Inverse Ratio Ventilation: Back to the Future?* Carlos Ferrando, MD, PhD Francisco Javier Belda, MD, PhD Department of Anesthesiology and Surgical Intensive Care Hospital Clínico Universitario Valencia, Spain
I
n this issue of Critical Care Medicine, Boehme et al (1) report that inverse ratio ventilation (IRV) decreases cyclic recruitment and derecruitment (c-R/D) of atelectatic lung tissue, which consequently would reduce ventilator-induced lung injury (VILI). It is an experimental study in piglets with mild saline lavage acute respiratory distress syndrome (ARDS) to induce maximal R/D during tidal ventilation. VILI plays a major role in the poor prognosis of patients with ARDS, as shown by many experimental and clinical evidences. During the past 2 decades, many lung-protective ventilatory strategies had been proposed to minimize the two main causes of VILI in patients with ARDS: alveolar overdistension and c-R/D. However, nowadays, there is no consensus yet on the best ventilator strategy to be individually applied at the bedside for VILI prevention. Although many studies have shown that overdistension is a major cause of VILI and most studies indicate that decreasing driving pressures is beneficial by reducing overdistension (2), c-R/D due to insufficient recruitment and positive end-expiratory pressure (PEEP) seems to have similar or even greater effect on lung injury (3). In contrast with the solid experimental evidence, clinical data confirming this hypothesis are poor and many uncertainties remain about the actual impact of the recruitment maneuvers and PEEP selection. These are the reasons why until today debate remains regarding the most appropriate approach to minimized c-R/D maybe justifying the back to the future of the IRV. Increase of mean airway pressure improves oxygenation mainly by recruiting previously collapsed tissue. When this is accompanied by an increase in the end-expiratory lung volume, this mechanism also prevents c-R/D within each tidal cycle, a process associated with high shear forces capable of producing VILI. The increase in mean airway pressures can be made by raising PEEP, which nowadays could be considered the more physiological approach. Physiologically, it is known that best PEEP only could be known after a maximum alveolar recruitment (4). Although there are lacking clinical evidence about how the PEEP setting should be apply probably because the application of many suboptimal strategies. The other approach (IRV) *See also p. e65. Key Words: acute respiratory distress syndrome; inverse ratio ventilation; lung-protective ventilation; oxygenation; recruitment/derecruitment The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000000834
724
www.ccmjournal.org
increases mean airway pressures and end-expiratory lung pressures by increasing the inspiratory time and the intrinsic PEEP at normal respiratory rates. Both approaches, conventional and inverse ratio, favor alveolar recruitment and prevent recollapse, so large differences among alternative techniques would not be expected in oxygenation or VILI. A very interesting point of this report (1) is the method used for measuring tidal R/D in dynamic conditions during mechanical ventilation without applying pauses. They used an ultrafast (10 Hz temporal resolution) indwelling oxygen sensing probe attached to a multifrequency phase fluorimetry (MFPF) analyzer via fiber optic cable. The MFPF measurement principle is based on fluorescence quenching of oxygen by an open ruthenium source at the probe tip. Oxygen diffuses into the sensor coating, where it alters the nature of the fluorescence of ruthenium. By looking at how the fluorescence is altered in the presence of oxygen, the oxygen level can be quickly and accurately determined. This method has been previously tested in experimental settings (5, 6). This very fast analysis can determine fluctuations in partial pressure of oxygen between end-inspiration and end-expiration (ΔPao2) related to changes in shunt fraction due to atelectasis formation that collapse and reopen within the respiratory cycle. With this method, c-R/D is defined as ΔPao2 of greater than 50 mm Hg. The velocity of tidal R/D was also evaluated through the time constants as the time-dependent changes in Pao2 at end-inspiration and end-expiration. Unfortunately, this method is not available for clinical use yet. Furthermore, to assess the effect of inspiration to expiration (I:E) ratio on regional ventilation distribution, an electrical impedance tomography system that obtained 13 slice scans per second (13 Hz) was used to dynamically measure the relative impedance changes for each respiratory cycle in ventral, middle, and dorsal regions. Authors showed that after random application of different I:E ratios (1:4, 1:2, 1:1, 2:1, 4:1), diminished exhalation time by IRV is associated with a significant reduction of ΔPao2 (indicating less c-R/D) and high Pao2/Fio2 ratio, indicating a higher end-expiratory recruitment. According to these findings, they observed redistribution of regional ventilation from ventral and middle to dorsal lung regions during IRV. Conversely, the literature is consistent in this regard showing no differences in oxygenation between conventional ventilation and IRV with moderate PEEP levels that prevent derecruitment (7, 8). Only with low PEEP levels during conventional ventilation, IRV is successful in improving Pao2. Furthermore, when high PEEP levels are required in severe ARDS, oxygenation is better preserved with conventional ventilation due to a lower shunt fraction because redistribution of pulmonary blood flow from well-aerated to nonaerated lung regions is related to the inspiratory time (9). Regarding gas distribution, it was suggested that intrinsic PEEP caused by IRV produces more homogeneous aeration and less overdistension of March 2015 • Volume 43 • Number 3
Editorials
healthy lung parenchyma, but data of different studies did not support this hypothesis when higher PEEP levels minimizing derecruitment are used during conventional ventilation (9). Furthermore, the results of this report must be cautiously interpreted by clinicians when considering its translation to clinical practice. First, the model is a mild ARDS in which IRV would be never clinically indicated because less aggressive treatments are available. Remember that IRV was abandoned, in part, because of its hemodynamic side effects and the necessity of neuromuscular paralysis, which increase complications related to mechanical ventilation (10). These drawbacks are still present and one would never use IRV in patients with mild-onset ARDS (Pao2/ Fio2 ratio, 200–300). Second, IRV was applied not allowing spontaneous breathing activity. Clear evidence regarding the clinical benefits of patients triggering during assist control ventilation is scarce, but the current evidence suggests that spontaneous breathing activity is beneficial in mild to moderate ARDS (11). Third and most important, the ARDS model was chosen to induce high amounts of recruitable and less fixed atelectasis to investigate c-R/D, and no conclusions can be extrapolated to more severe ARDS with more fixed atelectasis. In the same sense, in order to magnify tidal R/D, the ventilator was set at fixed end-inspiratory pressure of 40 mbar (VT of 20 mL/kg body weight) and a PEEP of 5 mbar at a respiratory rate of 6 breaths/ min, which prevents gas trapping due to intrinsic PEEP but is really far from a clinical setting for patients with ARDS. Last but not least, authors hypothesized and demonstrated that IRV is superior to “high” PEEP (5 cm H2O) because shortening the exhalation time with IRV reduced the time available to derecruitment, resulting in more average recruitment. However, the study focused on comparing the effects of different I:E ratios, and this does not mean that the same effect on c-R/D (and oxygenation) can be obtained with an adequate PEEP level adjusted after a recruiting maneuver and a decremental PEEP trial (4). In future, a comparison of both strategies would be of real clinical interest.
Critical Care Medicine
In summary, from our point of view, the presented study simply demonstrates that progressive increases in I:E ratio reduce c-R/D as measured by respiratory-dependent fluctuations in Pao2 in an experimental setting of mild ARDS. However, these results cannot be extrapolated to clinical practice, and further research comparing IRV versus current protective ventilatory strategies is warranted before IRV can be back to the future.
REFERENCES
1. Boehme S, Bentley AH, Hartmann EK, et al: Influence of Inspiration to Expiration Ratio on Cyclic Recruitment and Derecruitment of Atelectasis in a Saline Lavage Model of Acute Respiratory Distress Syndrome. Crit Care Med 2015; 43:e65–e74 2. Amato MB, Barbas CS, Medeiros DM, et al: Effect of a protectiveventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347–354 3. Caironi P, Cressoni M, Chiumello D, et al: Lung opening and closing during ventilation of acute respiratory distress syndrome. Am J Respir Crit Care Med 2010; 181:578–586 4. Suarez-Sipmann F, Böhm SH, Tusman G, et al: Use of dynamic compliance for open lung positive end-expiratory pressure titration in an experimental study. Crit Care Med 2007; 35:214–221 5. Hartmann EK, Boehme S, Bentley A, et al: Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model. Crit Care 2012; 16:R8 6. Baumgardner JE, Markstaller K, Pfeiffer B, et al: Effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on PaO2 oscillations after saline lavage. Am J Respir Crit Care Med 2002; 166:1556–1562 7. Lessard MR, Guerot E, Lorino H, et al: Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome. Anesthesiology 1994; 80:83–91 8. Zavala E, Ferrer M, Polese G, et al: Effect of inverse I:E ratio ventilation on pulmonary gas exchange in acute respiratory distress syndrome. Anesthesiology 1998; 88:35–42 9. Neumann P, Berglund JE, Andersson LG, et al: Effects of inverse ratio ventilation and positive end-expiratory pressure in oleic acid-induced lung injury. Am J Respir Crit Care Med 2000; 161:1537–1545 10. Marcy TW, Marini JJ: Inverse ratio ventilation in ARDS. Rationale and implementation. Chest 1991; 100:494–504 11. Yoshida T, Uchiyama A, Matsuura N, et al: The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury. Crit Care Med 2013; 41:536–545
www.ccmjournal.org
725
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
I
n this issue of Critical Care Medicine, Boehme et al (1) report that inverse ratio ventilation (IRV) decreases cyclic recruitment and derecruitment (c-R/D) of atelectatic lung tissue, which consequently would reduce ventilator-induced lung injury (VILI). It is an experimental study in piglets with mild saline lavage acute respiratory distress syndrome (ARDS) to induce maximal R/D during tidal ventilation. VILI plays a major role in the poor prognosis of patients with ARDS, as shown by many experimental and clinical evidences. During the past 2 decades, many lung-protective ventilatory strategies had been proposed to minimize the two main causes of VILI in patients with ARDS: alveolar overdistension and c-R/D. However, nowadays, there is no consensus yet on the best ventilator strategy to be individually applied at the bedside for VILI prevention. Although many studies have shown that overdistension is a major cause of VILI and most studies indicate that decreasing driving pressures is beneficial by reducing overdistension (2), c-R/D due to insufficient recruitment and positive end-expiratory pressure (PEEP) seems to have similar or even greater effect on lung injury (3). In contrast with the solid experimental evidence, clinical data confirming this hypothesis are poor and many uncertainties remain about the actual impact of the recruitment maneuvers and PEEP selection. These are the reasons why until today debate remains regarding the most appropriate approach to minimized c-R/D maybe justifying the back to the future of the IRV. Increase of mean airway pressure improves oxygenation mainly by recruiting previously collapsed tissue. When this is accompanied by an increase in the end-expiratory lung volume, this mechanism also prevents c-R/D within each tidal cycle, a process associated with high shear forces capable of producing VILI. The increase in mean airway pressures can be made by raising PEEP, which nowadays could be considered the more physiological approach. Physiologically, it is known that best PEEP only could be known after a maximum alveolar recruitment (4). Although there are lacking clinical evidence about how the PEEP setting should be apply probably because the application of many suboptimal strategies. The other approach (IRV) *See also p. e65. Key Words: acute respiratory distress syndrome; inverse ratio ventilation; lung-protective ventilation; oxygenation; recruitment/derecruitment The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000000834
724
www.ccmjournal.org
increases mean airway pressures and end-expiratory lung pressures by increasing the inspiratory time and the intrinsic PEEP at normal respiratory rates. Both approaches, conventional and inverse ratio, favor alveolar recruitment and prevent recollapse, so large differences among alternative techniques would not be expected in oxygenation or VILI. A very interesting point of this report (1) is the method used for measuring tidal R/D in dynamic conditions during mechanical ventilation without applying pauses. They used an ultrafast (10 Hz temporal resolution) indwelling oxygen sensing probe attached to a multifrequency phase fluorimetry (MFPF) analyzer via fiber optic cable. The MFPF measurement principle is based on fluorescence quenching of oxygen by an open ruthenium source at the probe tip. Oxygen diffuses into the sensor coating, where it alters the nature of the fluorescence of ruthenium. By looking at how the fluorescence is altered in the presence of oxygen, the oxygen level can be quickly and accurately determined. This method has been previously tested in experimental settings (5, 6). This very fast analysis can determine fluctuations in partial pressure of oxygen between end-inspiration and end-expiration (ΔPao2) related to changes in shunt fraction due to atelectasis formation that collapse and reopen within the respiratory cycle. With this method, c-R/D is defined as ΔPao2 of greater than 50 mm Hg. The velocity of tidal R/D was also evaluated through the time constants as the time-dependent changes in Pao2 at end-inspiration and end-expiration. Unfortunately, this method is not available for clinical use yet. Furthermore, to assess the effect of inspiration to expiration (I:E) ratio on regional ventilation distribution, an electrical impedance tomography system that obtained 13 slice scans per second (13 Hz) was used to dynamically measure the relative impedance changes for each respiratory cycle in ventral, middle, and dorsal regions. Authors showed that after random application of different I:E ratios (1:4, 1:2, 1:1, 2:1, 4:1), diminished exhalation time by IRV is associated with a significant reduction of ΔPao2 (indicating less c-R/D) and high Pao2/Fio2 ratio, indicating a higher end-expiratory recruitment. According to these findings, they observed redistribution of regional ventilation from ventral and middle to dorsal lung regions during IRV. Conversely, the literature is consistent in this regard showing no differences in oxygenation between conventional ventilation and IRV with moderate PEEP levels that prevent derecruitment (7, 8). Only with low PEEP levels during conventional ventilation, IRV is successful in improving Pao2. Furthermore, when high PEEP levels are required in severe ARDS, oxygenation is better preserved with conventional ventilation due to a lower shunt fraction because redistribution of pulmonary blood flow from well-aerated to nonaerated lung regions is related to the inspiratory time (9). Regarding gas distribution, it was suggested that intrinsic PEEP caused by IRV produces more homogeneous aeration and less overdistension of March 2015 • Volume 43 • Number 3
Editorials
healthy lung parenchyma, but data of different studies did not support this hypothesis when higher PEEP levels minimizing derecruitment are used during conventional ventilation (9). Furthermore, the results of this report must be cautiously interpreted by clinicians when considering its translation to clinical practice. First, the model is a mild ARDS in which IRV would be never clinically indicated because less aggressive treatments are available. Remember that IRV was abandoned, in part, because of its hemodynamic side effects and the necessity of neuromuscular paralysis, which increase complications related to mechanical ventilation (10). These drawbacks are still present and one would never use IRV in patients with mild-onset ARDS (Pao2/ Fio2 ratio, 200–300). Second, IRV was applied not allowing spontaneous breathing activity. Clear evidence regarding the clinical benefits of patients triggering during assist control ventilation is scarce, but the current evidence suggests that spontaneous breathing activity is beneficial in mild to moderate ARDS (11). Third and most important, the ARDS model was chosen to induce high amounts of recruitable and less fixed atelectasis to investigate c-R/D, and no conclusions can be extrapolated to more severe ARDS with more fixed atelectasis. In the same sense, in order to magnify tidal R/D, the ventilator was set at fixed end-inspiratory pressure of 40 mbar (VT of 20 mL/kg body weight) and a PEEP of 5 mbar at a respiratory rate of 6 breaths/ min, which prevents gas trapping due to intrinsic PEEP but is really far from a clinical setting for patients with ARDS. Last but not least, authors hypothesized and demonstrated that IRV is superior to “high” PEEP (5 cm H2O) because shortening the exhalation time with IRV reduced the time available to derecruitment, resulting in more average recruitment. However, the study focused on comparing the effects of different I:E ratios, and this does not mean that the same effect on c-R/D (and oxygenation) can be obtained with an adequate PEEP level adjusted after a recruiting maneuver and a decremental PEEP trial (4). In future, a comparison of both strategies would be of real clinical interest.
Critical Care Medicine
In summary, from our point of view, the presented study simply demonstrates that progressive increases in I:E ratio reduce c-R/D as measured by respiratory-dependent fluctuations in Pao2 in an experimental setting of mild ARDS. However, these results cannot be extrapolated to clinical practice, and further research comparing IRV versus current protective ventilatory strategies is warranted before IRV can be back to the future.
REFERENCES
1. Boehme S, Bentley AH, Hartmann EK, et al: Influence of Inspiration to Expiration Ratio on Cyclic Recruitment and Derecruitment of Atelectasis in a Saline Lavage Model of Acute Respiratory Distress Syndrome. Crit Care Med 2015; 43:e65–e74 2. Amato MB, Barbas CS, Medeiros DM, et al: Effect of a protectiveventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347–354 3. Caironi P, Cressoni M, Chiumello D, et al: Lung opening and closing during ventilation of acute respiratory distress syndrome. Am J Respir Crit Care Med 2010; 181:578–586 4. Suarez-Sipmann F, Böhm SH, Tusman G, et al: Use of dynamic compliance for open lung positive end-expiratory pressure titration in an experimental study. Crit Care Med 2007; 35:214–221 5. Hartmann EK, Boehme S, Bentley A, et al: Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model. Crit Care 2012; 16:R8 6. Baumgardner JE, Markstaller K, Pfeiffer B, et al: Effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on PaO2 oscillations after saline lavage. Am J Respir Crit Care Med 2002; 166:1556–1562 7. Lessard MR, Guerot E, Lorino H, et al: Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome. Anesthesiology 1994; 80:83–91 8. Zavala E, Ferrer M, Polese G, et al: Effect of inverse I:E ratio ventilation on pulmonary gas exchange in acute respiratory distress syndrome. Anesthesiology 1998; 88:35–42 9. Neumann P, Berglund JE, Andersson LG, et al: Effects of inverse ratio ventilation and positive end-expiratory pressure in oleic acid-induced lung injury. Am J Respir Crit Care Med 2000; 161:1537–1545 10. Marcy TW, Marini JJ: Inverse ratio ventilation in ARDS. Rationale and implementation. Chest 1991; 100:494–504 11. Yoshida T, Uchiyama A, Matsuura N, et al: The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury. Crit Care Med 2013; 41:536–545
www.ccmjournal.org
725
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
