interference with the dose of calcineurin inhibitors, a factor that might improve graft outcomes by lowering rejection rates. Currently, in South Africa, we are using raltegravir in salvage regimens only, but once these drugs become more affordable and available in South Africa, it will be interesting to see whether they are a good option for HIV-positive patients who receive a transplant. In our study, all the patients had completely mismatched human leukocyte antibodies with the donors, and the levels of panel reactive antibody ranged from 0 to 90%. We agree that

this factor might be important in the high kidney-rejection rates among our patients. Elmi Muller, M.B., Ch.B., M.Med. Zunaid Barday, M.B., Ch.B. Delawir Kahn, M.B., Ch.B., Ch.M. University of Cape Town Cape Town, South Africa [email protected] Since publication of their article, the authors report no further potential conflict of interest. 1. Stock PG, Barin B, Murphy B, et al. Outcomes of kidney

transplantation in HIV-infected recipients. N Engl J Med 2010; 363:2004-14. DOI: 10.1056/NEJMc1503288

Driving Pressure as a Key Ventilation Variable To the Editor: Amato et al. (Feb. 19 issue)1 state that in patients with the acute respiratory distress syndrome (ARDS), there is a reverse association between respiratory-system compliance (Crs), which reflects functional lung size during disease, and the driving pressure (ΔP = Vt/Crs, where Vt indicates tidal volume) that is used for ventilation. Decreases in driving pressure were associated with increased rates of survival in their study. However, functional lung size is calculated from static compliance, whereas driving pressure is calculated from dynamic compliance, and dynamic compliance is usually lower than static compliance in patients with ARDS. Which is the appropriate compliance to consider? Hamidreza Jamaati, M.D. Chronic Respiratory Diseases Research Center Tehran, Iran

Seyed A. Mohajerani, M.D. National Research Institute of Tuberculosis and Lung Disease Tehran, Iran

S. Mohammadreza Hashemian, M.D. Shahid Beheshti University of Medical Sciences Tehran, Iran [email protected] No potential conflict of interest relevant to this letter was reported.

ance, which depends on the volume of lung available to receive the tidal breath. Higher respiratorysystem compliance allows for a lower driving pressure to achieve the same tidal volume.1 A lower driving pressure may decrease cyclic lung strain and thereby improve outcomes. We share our observations regarding a physical maneuver that increased respiratory-system compliance in a patient with ARDS. During routine abdominal palpation, the tidal volume increased significantly in a patient receiving lungprotective ventilation by means of pressure control but only when compressions were performed during exhalation. Abdominal compressions that were timed with exhalation maintained this higher tidal volume, which allowed for a reduction in the driving pressure. Respiratory mechanics returned to the initial values when the maneuver was stopped. We suspect that this maneuver resulted in ventilation on a steeper portion of the pressure–volume curve. Can this maneuver provide insights into lung mechanics or be useful to lower the driving pressure? Luisa Morales-Nebreda, M.D. Manu Jain, M.D. Thomas C. Corbridge, M.D.

1. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure

Northwestern University Chicago, IL [email protected]

DOI: 10.1056/NEJMc1503487

No potential conflict of interest relevant to this letter was reported.

To the Editor: Amato et al. describe correlations between tidal volume and survival only when tidal volume was related to respiratory-system compli-

1. Gattinoni L, Pesenti A. The concept of “baby lung.” Intensive

and survival in the acute respiratory distress syndrome. N Engl J Med 2015;372:747-55.

Care Med 2005;31:776-84.

DOI: 10.1056/NEJMc1503487

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To the Editor: Whether the driving pressure is indeed the mediator of improved survival among patients with ARDS, as suggested in the complicated mediation analysis presented by Amato et al., remains to be proved in a prospective, randomized trial. We think that any future study that uses driving pressure as the target in mechanical ventilation will need to use a strategy guided by the transpulmonary pressure to evaluate the effects of the driving-pressure strategy on outcomes.1,2 In our opinion, such a trial would require the universal use of pressure-controlled ventilation. Can the authors comment on the design of such a trial? Sahajal Dhooria, M.D., D.M. Inderpaul S. Sehgal, M.D., D.M. Ritesh Agarwal, M.D., D.M. Postgraduate Institute of Medical Education and Research Chandigarh, India [email protected] No potential conflict of interest relevant to this letter was reported. 1. Talmor DS, Fessler HE. Are esophageal pressure measure-

ments important in clinical decision-making in mechanically ventilated patients? Respir Care 2010;55:162-72. 2. Agarwal R, Aggarwal AN, Gupta D, Behera D, Jindal SK. Etiology and outcomes of pulmonary and extrapulmonary acute lung injury/ARDS in a respiratory ICU in North India. Chest 2006;130:724-9. DOI: 10.1056/NEJMc1503487


m e dic i n e

sure–volume curve. This occurs in some patients under pressure-controlled ventilation at high levels of PEEP, which leads to increasing tidal volume when gentle pressure is applied over the chest or abdomen. However, limiting these compressions to the expiratory phase results in a decrease in distending (transpulmonary) pressures that are present only during the expiratory phase. In this situation, the driving pressure is no longer a reasonable surrogate for the oscillation in transpulmonary pressures. With the proposed maneuver, oscillations in transpulmonary pressures will increase with each breath regardless of the location on the pressure–volume curve, even though the applied driving pressure will not change. In response to Dhooria et al.: we agree that a prospective, randomized, controlled trial is necessary to test the hypothesis that the targeting of driving pressure is better than the current standard of care. Any ventilator mode could be used, given that the tidal volume could be targeted according to static compliance. For pragmatic reasons, we think that it would be better not to use esophageal-pressure measurement, even though it may more accurately reflect the potential for ventilator-induced lung injury. This assumption is justified because high pleural pressures (e.g., in obese patients) are typically caused by a mass-load effect, which causes a similar increase in the pleural pressure at the end of expiration and the end of inspiration. Thus, this offset pressure is subtracted from both terms in the estimation of driving pressure. We argue that except for patients with extremely low chest-wall compliance, the measurement of esophageal pressures would just reveal a fixed elastic component (chest wall), in series with lung elastance. The magnitude of this component is typically 2 cm of water or less with the use of a tidal volume of 6 ml per kilogram of predicted body weight. Eduardo L.V. Costa, M.D.

The authors reply: Jamaati and colleagues question our use of driving pressure to normalize the tidal volume to lung size. They are right in pointing out that static compliance is the correct measurement to use for this normalization. This is in fact what we did. The confusion arises because there are two common definitions of driving pressure: the difference between peak inspiratory pressure and positive end-expiratory pressure (PEEP) and the difference between plateau pressure and PEEP. We used the latter, which represents the quasistatic elastic behavior of the respiratory system. We favor this approach with driving pressure computed during a brief pause at full inspiration, in the absence of muscle ef- University of São Paulo fort, because it more closely represents lung dis- São Paulo, Brazil tention, whereas dynamic compliance is also in- Arthur S. Slutsky, M.D. fluenced by airway resistance and nonuniform St. Michael’s Hospital Toronto, ON, Canada distribution of pulmonary time constants. In response to Morales-Nebreda et al.: abdomi- Marcelo B.P. Amato, M.D. nal compressions tend to increase pleural pres- University of São Paulo São Paulo, Brazil sures, which externally compress the lungs. In [email protected] overdistended lungs, this increase in pleural Since publication of their article, the authors report no furpressures throughout the respiratory cycle could ther potential conflict of interest. move the lung to a steeper portion of its pres- DOI: 10.1056/NEJMc1503487 2072

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