Ultimately, generalised convulsions of a tonic-clonic nature occur. If a sufficiently large dose, or rapid intravenous injection of local anaesthetic is given, the initial signs of excitation may progress very rapidly to generalised CNS depression and coma. Respiratory depression may result in respiratory arrest. CNS toxicity is exacerbated by hypercarbia and acidosis. Cardiovascular toxicity usually occurs at doses and blood concentrations which are higher than those required to produce CNS toxicity.
Local anaesthetics can exert a direct effect both on the heart and the peripheral blood vessels.
Extremely high concentrations of local anaesthetics depress spontaneous pacemaker activity in the sinus node resulting in sinus bradycardia and sinus arrest. They also exert a dose - dependent negative inotropic action on isolated cardiac tissue. The more potent local anaesthetics depress cardiac contractility at lower concentrations than the less potent drugs. Local anaesthetic agents appear to exert a biphasic effect on peripheral vascular smooth muscle. In lower doses they may increase peripheral vascular resistance, and in higher doses, reduce it.