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Respiratory Failure Medicine 2 Noel V. Bautista December 20, 2007

Respiration

- The exchange of gases between the organism and the environment

�Remember that respiration not only involved the lungs but all the organs

Respiratory Failure

- Respiratory failure is a condition in which the respiratory system is unable to perform its gas-exchange function i.e. oxygenation and/or carbon dioxide elimination

Extended Concept of Respiration

�The respiratory system is a pump that facilitates gas exchange → main function: maintain metabolic function

- Ventilation and perfusion of organs should be properly matched for ideal oxygenation of blood which delivers oxygen to individual organ systems to maintain optimum metabolic activity and homeostasis

- Oxygen is important in aerobic glycolysation - Carbon dioxide should also be effectively eliminiated → or

would lead to acidosis �External Respiration → exchange of gas between environment and respiratory system �Internal Respiration → exchange of gas at cellular level �Cellular metabolism → driving force of ventilation Better Definition of Respiratory Failure

- Respiratory failure is present when the pulmonary system is unable to meet the metabolic demands of the body

�Classification of acute and chronic is very arbitrary → there is no defining line �Acute respiratory failure → subcellular level has not yet been able to adapt to the disturbance �Major adaptation in gas exchange is achieved by kidneys → however before the kidney participates, a buffer system first tries to compensate �Chronic respiratory failure → kidneys have already adapted; kidney adaptation could happen in a matter of hours or days → which is why classification into acute or chronic is arbitrary

Causes of Respiratory Failure

Organ/System Examples

Central Nervous System

Stroke, Drug overdose, Trauma, Myxedema

Peripheral Nervous System

Guillain-Barre syndrome, Spinal cord compression, Poliomyelitis

Neuromuscular System

Myasthenia gravis, Tetanus, Hypokalemic paralysis, Multiple sclerosis, Botulism, Organophosphate poisoning, Antibiotics (Kanamycin, Polymyxin), Curariform drugs

Thorax and Pleura

Severe kyphoscoliosis, Flail chest, Massive pneumothorax or pleural effusion

Upper Airway Epiglotitis, Tracheobronchitis, Vocal cord paralysis

Lower Airway and Alveoli

Pneumonia, COPD, Asthma, ARDS

Cardiovascular System

Heart failure

Blood Anemia, Polycythemia

Cell/Tissue Sepsis, Cyanide poisoning

�We could therefore investigate causes of respiratory failure according to the structures involved in respiration �Hemoglobin → carries 98% of oxygen to be delivered to body cells Types of Respiratory Failure

Type 1 (Normocapnic Respiratory Failure) → Hypoxemia with eucapnia or hypocapnia

- Pure oxygen problem Type 2 (Hypercapnic Respiratory Failure) → Hypoxemia with hypercapnia

- Oxygenation and ventilation (e.g. involving CO2) problem �RF will always produce acidosis. Thus it is important to know oxygenation status (by looking at ABG) and ventilation status (by looking at CO2 status)

- ABG involves - Oxygenation status - Ventilatory status - Acid-base disturbance

�Ventilation failure usually involves CNS, thorax, respiratory muscles; most of time lungs not affected. �Oxygenation failure usually parenchyma of lungs Ventilation and PaCO2 Ficke equation:

PaCo2 = VCO2 x 0.863 VA

↑PaCO2 ~ ↓ VA - the lower the ventilation, the more CO2 accumulates

VE = VA + VD VE – minute ventilation VE = VT x f VA – alveolar ventilation VA = (VT x f) – VD VD – dead space ventilation VT – tidal volume f – respiratory rate

�CO2 elimination is usually 250 mL/min �How do get an idea of the status of alveolar ventilation: check PaCO2

Respiratory Failure

Acute Acute

Develops in Minutes to a

few hours

Develops over several hours or longer Kidneys compensate for the respiratory acidosis

Respiratory Failure

Hypoxemia Hypercapnia

Oxygenation Failure Ventilatory Failure

Respiratory System Disorders �Aiways �Lungs

Ventilatory Pump Disorders �Nervous System �Thorax �Respiratory Muscles

�Respiratory System

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�Minute ventilation affected by: Tidal volume, respiratory rate, and dead space ventilation �↑ Respiratory rate (tachypneic) does not assure you adequacy of ventilation Ventilatory Pump Failure

- Central nervous system - Peripheral nervous system - Thorax & Pleura - Respiratory muscles → myasthenia gravis �Hypercapnia results from disturbance in ventilatory pump

Causes of Hypoventilation (Hypercapnia)

- Brainstem - brainstem injury due to trauma, hemorrhage, infarction,

hypoxia, infection etc - metabolic encephalopathy - depressant drugs

- Spinal cord - trauma, tumor, transverse myelitis

- Nerve root injury - Nerve

- trauma - neuropathy eg Guillain Barre - motor neuron disease

- Neuromuscular junction - myasthenia gravis - neuromuscular blockers

- Respiratory muscles - fatigue - disuse atrophy - myopathy - malnutrition

- Respiratory system - airway obstruction (upper or lower) - decreased lung, pleural or chest wall compliance

Causes of Ventilatory Failure

Increased VCO2 Fever, hypermetabolism

Increased VD and Decreased VA

Lung parenchyma disorders e.g. COPD, asthma, ARDS, pulmonary embolism

Decreased VA Decreased ventilatory drive e.g. sedation or “Pump” failure e.g. neuromuscular disease

�If blood gases reveal hypercapnea, try to categorize them into the above three pathophysiological processes:

1. Increased CO2 production; rarely the cause, but can be an additional factor that adds to hypercapnea

�More important factor is still diminished alveolar ventilation, not increase CO2 production so can forget about this, usually it is only co-conspirator however by itself will not cause hypercapnia 2. Increase in dead space (Minute ventilation is sum of alveolar

ventilation and dead space ventilation) which will decrease alveolar ventilation. CO2 accumulates. Seen in obstructive airway diseases

3. Decreased alveolar ventilation

Respiratory System Oxygenation - Inspired gases (PiO2, PiCO2) - Alveolar ventilation (Va, PAO2, PACO2) - Diffusion of gas through the respiratory membrane (DmO2) - Perfusion of pulmonary capillaries - Ventilation-perfusion matching (V/Q) �Whenever there is hypercapnea, find reason. Do not rely on respiratory rate → request for PaCO2 �oxygenation failure – so many causes

Inspired Air

Dalton’s Law: PB (barometric pressure) = PN2 + PO2 + PCO2 + PH2O

= 760 mmHg (at sea level) � normal atmospheric pressure

�Barometric pressure is the sum of all the partial pressures of the most important gases in atmosphere �Nitrogen is an inert gas; we breathe it without any physiological consequence �Gas that we inhale is humidified

PiO2 = FiO2 x PB FiO2 = PiO2/PB = 160/760 = 21%

�PiO2 → fraction contributed by O2 �FiO2 → available oxygen

Effects of Altitude on Barometric Pressure

Altitude (Feet) PB (mmHg) PiO2 (mmHg)

0 10,000 20,000 30,000 40,000 50,000

760 523 349 226 141 87

159 110 73 47 29 18

�In the urban setting, decreased FiO2 is rarely the reason for respiratory failure, except in cases of fire, CO poisoning Alveolar Gases

- amount O2 that reaches alveoli

Alveolar air equation: PAO2 = (PB – PH2O) x FiO2 – (PaCO2/RQ) = (760 – 47) x FiO2 – (PaCO2/RQ) = 713 x FiO2 – (PaCO2/RQ) = 713 x 0.21 – (40/0.8) = 99.7 mmHg

Alveolar Capillary Membrane

- When O2 reaches alveoli, next step is perfusion - Fick’s law: involves diffusion of gas on surface

Fick’s Law of Diffusion: VO2 = DmO2 x ( PAO2 – PCO2)

�Dm = Diffusing Capacity (Note: D is directly proportional to Area and Diffusion Coefficient for the gas and inversely proportional to diffusion Distance ~ D = [A x Dc]/T) *No need to memorize or apply equation → what is important is that alveolar membrane should be in tip-top shape for the respiratory gases to diffuse through �Diffusion is fast → takes only a quarter of a second for desaturated gas to be completely oxygenated �So even if you exercise → diffusion or the respiratory system is usually not the problem but the cardiovascular system �Exercise can improve the cardiovascular system improve oxygen delivery from 10-15x, but the reserve capacity of the cardiovascular system is even more (20-25x) in a normal resting physiologic bodies �Bottomline: Diffusion is not a usual cause of hypoxemia

Alveolar Air Saturated O2 100 mmHg (13%) N2 573mmHg (76%) CO2 5mmHg (40%) H2O 47mmHg (6%)

Tracheal Air: Saturated O2 150 mmHg (20%) N2 563 mmHg (74%) CO2 0 mmHg (0%) H2O 47 mmHg (6%)

Inspired Air: dry O2 160 mmHg (21%) N2 600 mmHg (79%) CO2 0 mmHg (0%) H2O 0 mmHg (0%)

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Va = 5L/min

Q = 0L/min

Ventilation

Perfusion

Ventilation-Perfusion Matching - The usual cause of hypoxemia

�VQ matching or mismatching comes in a spectrum of physiologic events

A → complete ventilation but no perfusion; physiologic dead space B → ideal VQ; ventilation is matched by perfusion. Normal VQ → slightly more perfusion than ventilation; some of blood flow goes back to heart unoxygenated. D→ no ventialtion but complete perfusion; shunt

�Hard to determine A and D from one another; often lumped together Alveolar-Arterial Oxygen Gradient

Mechanisms of Hypoxemia

- Decreased inspired oxygen tension (FiO2) - Hypoventilation* - Ventilation – Perfusion (V/Q) mismatching* - Shunt defect* - Diffusion defect *The more common causes of hypoxemia

Normal Gas Exchange

Hypoventilation

- Hypoventilation can also lead to decrese in arterial oxygen, even if there’s no problem in parenchyma involved in gas exchange. Thus hypoxygenation can lead to hypoxemia.

↓Va → ↓PAO2 → ↓PaO2

Effect of Hypoventilation on Hypoxemia

↓Va → ↓PAO2 → ↓PaO2 ↓Va → ↑PaCO2 → ↓PaO2

1mmHg ~ 1.25mmHg Fixed Variable

PB = PN2 + PH2O + PCO2 + PO2 760 573 47 40 100 mmHg

�Example:

PaCO2 = 55 mmHg (change = 55 – 40 = 15) Expected PaO2 = 80 mmHg (80 – 15 x 1.25) = 61.25 If actual < expected → hypoventilation (plus other) Actual PaO2 = 60 mmHg Hypoventilation

Ventilation-Perfusion Mismatching

- Causes: - Airway disorders - Lung parenchymal disorders �Most common cause of V/Q mismatch: Obstructive airway disease

Shunt Defect

Shunt Equation: Qs = CcO2 – CaO2 = 5-8% QT CcO2 – CvO2

Causes:

- Intracardiac - Right to left shunt e.g. Fallot's tetralogy, Eisenmenger's

syndrome - Pulmonary

- Pneumonia - Pulmonary edema - Atelectasis - Pulmonary haemorrhage - Pulmonary contusion

Dead Space Ventilation

- Causes

- Pulmonary embolism - Thrombus - Fat - Tumor - Air - Septic

- Pulmonary vasculitis Diffusion Defect

- Causes: - Acute Respiratory Distress Syndrome - Interstitial lung disease - Fibrotic lung disease

Tracheobronchial Tree �Airways divide dichotomously �Airway decreases in size → ↑ surface area 70m2 �80-120mL blood in capillaries for gas exchange

Perfusion

Diffusion

Ventilation

PaO2 = 80 – 100 mmHg

Dead space High V/Q Low V/Q Shunt Ventilation Ventilation Ventilation

Normal V/Q ratio = 0.8

PAO2 = 100 – 115 mmHg

P(A-a)O2 = 15=20 mmHg

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Diffusion Time

Extended Definition of Respiratory Failure

Condition Definition

Ventilatory Failure Abnormality of CO2 elimination by the lungs

Failure of arterial oxygenation

Abnormality of O2 uptake by the lungs

Failure of O2 transport Limitation of O2 delivery to peripheral tissues so that aerobic metabolism cannot be maintained

Failure of O2 uptake and/or utilization

Inability of tissues to extract O2 from blood and use it for aerobic metabolism

Oxygen Transport

O2 transport (or delivery) (DO2) DO2 = Q x CaO2 = 5 L/min x 20 mL/dL x 10

= 1,000 ml/min �Q → cardiac output

O2 content (CaO2) CaO2 = (1.39 x Hb x %Sat) + (0.003 x PaO2)

= 1.39 x 15 x 0.98 + 0.003 x 98 = 20 ml/dl (vol%) Oxygenation Dissociation Curve

�Note points

PO2 = 40 mmHg g Saturation → 75% (PvO2 for a normal person at rest) PO2 = 60 mmHg g Saturation → 90% PO2 = 100 mmHg g Saturation → 97.5% (PaO2 for a normal person at rest and in exercise) P50 = 26 mmHg g Saturation → 50% (for normal Hb

�In sepsis, may have no hypoxemia, but hypoxia �Hypoxemia → <50 mmHg

Factors Affecting O2 Dissociation Curve

Carbon Dioxide Dissociation Curve

�As PCO2 increases, oxygen carrying capacity diminishes. As PO2 increases (especially in venous blood) there is decrease in CO2 carrying capacity → Bohr effect Oxygen Consumption

O2 Consumption (VO2) VO2 = Q x (CaO2 – CvO2) = 5 L/min x 5 mL/dL = 250 ml/min �CvO2 → oxygen content (venous)

O2 Extraction ratio O2 ER = VO2 / DO2 = 250 mL/min / 1,000 mL/min = 0.25 (25%)

�Safety mechanism at subcellular level has good application for cardiac arrest → must be able to resuscitate within 3-5 min → still be able to avoid brain damage/death/organ failure

Clinical Manifestations of Respiratory Failure - Apnea → respiratory failure - Cyanosis → 5 mg of desaturated Hb already; only 20% of

patients with respiratory failure will present with cyanosis → not a good parameter to measure

- Altered level of consciousness - Dyspnea - Signs of respiratory distress - Signs/symptoms of hypoxemia - Signs/symptoms of hypercapnea - Signs/symptoms of underlying pathology

Manifestations of Respiratory Distress and Respiratory Failure

- Tachypnea and tachycardia - Flaring of ala nasae - Use of accessory muscles of respiration - Supraclavicular fossa excavation - “Pump” handle breathing - Tracheal tug and decreased tracheal length - External jugular venous distension in expiration - Costal paradox - Pulsus paradoxus - Abdominal paradox and asynchrony Respirator distress; but - Respiratory alternans there is impending - Cyanosis apnea → ventilation - Altered level of consciousness failure in the next 15min �Respiratory failure is not synonymous with respiratory distress. If there’s respiratory distress, investigate if there is RF

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Signs of Respiratory Distress

- Tachypnea and tachycardia - Flaring of ala nasae - Use of accessory muscles of respiration - Intercostal muscle retraction - Sternocleidomastoid muscle contraction - Costal paradox (Hoover’s sign) - “Pump” handle breathing - Supraclavicular fossae excavation - External jugular venous distension in expiration - Tracheal tug and decreased tracheal length - Abdominal paradox and asynchrony - Respiratory alternans

Signs and Symptoms of Hypercapnea

- Symptoms Headache Mild sedation → Drowsiness → Coma

- Signs Vasodilation → redness of skin, sclera and conjunctiva secondary to increased cutaneous blood flow; sweating Sympathetic response → hypertension tachycardia

�”Antok” Signs and Symptoms of Hypoxia

- Symptoms Ethanol-like symptoms → confusion, loss of judgment, paranoia, restlessness, dizziness

- Signs Sympathetic response → tachycardia, mild hypertension, peripheral vasoconstriction Non-sympathetic response → bradycardia, hypotension

�”Lasing” - Inhibitions depressed

�COPD → chronic hypoxemia, irritable Diagnosis of Respiratory Failure

- Patient is in respiratory distress - Hypoxemia (PaO2 < 60 mmHg) - Hypercapnia (PaCO2 > 50 mmHg) - Arterial pH shows significant acidemia (respiratory acidosis) *At least 2 of the 4 criteria should be fulfilled �Only way to diagnose RF is to do ABG. It is a laboratory diagnosis, not a clinical diagnosis

Other Diagnostic Modalities - Laboratory

- CBC - Electrolytes

- Imaging studies - Chest x-ray - CT scan - Ventilation-perfusion scan

Evaluation of Causes of Hypercapnia

Evaluation of Hypoxemia - Normal P(A-a)O2

- Decreased FiO2 - Hypoventilation

- Increased P(A-a)O2 - Ventilation-Perfusion mismatching - Shunt defect - Diffusion defect

�Most common cause of hypoxemia: hypoventilation, V/Q mismatch & shunt �If with hypoxemia → calculate first P(A-a)O2 gradient

- Normal gradient → no problem in respiratory membrane & V/Q, it will still go to arterial system

Indices of Oxygenation

Indices Normal Values

PaO2

SaO2 P(A-a)O2 PaO2/PAO2 PaO2/FiO2 QS/QT

80 – 100 mmHg 95 – 100 vol% 25 – 65 mmHg 0.75 350 – 450 < 5 %

�PAO2 = (PB – PH2O) x FiO2 – (PaCO2/RQ) = (760 – 47) x FiO2 – (PaCO2/RQ) = 713 x FiO2 – (PaCO2/RQ) � PaO2/PAO2 = 0.15 → severe respiratory failure �There are many oxygenation parameters. It is not adequate to look at just PaO2. Must look at other oxygenation parameters Algorithm of Hypoxemia

Principles of Treatment

- Maintain adequate oxygenation - Support ventilation with mechanical ventilation when needed - Treat underlying illness or pathophysiologic derangements - Maintain fluid and electrolyte balance - Provide adequate nutrition - Avoid complications

Transcribed by: Fred Monteverde Notes from: Cecile Ong Lecture recorded by: Lala Nieto

Minute Ventilation (VE)

Increased VE Decreased VE

Increased VCO2 Increased VD & Decreased VA

P(A-a)O2

Normal Increased

PaCO2 Challenge with

100% FiO2

Increased Normal or

Decreased

Decreased VA

Airway or Lung parenchyma

disorders

Decreased ventilatory

drive

“Pump”

disorders

Fever

Hypermetabolism

COPD, ARDS, Asthma, PE

Sedation

Stroke

Neuromuscular disorder Pleural effusion

Corrected

PaO2

Uncorrected

PaO2

Hypo -

ventialtion

Decreased

FiO2

V/Q mismatch Shunt <10%

Diffusion defect

Shunt

>10%

Fred Monteverde Emy Onishi Cecile Ong Mitzel Mata Regina Luz

Mae Olivarez Lala Nieto Chok Porciuncula

Section C 2009!