What is the effect of continuous positive airway pressure (CPAP) in limiting symptoms of nocturnal reflux?
J.P. Shoenut, P. Kerr, M.H. Kryger (Winnipeg)
This paper details collaboration between a gastrointestinal and a sleep laboratory to use a form of treatment for obstructive sleep apnea, nasal continuous positive airway pressure (CPAP), and a technology for measuring gastroesophageal reflux, 24-hour ambulatory esophageal pH, to determine the effect of raising intrathoracic pressure on nocturnal reflux.
Nasal continuous positive airway pressure
In 1981, Sullivan et al.  described the first use of nasal CPAP to treat patients with obstructive sleep apnea (OSA). Nasal CPAP is delivered by mechanical means using a portable device that pressurizes the upper airway (Figure 1). Nasal CPAP has become the treatment of choice in OSA patient; until 1981, tracheostomy was most widely used .
Figure 1. Typical, portable CPAP machine.
When sufficient airway pressure is used, patient apnea is eliminated  and cognitive function is improved . The compliance in the use of nasal CPAP in OSA patients has been reported to range from 64% to 91% [4-7]. Major complications are very rare using this treatment, pneumocephalus , massive epistaxis  and bacterial meningitis  have been described. Patients are more likely to experience upper airway dryness, congestion or local skin irritation .
24-hour ambulatory esophageal pH monitoring
In 1974, Johnson and DeMeester published the use of indwelling pH electrodes in the continuous documentation of distal esophageal pH levels . By 1980, digital recording devices were commercially available that were portable and capable of recording 24-hour of pH data. The technique of measuring gastroesophageal reflux (GER) as pH changes in the esophagus, has evolved somewhat over the intervening 15 years. The pH electrodes that are now available have probably changed the most. The two most widely used electrodes being the antimony electrode and the bipolar glass electrode; the antimony electrode having a significant cost advantage over the glass. The technique involves placing the sensor-end of the pH electrode 5 cm above the gastroesophageal junction. At our facility, fluoroscopy is then employed to document catheter position and to assure that the electrode has not doubled over upon itself .
Data are recorded over the subsequent 24-hours and downloaded onto a computer for analysis. The elements of the reflux data that are widely studied are: % total time pH < 4.0, % time pH < 4.0 (upright), % time pH < 4.0 (supine), numbers of reflux episodes and numbers of reflux events that are < 5.0 minutes.
The evaluation of the early results of 24-hour pH monitoring indicated that recumbent GER in control subjects was much less than upright reflux, but in symptomatic patients supine acid exposure was associated with a higher incidence of esophagitis than upright reflux . Delayed or impaired clearance was suggested as the mechanism. In a more recent study, Gotleg et al.  demonstrated again that supine reflux was rare in control subjects, 0.6% time < pH 4.0. In that same study, in patients who were symptomatic, the % time pH < 4.0 (supine) was 15.8%.
GER is a common multifactorial disease, complicated by the host of agents that may be responsible for esophageal damage; gastric acid, pepsin, trypsin and bile acids at various pH levels have all been implicated. Treatment for esophageal damage patients is complicated by alkaline refluxate. Recent reports have indicated that mixed refluxates of gastric acid and duodenal contents are more deleterious to esophageal mucosa than gastric acid alone [16, 17]. This mitigates somewhat against the use of a single pharmacologic agent such as omeprazole. Omeprazole has been found to be more efficacious than H2 - antagonists in healing esophagitis [18, 19]. In our laboratory , in a series of 162 patients with reflux (> 6% total time pH < 4.0), 48% were treated with omeprazole alone or in combination with a prokinetic agent, compared with 10% who were treated with an H2-antagonist, with or without a prokinetic agent . Surgery can be an attractive alternative for patients with refractory reflux. Patients with incompetent sphincters or those who do not respond to medical therapy are certainly candidates. Surgery can restore some patients to a normal lifestyle with regard to medication, posture and meals. Some authors have suggested that patients facing lifelong medication or lifestyle restrictions should undergo surgery and beyond this, that medical therapy should be directed at acute symptomatic episodes .
CPAP and nocturnal reflux
Difficulties in treating patients with refractory recumbent reflux, lead us to consider nasal CPAP; anecdotal reports have suggested CPAP reduced GER in OSA patients [22, 23]. However, no studies have been reported documenting the types of patients treated, esophageal function in these patients, the extent of reflux or the mechanism exerted by CPAP which may attenuate acid exposure.
We began by identifying 6 OSA patients who complained of heartburn or regurgitation. These 6 patients underwent 2 consecutive 24-hour periods of study. This consisted of an initial esophageal motility examination, followed by intubation with a pH catheter. The daytime portion of study was conducted on an outpatient basis with patients logging meal-times and the onset of any symptoms. The night-time portion was conducted in the sleep laboratory where polysomnography was carried out on both nights with nasal CPAP applied (8 cm pressure) on the second study night. Complete results of that study have been reported elsewhere . We found that the significant factors from the sleep studies that related to reflux were: arousal (p < 0.028), movement (p < 0.028) and swallowing (p < 0.043) (Figure 2). The mean hourly reflux patterns were then compared (Figures 3 and 4). No significant group differences in daytime reflux were found, however nocturnal reflux was reduced significantly, % time pH < 4.0 (supine), 6.3 ± 2.1% day 1 vs. 0.1 ± 0.1% day
Figure 2. Factors related to nocturnal reflux. The odds risk ratio was calculated to describe the probability of association between abnormal sleep events and reflux. The control odds ratio is 1. Error bars represent 95% confidence intervals. P-values were derived by comparing pre-reflux frequency of factors with frequency during control period. (Reproduced from  with permission.)
Figure 3. Mean hourly reflux over first (control) day. The hourly percent time pH < 4 for all six patients was averaged. No data were collected between 6 a.m. and 8 a.m. Significant daytime and nocturnal reflux occurred. (Reproduced from  with permission.)
Figure 4. Mean hourly reflux over second (nocturnal CPAP) day. No data were collected between 6 a.m. and 8 a.m. Daytime reflux was comparable to that on day 1. Nocturnal reflux was significantly reduced by nasal CPAP. (Reproduced from  with permission.)
2 (p < 0.025). CPAP was also found to significantly reduce the numbers of reflux episodes (p < 0.03) and the lengths of the longest reflux episodes (p < 0.02) (Figures 5 and 6).
These results lead us to examine the effect of nasal CPAP in non-OSA patients with nocturnal reflux . The same 48-hour protocol was used in 6 patients, having normal esophageal motility, no sleep apnea, but documented nocturnal reflux > 5% of recumbent time. We found that CPAP significantly reduced the % of recumbent time below pH 4.0 (27.7 ± 10.0% vs. 5.8 ± 2.6%) (p < 0.004) (Figure 7). The length of the longest reflux episodes were also reduced significantly, 84.3 ± 32.6 min vs 13.8 ± 6.9 min (p < 0.01) (Figure 8). The results from these two investigations lead us to examine the effect of nasal CPAP on the esophageal function in 6 normal volunteers, during an esophageal motility study . These control subjects underwent 2 complete esophageal motility studies, the second of which included the application of 8 cm nasal CPAP. The elements of the motility studies we examined included wave duration, amplitude and velocity, and LES and mid-esophageal resting pressures. The CPAP was not found to have a significant impact upon wave characteristics (Figure 9), however resting LES tone and intra-esophageal resting pressure were both significantly increased, p < 0.02 and p < 0.01, respectively (Figure 10).
Figure 5. Effect of nasal CPAP on nocturnal reflux frequency. The number of reflux episodes remained elevated in the patient with OSAS not adequately treated by nasal CPAP (asterisk) but was significantly reduced in the remaining five subjects. (Reproduced from  with permission.)
Figure 6. Effect of nasal CPAP on the length of the longest nocturnal reflux episode. Longest reflux duration remained abnormal in the patient with OSAS not adequately treated by nasal CPAP (asterisk) but was significantly reduced in the remaining five subjects. Normal value was obtained from studies done by Johnson and DeMeester . (Reproduced from  with permission.)
Figure 7. Effect of continuous positive airway pressure (CPAP) on esophageal pH. The CPAP significantly reduced the percentage of time nocturnal esophageal pH < 4, GER, gastroesophageal reflux. (Reproduced with permission from .)
Figure 8. Effect of continuous positive airway pressure (CPAP) on reflux duration. The length of the longest nocturnal reflux episode was significantly reduced by CPAP. (Reproduced with permission from .)
These preliminary results show that nasal CPAP, applied at the pressures we used, was able to significantly reduce nocturnal reflux in both OSA and non-OSA patients. The effect or mechanism of action of CPAP appears to be to increase sphincter tone and mid-intraesophageal resting pressure.
We believe that nasal CPAP may have a place in the treatment of patients with intractable nocturnal reflux. The mechanism of action of CPAP on esophageal function needs further elucidation. A trial of different CPAP pressures certainly appears warranted.
Figure 9. Effect of continuous positive airway pressure (CPAP) on esophageal peristalsis in six normal adults. The CPAP did not alter wave amplitude, duration, or velocity. NS, not significant. (Reproduced with permission from .)
Figure 10. Effect of continuous positive airway pressure (CPAP) on esophageal resting pressures in six normal adults. The antireflux activity of nasal CPAP is likely due to its ability to elevate lower esophageal sphincter and esophageal body pressures. (Reproduced with permission from .)
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