Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine administration.

To determine absorption characteristics of endotracheal lidocaine, we administered lidocaine to hemodynamically stable patients by different techniques. Blood samples were taken for measurement of lidocaine plasma concentrations (fluorescence polarization immunoassay), and pharmacokinetics were calculated by regression analysis. Plasma concentrations at 1.5 and 2 min after drug administration were higher (P < 0.05) after instillation into the endotracheal tube (1.40 +/- 0.19 and 1.26 +/- 0.14 microgram/mL) than after deep endobronchial administration (1.00 +/- 0.08 and 0.83 +/- 0.05 microgram/mL). A biphasic absorption with a division of the area under the curve (AUCtot) into two parts (AUC1 and AUC2) could be assumed. After tube instillation, the AUC1/AUCtot ratio (2.6%) was higher (P < 0.05) than after deep endobronchial instillation (1.1%). To achieve high plasma concentrations within a short time, AUC1, representing a nearly instantaneous absorption, seems to be more important than AUC2, representing a higher but delayed absorption (depot effect). Because deep endobronchial lidocaine administration accentuated the late absorption, presumably by preventing drug distribution to the whole lung, this technique was detrimental to obtaining high plasma concentrations within a short period of time.

Endobronchial drug administration: does deep endobronchial delivery have advantages in comparison with simple injection through the endotracheal tube?

Endobronchial administration of drugs is a valuable alternative to intravenous delivery when venous access cannot be established quickly enough. Some authors propose that deep endobronchial administration through a catheter or similar auxiliary device should give better absorption than simple injection through the endotracheal tube. To test this proposal in the present study two groups of each 6 patients during general anesthesia were administered 3 ml aqueous lidocaine solution at a dose of 2 mg/kg, either deep endobronchially through a catheter or simply through the endotracheal tube. The unusually low volume of administration of 3 ml was chosen because it was thought that the advantages of deep endobronchial administration would then be particularly apparent as 3 ml would lead to a more localized deposit with deep endobronchial administration thus being clearly different from simple injection. No difference in the PaO2 between the two groups could be statistically established. However, the mean lidocaine plasma concentration in the group with the deep endobronchially administered drug was in tendency lower than in the control group (P less than 0.05 at 5 min after delivery). Presumably because of the low volume of administration the mean lidocaine plasma concentrations in both groups always remained under the therapeutic level of at least 1.5 micrograms/ml. Thus, at least for small volumes and stable circulation the results after deep endobronchial administration through a catheter were somewhat worse than after simple injection through the endotracheal tube.

Plasma lidocaine levels and PaO2 with endobronchial administration: dilution with normal saline or distilled water?

STUDY OBJECTIVE: To determine whether water or 0.9% saline should be used as diluent for endobronchial drug administration. PARTICIPANTS: Twelve adult patients. INTERVENTIONS: Patients were endobronchially administered 2 mg/kg lidocaine as marker substance in either 10 mL 0.9% saline or 10 mL distilled water during general anesthesia. MEASUREMENTS AND MAIN RESULTS: The differences in mean lidocaine plasma levels at five minutes (water vs saline, 2.35 vs 1.59 micrograms/mL) and ten minutes (water vs saline: 2.67 vs 1.88 micrograms/mL) were significant (P less than .05). With the initial mean PaO2 being almost (157 mm Hg; F1O2, 0.3) in the two groups, there was a mean drop of about 60 mm Hg in the saline-diluent group, but only about 40 mm Hg in the water-diluent group one minute after administration (P less than .05). CONCLUSION: The use of water resulted in better absorption of lidocaine and less impairment of the PaO2.

What is the optimal volume of administration for endobronchial drugs?

During general anesthesia, three groups of six patients each received 2 mg/kg lidocaine as a marker substance endobronchially in either 10, 5, or 3 mL distilled water. It was found that the group receiving 10 mL initially exhibited the highest lidocaine plasma concentration with a mean of 2.01 micrograms/mL, in comparison with 1.25 micrograms/mL in the 5 mL group and 0.95 micrograms/mL in the 3 mL group. After about 10 minutes, concentration courses were almost the same in the 10 mL and the 5 mL groups. The PaO2 in the 10 mL group dropped initially by approximately 40 mm Hg on average and remained low over 60 minutes. By this time the PaO2 in the 5 mL group (initial drop 46 mm Hg) had come back to the original value (P less than .05). The 3 mL group exhibited even more favorable courses in the PaO2 (initial drop 16 mm Hg on average). However, the lidocaine plasma concentration was at the lowest at all times in this group and, moreover, under the therapeutic level of 1.5 micrograms/mL with the dosage used.