Aneurysmal subarachnoid hemorrhage complications

Aneurysmal subarachnoid hemorrhage complications

Vasospasm is an important cause for mortality following aneurysmal subarachnoid hemorrhage aSAH affecting as many as 70% of patients. It usually occurs between 4th and 21st days of aSAH and is responsible for delayed ischemic neurological deficit (DIND) and cerebral infarction

It is one of the factors that can most significantly worsen the prognosis despite different treatments.

Transcranial doppler (TCD) evidence of vasospasm is predictive of delayed cerebral ischemia (DCI) with high accuracy. Although high sensitivity and negative predictive value make TCD an ideal monitoring device, it is not a mandated standard of care in aneurysmal subarachnoid hemorrhage (aSAH) due to the paucity of evidence on clinically relevant outcomes, despite recommendation by national guidelines. High-quality randomized trials evaluating the impact of TCD monitoring on patient-centered and physician-relevant outcomes are needed 1).


A greater proportion of aneurysmal subarachnoid hemorrhage patients, are surviving their initial hemorrhagic event but remain at increased risk of a number of complications, including delayed cerebral ischemia, epilepsy, nosocomial infections, cognitive impairment, shunt dependent hydrocephalus, and shunt related complications 2).

Intracranial complications including delayed cerebral ischemia (vasospasm), aneurysm rebleeding, and hydrocephalus form the targets for initial management. However, the extracranial consequences including hypertensionhyponatremia, and cardiopulmonary abnormalities can frequently arise during the management phase and have shown to directly affect clinical outcome.

Although the intracranial complications of SAH can take priority in the initial management, the extracranial complications should be monitored for and recognized as early as possible because these complications can develop at varying times throughout the course of the condition. Therefore, a variety of investigations, as described by this article, should be undertaken on admission to maximize early recognition of any of the extracranial consequences. Furthermore, because the extracranial complications have a direct effect on clinical outcome and can lead to and exacerbate the intracranial complications, monitoring, recognizing, and managing these complications in parallel with the intracranial complications is important and would allow optimization of the patient’s management and thus help improve their overall outcome 3).

Intracranial hemorrhage

Aneurysmal subarachnoid hemorrhage is complicated by intracerebral hemorrhage in 20—40 %, by intraventricular hemorrhage in 13-28%, and by subdural blood in 2-5% (usually due to posterior communicating aneurysm when over convexity, or distal anterior intracerebral artery (DACA) aneurysm with interhemispheric subdural).

The intracranial effects of aSAH causing death and disability are from vasospasm, direct effects of the initial bleed, increased intracranial pressure (ICP) and rebleeding 4).

Early brain injury and hydrocephalus (HCP) are important mediators of poor outcome in subarachnoid hemorrhage (SAH) patients. Injection of SAH patients’ CSF into the rat ventricle leads to HCP as well as subependymal injury compared with injection of control CSF 5).

Fever is a common occurrence (70%) especially in poor grades, contributes to adverse outcome and may not always respond to conventional treatment.

Persistent hyperglycemia (>200 mg/dl for >2 consecutive days) increases the likelihood of poor outcome after aSAH.

Management of patients following aSAH includes four major considerations:

(1) prediction of patients at highest risk for development of DCI,

(2) prophylactic measures to reduce its occurrence,

(3) monitoring to detect early signs of cerebral ischemia,

(4) treatments to correct vasospasm and cerebral ischemia once it occurs 6).

Vasospasm

Delayed cerebral ischemia

The risk of delayed cerebral ischemia is reduced with oral nimodipine and probably by maintaining circulatory volume 7).

Failure of cerebral autoregulation has been shown in patients with aSAH even before vasospasm sets in and contributes to delayed ischemic neurological deficits (DIND) along with vasospasm 8).

Rebleeding

Pulmonary complications

Subarachnoid hemorrhage (SAH) is often accompanied by pulmonary complications, which may lead to poor outcomes and death.

Sympathetic activation of the cardiovascular system in aneurysmal subarachnoid hemorrhage not only triggers the release of atrial and brain natriuretic peptides it can also lead to increased pulmonary venous pressures and permeability causing hydrostatic pulmonary edema 9).

see Neurogenic pulmonary edema.

Cardiac manifestations

Cardiac manifestations of intracranial subarachnoid hemorrhage patients include mild electrocardiogram variability, Takotsubo cardiomyopathy, non-ST elevation myocardial infarction, ST-elevation myocardial infarction and cardiac arrest, but their clinical relevance is unclear.

Among patients suffering from cardiac events at the time of aneurysmal subarachnoid hemorrhage, those with myocardial infarction and in particular those with a troponin level greater than 1.0 mcg/L had a 10 times increased risk of death 10).

Acute kidney injury

Hyponatremia

Hypokalemia

Hypokalemia is a common electrolyte disorder in the intensive care unit. Its cause often is complex, involving both potassium losses from the body and shifts of potassium into cells.

We present a case of severe hypokalemia of sudden onset in a patient being treated for subarachnoid hemorrhage in the surgical intensive care unit in order to illustrate the diagnosis and management of severe hypokalemia of unclear cause. The patient received agents that promote renal potassium losses and treatments associated with a shift of potassium into cells. Ibanez et al. outline the steps in diagnosis and management, focusing on the factors regulating the transcellular distribution of potassium in the body 11).

Hydrocephalus

Intraventricular hemorrhage

The clinical outcome after aneurysm rupture is at least in part determined by the severity of IVH. Knowledge of the effect of IVH may help guide physicians in the care of patients with aneurysmal bleeding 12).

Cognitive disorder

Neuropsychiatric disturbance

Deep vein thrombosis

Overall rates of VTE (Deep vein thrombosis DVT or PE), DVT, and PE were 4.4%, 3.5%, and 1.2%, respectively. On multivariate analysis, the following factors were associated with increased VTE risk: increasing age, black race, male sex, teaching hospital, congestive heart failure, coagulopathy, neurologic disorders, paralysis, fluid and electrolyte disorders, obesity, and weight loss. Patients that underwent clipping versus coiling had similar VTE rates. VTE was associated with pulmonary/cardiac complication (odds ratio [OR] 2.8), infectious complication (OR 2.8), ventriculostomy (OR 1.8), and vasospasm (OR 1.3). Patients with VTE experienced increased non-routine discharge (OR 3.3), and had nearly double the mean length of stay (p<0.001) and total inflation-adjusted hospital charges (p<0.001). To our knowledge, this is the largest study evaluating the incidence and risk factors associated with the development of VTE after aSAH. The presence of one or more of these factors may necessitate more aggressive VTE prophylaxis 13).

Short course (<48h) administration of EACA in patients with aneurysmal subarachnoid hemorrhage is associated with an 8.5 times greater risk of Deep vein thrombosis (DVT) formation 14).

Routine compressive venous Doppler ultrasonography is an efficient, noninvasive means of identifying Deep vein thrombosis (DVT) as a screening modality in both symptomatic and asymptomatic patients following aneurysmal SAH. The ability to confirm or deny the presence of DVT allows one to better identify the indications for chemoprophylaxis. Prophylaxis for venous thromboembolism in neurosurgical patients is common. Emerging literature and anecdotal experience have exposed risks of complications with prophylactic anticoagulation protocols. The identification of patients at high risk-for example, those with asymptomatic DVT-will allow physicians to better assess the role of prophylactic anticoagulation 15).

Deep vein thrombosis (DVT) formation most commonly occurs in the first 2 weeks following aSAH, with detection in a cohort peaking between Days 5 and 9. Chemoprophylaxis is associated with a significantly lower incidence of DVT 16).

Prevention

Patient should be ideally monitored in the NICU for at least 1st 24 h after surgery. Anticonvulsants, osmotherapy and nimodipine must be continued. Hydrocephalus, vasospasm, seizures, and electrolyte disturbances can occur necessitating close observation and prompt management. One of the major challenges in the management of aSAH is identifying potential or ongoing perfusion deficits. Ischemic insults can occur following ictus, or due to raised ICP, hypotension and vasospasm. Early identification and appropriate treatment of postictal intracranial (ICP, TCD flow velocities) and cardiovascular (cardiac output, ECG, BP, CVP) changes is possible in dedicated NICU and is crucial for improving outcomes. Heuer et al. observed that raised ICP (>20 mmHg) occurred in >50% of patients after aSAH and was associated with poor outcomes. Factors associated with raised ICP included poor clinical and radiological grades of aSAH, intraoperative brain swelling, parenchymal and intraventricular bleed and rebleeding.

Seizure

References

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Kumar G, Shahripour RB, Harrigan MR. Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Neurosurg. 2015 Oct 23:1-8. [Epub ahead of print] PubMed PMID: 26495942.
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Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, et al: Guidelines for the manage- ment of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Asso- ciation/American Stroke Association. Stroke 43:1711–1737, 2012
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Hall A, O’Kane R. The Extracranial Consequences of Subarachnoid Hemorrhage. World Neurosurg. 2018 Jan;109:381-392. doi: 10.1016/j.wneu.2017.10.016. Epub 2017 Oct 16. Review. PubMed PMID: 29051110.
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Kassell MJ. Aneurysmal subarachnoid hemorrhage: An update on the medical complications and treatments strategies seen in these patients. Curr Opin Anaesthesiol. 2011;24:500–7.
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Li P, Chaudhary N, Gemmete JJ, Thompson BG, Hua Y, Xi G, Pandey AS. Intraventricular Injection of Noncellular Cerebrospinal Fluid from Subarachnoid Hemorrhage Patient into Rat Ventricles Leads to Ventricular Enlargement and Periventricular Injury. Acta Neurochir Suppl. 2016;121:331-4. doi: 10.1007/978-3-319-18497-5_57. PubMed PMID: 26463970.
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Dusick JR, Gonzalez NR. Management of arterial vasospasm following aneurysmal subarachnoid hemorrhage. Semin Neurol. 2013 Nov;33(5):488-97. doi: 10.1055/s-0033-1364216. Epub 2014 Feb 6. PubMed PMID: 24504612.
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van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet. 2007 Jan 27;369(9558):306-18. Review. PubMed PMID: 17258671.
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Sriganesh K, Venkataramaiah S. Concerns and challenges during anesthetic management of aneurysmal subarachnoid hemorrhage. Saudi J Anaesth. 2015 Jul-Sep;9(3):306-13. doi: 10.4103/1658-354X.154733. Review. PubMed PMID: 26240552; PubMed Central PMCID: PMC4478826.
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Lo BW, Fukuda H, Nishimura Y, Macdonald RL, Farrokhyar F, Thabane L, Levine MA. Pathophysiologic mechanisms of brain-body associations in ruptured brain aneurysms: A systematic review. Surg Neurol Int. 2015 Aug 11;6:136. doi: 10.4103/2152-7806.162677. eCollection 2015. PubMed PMID: 26322246.
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Ahmadian A, Mizzi A, Banasiak M, Downes K, Camporesi EM, Thompson Sullebarger J, Vasan R, Mangar D, van Loveren HR, Agazzi S. Cardiac manifestations of subarachnoid hemorrhage. Heart Lung Vessel. 2013;5(3):168-78. PubMed PMID: 24364008; PubMed Central PMCID: PMC3848675.
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Ybanez N, Agrawal V, Tranmer BI, Gennari FJ. Severe hypokalemia in a patient with subarachnoid hemorrhage. Am J Kidney Dis. 2014 Mar;63(3):530-5. doi: 10.1053/j.ajkd.2013.07.005. Epub 2013 Aug 20. PubMed PMID: 23972266.
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Mayfrank L, Hütter BO, Kohorst Y, Kreitschmann-Andermahr I, Rohde V, Thron A, Gilsbach JM. Influence of intraventricular hemorrhage on outcome after rupture of intracranial aneurysm. Neurosurg Rev. 2001 Dec;24(4):185-91. PubMed PMID: 11778824.
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Kshettry VR, Rosenbaum BP, Seicean A, Kelly ML, Schiltz NK, Weil RJ. Incidence and risk factors associated with in-hospital venous thromboembolism after aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2014 Feb;21(2):282-6. doi: 10.1016/j.jocn.2013.07.003. Epub 2013 Oct 13. PubMed PMID: 24128773.
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Foreman PM, Chua M, Harrigan MR, Fisher WS 3rd, Tubbs RS, Shoja MM, Griessenauer CJ. Antifibrinolytic therapy in aneurysmal subarachnoid hemorrhage increases the risk for deep venous thrombosis: A case-control study. Clin Neurol Neurosurg. 2015 Sep 10;139:66-69. doi: 10.1016/j.clineuro.2015.09.005. [Epub ahead of print] PubMed PMID: 26378393.
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Ray WZ, Strom RG, Blackburn SL, Ashley WW, Sicard GA, Rich KM. Incidence of deep venous thrombosis after subarachnoid hemorrhage. J Neurosurg. 2009 May;110(5):1010-4. doi: 10.3171/2008.9.JNS08107. PubMed PMID: 19133755.
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Liang CW, Su K, Liu JJ, Dogan A, Hinson HE. Timing of deep vein thrombosis formation after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2015 Oct;123(4):891-6. doi: 10.3171/2014.12.JNS141288. Epub 2015 Jul 10. PubMed PMID: 26162047; PubMed Central PMCID: PMC4591180.

Poor grade aneurysmal subarachnoid hemorrhage

Poor grade aneurysmal subarachnoid hemorrhage

Poor-grade subarachnoid hemorrhage (SAH), that is, World Federation of Neurosurgical Societies grading Grades IV and V, have high morbidity and mortality rates.

A total of 104 consecutive patients with poor-grade aSAH from the Department of Neurosurgery, The Second Hospital of Shandong University, Jinan, were enrolled between January 2010 and December 2017. All these patients underwent early microsurgical clipping or endovascular coiling within three days after onset. Microsurgical clipping or endovascular coiling was selected according to aneurysm patterns, patient clinical status, interdisciplinary consultation, and the decision-making of the family. The individual prognosis was evaluated using the modified Rankin scale (mRS), while the prognostic factors were analyzed using multivariate logistic regression analysis.

There were 58 patients with grade IV aSAH and 46 patients with grade V aSAH. Microsurgical clipping was performed in 71 cases, while endovascular coiling was performed in 33 cases. According to the statistical results, microsurgical clipping was preferred by patients with CT Fishergrade III-IV, WFNS grade V, cerebral hernia, intracranial hematoma and preoperative rebleeding. At six months after onset, the overall rate of favorable outcome (mRS ≤ 2) was 36.5%. Furthermore, the favorable outcome rate was 56.9% in grade IV patients and 11.1% in grade V patients. Moreover, the univariate and multivariate logistic regression analyses revealed that CT Fisher grade I-II, WFNS grade IV and endovascular coiling were associated with a favorable prognosis, while the CT low-density area was slightly correlated to a poor prognosis.

The treatment of aSAH at the early stage by microsurgical clipping or endovascular coiling should be highlighted, especially for patients with WFNS grade IV. CT Fisher grade I-II, WFNS grade IV and endovascular coiling may predict a favorable prognosis, and the CT low-density area appeared to be a possible risk factor for poor prognosis 1).


Goldberg et al., performed a retrospective analysis of the Bernese SAH database for poor-grade (World Federation of Neurosurgical Societies grade IV and V) elderly patients (age ≥60 years) suffering from aSAH admitted to our institution from 2005 to 2017. Patients were divided into 3 age groups (60-69, 70-79, and 80-90 years). Survival analysis was performed to estimate mean survival and hazard ratios for death. Binary logarithmic regression was used to estimate the odds ratio for favorable (modified Rankin Scale score of 0-3) and unfavorable (modified Rankin Scale score of 4-6) outcome. Results- Increasing age was associated with an increasing risk of death after aSAH. The hazard ratio increased by 6% per year of age ( P<0.001; hazard ratio, 1.06; 95% CI, 1.03-1.09) and 76% per decade ( P<0.001; hazard ratio, 1.76; 95% CI, 1.35-2.29). Mean survival was 56.3±8 months (patients aged 60-69 years), 31.6±7.6 months (70-79 years), and 7.6±5.8 months (80-90 years). Unfavorable outcomes 6 to 12 months after aSAH were strongly related to older age. The odds ratio increased by 11% per year of age ( P<0.001; odds ratio, 1.11; 95% CI, 1.05-1.18) and 192% per decade ( P<0.001; odds ratio, 2.92; 95% CI, 1.63-5.26). Conclusions- Risk for death and unfavorable outcome increases markedly with older age in elderly patients with poor-grade aSAH. Despite a high initial mortality, treatment resulted in a reasonable proportion of favorable outcomes up to 79 years of age and only a small number of patients who were moderately or severely disabled 6 to 12 months after aSAH. Mean survival and proportion of favorable outcomes decreased markedly in patients older than 80 years 2).


During the period 2004-2014, 248 patients with poor-grade SAH were treated in our institution. Poor-grade SAH was defined as World Federation of Neurological Surgeons grades IV-V on admission. Data including patient characteristics, treatment modality, radiologic features, and functional neurologic outcome were assessed and further analyzed. Outcome was assessed according to the modified Rankin Scale after 6 months and stratified into favorable (modified Rankin Scale score 0-2) versus unfavorable (modified Rankin Scale score 3-6). A multivariate analysis was performed to identify predictors of functional outcome.

A favorable outcome was achieved in 24% of patients with poor-grade SAH. Patients with a favorable outcome were significantly younger (P = 0.005), harbored significantly smaller aneurysms (P = 0.004), and had a lower initial World Federation of Neurological Surgeons grade (P < 0.0001). An unfavorable outcome was significantly more frequent in patients with additional space-occupying hematoma compared with patients without additional space-occupying hematoma (P = 0.0009). On multivariate analysis, patient age, World Federation of Neurological Surgeons grade V, signs of cerebral herniation, aneurysm size, and presence of space-occupying hematoma were identified as significant predictors of unfavorable outcome in patients with poor-grade SAH.

A favorable outcome was achieved in 24% of severely ill patients with poor-grade SAH. Therefore, treatment of patients with poor-grade SAH should not be omitted. Careful individualized decision making is necessary for each patient 3).


118 patients with World Federation of Neurosurgical Societies (WFNS) grades IV and V underwent surgical treatment. Ultra-early surgery was defined as surgery performed within 24 h of aSAH, and delayed surgery as surgery performed after 24 h. Outcome was assessed by modified Rankin Scale (mRS). The mean time of follow-up was 12.5±3.4 months (range 6-28 months).

47 (40%) patients underwent ultra-early surgery, and 71 (60%) patients underwent delayed surgery. Patients with WFNS grade V (p=0.011) and brain herniation (p=0.004) more often underwent ultra-early surgery. Postoperative complications were similar in ultra-early and delayed surgery groups. Adjusted multivariate analysis showed the outcomes were similar between the two groups. Multivariate analysis of predictors of poor outcome, ultraearly surgery was not an independent predictor of poor outcome, while advanced age, postresuscitation WFNS V grade, intraventricular haemorrhage, brain herniation and non-middle cerebral artery (MCA) aneurysms were associated with poor outcome.

Although patients with WFNS grade V and brain herniation more often undergo ultra-early surgery, postoperative complications and outcomes in selected patients were similar in the two groups. Patients of younger age, WFNS grade IV, absence of intraventricular haemorrhage, absence of brain herniation and MCA aneurysms are more likely to have a good outcome. Ultra-early surgery could improve outcomes in carefully selected patients with poor-grade aSAH 4).


The purpose of a study was to undertake a single-center randomized controlled feasibility trial comparing a strategy of early endovascular aneurysm treatment with treatment after neurologic recovery in this group of patients.

Patients with poor-grade SAH were randomized within 24 hours of admission to early treatment or treatment after neurologic recovery. If a patient was randomized to early treatment, the aneurysm was treated endovascularly within 24 hours of randomization. Recruitment rate, safety profile, and functional outcome at the time of discharge and at 6 months were assessed.

Fourteen of 51 patients screened were eligible for the trial. Of these 14, 8 patients were randomized (57%). All patients in the early coiling arm received treatment within 24 hours of randomization. There was no treatment-related complication. Overall, good outcome occurred in 25% of patients; the mortality rate was 75%. Patients in the early treatment arm (n = 5) had a good outcome rate of 20%, while those in treatment after neurologic recovery arm (n = 3) had a good outcome rate of 33.3%.

This was a feasibility study that demonstrated that recruitment and randomization for comparing management strategies in poor-grade SAH are feasible. The recruitment rate among eligible patients was encouraging (57%), though a number of patients had to be excluded due to ineligibility. A multicenter study is necessary to recruit the numbers required to compare the clinical outcomes of these management strategies 5).


Timing of surgery for poor-grade aneurysmal subarachnoid hemorrhage is still controversial, therefore this study aimed to identify the optimal time to operate on patients admitted in poor clinical condition.

Ninety-nine patients meeting the inclusion criteria were randomly assigned into three treatment groups. The early surgery group received operation within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the intermediate surgery group received operation from days 4 to 7, and surgery was performed on the late surgery group after day 7. Follow-up was performed 1, 3, and 6 months after aneurysm clipping. Primary indicators of outcome included the Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary indicators of outcome were assessed using the Barthel Index and mortality.

This was the first prospective, single-center, observer-blinded, randomized controlled trial to elucidate optimal timing for surgery in poor-grade subarachnoid hemorrhage patients. The results of this study will be used to direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage, thus improving clinical outcomes for patients 6)


A prospective investigation was conducted in 149 patients with SAH (mean age 50.9 +/- 12.9 years); these patients were studied for 162 +/- 84 hours (mean +/- standard deviation). Lesions were classified as low-grade SAH (WFNS Grades I-III, 89 patients) and high-grade SAH (WFNS Grade IV or V, 60 patients). After approval by the local ethics committee and consent from the patient or next of kin, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clip placement. The microdialysates were analyzed hourly for extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol. The 6- and 12-month outcomes according to the Glasgow Outcome Scale and functional disability according to the modified Rankin Scale were assessed. In patients with high-grade SAH, cerebral metabolism was severely deranged compared with those who suffered low-grade SAH, with high levels (p < 0.05) of lactate, a high L/P ratio, high levels of glycerol, and, although not significant, of glutamate. Univariate analysis revealed a relationship among hyperglycemia on admission, Fisher grade, and 12-month outcome (p < 0.005). In a multivariate regression analysis performed in 131 patients, the authors identified four independent predictors of poor outcome at 12 months, in the following order of significance: WFNS grade, patient age, L/P ratio, and glutamate (p < 0.03).

Microdialysis parameters reflected the severity of SAH. The L/P ratio was the best metabolic independent prognostic marker of 12-month outcome. A better understanding of the causes of deranged cerebral metabolism may allow the discovery of therapeutic options to improve the prognosis, especially in patients with high-grade SAH, in the future 7).


A prospectively audited, nonselected series of 177 consecutive poor-grade (i.e., World Federation of Neurological Surgeons Grades IV and V) patients with aneurysmal subarachnoid hemorrhage managed during a 9-year period was analyzed. A management policy of aggressive ultraearly surgery (not selected by age or by grade) was followed. Coiling was not available. Outcomes were assessed at 3 months.

Despite the aggressive management policy, surgery could be performed in only 132 poor-grade patients (75%). Twenty percent of all patients were 70 years of age or older (15% of the surgical cases). All surgery was performed within 12 hours of subarachnoid hemorrhage (majority <6 h). Preoperative rebleeding occurred within the first 12 hours (>85% within 6 h) in 20% of the patients, which is four times the rate found in good-grade patients managed according to the same policy. Outcome assessment performed at 3 months in the 132 poor-grade surgical patients revealed that 40% were independent, 15% were dependent, and 45% had died. There was no significant difference in outcomes for young and old (70+ yr) poor-grade surgical patients (P > 0.05).

The high ultraearly rebleeding rate indicates a need to urgently secure the ruptured aneurysm by performing surgery or coiling, and this indication is more pronounced for poor-grade patients than for good-grade patients. The outcome results of ultraearly surgery indicate that a nonselective policy does not lead to a large number of dependent survivors, even among elderly poor-grade patients 8).

References

1)

Wang X, Han C, Xing D, Wang C, Ding X. Early management of poor-grade aneurysmal subarachnoid hemorrhage: A prognostic analysis of 104 patients. Clin Neurol Neurosurg. 2019 Feb 5;179:4-8. doi: 10.1016/j.clineuro.2019.02.003. [Epub ahead of print] PubMed PMID: 30776564.
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Goldberg J, Schoeni D, Mordasini P, Z’Graggen W, Gralla J, Raabe A, Beck J, Fung C. Survival and Outcome After Poor-Grade Aneurysmal Subarachnoid Hemorrhage in Elderly Patients. Stroke. 2018 Dec;49(12):2883-2889. doi: 10.1161/STROKEAHA.118.022869. PubMed PMID: 30571422.
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Schuss P, Hadjiathanasiou A, Borger V, Wispel C, Vatter H, Güresir E. Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Factors Influencing Functional Outcome–A Single-Center Series. World Neurosurg. 2016 Jan;85:125-9. doi: 10.1016/j.wneu.2015.08.046. Epub 2015 Sep 2. PubMed PMID: 26341439.
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Zhao B, Zhao Y, Tan X, Cao Y, Wu J, Zhong M, Wang S. Factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage: a multicentre retrospective analysis. BMJ Open. 2015 Apr 15;5(4):e007410. doi: 10.1136/bmjopen-2014-007410. PubMed PMID: 25877280; PubMed Central PMCID: PMC4401840.
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Mitra D, Gregson B, Jayakrishnan V, Gholkar A, Vincent A, White P, Mitchell P. Treatment of poor-grade subarachnoid hemorrhage trial. AJNR Am J Neuroradiol. 2015 Jan;36(1):116-20. doi: 10.3174/ajnr.A4061. Epub 2014 Jul 24. PubMed PMID: 25059694.
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Zhang Q, Ma L, Liu Y, He M, Sun H, Wang X, Fang Y, Hui XH, You C. Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial. BMC Neurol. 2013 Aug 19;13:108. doi: 10.1186/1471-2377-13-108. PubMed PMID: 23957458; PubMed Central PMCID: PMC3751917.
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Sarrafzadeh A, Haux D, Küchler I, Lanksch WR, Unterberg AW. Poor-grade aneurysmal subarachnoid hemorrhage: relationship of cerebral metabolism to outcome. J Neurosurg. 2004 Mar;100(3):400-6. PubMed PMID: 15035274.
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Laidlaw JD, Siu KH. Poor-grade aneurysmal subarachnoid hemorrhage: outcome after treatment with urgent surgery. Neurosurgery. 2003 Dec;53(6):1275-80; discussion 1280-2. PubMed PMID: 14633294.

Nimodipine for aneurysmal subarachnoid hemorrhage

Nimodipine for aneurysmal subarachnoid hemorrhage

Nimodipine 60 mg every four hours is administered to all patients with aneurysmal subarachnoid hemorrhage, ideally within four days of SAH. The typical dose is 60 mg every four hours by mouth or nasogastric tube. Nimodipine must be given orally or by nasogastric tube because inadvertent intravenous administration has been associated with serious adverse events, including death. Treatment is continued for 21 days.

The calcium channel blocker nimodipine was initially studied in patients with SAH as a means to prevent vasospasm. However, despite the vasodilatory effects of nimodipine on cerebral vessels, there is no convincing evidence that nimodipine affects the incidence of either angiographic or symptomatic vasospasm 1) 2) 3) 4) 5) 6).

Nevertheless, nimodipine has been demonstrated to improve subarachnoid hemorrhage outcomes and is the standard of care in these patients 7) 8) 9) 10) 11) 12) 13).


Nimodipine can cause arterial hypotension requiring either a dosage reduction or its discontinuation. Aim of a study of Kieninger et al., from the University Hospital Regensburg, was to examine the effect of different nimodipine formulations on arterial blood pressure in aneurysmal or perimesencephalic SAH patients and to measure the plasma levels after both, peroral administration as tablet or solution and IA infusion.

In a prospective setting, over a 1-year observation period, data on the course of arterial blood pressure and nimodipine dosage were collected for 38 patients undergoing treatment for aneurysmal or perimesencephalic SAH in an intensive care unit. In addition, plasma concentrations of nimodipine were measured by liquid chromatography-tandem mass spectrometry.

The intended full dose of 60 mg of nimodipine given orally every 4 h could only be administered on 57.2% of the examined days. Ninety-seven episodes of relevant arterial hypotension probably caused by the administration of nimodipine were observed within the first 14 days of treatment. Drops in blood pressure occurred about three times as often after administration of nimodipine as oral solution than as tablet. However, there were no differences in nimodipine plasma levels between the two formulations. In patients suffering from higher-grade SAH, arterial hypotension and consequent dosage reduction or discontinuation of nimodipine were more frequent than in patients with lower-grade SAH. Plasma concentrations of nimodipine during CIAN did not exceed those achieved by oral administration.

Dosage reduction or discontinuation of oral nimodipine is often necessary in patients with higher-grade SAH. Oral nimodipine solutions cause drops in blood pressure more frequently than tablets. Intra-arterial infusion rates of less than 1 mg/h result in venous plasma concentrations of nimodipine similar to those observed after oral application of 60 mg every 4 h 14).

References

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