Is home continuous positive airway pressure a means of treatment for patients with nocturnal reflux resistant to treatment?
J.P. Shoenut, P. Kerr, M.H. Kryger (Winnipeg)
Gastroesophageal reflux (GER) is a common complaint; its sequela may include esophagitis, stricture, Barrett's epithelium and esophageal cancer. It has been reported that recumbent reflux is more deleterious than reflux that occurs while patients are upright. In this report we describe our experience using nasal continuous positive airway pressure to treat 3 different patient groups with pathological nocturnal reflux.
Nocturnal gastroesophageal reflux
GER is a common disorder that accounts for 75% of esophageal pathology [1, 2]. Up to 40% of Western adults experience regular reflux symptoms . In the United Kingdom, reflux accounts for 30% of all cases of dyspepsia . The technique which has become the gold standard for measuring acid reflux is 24-hour ambulatory esophageal pH monitoring. pH monitoring has been shown to be superior to radiographic examination, scintigraphy, endoscopy, and lower esophageal sphincter (LES) resting pressure in detection of reflux [4, 5]. This technology appears to have rendered the Bernstein test obsolete . Since the inception of the pH monitoring protocol by Johnson and DeMeester in 1974 , nocturnal reflux has been identified as a major factor in esophageal pathology. Nocturnal reflux has, since 1974, been implicated in the gamut of esophageal disease from esophagitis to Barrett's esophagus using pH testing as a standard [8-10]. The two mechanisms that have been identified as causing recumbent GER are an incompetent LES and transient LES relaxations (TLESRs). In early reports (before 24-hour pH testing), patients who were symptomatic for GER were found to have lower LES pressures than control subjects . Later, it was suggested that the intraabdominal position of the LES, and not the magnitude of the LES pressure that related to increased distal esophageal acid exposure [12-14]. Most recently, TLESR unrelated to swallowing, has been found to be responsible for the majority of reflux events. The Adelaide group and their associates in a recent elegant study have shown that in healthy subjects, TLESR was the mechanism of reflux in 82% of reflux episodes; that swallow related reflux events were responsible for 13% and lack of residual LES pressure for 1% of acid reflux events .
Treatment of patients with GER
It is generally agreed upon that there are three phases of treatment for patients with GER, and that the invasiveness increases with the severity of disease .
Patients are initially requested to avoid items in the diet that reduce the resting LES pressure, i.e. caffeine, peppermint, chocolate and fat . Patients are also requested to avoid alcohol and tobacco. Weight reduction and timing of meals can also be helpful in patients with minimal symptoms and disease. Raising the head of the bed 6 inches is a successful non-invasive technique to diminish nocturnal reflux. In one study, it was reported that combining raising the head of the bed and ranitidine therapy was more efficacious than either treatment alone . Antacids also give brief symptomatic relief in some patients.
In those patients with more severe disease or reflux complicated by other factors, 3 types of medications have been developed: H2-receptor antagonists, proton pump inhibitors and prokinetic agents. H2 blockers inhibit stimulation of the parietal cells by histamine; they do not alter LES resting pressure or esophageal acid clearance . Improvement in grading esophagitis in patients taking 1000-1600mg/day cimetidine compared to placebo has been reported . Ranitidine has been shown to reduce the numbers of reflux episodes and the severity of symptoms at dosages of 300-450 mg/day [20, 21]. The H2-antagonist famotidine used at 40 mg b.i.d. has been shown to heal esophagitis; 48% of patients with moderate to severe disease in 6 weeks . Comparative dosages for equivalent healing rates are cimetidine 400 mg b.i.d. and ranitidine 150 mg b.i.d.  and famotidine 40 mg and ranitidine 300 mg when taken in the evening following the last meal . The proton pump (H+/K+)-ATPase inhibitor omeprazole has gained wide acceptance treating acid related disease of the upper G.I. tract. Omeprazole has been shown to be superior to H2-receptor antagonists both in healing esophagitis and suppressing symptoms [24, 25]. In a long-term study, 20 mg daily omeprazole was found to be superior to 150 mg b.i.d. ranitidine, 70% of the patients taking omeprazole were in symptomatic and endoscopic remission after 1 year compared to 10% of the patients taking ranitidine . Prokinetic agents such as cisapride are used to improve the resting LES pressure and to increase gut motility . At dosages of 20 mg, cisapride provides maintenance treatment in GER patients healed by acid antisecretory drugs .
Various types of surgical procedures are available for those patients who prove to be refractory to medical treatment. Late outcomes have been reported to be satisfactory  and recently, laparoscopic approaches have been used. A recent report by the Adelaide group indicates that fundoplication both prevents complete LES relaxation and inhibits the triggering of TLESR . The treatment of patients with GER depends on many things; the availability of procedures, the willingness of patients to undergo invasive protocols and cost, not being the least. At our facility, in treating 162 consecutive patients with reflux disease (total time pH < 4.0 > 6.0%), 48% were treated with omeprazole, 17% by cisapride, 10% by H2-blockers and 12% of patients went to surgery .
The use of nasal CPAP in patients with recumbent reflux
We have recently documented a non-invasive application, used in the treatment of obstructive sleep apnea (OSA) patients, to treat patients with supine reflux. Nasal continuous positive airway pressure (CPAP) is achieved by means of a mechanical device which pressurizes the upper airway. These devices are commonly used in the home by patients with OSA. CPAP has been used in 3 different groups of patients in our laboratory to significantly reduce nocturnal reflux [32-34]. Nasal CPAP was first used to determine its effect on nocturnal reflux in 6 OSA patients . The OSA patients demonstrated nocturnal reflux (% time pH < 4.0) from 2.3 to 10.3% of their recumbent time, mean 6.3 ± 2.1 %. Nasal CPAP reduced acid exposure significantly to 0.1 ± 0.1% (p < 0.025). The number of reflux episodes dropped significantly , 10.1 ± 3.5 to 0.6 ± 0.3 (p < 0.03) and the number of the reflux episodes > 5 min fell significantly from 1.9 ± 0.6 to 0 (p < 0.02). The length of the longest reflux episodes was significantly reduced from 14.2 ± 4.5 min to 0.6 ± 0.4 min, p < 0.02. The esophageal function in the OSA patients was considered normal; the resting LES pressure ranged from 10 to 30 mmHg mean = 14.1 mmHg. Nasal CPAP was then used in a group of non-OSA patients with abnormal nocturnal reflux. Six patients were studied using the same two day protocol. The basal nocturnal reflux ranged 9.2 to 64.1% (27.7 ± 10.0%) this was reduced significantly on CPAP to 5.8 ± 2.6%, (p < 0.004). The lengths of the longest reflux events dropped significantly from 84.3 ± 32.6 min to 13.8 ± 6.9 min
(p < 0.01). All patients had resting LES pressure in excess of 10 mmHg. All patients were entered for study on the basis of an abnormal nocturnal reflux score, > 5% time pH < 4.0. The final group studied was comprised of 7 patients with known scleroderma esophagus and 6 treated achalasia patients . Individual patient response to CPAP is given, for both groups, in Figure 1. In the achalasia patients, the reflux on the first night ranged from 11.7 to 57.6% (38.5 ± 20.6). This was reduced significantly on night 2, range: 0 to 14.3% (2.9 ± 5.0%) p = 0.014. The numbers of nocturnal reflux episodes fell significantly on CPAP from 6.6 ± 6.5 to 1.8 ± 1.9 (p = 0.05) and the number of reflux episodes > 5 min were significantly reduced from 2.7 ± 2.1 to 0.5 ± 0.8 (p = 0.03). In the patients with sclerodema esophagus, a significant reduction in nocturnal reflux was not achieved. The % time the pH was < 4.0 was 33.9 ± 26.5% on night 1 and 23.2 ± 23.7 % on night 2 (p = 0.40). The number of reflux episodes on night 1 was 11.1 ± 12.6 and night 2, 4.4 ± 2.3 (p = 0.19). The numbers of reflux episodes > 5 min were 2.6 ± 2.0 on night 1 and 1.7 ± 1.7 on CPAP (p = 0.40). Representative 24-hour pH tracings on and off CPAP for achalasia and scleroderma patients are given in Figures 2 and 3 respectively. The resting LES in the achalasia patients range from 10 to 25 mmHg (mean = 17.1 ± 5.8 mmHg) and in the sclerodema patients 0 to 4 mmHg (mean = 2.4 ± 1.3 mmHg). there was no esophageal peristalsis or sleep apnea demonstrated in either group. The common feature that ties the reduction in nocturnal acid exposure to the patient groups is the resting pressure of the LES. In all groups save those with scleroderma esophagus, the resting LES exceeded 10 mmHg.
Figure 1. Comparison of reflux, night 1 vs night 2 (8 cm CPAP intervention) for patients with achalasia and scleroderma. (Reproduced with permission from .)
Figure 2. Effect of 8 cm pressure nasal CPAP in a treated (pneumatically dilated) patient with achalasia. A: basal; B: CPAP application during study period. (Reproduced with permission from .)
Figure 3. Effect of 8 cm pressure nasal CPAP in a patient with scleroderma esophagus. A: basal; B: CPAP application during study period. (Reproduced with permission from .)
The first two groups of patients (OSA and non-OSA) all complained of reflux symptoms and 4 of 5 patients in the non-OSA group had documented esophagitis. These patients responded well to CPAP intervention; indeed, 1 patient requested long-term use of CPAP. We expect that in symptomatic patients, compliance in the use of home CPAP would be similar to OSA patients (80%). The group of aperistaltic patients however, although more interesting, were more problematic. Only three of the scleroderma patients were symptomatic, and none of the achalasia patients . Significant GER is known to occur in both subsets of patients. Scleroderma esophagus patients have a common esophageal gastric cavity and are known to reflux freely both upright and supine [35, 36]. Gastroesophageal reflux has also been documented in both treated and untreated achalasia patients [37, 38]. The reflux in both groups has recently been shown to be highly reproducible  but in achalasia patients, it is usually asymptomatic (Figure 4).
Figure 4. 24-hour pH record in a 77 year old man treated for achalasia, 1 year previously, by limited, transthoracic myotomy. The patient was 12 months post-op and asymptomatic for reflux throughout the test period. The total % time pH < 4.0 = 30.7%, % time pH < 4.0 when recumbent = 43.1%.
M = meals, P = post prandial, S = supine.
The use of nasal CPAP to reduce nocturnal reflux needs to be documented in larger series of patients with nocturnal reflux and competent LES function. In those patients with esophagitis, it will be interesting to find out if healing occurs. The pressure used in the CPAP applications in our studies was 8 cm; abatement of GER in scleroderma esophagus patients could be attempted at greater pressures; however, since these patients may also have an obstructive lung disorder, such trials should be initiated in a laboratory where oxygenation can be monitored
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