Saliva concentrations of lignocaine in patients with acute myocardial ischaemia.

In order to know those agents whose clinical effects can be monitored by using saliva samples, in our earlier work we studied the salivary concentrations of lignocaine in healthy volunteers after a single 100 mg lignocaine injection (Kanto et al., 1982). The semilogarithmic concentration-time curves of lignocaine in saliva and plasma showed good parallelism especially 3 h after the drug administration in the elimination phase of this local anaesthetic. However, the study was performed under ideal conditions in healthy volunteers and only after a single i.v. administration. For the determination of clinical drug effects and side-effects, clinical studies during a continuous intravenous infusion of lignocaine are needed (Kanto etal., 1982). Six patients with acute myocardial ischaemia received intravenous lignocaine 4 mg/min for 3 h and thereafter 2-3 mg/min after a single initial i.v. bolus injection of 100 mg in order to treat or prevent cardiac arrhythmias. Their ages, weights and heights were 56.6 + 12.3 (s.d.) years, 75.2 + 6.6 kg, and 175.2 + 3.8 cm. Five of them had myocardial infarction and one had stenocardia and bigeminy. As an analgesic, oxycodone was used 5 mg i.v. every hour if needed. Other therapy was allowed including other antiarrhythmic drugs and ,8-adrenoceptor blocking agents. As a sedative-anxiolytic agent diazepam 5 mg i. v. was given when needed. There was one volunteer, in addition, a 26 year old healthy male weighing 70 kg, who was given during 6 h a continuous lignocaine infusion at a rate of 2 mg/min after an initial i.v. bolus injection of 100 mg. The samples were taken at 0.5, 3 and 6 h after starting the infusion. Blood samples were drawn from the contralateral cubital vein and mixed saliva was obtained by having the patients expectorate into glass vials while chewing Parafilm® . The saliva samples were centrifuged to remove any debris. Serum and saliva lignocaine levels were measured by gas chromatography using the method of Benowitz & Rowland (1973). The sensitivity of this method in our laboratory was 0.1 mg/l and the interassay precision of duplicate determinations 6.1% (C.V.). The results of this study can be seen in Table 1. The mean saliva/serum ratio of the six patients was 8.73. Clearly lower saliva/serum ratios were found in the volunteer (Table 1). The mean saliva/plasma ratio of healthy volunteers after a single 100 mg i.v. injection of lignocaine was 1.37 (Kanto et al., 1982, n = 8). Danhof & Breimer (1978) have reported a mean value of 1.78 (n = 3). However, the situation appears to differ completely when using a continuous lignocaine i.v. infusion to treat or prevent arrhythmias in patients in a coronary care unit. The pKa value of lignocaine is 7.86 and so is near the normal plasma pH value of approximately 7.40. Therefore, the concentrations of this weak basic compound in saliva will be higher than in plasma (Danhof & Breimer, 1978). In this study, this phenomenon was clearly more significant after the i.v. infusion in patients with acute myocardial ischaemia than after a single i.v. lignocaine injection in healthy volunteers (Kanto et al., 1982). The lower saliva/serum ratios of the healthy volunteers in the present study may be due to clearly larger saliva samples which were easily obtained in comparison with our patients. Our patients were ill and in pain, and apparently therefore, had a low saliva flow rate. Consequently, saliva samples were difficult to obtain. As saliva flow rate falls, saliva pH will fall (Mucklow, 1982), increasing the saliva/serum ratio of lignocaine. The marked intraas well as interindividual variation found in this respect in our patients may be due to this phenomenon.