甘露醇用药时间对脑脊液中抗生素浓度的影响

目的 探讨不同时间快速静脉输注甘露醇对脑眷液中抗生素浓度的影响,为临床合理安排甘露醇与抗生素的输注时间提供理论依据.方法 选取神经外科术后患者12例,采用自身对照法于术后第1天开始,分别于5个时间段使用抗生素头孢三嗪,即应用抗生素后60 min使用甘露醇(1组)、应用抗生素后30 min使用甘露醇(2组)、同时应用甘露醇和抗生素(3组)、应用抗生素前30 min使用甘露醇(4组)、应用抗生素前60 min使用甘露醇(5组).应用抗生素60 min后留取脑脊液标本,采用反相离子对高效液相色谱法测定脑脊液中抗生素的浓度.结果 应用抗生素后30 min使用甘露醇,其脑脊液药物浓度显著高于其它时段(均P＜0.01).结论 静脉输注抗生素后30 min使用甘露醇,血脑屏障开放为最佳状态,抗生素通过率最大,有助于预防和治疗中枢神经系统感染.     

静脉输注甘露醇开放血脑屏障对抗生素透过血脑屏障的影响

目的　通过快速静脉输注甘露醇可逆性开放血脑屏障 (BBB) ,探知此方法能否增加抗生素透过BBB的量 ,在何时达到最高峰 ,其通透量增加后临床上有无不良反应。方法　采用自身配伍设计 ,共 6个样本组。对照组仅使用抗生素 ;其余 5组分别在使用甘露醇前 60、3 0min ,同时使用甘露醇后 3 0、60min使用抗生素 ,各组皆取使用抗生素后 1h的脑脊液测其抗生素浓度。抗生素选用头孢三嗪。结果　测量值经过q检验 ,经 2 0 %甘露醇处理前后的CSF中的头孢三嗪浓度差异有非常显著性。全组患者经临床观察未出现神经系统的不良反应。结论　经静脉快速输注2 0 %甘露醇后可以使透过BBB的水溶性抗生素的量增加 ,两者使用的顺序是在抗生素使用 3 0min内即给予甘露醇快速滴注。该方法不会增加低神经毒性抗生素在中枢神经系统的不良反应。     

开颅手术对脑脊液中药物浓度的影响

目的通过测定开颅术后周围静脉血、皮下引流液及脑脊液中药物浓度,来评价开颅手术对脑脊液药物浓度的影响.方法开颅手术前半小时静脉滴注硫酸庆大霉素8万单位,6小时后分别测定周围静脉血、皮下引流液及脑脊液中庆大霉素浓度,分别对无需切开硬脑膜及需要切开硬脑膜的病例各20例进行对照观察.结果硬脑膜完整组:周围静脉血为0.47±0.15,皮下引流液为1.41±0.46,脑脊液0.27±0.18,以皮下引流液中浓度最高,周围静脉血其次,脑脊液最低,三者比较均有显著差异(P＜0.01);硬脑膜开放组:周围静脉血为0.56±0.19,皮下引流液为1.28±0.75,脑脊液为0.52±0.15,亦是皮下引流液中浓度最高,但周围静脉血与脑脊液无显著差异(P＞0.05).两组之间周围静脉血以及皮下引流液无显著差异(P＞0.05),而脑脊液有显著差异(P＜0.01).结论开颅术后的皮下引流液中含有较高的药物浓度,与脑脊液间存在着明显的浓度差,药物能通过脑脊液与皮下渗出液的交换而进入颅内,使脑脊液中的药物浓度上升.     

靶控输注异丙酚在脑脊液中药物浓度的实验研究

目的 研究靶控效应室浓度输注异丙酚时脑脊液浓度、效应室浓度以及BIS之间的相互关系,探讨靶控效应室浓度输注的准确性。方法 选择成年健康杂种犬12只,以3μg/ml为效应室靶浓度进行靶控输注15min。取脑脊液用高效液相色谱荧光检测法测定异丙酚的浓度。同时监测BIS以及血液动力学和呼气末CO2。结果 靶控效应室浓度输注后,模拟血浆浓度与效应室浓度在10.9min时达到平衡,并维持在3μg/ml的靶浓度水平。15min停止输注后模拟血浆和效应室浓度逐渐衰减。脑脊液峰值浓度约为0.29±0.14μg/ml,但各时点的浓度值均比效应室浓度低（P<0.05）,平均为效应室浓度的18·7％。BIS与脑脊液浓度均在5min达到峰值,而效应室浓度相对滞后。且BIS与脑脊液浓度的相关性（γ=0.9195）优于效应室浓度（γ=0.554）。给药后犬的血压下降但未出现严重的心血管副作用。结论 靶控效应室浓度输注异丙酚时,效应室浓度与BIS的变化不完全一致可能是药代动力学参数造成的差异。脑脊液浓度与BIS相关较好,比血药浓度更能反映效应部位的药代学特征。     

异丙酚预先给药对甘露醇诱导大鼠高渗性血脑屏障损伤的影响

目的观察不同剂量异丙酚预先给药对甘露醇诱导大鼠高渗性血脑屏障损伤的影响。方法24只健康、雄性SD大鼠随机分为三组(n=8):对照组(C组)、小剂量异丙酚组(P1组)和大剂量异丙酚组(P2组)。经大鼠颈内动脉以0.25 ml·kg-1·s-1的速率注射20%甘露醇30 s建立血脑屏障损伤模型,在血脑屏障损伤前,P1组和P2组分别经股静脉注射异丙酚20、40 mg·kg-1,以14C-a-氨基异丁酸(14C-AIB)和3H-葡聚糖(3H-dextran)作为同位素示踪物,在血脑屏障开放后取血及脑组织标本测定同位素放射活性,计算14C-AIB的血/脑转运系数(Ki)。结果C组、P1组和P2组应用甘露醇同侧大脑皮质的Ki分别是相应对侧大脑皮质的4.9、3.5和2.5倍(P<0.01),与C组同侧大脑皮质Ki比较, P2组降低47%(P<0.05),三组间对侧大脑皮质Ki比较差异无统计学意义。C组同侧大脑皮质的血浆容量高于对侧大脑皮质。结论大剂量异丙酚预先给药对甘露醇诱导大鼠高渗性血脑屏障损伤具有保护作用。     

抗生素在骨与关节中浓度分布的实验观测

本实验用健康成年新西兰家兔３６只，经静脉推注三种不同类型抗生素，不同时间取静脉血并处死动物采取肌肉，骨及关节标本，用微生物法测定血清及组织中浓度，并对预防性抗生素使用的给药时间，方法，剂量及药物选择进行探讨。实验结果表明头孢拉定较庆大霉素及环丙氟哌酸的骨与关节渗透性好，并可在骨与关节中维持较长时间的有效浓度，其结果为临床预防性抗生素使用提供了参考依据。     

止血带下骨与肌肉组织抗生素浓度变化的实验研究

[目的]探讨止血带下家兔肢体骨与肌肉组织的抗生素浓度变化.[方法]将头孢唑啉、克林霉素及环丙沙星分别于灌注给药后30、60、90、120 min以止血带阻断家兔肢体血液循环,并于阻断血液循环后30、60、90 min检测肢体骨与肌肉组织中抗生素浓度.[结果]骨与肌肉组织中头孢唑啉、克林霉素及环丙沙星浓度,在相同止血时机、相同止血时间实验组与对照组比较,浓度变化有显著性差异(P＜0.05)；在相同止血时机、不同止血时间实验组之间比较,浓度变化无显著性差异(P＞0.05)；不同止血时机实验组之间比较,浓度变化有显著性差异(P＜0.05).[结论]止血带阻断家兔肢体血液循环对抗生素在骨与肌肉组织分布有显著性影响,肢体血液循环阻断后对抗生素在骨与肌肉组织分布无显著性影响,止血时机是影响抗生素在骨与肌肉组织分布的主要因素.     

甘露醇在脑血管病急性期应用中有关问题的再探讨

甘露醇自1963年被Wise等应用于神经科临床以来，作为一种有效的降颅内压药物，长期应用于急性脑血管病的治疗。随着甘露醇在临床上的广泛应用，其对机体的各种不良反应亦日益受到重视。目前对甘露醇在脑血管病急性期的使用时机、用药剂量、作用时间等问题尚存在许多争议。现将其研究进展综述如下。     

硝普钠控制性降压对脑脊液和血中乳酸浓度的影响

将颅脑手术２４例分成两组：硝普钠降压组１１例，正常对照组１３例，检测脑脊液和动脉血中乳酸含量，观察其变化，厂解控制性降压６０分钟，血压恢复后６０分钟及正常手术对脑及全身代谢的影响。结果显示：二组在手术（降压）各阶段，脑脊液、动脉血中乳酸变化及其比较均无差异（Ｐ＞０．０５），说明颅脑手术期间控制性降压６０分钟对脑及全身代谢诸方面是安全的。这可能与麻醉药降低脑及全身的代谢、吸入气氧浓度提高及脑血流的自动调节机制不受破坏有关。     

等渗透剂量20%甘露醇与3%高渗盐水对大脑半球胶质瘤切除术患者血浆渗透浓度和电解质影响的比较

目的 比较择期大脑半球胶质瘤切除术中应用等渗透剂量的3%高渗盐水(hypertonie saline,HTS)和20%甘露醇(mannitol,M)降颅内压(intracranial pressure,ICP)的同时,患者血浆渗透浓度和电解质的变化及其临床意义. 方法 择期行大脑半球胶质瘤切除术患者40例,根据计算机随机分组表分为高渗盐水组(HTS组)和甘露醇组(M组)(n=20).两组均行静吸复合麻醉,异氟醚呼气末浓度达1 MAC后,在15 min内输注等渗透剂量3%HTS(5.33 ml/kg)或20%M(1 g/kg).记录输注前即刻(T0)、输注后即刻、输注后5、15、30、60、90、120 min(T1～T7)平均动脉压(MAP)、心率(HR),同时采取5 ml动脉血测定血球压积、血浆Na+、K+、Cl浓度、血pH、血浆渗透浓度,同时监测颅内压.结果 两组血浆渗透浓度在输注高渗溶液后均明显升高,在T1达高峰[HTS组:(305.1+4.3)mOsm/L;M组:(304.6±3.5)mOsm/kg](P<0.05),HTS组血浆Na+和cl浓度明显升高,于T1达高峰(152.3+5.2)mEq/kg(P<0.05),M组血浆Na+度降低,在T1达低谷(131.2±3.3)mEq/kg(P<0.05);血浆Cl-浓度在HTS组升高(P<0.05),M组降低(P<0.05).HTS组ICP在T2～T5降低(P<0.05),尤以T1～T2时段降低幅度更为明显,M组ICP在T3～T5降低(P<0.05).结论 在实施择期神经外科手术的患者,单剂静脉输注5.49 mOsm/kg的3%HTS和20%M引起同等程度的血浆渗透浓度上升,并在输注末达到高峰.     

Cerebrospinal Fluid Retrieval in the Conscious Dog: A Methods Development Study

A chronic cerebrospinal fluid access system is described for use in the conscious sling-restrained dog. In a pilot study of ten dogs, a fenestrated barium-impregnated silastic catheter was surgically implanted in the subarachnoid space of the second cervical vertebra through a dorsal laminectomy. This fenestrated catheter was coupled to a subcutaneous access port. Following surgery, cerebrospinal fluid was sampled weekly and evaluated for protein content and cytology. The cerebrospinal fluid albumin to serum albumin ratio was calculated for each sample to evaluate blood-brain barrier integrity. The instrumentation was successfully implanted in five of the first eight dogs using a midbody dorsal laminectomy. Cerebrospinal fluid access was maintained in these dogs for 21 ± 10 days. Using a slight modification of the original technique, the final two dogs were instrumented through a caudodorsal laminectotny of the second cervical vertebra. The cerebrospinal fluid access system remains patent after 444 days of study in these two dogs. Necropsy evaluation suggested that catheter failure in the immediate postoperative period was due to gross malposition of the catheter. Chronic catheter failure occurred secondary to obstruction by local fibrous tissue reaction. Using this instrumentation, a pharmacokinetic evaluation of the plasma and cerebrospinal fluid deposition of an intravenous bolus of acyclovir was successfully performed twice in a single dog without complications. This instrumentation could provide chronic cerebrospinal fluid access for multiple pharmacokinetic studies in the conscious dog.     

Entry Rate Kinetics of D-Mannitol and Carboxyl-lnulin for Transfer Across the Blood-Cerebrospinal Fluid Barrier

Abstract

This study evaluates the entry rate kinetics of hydrophilic compounds [³H]-D-mannitol and [¹⁴C]-carboxyl-inulin across the blood-cerebrospinal fluid (CSF) barrier in a rabbit experimental model. To maintain steady state levels of these tracers in circulation, 100 μCi of [³H]-D-mannitol and 150 μCi of [¹⁴C]-carboxyl-inulin were administered as a bolus and by slow infusion for four hours via a femoral venous catheter. Entry rate kinetics of [³H]-D-mannitol and [¹⁴C]-carboxyl-inulin from plasma into cisterna magna CSF were computed using a mathematical equation described by Davson.⁷ [³H]-D-mannitol and [¹⁴C]-carboxyl-inulin maintained steady state levels throughout the experiment. Entry rates for mannitol and carboxyl-inulin were represented by a straight line, from the slope of which K_out (or K_in) were computed; Kin values for mannitol and carboxyl-inulin were 0.06820 hr^-1 and 0.00023 hr^-1 respectively. Differences in the entry rate of mannitol and carboxyl-inulin may be explained by the molecular size and effective radius of these tracers. (J Spinal Cord Med 1997;20:391-394)     

Appearance of Pethidine and Norpethidine in Cerebrospinal Fluid of Man Following Intramuscular Injection of Pethidine

The plasma and cerebrospinal fluid (CSF) concentrations of pethidine and its main metabolite in plasma, norpethidine, were determined in 20 patients undergoing minor surgery who had received pethidine chloride as premedication in a standard dose of 100 mg intramuscularly. The disposition of pethidine and norpethidine in plasma was followed for 3–8 h after administration. The rate of transfer of the drug and its metabolite from plasma to CSF was assessed on the basis of a single sample of CSF taken from each patient. Pethidine appeared within less than 18 min in the CSF, reaching a maximum after about 90 min. After that, the pethidine concentration ratio CSF/plasma was relatively stable at 0.4-0.5. This is in agreement with the concept that the concentration of a drug in CSF is correlated with the concentration of unbound drug in plasma at equilibrium. Norpethidine which was present in rapidly increasing concentrations in plasma after a delay of 30 min, appeared in CSF in a slower and more erratic fashion as compared to the parent compound. However, after 240 min, the CSF/plasma concentration ratio was similar for pethidine and norpethidine. Thus, transfer from plasma to CSF occurs relatively rapidly. There is little evidence for a functionally significant blood-brain barrier for pethidine and norpethidine.     

腰大池置管持续引流治疗胸椎黄韧带骨化术后脑脊液漏

目的探讨腰大池置管持续引流治疗胸椎黄韧带骨化术后脑脊液漏的效果。方法2003年3月～2011年3月对15例胸椎黄韧带骨化术后脑脊液漏应用一次性颅脑外引流器从L3-4椎间隙行硬膜外穿刺,置管于蛛网膜下腔引流脑脊液。结果切口引流时间2～8d,平均4d;腰大池置管时间3～10d,平均6d。15例术后随访6个月,无一例出现脑脊液复发、切口感染和颅内感染并发症。结论腰大池置管持续引流治疗胸椎黄韧带骨化术后脑脊液漏安全、有效。     

腰椎MED手术发生脑脊液漏的原因分析及对策

目的分析显微椎间盘镜下髓核除手术(Micro Endoscopic Discectomy，MED)并发硬脊膜损伤或脑脊液漏的原因特点，探讨其预防办法。方法通过回顾性的方法对1999年12月至2003年12月期间452例MED手术发生硬脊膜损伤或脑脊液漏的15例患临床资料进行分析总结。结果术中发现硬脊膜损伤的13例患，有9例术后出现脑脊液漏；2例术中未发现硬脊膜损伤的患术后也出现了脑脊液漏；11例脑脊液漏患经术后正规的保守治疗于3～7d内治愈，无1例脑脊髓膜炎，无继发的深部感染。结论MED手术因其自身的特点，易发生硬脊膜损伤；但通过术前对病例仔细分析，术中具备一定的手术技巧，可以减少硬脊膜损伤的发生；术中对损伤硬脊膜及时堵塞或修补，术后采取正规的保守治疗措施，脑脊液漏均可治愈。     

Kinetics of Morphine in Cerebrospinal Fluid After Epidural Administration

Forty patients undergoing arthroscopy were given an epidural dose of 0.05 mg morphine-HCl in 0.1 ml saline/kg body weight to study the disposition of morphine in the cerebrospinal fluid (CSF). In each patient one to three CSF samples were collected (86 samples in total). A mean peak concentration of 13 890 nmol/l was achieved 75 min after morphine administration. The compiled data show an elimination half-life of 162 min (r = 0.98). Individual half-lives in seven patients with three samples ranged from 61-172 min. Large interindividual variations were found in CSF-concentrations of morphine, 9- and 8-fold at 3 and 8 h, respectively, after the dose. However, 16 h after administration no patient had a concentration less than 81 nmol/l. At 8 h after the dose, CSF concentrations of morphine were significantly higher (P less than 0.05) in a group of patients (n = 5) kept uptilted (80 degrees), as compared to those in the supine position (n = 5). Such a difference was not observed 3 h after the dose. The sampling procedure and age also seemed to influence CSF concentrations of morphine. There was no correlation between the dose given in mg and the CSF concentrations achieved. Strict standardization is thus mandatory when studying the disposition of opiates in CSF after epidural or intrathecal administration. Since our calculated half-lives of morphine in CSF were similar to those reported in plasma, the long-lasting effect is probably related to the high initial morphine concentrations in CSF.     

Evaluation of the Production and Absorption of Cerebrospinal Fluid

The traditional hypothesis of cerebrospinal fluid (CSF) hydrodynamics presumes that CSF is primarily produced in the choroid plexus (CP), then flows from the ventricles into the subarachnoid spaces, and mainly reabsorbed in the arachnoid granulations. This hypothesis is necessary to reconsider in view of recent research and clinical observations. This literature review presents numerous evidence for a new hypothesis of CSF hydrodynamics—(1) A significantly strong relationship exists between the CSF and interstitial fluid (IF), (2) CSF and IF are mainly produced and absorbed in the parenchymal capillaries of the brain and spinal cord. A considerable amount of CSF and IF are also absorbed by the lymphatic system, and (3) CSF movement is not unidirectional flow. It is only local mixing and diffusion.     

腰椎术后迟发脑脊液漏的预防和治疗

目的探讨腰椎术后迟发脑脊液漏的预防和治疗。方法通过回顾性的方法对1999年1月至2012年7月所发生的26例腰椎术后迟发脑脊液漏患者的临床资料进行分析总结,其中男19例,女7例;年龄25~70岁,平均32.8岁。结果经过卧床休息、延长拔管时间和伤口加压包扎等综合治疗1~3周后,所有患者的脑脊液漏症状治愈。经过平均3.3年的随访,术后未发现脑脊液漏,无硬脊膜假性囊肿形成和腰痛、头痛等症状。结论通过术前充分的准备,术中仔细操作并及时对硬膜损伤进行有效修补,术后采取正规的保守治疗,可以降低腰椎术后迟发脑脊液漏的发生。     

Quantitative Analysis of Cerebrospinal Fluid Pressure Gradients in Healthy Volunteers and Patients with Normal Pressure Hydrocephalus

Magnetic resonance imaging (MRI) can depict not only anatomical information, but also physiological factors such as velocity and pressure gradient. Measurement of these physiological factors is necessary to understand the cerebrospinal fluid (CSF) environment. In this study we quantified CSF motion in various parts of the CSF space, determined changes in the CSF environment with aging, and compared CSF pressure gradient between patients with idiopathic normal pressure hydrocephalus (iNPH) and healthy elderly volunteers. Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image.