Keishi Hashimoto

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.

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.

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.

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 &mgr;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 &mgr;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. 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.

Pulmonary Doppler flow velocity pattern during caudal epidural anaesthesia in children

Background: Haemodynamic effects of caudal anaesthesia in children have not been fully investigated. In the present study, we evaluated pulmonary haemodynamics during caudal anaesthesia in otherwise healthy children using Doppler‐echocardiography.