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Effects of Inhaled Anesthetics on Bronchomotor Tone

Appropriate anesthetic management of the patient with reactive airway disease has been extensively reviewed.[6] [7] [66] Volatile anesthetics may be an effective method of treating status asthmaticus when more conventional treatments have failed. Gold and Helrich[67] evaluated the effect of halothane in six intubated patients treated unsuccessfully for status asthmaticus for at least 72 hours with bronchodilators, steroids, and antibiotics. No significant change in airway resistance was recorded during or immediately after halothane exposure, but all patients improved within 3 days of treatment. The lack of a control group in this study confounded the interpretation of the results. Several subsequent studies have demonstrated that the use of inhaled

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Figure 6-4 Relaxation of 5-hydroxytryptamine-preconstricted rat bronchial segments with intact (A) and disrupted (B) epithelium to increasing concentrations of desflurane, sevoflurane, isoflurane, and halothane expressed as minimum alveolar anesthetic concentration (MAC) multiples. Desflurane was a more potent bronchodilator than sevoflurane (A), which was more potent than either halothane or isoflurane. Rubbing epithelium significantly blunted the bronchodilatory effects of all anesthetics (B). There were no differences between the agents. (Adapted from Park KW, Dai HB, Lowenstein E, et al: Epithelial dependence of the bronchodilatory effect of sevoflurane and desflurane in rat distal bronchi. Anesth Analg 86:646, 1998.)

anesthetics may be beneficial in patients with refractory status asthmaticus.[68] [69] [70] [71] [72] [73] [74] Halothane-induced increases in cardiac arrhythmias and depression of myocardial contractility suggest that other agents may be preferred in the treatment of status asthmaticus.[73] [75] However, 1% halothane administered to 12 patients in status asthmaticus was associated with a rapid improvement of bronchospasm, a reduced incidence of barotrauma, enhanced arterial blood gas tensions, and the absence of adverse hemodynamic effects including cardiac arrhythmias.[72]

Rooke and associates[76] compared the bronchodilating effects of halothane, isoflurane, sevoflurane, and thiopental or nitrous oxide in 66 healthy patients undergoing induction of anesthesia and tracheal intubation ( Fig. 6-5 ). In contrast to thiopental or nitrous oxide, all volatile


Figure 6-5 The percentage change in respiratory system resistance in patients after 5 and 10 minutes of maintenance anesthesia with 0.25 mg/kg/min thiopental plus 50% nitrous oxide; 1.1 minimum alveolar concentration (MAC) of sevoflurane, halothane, or isoflurane; or approximately 1 MAC of desflurane. All volatile anesthetics except desflurane decreased resistance. Sevoflurane decreased resistance more than isoflurane. (Adapted from Rooke GA, Choi J-H, Bishop MJ: The effect of isoflurane, halothane, sevoflurane, and thiopental/nitrous oxide on respiratory system resistance after tracheal intubation. Anesthesiology 86:1294, 1997 and from Goff MJ, Arain SR, Ficke DJ, et al: Absence of bronchodilation during desflurane anesthesia: A comparison to sevoflurane and thiopental. Anesthesiology 93:404, 2000.)

anesthetics significantly reduced respiratory system resistance. Equi-MAC sevoflurane and halothane decreased resistance to similar degrees, whereas isoflurane produced substantially less bronchodilation in vivo. Previously described animal studies demonstrating the equal potency of sevoflurane and isoflurane and the relatively greater potency of halothane for bronchodilation must be extrapolated with caution because Ascaris- or histamine-mediated experimental bronchospasm may not precisely mimic tracheal intubation-induced bronchospasm in humans. In contrast, Arakawa[75] showed that similar inspired concentrations of halothane, isoflurane, and sevoflurane produced nearly identical reductions in airway resistance in a patient with status asthmaticus.

The noble gas xenon has been used as an inhaled anesthetic for nearly 50 years, and advances in manufacturing technology and scavenging systems are making the use of xenon more economically feasible.[77] The effects of xenon on airway resistance differ markedly from those of volatile anesthetics because this gas has a higher density and viscosity than air.[78] [79] [80] In pentobarbital-anesthetized pigs, baseline airway resistance was significantly greater with 70% xenon-oxygen than 70% nitrous oxide-oxygen, although the measured peak and mean airway pressures were unaffected. In contrast, airway pressures and resistance were increased during xenon anesthesia and methacholine-induced bronchoconstriction.[79] The investigators argued that these effects were unlikely to be of significant clinical importance because the changes in airway pressure and resistance were only moderate. Pulmonary resistance during inhalation of 50% xenon

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was similar to that observed during 50% nitrous oxide or 70% nitrogen in methacholine-treated dogs.[81] A randomized, double-blind comparison of xenon and nitrous oxide showed that although both agents similarly increased expiratory lung resistance, fewer patients receiving xenon experienced decreases in oxygen saturation. [82] In contrast, 33% xenon has been demonstrated to transiently but significantly elevate peak airway pressures in long-term mechanically ventilated patients.[78] This increase in airway pressure was attenuated by a reduction in inspiratory flow rate. The higher density and viscosity of xenon increases the Reynolds number and probably causes the zone of transition from turbulent to laminar gas flow to move distally to smaller airways. However, an increase in flow resistance produced by mechanical loading during anesthesia does not significantly affect pulmonary gas exchange.[83] Other studies have shown that arterial oxygen and arterial carbon dioxide levels are not altered during xenon and nitrous oxide mixtures,[81] [84] but some investigators have nonetheless suggested caution when using xenon in patients with bronchospastic or obstructive pulmonary disease.

The effect of albuterol in the presence of halothane on airway reactivity was examined in dogs.[85] Halothane attenuated histamine-induced bronchoconstriction, and albuterol further dilated the airways, indicating an additive or synergistic effect. The dilatory effects of halothane did not adversely affect the ability of isoproterenol to dilate isolated, acetylcholine-preconstricted canine tracheal smooth muscle strips in vitro.[50] These findings support the use of β-adrenoceptor agonists for the treatment of bronchospasm in patients anesthetized with halothane. However, results may differ somewhat with other volatile anesthetics or β-agonists. For example, the β2 -adrenergic agonist fenoterol lowered respiratory system resistance after endotracheal intubation but did not further reduce resistance when administered in the presence of 1.3% isoflurane. [86] However, the technique used to determine respiratory system resistance may be partially responsible for these results, because this index incorporates alterations in lung and chest wall resistance as well as tissue viscosity.

The actions of inhaled anesthetics on bronchomotor tone depend on the agent eliciting contraction in vitro.[33] Relaxation of tracheal smooth muscle by halothane and isoflurane is greatest in the presence of the endogenous mediator serotonin (potentially representing anaphylactoid or immunologic reactions) compared with acetylcholine (representing the neurally derived mediator of reflex bronchospasm). In contrast to the relaxing effects of isoproterenol, the absolute amount of airway smooth muscle relaxation by halothane is independent of the extent of contraction. These findings suggest that inhaled anesthetics remain effective bronchodilators, even in the presence of severe bronchospasm that is refractory to β2 -adrenoceptor therapy.

Volatile anesthetic-induced decreases in bronchomotor tone and neurally mediated airway reflexes may be partially opposed by a simultaneous reduction in functional residual capacity (FRC) in the anesthetized patient. This increase in FRC increases airway resistance.[87] An increased risk for morbidity and mortality has been well established in patients with asthma during the perioperative period that may be partially attributed to these FRC-mediated increases in airway resistance. Exposure of airway smooth muscle to low temperatures may abolish the inhibitory effects of volatile anesthetics on carbachol-induced contraction. [88] These findings suggest that intraoperative hypothermia also may attenuate volatile anesthetic-induced bronchodilation. Future investigations in humans with newer inhaled anesthetics will benefit from advances in knowledge of mechanisms of inhaled anesthetic action on airway smooth muscle under normal and pathophysiologic conditions.

Bronchospasm may occur in respiratory diseases other than asthma. For example, healthy patients undergoing surgical stimulation of pulmonary parenchyma or airways are at risk of developing bronchospasm.[89] Clinically discernible bronchospasm is a common occurrence during stimulation of the trachea by an endotracheal tube in anesthetized patients. The choices of preoperative medication, induction agent, muscle relaxant, and the type of inhaled agent are all important factors in minimizing clinical symptoms in patients with known reactive airway disease.

Halothane may be a more potent bronchodilator than other inhaled anesthetics. The often-profound respiratory irritation produced in the upper airways (i.e., coughing, respiratory secretions, breath-holding, and laryngospasm, especially in the pediatric population) may outweigh the benefit of any direct bronchodilatory action of this agent. Differences in bronchodilating effects between inhaled anesthetics may exist, but of greater clinical importance is avoiding or minimizing airway irritation and maintaining adequate depth of anesthesia with the agent that is chosen.

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