260  Sleep Gr Hypercapnia

260.1 Summary

• Claim Credit Code: “24658”
• Why should inpatient hypercapnia matter to outpatient providers?
• Roadmap & Learning Goals
• Hypercapnic Respiratory Failure
• Causes of Hypercapnic Respiratory Failure
• How common is outpatient hypercapnia?
• Guidelines
• COPD
• How often do patients fall into a group with evidence-based of treatment?
• How common are admissions with hypercapnia?
• Support for frailty framework
• Acute Exacerbations: guidance for inpatient management

260.2 Slide outline

260.2.1 Slide 1

• Claim Credit Code: “24658”
• Three ways to claim credit:
• Via the CloudCME App
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• The evaluation for today’s RSS is available on the CloudCME App under “My Evaluations.”
• “Sleep Grand Rounds”
• “February 1, 2023” ### Slide 2
• Why should inpatient hypercapnia matter to outpatient providers?
• Brian Locke MD
• 3rd Year PCCM Fellow
• NIH T32 Research Fellow
• Masters of Science in Clinical Investigation Student
• ATS ASPIRE 2022—24 Fellow
• Disclosures: research support from the National Institutes of Health under Ruth L. Kirschstein National Research Service Award 5T32HL105321 and the American Thoracic Society ASPIRE program (supported by ResMed, Philips Respironics, and Fisher & Paykel). ### Slide 3
• Roadmap & Learning Goals
• What is hypercapnic respiratory failure?
• What guidelines say to do with hypercapnic respiratory failure?
• Goal: Understand limitations on current guidelines to the management of all-comers with hypercapnic respiratory failure.
• Who gets hypercapnic respiratory failure?
• Goal: What is known and unknown about the role of obesity and OSA
• Current Research
• How could we do it better? ### Slide 4
• Hypercapnic Respiratory Failure
• Build up here CO2 in blood rises
• Definition: Higher PaCO2 in the blood than it should be
• Cause: not enough alveolar ventilation for CO2 production
• Near synonyms:
• Ventilatory Failure
• Type 2 Respiratory Failure
• Hypoventilation
• Hypercapnia
• Except for REM sleep, our bodies keep PaCO2 within 3-5 mmHg despite huge changes in CO2 production ### Slide 5
• Causes of Hypercapnic Respiratory Failure
• Mechanisms:
• Decreased drive to breathe (OHS, Opiates)
• Increase need for ventilation (Obesity)
• Inefficient pulmonary function (Lung diseases)
• Muscle or inefficient weakness (NMD, COPD)
• Increased respiratory system loads
• Airway resistance (OSA, COPD)
• Stiff lungs or chest wall (Obesity)
• Frailty:
• Achievable ventilation ~ Acquired ventilation
• Drive to breathe is not stable / reliable
• Achievable Ventilation
• Required Ventilation ### Slide 6
• How common is outpatient hypercapnia?
• There is 0 data on prevalence of outpatient all-cause hypercapnia.
• Why? Fewer data sources, ABGs are invasive, less morbid population
• Based on low identification rates; still high NIV prescription: OHS is probably most common
• Fermi Estimate of Prevalence: 1 in 260 US adults
• 7.6% of adults US population BMI 40+
• Rate of mod+ OSA in BMI 40+ ~ 50%
• Rate of OHS in mod+ OSA ~10% ### Slide 7
• Guidelines
• Body mass index above 30 kg/m2
• Awake PaCO2 above 45 mmHg at sea level
• Exclusion of other causes of hypoventilation ### Slide 8
• COPD
• 13 RCTs; NIV vs std care
• Mortality risk: RR, 0.86; 95% CI, 0.58 to 1.27;
• Decrease in hospitalizations: mean difference, 1.26 fewer; 95% CI, 2.59 fewer to 0.08 more hospitalizations
• Improved QOL: standard MD [SMD], 0.48; 95% CI, 0.09 to 0.88
• improvement in dyspnea SMD, −0.51; 95% CI, −0.95 to −0.06 ### Slide 9
• TODO: No text extracted from this slide. ### Slide 10
• How often do patients fall into a group with evidence-based of treatment?
• Cause
• Treatment
• Outcome Improved
• LOE (Cochrane or ATS)
• Criteria (Resmed)
• Restrictive Thoracic Dz
• NIV
• Hospitalization, Mortality
• Meta-analysis of 3+ 3(mixed) RCTs
• Low
• ABG w/ PaCO2 over 45
• Sleep oximetry SpO2 < 88%
• OHS
• CPAP or BiPAP
• CO2, O2, ED visits, and mortality.
• Meta-analysis 3 RCTs , 12 nonrandomized studies, Low
• CPAP: Sleep study
• BiPAP: PaCO2 awake > 45 mmHg and FEV1 > FVC 70%
• COPD
• CO2, Hospitalization, QOL, dyspnea
• Meta-analysis of 14 RCTs
• Moderate
• PaCO2 over 45 or 52
• Sleep oximetry SpO2 < 5 minutes on 2L or usual O2
• OSA excluded or CPAP tried
• 2-4 weeks recovery from exac.
• Neuromuscular Dz
• Meta-analysis of 4+3 (mixed) RCTs
• MIP < 60cmH2o or FVC < 50%
• few trials of patient important outcomes in overlap syndromes have been done. ### Slide 11
• How common are admissions with hypercapnia?
• 2022: Liverpool AUS, 1 regional hospital services the entire district
• Identified by initial ABG (w/n 24h) PaCO2 over 45, excluded iatrogenic causes/sedation. N891 people, 1135 blood gasses (repeat hosp.)
• Normalized rates of hypercapnia to population demographics
• 150 per 100,000 person/year
• Acidosis in 55%.
• For Comparison: ### Slide 12
• Support for frailty framework
• Compared to Age 45-54:
• RR 55-64: 2.1
• RR 65-74: 6.2
• RR 75-84: 15.7
• RR 85-94: 26.2
• Frailty:
• Achievable ventilation ~ Acquired ventilation
• Drive to breathe is not stable / reliable ### Slide 13
• Acute Exacerbations: guidance for inpatient management
• NIV: Well Supported
• Acute outcomes are very good
• What we do after the inpatient admission is the unresolved question.
• More subsequent data supporting these indications ### Slide 14
• Post-exacerbation Management: OHS
• 30-70% of cases are diagnosed during an acute exacerbation (ERS) ### Slide 15
• No RCTs have addressed this question
• 10 observational studies (3 studies of hospitalized cohorts, 6 with hospitalized subgroups); serious risk of bias.
• “After adjusting for age, sex, and baseline PaCO2, the odds ratios (ORs) for [90-day] mortality were significantly lower in the group discharged on PAP (adjusted OR, 0.16; 95% CI, 0.08–0.33)” ### Slide 16
• TODO: No text extracted from this slide. ### Slide 17
• Inpatient Diagnostic Pathway for S.D.B. w Hypoventilation
• “Because arterial blood gas (ABG) was not available on all patients, we utilized a broad definition of hypoventilation defined as ABG during index admission with partial pressure of carbon dioxide (PCO2) ≥ 45 mmHg or end-tidal CO2 (ETCO2)/transcutaneous CO2 (TCCO2) during PSG ≥ 50 mmHg for at least 10 minutes”; inpatient sleep study requested by medicine team or pulm/cards consult.
• Retrospective Review
• Most frequently OHS or HFpEF
• Admitted with CHF exac, COPD exac, or other
• 90-day readmission was 19.5% in patients who were adherent to PAP therapy vs 55.5% in nonadherent patients (a 65% reduction). 20 of 45 (44.4%) excluded patients with hypoventilation had 90-day readmission.
• Minimal matching and control for healthy adherer bias ### Slide 18
• Do NOT start at hospitalization
• wait 2-4 weeks to see if acute on chronic becomes chronic.
• In-lab titration PSG not recommended for pure-COPD; attempt to normalize daytime pCO2.
• AVAPS not better than PS ### Slide 19
• Post-AECOPD trials
• Mode: BPAPS/T
• Driving pressure
• Timing of start after acute exacerbation
• RESCUE vs HOT-HMV
• (Not Post Exacerbation)
• Many in control resolved hypercapnia
• 21% excluded at 2-4 weeks. ### Slide 20
• Acute Hypercapnic Respiratory Failure
• Recurrent Hypercapnic Respiratory Failure
• Chronic Hypercapnia
• Acute on Chronic Hypercapnic Respiratory Failure
• Hypercapnia Trajectories
• Hypercapnia
• Normalization of Hypercapnia
• Normal CO2 on labs
• Hypercapnia on labs
• Increasing CO2
• Assessment 1
• Assessment
• 2
• Assessment 3
• Common: COPD
• Common: OHS
• PaCO2 at discharge (not HCO3), Severity classification are associated with persistence (DOI: 10.1159/000524845)
• High PaCO2 and Prior Acute NIV predict recurrence (DOI: 10.1111/resp.12652) ### Slide 21
• Timing of NIV: COPD vs OHS
• “Guidelines for chronic hypercapnic COPD recommend a 2- to 4-week recovery period following hospitalization for COPD exacerbation before assessing for noninvasive ventilation to confirm that chronic hypercapnia is persistent (eg, PaCO2 ≥ 52 mm Hg)”
• This recommendation is derived from the fact that 21% of patients with COPD recruited for the Home Oxygen Therapy-Home Mechanical Ventilation (HOT-HMV) trial were excluded because the hypercapnia on discharge resolved after 2 to 4 weeks.
• Conversely, the guidelines for OHS suggest hospitalized patients with OHS be continued on PAP therapy following hospital discharge until they undergo polysomnography, ideally within the first 3 months of discharge.6
• This recommendation is driven by a mortality difference at 3 months postdischarge between patients with OHS discharged without PAP (16.8%) and with PAP (2.3%).14 ### Slide 22
• COPD, Very Severe
• PaCO2 52 mmHg
• BMI 45 kg/m2
• AHI 50 event/hr
• PaCO2 50 mmHg
• COPD, mod severe
• AHI 50 events/hr
• AHI 10 events/hr
• Met. Alk loop diur
• Trial Data
• Decent Epi
• Few Cohorts
• Some Epi
• No tx data
• Limited epi data
• Swap any combination of:
• Muscular weakness
• Obesity
• Opiate use
• Lung disease
• Etc.
• ??? ### Slide 23
• Who are “all-comers with inpt hypercapnia”?
• Liverpool AUS: ABG w/n 24h of admission.
• Diagnostic codes: 52% Charlson Comorbidity 5+; Prevalence-based estimates: NMD under-represented
• Chung Y, Garden FL, Marks GB, Vedam H. Causes of hypercapnic respiratory failure and associated in-hospital mortality. Respirology. 2022
• All adult ED visits @ single Toronto ED w ABG <7.35/45+ OR VBG <7.34/50+ & CEDIS resp code for resp symptoms. Charts reviewed for 12 months.
• Giulia Cavalot, Vera Dounaevskaia, Fernando Vieira, Thomas Piraino, Remi Coudroy, Orla Smith, David A. Hall, Karen E. A. Burns & Laurent Brochard (2021) One-Year Readmission Following Undifferentiated Acute Hypercapnic Respiratory Failure, COPD: Journal of Chronic Obstructive Pulmonary Disease, 18:6, 602-611
• All patients with dyspnea or pulm disease admitted to hospital received capillary blood gas (some screening with VBG). Stratified by pH > 7.35 or pH < 7.35
• Hospital specializing in lung disease (unclear referral pattern):
• Vonderbank S, Gibis N, Schulz A, Boyko M, Erbuth A, Gürleyen H, Bastian A. Hypercapnia at Hospital Admission as a Predictor of Mortality. Open access emergency medicine : OAEM 2020; 12: 173-180. ### Slide 24
• Who gets on NIV?
• Registry of all patients: Lake Geneva area
• 2.5x increase from 2000 ’18
• Includes
• OVS
• Victoria, AUS & British Colombia, CA. ### Slide 25
• What does it matter?
• Only evaluated in-hospital outcomes
• Chung Y, Garden FL, Marks GB, Vedam H. Causes of hypercapnic respiratory failure and associated in-hospital mortality. Respirology. 2022
• Giulia Cavalot, Vera Dounaevskaia, Fernando Vieira, Thomas Piraino, Remi Coudroy, Orla Smith, David A. Hall, Karen E. A. Burns & Laurent Brochard (2021) One-Year Readmission Following Undifferentiated Acute Hypercapnic Respiratory Failure, COPD: Journal of Chronic Obstructive Pulmonary Disease, 18:6, 602-611
• 32% 1yr mortality.
• Vonderbank S, Gibis N, Schulz A, Boyko M, Erbuth A, Gürleyen H, Bastian A. Hypercapnia at Hospital Admission as a Predictor of Mortality. Open access emergency medicine : OAEM 2020; 12: 173-180.
• At one year, 150 patients (70.8%) were readmitted and 19 (9%) had died. ### Slide 26
• ↑ with PVD, active smoking, ILD and Bronchiectasis
• increased with compensation (bicarb 40-49 vs 20-29)
• Admissions with hypercapnia indicate high risk of morbidity; may be driven by treatable conditions ### Slide 27
• Admitted to hospital (Floor or ICU) with ABG showing PaCO2 over 45 mmHg and pH 7.35-7.45
• Collider bias ### Slide 28
• Sleep Disordered Breathing and Obesity?
• 5% dx’d obesity; 6% dx’d OSA
• Chung Y, Garden FL, Marks GB, Vedam H. Causes of hypercapnic respiratory failure and associated in-hospital mortality. Respirology. 2022
• Giulia Cavalot, Vera Dounaevskaia, Fernando Vieira, Thomas Piraino, Remi Coudroy, Orla Smith, David A. Hall, Karen E. A. Burns & Laurent Brochard (2021) One-Year Readmission Following Undifferentiated Acute Hypercapnic Respiratory Failure, COPD: Journal of Chronic Obstructive Pulmonary Disease, 18:6, 602-611
• 10.8% OSAS
• Vonderbank S, Gibis N, Schulz A, Boyko M, Erbuth A, Gürleyen H, Bastian A. Hypercapnia at Hospital Admission as a Predictor of Mortality. Open access emergency medicine : OAEM 2020; 12: 173-180.
• OSA/OHS – 19.3%
• Retrospective Reviews: mirrors what rate these are diagnosed (not what rate they present) ### Slide 29
• Why does this matter to sleep provider?
• COPD (66%)
• No COPD (33%)
• AHI Median
• [IQR]
• 31.9
• [14.3, 45.6]
• 66.0
• [48.0, 83.8]
• AHI > 15 present
• 66%
• 94%
• AHI > 30 present
• 51%
• 81%
• Excluded NMD, iatrogenic, or with persisting confusion
• 21% had been hospitalized in the last year for resp failure.
• Patients who were not treated for OSA had higher readmissions ### Slide 30
• Overall prevalence of OSA ( AHI > 30 ) in survivors over 50%
• & No prior OSA Dx ### Slide 31
• Our Research
• De-identified, patient-level data (not PHI, though recommended to be treated as such)
• Federated data from medical center EHRs
• Center for High Performance Computing protected environment
• We are only using cross-sectional (1-encounter) data
• Data Available
• Data unavailable
• Demographics
• Diagnosis
• Medications
• Procedures - what procedures were done. E.g. sleep study code
• Labs
• Cancer registry (NAACCR)
• Allergies
• Death Recoreds (in progress)
• Some notes
• Diagnostic reports
• DICOM image objects
• Providers
• Departments/clinics ### Slide 32
• Data Request
• Age > 18; Admission between 1-1-2018 and 9-28-2022
• An ICD code for Hypercapnic RF; ABG calendar day of admission with PaCO2 over 45 mmHg.
• Dataset: 925,512 patients from 70 Healthcare organizations
• 80+ gb of data; 1.2 Billion ‘facts’ in medications alone.
• Exclude: entries where any data element (demographics, lab tests, diagnostic codes, procedure codes, medications, vital signs) is empty to ensure complete data.
• Exclude: all repeat admissions ### Slide 33
• Patients:
• n118,981 first hypercapnia admission
• ~60% have ABGs; 35% have VBGs. 99%+ have BMPs, CBCs
• Vital signs: 80% with BP, 30% with RR charted
• Total
• ABG Group
• ICD Group
• N118,981
• N80,178
• N35,517
• Age
• 64 (±14)
• Female?
• 47% (55,838)
• 45% (36,056)
• 51% (18,219)
• Asian
• 1% (1,170)
• 1% (839)
• 1% (311)
• Black
• 22% (25,755)
• 20% (16,195)
• 25% (8,928)
• Native American / Alaska Native
• 0% (338)
• 0% (194)
• 0% (135)
• Native Hawaiian / Pacific Islander
• 0% (87)
• 0% (51)
• 0% (34)
• White
• 71% (84,585)
• 72% (57,988)
• 68% (24,190)
• Latino
• 3% (3,211)
• 3% (2,053)
• 3% (1,095)
• Location
• midwest
• 17% (20,797)
• 16% (13,137)
• 18% (6,492)
• northeast
• 30% (35,937)
• 32% (25,348)
• 30% (10,556)
• south
• 50% (58,988)
• 51% (41,087)
• 45% (15,918)
• west
• 3% (3,259)
• 1% (606)
• 7% (2,551) ### Slide 34
• Comorbidities
• 74,977 of 118,981 (63%) have at least 1 of: COPD, CHF, OSA
• 35% have OSA
• 17% Asthma; 33% nicotine dependence
• 5% NMD; 6% OUD; 8% dementia ### Slide 35
• Inpatient Management
• 56% have critical care services billed
• 24% have a TTE performed; 17% have a CT of the chest
• 52% with acidemia (<7.35 pH); higher likelihood of critical care (OR 1.77)
• CHF (OR 0.82) and OSA (OR 0.93) less likely academic
• More preventable?
• COPD (OR 1.16), CKD (1.21), and OUD (1.10) more likely ### Slide 36
• Who do guidelines apply to?
• Based on diagnostic codes present
• ATS OHS Guideline (2019): 28,337 (24%)
• ATS COPD NIV Guideline (2020): 17,960 (15%)
• Neither guideline: 61% ### Slide 37
• Limitations and next steps
• All single-encounter data due to data quality
• Will look at intubation and NIV inpt rates; hopefully LOS
• Can’t evaluate readmissions, mortality, outpatient management.
• Data quality: contingent on local practices (hard to assess)
• Next Steps
• Will evaluate how cohort definitions differ (last year’s Sleep GR)
• Will characterize patients using clustering: ?identify useful endotypes
• Request expanded data-set including patients without hypercapnia to evaluate features that correlate with presence of hypercapnia. ### Slide 38
• Roadmap & Learning Goals
• What is hypercapnic respiratory failure?
• What guidelines say to do with hypercapnic respiratory failure?
• Goal: Understand limitations on current guidelines to the management of all-comers with hypercapnic respiratory failure.
• Who gets hypercapnic respiratory failure?
• Goal: What is known and unknown about the role of obesity and OSA
• Current Research
• How could we do it better? ### Slide 39
• All-comers with Decompensated Hypercapnia?
• “For non-COPD patients recovering from an episode of AHRF, a referral to a home ventilation service for assessment of ‘domiciliary NIV use’ has been recommended, while continuing ‘nocturnal NIV’ till to the accomplishment of the evaluation.
• “Good practice point”, not recommendation based on empiric data
• What about other management strategies? (Acetazolamide, vascular congestion management, pulmonary rehab… ) ### Slide 40
• Medicare Nationwide Readmissions Database 2010-2016: 1.6 million COPD admissions
• 71% of readmission risk from obesity was attributable to OSA.
• Critique: correlative methods, no severity ### Slide 41
• Resmed & Inovalon Insights, LLC payor claims database: 6810 pts with a COPD diagnostic code in the year before device set up
• Matching: sex, comorbidities, COPD-related HC usage in prior year
• Propensity score for CPAP adherence
• Outcomes: ↓ER Visit and Hospitalizations
• Critique: healthy adherer bias ### Slide 42
• N32 RCT: BPAP-S vs CPAP
• Patients: OSA (AHI 59), BMI (43), PAP Naïve, No NMD, and COPD/Obst (FEV1 48% pred)
• 80% Power to detect 𝚫7 mmHg PaCO2 at 3 months
• Avg 15.8/9.7 BPAP; 12.7 CPAP
• Better spiro and SF-36 cog in BPAP group, but not powered for that ### Slide 43
• What do we do about the multiple component cause folks?
• Generalize? But does this work?
• “This patient is mostly OHS”  BiPAP or CPAP immediately
• “This patient is mostly COPD”  wait 2-4 weeks before NIV
• “Off-label”: can do for medications
• Payors? They want evidence to pay for machines ### Slide 44
• Leaky Pipeline from admission to treatment
• Presentation With Hypercapnia
• Hypercapnia is common, highly morbid, and likely increasing in frequency
• Correctly Recognized?
• Causes Correctly Diagnosed?
• Is there data to guide treatment?
• Is it logistically possible?
• Does it happen?
• Inpt Hypercapnia is frequently missed in practice
• Many patients do not receive definitive testing
• We don’t know what to do for many (most?) patients with hypercapnia
• Device qualification restrictions.
• Requires coordination between Inpt  Outpt. Consider CHF (CMS f/u after discharge)
• Marik, JICM 2012: 75% error rate.
• SDB: 30% vs 60-75%
• No good estimate ### Slide 45
• What is ‘hypercapnic respiratory failure’?
• Problems with PaCO2 > 45 mmHg (sea-level, current def)
• 97.5 Percentile of ‘normal’?
• “Hypercapnic respiratory failure is a syndrome”
• Syndrome (Greek: ‘con-currence’) a set of signs and symptoms that together suggest a common cause.
• Yet PaCO2 Lab finding (hypercapnia). Gap?
• If there is no agreed-upon reference standard test: perhaps ‘construct’ is a better term.
• 2 instrumental uses:
• Classification: e.g. “Hyperlipidemia”
• Prediction: “10-y ASCVD risk”
• Ideal Definition:
• Who is at risk for future/ongoing ventilatory failure?
• Who will respond to treatments? ### Slide 46
• Research Aims:
• Who are these patients with hypercapnic respiratory failure?
• How should we best identify patients with hypercapnia? (for study, and in practice)
• Where are the biggest gaps in management knowledge? ### Slide 47
• Roadmap & Learning Goals
• What is hypercapnic respiratory failure?
• What guidelines say to do with hypercapnic respiratory failure?
• Goal: OHS – CPAP/BPAP; ↑CO2 COPD – wait 2-4wks exac, high PIP NIV
• Goal: Unclear what to do with multifactorial-cause hypercapnia
• Who gets hypercapnic respiratory failure?
• Goal: Often multi-morbid. These patients have high utilization/mortality
• How could we do it better?
• Goal: Need better data to guide decisions
• Goal: Need better systems of care ### Slide 48
• Links
• Guidelines:
• ATS OHS (2019)
• ATS NIV COPD (2020)
• Questions?
• brian.locke@hsc.utah.edu

260.3 Learning objectives

• Claim Credit Code: “24658”
• Why should inpatient hypercapnia matter to outpatient providers?
• Roadmap & Learning Goals
• Hypercapnic Respiratory Failure
• Causes of Hypercapnic Respiratory Failure

260.4 Bottom line / summary

• Claim Credit Code: “24658”
• Why should inpatient hypercapnia matter to outpatient providers?
• Roadmap & Learning Goals
• Hypercapnic Respiratory Failure
• Causes of Hypercapnic Respiratory Failure

260.5 Approach

1. TODO: Outline the initial assessment or decision point.
2. TODO: Outline the next diagnostic or management step.
3. TODO: Outline follow-up or escalation criteria.

260.6 Red flags / when to escalate

• TODO: List red flags that require urgent escalation.

260.7 Common pitfalls

• TODO: Capture common errors or missed steps.

260.8 References

TODO: Add landmark references or guideline citations.

260.9 Slides and assets

• Presentations/2023-1-27 Sleep GR Hypercapnia.pptx

260.10 Source materials

• Presentations/2023-1-27 Sleep GR Hypercapnia.pptx