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Original Research: Sleep Disorders |

Postoperative Oxygen Therapy in Patients With OSA: A Randomized Controlled Trial FREE TO VIEW

Pu Liao, MD; Jean Wong, MD; Mandeep Singh, MBBS; David T. Wong, MD; Sazzadul Islam, MS; Maged Andrawes, MD; Colin M. Shapiro, MD; David P. White, MD; Frances Chung, MBBS
Author and Funding Information

FUNDING/SUPPORT: The study was supported by grants from the University Health Network Foundation, Toronto, ON, Canada; and the Department of Anesthesia, University Health Network-Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.

aDepartment of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada

bDepartment of Psychiatry, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada

cDepartment of Sleep Medicine, Brigham and Women's Hospital, Boston, MA

dDepartment of Medicine, Harvard Medical School, Boston, MA

CORRESPONDENCE TO: Frances Chung, MBBS, Room 405, 2McL Wing, Department of Anesthesia, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, ON, M5T 2S8, Canada


Copyright 2017, The Authors. All Rights Reserved.


Chest. 2017;151(3):597-611. doi:10.1016/j.chest.2016.12.005
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Published online

Background  Surgical patients with OSA are at increased risk for perioperative complications. Postoperative supplemental oxygen is commonly used, but it may contribute to respiratory depression in patients with OSA receiving opioids. The objective of the study is to investigate the effect of postoperative supplemental oxygen on arterial oxygen saturation (Sao2), sleep respiratory events, and CO2 level in patients with untreated OSA.

Methods  Consented patients with an apnea hypopnea index (AHI) > 5 events per hour on a preoperative polysomnography were randomized (1:1) to oxygen (O2 group) or no oxygen (control group). The O2 group received oxygen at 3 L/min via nasal prongs for three postoperative nights. The primary outcomes were polysomnographic parameters measuring Sao2, sleep respiratory events, and Pco2 measured by transcutaneous CO2 monitor (PtcCO2) on nights 1 through 3. The intention-to-treat and per protocol analysis were completed.

Results  There were 123 patients randomized (O2 group: n = 62; control group: n = 61). On night 3, the O2 vs control group had a higher average Sao2 (95.2% ± 3% vs 91.4% ± 4%, respectively; P < .001) and lower oxygen desaturation index (median, 2.3; 25th-75th percentile, 0.2-13.8 vs median, 18.5; 25th-75th percentile, 8.2-45.9 events per hour, respectively; P < .0001). The O2 group had a decreased AHI (median, 8.0; 25th-75th percentile, 2.1-19.9 vs median, 15.6; 25th-75th percentile, 9.5-45.8, respectively; P = .016), hypopnea index (P < .001), and central apnea index (P = .026) and a shortened longest apnea hypopnea duration (P = .002). Although time percentage with PtcCO2 ≥ 55 mm Hg ≥ 10% on postoperative night 1, 2, or 3 was found in 11.4% patients, there was no difference in PtcCO2 between the groups.

Conclusions  Postoperative supplemental oxygen was found to improve oxygenation and decrease the AHI without increasing the duration of apnea-hypopnea event or PtcCO2 level. A small number of patients had significant CO2 retention while receiving supplemental oxygen.

Trial Registry  ClinicalTrials.gov; No.: NCT01552304; URL: www.clinicaltrials.gov

Figures in this Article

OSA is the most common type of sleep-disordered breathing (SDB). In surgical patients, the prevalence of OSA by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes or polysomnography (PSG) is 7% to 10%,, with a large proportion remaining undiagnosed. Patients with OSA may have an increased sensitivity to anesthetics or opioids,,, greater upper airway collapsibility,, and increased risk of postoperative complications.,, CPAP therapy is the mainstay treatment for patients with moderate-to-severe OSA, but its adherence remains a challenge.,, For patients with newly diagnosed untreated OSA or suspected OSA, surgical timing may not allow adequate time to establish diagnosis and initiate treatment.

For surgical patients with OSA, supplemental oxygen may be more acceptable than CPAP therapy, but three clinical concerns exist. First, hypoxemia may play a critical role in respiratory arousal in surgical patients with OSA. When supplemental oxygen abolishes hypoxemia, the apnea duration may increase,,, causing hypoventilation as evidenced by hypercarbia, leading to possible life-threatening respiratory depression. Second, postoperative opioids may depress respiration centrally and impair the arousal threshold causing arousal failure, possibly leading to sporadic case of death. The third concern is that supplemental oxygen may mask the ability of oximetry to detect abnormalities in the level of ventilation.,

To date, no published study has investigated the effect of postoperative supplemental oxygen on patients with newly diagnosed untreated OSA. The objective of this randomized controlled trial (RCT) was to investigate the effect of postoperative supplemental oxygen on Sao2, sleep respiratory events, and CO2 level in patients with untreated OSA. We hypothesize that postoperative supplemental oxygen would improve oxygenation in patients with OSA, without significantly increasing the duration of sleep apneic episodes and arterial CO2 tension.

Trial Design

This prospective RCT was registered at ClinicalTrials.gov (No. NCT01552304). The study was completed at Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada, from February 2012 to December 2015, with Institutional Review Board approval (No. UHN 11-0302-AE). Supplemental oxygen at 3 L/min via nasal prongs was the trial intervention. The primary outcomes were PSG parameters measuring arterial oxygen saturation (Sao2), sleep respiratory events (frequency and duration), and Pco2 measured by transcutaneous CO2 monitor (PtcCO2) on postoperative night 3. Approximately 60% and 7% of patients at our institution receive supplemental oxygen on postoperative nights 1 and 3, respectively. To minimize the cross contamination of the control group, we chose night 3 as the time point for outcome measurement.

Eligibility and Trial Procedures

The inclusion criteria were as follows: (1) elective surgery with ≥ 3 nights stay, (2) age 18 to 80 years, and (3) patients at high risk of OSA (STOP-Bang questionnaire score ≥ 3) or with diagnosed untreated OSA. Patients with any of the following conditions were excluded: (1) unable to give informed consent; (2) diagnosed OSA with treatment; (3) possible postoperative ventilation; and (4) serum bicarbonate (HCO3) > 30 mml/L, indicating potential hypoventilation, such as obesity hypoventilation syndrome (OHS).

Eligible surgical patients attending preoperative clinic were consented (Fig 1). Recruited patients completed a preoperative PSG at home with a level II 10-channel portable device (Embletta x100; Embla) as previously described. The PSG recording montage consisted of two electroenephalographic channels (C3 and C4), left or right electroculogram, chin muscle electromyograms, nasal cannula (pressure), thoracic and abdominal respiratory effort bands, body position sensor, and pulse oximetry. This montage allows us to measure the parameters on sleep architecture, sleep respiratory events, arousal events, sleep positon, oxygen desaturation, and heart rate. The PSG recordings were manually scored by a PSG technologist according to the American Academy of Sleep Medicine 2007 criteria. Apnea was defined as ≥ 90% drop in air flow from baseline for ≥ 10 seconds. Apneic episodes were further classified as obstructive, central, or mixed apneas. Hypopnea was defined as ≥ 50% reduction in air flow for ≥ 10 seconds and ≥ 3% decrease in Sao2 or associated with arousal. Oxygen desaturation index (ODI) is the average number of episodes of desaturation ≥ 4% and lasting ≥ 10 seconds per hour of sleep.

Figure 1
Figure Jump LinkFigure 1 Flowchart of patient recruitment and follow-up. AHI = apnea hypopnea index; PSG = polysomnography.Grahic Jump Location

Patients with an apnea hypopnea index (AHI) ≥ 5 events per hour were equally randomized into the oxygen (O2) group or control group. Allocation was made via a computerized block randomization by a research analyst not involved in the study implementation. The research coordinator, the PSG technologist, and the chart reviewers were blinded to the group allocation. Patients in the control group were managed by anesthesiologists and surgeons as per routine practice, including supplemental oxygen or CPAP therapy as clinically indicated. In the O2 group, patients received 3 L/min nasal supplemental oxygen for 3 postoperative nights (nights 1-3) in addition to the routine care. Postoperative night 1 was defined as the night of surgery.

The study patients completed PSG on night 3. PtcCO2 was monitored with a CO2 monitor (TCM400; Radiometer Medical ApS) via a probe attached to the inner side of the patient’s arm on nights 1 to 3. A related model capable of monitoring both PtcCO2 and Sao2 (TOSCA 500 instrument; Radiometer Medical ApS) has demonstrated a stable long-term (6 hours) measurement of PtcCO2 without relevant drift. Repeated calibration against gas with a known CO2 concentration, autocalibration, and membrane replacement was performed according to the manufacturer’s recommendations. A total of 255 CO2 monitorings were done, and 18 (7.6%) failed (recording < 2 hours).

Recording between 9 pm and 6 am was selected. Unreliable data with extremely low readings (PtcCO2 < 20 mm Hg) were removed. The parameters of mean, median, highest PtcCO2, and time percent with PtcCO2 > 45 and 55 mm Hg were extracted from PtcCO2 recordings. Patients were visited daily by a research coordinator for assistance with the devices and data collection.

Statistical Analysis

Because, to our knowledge, there are no published studies with a similar design, the sample size estimation was based on two studies comparing supplemental oxygen and CPAP in nonsurgical patients with OSA that used cumulative time percentage with Sao2 < 90% (CT90)., Based on the average CT90 of these two studies (1.8% in O2 group vs 4.8% in control group) and the larger SD (4.5%), assuming a two-tailed two-sample t test, α error = 0.025, power = 0.85, and equal allocation into two groups, the estimated total sample size was 100. Accounting for a 20% dropout rate, the number of patients randomized would be 100 × 1.20 = 120 patients (60 per group).

Data were entered into a specifically designed Microsoft Access database (Microsoft) and checked for possible errors. SAS 9.3 for Windows (SAS Institute) was used for data analysis. Descriptive statistics were completed on the clinical data and the SDB parameters on the preoperative baseline PSG. An intention-to-treat analysis was first carried out according to randomization (O2 group vs control group). Missing PSG data (control group: n = 7; O2 group: n = 13) on night 3 were imputed with preoperative value (last observation carried forward). Because oxygen is often prescribed after surgery, supplementary analyses were carried out according to the dropout and actual use of oxygen (per protocol). In per protocol analyses, regardless of randomization, patients receiving oxygen on night 3 were grouped into the Oxygen group, and those not receiving oxygen were grouped into the No-Oxygen group.

Continuous variables with normal distribution are presented as mean ± SD, and comparison between groups was assessed using an independent two-sample t test. Variables with skewed distribution are presented as median (25th-75th percentile), and comparison between groups was performed with the nonparametric Mann-Whitney U test. Categorical data are presented as frequency and percentage, and χ2 test was used for statistical assessment. The P values for multiple comparisons were adjusted using the Holm-Bonferroni method. The potential risk factors for postoperative hypercapnia were evaluated by univariate logistic regression.

Study Population and Baseline Data

The recruitment and follow-up of patients are shown in Figure 1. There were 123 patients with AHI ≥ 5 events per hour randomized to the O2 group (n = 62) or control group (n = 61). The demographic data, average AHI, American Society of Anesthesiologists physical status, comorbidities, postoperative 72-hour opioids requirement, and type of surgery and anesthesia were similar between the groups (Table 1). Excluding the dropouts, 49 (O2 group) and 54 (control group) patients completed PSG on night 3, respectively (Fig 1). In the O2 group, one patient with a history of emphysema was excluded because of intubation as a result of hypercarbia and desaturation. The patient was extubated in the ICU 4 hours later. In patients receiving general surgery, four (6.5%) patients in the O2 group underwent upper abdominal procedures (gastric bypass: n = 3; gastrectomy: n = 1), and three (4.9%) patients in the control group received upper abdominal procedures (gastric bypass: n =2; gastroplasty: n = 1).

Table Graphic Jump Location
Table 1 Clinical Data
a Opioid requirement was presented as equivalent morphine dose in milligrams.

Data are presented as frequency (%), median (25th-75th percentile), or mean ± SD. AHI = apnea hypopnea index; ASA = American Society of Anesthesiologists; F = female; M = male.

Oxygen Therapy

In the control group, despite randomization to no supplemental oxygen, 11 (20%) of the patients received 3 L/min supplemental oxygen with nasal prongs on night 3, as ordered by the health-care teams. In the control group, more patients with severe OSA received supplemental oxygen on postoperative night 3: mild SDB: 10.3% (3/29); moderate SDB: 13.3% (2/15); and severe SDB: 35.3% (6/17). The difference was not significant (P = .090).

Nine patients in the control group also received supplemental oxygen during the daytime. Of them, 7 patients experienced desaturation because of bronchospasm (n = 2), atelectasis (n = 1), and undefined reasons (n = 4); other patients experienced hypotension, hypertension, inadequate pain control, and somnolence. In the O2 group, all patients received 3 L/min supplemental oxygen on night 3. No patient received CPAP therapy.

Effect of Oxygen on Sao2

There was no difference in the baseline variables regarding oxygen saturation (average Sao2, lowest Sao2, CT90, and ODI) on the preoperative PSG either based on the intention-to-treat (Fig 2A, Table 2) or per protocol (as treated) analysis (Fig 2C, Table 3). On night 3, supplemental oxygen significantly improved oxygen saturation per intention-to-treat (Fig 2B, Table 2) and per protocol analyses (Fig 2D, Table 3).

Figure 2
Figure Jump LinkFigure 2 A-D, Boxplot depicting changes in parameters measuring oxygen saturation. A, Preoperative, intention-to-treat analysis. B, Postoperative night 3, intention-to-treat analysis. C, Preoperative, per protocol analysis. D, Postoperative night 3, per protocol analysis. The box represents the interquartile range (IQR), the line inside the box represents the median, the upper whisker is drawn from the upper edge of the box to the largest value within 1.5× IQR, the lower whisker is drawn from the lower edge of box to the smallest value within 1.5× IQR, and colorful dot and triangles indicate the values outside 1.5× IQR. ASaO2 = average pulse oxygen saturation (%); CT90 = cumulative time percentage with SaO2 < 90% (%); LSaO2 = lowest pulse oxygen saturation (%); ODI = oxygen desaturation index (events/h); WASaO2 = wake average pulse oxygen saturation (%). *Adjusted P < .05 vs control or nonoxygen group.Grahic Jump Location
Table Graphic Jump Location
Table 2 Polysomnography Data (Intention-to-Treat)

Data are presented as median (25th-75th percentile), mean ± SD, or as otherwise indicated. Central apnea index = average hourly number of central apnea episodes; CT90 = cumulative time percentage with Sao2 < 90%; Hypopnea index = average hourly number of hypopnea episodes; Mixed apnea index = average hourly number of apnea episodes with characteristics of both obstructive or central apnea; NREM-AHI = apnea hypopnea index during non-rapid eye movement sleep; Obstructive apnea index = average hourly number of obstructive apnea episodes; REM-AHI = apnea hypopnea index during rapid eye movement sleep; RERA index = respiratory-related arousal index; Respiratory arousal index = average hourly sleep arousals because of respiratory events; Sao2 = arterial oxygen saturation; Wake Sao2 = average Sao2 while patient awake during polysomnography. See Table 1 legend for expansion of other abbreviation.

Table Graphic Jump Location
Table 3 Polysomnography Data (Per Protocol, 2 Polysomnographies)

Data are presented as median (25th-75th percentile), mean ± SD, or as otherwise indicated. See Table 1 and 2 legends for expansion of abbreviations.

Effect of Oxygen on SDB

The baseline parameters on the preoperative PSG were similar between the O2 and control groups (intention-to-treat) (Fig 3A, Table 2) or between the Oxygen and No-Oxygen groups (per protocol analysis) (Table 3). On night 3, based on the intention-to-treat analysis (Fig 3B, Table 2), the O2 group had a lower AHI, nonrapid eye movement (sleep) (NREM)-AHI, and hypopnea index. Based on per protocol analysis (Fig 3C, 3D, Table 3), the O2 group also demonstrated a lower AHI, NREM-AHI, rapid eye movement (sleep) (REM)-AHI, central apnea index, and hypopnea index. The longest apnea-hypopnea event duration was shortened. In the O2 group, AHI was significantly reduced from preoperative baseline to night 3 (median, 17.9; 25th-75th percentile, 8.8-32.8 to median, 4.4; 25th-75th percentile, 1.3-19.4 events per hour; P < .001) (Fig 3D). In the No-Oxygen group, AHI increased from a median 13.8 (25th-75th percentile, 9.1-28.1) preoperatively to 17.1 (25th-75th percentile, 10.2-58.4) events per hour on night 3 (P = .132) (Fig 3D). In all patients receiving oxygen supplementation on postoperative night 3, patients with severe SDB vs mild SDB had significantly more AHI reduction (median, −31.0; 25th-75th percentile, −41.4 to −11.1 vs median, −5.3; 25th-75th percentile, −7.8 to 5.7 events per hour, respectively; P < .05).

Figure 3
Figure Jump LinkFigure 3 A-D, Impact of oxygen therapy on frequency and duration of sleep-disordered breathing events. The boxplots represent the difference between the two groups in preoperative measurement, intention-to-treat analysis (A), postoperative night 3, intention-to treat analysis (B), and per protocol analysis (C). Panel D shows AHI change from preoperative to postoperative night 3 in two groups, per protocol analysis. AED = average event duration (s); CAI = central apnea index (events/h); HI = hypopnea index (events/h); LED = longest event (apnea-hypopnea) duration (s); OAI = obstructive apnea index (events/h); Postop = postoperative; Preop = preoperative. See Figure 1 legend for expansion of other abbreviation. *Adjusted P < .05 vs control or No-Oxygen group.Grahic Jump Location

No difference occurred in the sleep architecture between groups on preoperative baseline or night 3, either based on intention-to-treat or per protocol analysis (data not shown).

Effect of Oxygen on PtcCO2

The PtcCO2 data on nights 1 through 3, based on intention-to-treat analysis, were summarized in Figure 4A and Table 4. No difference was found between the control and O2 groups in the average PtcCO2, median PtcCO2, number of patients with PtcCO2 > 45 mm Hg or PtcCO2 > 55 mm Hg, and the overnight cumulated time percentage with PtcCO2 > 45 mm Hg or time percentage with PtcCo2 ≥ 55 mm Hg (PtcCO2-CT55). The per protocol analysis did not show a difference either (Fig 4B). However, a significant increase in PtcCO2 was found in a small number of patients. A total of 14 (11.4%) patients had PtcCO2-CT55 ≥ 10% on postoperative night 1, 2, or 3 (Table 5). Most (93%; 13/14) were receiving oxygen therapy at the time of elevated CO2 levels (control group: n = 7; O2 group: n = 6). A large number (9/14) experienced the highest PtcCO2 on night 1. Only one patient had the comorbidity of COPD. Two patients experienced prolonged overnight desaturation (Sao2 < 90%). No patient had life-threatening complications.

Figure 4
Figure Jump LinkFigure 4 A, B, Boxplot to show the impact of oxygen therapy on CO2 level of postoperative night 3. A, Intention-to-treat analysis. B, Per protocol analysis. aPtcCO2 = average Pco2 measured by transcutaneous CO2 monitor (mm Hg); CT45 = cumulative time percentage with Pco2 measured by transcutaneous CO2 monitor > 45 mm Hg (%); CT55 = cumulative time percentage with Pco2 measured by transcutaneous CO2 monitor > 55 mm Hg (%); hPtcCO2 = highest Pco2 measured by transcutaneous CO2 monitor (mm Hg); mPtcCO2 = median Pco2 measured by transcutaneous CO2 monitor (mm Hg); PostopN3 = postoperative night 3.Grahic Jump Location
Table Graphic Jump Location
Table 4 Transcutaneous Pco2 (PtcCO2) on First Three Postoperative Nights (Intention-to-Treat)

Data are presented as No. (%), median (25th-75th percentile), mean ± SD, or as otherwise indicated. PtcCO2 = Pco2 measured by transcutaneous CO2 monitor.

Table Graphic Jump Location
Table 5 Detailed Information of Patients With Time Percentage of PtcCO2 ≥ 55 mm Hg ≥ 10% on Postoperative Night 1, 2, or 3
a Postoperative complications include bronchospasm (expiratory wheezing), desaturation (Sao2 < 90% and/or cyanosis and/or Pao2 < 60 mm Hg requiring supplemental oxygen therapy), hypertension (systolic BP > 200 mm Hg for > 15 min), hypotension (systolic BP < 80 mm Hg for > 15 min), inadequate pain control (pain cannot be controlled by regular dose of narcotics), motor deficit (unexpected inability to lift the upper or lower extremity for > 1 h, excluding spinal or epidural anesthesia), and somnolence (state of feeling drowsy).

DM = diabetes mellitus; GERD = gastroesophageal reflux disease; HTN = hypertension; PtcCO2-CT55 = time percentage with PtcCO2 ≥ 55 mm Hg. See Table 1, 2, and 4 legends for expansion of other abbreviations.

To explore the potential risk factors for postoperative hypercapnia, we used PtcCO2-CT55 ≥ 10% as the dependent variable to individually evaluate its association with oxygen supplementation, age, sex, BMI, neck circumference, type of surgery and anesthesia, comorbidities (COPD, asthma, diabetes, and smoker), American Society of Anesthesiologists physical status, preoperative OSA severity, preoperative HCO3, average Sao2, lowest Sao2, CT90, or ODI. None of these factors was found significantly associated with postoperative hypercapnia, with CT90 and lowest Sao2 having a P value < 0.1 (P = .061 and P = .096, respectively).

To date, this is the first RCT on postoperative supplemental oxygen in surgical patients with newly diagnosed untreated OSA. Postoperative supplemental oxygen was found to improve oxygenation and decreased AHI without significantly increasing the apnea-hypopnea event duration or PtcCO2 level. Eleven percent of patients had significant CO2 retention while receiving supplemental oxygen.

Hypoxemia is an immediate consequence of apneic and hypopnea events. OSA-related complications could be induced by hypoxemia. Our data from the intention-to-treat analysis show that supplemental oxygen significantly decreased AHI, NREM-AHI, and hypopnea index. The results from the per protocol (as treated) analysis show that supplemental oxygen not only decreased AHI, NREM-AHI, and hypopnea index but also decreased REM-AHI, central apnea index, and longest apnea-hypopnea event duration. Because 20% of patients in the control group received supplemental oxygen, results from the per protocol analysis would better reflect the effects of supplemental oxygen on sleep respiratory events.

In previous studies of nonsurgical patients with OSA, the effect of supplemental oxygen on sleep respiratory events was inconsistent. Compared with breathing room air, breathing oxygen reduced the frequency of apnea, which may be related to increased Paco2, stimulating ventilation during sleep. In contrast, other studies found that the length of apnea was increased by breathing oxygen, and AHI was not decreased., In peritoneal dialysis patients with OSA, nocturnal oxygen therapy decreased hypopnea and central apnea. Oxygen effectively reduced central sleep apnea in patients with eucapnia, but obstructive and mixed apneas were unaffected by oxygen. In this study, the decrease in AHI was mainly caused by a drop in hypopnea index and, to a minor degree, central apnea. Because hypopnea index was not separated into central or obstructive hypopnea component, the contributing role of each cannot be determined. Another possible mechanism for the reduction of hypopnea events is caused by improvement of oxygenation by supplemental oxygen, rendering less events meeting hypopnea criterion (Tables 2, 3).

The discrepancy in the effect of supplemental oxygen on sleep respiratory events both between subjects and between studies may be caused by the various pathophysiologic mechanisms causing OSA. The mechanisms include the following: (1) an anatomically collapsible upper airway characterized by a high passive critical closing pressure; (2) inadequate response of the upper airway dilator muscles during sleep characterized by minimal increase in electromyographic activity in response to progressive negative pharyngeal pressure,; (3) waking up prematurely to airway narrowing characterized by a low respiratory arousal threshold,; and (4) an oversensitive ventilatory control system characterized by high loop gain. With the different pathophysiologic mechanisms, strategies to target treatment would be more effective.

Supplemental oxygen was shown to decrease AHI in patients with high loop gain, but not in patients with low loop gain. The high loop gain in patients with OSA is induced by intermittent hypoxia and can be reversed by preventing hypoxia with supplemental oxygen or CPAP therapy., Supplemental oxygen increases ventilatory stability in patients with ventilatory instability (high loop gain). Further work is needed to determine whether patients with OSA caused by other pathophysiologic processes would benefit from supplemental oxygen.

One concern for surgical patients with OSA is that supplemental oxygen could lead to longer apneas events with associated hypercapnia and sustained hypoventilation. In previous studies, the duration of apnea was found increased by supplemental oxygen., In a study of 28 asymptomatic men with heavy snoring, the frequency of apneas was not decreased, but the length of apnea was increased by supplemental oxygen. In another study of 20 obese men with sleep apnea and COPD, mean event duration and end apneic Pco2 were increased by supplemental oxygen (4 L/min). In this study, we found that the duration of the longest apnea-hypopnea events was shortened by supplemental oxygen. There are two possible reasons for our finding of shortening of longest apnea-hypopnea event duration. The first reason is because of the difference in study populations. In our study, only 3% of patients had COPD, whereas in the Alford et al study, all patients had COPD. We also excluded patients with possible OHS by not recruiting patients with HCO3 ≥ 30 mEq/L. Patients with COPD and OHS are more likely to suffer from respiratory suppression and CO2 retention with supplemental oxygen. The second reason is the definition of event duration. In our study, the duration was calculated based on both apnea and hypopnea events. Supplemental oxygen eliminated some of the hypopnea events by making them not meeting hypopnea criteria because of improved oxygen saturation, possibly leading to shortened duration of apnea-hypopnea events.

OHS is present in 10% to 20% of patients with OSA. Supplemental oxygen may worsen hypercapnia in patients with OHS. To avoid recruiting patients with OHS, patients with serum HCO3levels > 30 mmol/L were excluded. A low flow (3 L/min) of oxygen was used. These factors may contribute to no overall difference in PtcCO2 metrics between groups on nights 1 through 3, either on intention-to-treat or per protocol analysis. A small number (11.4%) of patients experienced substantial CO2 retention, especially those receiving oxygen on night 1. When opioids or hypnotics are used, administration of oxygen may cause significant CO2 retention in a small number of patients. To define the risk factors for postoperative hypercapnia, we need a study with a larger sample size.

Increased inspired oxygen may result in greater opioid-induced respiratory depression. When supplemental oxygen is given, it may mask the ability of oximetry to detect abnormalities in the level of ventilation., Additional methods for detecting hypoventilation, such as continuous measurement of respiratory rate and end-tidal CO2 monitoring, may be needed.

A limitation of this study is cross contamination. To ensure the safety of the participants, the perioperative care team could order oxygen or CPAP if deemed clinically necessary. Although no CPAP therapy was prescribed, a high percentage of patients in the control group received postoperative supplemental oxygen. This may interfere with the interpretation of the results. To minimize the effect of cross contamination, outcomes were measured on night 3 with less patients in the control group receiving oxygen, and data were subjected to per protocol (as treated) analysis to delineate the true effect of oxygen therapy. Another limitation is that the amplitude of postoperative change in PtcCO2 could not be determined because of the lack of preoperative baseline data of PtcCO2. This may have led to an underestimation of the true PtcCO2 changes with oxygen. Finally, the results are not generalizable to patients with OHS because of the exclusion of patients with serum HCO3> 30 mmol/L.

In conclusion, postoperative supplemental oxygen improved oxygenation in surgical patients with OSA. Supplemental oxygen decreased AHI, hypopnea index, and central apnea index and shortened the longest apnea-hypopnea event duration. Although no overall difference was found between groups in PtcCO2 level, a significant increase of PtcCO2 was found in 11.4% of patients, especially those receiving oxygen on postoperative night 1. Postoperative supplemental oxygen could be used as an alternative therapy for patients with OSA not adherent to CPAP, newly diagnosed patients without adequate time to initiate CPAP therapy, or patients with suspected OSA. Additional monitoring of respiratory rate or PtcCO2, especially on postoperative night 1, is recommended. Further work is needed to identify OSA phenotypes which would benefit from postoperative supplemental oxygen and to identify which patients should be monitored for hypoventilation with respiratory rate or PtcCO2.

Author contributions: F. C. takes responsibility for (is the guarantor of) the content of the article, including the data and analysis. P. L. helped to design the study, analyze the data, and write the manuscript. J. W. helped write the manuscript. M. S. helped write the manuscript. D. T. W. helped write the manuscript. S. I. helped conduct the study. M. A. helped conduct the study. C. M. S. helped write the manuscript. D. P. W. helped write the manuscript. F. C. helped design the study, conduct the study, and write the manuscript. F. C. has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. P. W. is the Chief Medical Officer of Apnicure, Inc, and is a consultant for Philips Respironics and Night Balance. F. C. reports that STOP-Bang is proprietary to the University Health Network and reports research grant support from Ontario Ministry of Health Innovation Grant, University Health Network Foundation, ResMed Foundation, Acacia and Medtronics. None declared (P. L., J. W., M. S., D. T. W., S. I., M. A., C. M. S.).

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

Other contributions: We acknowledge the help of Weimin Kang, MD (registered polysomnographic technologist, Department of Anesthesia, University Health Network, Toronto, ON, Canada) for his help in the conduct of the study.

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Singh M. .Liao P. .Kobah S. .et al Proportion of surgical patients with undiagnosed obstructive sleep apnoea. Br J Anaesth. 2013;110:629-636 [PubMed]journal. [CrossRef] [PubMed]
 
Brown K.A. .Laferriere A. .Lakheeram I. .et al Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Anesthesiology. 2006;105:665-669 [PubMed]journal. [CrossRef] [PubMed]
 
Doufas A.G. .Tian L. .Padrez K.A. .et al Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea. PLoS One. 2013;8:e54807- [PubMed]journal. [CrossRef] [PubMed]
 
Lam K.K. .Kunder S. .Wong J. .et al Obstructive sleep apnea, pain, and opioids: Is the riddle solved? Curr Opin Anaesthesiol. 2016;29:134-140 [PubMed]journal. [CrossRef] [PubMed]
 
Hillman D.R. .Walsh J.H. .Maddison K.J. .et al Evolution of changes in upper airway collapsibility during slow induction of anesthesia with propofol. Anesthesiology. 2009;111:63-71 [PubMed]journal. [CrossRef] [PubMed]
 
Isono S. . Obesity and obstructive sleep apnoea: mechanisms for increased collapsibility of the passive pharyngeal airway. Respirology. 2012;17:32-42 [PubMed]journal. [CrossRef] [PubMed]
 
Kaw R. .Chung F. .Pasupuleti V. .et al Meta-analysis of the association between obstructive sleep apnoea and postoperative outcome. Br J Anaesth. 2012;109:897-906 [PubMed]journal. [CrossRef] [PubMed]
 
Opperer M. .Cozowicz C. .Bugada D. .et al Does obstructive sleep apnea influence perioperative outcome? A qualitative systematic review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing. Anesth Analg. 2016;122:1321-1334 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Nagappa M. .Singh M. .et al CPAP in the perioperative setting: evidence of support. Chest. 2015;149:586-597 [PubMed]journal
 
Liao P. .Luo Q. .Elsaid H. .et al Perioperative auto-titrated continuous positive airway pressure treatment in surgical patients with obstructive sleep apnea: a randomized controlled trial. Anesthesiology. 2013;119:837-847 [PubMed]journal. [CrossRef] [PubMed]
 
Nagappa M. .Mokhlesi B. .Wong J. .et al The effects of continuous positive airway pressure on postoperative outcomes in obstructive sleep apnea patients undergoing surgery: a systematic review and meta-analysis. Anesth Analg. 2015;120:1013-1023 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Memtsoudis S. .Krishna Ramachandran S. .et al Society of Anesthesia and sleep medicine guideline on preoperative screening and assessment of patients with obstructive sleep apnea. Anesth Analg. 2016;123:452-473 [PubMed]journal. [PubMed]
 
Gold A.R. .Schwartz A.R. .Bleecker E.R. .et al The effect of chronic nocturnal oxygen administration upon sleep apnea. Am Rev Respir Dis. 1986;134:925-929 [PubMed]journal. [CrossRef] [PubMed]
 
Alford N.J. .Fletcher E.C. .Nickeson D. . Acute oxygen in patients with sleep apnea and COPD. Chest. 1986;89:30-38 [PubMed]journal. [CrossRef] [PubMed]
 
Mehta V. .Vasu T.S. .Phillips B. .et al Obstructive sleep apnea and oxygen therapy: a systematic review of the literature and meta-analysis. J Clin Sleep Med. 2013;9:271-279 [PubMed]journal. [PubMed]
 
Lynn L.A. .Curry J.P. . Patterns of unexpected in-hospital deaths: a root cause analysis. Patient Saf Surg. 2011;5:3- [PubMed]journal. [CrossRef] [PubMed]
 
Fu E.S. .Downs J.B. .Schweiger J.W. .et al Supplemental oxygen impairs detection of hypoventilation by pulse oximetry. Chest. 2004;126:1552-1558 [PubMed]journal. [CrossRef] [PubMed]
 
Niesters M. .Mahajan R.P. .Aarts L. .et al High-inspired oxygen concentration further impairs opioid-induced respiratory depression. Br J Anaesth. 2013;110:837-841 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Liao P. .Elsaid H. .et al Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology. 2014;120:299-311 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Yegneswaran B. .Liao P. .et al STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008;108:812-821 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Liao P. .Sun Y. .et al Perioperative practical experiences in using a level 2 portable polysomnography. Sleep Breath. 2010;15:367-375 [PubMed]journal. [PubMed]
 
Iber C. .Ancoli-Israel S. .Chesson A. Jr..et al The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specification.  2007;:17-49 [PubMed] American Academy of Sleep Medicine Westchester, Illinoisjournal
 
Randerath W.J. .Stieglitz S. .Galetke W. .et al Evaluation of a system for transcutaneous long-term capnometry. Respiration. 2010;80:139-145 [PubMed]journal. [CrossRef] [PubMed]
 
Mills P.J. .Kennedy B.P. .Loredo J.S. .et al Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea. J Appl Physiol. 2006;100:343-348 [PubMed]journal. [CrossRef] [PubMed]
 
Norman D. .Loredo J.S. .Nelesen R.A. .et al Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension. 2006;47:840-845 [PubMed]journal. [CrossRef] [PubMed]
 
Gilmartin G.S. .Lynch M. .Tamisier R. .et al Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol. 2010;299:H925-H931 [PubMed]journal. [CrossRef] [PubMed]
 
Block A.J. .Hellard D.W. .Cicale M.J. . Snoring, nocturnal hypoxemia, and the effect of oxygen inhalation. Chest. 1987;92:411-417 [PubMed]journal. [CrossRef] [PubMed]
 
Loredo J.S. .ncoli-Israel S. .Kim E.J. .et al Effect of continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: a placebo-CPAP-controlled study. Sleep. 2006;29:564-571 [PubMed]journal. [PubMed]
 
Kumagai T. .Ishibashi Y. .Kawarazaki H. .et al Effects of nocturnal oxygen therapy on sleep apnea syndrome in peritoneal dialysis patients. Clin Nephrol. 2008;70:332-339 [PubMed]journal. [CrossRef] [PubMed]
 
Franklin K.A. .Eriksson P. .Sahlin C. .et al Reversal of central sleep apnea with oxygen. Chest. 1997;111:163-169 [PubMed]journal. [CrossRef] [PubMed]
 
Eckert D.J. .White D.P. .Jordan A.S. .et al Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013;188:996-1004 [PubMed]journal. [CrossRef] [PubMed]
 
Gleadhill I.C. .Schwartz A.R. .Schubert N. .et al Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis. 1991;143:1300-1303 [PubMed]journal. [CrossRef] [PubMed]
 
Jordan A.S. .Wellman A. .Heinzer R.C. .et al Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans. Thorax. 2007;62:861-867 [PubMed]journal. [CrossRef] [PubMed]
 
Loewen A.H. .Ostrowski M. .Laprairie J. .et al Response of genioglossus muscle to increasing chemical drive in sleeping obstructive apnea patients. Sleep. 2011;34:1061-1073 [PubMed]journal. [PubMed]
 
Eckert D.J. .Owens R.L. .Kehlmann G.B. .et al Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci (Lond). 2011;120:505-514 [PubMed]journal. [CrossRef] [PubMed]
 
Younes M. . Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol (1985). 2008;105:1389-1405 [PubMed]journal. [CrossRef] [PubMed]
 
Wellman A. .Malhotra A. .Jordan A.S. .et al Effect of oxygen in obstructive sleep apnea: role of loop gain. Respir Physiol Neurobiol. 2008;162:144-151 [PubMed]journal. [CrossRef] [PubMed]
 
Deacon N.L. .Catcheside P.G. . The role of high loop gain induced by intermittent hypoxia in the pathophysiology of obstructive sleep apnoea. Sleep Med Rev. 2015;22:3-14 [PubMed]journal. [CrossRef] [PubMed]
 
Edwards B.A. .Sands S.A. .Owens R.L. .et al Effects of hyperoxia and hypoxia on the physiological traits responsible for obstructive sleep apnoea. J Physiol. 2014;592:4523-4535 [PubMed]journal. [CrossRef] [PubMed]
 
Wijesinghe M. .Williams M. .Perrin K. .et al The effect of supplemental oxygen on hypercapnia in subjects with obesity-associated hypoventilation: a randomized, crossover, clinical study. Chest. 2011;139:1018-1024 [PubMed]journal. [CrossRef] [PubMed]
 
Chau E.H. .Lam D. .Wong J. .et al Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and perioperative considerations. Anesthesiology. 2012;117:188-205 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 Flowchart of patient recruitment and follow-up. AHI = apnea hypopnea index; PSG = polysomnography.Grahic Jump Location
Figure Jump LinkFigure 2 A-D, Boxplot depicting changes in parameters measuring oxygen saturation. A, Preoperative, intention-to-treat analysis. B, Postoperative night 3, intention-to-treat analysis. C, Preoperative, per protocol analysis. D, Postoperative night 3, per protocol analysis. The box represents the interquartile range (IQR), the line inside the box represents the median, the upper whisker is drawn from the upper edge of the box to the largest value within 1.5× IQR, the lower whisker is drawn from the lower edge of box to the smallest value within 1.5× IQR, and colorful dot and triangles indicate the values outside 1.5× IQR. ASaO2 = average pulse oxygen saturation (%); CT90 = cumulative time percentage with SaO2 < 90% (%); LSaO2 = lowest pulse oxygen saturation (%); ODI = oxygen desaturation index (events/h); WASaO2 = wake average pulse oxygen saturation (%). *Adjusted P < .05 vs control or nonoxygen group.Grahic Jump Location
Figure Jump LinkFigure 3 A-D, Impact of oxygen therapy on frequency and duration of sleep-disordered breathing events. The boxplots represent the difference between the two groups in preoperative measurement, intention-to-treat analysis (A), postoperative night 3, intention-to treat analysis (B), and per protocol analysis (C). Panel D shows AHI change from preoperative to postoperative night 3 in two groups, per protocol analysis. AED = average event duration (s); CAI = central apnea index (events/h); HI = hypopnea index (events/h); LED = longest event (apnea-hypopnea) duration (s); OAI = obstructive apnea index (events/h); Postop = postoperative; Preop = preoperative. See Figure 1 legend for expansion of other abbreviation. *Adjusted P < .05 vs control or No-Oxygen group.Grahic Jump Location
Figure Jump LinkFigure 4 A, B, Boxplot to show the impact of oxygen therapy on CO2 level of postoperative night 3. A, Intention-to-treat analysis. B, Per protocol analysis. aPtcCO2 = average Pco2 measured by transcutaneous CO2 monitor (mm Hg); CT45 = cumulative time percentage with Pco2 measured by transcutaneous CO2 monitor > 45 mm Hg (%); CT55 = cumulative time percentage with Pco2 measured by transcutaneous CO2 monitor > 55 mm Hg (%); hPtcCO2 = highest Pco2 measured by transcutaneous CO2 monitor (mm Hg); mPtcCO2 = median Pco2 measured by transcutaneous CO2 monitor (mm Hg); PostopN3 = postoperative night 3.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Clinical Data
a Opioid requirement was presented as equivalent morphine dose in milligrams.

Data are presented as frequency (%), median (25th-75th percentile), or mean ± SD. AHI = apnea hypopnea index; ASA = American Society of Anesthesiologists; F = female; M = male.

Table Graphic Jump Location
Table 2 Polysomnography Data (Intention-to-Treat)

Data are presented as median (25th-75th percentile), mean ± SD, or as otherwise indicated. Central apnea index = average hourly number of central apnea episodes; CT90 = cumulative time percentage with Sao2 < 90%; Hypopnea index = average hourly number of hypopnea episodes; Mixed apnea index = average hourly number of apnea episodes with characteristics of both obstructive or central apnea; NREM-AHI = apnea hypopnea index during non-rapid eye movement sleep; Obstructive apnea index = average hourly number of obstructive apnea episodes; REM-AHI = apnea hypopnea index during rapid eye movement sleep; RERA index = respiratory-related arousal index; Respiratory arousal index = average hourly sleep arousals because of respiratory events; Sao2 = arterial oxygen saturation; Wake Sao2 = average Sao2 while patient awake during polysomnography. See Table 1 legend for expansion of other abbreviation.

Table Graphic Jump Location
Table 3 Polysomnography Data (Per Protocol, 2 Polysomnographies)

Data are presented as median (25th-75th percentile), mean ± SD, or as otherwise indicated. See Table 1 and 2 legends for expansion of abbreviations.

Table Graphic Jump Location
Table 4 Transcutaneous Pco2 (PtcCO2) on First Three Postoperative Nights (Intention-to-Treat)

Data are presented as No. (%), median (25th-75th percentile), mean ± SD, or as otherwise indicated. PtcCO2 = Pco2 measured by transcutaneous CO2 monitor.

Table Graphic Jump Location
Table 5 Detailed Information of Patients With Time Percentage of PtcCO2 ≥ 55 mm Hg ≥ 10% on Postoperative Night 1, 2, or 3
a Postoperative complications include bronchospasm (expiratory wheezing), desaturation (Sao2 < 90% and/or cyanosis and/or Pao2 < 60 mm Hg requiring supplemental oxygen therapy), hypertension (systolic BP > 200 mm Hg for > 15 min), hypotension (systolic BP < 80 mm Hg for > 15 min), inadequate pain control (pain cannot be controlled by regular dose of narcotics), motor deficit (unexpected inability to lift the upper or lower extremity for > 1 h, excluding spinal or epidural anesthesia), and somnolence (state of feeling drowsy).

DM = diabetes mellitus; GERD = gastroesophageal reflux disease; HTN = hypertension; PtcCO2-CT55 = time percentage with PtcCO2 ≥ 55 mm Hg. See Table 1, 2, and 4 legends for expansion of other abbreviations.

References

Ramachandran S.K. .Kheterpal S. .Consens F. .et al Derivation and validation of a simple perioperative sleep apnea prediction score. Anesth Analg. 2010;110:1007-1015 [PubMed]journal. [CrossRef] [PubMed]
 
Memtsoudis S.G. .Stundner O. .Rasul R. .et al The impact of sleep apnea on postoperative utilization of resources and adverse outcomes. Anesth Analg. 2014;118:407-418 [PubMed]journal. [CrossRef] [PubMed]
 
Singh M. .Liao P. .Kobah S. .et al Proportion of surgical patients with undiagnosed obstructive sleep apnoea. Br J Anaesth. 2013;110:629-636 [PubMed]journal. [CrossRef] [PubMed]
 
Brown K.A. .Laferriere A. .Lakheeram I. .et al Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Anesthesiology. 2006;105:665-669 [PubMed]journal. [CrossRef] [PubMed]
 
Doufas A.G. .Tian L. .Padrez K.A. .et al Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea. PLoS One. 2013;8:e54807- [PubMed]journal. [CrossRef] [PubMed]
 
Lam K.K. .Kunder S. .Wong J. .et al Obstructive sleep apnea, pain, and opioids: Is the riddle solved? Curr Opin Anaesthesiol. 2016;29:134-140 [PubMed]journal. [CrossRef] [PubMed]
 
Hillman D.R. .Walsh J.H. .Maddison K.J. .et al Evolution of changes in upper airway collapsibility during slow induction of anesthesia with propofol. Anesthesiology. 2009;111:63-71 [PubMed]journal. [CrossRef] [PubMed]
 
Isono S. . Obesity and obstructive sleep apnoea: mechanisms for increased collapsibility of the passive pharyngeal airway. Respirology. 2012;17:32-42 [PubMed]journal. [CrossRef] [PubMed]
 
Kaw R. .Chung F. .Pasupuleti V. .et al Meta-analysis of the association between obstructive sleep apnoea and postoperative outcome. Br J Anaesth. 2012;109:897-906 [PubMed]journal. [CrossRef] [PubMed]
 
Opperer M. .Cozowicz C. .Bugada D. .et al Does obstructive sleep apnea influence perioperative outcome? A qualitative systematic review for the Society of Anesthesia and Sleep Medicine Task Force on Preoperative Preparation of Patients with Sleep-Disordered Breathing. Anesth Analg. 2016;122:1321-1334 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Nagappa M. .Singh M. .et al CPAP in the perioperative setting: evidence of support. Chest. 2015;149:586-597 [PubMed]journal
 
Liao P. .Luo Q. .Elsaid H. .et al Perioperative auto-titrated continuous positive airway pressure treatment in surgical patients with obstructive sleep apnea: a randomized controlled trial. Anesthesiology. 2013;119:837-847 [PubMed]journal. [CrossRef] [PubMed]
 
Nagappa M. .Mokhlesi B. .Wong J. .et al The effects of continuous positive airway pressure on postoperative outcomes in obstructive sleep apnea patients undergoing surgery: a systematic review and meta-analysis. Anesth Analg. 2015;120:1013-1023 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Memtsoudis S. .Krishna Ramachandran S. .et al Society of Anesthesia and sleep medicine guideline on preoperative screening and assessment of patients with obstructive sleep apnea. Anesth Analg. 2016;123:452-473 [PubMed]journal. [PubMed]
 
Gold A.R. .Schwartz A.R. .Bleecker E.R. .et al The effect of chronic nocturnal oxygen administration upon sleep apnea. Am Rev Respir Dis. 1986;134:925-929 [PubMed]journal. [CrossRef] [PubMed]
 
Alford N.J. .Fletcher E.C. .Nickeson D. . Acute oxygen in patients with sleep apnea and COPD. Chest. 1986;89:30-38 [PubMed]journal. [CrossRef] [PubMed]
 
Mehta V. .Vasu T.S. .Phillips B. .et al Obstructive sleep apnea and oxygen therapy: a systematic review of the literature and meta-analysis. J Clin Sleep Med. 2013;9:271-279 [PubMed]journal. [PubMed]
 
Lynn L.A. .Curry J.P. . Patterns of unexpected in-hospital deaths: a root cause analysis. Patient Saf Surg. 2011;5:3- [PubMed]journal. [CrossRef] [PubMed]
 
Fu E.S. .Downs J.B. .Schweiger J.W. .et al Supplemental oxygen impairs detection of hypoventilation by pulse oximetry. Chest. 2004;126:1552-1558 [PubMed]journal. [CrossRef] [PubMed]
 
Niesters M. .Mahajan R.P. .Aarts L. .et al High-inspired oxygen concentration further impairs opioid-induced respiratory depression. Br J Anaesth. 2013;110:837-841 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Liao P. .Elsaid H. .et al Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology. 2014;120:299-311 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Yegneswaran B. .Liao P. .et al STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008;108:812-821 [PubMed]journal. [CrossRef] [PubMed]
 
Chung F. .Liao P. .Sun Y. .et al Perioperative practical experiences in using a level 2 portable polysomnography. Sleep Breath. 2010;15:367-375 [PubMed]journal. [PubMed]
 
Iber C. .Ancoli-Israel S. .Chesson A. Jr..et al The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specification.  2007;:17-49 [PubMed] American Academy of Sleep Medicine Westchester, Illinoisjournal
 
Randerath W.J. .Stieglitz S. .Galetke W. .et al Evaluation of a system for transcutaneous long-term capnometry. Respiration. 2010;80:139-145 [PubMed]journal. [CrossRef] [PubMed]
 
Mills P.J. .Kennedy B.P. .Loredo J.S. .et al Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea. J Appl Physiol. 2006;100:343-348 [PubMed]journal. [CrossRef] [PubMed]
 
Norman D. .Loredo J.S. .Nelesen R.A. .et al Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension. 2006;47:840-845 [PubMed]journal. [CrossRef] [PubMed]
 
Gilmartin G.S. .Lynch M. .Tamisier R. .et al Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol. 2010;299:H925-H931 [PubMed]journal. [CrossRef] [PubMed]
 
Block A.J. .Hellard D.W. .Cicale M.J. . Snoring, nocturnal hypoxemia, and the effect of oxygen inhalation. Chest. 1987;92:411-417 [PubMed]journal. [CrossRef] [PubMed]
 
Loredo J.S. .ncoli-Israel S. .Kim E.J. .et al Effect of continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: a placebo-CPAP-controlled study. Sleep. 2006;29:564-571 [PubMed]journal. [PubMed]
 
Kumagai T. .Ishibashi Y. .Kawarazaki H. .et al Effects of nocturnal oxygen therapy on sleep apnea syndrome in peritoneal dialysis patients. Clin Nephrol. 2008;70:332-339 [PubMed]journal. [CrossRef] [PubMed]
 
Franklin K.A. .Eriksson P. .Sahlin C. .et al Reversal of central sleep apnea with oxygen. Chest. 1997;111:163-169 [PubMed]journal. [CrossRef] [PubMed]
 
Eckert D.J. .White D.P. .Jordan A.S. .et al Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013;188:996-1004 [PubMed]journal. [CrossRef] [PubMed]
 
Gleadhill I.C. .Schwartz A.R. .Schubert N. .et al Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. Am Rev Respir Dis. 1991;143:1300-1303 [PubMed]journal. [CrossRef] [PubMed]
 
Jordan A.S. .Wellman A. .Heinzer R.C. .et al Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans. Thorax. 2007;62:861-867 [PubMed]journal. [CrossRef] [PubMed]
 
Loewen A.H. .Ostrowski M. .Laprairie J. .et al Response of genioglossus muscle to increasing chemical drive in sleeping obstructive apnea patients. Sleep. 2011;34:1061-1073 [PubMed]journal. [PubMed]
 
Eckert D.J. .Owens R.L. .Kehlmann G.B. .et al Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci (Lond). 2011;120:505-514 [PubMed]journal. [CrossRef] [PubMed]
 
Younes M. . Role of respiratory control mechanisms in the pathogenesis of obstructive sleep disorders. J Appl Physiol (1985). 2008;105:1389-1405 [PubMed]journal. [CrossRef] [PubMed]
 
Wellman A. .Malhotra A. .Jordan A.S. .et al Effect of oxygen in obstructive sleep apnea: role of loop gain. Respir Physiol Neurobiol. 2008;162:144-151 [PubMed]journal. [CrossRef] [PubMed]
 
Deacon N.L. .Catcheside P.G. . The role of high loop gain induced by intermittent hypoxia in the pathophysiology of obstructive sleep apnoea. Sleep Med Rev. 2015;22:3-14 [PubMed]journal. [CrossRef] [PubMed]
 
Edwards B.A. .Sands S.A. .Owens R.L. .et al Effects of hyperoxia and hypoxia on the physiological traits responsible for obstructive sleep apnoea. J Physiol. 2014;592:4523-4535 [PubMed]journal. [CrossRef] [PubMed]
 
Wijesinghe M. .Williams M. .Perrin K. .et al The effect of supplemental oxygen on hypercapnia in subjects with obesity-associated hypoventilation: a randomized, crossover, clinical study. Chest. 2011;139:1018-1024 [PubMed]journal. [CrossRef] [PubMed]
 
Chau E.H. .Lam D. .Wong J. .et al Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and perioperative considerations. Anesthesiology. 2012;117:188-205 [PubMed]journal. [CrossRef] [PubMed]
 
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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543