Swanson has reviewed several trials evaluating heparin (including the International Stroke Trial and the TOAST study) and suggested that there was no net benefit from heparin in acute stroke because of an excess of cerebral hemorrhages. However, in these series there was a low incidence, estimated as 2 percent, of recurrent stroke in the first weeks after a cerebral infarction in the untreated groups. An early recurrent stroke rate this low almost precludes demonstrating a benefit from the use of heparin or heparinoid drugs. The issue of administering heparin or low molecular weight heparin subcutaneously in cases of recent cardioembolic cerebral infarction, particularly as a “bridge,” while waiting for the effects of an oral anticoagulant to be established is addressed further on. Heparin is also used by some practitioners in stuttering small vessel lacunar stroke but the effects are uncertain.
In the event heparin is used, and assuming tPA has not been used in the preceding 24 h, heparin may be given intravenously, beginning with a bolus of 100 U/kg followed by a continuous drip (1,000 U/h) and adjusted according to the partial thromboplastin time (PTT). Bleeding into any organ may occur when the PTT is greater than 3 times the pretreatment level. When the PTT exceeds 100 s, it is preferable to discontinue the infusion, check the blood clotting values, and then reinstitute the infusion at a lower rate based on the test results (rather than simply lower the infusion rate). In circumstances of fluctuating basilar artery ischemia, it is our practice to permit higher values of PTT.
The use of low-molecular-weight heparin (enoxaparin or nadroparin) given subcutaneously within the first 48 h of the onset of symptoms have uncertain benefit. In a limited trial, there was no increase in the frequency of hemorrhagic transformation of the ischemic region when compared to placebo treatment (Kay et al). Because the outcome measures in this study were coarse (death or dependence 6 months after stroke), further investigations of this approach need to be carried out. We can only infer that the use of low-molecular-weight heparins appears to be safe but there is no compelling evidence supporting their use in acute ischemic stroke.
Treatment of Brain Swelling (Edema) and Raised Intracranial Pressure After Ischemic Stroke (See Also Chap. 34)
In the first few days following massive cerebral infarction, brain edema of the necrotic tissue may threaten life. Most often this occurs with a complete infarction in the territory of the middle cerebral artery, that is, encompassing the deep and distal vascular territory. Some degree of mass effect may be evident on a CT in the first 24 h. Additional infarction in the territory of the anterior cerebral artery (total carotid occlusion) worsens the situation. Clinical deterioration occurs usually on the third to fifth days, sometimes later, but may rarely evolve as quickly as several hours after the onset (Fig. 33-18). The clinical indicators of worsening—drowsiness, a fixed (but not necessarily enlarged) pupil, a Babinski sign on the side of the infarction (on the preserved side of the body), and changes in breathing pattern, as well as characteristic imaging signs—are all a result of secondary tissue shifts, as described in Chaps. 16 and 29 and are detailed in the studies of Hacke and colleagues (1996), and Ropper and Shafran. Frank has shown that clinical deterioration is not always associated with an initial elevation of intracranial pressure (ICP). It is not clear if it is advisable, in selected cases, to measure the ICP directly before embarking on an aggressive medical regimen to lower the pressure.