Respiratory Failure

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Author: Ata Murat Kaynar, MD; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM

Updated: Sep 28, 2010

Background
Respiratory failure is a syndrome in which the respiratory system fails in one or both of its gas exchange functions: oxygenation and carbon dioxide elimination. In practice, respiratory failure is defined as a PaO2 value of less than 60 mm Hg while breathing air or a PaCO2 of more than 50 mm Hg. Furthermore, respiratory failure may be acute or chronic. Although acute respiratory failure is characterized by life-threatening derangements in arterial blood gases and acid-base status, the manifestations of chronic respiratory failure are less dramatic and may not be as readily apparent.

Bilateral airspace infiltrates on chest radiograph film secondary to acute respiratory distress syndrome that resulted in respiratory failure.

Classification of respiratory failure

Respiratory failure may be classified as hypoxemic or hypercapnic and may be either acute or chronic. Hypoxemic respiratory failure (type I) is characterized by a PaO2 of less than 60 mm Hg with a normal or low PaCO2. This is the most common form of respiratory failure, and it can be associated with virtually all acute diseases of the lung, which generally involve fluid filling or collapse of alveolar units. Some examples of type I respiratory failure are cardiogenic or noncardiogenic pulmonary edema, pneumonia, and pulmonary hemorrhage. Hypercapnic respiratory failure (type II) is characterized by a PaCO2 of more than 50 mm Hg. Hypoxemia is common in patients with hypercapnic respiratory failure who are breathing room air. The pH depends on the level of bicarbonate, which, in turn, is dependent on the duration of hypercapnia. Common etiologies include drug overdose, neuromuscular disease, chest wall abnormalities, and severe airway disorders (eg, asthma, chronic obstructive pulmonary disease [COPD]).

Distinctions between acute and chronic respiratory failure

Acute hypercapnic respiratory failure develops over minutes to hours; therefore, pH is less than 7.3. Chronic respiratory failure develops over several days or longer, allowing time for renal compensation and an increase in bicarbonate concentration. Therefore, the pH usually is only slightly decreased. The distinction between acute and chronic hypoxemic respiratory failure cannot readily be made on the basis of arterial blood gases. The clinical markers of chronic hypoxemia, such as polycythemia or cor pulmonale, suggest a long-standing disorder.

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 sigmoidshaped 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-toleft shunt, alveolar PO2 is slightly higher than arterial PO2. However, an increase in alveolar-to-arterial 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, PaCO2 rises 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 PaO2 using 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.

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.[3] 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.[4] As more prospective association studies are performed, we will have a better knowledge of the impact of race on the outcome of respiratory failure.

History
The diagnosis of acute or chronic respiratory failure begins with clinical suspicion of its presence. Confirmation of the diagnosis is based on arterial blood gas analysis. Evaluation of an underlying cause must be initiated early, frequently in the presence of concurrent treatment for acute respiratory failure.
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The cause of respiratory failure is often evident after a careful history and physical examination. o Cardiogenic pulmonary edema usually develops in the context of a history of left ventricular dysfunction or valvular heart disease. o A history of previous cardiac disease, recent symptoms of chest pain, paroxysmal nocturnal dyspnea, and orthopnea suggest cardiogenic pulmonary edema. o Noncardiogenic edema (eg, acute respiratory distress syndrome [ARDS]) occurs in typical clinical contexts such as sepsis, trauma, aspiration, pneumonia, pancreatitis, drug toxicity, and multiple transfusions.

Physical
The signs and symptoms of acute respiratory failure reflect the underlying disease process and the associated hypoxemia or hypercapnia. Localized pulmonary findings reflecting the acute cause of hypoxemia, such as pneumonia, pulmonary edema, asthma, or COPD, may be readily apparent. In patients with acute respiratory distress syndrome (ARDS), the manifestations may be remote from the thorax, such as abdominal pain or long-bone fracture. Neurological manifestations include restlessness, anxiety, confusion, seizures, or coma.
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Asterixis may be observed with severe hypercapnia. Tachycardia and a variety of arrhythmias may result from hypoxemia and acidosis. Once respiratory failure is suspected on clinical grounds, arterial blood gas analysis should be performed to confirm the diagnosis and to assist in the distinction between acute and chronic forms. This helps assess the severity of respiratory failure and also helps guide management. Cyanosis, a bluish color of skin and mucous membranes, indicates hypoxemia. Visible cyanosis typically is present when the concentration of deoxygenated hemoglobin in the capillaries or tissues is at least 5 g/dL. Dyspnea, an uncomfortable sensation of breathing, often accompanies respiratory failure. Excessive respiratory effort, vagal receptors, and chemical stimuli (hypoxemia and/or hypercapnia) all may contribute to the sensation of dyspnea.

Both confusion and somnolence may occur in respiratory failure. Myoclonus and seizures may occur with severe hypoxemia. Polycythemia is a complication of longstanding hypoxemia. Pulmonary hypertension frequently is present in chronic respiratory failure. Alveolar hypoxemia potentiated by hypercapnia causes pulmonary arteriolar constriction. If chronic, this is accompanied by hypertrophy and hyperplasia of the affected smooth muscles and narrowing of the pulmonary arterial bed. The increased pulmonary vascular resistance increases afterload of the right ventricle, which may induce right ventricular failure. This, in turn, causes enlargement of the liver and peripheral edema. The entire sequence is known as cor pulmonale. Criteria for the diagnosis of acute respiratory distress syndrome o Clinical presentation - Tachypnea and dyspnea; crackles upon auscultation o Clinical setting - Direct insult (aspiration) or systemic process causing lung injury (sepsis) o Radiologic appearance - Three-quadrant or 4-quadrant alveolar flooding o Lung mechanics - Diminished compliance (< 40 mL/cm water) o Gas exchange - Severe hypoxia refractory to oxygen therapy (PaO2/FIO2 < 200) o Normal pulmonary vascular properties - Pulmonary capillary wedge pressure of less than 18 mm Hg

Causes
These diseases can be grouped according to the primary abnormality and the individual components of the respiratory system, as follows:
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Central nervous system disorders o A variety of pharmacological, structural, and metabolic disorders of the CNS are characterized by depression of the neural drive to breathe. o This may lead to acute or chronic hypoventilation and hypercapnia. o Examples include tumors or vascular abnormalities involving the brain stem, an overdose of a narcotic or sedative, and metabolic disorders such as myxedema or chronic metabolic alkalosis. Disorders of the peripheral nervous system, respiratory muscles, and chest wall o These disorders lead to an inability to maintain a level of minute ventilation appropriate for the rate of carbon dioxide production. o Concomitant hypoxemia and hypercapnia occur. o Examples include Guillain-Barr syndrome, muscular dystrophy, myasthenia gravis, severe kyphoscoliosis, and morbid obesity. Abnormalities of the airways o Severe airway obstruction is a common cause of acute and chronic hypercapnia. o Examples of upper airway disorders are acute epiglottitis and tumors involving the trachea; lower airway disorders include COPD, asthma, and cystic fibrosis. Abnormalities of the alveoli

The diseases are characterized by diffuse alveolar filling, frequently resulting in hypoxemic respiratory failure, although hypercapnia may complicate the clinical picture. o Common examples are cardiogenic and noncardiogenic pulmonary edema, aspiration pneumonia, or extensive pulmonary hemorrhage. These disorders are associated with intrapulmonary shunt and an increased work of breathing. Common causes of type I (hypoxemic) respiratory failure o Chronic bronchitis and emphysema (COPD) o Pneumonia o Pulmonary edema o Pulmonary fibrosis o Asthma o Pneumothorax o Pulmonary embolism o Pulmonary arterial hypertension o Pneumoconiosis o Granulomatous lung diseases o Cyanotic congenital heart disease o Bronchiectasis o Adult respiratory distress syndrome o Fat embolism syndrome o Kyphoscoliosis o Obesity Common causes of type II (hypercapnic) respiratory failure o Chronic bronchitis and emphysema (COPD) o Severe asthma o Drug overdose o Poisonings o Myasthenia gravis o Polyneuropathy o Poliomyelitis o Primary muscle disorders o Porphyria o Cervical cordotomy o Head and cervical cord injury o Primary alveolar hypoventilation o Obesity hypoventilation syndrome o Pulmonary edema o Adult respiratory distress syndrome o Myxedema o Tetanus
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Differentials
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Acute Respiratory Distress Syndrome

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Apnea, Sleep Asthma Atelectasis Cardiogenic Shock Cardiomyopathy, Diabetic Heart Disease Cardiomyopathy, Dilated Cardiomyopathy, Hypertrophic Cor Pulmonale Cyanosis Diaphragmatic Paralysis Emphysema Myocardial Infarction Myocardial Ischemia Pneumonia, Aspiration Pneumonia, Bacterial Pneumonia, Community-Acquired Pneumonia, Viral Pneumothorax Pulmonary Edema, Cardiogenic Pulmonary Edema, Neurogenic Pulmonary Embolism Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis, Interstitial (Nonidiopathic) Pulmonary Hypertension, Primary Pulmonary Hypertension, Secondary Respiratory Acidosis Restrictive Lung Disease Shock, Distributive Ventilation, Mechanical Ventilation, Noninvasive

Laboratory Studies
Respiratory failure may be associated with a variety of clinical manifestations. However, these are nonspecific, and very significant respiratory failure may be present without dramatic signs or symptoms. This emphasizes the importance of measuring arterial blood gases in all patients who are seriously ill or in whom respiratory failure is suspected. A complete blood count may indicate anemia, which can contribute to tissue hypoxia, whereas polycythemia may indicate chronic hypoxemic respiratory failure. A chemistry panel may be helpful in the evaluation and management of a patient in respiratory failure. Abnormalities in renal and hepatic function may either provide clues to the etiology of respiratory failure or alert the clinician to complications associated with respiratory failure. Abnormalities in electrolytes such as potassium, magnesium, and phosphate may aggravate respiratory failure and other organ function.

Measuring serum creatine kinase with fractionation and troponin I helps exclude recent myocardial infarction in a patient with respiratory failure. An elevated creatine kinase with a normal troponin I may indicate myositis, which occasionally can cause respiratory failure. In chronic hypercapnic respiratory failure, serum thyroid-stimulating hormone should be measured to evaluate the possibility of hypothyroidism, a potentially reversible cause of respiratory failure.

Imaging Studies
Chest radiograph
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Chest radiography is essential because it frequently reveals the cause of respiratory failure. However, distinguishing between cardiogenic and noncardiogenic pulmonary edema often is difficult. Increased heart size, vascular redistribution, peribronchial cuffing, pleural effusions, septal lines, and perihilar bat-wing distribution of infiltrates suggest hydrostatic edema; the lack of these findings suggests acute respiratory distress syndrome (ARDS).

Echocardiography
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Echocardiography need not be performed routinely in all patients with respiratory failure. However, it is a useful test when a cardiac cause of acute respiratory failure is suspected. The findings of left ventricular dilatation, regional or global wall motion abnormalities, or severe mitral regurgitation support the diagnosis of cardiogenic pulmonary edema. A normal heart size and normal systolic and diastolic function in a patient with pulmonary edema would suggest acute respiratory distress syndrome (ARDS). Echocardiography provides an estimate of right ventricular function and pulmonary artery pressure in patients with chronic hypercapnic respiratory failure.

Other Tests
Patients with acute respiratory failure generally are unable to perform pulmonary function tests (PFTs). However, PFTs are useful in the evaluation of chronic respiratory failure.
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Normal values of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) suggest a disturbance in respiratory control. A decrease in FEV1 -to-FVC ratio indicates airflow obstruction, whereas a reduction in both the FEV1 and FVC and maintenance of the FEV1 -to-FVC ratio suggest restrictive lung disease. Respiratory failure is uncommon in obstructive diseases when the FEV1 is greater than 1 L and in restrictive diseases when the FVC is more than 1 L.

An ECG should be performed to evaluate the possibility of a cardiovascular cause of respiratory failure; it also may detect dysrhythmias resulting from severe hypoxemia and/or acidosis.

Procedures
Right heart catheterization
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This remains a controversial issue in the management of critically ill patients. Invasive monitoring probably is not routinely needed in patients with acute hypoxemic respiratory failure, but when significant uncertainty about cardiac function, adequacy of volume resuscitation, and systemic oxygen delivery remain, right heart catheterization should be considered. Measurement of pulmonary capillary wedge pressure may be helpful in distinguishing cardiogenic from noncardiogenic edema. The pulmonary capillary wedge pressure should be interpreted in the context of serum oncotic pressure and cardiac function.

Medical Care
Hypoxemia is the major immediate threat to organ function. Therefore, the first objective in the management of respiratory failure is to reverse and/or prevent tissue hypoxia. Hypercapnia unaccompanied by hypoxemia generally is well tolerated and probably is not a threat to organ function unless accompanied by severe acidosis. Many experts believe that hypercapnia should be tolerated until the arterial blood pH falls below 7.2. Appropriate management of the underlying disease obviously is an important component in the management of respiratory failure. A patient with acute respiratory failure generally should be admitted to a respiratory care or intensive care unit. Most patients with chronic respiratory failure can be treated at home with oxygen supplementation and/or ventilatory assist devices along with therapy for their underlying disease. Extracorporeal membrane oxygenation (ECMO) may be more effective than conventional management for patients with severe but potentially reversible respiratory failure. Peek et al found that survival without severe disability was significantly higher in patients who were transferred to a single specialized center for consideration of ECMO. In a randomized, controlled trial in 180 patients with a Murray lung injury score of 3.0 or higher, or uncompensated hypercapnia with a pH less than 7.20 despite optimal conventional treatment, 36.7% of patients in the ECMO arm had died or were severely disabled 6 months after randomization compared with 52.9% of patients in the conventional treatment arm. Although average total costs were more than twice as high for ECMO than for conventional care, lifetime quality-adjusted life-years (QALYs) gained were 10.75 for the ECMO group compared with 7.31 for the conventional group.[5] Airway management

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Assurance of an adequate airway is vital in a patient with acute respiratory distress. The most common indication for endotracheal intubation (ETT) is respiratory failure. ETT serves as an interface between the patient and the ventilator. Another indication for ETT is airway protection in patients with altered mental status.

Correction of hypoxemia
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After securing an airway, attention must turn to correcting the underlying hypoxemia, the most life-threatening facet of acute respiratory failure. The goal is to assure adequate oxygen delivery to tissues, generally achieved with a PaO2 of 60 mm Hg or an arterial oxygen saturation (SaO2) of greater than 90%. Supplemental oxygen is administered via nasal prongs or face mask; however, in patients with severe hypoxemia, intubation and mechanical ventilation are often required.

Coexistent hypercapnia and respiratory acidosis may need to be addressed. This is done by correcting the underlying cause or providing ventilatory assistance.
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Mechanical ventilation is used for 2 essential reasons: (1) to increase PaO2 and (2) to lower PaCO2. Mechanical ventilation also rests the respiratory muscles and is an appropriate therapy for respiratory muscle fatigue.

Ventilator management
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The use of mechanical ventilation during the polio epidemics of the 1950s was the impetus that led to the development of the discipline of critical care medicine. Prior to the mid 1950s, negative-pressure ventilation with the use of iron lungs was the predominant method of ventilatory support. Currently, virtually all mechanical ventilatory support for acute respiratory failure is provided by positive-pressure ventilation. Nevertheless, negative-pressure ventilation still is used occasionally in patients with chronic respiratory failure. Over the years, mechanical ventilators have evolved from simple pressure-cycled machines to sophisticated microprocessor-controlled systems. A brief review of mechanical ventilation is presented as follows.

Overview of mechanical ventilation

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Positive-pressure versus negative-pressure ventilation: In order for air to enter the lungs, a pressure gradient must exist between the airway and alveoli. This can be accomplished either by raising pressure at the airway (positive-pressure ventilation) or by lowering pressure at the level of the alveolus (negative-pressure ventilation). The iron lung or tank ventilator is the most common type of negative-pressure ventilator used in the past. These ventilators work by creating subatmospheric pressure around the chest, thereby lowering pleural and alveolar pressure, and thus facilitating flow of air into the patient's lungs. These ventilators are bulky, poorly

tolerated, and are not suitable for use in modern critical care units. Positive-pressure ventilation can be achieved by an endotracheal or tracheostomy tube or noninvasively through a nasal mask or face mask. Controlled versus patient-initiated (ie, assisted): Ventilatory assistance can be controlled (AC) or patient-initiated. In controlled modes of ventilation, the ventilator delivers assistance independent of the patient's own spontaneous inspiratory efforts. In contrast, during patient-initiated modes of ventilation, the ventilator delivers assistance in response to the patient's own inspiratory efforts. The patient's inspiratory efforts can be sensed either by pressure or flow-triggering mechanisms (see Triggering mechanism, below). Pressure-targeted versus volume-targeted: During positive-pressure ventilation, either pressure or volume may be set as the independent variable. In volumetargeted (or volume preset) ventilation, tidal volume is the independent variable set by the physician and/or respiratory therapist, and airway pressure is the dependent variable. In volume-targeted ventilation, airway pressure is a function of the set tidal volume and inspiratory flow rate, the patient's respiratory mechanics (compliance and resistance), and the patient's respiratory muscle activity. In pressure-targeted (or pressure preset) ventilation, airway pressure is the independent variable and tidal volume is the dependent variable. The tidal volume during pressure-targeted ventilation is a complex function of inspiratory time, the patient's respiratory mechanics, and the patient's own respiratory muscle activity.

Interface between patient and ventilator (mask vs endotracheal intubation)

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Mechanical ventilation requires an interface between the patient and the ventilator. In the past, this invariably occurred through an endotracheal or tracheostomy tube, but in recent years, an increasing trend has occurred towards noninvasive ventilation, which can be accomplished by the use of either a full face mask (covering both the nose and mouth) or a nasal mask (see Noninvasive ventilatory support, below).[6] Care of an endotracheal tube includes correct placement of the tube, maintenance of proper cuff pressure, and suctioning to maintain a patent airway. Following intubation, the position of the tube in the airway (rather than esophagus) should be confirmed by auscultation of the chest and, ideally, by a carbon dioxide detector. As a general rule, the endotracheal tube should be inserted to an average depth of 23 cm in men and 21 cm in women (measured at the incisor). Confirming proper placement of the endotracheal tube with a chest radiograph is recommended. The tube should be secured to prevent accidental extubation or migration into the mainstem bronchus, and the endotracheal tube cuff pressure should be monitored periodically. The pressure in the cuff generally should not exceed 25 mm Hg. Endotracheal suctioning can be accomplished by either open-circuit or closedcircuit suction catheters. Routine suctioning is not recommended because suctioning may be associated with a variety of complications, including desaturation, arrhythmias, bronchospasm, severe coughing, and introduction of secretions into the lower respiratory tract.

Specific modes of ventilatory support

Pressure support ventilation (PSV): PSV can be categorized as patient-initiated, pressure-targeted ventilation. With PSV, ventilatory assistance occurs only in response to the patient's spontaneous inspiratory efforts. With each inspiratory effort, the ventilator raises airway pressure by a preset amount. When the inspiratory flow rate decays to a minimal level or to a percentage of initial inspiratory flow (eg, 25% of peak flow), inspiration is terminated. During PSV, the patients are free to choose their own respiratory rate; inspiratory time, inspiratory flow rate, and tidal volume are determined, in part, by the patient's respiratory efforts. This mode of ventilation should not be used in patients with unstable ventilatory drive, and care must be exercised when the patient's respiratory mechanics are changing because of bronchospasm, secretions, or varying levels of autopositive end-expiratory pressure (auto-PEEP). Intermittent mandatory ventilation (IMV): IMV is a mode whereby mandatory breaths are delivered at a set frequency, tidal volume, and inspiratory flow rate. However, the patient can breathe spontaneously between the machine-delivered breaths. Most modern ventilators have synchronized IMV (SIMV), whereby the ventilator attempts to deliver the mandatory breaths in synchrony with the patient's own inspiratory efforts. In essence, the ventilator allows the patient an opportunity to breathe. If the patient makes an inspiratory effort during a window of time determined by the IMV rate, the ventilator delivers a mandatory breath in response to the patient's inspiratory effort. However, if no inspiratory effort is detected by the ventilator, a time-triggered breath is delivered. Compared with IMV, SIMV may improve patient comfort and may limit dynamic hyperinflation, which may occur when a preset breath is delivered immediately after the patient's spontaneous inspiratory effort (ie, prior to exhalation). Assist-control ventilation: In assist-control ventilation, patients receive a fixed tidal volume and inspiratory flow rate with each inspiratory effort, regardless of their respiratory rate. However, a "back-up rate" is selected that guarantees that the patient receives a minimum number of breaths per minute. If the patient's respiratory rate falls below the back-up rate, the ventilator delivers the number of breaths necessary to reach the back-up rate; such breaths are delivered independently of any inspiratory effort by the patient. Volume-control: In this mode, respiratory rate, tidal volume, and inspiratory flow rate (or inspiratory time) are fixed. This mode is used most often in heavily sedated or paralyzed patients. Pressure-control: In contrast to volume control, in pressure-control mode, airway pressure is raised by a set amount at a fixed number of times per minute. The physician or respiratory therapist also sets the inspiratory-to-expiratory (I:E) ratio or the inspiratory time. This mode is used most often in heavily sedated or paralyzed patients. Pressure-control inverse-ratio ventilation (PCIRV): PCIRV is a variation of simple pressure-control ventilation. In this mode, inspiration is set to be longer than expiration. The I:E ratio should rarely, if ever, exceed 3:1.

Triggering mechanism: pressure versus flow triggering

In patient-initiated (assisted) ventilation, the ventilator must sense the patient's inspiratory effort in order to deliver assistance. Ventilator triggering may be based on either a pressure or a flow change. With pressure-triggering, the ventilator is set to detect a certain change in pressure. The ventilator is triggered whenever airway pressure drops by the set amount. For example, in a patient on no positive end-expiratory pressure (PEEP) with a trigger sensitivity set at 1 cm water, a breath is triggered whenever airway pressure falls below -1 cm water. In a patient on 5-cm water PEEP with the same trigger sensitivity, a breath is triggered whenever airway pressure falls below +4 cm water. In flow-triggering, a continuous flow of gas is sent through the ventilator circuit. In some ventilators, this continuous flow rate may be set by the physician or respiratory therapist, whereas in other ventilators, the continuous flow rate is fixed. A flow sensitivity is selected, and the ventilator senses the patient's inspiratory efforts by detecting a change in flow. When the patient makes an inspiratory effort, some of the gas that was previously flowing continuously through the circuit is diverted to the patient. The ventilator senses the decrease in flow returning through the circuit, and a breath is triggered. One problem with flow-triggering is that autotriggering sometimes results from leaks in the ventilator circuit.

Positive end-expiratory pressure

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By maintaining airway (and hence alveolar) pressure greater than zero, PEEP may recruit atelectatic alveoli and prevent their collapse during the succeeding expiration. PEEP also shifts lung water from the alveoli into the perivascular interstitial space and helps with recruitment of alveoli. However, it does not decrease the total amount of extravascular lung water. In patients with disorders such as acute respiratory distress syndrome (ARDS) or acute lung injury, PEEP is applied to recruit atelectatic alveoli, thereby improving oxygenation and allowing a reduction in FiO2 to nontoxic levels (FiO2 < 0.6). Applying PEEP of 3-5 cm water to prevent a decrease in functional residual capacity in patients with normal lungs is a common practice. In an ARDS Network trial, higher PEEP produced better oxygenation and lung compliance but no benefit to survival, time on ventilator, or nonpulmonary organ dysfunction. Although sufficient PEEP is essential in ventilator management of patients with acute respiratory distress syndrome (ARDS), this level varies from patient to patient. Ideal PEEP helps to achieve adequate oxygenation and decrease the requirement for high fractions of inspiratory oxygen without causing any of the harmful effects of PEEP. Current evidence does not support routine application of high PEEP strategy in people with ALI or acute respiratory distress syndrome (ARDS); however, a 2010 study by Briel et al found higher PEEP levels have been associated with improved survival among patients with ARDS.[7] PEEP causes an increase in intrathoracic pressure, which may decrease venous return and cardiac output, particularly in patients with hypovolemia.

Inspiratory flow

In volume-targeted ventilation, inspiratory flow is a variable that is set by the physician or respiratory therapist. The inspiratory flow rate is selected on the basis of a number of factors, including the patient's inspiratory drive and the underlying disease. Two flow patterns are used commonly: (1) a constant-flow (ie, square-wave) pattern and (2) a decelerating-flow pattern. With a constant-flow pattern, inspiratory flow is held constant throughout the breath, whereas with a decelerating-flow pattern, flow rises quickly to a maximal value and then decreases progressively throughout the breath. In pressure-targeted ventilation, the inspiratory flow rate is a dependent variable that varies as a function of the preset pressure and the patient's own inspiratory effort. Because airway pressure is held constant while alveolar pressure rises during inspiration, the pressure difference between airway and alveoli decreases, leading to a decelerating pattern of inspiratory flow.

Determinants of ventilator-associated lung injury

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Mechanical ventilation is associated with a variety of insults to the lung. In the past, physicians focused on barotrauma, including pneumothorax, pneumomediastinum, and subcutaneous and pulmonary interstitial emphysema. The manifestations of barotrauma likely occur because of excessive alveolar wall stress. Excessive airway pressure by itself does not appear to cause barotrauma. In critically ill patients, the manifestations of barotrauma can be subtle. For example, the earliest sign of pneumothorax in supine patients may be the deep-sulcus sign or a collection of air anteriorly along cardiophrenic angle. More recently, lung damage indistinguishable from acute respiratory distress syndrome (ARDS) has been recognized to possibly be caused by certain patterns of ventilatory support. Early experiments in animals showed that mechanical ventilation employing high peak airway pressures and high tidal volume led to the formation of pulmonary edema. The mechanism was thought to be due to direct parenchymal injury and altered microvascular permeability secondary to high peak alveolar pressures. Recently, other investigators have shown that excessive tidal volumes resulting in alveolar overdistension are the most important factor in ventilator-associated lung injury. A strategy of using low tidal volumes in patients with acute respiratory distress syndrome (ARDS) who are on mechanical ventilation has led to a reduced incidence of barotrauma and improved survival rates in recently published clinical trials.

Mechanical ventilation in specific diseases

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General guidelines o The mode of ventilation should be suited to the needs of the patient. Following the initiation of mechanical ventilation, the ventilator settings should be adjusted based on the patient's lung mechanics, underlying disease process, gas exchange, and response to mechanical ventilation. o SIMV and assist-control ventilation often are used for the initiation of mechanical ventilation.

In patients with intact respiratory drive and mild-to-moderate respiratory failure, PSV may be a good initial choice. Supplemental oxygen o The lowest FiO2 that produces an SaO2 greater than 90% and a PaO2 greater than 60 mm Hg generally is recommended. o The prolonged use of FiO2 less than 0.6 is unlikely to cause pulmonary oxygen toxicity. Acute respiratory distress syndrome o The primary objective is to accomplish adequate gas exchange while avoiding excessive inspired oxygen concentrations and alveolar overdistension. o The traditional ventilatory strategy of delivering high tidal volumes leads to high end-inspiratory alveolar pressures (ie, plateau pressure). o Many investigators currently believe that repeated cycles of opening and collapsing of inflamed and atelectatic alveoli are detrimental to the lung. Failure to maintain a certain minimum alveolar volume may further accentuate the lung damage. Furthermore, transalveolar pressure (reflected by plateau pressure) exceeding 25-30 cm water is considered to be an important risk factor for stretch injury to the lungs. o Patients with acute respiratory distress syndrome (ARDS) should be targeted to receive a tidal volume of 6 mL/kg. Importantly, remember that the set tidal volume should be based on ideal rather than actual body weight. If the plateau pressure remains excessive (>30 cm water), further reductions in tidal volume may be necessary. o ARDSNet, a prospective randomized clinical trial, demonstrated a striking reduction in hospital mortality in patient with acute respiratory distress syndrome (ARDS) who were ventilated with 6 mL/kg predicted body weight compared with 12 mL/kg. Patients who received the lower tidal volume strategy also had more ventilator-free and organ failure-free days. In the lower tidal volume group, the target tidal volume was 6 mL/kg of predicted body weight. This strategy may lead to respiratory acidosis, which requires either high respiratory rates and or sodium bicarbonate infusion.[1] o Application of PEEP sufficient to raise the tidal volume above the lower inflection point (Pflex) on the pressure-volume curve may minimize alveolar wall stress and improve oxygenation. A pressure-volume curve can be constructed for an individual patient by measuring plateau pressures at different lung volumes. Pflex is the point at which the slope of the curve changes, indicating that the lung is operating at the most compliant part of the curve. o A lung-protective strategy in which the PaCO2 is allowed to rise (permissive hypercapnia) may reduce barotrauma and enhance survival. o In some patients with acute respiratory distress syndrome (ARDS), the prone position may lead to significant improvements in oxygenation; whether this translates to improved outcome is unknown. Obstructive airway diseases o In patients with COPD or asthma, institution of mechanical ventilation may worsen dynamic hyperinflation (auto-PEEP or intrinsic PEEP [PEEPi]). The
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dangers of auto-PEEP include a reduction in cardiac output and hypotension (because of decreased venous return) and barotrauma. The goals of mechanical ventilation in obstructive airway diseases are to unload the respiratory muscles, achieve adequate oxygenation, and minimize the development of dynamic hyperinflation and its associated adverse consequences. Following the initiation of mechanical ventilation, patients with status asthmaticus frequently develop severe dynamic hyperinflation, which is often associated with adverse hemodynamic effects. The development of dynamic hyperinflation can be minimized by delivering the lowest possible minute ventilation in the least possible time. Therefore, the initial ventilatory strategy should involve the delivery of relatively low tidal volumes (eg, 8-10 mL/kg) and lower respiratory rates (eg, 8-12 breaths per min) with a high inspiratory flow rate. In the absence of hypoxia, hypercapnia generally is well tolerated in most patients. Even marked levels of hypercapnia are preferable to attempts to normalize the PCO2, which could lead to dangerous levels of hyperinflation. Patients often require large amounts of sedation and occasionally paralysis until the bronchoconstriction and airway inflammation have improved. If a decision is made to measure trapped-gas volume (VEI), as recommended by some investigators, an attempt should be made to keep it below 20 mL/kg. The routine measurement of VEI is not recommended because measurement of plateau pressure and auto-PEEP provide similar information and are much easier to perform. Patients with COPD have expiratory flow limitation and are prone to the development of dynamic hyperinflation. Here again, the goal of mechanical ventilation is to unload the respiratory muscles while minimizing the degree of hyperinflation. The use of extrinsic PEEP may be considered in spontaneously breathing patients in order to reduce the work of breathing and to facilitate triggering of the ventilator. Care must be exercised to avoid causing further hyperinflation, and the set level of PEEP should always be less than the level of auto-PEEP.

Facilitating patient-ventilator synchrony

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During mechanical ventilation, many patients sometimes experience asynchrony between their own spontaneous respiratory efforts and the pattern of ventilation imposed by the ventilator. This can occur with both controlled and patient-initiated modes of ventilation. In order to achieve synchrony, the ventilator must not only sense and respond quickly to the onset of the patient's inspiratory efforts, it also must terminate the inspiratory phase when the patient's "respiratory clock" switches to expiration. Asynchronous interactions, commonly referred to as "fighting the ventilator," may occur when ventilator breaths and patient efforts are out of phase. This may lead to excessive work of breathing, increased respiratory muscle oxygen consumption, and decreased patient comfort.

Patient-ventilator asynchrony should be minimized, and a variety of ways is available to achieve this. Modern ventilators are equipped with significantly better valve characteristics compared to older-generation ventilators. Flow-triggering (with a continuous flow rate) appears to be more sensitive and more responsive to patient's spontaneous inspiratory efforts. Patient-ventilator asynchrony often occurs in the presence of auto-PEEP. AutoPEEP creates an inspiratory threshold load and thereby decreases the effective trigger sensitivity. This may be partially offset by the application of external PEEP. Sometimes, additional sedation may be necessary to achieve adequate patientventilator synchrony.

Noninvasive ventilatory support

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The application of ventilatory support through a nasal or full face mask in lieu of ETT is being used increasingly for patients with acute or chronic respiratory failure. Noninvasive ventilation should be considered in patients with mild-to-moderate acute respiratory failure. The patient should have an intact airway, airway-protective reflexes, and be alert enough to follow commands. In clinical trials, noninvasive positive-pressure ventilation (NPPV) has proven beneficial in acute exacerbations of COPD and asthma, decompensated CHF with mild-to-moderate pulmonary edema, and pulmonary edema from hypervolemia. Reports conflict regarding its efficacy in acute hypoxemia due to other causes (eg, pneumonia). A variety of methods and systems are available for delivering noninvasive ventilatory support. The benefits of NPPV depend on the underlying cause of respiratory failure. In acute exacerbations of obstructive lung disease, NPPV decreases PaCO2 by unloading the respiratory muscles and supplementing alveolar ventilation. The results of several clinical trials support the use of NPPV in this setting. In a large randomized trial comparing NPPV with a standard ICU approach, the use of NPPV was shown to reduce complications, duration of ICU stay, and mortality.[8] In patients in whom NPPV failed, mortality rates were similar to the intubated group (25% vs 30%). Plant and colleagues recently published the largest prospective randomized study comparing NPPV with standard treatment in patients with COPD exacerbation. NPPV was administered on the ward; the nurses were trained for 8 hours in the preceding 3 months. Treatment failed in significantly more patients in the control group (27% vs 15%), and in-hospital mortality rates were significantly reduced by NPPV (20% to 10%). In addition, 3 Italian cohort studies with historical or matched control groups have suggested that long-term outcome of patients treated with NPPV is better than that of patients treated with medical therapy and/or endotracheal intubation. In acute hypoxemic respiratory failure, NPPV also helps maintain an adequate PaO2 until the patient improves. In cardiogenic pulmonary edema, NPPV improves oxygenation, reduces work of breathing, and may increase cardiac output.

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When applied continuously to patients with chronic ventilatory failure, NPPV provides sufficient oxygenation and/or carbon dioxide elimination to sustain life by reversing or preventing atelectasis and/or resting the respiratory muscles. Patients with obesity-hypoventilation syndrome benefit from NPPV by reversal of the alveolar hypoventilation and upper airway obstruction. Most studies have used NPPV as an intermittent rather than continuous mode of support. Most trials have used inspiratory pressures of 12-20 cm water; expiratory pressures of 0-6 cm water; and excluded patients with hemodynamic instability, uncontrolled arrhythmia, or a high risk of aspiration.

Weaning from mechanical ventilation

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Weaning or liberation from mechanical ventilation is initiated when the underlying process that necessitated ventilatory support has improved. In some patients, such as those recovering from uncomplicated major surgery or a toxic ingestion, withdrawal of ventilator support may be done without weaning. In patients who required more prolonged respiratory therapy, the process of liberating the patient from ventilatory support may take much longer. A patient who has stable underlying respiratory status, adequate oxygenation (eg, PaO2/FiO2 >200 on PEEP < 10 cm water), intact respiratory drive, and stable cardiovascular status should be considered for discontinuation of mechanical ventilation. Over the years, many criteria have been used to predict success in weaning, including a minute ventilation of less than 10 L/min, maximal inspiratory pressure more than -25 cm water, vital capacity more than 10 mL/kg, absence of dyspnea, absence of paradoxical respiratory muscle activity, and agitation or tachycardia during the weaning trial. However, recent studies suggest that the rapid-shallow breathing index, ie, the patient's tidal volume (in liters) divided by the respiratory rate (breaths per min) during a period of spontaneous breathing, may be a better predictor of successful extubation. In a recent study, a daily trial of spontaneous breathing in patients with a rapid-shallow breathing index of less than 105 resulted in a shorter duration of mechanical ventilation. A spontaneous breathing trial of only 30 minutes appears adequate to identify patients in whom successful extubation is likely. In patients who are not yet ready to be liberated from the ventilator, one should focus on the cause of ventilator dependency, such as excessive secretions, inadequate respiratory drive, impaired cardiac function, and ventilatory muscle weakness, rather than the type of ventilator or the mode of assistance. The weaning protocol could be designed with assist-control ventilation, with gradually increasing time spent in trials of spontaneous breathing or by gradually reducing the level of PSV. SIMV appears to result in less rapid weaning than PSV or trials of spontaneous breathing. Patient-ventilator desynchrony is an important component in a carefully designed weaning protocol.

Attention must be directed toward patient comfort, avoidance of fatigue, adequate nutrition, and prevention and treatment of medical complications during the weaning period. Ventilator monitoring: Peak inspiratory and plateau pressures should be assessed frequently. Attempts should be made to limit the plateau pressure to less than 25 cm water. Expiratory volume is checked initially and periodically (continuously if ventilator-capable) to assure that the set tidal volume is delivered. In patients with severe airflow obstruction, auto-PEEP (PEEPi) should be monitored on a regular basis.

Monitoring of patients with acute respiratory failure

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A patient with respiratory failure requires repeated assessments, which may range from bedside observations to the use of invasive monitoring. These patients should be admitted to a facility where close observation can be provided. Most patients who require mechanical ventilation are critically ill; therefore, constant monitoring in a critical care setting is a must. Cardiac monitoring, blood pressure, pulse oximetry, SaO2, and capnometry are recommended. An arterial blood gas determination should be obtained 15-20 minutes after the institution of mechanical ventilation. The pulse oximetry readings direct efforts to reduce FiO2 to a value less than 0.6, and the PaCO2 guides adjustments of minute ventilation.

Treatment of underlying cause

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After the patient's hypoxemia is corrected and the ventilatory and hemodynamic status have stabilized, every attempt should be made to identify and correct the underlying pathophysiologic process that led to respiratory failure in the first place. The specific treatment depends on the etiology of respiratory failure. In Medication, a brief discussion of medications used to treat common causes of respiratory failure, such as cardiogenic pulmonary edema, chronic obstructive pulmonary disease, and asthma, is provided. The reader is recommended to review the article specific to the disease for the workup and management of the various disorders, all of which progress by different means but ultimately converge on a final common pathway of respiratory failure.

Consultations
Consultation with a pulmonary specialist and an intensivist are often required. Patients with acute respiratory failure or exacerbations of chronic respiratory failure need to be admitted to the intensive care unit for ventilatory support.

Activity

Patients generally are prescribed bed rest during early phases of respiratory failure management. However, ambulation as soon as possible helps ventilate atelectatic areas of the lung.

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. View full drug information

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. View full drug information

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. View full drug information

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. View full drug information

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. View full drug information

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. View full drug information

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. View full drug information

Norepinephrine (Levophed)
Used in protracted hypotension following adequate fluid replacement. Stimulates beta1and 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. View full drug information

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. View full drug information

Terbutaline (Brethaire, Bricanyl)

Acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance. View full drug information

Albuterol (Proventil)
Beta-agonist useful in the treatment of bronchospasm. Selectively stimulate beta2adrenergic receptors of the lungs. Bronchodilation results from relaxation of bronchial smooth muscle, which relieves bronchospasm and reduces airway resistance. View full drug information

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. View full drug information

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. View full drug information

Methylprednisolone (Solu-Medrol, Depo-Medrol)

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

Complications
Pulmonary
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Common pulmonary complications of acute respiratory failure include pulmonary embolism, barotrauma, pulmonary fibrosis, and complications secondary to the use of mechanical devices. Patients are also prone to develop nosocomial pneumonia. Regular assessment should be performed by periodic radiographic chest monitoring. Pulmonary fibrosis may follow acute lung injury associated with acute respiratory distress syndrome (ARDS). High oxygen concentrations and the use of large tidal volumes may worsen acute lung injury.

Cardiovascular
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Common cardiovascular complications in patients with acute respiratory failure include hypotension, reduced cardiac output, arrhythmia, pericarditis, and acute myocardial infarction. These complications may be related to the underlying disease process, mechanical ventilation, or the use of pulmonary artery catheters.

Gastrointestinal
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The major gastrointestinal complications associated with acute respiratory failure are hemorrhage, gastric distention, ileus, diarrhea, and pneumoperitoneum. Stress ulceration is common in patients with acute respiratory failure; the incidence can be reduced by routine use of antisecretory agents or mucosal protectants.

Infectious
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Nosocomial infections, such as pneumonia, urinary tract infections, and catheterrelated sepsis, are frequent complications of acute respiratory failure. These usually occur with the use of mechanical devices. The incidence of nosocomial pneumonia is high and associated with significant mortality.

Renal
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Acute renal failure and abnormalities of electrolytes and acid-base homeostasis are common in critically ill patients with respiratory failure. The development of acute renal failure in a patient with acute respiratory failure carries a poor prognosis and high mortality. The most common mechanisms of renal failure in this setting are renal hypoperfusion and the use of nephrotoxic drugs (including radiographic contrast material).

Nutritional
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These include malnutrition and its effects on respiratory performance and complications related to administration of enteral or parenteral nutrition. Complications associated with nasogastric tubes, such as abdominal distention and diarrhea, also may occur. Complications of parenteral nutrition may be mechanical due to catheter insertion, infectious, or metabolic (eg, hypoglycemia, electrolyte imbalance).

Prognosis
The mortality rate for acute respiratory distress syndrome (ARDS) is approximately 40%. Younger patients (< 60 y) have better survival rates than older patients. Approximately two thirds of patients who survive an episode of acute respiratory distress syndrome (ARDS) manifest some impairment of pulmonary function 1 or more years after recovery. Significant mortality also occurs in patients admitted with hypercapnic respiratory failure. This is because these patients have a chronic respiratory disorder and other comorbidities such as cardiopulmonary, renal, hepatic, or neurologic disease. These patients also may have poor nutritional status. For patients with COPD and acute respiratory failure, the overall mortality rate has declined from approximately 26% to 10%.

Patient Education
For excellent patient education resources, visit eMedicine's Lung and Airway Center. Also, see eMedicine's patient education article Acute Respiratory Distress Syndrome.