Ischemic Penumbra and Ischemic Thresholds
Cortical potentials cease at 16-18 mL/100g/min, cell structure fails at 8-23 mL/100g/min. This also depends on duration – CBF of 18-23 mL/100g/min can be tolerated for two weeks, whereas 10-12 mL/100g/min can only be tolerated for 3 hours, and 8 mL/100g/min for one hour before neuronal death occurs [Acta Neurochir Suppl (Wien) 49: 2, 1990]
Several studies suggest that hyperglycemia exacerbates neuronal injury [Neurology 32: 1239, 1982; Am J Med 74: 540, 1983; Stroke 19: 764, 1988; Stroke 19: 185, 1988], although some studies of focal, permanent ischemic damage refute this [Stroke 18: 570, 1987; Stroke 20: 519, 1989]. Still, mild hypoglycemia may actually offer some neuronal protection during ischemia [Am J Med 74: 540, 1983; J Neurol Neurosurg Psychiatry 53: 847, 1990] and the idea of insulin as a neuroprotecting agent is gaining ground [Neurology 51S3: S39, 1998; J Neurol Neurosurg Psychiatry 53: 847, 1990]
Blood Pressure and Stroke
Blood pressure management in ischemic stroke is controversial – in most cases, BP will lower to normal levels within 48 hours [Stroke 17: 861, 1988]. In most cases, blood pressure should not be lowered, as this has repeatedly been shown to lead to neurologic decline [Stroke 25: 1901, 1994; Arch Neurol 50: 855, 1993; Neurology 43: 461, 1993; JAMA 246: 2177, 1981]. The major exception to this is patients who received thrombolytic therapy – they should be maintained at 185/100 or less. The other exception is in patients who are extremely hypertensive – MAPs > 130 or SBP > 200 should probably be treated [Stroke 25: 1901, 1994] although this has not been proven (a large, prospective, clinical trial is underway). Do NOT use nitroprusside as it may interfere with autoregulation and increase ICP [J Neurosurgery 48: 329, 1978; Anesthesiology 69: 870, 1988]
Induced hypertension was recently tested by Rordorf and colleagues [Stroke 28: 2461, 1998; Stroke 3: 135, 1971], who found that in 10 of 30 patients, neurologic deficits improved after phenylephrine administration. In a study of 19 patients in Germany, Levophed (norepinephrine) was used to raise MAP form 84 to 109 mm Hg – ICP increased from 11.6 to 11.8 mm Hg (p < 0.05), CPP rose from 72 to 97 (p < 0.0001), MCA velocity rose by 26 cm/s on the affected side and by 9 cm/s on the contralateral side [Stroke 33:998, 2002]
Hypotension after stroke is rare and the cause should be elucidated. Volume depletion is the most common cause but should not be assumed in all cases.
Edema and Stroke
15% of stroke patients will develop edema severe enough to cause a neurologic deterioration. Edema peaks between 3 and 5 days [Arch Neurol 41: 26, 1984]. Fixating on ICP is not advised, however, as only 26% of patients with large hemispheric strokes who deteriorate have ICP > 15 mm Hg. [Neurology 45: 1286, 1995]
Decompressive Craniectomy – Posterior Fossa and Malignant MCA
Cerebellar or other posterior fossa infarctions must be watched closely as deterioration can be rapid, and timely decompression can lead to excellent outcomes. [Stroke 23: 937, 1992; Stroke 13: 106, 1982; Stroke 23: 957, 1992]. Malignant MCA infarctions may also respond well to hemicraniectomy. [Stroke 29: 1888, 1998]
KEY POINT: Cushing’s Response
- Cushing’s Response is an APPROPRIATE response to elevated ICP.
- Antihypertensive therapy during Cushing’s response will prevent it from working effectively
Cerebral Blood Flow Measurements
Transcranial Dopplers use three windows – transtemporal (MCA, ACA, PCA), transorbital (OA, ICA. Note that flow reversal in the OA is a sign of proximal ICA occlusion), and transforamental (VA, VA). Remember that vasospasm is not the only cause of increased velocity – one must also consider fever, anemia, hypoxia, dominant vessels, and vasopressors. Pulsatility index = (S – D velocity)/(mean velocity) and is an indicator of flow resistance. The Lindegaard ratio is MCA/extracranial ICA velcities – values > 3 correlate with spasm. If the angle of the insonator is 15 degrees or more, velocity will be underestimated.
Cerebral Metabolism
AVDO2 and O2ER are inexpensive methods to assess cerebral metabolism. CMRO2 can increase 10% for every degree Celsius, and decrease 5% for every degree Celsius. Early hypothermia after traumatic brain injury has been shown in some studies to improve outcomes [NEJM 336: 540, 1997]. An AVDlactate/AVDO2 ratio > 0.8 is a reasonable indicator of increased anaerobic metabolism. [J Neurosurg 70: 222, 1989; Neurosurg Clin N Am 5: 633, 1994]
There are likely two ischemic states – the first, “compensated hypoperfusion” is characterized by low CBF and increased AVDO2 as well as O2ER. Ultimately the O2ER will reach its limit, at which point the second state arises, characterized by decreasing AVDO2 (as O2ER drops) as well as increased lactate production. As long as AVDlactate/AVDO2 ratio < 0.8, AVDO2 can predict the status of cerebral blood flow. [J Neurosurg 70: 222, 1989]
Several studies suggest that hyperglycemia exacerbates neuronal injury [Neurology 32: 1239, 1982; Am J Med 74: 540, 1983; Stroke 19: 764, 1988; Stroke 19: 185, 1988], although some studies of focal, permanent ischemic damage refute this [Stroke 18: 570, 1987; Stroke 20: 519, 1989]. Still, mild hypoglycemia may actually offer some neuronal protection during ischemia. [Am J Med 74: 540, 1983; J Neurol Neurosurg Psychiatry 53: 847, 1990] and the idea of insulin as a neuroprotecting agent is gaining ground. [Neurology 51S3: S39, 1998; J Neurol Neurosurg Psychiatry 53: 847, 1990]
Note that one third of TIAs will show evidence of cerebral infarction on MRI [Stroke 28: 1480, 1997; Stroke 34: 919, 2003]. Also, always keep in mind that half of stroke patients will have swallowing dysfunction [Lancet 362: 211, 2003]. Fever develops in 40% of cases, usually within 24 hours [J Int Med 246: 203, 1999; Stroke 32: 413, 2001] and the severity of fever correlates with the severity of stroke [Stroke 32: 413, 2001; Lancet 347: 422, 1996; Stroke 31: 410, 2000]. Seizures occur in 5% of stroke patients within 2 weeks [Arch Neurol 57: 1617, 2000]. MRI can diagnose 90% of strokes, and cardiac stents are NOT a contraindication. [JACC 42: 1295, 2003]
Aspirin following stroke reduces mortality by 1% and should be started the next day in patients given tPA or on the same day in the remainder [Lancet 362: 211, 2003, Lancet 349: 1641, 1997; Lancet 349: 1569, 1997]. Give 160-300 mg initially, and 75-150 mg qday afterwards.
Studies have shown that SBP < 130 mm Hg are associated by increased mortality [Stroke 37: 1565, 2006]. The ASA recommends treating BP 220/140 (or 185/110 in thrombolytics), although this appears to not be based on any data. Labetalol and nicardipine are the preferred agents as they preserve cerebral blood flow. [Stroke 34: 1056, 2003]
A retrospective study of 960 stroke patients showed that admission hyperglycemia >= 130 mg/dL was associated with a higher mortality rate (odds ratio = 3.15, p = 0.004). Persistent hyperglycemia for 48 hours was associated with even higher mortality rate (OR = 6.54, p < 0.001). Glycemic control was associated with a 4.6-fold decrease in mortality risk (p < 0.001). [Acad Emerg Med 13: 174, 2006]
Fever is known to be associated with worse outcome [Lancet 347: 422, 1996] and while the relationship is not necessarily causal.
Stroke Guidelines [Stroke 1997]
Controlled studies do NOT support the routine use of 3L/min oxygen by nasal cannula [191] but do support the maintenance of SpO2 at 92% or higher. [25, 192]
Increased body temperature is associated with higher mortality. However, there are no conclusive data showing an improvement in neurologic outcome after antipyretic medications. A review by Correia concluded that there is no evidence of hypothermia improving outcomes after stroke. [227]
While there are no data to support this, the general consensus remains that stroke patients should receive at least 24 hours of cardiac monitoring.
Both excessively elevated and lowered blood pressure are associated with increased mortality. Every 10 mm Hg above 180 mm Hg systolic increases the risk of neurologic deterioration by 40% and of poor outcome by 23%. A study of 115 Brazilian patients within 24 hours of stroke showed that lowering blood pressure increased adverse events, and that a 10% decline produced a odds ratio of 1.89 for unfavorable outcome [255]. Castillo studied 304 patients in Spain and found that drops of 20 mm Hg were associated with poor outcomes or death, and that early administration of antihypertensives for SBP > 180 was associated with marked increase in deterioration, poor outcome, and death [240]. The CHHIPS trial is currently evaluating blood pressure and stroke in a randomized, controlled setting. Until then, know that 185/110 is the cutoff for tPA eligibility, and that the ASA panel recommends treating blood pressure only if > 220/120. Remember, however, that uncontrolled hypertension is a major risk factor for stroke – when to start treating blood pressure is unknown. On the basis of the candesartan trial, it appears that medications can be started approximately one day after the stroke. [258]
Free Radical Scavengers Post-Brain Attack
Randomized, double-blind, placebo-controlled trial involving 1722 patients with acute ischemic stroke who were randomly assigned to receive a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours after the onset of the stroke. NXY-059 significantly improved the overall distribution of scores on the modified Rankin scale, as compared with placebo (p = 0.038 by the Cochran–Mantel–Haenszel test). Mortality and rates of serious and nonserious adverse events were each similar in the two groups. NXY-059 did not improve neurologic functioning as measured according to the National Institutes of Health Stroke Scale (NIHSS). Likewise, no improvement was observed according to the Barthel index (p = 0.14). In a post hoc analysis of patients who also received alteplase, NXY-059 was associated with a lower incidence of any hemorrhagic transformation (p = 0.001) and symptomatic intracranial hemorrhage (p = 0.036). [NEJM 354: 588, 2006]
