Effects of intravascular volume expansion on cerebral blood flow in patients with ruptured cerebral aneurysms

To clarify the effect of intravascular volume expansion on cerebral blood flow (CBF) in patients after subarachnoid hemorrhage (SAH), we performed 55 pairs of regional CBF measurements using the xenon-133 inhalation method before and after volume expansion in 35 patients with ruptured cerebral aneurysms. CBF was calculated as the hemispheric mean value of the initial slope index. To accomplish volume expansion, we transfused 500 ml of 5% human serum albumin in half an hour. After volume expansion with albumin, the hemoglobin value decreased significantly (P less than 0.005). Volume expansion did not change the mean arterial blood pressure. During the first 2 weeks after SAH, CBF decreased significantly after volume expansion (P less than 0.005). During the 3rd week after SAH and subsequently to the 4th week after SAH, volume expansion produced no change in CBF. In patients with symptomatic vasospasm, CBF decreased significantly after volume expansion (P less than 0.005). In patients without symptomatic vasospasm, volume expansion produced no change in CBF. The results of this study suggest that increasing the intravascular volume above normal by volume expansion does not increase CBF or reverse symptomatic vasospasm.     

Altered cerebral autoregulation and CO2 reactivity after aneurysmal subarachnoid hemorrhage

Disruption of local cortical blood flow (CBF) autoregulation and CO2 reactivity, or vasoparalysis, has been documented in humans after aneurysmal subarachnoid hemorrhage (SAH). Generally, the degree of vasoparalysis is related to the patient's clinical grade. Using intraoperative measurement of local CBF, we evaluated pressure autoregulation and CO2 reactivity in patients after SAH. Fourteen patients with SAH and 10 patients with asymptomatic aneurysm underwent craniotomy for clipping of their aneurysms. During operation, local CBF was recorded with thermal conductivity probes placed on the middle frontal gyrus, 4 to 6 cm from the nearest point of retraction. Before retractor placement, CBF was measured with the PCO2 at 25 and 35 mm Hg and the mean arterial blood pressure (MABP) between 70 and 80 mm Hg. After aneurysm clipping, flows were again measured. With the PCO2 at 25 mm Hg, the MABP was raised from 65 to 85 mm Hg. The PCO2 was then allowed to rise to 35 mm Hg, after which the MABP was lowered from 85 to 65 mm Hg. Six patients underwent operation within the 1st week after SAH (Grade I, n = 3; Grade II, n = 3). The remainder (n = 8) were operated on 9 days to 3 months after SAH. After aneurysm clipping, significant CBF changes (P less than 0.001) with PCO2 alteration occurred in control patients and those operated on more than 7 days after SAH. There was no significant change in CBF in patients operated on within 7 days after SAH. Changes in CBF reactivity to alteration of MABP were significantly larger in early operation patients than in other groups (P less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sequential changes of cerebral blood flow after aneurysmal subarachnoid haemorrhage

Summary A total of 226 measurements of cerebral blood flow (CBF) were performed in 96 postoperative patients with aneurysmal subarachnoid haemorrhage (SAH). The global CBF was significantly reduced in the first week after SAH, and the extent of the CBF reduction was less in the patients with good outcome than in those with fair/ poor outcome. The good outcome patients showed a progressive increase in CBF in the following 3 weeks. Although the CBF decreased further in the second week in some of those patients, it turned to a steady increase thereafter. On the other hand, in the fair/poor outcome patients CBF remained far below the normal control value for at least 3 months after SAH. When looking into the effect of age on CBF in the patients with good outcome, those in their thirties and forties had a significantly reduced CBF during the first 2 weeks, whereas in those in their fifties and sixties a significant reduction persisted for 3 months to 1 year after SAH. Management of the older patients needs special attention even if they are apparently in good clinical condition, since the CBF threshold to ischaemia is diminished.     

Computed tomography in the diagnosis of hemorrhage secondary to intracranial aneurysm. (author's transl)

In 168 patients with ruptured intracranial aneurysms, the pathology of intracranial hemorrhage visualized on CT was analyzed. Blood in the subarachnoid space could be visualized in 95% of cases within three days after SAH and 75% of 106 cases within two weeks after SAH. In one case blood clot in the subarachnoid space visible up to 13 days after SAH. Concerning the cases within two weeks after the bleeding, intracerebral hematomas were observed in 36% of anterior cerebral aneurysms and middle cerebral aneurysms, 16% of internal carotid aneurysms and none of vetebro-basilar aneurysms. The incidence of the intraventricular hemorrhage was as follows; vertebro-basilar, 44%; anterior cerebral, 38%; internal carotid, 28%; middle cerebral, 12%. On the basis of the pattern of distribution of extravasated blood the location of the ruptured aneurysm was properly predicted in 58% of anterior cerebral, 81% of middle cerebral, 58% of internal carotid and 30% of vertebro-basilar. Especially CT could contribute to predict which aneurysm has ruptured in patients with multiple aneurysms. It was possible to localize the site of bleeding in 11 out of 12 CT positive cases. The development of intracranial hemorrhage demonstrated by CT well correlated with the clinical grading of the patients and the clinical outcome. Patients merely showing subarachnoid hemorrhage were more likely to have good neurological grades, but ones showing complicated intracerebral hematomas and intraventricular hemorrhage had poor neurological grades at the time of the scan. The findings of extensive subarachnoid clot, which were followed by severe vasospasm, and marked intraventricular hemorrhage, usually correlated with poor prognosis. These pathology recognizable on CT was very helpful in determination of the timing of surgery and management of such patients. In conclusion CT is of great value in the examination of SAH when performed in the acute stage and should be the initial examination followed by angiography.     

Postoperative central conduction time and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage: Relationship with prognosis and ischemic conditions

Cerebral blood flow (CBF) and somatosensory evoked potential (SEP) were monitored periodically on 32 patients who underwent aneurysm clipping within 3 days after subarachnoid hemorrhage (SAH). From the SEP data, central conduction time (CCT) was obtained, and CCT fluctuations were categorized into three types. Patients with CCT prolongation over 7.5 ms within 10 days after SAH tended to have poor recovery of CBF and unfavorable outcome. Therefore, periodical monitoring of CCT was considered as a useful indicator for predicting prognosis and post-SAH changes of cerebral blood flow.     

Postoperative luxury perfusion syndrome in patients with severe subarachnoid hemorrhage treated by early aneurysmal clipping.

Cerebral blood flow (CBF) was measured in 90 patients who underwent early aneurysmal clipping after subarachnoid hemorrhage (SAH). Measurements were made by a noninvasive, two-dimensional method involving intravenous injection of 133Xe. Patients of Hunt and Hess grades I and II exhibited normal to slightly subnormal CBF, without significant changes, during the study period. Grades III-V patients had almost normal CBF in the early postoperative period, but their CBF gradually decreased, becoming significantly low after day 31. It is noteworthy that in grades IV and V patients, CBF was abnormally high in the acute stage, relative to their poor neurological condition; these patients were considered to have the "global luxury perfusion syndrome." The syndrome was not uncommon in patients with severe SAH. Possible causative or contributory factors are attempts to surgically reduce intracranial pressure, which leads to increased cerebral perfusion pressure, and concomitant global dysautoregulation. In patients with this syndrome, maneuvers intended to increase CBF should be avoided, as they may aggravate brain swelling or cause hemorrhagic events. Positron emission tomographic studies will provide more accurate and useful information concerning the management of SAH patients.     

An experimental study of the acute stage of subarachnoid hemorrhage

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.     

Spinal cord stimulation for cerebral vasospasm as prophylaxis

Cervical spinal cord stimulation (SCS) was used to increase cerebral blood flow (CBF) in 10 patients with secured cerebral aneurysms in Hunt and Hess grade 3 or 4 and with Fisher group 3 subarachnoid hemorrhage (SAH). The patients underwent preemptive electrical stimulation through a percutaneous lead following aneurysm surgery. All patients also received hypervolemic therapy and nicardipine. Efficacy of the treatment was evaluated using xenon computed tomography and cerebral angiography. The CBF in the distribution of the middle cerebral artery significantly increased following SCS (p < 0.05). Four of 10 patients showed angiographic vasospasm, but none developed severe sequelae of cerebral vasospasm. The overall outcome was good or excellent in seven of the 10 patients. No serious adverse effects due to SCS were observed. Fluid management and calcium antagonist have a beneficial effect on cerebral vasospasm following SAH, but is not tolerated or is ineffective in some patients. SCS as an adjunctive therapy for cerebral vasospasm following SAH may have a favorable effect on outcome.     

Coiling of recurrent and residual cerebral aneurysms after unsuccessful clipping.

We treated four patients with 3 recurrent and 1 residual aneurysm after surgical clipping by using Guglielmi detachable coils (GDCs). Three subjects presented after a second subarachnoid hemorrhage (SAH) occurring between 10 and 25 years after the first bleeding. Early postoperative angiography of the fourth patient showed an incompletely clipped aneurysm. In three poor grade patients we observed one good outcome, one fair result and one death due to the sequelae of SAH. One good grade patient remained in excellent condition postoperatively. Three aneurysms were totally occluded and in one a more than 90% occlusion was achieved with GDCs. We consider the treatment with GDC a viable alternative to reoperation in all patients with recurrent or residual aneurysms following failed attempt at surgical obliteration.     

Experimental subarachnoid hemorrhage: subarachnoid blood volume,mortality rate,neuronal death,cerebral blood flow,and perfusion pressure in three different rat models

OBJECTIVE: To investigate which of three subarachnoid hemorrhage (SAH) models is the most suitable for studies of pathological and pathophysiological processes after SAH. METHODS: SAH was induced in rats via intracranial endovascular perforation (perforation model), blood injection into the cisterna magna (300 microl), or blood injection into the prechiasmatic cistern (200 microl). The subarachnoid blood volume was quantitatively measured. Cerebral blood flow (CBF) (as assessed with laser Doppler flowmetry), intracranial pressure, and mean arterial blood pressure were recorded for 90 minutes after SAH. Mortality was recorded, and neuronal death was assessed in animals that survived 7 days after SAH. RESULTS: The subarachnoid blood volume was close to the injected amount after prechiasmatic SAH. In the other models, the volume varied between 40 and 480 microl. The mortality rates were 44% in the perforation SAH group, 25% in the prechiasmatic SAH group, and 0% in the cisterna magna SAH group; the corresponding values for neuronal death were 11, 44, and 28%. Cerebral perfusion pressure approached baseline values within 5 minutes after SAH in all three models. CBF decreased to approximately 35% of baseline values immediately after SAH in all groups; it gradually increased to normal values 15 minutes after SAH in the cisterna magna SAH group and to 60 and 89% of baseline values 90 minutes post-SAH in the perforation and prechiasmatic SAH groups. CBF was significantly correlated with the subarachnoid blood volume. CONCLUSION: The prechiasmatic SAH model seems to be the most suitable for study of the sequelae after SAH; it produces a significant decrease in CBF, an acceptable mortality rate, and substantial pathological lesions, with high reproducibility. The CBF reduction is predominantly dependent on the amount of subarachnoid blood.     

Experimental subarachnoid hemorrhage: cerebral blood flow and brain metabolism during the acute phase in three different models in the rat

OBJECTIVE: To study the cerebral metabolism and its relationship to cerebral blood flow (CBF) acutely after subarachnoid hemorrhage (SAH). METHODS: SAH was induced in rats by endovascular perforation of the internal carotid artery, blood injection into the prechiasmatic cistern or the cisterna magna. CBF (measured by laser Doppler flowmetry), cerebral perfusion pressure, O(2) tension, and extracellular levels of glucose, lactate, and pyruvate were monitored during 90 minutes after SAH. CBF (assessed by (125)I-antipyrine autoradiography), arteriovenous O(2) difference, and cerebral metabolic rate of O(2) were calculated at 15 or 90 minutes after SAH. RESULTS: After a transient reduction, cerebral perfusion pressure normalized within 5 minutes after SAH in all groups. There was a transient global decrease in CBF after SAH: its duration depended on the severity of the hemorrhage. CBF of less than 20% of baseline was observed for at least 15 minutes in 25% and 14% of the animals after perforation and prechiasmatic SAH, respectively. In all SAH groups, O(2) tension was suddenly reduced to approximately 40% of baseline and gradually increased, reaching 70 to 90% of baseline 90 minutes after SAH. The cerebral metabolic rate of O(2) was reduced only at 15 minutes after perforation and prechiasmatic SAH, but arteriovenous O(2) difference was normal in all groups. During 30 minutes after perforation SAH, a 50% decrease in glucose and a threefold increase in lactate and pyruvate levels were observed. CONCLUSION: The data suggest that SAH induced an acute global decrease in CBF together with a depression in the cerebral metabolism. The degree of the changes was related to the severity of the hemorrhage. The metabolic derangements were not always explained by ischemic episodes.     

短期应用高渗盐水对重症蛛网膜下腔出血患者颅内压、脑血流量的影响

目的 探讨23.4%高渗盐水(HTS)对重症蛛网膜下腔出血(SAH)患者颅内压、脑灌注压、脑血流量(CBF)的影响.方法 16例重症SAH患者(GCS≤8分)在颅压升高时接受静脉输注23.4%HTS,监测用药前及用药后30、60、90、120、150、180 min的颅内压(ICP),平均动脉压(MAP),脑灌注压(CPP)及脑血流速度(FV).结果 用药后30 min可见ICP显著降低,同时MAP、CPP及FV显著升高(P<0.05),ICP显著降低可持续180 min,CPP和FV的改善持续约90 min(P<0.05).结论 HTS能显著降低重症SAH患者的ICP,改善脑组织灌注,可用来纠正脑缺血引起的病生理变化.     

Blood coagulation and fibrinolysis after experimental subarachnoid hemorrhage

Background  

Aneurysmal rebleeding poses a serious risk in patients with subarachnoid hemorrhage (SAH). Studies have shown that antifibrinolytic therapy with tranexamic acid has a dramatic effect on the rate of rebleeding. Therefore, changes in the fibrinolytic system could be hypothesized.     

Development of new intracranial saccular aneurysms

Newly formed aneurysms developing from a cerebral vessel which had appeared to be normal in a previous angiographic study are very rare. Four cases of angiographically documented newly developed saccular aneurysms are described in this report. In all four patients, the new aneurysms were symptomatic, causing subarachnoid hemorrhage (SAH). Repeat angiography, performed after the second SAH, revealed new aneurysms that were not demonstrated on initial angiograms after the first SAH. They were clipped with good postoperative course. Our observations and literature data suggest that some patients with SAH need further neuroradiological followup. The presence of the risk factors and age of the patient should be taken into consideration.     

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

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.     

The significance of early operation in the management of ruptured intracranial aneurysms—An analysis of 251 cases hospitalized within 24 hours after subarachnoid haemorrhage

Summary An analysis of 251 patients who were hospitalized within 24 hours after rupture of supratentorial aneurysms and were not comatose during the very early stage was carried out. The patients were divided into three groups in relation to timing and methods of surgery. In 61 patients of Group A, the operation was planned to be delayed more than 10 days from subarachnoid haemorrhage (SAH). In 91 patients of Group B, clipping of aneurysms was performed within 48 hours of SAH and subarachnoid blood clots were simultaneously removed while approaching the aneurysms. In 99 patients of Group C, clipping of aneurysms was performed within 48 hours of SAH and radical and extensive removal of any subarachnoid blood clot identified on the computerized tomographic scan was tried at the same time. The outcome at 3 months after SAH was the most favourable in Group C patients and the least favourable in Group A patients.Early operation combined with radical removal of subarachnoid clots minimizes the overall mortality and morbidity in patients with ruptured intracranial aneurysms by preventing rebleeding and probably by avoiding vasospasm.     

Treatment of vasospasm after ruptured cerebral aneurysms by 'pellet-cisternal-drain: PCD' containing sustained-release vasodilators

Diltiazem or papaverine hydrochloride as vasodilators were polymerized with silicon polymer (MDX-4-4210: Dow Co.). The silicon pellets containing the drugs were placed in cisternal drainage tubes made of silicon, and used for the continuous cisternal drainage after the operations of ruptured cerebral aneurysms. This system was tentatively termed 'pellet-cisternal-drain; PCD'. The rate of diffusion of the drug from the pellets was examined in 30 patients who underwent surgery for ruptured cerebral aneurysms in the acute phase on the 0-4th postical days. 73.3% of patients had severe subarachnoid hemorrhage as group 3-4 in Fisher's classification in CT scan. The concentration of either drug in the cerebrospinal fluid on the 2nd to 3rd postoperative days reached the level of the maximum concentration obtained after bolus injection, and the level on the 5th to 10th postoperative days was similar to that observed several hours after bolus injection. The data showed that the sustained release pellet can act as a vasodilator, and its effects on cerebral vessels after an episode of subarachnoid hemorrhage continue for 2 to 3 weeks. All patients except one showed excellent results and returned to normal life.     

The long-term effects of transluminal balloon angioplasty for vasospasms after subarachnoid hemorrhage: analyses of cerebral blood flow and reactivity

BACKGROUND: Transluminal balloon angioplasty (TBA) has come into wide use for management of symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). The long-term effects of TBA in this clinical context on cerebral blood flow (CBF) and the functional properties of the arterial wall after aneurysmal SAH remain controversial. We therefore studied these effects. METHODS: All patients underwent unilateral TBA. Xenon-enhanced computed tomography was performed for an average of 18 days after TBA to measure CBF and cerebrovascular reactivity (CVR). Cerebral blood flow and CVR were compared between the side of TBA and the contralateral side. RESULTS: Nineteen vascular territories were treated successfully with TBA in 12 patients. Angiographic improvement of vasospasm was demonstrated in all 12 patients, and 9 (75%) patients showed neurological improvement. After balloon angioplasty, global CBF was 35.1 +/- 8.2 mL/100 g per minute, with CBF on the side with TBA (37.8 +/- 10.3 mL/100 g per minute) being essentially the same as that on the other side (P = .0671, paired Student t test). Likewise, reactivity to acetazolamide did not differ significantly between sides (P = .0817). CONCLUSION: Transluminal balloon angioplasty increased proximal vessel diameters but showed no significant influence on CBF or vascular reactivity 3 weeks later. Benefits presumably were short term, but the procedure was clinically safe.     

Serum immunocomplexes in patients with subarachnoid hemorrhage

Immunocomplexes (IC) in serum were analyzed in 54 patients with subarachnoid hemorrhage (SAH) from ruptured arterial aneurysms. A previous study had shown that patients with SAH and vasospasm had a significantly higher incidence of ICs in the blood than patients without vasospasm. The aim of the present study was to study how the IC content varied with time and compare this pattern with the clinical picture. Forty-two patients presented clinical or radiological signs of cerebral vasospasm during their hospital stays, whereas 12 patients showed no such signs. The patients with vasospasm had a significantly higher amount of ICs in serum than those without vasospasm. In 37 patients with vasospasm, the changes of IC content during the 1st weeks after SAH correlated well with the clinical course. Data indicated that a high IC content preceded the onset of vasospasm and a low content preceded clinical improvement. This observation supports the idea that the presence of ICs might be the cause and not the result of vasospasm.     

Prognosis in contre-coup intracranial haematomas — a clinical and radiological study of 63 patients

Summary Assessment of cerebral perfusion on patients with subarachnoid haemorrhage (SAH) in the Neurologic Intensive Care Unit is difficult since nuclear medicine imaging modalities capable of measuring cerebral blood flow (CBF) are not generally available. We performed 101 quantitative (ml/100g-min) bedside CBF measurements on 40 individual patients to correlate SAH grade with CBF and to assess the effect of surgical intervention on CBF. Global CBF (G-CBF) and bihemispheric CBF (B-CBF) asymmetry were correlated with the grade of SAH pre- and post-operatively.Data analysis showed that pre-operative patients with low grade SAH (Hunt and Hess grades 0 to 2) had higher mean G-CBF values [44.2±.71] than those with high grade SAH (Hunt and Hess grades 3 to 4): [mean G-CBF=34.1±1.7]. Post-surgery there was a significant improvement in G-CBF; CBF increased [5.3±1.07] in the group of patients with low grade SAH. Patients with high grade SAH showed no significant improvement in their G-CBF during the first week post-operatively compared to pre-operative values.We conclude that portable units capable of measuring bedside CBF values are useful in monitoring CBF changes in patients with SAH. Patients with low grade SAH have G-CBF within normal limits both pre-operatively and post-operatively, with a statistically significant increase in CBF during two weeks post-operatively. Patients with high grade SAH show no significant increase in CBF one week post-operatively compared to their pre-operative measures.