© 2003 American Thoracic Society
Measurement of the co2 apneic thresholdTo the Editor:
In 1998, we described a method for measuring PCO2 apneic threshold (1); pressure support is increased in small steps, each lasting 3–5 minutes, until central apnea develops. End-tidal PCO2 at the penultimate pressure support level is apneic threshold. Because respiratory muscle pressure (Pmus) decreases progressively as pressure support increases, tidal volume and ventilation change little before apnea (provided patient-ventilator synchrony is maintained), minimizing the confounding neuromechanical inhibition. Since PCO2 decreases very slowly (2–5 mm Hg over 10–20 minutes), the reduction in end-tidal PCO2 (i.e.
Xie and colleagues used a similar (according to the text) approach, without attribution, to compare apneic threshold, (1) Without information about leak magnitude around the face mask (2) (e.g., volume drift) their ventilatory response data are suspect. (2) Trigger sensitivity was -2 cm H2O (3). Since some volume was delivered in untriggered breaths, Pmus required for triggering was greater than 2. Pmus in unassisted sleeping humans, on continuous positive airway pressure, is approximately 6 cm H2O (4). Thus, Pmus required for triggering was a large fraction of unassisted Pmus. This creates two problems: first, apnea may not develop; once Pmus decreases below trigger threshold, PCO2 no longer decreases (triggering stops). This happened frequently (2, 3). In response, they reported PCO2 threshold for ineffective efforts. This is physiologically meaningless; it reflects ventilator response, a nonphysiologic, unreliable variable. Second, when Pmus required for triggering is a high fraction of peak Pmus, triggering occurs late in inspiration. As peak Pmus decreases, the fraction increases. Triggering is further delayed until it is missed. Thus, more assist pushes inflation further into expiration. When ventilator cycle extends beyond neural inspiration, reduction in Pmus no longer influences tidal volume (5); tidal volume increases as assist increases (e.g., as demonstrated in [3]). With a progressively increasing tidal volume, delivered largely during expiration, neuromechanical inhibition cannot be discounted. (3) With this approach (1), end-tidal PCO2 should decrease very slowly. In Figure 1 (2), the entire reduction in end-tidal PCO2, from "no-assist" level to apneic level, occurred in four breaths! How can that happen? Is it possible that they applied large step increases in pressure support (as in [6]) to circumvent triggering problems? Regardless, how can apneic threshold be determined from a rapidly changing end-tidal PCO2? Their definition of apneic threshold was arbitrary, and differed in each of three recent studies (2, 3, 6). Even if one generously accepts their current (2) justification (it reflects peripheral chemoreceptor PCO2 at apnea [ignoring mixing effect]), what about central PCO2? Hypocapnia limited to peripheral chemoreceptors does not produce apnea (7). Central PCO2 must decrease. How can one infer change in central PCO2 from rapidly changing end-tidal PCO2? Could the results have been affected by differences between the two patient groups in the dynamic relation between end-tidal and central PCO2 (e.g., differences in thoracic blood volume, circulation time, central diffusion dynamics, etc.)?
University of Toronto Toronto, Ontario, Canada REFERENCES
From the Authors:We are pleased to respond to each of Dr. Younes' comments. We have referred to his work (1) in each of our previous three papers, which investigated the hypocapnia-induced apneic threshold (2–4).We used a full-face mask that was carefully affixed with actor's glue. The mechanical ventilator displayed the difference between inspiratory and expiratory volumes with any change indicating the presence of a leak that was quickly corrected. Thus, we are confident that the hypocapnic ventilatory response data reported are reliable and not compromised by mask leak. We found that a small triggering pressure was associated with spurious triggering of the ventilator. Thus, we chose a trigger level that minimized the number of hypopneas without spurious triggering of the ventilator. We chose to report the hypopneic threshold (in addition to the apneic threshold) because it does have physiologic meaning. The hypopneic threshold indicated a reduction in ventilatory drive below that needed to trigger the ventilator. Using published estimates of elastance (1), a reduction in inspiratory drive sufficient to cause a missed trigger in our system would be equivalent to a tidal volume of 100 ml, i.e., hypopnea. Younes speculates that we delivered high tidal volumes largely during neural expiration; therefore, neuromechanical inhibition would be important in causing apnea. Both points are incorrect. Based on data from indwelling diaphragm electromyogram electrodes in the sleeping dog (4), we determined that 90–100% of the tidal volume achieved with pressure support ventilation was delivered during neural inspiration. Secondly, our apneas definitely required hypocapnia in both dogs and humans, because when we added CO2 to the inspirate to maintain a normocapnic end-tidal PCO2 (PETCO2) during pressure support ventilation (4) or during assist control mechanical ventilation (5), no apneas occurred. Furthermore, our apneas, which occurred very quickly after a transient ventilatory overshoot (produced via pressure support ventilation), also required carotid chemoreceptors (6) (see below). Younes also speculates that PCO2AT could not be determined from a rapidly changing PETCO2 because "central PCO2 must fall" to cause apnea. Again the findings disagree with these assertions. Our most recent findings show that apnea occurs normally after a ventilatory overshoot within 10–12 seconds of reducing PETCO2 below the apneic threshold in intact sleeping humans (7) and dogs (6), whereas apnea did not occur until after 25 seconds in the carotid body denervated animal (6). So carotid chemoreceptors are obligatory for the common type of central sleep apnea that occurs in response to transient ventilatory overshoots. Experiments are underway to reconcile these carotid body denervation effects with those obtained via isolated carotid chemoreceptor hypocapnia (8). In summary, the methods and findings in our studies of apneic threshold lability are valid.
University of Wisconsin and the Middleton Memorial Veterans Hospital Madison, Wisconsin REFERENCES
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PCO2) reflects the reduction in PCO2 at all chemoreceptors. The ratio of baseline ventilation to