholar]
  • 35.Thomalla G, Hartmann F, Juettler E, et al. (2010) Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: A prospective multicenter observational study. Ann Neurol 68:435–445 [DOI] [PubMed] [Google Scholar]
  • 36.Kruetzelmann A, Hartmann F, Beck C, et al. (2014) Combining magnetic resonance imaging within six-hours of symptom onset with clinical follow-up at 24 h improves prediction of “malignant” middle cerebral artery infarction. Int J Stroke 9:210–4 [DOI] [PubMed] [Google Scholar]
  • 37.Bevers MB, Vaishnav NH, Pham L, Battey TW, Kimberly WT (2016) Hyperglycemia is associated with more severe cytotoxic injury after stroke. J Cereb Blood Flow Metab 0271678X16671730 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Helbok R, Olson DM, Le Roux PD, Vespa P (2014) Intracranial pressure and cerebral perfusion pressure monitoring in non-TBI patients: special considerations. Neurocrit Care 21 Suppl 2:S85–94 [DOI] [PubMed] [Google Scholar]
  • 39.Paldor I, Rosenthal G, Cohen JE, Leker R, Harnof S, Shoshan Y, Itshayek E (2015) Intracranial pressure monitoring following decompressive hemicraniectomy for malignant cerebral infarction. J Clin Neurosci 22:79–82 [DOI] [PubMed] [Google Scholar]
  • 40.Parienti J-J, Mongardon N, Mégarbane B, et al. (2015) Intravascular Complications of Central Venous Catheterization by Insertion Site. N Engl J Med 373:1220–9 [DOI] [PubMed] [Google Scholar]
  • 41.Ryu JH, Walcott BP, Kahle KT, Sheth SA, Peterson RT, Nahed B V, Coumans JVCE, Simard JM (2013) Induced and sustained hypernatremia for the prevention and treatment of cerebral edema following brain injury. Neurocrit Care 19:222–231 [DOI] [PubMed] [Google Scholar]
  • 42.Fisher LA, Ko N, Miss J, Tung PP, Kopelnik A, Banki NM, Gardner D, Smith WS, Lawton MT, Zaroff JG (2006) Hypernatremia predicts adverse cardiovascular and neurological outcomes after SAH. Neurocrit Care 5:180–5 [DOI] [PubMed] [Google Scholar]
  • 43.Kamel H, Navi BB, Nakagawa K, Hemphill JC, Ko NU (2011) Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure - A meta-analysis of randomized clinical trials. Crit Care Med 39:554–9 [DOI] [PubMed] [Google Scholar]
  • 44.Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, Witte S, Jenetzky E, Hacke W (2007) Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke (00392499) 38:2518–2525 [DOI] [PubMed] [Google Scholar]
  • 45.* Vahedi K, Hofmeijer J, Juettler E, et al. (2007) Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol 6:215–222 * This is a pooled analysis of three trials of hemicraniectomy for malignant middle cerebral artery infarction demonstrating survival and outcome benefit of decompressive surgery.
  • 46.Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB (2009) Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol 8:326–333 [DOI] [PubMed] [Google Scholar]
  • 47.Jüttler E, Unterberg A, Woitzik J, et al. (2014) Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke. N Engl J Med 370:1091–1100 [DOI] [PubMed] [Google Scholar]
  • 48.St Louis EK, Wijdicks EF, Li H (1998) Predicting neurologic deterioration in patients with cerebellar hematomas. Neurology 51:1364–1369 [DOI] [PubMed] [Google Scholar]
  • 49.St Louis EK, Wijdicks EF, Li H, Atkinson JD (2000) Predictors of poor outcome in patients with a spontaneous cerebellar hematoma. Can J Neurol Sci 27:32–36 [DOI] [PubMed] [Google Scholar]
  • 50.Sheth KN, Elm JJ, Molyneaux BJ, et al. (2016) Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 15:1160–1169 [DOI] [PubMed] [Google Scholar]
  • 51.Terruso V, D’Amelio M, Di Benedetto N, et al. (2009) Frequency and determinants for hemorrhagic transformation of cerebral infarction. Neuroepidemiology 33:261–265 [DOI] [PubMed] [Google Scholar]
  • 52.Turner RJ, Sharp FR (2016) Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke. Front Cell Neurosci 10:56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Piccardi B, Palumbo V, Nesi M, et al. (2015) Unbalanced metalloproteinase-9 and tissue inhibitors of metalloproteinases ratios predict hemorrhagic transformation of lesion in ischemic stroke patients treated with thrombolysis: Results from the MAGIC study. Front Neurol 6:1–7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Levy JH, Welsby I, Goodnough LT (2014) Fibrinogen as a therapeutic target for bleeding: A review of critical levels and replacement therapy. Transfusion 54:1389–1405 [DOI] [PubMed] [Google Scholar]
  • 55.Sarode R, Milling TJ, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN (2013) Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: A randomized, plasma-controlled, phase IIIb study. Circulation 128:1234–1243 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Frontera J a., Gordon E, Zach V, Jovine M, Uchino K, Hussain MS, Aledort L (2014) Reversal of Coagulopathy Using Prothrombin Complex Concentrates is Associated with Improved Outcome Compared to Fresh Frozen Plasma in Warfarin-Associated Intracranial Hemorrhage. Neurocrit Care 397–406 [DOI] [PubMed] [Google Scholar]
  • 57.Pollack CV, Reilly P a, Eikelboom J, et al. (2015) Idarucizumab for Dabigatran Reversal. N Engl J Med 1–10 [DOI] [PubMed] [Google Scholar]
  • 58.Frontera JA, Lewin JJ, Rabinstein AA, et al. (2016) Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 24:6–46 [DOI] [PubMed] [Google Scholar]
  • 59.Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) Investigators (2010) Antihypertensive treatment of acute cerebral hemorrhage. Crit Care Med 38:637–48 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Anderson CS, Huang Y, Wang JG, et al. (2008) Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol 7:391–399 [DOI] [PubMed] [Google Scholar]
  • 61.Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, Karimi A, Shaw MD., Barer DH (2005) Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Intracerebral Hematomas in the International Surgical Trial in Intracerebral Hemorrhage (STICH): A Randomized Trial. Lancet 14:41 [Google Scholar]
  • 62.Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM (2013) Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): A randomised trial. Lancet 382:397–408 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.* Chinese Acute Stroke Trial Collaborative Group (1997) CAST : randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke. 349:1641–1649 * One of two key trials establishing the efficacy of aspirin to prevent recurrent stroke.
  • 64.* The International Stroke Trial Collaborative Group (1997) The International Stroke Trial (IST): A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke. Lancet 349:1569–1581 * One of two key trials establishing the efficacy of aspirin to prevent recurrent stroke.
  • 65.Howard G, McClure L a, Krakauer JW, Coffey CS (2007) Stroke and the statistics of the aspirin/clopidogrel secondary prevention trials. Curr Opin Neurol 20:71–77 [DOI] [PubMed] [Google Scholar]
  • 66.Johnston SC, Amarenco P, Albers GW, et al. (2016) Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. New Engl J Med 375:35–43 [DOI] [PubMed] [Google Scholar]
  • 67.Wang YY, Zhao X, Liu L, et al. (2013) Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 369:11–9 [DOI] [PubMed] [Google Scholar]
  • 68.Derdeyn CP, Chimowitz MI, Lynn MJ, et al. (2014) Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): The final results of a randomised trial. Lancet 383:333–341 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Berge E, Abdelnoor M, Nakstad PH, Sandset PM (2000) Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. Lancet 355:1205–1210 [DOI] [PubMed] [Google Scholar]
  • 70.The TOAST Investigators (1998) Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Jama 279:1265–72 [PubMed] [Google Scholar]
  • 71.Markus HS, Hayter E, Levi C, et al. (2015) Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): A randomised trial. Lancet Neurol 14:361–367 [DOI] [PubMed] [Google Scholar]
  • 72.Molina CA, Alvarez-Sabín J, Schonewille W, Montaner J, Rovira A, Abilleira S, Codina A (2000) Cerebral microembolism in acute spontaneous internal carotid artery dissection. Neurology 55:1738–1740 [DOI] [PubMed] [Google Scholar]
  • 73.Leung TW, Wabnitz M, Miao Z, Chimowitz I (2016) Angioplasty and Stenting. 40:152–163 [DOI] [PubMed] [Google Scholar]
  • 74.Schonewille WJ, Wijman CAC, Michel P, et al. (2009) Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol 8:724–730 [DOI] [PubMed] [Google Scholar]
  • 75.Prasad K, Krishnan PR (2010) Fever is associated with doubling of odds of short-term mortality in ischemic stroke: An updated meta-analysis. Acta Neurol Scand 122:404–408 [DOI] [PubMed] [Google Scholar]
  • 76.Bruno A, Biller J, Adams HP, Clarke WR, Woolson RF, Williams LS, Hansen MD (1999) Acute blood glucose level and outcome from ischemic stroke. Neurology 52:280. [DOI] [PubMed] [Google Scholar]
  • 77.Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress Hyperglycemia and Prognosis of Stroke in Nondiabetic and Diabetic Patients: A Systematic Overview. Stroke 32:2426–2432 [DOI] [PubMed] [Google Scholar]
  • 78.Murros K, Fogelholm R, Kettunen S, Vuorela AL, Valve J (1992) Blood-Glucose, Glycosylated Hemoglobin, and Outcome of Ischemic Brain Infarction. J Neurol Sci 111:59–64 [DOI] [PubMed] [Google Scholar]
  • 79.Weir CJ, Murray GD, Dyker AG, Lees KR (1997) Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long term follow up study. BMJ 314:1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Stead LG, Gilmore RM, Bellolio MF, Mishra S, Bhagra A, Vaidyanathan L, Decker WW, Brown RD (2009) Hyperglycemia as an independent predictor of worse outcome in non-diabetic patients presenting with acute ischemic stroke. Neurocrit Care 10:181–186 [DOI] [PubMed] [Google Scholar]
  • 81.Bruno A, Kent TA, Coull BM, Shankar RR, Saha C, Becker KJ, Kissela BM, Williams LS (2008) Treatment of hyperglycemia in ischemic stroke (THIS): A randomized pilot trial. Stroke 39:384–389 [DOI] [PubMed] [Google Scholar]
  • 82.Gray CS, Hildreth AJ, Sandercock PA, O’Connell JE, Johnston DE, Cartlidge NEF, Bamford JM, James OF, Alberti KGMM (2007) Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol 6:397–406 [DOI] [PubMed] [Google Scholar]
  • 83.Johnston KC, Hall CE, Kissela BM, Bleck TP, Conaway MR (2009) Glucose Regulation in Acute Stroke Patients (GRASP) Trial: A Randomized Pilot Trial. Stroke 40:3804–3809 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Bruno A, Durkalski VL, Hall CE, Juneja R, Barsan WG, Janis S, Meurer WJ, Fansler A, Johnston KC (2014) The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial protocol: A randomized, blinded, efficacy trial of standard vs. intensive hyperglycemia management in acute stroke. Int J Stroke 9:246–251 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.NICE-SUGAR Study Investigators (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–97 [DOI] [PubMed] [Google Scholar]

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