Effect of PEEP and Tidal Volume on Ventilation Distribution and End-Expiratory Lung Volume: A Prospective Experimental Animal and Pilot Clinical Study

<div><p>Introduction</p><p>Lung-protective ventilation aims at using low tidal volumes (V_T) at optimum positive end-expiratory pressures (PEEP). Optimum PEEP should recruit atelectatic lung regions and avoid tidal recruitment and end-inspiratory overinflation. We examined the effect of V_T and PEEP on ventilation distribution, regional respiratory system compliance (C_RS), and end-expiratory lung volume (EELV) in an animal model of acute lung injury (ALI) and patients with ARDS by using electrical impedance tomography (EIT) with the aim to assess tidal recruitment and overinflation.</p><p>Methods</p><p>EIT examinations were performed in 10 anaesthetized pigs with normal lungs ventilated at 5 and 10 ml/kg body weight V_T and 5 cmH₂O PEEP. After ALI induction, 10 ml/kg V_T and 10 cmH₂O PEEP were applied. Afterwards, PEEP was set according to the pressure-volume curve. Animals were randomized to either low or high V_T ventilation changed after 30 minutes in a crossover design. Ventilation distribution, regional C_RS and changes in EELV were analyzed. The same measures were determined in five ARDS patients examined during low and high V_T ventilation (6 and 10 (8) ml/kg) at three PEEP levels.</p><p>Results</p><p>In healthy animals, high compared to low V_T increased C_RS and ventilation in dependent lung regions implying tidal recruitment. ALI reduced C_RS and EELV in all regions without changing ventilation distribution. Pressure-volume curve-derived PEEP of 21±4 cmH₂O (mean±SD) resulted in comparable increase in C_RS in dependent and decrease in non-dependent regions at both V_T. This implied that tidal recruitment was avoided but end-inspiratory overinflation was present irrespective of V_T. In patients, regional C_RS differences between low and high V_T revealed high degree of tidal recruitment and low overinflation at 3±1 cmH₂O PEEP. Tidal recruitment decreased at 10±1 cmH₂O and was further reduced at 15±2 cmH₂O PEEP.</p><p>Conclusions</p><p>Tidal recruitment and end-inspiratory overinflation can be assessed by EIT-based analysis of regional C_RS.</p></div

Respiratory and hemodynamic data of the studied patients.

<p>Data are shown as mean values ± standard deviation. V_T: tidal volume, F_Io₂: fraction of inspired oxygen, PEEP: positive end-expiratory pressure, PIP, peak inspiratory pressure, C_RS: respiratory system compliance, P_aco₂: end-expiratory partial pressure of carbon dioxide, HR: heart rate.</p><p>*The measurement at LIP+7 and high V_T was not conducted in patient 1 due to excess of peak inspiratory pressure limit of 40 cm H₂O (see Methods for further details).</p

Regional ventilation and respiratory system compliance.

<p>Ventrodorsal profiles of regional tidal volume (V_T) (A), regional respiratory system compliance (C_RS) (C) and differences in regional V_T (ΔV_T) (B) and regional C_RS (ΔC_RS) (D) with respect to baseline (mean values ±SD in 10 animals). Panel A (V_T [%]) shows the relative distribution of V_T in 32 horizontal layers in% of overall V_T in the chest cross-section. Panel B (ΔV_T [%]) indicates the respective differences in regional V_T compared with baseline. It shows a shift in ventilation toward the dorsal regions already with higher V_T at time point 1 in normal lung and more pronounced shifts at points 3 through 6 with a PEEP set 2 cm H₂O above the lower inflection point in acute lung injury (ALI). Panel C (C_RS [ml/kg H₂O]) shows regional C_RS in the same 32 layers with the respective differences to baseline provided in panel D (ΔC_RS [ml/kg H₂O]). The differences in regional C_RS indicate slightly lower and higher C_RS in the ventral and dorsal regions at time point 1. Significantly lower values were found in layers 7 to 12 and significantly higher ones in layers 16 to 25 (layers counting from 1 to 32 in the ventrodorsal direction). ALI (time point 2) resulted in significant decrease in C_RS in all layers. A small increase in C_RS in the dorsal regions (significant in layers 23 and 24) with the decreased C_RS in the ventral regions (significant in layers 1 to 17 and 27 and 28) at time point 3/5. At all other three time points, the findings were comparable. High V_T, ventilation with 10 ml/kg BW, low V_T, ventilation with 5 ml/kg BW.</p

End-expiratory lung volume.

<p>Changes in end-expiratory lung volume (ΔEELV) at individual measurement time points in comparison to baseline. The median, the 25th and the 75th percentile, minimum and maximum values of ten animals are shown. The gray areas in the diagram show the positive end-expiratory pressure (PEEP) values during the individual time points. Significant differences between the measurements are indicated. Left Y axis: ΔEELV, right Y axis: PEEP. High V_T, ventilation with 10 ml/kg BW, low V_T, ventilation with 5 ml/kg BW.</p

Respiratory and hemodynamic data.

<p>Data are shown as mean values ± standard deviation. V_T: tidal volume, F_Io₂: fraction of inspired oxygen, PEEP: positive end-expiratory pressure, PIP: peak inspiratory pressure, C_RS: respiratory system compliance, Pco₂: end-expiratory partial pressure of carbon dioxide, MAP: mean arterial pressure, HR: heart rate. Due to the crossover design data obtained at identical V_T/ILA settings were combined resulting in the merged time points 5/3 and 6/4 for low V_T and 3/5 and 4/6 for high V_T ventilation.</p><p>*: vs. baseline (P<0.05).</p>‡<p>: vs. baseline (P<0.01).</p>†<p>: vs. baseline (P<0.0001).</p>††<p>: vs. time point 1 (P<0.05).</p>‡‡<p>: vs. time point 1 (P<0.001).</p>§<p>: vs. time point 1 (P<0.0001).</p><p>$: vs. time point 2 (P<0.01).</p><p>&: vs. time point 2 (P<0.05).</p

Gas exchange data.

<p>Data are shown as mean values ± standard deviation. ALI: acute lung injury, F_Io₂: arterial oxygen saturation, P_ao₂: arterial partial pressure of oxygen, P_aco₂: arterial partial pressure of carbon dioxide, P: pressure, V: volume.</p><p>At the time point ‘PV maneuver’, data was obtained immediately after the low-flow inflation maneuver during ventilation with high V_T and with PEEP set 2 cmH₂O above the lower inflection point.</p><p>*: vs. time point 1 (P<0.05).</p><p>**: vs. time point 1 (P<0.001).</p>†<p>: vs. PV maneuver (P<0.0001).</p

Study flowchart.

<p>Ten animals were studied during volume-controlled ventilation during ventilation with 5 ml/kg (baseline) and 10 ml/kg tidal volume (V_T) (measurement time point 1) in the normal lung (NL) as well as after induction of acute lung injury (ALI) (time point 2) at inspired fractions of oxygen of 0.5 and 1.0, respectively. Then a constant low-flow inflation maneuver (pressure-volume (PV) maneuver) was performed and positive end-expiratory pressure (PEEP) was set 2 cm H₂O above the lower inflection point (LIP) identified in the PV curve. Using a crossover design, further measurements were performed 5 and 30 min after ventilation with low V_T and active interventional lung assist (ILA) and after another 5 and 30 min with high V_T and inactive ILA (no ILA) (time points 3–6). Five animals were randomly ventilated in the reversed chronological order. Ventilator settings of V_T and PEEP at each measurement time point are shown in the lower part of the Figure. *, time elapsed after the change in ventilator and ILA settings.</p

Regional ventilation distribution.

<p>Examples of functional EIT scans of regional lung ventilation in animal 2 during all measurement time points (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072675#pone-0072675-g001" target="_blank">Figure 1</a> for explanation). The orientation of the scans is indicated (ant., anterior; post., posterior). Panel A: Ventilated areas within the chest cross-section exhibit higher values of relative impedance change and are shown in red tones. In normal lungs (NL), symmetrical ventilation distribution between the right and left lung regions was found. With induction of acute lung injury (ALI), higher ventilation in the right lung region with pronounced ventilation in its ventral part and reduced left lung ventilation especially in its dorsal part were found. After PEEP was set 2 cm H₂O above the lower inflection point (LIP) according to the pressure-volume curve, a shift in ventilation toward the dependent (dorsal) lung regions was observed. No obvious difference between ventilation with 10 ml/kg V_T and inactive interventional lung assist (ILA) (high V_T, no ILA) and ventilation with 5 ml/kg V_T and active ILA (low V_T, ILA) was detected. Panel B: Ventilation difference scans of the same animal. Red color indicates increase in regional ventilation, blue color shows the decrease in ventilation compared with baseline.</p

Center of ventilation.

<p>Ventilation distribution during individual measurement time points represented by the geometrical center of ventilation. The center of ventilation is given in percent of the anteroposterior chest diameter. Values above 50 indicate a location in the dorsal half of the chest cross-section. The median, the 25th and the 75th percentile, minimum and maximum values of ten animals are shown. The gray areas in the diagram show the positive end-expiratory pressure (PEEP) values during the individual measurement time points. Significant differences between corresponding high V_T and low V_T are indicated. Every group with ALI and high PEEP is significantly different from normal lung and ALI with PEEP 10 cm H₂O (Time point 2). Left Y axis: center of ventilation, right Y axis: PEEP. High V_T, ventilation with 10 ml/kg BW, low V_T, ventilation with 5 ml/kg BW.</p

Acid Sphingomyelinase Serum Activity Predicts Mortality in Intensive Care Unit Patients after Systemic Inflammation: A Prospective Cohort Study

<div><p>Introduction</p><p>Acid sphingomyelinase is involved in lipid signalling pathways and regulation of apoptosis by the generation of ceramide and plays an important role during the host response to infectious stimuli. It thus has the potential to be used as a novel diagnostic marker in the management of critically ill patients. The objective of our study was to evaluate acid sphingomyelinase serum activity (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit population before, during, and after systemic inflammation.</p><p>Methods</p><p>40 patients admitted to the intensive care unit at risk for developing systemic inflammation (defined as systemic inflammatory response syndrome <i>plus</i> a significant procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission, before (<i>PCT_before)</i>, during (<i>PCT_peak</i>) and after (<i>PCT_low)</i> onset of SIRS. Patients undergoing elective surgery served as control (N = 8). Receiver-operating characteristics curves were computed.</p><p>Results</p><p>ASM significantly increased after surgery in the eight control patients. Patients from the intensive care unit had significantly higher ASM on admission than control patients after surgery. 19 out of 40 patients admitted to the intensive care unit developed systemic inflammation and 21 did not, with no differences in ASM between these two groups on admission. In patients with SIRS and PCT peak, ASM between admission and <i>PCT_before</i> was not different, but further increased at <i>PCT_peak</i> in non-survivors and was significantly higher at <i>PCT_low</i> compared to survivors. Survivors exhibited decreased ASM at <i>PCT_peak</i> and <i>PCT_low</i>. Receiver operating curve analysis on discrimination of ICU mortality showed an area under the curve of 0.79 for ASM at <i>PCT_low</i>.</p><p>Conclusions</p><p>In summary, ASM was generally higher in patients admitted to the intensive care unit compared to patients undergoing uncomplicated surgery. ASM did not indicate onset of systemic inflammation. In contrast to PCT however, it remained high in non-surviving ICU patients after systemic inflammation.</p></div