Which of these tests should be performed for a patient with a suspected stroke as early as possible?

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Acute Stroke Management

Acute Stroke Management

• Definitions
• 1. Stroke Awareness Recognition and Response
• 2. Outpatient Management of TIA and Non-Disabling Stroke
• 3. Emergency Medical Services Management of Acute Stroke Patients
• 4. Emergency Department Evaluation and Management of Patients with Acute Stroke and TIA
  • 4.0 Emergency Department Evaluation
  • 4.1 Initial ED Evaluation
  • 4.2 Neurovascular (Brain and Vascular) Imaging (For 2018, all imaging recommendations have been consolidated into this section)
  • 4.3 Acute Blood Pressure Management
  • 4.4 Cardiovascular Investigations
  • 4.5 Blood Glucose Abnormalities
  • 4.6 Additional Management Considerations in the Emergency Department
  • Clinical Considerations: (New for 2018)
• 5. Acute Ischemic Stroke Treatment
• 6. Acute Antiplatelet Therapy
• 7. Early Management of Patients Considered for Hemicraniectomy
• 8. Acute Stroke Unit Care
• 9. Inpatient Prevention and Management of Complications following Stroke
• 10. Advanced Care Planning
• 11. Palliative and End of Life Care

4.0 Emergency Department Evaluation

1. All patients presenting to an Emergency Department with suspected acute stroke or transient ischemic attack must have an immediate clinical evaluation and investigations to establish a diagnosis, rule out stroke mimics, determine eligibility for intravenous thrombolytic therapy and endovascular thrombectomy treatment (EVT), and develop a plan for further management, including goals for care [Evidence Level A].

Note: If initial brain imaging reveals a hemorrhagic stroke, then refer to new CSBPR for Hemorrhagic Stroke for guidance on further investigations, acute treatments and ongoing management. (For release Fall 2019)

4.1 Initial ED Evaluation

1. Patients with suspected acute stroke should have a rapid initial evaluation for airway, breathing and circulation [Evidence Level A].
2. A neurological examination should be conducted to determine focal neurological deficits and assess stroke severity [Evidence Level A].
   1. A standardized stroke scale should be used (such as the National Institutes of Health Stroke Scale [NIHSS) [Evidence Level C].
3. Assessment in the acute phase should include heart rate and rhythm, blood pressure, temperature, oxygen saturation, hydration status, and presence of seizure activity [Evidence Level B].
4. Acute blood work should be conducted as part of the initial evaluation [Evidence Level B]. Initial blood work should include: electrolytes, random glucose, complete blood count (CBC), coagulation status (INR, aPTT), and creatinine. Refer to Table 2B for Recommended Laboratory Investigations for Acute Stroke and Transient Ischemic Attack for additional information.
   1. Note, these tests should not delay imaging or treatment decisions and treatment initiation for intravenous thrombolysis and endovascular thrombectomy.
5. Seizure Assessment: New-onset seizures at the time of an acute stroke, occurring either immediately before or within 24 hours of the stroke onset, should be treated using appropriate short-acting medications (e.g. lorazepam IV) if they are not self-limited [Evidence Level C].
   1. A single, self-limiting seizure occurring at the onset, or within 24 hours after an acute stroke (considered an “immediate” post-stroke seizure) should not be treated with long-term anticonvulsant medications [Evidence Level C].
   2. Patients that have an immediate post-stroke seizure should be monitored for recurrent seizure activity during routine monitoring of vital signs and neurological status. Recurrent seizures in patients with ischemic stroke should be treated as per treatment recommendations for seizures in other neurological conditions [Evidence Level C].
   3. Seizures are a common presentation with stroke in neonates and children. Consider enhanced or prolonged electroencephalogram (EEG) in at-risk populations such as neonates, children with stroke and adults with otherwise unexplained reduced level of consciousness [Evidence Level C].
   4. Prophylactic use of anticonvulsant medications in patients with acute stroke is not recommended [Evidence Level C]. There is no evidence to support the prophylactic use of anticonvulsant medications in patients with acute stroke and there is some evidence to suggest possible harm with negative effects on neural recovery.

4.2 Neurovascular (Brain and Vascular) Imaging (For 2018, all imaging recommendations have been consolidated into this section)

1. All patients with suspected acute stroke should undergo brain imaging with non-contrast CT or MRI [Evidence Level A].
2. All patients with suspected acute ischemic stroke who arrive within 4.5 hours and are potentially eligible for intravenous thrombolysis (Refer to criteria in Box 4A, 5B) should undergo immediate brain imaging with non-contrast CT (NCCT) without delay to determine eligibility for thrombolysis [Evidence Level A].
3. All patients with suspected acute ischemic stroke who arrive within 6 hours and are potentially eligible for endovascular thrombectomy (refer to criteria in Box 4B, 5C) should undergo immediate brain imaging with non-contrast CT and CT angiography (CTA) without delay, from arch-to-vertex including the extra- and intra-cranial circulation, to identify large vessel occlusions eligible for endovascular thrombectomy [Evidence Level A].
   Note: Primary stroke centres that cannot do CTA should have pre-planned arrangements for rapid transfer of appropriate patients. They should complete NCCT and offer intravenous alteplase as appropriate and then rapidly transfer the patient to a CSC for more advanced imaging and consideration for EVT.
   1. A validated triage tool (such as ASPECTS) should be used to rapidly identify patients who may be eligible for endovascular thrombectomy treatment and may require transfer to a different facility for EVT [Evidence Level B]. [New for 2018]
   2. Advanced CT imaging such as CT perfusion (CTP) or multiphase or dynamic CTA (to assess pial collateral vessels) can be considered as part of initial imaging to aid patient selection [Evidence Level B]. However this must not substantially delay decision and treatment with intravenous thrombolysis with alteplase or endovascular thrombectomy treatment. Refer to Box 4C and 5C.
      Note: if there are signs of hemorrhage on initial CT images there is no need to proceed to CTP imaging as part of initial imaging and CTA should be completed based on the clinical judgement of the treating physician.
4. All patients with suspected ischemic stroke who arrive at 6-24 hours after stroke onset (late presentation and stroke on awakening with unknown onset time) and are potentially eligible for late window endovascular thrombectomy treatment (Refer to Box 4D) should undergo immediate brain imaging with non-contrast CT with CTA and CT perfusion, or MRI with MRA and MRP [Evidence Level B]. Note: In most Canadian centres a CT approach may be more practical and more readily available than an MR approach. Choice of imaging modality should be based on most immediate availability and local resources.

Refer to Section 5 for information on alteplase administration and endovascular thrombectomy.

4.3 Acute Blood Pressure Management

1. The ideal level of blood pressure target to achieve and sustain in the hyperacute phase is unknown at this time. Pharmacological agents and routes of administration should be chosen to avoid precipitous falls in blood pressure [Evidence Level C].
2. Ischemic stroke patients eligible for thrombolytic therapy: Very high blood pressure (greater than 185/110 mm Hg) should be treated concurrently with thrombolysis to reduce the risk of hemorrhagic transformation [Evidence Level B]. Blood pressure should be lowered and sustained below 185/110 prior to alteplase therapy and to below 180/105 mmHg for the next 24 hours after alteplase administration [Evidence Level C].
3. Ischemic stroke patients not eligible for thrombolytic therapy: Treatment of hypertension in the setting of acute ischemic stroke or transient ischemic attack should not be routinely treated [Evidence Level C].
4. Extreme blood pressure elevation (e.g. systolic BP greater than 220 or diastolic BP greater than 120 mmHg) should be treated to reduce the blood pressure by approximately 15 percent, and not more than 25 percent, over the first 24 hours with further gradual reduction thereafter to targets for long-term secondary stroke prevention [Evidence Level C].
5. Avoid rapid or excessive lowering of blood pressure because this might exacerbate existing ischemia or might induce ischemia, particularly in the setting of intracranial or extracranial arterial occlusion [Evidence Level C].
6. Choice of agents for managing blood pressure should be based on current Hypertension Canada Blood Pressure treatment guidelines (hypertension.ca)

Note: For guidance on blood pressure management of hemorrhagic stroke, refer to Canadian Stroke Best Practices Management Intracerebral Hemorrhagic Stroke module(new recommendations, expected release Fall 2019).

4.4 Cardiovascular Investigations

1. Patients with suspected transient ischemic attack or ischemic stroke should have a 12-lead ECG to assess cardiac rhythm and identify atrial fibrillation or flutter or evidence of structural heart disease (e.g. myocardial infarction, left ventricular hypertrophy) [Evidence Level B].
2. Unless a patient is hemodynamically unstable, electrocardiogram should not delay assessment for intravenous thrombolysis and endovascular thrombectomy and can be deferred until after a decision regarding acute treatment is made [Evidence Level C].
   Note: For patients being investigated for an acute embolic ischemic stroke or TIA of undetermined source whose initial short-term ECG monitoring does not reveal atrial fibrillation but a cardioembolic mechanism is suspected, refer to Canadian Stroke Best Practices Secondary Prevention of Stroke module, section 7 on Management of Atrial Fibrillation in Stroke for additional information.
3. Echocardiography (2D or TEE) may be considered in patients where a cardiac cause of stroke is suspected, including in young adults and children who present with stroke, and when infectious endocarditis is suspected [Evidence Level C].

4.5 Blood Glucose Abnormalities

1. All patients with suspected acute stroke should have their blood glucose concentration checked upon arrival to the Emergency Department (note: For patients arriving by EMS, the capillary glucose measured by EMS should be reviewed by the Emergency Department team for any immediate management required) [Evidence Level B]. Refer to Table 2B Recommended Laboratory Investigations for Patients with Acute Stroke or Transient Ischemic Attack for further details. Refer to Section 3 of this module for further details regarding EMS management.
2. Hypoglycemia should be corrected immediately [Evidence Level B].
3. Although no optimal glucose target has been identified, it is reasonable to treat hyperglycemia which has been associated with hemorrhagic transformation when treating with IV alteplase thrombolysis [Evidence Level C].

4.6 Additional Management Considerations in the Emergency Department

1. Chest X-Ray: A chest x-ray should be completed when the patient has evidence of acute heart disease or pulmonary disease [Evidence Level B]. Unless a patient is hemodynamically unstable, chest x-ray can be deferred until after a decision regarding acute treatment and it should not delay assessment for thrombolysis and endovascular thrombectomy.
2. Swallowing Assessment: Patient swallowing screen should be completed as early as possible by a practitioner trained to use a validated swallowing screening tool as part of initial assessment, but should not delay decision-making regarding eligibility for acute stroke treatments [Evidence Level A].
   1. Ideally swallow screening should be done within 24 hours of hospital arrival, including patients that receive acute stroke treatments (intravenous alteplase and endovascular thrombectomy) [Evidence Level C].
   2. Patients should remain NPO (nil per os – no oral intake) until swallowing screen completed for patient safety [Evidence Level B];
   3. Oral medications should not be administered until swallowing screen using a validated tool has been completed and found normal [Evidence Level B]; alternate routes such as intravenous and rectal administration should be considered while a patient is NPO;
   4. A patient’s clinical status can change in the first hours following a stroke or TIA, therefore patients should be closely monitored for changes in swallowing ability following initial screening [Evidence level C];
   5. Patients found to have abnormal swallowing ability on screening should be referred to a healthcare professional with expertise in swallowing assessments for an in-depth swallowing assessment [Evidence Level B].
      Refer to Section 9, and Stroke Rehabilitation Module, Section 7, for additional information on screening for swallowing ability and dysphagia management.
3. Urethral Catheters: The use of chronic indwelling urethral catheters should generally be avoided due to the risk of urinary tract infections [Evidence Level A]. Refer to Section 9 for additional information.
   1. Insertion of an indwelling urethral catheter could be considered for patients undergoing endovascular thrombectomy, but should not delay achieving reperfusion. The need for retaining the catheter should be reconsidered after the end of the endovascular thrombectomy procedure, and it should be discontinued as soon as the patient can be expected to resume voiding on their own [Evidence Level C].
   2. Insertion of an indwelling urethral catheter is not routinely needed prior to intravenous thrombolysis, unless the patient is acutely retaining urine and is unable to void. If inserted for patient-specific reasons, it should not delay acute treatment [Evidence Level C].
   3. If used, indwelling catheters should be assessed daily and removed as soon as possible [Evidence Level A].
   4. Fluid status and urinary retention should be assessed as part of vital sign assessments [Evidence Level C].
   5. Excellent pericare and infection prevention strategies should be implemented to minimize risk of infections [Evidence Level C].
4. Temperature should be routinely monitored and treated if above 37.5 Celsius [Evidence Level B]. Refer to CSBPR Stroke Key Quality Indicators and Case Definitions document.
5. Oxygen: Supplemental oxygen is not required for patients with normal oxygen saturation levels [Evidence Level C].

Clinical Considerations: (New for 2018)

1. There is no evidence to support the practice of routine reversal of anticoagulation, either during non-thrombolytic conservative care or in order to give alteplase in patients presenting with acute ischemic stroke who are on warfarin or direct oral anticoagulants. Endovascular thrombectomy may be considered despite anticoagulation if patients are otherwise eligible.

Rationale +-

Patients who present to hospital with suspected stroke often also have significant physiological abnormalities and comorbidities. These can complicate management of stroke. Signs and symptoms that may explain the cause of the stroke or predict later complications (such as space-occupying infarction, bleeding, or recurrent stroke) and medical conditions such as hypertension or the presence of a coagulopathy, will have an impact on treatment decisions. An efficient and focused assessment is required to understand the needs of each patient.

It is impossible to reliably differentiate infarct from hemorrhage by clinical examination alone. Brain imaging is required to guide management, including the selection of time-sensitive acute stroke treatments. A CT scan or magnetic resonance (MR) imaging is essential to differentiate between ischemic stroke and intracerebral hemorrhage, and stroke mimics, since clinicians may disagree on the clinical diagnosis of stroke (versus not stroke) in about 20 percent of patients.

Initial management of elevated blood pressure in acute stroke patients remains controversial due to the lack of evidence to clearly guide practice. At the same time, this is an area where clinicians often seek guidance from stroke specialists. The recommendations for this area emphasize caution and diligence in monitoring and treating extremely high blood pressure in the first hours after stroke onset.

Diabetes is a major modifiable risk factor for vascular disease that may be first diagnosed at the time of a stroke at the time acute stroke is associated with increased size of the infarcted area in experimental animals, a greater risk of symptomatic hemorrhage after intravenous alteplase treatment, and is associated with poor clinical outcomes in epidemiological studies.

System Implications +-

1. Local protocols to ensure all stroke patients have rapid access to computed tomography (CT) with CT angiography (CTA) of the extracranial and intracranial vessels completed at the same time as the initial brain imaging.
2. Protocols for ‘code stroke’ activation of the stroke team and diagnostic services prompted by receiving pre-notification by paramedics of an incoming suspected stroke patient.
3. Protocols should be in place to prioritize suspected stroke patients in triage queues at emergency departments to ensure timely access to diagnostic services and EVT, where applicable.
4. Agreements to ensure patients initially managed in rural hospitals without neurovascular imaging capability have timely access to CTA with imaging of the extracranial and intracranial vessels at partnering hospitals.
5. Protocols and standing orders to guide initial blood work and other clinical investigations.
6. Local protocols, especially in rural and remote locations, for rapid access to clinicians experienced in interpretation of diagnostic imaging, including access through telemedicine technology.
7. Provinces and regions should ensure availability of physicians and other healthcare professionals with stroke expertise, including recruitment and retention strategies to increase accessibility of acute stroke services for all Canadians.

Performance Measures +-

1. Median time from patient arrival to hospital to first/qualifying imaging scan.
2. Median time from patient arrival to hospital to first CTA of extracranial and intracranial vessels.
3. Proportion of stroke patients who receive initial brain imaging (either CT or CTA) within 30 minutes of hospital arrival for those patients who arrive within acute stroke treatment times.
4. Proportion of stroke patients who receive a brain CT/CTA within 24 hours of hospital arrival (core).
5. The proportion of patients with carotid territory events who undergo carotid imaging in the ED.
6. The proportion of patients who do not have carotid imaging in the ED but who have arrangements made for carotid imaging as an outpatient.
7. The median time from CBC, INR and thrombin time, Cr/eGFR draw to having results available.
8. Proportion of patients with blood glucose levels documented during assessment in the Emergency Department.
9. Proportion of stroke patients who receive a CT scan in less than 25 minutes from hospital arrival in patients arriving less than 4.5 hours from last known well time, and without contraindications to thrombolysis.
10. Median time from stroke symptom onset to carotid imaging.

Measurement Notes

1. Data may be obtained from laboratory reports or patient chart.
2. CT and CTA imaging time should be based on time of first slice by the scanner. Specify in your results which type of scan (CT or CTA, separately or combined) was being measured and reported
3. Stratify analysis for patients who arrive within 3.5 hours of stroke symptom onset and those who arrive within 4.5, 6 and 24 hours from stroke symptom onset.
4. Performance measure 1: apply to patients who may be candidates for acute thrombolysis (i.e. who arrive at hospital within 4.5 hours of stroke onset) and for patients who may be eligible for other time-sensitive interventions.
5. Performance measures 1 and 2: Time interval measurements for CT and MRI should be calculated from the time the patient enters the Emergency Department until the time noted on the actual brain imaging scan.
6. Performance measure 3: For outpatient carotid imaging, a notation should appear in the discharge summary, or in nursing notes, with an indication that the test has actually been requested or requisitioned prior to the patient leaving the hospital.
7. Performance measure 5: Use medical history to determine whether patient was known to have diabetes prior to the stroke event.

Summary of the Evidence +-

Evidence Table 4

Initial Assessment 

Patients require immediate evaluation when presenting to the Emergency Department (ED) with suspected stroke or transient ischemic attack (TIA). For those patients presenting with TIA, their risk for imminent stroke (i.e. within one week) can be evaluated, and investigations/treatment initiated to prevent a future stroke. Standard assessments for patients with suspected acute stroke include a neurological examination, monitoring of vital signs, blood work, imaging and cardiovascular investigations, dysphagia screens and seizure assessment. It is also important to identify patients who are TIA ‘mimics’, to avoid unnecessary and expensive investigations, incorrect diagnostic labelling and inappropriate long-term prevention treatments. Patients presenting with stroke symptoms may ultimately be diagnosed with other conditions such as migraine headache, vertigo, metabolic disturbances, brain tumors, presyncope/ syncope or anxiety (Karliński et al. 2015, Lee & Frayne 2015). The percentage of stroke mimics among patients presenting to the emergency department with acute symptoms has been estimated to be approximately 30% (Goyal et al. 2016, Merino et al. 2013).

Neurovascular Imaging

Immediate access to brain and vascular imaging is required for all patients arriving to hospital with suspected stroke or TIA. A non-contrast CT scan is considered the imaging standard to be used initially to identify acute ischemic stroke and to rule out intracranial hemorrhage. CT scans are quick to perform, easy to tolerate, and are known to be very reliable for the detection of intracerebral hemorrhage. Early detection of hemorrhage is essential since the presence of blood in the brain or subarachnoid space is the main contraindication for the administration of aspirin, anticoagulants and thrombolytic therapy. Early imaging is particularly important for patients who may be potential candidates for thrombolytic therapy, since it has a narrow therapeutic window for administration.  Wardlaw et al. (2004) found that a computed tomography (CT) scan for all patients with suspected stroke on admission to hospital was the most cost-effective strategy, despite the increased cost of scans being performed during “off hours”. The higher costs were offset by savings realized through decreased lengths of hospital stay.

CT angiography (CTA) should be performed as part of the initial acute stroke CT imaging protocol.  It is fast, simple and helps to identify patients with small core infarcts (ASPECTS 6 or higher) in the anterior circulation, who should be considered for endovascular therapy.  Either multiphase or dynamic CTA is recommended over single-phase CTA, as the former can be used to assess for both intracranial arterial occlusion and also pial arterial collateral circulation (Menon et al. 2015).  Evidence of adequate pial collaterals may predict better response to reperfusion and outcomes in acute ischemic stroke patients (Christoforidis et al. 2005). CTA is well-tolerated with a very low risk of allergic reaction or renal impairment from contrast administration, and does not pharmacologically interact with t-PA.

CT perfusion (CTP) is another advanced CT imaging modality that can be used to determine infarct core size (based on cerebral blood volume [CBV] maps) and ischemic penumbra (using cerebral blood flow [CBF] or time maps).  CTP has been used in recent trials of endovascular therapy to identify patients who were candidates for treatment. In the EXTEND-IA trial, (Campbell et al. 2015), inclusion required a 20% mismatch between core infarct and ischemic penumbra identified using CTP.  Due to variability in vendor software, specific CBV volume cut-offs for core infarct size is not standardized.  The use of CTP for acute stroke patients should be reserved for centres with well-established CTP protocols and experience in interpreting CTP, or the use of quantitative CTP software, and must not substantially delay decisions for acute stroke treatments.

While CT scans are recommended for initial brain imaging following stroke, there are cases where magnetic resonance imaging (MRI) with diffusion-weighted sequences (DWI) may be superior. MRI has been shown to be more sensitive in detection of the early changes associated with ischemia, especially in patients with small infarcts. Using the results from 8 studies, Brazzelli et al. (2009) reported that the sensitivity of magnetic resonance imaging (MRI) may be higher than CT scans for the identification of ischemic stroke (99% vs. 39%), although the authors questioned the generalizability of their findings. If an MRI is available and performed in place of CT, enhanced imaging in the form of DWI, GRE and FLAIR is indicated.  Brunser et al. (2013) included 842 patients admitted to the Emergency Department with a suspected ischemic stroke. Diffusion-weighted imaging (DWI) examinations were performed for all patients. For patients with a final diagnosis of stroke, the sensitivity of DWI in detecting ischemic stroke was 90% (95% CI 87.9 to 92.6), and specificity was 97% (95% CI 91.8 to 99.0).

Cardiovascular Investigations

An electrocardiogram (ECG) should be performed immediately to identify arrhythmias for all patients with stroke and TIA presenting to the Emergency Department. Atrial fibrillation (AF) is commonly diagnosed post-stroke, and is of particular concern due to its role in forming emboli. Sposato et al. (2015) included the results from 11 studies in which cardiac monitoring was initiated in the ED. An estimated 7.7% of patients, without a history of AF, were newly diagnosed.  Suissa et al. (2012) included 946 patients with ischemic stroke without history of AF and found that the odds of detection were greatest within the first 24 hours of stroke (OR= 9.82; 95% CI 3.01 to 32.07). Patients who received continuous cardiac monitoring group were more likely to be identified with AF compared with those who received a baseline ECG, 24-hour Holter monitor and additional ECGs when necessary (adj OR= 5.29; 95% CI 2.43 to 11.55). Regardless of the type of monitoring used, the initial ECG will not always detect all cases of AF. In the same study, it was found that ECG monitoring beyond the baseline assessment resulted in the identification of additional cases of AF in 2.3%-14.9% of the population (Suissa et al. 2012). The use of serial ECG assessments over the first 72 hours following stroke can be an effective means of diagnosing AF. For example, Douen et al.(2008) reported there was no significant difference in detection rates between cardiac monitoring groups. AF was identified in 15 new patients using serial ECG and in 9 new patients using a Holter monitor. The majority of these cases were identified within 72 hours (83%).

The use of a transesophageal echocardiography (TEE) is indicated when there is suspected cardiac embolism involvement. For patients with an unknown cause of stroke following baseline diagnostic assessments, and no contraindications to anticoagulation therapy, TEE was found to identify possible sources of cardiac embolism (de Bruijn et al. 2006). In 231 patients with recent stroke (all types) or TIA, TEE was found to perform significantly better than transthoracic echocardiography (TTE) in identifying possible sources of cardiac embolism (55% vs. 39%). Among the 39 patients ≤45 years, a potential cardiac source was identified in 13 patients. Of these, the abnormality was identified by TEE in 10 cases and in 3 cases using TTE. Among 192 patients >45 years, a potential cardiac source of embolism was identified in 59% of patients. TEE confirmed the potential cardiac source in 34 patients, but also detected a potential cardioembolic source in an additional 80 patients.

Acute Blood Pressure Management

There is no evidence to suggest that interventions to manage extreme perturbations in blood pressures with vasoactive agents help to improve stroke outcome. In the CATIS trial (He et al. 2014), 4071 patients with acute ischemic stroke were randomized to receive or not receive antihypertensive therapy during hospitalization. Although mean systolic blood pressure was significantly lower among patients in the intervention group, treatment was not associated with significant reduction in the risk of death or major disability at either 14-days (OR= 1.00, 95% CI 0.88 to 1.14) or 3-months (OR= 0.99, 95% CI 0.86 to 1.15) following study entry. Two Cochrane reviews have examined the potential benefits of artificially raising and lowering blood pressure with vasoactive drugs within the first week of stroke. One of the reviews was restricted to the inclusion of RCTs, and included the results from 12 trials (Geeganage & Bath, 2008), while the other included non RCTs as well (Geeganage & Bath, 2010). In both reviews, the focus of most of the included studies was blood pressure reduction. Treatment was associated with significant early and late reductions in SBP and DBP, but was not associated with significant reduction in the risk of death or a poor outcome within one month, or the end of follow-up. However, the use of vasoactive drugs used to raise blood pressure significantly increased in the odds of death or disability at the end of the trial (OR= 5.41; 95% CI 1.87 to 15.64) (Geeganage & Bath, 2010). Further evidence from a meta-regression study (Geeganage & Bath, 2009), which included the results from 37 trials, also suggests that large changes in blood pressure in the early post-stroke period are associated with an increased risk or death and the combined outcome of death/dependency. While the authors also suggested that a decrease in blood pressure between 8mmHg and 14.6mmHg was associated with the lowest odds of poor outcome (death, dependency and intracerebral hemorrhage), the results were not statistically significant. (Geeganage & Bath, 2009).

For patients treated with thrombolysis, reductions in blood pressure may be indicated, when elevations are extreme (eg., SBP ≥220 mm Hg or DBP≥120 mm Hg). Using the results of 11080 patients included in the SITS-ISTR study who were treated with thrombolysis, Ahmed et al (2009) reported that high systolic BP, 2 to 24 hours after thrombolysis was associated with worse outcome (p>0.001). Blood pressures greater than 170 mmHg were associated with higher odds of death, dependency and subsequent hemorrhage compared to blood pressures between 141 and 150 mmHg. The results from the blood pressure-lowering arm of the ENCHANTED trial, when released, will provide additional information to guide patient management.

Glucose Management

Baseline hyperglycemia has been identified as independent predictor of poor stroke outcome and may be a marker of increased stroke severity. The presence of hyperglycemia may be of particular concern among patients without a history of premorbid diabetes. Using patient data from the ECASS II trial, Yong & Kaste (2008) examined the association between stroke outcomes and four patterns of serum glucose over the initial 24-hour period post stroke. Among 161 patients with pre-morbid diabetes, the odds of poor outcome were not increased significantly for patients with persistent hyperglycemia, or among patients with hyperglycemia at 24 hours, compared with patients with persistent normoglycemia. However, among 587 non-diabetics, patients with persistent hyperglycemia experienced significantly worse outcomes compared to those with persistent normoglycemia. The odds of a good functional outcome at 30 days, minimal disability at 90 days or neurological improvement over 7 days were significantly reduced compared with patients with persistent normoglycemia, while the odds of 90-day mortality and parenchymal hemorrhage were increased significantly. Since initial hyperglycemia has been associated with poor stroke outcome, several trials have evaluated the potential benefit of tight blood glucose control early following stroke. The largest such study was the GIST-UK trial (Gray et al. 2007) in which 899 patients were randomized to receive variable-dose-insulin glucose potassium insulin (GKI) to maintain blood glucose concentration between 4-7mmol/L or saline (control) as a continuous intravenous infusion for 24 hours. For patients in the control group, if capillary glucose > 17 mmol/L, insulin therapy could be started, at the discretion of the treating physician. Treatment with GKI was not associated with a significant reduction in 90-day mortality (OR= 1.14; 95% CI 0.86 to 1.51; p=0.37) or the avoidance of severe disability (OR= 0.96; 95% CI 0.70 to 1.32). Rescue dextrose was given to 15.7% of GKI-treated patients for asymptomatic prolonged hypoglycemia. The trial was stopped prematurely due to slow enrolment. More recently, Rosso et al. (2012) randomized 120 patients to receive intravenous administration of insulin (IIT) on a continuous basis or subcutaneous administration (every 4 hours) for 24 hours (SIT). The stop point for treatment was <5.5 mmol/L in the IIT group and 8 mmol/L in the SIT group. Although a significantly higher number of patients in the IIT group achieved and maintained a mean blood glucose level of <7mmol/L, the mean size of infarct growth was significantly higher among patients in the IIT group (27.9 vs. 10.8 cm3, p=0.04), there were significantly more asymptomatic hypoglycemia events among patients in the IIT group (8 vs. 0, p=0.02) and there was no significant difference in the number of patients who experienced a good outcome (45.6% vs. 45.6%) or death (15.6% vs. 10.0%) at 3 months. In a Cochrane review (Bellolio et al. 2014) used the results of 11 RCTs including 1583 adult patients with blood glucose level of > 6.1mmol/L obtained within 24 hours of stroke, Blood-glucose-lowering treatment was not associated with reductions in death or dependency (OR=0.99, 95% CI 0.79-1.2) or final neurological deficit, but treatment did increase the risk of was associated symptomatic and asymptomatic hypoglycemia events.  

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