High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious

Abstract

Rationale: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious.

Objectives: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP).

Methods: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS.

Measurements and main results: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients).

Conclusions: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

Keywords: PEEP; acute respiratory distress syndrome; spontaneous breathing; ventilator-induced lung injury.

Figures

Figure 1.

Intensity of spontaneous effort in high versus low positive end-expiratory pressure (PEEP) in rabbit and pig. The intensity of inspiratory effort was evaluated as the magnitude of the negative swing in esophageal pressure (ΔPes). (A) In the rabbit, ΔPes was lower in high than in low PEEP throughout the protocol, despite higher doses of sedatives (titrated to prevent spontaneous limb movement). ΔPes became significantly more negative in low PEEP as lung injury progressed. (B) In the pig, ΔPes was lower in high than in low PEEP throughout the protocol, despite higher doses of sedatives (titrated to similar target levels of ∆EAdi in both groups). Data shown as mean ± SD. EAdi = electrical activity of the diaphragm; SB = spontaneous breathing. *P < 0.05 versus low PEEP + SB; †P < 0.05 versus start of the protocol within the group.

Figure 2.

Intensity of spontaneous effort in high versus low positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome. (A) Vt was significantly decreased in all patients with acute respiratory distress syndrome at high PEEP versus low PEEP. (B and C) High PEEP (PEEP of 15 cm H2O; PEEP15) decreased ∆Pes (B) and thus peak ∆PL (C), compared with low PEEP (PEEP of 5 cm H2O; PEEP5). (D) However, the response of ∆EAdi was variable after increased PEEP. The black solid line and the error bars indicate mean and SD of all data. The black dotted lines connect each variable at different PEEP levels measured in the same patient. The data shown in colored lines correspond to the same patients (A and D). EAdi = electrical activity of the diaphragm; Pes = esophageal pressure; Pl = transpulmonary pressure.

Figure 3.

Intensity of spontaneous effort in high versus low positive end-expiratory pressure in a patient with acute respiratory distress syndrome. Representative waveforms were obtained from patient 1. The magnitude of the negative swings of esophageal pressure was reduced by approximately 50% when positive end-expiratory pressure was increased from 5 to 15 cm H2O. Note that high positive end-expiratory pressure did not substantially reduce respiratory rate. The red dotted lines outline the esophageal pressures.

Figure 4.

Regional lung injury (quantitative). During spontaneous breathing (SB) low positive end-expiratory pressure (PEEP) increased injury in all lung regions, especially in dependent lung (severest among all groups); but high PEEP during SB reduced injury in all lung regions. In contrast, low PEEP during paralysis increased injury in nondependent and especially in middle lung regions (severest among all groups). High PEEP during paralysis reduced injury in nondependent and middle lung, but not in dependent lung. *P < 0.05 versus low PEEP + SB; #P < 0.05 versus low PEEP − SB; †P < 0.05 compared with other groups.

Figure 5.

Regional lung injury (illustrative). Representative images (hematoxylin and eosin; scale bars, 100 μm) are shown. (A) High positive end-expiratory pressure (PEEP) + spontaneous breathing (SB). (B) Low PEEP + SB. (C) High PEEP − SB. (D) Low PEEP − SB.

Figure 6.

Distribution of inflammation in lung. Representative positron emission tomography (PET) scan images of [18F]fluoro-2-deoxy-d-glucose (18F-FDG) uptake after lung injury (first PET scan) and after 16 hours (second PET scan) in high versus low positive end-expiratory pressure (PEEP). Pixels are represented in the heat color scale, showing higher 18F-FDG uptake as lighter shades. Spontaneous effort with low PEEP increased lung inflammation, especially in dependent regions close to the diaphragm; in contrast, high PEEP during spontaneous effort resulted in less lung inflammation in these regions. CT = computed tomography.

Figure 7.

Local volutrauma and inflammation. Representative electrical impedance tomography (EIT) and positron emission tomography (PET) in low positive end-expiratory pressure images are presented. This EIT image shows lung regions where lung stretch was increased because of pendelluft (translocation of gas from nondependent to dependent lung regions during inspiration), as white. Vt was maintained at 7 ml/kg, but the magnitude of local dependent lung stretch (white regions), due to the localization of more negative ∆ pleural pressure (i.e., higher local lung stress), was equivalent to that applied by Vt of 14 ml/kg during muscle paralysis (i.e., local volutrauma). Correspondingly, PET imaging confirmed that lung inflammation predominantly occurred in the dependent regions, the same regions where local volutrauma occurred. 18F-FDG = [18F]fluoro-2-deoxy-d-glucose.