search
for
 About Bioline  All Journals  Testimonials  Membership  News


Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 50, Num. s1, 2002, pp. S37-S49

Neurology India, Vol. 50, (Suppl. 1), Dec, 2002, pp. S37-S49

Critical Care Management of Acute Stroke

A.K. Meena, A. Suvarna, S. Kaul

Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082, India.
Correspondence to : Dr. A.K. Meena, Department of Neurology, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad - 500 082, India.

Code Number: ni02161

Summary

Treatment of acute stroke in an intensive care unit improves the outcome by reducing the mortality and morbidity. In addition to the primary neurological condition that affects the outcome, the secondary complications and associated co-morbid conditions also influence the outcome. It is essential to monitor and maintain the general physiological conditions in the neurologically sick patients. Maintenance of a clear airway is important to prevent hypoxic insult to the brain in stroke patients whose airway is compromised. Mean arterial blood pressure should be maintained > 110mm of Hg. The choice of antihypertensive is labetolol. Drugs causing raised intracranial pressure (ICP) should be generally avoided. Cardiac arrhythmias should be monitored and treated. Treatment of ICP by osmotic agents is the usual practice. Hyperventilation is reserved for patients who are coning and is only a temporizing measure prior to surgery. Hemicraniectomy in malignant middle cerebral artery territory infarcts reduces the mortality significantly. Insulin therapy may be required to maintain a normoglycemic state for preserving the functionally impaired neurons. Infections should be treated by appropriate antibiotics. Care should be taken to prevent aspiration, and deep vein thrombosis. Intravenous thrombolysis for the eligible candidates and Aspirin for the rest is the recommended therapy for acute ischemic stroke.

Key words : Acute stroke, Intensive care, Hypertension, ICP.

Introduction

Intensive treatment of stroke especially in stroke units or intensive care units (ICU) definitely improves outcome and lowers mortality after stroke.1 There are three main areas in the treatment of acute stroke. i) Treatment of general physiological conditions that need to be optimized in the setting of acute stroke. ii) Prophylactic treatment of potential complications which may be either neurological or medical. iii) Specific therapy directed against different aspects of stroke pathogenesis which include treatment for recanalization and neuroprotection.

Although most stroke patients can be cared for in a general neurology ward, it becomes important to recognize when patients with stroke are in need of more specialized monitoring. Indications for admission to intensive care units or stroke unit include requirement for airway management, hemodynamic monitoring, treatment for increased intracranial pressure (ICP), observation for neurological deterioration and patients receiving thrombolytic therapy.

Airway management

Stroke patients may require intubation for either airway obstruction or acute respiratory failure. Airway obstruction develops due to three reasons. First, in acute stroke patients with decreased level of sensorium the tongue falls backward, intermittently obstructing the airway, due to lack of tone in the tongue and pharyngeal muscles. Second, in patients with brainstem stroke, the gag and cough reflex is reduced. In addition patients may be unable to clear the secretions.2 The criteria for intubation and extubation are given in table I.3 Stroke patients may develop respiratory failure from aspiration or community acquired pneumonia.

Initial management of intermittent airway include, placement of oral or nasal airway to prevent obstruction and allow easier access for suctioning. Frequent assessments are necessary to check for sonorous respiration, presence of rhonchi, increased respiratory rate, decreased oxygen saturation, or increasing suctioning requirements. Any of these should alert the physicians to a worsening respiratory status. Use of mechanical ventilation in a patient with reduced level of consciousness due to large infarcts remains controversial. Mortality of 51-90% has been reported in patients receiving mechanical ventilation.4-7 These patients are usually intubated to secure airway and to institute therapies such as hyperventilation. Very few patients with ischemic stroke require intubation (6-8%) and those who do, have a poor prognosis.7,9 Independent predictors of death in patients requiring ventilators include, age, poor Glasgow coma scale(GCS) score and respiratory failure.10 Patients with brainstem stroke who require ventilator have very poor outcome.10

At the time of intubation, the use of medication, that provide adequate muscle relaxation, without leading to haemodynamic instability and prevent elevated ICP from tracheal stimulation) is recommended.3,11 If anesthesia is used for intubation, thiopental (3-5 mg/kg IV) can be used in hemodynamically stable patients whereas, etomide is an ideal drug, in a hemodynamically unstable patient, but it is short acting (0.3-0.5m/kg/IV). Propofol (2-2.5mg/kg IV) can be used but it causes seizures and hypotension.12,13 Muscle paralysis is usually avoided, as frequent neurological examination cannot be performed. In patients with increased ICP, neuromuscular blockade should be induced with vecuronium.14 Succinylcholine is usually avoided as it increases ICP and causes hyperkalemia in patients with neuromuscular disease. Despite all efforts to avoid hemodynamic compromise during intubation, hypotension may result especially in aged patients.

Modes of mechanical ventilation : Oral intubation is the safest method of intubation in patients with stroke.15 The choice of ventilation is usually based on the reasons for intubation, either neurological (airway protection) or primary respiratory failure. In the former case, pressure support ventilation is the used. The amount of additional pressure is adjusted to achieve a total volume of 5-8ml/kg and a respiratory rate <25 breaths/minute. Patients with coma or patients with an abnormal respiratory pattern, need controlled mechanical ventilation.16 Synchronised intermittent mandatory ventilation (SIMV) is the preferred method of ventilation. Positive end expiratory pressure (PEEP) during ventilation should be avoided in patients with significantly increased ICP although setting up to 10cm H2O can be tolerated.17,18 Patients with impaired oxygenation (Pneumonia, ARDS, neurogenic pulmonary edema) require complicated mode of ventilation such as pressure control, inverse ratio ventilation, high level of PEEP and inhaled nitrous oxide, If no improvement is seen within 7-10 days, tracheostomy should be instituted as early as possible.

Hemodynamic monitoring

Management of haemodynamics in patients with cerebrovascular disease is complex. Cardiovascular abnormalities (arrhythmia and blood pressure) are often responsible for acute neurological illness, such as stroke and vice versa. Because the risk factors are shared, patients with cerebrovascular diseases are also at high risk for cardiac ischemia. Most haemodynamic manipulation in the neurological intensive care unit involves : i) management of hypertension in the setting of an acute neurological insult ii) management of cardiac arrhythmia and functional cardiac disturbances concurrent with or caused by acute neurological insults iii) treatment of vasospasm following subarachnoid haemorrhage

Management of hypertension : Blood pressure (BP) management is a critical and controversial issue and depends on the clinical circumstances.19-24 Hypertension (HTN) is a well-known risk factor for stroke and 70-80% of patients with acute stroke have high blood pressure at admission25-27 and BP spontaneously normalizes over a few hours to 7-10 days.26-28 Continuous BP monitoring should be done to avoid the 'white coat effect'.29, 30 In animal studies it has been shown that high BP increased the risk of hemorrhagic transformation. However the data in human is inconclusive.31-32 Although uncontrolled HTN might worsen the cerebral edema and outcome may be poor, experimental data regarding this has been inconsistent.33 Very few studies in humans have shown that treatment of HTN within 24 hours definitely reduced cerebral edema and improved outcome in ischemic stroke patients.34 In fact, review of the available data in humans has not shown any convincing link between hypertension at admission and morbidity and mortality.35-37 Aggressive treatment of BP in chronically hypertensive patients might in fact reduce the cerebral blood flow (CBF) and worsen the ischemic damage and neurodeficit,37 as cerebral auto regulation is often set at a higher pressure in chronic hypertensives , and may actually be impaired in older people and in patients with ischemic stroke.38-40 Neurons in the penumbral region which are functionally impaired but still viable, are vulnerable to the reduction in BP in the face of reduced blood supply.41 In patients with ischemic stroke who have high grade vascular stenosis, lowering of BP might increase the ischemia and facilitate complete occlusion of vessels.24 Anecdotal case reports and recent studies have shown that lowering of BP was associated with worse outcome.42,43 SPECT studies on patients randomized to nicardipine within 72 hours had shown a decrease in CBF associated with drop in BP.44

Recommendations for blood pressure management : As there are no controlled studies addressing the impact of HTN treatment on outcome in ischemic stroke, recommendations are largely empirical. The American Heart Association, suggests that blood pressure in acute stroke should not be treated unless patients have severe HTN (mean arterial pressure >130mm or systolic BP > 220 mm of Hg).45 Occasionally, other serious diseases mandate aggressive lowering of blood pressure in people with ischemic stroke. These include acute myocardial infarction, acute renal failure and dissection of aorta.23 For patients receiving rt-PA, guidelines recommend stricter BP control at a systolic pressure of 185 mmHg and diastolic pressure of 110 mmHg.46

Choice of antihypertensive drug : The most ideal antihypertensive drug in ICU setting would be the one with a short half-life, moderate efficacy and devoid of side effects like sedation. It should not reduce CBF or ICP. Characteristics of various drugs used in the treatment of hypertension in acute stroke are summarized in table II and III. Labetolol, a combined a and b blocker is the ideal drug of choice. Angiotensin converting enzyme inhibitors are preferred because they do not have any effect on ICP and CBF.47,48 Calcium channel blockers may increase the ICP but they maintain or increase CBF. When indicated, we preferably use intravenous labetolol, or ACE inhibitors in our Intensive Care and Stroke unit. Conventional drugs, which act as primary vasodilators such as nitroglycerine, sodium nitroprusside and hydralazine, can increase ICP and should be used with caution.

Hemodynamic augmentation

Experimental models of ischemic stroke have shown that induced hypertension can decrease the infarct size by increasing the CBF. Studies in humans have shown that vasopressor use in stroke patients improved the outcome and it was safer.49,50 However this form of therapy needs further evaluation.

ECG changes, cardiac arrhythmias and myocardial damage

More than 85% of patients with stroke have abnormal ECGs. New onset ECG changes have been reported to occur in about 15-30% of ischemic and hemorrhagic strokes.51,52 These include QT prolongation, U waves, T wave abnormalities and ST segment elevation or depression. The exact nature of these ECG changes is unclear. In many cases the changes are transient and may be due to stroke itself. However, many patients have concomitant cardiovascular disease; 30-65% of patients with stroke have asymptomatic coronary artery disease.53 In one study 15% of patients with stroke were found to have a coincident myocardial infarction based on ECG criteria.51 However, accurate data to support this incidence of true myocardial damage is scanty. Elevated CK - MB levels have been found in 11% of patients, however, these levels rise slowly and peak 4 days after the event unlike true myocardial infarction.54 These changes are thought to be due to increased sympathetic activity and are reported more frequently with left insular damage.55 There is one case report of "stunned myocardium" in stroke similar to that seen in subarachnoid hemorrhage.56 Stroke patients have a 25-39% incidence of arrhythmias on admission ECG, the most common of which is atrial fibrillation. Holter studies, however, show a higher incidence of arrhythmias.57,58 Patients with recent onset ECG changes have a higher mortality, especially those with ventricular arrhythmias. Despite this, the value of routine ambulatory Holter monitoring in patients with stroke has been questioned because it does not usually lead to a significant alteration in management.59

Elevated ICP and brain edema

Ischemic brain edema occurs during the first 24-48 hours after ischemic infarcts. In younger patients with complete middle cerebral artery (MCA) infarction, brain edema and elevated ICP may become a major complication and may lead to herniation and death.60 These patients usually show a rapid decline in consciousness and develop the signs of herniation 2-4 days after the onset of symptoms. Outcome was fatal in the majority of these patients, with a mortality of about 80% with standard treatment.60,61 Appropriate treatment of raised ICP in large infarcts depends on the knowledge of ICP and the simplest way is to measure the ICP by intraparenchymal fiberoptic pressure monitor. However in patients with large hemispheric infarcts, the neurologic examination is more sensitive than the transduced ICP for predicting outcome.62,63 The insensitivity of ICP monitoring in ischemic stroke is most likely related to the fact that transtentorial herniation occurs because of local tissue shifts, which are seen before a global rise in ICP.50

General care of patients with raised ICP

Patient Positioning : Cerebral perfusion pressure is optimized when the head of the bed is at 15-30o above the horizontal.64-66 Because head turning can impair jugular venous return, patients should be kept supine with the head positioned straight ahead.

Intubation : The anesthesiologist should always be apprised of patients with increased or potentially increased ICP as this may change their intubation protocol. For instance, succinylcholine can increase ICP,67 while standard rapid induction techniques may decrease MCA blood 'flow'. In general, induction of anesthesia should be done with an agent that may have neuroprotective and ICP lowering effects, such as midazolam, etomidate or thiopental. The cough reflex, which can increase ICP, should be suppressed with lidocaine and neuromuscular blockade achieved with a non-depolarizing agent like rocuronium or vecuronium. Aggressive suctioning and neck procedures should be done with caution.

Fluid management : Raised ICP was historically managed by fluid restriction in an effort to avoid increasing brain water. It was later discovered that hypovolemia could rapidly lead to decrease in cerebral perfusion pressure (CPP) and thus increasing the hypoxic-ischaemic injury. Also there is no evidence that fluid restriction improves brain edema.67 Free water should be avoided and isotonic fluids should be given. Normal serum osmolality should be maintained. Patients should be kept euvolemic at all times. Hypertension and hyperthermia should be treated appropriately as both fever and high BP increase cerebral edema.

Treatment for increased ICP

Various modes of treatment available for management of raised ICP are summarized in table IV and are as follows.

Osmotherapy
Mannitol : Osmotherapy is usually accomplished with mannitol, which has an osmolality of 5.5 mOsm/kg. In addition to its osmotic effects, mannitol decreases blood viscosity and causes vasoconstriction. Complications of therapy include hypovolemia, decreased CPP, hyperkalemia, renal failure, and rebound edema.69 The other osmotic agents are glycerol and urea, the clinical effects of which are unproven.

Hypertonic saline
Clinical studies show that hypertonic fluids can effectively reduce ICP when standard therapies have failed.70-72 An increase in serum sodium concentrations to 145 to 155 mmol/L will reduce the mean ICP and decrease lateral displacement of the brain in patients with head trauma and postoperative edema.73 In patients with large hemispheric infarcts, treatment with hypertonic saline in hetastarch was found more effective in treating elevated ICP than mannitol.74 Complications of hypertonic saline therapy include diabetes insipidus, pulmonary edema, congestive heart failure, rebound edema and theoretically, increased mid-line shift.

Hyperventilation Hyperventilation decreases ICP because it causes vasoconstriction of the cerebral vessels and thereby decreases cerebral blood volume (CBV).75 Since hyperventilation causes vasoconstriction, it can exacerbate cerebral ischemia.76 Hyperventilation is the most effective treatment of acute herniation, but the efficacy of hyperventilation wanes quickly.77 Chronic hyperventilation also has been associated with worse outcome in clinical studies.78 Hyperventilation is most effective when CBF is hyperemic and should be done with SjvO2 (jugular vein O2 saturation) or AVDO2 (arterio-venous difference of O2) monitoring.79 Hyperventilation is best achieved by increasing the ventilatory rate to 16- 20/sec. The peak effect is achieved within 30 minutes. Once ICP is stabilized, hyperventilation should be tapered gradually over 6-12 hours to prevent rebound increase in ICP.

High dose Barbiturates
Barbiturates are often used to treat patients with refractory increase in ICP. Barbiturates decrease the CBF thereby reducing the CBV and ICP.80 Early experimental studies in stroke suggested that barbiturates may improve outcome, but a systematic review of these studies suggest that the benefit was primarily related to hypothermia.81 In a recent observational study in patients with large hemispheric infarcts barbiturate therapy did not improve clinical outcome.63 Its clinical utility is limited by systemic side effects, including hypotension and cardiac depression, and requires EEG monitoring. Use of barbiturate coma in stroke is not recommended based on the existing data.

Induced hypothermia
Small increases in core temperature can lead to significant increase in CMRO2.83 Induced hypothermia can be used to treat refractory elevations in ICP. During hypothermia CMRO2 is reduced there by decreasing the CBV and ICP.84 Hypothermia is found to be neuro-protective in experimental stroke models. Recently Schwab et al showed that hypothermia reduces mortality in large hemispheric strokes. It is also found to be of benefit in head injury patients.85

Hemodilution
Hemodilution therapy has been popularly used in stroke treatment especially in European countries. There are experimental evidences that moderate isovolemic hemodilution increase CBF and decrease infarct volume,86,87 but in prospectively randomized controlled trials hemodilution failed to improve clinical outcome.88,89

De-compressive surgery
Malignant MCA Infarction : The rationale of decompressive surgery is to allow expansion of the edematous tissue away from the lateral ventricle, the diencephalon and the mesencephalon, to reduce ICP, to increase perfusion pressure and to preserve CBF by preventing further compression of the collateral vessels. These factors may help to increase CBF in areas surrounding ischemic regions, thereby preventing further brain tissue necrosis. In large prospective uncontrolled case series, surgical decompressive therapy in hemispheric spaceoccupying infarction lowers mortality from roughly 80% down to 40% without increasing the rate of severely disabled survivors.61 Early decompressive surgery (e.g. within the first 24 h after stroke onset) can reduce mortality even more pronouncedly.90 A prospective, multicentre study protocol has been recently developed and is now underway.

Cerebellar Infarction : Decompressive surgery is widely considered the treatment of choice for a spaceoccupying cerebellar infarction, although the scientific basis for this is by no means any more solid than in hemispheric infarction. Comatose patients with space-occupying cerebellar infarctions have a mortality of about 80% if treated conservatively. This high mortality can be lowered down to 30% if decompressive surgery is performed.91,92 Like in space-occupying supratentorial infarction, the operation should be performed before signs of herniation are present. The prognosis among survivors is very good, even if they were comatose when the operation was performed. Most of them regain a Barthel Index of 85 or higher. It should be noted, however, that these are the results of open, small or medium-sized case series, one of them prospective, but mostly retrospective. Data from controlled, randomized trials are lacking.

Temperature control
Fever is very common in neurointensive care units (NICU) affecting 30-60% of patients with ischemic stroke and intracerebral hemorrhage,93 SAH94 and head injury. Hyperthermia is a proven factor for cerebral injury in experimental models of focal and global cerebral ischemia95-97 and its harmful effect persists even if it appears days after the start of ischemia.98,99 The association between hyperthermia, early neurological deterioration, increased morbidity and mortality has also been documented in patients with acute stroke.100 Hyperthermia causes neuronal injury by several mechanisms.

The cause of post-stroke fever is unclear but in acute stages it is generally related to the stroke itself, CNS inflammation or due to the production of endogenous pyrogens. Fever in the later phases of stroke is usually due to infectious causes. Although it is generally accepted that fever should be reduced by aggressive measures the most effective method remains unclear. Two types of interventions can be used to reduce increased body temperature: Antipyretics (Acetoaminophen, aspirin and NSAIDS) and external cooling. Antipyretics act by lowering the hypothalamic set point which is increased in fever.101 Antipyretics are not effective in fever due to an impaired thermoregulatory mechanism. In such instances achieving a core temperature of 30oC requires invasive measures and has potential life threatening complications. Presently the most recommended method of external body cooling is aircirculating blankets, which is minimally invasive.102 Other methods of surface cooling is by ice packs, fans, water cooled blankets. Fever due to infectious causes responds to antipyretics combined with aggressive treatment with appropriate antibiotics.

Glucose metabolism
Both hyperglycemia and hypoglycemia can contribute to worsening of neuronal injury in acute ischemic stroke through several mechanisms.103-105 Experimental studies suggest that insulin-induced normoglycemia may improve stroke outcome.105 Hence monitoring of glucose level in diabetic stroke patients especially patients on steroids becomes an important task in intensive care units.106 Aggressive attempts to normalize blood glucose levels are recommended especially because combination of insulin and glucose improves substrate delivery to ischemic tissue.107 A target blood glucose level of <200mg/dl is achieved by administering insulin by sliding scale coverage. If it fails a continuous infusion may be necessary.

Nutrition
Brain injured patients are hypermetabolic and hypercatabolic. Therefore, adequate nutritional support is important for their recovery.108,109 If a patient is unable to eat safely, enteral feeding should be initiated as soon as possible via a nasogastric tube. Gastric feeding, although the commonest route often, results in inadequate nutritional support due to delayed gastric emptying. The ideal enteral formula should contain adequate caloric intake (25 to 30 Kcal/Kg/day) and avoid hypo-osmolarity and hyperglycemia.109 To prevent reflux and aspiration during tube feeding, elevating the head of the bed, monitoring gastric residuals and administering metoclopramide (10mg per tube every 6 hours) are usually effective. Some patients with persistent delayed gastric emptying will need feedings into the small bowel. Jejunal feeding is well tolerated and it enables early, within 72 hours, a high caloric intake and better nitrogen balance while preventing regurgitation and aspiration.110 Tube feedings along with sucralfate or histamine-2 blockers are used to prevent stress ulcers.111,112 Care must be taken to avoid giving sucralfate at the same time as phenytoin because it will interfere with phenytoin absorption.

Sedation
Agitation is common in acute stroke.113 Oxygen consumption is increased in such patients. Short acting or easily reversible analgesic and anxiolytic should be used so that clinical examination can be performed. Propofol is the preferred drug of choice.114 However short acting benzodiazepins like midazolam can also be used.115 These drugs do not affect ICP, CPP, and CMRO2. Propofol actually reduces ICP and CMRO2.116

Deep venous thrombosis (DVT) prophylaxis
An autopsy series of 101 patients with neurologic disorders found a 24.8% incidence of pulmonary embolism (PE).117 Stroke patients are at high risk for DVT and subsequent PE due to their immobility and advanced age. Pneumatic compression boots decrease the incidence of DVTs but not PE in neurosurgical patients,118 and should be used on all patients until they are mobile. The combination of pneumatic compression boots and low-dose heparin may decrease the incidence of PE.119 Therefore, patients at low risk of hemorrhagic complications, such as those with ischemic stroke, should also be administered low dose heparin (5000u SC bid). Neurologic contraindications for subcutaneous heparin include intracranial hemorrhage (relative), unprotected intracerebral aneurysm and hematomyelia.117

Fluid and electrolyte management
Stroke patients should have a balanced fluid and electrolyte status to avoid plasma volume contraction, raised hematocrit and impairment of blood rheology (sludging). Uncontrolled volume replacement leads to pulmonary edema, cardiac failure and cerebral edema. In such instances a central venous catheter is mandatory. Serious electrolyte abnormalities are rare in stroke. Hyponatremia may occur due to SIADH (Syndrome of inappropriate secretion of anti diuretic harmone) or due to excess release of atrial natriuretic factor (ANF).120 Cerebral salt wasting (CSW) syndrome is due to centrally mediated renal sodium wasting.121,122 Existence of CSW syndrome remains controversial.123 The relation between hyponatremia, natriuresis and volume depletion is emphasized by many studies.121,124 SIADH is managed by fluid restriction or hypertonic saline, whereas normovolemia should be maintained along with oral salt supplementation if excess ANF is suspected.

Nosocomial infections
There are very few studies on the prevalence and incidence of nosocomial infections in neurointensive care units. The reported incidence varies.125 Review of the available literature from India shows an incidence of 18-39 %.126,127 Stroke patients are at high risk for silent aspiration, with pneumonia contributing to 34% of stroke deaths.128 Careful evaluation of cough and gag reflexes and a thorough swallowing is essential. Antibiotics are only recommended if the patient develops signs and symptoms of infection.129 Intubated patients have 7- 21 fold higher rate of pneumonia.130,131 The common organisms are staphylococcus, pseudomonas, enterobacter and klebsiella. Initial antibiotics recommended are a combination of third generation cephalosporins and aminoglycoside. Urinary tract infections are the commonest nosocomial infections with a reported incidence of 30-40%.132 Indwelling catheter increases the risk by 4-7 times.133 Commonest organisms are gram-negative aerobic bacilli and they are usually polymicrobial, followed by the fungi. Blood stream infections are also common in ICU set up. They are often due to coagulase negative staphylococcus followed by gramnegative organisms and candida. Nosocomial septicemia increases the risk of fatality by 25-50%.134 Empirical treatment should include vancomycin plus third generation cephalosporins, pending the culture report.

Decubitus ulcers
Frequent turning of immobilized patients is useful for prevention of pressure sores. The skin of the incontinent patient must be kept dry. Air or fluid filled mattress system should be used. If the decubitus ulcers does not respond to conservative therapy antibiotic therapy may be given for several days preceding surgical debridement.

Pharmacotherapy of acute ischemic stroke

Platelet inhibitors : The results of two large randomized, non blinded intervention studies, namely International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST)135,136 indicate that aspirin given within 24-48 hours after stroke seems to significantly reduce mortality and rate of recurrent stroke. The positive effect of aspirin may be due to its effect on the infarct itself or due to prevention of recurrent infarction or because of anti inflammatory effect of aspirin. Use of heparin, low molecular heparin or heparinoids in treatment of acute stroke is not recommended, because several studies failed to show an overall benefit (IST, The TOAST publication Committee).135,137 Little benefit even if observed was counterbalanced by increased number of hemorrhagic complications. Treatment of stroke in progression depends on an understanding of the pathophysiology of the stroke and the mechanism of progression, whether due to progressive thrombosis or progressing edema. Anticoagulation is considered the standard therapy for stroke caused by basilar artery thrombosis or stenosis and arterial dissections, although there is little evidence to support its use in either situation.

Thrombolytic therapy : Thrombolytic therapy with rtPA (0.9 mg/kg body weight) given within 3 hours after stroke onset is the recommended treatment of acute ischemic stroke.46 Intra-arterial treatment of acute middle cerebral artery occlusion in a 6-hour window period using pro-urokinase has also been shown to result in significantly improved outcome.138

Conclusion

Most patients with acute stroke do not require ICU care. It is essential to identify those patients who need close hemodynamic and airway monitoring. Patients who are likely to deteriorate and those receiving thrombolytic therapy should be admitted in ICU. As the treatment and prognosis in stroke patients are codetermined by underlying and associated systemic diseases these problems should be treated with appropriate medical therapies. Complications, which arise in ICU, should be identified and treated accordingly, to ensure better outcome. Thrombolysis with intravenous rtPA within 3 hours is recommended for suitable patients of ischemic stroke. In nonthrombolysed patients, Aspirin administered within 24-48 hours of stroke onset is the recommended treatment.

References

  1. Stroke - units Trialists Collaboration : Systematic review of the randomized trials of organized inpatient (Stroke Unit) Care after stroke BMJ 1997; 314 : 1151-1159.
  2. Borel CO, Guy J : Ventilatory management in critical neurologic illness. Neurol Clin 1995; 13 : 627-644.
  3. Deibert E, Diringer MN : The intensive care management of acute ischemic stroke. The Neurologist 1999; 5 : 313-325.
  4. Mayer SA, Boden-Albala B, Bernadini GL et al : Intubation for life threatening stroke : A population based study (abstract). Neurology 1997; 48 : A367.
  5. El-Ad B, Bornstein NM, Fuchs P et al : Mechanical ventilation in stroke patients : Is it worthwhile? Neurology 1996; 47 : 657-659.
  6. Cruz-Flores A, Thimpson DW, Burch CM et al : Outcome of patients with ischemic stroke requiring mechanical ventilation (abstract). Neurology 1997; 48 : A307.
  7. Ludwigs UG, Bachrendtz S, Wanecek M et al : Mechanical ventilation in medical and neurological diseases : 11 years of experience. J Intern Med 1991; 229 : 798-802.
  8. Gotta J, Pasteur W, Khwaja G et al : Elective intubation for neurologic deterioration after stroke. Neurology 1995; 45 : 640-644.
  9. Gujjar AR, Deibert E, Manno EM et al : Mechanical ventilation for ischemic stroke and intracerebral hemorrhage : Indications, timing, and outcome. Neurology 1998; 51 : 447-451.
  10. Steiner T, Mendoza G, De Georgia M et al : Prognosis of stroke patients requiring mechanical ventilation in a neurological critical care unit. Stroke 1997; 28 : 711-715.
  11. Diringer MN : Intracerebral hematoma: pathophysiology and management. Crit Care Med 1993; 21 : 1591-1603.
  12. Makela JP, Livanainen M, Pieninkeroinen IP et al : Seizures associated with propofol anesthesia. Epilepsia 1993; 34 : 832-835.
  13. Surherland MJ, Burt P : Propofol and seizures. Anaesth Intensive Care 1994; 22 : 733-737.
  14. Schramm WM, Strasser K, Bartunek A et al : Effects of rocuronium and vecuronium on intracranial pressure, mean arterial pressure and heart rate in neurosurgical patients. Br J Anaesth 1996; 77 : 607-611.
  15. Shibutani T, Hirota Y, Niwa H et al : Cerebral arterial blood flow velocity during induction of general anesthesia: Rapid intravenous induction versus awake intubation. Anesth Prog 1993; 40 : 122-126.
  16. Marina PL : The ICU book. 2nd ed. Baltimore: Williams and Wilkens 1998.
  17. Burchiel KJ, Steege TD, Wyler AR : Intracranial pressure changes in brain-injured patients requiring positive endexpiratory pressure ventilation. Neurosurgery 1981; 8 : 443- 449.
  18. Cooper KR, Boswell PA, Choi SC : Safe use of PEEP in patients with severe head injury. J Neurosurg 1985; 63 : 552-555.
  19. Powers W : Acute hypertension after stroke. The scientific basis for treatment decisions. Neurology 1993; 43 : 61-71.
  20. Schrader J, Rothemeyer M, Luders S et al : Hypertension and stroke - rationale behind the ACCESS trial. Basic Res Cardiol 1998; 93(Suppl 2) : 69-78.
  21. Ringleb PA, Bertram M, Keller E et al : Hypertension in patients with cerebrovascular accident. To treat or not to treat. Nephrol Dial Transplant 1998;13 : 2179-2181.
  22. Mzimba ZS, Beevers DG, Lip GYH : Antihypertensive therapy before, during and after stroke. Basic Res Cardiol 1998; 93 (Suppl 2) : 59-62.
  23. Spence DJ, DelMaestro RF : Hypertension in acute ischemic strokes. Treat. Arch Neurol 1985; 42 : 1000-1002.
  24. Yatsu FM, Zivin J : Hypertension in acute ischemic strokes. Not to treat. Arch Neurol 1985; 42 : 999-1000.
  25. Britton M, Carlsson A, deFaire U : Blood pressure course in patents with acute stroke and matched controls. Stroke 1986; 17 : 861-864.
  26. Wallace JD, Levy LL : Blood pressure after stroke. JAMA 1981; 246 : 2177-2180.
  27. Morfis L, Schwartz RS, Poulos R et al : Blood pressure changes in acute cerebral infarction and hemorrhage. Stroke 1997; 28 : 1401-1405.
  28. Britton M, Carlsson A : Very high blood pressure in acute stroke. J Intern Med 1990; 228 : 611-615.
  29. Harper G, Fotherby MD, Panayiotou BJ et al : The changes in blood pressure after acute stroke: abolishing the 'white coat effect' with 24-h-ambulatory monitoring. J Intern Med 1994; 235 : 343-346.
  30. O'Connell JE, Gray CS : Treating hypertension after stroke. BMJ 1994; 3081 : 523-524.
  31. Okada Y, Yamaguchi T, Minematsu K et al : Hemorrhagic transformation in cerebral embolism. Stroke 1989; 20 : 598- 603.
  32. Shields RW JR, Laureno R, Lichman T et al : Anticoagulantrelated hemorrhage in acute cerebral embolism Stroke 1984; 15 : 426-437.
  33. Strandgaarad S, Olesen J, Skinhoj E et al : Autoregulation of brain circulataion in severe arterial hypertension. BMJ 1973; 1 : 507-510.
  34. Chamorro A, Vila N, Ascaso C et al : Blood pressure and functional recovery in acute ischemic stroke. Stroke 1998; 29 : 1850-1853.
  35. Bourestom NC : Predictors of long term recovery in cerebrovascular disease. Arch Phys Med Rehab 1967; 48 : 415-419.
  36. Marquarsden J : The natural history of acute cerebrovascular disease; a retrospective study of 796 patients. Acta Neurol Scand 1969; 45(S38) : 192.
  37. Carlberg B, Asplund K, Hagg E : The prognostic value of admission blood pressure in patients with acute stroke. Stroke 1993; 24 : 1372-1375.
  38. Wollner L, McCarthy ST, Soper NDW et al : Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly. BMJ 1979; 1 : 1117-1118.
  39. Fieschi C, Angnoli A, Battistini N et al : Derangement of regional cerebral blood flow and of its regulatory mechanisms in acute cerebrovascular lesions. Neurology 1968; 18 : 1116-1179.
  40. Meyer JS, Shimazu K, Fukuuchi Y et al : Impaired neurogenic cerebrovascular control and dysautoregulation after stroke. Stroke 1973; 4 : 169-186.
  41. Astrup J, Siesjo B, Symon L : Thresholds in cerebral ischemia: the ischemic penumbra. Stroke 1981; 12 : 723- 725.
  42. Wahlgren NG, MacMahon DG, DeKeyser J et al : Intravenous Nimodipine West European Stroke Trial (INWEST) of nimodipine in the treatment of acute stroke. Cerebrovasc Dis 1994; 4 : 204-210.
  43. Squire IB, Lees KR, Pryse-Philips W et al : The effects of lifarizine in acute cerebral infarction: a pilot safety study. Cerbrovasc Dis 1996; 6 : 156-160.
  44. Lisk DR, Grotta JC, Lamki LM et al : Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography. Arch Neurol 1993; 50 : 855-862.
  45. Adams HP JR, Brott TG, Crowell RM et al : Guidelines for the management of patients with acute ischemic stroke. A statement for health care professionals from a special writing group of the Stroke Council, American Heart Associataion. Stroke 1994; 25 : 1901-1914.
  46. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333 : 1581- 1587.
  47. Paulson OB, Jarden JO, Goftfredsen J et al : Cerebral blood flow in patients with congestive heart failure treated with captopril. Am J Med 1984; 76 : 91-95.
  48. Walters MR, Bolster A, Dyker AG et al : Effect of perindopril on cerebral and renal perfusion in stroke patients with carotid disease. Stroke 2001; 32 : 473-478.
  49. Wise G, Sutter R, Burkholder J : The treatment of brain ischemia with vasopressor drugs. Stroke 1972; 3 : 135-140.
  50. Rordorf, Cramer SC, Efrid JT et al : Pharmacological elevation of blood pressure in acute stroke. Clinical effects and safety. Stroke 1997; 28 : 2133-2138.
  51. Davis TP, Alexander J, Lesch M : Electrocardiographic changes associated with acute cerebrovascular disease. A clinical review. Prog Cardiovasc Dis 1993; 36 : 245-260
  52. Oppenheimer SM, Hachinski V : The cardiac consequences of stroke. Neurologic Clinics 1992; 10 : 167-177.
  53. Chin PL, Kaminiski J, Rout M : Myocardial infarction coincident with cerebrovascular accidents in the elderly. Age Aging 1977; 6 : 29-37.
  54. Norris JW, Hachinski VC, Myers M et al : Serum Cardiac enzymes in stroke. Stroke 1979; 10 : 548-533.
  55. Oppenheimer SM : Neurogenic cardiac effects of cerebrovascular disease. Current Op Neurol 1994; 7 : 20-24.
  56. Wang T, Wu C, Lee Y : Myocardial stunning after cerebral infarction. Int J Cardiology 1997; 58 : 308-311.
  57. Norris JW, Frogatt GM, Hachinski VC : Cardiac arrhythmias in acute stroke. Stroke 1978; 4 : 392-396.
  58. Rem JA, Hachinski VC, Boughner DR et al : Value of cardiac monitoring and echocardiography in TIA and stroke patients. Stroke 1985; 16 : 950-956.
  59. Kessler DK, Kessler KM : Is ambulatory electrocardiography useful in the evaluation of patients with recent stroke? Chest 1995; 107 : 916-918.
  60. Hacke W, Schwab S, Horn M et al : Malignant middle cerebral artery territory infarction : Clinical course and prognostic signs. Arch Neurol 1996; 53 : 309-315.
  61. Ricke K, Schwab S, Krieger D et al : Decompressive surgery in space-occupying hemispheric infaraction: Results of an open, prospective trial. Crit Care Med 1995; 23 : 1576-1587.
  62. Frank JI : Large hemispheric infarction, deterioration, and intracranial pressure. Neurology 1995; 45 : 1286-1290.
  63. Schwab S, Spranger M, Schwarz S et al : Barbiturate coma in severe hemispheric stroke : Useful or obsolete? Neurology 1997; 48 : 1608-1613.
  64. Mixensberger J, Baunach S, Amschler J et al : Influence of body position on tissue-pO2, cerebral perfusion pressure and intraacranial pressure in patients with acute brain injury. Neurol Res 1997; 19(3) : 249-253.
  65. Feldman Z, Kanter MJ, Robertson CS et al : Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. J Neurosurg 1992; 76(2) : 207-211.
  66. Durward QJ, Amacher AL, Del Maestro RF et al : Cerebral and cardiovascular responses to changes in head elevation in patients with intracranial hypertension. J Neurosurg 1983; 59(6) : 938-944.
  67. Minton MD, Grosslight K, Stirt JA et al : Increases in intracranial pressure from succinylcholine: prevention by prior nondepolarizing blockade. Anesthesiology 1986; 65(2) : 165-169.
  68. Shackford SR : Fluid resuscitation in head injury. J Intensive Care Med 1990; 5 : 59-68
  69. Garcia-Sola R, Pulido P, Capilla P : The immediate and long-term effects of mannitol and glycetol: A comparative experimental study. Acta Neurochir 1991; 109 : 114-121.
  70. Hartl R, Ghajar J, Hochleuthner H et al : Hypertonic/hyperoncotic saline reliably reduces ICP in several head-injured patients with intracranial hypertension. Acta Neurochir Suppl 1997; 70 : 126-129.
  71. Horn P, Munch E, Vajkoczy P et al : Hypertonic saline solution for control of elevated intracranial pressure in patients with exhausted response to mannitol and barbiturates. Neurol Rea 1999; 21(8) : 758-764.
  72. Schatzmann C, Heissler HE, Koning K et al : Treatment of elevated intracranial pressure by infusions of 10% saline in severely head injured patients. Acta Neurochir Suppl 1998; 71 : 31-33.
  73. Qureshi AI, Suarez JI, Bhardwaj A et al : Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain. Crit Care Med 1998; 26(3) : 440- 446.
  74. Schwarz S, Schwab S, Bertram M et al : Effects of hypertonic saline hydroxyethyl starch solution and mannitol in patients with increased intracranial pressure after stroke. Stroke 1998; 29(8) : 1550-1555.
  75. Fortune JB, Feustel PJ, deLuna C et al : Cerebral blood flow and blood volume in response to O2 and CO2 changes in normal humans. J Trauma 1995; 39(3) : 463-471.
  76. Schneider GH, Sarrafzadeh AS, Kiening KL et al : Influence of hyperventilation on brain tissue-PO2, PCO2, and pH in patients with intracranial hypertension. Acta Neurochir Suppl 1998; 71 : 62-65.
  77. Muizelaar JP, van der Poel HG, Li ZC et al : Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit. J Neurosurg 1988; 69(6) : 923-927.
  78. Muizelaar JP, Marmarou A, Ward JD et al : Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 1991; 75(5) : 731-739.
  79. Ausina A, Baguena M, Nadal M et al : Cerebral hemodynamic changes during sustained hypocapnia in severe head injury: can hyperventilation cause cerebral ischemia? Acta Neurochir Suppl (Wien) 1998; 71 : 1-4.
  80. Miyauchi Y, Sakabe T, Maekawa T et al : Responses of EEG, cerebral oxygen consumption and blood flow to peripheral nerve stimulation during thiopentone anesthesia in the dog. Can Anaesth Soc J 1985; 32 : 491-498.
  81. Bleyaert AL, Nemoto EM, Safar P et al : Thiopental amelioration of brain damage after global ischemia in monkeys. Anesthesiology 1978; 49 : 390-398.
  82. Yatsu FM, Diamong I, Grazxiano C et al : Experimental brain ischemia: Protection from irreversible damage with a rapidacting barbiturate (methohexital). Stroke 1972; 3 : 726-732.
  83. Nilsson L, Kogure K, Busto R : Effects of hypothermia and hyperthermia on brain energy metabolism. Acta Anaesthesiol Scand 1975; 19(3) : 199-205.
  84. Rumana CS, Gopinath SP, Uzura M et al : Brain temperature exceeds systemic temperature in head-injured patients. Crit Care Med 1998; 26(3) : 562-567.
  85. Schwab S, Schwarz S, Aschoff A et al : Moderate hypothermia and brain temperature in patiens with severe middle cerebral artery infarction. Acta Neurochir Suppl 1998; 71 : 131-134.
  86. Cole DJ, Drummond JC, Shapiro HM et al : The effect of hypervolemic hemodilution with and without hypertension on cerebral blood flow following middle cerebral artery occlusion in rats anesthetized with isoflurane. Anesthesiology 1989; 71 : 580-585.
  87. Perez-Trepichio AD, Furlan AJ, Little JR et al : Hydroxyethyl starch 200/0.5 reduces infaract volume after embolic stroke in rats. Stroke 1992; 23 : 1782-1790.
  88. Haemodilution in acute stroke : Results of the Italian haemodilution trial. Italian Acute Stroke Study group. Lancet 1998; 1 : 318.
  89. Multicenter trial of hemodilution in acute ischemic stroke. Results in the total patient population. Scandinavian Stroke Study Group. Stroke 1987; 18 : 691.
  90. Schwab S, Steiner T, Aschoff A et al : Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke 1998; 29(9) : 1888-1893.
  91. Heros R : Surgical treatment of cerebellar infarction. Stroke 1992; 23 : 937-938.
  92. Rieke K, Krieger D, Adams HP et al : Therapeutic strategies in space-occupying cerebellar infarction based on clinical, neuroradiological and neurophysiological data. Cerebrovasc Dis 1993; 3 : 45-55.
  93. Georgilis K, Plomaaritoglou A, Dafni U et al : Aetiology of fever in patients with acute stroke. J Intern Med 1999; 246 : 203-209.
  94. Schwarz S, Hafner K, Aschoff A et al : Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology 2000; 54 : 354-361.
  95. Albrecht RF, Wass CT, Lanier WL : Occurrence of potentially detrimental temperature alterations in hospitalized patients at risk for brain injury. Mayo Clin Proc 1998; 73 : 629-635.
  96. Ginsberg MD, Sternau LL, Glubus MY-T et al : Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc Brain Metab Rev 1992; 4 : 189- 225.
  97. Meden P, Overgaard K, Pedersen H et al :The influence of body temperature on infarct volume and thrombolytic therapy in a rat embolic stroke model. Brain Res 1994; 647 : 131-138.
  98. Kim Y, Busto R, Dietrich WD et al : Delayed postischemic hyperthermia in awake rats worsens the histopathological outcome of transient focal cerebral ischemia. Stroke 1996; 27 : 2274-2281.
  99. Baena RC, Busto R, Dietrich WD et al : Hyperthermia delayed by 24 hours aggravates neuronal damage in rata hippocampus following global ischemia. Neurology 1997; 48 : 768-773.
  100. Reith J, Jorgensen HS, Pedersen PM et al : Body temperature in acute stroke: relations to stroke severity, infarct size, mortality, and outcome. Lancet 1996; 347 : 422-425.
  101. Holtzclaw BJ : The febrile response in critical care: state of the science. Heart Lung 1992; 21 : 482-501.
  102. Mayer SA, Commichau C, Scarmeas N et al : Clinical trial of an air-circulating cooling blanket for fever control in critically ill neurologic patients. Neurology 2001; 56 : 292-298.
  103. Sieber FE, Traystman RJ : Special issues : Glucose and the brain. Crit Care Med 1992; 20 : 104-114.
  104. Yip PK, He YY, Hsu CY et al : Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. Neurology 1991; 41 : 899-905.
  105. Warner DS, Gionet TX, Todd MM et al :Insulin-induced normoglycemia improves ischemic outcome in hyperglycemic rats. Stroke 1992; 23 : 1775-1780.
  106. Wass CT, Lanier WL : Glucose modulation of ischemic brain injury: Review and clinical recommendataions. Mayo Clin Proc 1996; 71 : 801-811.
  107. Lazar HL : Enhanced preservation of acutely ischemic myocardium and improved clinical outcomes using glucoseinsulin- potassium (GIK) solutions. Am J Cardiol 1997; 80 : 90A.
  108. Young B, Ott L, Norton J et al :The metabolic and nutritional sequela of the non-steroid treated head injury patient. Neurosurgery 1985; 17 : 784-791.
  109. Gadisseux P, Ward JD, Young HF et al : Nutrition and the neurosurgical patient. J Neurosurg 1984; 60 : 219-232.
  110. Graham T, Zadrozny R, Harrington T : The benefits of early jejunal hyperalimentation in the head injured patient. Neurosurgery 1989; 25 : 729-735.
  111. Pingleton SK, Hadzima KD : Enteral alimentation and gastrointestinal bleeding in mechanically ventilated patients. Crit Care Med 1983; 11 : 13-16.
  112. Cannon LA, Heiselman D, Gardner W et al : Prophylaxis of upper gastrointestinal bleeding in mechanically ventilated patients : A randomized study comparing the efficacy of surcralfate, cimetidine and antacids. Arch Intern Med 1987; 147 : 2101-2106.
  113. Henon H, Lebert F, Durieu I et al : Confusional state in stroke : Relataion to preexisting dementia, patient characteristics and outcome. Stroke 1999; 30 : 773-779.
  114. Sanchez-Izquierdo-Riera JA, Caballero-Cubedo RE, Perez- Vela JL et al : Propofol versus midazolam : Safety and efficacy for sedating the severe trauma patient. Anesth Anag 1998; 86 : 1219-1224.
  115. Papazian L, Albanese J, Thirion X et al : Effect of bolus doses of midazolam on intracranial pressure and cerebral perfusion pressure in patients with severe head injury. Br J Anaesth 1993; 71 : 267-271.
  116. Kelly DF, Goodale DB, Williams J et al : Propofol in the treatment of moderate and severe head injury : A randomized, prospective double-blinded pilot trial. J Neurosurg 1999; 90 : 1042-1052.
  117. Hamilton MG, Hull RD, Pineo GF : Venous thromboembolism in neurosurgery and neurology patients: A review. Neurosurgery 1994; 34 : 280-296.
  118. Black PM, Baker MF, Snook CP : Experience with external pneumatic calf compression in neurology and neurosurgery. Neurosurgery 1986; 18 : 440-444.
  119. Frim DM, Barker FG, Poletti CE et al : Postoperative low dose heparin decreases thromboembolic complications in neurosurgical patients. Neurosurgery 1992; 30 : 830-833.
  120. Diringer M, Ladenson P, Stern B et al : Plasma atrial natriuretic factor and subarachnoid hemorrhage. Stroke 1988; 19 : 1119-1124.
  121. Cort JH : Cerebral salt wasting. Lancet 1954; 1 : 752-754.
  122. Peter JP, Welt LG, Sims EAH : A salt-wasting syndrome associated with cerebral disease. Trans Assoc Am Physicians 1950; 63 : 57-64.
  123. Diringer MN, Ladenson PW, Borel C et al : Sodium and volume regulation in a patient with cerebral salat wasting. Arch Neurol 1989; 42 : 928-930.
  124. Oh MS, Carroll HJ : Disorders of sodium metabolism: hypernatremia and hyponatremia. Crit Care Med 1992; 20 : 94-103.
  125. Reigler R, Schmutzhard E, Skladal D et al : Nosokomiale infekitonen bei neurologischen intensivpatienten. Eine retrospective klinische und epidemiologische analyse. Antibiotic Monitor (Austra) 1990; 6 : 93-95.
  126. Basavakumar DG : Prospective study of post-operative infections in neurosurgery. Thesis submitted in partial fulfillment of regulations of M.Ch Degree in Neurosurgery. Bangalore University. 1989.
  127. Khanna N, Arunodaya GR, Umamaheshwar Rao GS et al : Infections in the Neurology / Neurosurgery ICU: A prospective study. Neurol India 1999; 47 (Suppl. 1) : 53.
  128. Roth EJ : Medical complications encountered in stroke rehabilitation. Phys Med Rehab Clin North Am 1991; 2 : 563-578.
  129. Bartlett JG, Breiman RF, Mandell LA et al : Communityacquired pneumonia in adults: Guidelines for management. The Infectious Diseases Society of America. Clin Infect Dis 1998; 26 : 811-838.
  130. Cravin DE, Steger KA, Barber TW : Preventing nosocomial pneumonia: State of the art and perspectives for the 1990s. Am J Med 1991; 91 : 44S-53S.
  131. Craven DE, Steger KA : Nosocomial pneumonia in mechanically ventilated adult patients: Epidemiology and prevention in 1996. Semin Respir Infect 1996; 11 : 32-53.
  132. Stamm WE, Hooten TM : Management of urinary tract infection in adults. N Engl J Med 1993; 329 : 1328-1334.
  133. Amin M : Antibacterial prophylaxis in urology: a review. Am J Med 1992; 92(Suppl 4A) : 114-117.
  134. Pittet D, Tarara D, Wenzel RP : Nosocomial bloodstream infection in critically ill patients. JAMA 1994; 271 : 1598- 1601.
  135. International Stroke Trial Collaborative Group : The International Stroke Trial (IST): A randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997; 349 : 1569-1581.
  136. Chinese Acute Stroke Trial (CAST) : Randomised placebocontrolled of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1999; 349 : 1641-1649.
  137. The TOAST Publication Committee: Low molecular weight heparinoid, ORG 10172 and outcome after acute ischemic stroke. JAMA 1998; 279 : 1265-1272.
  138. Furlan A, Higashida R, Wechsler L et al : Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. Jama 1999; 282 : 2003-2011.

Copyright 2002 - Neurology India. Also available online at http://www.neurologyindia.com

The following images related to this document are available:

Photo images

[ni02161t3.jpg] [ni02161t4.jpg] [ni02161t1.jpg] [ni02161t2.jpg]
Home Faq Resources Email Bioline
© Bioline International, 1989 - 2024, Site last up-dated on 01-Sep-2022.
Site created and maintained by the Reference Center on Environmental Information, CRIA, Brazil
System hosted by the Google Cloud Platform, GCP, Brazil