REBUTTAL FROM DR. YOUNES

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My concerns with evidence supporting neuromechanical inhibition (NMI) as the cause of mechanical ventilation (MV)-associated apnea were not moderated after reading Madison's article. I must, however, address two other issues:

First, partial inhibition during synchronized MV (e.g. [1]) received much emphasis (weren't we debating apnea?). There was an  50% reduction in inspiratory output during MV (1). Given that reducing PCO₂  2 mm Hg abolishes inspiratory output during sleep, this inhibition is equivalent to reducing PCO₂  1 mm Hg. Most inhibitory artifacts listed in the Con article apply also to synchronized MV, albeit to a lesser extent. Partial inhibition could well be from the same artifacts. Additional inhibition results from conventional NMI that operates on a breath-by-breath basis; an increase in flow/volume, in phase with inspiration, reduces inspiratory time (TI) and, hence, peak activity (2, 3).

Second, several publications originating outside Madison were cited to support Madison's version of NMI. I have two comments here. First, the same concerns regarding Madison's data apply to the external data. Second, Madison's use of this external evidence exemplifies beautifully how two allegedly seasoned scientists can interpret the same data in diametrically opposite ways. Two examples follow: (a) Morrell's results (4) are cited as supporting NMI; diaphragm EMG decreased in sleeping subjects placed on PSV despite no "significant" reduction in PET_CO2. These results, clearly, cannot support NMI as neither VT nor RR increased. PET_CO2 decreased in all subjects, but the average change (2 mm Hg) just missed significance (p = 0.06) because of small n. Rather than supporting NMI, this study reflects exquisite sensitivity to CO₂. (b) Madison cites Lawson's study (5) as demonstrating delayed inhibitory effects after stimulating pulmonary afferents in the vagus. However, important poststimulus inhibition occurred only after laryngeal, but not vagal, simulation.

Demonstration of neuromechanical reflexes with slow dynamics is extremely difficult in humans as one must ensure that other sources of drive remain absolutely constant over a long period or, if changes must occur, that they are identical in the "control" and experimental periods. Comparing respiratory output with and without MV during total cardiopulmonary bypass, or during rebreathing, exemplifies what is required. Only one study met these criteria (6) and, here, no NMI was found.

Acknowledgments: Supported by NHLBI and the VA Merit Review.

Supported by the Medical research Council of Canada.

	References

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1. Wilson CR, Satoh M, Skatrud JB, Dempsey JA. Non-chemical inhibition of respiratory motor output during mechanical ventilation in sleeping humans. J Physiol 1999; 518: 605-618 [Abstract/Free Full Text].

2. Clark FJ, von Euler C. On the regulation of depth and rate of breathing. J Physiol 1972; 222: 267-295 [Abstract/Free Full Text].

3. Fernandez R, Mendez M, Younes M. Effect of ventilator flow rate on respiratory timing in normal humans. Am J Respir Crit Care Med 1999; 159: 710-719 [Abstract/Free Full Text].

4. Morrell MJ, Shea SA, Adams IL, Guz A. Effect of inspiratory pressure support upon breathing in humans during wakefulness and sleep. Respir Physiol 1993; 93: 57-70 [Medline].

5. Lawson EE. Recovery from central apnea: effect of stimulus duration and end-tidal PCO2 partial pressure. J Appl Physiol 1982; 53: 105-109 [Abstract/Free Full Text].

6. Georgopoulos D, Mitrouska I, Webster K, Bshouty Z, Younes M. Effects of inspiratory muscle unloading on the response of respiratory motor output to CO2. Am J Respir Crit Care Med 1997; 155: 2000-2009 [Abstract].