Abstract
Background
In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might ...reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO
2
/FiO
2
and compliance.
Methods
Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units.
Results
Percentage of unmatched units was significantly higher in non-survivors compared to survivors (3227–47% vs. 2117–27%,
p
< 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07–1.39,
p
= 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79–0.97,
p
< 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 27–38% vs. 18 13–21%,
p
< 0.001), while the opposite was true for perfusion (28 22–38% vs. 36 32–44%,
p
< 0.001).
Higher percentage of only perfused units was correlated with lower dorsal ventilation (
r
= − 0.486,
p
< 0.001) and with lower PaO
2
/FiO
2
ratio (
r
= − 0.293,
p
= 0.039).
Conclusions
EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.
Abstract
Purpose
In the acute respiratory distress syndrome (ARDS), decreasing Ventilation-Perfusion
$$\left( {{{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. ...\kern-\nulldelimiterspace} {\dot{Q}}} \right)$$
V
˙
/
Q
˙
mismatch might enhance lung protection. We investigated the regional effects of higher Positive End Expiratory Pressure (PEEP) on
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
mismatch and their correlation with recruitability. We aimed to verify whether PEEP improves regional
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
mismatch, and to study the underlying mechanisms.
Methods
In fifteen patients with moderate and severe ARDS, two PEEP levels (5 and 15 cmH
2
O) were applied in random order.
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
mismatch was assessed by Electrical Impedance Tomography at each PEEP. Percentage of ventilation and perfusion reaching different ranges of
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
ratios were analyzed in 3 gravitational lung regions, leading to precise assessment of their distribution throughout different
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
mismatch compartments. Recruitability between the two PEEP levels was measured by the recruitment-to-inflation ratio method.
Results
In the non-dependent region, at higher PEEP, ventilation reaching the normal
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
compartment (
p
= 0.018) increased, while it decreased in the high
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
one (
p
= 0.023). In the middle region, at PEEP 15 cmH
2
O, ventilation and perfusion to the low
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
compartment decreased (
p
= 0.006 and
p
= 0.011) and perfusion to normal
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
increased (
p
= 0.003). In the dependent lung, the percentage of blood flowing through the non-ventilated compartment decreased (
p
= 0.041). Regional
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
mismatch improvement was correlated to lung recruitability and changes in regional tidal volume.
Conclusions
In patients with ARDS, higher PEEP optimizes the distribution of both ventilation (in the non-dependent areas) and perfusion (in the middle and dependent lung). Bedside measure of recruitability is associated with improved
$${{\dot{V}} \mathord{\left/ {\vphantom {{\dot{V}} {\dot{Q}}} \right. \kern-\nulldelimiterspace} {\dot{Q}}}$$
V
˙
/
Q
˙
mismatch.
Patient self-inflicted lung injury (P-SILI) is a major challenge for the ICU physician: although spontaneous breathing is associated with physiological benefits, in patients with acute respiratory ...distress syndrome (ARDS), the risk of uncontrolled inspiratory effort leading to additional injury needs to be assessed to avoid delayed intubation and increased mortality. In the present review, we analyze the available clinical and experimental evidence supporting the existence of lung injury caused by uncontrolled high inspiratory effort, we discuss the pathophysiological mechanisms by which increased effort causes P-SILI, and, finally, we consider the measurements and interpretation of bedside physiological measures of increased drive that should alert the clinician. The data presented in this review could help to recognize injurious respiratory patterns that may trigger P-SILI and to prevent it.
Reducing the respiratory rate during extracorporeal membrane oxygenation (ECMO) decreases the mechanical power, but it might induce alveolar de-recruitment. Dissecting de-recruitment due to lung ...edema vs. the fraction due to hypoventilation may be challenging in injured lungs.
We characterized changes in lung physiology (primary endpoint: development of atelectasis) associated with progressive reduction of the respiratory rate in healthy animals on ECMO.
Six female pigs underwent general anesthesia and volume control ventilation (Baseline: PEEP 5 cmH
O, Vt 10 ml/kg, I:E = 1:2, FiO
0.5, rate 24 bpm). Veno-venous ECMO was started and respiratory rate was progressively reduced to 18, 12, and 6 breaths per minute (6-h steps), while all other settings remained unchanged. ECMO blood flow was kept constant while gas flow was increased to maintain stable PaCO
.
At Baseline (without ECMO) and toward the end of each step, data from quantitative CT scan, electrical impedance tomography, and gas exchange were collected. Increasing ECMO gas flow while lowering the respiratory rate was associated with an increase in the fraction of non-aerated tissue (i.e., atelectasis) and with a decrease of tidal ventilation reaching the gravitationally dependent lung regions (
= 0.009 and
= 0.018). Intrapulmonary shunt increased (
< 0.001) and arterial PaO
decreased (
< 0.001) at lower rates. The fraction of non-aerated lung was correlated with longer expiratory time spent at zero flow (
= 0.555,
= 0.011).
Progressive decrease of respiratory rate coupled with increasing CO
removal in mechanically ventilated healthy pigs is associated with development of lung atelectasis, higher shunt, and poorer oxygenation.
Abstract Background Assessment of regional ventilation/perfusion (V′/Q) mismatch using electrical impedance tomography (EIT) represents a promising advancement for personalized management of the ...acute respiratory distress syndrome (ARDS). However, accuracy is still hindered by the need for invasive monitoring to calibrate ventilation and perfusion. Here, we propose a non-invasive correction that uses only EIT data and characterized patients with more pronounced compensation of V′/Q mismatch. Methods We enrolled twenty-one ARDS patients on controlled mechanical ventilation. Cardiac output was measured invasively, and ventilation and perfusion were assessed by EIT. Relative V′/Q maps by EIT were calibrated to absolute values using the minute ventilation to invasive cardiac output (MV/CO) ratio (V′/Q-ABS), left unadjusted (V′/Q-REL), or corrected by MV/CO ratio derived from EIT data (V′/Q-CORR). The ratio between ventilation to dependent regions and perfusion reaching shunted units ( $${\text{V}}_{{\text{D}}}^{\prime }$$ V D ′ /Q SHUNT ) was calculated as an index of more effective hypoxic pulmonary vasoconstriction. The ratio between perfusion to non-dependent regions and ventilation to dead space units (Q ND / $${\text{V}}_{{{\text{DS}}}^{\prime }$$ V DS ′ ) was calculated as an index of hypocapnic pneumoconstriction. Results Our calibration factor correlated with invasive MV/CO (r = 0.65, p < 0.001), showed good accuracy and no apparent bias. Compared to V′/Q-ABS, V′/Q-REL maps overestimated ventilation ( p = 0.013) and perfusion ( p = 0.002) to low V′/Q units and underestimated ventilation ( p = 0.011) and perfusion ( p = 0.008) to high V′/Q units. The heterogeneity of ventilation and perfusion reaching different V′/Q compartments was underestimated. V′/Q-CORR maps eliminated all these differences with V′/Q-ABS ( p > 0.05). Higher $$V_{D}^{\prime } /Q_{SHUNT}$$ V D ′ / Q SHUNT correlated with higher PaO 2 /FiO 2 (r = 0.49, p = 0.025) and lower shunt fraction (ρ = − 0.59, p = 0.005). Higher $$Q_{ND} /V_{DS}^{\prime }$$ Q ND / V DS ′ correlated with lower PEEP (ρ = − 0.62, p = 0.003) and plateau pressure (ρ = − 0.59, p = 0.005). Lower values of both indexes were associated with less ventilator-free days ( p = 0.05 and p = 0.03, respectively). Conclusions Regional V′/Q maps calibrated with a non-invasive EIT-only method closely approximate the ones obtained with invasive monitoring. Higher efficiency of shunt compensation improves oxygenation while compensation of dead space is less needed at lower airway pressure. Patients with more effective compensation mechanisms could have better outcomes.
There is increasing recognition that traumatic brain injury (TBI) may initiate long-term neurodegenerative processes, particularly chronic traumatic encephalopathy. However, insight into the ...mechanisms transforming an initial biomechanical injury into a neurodegenerative process remain elusive, partly as a consequence of the paucity of informative pre-clinical models. This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: −30%) and external capsule (EC: −21%). Parallel neuropathological studies indicated reduction in neuronal density, with evidence of microgliosis and astrogliosis in the il-cortex, with further evidence of microgliosis and astrogliosis in the il-thalamus. One year after TBI there was also a decrease in FA in the contralateral (cl) CC (−17%) and EC (−13%), corresponding to histopathological evidence of white matter loss (cl-CC: −68%; cl-EC: −30%) associated with ongoing microgliosis and astrogliosis.
These findings indicate that a single severe TBI induces bilateral, long-term and progressive neuropathology at up to one year after injury. These observations support this model as a suitable platform for exploring the mechanistic link between acute brain injury and late and persistent neurodegeneration.
Display omitted
•Longitudinal effects of single severe TBI by controlled cortical impact were examined.•TBI triggers an evolving damage that at chronic stages spreads to the contralateral hemisphere.•Contralateral pathology at one year post TBI, shows a prominent involvement of white matter with ongoing neuroinflammation.•Findings support the model for studies interrogating the link between biomechanical impact and late neurodegeneration.
Abstract
Background
Nasal high flow delivered at flow rates higher than 60 L/min in patients with acute hypoxemic respiratory failure might be associated with improved physiological effects. However, ...poor comfort might limit feasibility of its clinical use.
Methods
We performed a prospective randomized cross-over physiological study on 12 ICU patients with acute hypoxemic respiratory failure. Patients underwent three steps at the following gas flow: 0.5 L/kg PBW/min, 1 L/kg PBW/min, and 1.5 L/kg PBW/min in random order for 20 min. Temperature and FiO
2
remained unchanged. Toward the end of each phase, we collected arterial blood gases, lung volumes, and regional distribution of ventilation assessed by electrical impedance tomography (EIT), and comfort.
Results
In five patients, the etiology was pulmonary; infective disease characterized seven patients; median PaO
2
/FiO
2
at enrollment was 213 IQR 136–232. The range of flow rate during NHF 1.5 was 75–120 L/min. PaO
2
/FiO
2
increased with flow, albeit non significantly (
p
= 0.064), PaCO
2
and arterial pH remained stable (
p
= 0.108 and
p
= 0.105). Respiratory rate decreased at higher flow rates (
p
= 0.014). Inhomogeneity of ventilation decreased significantly at higher flows (
p
= 0.004) and lung volume at end-expiration significantly increased (
p
= 0.007), but mostly in the non-dependent regions. Comfort was significantly poorer during the step performed at the highest flow (
p
< 0.001).
Conclusions
NHF delivered at rates higher than 60 L/min in critically ill patients with acute hypoxemic respiratory failure is associated with reduced respiratory rate, increased lung homogeneity, and additional positive pressure effect, but also with worse comfort.
Marongiu et al descibe the study which aims to characterize bilateral lung injury owing to unilateral ligation of the pulmonary artery in healthy swine undergoing controlled mechanical ventilation ...and its prevention by 5% CO2 inhalation and to investigate relevant pathophysiological mechanisms. Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (ligation group), seven to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (ligation-FiCO2 5%), and six to no intervention (no ligation). Then, all animals received mechanical ventilation with Vt 10 ml/kg, positive end-expiratory pressure 5 cm H2O, respiratory rate 25 breaths/min, and FiO2 50% for 48 hours or until development of severe lung injury. Mechanical ventilation induces bilateral lung injury within 48 hours in healthy pigs undergoing left pulmonary artery ligation. Inhalation of 5% CO2 prevents injury, likely through decreased stress to the right lung and antiinflammatory effects.
PDF
