Plasma lidocaine levels and risks after liposuction with tumescent anaesthesia

BACKGROUND: It is common today to use tumescent anaesthesia with large doses of lidocaine for liposuction. The purpose of the present study was to evaluate lidocaine plasma levels and objective and subjective symptoms during 20 h after tumescent anaesthesia with approximately 35 mg per kg bodyweight of lidocaine for abdominal liposuction. METHODS: Three litres of buffered solution of 0.08% lidocaine with epinephrine was infiltrated subcutaneously over the abdomen in eight female patients during monitored intravenous (i.v.) light sedation. Plasma levels of lidocaine and signs of subjective and objective symptoms were recorded every 3 h for 20 h after liposuction. RESULTS: Lidocaine 33.2 +/- 1.8 mg/kg was given at a rate of 116 +/- 11 ml/min. Peak plasma levels (2.3 +/- 0.63 microg/ml) of lidocaine occurred after 5-17 h. No correlation was found between peak levels and dose per kg bodyweight or total amount of lidocaine infiltrated. One patient experienced tinnitus after 14 h when a plasma level of 3.3 microg/ml was recorded. CONCLUSION: Doses of lidocaine up to 35 mg/kg were sufficient for abdominal liposuction using the tumescent technique and gave no fluid overload or toxic symptoms in eight patients, but with this dose there is still a risk of subjective symptoms in association with the peak level of lidocaine that may appear after discharge.     

Abolition of prenatal lipopolysaccharide‐induced reproductive disorders in rat male offspring by fulvestrant

During prenatal and early postnatal periods of development, multiple environmental factors have profound and long‐lasting effects on the immune and reproductive functions. The aim of this study was to investigate the effects of maternal lipopolysaccharide (LPS) exposure (50 mg/kg, i.p.) at day 12 of pregnancy and estradiol antagonist treatment (fulvestrant, 1.5 mg/kg, s.c. in neck) at postnatal days 5–14 (PND5–14) with high estradiol levels on reproductive parameters in adult rat males. Serum steroid concentrations were measured in male offspring at PND80 by ELISA. Body, testis weights and ano‐genital distance (AGD) were recorded at different stages of postnatal development. Testis was also processed to cytohistological studies at PND80. Our results demonstrate that body weight was decreased from PND14 to 30 after prenatal LPS treatment and was increased after fulvestrant treatment. AGD was decreased after prenatal LPS treatment and was increased after fulvestrant injections. Testis weight, testosterone level, seminiferous tubule diameter, and number of Sertoli and spermatid cells were also decreased in rats exposed prenatally to LPS and were restored to the normal control level after fulvestrant treatment. According to results, we can conclude that the development of sexual disorders in males after prenatal immune stress is potentiated by estradiol during the pre‐pubertal period.     

Characterization of pressor and visceromotor reflex responses to bladder distention in rats: sources of variability and effect of analgesics

PURPOSE: We assessed the usefulness of cardiovascular and visceromotor responses to bladder distention as measures of acute visceral nociception in rats by determining the reliability of these responses. MATERIALS AND METHODS: Halothane anesthetized male and female Sprague-Dawley rats were acutely instrumented with tracheal, jugular venous, carotid arterial and bladder cannulas. Wires were inserted into the abdominal musculature to enable myoelectrical activity measurement. Anesthesia was decreased until flexion reflexes were present. Repeat phasic and graded bladder distention was administered, and arterial blood pressure and abdominal electromyography activity were continuously monitored. We determined the effects of gender, vaginal smear estrous cycle stage and drug treatment on the measured responses. RESULTS: Bladder distention produced reliable pressor and visceromotor (abdominal contractile) responses. There was great inter-animal variability in response vigor but good reproducibility was noted within individual animals. During slow bladder filling bladder contractions were not noted at this level of anesthesia. Sex differences included a more vigorous reflex response in females than in males, which was most vigorous in females in proestrus. Repeat bladder distention led to increasingly vigorous pressor responses and the improved reliability of visceromotor responses. Intravenous morphine and lidocaine dose dependently inhibited the reflex responses. CONCLUSIONS: Pressor and visceromotor responses to bladder distention in halothane anesthetized rats are reliable measures of acute bladder nociception that may prove useful for analgesic screening and in studies of hormonal effects on nociception.     

Effect of midazolam pretreatment on the intravenous toxicity of lidocaine with and without epinephrine in rats

The effect of the benzodiazepine midazolam on the intravenous toxicity of lidocaine with and without epinephrine was studied in male Sprague-Dawley rats. Test rats with and control rats without midazolam premedication (2.5 mg/kg intraperitoneally, 10% of the median dose that caused loss of the righting reflex in a third group of rats) were given 2% lidocaine with and without 10 micrograms/ml epinephrine intravenously in doses sufficient to construct log-dose response curves for both convulsant and lethal responses. In control rats the median convulsant dose (CD50) of lidocaine was 15.2 mg/kg given alone and 10.9 mg/kg with epinephrine (a statistically significant difference); respective values for the median lethal dose (LD50) were 26.4 and 18.5 mg/kg (also statistically significant). While epinephrine enhanced lidocaine seizure activity and lethality by approximately 50%, midazolam almost completely prevented lidocaine-induced convulsions but had no significant effect on mortality.     

孕早期氯胺酮麻醉对子代大鼠海马c-fos mRNA和c-jun mRNA表达的影响

目的 探讨孕早期氯胺酮麻醉对子代大鼠海马c-fos mRNA和c-jun mRNA表达的影响.方法 孕5～13 d的SD大鼠30只,体重250～300 g,随机分为2组(n=15):对照组(C组)和氯胺酮组(K组).K组经尾静脉注射氯胺酮20 mg/kg,随后以130 mg·kg-1·h-1的速率静脉输注2 h;C组以等量生理盐水替代氯胺酮.子代大鼠于出生后20和30 d时测定认知功能,取海马组织,测定c-fosmRNA和c-jun mRNA表达水平并观察超微结构.结果 与C组比较,K组子代大鼠出生后30 d时认知功能测定第2天逃避潜伏期延长(P＜0.05),海马c-fos mRNA和c-jun mRNA的表达水平差异无统计学意义,出生后20 d上述指标差异无统计学意义(P＞0.05).K组海马神经元发生损伤.结论 孕早期氯胺酮麻醉抑制子代大鼠认知功能的机制与海马神经元受损有关,但与海马c-fos mRNA和c-jun mRNA表达无关.     

Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the rat.

Clinical investigations have suggested a synergistic interaction between the analgesic effects of intrathecal opioids and local anesthetics; however, basic pharmacologic evidence for this observation has not been reported. Therefore, the authors have used models of visceral and somatic nociception to quantify the interaction between intrathecal morphine and lidocaine in a crossover study of 24 rats in four equal groups. Combinations of morphine and lidocaine were administered separately, corresponding to time of peak effect for each drug. Colorectal distention, as a noxious visceral stimulus, was applied to two groups while cardiovascular and visceromotor responses, respectively, were recorded. A third group received hot plate testing as a somatic nociceptive stimulus. Intrathecal morphine and lidocaine both attenuated the cardiovascular and visceromotor responses to colorectal distention and increased hot plate latencies in a dose- and time-dependent manner. With the use of isobolographic analysis, the coadministration of morphine and lidocaine demonstrated a synergistic, supraadditive interaction during visceral nociception (P less than 0.001) and somatic nociception (P less than 0.005). In a fourth group, motor function was evaluated by an inclined screen method. Intrathecal lidocaine in the dosage range tested during isobolographic analysis revealed no motor deficits. These data clearly demonstrate antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception at dosages that do not impair motor function.     

The comparative neurotoxicity of intrathecal lidocaine and bupivacaine in rats

There is a considerable difference in the number of reports of neurologic injury in the literature between lidocaine and other local anesthetics. Few in vivo animal studies have produced convincing results showing a difference in neurotoxicity among anesthetics. We investigated whether lidocaine and bupivacaine differ with respect to sensory impairment and histologic damage when equipotent doses of the two are administered intrathecally in rats. First, to determine relative anesthetic potency, rats intrathecally received 20 muL of saline, 0.625%, 1.25%, 2.5%, or 5% lidocaine, or 0.125%, 0.25%, 0.5%, or 1.0% bupivacaine, and were examined with the tail-flick test for 90 min. The potency ratio calculated was approximately 1:4.70 (95% confidence interval, 3.65-6.07) for lidocaine/bupivacaine. In the next experiment, 45 rats intrathecally received 20 muL of saline, 2.13% bupivacaine (approximately 1.5 mg/kg), or 10% lidocaine (approximately 6.9 mg/kg), and were examined for persistent functional impairment and morphologic damage. Rats given lidocaine developed significantly more prolonged tail-flick latencies than those in other groups 4 days after injection and incurred more morphologic damage than those given saline or bupivacaine. In conclusion, although the doses of anesthetics administered were larger than those used clinically, the present results suggest that bupivacaine is less neurotoxic than lidocaine when administered intrathecally at equipotent concentrations in the rat model. IMPLICATIONS: Bupivacaine induces less severe functional impairment and morphologic damage than lidocaine when the two anesthetics are intrathecally administered at equipotent concentrations in the rat.     

Hypoxia Causes Apnea during Epidural Anesthesia in Rabbits

Background: Although pulmonary function is minimally changed by neuraxial blockade in most cases, ventilatory arrest may ensue in rare cases. The authors examined the mechanism of apnea in a rabbit model of sudden ventilatory arrest during the combination of epidural anesthesia and hypoxia.

Methods: Rabbits were studied during alpha-chloralose sedation and spontaneous ventilation through a tracheostomy tube. Heart rate and mean arterial pressure were monitored by intraarterial cannulation. Respiratory rate and tidal volume were measured by pneumotachograph. Responses were recorded during administration of oxygen at inspired oxygen concentrations of 11% for 2.5 min and 0% for 40 s, before and after either thoracolumbar epidural blockade (0.4 ml/kg lidocaine, 1.5%) or intramuscular lidocaine (15 mg/kg). In a third group of animals, epinephrine was given intravenously during epidural blockade to return mean arterial pressure to baseline values before hypoxia. In a fourth group of animals, which did not get lidocaine, sympathetic blockade and hypotension were produced with intravenously administered trimethaphan rather than epidural blockade.

Results: Thoracolumbar epidural anesthesia decreased mean arterial pressure from 76 +/- 4 mmHg (mean +/- SE) to 42 +/- 2 mmHg. Apnea during hypoxia occurred in 90% of these animals (nine of ten) but in only 11% of animals (one of nine) after intramuscularly administered lidocaine (P < 0.01). Treatment of epidural hypotension with epinephrine prevented apnea (zero of nine animals). Apnea during hypoxia occurred in 50% (three of six) of animals given trimethaphan. Apnea in all groups was sudden in onset, with no preceding decreases in respiratory rate or tidal volume.     

Lidocaine sprayed down the endotracheal tube attenuates the airway-circulatory reflexes by local anesthesia during emergence and extubation

To determine whether lidocaine sprayed down the endotracheal tube (ETT) would attenuate airway-circulatory reflexes during emergence, we compared the reflex responses after endotracheal or IV lidocaine (IVL) in 75 patients receiving a standardized anesthetic protocol. At the end of surgery, the patients were divided into 3 groups (n = 25 for each group) and given no drug (Group 1), given 1 mg/kg of 2% lidocaine sprayed down the ETT 5 min before (Group 2), or given the same dose of IVL 3 min before extubation (Group 3). Blood pressure and heart rate were recorded at predetermined time points from 5 min (baseline) before until 5 min after extubation. The number of coughs per patient was continuously monitored during this period. The number (mean +/- SD) of coughs was decreased in Group 2 (4.5 +/- 3.7) compared with the control (10.2 +/- 6.0) (P < 0.01) with no difference for the control versus Group 3 (7.8 +/- 4.6). The increase in blood pressure was only attenuated immediately before extubation (P < 0.05), whereas the increase in heart rate was attenuated (P < 0.05) at all (except baseline) time points (P < 0.05) in Group 2 compared with the control with no difference for the control versus Group 3. The results indicate that lidocaine sprayed down the ETT suppresses the reflexes whereas using the same dose IVL does not, which is probably attributable to the mucosa-anesthetizing effect of lidocaine. IMPLICATIONS: Lidocaine sprayed down the endotracheal tube suppresses the airway-circulatory reflex responses whereas using the same dose IV lidocaine does not. This effect seems to be from the direct local anesthesia rather than from systemic absorption from the airway.     

支气管内超声引导针吸活检术患者复合咪达唑仑-吗啡时TCI不同浓度异丙酚麻醉的效果

目的 评价支气管内超声引导针吸活检术患者复合咪达唑仑-吗啡时TCI不同浓度异丙酚麻醉的效果.方法 择期行支气管内超声引导针吸活检术患者40例,ASA分级Ⅰ或Ⅱ级,随机分为2组(n=20),P1组和P2组静脉注射咪达唑仑0.03 mg/kg和吗啡0.05 mg/kg,于咽喉部行表面麻醉,TCI异丙酚,P1组和P2组血浆靶浓度分别为3、4 μg/ml.输注异丙酚5 min时开始手术.手术开始后30 min采集动脉血样,进行动脉血气分析;手术结束时记录PETCO2.记录连续呛咳次数、体动、利多卡因用量、定向力恢复时间、患者对麻醉满意度、术中及术后不良反应的发生情况.结果 与P1组比较,P2组pH值和PaO2降低,PaCO2和PETCO2升高(P＜0.05),连续呛咳次数、体动、利多卡因用量、定向力恢复时间、患者对麻醉满意度及不良反应发生率差异无统计学意义(P＞0.05).结论复合咪达唑仑0.03 mg/kg和吗啡0.05 mg/kg时支气管内超声引导针吸活检术患者TCI异丙酚(血浆靶浓度3μg/ml)的麻醉效果好,术后恢复快,安全性良好.     

丙泊酚对新生鼠神经干细胞增殖及学习记忆的影响

目的 研究丙泊酚对新生鼠神经干细胞增殖及学习记忆的影响.方法 出生后7 d Wistar乳鼠104只随机均分成四组:丙泊酚50 mg/kg组(A组)、丙泊酚100 mg/kg组(B组)、生理盐水10 ml/kg组(C组)、脂肪乳剂10 ml/kg组(D组),各组均为腹腔注射,连续注射7 d,第7天每组取10只腹腔注射300 mg/kg 5-溴脱氧尿苷(Brdu),12 h后灌注切脑片做Brdu免疫组化,6只取海马提蛋白westerblo0t检测脑源性神经营养因子(BDNF),剩下10只饲养2个月后行Morris水迷宫测试.结果 与C组比较,D组对Brdu阳性细胞无影响,A、B组Brdu阳性细胞数明显减少(P＜0.05),其中B组阳性细胞数又明显少于A组(P＜0.05).A、B组BDNF含量减少,但只有B组明显抑制成年后鼠的学习记忆功能.结论 丙泊酚能抑制新生鼠神经干细胞增殖,大剂量丙泊酚可损害鼠成年后学习记忆功能,可能与丙泊酚减少BDNF分泌有关.     

Intrathecal lidocaine prevents cardiovascular collapse and neurogenic pulmonary edema in a rat model of acute intracranial hypertension

Sympathetic hyperactivity during sudden intracranial hypertension leads to cardiovascular instability, myocardial dysfunction, and neurogenic pulmonary edema. Because spinal anesthesia is associated with sympatholysis, we investigated the protective effects of intrathecal lidocaine in a rodent model. Halothane-anesthetized rats were given a 10-microL intrathecal injection of saline (n = 10) or lidocaine 1% (n = 6). A subdural balloon catheter was inflated for 60 s to produce intracranial hypertension. Hemodynamics were monitored, and hearts and lungs were harvested for histological examination. In Saline versus Lidocaine-Treated rats, peak mean arterial blood pressure during balloon inflation was 115 +/- 4 mm Hg versus 78 +/- 8 mm Hg (P < 0.05), mean arterial blood pressure 30 min after balloon deflation was 47 +/- 2 mm Hg versus 67 +/- 3 mm Hg (P < 0.05), and lung weight was 1.54 +/- 0.03 g versus 1.41 +/- 0.04 g (P < 0.05), respectively. Cardiac dysrhythmias and electrocardiographic changes were more frequent in the Saline-Treated group (P < 0.05). Saline-Treated rats had extensive, hemorrhagic pulmonary edema, whereas the Lidocaine-Treated rats had only patchy areas of lung abnormality. Histological changes in the myocardium were rare, and no difference was found between the two groups. We conclude that intrathecal lidocaine prevents cardiovascular collapse and neurogenic pulmonary edema in a rat model of acute intracranial hypertension. IMPLICATIONS:In a rat model of intracranial balloon inflation, intrathecal lidocaine prevented cardiovascular collapse and neurogenic pulmonary edema. Descending neural pathways are involved in the development of cardiopulmonary complications associated with acute intracranial hypertension.     

The electrophysiologic actions of lidocaine and bupivacaine in the isolated, perfused canine heart

To discriminate between the electrophysiologic and arrhythmogenic effects of lidocaine and those of bupivacaine, isolated, perfused canine hearts were exposed to toxic concentrations of the drugs. The preparations included the sinus node and right atrium, and, in some cases, the AV node and interventricular septum as well. Action potentials were recorded from these areas, and right atrial twitch amplitude and spontaneous rate and rhythm were monitored. Heart rate was depressed in a dose-dependent manner by both drugs, as was atrial twitch amplitude. In the absence of arrhythmias, the spontaneous rate decreased less than 30% with lidocaine up to 50 micrograms/ml, and with bupivacaine up to 5 micrograms/ml. The twitch depression reflected a potency ratio for bupivacaine (mol. wt. 288) to lidocaine (mol. wt. 234) on a mass basis of 8.1:1. The most prominent arrhythmia found was sinoatrial block, which was caused by both drugs with a potency ratio for bupivacaine to lidocaine of 15.4:1 and was reversed by 0.02 microgram/ml norepinephrine. Sinus arrhythmias, block of retrograde conduction from AV node to atrium, and irregular rhythms originating within the AV node were observed with both drugs at concentrations similar to those which produced sinoatrial block. The atrial action potential revealed decreased upstroke velocity, overshoot, and height with both lidocaine and bupivacaine, with potency ratios (bupivacaine:lidocaine) ranging from 15:1 to 26:1. In septal cells, both drugs depressed upstroke velocity, and bupivacaine lengthened action potentials by up to 14%, but lidocaine did not. The major difference between bupivacaine and lidocaine in this study was the higher potency of the former agent with respect to electrophysiologic end-points.     

吸脂术中大剂量使用利多卡因的血药浓度监测及意义

目的 探讨作为局部麻醉剂的利多卡因在肿胀法脂肪抽吸术中的有限剂量是多少，既能达到良好的镇痛效果，又有安全地使用而不产生毒副作用。方法 对１４例大剂量使用低浓度利多卡因作为局麻药的脂肪抽吸术的术中和术后血清利多卡因浓度以免疫荧光测定法进行了动态监测，作出其时间－浓度曲线，并与临床表现相对照。结果 在此类手术中，利多卡因在０．１ｍｇ／ｍｌ的浓度下，加入１／１百万￣１／２百万肾上腺素，其用量可达３５ｍｇ     

吸脂术中大剂量使用利多卡因的血药浓度监测及意义

目的探讨作为局部麻醉剂的利多卡因在肿胀法脂肪抽吸术中的极限剂量是多少,既能达到良好的镇痛效果,又能安全地使用而不产生毒副作用。方法对１４例大剂量使用低浓度利多卡因作为局麻药的脂肪抽吸术的术中和术后血清利多卡因浓度以免疫荧光测定法进行了动态监测,作出其时间浓度曲线,并与临床表现相对照。结果在此类手术中,利多卡因在０１ｍｇ／ｍｌ的浓度下,加入１／１百万～１／２百万肾上腺素,其用量可达３５ｍｇ／ｋｇ体重而血清高峰浓度仍在安全范围内,无中毒症状,既可减轻病人的疼痛,又可减少出血,提高安全性,增加脂肪抽吸量。结论本研究为肿胀法吸脂术中大剂量使用利多卡因的临床实践提供了理论依据。     

Changes in Properties of Substantia Gelatinosa Neurons after Surgical Incision in the Rat: In Vivo Patch-clamp Analysis

Background: Noxious information through A[delta] and C afferent fibers is transmitted to substantia gelatinosa, a process that plays an important role in plastic changes of nociceptive processing in pathophysiological conditions. In this study, changes in properties of substantia gelatinosa neurons and their sensitivity to systemic administration of lidocaine after surgical incision were investigated using the in vivo patch-clamp technique.

Methods: Under urethane anesthesia, in the current clamp mode, spontaneous activities and responses of substantia gelatinosa neurons to nonnoxious air-puff stimuli and noxious pinch stimuli were recorded before and after 1-cm-long incisions had been made in hairy skin of the hindquarters of rats. Systemic administration of lidocaine (2 mg/kg) was applied at 30 min after the incision.

Results: Stable recordings for 30 min or more after the incision were obtained from 18 substantia gelatinosa neurons that were classified as multireceptive (n = 8), nociceptive (n = 5), and subthreshold (n = 5) neurons. Action potential firing disappeared immediately after completion of the wound closure in most multireceptive and nociceptive neurons, and sustained spontaneous action potential firing was observed in 23% of these substantia gelatinosa neurons. Responsiveness of these substantia gelatinosa neurons, but not that of subthreshold neurons, increased after the incision. Systemic administration of lidocaine suppressed spontaneous firings of action potentials of the substantia gelatinosa neurons and reversed the increased responsiveness of the neurons.     

吸脂术中大剂量使用利多卡因的血药浓度监测及意义

目的探讨作为局部麻醉剂的利多卡因在肿胀法脂肪抽吸术中的极限剂量是多少,既能达到良好的镇痛效果,又能安全地使用而不产生毒副作用。方法对14例大剂量使用低浓度利多卡因作为局麻药的脂肪抽吸术的术中和术后血清利多卡因浓度以免疫荧光测定法进行了动态监测,作出其时间-浓度曲线,并与临床表现相对照。结果在此类手术中,利多卡因在0.1mg/ml的浓度下,加入1/1百万～1/2百万肾上腺素,其用量可达35mg/kg 体重而血清高峰浓度仍在安全范围内,无中毒症状,既可减轻病人的疼痛,又可减少出血,提高安全性,增加脂肪抽吸量。结论本研究为肿胀法吸脂术中大剂量使用利多卡因的临床实践提供了理论依据。     

Comparative Neurotoxicity of Intrathecal and Epidural Lidocaine in Rats

Background: Although there is a considerable difference in the number of clinical reports of neurologic injury between spinal anesthesia and other regional techniques, there are no animal data concerning a difference in the local anesthetic neurotoxicity between intrathecal and epidural administration. In the current study, the functional and morphologic effects of lidocaine administered intrathecally and epidurally were compared in rats.

Methods: Male rats were implanted with an intrathecal or epidural catheter through L4-L5 vertebra in the caudal direction. In experiment 1, to determine relative anesthetic potency, 16 rats received repetitive injections of 2.5% lidocaine into intrathecal or epidural space in different volumes and were examined for tail flick test for 90 min. In experiment 2, to ascertain whether the relative potency obtained in experiment 1 would apply to other concentrations of lidocaine, additional rats received saline, 1%, 2.5%, or 5% lidocaine in a volume of 20 or 100 [mu]l through the intrathecal or epidural catheter, respectively. In experiment 3, additional rats that received saline, 2.5% lidocaine, or 10% lidocaine in a volume of 20 or 100 [mu]l through the intrathecal or epidural catheter, respectively, were examined for persistent functional impairment and morphologic damage.

Results: In experiment 1, the two techniques produced parallel dose-effect curves that significantly differed from each other. The potency ratio calculated was approximately 4.72 (3.65-6.07):1 for intrathecal:epidural lidocaine. In experiment 2, every lidocaine solution produced a similar increase in tail flick latency for the two techniques. In experiment 3, five of eight rats given 10% intrathecal lidocaine incurred functional impairment 4 days after injection, whereas no rats in the other groups did. Significantly more morphologic damage was observed in rats given 10% intrathecal lidocaine than in those given 10% epidural lidocaine.     

Comparative neurotoxicity of intrathecal and epidural lidocaine in rats

BACKGROUND: Although there is a considerable difference in the number of clinical reports of neurologic injury between spinal anesthesia and other regional techniques, there are no animal data concerning a difference in the local anesthetic neurotoxicity between intrathecal and epidural administration. In the current study, the functional and morphologic effects of lidocaine administered intrathecally and epidurally were compared in rats. METHODS: Male rats were implanted with an intrathecal or epidural catheter through L4-L5 vertebra in the caudal direction. In experiment 1, to determine relative anesthetic potency, 16 rats received repetitive injections of 2.5% lidocaine into intrathecal or epidural space in different volumes and were examined for tail flick test for 90 min. In experiment 2, to ascertain whether the relative potency obtained in experiment 1 would apply to other concentrations of lidocaine, additional rats received saline, 1%, 2.5%, or 5% lidocaine in a volume of 20 or 100 microl through the intrathecal or epidural catheter, respectively. In experiment 3, additional rats that received saline, 2.5% lidocaine, or 10% lidocaine in a volume of 20 or 100 microl through the intrathecal or epidural catheter, respectively, were examined for persistent functional impairment and morphologic damage. RESULTS: In experiment 1, the two techniques produced parallel dose-effect curves that significantly differed from each other. The potency ratio calculated was approximately 4.72 (3.65-6.07):1 for intrathecal:epidural lidocaine. In experiment 2, every lidocaine solution produced a similar increase in tail flick latency for the two techniques. In experiment 3, five of eight rats given 10% intrathecal lidocaine incurred functional impairment 4 days after injection, whereas no rats in the other groups did. Significantly more morphologic damage was observed in rats given 10% intrathecal lidocaine than in those given 10% epidural lidocaine. CONCLUSIONS: Persistent functional impairment occurred only after intrathecal lidocaine. Histologic damage in the nerve roots and the spinal cord was less severe after epidural lidocaine than after intrathecal lidocaine. The current results substantiate the clinical impression that neurologic complications are less frequent after epidural anesthesia than after spinal anesthesia.     

Antimitotic drugs (cyclophosphamide and vinblastine) in the male rat. Deaths and behavioral abnormalities in the offspring

The spermatogenesis and the offspring of male rats treated either with cyclophosphamide alone, or with both cyclophosphamide and vinblastine were investigated. The offspring were evaluated for the mean number of pups per litter, sex ratio, the frequency of apparent external malformations and, within the first 4 months of life, growth and mortality. When they reached adulthood and were between 12 and 16 weeks of age, the offspring were also examined for spontaneous activity and learning capacity. Treatment with cyclophosphamide or cyclophosphamide and vinblastine resulted in a decrease in the number of both primary spermatocytes and spermatids; the effect, however, lasted longer for the combined drug regimen. At birth, the animals sired by the treated males did not show any apparent malformations. However, compared with the control population the mortality rate of the offspring was significantly higher within the first 40 days of life; at adult age, the proportion of animals that failed in the learning ability test was significantly increased and those that did succeed showed impaired learning capacity. The difference, however, was significant only in the male offspring. Finally, the offspring's spontaneous activity was significantly decreased. No difference was found in mortality or behavior between the animals born of the cyclophosphamide or cyclophosphamide plus vinblastine-treated males. The behavioral disorders shown in the adult offspring confirm the existence of a long-term risk of paternal origin. This risk, essentially functional and independent of any morphologic pathology, should be taken into account in the context of environmental genotoxicity.