James E. Heavner

Diazepam Prevents Local Anesthetic Seizures

Diazepam (Valium) proved to be effective in preventing local anesthetic-induced convulsions. In cats with recording electrodes permanently implanted in the brain, the median intravenous convulsant dose of lidocaine (CD50) was 8.4 mg/kg. One hour after pretreatment with 0.25 mg/kg of intramuscular diazepam, the lidocaine CD50 doubled to 16.8 mg/kg. This dose of diazepam had no discernible effect on behavior or EEG. However, larger doses of diazepam (0.33 and 0.5 mg/kg) caused ataxia and shifted the EEG to slow high-voltage patterns—without appreciably improving protection against seizures.

Lidocaine Blocking Concentrations for B- and C-nerve Fibers

Rabbit cervical sympathetic trunk contains myelinated preganglionic axons (B-fibers) and unmyelinated postganglionic axons (C-fibers). Using this nerve, we found B-fibers to be three times more sensitive than C-fibers to lidocaine blockade. At 38C and pH 7.5, 100 μM (-0.003 per cent) lidocaine depresses the B-fiber compound action potential by 50 per cent. In contrast, 300 μM (-0.009 per cent) lidocaine is necessary to halve the C-fiber potential amplitude. These in citro findings support clinical evidence that sympathetic block is more extensive than sensory block during spinal anesthesia.

Local anesthetic seizure prevention: diazepam versus pentobarbital.

Diazepam and pentobarbital both elevate the lidocaine seizure threshold in cats with recording electrodes permanently imbedded in the brain. Ten mg/kg of pentobarbital and 0.25 mg/kg of diazepam, given intramuscularly one hour prior to local anesthetic injection, afforded approximately equal protection against lidocaine-induced seizures. The median iv convulsant dose (CD50) of lidocaine was 16.8 mg/kg in diazepam-treated and 17.6 mg/kg in pentoborbital-treated cats—as against 8.4 mg/kg in unprotected cats. However, CNS and cardiorespiratory depression following pentobarbital and lidocaine was much more profound and prolonged than that which followed diazepam and lidocaine. One hour after injection, diazepam is a better premedicant than pentobarbital for protecting against local anesthetic convulsions.

Diazepam Prevents and Aborts Lidocaine Convulsions in Monkeys

Prophylaxis of local anesthetic convulsions in six rhesus monkeys was gauged by bracketing seizure-producing lidocaine doses before and after diazepam premedication. The control median intravenous convulsant dose (CD50) of lidocaine was 12.8 mg/kg. Sixty minutes after 0.25 mg/kg diazepam (im) the CD

Correlation of the Ethrane Electroencephalogram with Motor Activity in Cats

Six EEG levels of Ethrane anesthesia, similar to those of ether, were observed in cats with chronically implanted recording electrodes. With the onset of surgical anesthesia (EEG level III and deeper), high-amplitude spikes and/or spike-wave-complexes invariably appeared in all leads. In three cats faint twitching of the muscles of the face and tongue synchronous with spike discharges appeared at levels III and IV. Deepening or lightening the level of anesthesia stopped the twitching. As anesthesia deepened and the duration of burst suppression lengthened, spiking became more rhythmic Bursts of single or grouped high-voltage spikes arising from a nearly flat baseline commonly were the only major ongoing electrical activity observed in deep level V and in level VI. Noise increased the frequency of spike-like discharges in two deeply anesthetized (level V) animals

Nitrous oxide elevates local anesthetic seizure threshold

Abstract The median intravenous convulsant dose (CD50) of lidocaine in awake unoperated cats breathing air was 7.65 mg/kg. In acute experiments on cats ventilated with nitrous oxide and having noninvasive extradural cortical recording electrodes, the lidocaine CD50 was 11.43 mg/kg—an elevation of the CD50 in air-breathing animals of nearly 50%. When cortical as well as depth (limbic) electrodes were placed in cats ventilated with nitrous oxide the lidocaine CD50 was 12.55 mg/kg. This too was some 50% greater than the 8.16 mg/kg CD50 in awake cats with chronically implanted cortical and limbic electrodes. Nitrous oxide or unidentified intraoperative factors (or both) alter CNS responses to local anesthetics. Cats with chronically implanted electrodes appear to respond normally.

Effects of Nitrous Oxide on the Lidocaine Seizure Threshold and Diazepam Protection

Nitrous oxide raises the lidocaine seizure threshold 50 per cent above the value measured in awake cats. In 11 awake intact cats breathing air, the median convulsant dose (CD50) of lidocaine was 7.6 mg/kg. In 17 cats ventilated with 70 per cent nitrous oxide the lidocaine CD50 was 11.4 mg/kg. One hour after a 0.25 mg/kg im dose of diazepam, the lidocaine CD50 was 16.8 mg/kg, whether the inspired gas was air or nitrous oxide. Nitrous oxide supplementation thus reduces the CNS toxicity of local anesthetics, and diazepam reduces it further.

Kindling Phenomenon: Impairment by Auditory Stimuli

Summary: By coupling kindling stimuli with tones, it is shown that kindled epileptiform activity is not easily classically conditioned such that it can be evoked by an auditory stimulus. On the contrary, a tone presented 400 msec before and during the kindling stimulus impedes the rate of kindling.

Gas chromatographic assay of volatile anesthetics: some problems and a solution.

A modification of the gas chromatographic procedure of Fink and Morikawa (ANESTHESIOLOGY 32:451-455, 1970) for measuring inhalation anesthetics is presented. Emphasis is placed on separating vehicular gas from anesthetic vapor by using appropriate column packing material and assay conditions.

Convulsions induced by local anaesthetic: Time course of diazepam prophylaxis

SummaryThe time course of diazepam prophylaxis of convulsions induced by local anaesthetic was gauged by dose-response assays in 12 cats. Curves relating seizure incidence to intravenous lidocaine dose yielded the median convulsant dose (CD50) of lidocaine for each of seven post-diazepam time periods.The control CD50 for lidocaine was 7.5 mg/kg. Fifteen minutes after 0.25 mg/kg diazepam (I.M.) the lidocaine CD50 already was 187 per cent of control (14.1 mg/kg) and it peaked to 232 per cent (17.4 mg/kg) at 30 minutes after diazepam. Two hours after diazepam the CD50 still remained at nearly double the control value (14.5 mg/kg), and even five hours later was more than one and a half times the control CD50 (11.9 mg/kg). Diazepam protection against convulsions induced by local anaesthetic begins soon after intramuscular injection and lasts at least five hours.RésuméLes convulsions sont une complication sérieuse de l’administration des anesthésiques locaux et ont les rencontre de plus en plus souvent avec l’usage croissant de la Lidocaïne et de la médication antiarythmique.Le Diazepam protège non seulement les animaux de laboratoire contre les convulsions induites par les anesthésiques locaux mais il a aussi légèrement plus d’effets indésirables qu’une dose protectrice équivalente de barbituriques. L’acceptation du Diazepam en clinique comme agent de pré-médication pour les cas d’anesthésie locale requiert cependant que l’on connaisse à quel moment le Diazepam atteint son action anticonvulsivante maximum et durant combien de temps il conserve son action prophylactique.Nous avons évalué l’activité anticonvulsivante du Diazepam en comparant l’incidence des convulsions à la dose de Lidocaïne employée et au temps d’appartition après l’injection de Diazepam. Les doses convulsivantes médianes (CD-50) de Lidocaïne ont été compilées à partir des courbes de dose-effet. Le pouvoir prophylactique relatif fut exprimé comme le rapport du CD-50 post-Diazepam sur pré-Diazepam.Chez un groupe contrôle de 12 chats non prémédiqués, la dose convulsivante médiane (CD-50) de Lidocaïne était de 7.5 mg/kg. Quinze minutes après 0.25 mg/kg de Diazepam i.m., le CD-50 de la Lidocaïne s’élève à 187 pour cent de la valeur contrôle (14.1 mg/kg). La protection maximum anticonvulsivante se produit à 30 minutes après l’injection de Diazepam, à ce moment le CD-50 de la Lidocaïne atteint un sommet à 232 pour cent de la valeur contrô1e (soit 17.4 mg/kg).Deux heures après 1’injection de Diazepam, le CD-50 de la Lidocaïne est encore à près du double de la valeur contrôle (14.5 mg/kg, et même 5 heures après, le CD-50 est encore à plus de 1.5 fois celui de la valeur contrôle (11.9 mg/kg). La protection du Diazepam contre les convulsions induites par les agents anesthésiques locaux commence tôt après l’injection intra-musculaire et dure au moins durant cinq heures.