The neurotoxicity of drugs given intrathecally (spinal)

Overall, most spinal drugs in clinical use have been poorly studied for spinal cord and nerve root toxicity. Laboratory studies indicate that all local anesthetics are neurotoxic in high concentrations and that lidocaine and tetracaine have neurotoxic potential in clinically used concentrations. However, spinal anesthesia (including lidocaine and tetracaine) has a long and enviable history of safety. Spinal analgesics such as morphine, fentanyl, sufentanil, clonidine, and neostigmine seem to have a low potential for neurotoxicity based on laboratory and extensive clinical use. Most antioxidants, preservatives, and excipients used in commercial formulations seem to have a low potential for neurotoxicity. In addition to summarizing current information, we hope that this review stimulates future research on spinal drugs to follow a systematic approach to determining potential neurotoxicity. Such an approach would examine histologic, physiologic, and behavioral testing in several species, followed by cautious histologic, physiologic, and clinical testing in human volunteers and patients with terminal cancer refractory to conventional therapy.     

A simple technique to reduce the incidence of accidental dural puncture

We would like to respond to recent comments (Reynolds. Anaesthesia 2001: 56 : 1129) on our epidural technique. In our practice we apply loss of resistance to air technique, which helps identify a nick in the dura with a small leak of CSF. On many occasions, only a few drops of CSF and not a constant leak helped identify dural puncture, which could have been missed with the use of saline. Upon inserting the epidural needle, we remove the stylet when the needle is engaged in the interspinous ligament or the ligamentum flavum. Very often, it is difficult for our residents to advance the epidural needle with one hand and apply constant pressure on the plunger with the other hand. Excessive pressure with one hand, by a resident, had caused dural puncture when the needle was pushed in too far. By reinserting the stylet with each advancement of the needle, we remove tissues that may enter and occlude the epidural needle. It is quite possible that constant plunger pressure with saline may also avert this problem.     

鞘内注射不同剂量右美托咪啶对大鼠的抗伤害效应和脊髓神经毒性

目的 评价鞘内注射右美托咪啶对大鼠的抗伤害效应和脊髓神经毒性.方法 雄性SD大鼠60只,体重180～220 g,采用随机数字表法,将其随机分为5组(n=12):对照组(C组)不做任何处理;生理盐水组(N组)鞘内注射生理盐水10 μl;不同剂量右美托咪啶组分别鞘内注射右美托咪啶0.75μg/kg组(D1组)、1.50μg/kg组(D2组)、3.00 μg/kg组(D3组),均用生理盐水稀释至10 μl.于鞘内给药前和给药后30 min时测定机械缩足阈值(PWMT),于鞘内给药前和给药后60min时测定辐射热甩尾潜伏期(TFL),计算最大抗伤害效应(MPE)百分比.于给药后7、24和48 h时,取L4-6脊髓节段,观察病理学结果,并采用免疫组化法测定c-Fos蛋白表达水平.结果 与C组和N组比较,D1组、D2组和D3组给药后30min时PWMT升高,给药后60min时TFL和MPE百分比升高(P＜0.05);与D1组和D2组比较,D3组给药后30 min时PWMT升高,给药后60min时TFL和MPE百分比升高(P＜0.05);D1组和D2组PWMT、TFL和MPE百分比差异无统计学意义(P＞0.05).与C组和N组比较,D1组和D2组给药后各时点脊髓背角c-Fos蛋白表达差异无统计学意义(P＞0.05),D3组给药后7和24 h时脊髓背角c-Fos蛋白表达上调(P＜0.05),给药后48h时脊髓背角c-Fos蛋白表达差异无统计学意义(P＞0.05);与D1组和D2组比较,D3组给药后24 h时脊髓背角c-Fos蛋白表达上调(P＜0.05).D3组给药后24 h时可见脊髓轻度损伤.结论 鞘内注射右美托咪啶对大鼠可产生抗伤害效应.鞘内注射3.00μg/kg右美托咪啶抗伤害效应最强,但可产生短暂的脊髓神经毒性.

Abstract：

Objective To investigate the analgesic efficacy and spinal neurotoxicity of intrathecal (IT) different doses of dexmedetomidine in rats. Methods Sixty male SD rats weighing 180-220 g were randomly divided into 5 groups ( n = 12 each): groupnormal control (group C); group IT normal saline (group N); different doses of dexmedetomidine groups received IT dexmedetomidine 0.75, 1.50 and 3.00 μg/kg respectively (groups D1.3). Paw withdrawal threshold to mechanical stimulation (PWMT)with yon Frey filaments and tail flick latency (TFL) to a thermal nociceptive stimulus were measured before (To, baseline) and at 30 or60 rin after IT dexmedetomidine or normal saline administration (T1, T2 ) and the percentage of the maximum possible effect ( MPE ) was calculated. Lumbar segment of the spinal cord ( L4-6 ) was removed for microscopic examination and determination of c-Fos expression (by immuno-histochemistry) at 7, 24 and 48 h after IT dexmedetomidine or normal saline administration. Results PWMT, TFL and the percentage of MPE were significantly increased after IT dexmedetomidine as compared with the baseline values at T0 in groups D1-3 ( P ＜ 0.05). PWMT was significantly higher at T1 and TFL and the percentage of MPE were higher at T2 in groups D1-3 than in groups C and N,and in group D3 than in groups D1,2 ( P ＜ 0.05). At 7,24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in groups C and N( P ＜ 0.05). There was no significant difference in c-Fos expression at 48 h after IT dexmedetomidine between group D3 and groups C and N ( P ＞ 0.05 ). At 24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in other 4 groups( P ＜ 0.05). Slight spinal cord injury was observed at 24 h after IT dexmedetomidine in group D3. Conclusion IT dexmedetomidine has antinociceptive effect. High dose dexmedetomidine IT can produce transient reversible toxicity to the spinal cord.     

T型钙通道在鞘内注射利多卡因致大鼠脊髓神经毒性中的作用

目的 评价T型钙通道在鞘内注射利多卡因致大鼠脊髓神经毒性中的作用.方法 鞘内置管成功的成年雄性SD大鼠48只,体重230～ 270 g,采用随机数字表法,将其随机分为4组(n=12):二甲基亚砜组(D组)、10％利多卡因组(L组)、米贝地尔+利多卡因组(M组)和生理盐水+利多卡因组(N)组,另取12只大鼠作为正常对照组(C组).D组和L组分别鞘内注射二甲基亚砜和10％利多卡因20 μl,M组和N组分别鞘内注射米贝地尔200 μg/10μl和生理盐水10μl后鞘内注射10％利多卡因20μl.于鞘内给药前、给药后2、4、8、12 h、1、2、3、4和5 d(T0-9)时测定大鼠后肢机械缩足反应阈值(MWT)和热缩足反射潜伏期(TWL).于T6时每组随机取4只大鼠处死取脊髓腰膨大,光镜下观察病理学结果.结果 与C组比较,D组各时点MWT和TWL差异无统计学意义(P＞0.05),L组和N组T1-8时MWT升高,T1-7时TWL延长,M组T1-6时MWT升高,TWL延长(P＜0.05);与L组和N组比较,M组T1-4时MWT降低,TWL缩短(P＜0.05).M组较L组和N组脊髓病理学损伤减轻.结论 T型钙通道参与了鞘内注射利多卡因致大鼠脊髓神经毒性的过程.     

A simple technique of regional anesthesia to reduce opioid requirements postoperatively in laparoscopic incisional hernia repairs

Laparoscopic incisional hernia repair can be associated with initial postoperative pain requiring opioids in the form of patient controlled analgesia (PCA). Our study demonstrates the use of an innovative form of intra-operative regional anaesthesia in the form of an abdominal extraperitoneal block (AEP) which reduced mean opioid consumption in our patients by 62% without any intra-operative complications.     

A possible perianesthetic serotonin syndrome related to intrathecal fentanyl

Serotonin syndrome occurs with selective serotonin reuptake inhibitors, opioids, and other serotonergic agents. We describe a possible serotonin syndrome related to intrathecal fentanyl in a patient taking multiple drugs and substances such as ergot alkaloids, marijuana, methylenedioxy-N-methylamphetamine, and ephedrine.     

Ertapenem-associated neurotoxicity in the spinal cord injury (SCI) population: A case series

Objectives: The primary objective was to review the literature regarding methodologies to assess fracture risk, to prevent and treat osteoporosis and to manage osteoporotic fractures in SCI/D.

Study Design: Scoping review.

Settings/Participants: Human adult subjects with a SCI/D.

Outcome measures: Strategies to identify persons with SCI/D at risk for osteoporotic fractures, nonpharmacological and pharmacological therapies for osteoporosis and management of appendicular fractures.

Results: 226 articles were included in the scoping review. Risk of osteoporotic fractures in SCI is predicted by a combination of DXA-defined low BMD plus clinical and demographic characteristics. Screening for secondary causes of osteoporosis, in particular hyperparathyroidism, hyperthyroidism, vitamin D insufficiency and hypogonadism, should be considered. Current antiresorptive therapies for treatment of osteoporosis have limited efficacy. Use of surgery to treat fractures has increased and outcomes are good and comparable to conservative treatment in most cases. A common adverse event following fracture was delayed healing.

Conclusions: Most of the research in this area is limited by small sample sizes, weak study designs, and significant variation in populations studied. Future research needs to address cohort definition and study design issues.     

Studies on the development of tolerance and potential spinal neurotoxicity after chronic intrathecal carbachol-antinociception in the rat

The antinociceptive effect in rats produced by chronic intrathecal administration of carbachol was studied for 14 days by the tail immersion test and the paw compression test. Daily injection of 10 μg carbachol intrathecally (lumbar level) to 8 rats produced an increase in latency times lasting from day 1 to day 4. The effect was statistically significant during the first 4 days, but not thereafter in both the tail immersion test and the paw compression test as compared to the rats (n = 6) injected with saline. Histopathological examinations of the lumbar spinal cord by light and electron microscopy revealed no signs of neurotoxic reactions of the neurons, nor the spinal tracts. Quantitative morphometric analyses were made by the "disector method", which is an unbiased stereological estimator of cell number and mean cell volume. In the laminae I-III of the L:I segment, an average number of 88000 cells/mm³ was found and the mean cell volume was calculated at 560 μm³. Comparison with untreated rats (n = 4) and those injected with saline showed no statistically significant differences. In the present study, the combination of different morphological analyses offers a sensitive method to trace toxic reactions of the nervous tissue. According to these results, intrathecal carbachol produces antinociception, and seems atoxic to spinal nervous tissue, but before intrathecal administration of carbachol to humans is considered, more neurotoxicological data must be obtained.     

A simple technique to perform combined ultrafiltration

To combine the advantages of conventional and modified ultrafiltration while keeping cardiopulmonary bypass technique simple, we have developed a simplified circuit of combined ultrafiltration, which is presently used in our pediatric patients. In addition to the benefits of combined ultrafiltration, this circuit allows the rewarming and prevention of heat loss in small children and neonates.     

A simple strategy to reduce stereotype threat for orthopedic residents

Background

Stereotype threat, defined as the predicament felt by people in either positive or negative learning experiences where they could conform to negative stereotypes associated with their own group membership, can interfere with learning. The purpose of this study was to determine if a simple orientation session could reduce stereotype threat for orthopedic residents.

Methods

The intervention group received an orientation on 2 occasions focusing on their possible responses to perceived poor performance in teaching rounds and the operating room (OR). Participants completed a survey with 7 questions typical for stereotype threat evaluating responses to their experiences. The questions had 7 response options with a maximum total score of 49, where higher scores indicated greater degree of experiences typical of stereotype threat.

Results

Of the 84 eligible residents, 49 participated: 22 in the nonintervention and 27 in the intervention group. The overall scores were 29 and 29.4, and 26.2 and 25.8 in the nonintervention and intervention groups for their survey responses to perceived poor performance in teaching rounds (p = 0.85) and the OR (p = 0.84), respectively. Overall, responses typical of stereotype threat were greater for perceived poor performance at teaching rounds than in the OR (p = 0.001).

Conclusion

Residents experience low self-esteem following perceived poor performance, particularly at rounds. A simple orientation designed to reduce stereotype threat was unsuccessful in reducing this threat overall. Future research will need to consider longer-term intervention as possible strategies to reduce perceived poor performance at teaching rounds and in the OR.     

Nasotracheal intubation: a simple and effective technique to reduce nasopharyngeal trauma and tube contamination

Our hypothesis was that nasopharyngeal passage of an endotracheal tube can be facilitated by a nasopharyngeal airway (Wendl tube) acting as a "pathfinder." Accordingly, we performed a randomized, controlled trial with blinded assessment of nasopharyngeal bleeding and contamination of the tip of the endotracheal tube. After the induction of anesthesia, a Wendl tube (28 Ch) was inserted into the more patent nostril. In the control group (n = 30), the Wendl tube was retrieved before nasopharyngeal passage was attempted with an endotracheal tube (inner diameter, 7.0 mm). In the intervention group (n = 30), the Wendl tube was kept in position and only its adjustable flange was removed. Then, we inserted the tip of the endotracheal tube into the trailing end of the Wendl tube. Subsequently, the endotracheal tube was advanced under visual control to the oropharynx guided by the Wendl tube. After the endotracheal tube was positioned in the oropharynx, the Wendl tube was removed and intubation completed. Six hours after surgery, we determined the patients' nasal pain. The "pathfinder" technique reduced the incidence (P < 0.001) and severity (P = 0.001) of bleeding, decreased tube contamination with blood and mucus (P < 0.001), and diminished postoperative nasal pain (P = 0.036). IMPLICATIONS: Nasopharyngeal passage of an endotracheal tube can be facilitated by a flexible Wendl tube (nasopharyngeal airway) covering and guiding the rigid tube tip. This technique is helpful in reducing the incidence and severity of nosebleeds and in minimizing contamination of the tip of the endotracheal tube with blood and mucus.