The Influence of Acid‐Base Changes on Central Nervous System Toxicity of Local Anaesthetic Agents II

Abstract

This study is a detailed analysis of data obtained from 127 experiments on 90 paralysed and ventilated cats regarding the CNS toxicity of nine local anaesthetic agents as evidenced by seizure activity on the EEG. It is shown that an increase in Pco2 or aH+ caused increased CNS toxicity, i.e., smaller i.v. doses were required to elicit seizure activity, and that the underlying metabolic acid‐base state can considerably modify this, a metabolic alkalosis decreasing toxicity, and vice‐versa. The probable mechanisms of this process involving relationships between pH and the local anaesthetic cation/base ratios in plasma and neural tissue are discussed. It is finally recommended that local anaesthetic convulsions be treated by adequate artificial ventilation, which by lowering the Pco2 in the brain will diminish the local anaesthetic toxicity and thus treat the root cause.ZUSAMMENFASSUNGDiese Untersuchung stellt die Detailanalyse von Ergebnissen dar, die bei 127 Experimental an 90 paralysierten und künstlich beatmeten Katzen gewonnen wurden in Hinblick auf die ZNS‐Toxizität von neun Lokalanaesthetika, dargestellt mittels Krampfaktivität im EEC Es zeigte sich, daß eine Erhöhung des PCo2 oder der Wasserstoffionenaktivität (aH+) die ZNS‐Toxizität erhöhte, d.h. es waren geringere i.v. Dosen erforderlich, urn Krampfpotentiale auszulösen. Es zeigte sich ferner, daß der zugrundeliegende metabolische Säure‐Basen‐Status dies beträchtlich modifizieren kann, wobei metabolische Alkalose die Toxizität reduziert und umgekehrt. Der wahrscheinliche Mechanismus, an dem wohl Beziehungen zwischen pH und der Lokalanaesthetika‐Kationen‐Basen‐Relationen im Plasma und im Nervengewebe beteiligt sind, wird diskutiert. Schließlich wird empfohlen, durch Lokalanesthetika bedingte Krämpfe mit adäquater künstlicher Beatmung zu behandeln, damit der Senkung des Pco2 im Gehirn die Toxizität des Lokalanaesthetikums vermindert und mithin das Übel an der Wurzel gepackt wird.

Effect of PaCO2 and PaO2 on Lidocaine and Articaine Toxicity

“…It has been shown that increased plasma PaCO 2 and consequent changes in the acid-base state caused an exponential increase in the central toxicity of many local anesthetic agents. 15,16 In this same way Ryan et al 33 affirmed that hypercarbia decreases the convulsive threshold of local anesthetic agents. It is also important to note the cerebral vasculature response to PaCO 2 as a factor affecting toxicity.…”

“…10,14 Studies in cats have shown that the acid-base state is an important factor, in that acidosis increased, while alkalosis reduced, anesthetic toxicity. 15,16 An increase in the levels of PaCO 2 can worsen the convulsive threshold, and a decrease in PaCO 2 levels tends to have the opposite effect. 17,18 The duration of seizure activity is related to the local anesthetic blood level and is directly related to the arterial PaCO 2 level.…”

Dibucaine Toxicosis in a Dog

“…Maintenance of a patent airway and respiratory support is essential. Studies using cats, dogs, and sheep have shown that LA intoxication is more severe in the presence of acidosis (respiratory or metabolic), hypercarbia, and hypoxia [31][32][33][34]. Thus, avoidance of hypoventilation causing respiratory acidosis and hypoperfusion causing metabolic acidosis is key.…”

“…Continuous or frequent intermittent monitoring of systemic blood pressure and ECG is also prudent if present cardiopulmonary arrest should be treated with standard cardiopulmonary resuscitation, which historically has been relatively refractory to treatment [26,38]. The most effective positive ionotrope, vasopressor, or antiarrhythmic remains unknown, although correction of hypotension and arrhythmias leading to hypoperfusion appears to be essential [16,[31][32][33]. Kasten et al described effective cardiovascular resuscitation after bupivicaine overdose in anesthetized dogs using open-chest cardiac massage, bretylium, atropine, epinephrine, and intravenous crystalloid fluids [27].…”

Acute toxicity profile of tolperisone in overdose: Observational poison centre-based study

“…14 Although severe cardiotoxicity was rarely seen in our study, there might be a risk for cardiac arrhythmias, which are a characteristic manifestation of local anaesthetic agent toxicity. As acidosis is known to increase local anaesthetic toxicity 28 it seems plausible that conditions such as seizures and respiratory depression, which are observed in tolperisone overdose and are associated with acidosis, will further exacerbate tolperisone toxicity.…”