Draft

117  Aspre Presention 1 Slides

117.1 Summary

  • Populations that may benefit from aggressive OSA case finding?
  • Acute Hypercapnic Respiratory Failure
  • No RCTs have addressed this question
  • Post-AECOPD trials
  • Timing of NIV: COPD vs OHS
  • Admitted to hospital (Floor or ICU) with ABG showing PaCO2 over 45 mmHg and pH 7.35-7.45
  • Do NOT start at hospitalization
  • Resmed & Inovalon Insights, LLC payor claims database: 6810 pts with a COPD diagnostic code in the year before device set up
  • Critique of the Sufficient-Component Model
  • Consider this as a missing data problem? What is the propensity of p(ABG)?
  • CO2 Homeostasis: Factors Causing Frailty
  • Predispositions to Exacerbations

117.2 Slide outline

117.2.1 Slide 1

  • TODO: No text extracted from this slide. ### Slide 2
  • Populations that may benefit from aggressive OSA case finding?
  • Cardiovascular disease prevention: patient selection and/or effect size?
  • Cognitive outcomes? Cancer outcomes? Developing
  • Ventilatory Failure: very high rate of unrecognized disease; very high risk of readmission; preliminary data of effectiveness in some subgroups
  • Data (Overlap) [ ] find Paper
  • Need: characterize comorbidity profiles, what physiologic endotypes are present, and which features predict risk or treatment response. ### Slide 3
  • 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 4
  • 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 5
  • 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 6
  • 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 7
  • Admitted to hospital (Floor or ICU) with ABG showing PaCO2 over 45 mmHg and pH 7.35-7.45
  • Collider bias ### Slide 8
  • Do NOT start at hospitalization
  • wait 2-4 weeks to see if acute on chronic becomes chronic.
  • In-lab PSG not recommended for pure-COPD; attempt to normalized pCO2.
  • AVAPS not better than PS ### Slide 9
  • 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 10
  • Critique of the Sufficient-Component Model
  • Consider PKU: Genetic defect causes disease when phenylalinine consumed.
  • -> in practice, everyone eats phenylalinine: genetic attributable fraction 100%
  • -> however, modification of diet avoids development. Thus, if phenylalanine consumption varies then environment contributes
  • Consider, the hypothetical world where everyone has the PKU gene, but phenylalanine varies (lower diagram) – then, the disease is ALL environmental.
  • what is the relationship to mendelian randomization?
  • -> population attributable fraction (and percent variance explained) is not generalizable, and changes as covariates change. Applied to Hypercapnia? ### Slide 11
  • Consider this as a missing data problem? What is the propensity of p(ABG)?
  • Could P(ABG) – by provider ideall (or institution) work as an instrument? (to wiggle the likelihood of a diagnosis… could you test that? Are high p(ABG) environments or providers more likely to apply the diagnosis?
  • CO2 Homeostasis: Factors Causing Frailty
  • High ventilatory need:
  • Increased CO2 Production
  • Increased Deadspace ‘Wasted Vent’
  • Low desired PaCO2
  • Fever, Infection, or Inflammation
  • Advanced malignancy
  • Muscle activity
  • Seizures
  • Exercise
  • ↑↑ Work of breathing
  • Toxic ingestion
  • Obesity
  • Anatomic
  • shallow breathing
  • Physiologic
  • Pulmonary embolism
  • Pulmonary hypertension
  • Congestive heart failure
  • Parenchymal lung disease of any kind
  • Metabolic acidosis
  • Hypoxia
  • Unable to breathe:
  • Muscle weakness or inefficiency
  • Increased respiratory system loads
  • Neuromuscular disease
  • Lung Hyperinflation
  • Respiratory muscle hypoxia
  • Elevated airway resistance
  • COPD, Asthma
  • Mucus
  • Upper-airway obstruction
  • Stiff Lungs
  • Parenchymal lung disease
  • Pulmonary edema
  • Stiff Chest Wall
  • Pleural disease
  • Excess or stiff chest wall tissue
  • Decreased Drive to Breathe:
  • Opiates and other sedatives
  • Brainstem lesions
  • Compensated hypercapnia
  • Sleep
  • Metabolic alkalosis
  • Red OHS, as an example ### Slide 13
  • Predispositions to Exacerbations
  • Parabola assumes constant production of CO2 and efficiency of the lung
  • As Ventilation drops, each further drop causes proportionally more CO2 accumulation.
  • Analogous to creatinine & GFR ### Slide 14
  • PAO2 FiO2 (PB-47)—(PaCO2/R)  O2 17.8 mmHg lower at 4500ft
  • Hypercapnia in SLC
  • SpO2 is routinely obtained in clinical practice, PaCO2 (or TcCO2) is not
  • SLC  earlier identification ### Slide 15
  • Hypotheses: on first (physiologic) principles
  • Many will have the first time they manifest respiratory frailty during an exacerbation
  • This group will be at high risk for repeat exacerbations
  • Major source of morbidity, mortality, and cost to the system
  • Interventions to reduce frailty or physiologic stressors may reduce exacerbations
  • Better evidence is needed to support these practices to streamline payor funding
  • If many of these patients are missed during presentation, or proper management is not instituted, this is a lost opportunity. ### Slide 16
  • Cohort Definitions Identified in the Literature
  • Study
  • Definition Used
  • Aim
  • Thille et al 2017 https://doi.org/10.1007/s00134-017-4998-3
  • ICU; pH<7.35 & PaCO2 45+; treated with NIV or IMV; survivors
  • What is the rate of undiagnosed OSA among survivors?
  • Ouanes-Besbes et al. 2021, Tunisia PubMed: 33171053
  • Admitted to ICU 2015-2018, PaCO2 > 6kpa, pH < 7.35. No prior OSA syndrome diagnosis.
  • Prev of undx’d OSA
  • Wilson et al., 2021. USA (Michigan) PubMed: 33951397
  • 18+, hospitalized w/ ABG showing CO2 over 45 and pH 7.35-7.45
  • Outcomes of compensated hypercap
  • Cavalot et al 2021, Toronto https://doi.org/10.1080/15412555.2021.1990240
  • ABG with pH < 7.35 and PaCO2 > 45 mmHg OR VBG pH 7.34 and PvVO2 > 50 mmHg & presence of respiratory symptoms (CEDIS codes). Exclude CF, NM dz, ILD, thoracic dz, lung ca, CNS dz, Overdose, or trach
  • 1 yr readmission rate
  • Adler et al. 2016, Switzerland DOI: 10.1164/rccm.201608-1666OC
  • Recruited at ICU discharge after surviving: primary admission for Resp failure, PaCO2 over 6.3 kpa and requiring NIV or IMV
  • What are the comorbidities in survivors?
  • Meservey et al 2020. USA (Vermont) https://doi.org/10.1007/s00408-019-00300-w
  • 18 y/o+ admitted (either ICU or floor) with diagnostic code for hypercapnic respiratory failure
  • What features of patients admitted for hypercapnic respiratory failure predict readmission?
  • Bulbul et al. 2014. Turkey.
  • doi: 10.4103/1817-1737.128851
  • Hospitalized adults with PaCO2 over 45, no acidosis, and breathing room air
  • What comorbidities occur with inpatient, compensated hypoventilation
  • Marik 2016. USA (Virginia)
  • DOI: 10.1002/osp4.27
    1. age 18-90 (ii) a BMI ≥ 40 kg m−2; (iii) a daytime PaCO2 > 45 mmHg and (iv) an admission HCO3 > 28 mEq L−1. Exluded: (i) intrinsic lung disease, (ii) thoracic MSK/NMD (iii) 20+ pack year smoking, COPD
  • What is the prevalence of undiagnosed Obesity Hypoventilation among hospitalized adults?
  • Chung et al, AUS, 2021 DOI: https://doi.org/10.1164/rccm.202108-1912LE
  • Identified by initial ABG PaCO2 over 45, excluded iatrogenic causes/sedation.
  • What is the population prevalence of hypercapnia from any cause
  • Vonderbank et al 2020 – Germany
  • https://doi.org/10.2147%2FOAEM.S242075
  • All patients with dyspnea or pulm disease admitted to hospital received capillary blood gas (some screening with VBG). Hypercapnia PaCO2 45 mmHg.
  • Is hypercapnia predictive of mortality at a specialty hospital? ### Slide 17
  • Gap
  • Clinical impression suggests that patients admitted with hypercapnia are a clinically heterogenous group, but few multi-center descriptions exist.
  • It is not clear if physiologically important subgroups (e.g. high-drive to breathe vs low; ventilatory failure vs hypercapnic respiratory success) can be discriminated on the basis of data elements in the EHR
  • A variety of methods have been used in prior studies, generally using blood gas-based assessments, diagnostic-codes, procedure codes for ventilation, or some combination of these.
  • However, it is not clear if the methods that have used these criteria select similar groups of patients, or if they select representative patients.
  • This is a problem for interpreting the meaning of findings

117.3 Learning objectives

  • Populations that may benefit from aggressive OSA case finding?
  • Acute Hypercapnic Respiratory Failure
  • No RCTs have addressed this question
  • Post-AECOPD trials
  • Timing of NIV: COPD vs OHS

117.4 Bottom line / summary

  • Populations that may benefit from aggressive OSA case finding?
  • Acute Hypercapnic Respiratory Failure
  • No RCTs have addressed this question
  • Post-AECOPD trials
  • Timing of NIV: COPD vs OHS

117.5 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.

117.6 Red flags / when to escalate

  • TODO: List red flags that require urgent escalation.

117.7 Common pitfalls

  • TODO: Capture common errors or missed steps.

117.8 References

TODO: Add landmark references or guideline citations.

117.9 Slides and assets

117.10 Source materials