Hemodynamic Management in the Prevention and Treatment of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

One of the most serious complications after subarachnoid hemorrhage (SAH) is delayed cerebral ischemia, the cause of which is multifactorial. Delayed cerebral ischemia considerably worsens neurological outcome and increases the risk of death. The targets of hemodynamic management of SAH have widely changed over the past 30 years. Hypovolemia and hypotension were favored prior to the era of early aneurysmal surgery but were subsequently replaced by the use of hypervolemia and hypertension. More recently, the concept of goal-directed therapy targeting euvolemia, with or without hypertension, is gaining preference. Despite the evolving concepts and the vast literature, fundamental questions related to hemodynamic optimization and its effects on cerebral perfusion and patient outcomes remain unanswered. In this review, we explain the rationale underlying the approaches to hemodynamic management and provide guidance on contemporary strategies related to fluid administration and blood pressure and cardiac output manipulation in the management of SAH.

Diffuse Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage in a 15-Year-Old Girl: A Case Report.

Diffuse cerebral vasospasm after subarachnoid hemorrhage (SAH) is a complication resulting in an ischemic condition presenting with altered mentality and followed by motor or speech impairment. It is uncommon in pediatric population and requires differential diagnosis from Moyamoya disease, which is relatively common in Korea. We report a case of a 15-year-old girl who was presented with a seizure and subsequent headache, poor oral intake, and altered mentality, who was finally diagnosed with sporadic vasospasm followed by multiple aneurysm ruptures. The patient had recurrent seizures and persistent headache at the time of transfer. On the second day after transfer, she showed focal motor weakness and dysarthria, and her symptoms gradually progressed, showing paraplegia and aphasia on the third hospitalization day. Brain magnetic resonance imaging and magnetic resonance angiography demonstrated diffuse narrowing cerebral vasospasm of bilateral middle cerebral arteries, anterior cerebral arteries, and distal internal carotid arteries and three unruptured aneurysms. The patient was treated with intravenous hydration and nimodipine to expand the narrowed vessels. After confirming that the vessels were enlarged, we successfully executed the endovascular coil embolization. Her neurological deficits were improved through medical, interventional, and rehabilitation treatments and fully restored 11 months after discharge.

Rapid Evolution and Rupture of an Incidental Aneurysm During Hyperdynamic Therapy for Cerebral Vasospasm.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Among the most common sequelae of aSAH is delayed cerebral ischemia. Hyperdynamic therapy (fluid supplementation and hypertension) is used to increase cerebral perfusion. However, the safety of hyperdynamic therapy in patients with separate unruptured, unsecured intracranial aneurysms is not well-established. Herein, a rare case demonstrating the rapid evolution and rupture of an incidental unsecured aneurysm in the setting of hyperdynamic therapy is presented. CASE DESCRIPTION: A 56-year-old woman without significant medical history presented with aSAH secondary to rupture of a 3-mm left posterior inferior cerebellar artery aneurysm. After endovascular treatment of this aneurysm, she developed symptomatic vasospasm prompting initiation of hyperdynamic therapy. Seven days after initiation of hyperdynamic therapy, she experienced rupture of an incidental pericallosal artery aneurysm that was found to have increased in size during the hyperdynamic therapy. She ultimately survived and was functionally independent approximately 1 year after her initial ictus. CONCLUSIONS: This case demonstrates that enlargement and rupture of an incidental, previously unruptured aneurysm may occur during hyperdynamic therapy.

The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms.

OBJECT: Vasopressor-induced hypertension (VIH) is an established treatment for patients with aneurysmal subarachnoid hemorrhage (SAH) who develop vasospasm and delayed cerebral ischemia (DCI). However, the safety of VIH in patients with coincident, unruptured, unprotected intracranial aneurysms is uncertain. METHODS: This retrospective multiinstitutional study identified 1) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who required VIH therapy (VIH group), and 2) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who did not require VIH therapy (non-VIH group). All patients had previously undergone surgical or endovascular treatment for the presumed ruptured aneurysm. Comparisons between the VIH and non-VIH patients were made in terms of the patient characteristics, clinical and radiographic severity of SAH, total number of aneurysms, number of ruptured/unruptured aneurysms, aneurysm location/size, number of unruptured and unprotected aneurysms during VIH, severity of vasospasm, degree of hypervolemia, and degree and duration of VIH therapy. RESULTS: For the VIH group (n = 176), 484 aneurysms were diagnosed, 231 aneurysms were treated, and 253 unruptured aneurysms were left unprotected during 1293 total days of VIH therapy (5.12 total years of VIH therapy for unruptured, unprotected aneurysms). For the non-VIH group (n = 73), 207 aneurysms were diagnosed, 93 aneurysms were treated, and 114 unruptured aneurysms were left unprotected. For the VIH and non-VIH groups, the mean sizes of the ruptured (7.2 ± 0.3 vs 7.8 ± 0.6 mm, respectively; p = 0.27) and unruptured (3.4 ± 0.2 vs 3.2 ± 0.2 mm, respectively; p = 0.40) aneurysms did not differ. The authors observed 1 new SAH from a previously unruptured, unprotected aneurysm in each group (1 of 176 vs 1 of 73 patients; p = 0.50). Baseline patient characteristics and comorbidities were similar between groups. While the degree of hypervolemia was similar between the VIH and non-VIH patients (fluid balance over the first 10 days of therapy: 3146.2 ± 296.4 vs 2910.5 ± 450.7 ml, respectively; p = 0.67), VIH resulted in a significant increase in mean arterial pressure (mean increase over the first 10 days of therapy relative to baseline: 125.1% ± 1.0% vs 98.2% ± 1.2%, respectively; p < 0.01) and systolic blood pressure (125.6% ± 1.1% vs. 104.1% ± 5.2%, respectively; p < 0.01). CONCLUSIONS: For small, unruptured, unprotected intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during VIH therapy is rare. The authors do not recommend withholding VIH therapy from these patients.

The challenges of hypervolemic therapy in patients after subarachnoid haemorrhage.

PURPOSE: The triple-H therapy is widely used for cerebral vasospasm (CV) prevention and treatment in patients after subarachnoid haemorrhage (SAH). However, this practice is based on low level evidence. Aim of this study was to evaluate errors in fluid administration, fluid balance monitoring and bedside charts completeness during a trial of triple-H therapy. MATERIALS AND METHODS: An audit of the SAH patient charts was performed. A total of 508 fluid measurements were performed in 41 patients (6 with delayed cerebral ischaemia; DCI) during 14 days of observation. RESULTS: Underestimating for intravenous drugs was the most frequent error (80.6%; 112), resulting in a false positive fluid balance in 2.4% of estimations. In 38.6% of the negative fluid balance cases, the physicians did not order additional fluids for the next 24h. In spite of that, the fluid intake was significantly increased after DCI diagnosis. The mean and median intake values were 3.5 and 3.8l/24h respectively, although 40% of the fluid balances were negative. The positive to negative fluid balance ratio was decreasing in the course of the 14 day observation. CONCLUSIONS: This study revealed inconsistencies in the fluid orders as well as mistakes in the fluid monitoring, which illustrates the difficulties of fluid therapy and reinforces the need for strong evidence-based guidelines for hypervolemic therapy in SAH.

Endovascular treatment of cerebral vasospasm: vasodilators and angioplasty.

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a delayed, reversible narrowing of the intracranial vasculature that occurs most commonly 4 to 14 days after aneurysmal SAH and can lead to permanent ischemic injury. Angiographic spasm occurs in up to 70% of patients following SAH, and approximately half become symptomatic. Estimates of patients who are disabled by vasospasm, or die because of it, range from 5% to 9%, with vasospasm accounting for 12% to 17% of all fatalities or cases of disability after SAH. This article discusses the multiple medical and endovascular therapies used to prevent or treat vasospasm.

Pharmacologic Options for Prevention and Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Background: Cerebral vasospasm and delayed cerebral ischemia continue to be major contributors to morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Purpose: The purpose of this review was to evaluate the pharmacotherapy interventions for the prevention and management of cerebral vasospasm in patients with SAH. Methods: A search of MEDLINE (January 1966-April 2012) and EMBASE (January 1974-April 2012) was conducted to retrieve relevant studies of pharmacotherapy options for prevention or treatment of cerebral vasospasm in SAH. Results: Triple-H therapy (hypervolemia, hemodilution, hypertension) has been a widely accepted option by many clinicians for the management of cerebral vasospasm and delayed cerebral ischemia. However, implementation of Triple-H therapy varies considerably at individual institutions. Nimodipine and nicardipine have demonstrated the most dependable improvements in patient outcomes to date. High doses of intravenous magnesium have failed to show consistent benefits. Magnesium supplementation to prevent hypomagnesaemia should be employed. Statin therapy should be continued in patients who are taking statins prior to hospital admission. Use of statins in naive patients may be recommended when the results of an ongoing prospective study are available. Of the available locally administered pharmacologic therapies, nicardipine and thrombolytics appear to provide the most intriguing benefit-to-risk ratio. However, the data supporting the use of locally administered therapy are modest at best and require careful consideration prior to application. Conclusions: Clinical studies have tested a variety of pharmacotherapy interventions for the prevention and treatment of cerebral vasospasm. Of available therapies, nimodipine has demonstrated consistent benefits and should be employed routinely. Demonstration of reduced cerebral vasospasm and improved neurological outcomes in larger prospective studies are needed for most pharmacologic therapy options prior to recommending their routine use.

The Relationship between Pulmonary Dysfunction and Age in Vasospasm Patients Receiving Triple H Therapy.

BACKGROUND AND INTRODUCTION: Triple H therapy is conventionally used to treat vasospasm following sub-arachnoid hemorrhage (SAH) but can sometimes have side effects. In order to investigate pulmonary complications in SAH patients and relationship with age we conducted the following study. METHODS: The charts of 121 sub-arachnoid hemorrhage patients who underwent clipping or coiling of an aneurysm were retrospectively reviewed. The diagnosis of vasospasm was documented based on Doppler and angiographic findings. All patients with vasospasm received the standard Triple H therapy (hematocrit 33-38%, central venous pressure 10-12 mmHg, systolic blood pressure 160-200 mmHg). We studied intravenous intake, artificial ventilation, hypoxemia/pulmonary edema, postoperative fever, pneumonia and death rates as outcome variables. RESULTS: Sixty five patients developed vasospasm (15 mild, 23 moderate, 27 severe). These were significantly younger than non-vasospasm patients (51 years vs. 61 years, p=0.004). The average daily intravenous input was 1,730 cc in novasospasm patients, 2,123 cc in the mild vasospasm group, 2,399 cc in the moderate vasospasm group, and 3,040 cc in the severe vasospasm group. Younger patients with moderate to severe vasospasm received more fluids than older patients. Ten patients (8.3%) developed hypoxemia or pulmonary edema. No patient developed hypoxemia/pulmonary edema in the mild vasospasm group and the rates did not show a trend and were not statistically different (7.1%, 0.0%, 13.0%, 11.1%, p>0.05) between vasospasm and non-vasospasm groups. Likewise, postoperative fever and pneumonia rates were not different between the vasospasm and non-vasospasm groups. Using the mean age as a threshold, pulmonary-related complications including death rates tended to be higher in the older group. The rates of postoperative ventilation (30.8% vs. 57.1%, P<0.01) and hypoxemia/pulmonary edema (3.1% vs. 14.3%, P<0.05) rates were statistically higher in the older group. Patients who developed hypoxemia/pulmonary edema in the vasospasm group tended to be younger than those who developed hypoxemia/pulmonary edema in the non-vasospasm group. CONCLUSION: Younger patients are at a higher risk of developing vasospasm than older patients possibly referable to vessel elasticity and reactive sensitivity factors. Likewise, patients who developed hypoxemia/pulmonary edema in the vasospasm group were younger than in the non-vasospasm group possibly secondary to fluid overload from triple H therapy.

Triple-H Therapy for Cerebral Vasospasm Following Spontaneous Subarachnoid Hemorrhage / 国际脑血管病杂志

Cerebral vasospasm is the leading cause of disability and death in patients with spontaneous subarachnoid hemorrhage,and there is no definitive and effective treatment for it yet.Triple-H therapy is now the first choice in the treatment of cerebral vasospasm,but there are still more controversies about it. In recent years,there have been a number of studies about Triple-H therapy. This article reviews the implementation of Triple-H therapy,fluid selection,and prophylactic application.

Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm / 第三军医大学学报

Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100～200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure-diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step-wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure-induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra-physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.

Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm / 第三军医大学学报

Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100～200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure-diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step-wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure-induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra-physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.

Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm / 第三军医大学学报

Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100～200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure-diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step-wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure-induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra-physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.