“Dephlogisticated Air” Revisited

by these new techniques. To be sure, most of these publications represent very little careful scien¬ tific evaluation of this burgeoning technology. The report by de Campos et al in this issue of CHEST (see page 494) takes a careful look at one well-defined group of patients, namely, children and adolescents. Although they did not perform any cardio¬ vascular procedures using thoracoscopy, they did ex¬ amine all of their patients who received thoracoscopic This group of investigators challenged the procedures. old concept that children are not just small adults. Their investigation seems to bear this out. In fact, these investigators have discovered that there are significant differences based on age groups. They found that in patients under 2 years of age was most often used for pleural diag¬ thoracoscopy nostic and therapeutic reasons. Between the ages of 2 and 8 years of age, lung biopsy became an impor¬ tant procedure, while pleural procedures remained important also. However, after the age of 8 years, the indications for thoracoscopy were essentially the same as in the adult series. this is a simple analysis, it has shed a new Although on the light way thoracoscopy is applied in the There have been 25 previous pediatric population. in thoracos¬ the published papers these area of pediatric have ad¬ copy. Although publications may vanced certain forms of the technique, they have failed to shed as much insight as this short analysis. The authors deserve congratulations for their pow¬ ers of observation on their very significant series of cases. May other investigators be stimulated to re¬ view their own series of operations in such a fresh way. Joseph LoCicero III, MD, FCCP on

Boston

Associate Professor and Chief, General Thoracic vard Medical School.

"Dephlogisticated Air"

Surgery, Har¬

Revisited Oxygen Treatment for Central Sleep Apnea Syndrome of the history of respiratory physiology Students may recall reading about the discovery of oxygen by Joseph Priestley in 1774: by heating mercuric oxide, he obtained a gas that could increase the intensity of a candle's flame dramatically, but would not burn by itself. Conforming to the popular theo¬ ries of the day, he named this gas "dephlogisticated air," believing that combustion was the process by

which the mysterious substance "phlogiston" left a burning material. Although confused in theory, Priestley did hazard that "... the greater strength and vivacity of the flame of a candle in this pure air might be peculiarly salutary to the lungs in certain morbid cases."1 Modern medical practice has certainly proven the accuracy of Priestley's forecast, and in a recent issue of CHEST, Franklin and colleagues2 provide further evidence supporting the use of "dephlogisticated air" in yet another "morbid case": central sleep apnea (CSA) of the CheyneStokes variety. When considering treatment strategies for CSA, it is of paramount importance to recognize the heter¬ ogeneity of this condition. Bradley and coworkers3 introduced the most useful nosology when they distinguished CSA accompanying diurnal ventilatory failure from CSA associated with awake eucapnia or hypocapnia. Both groups of patients frequently com¬ and restless sleep. plain of daytime hypersomnolence However, patients with hypoventilation and CSA almost always present with a history of recurrent ventilatory failure, and often exhibit the sequelae of chronic hypoxia, including signs of cor pulmonale. Pathogenesis usually involves neurologic or neuro¬ muscular disease affecting either central ventilatory drive or respiratory muscle function, while treatment commonly centers around a ventilatory assistance device, such as nasal bilevel positive airway pressure. Oxygen treatment is often found to be unhelpful or even counterproductive, with reports of oxygen caus¬ ing worsening ventilatory failure4 appearing with .

.

regularity. eucapnia or hypocapnia is more fre¬ quently associated with snoring, nocturnal choking and/or breathlessness, and systemic hypertension, and only rarely with cor pulmonale.3 This type of CSA can be traced to an instability in central venti¬ latory control, and because this instability can take a variety of forms, eucapnic/hypocapnic CSA itself is somewhat heterogeneous. The ventilatory instability is often partly due to the fact that the transition from to light sleep is accompanied by drowsy wakefulness an increase in the Pco2 set point, but may also involve one or more other factors:5 hyperventilation; abnormal function of the central ventilatory control¬ ler (alinearity or excess gain); insufficient damping (eg, reduced lung stores of 02 or C02); instability induced by prolongation of the time taken for changes in controlled variables (eg, Pco2) to be communicated back to the central controller; or reflex inhibition of respiratory drive initiated by upper airway irritant receptors. These factors, alone or in combination with the sleep state-dependent changes in respiratory drive, produce the respiratory dysrhythmia. For instance, CSA at high altitude some

CSA with

CHEST / 111 / 2 / FEBRUARY, 1997

269

appears to result from hypoxic hyperventilation caus¬ ing arterial Pco2 to fall to a level just above the apneic threshold. With sleep onset, the apneic threshold rises to above arterial Pco2 and an apnea ensues. When Pco2 rises above the new threshold, ventilation resumes, the patient arouses, and the stage is set for another cycle of apnea. Certain func¬ neurologic disorders are thought to disruptorthealterna¬ the central tion of ventilatory controller, invoking a mecha¬ tively can causeto hyperventilation, that associated with CSA of high nism similar altitude. Congestive heart failure (CHF) can lengthen the time required to feed changes in Pco2 back to the brainstem ventilatory controller (pro¬ hyperventilation longed circulation time), or orproduce (either through hypoxemia stimulation of J-receptors) and thus CSA. In some patients, CSA may result from upper airway closure, stimulation of irritant receptors, and reflex inhibition of respiratory drive; this could account for the response of some patients with CSA to nasal continuous positive airway pressure (CPAP). CSA is also heterogeneous in terms of breathing pattern: the apneas may appear as abrupt cessations in ventilation or may assume the waning/waxing of Cheyne-Stokes ventilation, with each pat¬ rhythm more tern commonly associated withwithspecific etiolo¬ hemispheric gies. In particular, CSA associated stroke or with CHF presents more frequently with the Cheyne-Stokes appearance. Given this heterogeneity, it would not be surpris¬ ing if management might differ from one type of CSA to another. Consequently, any study of treat¬ ment in these disorders must exhibit a fair degree of precision in defining the type of CSA involved. When one applies this precept to the study by Franklin et al,2 it quickly becomes apparent that their results apply almost exclusively to patients with CSA of the Cheyne-Stokes variety, with underlying patients had etiologies of CHF or stroke: 189 out of 20had Cheyne-Stokes respiration; patients CHF, 3 were studied after a stroke, and 7 had CHF as well as a history of stroke. Only one patient had neither CHF nor stroke; he was receiving treatment with morphine, and exhibited a non-Cheyne-Stokes pat¬ tern of CSA. Their findings, nonetheless, are com¬ central apnea-hypopnea index fell pelling.33.5Median to 5.0 events/hour, and improvement from occurred in all sleep postures and stages. In addition, no differences in response rate were found when the CHF, stroke, or CHF combined with stroke groups were compared. Arousals were reduced as well, although the magnitude was small. The median arousal index fell from 17.3 to 15.5 per hour of

sleep.2

These data confirm and extend (to

270

patients

with

stroke) the observations of Hanly et al6 who studied

Cheyne-Stokes

nine patients with CHF and respira¬ tion during sleep. They found a substantial reduction in sleep-disordered breathing, and improvement in sleep quality, when oxygen was administered. In

Franklin's data,2 the effect predominated sleep. Interestingly, the data of both et al6 and Franklin et al2 are limited in yet Hanly another way: all but one patient (in the study by Franklin et al) were male, and future investigations should examine women in order to generalize the results to both sexes. How then does oxygen exert this salutary effect

contrast to

in non-REM

on

Cheyne-Stokes respiration during sleep? Hanly

al6 advanced a number of theories for the response in their patients with CHF: an increase in oxygen stores, resulting in a higher damping factor; elimination of hyperventilation due to hy¬ poxemia, thus reducing the likelihood that Pco2 would fall below the apneic threshold during sleep; or resolution of hypoxemia and its tendency to increase central controller gain. However, their study provides no data (such as Pco2 values on oxygen) that could support any of these hypothe¬ ses. Franklin et al2 did perform arterial blood gas determinations with and without oxygen on their awake subjects, and demonstrated a small, but with the ex¬ significant, increase inin Pco2 alongcombined with This, Po2. pected improvement data from studies of other therapeutic modalities in Cheyne-Stokes respiration, may provide part of the answer. For instance, Steens et al7 reported a reduction in Cheyne-Stokes respiration in CHF patients receiving 3% C02 during sleep. In addi¬ tion, there are several reports of improvement in respiration in CHF using nasal Cheyne-Stokes CPAP, and Naughton and coworkers8 have sug¬ gested that one explanation might relate to the expiratory load nasal CPAP can represent, with a consequent elevation in Pco2. Unfortunately, all three therapies also have in common an improve¬ ment in oxygenation, and therefore an unequivocal conclusion as to mechanism must await further et

investigation. The clinician, however, need not wait for the final word on mechanism before putting these findings to good use. The data of Hanly et al,6 and now of Franklin and colleagues,2 indicate that we should now consider prescribing Priestley's "dephlogisti¬ cated air" for another therapeutic indication:

Cheyne-Stokes respiration.

However,

to

prevent

confusion on the part of your respiratory therapists, I recommend simply ordering "oxygen."

Lee K. Broivn, MD, FCCP Phoenix, Arizona Editorials

Professor of Clinical Medicine, Department of Internal Medi¬ cine, University of Arizona College of Medicine Phoenix Pro¬ grams. requests: Dr. Lee Brown, Dept of Internal Medicine, 350 Reprint West Thomas Road, Phoenix, AZ 85013

References

Perkins JF Jr. Historical development of respiratory physiol¬ ogy. In: Fenn WO, Rahn H, eds. Handbook of physiology. Section 3: Respiration, Volume 1. Washington, DC: American

Physiological Society, 1964; 1-62 Franklin KA, Eriksson P, Sahlin C, et al. Reversal of central sleep apnea with oxygen. Chest 1997; 111:163-69 Bradley TD, McNicholas WT, Rutherford R, et al. Clinical and physiologic heterogeneity of the central sleep apnea syndrome. Am Rev Respir Dis 1986; 134:217-21

Edmonds LC. Severe hypercapnia after low-flow therapy in patients with neuromuscular disease and diaphragmatic dysfunction. Mayo Clin Proc 1995; 70:327-30 5 Khoo MCK, Kronauer RE, Strohl KP, et al. Factors inducing periodic breathing in humans: a general model. J Appl Physiol: Respirat Environ Exercise Physiol 1982; 53:644-59 6 Hanly PJ, Millar TW, Steljes DG, et al. The effect of oxygen on respiration and sleep in patients with congestive heart failure. Ann Intern Med 1989; 111:777-82 7 Steens RD, Millar TW, Xiaoling S, et al. Effect of inhaled 3% C02 on Cheyne-Stokes respiration in congestive heart failure. Sleep 1994^17:61-68 8 Naughton MT, Benard DC, Rutherford R, et al. Effect of continuous positive airway pressure on central sleep apnea

4

Gay PC, oxygen

and nocturnal Pco2 in heart failure. Am Med 1994; 150:1598-1604

J Respir Crit Care

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O F

Mechanical

PHYSICIAN

ventilation

The First Annual Symposium and Workshopfor Critical Care Providers June 26-28, 1997 San Diego, California

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CHEST / 111 / 2 / FEBRUARY, 1997

271