Respiratory Failure

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, it may be classified as either hypoxemic or hypercapnic.

Hypoxemic respiratory failure (type I) is characterized by an arterial oxygen tension (PaO₂) lower than 60 mm Hg with a normal or low arterial carbon dioxide tension (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 higher 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 and chronic obstructive pulmonary disease [COPD]).

Respiratory failure may be further classified as either 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.

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.

Arterial blood gases should be evaluated in all patients who are seriously ill or in whom respiratory failure is suspected. Chest radiography is essential. Echocardiography is not routine but is sometimes useful. Pulmonary functions tests (PFTs) may be helpful. Electrocardiography (ECG) should be performed to assess the possibility of a cardiovascular cause of respiratory failure; it also may detect dysrhythmias resulting from severe hypoxemia or acidosis. Right-sided heart catheterization is controversial (see Workup).

Hypoxemia is the major immediate threat to organ function. 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 (see Treatment).

For patient education resources, see the Lung and Airway Center, as well as Acute Respiratory Distress Syndrome.

• References

Pathophysiology

Respiratory failure can arise from an abnormality in any of the components of the respiratory system, including the airways, alveoli, central nervous system (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.

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.

Respiratory physiology

The act of respiration engages the following three processes:

• Transfer of oxygen across the alveolus
• Transport of oxygen to the tissues
• 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.

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. After diffusing 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 oxygen tension (PO₂) gradient. 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 have a large ventilation-to-perfusion ratio (V/Q) and are called high-V/Q units (which act like dead space). Alveoli that are optimally perfused but not adequately ventilated are called low-V/Q units (which act like a shunt).

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 relation is expressed by the following equation:

V_A = K × VCO₂/ PaCO₂

where K is a constant (0.863), V_A is alveolar ventilation, and VCO₂ is carbon dioxide ventilation. This relation determines 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 the alveolar-arterial PO₂ gradient. This difference is calculated by the following equation:

P_AO₂ = FiO₂ × (P_B – PH₂ O) – P_ACO₂/R

where P_A O₂ is alveolar PO₂, FiO₂ is fractional concentration of oxygen in inspired gas, P_B is barometric pressure, PH₂O is water vapor pressure at 37°C, P_ACO₂ is alveolar PCO₂ (assumed to be equal to PaCO₂), and R is respiratory exchange ratio. R depends on oxygen consumption and carbon dioxide production. At rest, the ratio of VCO₂ to oxygen ventilation (VO₂) is approximately 0.8.

Even normal lungs have some degree of V/Q mismatching and a small quantity of right-to-left shunt, with P_AO₂ slightly higher than PaO₂. However, an increase in the alveolar-arterial PO₂ gradient above 15-20 mm Hg indicates pulmonary disease as the cause of hypoxemia.

Hypoxemic respiratory failure

The pathophysiologic mechanisms that account for the hypoxemia observed in a wide variety of diseases are V/Q mismatch and shunt. These 2 mechanisms lead to widening of the alveolar-arterial PO₂ gradient, which normally is less than 15 mm Hg. They can be differentiated by assessing the response to oxygen supplementation or calculating the shunt fraction after inhalation of 100% oxygen. In most patients with hypoxemic respiratory failure, these 2 mechanisms coexist.

V/Q mismatch

V/Q mismatch is the most common cause of hypoxemia. Alveolar units may vary from low-V/Q to high-V/Q in the presence of a disease process. The low-V/Q units contribute to hypoxemia and hypercapnia, whereas the high-V/Q units waste ventilation but do not affect gas exchange unless the abnormality is 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 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:

Q_S/Q_T = (C_CO₂ – C_aO₂)/C_CO₂ – C_vO₂)

where Q_S/Q_T is the shunt fraction, C_CO₂ is capillary oxygen content (calculated from ideal P_AO₂), C_aO₂ is arterial oxygen content (derived from PaO₂ by using the oxygen dissociation curve), and C_vO₂ is mixed venous oxygen content (assumed or measured by drawing mixed venous blood from a pulmonary arterial catheter).

Anatomic shunt exists in normal lungs because of the bronchial and thebesian circulations, which account 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%). Compared with V/Q mismatch, hypoxemia produced by shunt is difficult to correct by means of oxygen administration.

Hypercapnic respiratory failure

At a constant rate of carbon dioxide production, PaCO₂ is determined by the level of alveolar ventilation according to the following equation (a restatement of the equation given above for alveolar ventilation):

PaCO₂ = VCO₂ × K/V_A

where K is a constant (0.863). The relation between PaCO₂ and alveolar ventilation is hyperbolic. As ventilation decreases below 4-6 L/min, PaCO₂ rises precipitously. 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.

Hypoventilation 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. Hypoventilation can be differentiated from other causes of hypoxemia by the presence of a normal alveolar-arterial PO₂ gradient.

• References

Etiology

These diseases can be grouped according to the primary abnormality and the individual components of the respiratory system (eg, CNS, peripheral nervous system, respiratory muscles, chest wall, airways, and alveoli).

A variety of pharmacologic, structural, and metabolic disorders of the CNS are characterized by depression of the neural drive to breathe. This may lead to acute or chronic hypoventilation and hypercapnia. 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 lead to an inability to maintain a level of minute ventilation appropriate for the rate of carbon dioxide production. Concomitant hypoxemia and hypercapnia occur. Examples include Guillain-Barré syndrome, muscular dystrophy, myasthenia gravis, severe kyphoscoliosis, and morbid obesity.

Severe airway obstruction is a common cause of acute and chronic hypercapnia. Examples of upper-airway disorders are acute epiglottitis and tumors involving the trachea; lower-airway disorders include COPD, asthma, and cystic fibrosis.

Diseases of the alveoli are characterized by diffuse alveolar filling, frequently resulting in hypoxemic respiratory failure, although hypercapnia may complicate the clinical picture. 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 include the following:

• COPD
• Pneumonia
• Pulmonary edema
• Pulmonary fibrosis
• Asthma
• Pneumothorax
• Pulmonary embolism
• Pulmonary arterial hypertension
• Pneumoconiosis
• Granulomatous lung diseases
• Cyanotic congenital heart disease
• Bronchiectasis
• Acute respiratory distress syndrome (ARDS)
• Fat embolism syndrome
• Kyphoscoliosis
• Obesity

Common causes of type II (hypercapnic) respiratory failure include the following:

• COPD
• Severe asthma
• Drug overdose
• Poisonings
• Myasthenia gravis
• Polyneuropathy
• Poliomyelitis
• Primary muscle disorders
• Porphyria
• Cervical cordotomy
• Head and cervical cord injury
• Primary alveolar hypoventilation
• Obesity-hypoventilation syndrome
• Pulmonary edema
• ARDS
• Myxedema
• Tetanus

• References

Epidemiology

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 in this article can be found in the Medscape Reference articles specific to each disease.

The relationship between acute respiratory failure and race is still debated. A study 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.^[1] Moss and Mannino reported worse outcome for African Americans with ARDS than for whites after adjustment for case mix.^[2] Future prospective association studies should yield a better knowledge of the impact of race on the outcome of respiratory failure.

• References

Prognosis

The mortality associated with respiratory failure varies according to the etiology. For ARDS, mortality is approximately 40-45%; this figure has not changed significantly over the years.^{[3, 4]} Younger patients (< 60 y) have better survival rates than older patients. Approximately two thirds of patients who survive an episode of 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 has declined from approximately 26% to 10%. Acute exacerbation of COPD carries a mortality 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 among patients with acute respiratory failure.^[5] Although cessation exacerbates the mortality, predischarge initiation of beta-blockers is also associated with an improved 1-year mortality.

• References

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 (see Workup). Evaluation of an underlying cause must be initiated early, frequently in the presence of concurrent treatment for acute respiratory failure. The cause of respiratory failure is often evident after a careful history and physical examination.

Cardiogenic pulmonary edema usually develops in the context of a history of left ventricular dysfunction or valvular heart disease. A history of previous cardiac disease, recent symptoms of chest pain, paroxysmal nocturnal dyspnea, and orthopnea suggest cardiogenic pulmonary edema. 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.

A study by Canet et al, examining acute respiratory failure in kidney transplant recipients, determined that 200 of 6,819 kidney transplant recipients required admission to the intensive care unit (ICU) for acute respiratory failure, which was associated with high mortality and graft loss rates.^[6] Early ICU admission and increased bacterial and Pneumocystis prophylaxis may improve outcomes.

• References

Physical Examination

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 (eg, pneumonia, pulmonary edema, asthma, or chronic obstructive pulmonary disease [COPD]), may be readily apparent. In patients with ARDS, the manifestations may be remote from the thorax, such as abdominal pain or long-bone fracture. Neurologic manifestations include restlessness, anxiety, confusion, seizures, or coma.

Asterixis may be observed with severe hypercapnia. Tachycardia and a variety of arrhythmias may result from hypoxemia and acidosis.

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 long-standing 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 ARDS include the following:

• Clinical presentation - Tachypnea and dyspnea; crackles upon auscultation
• Clinical setting - Direct insult (aspiration) or systemic process causing lung injury (sepsis)
• Radiologic appearance - 3-quadrant or 4-quadrant alveolar flooding
• Lung mechanics - Diminished compliance (< 40 mL/cm water)
• Gas exchange - Severe hypoxia refractory to oxygen therapy (ratio of arterial oxygen tension to fractional concentration of oxygen in inspired gas [PaO₂/FiO₂] < 200)
• Normal pulmonary vascular properties - Pulmonary capillary wedge pressure lower than 18 mm Hg

• References

Complications

Complications of acute respiratory failure may be pulmonary, cardiovascular, gastrointestinal (GI), infectious, renal, or nutritional.

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 ARDS. High oxygen concentrations and the use of large tidal volumes may worsen acute lung injury.

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

The major GI 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.

Nosocomial infections, such as pneumonia, urinary tract infections, and catheter-related 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.

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 complications 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 (resulting from catheter insertion), infectious, or metabolic (eg, hypoglycemia, electrolyte imbalance).

• References

Approach Considerations

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.

Chest radiography is essential. Echocardiography is not routinely done but is sometimes useful. Pulmonary functions tests (PFTs), if feasible, may be helpful, although more useful in terms of defining recovery potential. Electrocardiography (ECG) should be performed to evaluate the possibility of a cardiovascular cause of respiratory failure; it also may detect dysrhythmias resulting from severe hypoxemia or acidosis. Right-sided heart catheterization is controversial.

• References

Laboratory Studies

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 helps guide management.

A complete blood cell (CBC) 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 level with a normal troponin I level may indicate myositis, which occasionally can cause respiratory failure.

In chronic hypercapnic respiratory failure, serum levels of thyroid-stimulating hormone (TSH) should be measured to evaluate the possibility of hypothyroidism, a potentially reversible cause of respiratory failure.

• References

Radiography

Chest radiography is essential in the evaluation of respiratory failure because it frequently reveals the cause (see the images below). However, distinguishing between cardiogenic and noncardiogenic pulmonary edema is often 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).

View Image

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

View Image

Extensive left-lung pneumonia caused respiratory failure; the mechanism of hypoxia is intrapulmonary shunting.

View Image

A 44-year-old woman developed acute respiratory failure and diffuse bilateral infiltrates. She met the clinical criteria for the diagnosis of acute re....

View Image

This patient developed acute respiratory failure that turned out to be the initial presentation of systemic lupus erythematosus. The lung pathology ev....

• References

Echocardiography

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 ARDS.

Echocardiography provides an estimate of right ventricular function and pulmonary artery pressure in patients with chronic hypercapnic respiratory failure.

• References

Pulmonary Function Tests

Patients with acute respiratory failure generally are unable to perform PFTs; however, these tests are useful in the evaluation of chronic respiratory failure.

Normal values for forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) suggest a disturbance in respiratory control. A decrease in the FEV₁ -to-FVC ratio (FEV₁/FVC) indicates airflow obstruction, whereas a reduction in both FEV₁ and FVC and maintenance of FEV₁/FVC suggest restrictive lung disease.

Respiratory failure is uncommon in obstructive diseases when FEV₁ is greater than 1 L and in restrictive diseases when FVC is greater than 1 L.

See Pulmonary Function Testing for further details.

• References

Right-Sided Heart Catheterization

Right-sided heart catheterization (also known as pulmonary artery catheterization or Swan-Ganz catheterization) 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-sided 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.

• References

Approach Considerations

The risks of oxygen therapy are oxygen toxicity and carbon dioxide narcosis. Pulmonary oxygen toxicity rarely occurs when a fractional concentration of oxygen in inspired gas (FiO₂) lower than 0.6 is used; therefore, an attempt to lower the inspired oxygen concentration to this level should be made in critically ill patients.

Carbon dioxide narcosis occasionally occurs when some patients with hypercapnia are given oxygen to breathe. Arterial carbon dioxide tension (PaCO₂) increases sharply and progressively with severe respiratory acidosis, somnolence, and coma. The mechanism is primarily the reversal of pulmonary vasoconstriction and the increase in dead space ventilation.

Hypoxemia is the major immediate threat to organ function. 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.

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.

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.

• References

Correction of Hypoxemia

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 unit or intensive care unit (ICU). 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.^[7] In a randomized, controlled trial in 180 patients either with a Murray lung injury score of 3.0 or higher or with uncompensated hypercapnia and a pH lower 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 in this study, lifetime quality-adjusted life-years (QALYs) gained were 10.75 for the ECMO group and 7.31 for the conventional group.^[7]

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

Once the airway is secured, attention is turned toward 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 an arterial oxygen tension (PaO₂) of 60 mm Hg or an arterial oxygen saturation (SaO₂) 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 have to be addressed. This is done by correcting the underlying cause or providing ventilatory assistance.

While correcting for hypoxemia, the physiologic parameters have to be remembered. One of the concepts relevant to mechanical ventilation is the so-called “driving pressure” or “transmural pressure”. For any hollow structure (be it the heart or lung), the distending pressure is defined by the difference between the cavity pressure—in this case, the airway pressures—and the intrathoracic pressures. The difference between these two pressures is the determinant of the driving pressure and in the case of a stiff chest wall due to blunt trauma, burns, or increased intra-abdominal pressures, the extra-alveolar pressures may overcome the alveolar pressures and decrease the effective distending pressures. To address this concept, work by Talmor and others used an approach to guide the mechanical ventilation with the use of esophageal manometry.^[8] In this work, esophageal pressures were used as a surrogate for intrathoracic pressures and these numbers were subtracted from airway pressures to define the actual driving pressures. The study was conducted in patients with ARDS and they were able to show decreased inflammatory cytokines in the intervention group.

• References

Principles of Mechanical Ventilation

Mechanical ventilation is used for two 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.

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. Before 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.

Types of mechanical ventilation

Over the years, mechanical ventilators have evolved from simple pressure-cycled machines to sophisticated microprocessor-controlled systems. The following is a brief overview of the basic principles of their use.

Positive-pressure versus negative-pressure ventilation

For air to enter the lungs, a pressure gradient must exist between the airway and the 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 facilitating flow of air into the patient’s lungs. These ventilators are bulky and poorly tolerated and are not suitable for use in modern critical care units. Positive-pressure ventilation can be achieved via an endotracheal or tracheostomy tube or noninvasively through a nasal mask or face mask.

Controlled versus patient-initiated ventilation

Ventilatory assistance can be controlled or patient-initiated. In controlled ventilation, the ventilator delivers assistance independent of the patient’s own spontaneous inspiratory efforts. In contrast, during patient-initiated 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.

Pressure-targeted versus volume-targeted ventilation

During positive-pressure ventilation, either pressure or volume may be set as the independent variable.

In volume-targeted (or volume preset) ventilation, tidal volume is the independent variable set by the physician or respiratory therapist, and airway pressure is the dependent variable. In this type of 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.

Endotracheal intubation

Mechanical ventilation requires an interface between the patient and the ventilator. In the past, this invariably occurred through an endotracheal or tracheostomy tube, but there is a growing trend toward 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).^[9] Care of an endotracheal tube includes correct placement of the tube, maintenance of proper cuff pressure, and suctioning to maintain a patent airway.

After intubation, the position of the tube in the airway (rather than the 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 via either open-circuit or closed-circuit 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.

Ventilator modes

Pressure support ventilation (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, 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 auto–positive end-expiratory pressure (auto-PEEP).

Intermittent mandatory ventilation (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 are capable of 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 standard 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, before exhalation).

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 backup 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 backup rate, the ventilator delivers the number of breaths necessary to reach that rate; such breaths are delivered independent of any inspiratory effort by the patient.

In volume-control 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.

In pressure-control mode, as contrasted with volume-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) 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 mechanisms

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 a change in either pressure or flow.

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.

With 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 automatic triggering sometimes results from leaks in the ventilator circuit.

Positive end-expiratory pressure

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 (ALI), PEEP is applied to recruit atelectatic alveoli, thereby improving oxygenation and allowing a reduction in FiO₂ to nontoxic levels (< 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.^[3] Although sufficient PEEP is essential in ventilator management of patients with 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 ARDS; however, a study by Briel et al found higher PEEP levels have been associated with improved survival among patients with ARDS.^[10]

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 (see the image below) 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.

View Image

Wave forms of a volume-targeted ventilator: Pressure, flow, and volume waveforms are shown with square-wave flow pattern. A is baseline, B is increase....

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.

Ventilator-associated lung injury

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 probably result from 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.

It is now recognized that lung damage indistinguishable from ARDS may be caused by certain patterns of ventilatory support. Early animal experiments showed that mechanical ventilation employing high peak airway pressures and high tidal volume led to pulmonary edema, possibly as a result of direct parenchymal injury and altered microvascular permeability secondary to high peak alveolar pressures. Subsequent work indicates that excessive tidal volumes resulting in alveolar overdistention are the most important factor in ventilator-associated lung injury.

A strategy of using low tidal volumes in patients with ARDS who are on mechanical ventilation has led to a reduced incidence of barotrauma and improved survival rates in clinical trials.

• References

Ventilation Approaches for Specific Diseases

The mode of ventilation should be suited to the needs of the patient. After the initiation of mechanical ventilation, ventilator settings should be adjusted on the basis of the patient’s lung mechanics, underlying disease process, gas exchange, and response to mechanical ventilation. SIMV and assist-control ventilation are often 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.

The lowest FiO₂ that produces an SaO₂ greater than 90% and a PaO₂ greater than 60 mm Hg generally is recommended. The prolonged use of an FiO₂ lower than 0.6 is unlikely to cause pulmonary oxygen toxicity.

Acute respiratory distress syndrome

In ARDS, the primary objective of mechanical ventilation is to accomplish adequate gas exchange while avoiding excessive inspired oxygen concentrations and alveolar overdistention.

The traditional ventilatory strategy of delivering high tidal volumes leads to high end-inspiratory alveolar pressures (ie, plateau pressure). Many investigators now 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.

Patients with ARDS should be targeted to receive a tidal volume of 6 mL/kg. It is important to 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.

ARDSNet, a prospective randomized clinical trial, demonstrated a striking reduction in hospital mortality in ARDS patients who were ventilated with 6 mL/kg predicted body weight rather than with 12 mL/kg.^[3] Patients who received the lower tidal volume strategy also had more ventilator-free and organ failure-free days. This strategy may lead to respiratory acidosis, which requires either high respiratory rates and or sodium bicarbonate infusion.

Application of PEEP sufficient to raise the tidal volume above the lower inflection point (P_flex) 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 (see the image below). P_flex is the point where the slope of the curve changes, indicating that the lung is operating at the most compliant part of the curve.

View Image

Pressure-volume curve of a patient with acute respiratory distress syndrome (ARDS) on mechanical ventilation can be constructed. The lower and the upp....

A lung-protective strategy in which the PaCO₂ is allowed to rise (permissive hypercapnia) may reduce barotrauma and enhance survival.

In some patients with ARDS, the prone position may lead to significant improvements in oxygenation; whether this translates to improved outcome is unknown.

Lower end-inspiratory (plateau) airway pressures, lower tidal volumes (VT), and higher positive end-expiratory pressures (PEEPs) can decrease mortality in ARDS; however, the contributions of these individual components is not clear. Work by Amato et al attempted to dissect these relations.^[11] The group studied the dynamic compliance (C_dyn) in relation to VT, and their results suggest that in this dynamic relationship, the driving pressure (ΔP=VT/C_dyn) has a better predictive value than PEEP or VT for survival from ARDS.

Obstructive airway diseases

In patients with chronic obstructive pulmonary disease (COPD) or asthma, initiation of mechanical ventilation may worsen dynamic hyperinflation (auto-PEEP or intrinsic PEEP [PEEPi]). The dangers of auto-PEEP include reduction in cardiac output and hypotension (because of decreased venous return), as well as 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.

After 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, 6 mL/kg) and lower respiratory rates (eg, 8-12 breaths/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 carbon dioxide tension (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 (ie, end-inspiratory volume [V_EI]), as recommended by some investigators, an attempt should be made to keep it below 20 mL/kg. Routine measurement of V_EI 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.

Patient-ventilator synchrony

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.

To achieve synchrony, the ventilator not only must sense and respond quickly to the onset of the patient’s inspiratory efforts but also must terminate the inspiratory phase when the patient’s “respiratory clock” switches to expiration. Asynchronous interactions (“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.

There are several ways of minimizing patient-ventilator asynchrony. Modern ventilators are equipped with significantly better valve characteristics than older-generation ventilators had. In addition, 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. Auto-PEEP 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 patient-ventilator synchrony.

• References

Noninvasive Ventilatory Support

Ventilatory support via a nasal or full-face mask rather than via an endotracheal tube (see the images below) is increasingly being employed 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.

View Image

Headgear and full face mask commonly are used as the interface for noninvasive ventilatory support.

View Image

Noninvasive ventilation with bilevel positive airway pressure for acute respiratory failure secondary to exacerbation of chronic obstructive pulmonary....

In clinical trials, noninvasive positive-pressure ventilation (NPPV) has proven beneficial in acute exacerbations of COPD and asthma, decompensated congestive heart failure (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.^[12] In patients in whom NPPV failed, mortality rates were similar to the intubated group (25% vs 30%).

In the largest prospective randomized study comparing NPPV with standard treatment in patients with COPD exacerbation, Plant et al found that treatment failed in significantly more patients in the control group (27% vs 15%) and that in-hospital mortality rates were significantly reduced by NPPV (20% to 10%). NPPV was administered on the ward; the nurses were trained for 8 hours in the preceding 3 months.^[13]

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.^{[14, 15, 16]}

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.

When applied continuously to patients with chronic ventilatory failure, NPPV provides sufficient oxygenation or carbon dioxide elimination to sustain life by reversing or preventing atelectasis or resting the respiratory muscles.

Patients with obesity-hypoventilation syndrome benefit from NPPV as a consequence of 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 and expiratory pressures of 0-6 cm water and have excluded patients with hemodynamic instability, uncontrolled arrhythmia, or a high risk of aspiration.

• References

Weaning From Ventilator

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 discontinuance of mechanical ventilation.

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, the rapid-shallow breathing index—that is, the patient’s tidal volume (in liters) divided by the respiratory rate (in breaths/min) during a period of spontaneous breathing—may be a better predictor of successful extubation.

In one 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.

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.

• References

Long-Term Monitoring

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.

• References

Guidelines Summary

Summary of guidelines on acute respiratory failure (ARF) by the European Respiratory Society/American Thoracic Society

Bilevel noninvasive mechanical ventilation (NIV) may be considered in chronic obstructive pulmonary disease (COPD) patients with an acute exacerbation in the following three clinical settings^[17] :

• To prevent acute respiratory acidosis (ie, when the arterial carbon dioxide tension [PaCO₂] is normal or elevated but pH is normal)
• To prevent endotracheal intubation and invasive mechanical ventilation in patients with mild-to-moderate acidosis and respiratory distress, with the aim of preventing deterioration to a point when invasive ventilation would be considered
• As an alternative to invasive ventilation in patients with severe acidosis and more severe respiratory distress

Bilevel NIV also may be used as the only method for providing ventilatory support in patients who are not candidates for or decline invasive mechanical ventilation.^[17]

Bilevel NIV is recommended as follows^[17] :

• Patients with ARF leading to acute or acute-on-chronic respiratory acidosis (pH ≤7.35) due to COPD exacerbation
• Patients considered to require endotracheal intubation and mechanical ventilation, unless the patient is immediately deteriorating

Either bilevel NIV or continuous positive airway pressure (CPAP) is recommended for patients with ARF due to cardiogenic pulmonary edema.^[17]

CPAP or bilevel NIV is suggested for patients with ARF due to cardiogenic pulmonary edema in the prehospital setting.^[17]

Early NIV is suggested for immunocompromised patients with ARF.^[17]

NIV use is suggested as follows^[17] :

• For patients with postoperative ARF
• Can be offered to dyspneic patients for palliation in the setting of terminal cancer or other terminal conditions
• For the prevention of postextubation respiratory failure in high-risk patients; not suggested to prevent postextubation respiratory failure in non–high-risk patients
• To facilitate weaning from mechanical ventilation in patients with hypercapnic respiratory failure

• References

Medication Summary

Pharmacotherapy for cardiogenic pulmonary edema and acute exacerbations of chronic obstructive pulmonary disease (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 have to be modified for some patients. Diuretics, nitrates, analgesics, and inotropes are used in the treatment of acute pulmonary edema.

• References

Furosemide (Lasix)

• Dosing, Interactions, etc.

Clinical Context:  Administer loop diuretics such as furosemide intravenously (IV) because this allows both superior potency and a higher peak concentration despite an increased incidence of adverse effects, particularly ototoxicity.

• References

Metolazone (Zaroxolyn)

• Dosing, Interactions, etc.

Clinical Context:  Metolazone has been used as adjunctive therapy in patients initially refractory to furosemide. It has been demonstrated to be synergistic with loop diuretics in treating refractory patients and causes a greater loss of potassium. Metolazone is a potent thiazide-related diuretic that sometimes is used in combination with furosemide for more aggressive diuresis. It is also used for initiating diuresis in patients with a degree of renal dysfunction.

• References

Class Summary

First-line therapy generally includes a loop diuretic such as furosemide, which inhibits sodium chloride reabsorption in the ascending loop of Henle.

• References

Nitroglycerin sublingual (Nitro-Bid, NitroMist, Nitrostat, Nitrolingual)

• Dosing, Interactions, etc.

Clinical Context:  Sublingual nitroglycerin tablets and spray are particularly useful in the patient who presents with acute pulmonary edema with a systolic blood pressure of at least 100 mm Hg. As with sublingual nitroglycerin tablets, the onset of action of nitroglycerin spray is 1-3 minutes, with a half-life of 5 minutes. Administration of the spray may be easier, and it can be stored for as long as 4 years.

Topical nitrate therapy is reasonable in a patient presenting with class I-II congestive heart failure (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, because of their delayed absorption, play little role in the management of acute pulmonary edema.

• References

Nitroprusside sodium (Nitropress)

• Dosing, Interactions, etc.

Clinical Context:  Nitroprusside produces vasodilation of venous and arterial circulation. At higher dosages, it may exacerbate myocardial ischemia by increasing heart rate. It is easily titratable.

• References

Class Summary

Nitrates reduce myocardial oxygen demand by lowering preload and afterload. In severely hypertensive patients, nitroprusside causes more arterial dilatation than nitroglycerin. Nevertheless, in view of 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.

• References

Morphine sulfate (Duramorph, Astramorph)

• Dosing, Interactions, etc.

Clinical Context:  Morphine sulfate is the drug of choice for narcotic analgesia because of its 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 the desired effect is obtained.

• References

Class Summary

Morphine IV is an excellent adjunct in the management of acute pulmonary edema. In addition to anxiolysis and analgesia, its most important effect is venodilation, which reduces preload. It also causes arterial dilatation, which reduces systemic vascular resistance and may increase cardiac output.

• References

Dopamine

• Dosing, Interactions, etc.

Clinical Context:  Dopamine is a positive inotropic agent that stimulates both adrenergic and dopaminergic receptors. Its hemodynamic effects depend on the dose. Lower doses stimulate mainly dopaminergic receptors that produce renal and mesenteric vasodilation; higher doses produce cardiac stimulation and renal vasodilation. Doses of 2-10 µg/kg/min can lead to tachycardia, ischemia, and dysrhythmias. Doses higher than 10 µg/kg/min cause vasoconstriction, which increases afterload.

• References

Norepinephrine (Levophed)

• Dosing, Interactions, etc.

Clinical Context:  Norepinephrine is used in protracted hypotension after adequate fluid replacement. It stimulates beta1- and alpha-adrenergic receptors, which leads to increased cardiac muscle contractility and heart rate, as well as vasoconstriction. As a result, norepinephrine 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.

• References

Dobutamine

• Dosing, Interactions, etc.

Clinical Context:  Dobutamine produces vasodilation and increases the inotropic state. At higher dosages, it may cause increased heart rates, thus exacerbating myocardial ischemia. It is a strong inotropic agent with minimal chronotropic effect and no vasoconstriction.

• References

Class Summary

The principal inotropic agents are dopamine, dobutamine, inamrinone (formerly amrinone), milrinone, dopexamine, and digoxin. In patients with hypotension who present with CHF, dopamine and dobutamine usually are employed. Inamrinone and milrinone inhibit phosphodiesterase, resulting in increased intracellular cyclic adenosine monophosphate (cAMP) and altered calcium transport. As a result, they increase cardiac contractility and reduce vascular tone by vasodilatation.

• References

Terbutaline (Brethaire, Bricanyl)

• Dosing, Interactions, etc.

Clinical Context:  Terbutaline acts directly on beta2 receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.

• References

Albuterol (Proventil)

• Dosing, Interactions, etc.

Clinical Context:  Albuterol is a beta-agonist useful in the treatment of bronchospasm. It selectively stimulates beta2-adrenergic receptors of the lungs. Bronchodilation results from relaxation of bronchial smooth muscle, which relieves bronchospasm and reduces airway resistance.

• References

Class Summary

Bronchodilators 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.

• References

Theophylline (Elixophyllin Elixir, Theo-24)

• Dosing, Interactions, etc.

Clinical Context:  Theophylline has a number of physiologic effects, including increases in collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. It partially acts by inhibiting phosphodiesterase, elevating cellular cAMP levels, or antagonizing adenosine receptors in the bronchi, resulting in relaxation of smooth muscle. However, its clinical efficacy is controversial, especially in the acute setting.

• References

Class Summary

Xanthine derivatives may relax smooth muscle of the bronchi.

• References

Ipratropium bromide (Atrovent HFA)

• Dosing, Interactions, etc.

Clinical Context:  Ipratropium bromide is an anticholinergic medication that appears to inhibit vagally mediated reflexes by antagonizing the 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. Ipratropium can be combined with a beta-agonist because it may require 20 minutes to begin having an effect.

• References

Class Summary

Anticholinergics antagonize the action of acetylcholine with muscarinic receptor on bronchial smooth muscle.

• References

Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol)

• Dosing, Interactions, etc.

Clinical Context:  Methylprednisolone is usually given IV in the ED for initiation of corticosteroid therapy, although in theory, oral administration should be equally efficacious.

• References

Class Summary

Corticosteroids 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 emergency department (ED), they have some effect 6-8 hours into therapy; therefore, early dosing is critical.

• References