Respiratory failure

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Respiratory failure
Classification and external resources

ICD-10

J96.

ICD-9

518.81

DiseasesDB

6623

eMedicine

med/2011

MeSH

D012131

The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known ashypoxia; a rise in arterial carbon dioxide levels is called hypercapnia. The normal reference values are: oxygen PaO2 greater than 80 mmHg (11 kPa), and carbon dioxide PaCO2 less than 45 mmHg (6.0 kPa). Classification into type I or type II relates to the absence or presence of hypercarbia respectively.
Contents
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1 Types 1.1 Type 1 1.2 Type 2 2 Causes 3 Treatment 4 See also 5 References

[edit]Types [edit]Type

Type 1 respiratory failure is defined as hypoxia without hypercarbia, and indeed the PaCO2 may be normal or low. It is typically caused by a ventilation/perfusion (V/Q) mismatch; the volume of air flowing in and out of the lungs is not matched with the flow of blood to the lungs. The basic defect in type 1 respiratory failure is failure of oxygenation characterized by:

PaO2

low (< 60 mmHg (8.0 kPa))

PaCO2 normal or low

PA-aO2 increased

This type of respiratory failure is caused by conditions that affect oxygenation such as:

[edit]Type

Parenchymal disease (V/Q mismatch) Diseases of vasculature and shunts: right-to-left shunt, pulmonary embolism interstitial lung diseases: ARDS, pneumonia, emphysema.

The basic defect in type 2 respiratory failure is characterized by:

PaO2

decreased

PaCO2 increased

PA-aO2 normal

pH

decreased

Type 2 respiratory failure is caused by increased airway resistance; both oxygen and carbon dioxide are affected. Defined as the build up of carbon dioxide levels (PaCO2) that has been generated by the body. The underlying causes include:

Reduced breathing effort (in the fatigued patient) A decrease in the area of the lung available for gas exchange (such as
in emphysema).

Neuromuscular problems like, GB syndrome.[1] Flail chest.[2]

[edit]Causes

Chest X-ray showing ARDS

Pulmonary dysfunction
Asthma Emphysema Chronic Obstructive Pulmonary Disease Pneumonia Pneumothorax Pulmonary contusion[3] Hemothorax Acute Respiratory Distress Syndrome (ARDS) is a specific and life-

threatening type of respiratory failure.

Cystic Fibrosis

Cardiac dysfunction Other

Fatigue due to prolonged tachypnoea in metabolic acidosis Intoxication with drugs (e.g., morphine, benzodiazepines) that suppress Pulmonary edema Cerebrovascular Accident Arrhythmia Congestive heart failure Valve pathology

respiration.

Neurological Disease Toxic Epidermal Necrolysis

[edit]Treatment

Mechanical Ventilator

Emergency treatment follows the principles of cardiopulmonary resuscitation. Treatment of the underlying cause is required. Endotracheal intubation and mechanical ventilation may be required. Respiratory stimulants such as doxapram may be used, and if the respiratory failure resulted from an overdose of sedative drugs such as opioids or benzodiazepines, then the appropriate antidote such as naloxone or flumazenilwill be given.

Pathophysiology
Respiratory failure can arise from an abnormality in any of the components of the respiratory system, including the airways, alveoli, CNS, peripheral nervous system, respiratory muscles, and chest wall. Patients who have hypoperfusion secondary to cardiogenic, hypovolemic, or septic shock often present with respiratory failure.

Hypoxemic respiratory failure

The pathophysiologic mechanisms that account for the hypoxemia observed in a wide variety of diseases are ventilation-perfusion (V/Q) mismatch and shunt. These 2 mechanisms lead to widening of the alveolar-arterial oxygen difference, which normally is less than 15 mm Hg. With V/Q mismatch, the areas of low ventilation relative to perfusion (low V/Q units) contribute to hypoxemia. An intrapulmonary or intracardiac shunt causes mixed venous (deoxygenated) blood to bypass ventilated alveoli and results in venous admixture. The distinction between V/Q mismatch and shunt can be made by assessing the response to oxygen supplementation or calculating the shunt fraction following inhalation of 100% oxygen. In most patients with hypoxemic respiratory failure, these 2 mechanisms coexist.

Hypercapnic respiratory failure

At a constant rate of carbon dioxide production, PaCO2 is determined by the level of alveolar ventilation (Va), in which VCO2 is ventilation of carbon dioxide and K is a constant value (0.863). (Va = K x VCO2)/PaCO2 A decrease in alveolar ventilation can result from a reduction in overall (minute) ventilation or an increase in the proportion of dead space ventilation. A reduction in minute ventilation is

observed primarily in the setting of neuromuscular disorders and CNS depression. In pure hypercapnic respiratory failure, the hypoxemia is easily corrected with oxygen therapy.

Ventilatory capacity versus demand

Ventilatory capacity is the maximal spontaneous ventilation that can be maintained without development of respiratory muscle fatigue. Ventilatory demand is the spontaneous minute ventilation that results in a stable PaCO2. Normally, ventilatory capacity greatly exceeds ventilatory demand. Respiratory failure may result from either a reduction in ventilatory capacity or an increase in ventilatory demand (or both). Ventilatory capacity can be decreased by a disease process involving any of the functional components of the respiratory system and its controller. Ventilatory demand is augmented by an increase in minute ventilation and/or an increase in the work of breathing.

Pathophysiologic mechanisms in acute respiratory failure

The act of respiration engages 3 processes: (1) transfer of oxygen across the alveolus, (2) transport of oxygen to the tissues, and (3) removal of carbon dioxide from blood into the alveolus and then into the environment. Respiratory failure may occur from malfunctioning of any of these processes. In order to understand the pathophysiologic basis of acute respiratory failure, an understanding of pulmonary gas exchange is essential.

Physiology of gas exchange

Respiration primarily occurs at the alveolar capillary units of the lungs, where exchange of oxygen and carbon dioxide between alveolar gas and blood takes place. Following diffusion into the blood, the oxygen molecules reversibly bind to the hemoglobin. Each molecule of hemoglobin contains 4 sites for combination with molecular oxygen, 1 g of hemoglobin combines with a maximum of 1.36 mL of oxygen. The quantity of oxygen combined with hemoglobin depends on the level of blood PaO2. This relationship, expressed as the oxygen hemoglobin dissociation curve, is not linear but has a sigmoid-shaped curve with a steep slope between a PaO2 of 10 and 50 mm Hg and a flat portion above a PaO2 of 70 mm Hg. The carbon dioxide is transported in 3 main forms: (1) in simple solution, (2) as bicarbonate, and (3) combined with protein of hemoglobin as a carbamino compound. During ideal gas exchange, blood flow and ventilation would perfectly match each other, resulting in no alveolar-arterial PO2 difference. However, even in normal lungs, not all alveoli are ventilated and perfused perfectly. For a given perfusion, some alveoli are underventilated while others are overventilated. Similarly, for known alveolar ventilation, some units are underperfused while others are overperfused. The optimally ventilated alveoli that are not perfused well are called high V/Q units (acting likedead space), and alveoli that are optimally perfused but not adequately ventilated are called low V/Q units (acting like ashunt).

Alveolar ventilation
At steady state, the rate of carbon dioxide production by the tissues is constant and equals the rate of carbon dioxide elimination by the lung. This relationship is expressed as PaCO2 = VCO2 x 0.862/Va. This relationship signifies whether the alveolar ventilation is adequate for metabolic needs of the body. The efficiency of lungs at carrying out of respiration can be further evaluated by measuring alveolar-to-arterial PaO2 difference. This difference is calculated by the following equation: PA O2 = FIO2 x (PB PH2 O) PA CO2/R For the above equation, PA O2 = alveolar PO2, FIO2 = fractional concentration of oxygen in inspired gas, PB = barometric pressure, PH2 O = water vapor pressure at 37C, PA CO2 = alveolar PCO2, assumed to be equal to arterial PCO2, and R = respiratory exchange ratio. R depends on oxygen consumption and carbon dioxide production. At rest, VCO2/VO2 is approximately 0.8. Even normal lungs have some degree of V/Q mismatching and a small quantity of right-to-left shunt, alveolar PO2 is slightly higher than arterial PO2. However, an increase in alveolar-toarterial PO2 above 15-20 mm Hg indicates pulmonary disease as the cause of hypoxemia.

Pathophysiologic causes of acute respiratory failure

Hypoventilation, V/Q mismatch, and shunt are the most common pathophysiologic causes of acute respiratory failure. These are described in the following paragraphs.

Hypoventilation
Hyperventilation is an uncommon cause of respiratory failure and usually occurs from depression of the CNS from drugs or neuromuscular diseases affecting respiratory muscles. Hypoventilation is characterized by hypercapnia and hypoxemia. The relationship between PaCO2 and alveolar ventilation is hyperbolic. As ventilation decreases below 4-6 L/min, PaCO2rises precipitously. Hypoventilation can be differentiated from other causes of hypoxemia by the presence of a normal alveolar-arterial PO2 gradient.

V/Q mismatch
V/Q mismatch is the most common cause of hypoxemia. V/Q units may vary from low to high ratios in the presence of a disease process. The low V/Q units contribute to hypoxemia and hypercapnia in contrast to high V/Q units, which waste ventilation but do not affect gas exchange unless quite severe. The low V/Q ratio may occur either from a decrease in ventilation secondary to airway or interstitial lung disease or from overperfusion in the presence of normal ventilation. The overperfusion may occur in case of pulmonary embolism, where the blood is diverted to normally ventilated units from regions of lungs that have blood flow obstruction secondary to embolism. Administration of 100% oxygen eliminates all of the low V/Q units, thus leading to correction of hypoxemia. Hypoxemia increases minute ventilation by chemoreceptor stimulation, but the PaCO2 level generally is not affected.

Shunt
Shunt is defined as the persistence of hypoxemia despite 100% oxygen inhalation. The deoxygenated blood (mixed venous blood) bypasses the ventilated alveoli and mixes with oxygenated blood that has flowed through the ventilated alveoli, consequently leading to a reduction in arterial blood content. The shunt is calculated by the following equation: QS/QT = (CCO2 CaO2)/CCO2 CvO2) QS/QT is the shunt fraction, CCO2 (capillary oxygen content) is calculated from ideal alveolar PO2, CaO2 (arterial oxygen content) is derived from PaO2using the oxygen dissociation curve, and CVO2 (mixed venous oxygen content) can be assumed or measured by drawing mixed venous blood from pulmonary arterial catheter. Anatomical shunt exists in normal lungs because of the bronchial and thebesian circulations, accounting for 2-3% of shunt. A normal right-to-left shunt may occur from atrial septal defect, ventricular septal defect, patent ductus arteriosus, or arteriovenous malformation in the lung. Shunt as a cause of hypoxemia is observed primarily in pneumonia, atelectasis, and severe pulmonary edema of either cardiac or noncardiac origin. Hypercapnia generally does not develop unless the shunt is excessive (>60%). When compared with V/Q mismatch, hypoxemia produced by shunt is difficult to correct by oxygen administration.

Epidemiology
Frequency
United States Respiratory failure is a syndrome rather than a single disease process, and the overall frequency of respiratory failure is not well known. The estimates for individual diseases mentioned here can be found in the appropriate eMedicine article.

Mortality/Morbidity
The mortality rate associated with respiratory failure varies according to the etiology. For acute respiratory distress syndrome, the mortality rate is approximately 45% in most studies; this percentage has not changed over the years.[1, 2] Acute exacerbation of COPD carries a mortality rate of approximately 30%. The mortality rates for other causative disease processes have not been well described.

A study by Noveanu et al suggests a strong association between the preadmission use of beta-blockers and in-hospital and 1-year mortality rate among patients with acute respiratory failure. Although the cessation exacerbates the mortality rate, predischarge initiation of betablockers is also associated with an improved 1-year mortality rate.[3]

Race
The relation between acute respiratory failure and race is still debated. A recent work by Khan et al suggested that no differences in mortality exist in patients of Asian and Native Indian descent with acute critical illness after adjusting for differences in case mix.[4] Moss and Mannino, in a 2002 manuscript, showed worse outcome for African-Americans suffering from acute respiratory distress syndrome (ARDS) as compared with whites when adjusted for case mix.[5] As more prospective association studies are performed, we will have a better knowledge of the impact of race on the outcome of respiratory failure.

Medication Summary
The pharmacotherapy of cardiogenic pulmonary edema and acute exacerbations of COPD is discussed here. The goals of therapy in cardiogenic pulmonary edema are to achieve a pulmonary capillary wedge pressure of 15-18 mm Hg and a cardiac index greater than 2.2 L/min/m2, while maintaining adequate blood pressure and organ perfusion. These goals may need to be modified for some patients. Diuretics, nitrates, analgesics, and inotropics are used in the treatment of acute pulmonary edema.

Diuretics
Class Summary
First-line therapy generally includes a loop diuretic such as furosemide, which inhibits sodium chloride reabsorption in the ascending loop of Henle.
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Furosemide (Lasix)
Administer loop diuretics IV because this allows for both superior potency and a higher peak concentration despite increased incidence of adverse effects, particularly ototoxicity.
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Metolazone (Mykrox, Zaroxolyn)

Has been used as adjunctive therapy in patients initially refractory to furosemide. Has been demonstrated to be synergistic with loop diuretics in treating refractory patients and causes a greater loss of potassium. Potent loop diuretic that sometimes is used in combination with Lasix for more aggressive diuresis. Also used in patients with a degree of renal dysfunction for initiating diuresis.

Nitrates
Class Summary
These agents reduce myocardial oxygen demand by lowering preload and afterload. In severely hypertensive patients, nitroprusside causes more arterial dilatation than nitroglycerin. Nevertheless, due to the possibility of thiocyanate toxicity and the coronary steal phenomenon associated with nitroprusside, IV nitroglycerin may be the initial therapy of choice for afterload reduction.
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Nitroglycerin sublingual (Nitro-Bid, Nitrol)

SL nitroglycerin and Nitrospray are particularly useful in the patient who presents with acute pulmonary edema with a systolic blood pressure of at least 100 mm Hg. Similar to SL, onset of Nitrospray is 1-3 min, with a half-life of 5 min. Administration of Nitrospray may be easier, and it can be stored for as long as 4 y. One study demonstrated significant and rapid hemodynamic improvement in 20 patients with pulmonary edema who were given Nitrospray.

Topical nitrate therapy is reasonable in a patient presenting with class I-II CHF. However, in patients with more severe signs of heart failure or pulmonary edema, IV nitroglycerin is preferred because it is easier to monitor hemodynamics and absorption, particularly in patients with diaphoresis. Oral nitrates, due to delayed absorption, play little role in the management of acute pulmonary edema.
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Nitroprusside sodium (Nitropress)

Produces vasodilation of venous and arterial circulation. At higher dosages, may exacerbate myocardial ischemia by increasing heart rate. Easily titratable.

Analgesics
Class Summary
Morphine IV is an excellent adjunct in the management of acute pulmonary edema. In addition to being both an anxiolytic and an analgesic, its most important effect is venodilation, which reduces preload. Also causes arterial dilatation, which reduces systemic vascular resistance and may increase cardiac output.
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Morphine sulfate (Duramorph, Astramorph, MS Contin)

DOC for narcotic analgesia due to reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate administered IV may be dosed in a number of ways and commonly is titrated until desired effect is obtained.

Inotropics
Class Summary
Principal inotropic agents include dopamine, dobutamine, inamrinone (formerly amrinone), milrinone, dopexamine, and digoxin. In patients with hypotension presenting with CHF, dopamine and dobutamine usually are employed. Inamrinone and milrinone inhibit phosphodiesterase, resulting in an increase of intracellular cyclic AMP and alteration in calcium transport. As a result, they increase cardiac contractility and reduce vascular tone by vasodilatation.
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Dopamine (Intropin)
Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effects depend on the dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation are produced by higher doses. Positive inotropic agent at 2-10 mcg/kg/min that can lead to tachycardia, ischemia, and dysrhythmias. Doses >10 mcg/kg/min cause vasoconstriction, which increases afterload.
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Norepinephrine (Levophed)
Used in protracted hypotension following adequate fluid replacement. Stimulates beta1- and alpha-adrenergic receptors, which in turn increases cardiac muscle contractility and heart rate, as well as vasoconstriction. As a result, increases systemic blood pressure and cardiac output. Adjust and maintain infusion to stabilize blood pressure (eg, 80-100 mm Hg systolic) sufficiently to perfuse vital organs.
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Dobutamine (Dobutrex)
Produces vasodilation and increases inotropic state. At higher dosages, may cause increased heart rate, thus exacerbating myocardial ischemia. Strong inotropic agent with minimal chronotropic effect and no vasoconstriction.

Bronchodilators

Class Summary
These agents are an important component of treatment in respiratory failure caused by obstructive lung disease. These agents act to decrease muscle tone in both small and large airways in the lungs. This category includes beta-adrenergics, methylxanthines, and anticholinergics.
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Terbutaline (Brethaire, Bricanyl)

Acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.
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Albuterol (Proventil)
Beta-agonist useful in the treatment of bronchospasm. Selectively stimulate beta2-adrenergic receptors of the lungs. Bronchodilation results from relaxation of bronchial smooth muscle, which relieves bronchospasm and reduces airway resistance.
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Theophylline (Theo-Dur, Slo-bid, Theo-24)

Has a number of physiological effects, including increases in collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. Partially acts by inhibiting phosphodiesterase, elevating cellular cyclic AMP levels, or antagonizing adenosine receptors in the bronchi, resulting in relaxation of smooth muscle. However, clinical efficacy is controversial, especially in the acute setting.
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Ipratropium bromide (Atrovent)

Anticholinergic medication that appears to inhibit vagally mediated reflexes by antagonizing action of acetylcholine, specifically with the muscarinic receptor on bronchial smooth muscle. Vagal tone can be significantly increased in COPD; therefore, this can have a profound effect. Dose can be combined with a beta-agonist because ipratropium may require 20 min to begin having an effect.

Corticosteroids
Class Summary
Have been shown to be effective in accelerating recovery from acute COPD exacerbations and are an important anti-inflammatory therapy in asthma. Although they may not make a clinical difference in the ED, they have some effect 6-8 h into therapy; therefore, early dosing is critical.
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Methylprednisolone (Solu-Medrol, Depo-Medrol)

Usually given IV in ED for initiation of corticosteroid therapy, although PO should theoretically be equally efficacious.