Ventilator - Induced Lung Injury

By Neil R. MacIntyre, MD, FCCP

Conventional Mechanical Ventilation Strategies for Providing Lung Protection

Modes. Generally, severe respiratory failure is managed during the acute phases with an assist control mode of ventilation. This assures that all breaths have positive pressure supplied by the ventilator to provide virtually all of the work of breathing.⁵⁵

Choosing pressure- vs flow/volume-targeted ventilation for total support depends upon the clinical situation. Flow/volume-targeted ventilation 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. Worsening of compliance or resistance in a sick lung region can thus increase airway/alveolar pressures and divert tidal volume to healthier regions with consequent regional overdistention (Fig 2). 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. With pressure-targeted ventilation, worsening of compliance or resistance in a sick region results in a loss of overall tidal volume but no change in pressures or distention in the healthier regions.

Pressure-targeted ventilation also has a variable decelerating flow wave form. On one hand, this flow pattern may improve gas mixing⁶³ and may interact with any patient efforts more synchronously.⁶⁴ However, the recent demonstration in animals that very rapid inspiratory pressure changes can produce a shear stress injury (see above^32,33) raises the concern that the rapid initial flows of pressure-targeted breaths may be detrimental.

The ultimate choice of pressure- vs volume-targeted breaths depends on which features are required for the clinical goal. Specifically, if CO₂ clearance is of primary concern and patient comfort and lung stretch are less of an issue (eg, mild lung injury with a cerebral mass lesion), flow/volume-targeted ventilation would be preferable. On the other hand, if overdistention risk is high and/or patient synchrony is more of an issue than CO₂ clearance (eg, severe ARDS with normal cardiac and neurologic function), pressure-targeted ventilation is probably the correct choice. The ability to limit initial flow may be important if there is clinical concern about the shear-stress phenomenon noted above. With a flow/volume-targeted breath, this can be accomplished by direct clinician control of the flow pattern. With a pressure-targeted breath, this can be accomplished on newer ventilators with "rate of rise" adjusters.⁶⁵

There are several ventilator modes that offer pressure-targeting and volume-cycling features.⁶⁶ While these modes do offer the decelerating flow wave form of pressure-targeted breaths, 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. To date, there are no clinical studies suggesting benefit to these combined modes.

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 < 30 to 35 cm H₂O (or some other index of overdistention does not occur). Generally, this involves a tidal volume (VT) of 5 to 7 mL/kg as was used in the NIH ARDS Network trial.²⁷ 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 overdistention better appreciated, this need has disappeared.

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/min. 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.⁶⁷ Under these conditions, minute ventilation will either decrease (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/min, although it can occur at much lower frequencies if the inspiratory to expiratory (I:E) ratio is high or the time constant for lung emptying (resistance x compliance) is very high.

In an effort to provide overdistention protection, alveolar ventilation may be compromised and hypercapnia can develop (permissive hypercapnia). As long as the pH remains above 7.1 to 7.2, this appears well-tolerated in most patients (exceptions might include CNS injuries and unstable cardiovascular systems).⁶⁸ A new technique, tracheal gas insufflation, flushes the endotracheal tube free of CO₂ during expiration and may be helpful under these circumstances.^69,70

PEEP/ Fio₂. The goal of PEEP application is to maintain patency of alveoli that are opened (recruited) by a positive-pressure breath. In this sense, PEEP acts to prevent derecruitment. It then should follow that the initial application, a reinstitution, or an increase in PEEP should be accompanied by a "volume recruitment" maneuver.^26,71 Recommended strategies include lung inflation to near-maximum (ie, pressures of 30 to 40 cm H₂O) for 30 to 60 s.²⁶

Determining the proper PEEP level can utilize either mechanical criteria or gas exchange criteria. Mechanical criteria involve assessments that attempt to insure that PEEP recruits "recruitable" alveoli but does not overdistend alveoli already recruited. Two approaches have been reported: (1) Use PV curves to set the PEEP above the lower inflection point on the PV curve (see above⁵⁹); and (2) use step increase in PEEP to determine the PEEP level that gives the best compliance.⁵⁴ As noted previously, both of these approaches are technically challenging and time-consuming.

Gas exchange criteria to guide PEEP application involve balancing PaO₂ goals, FIO₂ goals, and lung distention goals. In general, these strategies provide some minimal level of PEEP at one extreme (eg, a minimal PEEP of 5 cm H₂O is unlikely to produce overdistention) and some maximal level of PEEP at the other extreme (eg, a maximal PEEP of 25 cm H₂O will still maintain plateau pressures < 30 to 35 cm H₂O with a minimal VT). In between these extremes, PEEP and FIO₂ are adjusted to maintain an oxygenation goal. One such strategy is the one used in the NIH ARDS Network trial²⁷ (Table 1). Note that this approach may not produce the maximal PaO₂/FIO₂ ratio or the minimal shunt. This tradeoff, however, may be important in providing lung protection from overdistention.

Inspiratory:expiratory timing. Setting the inspiratory time and the I:E ratio involves several considerations. The normal I:E ratio is roughly 1:2 to 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.

I:E prolongation beyond the physiologic range of 1:2 to 1:4 can be conceptually employed as an alternative to increasing PEEP to recruit lung units and improve ventilation/perfusion relationships in severe respiratory failure.^72-74 Generally, inspiratory time prolongation is reserved for patients in whom the plateau pressure from the PEEP-VT combination has approached 30 to 35 cm H₂O and/or potentially toxic concentrations of FIO₂ are being employed without meeting arterial oxygen saturation 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.⁶⁷ A number of studies have shown improved gas exchange as a consequence of longer inspiratory times but it is not clear which of these physiologic mechanisms is or are responsible.

A novel approach to improving comfort with a pressure-controlled long inspiratory time strategy is the use of a pressure relief mechanism. This permits spontaneous breathing during the long inflation period and has been termed airway pressure release ventilation (APRV; also called biphasic or bilevel ventilation).⁷⁷ It must be appreciated that with APRV, the spontaneous breaths during the long inflation period can further increase end-inspiratory lung volume beyond that set by the inflation pressure. APRV may thus be less effective as a strategy to limit alveolar overdistention.

It must be emphasized that none of the prolonged inspiratory time strategies to limiting maximal pressure have been evaluated in any meaningful outcome study. Indeed, it is conceivable that long inspiratory times, in and of themselves, may have injury potential through the rapid initial flow pattern, the long duration of inflation pressures, or the need for heavy sedation. Their use, therefore, should be reserved for only selected situations and provided only by clinicians well versed in lung mechanics.

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