Spontaneous multicentric myxoma of the dermal nerve sheaths in farmed European eels Anguilla anguilla.

This report describes a peripheral nerve sheath tumour in 8 European eels Anguilla anguilla L. from a fish farm located in Croatia. The newborn tissue appeared as smooth and soft skin nodules without pronounced colour change. Nodules were dome-shaped with a pale crater and were present on different body areas. In general, nodules were located as series of differently sized protrusions extending along the lateral line on both sides of the fish, as well as sensory canals on the head. Cut sections showed a homogeneous, pale white-grey texture. Histologically, the pathological tissue was located in the dermis, occasionally intruding into the hypodermis, and pushing as a space-occupying mass against the underlying muscle tissue without any evident boundaries. The pressure also caused changes in the overlying epidermis, such as atrophy, spongiosis and erosion. In some areas, the epidermis was 1 cell thick and club and goblet cells had completely disappeared. Ultimately, these changes resulted in shallow ulceration. Tumour tissue was characterized by a scant population of spindle or stellate cells, with oval, hyperchromatic nuclei and pale cytoplasm embedded in a copious myxoid matrix. Cells were arranged in fascicles and whorls, extending in a poorly defined manner among the dermal collagen bundles. Occasionally, adipose cells were also detected, mainly in the central portion of the bulges. Myxoid areas appeared rich in metachromatic and alcianophilic mucous ground substance. Reticular fibres and collagenous connective tissue were scarce. Immunohistochemistry (IHC) using antibodies against S-100 and glial fibrillary acidic protein caused a slight positive reaction in neoplastic dendritic cells. High magnification showed the immunostaining to be cytoplasmic in all tumour cells. IHC with anti-calretinin antibody gave only negative results. Macroscopic, histological, histochemical and immunohistochemical findings were consistent with a diagnosis of multicentric myxoma of the dermal nerve sheaths, a tumour not yet reported in fish.

Epinephrine increases the neurotoxic potential of intrathecally administered lidocaine in the rat.

BACKGROUND: Epinephrine is commonly added to lidocaine solutions to increase the duration of spinal anesthesia. Despite this common usage, the effect of epinephrine on the neurotoxic potential of this anesthetic is not known. The current experiments investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat. METHODS: Eighty rats were divided into four groups to receive an intrathecal injection of normal saline containing either 5% lidocaine, 5% lidocaine with 0.2 mg/ml of epinephrine, 0.2 mg/ml of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail-flick test administered 4 and 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. RESULTS: Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls. CONCLUSIONS: The neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine.

Low concentrations of halothane increase response to a noxious thermal stimulus and attenuate the antinociceptive effect of intraventricular but not intrathecal morphine.

BACKGROUND: Classically, the first plane of anesthesia is known as the stage of analgesia. Nonetheless, clinical evidence suggests that low doses of inhaled agents might enhance pain perception. The present experiments test the hypothesis that low concentrations of halothane increase response to a noxious thermal stimulus and attenuate the antinociceptive effect of intraventricular morphine via disruption of descending inhibition. METHODS: In the first experiment, the temperature at which rats withdraw their tails from a heat source was measured in animals breathing various concentrations of halothane. In the second experiment, the effect of intraventricular or intrathecal morphine on tail-flick latency was assessed in rats breathing either oxygen or 0.23% halothane. RESULTS: Low concentrations of halothane decreased the temperature threshold for tail-flick with a maximum effect at 0.06% atmospheres. Halothane attenuated the antinociceptive potency of intraventricular morphine but enhanced the efficacy of intrathecal morphine. CONCLUSIONS: Subanesthetic concentrations of halothane may enhance response to a noxious stimulus. The differential effect on intraventricular and intrathecal morphine suggests that this enhancement results from disruption of descending inhibition.

Toxicity of spinal local anaesthetics.

Recent reports of severe neurological injury after spinal anaesthesia have generated concerns about the neurotoxic potential of local anaesthetics and, in particular, of lignocaine. Further, there is an increasing body of evidence indicating that transient neurological symptoms commonly occur after uneventful lignocaine spinal anaesthesia but not after bupivacaine. Results from an epidemiological study suggest that patient positioning and outpatient status are major co-factors. Neither the dose nor the concentration of lignocaine appear to reduce the risk for transient neurological symptoms. Available data on alternative short-acting local anaesthetics with respect to transient neurological symptoms are limited and conflicting. Experimental data provide further information on factors contributing to local anaesthetic induced neurotoxicity: adrenaline significantly increases the neurotoxic effects of lignocaine in vivo, whereas the addition of glucose does not.

Comparative toxicity of glucose and lidocaine administered intrathecally in the rat.

BACKGROUND AND OBJECTIVES: Glucose is a common component of anesthetic solutions used for spinal anesthesia. However, its possible contribution to recent injuries occurring with spinal anesthesia has not been adequately addressed. Accordingly, the present studies compare the functional and morphologic effects of intrathecally administered glucose with those of lidocaine. METHODS: Twenty rats, implanted with intrathecal catheters, were divided into three groups to receive a 1-hour infusion of 5% lidocaine (n = 6), 10% glucose (n = 7), or normal saline (n = 7). Four days after infusion, animals were evaluated for persistent sensory impairment using the tail-flick test. Three days later, the animals were sacrificed, and the spinal cord and nerve roots were examined by a neuropathologist blinded to the solution received and the results of sensory testing. RESULTS: Lidocaine-treated animals exhibited persistent sensory impairment, whereas glucose- and saline-treated animals did not. Neuropathologic evaluation revealed moderate to severe nerve root injury in lidocaine-treated animals. Histologic changes in glucose- and saline-treated animals were minimal, similar, and restricted to the area adjacent to the catheter. Morphologic damage associated with lidocaine preferentially affected the nerve roots, with relative sparing of the spinal cord and dorsal root ganglia. CONCLUSIONS: These results suggest that, at clinically relevant concentrations, glucose does not induce neurologic injury, providing indirect evidence that recent clinical injuries occurring after spinal anesthesia resulted from a neurotoxic effect of the local anesthetic. Additionally, the present studies suggest that deficits resulting from neurotoxicity of intrathecally administered anesthetic result from injury to the axon.

Transient neurologic symptoms after spinal anesthesia: an epidemiologic study of 1,863 patients.

BACKGROUND: Recent evidence suggests that transient neurologic symptoms commonly follow lidocaine spinal anesthesia. However, information concerning factors that affect their occurrence is limited. Accordingly, to evaluate many potential risk factors, the authors undertook a prospective, multicenter, epidemiologic study. METHODS: On a voluntary basis, anesthetists at 15 participating centers forwarded a data sheet on patients who had spinal anesthesia to a research nurse blinded to the details of anesthesia and surgery. A subset was randomly selected for follow-up. The pressure [corrected] of transient neurologic symptoms, defined as leg or buttock pain, was the principal outcome variable. Logistic regression was used to control for potential confounders, and adjusted odds ratios and confidence intervals were used to estimate relative risk. RESULTS: During a 14-month period, 1,863 patients were studied, of whom 47% received lidocaine, 40% bupivacaine, and 13% tetracaine. Patients given lidocaine were at higher risk for symptoms compared with those receiving bupivacaine (relative risk, 5.1; 95% CI, 2.5 to 10.2) or tetracaine (relative risk, 3.2; 95% CI, 1.04 to 9.84). For patients who received lidocaine, the relative risk of transient neurologic symptoms was 2.6 (95% CI, 1.5 to 4.5) with the lithotomy position compared with other positions, 3.6 (95% CI, 1.9 to 6.8), for outpatients compared with inpatients, and 1.6 (95% CI, 1 to 2.5) for obese (body mass index >30) compared with nonobese patients. CONCLUSIONS: These results indicate that transient neurologic symptoms commonly follow lidocaine spinal anesthesia but are relatively uncommon with bupivacaine or tetracaine. The data identify lithotomy position and outpatient status as important risk factors in patients who receive lidocaine. Among other factors postulated to increase risk, obesity had an effect of borderline statistical significance, whereas age, sex, history of back pain, needle type, and lidocaine dose and concentration failed to affect risk.

Lidocaine toxicity in primary afferent neurons from the rat.

Evidence from both clinical studies and animal models suggests that the local anesthetic, lidocaine, is neurotoxic. However, the mechanism of lidocaine-induced toxicity is unknown. To test the hypothesis that toxicity results from a direct action of lidocaine on sensory neurons we performed in vitro histological, electrophysiological and fluorometrical experiments on isolated dorsal root ganglion (DRG) neurons from the adult rat. We observed lidocaine-induced neuronal death after a 4-min exposure of DRG neurons to lidocaine concentrations as low as 30 mM. Consistent with an excitotoxic mechanism of neurotoxicity, lidocaine depolarized DRG neurons at concentrations that induced cell death (EC50 = 14 mM). This depolarization occurred even though voltage-gated sodium currents and action potentials were blocked effectively at much lower concentrations. (EC50 values for lidocaine-induced block of tetrodotoxin-sensitive and -resistant voltage-gated sodium currents were 41 and 101 microM, respectively.) At concentrations similar to those that induced neurotoxicity and depolarization, lidocaine also induced an increase in the concentration of intracellular Ca++ ions ([Ca++]i; EC50 = 21 mM) via Ca++ influx through the plasma membrane as well as release of Ca++ from intracellular stores. Finally, lidocaine-induced neurotoxicity was attenuated significantly when lidocaine was applied in the presence of nominally Ca(++)-free bath solution to DRG neurons preloaded with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Our results indicate: 1) that lidocaine is neurotoxic to sensory neurons; 2) that toxicity results from a direct action on sensory neurons; and 3) that a lidocaine-induced increase in intracellular Ca++ is a mechanism of lidocaine-induced neuronal toxicity.

A comparative study of low-dose hyperbaric spinal lidocaine 0.5% versus 5% for continuous spinal anesthesia.

BACKGROUND AND OBJECTIVES: Concerns of cauda equina syndrome have discouraged clinicians to use 5% lidocaine for continuous spinal anesthesia. Earlier reports indicated that single-shot spinal lidocaine 0.5% is effective for minor gynecologic and perianal surgery. In the present study, we evaluate the anesthetic and hemodynamic effects of low dose hyperbaric 0.5% lidocaine for continuous spinal anesthesia and compare with those of the 5% lidocaine solution in patients undergoing urologic surgery. METHODS: Spinal anesthesia was induced via an indwelling subarachnoid catheter in 42 elderly male patients (range, 57-84 years) undergoing transurethral prostate and bladder procedures. Patients were randomly assigned to receive an initial 30-mg bolus of hyperbaric lidocaine in the form of either 6 mL of 0.5% solution or 0.6 mL of 5% solution. Additional 30-mg boluses (to a total of 90 mg) were given, if necessary, to establish initial sensory block to T10 or higher and lower limb paralysis. Supplemental doses of 30 mg or less were given during surgery, as needed. Dermatomal level of sensory anesthesia and degree of motor blockade were assessed at regular intervals by a blinded observer. Heart rate and blood pressure (mean systolic and diastolic) values were monitored at regular intervals. RESULTS: Forty patients were studied successfully. Both hyperbaric 0.5% and 5% lidocaine provided adequate surgical anesthesia in 75% (30/40) of patients after a single 30-mg dose. A median peak sensory level of T5 (range, T2-T9) achieved within 11.1 +/- 4.5 minutes in patients receiving the 0.5% solution was significantly higher than the peak sensory level of T7 (range, T4-T12) in the 5% group (P = .043). The duration of surgical anesthesia after a 30-mg dose was similar in both groups--48.1 +/- 12.1 minutes versus 50.8 +/- 16.5 minutes respectively. Of the 30 patients (15 in each group) who received 30 mg initially, 25 required repeat lidocaine dosing through the catheter during surgery. The maximum decrease in heart rate and blood pressure values was within 10% and 20%, respectively, of baseline values in both groups. In the remaining patients (10/40), anesthesia was achieved successfully in five patients in the 0.5% group and three patients in the 5% group after two 30-mg lidocaine boluses (60 mg) and two patients in the 5% group after three 30-mg boluses (90 mg). CONCLUSIONS: Continuous spinal anesthesia produced by 0.5% lidocaine with 7.5% dextrose is as effective as that produced by the 5% lidocaine solution in elderly patients undergoing urologic surgery. An initial 30-mg bolus delivered via indwelling subarachnoid catheter was sufficient to achieve surgical anesthesia for approximately 50 minutes in most patients. Hemodynamic effects of the two lidocaine solutions were also comparable.

Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.

BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.

The addition of phenylephrine contributes to the development of transient neurologic symptoms after spinal anesthesia with 0.5% tetracaine.

BACKGROUND: Recent reports indicate that transient neurologic symptoms commonly occur after single-injection spinal anesthesia with lidocaine. Information regarding tetracaine has been limited to a single case report. In addition, little is known about the cause of these symptoms or the cofactors that affect their occurrence. The present study sought to determine whether the presence of phenylephrine or the concentration of glucose in the anesthetic solution affects the incidence of transient neurologic symptoms after spinal anesthesia with 0.5% tetracaine. METHODS: One-hundred sixty patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for elective surgery on a lower limb or perineum were sequentially assigned to one of four equal groups to receive intrathecal 0.5% tetracaine in 7.5% or 0.75% glucose, with or without 0.125% phenylephrine. Patients were evaluated on postoperative day one for the presence of pain, dysesthesia, or both in the legs or buttocks by an investigator unaware of the drug given. RESULTS: Symptoms were present in 10 patients (12.5%) receiving a spinal anesthetic containing phenylephrine, but in only one patient (1.3%) receiving spinal anesthesia without phenylephrine. There was no significant difference in the incidence of symptoms between groups receiving 7.5% glucose and those receiving 0.75% glucose (8.8% and 5% of patients, respectively). CONCLUSIONS: These results suggest that adding phenylephrine to tetracaine for spinal anesthesia increases the potential for transient neurologic symptoms, but that the concentration of glucose does not affect their occurrence.

Intrathecal catheterization in the rat. Improved technique for morphologic analysis of drug-induced injury.

BACKGROUND: The authors previously described an in vivo model suitable for investigation of functional impairment induced by intrathecally injected local anesthetic. However, meaningful histologic analysis could not be performed because catheterization, per se, induced morphologic changes in control animals. In the current experiments, the authors sought to identify an alternative, less reactive, catheterization technique for intrathecal drug administration. METHODS: Twenty-five rats received an intrathecal infusion of normal saline through a catheter composed of either 28-gauge polyurethane, 32-gauge polyimide, 32-gauge polyurethane, PE-10 polyethylene, or PE-10 polyethylene that had been stretched to twice its original length. Seven days after infusion, sensory function was assessed using the tail-flick test, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. RESULTS: There was no significant difference in sensory function among groups. Animals in which 28-gauge polyurethane, 32-gauge polyimide, PE-10, and double-stretched PE-10 had been implanted had moderate to severe nerve injury in 11%, 14%, 23%, and 8% of fascicles, respectively, whereas none of the animals in which 32-gauge polyurethane was implanted had any evidence of moderate or severe damage. CONCLUSIONS: Morphologic changes induced by intrathecal catheterization in the rat can be minimized by the use of 32-gauge polyurethane tubing.

A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5% lidocaine.

Recent reports suggest that transient neurologic symptoms are common after spinal anesthesia with 5% lidocaine. To determine whether reducing the anesthetic concentration might decrease the incidence of symptoms, 50 ASA class I or II patients undergoing brief gynecologic procedures under spinal anesthesia were randomly allocated to receive 1 mg/kg of either 5% or 2% lidocaine in 7.5% glucose. Patients were evaluated on the first postoperative day by an anesthesiologist who was unaware of the solution administered or the details of the anesthetic procedure. Symptoms suggestive of transient radicular irritation were observed in 8 patients (32%) receiving 5% lidocaine, and in 10 patients (40%) receiving 2% lidocaine (NS). These results confirm our previous findings that transient neurologic symptoms may occur in up to one third of the patients receiving 5% lidocaine, and indicate that a modest reduction in lidocaine concentration does not reduce risk.

[Neurologic sequelae of spinal anesthesia: local anesthetic toxicity].

Recent reports of cauda equina syndrome following continuous spinal anesthesia have generated concern regarding the safety of not only this particular technique but also of the local anesthetic agent itself. This concern has been reinforced by data suggesting that similar injuries have occurred with repeated injection after a "failed spinal", and by reports of transient radicular irritation following single subarachnoid injection. This paper summarizes the above cases and reviews recent experiments performed to determine the mechanisms underlying local anesthetic toxicity and the factors that contribute to injury. These experiments suggest that the recent injuries resulted from a direct effect of the local anesthetic and that anesthetic-induced impairment does not result from blockade of the sodium channel, per se. These experiments also suggest that development of a safer anesthetic is a realistic goal.

Transient radicular pain following spinal anesthesia: review of the literature and report of a case involving 2% lidocaine.

Recent reports of transient radicular irritation following intrathecal administration of 5% lidocaine in 7.5% dextrose, a common drug choice in many obstetric centers, have generated concern that its use for single injection spinal anesthesia can result in transient neurologic toxicity. Accordingly, many have advocated dilution of this anesthetic solution prior to subarachnoid administration. The present report describes a case in which transient neurologic symptoms occurred following intrathecal injection of a solution containing approximately 2% lidocaine. The similarity of the present case to those previously reported implies a common etiology and suggests that risk is not restricted to the use of 5% lidocaine with 7.5% glucose. It underscores the need for carefully controlled prospective evaluation of the factors that affect transient neurologic dysfunction following spinal anesthesia.

Local anesthetic neurotoxicity does not result from blockade of voltage-gated sodium channels.

To investigate whether local anesthetic neurotoxicity results from sodium channel blockade, we compared the effects of intrathecally administered lidocaine, bupivacaine, and tetrodotoxin (TTX), the latter a highly selective sodium channel blocker, on sensory function and spinal cord morphology in a rat model. First, to determine relative anesthetic potency, 25 rats implanted with intrathecal catheters were subjected to infusions of lidocaine (n = 8), bupivacaine (n = 8), or TTX (n = 9). The three drugs produced parallel dose-effect curves that differed significantly from one another: the EC50 values for lidocaine, bupivacaine, and TTX were 28.2 mM (0.66%), 6.6 mM (0.19%), and 462 nM, respectively. Twenty-five additional rats were then given intrathecal lidocaine (n = 8), bupivacaine (n = 8), or TTX (n = 9) at concentrations 10 times the calculated EC50 for sensory block. Lidocaine and bupivacaine induced persistent sensory impairment, whereas TTX did not. Finally, 28 rats were given either intrathecal bupivacaine (n = 10) or TTX (n = 9) at 10 times the EC50, or normal saline (n = 9). Significant sensory impairment again occurred after infusion of bupivacaine, but not after infusion of TTX or saline. Neuropathologic evaluation revealed moderate to severe nerve root injury in bupivacaine-treated animals; histologic changes in TTX- and saline-treated animals were minimal, similar, and restricted to the area adjacent to the catheter. These results indicate that local anesthetic neurotoxicity does not result from blockade of the sodium channel, and suggest that development of a safer anesthetic is a realistic goal.