Feasibility of Optic Nerve Sheath Diameter to Guide the Treatment of Dehydration in Patients Undergoing Glioma Surgery
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摘要:
目的 探讨超声测量视神经鞘直径(ONSD)对神经胶质瘤手术患者颅高压(ICH)脱水治疗效果的可行性。 方法 选取择期行额部神经胶质瘤切除术的颅高压患者共40例,随机分为2组(n = 20)。在气管插管10 min后,甘露醇组(M组)予20%甘露醇0.5 g/kg在15 min内静脉滴注完毕,对照组(C组)予等量生理盐水在15 min内静脉滴注完毕。测量麻醉诱导前(T0)、气管插管后即刻(T1)、药物开始滴注时(T2)、药物滴注完毕后30 min(T3)、手术结束即刻(T4)、术后24 h(T5)双眼的ONSD值。检测各时刻血清中VEGF-A、MMP-9和ET-1水平。记录打开硬脑膜时的大脑松弛评分(BRS)。 结果 T3、T4、T5时刻,M组患者的ONSD值、血清中VEGF-A 、MMP-9、ET-1的浓度明显低于C组患者(P < 0.05);M组患者的BRS评分明显低于C组患者(P < 0.05)。 结论 对术前存在颅内高压的神经胶质瘤患者,在视神经鞘直径的指导下提前给予脱水治疗,可有效减轻脑水肿。 Abstract:Objective To investigate the feasibility of ultrasonic measurement of optic nerve sheath diameter (ONSD) in the treatment of dehydration of intracranial hypertension (ICH) in patients undergoing glioma surgery. Methods A total of 40 patients with cranial hypertension who underwent elective frontal glioma resection were randomly divided into 2 groups (n = 20). After 10 minutes of endotracheal intubation, Group M was given 20% mannitol 0.5 g/kg intravenously within 15 minute; Group C was given the same amount of normal saline intravenously within 15 minutes. ONSD values of both eyes were measured before anesthesia induction (T0), immediately after endotracheal intubation (T1), at the beginning of drug infusion (T2), 30 min after drug infusion (T3), immediately after surgery (T4), and 24 h after surgery (T5). The levels of VEGF-A, MMP-9 and ET-1 in serum at each time were detected. Cerebral relaxation score (BRS) was recorded when the dura was opened. Results At T3, T4 and T5, the ONSD value and serum concentrations of VEGF-A, MMP-9 and ET-1 in group M were significantly lower than those in group C (P < 0.05). BRS score in M group was significantly lower than that in C group (P < 0.05). Conclusion For glioma patients with intracranial hypertension before operation, dehydration treatment in advance under the guidance of optic nerve sheath diameter can effectively reduce cerebral edema. -
Key words:
- Optic nerve sheath diameter /
- Glioma /
- Intracranial pressure /
- Dehydration
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神经胶质瘤是最常见的中枢神经系统恶性肿瘤,部分患者可伴有肿瘤周围脑水肿,导致颅内压(intracranial hypertension,ICH)增高,是胶质瘤患者发病和死亡的主要原因[1-2]。脑水肿的识别和治疗对胶质瘤的管理至关重要,在ICH的早期应尽早开始降低颅内压(intracranial pressure,ICP)的干预措施,以优化脑灌注压,减轻对神经功能的损害[3]。
近年有研究表明,超声测量视神经鞘直径(optic nerve sheath diameter ,ONSD)是一种可靠、简便、有效测量ICP的无创方法,具有较高的灵敏度和特异性[4]。目前,超声测量ONSD评估ICP的应用并不广泛,且在ONSD监测下指导甘露醇脱水治疗的相关临床研究尚未见报道。因此,本研究拟对神经胶质瘤手术患者进行ONSD测量,对术前发现ONSD增大的ICH患者,提前给予甘露醇脱水治疗,并观察患者ONSD的变化、打开硬脑膜时的大脑松弛评分(brain relaxation score,BRS)、血管内皮生长因子A(vascular endothelial growth factor-A, VEGF-A)、基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)、内皮素1(endothelin-1,ET-1)的变化,为ONSD指导神经胶质瘤手术患者的脱水治疗提供依据。
1. 资料与方法
1.1 纳入标准
本研究经昆明医科大学第一附属医院伦理委员会的批准。选取昆明医科大学第一附属医院2019年10月至2020年9月择期行额部神经胶质瘤切除术的患者。ASA分级I~II级,年龄 ≥ 18岁,BMI18~24 kg/m2,性别不限。入室后对患者行超声测量ONSD,最终纳入双眼ONSD值均 > 5.8 mm的患者共40例。所有患者及家属均知晓且自愿签署知情同意书。
1.2 排除标准
(1)既往有神经外科手术或眼科手术史;(2)既往有眼部或神经系统疾病;(3)对本研究药物过敏;(4)心、肺、肝、肾、内分泌等功能不全;(5)困难气道患者;(6)围术期输血者;(7)酒精或精神药物滥用史;(8)术前电解质紊乱者;(9)术前24 h内接受高渗液体治疗的患者。
1.3 实验分组
按照随机数字表法,将患者分为2组(n = 20):对照组(C组)和甘露醇组(M组)。M组:气管插管10 min后,予20%甘露醇0.5 g/kg在15 min内静脉滴注完毕。C组:气管插管10 min后,予等量生理盐水在15 min内静脉滴注完毕。
1.4 观察指标
(1)在麻醉诱导前(T0)、气管插管后即刻(T1)、药物开始滴注时(T2)、药物滴注完毕后30 min(T3)、手术结束即刻(T4)、术后24 h(T5)实时测量双眼的ONSD。(2)手术医生在打开硬脑膜时,用四分制进行BRS评分[5]:1分 = 完全松弛,2分 = 满意地松弛,3分 = 大脑僵硬,4分 = 大脑鼓胀。(3)在T0~T5时刻采集患者的中心静脉血液3 mL检测血清VEGF-A、 MMP-9和 ET-1水平。
1.5 统计学处理
采用SPSS26.0软件系统进行统计分析。计量资料以均数±标准差(
$ \bar x \pm s$ )表示,组间比较采用独立样本t检验,不同时刻的组间及组内比较采用重复测量方差分析。计数资料采用χ2检验。P < 0.05为差异有统计学意义。2. 结果
2.1 2组患者一般情况的比较
2组患者的年龄、性别、BMI、ASA分级、肿瘤位置、肿瘤体积比较差异均无统计学意义(P > 0.05),见表1。
表 1 2组患者一般情况的比较($\bar x \pm s $ ,n = 20)Table 1. Comparison of general conditions between two groups of patients($\bar {\boldsymbol{x}} \pm {\boldsymbol{s}}$ ,n = 20)组别 年龄
(岁)性别
男/女(n)BMI
(kg/m2)ASAI/II
(n)肿瘤位置
左/右(n)肿瘤体积
(cm3)C组 41.7 ± 9.8 8/12 21.9 ± 1.1 10/10 11/9 44.5 ± 2.7 M组 41.4 ± 10.1 11/9 22.0 ± 1.0 11/9 13/7 45.6 ± 2.4 t/χ2 0.006 0.902 0.121 0.100 0.417 1.935 P 0.937 0.342 0.730 0.752 0.519 0.172 2.2 2组患者在不同时刻ONSD的比较
在T3、T4、T5时刻,M组患者双侧的ONSD值明显低于C组患者(P < 0.05)。 2组患者在T1时刻双侧的ONSD值均明显高于T0时刻(P < 0.05)。M组患者在T3、T4、T5时刻较T0时刻双侧的ONSD值均明显下降(P < 0.05),且在T4时降到最低;C组患者仅在T4、T5时刻较T0时刻双侧的ONSD值下降(P < 0.05),同样在T4时降到最低(表2)。
表 2 2组患者在不同时刻双侧ONSD值的比较($\bar x \pm s $ ,n = 20,mm)Table 2. Comparison of bilateral ONSD values between two groups at different time($\bar {\boldsymbol{x}} \pm {\boldsymbol{s}}$ ,n = 20,mm)部位 组别 T0 T1 T2 T3 T4 T5 左侧 C组 6.31 ± 0.28 7.18 ± 0.35* 6.31 ± 0.28 6.29 ± 0.30 4.99 ± 0.18* 5.51 ± 0.16* M组 6.43 ± 0.29 7.26 ± 0.37* 6.43 ± 0.28 6.00 ± 0.24*# 4.46 ± 0.19*# 5.10 ± 0.20*# F 2.410 0.729 2.128 14.948 128.119 78.090 P 0.137 0.404 0.161 < 0.01# < 0.01# < 0.01# 右侧 C组 6.22 ± 0.21 7.00 ± 0.23* 6.21 ± 0.18 6.18 ± 0.12 4.82 ± 0.10* 5.38 ± 0.08* M组 6.24 ± 0.22 7.03 ± 0.16* 6.25 ± 0.20 5.89 ± 0.19*# 4.41 ± 0.19*# 4.93 ± 0.20*# F 0.416 0.222 1.976 60.181 105.733 90.717 P 0.527 0.643 0.176 < 0.01# < 0.01# < 0.01# 与T0时刻比较,*P < 0.05;与C组比较,#P < 0.05 2.3 2组患者BRS评分的比较
M组患者的BRS评分明显低于C组患者(P < 0.05),见表3。
表 3 2组患者BRS评分的比较($\bar x \pm s$ ,n = 20,分)Table 3. Comparison of BRS score between two groups($\bar {\boldsymbol{x}} \pm{\boldsymbol{ s}}$ ,n = 20,Points)组别 BRS评分 C组 3.0 ± 0.6 M组 1.7 ± 0.5# t 5.814 P < 0.01# 与C组比较,#P < 0.05。 2.4 2组患者在不同时刻VEGF-A 、MMP-9、ET-1浓度的比较
在T3、T4、T5时刻,M组患者血清中VEGF-A 、MMP-9、ET-1的浓度明显低于C组患者(P < 0.05)。C组患者在T4、T5时刻较T0时刻血清中VEGF-A 、MMP-9、ET-1的浓度降低(P < 0.05)。M组患者在T3、T4、T5时刻较T0时刻血清中VEGF-A 、MMP-9、ET-1的浓度明显降低(P < 0.05),见表4,图1。
表 4 2组患者在不同时刻血清VEGF-A、MMP-9、ET-1浓度的比较($\bar x \pm s $ ,n = 20,pg/mL)Table 4. Comparison of serum VEGF-A, MMP-9 and ET-1 concentrations between 2 groups at different time points($\bar {\boldsymbol{x}} \pm {\boldsymbol{s}}$ ,n = 20,pg/mL)指标 组别 T0 T3 T4 T5 VEGF-A C组 162.11 ± 9.60 161.56 ± 9.52 143.29 ± 10.33* 158.15 ± 10.05* M组 160.59 ± 11.61 149.14 ± 11.32*# 123.01 ± 11.44*# 130.18 ± 10.10*# F 1.084 59.675 102.747 90.252 P 0.311 < 0.01# < 0.01# < 0.01# MMP-9 C组 23.28 ± 2.72 23.53 ± 2.51 19.15 ± 2.59* 20.71 ± 2.07* M组 23.41 ± 2.78 19.70 ± 2.43*# 15.52 ± 2.16*# 17.38 ± 1.94*# F 0.459 285.752 280.944 126.377 P 0.506 < 0.01# < 0.01# < 0.01# ET-1 C组 86.74 ± 8.30 86.34 ± 7.79 67.68 ± 8.87* 73.89 ± 8.54* M组 86.40 ± 9.14 80.08 ± 7.35*# 52.52 ± 8.70*# 64.20 ± 8.05*# F 0.245 63.927 515.625 171.555 P 0.626 < 0.01# < 0.01# < 0.01# 与T0时刻比较,*P < 0.05;与C组比较,#P < 0.05。 3. 讨论
肿瘤周围脑水肿不仅可造成脑组织的压迫损伤,引起ICH,导致脑缺血、脑移位、脑疝和死亡等严重后果,还增大了手术切除的难度,影响预后[6-7]。因此,对于开颅行神经胶质瘤切除术的患者,减轻脑水肿、降低ICP显得尤为重要。术中持续监测ICP不仅能动态、实时地反映ICP变化,还能及早发现ICH,对患者及时进行脱水干预治疗,有助于神经功能的顺利和快速恢复,最大限度地减少了颅内并发症的发生。
ICP监测是指导ICH治疗的有效方法。目前,有创性ICP测量被认为是ICP早期诊断和随访评估的金标准,其测量准确、实时,但创伤大、价格昂贵、导管易阻塞及打折,且会诱发脑膜炎和颅内出血等并发症,在临床中的应用受到限制[8]。有创ICP测量可被一些无创监测手段替代,包括经颅多普勒、鼓膜位移、CT和磁共振成像(magnetic resonance imaging,MRI)检查等,但这些手段均有一定的局限性。比如经颅多普勒技术难度大, 测量的失败率较高;鼓膜移位在年轻人群中效果最好,但对老年人准确性较低;CT和MRI耗时、费用高,不方便床旁操作[9]。
超声测量ONSD是检测ICP升高的一种实时、方便、无创的工具,在发展为视乳头水肿之前,异常增宽的ONSD可能是ICP升高的早期发现,并且ONSD与ICP具有很好的相关性。既往研究一般认为ONSD > 5.8 mm是预测ICP > 20 mmhg的可靠指标[10-13]。对于创伤性脑损伤患者,超声测量ONSD可在48 h内有效预测ICP的升高,ONSD的测量值越大,发生ICH的风险就越高[14]。接受开颅手术的中线移位的胶质瘤患者在硬脑膜打开后脑肿胀的风险非常高,因此建议在打开硬脑膜之前进行脱水治疗,以最大限度地使大脑松弛并促进肿瘤暴露[15]。Launey等[16]的研究证实,在重型颅脑损伤或动脉瘤性蛛网膜下腔出血患者的ICP持续升高的情况下,甘露醇输注后ONSD的显著降低与ICP的下降相关。此外有研究表明VEGF-A、MMP-9和ET-1浓度和脑水肿相关[17-19]。因此,在本研究中笔者在术前对患者进行了ONSD的超声测量,当双眼ONSD值均 > 5.8 mm时认为存在ICH。在甘露醇滴注完毕后30 min,M组患者双侧的ONSD值VEGF-A、MMP-9和ET-1浓度均较术前明显下降。在外科医生打开硬脑膜后,M组的BRS评分明显低于C组,为外科医生提供了满意的脑松弛和有利的手术条件。上述结果表明超声测量ONSD可用于术前评估神经胶质瘤患者ICP的增高,能有效预测脑肿胀,指导麻醉医生及时给予患者甘露醇脱水治疗,有效降低ICP,避免严重脑部并发症的发生,促进神经功能的预后。在ICP升高期间,尤其是在无法进行有创ICP监测时,ONSD监测不仅可早期辅助诊断ICH,还有助于监测渗透疗法的疗效。
综上所述,应用超声测量ONSD能对择期行胶质瘤开颅手术患者麻醉前的ICP进行可靠评估,对于ICP增高的患者,可针对性地在术前给予甘露醇脱水治疗,减轻开颅手术中的脑肿胀和脑水肿,降低ICP,改善预后,促进康复。在开颅手术中,ONSD指导神经胶质瘤手术患者脱水治疗是可行且安全的,后续可多中心、大样本做进一步深入研究,拓展超声测量ONSD的应用范围。
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表 1 2组患者一般情况的比较(
$\bar x \pm s $ ,n = 20)Table 1. Comparison of general conditions between two groups of patients(
$\bar {\boldsymbol{x}} \pm {\boldsymbol{s}}$ ,n = 20)组别 年龄
(岁)性别
男/女(n)BMI
(kg/m2)ASAI/II
(n)肿瘤位置
左/右(n)肿瘤体积
(cm3)C组 41.7 ± 9.8 8/12 21.9 ± 1.1 10/10 11/9 44.5 ± 2.7 M组 41.4 ± 10.1 11/9 22.0 ± 1.0 11/9 13/7 45.6 ± 2.4 t/χ2 0.006 0.902 0.121 0.100 0.417 1.935 P 0.937 0.342 0.730 0.752 0.519 0.172 表 2 2组患者在不同时刻双侧ONSD值的比较(
$\bar x \pm s $ ,n = 20,mm)Table 2. Comparison of bilateral ONSD values between two groups at different time(
$\bar {\boldsymbol{x}} \pm {\boldsymbol{s}}$ ,n = 20,mm)部位 组别 T0 T1 T2 T3 T4 T5 左侧 C组 6.31 ± 0.28 7.18 ± 0.35* 6.31 ± 0.28 6.29 ± 0.30 4.99 ± 0.18* 5.51 ± 0.16* M组 6.43 ± 0.29 7.26 ± 0.37* 6.43 ± 0.28 6.00 ± 0.24*# 4.46 ± 0.19*# 5.10 ± 0.20*# F 2.410 0.729 2.128 14.948 128.119 78.090 P 0.137 0.404 0.161 < 0.01# < 0.01# < 0.01# 右侧 C组 6.22 ± 0.21 7.00 ± 0.23* 6.21 ± 0.18 6.18 ± 0.12 4.82 ± 0.10* 5.38 ± 0.08* M组 6.24 ± 0.22 7.03 ± 0.16* 6.25 ± 0.20 5.89 ± 0.19*# 4.41 ± 0.19*# 4.93 ± 0.20*# F 0.416 0.222 1.976 60.181 105.733 90.717 P 0.527 0.643 0.176 < 0.01# < 0.01# < 0.01# 与T0时刻比较,*P < 0.05;与C组比较,#P < 0.05 表 3 2组患者BRS评分的比较(
$\bar x \pm s$ ,n = 20,分)Table 3. Comparison of BRS score between two groups(
$\bar {\boldsymbol{x}} \pm{\boldsymbol{ s}}$ ,n = 20,Points)组别 BRS评分 C组 3.0 ± 0.6 M组 1.7 ± 0.5# t 5.814 P < 0.01# 与C组比较,#P < 0.05。 表 4 2组患者在不同时刻血清VEGF-A、MMP-9、ET-1浓度的比较(
$\bar x \pm s $ ,n = 20,pg/mL)Table 4. Comparison of serum VEGF-A, MMP-9 and ET-1 concentrations between 2 groups at different time points(
$\bar {\boldsymbol{x}} \pm {\boldsymbol{s}}$ ,n = 20,pg/mL)指标 组别 T0 T3 T4 T5 VEGF-A C组 162.11 ± 9.60 161.56 ± 9.52 143.29 ± 10.33* 158.15 ± 10.05* M组 160.59 ± 11.61 149.14 ± 11.32*# 123.01 ± 11.44*# 130.18 ± 10.10*# F 1.084 59.675 102.747 90.252 P 0.311 < 0.01# < 0.01# < 0.01# MMP-9 C组 23.28 ± 2.72 23.53 ± 2.51 19.15 ± 2.59* 20.71 ± 2.07* M组 23.41 ± 2.78 19.70 ± 2.43*# 15.52 ± 2.16*# 17.38 ± 1.94*# F 0.459 285.752 280.944 126.377 P 0.506 < 0.01# < 0.01# < 0.01# ET-1 C组 86.74 ± 8.30 86.34 ± 7.79 67.68 ± 8.87* 73.89 ± 8.54* M组 86.40 ± 9.14 80.08 ± 7.35*# 52.52 ± 8.70*# 64.20 ± 8.05*# F 0.245 63.927 515.625 171.555 P 0.626 < 0.01# < 0.01# < 0.01# 与T0时刻比较,*P < 0.05;与C组比较,#P < 0.05。 -
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