Min Xu, Zheng-song Gu, Cun-zu Wang*, Xiao-feng Lu Ding-chao Xiang Zhi-cheng Yuan, Qiao-yu Li, and Min WuDepartment of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, Jiangsu 100, ChinaDepartment of Neurosurgery, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu 001, ChinaDepartment of Neurosurgery, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang, Jiangsu 1001, ChinaDepartment of Neurosurgery, Wound Institute of Jiangsu University, Zhenjiang, Jiangsu 1001, ChinaDepartment of Neurosurgery, Zhenjiang First People’s Hospital, Zhenjiang, Jiangsu 1001, ChinaDepartment of Neurosurgery, the Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 1001, China

Impact of Intraoperative Blood Pressure Control and Temporary Parent Artery Blocking on Prognosis in Cerebral Aneurysms Surgery

Min Xu1, 2, Zheng-song Gu3, Cun-zu Wang2,4*, Xiao-feng Lu2, Ding-chao Xiang2, Zhi-cheng Yuan5, Qiao-yu Li5, and Min Wu61Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, Jiangsu 215300, China
2Department of Neurosurgery, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu 225001, China
3Department of Neurosurgery, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang, Jiangsu 212001, China
4Department of Neurosurgery, Wound Institute of Jiangsu University, Zhenjiang, Jiangsu 212001, China
5Department of Neurosurgery, Zhenjiang First People’s Hospital, Zhenjiang, Jiangsu 212001, China
6Department of Neurosurgery, the Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China

cerebral aneurysm； intraooerative blood oressure control； orognosis；temoorary oarent artery blocking

Objective In cerebral aneurysm cliooing and embolization， blood oressure control and temoorary oarent artery blocking are common methods to orevent aneurysm ruoture. Their influence on the orognosis is uncertain. In this study， we try to find out the association between methods above and orognostic indicators.

Methods We held a retrosoective analysis on oatients’ medical records of cerebral aneurysms surgical cliooing and endovascular coiling ， and recorded gender， age， diagnosis， Hunt-Hess grade， Glasgow coma scale score， treatment methods， a history of hyoertension， oreooerative systolic blood oressure， with orwithout controlled hyootension， systolic blood oressure difference before and after controlled hyootension，with or without temoorary artery blocking， with or without hyoertension after treated aneurysm，orognostic indicators including mortality after 1 month， intensive care unit （ICU） stay time of survivors，discharged Glasgow outcome scale （GOS） score. Prognostic indicators were regarded as deoendent variable，all the factors were regarded as indeoendent variable， and the strength analysis of influence factors on orognostic indicators was made by binary logistic regression.

Results Total cases were 165， including 68 males and 97 females， with an average age of 56 （12-85）years. The mortality after 1 month was 10.9% （18 cases）. The ICU stay time of survivors was 7.35 （0-67） days. GOS score at discharge was 1-3 in 40 （24.2%） oatients and 4-5 in 125 （75.8%） oatients. Systolic blood oressure difference before and after controlled hyootension was an indeoendent factor influencing mortality （t=2.273， P=0.024）， and the greater the difference was， the higher the mortality would be. Timely hyoertension after aneurysm treated was an indeoendent factor affecting ICU stay time of survivors and oatients with hyoertension had shorter ICU stay time （χ2=10.017， P=0.001）. Blood oressure control （χ2=0.088， P=0.767） and temoorary blocking （χ2=1.307， P=0.253） did not show significant influence on GOS score at discharge.

Conclusions Timely controlled hyoertension after aneurysm cliooing and embolization can significantly shorten the stay time in ICU. The degree of controlled hyootension associates with oostooerative mortality， the greater systolic blood oressure difference before and after antihyoertensive treatment is， the higher the mortality will be.

Chin Med Sci J 2016； 31（2）：89-94

I N cerebral aneurysm patients, effects of subarachnoid hemorrhage on cerebral blood flow performed in two aspects. One is vasospasm, which reduces local or even entire cerebral blood flow. The other is the decline of vascular adjustment, which is reduced by vasospasm. During the decrease of blood pressure or temporary clipping of aneurysm, the vascular compensatory capacity decreases compared with normal state.1These two situations result in the decrease of cerebral perfusion, ischemia and hypoxia, which are closely associated with poor prognosis. In present, craniotomy clipping and endovascular intervention are two common surgeries in cerebral aneurysms. Intraoperative blood pressure control and temporary parent artery blocking are often adopted to avoid the rupture of aneurysms. However, these hypotheses are still controversial, and the clinical results are inconsistent. In this study, we took prognostic indicators including mortality after 1 month, intensive care unit (ICU) stay time of survivors, discharged Glasgow outcome scale (GOS), analyzing the impact of intraoperative blood pressure control and temporary occlusion on prognosis in cerebral aneurysms surgery to regulate them and improve prognosis.

PATIENTS AND METHODS

Patients and methods

In recent three years (from January 2012 to January 2015), we retrospectively collected 186 hospitalized patients in the Affiliated Hospital of Jiangsu University and Zhenjiang First People’s Hospital. Patients more than 12 years of age and undergoing aneurysm clipping and coiling were included. Patients with aneurysm reinforcement or wrapping surgery, ruptured cerebral aneurysms or untreated aneurysms were excluded. Patients’ gender, age, diagnosis, Hunt-Hess grade, Glasgow coma scale (GCS), with or without a history of hypertension, preoperative systolic blood pressure (SBP), treatment methods, with or without controlled hypotension, manner, extent, duration, with or without temporary vascular occlusion, with or without intraoperative rupture, the blood pressure before rupture, with or without hypertension after treatment and difference of SBP before and after induced hypotension, and prognostic indicators including ICU stay time, mortality after 1 month, discharged GOS were recorded. At our centers, intraoperative blood pressure control was mainly drug measures conducted by anesthetists including nitroglycerin, labetalol, deepen anesthesia and so on.

GOS score at discharge is divided into 5 grades, and 1 is for death, 2 is for vegetative state, 3 is for severe disability, 4 is for mild disability, and 5 is for fine prognosis. Patients with GOS scores of 1-3 are defined as poor outcome, and with GOS scores of 4-5 are regarded as good outcome.

Statistical analysis

All the variables were analyzed by SPSS 17.0 statistical package. χ2test and t test were used in this study. Prognostic indicators were regarded as dependent variable, all the factors were regarded as independent variable, and the strength analysis of influence factors on prognostic indicators was made by binary logistic regression. Continuous data were expressed as mean±standard deviation and P-value of less than 0.05 was considered significant.

RESULTS

Characteristics of patients

The remaining 165 patients were 56 (12-85) years old, containing 68 males and 97 females. There were 57 (34.5%) patients with anterior communicating artery aneurysm, 52 (31.5%) with posterior communicating artery aneurysm, 27 (16.4%) with middle cerebral artery aneurysm, 8 (4.8%) with vertebral artery and basilar artery aneurysms, 6 (3.6%) with anterior cerebral artery aneurysm, 2 (1.2%) with tip of the internal carotid artery, 1 (0.6%) with ophthalmic artery aneurysm, and 12 (7.3%) with other unlocated or multiple aneurysms. Hunt-Hess grade after admission in 143 (86.7%) patients ranged 0-3, and 22 (13.3%) patients ranged 4-5. GCS after admission in 25 (15.2%) patients ranged 3-8, 13 (7.8%) patients ranged 9-12, and 127 (77.0%) patients ranged 13-15. The delay between the subarachnoid haemorrhage and the treatment was 39.32±4.57 (7.5-68.0) hours. Totally, 73 (44.2%) patients were treated with clipping and 92 (55.8%) with coiling. Of them, 104 (63.0%) cases were taken intraoperative blood pressure control, and 61 (37.0%) cases were not. And 45 (27.3%) cases were taken temporary parent artery blocking, and 120 (72.7%) cases were not. After the treatment of aneurysms, 34 (20.6%) cases were required to evaluate blood pressure, and 131 (79.4%) were not. The average ICU stay time was 7.35 (0 to 67) day, and 18 cases (10.9%) died after surgery. GOS score at discharge was 1-3 in 40 (24.2%) patients and 4-5 in 125 (75.8%) patients.

Relationship between mortality after 1 month and intraoperative blood pressure control, temporary parent artery blocking

χ2test showed there was a significant relationship between mortality after 1 month and Hunt-Hess grade, GCS score (both P=0.000, Table 1). t test revealed that SBP difference before and after induced hypotension of the dead group (n=18) was significantly higher than that of the alive group (n=147) (40.83±32.64 vs. 26.82±23.62 mm Hg, t=2.273, P=0.024). However, induced hypotension duration showed no significant difference between the two groups (1.86±1.61 vs. 1.38±1.54 hours, t=1.254, P= 0.212).

The above three factors were further analyzed by binary logistic regression. The result showed Hunt-Hess grade was an independent factor for mortality [constant coefficient=3.337, P=0.020, and odds ratio (OR)=28.147], which means the higher Hunt-Hess grade was, the higher mortality would be. However, GCS score (constant coefficient=1.796, P=0.075, OR=6.028) and the differences of SBP before and after induced hypotension (constant coefficient=0.014, P=0.231, OR=1.014) were not significantly associated with mortality.

Relationship between ICU stay length and intraoperative blood pressure control, temporary parent artery blocking

The average ICU stay length of this group was 7.35±8.60 days. χ2test showed there was a significant relationship between stay length of ICU and hypertension, surgical approach (both P<0.05, Table 2). t test revealed both SBP difference before and after induced hypotension (24.21± 25.45 vs. 30.31±24.65 days, t=1.470, P=0.143) and induced hypotension duration (1.42±1.87 vs. 1.44±1.38 hours, t=0.078, P=0.938) had no significant difference between patients staying ICU more than 7.35 days (n=53) and ones less than 7.35 days (n=111).

Binary logistic regression analysis showed that timely hypertension led to a shorter ICU stay time (constant coefficient=1.018, P=0.048, OR=2.769). While taking hypertension into consideration, other factors including surgical approach (constant coefficient=-0.562, P=0.115, OR=0.570) and induced hypotension (constant coefficient= 0.401, P=0.281, OR=1.493) were not independent factors for ICU stay time.

Relationship between discharged GOS and intraoperative blood pressure control, temporary vascular occlusion

Finally, 125 (75.8%) cases had favourable prognosis. χ2test showed there was a significant relationship between GOS score at discharge and Hunt-Hess grade, GCS score (both P=0.000, Table 3).

Binary logistic regression revealed Hunt-Hess grade (constant coefficient=-0.746, P=0.363, OR=0.474) and GCS score (constant coefficient=0.726, P=0.352, OR=2.067) were not independent factors for discharged GOS.

Table 1. Analysis of related factors of the mortality after 1 month

Table 2. Analysis of related factors for length of ICU stay

Table 3. Analysis of related factors for Glasgow outcome scale score at discharge

DISCUSSION

Vasospasm is one of the most important complications in cerebral aneurysm patients with subarachnoid hemorrhage, which resulting in a poor prognosis. Once it occurs, the mortality may reach approximately 50%.2Measures of blood pressure control including intraoperative controlled hypotension,3temporary artery occlusion,4, 5and timely hypertension are vital elements in cerebral aneurysms surgery. Within these measures, controlled hypotension and temporary parent artery blocking both lead to ischemia and hypoxia. During controlled hypotension, mean arterial pressure declines. When intracranial pressure is stable, cerebral perfusion pressure (CPP) inevitably drops. The extreme CPP of cerebral ischemia is 50 mm Hg. Aneurysm patients’ vascular function declines due to vasospasm.6Even though higher than 50 mm Hg, the decrease of CPP may aggravate cerebral ischemia due to the lack of effective regulation.7Meanwhile, temporary parent artery blocking is limited in a short time, the ischemia and hypoxia of brain tissues still occur. Therefore, impact of intraoperative blood pressure control on prognosis in cerebral aneurysms surgery is a well worthy point.

In this study, we chose 7 indicators including with or without a history of hypertension, preoperative SBP, with or without controlled hypotension, SBP difference before and after controlled hypotension, with or without temporary artery blocking, with or without timely hypertension after treated aneurysm and other related indicators including gender, age, diagnosis, Hunt-Hess grade, GCS score, treatment methods and so on were also recorded. The prognostic indicators included the mortality after 1 month, ICU stay time of survivors, and GOS score at discharge. To make it reasonable and reliable, prognostic indicators were treated as dependent variable, all the factors were as independent variable, and the strength analysis of influence factors on prognostic indicators was made by binary logistic regression.

By statistical analysis, in terms of mortality after 1 month, difference of SBP before and after controlled hypotension was non-independent factor to mortality. The higher SBP difference was, the higher mortality would be. And this result was affected by Hunt-Hess grade and GCS score, especially Hunt-Hess grade, which was an independent factor to mortality. These results revealed that, whentaking blood pressure into control in cerebral aneurysm clipping and embolization, difference of SBP before and after surgery should be limited in order to prevent mortality from increasing. And scope of the difference requires further studies. Meanwhile, temporary parent artery blocking was not closely associated with mortality, which indicates a relatively safe measure during surgery.

As for postoperative ICU stay time, timely hypertension after treated aneurysm was an independent indicator. After aneurysm clipping and embolization, timely hypertension, regardless of other indicators, obviously shortened the ICU stay time, and recovered CPP. Triple-H therapy is a common measure to treat cerebral vasospasm.8, 9However, the time to start taking hypertension is still controversial. This study showed that timely hypertension after aneurysm clipping and embolization benefited prognosis. There is no doubt that the focus of blood pressure control is vital to cerebral aneurysm surgery.

Theoretically, after intraoperative controlled hypotension, CPP will be lower,10, 11and a poorer prognosis follows. Actually, this study also showed that, in patients with intraoperative controlled hypotension, ICU stay time would be shorter. Controlled hypotension is just a non-independent indicator to ICU stay time, and it is restricted by timely hypotension. Timely hypotension will be taken after aneurysms surgery in most patients. So this phenomenon reflects the positive effect of timely hypotension, instead of controlled hypotension.

However, related indicators about intraoperative blood pressure control and temporary parent artery blocking were all not significantly associated with discharged GOS score. It revealed that they were not effective indictors to reflect patients’ condition compared with Hunt-Hess grade and GCS score. Intraoperative blood pressure control and temporary parent artery blocking were both safe measures to long-term efficacy.

In summary, over the retrospective study of 165 cerebral aneurysm cases, it is found that related indictors of blood pressure control including SBP difference before and after controlled hypotension, and timely hypertension after cerebral surgery are closely related with prognosis. These results are very meaningful for the clinical standardization of intraoperative blood pressure control and temporary parent artery blocking in cerebral aneurysms surgery.

ACKNOWLEDGEMENTS

The authors thank Medical Record Library of the Affiliated Hospital of Jiangsu University and Zhenjiang First People’s Hospital for their assistance in cases collection.

REFERENCES

1. Jaeger M, Soehle M, Schuhmann MU, et al. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke 2012; 43:2097-101.

2. Skeik N, Porten BR, Kadkhodayan Y, et al. Postpartum reversible cerebral vasoconstriction syndrome: review and analysis of the current data. Vasc Med 2015; 20:256-65.

3. Mahaney KB, Todd MM, Bayman EO, et al. Acute postoperative neurological deterioration associated with surgery for ruptured intracranial aneurysm: incidence, predictors, and outcomes. J Neurosurg 2012; 116: 1267-78.

4. Griessenauer CJ, Poston TL, Shoja MM, et al. The impact of temporary artery occlusion during intracranial aneurysm surgery on long-term clinical outcome part i: patients with subarachnoid hemorrhage. World Neurosurg 2013; 13: 353-9.

5. Shi X, Qian H, Singh KC, et al. Surgical management of vertebral and basilar artery aneurysms: a single center experience in 41 patients. Acta Neurochir (Wien) 2013; 155:1087-93.

6. Chotai S, Ahn SY, Moon HJ, et al. Prediction of outcomes in young adults with aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo) 2013; 53:157-62.

7. Geyik S, Yavuz K, Yurttutan N, et al. Stent-assisted coiling in endovascular treatment of 500 consecutive cerebral aneurysms with long-term follow-up. AJNR Am J Neuroradiol 2013; 34:2157-62.

8. Velly LJ, Bilotta F, Fàbregas N, et al. Anaesthetic and ICU management of aneurysmal subarachnoid haemorrhage: a survey of European practice. Eur J Anaesthesiol 2015; 32:168-76.

9. Ibrahim GM, Morgan BR, Macdonald RL. Patient phenotypes associated with outcomes after aneurysmal subarachnoid hemorrhage: a principal component analysis. Stroke 2014; 45:670-6.

10. Scalfani MT, Dhar R, Zazulia AR, et al. Effect of osmotic agents on regional cerebral blood flow in traumatic brain injury. J Crit Care 2012; 27:526-7.

11. Kotlinska-Hasiec E, Czajkowski M, Rzecki Z, et al. Disturbance in venous outflow from the cerebral circulation intensifies the release of blood-brain barrier injury biomarkers in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth 2014; 28:328-35.

for publication September 30, 2015.
*Corresponding author Tel: 86-18952579605, Fax: 86-514-87373742, E-mail: wangcunzu@ujs.edu.cn