Neurotoxicity secondary to local tetracaine use.

INTRODUCTION: Systemic reactions from local tetracaine use are often an anomaly - not only is tetracaine short-acting and quickly metabolized by the pseudocholinesterase system leading to very limited systemic uptake, but most adverse reactions are usually associated with dental or spinal anesthesia. Furthermore, reactions to local anesthetics manifest in standard allergy-type reactions. When local anesthetics lead to nervous or cardiac system abnormalities, it is termed a local anesthetic systemic toxicity - an event with an incidence currently estimated to be 0.03%. CASE PRESENTATION: We present a case of a 56-year-old female who experienced a systemic reaction to tetracaine 1% while undergoing a fine needle biopsy of a thyroid nodule. The patient had previous allergic reactions to lidocaine. Upon conclusion of the procedure, the patient began convulsing and became rigid and non-verbal. She was able to move all extremities, had no respiratory distress, no swelling, hives, or redness, and was swallowing without difficulty. After about 5 min, the patient began to improve and experienced reversal of all previous symptoms. Her physical exam and labs were otherwise normal, she returned to her baseline functioning, and was discharged without any medical interventions. DISCUSSION: This case illustrates a case of LAST in a patient with previous Lidocaine allergy without any other obvious risk factors. There have been no cases of cross-reaction between lidocaine and tetracaine so it explores the possibility of patients having cross reaction to those two different kinds of local anesthetic.

Effect of topical anesthetic agents and ethanol on corneoepithelial wound healing in an ex vivo whole-globe porcine model.

PURPOSE: To assess the impact of topical anesthetic agents and ethanol on ocular surface wound healing using an ex vivo whole-globe porcine model. SETTING: Department of Ophthalmology, Inselspital, University of Bern, Bern, Switzerland. DESIGN: Experimental study. METHODS: Standardized corneoepithelial lesions (5.0 mm diameter, 40 µm depth) were created with excimer laser light in freshly enucleated porcine eyes. The globes (6 per group) were exposed to different concentrations of ethanol (2.0% to 99.0%), cocaine (2.0% to 10.0%), procaine hydrochloride (0.4%), tetracaine (0.5% to 1.0%), or lidocaine (2.0%), 3 drops/hour for 3 hours. Control solutions were physiologic saline, balanced salt solution, and tissue-culture medium. After 20 to 26 hours, wound-healing response was compared by measuring the diameter of each corneoepithelial lesion. RESULTS: The mean diameter of corneoepithelial lesions exposed to physiologic saline decreased from 4.78 mm ± 0.19 (SD) to 4.44 ± 0.17 mm between 20 and 26 hours. After 24 hours, the mean lesion size, compared with physiological saline, was larger after cocaine 5.0% (5.20 ± 0.26 mm) and 10.0% (5.39 ± 0.12 mm), tetracaine 0.5% (5.59 ± 0.35 mm) and 1.0% (5.55 ± 0.27 mm), and procaine hydrochloride 0.4% (5.76 ± 0.12 mm), but not after lidocaine 2.0% (5.01 ± 0.17 mm). Balanced salt solution, tissue-culture medium, ethanol 2.0% to 99.0%, and cocaine 2.0% did not inhibit the wound-healing response. CONCLUSIONS: In an ex vivo whole-globe porcine model, lidocaine 2.0% and cocaine 2.0% were the least toxic anesthetic agents. At all concentrations, ethanol had no impact on wound healing. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Effect of reversible inactivation of the reuniens nucleus on spatial learning and memory in rats using Morris water maze task.

The involvement of thalamic midline nuclei (MLN) in early stage of Alzheimer's disease and in diencephalic amnesia has drawn attention to the connectivity between the nucleus reuniens (RE) and structures of medial temporal lobe. RE is major source of thalamic afferents to the hippocampus and has been shown to exert powerful excitatory action on CA1 of hippocampus, which is supposed to be involved in learning and memory processes. However, the role of the RE on spatial memory is a controversial issue. The present study was designed to evaluate the role of the RE in acquisition, consolidation and retrieval of spatial reference memory (RM) and working memory (WM). We assessed the effect of reversible inactivation of RE with tetracaine (0.5 microl, 2%) on different stages of memory. Rats were trained on RM and WM versions of the Morris water maze (MWM) task. RE was inactivated before or immediately after training or before the probe trial of retrieval tests. The data showed that reversible inactivation of the RE significantly impaired both RM and WM versions of MWM. Therefore, it seems that nucleus reuniens of thalamus plays a role in spatial RM and WM version of the MWM task in rats.

In vitro interactions with the Cytochrome P450 system, toxicity, and local anaesthetic effects of Fomocaine Alkylmorpholine derivatives in rats.

Fomocaine (CAS 56583-43-8) is a basic ether-type local anaesthetic used in dermatological practice for surface anaesthesia. For many years, modifications of the fomocaine molecule have been pursued, e.g. to improve its affinity to the sodium channel and also in view of possible new (systemic) applications. In the present study fomocaine and eight fomocaine derivatives with an additional alkyl chain in 2- or 3-position of different length (C1 up to C4), or with a branched C3 chain in 3-position, respectively, at the morpholine ring were evaluated in vitro for possible structure-activity relationships with respect to the interactions with cytochrome P450 (CYP) mediated monooxygenase and oxidase functions using rat liver 9000 g supernatants or microsomes. Results were compared to in vivo data from rats on toxicity (LD50), paresis of the N. ischiadicus and surface and conduction anaesthesia (cornea, N. ischiadicus). In general, the influence of the derivatives on the CYP system was less than that of fomocaine, showing a further decline with enlarging chain length. Toxicity of the derivatives was comparable to that of fomocaine and lower only with the compound with a C4 alkyl chain in 2-position. The derivatives caused a stronger surface anaesthesia than fomocaine, exhibiting an additional increase with enlarging chain length. No clear-cut structure-activity relationships were observed with respect to paresis of the N. ischiadicus and to conduction anaesthesia. Especially the derivatives having a C2 or C4 chain in 2- or a C3 chain in 3-position, respectively, may be of interest for further investigations. In comparison to fomocaine they caused a stronger surface anaesthesia combined with a lower interaction capacity with the CYP system.

Corneal endothelial toxicity of topical anesthesia.

PURPOSE: To determine the relative corneal endothelial toxicities of the following topical anesthetic agents: bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, proparacaine HCl 0.5%, and tetracaine HCl 0.5%. METHODS: The experiment was conducted using pigmented rabbits. Approximately nine animals each were randomly assigned to eight groups. Right eyes received injections of 0.2 ml of one of the four anesthetic agents at one of two concentrations and left eyes received injections of 0.2 ml of balanced salt solution. Corneal thickness and clarity were measured before surgery and on postoperative days 1, 3, and 7. RESULTS: A statistically significant increase (P < 0.05) in corneal thickness and opacification over preoperative measurements was noted with injections of bupivacaine, lidocaine, and proparacaine, controlling for changes occurring in control eyes from surgery alone. Proparacaine was statistically more toxic than were the others. The toxicity of tetracaine was statistically indistinguishable from balanced salt solution, although mild toxicity was evident clinically. Injection of 1:10 dilutions of the same anesthetic agents failed to produce a statistically significant increase in corneal thickness or opacification on any postoperative examination. CONCLUSIONS: Anterior chamber injection of bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, and proparacaine HCl 0.5% produces corneal thickening and opacification that is clinically and statistically significant. Tetracaine HCl 0.5% injection produces corneal thickening and opacification that is clinically apparent in some eyes but statistically insignificant. Ophthalmic surgeons should be aware of the potential for endothelial cell injury if anesthetic agents enter or are injected into the eye during cataract surgery in the concentrations supplied commercially.

The effect of local anaesthetics on the thermal sensitivity of HTC cells.

Local anaesthetics caused death of HTC cells, and the order of toxicity (dibucaine > tetracaine > procaine) correlated with their oil:water partition coefficients. Cytotoxic effects of hyperthermia were enhanced by subtoxic levels of anaesthetics and again, their potency was related to the oil:water partition coefficients. DPH fluidity in plasma membranes at 37 degrees C was increased by dibucaine and tetracaine but not by procaine up to 5mM. At 43 degrees C, plasma membrane fluidity was increased by dibucaine but not by tetracaine or procaine. The results suggest that fluidisation of the hydrophobic core of the membrane may contribute to anaesthetic potentiation of heat cell death.