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Original Research: Sleep Disorders |

Does Autotitrating Positive Airway Pressure Therapy Improve Postoperative Outcome in Patients at Risk for Obstructive Sleep Apnea Syndrome?Does APAP Improve Postoperative Outcome?: A Randomized Controlled Clinical Trial FREE TO VIEW

Susan M. O’Gorman, MBBS; Peter C. Gay, MD, FCCP; Timothy I. Morgenthaler, MD, FCCP
Author and Funding Information

From the Internal Medicine Residency Program (Dr O’Gorman) and Division of Pulmonary and Critical Care Medicine (Drs Gay and Morgenthaler), Mayo Clinic, Rochester, MN.

Correspondence to: Timothy I. Morgenthaler, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: morgenthaler.timothy@mayo.edu


For editorial comment see page 5

Funding/Support: This work was supported by an unrestricted grant from the ResMed Research Foundation and by the Mayo Clinic Foundation.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(1):72-78. doi:10.1378/chest.12-0989
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Background:  Obstructive sleep apnea has been associated with postoperative complications. We hypothesized that postoperative autotitrating positive airway pressure (APAP) applied to patients at high risk for obstructive sleep apnea would shorten hospital stay and reduce postoperative complications.

Methods:  Included were patients aged 18 to 100 years scheduled for elective total knee or hip arthroplasty who were able to give informed consent. Patients without contraindication to positive airway pressure therapy were divided into a high- or low-risk group on the basis of the Flemons sleep apnea clinical score. Low-risk patients received standard care. High-risk patients were randomized to receive standard care or standard care plus postoperative APAP. All patients were administered a predismissal cardiorespiratory sleep study. The primary end point was length of stay, and secondary end points were a range of postoperative complications.

Results:  One hundred thirty-eight patients were enrolled in the study (52 in the low-risk group, 86 in the high-risk group). Within the high-risk group, 43 were randomized to standard care and 43 to standard care plus postoperative APAP. There were no significant differences in the length of stay (P = .65) or any of the secondary end points between the randomized groups. On subgroup analysis of patients with an apnea-hypopnea index of ≥ 15, patients randomized to APAP had a longer postoperative stay (median, 5 vs 4 days; P = .02).

Conclusions:  The role for empirical postoperative APAP requires further study, but the findings did not show benefit for APAP applied postoperatively to positive airway pressure-naive patients at high risk for sleep apnea.

Figures in this Article

Obstructive sleep apnea (OSA) has an estimated prevalence of 7% to 22% in adult surgical populations1,2 and has been associated with increased rates of postoperative complications.3,4 The American Society of Anesthesiologists recommends that patients at increased risk for OSA be identified preoperatively and have a perioperative management plan in place.5 There is a paucity of evidence to guide the physician’s decision on whether to implement positive airway pressure (PAP) in the postoperative setting in patients at high risk for OSA who did not use CPAP preoperatively. A retrospective case-control study in surgical patients with OSA by Gupta et al3 indicated that preoperative use of home CPAP therapy was associated with a reduced risk of serious complications, a nonsignificant trend toward reduction of any complication, and a shorter hospital stay. However, to our knowledge, the effect of postoperative PAP in patients with suspected OSA has not been prospectively evaluated. We hypothesized that postoperative autotitrating positive airway pressure (APAP) applied to patients identified by a preoperative screening tool as at high risk for OSA would shorten hospital stay and reduce postoperative complications.

Patient Selection

From 2002 to 2005, patients were solicited for participation from an orthopedic clinic or preoperative evaluation center. All participants provided informed consent, and the study was approved by the Mayo Clinic Institutional Review Board (IRB#942-01). Included were patients aged 18 to 100 years scheduled for elective total hip arthroplasty or total knee arthroplasty. Patients with known OSA, prior CPAP therapy, prior recommendation for CPAP, chronic respiratory insufficiency, claustrophobia, or orofacial abnormality or tracheostomy precluding nasal CPAP application were excluded from enrollment. For patient safety, those identified as both high risk for OSA and with > 10% risk for postoperative cardiac complications as estimated by American College of Physicians criteria6 were advised to undergo overnight oximetry. If oximetry was abnormal, a preoperative sleep center evaluation was recommended, and the patients were excluded from the study. Patients were enrolled if their overnight oximetry was normal or if overnight oximetry or evaluations were declined.

Trial Design

Patients were divided into high- or low-risk groups for sleep apnea on the basis of the previously validated Flemons sleep apnea clinical score (SACS).7 A SACS < 15 was chosen to indicate low risk, and this group received standard postoperative care. Patients with a SACS ≥ 15 were classified as high risk and randomized to either standard care or standard care plus postoperative APAP. Patients receiving standard care did not receive special monitoring beyond that which had been standard at our institution. Those randomized to APAP received APAP education, a videotape, verbal instruction, mask fitting, and 15 to 30 min breathing on PAP preoperatively. All patients underwent a preoperative cognitive evaluation using the Mini-Mental State Examination and the Memorial Delirium Assessment scale.5,8

A standardized anesthetic approach was taken for all patients. Patients randomized to receive APAP were provided with APAP postoperatively (AutosetT or Spirit T; ResMed), with the minimum pressure set to 5 cm H2O and the maximum pressure set to 15 cm H2O. Use began in the recovery room or as soon as possible and was administered at night (10:00 pm-6:00 am) and whenever patients anticipated sleeping. In all other respects, patients received standard care, including initiation of oxygen and all tests or therapies believed to be clinically indicated by the surgical team.

Continuous pulse oximetry was recorded in all patients for 24 h postoperatively. The surgical team was blinded to protocol overnight oximetry results, with alarms and displays rendered inoperable. Clinically indicated oximetry ordered by the surgical team was not restricted.

The orthopedic team decided the timing of hospital dismissal. On the night prior to dismissal, all patients were administered a predismissal cardiorespiratory sleep study (Embletta; Embla Systems), which recorded airflow through a pressure transducer, thoracoabdominal respiratory movement by impedance plethysmography, oxygen saturation, pulse rate, position, and motion. This was performed while off APAP in all patients. Apneas were defined as cessation of airflow for at least 10 s, and hypopneas were defined as declines in airflow of at least 30% from baseline accompanied by a fall in oxygen saturation by ≥ 4%. Apneas that occurred in the absence of thoracoabdominal movement were considered central apneas, whereas those occurring with thoracoabdominal movement were considered obstructive. The apnea-hypopnea index (AHI) in this study reflects the number of apneas plus hypopneas divided by hours of recording while not positioned upright or in excessive motion as detected by the device. When the cardiorespiratory sleep study found an AHI ≥ 5, both the patient and his or her referring physician were advised and encouraged to seek sleep center evaluations. Predismissal patients repeated the cognitive evaluations and completed a questionnaire regarding APAP tolerability.

Specific Aims

The aim was to evaluate the effect of treating orthopedic surgical patients identified as high risk for OSA with postoperative APAP on postoperative outcome. We hypothesized that APAP therapy would decrease postoperative complications and shorten hospital stays. The primary end point was postoperative days, and secondary end points were unplanned ICU transfer, adjustment of oxygen therapy in response to arterial oxygen saturation < 90 or dyspnea, acute arrhythmia, a myocardial ischemic event, delirium, and a new infiltrate or atelectasis. We recorded postoperative narcotic use in all patients.

Statistical Analysis

We evaluated the effect of APAP therapy on number of postoperative days using an intention-to-treat analysis. Secondary end points were analyzed individually and as a global outcome of any complication, which was defined as having any vs none of the secondary end points. The mean change in cognitive test scores (postoperative − baseline) was compared between the two groups. We repeated the analyses described previously as restricted to patients with an AHI ≥ 15 on the predismissal sleep study. The Wilcoxon rank sum test was used for comparisons of continuous data, and Fisher exact test was used for comparisons of categorical data. Statistical analyses were performed using JMP, version 9 (SAS Institute Inc) software. Data are presented as median (interquartile range [IQR]) unless otherwise indicated, and P < .05 was considered significant.

Statistical Power Analysis

To detect a 1-day difference in hospital stay with a power of 0.8 and an α = .05, we calculated that we would need 208 patients assigned to the high-risk group. Cardiopulmonary sleep study testing of the low-risk group (predicted AHI < 15) was required to determine the sensitivity and specificity of the clinical prediction rule, and we calculated a requirement for 52 patients for the low-risk group.

We screened 2,375 patients, with subsequent enrollment of 138 patients. On the basis of the Flemons SACS, 52 and 86 patients were found to be low and high risk, respectively. Within the high-risk group, 43 were randomized to standard postoperative care and 43 to standard postoperative care plus postoperative APAP (Fig 1).

Figure Jump LinkFigure 1. Consort diagram. APAP = autotitrating positive airway pressure.Grahic Jump Location

Demographic data are displayed in Table 1. The patients tended to be obese (mean BMI, 33.9 kg/m2), elderly (median age, 65.5 y), and men (68.8%). The high-risk group had a greater proportion of male patients and a higher BMI (P < .0001 for both comparisons). It also had a higher prevalence of comorbidities. After randomization within the high-risk group, male patients were more prevalent in the standard care group (P = .03), but other characteristics were similar (Table 2).

Table Graphic Jump Location
Table 1 —Patient Demographics

Data are presented as No. (%), median (interquartile range), or mean ± SD. MDA = Memorial Delirium Assessment Scale; MMSE = Mini-Mental State Examination.

a 

Analyzed by Wilcoxon rank sum test. All others analyzed by Fisher exact test.

Table Graphic Jump Location
Table 2 —High-Risk Group Demographics

Data are presented as No. (%), median (interquartile range), or mean ± SD. APAP = autotitrating positive airway pressure.

a 

Analyzed by Wilcoxon rank sum test. All others analyzed by Fisher exact test.

The median usage of APAP on the first night was 373 min (IQR, 81.5-562.5 min). The median postoperative daily usage was 184.5 min (IQR, 64.3-451 min). Twenty-seven patients (63%) used APAP 100% of their postoperative nights, with a further six (14%) using it for two-thirds of their postoperative nights. The median pressure was 5.0 cm H2O, and the 95th percentile pressure was 9.2 cm H2O, with a median leak of 0.1 L/s (Table 3). There was no significant difference in the primary end point, length of stay (LOS) (P = .65), or secondary end points between the randomized groups (Table 3).

Table Graphic Jump Location
Table 3 —APAP vs No APAP End Points in High-Risk Group

Data are presented No. (%), median (interquartile range), or mean ± SD. AHI = apnea-hypopnea index; O2 = oxygen. See Table 1 and 2 legends for expansion of other abbreviations.

a 

Analyzed by Wilcoxon rank sum test. All others analyzed by Fisher exact test.

In the 38 patients who used APAP, 14 had effective control of sleep-disordered breathing, which was defined as an AHI < 10 recorded while receiving APAP (on the basis of the device’s downloaded estimate of AHI). Comparisons of end points between the high-risk patients who had effective APAP therapy and the high-risk patients who had ineffective APAP therapy showed no significant difference in LOS (P = .75) or in any of the secondary end points. Additionally, when this comparison is narrowed to patients with an AHI ≥ 15 measured by portable monitor while off APAP on the night prior to dismissal, effective treatment with APAP did not influence LOS (P = .69) or any of the secondary end points. No patient in the study required emergent intubation.

In patients with an AHI ≥ 15 by portable sleep test, those randomized to APAP had a statistically significant longer postoperative stay (5 days vs 4 days, P = .02), with no significant difference observed in the secondary end points (e-Table 1). Within the group randomized to postoperative APAP, the LOS was also analyzed on the basis of the length of usage of APAP per night. Use for ≥ 2 h/night was associated with a prolonged LOS (5 days vs 4 days, P = .02) (see e-Table 1). Similarly, those who used APAP ≥ 4 h/night had a significantly longer LOS (5 days vs 4 days, P = .04). Secondary end points were not significantly affected by length of usage of APAP per night (e-Table 2).

In the first 24 h postoperatively, all patients underwent overnight oximetry. The high-risk group randomized to standard care plus APAP spent more time with oxygen saturations < 90% than the high-risk group randomized to standard care only (P = .009) (Table 4). Mean and minimum oxygen saturation and oxygen desaturation index (number of ≥ 4% desaturations per hour of recording) did not significantly differ across groups in this immediate postoperative period.

Table Graphic Jump Location
Table 4 —Oximetry and Sleep Study

Data are presented as median (interquartile range). All P-values analyzed by Wilcoxon rank sum test. See Table 1-3 legends for expansion of abbreviations.

On the basis of the predismissal cardiorespiratory sleep study performed on the night prior to dismissal, the median AHI of the high-risk group was higher than that of the low-risk group (24.2 vs 12.7, P ≤ .001), with no significant difference between the high-risk groups. The findings indicated a prevalence of 57% for an AHI ≥ 15 in this population.

We gathered APAP tolerability data in 36 of the 38 patients who used APAP. Thirteen (36%) reported it to be very uncomfortable or worse, and six of these 13 patients (46%) reported that it was intolerable. The ability of the Flemons SACS we used to identify patients who had significant sleep-disordered breathing in the postoperative period is detailed in e-Appendix 1. The confusion matrix for the Flemons SACS in our population is shown in e-Table 3. Also in the supplement are comparisons between the low-risk group and the two high-risk cohorts (e-Table 4).

In this prospective study, we used the Flemons SACS to randomize patients at high risk for OSA to standard care or to standard care plus APAP therapy and hypothesized that APAP would improve postoperative outcomes. On the basis of an intention-to-treat analysis, the results failed to show any reduction in the primary end point of LOS. Similarly, no difference was seen in the rate of postoperative complications.

There are several possible reasons why APAP may not have improved postoperative outcomes. The overall complication rate was low, with 16% of patients having one or more complications, and there may have been a floor effect. The median age of 65 years coupled with the elective nature of the surgery may explain this finding. In a previous case-control study of postoperative complications in a similar population at our center,3 39% of patients in the group with OSA and 18% in the control group (patients without OSA) had a postoperative complication. In the current study, the exclusion of patients with known OSA may have selected those with a lower risk of postoperative complications. The standardized anesthetic protocol may also have resulted in some reduction.

An additional consideration is that compliance with APAP was not complete. Of the 43 patients randomized to receive APAP, 38 had the therapy successfully implemented (Fig 1), and the median usage was 184.5 min per night. The estimated AHI during APAP was 13.5 compared with 22.2 during the predismissal sleep study, suggesting that the APAP therapy may not have been effective. The APAP device used in this study was not equipped with forced oscillation technique; therefore, we are unable to differentiate central from obstructive events during APAP usage. This particular device does not increase pressure in response to apneas (but does in response to hypopneas or flow limitation) when the pressure is > 10 cm H2O. Prior work showed that many apneas in the immediate postoperative period, particularly while receiving opioid analgesia, may be central, and speculatively, the high residual AHI during APAP may reflect the device’s lack of response to central apneas. Although within the group randomized to APAP effective therapy (defined as an estimated AHI < 10 during APAP) did not result in improvements in LOS or complications, this subgroup was small, and conclusions must be tentative.

The results may reflect a type II error. Eighty-six patients were randomized despite the intention to randomize 208. We believe that slow recruitment reflected, in part, increased physician and patient awareness of postoperative complications associated with OSA and an unwillingness for patients identified at high risk for OSA to be randomized to standard care (a loss of equipoise over the course of the study). Notably, the observed SD and LOS differed significantly from that used in the initial power calculation, and we determined in retrospect that a sample of 45 in both the high-risk standard care group and the high-risk standard care plus APAP group would have had 80% power to detect a difference of 1 day in LOS by group t test, with a two-sided P < .05.

An alternative explanation to a type II error might be that APAP not only is ineffective but also may actually inhibit recovery. In this study, patients who had a measured AHI ≥ 15 (as opposed to those at high risk for OSA) and were randomized to standard care plus APAP had a median LOS of 5 days vs 4 days in the standard care-only group (P = .02) (e-Table 1), and more APAP use was associated with an increased LOS (e-Table 2). Because the salutary effects of APAP on sleep-disordered breathing are well established, perhaps APAP exerts a negative effect on other aspects of postoperative recovery. Aerophagia from APAP may slow bowel recovery from anesthesia, or APAP use may reduce mobility. Additionally, in patients unaccustomed to APAP, sleep disruption and fragmentation may have negatively affected their postoperative recovery. We did not collect data on these items, so we urge further study to discern unanticipated effects of APAP on postoperative recovery.

Of concern, the high-risk group randomized to standard care plus APAP spent more time with an oxygen saturation of < 90% than the high-risk group randomized to standard care only. None of the patients had baseline long-term oxygen requirements. As standard practice at our institution, patients are administered oxygen at a rate of 2 L/min by nasal cannula for their first postoperative night, and this practice was not altered in the study protocol. On review, the rate of oxygen flow was not increased upon connection to APAP. A higher flow rate of oxygen is required when diluted by a CPAP flow to provide the same fractional oxygen concentration.9,10 The nursing staff on the ward may not have been sufficiently familiar with the APAP device to administer appropriate supplemental oxygen.

All the study patients were APAP naive (see exclusion criteria), and the findings may indicate that in such patients, the postoperative setting is not the ideal time to introduce PAP therapy. We also found several system-based obstacles to adherence. The nursing staff was, at times, ill-acquainted to troubleshoot APAP compliance problems; rooms had insufficient space for equipment to allow for unobstructed bathroom trips and so forth. From the tolerability data, we know that the patients were frequently uncomfortable with APAP. Previous findings by Gupta et al3 showed improved outcomes with preoperative use of home CPAP despite poor postoperative CPAP compliance, suggesting a protective carryover effect of therapy. Whatever the mechanism, perhaps the most important time to intervene with CPAP is preoperatively.

The role for postoperative APAP requires further study. We believe that APAP is not ideal for use in unmonitored CPAP-naive patients.

Author contributions: Drs O’Gorman and Morgenthaler had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Dr O’Gorman: contributed to the analysis of data and to the composition and review of the manuscript.

Dr Gay: contributed to the design of the study, review of the data and analysis, and review and editing of the manuscript.

Dr Morgenthaler: contributed to the design and execution of the study, analysis of data, and to the composition and review of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Morgenthaler was a recipient of a grant from ResMed for a different study evaluating treatment of Complex Sleep Apnea Syndrome. Drs O’Gorman and Gay have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: The work was performed at Mayo Clinic, Rochester, MN. The authors acknowledge the contributions of Terese T. Horlocker, MD, and Arlen D. Hanssen, MD, for their assistance in the design of the study protocol.

Additional information: The e-Appendix and e-Tables can be found in the “Supplemental Materials” area of the online article.

AHI

apnea-hypopnea index

APAP

autotitrating positive airway pressure

IQR

interquartile range

LOS

length of stay

OSA

obstructive sleep apnea

PAP

positive airway pressure

SACS

sleep apnea clinical score

Finkel KJ, Searleman AC, Tymkew H, et al. Prevalence of undiagnosed obstructive sleep apnea among adult surgical patients in an academic medical center. Sleep Med. 2009;10(7):753-758. [CrossRef] [PubMed]
 
Ramachandran SK, Kheterpal S, Consens F, et al. Derivation and validation of a simple perioperative sleep apnea prediction score. Anesth Analg. 2010;110(4):1007-1015. [CrossRef] [PubMed]
 
Gupta RM, Parvizi J, Hanssen AD, Gay PC. Postoperative complications in patients with obstructive sleep apnea syndrome undergoing hip or knee replacement: a case-control study. Mayo Clin Proc. 2001;76(9):897-905. [PubMed]
 
Liao P, Yegneswaran B, Vairavanathan S, Zilberman P, Chung F. Postoperative complications in patients with obstructive sleep apnea: a retrospective matched cohort study. Can J Anaesth. 2009;56(11):819-828. [CrossRef] [PubMed]
 
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. [CrossRef] [PubMed]
 
American College of Physicians. Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery. Ann Intern Med. 1997;127(4):309-312. [CrossRef] [PubMed]
 
Flemons WW, Whitelaw WA, Brant R, Remmers JE. Likelihood ratios for a sleep apnea clinical prediction rule. Am J Respir Crit Care Med. 1994;150(5 pt 1):1279-1285. [CrossRef] [PubMed]
 
Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K, Passik S. The Memorial Delirium Assessment Scale. J Pain Symptom Manage. 1997;13(3):128-137. [CrossRef] [PubMed]
 
Yoder EA, Klann K, Strohl KP. Inspired oxygen concentrations during positive pressure therapy. Sleep Breath. 2004;8(1):1-5. [CrossRef] [PubMed]
 
Schwartz AR, Kacmarek RM, Hess DR. Factors affecting oxygen delivery with bi-level positive airway pressure. Respir Care. 2004;49(3):270-275. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Consort diagram. APAP = autotitrating positive airway pressure.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Patient Demographics

Data are presented as No. (%), median (interquartile range), or mean ± SD. MDA = Memorial Delirium Assessment Scale; MMSE = Mini-Mental State Examination.

a 

Analyzed by Wilcoxon rank sum test. All others analyzed by Fisher exact test.

Table Graphic Jump Location
Table 2 —High-Risk Group Demographics

Data are presented as No. (%), median (interquartile range), or mean ± SD. APAP = autotitrating positive airway pressure.

a 

Analyzed by Wilcoxon rank sum test. All others analyzed by Fisher exact test.

Table Graphic Jump Location
Table 3 —APAP vs No APAP End Points in High-Risk Group

Data are presented No. (%), median (interquartile range), or mean ± SD. AHI = apnea-hypopnea index; O2 = oxygen. See Table 1 and 2 legends for expansion of other abbreviations.

a 

Analyzed by Wilcoxon rank sum test. All others analyzed by Fisher exact test.

Table Graphic Jump Location
Table 4 —Oximetry and Sleep Study

Data are presented as median (interquartile range). All P-values analyzed by Wilcoxon rank sum test. See Table 1-3 legends for expansion of abbreviations.

References

Finkel KJ, Searleman AC, Tymkew H, et al. Prevalence of undiagnosed obstructive sleep apnea among adult surgical patients in an academic medical center. Sleep Med. 2009;10(7):753-758. [CrossRef] [PubMed]
 
Ramachandran SK, Kheterpal S, Consens F, et al. Derivation and validation of a simple perioperative sleep apnea prediction score. Anesth Analg. 2010;110(4):1007-1015. [CrossRef] [PubMed]
 
Gupta RM, Parvizi J, Hanssen AD, Gay PC. Postoperative complications in patients with obstructive sleep apnea syndrome undergoing hip or knee replacement: a case-control study. Mayo Clin Proc. 2001;76(9):897-905. [PubMed]
 
Liao P, Yegneswaran B, Vairavanathan S, Zilberman P, Chung F. Postoperative complications in patients with obstructive sleep apnea: a retrospective matched cohort study. Can J Anaesth. 2009;56(11):819-828. [CrossRef] [PubMed]
 
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. [CrossRef] [PubMed]
 
American College of Physicians. Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery. Ann Intern Med. 1997;127(4):309-312. [CrossRef] [PubMed]
 
Flemons WW, Whitelaw WA, Brant R, Remmers JE. Likelihood ratios for a sleep apnea clinical prediction rule. Am J Respir Crit Care Med. 1994;150(5 pt 1):1279-1285. [CrossRef] [PubMed]
 
Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K, Passik S. The Memorial Delirium Assessment Scale. J Pain Symptom Manage. 1997;13(3):128-137. [CrossRef] [PubMed]
 
Yoder EA, Klann K, Strohl KP. Inspired oxygen concentrations during positive pressure therapy. Sleep Breath. 2004;8(1):1-5. [CrossRef] [PubMed]
 
Schwartz AR, Kacmarek RM, Hess DR. Factors affecting oxygen delivery with bi-level positive airway pressure. Respir Care. 2004;49(3):270-275. [PubMed]
 
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