Research Papers

Targeted Versus Continuous Delivery of Volatile Anesthetics During Cholinergic Bronchoconstriction

[+] Author and Article Information
Jarred R. Mondoñedo

Department of Biomedical Engineering,
School of Medicine,
Boston University,
Boston, MA 02215

John S. McNeil

Department of Anesthesiology,
University of Virginia,
Charlottesville, VA 22903

Jacob Herrmann

Department of Anesthesiology;
Department of Biomedical Engineering,
University of Iowa,
Iowa City, IA 52242

Brett A. Simon

Department of Anesthesiology
and Critical Care Medicine;
Department of Surgery,
Memorial Sloan Kettering Cancer Center,
New York, NY 10065

David W. Kaczka

Department of Anesthesiology, Biomedical
Engineering, and Radiology;
Department of Biomedical Engineering;
Department of Radiology,
University of Iowa Hospitals and Clinics,
Iowa City, IA 52242
e-mail: david-kaczka@uiowa.edu

1Corresponding author.

Manuscript received January 24, 2018; final manuscript received April 13, 2018; published online May 9, 2018. Assoc. Editor: Geoffrey Maksym.

ASME J of Medical Diagnostics 1(3), 031003 (May 09, 2018) (10 pages) Paper No: JESMDT-18-1001; doi: 10.1115/1.4040001 History: Received January 24, 2018; Revised April 13, 2018

Volatile anesthetics have been shown to reduce lung resistance through dilation of constricted airways. In this study, we hypothesized 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 (RL) and elastance (EL) 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 RL, EL, and anatomic dead space (VD) in canines (N = 5) during pharmacologically induced bronchoconstriction with intravenous methacholine, and following treatments with: (1) targeted anesthetic delivery to VD 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 RL or EL 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 RL and EL.

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Grahic Jump Location
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; Pao, airway pressure; V˙, airway flow. Check valves included to prevent back flow into the inspiratory limb as the gas travels to the scavenger system during expiration.

Grahic Jump Location
Fig. 2

Timeline of experimental protocol and drug administration. Baseline measurements of RL, EL, and VD 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.

Grahic Jump Location
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 (VD), and the effective alveolar volume (Valv), respectively.

Grahic Jump Location
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 (Vth) 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.

Grahic Jump Location
Fig. 5

Summary of: (a) and (b) lung resistance (RL); (c) and (d) lung elastance (EL); and (e) and (f) anatomic dead space (VD) 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.

Grahic Jump Location
Fig. 6

Examples of (a) and (b) lung resistance (RL); (c) and (d) lung elastance (EL); and (e) and (f) anatomic dead space (VD) 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.

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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.

Grahic Jump Location
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.



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