Page 625 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 51: Ventilator-Induced Lung Injury 445

that serum from rabbits that were ventilated with an injurious ventilation Ptp maintained between 0 and 10 cm H O at end expiration. In the control
2
strategy was capable of increasing the rate of apoptosis of cultured epi- group PEEP was set according to a fixed PEEP/Fi O 2 combination table. In
thelial cells from the kidney and villi of the small intestine. Functionally, both groups V was 6 mL/kg PBW. The study stopped early because the
t
this correlated with biochemical evidence of worsened renal function patients treated with the Ptp ventilatory strategy had better oxygenation,
when intact animals were studied. and respiratory mechanics compared to controls. Moreover, although not
102
That distal organ injury in humans may be mediated by mechanical the primary endpoint of the study, 28-day mortality in the patients treated
ventilation is supported by three observations. First, studies in humans with the esophageal pressure–guided approach tended to be lower (17% vs
have shown that an injurious ventilator strategy leads to an increase in 39%). Whether to use esophageal pressure measurements to guide venti-
102
circulating cytokine levels. Ranieri and coworkers randomized 44 patients lator strategy requires further investigation.
to receive either mechanical ventilation to maintain normal blood gases Another approach described above is to use the P-V curve to set PEEP.
(n = 19) or a lung-protective strategy attentive to both lung distention There are a number of concerns about using this approach. 103,104 The use
and maintenance of an adequate EELV. Despite similar levels of circu- of PEEP a few cm H O above the LIP does not ensure that the lung is
72
2
lating cytokines at baseline, patients in the lung-protective strategy group recruited; indeed recruitment takes place over the entire steep portion
had reduced plasma concentrations of IL-6, soluble TNF-α receptor 75, of the P-V curve. 105-107 Additionally, the UIP may indicate the comple-
and IL-1 receptor antagonist. In a subsequent analysis, levels of soluble tion of recruitment, rather than the development of overdistension.
107
serum Fas ligand (shown to induce apoptosis in human epithelial cells in Moreover, some authors argued that a decremental PEEP trial or the
107
vitro 97,98 ) and creatinine were found to be elevated in the controls. These deflation limb analysis of the P-V curve could be better to set properly
108
92
clinical observations were also validated in the multicenter ARDSNet trial the PEEP. The physiological concept underling this strategy is that after
where lower levels of IL-6 plasma concentrations were found in the inter- opening the lung with inspiration near to total lung capacity, higher
vention arm treated with lung volume reduction. 2,99,100 PEEP level makes end-expiratory alveolar inflation more homogeneous.
Ultimately, in a busy clinical environment, the use of P-V curves analysis
LUNG-PROTECTIVE STRATEGIES: DO NO HARM may not be safe or practical.
An alternative approach is the analysis of the dynamic airway opening
• CT scan analysis providing regional information of lung aeration is pressure/time (P/t) profile during constant-flow inflation. 109,110 In studies
the gold standard to assess alveolar overinflation and opening/ closing; in humans and animals a downward concavity on the P/t profile during
unfortunately it is not a bedside tool useful for clinical practice. constant flow inflation corresponded to a static P-V curve with a distinct
• Tidal volume to maintain Pplat <30 cm H O (ARMA study) and LIP, a continuous increase in compliance (ie, progressive recruitment
2
tidal volumes of 6 mL/kg PBW have been associated with reduced with inflating volume), and lung CT scan evidence of atelectrauma. 109,110
mortality in ARDS. On the other hand, an upward concavity on the P/t profile during con-
• Atelectrauma may be counterbalanced by adequate levels of PEEP. stant flow inflation corresponded to a static P-V curve with a distinct
UIP, a continuous reduction in compliance (ie, progressive overdisten-
When applying higher levels of PEEP, the potential benefit of avoid- 109,110
ing atelectrauma may be eclipsed by the risk of overdistension. sion with inflating volume), and lung CT scan signs of overinflation.
Based on these results, the authors suggested that analysis of the shape of
• New lung imaging techniques (ie, electrical impedence tomography the P/t curve during constant flow inflation could be a useful tool to set a
[EIT]) available at the bedside may be useful in the near future in protective ventilatory strategy at the bedside. There are insufficient data
determining an appropriate protective ventilation strategy. to recommend this approach in routine clinical practice.
Traditionally, the goals of mechanical ventilation have been to main- In the future, various imaging techniques may prove useful in set-
tain adequate arterial oxygenation, normocarbia and maintain normal ting ventilatory strategy. Electrical impedance tomography (EIT) 111,112
blood pH. To achieve these goals, patients with acute respiratory failure is a noninvasive, radiation-free, bedside imaging tool that can provide
were often ventilated using strategies consisting of variable levels of anatomical and functional images of the lung. EIT assessment is based
PEEP and oxygen, and V of ∼10 to 15 mL/kg. Based on the forgoing on the concept that different components of tissues, extracellular water,
t
discussion, adopting such a strategy may be theoretically deleterious. air, bone, have different electrical impedance. 113,114 In practice, high-
The principal objectives of a lung-protective strategy are to limit alveo- frequency and low-amplitude electrical currents from electrodes around
lar distention and maintain alveolar patency. Indeed there is mount- the chest are generated and their relative impedances are determined
113,114
ing evidence to support the notion that a lung-protective strategy be and provide a breath-by-breath imaging of the lung. Using this
implemented early in the course of respiratory failure to prevent the method, it may be possible to monitor dynamically overinflation and
development of VILI. Recent evidence from a meta-analysis suggested opening and closing phenomena bedside in each patient. Ongoing
beneficial effects of protective mechanical ventilation with low tidal refinements in this method and improvement in image resolution may
volume in patients who did not have ARDS at the onset of mechanical make this a useful research and clinical tool.
ventilation. The analysis included 2822 patients in the ICU or operating ■ CLINICAL TRIALS
room with a median duration of mechanical ventilation of 7 hours, and
demonstrated that 4.2% in the low-tidal-volume strategy went on to • Low tidal volume (V 6 mL/kg) pressure limited (Pplat <30 cm H O)
t
2
2
develop ARDS, compared to 12.7% in the high-tidal-volume ventilation protective ventilation in the ARMA study was associated with an
strategy. Of interest, the protective ventilation strategy was also associ- improvement in mortality.
ated with lower rates of pulmonary infection and atelectasis, as well as • Higher PEEP levels in conjunction with low tidal volume pressure
mortality. 101 limited (Pplat <30 cm H O) protective ventilation failed to demon-
2
There are several potential strategies, not mutually exclusive, to minimize strate superiority compared to lower PEEP in ALI, but based on a
alveolar overdistention and derecruitment. The first strategy was based on meta-analysis, higher PEEP levels appear to be protective in severe
the ARDSNet study, which achieved a 22% reduction in mortality using a ARDS (P/F <200).
tidal volume of 6 mL/kg PBW and maintaining plateau pressure <30 cm • In life-threatening severe ARDS, high-frequency oscillatory ventilation
H O. A better estimation of alveolar distending pressure may result from (HFOV), prone position ventilation, and extracorporeal lung–assist
2
2
transpulmonary pressure (Ptp) calculated as the difference between pla- devices may be viable adjuncts to conventional mechanical ventilation.
teau pressure (Pplat) and esophageal pressure (Pes). Moreover, Ptp may
guide PEEP setting in combination with limiting tidal volume. Using this Based on the foregoing discussions, several controlled clinical trials have
approach, Talmor et al randomized ARDS patients to two ventilatory evaluated the effects of lung-protective strategies in ARDS (Table 51-3).
102
strategies. One group was managed according to Ptp measurements with Initial randomized clinical trials evaluating the effect of lower tidal

section04.indd 445 1/23/2015 2:19:30 PM