胸段硬膜外阻滞对家兔颈迷走神经传出放电的影响

目的通过胸段硬膜外阻滞(TEA)交感神经,探讨TEA对迷走神经传出放电频率的影响。方法健康日本大耳白兔28只,随机均分为假手术(Sham)组、TEA组、硝普钠(SNP)组、胸段硬膜外麻醉+麻黄碱(TEA+EPH)组。在记录MAP、迷走传出端基础电位后,TEA组硬膜外腔给予0.5%布比卡因0.4ml/kg;Sham组在同样时点硬膜外腔注射等容量生理盐水;SNP组记录基础电位后静脉注射硝普钠盐溶液控制性降压,模拟TEA的降压过程,硬膜外腔隙注射等量生理盐水;TEA+EPH组通过硬膜外导管给予0.5%布比卡因0.4ml/kg后肌注麻黄碱维持血压在正常范围。应用BL-420S电生理系统记录并分析硬膜外腔注射前、注射后1、2、3h迷走神经传出放电变化。结果四组家兔注射前基础放电频率差异无统计学意义。TEA组、TEA+EPH组在注射后1、2、3h放电频率明显高于SNP组和Sham组(P0.05)。TEA组、SNP组的MAP在注射后1、2、3h明显低于TEA+EPH组和Sham组(P0.05)。TEA组和TEA和EPH组HR在注射后1、2、3h时明显慢于Sham组(P0.05);SNP和TEA+EPH组在注射后1、2、3h时HR均明显快于TEA组(P0.05)。结论 TEA可能通过阻滞交感神经,使迷走神经传出产生绝对兴奋,这种兴奋并不是因为TEA所致的血管扩张而引起的血压降低所致。     

动脉阻断致颈髓急性缺血性损伤的实验研究

[目的]研究颈髓脊髓前动脉、前根动脉阻断对颈髓缺血性损伤的影响。[方法]将48只家兔随机分为阻断脊髓前动脉组和间接阻断前根动脉组（阻断脊髓前动脉＋双侧椎动脉），两组均设有对照组。每组各在术后6、24、72h检测颈髓血流灌注量，运动诱发电位、组织能量代谢变化，电镜观察细胞形态学改变。[结果]脊髓前动脉阻断后颈髓前部表面血流量下降了50．28％，随后有所回升；运动诱发电位潜伏期延长；ATP和EC进行性下降，出现急性缺血性改变；间接阻断前根动脉组其各指标变化更加明显，同阻断脊髓前动脉相比，存在显著差异，P〈0．05。[结论]脊髓前动脉对颈髓前部血流起着重要的作用，阻断后造成脊髓缺血性损伤，但有部分代偿；前根动脉对颈髓血供有重要的补充和支持作用，临床上各种原因造成的根动脉损伤势必对颈髓带来损害。     

无骨折脱位型颈脊髓损伤患者血压变化分析

目的探讨无骨折脱位型颈脊髓损伤患者的血压变化及相关因素，提高护理质量。方法记录5例无骨折脱位型颈脊髓损伤患者从脊髓休克期至肌力基本恢复期的血压及24h出入量．观察分析其血压变化。结果随着脊髓休克的好转及肌力的恢复．血压逐渐回升。结论颈脊髓损伤患者血压变化存在一定的规律，在护理中主张脊髓休克期取平卧位，随着患者神经功能的恢复，可逐渐进行斜立位训练，以提高自身对血压的调节能力；注意避免自主神经不良反应(AD)的诱因，对出现AD者立即采取措施．控制血压。     

家兔鞘内注射复方倍他米松的神经毒性

目的观察鞘内注射复方倍他米松的神经毒性。方法选择24只成年家兔，随机分为四组。Ⅰ组：不施加任何处理；Ⅱ组：经枕骨大孔向兔蛛网膜下腔注射生理盐水0．2ml，每周1次；Ⅲ组：除注射药为复方倍他米松200μg(0．2ml)外，其余处理同Ⅱ组；Ⅳ组：注射复方倍他米松400μg(0．2ml)，其余处理同Ⅱ组。3周后处死动物，用生理盐水及戊二醛灌注，取出颈部脊髓(C1-6)放入4℃2％戊二醛内做后固定。观察脊髓组织细胞形态的变化。结果Ⅰ、Ⅱ组脊髓组织细胞形态未见异常；Ⅲ、Ⅳ组脊髓组织细胞的病理改变主要为神经纤维水肿、脱髓鞘、神经元突起消失、结构模糊，线粒体肿胀、空泡变性。结论鞘内注射复方倍他米松可引起脊髓的损害。     

血小板活化因子及其受体拮抗剂对颈髓损伤后血脊髓屏障病理损害的影响

目的 探讨血小板活化因子(PAF)及其受体拮抗剂对猫颈髓损伤后血脊髓屏障损害的作用。方法 采用鞘内注射PAF及静脉注射PAF受体拮抗剂BN52021，观察其对颈髓损伤后脊髓组织PAF含量、血脊髓屏障的影响。结果 颈髓损伤后颈髓伤区及邻近脊髓组织PAF含量、伊文思蓝含量、水含量均明显增加，鞘内注射PAF可使伤后PAF含量、伊文思蓝含量、水含量增加更为显著。BN52021可抑制伤后颈髓组织PAF含量升高，降低颈髓组织伊文思蓝含量及水含量。结论 PAF是导致颈髓损伤后血脊髓屏障损害的重要因子，而BN52021叫可有效减轻血脊髓屏障的病理损害。     

鞘内注射新斯的明对术后疼痛大鼠脊髓背角NOS表达的影响

目的：观察大鼠术前或术后鞘内注射新斯的明(NEO)对脊髓背角一氧化氮合成酶(NOS)表达的影响。方法：16只SD大鼠在鞘内置管成功5天后，随机分为四组。每组4只。I组为假手术组；Ⅱ组在术前30min鞘内注射0．9％NaCl；Ⅲ和Ⅳ组分别于术后或术前30min鞘内注射NEO10μg.用累积疼痛评分法测定疼痛程度；用NADPH-d酶组织化学法显示脊髓NOS阳性神经元。结果：Ⅲ组和Ⅳ组的累积疼痛评分均显著低于Ⅱ组。但Ⅲ组与Ⅳ组组同比较无明显差异。Ⅱ组手术侧脊髓背角浅表面NOS阳性神经元明显多于对侧及I组。与Ⅱ组比较。Ⅲ组和Ⅳ组相同部位的NOS阳性神经元均明显减少。尤以Ⅳ组减少为显著。而NEO用药组(Ⅲ组和Ⅳ组)比较也存在显著性差异。结论：在大鼠切口疼痛模型中，术前或术后鞘内注射NEO均具有明显的镇痛作用，同时脊髓背角NOS的表达明显减少，尤以术前用药组为显著。提示鞘内NEO的抗伤害作用可能与NO有关。     

硬膜外注射吗啡对兔和鼠生理和免疫功能的影响

研究用家兔硬膜外腔注射吗啡和大鼠鞘内注射吗啡作为术后镇痛动物模型，结果观察到：家兔硬膜外腔注射吗啡（２ｍｇ／ｋｇ）后，１５分钟内肠蠕动强度即从用药前的１．９７±０．１７降至０．７８±０．０３（Ｐ＜０．０１），９０分钟以后仍呈明显抑制状态（Ｐ＜０．０１），同时呼吸频率也呈明显降低（Ｐ＜０．０１）；大鼠鞘内注射吗啡（４０μｇ）后，虽然脾脏淋巴细胞总数下降不明显（Ｐ＞０．０５），但是，脾脏淋巴细胞转化和白细胞介素－２（ＩＬ－２）诱生水平呈明显下降（Ｐ＜０．０１），细胞免疫功能受到明显抑制。故病人在用吗啡镇痛时不仅应考虑生理功能受抑制，更应注意其免疫功能的下降，以便进行适当保护，增强其抗病能力。     

阿片肽、纳洛酮与休克研究的现状

阿片肽特别是β-内啡肽参与出血性、内毒素性、过敏性休克和脊髓休克的发病过程。通过减弱交感神经紧张性或增强副交感神经紧张性;5-HT 通路及直接作用于心肌细胞受体等途径而发挥作用。也可以通过某些体液因子间接作用于心血管系统。纳洛酮(Naloxo-ne)在多种类型休克的治疗中作用显著。通过阻断阿片肽与中枢、外周组织受体的结合;增加心肌收缩力;影响细胞功能和代谢及增加重要生命器官的血液灌注等环节,明显改善休克状态。     

急性脊髓前动脉及双侧椎动脉阻断对颈髓血流量影响的实验研究

目的：研究颈部脊髓前动脉及双侧椎动脉阻断对颈髓血流量的影响及其病理学变化。方法：将48只家兔随机分为阻断脊髓前动脉组与阻断脊髓前动脉和双侧椎动脉组，术后6h、24h、72h采用激光多普勒血流测定仪检测颈髓血流灌注量，电镜观察颔髓组织细胞形态学、免疫组化检测神经丝的变化。结果：脊髓前动脉阻断后颈髓血流量下降1/2，随后有所回升，但依然处于低灌注状态；阻断脊髓前动脉和双侧椎动脉后．其血流量下降更为湿著，为对照组的1/3，电镜及免疫组化显示两组均出现了缺血性改变，经统计学检验两组每一时相点的血流量和神经丝表达程度均有显著性差异（P〈0．05）。结论：颈髓前部血流量除与脊髓前动脉有关外．前根动脉也有一定的作用，临床上各种原因造成脊髓前动脉或根动脉的损伤均可能导致颈髓缺血性损伤。     

鞘内注射吗啡对福尔马林炎性疼痛大鼠脊髓背角环氧化酶-2表达的影响

目的评价鞘内注射吗啡对福尔马林炎性疼痛大鼠脊髓背角环氧化酶-2（COX-2）表达的影响。方法32只鞘内置管成功的雄性SD大鼠，随机分为4组（n=8）：对照组（C组）、模型组（F组）、生理盐水组（NS组）及吗啡组（M组）。鞘内置管后5d，F组、NS组及M组大鼠于左后足掌部皮下注射5％福尔马林50μl，注射福尔马林前30min，NS组鞘内注射20μl生理盐水，M组鞘内注射10μl（10μg）吗啡和10出生理盐水，C组不给任何处理，采用疼痛加权评分评价疼痛行为学。F组、NS组及M组于注射福尔马林后24h，C组于鞘内置管后6d处死大鼠，取L5脊髓，采用免疫组织化学方法观察脊髓背角COX-2表达。结果吗啡可减轻福尔马林炎性疼痛；与C组比较，F组、NS组脊髓背角COX-2表达增加（P〈0．01）；与F组、NS组比较，M组脊髓背角COX-2表达降低（P〈0．01）。结论鞘内注射吗啡可抑制福尔马林炎性疼痛引起的脊髓中COX-2表达增加，可能与吗啡的抗伤害和镇痛作用有关．     

缺血和再灌流对脊髓血流量及运动诱发电位的影响

本文采用家兔失血性休克模型，使血压下降至３０ｍｍＨｇ维持３０ｍｉｎ后再灌流，让血压回升到正常范围。观察缺血再灌流期 ＳＣＢＦ和 ＳＥＰ变化。缺血期平均动脉压 ３０～４０ｍｍＨｇ，脊髓 Ｔ１２及Ｌｌ节段灰质血流量减少５７％～６４％，白质血流量减少３２％～５０％；ＳＭＥＰ的潜伏期明显延长（Ｐ＜０．００１），各波的波幅降低并有２５％～６７％的波幅消失。再灌流期当血压回升到９０～１３０ｍｍＨｇ时，灰质血流量仍低于伤前（Ｐ＜０．０１），白质血流量无显著差异．ＳＭＥＰ潜伏期仍明显延长（Ｐ＜０．０５），除Ｐｌ波波幅下降有统计意义外，其它各波幅无差异，波幅消失占２５％～３３．３％。光镜下见脊髓存在损伤性病理变化，显示缺血再灌流后脊髓组织仍然存在继发缺血性病理损害和神经功能障碍。     

The effects of intrathecally administered neostigmine on somato-sympathetic reflex potentials

BACKGROUND: Antinociceptive effect of intrathecal neostigmine has been investigated using withdrawal responses in laboratory experiments. However, neostigmine administered in this route can induce muscle weakness or sedation. As a result, these effect can modify withdrawal responses. In this study we investigated the antinociceptive effect of intrathecally administered neostigmine bromide (NB) in cats objectively and quantitatively using somato-sympathetic reflex potentials. METHODS: Anesthetized cats were inserted with a spinal catheter via atlanto-occipital membrane and 10 micrograms (n = 5), 50 micrograms (n = 5), 250 micrograms (n = 8) or 2 mg (n = 5) of NB was administered through this route. Somato-sympathetic reflex potentials (A and C reflex) derived from lumbar sympathetic ganglion by stimulation of the femoral nerve and mean arterial blood pressure (MAP) and heart rate (HR) in each dose were monitored and recorded. RESULTS: Reflex potential was reduced in a dose dependent fashion by NB but these changes were not significant. On the other hand, 250 micrograms and 2 mg of NB maximally reduced C reflex potential to 55.2% and 24.0% of control values respectively 20 minutes after the administration (P < 0.01), and this reduction was reversed by 250 to 2 mg of intrathecal administration of atropine sulfate to 89.4%, 68.6% of control values respectively. MAP and HR decreased in dose dependent fashion by NB to 57.6%, 65.2% of control values after the administration of 2 mg of NB and these cardiovascular changes recovered by intrathecally administered atropine sulfate. CONCLUSION: These results objectively indicate that intrathecally administered neostigmine bromide shows antinociceptive effect and this inhibition is partially mediated by cholinergic mechanism.     

Spinal Action of Ketorolac, S(+)- and R(-)-ibuprofen on Non-noxious Activation of the Cathechol Oxidation in the Rat Locus Coeruleus: Evidence for a Central Role of Prostaglandins in the Strychnine Model of Allodynia

Background: Blockade of spinal glycine receptors with intrathecal strychnine produces an allodynia-like state in the anesthetized rat. Innocuous hair deflection in the presence of intrathecal strychnine induces a nociceptive-like activation of catechol oxidation in the locus coeruleus and enhances cardiovascular responses. Because prostaglandins play a central role in augmenting pain, this study evaluated the effect of intrathecal nonsteroidal antiinflammatory drugs in strychnine-induced allodynia.

Methods: In urethane-anesthetized rats, changes in catechol oxidation in the locus coeruleus, measured using in vivo voltammetry, and cardiovascular parameters evoked by hair deflection of caudal dermatomes were determined after strychnine (40 [micro sign]g) or saline were administered intrathecally. Subsequently, the effects of 30 [micro sign]g ketorolac, 10 [micro sign]g S(+)-ibuprofen, and 10 [micro sign]g R(-)-ibuprofen administered intrathecally were evaluated.

Results: After strychnine was administered intrathecally, hair deflection evoked an increase in the locus coeruleus catechol oxidation (peak, 149.7 +/- 7.2% of baseline) and mean arterial blood pressure (peak, 127.5 +/- 3.8% of baseline). These responses were not observed after saline was administered intrathecally. All hair deflection-evoked, strychnine-dependent peak responses were attenuated significantly with intrathecally administered ketorolac and S(+)-ibuprofen but not with R(-)-ibuprofen.     

Site of hemodynamic effects of intrathecal alpha 2-adrenergic agonists.

Intrathecally administered alpha 2-adrenergic agonists produce analgesia in humans but may also produce hypotension and bradycardia. To further characterize hemodynamic depression produced by intrathecally administered alpha 2-adrenergic agonists, clonidine (100-1,500 micrograms) was injected into the cervical, thoracic, or lumbar intrathecal space of conscious sheep. Only thoracic intrathecal clonidine injection (100 or 300 micrograms) decreased blood pressure, whereas these doses did not affect blood pressure when injected at other sites. A greater clonidine dose (1,500 micrograms) increased blood pressure to a similar degree at all sites. Hypotension after thoracic intrathecal clonidine injection was inhibited by pretreatment with the alpha 2-adrenergic antagonist idazoxan (1 mg, intrathecally) or the depleter of acetylcholine stores hemicholinium-3 (2 mg, intrathecally), suggesting an action at alpha 2-adrenoceptors on cholinergic preganglionic sympathetic neurons. ST-91, a polar clonidine analog, did not decrease blood pressure after thoracic intrathecal injection. Intrathecal injection of the muscarinic receptor agonist carbamylcholine increased blood pressure. These data describe a complex action of intrathecal alpha 2-adrenergic agonists on hemodynamic parameters that is dependent on site of injection, drug dose, and drug lipophilicity; that can be explained by anatomic factors; and that may possibly be exploited to minimize hemodynamic depression from these agents.     

Haemodynamic changes induced by hyperbaric bupivacaine during lateral decubitus or supine spinal anaesthesia

BACKGROUND AND OBJECTIVE: Hypotension, the commonest side-effect of spinal anaesthesia, results from sympathetic denervation. This study compared patient positioning (supine vs. decubitus) on haemodynamic variables during spinal anaesthesia. METHODS: After intravenous crystalloid preloading with 5 mL kg(-1), hyperbaric bupivacaine 0.5% 2.5 mL was injected intrathecally at the L2-3 or L3-4 interspace. Patients were then randomly assigned to be positioned immediately supine and horizontal for 30 min (Group SUP, n = 12), or remained in the lateral decubitus position (fractured hip dependent) for 30 min (Group LAT, n = 14). Systolic blood pressure, mean arterial pressure, and loss of sensation of pinprick sensation were recorded prior to induction of spinal anaesthesia (baseline) and at 1, 2, 3, 5, 10, 15, 30, 45, 60, 90 and 120 min after intrathecal injection. RESULTS: In Group SUP, the percent maximum systolic blood pressure (36 +/- 13%) and percent maximum mean arterial pressure decreases (27 +/- 13%) were significantly greater (P < 0.05) than in Group LAT (30 +/- 8% and 23 +/- 11%, respectively). Additionally, there was a borderline significant delay in the time to maximum systolic blood pressure decrease in Group LAT (38 +/- 30 min) when compared with Group SUP (20 +/- 17 min, P = 0.06), while the total dose of ephedrine required in the SUP group (30 mg) was greater than that required in the LAT group (15 mg, P = 0.05). In Group LAT patients, the mean level of denervation on the operative side extended 2 dermatomes more cephalad than in Group SUP. CONCLUSIONS: Lateral positioning for spinal anaesthesia delays the onset of hypotension, while requiring smaller total doses of vasoconstrictors for blood pressure maintenance.     

Intrathecal Ropivacaine in Rabbits: Pharmacodynamic and Neurotoxicologic Study

Background: Ropivacaine is available for spinal or intrathecal use in humans, although data on neurotoxicity after spinal injection are not yet available. The authors experimentally determined the relationship between doses of intrathecal ropivacaine and spinal effects and local neurotoxic effects.

Methods: Eighty rabbits equipped with an intrathecal lumbar catheter were studied. Sixty were randomly assigned to receive 0.2 ml of intrathecal solutions as a sole injection of: 0.2%, 0.75%, 1.0%, and 2.0% ropivacaine (doses from 0.4-4.0 mg; groups R0.2 to R2.0), 5.0% lidocaine (10 mg; group L), or 0.9% NaCl as control (group C). Twenty other rabbits received either repeated injections of 0.2 ml of 0.2% ropivacaine every 2 days during 2 weeks (total dose of 2.8 mg; group RINT); or a continuous intrathecal infusion of 0.2% ropivacaine at the rate of 1.8 ml/h over 45 min (2.7 mg; group RCONT). Injection rate was 30 s in all groups except Rcont. Time to onset, duration and extent of motor block, and variations of mean arterial blood pressure were recorded in all groups. Somatosensory evoked potentials were also recorded in group RCONT and RINT. Seven days after the last intrathecal injection spinal cord and nerves were sampled for histopathologic study.

Results: In groups R0.2 and RINT, the lowest dose of ropivacaine induced a clinically visible spinal block in only 50% of rabbits, but SEPs recorded in group RINT were decreased by 70% in the lumbar dermatome. Complete motor block was observed with doses greater than 1.5 mg of ropivacaine (group RCONT and R0.75 to R2.0). Onset time was shorter and duration of block increased as doses of ropivacaine increased. Significant hypotension was observed only with 4.0 mg of ropivacaine (concentration of 2.0%). Complete paralysis and hypotension were observed with 5.0% lidocaine. No neurologic clinical lesion was observed in rabbits receiving saline or ropivacaine within the 7 days after the last intrathecal injection, and histopathologic study revealed no sign of neurotoxicity in these groups. In contrast, intrathecal lidocaine induced clinical and histopathologic changes.     

Intrathecal and oral clonidine as prophylaxis for postoperative alcohol withdrawal syndrome: a randomized double-blinded study

In this study, we evaluated the effect of intrathecal and oral clonidine as supplements to spinal anesthesia with lidocaine in patients at risk of postoperative alcohol withdrawal syndrome (AWS). We hypothesized that clonidine would have a prophylactic effect on postoperative AWS. Forty-five alcohol-dependent patients (daily ethanol intake >60 g) scheduled for transurethral resection of the prostate were double-blindly randomized into three groups. All patients received hyperbaric lidocaine 100 mg intrathecally. The diazepam group (DiazG) was premedicated with diazepam 10 mg orally; the intrathecal clonidine group (Clon(i/t)G) received a placebo (saline) tablet and clonidine 150 microg intrathecally; and the oral clonidine group (Clon(p/o)G) received clonidine 150 microg orally. For patients diagnosed with AWS, the Clinical Institute Withdrawal Assessment for Alcohol, revised scale, was used. Twelve patients in the DiazG had symptoms of AWS, compared with two in the Clon(i/t)G and one in the Clon(p/o)G. The median Clinical Institute Withdrawal Assessment for Alcohol, revised scale, score was 12 in the DiazG versus 1 in the clonidine-treated groups. Two patients in the DiazG had severe delirium. Patients receiving oral clonidine had a slightly decreased mean arterial blood pressure 6-12 h after spinal anesthesia (P < 0.05); patients in the DiazG had a hyperdynamic circulatory reaction 24-72 h after surgery. In conclusion, preoperative clonidine 150 microg, intrathecally or orally, prevented significant postoperative AWS in ethanol-dependent patients. IMPLICATIONS: In this randomized, double-blinded study, clonidine 150 microg both intrathecally and orally prevented postoperative alcohol-withdrawal symptoms in alcohol-dependent men. The effect was superior to that with a single dose of diazepam 10 mg orally.     

The advantages of intrathecal opioids for spinal fusion in children

Two groups of 40 homogeneous patients (ASA physical status (1–2)) with idiopathic scoliosis undergoing spinal fusion with CD instrumentation were studied prospectively. Group A (intrathecal) received a mixture of morphine and sufentanil administered intrathecally at the level of L3–L4 after the induction of anaesthesia. Group B (control) had inhalation and intravenous narcotic anaesthesia. The use of intrathecal opioids resulted in a significant reduction of blood pressure without the use of any hypotensive agents and produced prolonged postoperative analgesia. There was no adverse effect on somatosensory evoked potentials. The dose requirement for the anaesthetic agents was significantly reduced and the blood loss was 27% of their blood volume compared with 53% in the control group. No long or short term impairment of cerebral or spinal function was observed. The use of intrathecal opioids supplemented with other anaesthetic agents is an alternative method with multiple benefits for any major surgery such as spinal fusion.     

Increase in rat spinal cord blood flow with the calcium channel blocker, nimodipine

Nimodipine, a calcium channel blocker, is known to increase cerebral blood flow. In the present study, the authors investigated the effect of nimodipine on spinal cord blood flow in normal rats. Cardiovascular parameters, including mean systemic arterial blood pressure, cardiac output, and heart rate, were recorded during infusion of nimodipine in a dose-response fashion. The experiment was a randomized blind study in which four groups of five rats received different doses of nimodipine (0.001, 0.01, 0.05, and 0.10 mg/kg) intravenously over 30 minutes, and a control group of five rats received only the diluent. The hydrogen clearance and thermodilution techniques were used to measure spinal cord blood flow and cardiac output, respectively. The 0.05-mg/kg dose of nimodipine caused the largest increase in spinal cord blood flow, with a 40% increase over the preinfusion level, although there was a 25% reduction in mean arterial pressure. The 0.10-mg/kg dose did not increase spinal cord blood flow more than the 0.05-mg/kg dose, most likely due to the concomitant 37% reduction in mean arterial pressure. Cardiac output was significantly increased by the 0.05- and 0.10-mg/kg doses secondary to the drop in total peripheral resistance. The increase in spinal cord blood flow produced by nimodipine lasted approximately 20 minutes after the termination of the infusion. Thus, nimodipine at a dose of 0.05 mg/kg markedly increased blood flow in the normal spinal cord even though there were major changes in mean systemic arterial pressure and cardiac output. Further research is required to determine whether this drug might be beneficial in treating ischemic states of the spinal cord, such as posttraumatic ischemia.     

Intrathecal ropivacaine in rabbits: pharmacodynamic and neurotoxicologic study

BACKGROUND: Ropivacaine is available for spinal or intrathecal use in humans, although data on neurotoxicity after spinal injection are not yet available. The authors experimentally determined the relationship between doses of intrathecal ropivacaine and spinal effects and local neurotoxic effects. METHODS: Eighty rabbits equipped with an intrathecal lumbar catheter were studied. Sixty were randomly assigned to receive 0.2 ml of intrathecal solutions as a sole injection of: 0.2%, 0.75%, 1.0%, and 2.0% ropivacaine (doses from 0.4-4.0 mg; groups R0.2 to R2.0), 5.0% lidocaine (10 mg; group L), or 0.9% NaCl as control (group C). Twenty other rabbits received either repeated injections of 0.2 ml of 0.2% ropivacaine every 2 days during 2 weeks (total dose of 2.8 mg; group RINT); or a continuous intrathecal infusion of 0.2% ropivacaine at the rate of 1.8 ml/h over 45 min (2.7 mg; group RCONT). Injection rate was 30 s in all groups except Rcont. Time to onset, duration and extent of motor block, and variations of mean arterial blood pressure were recorded in all groups. Somatosensory evoked potentials were also recorded in group RCONT and RINT. Seven days after the last intrathecal injection spinal cord and nerves were sampled for histopathologic study. RESULTS: In groups R0.2 and RINT, the lowest dose of ropivacaine induced a clinically visible spinal block in only 50% of rabbits, but SEPs recorded in group RINT were decreased by 70% in the lumbar dermatome. Complete motor block was observed with doses greater than 1.5 mg of ropivacaine (group RCONT and R0.75 to R2.0). Onset time was shorter and duration of block increased as doses of ropivacaine increased. Significant hypotension was observed only with 4.0 mg of ropivacaine (concentration of 2.0%). Complete paralysis and hypotension were observed with 5.0% lidocaine. No neurologic clinical lesion was observed in rabbits receiving saline or ropivacaine within the 7 days after the last intrathecal injection, and histopathologic study revealed no sign of neurotoxicity in these groups. In contrast, intrathecal lidocaine induced clinical and histopathologic changes. CONCLUSION: Ropivacaine induced dose-dependent spinal anesthesia, and did not induce any neurotoxicologic lesion in this experimental animal model.