Hypercapnic Respiratory Failure

Erik van Lunteren, M.D.

Outline

• Carbon Dioxide

• Causes of Hypercapnic Respiratory Failure

• Management of Hypercapnic Respiratory Failure

Carbon Dioxide

Carbon Dioxide: History• Discovered by Jan Baptista van Helmont around

1630 as the gas given off by burning wood, who called it sylvestre ("wood gas").

• Studied extensively by Joseph Black (1728–1799), who proved that carbon dioxide occurred in the atmosphere and that it could form other compounds. – He also identified carbon dioxide in the breath

exhaled by humans.

• First practical use of carbon dioxide was by Joseph Priestley (1733–1804) in the mid-1700s. Priestley found that by dissolving carbon dioxide in water he could produce a fresh, sparkling beverage with a pleasant flavor.

Properties of Carbon Dioxide

• Colorless• Odorless• Non-combustible• Density ~1.5 times

that of air

Pure carbon dioxide gas can be poured because it is heavier than air. (From www.scienceclarified.com)

Properties of Carbon Dioxide• Gas easily converted to solid (dry ice), which

goes directly back to gas phase at atmospheric pressure (sublimates)

Some Uses of Carbon Dioxide

• Carbonated soft drinks• Coolants and refrigerants• Fire extinguishers (especially for electrical and

oil fires, which can not be put out with water)• Retarding food spoilage• Propellant for guns

– BB guns– Paintball guns

• Lasers

Carbon Dioxide and Environment

• Carbon dioxide captures heat radiated from earth’s atmosphere

• Responsible for keeping the planet sufficiently warm to allow life

• Increasing concentrations of carbon dioxide are raising earth’s temperature

• One of the three most important “greenhouse” gasses

Atmospheric Concentrations of CO2

Carbon Dioxide Emissions

CO2 Air Pollution: Asthma

Hypercapnic Disorders: Definitions

Hypercapnia: PaCO2 ≥ 45 mm Hg

Hypercapnic respiratory failure: hypercapnia plus acidosis– Acute: no or minimal metabolic compensation– Chronic: appropriate metabolic compensation

Causes of Hypercapnic Resp. FailureNeural & Neuromuscular• Brain

– Drugs

• Motor neurons• Neuromuscular junction• Respiratory muscles

Chest Wall• Kyphoscoliosis• Ankylosing spondylitis• Flail chest

“Medical” Diseases• COPD• Severe asthma• Late stage interstitial lung

disease• Pulmonary edema• Sleep apnea / obesity-

hypoventilation• Hypothyroidism

Environmental

Iatrogenic

Causes of Hypercapnic Resp. FailureNeural & Neuromuscular• Brain

– Drugs

• Motor neurons• Neuromuscular junction• Respiratory muscles

Chest Wall• Kyphoscoliosis• Ankylosing spondylitis• Flail chest

“Medical” Diseases• COPD• Severe asthma• Late stage interstitial lung

disease• Pulmonary edema• Sleep apnea / obesity-

hypoventilation• Hypothyroidism

Environmental

Iatrogenic

Causes of Hypercapnic Resp. FailureNeural & Neuromuscular• Brain

– Drugs

• Motor neurons• Neuromuscular junction• Respiratory muscles

Chest Wall• Kyphoscoliosis• Ankylosing spondylitis• Flail chest

“Medical” Diseases• COPD• Severe asthma• Late stage interstitial lung

disease• Pulmonary edema• Sleep apnea / obesity-

hypoventilation• Hypothyroidism

Environmental

Iatrogenic

Causes of Hypercapnic Resp. FailureNeural & Neuromuscular

Brain– Drugs

• Motor neurons• Neuromuscular junction• Respiratory muscles

Chest Wall• Kyphoscoliosis• Ankylosing spondylitis• Flail chest

“Medical” Diseases• COPD• Severe asthma• Late stage interstitial lung

disease• Pulmonary edema• Sleep apnea / obesity-

hypoventilation• Hypothyroidism

Environmental

Iatrogenic

Causes of Hypercapnic Resp. FailureNeural & Neuromuscular• Brain

– Drugs

• Motor neurons• Neuromuscular junction• Respiratory muscles

Chest Wall• Kyphoscoliosis• Ankylosing spondylitis• Flail chest

“Medical” Diseases• COPD• Severe asthma• Late stage interstitial lung

disease• Pulmonary edema• Sleep apnea / obesity-

hypoventilation• Hypothyroidism

Environmental – Industrial, Natural

Iatrogenic - Drugs, Ventilators

Causes of Hypercapnic Resp. FailureNeural & Neuromuscular• Brain

– Drugs

• Motor neurons• Neuromuscular junction• Respiratory muscles

Chest Wall• Kyphoscoliosis• Ankylosing spondylitis• Flail chest

“Medical” Diseases• COPD• Severe asthma• Late stage interstitial lung

disease• Pulmonary edema• Sleep apnea / obesity-

hypoventilation• Hypothyroidism

Environmental – Industrial, Natural

Iatrogenic - Drugs, Ventilators

Neuromuscular Causes of Hypercapnic Respiratory Failure

• Skeletal Muscle Diseases– Some (but not all) of the Muscular Dystrophies

• Duchenne muscular dystrophy• Merosin-negative congenital muscular dystrophy• Myotubular myopathy 1 • Autosomal dominant distal myopathy• One of the autosomal recessive limb-girdle

muscular dystrophies– Myotonic Dystrophy– Polymyositis/dematomyositis

Neuromuscular Causes of Hypercapnic Respiratory Failure

• Neuromuscular Junction Disorders– Myasthenia gravis– Lambert Eaton myasthenic syndrome– Botulism– Organophosphate poisoning

• Motor Neuron Disorders– Amyotrophic lateral sclerosis– Guillain-Barre syndrome– Poliomyelitis– Spinal cord injury

Famous People & Motor Neuron Disorders • Guillain Barre

– Joseph Heller, Andy Griffith

• Polio vs Guillain Barre– Franklin D Roosevelt

• Polio– Sports: Jack Nicklaus– Acting/Movies: Alan Alda, Francis Ford Coppola, Mia Farrow– Musicians: Donovan, Joni Mitchell, Itzhak Perlman, David

Sanborn, Neil Young, Dmitri Shostakovich– Other: Arthur Guyton, Arthur C. Clarke

• Amyotrophic lateral sclerosis– Lou Gehrig, Lead Belly, Catfish Hunter– Stephen Hawking may have different type of motoneuron disease

• Spinal cord injury– Christopher Reeve

Most of information from Wikipedia

Iatrogenic Hypercapnia and Mechanical Ventilation

• Study of low vs conventional tidal volume / pressure mechanical ventilation for ARDS

• Much higher incidence of hypercapnia (pCO2 > 50 mm Hg) in low tidal volume / low pressure group

Stewart et al., NEJM 1998

Iatrogenic Hypercapnia and Mechanical Ventilation “Permissive Hypercapnia”• Study of low vs conventional tidal volume / pressure

mechanical ventilation for ARDS• Much higher incidence of hypercapnia (pCO2 > 50 mm

Hg) in low tidal volume / low pressure group

Stewart et al., NEJM 1998

Pickwickian Syndrome

Did Mr. Pickwick have:1. Sleep apnea with hypersomnolence2. Obesity-hypoventilation syndrome3. Both4. Neither

Pickwickian Syndrome

Little boy whowould alwaysfall asleep

Obesity Hypoventilation Syndrome(OHS)

• Definition– BMI > 30 kg/m2

– Awake arterial pCO2 > 45 mm Hg– No other causes for hypercapnia

OHS in Hospitalized Patients• Studied 4332 admissions to medical services• 277 (6%) were severely obese (BMI > 35 kg/m2)• OHS present in 31% with severe obesity

– Mean pCO2 of 52 ± 7 vs 37 ± 6 mm Hg in subjects with simple obesity

• When BMI > 50 kg/m2, prevalence OHS was 48%

Nowbar et al., Am J Med 2004

Dark bars OHS, light bars simple obesity

Outcome Following Discharge• Survival curves for patients with obesity-associated hypoventilation

or simple obesity after discharge from hospital• Adjusted for age, sex, body mass index, electrolyte abnormalities,

renal insufficiency, history of thromboembolism, and history of hypothyroidism.

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Prevalance OHS Among OSA• Obesity hypoventilation syndrome (OHS) among

subjects with obstructive sleep apnea (OSA)– Prevalence of 20-30%

• Predictors of OHS:– Serum bicarbonate level (P < 0.001)– Apnea hypopnea index (P = 0.006)– Lowest oxygen saturation during sleep (P < 0.001)

• Threshold bicarbonate level of 27 mEq/l:– Sensitivity 92%– Specificity 50%

Mokhlesi et al., Sleep Breath, 2007

US President with Probable OSA

He frequently fell asleep "in the middle of the day’s business -- at his desk, at a public affair, or while signing commissions.“ Publicly, he slept at the opera, at funerals, and, "invariably," in church. He fell asleep while playing cards, and while sitting upright in his car, even an open car on Fifth Avenue in New York City. On a cross-country drive "his great bulk would lunge from side to side as the car turned or jolted over street-car tracks and crossings, yet he would never wake.“ He could sleep while standing.

Who is this?

US President with Probable OSA

He frequently fell asleep "in the middle of the day’s business -- at his desk, at a public affair, or while signing commissions.“ Publicly, he slept at the opera, at funerals, and, "invariably," in church. He fell asleep while playing cards, and while sitting upright in his car, even an open car on Fifth Avenue in New York City. On a cross-country drive "his great bulk would lunge from side to side as the car turned or jolted over street-car tracks and crossings, yet he would never wake.“ He could sleep while standing.

Who is this?

US President with Probable OSA

He frequently fell asleep "in the middle of the day’s business -- at his desk, at a public affair, or while signing commissions.“ Publicly, he slept at the opera, at funerals, and, "invariably," in church. He fell asleep while playing cards, and while sitting upright in his car, even an open car on Fifth Avenue in New York City. On a cross-country drive "his great bulk would lunge from side to side as the car turned or jolted over street-car tracks and crossings, yet he would never wake.“ He could sleep while standing.

President Taft

How is this related to hypercapnic respiratory failure?

Lake Nyos, Cameroon

Limnic Eruption of Lake Nyos• Geology

– Deep lake high on an inactive volcano– Pocket of magma lies beneath its waters and leaks

carbon dioxide into the waters– Water in deep layers is supersaturated with carbon

dioxide

• August 1986, the lake released a large cloud of carbon dioxide in a limnic eruption– Deep water layers came to surface, and reduction in

pressure resulted in CO2 release– 1.6 million tons of CO2 were released

• Killed 1,746 people and up to 3,500 livestock– Mainly carbon dioxide, with traces of carbon sulfide,

hydrogen sulfide and sulfur dioxide

Long-Term Sequela from Lake Nyos

• Study compared 381 exposed with 128 non-exposed subjects

• No difference in frequency of dyspnea, cough, sputum

• No difference in peak expiratory flow

Danger of Repeated Episode

• Carbon dioxide levels have built up again to previous levels, so another limnic eruption could occur

• Natural dam holding lake in place is said to be weak, which could release deep supersaturated waters and cause carbon dioxide release

Degassing Lake Nyos

Management of Hypercapnia

• Is it acute or chronic or acute on chronic?• What is the underlying etiology?

• Treatment options

– Specific therapy for underlying cause

– No mechanical ventilation– Non-invasive mechanical ventilation– Invasive mechanical ventilation

Hypercapnic Respiratory FailureEarly Treatment Modalities

Severinghaus et al,Am J Resp Crit Care Med 157: S114-S122, 1998

Polio EpidemicDenmark,1952

Polio -- Iron Lung Ward – 1950’s

Rancho Los Amigos Hospital

Mechanical Ventilation for Acute Hypercapnic Respiratory Failure

• Intubation with conventional mechanical ventilation

• Non-invasive positive pressure ventilation (NPPV)

Selection criteria (at least two should be present)

• Moderate to severe dyspnea with use of accessory muscles and paradoxical abdominal motion

• Moderate to severe acidosis (pH 7.30-7.35) and hypercapnia (PaCO2 45-60 mm Hg)

• Respiratory frequency > 25 breaths/min

Pauwels et al, Am J Resp Crit Care Med 163: 1256, 2001

Criteria for Non-Invasive Ventilation in COPD

Criteria for Non-Invasive Ventilation in COPD

Exclusion criteria (any may be present)• Respiratory arrest• Cardiovascular instability (hypotension,

arrythmias, MI)• Somnolence, impaired mental status,

uncooperative patient• High aspiration risk• Viscous or copious secretions• Recent facial or gastroesophageal surgery• Craniofacial trauma• Fixed nasopharyngeal abnormalities• Extreme obesity

Pauwels et al, Am J Resp Crit Care Med 163: 1256, 2001

Masks for Non-Invasive Ventilation

• Types of mask– Nasal

• More comfortable• Patient can eat• Minimal aspiration risk• Communication easier

– Whole face• No entrainment of room air• May allow better ventilation

• Choice of mask– Hypercapnic respiratory failure

• Nasal mask often sufficient• Sometimes need whole face mask

– Hypoxic respiratory failure• Always need whole face mask

Ventilator Devices for Non-Invasive Ventilation

• Types of Ventilator Devices– BiPAP

• Simple BiPAP – oxygen set by liter flow• Advanced BiPAP – can set FiO2

– Conventional Ventilator

• Choice of Ventilator Device– Hypercapnic respiratory failure

• Simple BiPAP is sufficient• Any of above may be used

– Hypoxic respiratory failure• Need advanced BiPAP or conventional ventilator

Inspiratory and Expiratory Pressures

• Hypercapnic respiratory failure– Inspiratory pressure typically in 12 to 20 cm H2O

range• Lower values better tolerated• Higher values give better ventilation

– Expiratory pressure not really needed• Except: many BiPAP machines require several cm H2O to

function properly

• Hypoxic respiratory failure– Inspiratory pressure typically in 12 to 20 cm H2O

range– Expiratory pressure gradually increased to improve

oxygenation

COPD – Non-Invasive Ventilation

• Total of 85 patients with COPD exacerbation from five hospitals in France, Italy and Spain

• Non-invasive ventilation– Face mask with foam inside to reduce dead space– Pressure support ventilator system with back-up

rate– Inspiratory pressure 20 cm H2O, no expiratory

pressure – Oxygen to achieve saturation > 90%– At least 6 hours/day, up to 22 hours/day if needed

Brochard et al., NEJM 333:817, 1995

COPD – Non-Invasive Ventilation

Non-invasive ventilation signficantly improved PaCO2 and PaO2

Brochard et al., NEJM 333:817, 1995

COPD – Non-Invasive Ventilation

Changes one hour after entry into study: worsening in conventional group vs improvement in non-invasive group

Brochard et al., NEJM 333:817, 1995

COPD – Non-Invasive VentilationOutcomes• Reduced need for intubation

– Non-invasive group 26% intubated (11/43) – Conventional group 74% intubated (31/42) (P <

0.001)

• Reduced complication rate– Non-invasive group 16% (7/43)– Conventional group 48% (20/42) (P = 0.001)

• Improved survival to hospital discharge– Non-invasive group 91% (39/43)– Conventional group 71% (30/42) (P = 0.02)

Brochard et al., NEJM 333:817, 1995

COPD – Non-Invasive Ventilation

Outcomes (cont’d)• Reduced length of stay in hospital

– Non-invasive group 23 ± 17 days – Conventional group 35 ± 33 days (P = 0.02)

• Lower proportion with length of stay > 4 weeks

– Non-invasive group 18% (7/43)

– Conventional group 47% (14/42) (P = 0.004)

Brochard et al., NEJM 333:817, 1995

Meta-Analysis: COPD and Non-Invasive Ventilation

Lightowler et al., BMJ 326:185, 2003

2003

British Medical Journal

Lightowler et al., BMJ 326:185, 2003

Risk of treatment failure (mortality, need for intubation, intolerance)Relative risk 0.51

Meta-Analysis: COPD and Non-Invasive Ventilation

Risk of mortalityRelative risk 0.41

Lightowler et al., BMJ 326:185, 2003

Meta-Analysis: COPD and Non-Invasive Ventilation

Lightowler et al., BMJ 326:185, 2003

Risk of intubationRelative risk 0.42

Meta-Analysis: COPD and Non-Invasive Ventilation

Lightowler et al., BMJ 326:185, 2003

Other significant outcome improvements with non-invasive ventilation in COPD

• Reduced rate of complications• Reduced hospital length of stay• Improved pH, pCO2 and respiratory rate within one

hour of initiation

Meta-Analysis: COPD and Non-Invasive Ventilation

Ventilation for Chronic Hypercapnia• Clear role for chest wall and neuromuscular disease, and

congenital central hypoventilation syndrome• Often used for obesity-hypoventilation with sleep apnea

(ie use BiPAP rather than CPAP)• Controversial for obstructive lung diseases

• For neuromuscular diseases, often able to start with nocturnal only, and then move to 24 hours/day with disease progression

• Non-invasive ventilation generally preferred over invasive ventilation, unless prominent bulbar problems or subject completely dependent on ventilator (eg. high spinal cord injury)

Long-Term Non-Invasive Ventilation and Restrictive Disorders

American College of Chest Physicians Guidelines, 1999

NPPV and Restrictive Disorders

Perrin et al., Muscle Nerve2004

Use of Home Chronic Ventilation

• Prospective 7 year follow up of patients treated at home with nasal positive pressure ventilation

• Two university hospitals and a pulmonary rehabilitation center

• Mean 6.9 hours of ventilation per 24 hours

Ventilator Modality

Blood Gas Changes

Survival: 7 Year Follow Up

Examples of People Undergoing Long Term Mechanical Ventilation

Christopher Reeve Stephen Hawking1995 to 2004 ~1985 to present

Long-Term Ventilation Not for Everyone

Morris Schwartz, Ph.D., Professor of Sociology, Brandeis University

The End