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 (17331804) 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 earths atmosphere Responsible for keeping the planet sufficiently warm to allow life

Increasing concentrations of carbon dioxide are raising earths 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. Failure

Neural & 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 / obesityhypoventilation Hypothyroidism Environmental Iatrogenic

Causes of Hypercapnic Resp. Failure

Neural & 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 / obesityhypoventilation Hypothyroidism Environmental Iatrogenic

Causes of Hypercapnic Resp. Failure

Neural & 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 / obesityhypoventilation Hypothyroidism Environmental Iatrogenic

Causes of Hypercapnic Resp. Failure

Neural & 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 / obesityhypoventilation Hypothyroidism Environmental Iatrogenic

Causes of Hypercapnic Resp. Failure

Neural & 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 / obesityhypoventilation Hypothyroidism

Environmental Industrial, Natural

Iatrogenic - Drugs, Ventilators

Causes of Hypercapnic Resp. Failure

Neural & 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 / obesityhypoventilation 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 hypersomnolence 2. Obesity-hypoventilation syndrome 3. Both 4. Neither

Pickwickian Syndrome

Little boy who would always fall 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%

Dark bars OHS, light bars simple obesity

Nowbar et al., Am J Med 2004

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.

Nowbar et al., Am J Med 2004

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

Who is this?

He frequently fell asleep "in the middle of the days 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.

US President with Probable OSA

Who is this?

He frequently fell asleep "in the middle of the days 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.

US President with Probable OSA

He frequently fell asleep "in the middle of the days 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 nonexposed 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 Failure

Early Treatment Modalities

Polio Epidemic Denmark, 1952

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

Polio -- Iron Lung Ward 1950s

Rancho Los Amigos Hospital

Mechanical Ventilation for Acute Hypercapnic Respiratory Failure

Intubation with conventional mechanical ventilation Non-invasive positive pressure ventilation (NPPV)

Criteria for Non-Invasive Ventilation in COPD

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

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 Ventilation

Outcomes
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 (contd)
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

British Medical Journal

2003
Lightowler et al., BMJ 326:185, 2003

Meta-Analysis: COPD and Non-Invasive Ventilation

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

Lightowler et al., BMJ 326:185, 2003

Meta-Analysis: COPD and Non-Invasive Ventilation

Risk of mortality Relative risk 0.41

Lightowler et al., BMJ 326:185, 2003

Meta-Analysis: COPD and Non-Invasive Ventilation

Risk of intubation Relative risk 0.42

Lightowler et al., BMJ 326:185, 2003

Meta-Analysis: COPD and Non-Invasive Ventilation

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

Lightowler et al., BMJ 326:185, 2003

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 Nerve 2004

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 1995 to 2004

Stephen Hawking ~1985 to present

Long-Term Ventilation Not for Everyone

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

The End