**5. General supportive care**

Issues to be focused on include: Airway management, hydration, increased intracranial pressure (ICP), Blood pressure control, Blood sugar control, Temperature.

#### **5.1. Airway management**

Coma is uncommon with ischaemic stroke patients. Patients who have neurological decline with reduced level of consciousness have challenges in maintaining their airway due to loss of protective reflexes [19]. This can result in aspiration, hypoxaemia or hypercapnia that may increase intracranial pressure by causing cerebral vasodilatation. The role of oxygen therapy in ischaemic stroke has been controversial due to failure of three clinical trials of hyperbaric oxygen to demonstrate efficacy. Supplemental oxygen can be administered at a dose of 10-15 L/min if there is evidence of hypoxia by pulse oximetry. This was shown to slow down the process of ischaemia and extend the therapeutic time window for thrombolysis [20, 21]. Patients with depressed level of consciousness should be intubated to avoid the risk of aspiration [22].

### **5.2. Hydration**

Patients with ischaemic stroke should be routinely hydrated with isotonic saline. This helps ensure adequate perfusion to the ischaemic penumbra and may prevent infarct extension. Hypotonic solutions should be avoided as this may lead to increased cerebral oedema.

Antihypertensives given when considering re-perfusion therapy include IV Labetalol 10–20 mg over 1–2 minutes, may be repeated once, IV Nicardipine 5 mg/h, titrating up by 2.5 mg/h every 5–15 minutes, maximum 15 mg/h; when desired BP is reached, adjust to maintain proper BP levels. Other drugs such as hydralazine, enalaprilat, etc. may be considered where necessary. Do not administer rt-PA if the blood pressure is not maintained at or below 185/110 mm Hg. Blood pressure should be monitored every 15 minutes for 2 hours from the start of rt-PA therapy, then every 30 minutes for 6 hours, and then every hour for 16 hours. If the blood pressure still remains uncontrolled or diastolic BP >140 mm Hg, consider IV sodium

Emergency Management of Acute Ischaemic Stroke http://dx.doi.org/10.5772/intechopen.75305 233

Hyperglycaemia occurs in about 20–40% of acute stroke patients with no previous diagnosis of diabetes mellitus [35]. There is overwhelming clinical evidence that correlates hyperglycaemia at the onset of acute ischaemic stroke with a negative outcome [36]. Hyperglycaemia influences neuronal damage by encouraging anaerobic metabolism and lactic acidosis within the ischaemic tissue, thus worsening outcome and heightening the risk of haemorrhagic transformation after thrombolysis [37]. Hyperglycaemia should be treated with insulin to achieve a blood sugar control between 7.7 and 10.0 mmol/l with close monitoring to avoid hypoglycaemia [16]. Insulin is indicated in the treatment of hyperglycaemia in acute ischaemic stroke because of its ability to reduce neuronal necrosis regardless of its effect on glucose levels [38].

About one third of patients presenting with stroke develop fever in the first few hours after stroke onset [39]. Increased body temperature of 37.5°C is associated with poor neurological outcome secondary to increased free radical production, increased metabolic demands and

The source of the fever should be determined. Some of the possible causes of the fever include aspiration pneumonia and other respiratory infections, urinary tract infections or line infections, infective endocarditis, deep vein thrombosis/pulmonary embolism and cocaine intoxication. The guideline for the early management of acute ischaemic stroke recommends the lowering of temperature during the acute stroke period. Fever is managed strictly with antipyretics and appropriate antibiotics given if infection is suspected. The most frequently used antipyretic is acetaminophen. Aspirin, ibuprofen and indomethacin have also been consid-

The commonly used antiplatelets include aspirin, clopidogrel and dipyridamole. The use of aspirin in acute ischaemic stroke was examined in CAST (the Chinese Acute Stroke Trial) and IST (the International Stroke Trial). In IST study, aspirin at a dose of 300 mg/day was found to reduce stroke recurrence within the first 14 days with no effect on early mortality. In the CAST study, aspirin 160 mg/day reduced the risk of recurrence and mortality in the first

nitroprusside [16].

**5.5. Management of blood sugar**

**5.6. Temperature control**

**5.7. Antiplatelet therapy**

increased release of neurotransmitters [39, 40].

ered in patients with reduced risk of bleeding [41].

#### **5.3. Increased intracranial pressure (ICP)**

The head of the bed should be elevated at 30 degrees. Other measures to reducing ICP include administration of 0.5-1 g/kg of 20% mannitol as a bolus. Infusion of hypertonic saline solution (23.4%) can also be administered at a dose of 0.5–2.0 ml/kg as an alternative to mannitol especially in the setting of hypotension. Hyperventilation to a pCO2 of 28-35 mmHg has also been employed as a measure in reducing ICP.

#### **5.4. Blood pressure management**

High blood pressure is a frequent occurrence in acute ischaemic stroke. Although blood pressure declines spontaneously within 90 mins after stroke onset [23], about one third of the patients continue to have hypertension with an increased risk of poor outcome [24, 25]. The mechanisms implicated for the increase in blood pressure are multifactorial and include a previous history of hypertension, release of endogenous catecholamines, raised intracranial pressure (Cushing's reflex), infection, "White coat hypertension effect", prior alcohol intake, pain from urinary retention, impaired baroreceptor sensitivity and stress relating to hospitalization [25–29].

Hypotension, though uncommon in acute stroke, correlates with a poor clinical outcome. Causes implicated include infection, cardiac failure, arrhythmias, hypovolaemia and aortic dissection [30].

Rapid blood pressure reduction in acute ischaemic stroke reduces the cerebral blood flow thereby increasing the area of cerebral infarction and worsening neurological outcome [31]. For over three decades, there has been a controversy regarding the treatment of high blood pressure in the setting of acute ischaemic stroke [32, 33]. Some studies have observed a U-shaped relationship between the admission blood pressure and good clinical outcomes, with an optimal systolic blood pressure ranging from 121 to 200 mm Hg and diastolic blood pressure ranging from 81 to 110 mm Hg [34]. High blood pressure should not be treated in the first 24 hours after ischaemic stroke unless the systolic blood pressure is greater than 220, the diastolic blood pressure is greater than 120, the mean arterial blood pressure is greater than 130 mmHg or there are associated complications such as presence of myocardial infarction, aortic dissection or heart failure. At such times, the goal would be to reduce the blood pressure by 15%.

Recommendations for blood pressure control have been established regarding patients undergoing fibrinolytic therapy. The recommendations include a gradual approach to reducing the pressure below 185/110 mm Hg to qualify for fibrinolytic therapy with intravenous recombinant tissue plasminogen activator (rt-PA). Once intravenous (rt-PA) is given, the blood pressure must be maintained below 180/105 mm Hg to reduce the risk of intracerebral haemorrhage [16].

Antihypertensives given when considering re-perfusion therapy include IV Labetalol 10–20 mg over 1–2 minutes, may be repeated once, IV Nicardipine 5 mg/h, titrating up by 2.5 mg/h every 5–15 minutes, maximum 15 mg/h; when desired BP is reached, adjust to maintain proper BP levels. Other drugs such as hydralazine, enalaprilat, etc. may be considered where necessary. Do not administer rt-PA if the blood pressure is not maintained at or below 185/110 mm Hg. Blood pressure should be monitored every 15 minutes for 2 hours from the start of rt-PA therapy, then every 30 minutes for 6 hours, and then every hour for 16 hours. If the blood pressure still remains uncontrolled or diastolic BP >140 mm Hg, consider IV sodium nitroprusside [16].

#### **5.5. Management of blood sugar**

**5.2. Hydration**

dissection [30].

haemorrhage [16].

**5.3. Increased intracranial pressure (ICP)**

232 Essentials of Accident and Emergency Medicine

been employed as a measure in reducing ICP.

**5.4. Blood pressure management**

Patients with ischaemic stroke should be routinely hydrated with isotonic saline. This helps ensure adequate perfusion to the ischaemic penumbra and may prevent infarct extension. Hypotonic solutions should be avoided as this may lead to increased cerebral oedema.

The head of the bed should be elevated at 30 degrees. Other measures to reducing ICP include administration of 0.5-1 g/kg of 20% mannitol as a bolus. Infusion of hypertonic saline solution (23.4%) can also be administered at a dose of 0.5–2.0 ml/kg as an alternative to mannitol especially in the setting of hypotension. Hyperventilation to a pCO2 of 28-35 mmHg has also

High blood pressure is a frequent occurrence in acute ischaemic stroke. Although blood pressure declines spontaneously within 90 mins after stroke onset [23], about one third of the patients continue to have hypertension with an increased risk of poor outcome [24, 25]. The mechanisms implicated for the increase in blood pressure are multifactorial and include a previous history of hypertension, release of endogenous catecholamines, raised intracranial pressure (Cushing's reflex), infection, "White coat hypertension effect", prior alcohol intake, pain from urinary retention, impaired baroreceptor sensitivity and stress relating to hospitalization [25–29].

Hypotension, though uncommon in acute stroke, correlates with a poor clinical outcome. Causes implicated include infection, cardiac failure, arrhythmias, hypovolaemia and aortic

Rapid blood pressure reduction in acute ischaemic stroke reduces the cerebral blood flow thereby increasing the area of cerebral infarction and worsening neurological outcome [31]. For over three decades, there has been a controversy regarding the treatment of high blood pressure in the setting of acute ischaemic stroke [32, 33]. Some studies have observed a U-shaped relationship between the admission blood pressure and good clinical outcomes, with an optimal systolic blood pressure ranging from 121 to 200 mm Hg and diastolic blood pressure ranging from 81 to 110 mm Hg [34]. High blood pressure should not be treated in the first 24 hours after ischaemic stroke unless the systolic blood pressure is greater than 220, the diastolic blood pressure is greater than 120, the mean arterial blood pressure is greater than 130 mmHg or there are associated complications such as presence of myocardial infarction, aortic dissection

or heart failure. At such times, the goal would be to reduce the blood pressure by 15%.

Recommendations for blood pressure control have been established regarding patients undergoing fibrinolytic therapy. The recommendations include a gradual approach to reducing the pressure below 185/110 mm Hg to qualify for fibrinolytic therapy with intravenous recombinant tissue plasminogen activator (rt-PA). Once intravenous (rt-PA) is given, the blood pressure must be maintained below 180/105 mm Hg to reduce the risk of intracerebral Hyperglycaemia occurs in about 20–40% of acute stroke patients with no previous diagnosis of diabetes mellitus [35]. There is overwhelming clinical evidence that correlates hyperglycaemia at the onset of acute ischaemic stroke with a negative outcome [36]. Hyperglycaemia influences neuronal damage by encouraging anaerobic metabolism and lactic acidosis within the ischaemic tissue, thus worsening outcome and heightening the risk of haemorrhagic transformation after thrombolysis [37]. Hyperglycaemia should be treated with insulin to achieve a blood sugar control between 7.7 and 10.0 mmol/l with close monitoring to avoid hypoglycaemia [16]. Insulin is indicated in the treatment of hyperglycaemia in acute ischaemic stroke because of its ability to reduce neuronal necrosis regardless of its effect on glucose levels [38].

#### **5.6. Temperature control**

About one third of patients presenting with stroke develop fever in the first few hours after stroke onset [39]. Increased body temperature of 37.5°C is associated with poor neurological outcome secondary to increased free radical production, increased metabolic demands and increased release of neurotransmitters [39, 40].

The source of the fever should be determined. Some of the possible causes of the fever include aspiration pneumonia and other respiratory infections, urinary tract infections or line infections, infective endocarditis, deep vein thrombosis/pulmonary embolism and cocaine intoxication. The guideline for the early management of acute ischaemic stroke recommends the lowering of temperature during the acute stroke period. Fever is managed strictly with antipyretics and appropriate antibiotics given if infection is suspected. The most frequently used antipyretic is acetaminophen. Aspirin, ibuprofen and indomethacin have also been considered in patients with reduced risk of bleeding [41].

#### **5.7. Antiplatelet therapy**

The commonly used antiplatelets include aspirin, clopidogrel and dipyridamole. The use of aspirin in acute ischaemic stroke was examined in CAST (the Chinese Acute Stroke Trial) and IST (the International Stroke Trial). In IST study, aspirin at a dose of 300 mg/day was found to reduce stroke recurrence within the first 14 days with no effect on early mortality. In the CAST study, aspirin 160 mg/day reduced the risk of recurrence and mortality in the first 28 days. Clopidogrel at a dose of 75 mg was found to have a risk reduction of 8.7% in the prevention of cerebrovascular and cardiovascular events [42]. Various studies have shown that the combination of dipyridamole and aspirin is superior to aspirin alone as an antithrombotic therapy after cerebral ischemia of arterial origin [43, 44].

**Inclusion criteria**

 Aged ≥18 years **Exclusion criteria**

Diagnosis of ischemic stroke causing measurable neurological deficit

Onset of symptoms <3 hours before beginning treatment

Significant head trauma or prior stroke in previous 3 months

Arterial puncture at non-compressible site in previous 7 days

Intracranial neoplasm, arteriovenous malformation, or aneurysm

Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg)

Heparin received within 48 hours, resulting in abnormally elevated aPTT greater than the upper limit of normal

Emergency Management of Acute Ischaemic Stroke http://dx.doi.org/10.5772/intechopen.75305 235

 Recent experience suggests that under some circumstances—with careful consideration and weighting of risk to benefit—patients may receive fibrinolytic therapy despite 1 or more relative contraindications. Consider risk to

benefit of IV rt-PA administration carefully if any of these relative contraindications are present:

Adapted from Guidelines for the early management of patients with acute ischaemic stroke. Stroke 2013.

The checklist includes some FDA-approved indications and contraindications for administration of IV rt-PA for acute ischemic stroke. Recent guideline revisions have modified the original FDA-approved indications. A physician with

Onset time is defined as either the witnessed onset of symptoms or the time last known normal if symptom onset was

In patients without recent use of oral anticoagulants or heparin, treatment with IV rt-PA can be initiated before availability of coagulation test results but should be discontinued if INR is >1.7 or PT is abnormally elevated by local

In patients without history of thrombocytopenia, treatment with IV rt-PA can be initiated before availability of platelet

aPTT indicates activated partial thromboplastin time; CT, computed tomography; ECT, ecarin clotting time; FDA, Food and Drug Administration; INR, international normalized ratio; IV, intravenous; PT, partial thromboplastin time; rt-PA,

**Table 1.** Inclusion and exclusion characteristics of patients with ischemic stroke who could be treated with IV rtPA

.

Only minor or rapidly improving stroke symptoms (clearing spontaneously)

Recent gastrointestinal or urinary tract haemorrhage (within previous 21 days)

Seizure at onset with postictal residual neurological impairments

Recent acute myocardial infarction (within previous 3 months)

count but should be discontinued if platelet count is <100,000/mm<sup>3</sup>

recombinant tissue plasminogen activator; and TT, thrombin time.

Major surgery or serious trauma within previous 14 days

expertise in acute stroke care may modify this list.

Symptoms suggest subarachnoid haemorrhage

History of previous intracranial haemorrhage

Acute bleeding diathesis, including but not limited to

Recent intracranial or intraspinal surgery

Active internal bleeding

Platelet count <100,000/mm<sup>3</sup>

**Relative exclusion criteria**

Pregnancy

not witnessed.

laboratory standards.

within 3 hours from symptom onset.

#### **5.8. Anticoagulant therapy**

Heparin is not indicated for routine use in the treatment of acute ischaemic stroke. Some of the indications for its use include cerebral venous thrombosis, acute infarct with high grade carotid stenosis, cardiogenic emboli with high risk of recurrence, hypercoagulable states such as protein C deficiency, protein S deficiency, antithrombin III deficiency and antiphospholipid antibody syndrome. Other anticoagulants include warfarin which is useful in the prevention of stroke recurrence in atrial fibrillation patients [45]. Dabigatran has also been found to reduce the occurrence of stroke among non-valvular atrial fibrillation patients [46].

#### **5.9. Statins**

Statins have been observed to be efficacious in both primary and secondary prevention of stroke independent of cholesterol levels. This might be due to other beneficial effects of statins such as stabilization of atherosclerotic plaques, improvement of endothelial function, antioxidant properties, increased nitric oxide bioavailability, inhibition of inflammatory responses and immunomodulatory actions [47, 48]. The use of Statin early in stroke patients has been found to be strongly associated with improved post stroke survival, and discontinuation of statin, even for a brief period, has been associated with worsened survival [49].
