Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline

Evidencetable E1: Should serum bicarbonate (HCO3 -) rather than partial pressure of carbon dioxide in arterial blood (PaCO2) be used to screen for OHS in obese adults with sleep-disordered breathing? Patient or population: obese adults with OSA New test: serum bicarbonate | Cut-off value: 27 mmol/l Pooled sensitivity: 0.86 (95% CI: 0.70 to 0.94) | Pooled specificity: 0.77 (95% CI: 0.60 to 0.89) Test result Number of results per 1,000 patients tested (95% CI) Number of participants (studies) Certainty of the Evidence (GRADE) Prevalence 5% Typically seen in patients with OSA and BMI 30-34 Prevalence 10% Typically seen in patients with OSA and BMI 35-40

## Prevalence 20%
Typically seen in patients with Explanations a. One more study included very few patients with OHS and was excluded from analysis . Sensitivity analysis including this study did not show a difference in accuracy.

## References:
1) Bingol Z, Pihtili A, Cagatay P, Okumus G, Kiyan E. Clinical predictors of obesity hypoventilation syndrome in obese subjects with obstructive sleep apnea. Respir Care 2015;60:666-672. *We acknowledge Drs. Esen Kiyan and Zuleyha Bingol for sharing revised data for g. Studies reported the range of resolution of OHS between 1.5% and 62%. We could not explain these differences with either length of follow-up, apparent severity of disease, or mode of ventilation. h. One study enrolled patients without severe OSA and the effect in this population was smaller but excluding this study would not change the overall estimate. RR among those with severe OSA: 1.27 (95% CI: 1.01 to 1.6) and among those without: 1.07 (95% CI: 0.74 to 1.54). There were some baseline imbalances in the proportions of patients with ESS10. The average change from baseline in the proportion of those who had ESS 10 among those with severe OSA was 23% more in PAP (NIV or CPAP) group and 7% more in controls , and among those without severe OSA there was a decrease of 3% in those receiving NIV and did not change in controls [bib_ref] Noninvasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnea: A..., Masa [/bib_ref] i. One recent observational study with a control group (Bouloukaki 2018) observed patients with NIV and CPAP for 2 years and found similar probability of resolution of OHS in both groups, but the results were not adjusted for baseline differences (NIV was used only in those in whom "oxygen desaturation persisted after obstructive apneas and hypopneas had been eliminated with CPAP"): 114/141 (80.9%) with NIV and 70/84 (83.3%) with CPAP; RR 0.97, 95% CI: 0.86 to 1.10; RD: 25 fewer per 1,000, 95% CI: from 117 fewer to 83 more). j. One study was not blinded and the other did not report the methodology in sufficient detail to assess risk of bias. k. Assuming that MID would be ~2-3 points, the CI does not exclude an appreciable benefit with NIV or no difference. l. One recent observational study with a control group (Bouloukaki 2018) observed patients with NIV and CPAP for 2 years and found slightly lower probability of resolution of daytime sleepiness with NIV compared to CPAP, but the results were not adjusted for baseline differences (NIV was used only in those in whom "oxygen desaturation persisted after obstructive apneas and hypopneas had been eliminated with CPAP"): 133/141 (94.3%) with NIV and 84/84 (100.0%) with CPAP; RR 0.95, 95% CI: 0.90 to 0.99; RD: 5 fewer per 100, 95% CI: from 1 fewer to 10 fewer). m. Results were not adjusted for baseline differences (NIV was used only in those in whom "oxygen desaturation persisted after obstructive apneas and hypopneas had been eliminated with CPAP") and 8% were lost to follow-up. n. Assuming that MID would be ~20 to 40 m, the CI does not exclude an appreciable benefit with NIV or no difference. o. One recent observational study with a control group (Bouloukaki 2018) observed patients with NIV and CPAP for 2 years found that the probability of not requiring supplemental O2 was similar in both groups, but the results were not adjusted for baseline differences (NIV was used only in those in whom "oxygen desaturation persisted after obstructive apneas and hypopneas had been eliminated with CPAP"): 137/141 (97.2%) with NIV and 84/84 (100.0%) with CPAP; RR 0.97, 95% CI: 0.94 to 1.01; RD: 3 fewer per 100, 95% CI: from 6 fewer to 1 more). p. see description of results q. Only 169 patients which likely does not meet optimal information size.
[formula] Resolution of OHS -not reported - - - - - - - - - - - - CRITICAL Motor vehicle accidents -not measured - - - - - - - - - - - - CRITICAL Quality of life -not measured - - - - - - - - - - - - CRITICAL Daytime sleepiness -not reported - - - - - - - - - - - - CRITICAL Cardiovascular events -not reported - - - - - - - - - - - - CRITICAL Hospitalization -not reported - - - - - - - - - - - - [/formula]
CRITICAL CI: Confidence interval; OR: Odds ratio; RD: Risk difference Explanations a. Analysis of individual patient data from several single-arm studies or individual arms of comparative studies; we were not able to obtain data from 1 study [bib_ref] Obesity-associated hypoventilation in hospitalized patients: Prevalence, effects, and outcome, Nowbar [/bib_ref] ; we did not perform an individual patient data meta-analysis for this guideline but we assumed that given the scarcity and limitations of the source data the results would be similar and not more certain. b. This was an indirect comparison across several single-arm studies. We did not lower the certainty of evidence for this reason because it has already been very low and the analysis attempted to account for that (IPD). c. There were few events in total which do not meet the optimal information size; the confidence interval in the adjusted analysis did not exclude both benefit and small harm. d. Analysis was adjusted for age, sex and baseline PaCO2. d. Analysis was adjusted for age and sex. Evidence table E5: Should a weight loss intervention or no such intervention be used for adults with OHS?
[table] table E2: Should adults with OHS be treated with positive airway pressure (PAP)-either continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV)-or not be treated with PAP? CI: Confidence interval; MD: Mean difference; RR: Risk ratio; OR: Odds ratioExplanations a. Studies were not blinded and other risk of bias criteria was suboptimally reported. b. No events c. Series of cases; no direct comparison with a control group d. Studies reported mortality between 4% and 36%; we were not able to explain it with duration of observation, patient age, or severity of disease. e. Confidence interval does exclude an appreciable benefit with PAP or small and likely negligible difference. f. CI does not exclude an appreciable benefit or almost no difference. [/table]
[table] table E3: Should adults with OHS be treated with CPAP or with NIV? Daytime sleepiness (assessed with: change from baseline in Epworth Sleepiness Scale (range of scores: 0-24; lower score is better; MID ~2-3 points)) 5 CI: Confidence interval; RR: Risk ratio; SMD: Standardised mean difference; MD: Mean difference; PSQI: Pittsburgh Sleep Quality Index; *: Adjusted for age, sex, smoking habits and forced vital capacity. One recent observational study with a control group (Bouloukaki 2018) observed patients with NIV and CPAP for 2 years and found similar risk of death in both groups, but the results were not adjusted and very imprecise (7/141 with NIV and 4/84 with CPAP, RR: 1.04, 95% CI: 0.31 to 3.46, RD: 2 more per 1,000, 95% CI: from 33 fewer to 117 more). e. Confidence interval does not exclude an appreciable benefit with either intervention compared to the other. f. Confidence interval does not exclude a small additional benefit with either intervention compared to the other. g. One relatively small study reported results as median and IQR --if this study were not included in analysis the SMD would [/table]
[table] table E4: Should hospitalized adults suspected of having OHS, in whom the diagnosis has not yet been confirmed, be discharged from hospital with or without PAP treatment while awaiting confirmation of the diagnosis? [/table]
[table] Table E5A: Laparoscopic adjustable gastric banding (LAGB) compared to intensive nutritional care in patients with OHS a Resolution of OHS (follow up: 3 years; assessed with: weaning from NIV) Apnea-hypopnea index (AHI) (follow up: 1 years; assessed with: change from baseline of 52 episodes/h) CI: Confidence interval; RR: Risk ratio; MD: Mean difference 1. Feigel-Guiller B, Drui D, Dimet J, Zair Y, Le Bras M, Fuertes-Zamorano N, et al. Laparoscopic gastric banding in obese patients with sleep apnea: A 3-year controlled study and follow-up after 10 years. Obes Surg 2015;25:1886-1892. [/table]
[table] Table E5B: Gastric bypass compared to no bariatric surgery in patients with OHS Average weight loss: -50 kg (95% CI: 39 to 60) from baseline 155 kg in 30 patients (Sugerman 1986) -44 kg (95% CI: 33 to 55) from baseline 163 kg in 38 patients (Sugerman 1992) Pulmonary artery pressure (follow up: 3-6 months) Pulmonary artery pressure fell on average 13 mm Hg (95% CI: 5.8 to 20.2) from baseline 36 mm Hg  VERY LOW IMPORTANT CI: Confidence interval; MD: Mean difference Explanations a. Series of cases; no direct comparison with a control group b. Only 2 events among 29 patients c. Based on "improved or cured" but definition not provided. d. Only 29 patients. [/table]
[table] Table E5C: Biliopancreatic diversion with duodenal switch (BPD/DS) compared to no bariatric surgery in patients with OHS Resolution of OHS (follow up: 5-7 years) CI: Confidence interval Explanations a. Series of cases; no direct comparison with a control group b. Only 16 cases [/table]