Nizofenone administration in the acute stage following subarachnoid hemorrhage

1986 ◽  
Vol 64 (3) ◽  
pp. 420-426 ◽  
Author(s):  
Tomio Ohta ◽  
Haruhiko Kikuchi ◽  
Kazuo Hashi ◽  
Yoshio Kudo
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Placebo Treatment ◽  
Clinical Findings ◽  
Acute Stage ◽  
Test Drug ◽  
Double Blind ◽  
Content Type ◽  
Significant Difference ◽  
Grade Ii ◽  
Fine Print

✓ A multi-center controlled double-blind clinical study was carried out to evaluate the effects of nizofenone in patients with subarachnoid hemorrhage who were treated within 2 weeks of the ictus. The test drug was administered as an addition to conventional therapy, which was maintained during the study. Of 208 patients studied, 102 were treated with nizofenone and 106 with placebo. Treatment with nizofenone was significantly more effective (p < 0.05) than that with placebo based on functional recovery and other clinical findings. Although no significant difference was found in mortality rate between the nizofenone- and placebo-treated groups, a higher percentage of survivors in the former group exhibited a good outcome (p < 0.05). The effects of nizofenone administration were found to be especially notable in patients with delayed ischemic symptoms, moderately severe preoperative deficits (Hunt and Hess Grade II or III), and diffuse high-density areas in preand postoperative computerized tomography scans. No significant side effects were observed.

An experimental study of the acute stage of subarachnoid hemorrhage

1983 ◽  
Vol 59 (6) ◽  
pp. 917-924 ◽  
Author(s):  
Ken Kamiya ◽  
Hideyuki Kuyama ◽  
Lindsay Symon
Keyword(s):  
Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Acute Stage ◽  
Flow Measurements ◽  
Content Type ◽  
Baboon Model ◽  
Differential Increase ◽  
Blood Flow Measurements ◽  
Fine Print ◽  
Made In

✓ A baboon model of subarachnoid hemorrhage (SAH) has been developed to study the changes in cerebral blood flow (CBF), intracranial pressure (ICP), and cerebral edema associated with the acute stage of SAH. In this model, hemorrhage was caused by avulsion of the posterior communicating artery via a periorbital approach, with the orbit sealed and ICP restored to normal before SAH was produced. Local CBF was measured in six sites in the two hemispheres, and ICP monitored by an implanted extradural transducer. Following sacrifice of the animal, the effect of the induced SAH on ICP, CBF, autoregulation, and CO2 reactivity in the two hemispheres was assessed. Brain water measurements were also made in areas of gray and white matter corresponding to areas of blood flow measurements, and also in the deep nuclei. Two principal patterns of ICP change were found following SAH; one group of animals showed a return to baseline ICP quite quickly and the other maintained high ICP for over an hour. The CBF was reduced after SAH to nearly 20% of control values in all areas, and all areas showed impaired autoregulation. Variable changes in CO2 reactivity were evident, but on the side of the hemorrhage CO2 reactivity was predominantly reduced. Differential increase in pressure lasting for over 7 minutes was evident soon after SAH on the side of the ruptured vessel. There was a significant increase of water in all areas, and in cortex and deep nuclei as compared to control animals.

A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results

1993 ◽  
Vol 78 (4) ◽  
pp. 548-553 ◽  
Author(s):  
E. Clarke Haley ◽  
Neal F. Kassell ◽  
James C. Torner ◽  
_ _
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Doppler Ultrasound ◽  
Transcranial Doppler ◽  
Transcranial Doppler Ultrasound ◽  
High Dose ◽  
Content Type ◽  
Central Registry ◽  
Significant Difference ◽  
Fine Print ◽  
Flow Velocities

✓ Calcium antagonist drugs were proposed for use in patients with recent aneurysmal subarachnoid hemorrhage (SAH) because of their ability to block the effects of a wide variety of vasoconstrictor substances on cerebral arteries in vitro. It was suggested that these agents might, therefore, be useful in ameliorating cerebral vasospasm and its ischemic consequences which frequently complicate SAH. This hypothesis was tested in an arm of a randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine in patients with recently ruptured aneurysms. Participating investigators were required to send selected copies of all admission and follow-up angiograms obtained between Days 7 and 11 following hemorrhage (the peak period of risk for vasospasm) to the Central Registry of the Cooperative Aneurysm Study for blinded interpretation and review for the presence and severity of angiographic vasospasm. In centers with transcranial Doppler ultrasound (TCD) capabilities, middle cerebral artery (MCA) mean flow velocities were measured and recorded. Angiograms obtained between Days 7 and 11 were available for 103 (23%) of 449 patients receiving nicardipine and 121 (26%) of 457 receiving placebo. There was a balance of prognostic factors for vasospasm between the groups. Fifty-one percent of placebo-treated patients had moderate or severe vasospasm on “Day 7–11 angiograms” compared to 33% of nicardipine-treated patients. This difference is statistically significant (p < 0.01). Sixty-seven (49%) of 137 placebo-treated patients examined with TCD between Days 7 and 11 had mean MCA flow velocities exceeding 120 cm/sec compared to 26 (23%) of 112 nicardipine-treated patients (significant difference, p < 0.001). These data suggest that high-dose intravenous nicardipine reduces the incidence and severity of delayed cerebral arterial narrowing in patients following aneurysmal SAH.

No effect of enoxaparin on outcome of aneurysmal subarachnoid hemorrhage: a randomized, double-blind, placebo-controlled clinical trial

2003 ◽  
Vol 99 (6) ◽  
pp. 953-959 ◽  
Author(s):  
Jari Siironen ◽  
Seppo Juvela ◽  
Joona Varis ◽  
Matti Porras ◽  
Kristiina Poussa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Molecular Weight ◽  
Subarachnoid Hemorrhage ◽  
Low Molecular Weight Heparin ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Intracranial Bleeding ◽  
Low Molecular Weight ◽  
Double Blind ◽  
Content Type ◽  
Fine Print

Object. From the moment an intracranial aneurysm ruptures, cerebral blood flow is impaired, and this impairment mainly determines the outcome in patients who survive after the initial bleeding. The exact mechanism of impairment is unknown, but activation of coagulation and fibrinolysis correlate with clinical condition and outcome after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether enoxaparin, a low-molecular-weight heparin, which is a well-known anticoagulating agent, has any effect on the outcome of aneurysmal SAH postoperatively. Methods. In this randomized, double-blind, single-center clinical trial, 170 patients (85 per group) with aneurysmal SAH were randomly assigned to receive either enoxaparin (40 mg subcutaneously once daily) or a placebo, starting within 24 hours after occlusion of the aneurysm and continuing for 10 days. Analysis was done on an intention-to-treat basis. Outcome was assessed at 3 months on both the Glasgow Outcome and modified Rankin Scales. Patients were eligible for the study if surgery was performed within 48 hours post-SAH, and no intracerebral hemorrhage was larger than 20 mm in diameter on the first postoperative computerized tomography scan. At 3 months, there were no significant differences in outcome by treatment group. Of the 170 patients, 11 (6%) died, and only 95 (56%) had a good outcome. Principal causes of unfavorable outcome were poor initial condition, delayed cerebral ischemia, and surgical complications. There were four patients with additional intracranial bleeding in the group receiving enoxaparin. The bleeding was not necessarily associated with the treatment itself, nor did it require treatment, and there were no such patients in the placebo group. Conclusions. Enoxaparin seemed to have no effect on the outcome of aneurysmal SAH in patients who had already received routine nimodipine and who had received triple-H therapy when needed. Routine use of low-molecular-weight heparin should be avoided during the early postoperative period in patients with SAH, because this agent seems to increase intracranial bleeding complications slightly, with no beneficial effect on neurological outcome.

Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage

2000 ◽  
Vol 93 (6) ◽  
pp. 1014-1018 ◽  
Author(s):  
Toshiaki Hayashi ◽  
Akifumi Suzuki ◽  
Jun Hatazawa ◽  
Iwao Kanno ◽  
Reizo Shirane ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Circulation ◽  
Cerebral Blood Volume ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Metabolism ◽  
Aneurysm Rupture ◽  
Acute Stage ◽  
Content Type ◽  
Positron Emission ◽  
Fine Print

Object. The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further.Methods. The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia.Conclusions. The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO2 at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH.

Chronic subdural hematoma presenting as spontaneous subarachnoid hemorrhage

1985 ◽  
Vol 63 (5) ◽  
pp. 691-692 ◽  
Author(s):  
Zbigniew Kotwica ◽  
Jerzy Brzeziński
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Subdural Hematoma ◽  
Chronic Subdural Hematoma ◽  
Clinical Findings ◽  
Content Type ◽  
Acute Subarachnoid Hemorrhage ◽  
Spontaneous Subarachnoid Hemorrhage ◽  
Fine Print

✓ Six cases of chronic subdural hematoma presenting with the clinical findings of acute subarachnoid hemorrhage are reported. No systemic or focal cause for the bleeding was found, and possible mechanisms are discussed.

Nimodipine treatment in poor-grade aneurysm patients

1988 ◽  
Vol 68 (4) ◽  
pp. 505-517 ◽  
Author(s):  
Kenneth C. Petruk ◽  
Michael West ◽  
Gerard Mohr ◽  
Bryce K. A. Weir ◽  
Brien G. Benoit ◽  
...  
Keyword(s):  
Outcome Analysis ◽  
Double Blind ◽  
Content Type ◽  
Poor Grade ◽  
Good Outcome ◽  
Significant Difference ◽  
Delayed Neurological Deterioration ◽  
Repeat Angiography ◽  
Grade 3 ◽  
Fine Print

✓ A multicenter, randomized placebo-controlled double-blind trial of nimodipine in poor-grade aneurysm patients was carried out in 17 Canadian hospitals. Of 188 patients enrolled in the trial, 32 were excluded for protocol violations and two were excluded due to statistical considerations, leaving 154 patients for valid outcome analysis. Nimodipine treatment was associated with a significantly better outcome (p < 0.001): 21 (29.2%) of 72 nimodipine-treated patients had a good outcome at 3 months after subarachnoid hemorrhage (SAH) compared to eight (9.8%) of 82 placebo-treated patients. Delayed ischemic deficits from vasospasm alone were significantly less frequent in the nimodipine group (p < 0.05) with permanent deficits occurring in five nimodipine-treated patients (6.9%) and in 22 placebo-treated patients (26.8%). Improvement in the good outcome rate and reduction in delayed ischemic deficits from vasospasm alone occurred in both Grade 3 and 4 patients, with no difference between nimodipine- and placebo-treated patients being found in Grade 5 patients. Repeat angiography after Day 4 was carried out in 124 patients. There was no significant difference in the incidence of moderate or severe diffuse spasm, which was seen in 64.3% of nimodipine-treated patients and 66.2% of placebo-treated patients. The authors conclude that nimodipine treatment in poor-grade patients with SAH results in an increase in the number of good outcomes and a reduction in the incidence of delayed neurological deterioration due to vasospasm. This effect occurs by a mechanism other than prevention of large-vessel spasm as visualized on angiography.

Intracranial vertebral artery dissection with subarachnoid hemorrhage: clinical characteristics and outcomes in conservatively treated patients

2004 ◽  
Vol 101 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Masaru Yamada ◽  
Takao Kitahara ◽  
Akira Kurata ◽  
Kiyotaka Fujii ◽  
Yoshio Miyasaka
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Conservative Treatment ◽  
Vertebral Artery ◽  
Vertebral Artery Dissection ◽  
Delayed Diagnosis ◽  
Acute Stage ◽  
Artery Dissection ◽  
Content Type ◽  
String Structure ◽  
Fine Print

Object. Intracranial vertebral artery (VA) dissection with subarachnoid hemorrhage is notorious for frequent rebleeding and a poor prognosis. Nevertheless, some patients survive with a good final outcome. The factors associated with the prognosis of this disease are not fully understood and appropriate treatment strategies continue to be debated. The authors retrospectively evaluated the clinical features of conservatively treated patients to elucidate the relationship between the clinical and angiographic characteristics of the disease and final outcomes. Methods. This study includes 24 patients who were treated by conservative methods between 1990 and 2000. Conservative treatment was chosen because of delayed diagnosis, poor clinical condition, or anatomical features such as bilateral lesions and contralateral VA hypoplasia. Of nine patients with an admission Hunt and Kosnik Grade I or II, eight had good outcomes (mean follow-up period 8 years and 4 months). All 15 patients with Grade III, IV, or V died and in 10 of these the cause of death was rebleeding. Among the 24 patients, 14 suffered a total of 35 rebleeding episodes; in 10 (71.4%) of these 14 patients rebleeding occurred within 6 hours and in 13 (93%) within 24 hours. Compared with the survivors, there was a female preponderance (0.022) among patients who died. These patients also had significantly shorter intervals between onset and hospital admission (p = 0.0067), a higher admission Hunt and Kosnik grade (p = 0.0001), a higher incidence of prehospitalization (p = 0.0296) and postadmission (p = 0.0029) rebleeding episodes, and a higher incidence of angiographically confirmed pearl-and-string structure of the lesion (p = 0.0049). Conclusions. In our series of preselected patients, poor admission neurological grade, rebleeding episode(s), and lesions with a pearl-and-string structure were predictive of poor outcomes. Our findings indicate that patients with these characteristics may be candidates for aggressive attempts to prevent rebleeding during the acute stage. Patients without these characteristics may be good candidates for conservative treatment, especially those who survive the acute phase without rebleeding.

Timing of operation for ruptured supratentorial aneurysms: a prospective randomized study

1989 ◽  
Vol 70 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Juha Öhman ◽  
Olli Heiskanen
Keyword(s):  
Aneurysmal Subarachnoid Hemorrhage ◽  
Anterior Part ◽  
Controlled Trial ◽  
Randomized Study ◽  
Prospective Randomized Study ◽  
Double Blind ◽  
Content Type ◽  
Acute Surgery ◽  
Significant Difference ◽  
Fine Print

✓ A total of 216 patients with a ruptured aneurysm of the anterior part of the circle of Willis were enrolled into this prospective randomized study of timing of the operation after aneurysmal subarachnoid hemorrhage (SAH). Only patients in clinical Grades I to III (according to the classification of Hunt and Hess) who were admitted and randomly assigned to a treatment group within 72 hours after the SAH were included in the trial. The patients were randomly assigned to one of three operation groups: acute surgery (AS: 0 to 3 days after the SAH; day of SAH = Day 0), intermediate surgery (IS: 4 to 7 days after the SAH), or late surgery (LS: 8 days to an indefinite time after the SAH). Three patients (4.3%) in the IS group and six patients (8.6%) in the LS group died before surgery was undertaken. At 3 months post-SAH, 65 patients (91.5%) from the AS group were classified as independent compared to 55 (78.6%) from the IS group and 56 (80.0%) from the LS group. The management mortality rate in the AS group was 5.6% compared to 12.9% in the LS group. Of the 216 patients enrolled in the timing study, 159 were randomly assigned to an independent double-blind placebo-controlled trial of nimodipine in Grade I to III patients. A total of 79 patients received nimodipine and 80 placebo. When the nimodipine group and the no-nimodipine group (the 80 placebo-treated patients plus the 52 patients who were not entered into the nimodipine trial) were analyzed separately, a significant difference was seen in the outcome of the no-nimodipine group (dependent AS vs. dependent IS, p = 0.01). Nimodipine treatment was associated with a significant reduction of delayed ischemic deterioration (all operation groups combined, nimodipine vs. no nimodipine p = 0.01; LS with nimodipine vs. LS with no nimodipine, p = 0.03).

Relationship between hemispheric cerebral blood flow, central conduction time, and clinical grade in aneurysmal subarachnoid hemorrhage

1985 ◽  
Vol 62 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Jacob Rosenstein ◽  
Alexander Dah-Jium Wang ◽  
Lindsay Symon ◽  
Mikio Suzuki
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Initial Slope ◽  
Conduction Time ◽  
Clinical Grade ◽  
Content Type ◽  
Significant Difference ◽  
Fine Print

✓ The relationship between central conduction time (CCT) and hemispheric cerebral blood flow (CBF) has been examined in 20 patients presenting with subarachnoid hemorrhage. A total of 63 combined CCT/CBF recordings were performed at various times throughout the hospital course of these patients, and the findings were correlated to clinical status. The initial-slope index of the CBF (CBFisi) was found to correlate well with clinical grade, and a gradation in flow was noted between the different neurological grades. Patients in Grades I and II (Hunt and Hess classification) had the highest flows (mean CBFisi = 47.2 ± 8.1); Grade III patients had intermediate flows (mean CBFisi = 39.6 ± 7.8); and Grade IV patients had the lowest flows (mean CBFisi = 32.0 ± 6.4). While CCT tended to become increasingly prolonged with worsening grade, a significant difference could not be demonstrated between Grade I, II, and III patients. Only when Grade IV status was reached was the CCT significantly prolonged. When CBFisi and CCT were examined, a threshold relationship was noted between CBFisi and CCT prolongation. At flow values above 30, little change was noted in CCT, and CCT remained in the normal range. However, at flow values below 30, CCT became increasingly prolonged as blood flow diminished. The degree of CCT prolongation appeared to be directly proportional to the degree of blood flow diminution at flows below threshold.

Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study

2002 ◽  
Vol 97 (4) ◽  
pp. 771-778 ◽  
Author(s):  
Jan Hillman ◽  
Steen Fridriksson ◽  
Ola Nilsson ◽  
Zhengquan Yu ◽  
Hans Säveland ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Tranexamic Acid ◽  
Hospital Admission ◽  
Acid Treatment ◽  
Aneurysm Rupture ◽  
Clinical Findings ◽  
Ct Scans ◽  
Content Type ◽  
Fisher Grade ◽  
Fine Print

Object. By pursuing a policy of very early aneurysm treatment in neurosurgical centers, in-hospital rebleeds can be virtually eliminated. Nonetheless, as many as 15% of patients with aneurysm rupture suffer ultraearly rebleeding with high mortality rates, and these individuals are beyond the reach of even the most ambitious protocol for diagnosis and referral. Only drugs given immediately after the diagnosis of subarachnoid hemorrhage (SAH) has been established at the local hospital level can, in theory, contribute to the minimization of such ultraearly rebleeding. The object of this randomized, prospective, multicenter study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding. Methods. Only patients suffering SAH verified on computerized tomography (CT) scans within 48 hours prior to the first hospital admission were included. A 1-g dose of tranexamic acid was given intravenously as soon as diagnosis of SAH had been verified in the local hospitals (before the patients were transported), followed by doses of 1 g every 6 hours until the aneurysm was occluded; this treatment did not exceed 72 hours. In this study, 254 patients received tranexamic acid and 251 patients were randomized as controls. Age, sex, Hunt and Hess and Fisher grade distributions, as well as aneurysm locations, were congruent between the groups. Outcome was assessed at 6 months post-SAH by using the Glasgow Outcome Scale (GOS). Vasospasm and delayed ischemic neurological deficits were classified according to clinical findings as well as by transcranial Doppler (TCD) studies. All events classified as rebleeding were verified on CT scans or during surgery. Conclusions. More than 90% of patients reached the neurosurgical center within 12 hours of their first hospital admission after SAH; 70% of all aneurysms were clipped or coils were inserted within 24 hours of the first hospital admission. Given the protocol, only one rebleed occurred later than 24 hours after the first hospital admission. Despite this strong emphasis on early intervention, however, a cluster of 27 very early rebleeds still occurred in the control group within hours of randomization into the study, and 13 of these patients died. In the tranexamic acid group, six patients rebled and two died. A reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding with tranexamic acid treatment can therefore be inferred. Favorable outcome according to the GOS increased from 70.5 to 74.8%. According to TCD measurements and clinical findings, there were no indications of increased risk of either ischemic clinical manifestations or vasospasm that could be linked to tranexamic acid treatment. Neurosurgical guidelines for aneurysm rupture should extend also into the preneurosurgical phase to guarantee protection from ultraearly rebleeds. Currently available antifibrinolytic drugs can provide such protection, and at low cost. The number of potentially saved lives exceeds those lost to vasospasm.

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