Neil R. MacIntyre, MD
Duke University Medical Center
Durham, NC 27710

Presentation at Conference May 1999
Wisconsin Society for Respiratory Care
Reprinted with Permission


1. Understand concept of lung protection

2. Understand protective ventilatory support strategies

3. Understand the results of various clinical trials

4. Understand potential future strategies


Numerous animal studies have shown that the lung is subject to physical injury during mechanical ventilation in two ways: a shear stretch injury from repeated opening and closing of diseased alveoli and an over stretch injury induced by excessive distention at end inspiration from the combination of the delivered tidal stretch (VT) and baseline stretch (PEEP). To minimize this injury potential, the first goal is to provide enough PEEP to recruit the “recruitable” alveoli while at the same time not applying so much PEEP that healthier regions are unnecessarily overdistended. The second goal is to avoid a PEEP/VT combination that unnecessarily overdistends lung regions at end inspiration, generally reflected by elevations in plateau pressure (end inspiratory alveolar pressure) above approximately 35 cm H2O. Better estimates of lung mechanical properties might be obtained by static pressure volume (PV) curves and these might be further enhanced by using esophageal/pleural pressures to account for any chest wall abnormalities that may be present. Unfortunately, clinical monitors to easily and reliably make these static PV measurements are not widely available.


Modes. Generally, severe respiratory failure is managed during the acute phases with an assist control mode of ventilation (ACV). This assures that all breaths have positive pressure supplied by the ventilator to provide virtually all of the work of breathing. The assist capabilities of ACV allow the patient to trigger breaths. This may help in controlling CO2 and improving patient comfort. If an inappropriate respiratory drive exists or patient triggering of assisted breaths is uncomfortable, sedation and/or paralysis may be needed such that only the control breaths of ACV are provided. It should be remembered, however, that unless the patient is grossly dys-synchronous with the ventilator despite every effort to make the assisted breaths comfortable, paralysis to eliminate muscle activity should be avoided. Similarly, strategies that routinely employ paralysis and controlled ventilation to reduce oxygen consumption (V02) should also be avoided as the potential decrease in V02 is generally small and the risk of long term myopathy is substantial.

Choosing pressure vs. volume targeted ventilation for total support depends upon the clinical situation. Volume targeted ventilation (volume assist-control ventilation - VACV) guarantees a certain tidal volume. This, in turn, gives clinician control over minute ventilation and CO2 clearance. Under these conditions, however, airway and alveolar pressures are dependent variables and will rise or fall depending upon changes in lung mechanics or patient effort. Sudden worsening of compliance or resistance can, thus, cause abrupt increases in airway and alveolar pressures. Pressure targeted ventilation, on the other hand, does not guarantee volume but rather controls airway pressure. Volume is thus a dependent variable and will change as lung mechanics or patient efforts change. Sudden worsening of compliance or resistance with pressure targeted ventilation results in a loss of volume. Pressure targeted ventilation also has a variable decelerating flow wave form which may improve gas mixing and may interact with any patient efforts more synchronously.

The choice of pressure vs volume targeted breaths depends on which feature is required for the clinical goal. Specifically, if CO2 clearance is of primary concern and patient comfort and lung stretch are less of an issue (e.g., mild lung injury with a cerebral mass lesion), volume targeted ventilation would be preferable. On the other hand, if over distention risk is high and/or patient synchrony is more of an issue the CO2 clearance (e.g., severe ARDS with normal cardiac and neurologic function) pressure targeted ventilation is probably the correct choice. There are several ventilator modes that offer pressure targeting and volume cycling features. While these modes do offer the decelerating wave form of pressure targeted breaths and thus may help patient comfort and gas mixing, the volume guarantee means that pressure must increase if lung mechanics worsen. Thus, while these breaths in these modes have pressure targeting features, they are not pressure limiting.

Frequency-tidal volume settings. The tidal breath, in conjunction with the baseline pressure, should be set in such a way that the plateau pressure is < 35 cm H2O (or some other index of over distention does not occur). Generally, this involves tidal volumes (VT) of 8-10 ml/kg although VT as low as 5-6 ml/kg may be needed. Older strategies of using higher tidal volumes arose from a need to prevent atelectasis. Now that PEEP strategies are better understood and the risk of over distention better appreciated, this need has lessened.

The set ventilator frequency is generally used to control the CO2. A reasonable starting point is a normal frequency of between 12 and 20 breaths per minute. Increasing the frequency will increase minute ventilation and generally will increase CO2 clearance. At some point, however, air trapping will develop because of inadequate expiratory times. Under these conditions, minute ventilation will either start to fall off (pressure targeted ventilation) or airway pressures will start to rise (volume targeted ventilation). In general, this begins to happen at breathing frequencies of approximately 35 breaths per minute although it can occur at much lower frequencies if the inspiratory to expiratory ratio is high or the time constant for lung emptying (resistance x compliance) is very high.

PEEP/FiO2. The goal of PEEP therapy is to recruit “recruitable” alveoli while not over distending already patent alveoli. PEEP performs its recruitment action primarily by preventing the deflation and collapse of an alveoli opened by a tidal breath. This may be enhanced by performing a volume recruitment maneuver consisting of 1-2 minutes of PEEP values in the 15-25 cm H2O range and then returning to an optimal setting as described below. In determining the ultimate optimal setting, two basic approaches exist that use either mechanical criteria or gas exchange criteria.

Mechanical criteria involve assessments that attempt to insure that PEEP recruits “recruitable” alveoli but not over distends alveoli already recruited. Two approaches have been reported: 1) Use pressure volume curves to set the PEEP/VT combination between the upper and lower inflection points. A modification of the conventional static approach uses a very slow inspiratory flow and then measures upper and lower inflection points from the resulting dynamic pressure volume curves. As noted above, using an esophageal pressure to account for chest wall mechanic enhances these techniques. 2) Use step increase in PEEP to determine the PEEP level that gives the best compliance.

Gas exchange criteria to guide PEEP application involve several potential strategies. One approach would be to do a PEEP titration curve (after a volume recruitment maneuver - see above) to determine the lowest Fi02 that could be achieved. Another approach would be to use algorithms designed to provide adequate values for Pa02 while minimizing FiO2. Note that constructing a PEEP/Fi02 algorithm is usually an empirical exercise in balancing Sa02 with Fi02 and depends upon the clinician’s perception of the relative “toxicities” of high thoracic pressures, high Fi02 and low Sa02.

In general, commonly used “operational” ranges for PEEP in parenchymal lung injury are 5 - 25 cm H20. However, some argue that, at least in the initial phases of lung injury, the range should be higher (eg., 12 - 25 cm H20) and that a volume recruitment maneuver should be performed to assure optimal recruitment. With this approach, PEEP would only be weaned when the Fi02 is £ 0.4.

Inspiratory : expiratory timing. Setting the inspiratory time and the inspiratory to expiratory ratio (I:E) involves several considerations. The normal I:E ratio is roughly 1:2-1:4. This produces the most comfort and thus is the usual initial setting. Assessment of the flow graphic should also be done to insure that an adequate expiratory time is present to avoid air trapping.

Inspiratory expiratory (I:E) prolongation beyond the physiologic range of 1:2 to 1:4 can be employed as an alternative to increasing PEEP to improve V/Q matching in severe respiratory failure. Generally, inspiratory time prolongation is reserved for patients in whom the plateau pressure from the PEEP/tidal volume combination has approached 35 cm H2O and potentially toxic concentrations of FiO2 are being employed without meeting Sa02 on or oxygen delivery goals. Inspiratory time prolongation has several important physiologic effects. First, a longer inspiratory time results in a longer alveolar - conducting airway gas mixing time. Second, a longer inspiratory time can give slower filling alveolar units time to be ventilated and recruited. Finally, if expiratory time is inadequate for lung emptying, air trapping and intrinsic PEEP can develop. A number of studies have shown improved gas exchange as a consequence of longer inspiratory times but sorting out which physiologic mechanism is responsible is not clear. Indeed, long inspiratory times without air trapping have been shown in one study to improve PaO2 while others have argued that improved PO2 occurs only as a consequence of PEEPi development.

Several other aspects of long inspiratory times strategies need to be considered when using this technique. First, the development of air trapping has different effects on pressure vs. volume targeted ventilation. Second, although long inspiratory times are often used with pressure controlled breaths to utilize the rapid initial flow pattern and the pressure limit feature, long inspiratory time strategies have also been used with volume targeted breaths, generally by adding an inspiratory pause. Third, long inspiratory time will increase mean airway pressure and thus can reduce cardiac filling. Moreover, in the presence of air trapping, the mean alveolar pressure will be higher than the mean airway pressure making monitoring of intrathoracic pressure more difficult. Fourth, lengthening the inspiratory to expiratory ratio beyond 1:1 is also quite uncomfortable and usually requires heavy sedation and/or paralysis.

One approach to using long inspiratory time strategies would avoid air trapping. The rationale behind this approach is to use longer inspiratory times for their mixing and filling effects but not to produce PEEPi. This is because there is no evidence that intrinsic PEEP produces any better improvement in V/Q matching than extrinsic or applied PEEP. Moreover, intrinsic PEEP may be more pronounced in lung regions with airway dysfunction and good compliance as compared to the stiff alveolar regions that require recruitment.. This contrasts with applied PEEP which is more homogeneously distributed. Another reason to avoid air trapping and intrinsic PEEP with long inspiratory time strategies is because of their effects on desired ventilator settings noted above.


The original clinical trial that introduced this concept was that of Hickling et al. They used historical controls to illustrate that a mechanical ventilator strategy designed to limit maximal distension in severe lung injury could improve mortality. They concluded that the benefits of a lung “protective” ventilator support strategy were worth the tradeoff of a substantial respiratory acidosis.

In the last 5 years, 4 large clinical trials have been conducted to address this issue. Three have been published. The patient selection criteria, ventilator strategies, and important outcomes from those which have been published are summarized in Table 1.

(Editorial note: Information about the 4th trial, a NIH ARDS Network trial, has been deleted from this article as on March 15, 1999 the NIH issued a press release stating that the clinical trial was stopped early because of significant positive clinical results for lung protection. This NIH Press Release is available as a separate article in this section of the ARDS Support Center website.)























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Note from the Table that one study shows benefit from a lung “protective” strategy while the other two do not. There are two important points to be made about these 3 studies, however: First, only the study in which the control group had potentially “toxic” overdistension pressures showed benefit from a low distension strategy. Second, this same study showing benefit also used much higher PEEP levels in the lung “protective” group.


Potential respiratory support strategies that might enhance lung protection include:

1. High frequency ventilation. By providing low maximal pressures and high recruitment pressures, HFV might be the "ultimate" lung protective strategy for a positive pressure ventilatory support system.

2. Partial liquid ventilation. An oxygen soluble flurocarbon can be used to provide alveolar recruitment and improved lung mechanics.

3. Surfactant replacement. When instilled in large quantities, surfactant (along with surfactant related proteins) can improve lung mechanics.

4. NO. Nitric oxide is a pulmonary vasodilator that may spare the lung from unneccessary O2 exposure.

5. ECMO. Extracorporeal systems can reduce (or eliminate) the need for positive


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