Critical Care Update
David J. Dries, MSE, MD
Mechanical Ventilation: History and Harm Slutsky AS. History of mechanical ventilation. From Vesalius to ventilator-induced lung injury. Am J Respir Crit Care Med. 2015;191:1106-1115. Marini JJ. Mechanical ventilation: past lessons and the near future. Crit Care. 2013;17(suppl 1):S1.
Early Years Contemporary approaches to mechanical ventilation began in the 1700s with the discovery of oxygen and subsequently the importance of respiration in the delivery of oxygen. Mouth-to-mouth resuscitation had been described by this time. Ironically, as Slusky notes, mouth-to-mouth resuscitation was discontinued after the discovery of oxygen because it was believed that exhaled air was lacking in oxygen because it had already been processed in another person’s lungs. Ventilator therapy based on contemporary appreciation of applied physiology began to appear in the 19th century. At this time, ventilation was provided using subatmospheric pressure delivered around the patient to replace or augment work done by respiratory muscles. Patients could sit or lay in a box that enclosed the body from the neck down or contained the entire patient. A plunger or other mechanism was used to decrease air pressure in the box, causing inspiration while the reverse produced expiration. The first workable iron lung was introduced in 1876 and replaced the previous box devices. The iron lung was used in Boston to treat polio patients in the early 20th century. A major problem with all of these devices was the extreme difficulty associated with nursing patients because it was difficult to get access to the body. To address this problem, respirator rooms were developed in which the patient lay with their head outside the room while inside huge pistons generated pressure changes sufficient to cause air to move into and out of the lungs. The ventilator room had a door so that the medical staff could enter the ventilator to care for the patient. Ultimately, rooms were developed in which multiple patients could be treated. This technology again was used in Boston for patients afflicted by several epidemics. When polio reappeared in the 1950s, it was a watershed event in the history of mechanical ventilation. Before this time, mechanical ventilation appeared to have usefulness but was not widely used. After the 1950s outbreak of polio, the benefits of ventilation were dramatic and obvious, leading to widespread use worldwide. In 1951, an international polio conference in Copenhagen was attended by most of the world’s polio experts. The following summer, Copenhagen experienced a terrible polio epidemic likely triggered by the carriage of polio virus to Copenhagen during the previous year’s conference. At the height of the epidemic, 50 patients 12
per day were being admitted to the hospital, many with respiratory failure. Mortality in these patients exceeded 80%. At the time, most physicians believed that patients were dying from renal failure associated with systemic viremia. Ibsen, an anesthesiologist trained in Boston, realized that death in these patients was associated with respiratory failure and recommended tracheostomy and positive pressure ventilation (PPV). With the introduction of PPV, mortality immediately dropped from greater than 80% to approximately 40%. Delivering care to these patients was a logistical problem because there were no mechanical positive pressure ventilators. Patients had to be hand bagged. It is estimated that at the height of the polio epidemic, 70 patients were simultaneously being manually ventilated. At the end of the polio epidemic, approximately 1,500 (medical) students provided manual ventilation for a total of 165,000 hours. One approach to the logistical challenge was to take care of these patients in 1 location. This led to the first intensive care units as we know them today. The initial emphasis in providing support with assisted ventilation was replacement of respiratory muscle activity. Over ensuing decades, this changed with a greater focus on oxygenation failure stimulated in part by improved technology for the measurement of blood gases and identification of the acute respiratory distress syndrome (ARDS). The 1960s were also a pivotal decade in the development of PPV influenced by advances in physiology and surgery and the need to address problems of postoperative lung collapse and traumatic lung injuries from battlefield conflict. Pressure-cycled devices were introduced, which delivered intermittent positive pressure not only to replace the work of respiratory muscles but to aid coughing, reduce basal lung collapse, and improve delivery of therapeutic aerosols. Improved control of inflation and deflation was developed so that these phases of each breath could be separately regulated. Treatment of ARDS was a central driver of new approaches to mechanical ventilation for respiratory failure but not the only one. Clinicians needed techniques to provide partial respiratory support, recondition respiratory muscles after pulmonary disease, and gauge readiness of the patient to assume the entire ventilatory workload.
Tobin MJ. Mechanical ventilation. N Engl J Med. 1994;330:1056-1061. Tobin MJ. Advances in mechanical ventilation. N Engl J Med. 2001;344:1986-1996.
Contemporary Practice PPV can be lifesaving in patients with hypoxemia or hypercarbia that cannot be addressed by other means. Mechanical Air Medical Journal 35:1
Table 1. Standard Ventilator Settings Settings • Rate 8-12 breaths/min • Tidal (breath) volume 6-10 mL/kg (follow plateau pressure) • FiO2 100% → titrate to pulse oximetry (typical goal 90% saturation) • PEEP 5-10 cm H2O • Mode: see text • If ventilator pressure is titrated to provide breaths or assist patient breaths, provide set pressure sufficient to achieve tidal volume in the above range FiO2 fraction of inspired oxygen; PEEP positive end-expiratory pressure (consistent airway pressure maintaining alveolar and airway patency). Tidal volume is the gas volume in each breath.
ventilation may also substitute for the action of respiratory muscles. In patients with severe respiratory distress, respiratory muscles may account for as much as 50% of total body oxygen consumption. Mechanical ventilation, in this situation, allows oxygen to be rerouted to other tissue beds that may be vulnerable. PPV may reverse and prevent lung collapse by allowing inspiration at a more compliant region of the pulmonary pressure-volume curve, and it may decrease the work of breathing. In its essence, the lung is given an opportunity to heal if mechanical ventilation improves pulmonary gas exchange and provides relief from excessive respiratory muscle work. Simple controlled ventilation rapidly leads to atrophy of respiratory muscles. Assisted modes that are triggered by patient effort are preferred. Most common triggered modes are (volume) assist control ventilation, (pressure) assist control ventilation, (synchronized) intermittent mandatory ventilation, and pressure support ventilation. With assist control ventilation modes, the ventilator delivers a breath either when triggered by patient inspiratory effort or independently if such effort does not occur within a preset period. With synchronized intermittent mandatory ventilation, the patient receives periodic positive pressure breaths at a preset volume and rate. The ventilator is programmed to match patient effort as possible. Spontaneous breathing is also allowed by opening a demand valve. Unfortunately, spontaneous breathing with synchronized intermittent mandatory ventilation may considerably increase the work of breathing. Pressure support ventilation differs from the previously described modes in that the physician sets a level of pressure to augment every spontaneous effort. Airway pressure is maintained at a preset level until the inspiratory flow falls below a certain level (usually approximately 25% of peak flow). Tidal volume is determined by the level of pressure set, patient effort, and pulmonary mechanics. Typical ventilator settings are provided in Table 1. Most ventilators are triggered by a change in airway pressure and sensitivity is set at 1 to 2 cm/H2O. However, if the trigger setting is too sensitive, the ventilator will cycle too frequently, and severe respiratory alkalosis may result. Some patients, particularly those with chronic obstructive pulmonary disease and high minute ventilation, require additional management of triggering and timing of breaths. An inspiratory gas flow rate of 60 L/min is used with most January-February 2016
patients during standard ventilatory modes. Again, underlying lung disease may require a change in these settings.
Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013;369:2126-2136.
Potential Harm Mechanical ventilation was indispensable during the polio epidemics of the 1950s. Despite obvious benefits with this therapy, many patients eventually died after the initiation of mechanical ventilation even with normal blood gas values. Multiple factors have been identified including mechanical trauma to the lungs, oxygen toxicity, and hemodynamic collapse with elevated intrathoracic pressures. During the polio epidemic, investigators noted that mechanical ventilation could cause structural damage to the lung. In the 1960s, the term “respirator lung” was coined to describe diffuse alveolar infiltrates and hyaline membranes that were found on postmortem examination of patients who had undergone mechanical ventilation. More recent studies characterize lung damage with mechanical ventilation to include inflammatory cell infiltrates, hyaline membrane formation, pulmonary edema, and increased vascular permeability. This constellation of pulmonary consequences of mechanical ventilation has been termed ventilator-induced lung injury (VILI). A more recent study (see later) showed the clinical importance of VILI by confirming that a ventilator strategy designed to reduce lung injury decreased mortality among patients with ARDS. Regional lung overdistension is a key factor in generating VILI. Because there is no well-accepted clinical method of measuring regional overdistension in the lung, limiting inflation pressure during mechanical ventilation is a common surrogate strategy to limit lung overdistension. Alveolar pressure is relatively easy to estimate clinically as the airway pressure during a period of zero flow. In a patient undergoing mechanical ventilation who is not making spontaneous breathing efforts, airway pressure is measured during a period when airflow is stopped at end inspiration, which is called the plateau pressure. The measurement of plateau pressure, however, does not describe a second important factor—pressure in the pleural space around the lungs. Plateau pressure also has nuances. For example, the morbidly obese patient or the patient with a stiff chest wall requires increased airway pressure to maintain a given tidal volume. 13
Although conventional wisdom indicates that high airway pressure is damaging, in the setting of obesity or a stiff chest wall, most of the applied pressure is actually delivered to lift the chest wall rather than expand the lungs. On the other hand, if the patient is distressed and gasping for air, large negative pressures may be generated around the lung, and lung stretch can be extremely high despite low measured airway pressures. In the laboratory, other factors such as respiratory frequency, pulmonary vascular pressure, and body temperature have been shown to contribute to VILI. Lung injury may occur because of ventilation at high lung volumes leading to rupture of alveoli with air leaks and gross changes such as pneumothorax and subcutaneous emphysema. More subtle injury may present as pulmonary edema. Classic preclinical work showed that high tidal volume rather than airway pressure per se was the more important factor in determining injury to the lung. Ventilation at low lung volumes may also cause injury through mechanisms including repetitive opening and closing of airways and lung units, compromise of surfactant function, and regional hypoxia. This type of injury is characterized by epithelial loss and pulmonary edema. Lung injury is amplified in lungs in which distribution of gas is not homogeneous. The physical forces described previously may cause release of intracellular mediators from either direct cell injury or activation of epithelial, endothelial, or inflammatory cells. Mediator release may directly injure the lung. Other mediators may set the stage for remote organ injury and recruitment of inflammatory cells to the lung. This process has been termed “biotrauma.”
The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-1308. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome. JAMA. 2012;308:1651-1659. Determann RM, Royakkers A, Wolthuis EK, et al. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14:R1. Futier E, Constantin JM, Paugam-Burtz C, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369:428-437.
Low Tidal Volume Recognition of the importance of VILI has led to changes in the philosophy of providing mechanical ventilation. Previous goals for mechanical ventilation were to maintain normal 14
blood gas values with reduction in the work of breathing. An additional goal has been established—to provide gas exchange that sustains life while minimizing VILI. Mechanisms for VILI have been described earlier. Reduction in the risk of VILI frequently requires trade-offs. Is it better to use a smaller tidal volume and let the partial pressure of arterial carbon dioxide increase for a given respiratory rate despite risks associated with hypercarbia (such as intracranial hypertension) or use larger tidal volumes to maintain a normal partial pressure of carbon dioxide in arterial blood but increase the risk of lung injury? The traditional approach to mechanical ventilation used tidal volumes of 10 to 15 mL/kg of body weight. These volumes are larger than those in normal subjects breathing at rest (5-7 mL/kg). Higher tidal volumes historically were thought necessary to achieve normal values for pH and partial pressure of carbon dioxide in arterial blood. With higher tidal volumes, inspiratory airway pressures were frequently high, suggesting extensive distension or stretch of the ventilated lung. Preclinical studies with the use of large tidal volumes showed disruption of the pulmonary epithelium and endothelium with lung inflammation, segmental collapse, hypoxemia, and release of inflammatory mediators. Injury to remote organs could be shown in association with mediator release from injured lungs. Initial work favoring the use of smaller tidal volumes in mechanical ventilation is highlighted by the sentinel trial of the ARDSNet Group in which a tidal volume of 6 mL/kg was compared with a tidal volume of 12 mL/kg in patients with hypoxemic respiratory failure or ARDS. Patients receiving traditional ventilation with an initial tidal volume of 12 mL/kg of predicted body weight experienced measured airway pressure during an inspiratory pause (plateau pressure) of 50 cm H2O or less, whereas ventilation with a lower tidal volume, which involved an initial tidal volume of 6 mL/kg of predicted body weight or less, resulted in the measured plateau pressure of 30 cm H2O or less. This trial, which established the value of low tidal volume ventilation, was stopped early because of lower mortality in the group treated with smaller tidal volumes. The duration of mechanical ventilation was also greater in patients receiving larger tidal volumes. The authors measured inflammatory markers in the plasma and noted a reduction in a key marker (interleukin 6) in patients treated with lower tidal volumes. One seeming contradictory result was a similar incidence of pneumothorax between experimental groups. Nonetheless, this was the pivotal trial that reset traditional practice of mechanical ventilation to include smaller tidal volume settings. Other investigators have shown benefit from smaller tidal volumes in patients receiving anesthesia and those receiving critical care for indications beside respiratory failure. Finally, positive end-expiratory pressure is applied to avoid lung collapse between breaths. Values for positive end-expiratory pressure of 5 to 10 cm H2O are typically used. Air Medical Journal 35:1
Suzuki S, Eastwood GM, Glassford NJ, et al. Conservative oxygen therapy in mechanically ventilated patients: a pilot before-and-after trial. Crit Care Med. 2014;42:1414-1422.
Oxygen Oxygen use is ubiquitous in the management of mechanically ventilated patients. The goal of oxygen therapy is to prevent or correct hypoxemia. The prevention or treatment of hypoxemia may induce hyperoxemia, which may also be injurious. For example, a high fraction of inspired oxygen may impair the immune response. Prolonged exposure to a high fraction of inspired oxygen has caused neurologic and respiratory symptoms in volunteers. Other physiologic studies suggest that hyperoxemia may increase vascular resistance, decrease cardiac output, and generate free radicals in various organs. Clinical studies suggest that hyperoxemia is associated with exacerbations of chronic obstructive pulmonary disease and critical illness. This before-after study suggests a significant reduction in the amount of oxygen given with a conservative rather than aggressive goal of oxygen administration based on simple pulse oximetry. Although no safety issues were identified, an intriguing outcome is a reduced incidence of new, nonrespiratory organ failure. These authors used a target saturation with oximetry of 90% to 92% in mechanically ventilated patients. Although this evidence clearly has not reached the level of fundamental information for guideline creation, I add this article and brief comment so that all may be aware of some of the “buzz” in respiratory research circles.
January-February 2016
Summary Points • Standard goals for mechanical ventilation are treatment of hypoxemic or hypercarbic respiratory insufficiency and to decrease respiratory muscle work in breathing. • Conventional ventilator settings are designed to mimic comfortable breathing. However, in the setting of respiratory failure, standard settings are associated with risk of injury to the ventilated lung. • Lung injury may come from high airway pressure or lung overexpansion. In general, overexpansion of the lung is more dangerous. Airway pressure is easier to measure and commonly discussed. • Where clinically appropriate, we may be able to accept a lower fraction of inspired oxygen without injury to the lungs or the patient. David J. Dries, MSE, MD, is assistant medical director for surgical services at HealthPartners Medical Group and professor of surgery and anesthesiology at the University of Minnesota in St Paul, MN, and can be reached at [email protected]. Acknowledgment The author acknowledges the assistance of Ms. Sherry Willett in preparation of this series for Air Medical Journal. 1067-991X/$36.00 Copyright 2015 by Air Medical Journal Associates http://dx.doi.org/10.1016/j.amj.2015.10.006
15
David J. Dries, MSE, MD
Mechanical Ventilation: History and Harm Slutsky AS. History of mechanical ventilation. From Vesalius to ventilator-induced lung injury. Am J Respir Crit Care Med. 2015;191:1106-1115. Marini JJ. Mechanical ventilation: past lessons and the near future. Crit Care. 2013;17(suppl 1):S1.
Early Years Contemporary approaches to mechanical ventilation began in the 1700s with the discovery of oxygen and subsequently the importance of respiration in the delivery of oxygen. Mouth-to-mouth resuscitation had been described by this time. Ironically, as Slusky notes, mouth-to-mouth resuscitation was discontinued after the discovery of oxygen because it was believed that exhaled air was lacking in oxygen because it had already been processed in another person’s lungs. Ventilator therapy based on contemporary appreciation of applied physiology began to appear in the 19th century. At this time, ventilation was provided using subatmospheric pressure delivered around the patient to replace or augment work done by respiratory muscles. Patients could sit or lay in a box that enclosed the body from the neck down or contained the entire patient. A plunger or other mechanism was used to decrease air pressure in the box, causing inspiration while the reverse produced expiration. The first workable iron lung was introduced in 1876 and replaced the previous box devices. The iron lung was used in Boston to treat polio patients in the early 20th century. A major problem with all of these devices was the extreme difficulty associated with nursing patients because it was difficult to get access to the body. To address this problem, respirator rooms were developed in which the patient lay with their head outside the room while inside huge pistons generated pressure changes sufficient to cause air to move into and out of the lungs. The ventilator room had a door so that the medical staff could enter the ventilator to care for the patient. Ultimately, rooms were developed in which multiple patients could be treated. This technology again was used in Boston for patients afflicted by several epidemics. When polio reappeared in the 1950s, it was a watershed event in the history of mechanical ventilation. Before this time, mechanical ventilation appeared to have usefulness but was not widely used. After the 1950s outbreak of polio, the benefits of ventilation were dramatic and obvious, leading to widespread use worldwide. In 1951, an international polio conference in Copenhagen was attended by most of the world’s polio experts. The following summer, Copenhagen experienced a terrible polio epidemic likely triggered by the carriage of polio virus to Copenhagen during the previous year’s conference. At the height of the epidemic, 50 patients 12
per day were being admitted to the hospital, many with respiratory failure. Mortality in these patients exceeded 80%. At the time, most physicians believed that patients were dying from renal failure associated with systemic viremia. Ibsen, an anesthesiologist trained in Boston, realized that death in these patients was associated with respiratory failure and recommended tracheostomy and positive pressure ventilation (PPV). With the introduction of PPV, mortality immediately dropped from greater than 80% to approximately 40%. Delivering care to these patients was a logistical problem because there were no mechanical positive pressure ventilators. Patients had to be hand bagged. It is estimated that at the height of the polio epidemic, 70 patients were simultaneously being manually ventilated. At the end of the polio epidemic, approximately 1,500 (medical) students provided manual ventilation for a total of 165,000 hours. One approach to the logistical challenge was to take care of these patients in 1 location. This led to the first intensive care units as we know them today. The initial emphasis in providing support with assisted ventilation was replacement of respiratory muscle activity. Over ensuing decades, this changed with a greater focus on oxygenation failure stimulated in part by improved technology for the measurement of blood gases and identification of the acute respiratory distress syndrome (ARDS). The 1960s were also a pivotal decade in the development of PPV influenced by advances in physiology and surgery and the need to address problems of postoperative lung collapse and traumatic lung injuries from battlefield conflict. Pressure-cycled devices were introduced, which delivered intermittent positive pressure not only to replace the work of respiratory muscles but to aid coughing, reduce basal lung collapse, and improve delivery of therapeutic aerosols. Improved control of inflation and deflation was developed so that these phases of each breath could be separately regulated. Treatment of ARDS was a central driver of new approaches to mechanical ventilation for respiratory failure but not the only one. Clinicians needed techniques to provide partial respiratory support, recondition respiratory muscles after pulmonary disease, and gauge readiness of the patient to assume the entire ventilatory workload.
Tobin MJ. Mechanical ventilation. N Engl J Med. 1994;330:1056-1061. Tobin MJ. Advances in mechanical ventilation. N Engl J Med. 2001;344:1986-1996.
Contemporary Practice PPV can be lifesaving in patients with hypoxemia or hypercarbia that cannot be addressed by other means. Mechanical Air Medical Journal 35:1
Table 1. Standard Ventilator Settings Settings • Rate 8-12 breaths/min • Tidal (breath) volume 6-10 mL/kg (follow plateau pressure) • FiO2 100% → titrate to pulse oximetry (typical goal 90% saturation) • PEEP 5-10 cm H2O • Mode: see text • If ventilator pressure is titrated to provide breaths or assist patient breaths, provide set pressure sufficient to achieve tidal volume in the above range FiO2 fraction of inspired oxygen; PEEP positive end-expiratory pressure (consistent airway pressure maintaining alveolar and airway patency). Tidal volume is the gas volume in each breath.
ventilation may also substitute for the action of respiratory muscles. In patients with severe respiratory distress, respiratory muscles may account for as much as 50% of total body oxygen consumption. Mechanical ventilation, in this situation, allows oxygen to be rerouted to other tissue beds that may be vulnerable. PPV may reverse and prevent lung collapse by allowing inspiration at a more compliant region of the pulmonary pressure-volume curve, and it may decrease the work of breathing. In its essence, the lung is given an opportunity to heal if mechanical ventilation improves pulmonary gas exchange and provides relief from excessive respiratory muscle work. Simple controlled ventilation rapidly leads to atrophy of respiratory muscles. Assisted modes that are triggered by patient effort are preferred. Most common triggered modes are (volume) assist control ventilation, (pressure) assist control ventilation, (synchronized) intermittent mandatory ventilation, and pressure support ventilation. With assist control ventilation modes, the ventilator delivers a breath either when triggered by patient inspiratory effort or independently if such effort does not occur within a preset period. With synchronized intermittent mandatory ventilation, the patient receives periodic positive pressure breaths at a preset volume and rate. The ventilator is programmed to match patient effort as possible. Spontaneous breathing is also allowed by opening a demand valve. Unfortunately, spontaneous breathing with synchronized intermittent mandatory ventilation may considerably increase the work of breathing. Pressure support ventilation differs from the previously described modes in that the physician sets a level of pressure to augment every spontaneous effort. Airway pressure is maintained at a preset level until the inspiratory flow falls below a certain level (usually approximately 25% of peak flow). Tidal volume is determined by the level of pressure set, patient effort, and pulmonary mechanics. Typical ventilator settings are provided in Table 1. Most ventilators are triggered by a change in airway pressure and sensitivity is set at 1 to 2 cm/H2O. However, if the trigger setting is too sensitive, the ventilator will cycle too frequently, and severe respiratory alkalosis may result. Some patients, particularly those with chronic obstructive pulmonary disease and high minute ventilation, require additional management of triggering and timing of breaths. An inspiratory gas flow rate of 60 L/min is used with most January-February 2016
patients during standard ventilatory modes. Again, underlying lung disease may require a change in these settings.
Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013;369:2126-2136.
Potential Harm Mechanical ventilation was indispensable during the polio epidemics of the 1950s. Despite obvious benefits with this therapy, many patients eventually died after the initiation of mechanical ventilation even with normal blood gas values. Multiple factors have been identified including mechanical trauma to the lungs, oxygen toxicity, and hemodynamic collapse with elevated intrathoracic pressures. During the polio epidemic, investigators noted that mechanical ventilation could cause structural damage to the lung. In the 1960s, the term “respirator lung” was coined to describe diffuse alveolar infiltrates and hyaline membranes that were found on postmortem examination of patients who had undergone mechanical ventilation. More recent studies characterize lung damage with mechanical ventilation to include inflammatory cell infiltrates, hyaline membrane formation, pulmonary edema, and increased vascular permeability. This constellation of pulmonary consequences of mechanical ventilation has been termed ventilator-induced lung injury (VILI). A more recent study (see later) showed the clinical importance of VILI by confirming that a ventilator strategy designed to reduce lung injury decreased mortality among patients with ARDS. Regional lung overdistension is a key factor in generating VILI. Because there is no well-accepted clinical method of measuring regional overdistension in the lung, limiting inflation pressure during mechanical ventilation is a common surrogate strategy to limit lung overdistension. Alveolar pressure is relatively easy to estimate clinically as the airway pressure during a period of zero flow. In a patient undergoing mechanical ventilation who is not making spontaneous breathing efforts, airway pressure is measured during a period when airflow is stopped at end inspiration, which is called the plateau pressure. The measurement of plateau pressure, however, does not describe a second important factor—pressure in the pleural space around the lungs. Plateau pressure also has nuances. For example, the morbidly obese patient or the patient with a stiff chest wall requires increased airway pressure to maintain a given tidal volume. 13
Although conventional wisdom indicates that high airway pressure is damaging, in the setting of obesity or a stiff chest wall, most of the applied pressure is actually delivered to lift the chest wall rather than expand the lungs. On the other hand, if the patient is distressed and gasping for air, large negative pressures may be generated around the lung, and lung stretch can be extremely high despite low measured airway pressures. In the laboratory, other factors such as respiratory frequency, pulmonary vascular pressure, and body temperature have been shown to contribute to VILI. Lung injury may occur because of ventilation at high lung volumes leading to rupture of alveoli with air leaks and gross changes such as pneumothorax and subcutaneous emphysema. More subtle injury may present as pulmonary edema. Classic preclinical work showed that high tidal volume rather than airway pressure per se was the more important factor in determining injury to the lung. Ventilation at low lung volumes may also cause injury through mechanisms including repetitive opening and closing of airways and lung units, compromise of surfactant function, and regional hypoxia. This type of injury is characterized by epithelial loss and pulmonary edema. Lung injury is amplified in lungs in which distribution of gas is not homogeneous. The physical forces described previously may cause release of intracellular mediators from either direct cell injury or activation of epithelial, endothelial, or inflammatory cells. Mediator release may directly injure the lung. Other mediators may set the stage for remote organ injury and recruitment of inflammatory cells to the lung. This process has been termed “biotrauma.”
The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301-1308. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome. JAMA. 2012;308:1651-1659. Determann RM, Royakkers A, Wolthuis EK, et al. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14:R1. Futier E, Constantin JM, Paugam-Burtz C, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369:428-437.
Low Tidal Volume Recognition of the importance of VILI has led to changes in the philosophy of providing mechanical ventilation. Previous goals for mechanical ventilation were to maintain normal 14
blood gas values with reduction in the work of breathing. An additional goal has been established—to provide gas exchange that sustains life while minimizing VILI. Mechanisms for VILI have been described earlier. Reduction in the risk of VILI frequently requires trade-offs. Is it better to use a smaller tidal volume and let the partial pressure of arterial carbon dioxide increase for a given respiratory rate despite risks associated with hypercarbia (such as intracranial hypertension) or use larger tidal volumes to maintain a normal partial pressure of carbon dioxide in arterial blood but increase the risk of lung injury? The traditional approach to mechanical ventilation used tidal volumes of 10 to 15 mL/kg of body weight. These volumes are larger than those in normal subjects breathing at rest (5-7 mL/kg). Higher tidal volumes historically were thought necessary to achieve normal values for pH and partial pressure of carbon dioxide in arterial blood. With higher tidal volumes, inspiratory airway pressures were frequently high, suggesting extensive distension or stretch of the ventilated lung. Preclinical studies with the use of large tidal volumes showed disruption of the pulmonary epithelium and endothelium with lung inflammation, segmental collapse, hypoxemia, and release of inflammatory mediators. Injury to remote organs could be shown in association with mediator release from injured lungs. Initial work favoring the use of smaller tidal volumes in mechanical ventilation is highlighted by the sentinel trial of the ARDSNet Group in which a tidal volume of 6 mL/kg was compared with a tidal volume of 12 mL/kg in patients with hypoxemic respiratory failure or ARDS. Patients receiving traditional ventilation with an initial tidal volume of 12 mL/kg of predicted body weight experienced measured airway pressure during an inspiratory pause (plateau pressure) of 50 cm H2O or less, whereas ventilation with a lower tidal volume, which involved an initial tidal volume of 6 mL/kg of predicted body weight or less, resulted in the measured plateau pressure of 30 cm H2O or less. This trial, which established the value of low tidal volume ventilation, was stopped early because of lower mortality in the group treated with smaller tidal volumes. The duration of mechanical ventilation was also greater in patients receiving larger tidal volumes. The authors measured inflammatory markers in the plasma and noted a reduction in a key marker (interleukin 6) in patients treated with lower tidal volumes. One seeming contradictory result was a similar incidence of pneumothorax between experimental groups. Nonetheless, this was the pivotal trial that reset traditional practice of mechanical ventilation to include smaller tidal volume settings. Other investigators have shown benefit from smaller tidal volumes in patients receiving anesthesia and those receiving critical care for indications beside respiratory failure. Finally, positive end-expiratory pressure is applied to avoid lung collapse between breaths. Values for positive end-expiratory pressure of 5 to 10 cm H2O are typically used. Air Medical Journal 35:1
Suzuki S, Eastwood GM, Glassford NJ, et al. Conservative oxygen therapy in mechanically ventilated patients: a pilot before-and-after trial. Crit Care Med. 2014;42:1414-1422.
Oxygen Oxygen use is ubiquitous in the management of mechanically ventilated patients. The goal of oxygen therapy is to prevent or correct hypoxemia. The prevention or treatment of hypoxemia may induce hyperoxemia, which may also be injurious. For example, a high fraction of inspired oxygen may impair the immune response. Prolonged exposure to a high fraction of inspired oxygen has caused neurologic and respiratory symptoms in volunteers. Other physiologic studies suggest that hyperoxemia may increase vascular resistance, decrease cardiac output, and generate free radicals in various organs. Clinical studies suggest that hyperoxemia is associated with exacerbations of chronic obstructive pulmonary disease and critical illness. This before-after study suggests a significant reduction in the amount of oxygen given with a conservative rather than aggressive goal of oxygen administration based on simple pulse oximetry. Although no safety issues were identified, an intriguing outcome is a reduced incidence of new, nonrespiratory organ failure. These authors used a target saturation with oximetry of 90% to 92% in mechanically ventilated patients. Although this evidence clearly has not reached the level of fundamental information for guideline creation, I add this article and brief comment so that all may be aware of some of the “buzz” in respiratory research circles.
January-February 2016
Summary Points • Standard goals for mechanical ventilation are treatment of hypoxemic or hypercarbic respiratory insufficiency and to decrease respiratory muscle work in breathing. • Conventional ventilator settings are designed to mimic comfortable breathing. However, in the setting of respiratory failure, standard settings are associated with risk of injury to the ventilated lung. • Lung injury may come from high airway pressure or lung overexpansion. In general, overexpansion of the lung is more dangerous. Airway pressure is easier to measure and commonly discussed. • Where clinically appropriate, we may be able to accept a lower fraction of inspired oxygen without injury to the lungs or the patient. David J. Dries, MSE, MD, is assistant medical director for surgical services at HealthPartners Medical Group and professor of surgery and anesthesiology at the University of Minnesota in St Paul, MN, and can be reached at [email protected]. Acknowledgment The author acknowledges the assistance of Ms. Sherry Willett in preparation of this series for Air Medical Journal. 1067-991X/$36.00 Copyright 2015 by Air Medical Journal Associates http://dx.doi.org/10.1016/j.amj.2015.10.006
15
