Nimodipine for Treating Acute Massive Cerebral Infarction
Nimodipine for Treating Acute Massive Cerebral Infarction
Massive cerebral infarction is an ischemic stroke caused by complete blockage of the internal
 carotid artery, middle cerebral artery, or their cortical branches. The widespread
 infarction, pathological severity and high fatality rate associated with massive cerebral
 infarction pose a major threat to affected patients. However, there is a lack of unified
 diagnostic criteria. Many researchers use Adams' classification, in which massive cerebral
 infarction is diagnosed when the following criteria are met: infarct size > 13 cm2; a major
 brain-feeding artery is involved; the focal site affects more than two cerebral lobes;
 infarct diameter line ≥ 3 cm in internal capsule of striatum.

 Prolonged cerebral ischemia/reperfusion can induce complex secondary changes in brain tissue,
 so the use of neuroprotective agents is very important. Remarkable progress has been made
 over the last decade in understanding the protective effect of calcium antagonists against
 cerebral ischemia. In particular, the liposoluble dihydropyridine Ca2+ antagonist nimodipine
 selectively acts on cerebral vessels and neurons and can protect ischemic brain tissue,
 providing a new way of treating ischemic cerebrovascular disease.

 Preclinical and clinical tests have shown that nimodipine has a protective effect on ischemic
 brain tissue, and indicate that patients should take the drug as soon as possible. However,
 there are no reports of double-blind, randomized, controlled clinical trials addressing the
 administration of nimodipine via intravenous drip within the time window for successful
 treatment of acute massive cerebral infarction.
In the clinic, physicians are reluctant to use thrombolysis, Defibrase and anticoagulation
 therapy because of the severity of symptoms, poor prognosis, risk of hemorrhage and high
 fatality rate that occur with acute massive cerebral infarction. Nimodipine, as a selective
 Ca2+ antagonist, is highly liposoluble, effectively crosses the blood-brain barrier,
 selectively acts on intracranial blood vessels, and is an accepted neuroprotective agent that
 can be applied in the clinic. The aim of the present study is to perform a double-blind,
 randomized and controlled trial of the clinical efficacy and safety of nimodipine
 administered as an intravenous drip in the early stages of acute massive cerebral infarction.

 Patients will receive nimodipine within 3 days of infarction onset. We will closely monitor
 the following: (1) Blood pressure and heart rate of the patient before treatment, since
 nimodipine is contraindicated in patients with hypotension and low heart rate. Where blood
 pressure is ≥ 100/80 mmHg and heart rate ≥ 60 BPM, nimodipine will be administered. (2) Speed
 of infusion. This should not be too fast; we suggest 1-2 drops per minute initially,
 increasing gradually until the drop in systolic pressure exceeds 10 mmHg. The average drip
 speed should be 6-8 drops/minute, and the fastest drip speed 10 drops/minute. (3) During the
 infusion, physicians should monitor adverse reactions such as headache, dizziness, flushing
 or sweating. If any occur, the infusion speed must be reduced. If the patients remain
 uncomfortable, nimodipine should be withdrawn. (4) Liver and kidney function should be
 monitored throughout nimodipine administration.

 Although nimodipine is relatively safe, there is still a risk of some adverse effects, such
 as cardiovascular system reactions (blood pressure decreases, bradycardia, angina, and
 atrioventricular block), headache, dizziness, edema, and liver and kidney dysfunction. It is
 necessary to determine the optimal therapeutic time window and dose of nimodipine in
 multi-center, large-scale clinical trials.
Inclusion Criteria:

 -  First onset at age ≤ 80 years, no other severe medical complications;

 -  Clear consciousness or mild disturbance of consciousness; paralysis of upper and lower
 extremities on one side with grade 0-3 muscle strength in paralyzed limbs;

 -  CT reveals early massive cerebral infarction (without cerebral hemorrhage or old
 infarction);

 -  Blood pressure within, or higher than, the normal range.

 Exclusion Criteria:

 -  Clinical manifestations are noticeably improved before treatment;

 -  Disorders of consciousness, manifesting as severe lethargy or coma;

 -  Mild neurological deficits, such as pure sensory disturbances, ataxia, dysarthria, and
 hemiparesis;

 -  Severe hypotension (systolic pressure < 90 mmHg, diastolic pressure < 60 mmHg);

 -  Heart rate < 60 BPM; sinus bradycardia;

 -  Severe heart, brain or kidney dysfunction, or malignant tumor.