Role of cardiac vagal C-fibers in cardiovascular control.

Intravenous lidocaine can attenuate bronchial hyperreactivity. However, lidocaine inhalation might yield the same or better results at higher airway and lower lidocaine plasma concentrations. Therefore, we tested in awake volunteers with bronchial hyperreactivity the effect of lidocaine on histamine-induced bronchoconstriction administered either intravenously or as an aerosol. After approval of the local ethics committee, 15 volunteers were enrolled in this placebo-controlled, double-blinded, randomized study. Volunteers were selected by showing a decrease in FEV1 greater than 20% of baseline (PC20) in response to histamine inhalation. On three different days the challenge was repeated after pretreatment with either intravenous lidocaine, inhaled lidocaine, or placebo. Blood samples for determination of lidocaine plasma concentration were drawn. Comparisons were made using the Friedman and Wilcoxon signed-rank tests. Baseline PC20 was 6.4 +/- 1.1 mg. ml-1. Both inhalation of lidocaine and intravenous administration significantly increased PC20 to 14.8 +/- 3.5 mg. ml-1 and 14.2 +/- 2. 5 mg. ml-1, respectively (p = 0.0007). Peak plasma lidocaine concentrations at the end of challenges were 0.7 +/- 0.1 microg. ml-1 (inhaled) and 2.2 +/- 0.1 microg. ml-1 (i.v.). However, 7 of 15 subjects showed an initial decrease of FEV1 greater than 5% following lidocaine inhalation. While both intravenous as well as inhaled lidocaine attenuate reflex bronchoconstriction significantly, lidocaine plasma concentrations are significantly lower after inhalation. However, the high incidence of initial bronchoconstriction to lidocaine inhalation may limit its use in patients with asthma and thus offers therapeutic advantages for intravenous lidocaine.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.159.2.9806102

Both Intravenous and Inhaled Lidocaine Attenuate Reflex Bronchoconstriction but at Different Plasma Concentrations

Circulatory responses to shortlasting occlusions of one coronary artery (left anterior descendent or right coronary artery) were studied in chloralose-anesthetized cats. — When the carotid sinus baroreceptors were left functionally intact, coronary occlusion induced moderate reflex reductions of heart rate and blood pressure and slight increases of resistance and capacitance vessel tone in the calf muscles. When the buffering influences from the baroreceptors were largely eliminated by bilateral carotid occlusion, the reflex fall of blood pressure and heart rate became more pronounced and a clearcut vasodilatation was now observed. After cold block of the cervical vagi, the blood pressure fall upon coronary obstruction was markedly diminished, the heart rate response was reversed to a slight tachycardia and a marked peripheral vasocon-striction ensued. After i.v. administration of local anesthetics (lidocaine 3–4 mg/kg b.wt.) the reflex response to coronary obstruction and to shortlasting occlusions of the ascending aorta were almost completely eliminated. — It is concluded that acute occlusions of one coronary artery induce a reflex bradycardia and vasodilatation, in all probability due to activation of left ventricular mechanoreceptors. The vascular responses in this inhibitory reflex seem to be significantly moderated by influences from the arterial baroreceptors.

Evidence for a depressor reflex elicited from left ventricular receptors during occlusion of one coronary artery in the cat.

Background Airway instrumentation in persons with asthma is linked to the risk of life-threatening bronchospasm. To attenuate the response to airway irritation, intravenous lidocaine is recommended (based on animal experiments) and mitigates the response to histamine inhalation in asthmatic volunteers. However, the effects of lidocaine have not been compared with standard prophylaxis with beta-sympathomimetic aerosols. Therefore, the effect of lidocaine, salbutamol, combined treatment, and placebo control were tested in awake volunteers with bronchial hyperreactivity. Methods After approval from the local ethics committee, 15 persons, who were selected because they showed a decrease in forced expiratory volume in 1 s (FEV1) more than 20% of baseline in response to inhaled histamine in a concentration less than 18 mg/ml (PC20), were enrolled in a placebo-controlled, double-blind, and randomized study. The challenge was repeated on four different days and the volunteers were pretreated with either intravenous lidocaine, inhalation of salbutamol, inhalation of salbutamol plus intravenous lidocaine, or placebo. Lidocaine plasma concentrations were also measured. Statistical analyses included the Friedman test and Wilcoxon's rank sum. Results The baseline PC20 was 6.4 +/- 4.3 mg/ml. Intravenous lidocaine and salbutamol aerosol both significantly increased the histamine threshold to 14.2 +/- 9.5 mg/ml and 16.8 +/- 10.9 mg/ml, respectively (mean +/- SD). However, the combination of lidocaine and salbutamol significantly increased the PC20 even further to 30.7 +/- 15.7 mg/ml than did salbutamol or lidocaine alone. Conclusions In volunteers with bronchial hyperreactivity, both lidocaine and salbutamol attenuate the response to an inhalational histamine challenge, and their combined administration has much greater effects than does either drug alone. Accordingly, pretreatment of patients with bronchial hyperreactivity with both beta-mimetic aerosol and intravenous lidocaine is recommended before airway irritation.

Combined intravenous lidocaine and inhaled salbutamol protect against bronchial hyperreactivity more effectively than lidocaine or salbutamol alone.

Background In standard textbooks, intravenous lidocaine is recommended for intubation of patients with bronchial hyperreactivity. However, whether and to what extent intravenous local anesthetics attenuate bronchial hyperreactivity in humans is unknown. Accordingly, nine awake volunteers with known bronchial hyperreactivity were subjected to an inhalational challenge with acetylcholine before and during intravenous infusion of lidocaine, bupivacaine, or placebo in a randomized, double-blinded fashion. Methods Baseline acetylcholine threshold concentrations were determined 3-5 days before initiation of the investigation. The response to the acetylcholine challenge was defined as hyperreactive, if forced expiratory volume in 1 s decreased by at least 20%. In addition, the acetylcholine threshold for a 100% increase in airway resistance was obtained by body plethysmography. On seven different days, the acetylcholine challenge was repeated at the end of a 30-min intravenous infusion period of three doses of lidocaine (1, 3, and 6 mg.min(-1)) or bupivacaine (0.25, 0.75, and 1.5 mg.min(-1)), during saline placebo infusion, respectively. Acetylcholine-threshold concentrations were presented with the respective plasma concentrations of the local anesthetic. Results The infusion of lidocaine and bupivacaine resulted in plasma concentrations (means +/- SD) of 0.29 +/- 0.11, 1.14 +/- 0.39, and 2.02 +/- 0.5 microg.ml(-1) for lidocaine and 0.11 +/- 0.04, 0.31 +/- 0.09, and 0.80 +/- 0.18 microg.ml(-1) for bupivacaine, respectively. Compared to baseline, the acetylcholine threshold for a 20% decrease of forced expiratory volume in 1 s as well as the threshold for a 100% increase in total airway resistance increased significantly with increasing plasma concentrations of both local anesthetics. Compared to placebo, acetylcholine threshold was almost quadrupled for lidocaine and tripled for bupivacaine with the highest plasma concentration of each local anesthetic. Conclusions In awake humans, intravenous lidocaine and bupivacaine both dose-dependently attenuated the hyperreactive response to a nonspecific inhalational challenge with acetylcholine.

Intravenous Lidocaine and Bupivacaine Dose-dependently Attenuate Bronchial Hyperreactivity in Awake Volunteers

A review is given on our present pharmacological knowledge of those drugs which exert stimulating, sensitizing or depressing actions on sensory receptors and in particular on viscero-afferent receptors.

H. F. Zipf

Papers

The pharmacology of viscero-afferent receptors with special reference to endoanaesthesia