Targeted Versus Continuous Delivery of Volatile Anesthetics During Cholinergic Bronchoconstriction

Abstract

Volatile anesthetics have been shown to reduce lung resistance through dilation of constricted airways. In this study, we hypothesized that that diffusion of inhaled anesthetics from airway lumen to smooth muscle would yield significant bronchodilation in vivo, and systemic recirculation would not be necessary to reduce lung resistance (R_L ) and elastance (E_L ) during sustained bronchoconstriction. To test this hypothesis, we designed a delivery system for precise timing of inhaled volatile anesthetics during the course of a positive pressure breath. We compared changes in R_L , E_L , and anatomic dead space (V_D ) in canines (N=5) during pharmacologically-induced bronchoconstriction with intravenous methacholine, and following treatments with: 1) targeted anesthetic delivery to V_D ; and 2) continuous anesthetic delivery throughout inspiration. Both sevoflurane and isoflurane were used during each delivery regimen. Compared to continuous delivery, targeted delivery resulted in significantly lower doses of delivered anesthetic and decreased end-expiratory concentrations. However, we did not detect significant reductions in R_L or E_L for either anesthetic delivery regimen. This lack of response may have resulted from an insufficient dose of the anesthetic to cause bronchodilation, or from the preferential distribution of air flow with inhaled anesthetic delivery to less constricted, unobstructed regions of the lung, thereby enhancing airway heterogeneity and increasing apparent R_L and E_L .

Fig. 1

Schematic of inhaled anesthetic delivery system. Arrows within the ventilator circuit denote direction of flows. NO Sol, normally open solenoid valve; NC Sol, normally closed solenoid valve; A/D, analog-to-digital converter; D/A, digital-to-analog converter; P_ao, airway pressure; $\dot{V}$, airway flow. Check valves included to prevent back flow into the inspiratory limb as the gas travels to the scavenger system during expiration.

Fig. 2

Timeline of experimental protocol and drug administration. Baseline measurements of R_L, E_L, and V_D were obtained after anesthetic induction and intubation. Intravenous MCh was then used to induce sustained bronchoconstriction, followed by either targeted or continuous delivery of the inhaled anesthetic. Intravenous atropine was administered after treatment with inhaled anesthetic. Neostigmine and glycopyrrolate were used at the end of the protocol, to reverse neuromuscular blockade.

Fig. 3

Real-time estimation of anatomic dead space using the technique of volume capnography in a representative dog; this analysis was automated for each breath as part of the solenoid-valve control software. A line tangent to phase III (sloping upward dashed) and a vertical line through phase II (vertical dashed) are positioned such that areas p and q are equal. Volumes along the x-axis to the left and right of the vertical line are assumed to correspond to the dead space volume (V_D), and the effective alveolar volume (V_alv), respectively.

Fig. 4

Isoflurane was delivered to a section of corrugated tubing (∼150 ml, gray cylinder) in series with a pair of spring-loaded bellows (as shown on the right in the schematic), ventilated with tidal volume 500 ml and rate 20 min⁻¹: (a) characteristic trace of flow measured for two breaths; (b) corresponding tidal volume (solid) with real-time generation of actuating signal denoting anesthetic delivery window at the end of inspiration (dashed). The delivery threshold (V_th) was set to 300 ml to account for the delay in switching between sublimbs and engaging the anesthetic vaporizer; and (c) three traces of isoflurane concentration characterizing anesthetic distribution throughout the dead space compartment. Isoflurane concentration detected at the interface between dead space and alveolar compartments was negligible.

Fig. 5

Summary of: (a) and (b) lung resistance (R_L); (c) and (d) lung elastance (E_L); and (e) and (f) anatomic dead space (V_D) during targeted and continuous delivery. Data are shown for sevoflurane (left panels) and isoflurane (right panels), and are averaged across all animals, with error bars denoting standard deviations. *Significantly different compared to baseline; ^#significantly different compared to atropine. For all comparisons, P < 0.05.

Fig. 6

Examples of (a) and (b) lung resistance (R_L); (c) and (d) lung elastance (E_L); and (e) and (f) anatomic dead space (V_D) during targeted and continuous delivery for two representative dogs. Data are shown for a positive responder (left panels) and a nonresponder (right panels) during targeted and continuous sevoflurane delivery. Symbols denote the mean value from 20 breaths. Errors bars, when larger than the symbol, denote standard deviations.

Fig. 7

Example concentration profiles of sevoflurane (solid line) and isoflurane (solid line) measured at the airway opening during (a) and (c) targeted and (b) and (d) continuous delivery, superimposed on corresponding tidal volumes (dashed black line). Note the relatively higher end-expiration concentration for continuous compared to targeted delivery.

Fig. 8

Comparison of: (a) average inhaled anesthetic dose per breath; (b) end-inspiratory anesthetic concentration; and (c) end-expiratory anesthetic concentration measured during targeted and continuous delivery. Data are shown for sevoflurane (left bars) and isoflurane (right bars). Data are averaged across animals, with error bars denoting SD. *Significantly greater compared to targeted sevoflurane or isoflurane delivery at both 10 and 20 min, P < 0.05.