Imbalances in regional lung ventilation, with gravity-dependent collapse and overdistention of nondependent zones, are likely associated to ventilator-induced lung injury. Electric impedance ...tomography is a new imaging technique that is potentially capable of monitoring those imbalances. The aim of this study was to validate electrical impedance tomography measurements of ventilation distribution, by comparison with dynamic computerized tomography in a heterogeneous population of critically ill patients under mechanical ventilation. Multiple scans with both devices were collected during slow-inflation breaths. Six repeated breaths were monitored by impedance tomography, showing acceptable reproducibility. We observed acceptable agreement between both technologies in detecting right-left ventilation imbalances (bias = 0% and limits of agreement = -10 to +10%). Relative distribution of ventilation into regions or layers representing one-fourth of the thoracic section could also be assessed with good precision. Depending on electrode positioning, impedance tomography slightly overestimated ventilation imbalances along gravitational axis. Ventilation was gravitationally dependent in all patients, with some transient blockages in dependent regions synchronously detected by both scanning techniques. Among variables derived from computerized tomography, changes in absolute air content best explained the integral of impedance changes inside regions of interest (r(2) > or = 0.92). Impedance tomography can reliably assess ventilation distribution during mechanical ventilation.
Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response ...and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and the functional impact of variants in pharmacokinetic (PK) genes was assessed using an array of functionality prediction methods. Low-density lipoprotein cholesterol (LDL-c) response to statins (reduction ≥ 50%) and statin-related adverse event (SRAE) risk were assessed in carriers of deleterious variants in PK-related genes using multivariate linear regression analyses. Fifty-eight (50.8%) FH patients responded to statins, and 24 (21.0%) had SRAE. Results of the multivariate regression analysis revealed that ABCC1 rs45511401 significantly increased LDL-c reduction after statin treatment (p < 0.05). In silico analysis of the amino-acid change using molecular docking showed that ABCC1 rs45511401 possibly impairs statin efflux. Deleterious variants in PK genes were not associated with an increased risk of SRAE. In conclusion, the deleterious variant ABCC1 rs45511401 enhanced LDL-c response in Brazilian FH patients. As such, this variant might be a promising candidate for the individualization of statin therapy.
Background
The way in which hyperoxia affects pulmonary ventilation and perfusion is not fully understood. We investigated how an increase in oxygen partial pressure in healthy young volunteers ...affects pulmonary ventilation and perfusion measured by thoracic electrical impedance tomography (EIT).
Methods
Twelve semi‐supine healthy male volunteers aged 21–36 years were studied while breathing room air and air–oxygen mixtures (FiO2) that resulted in predetermined transcutaneous oxygen partial pressures (tcPO2) of 20, 40 and 60 kPa. The magnitude of ventilation (ΔZv) and perfusion (ΔZQ)‐related changes in cyclic impedance variations, were determined using an EIT prototype equipped with 32 electrodes around the thorax. Regional changes in ventral and dorsal right lung ventilation (V) and perfusion (Q) were estimated, and V/Q ratios calculated.
Results
There were no significant changes in ΔZv with increasing tcPO2 levels. ΔZQ in the dorsal lung increased with increasing tcPO2 (P = 0.01), whereas no such change was seen in the ventral lung. There was a simultaneous decrease in V/Q ratio in the dorsal region during hyperoxia (P = 0.04). Two subjects did not reach a tcPO2 of 60 kPa despite breathing 100% oxygen.
Conclusion
These results indicate that breathing increased concentrations of oxygen induces pulmonary vasodilatation in the dorsal lung even at small increases in FiO2. Ventilation remains unchanged. Local mismatch of ventilation and perfusion occurs in young healthy men, and the change in ventilation/perfusion ratio can be determined non‐invasively by EIT.
To reevaluate the clinical impact of external positive end-expiratory pressure (external-PEEP) application in patients with severe airway obstruction during controlled mechanical ventilation. The ...controversial occurrence of a paradoxic lung deflation promoted by PEEP was scrutinized.
External-PEEP was applied stepwise (2 cm H(2)O, 5-min steps) from zero-PEEP to 150% of intrinsic-PEEP in patients already submitted to ventilatory settings minimizing overinflation. Two commonly used frequencies during permissive hypercapnia (6 and 9/min), combined with two different tidal volumes (VT: 6 and 9 mL/kg), were tested.
A hospital intensive care unit.
Eight patients were enrolled after confirmation of an obstructive lung disease (inspiratory resistance, >20 cm H(2)O/L per sec) and the presence of intrinsic-PEEP (> or =5 cm H(2)O) despite the use of very low minute ventilation.
All patients were continuously monitored for intra-arterial blood gas values, cardiac output, lung mechanics, and lung volume with plethysmography.
Three different responses to external-PEEP were observed, which were independent of ventilatory settings. In the biphasic response, isovolume-expiratory flows and lung volumes remained constant during progressive PEEP steps until a threshold, beyond which overinflation ensued. In the classic overinflation response, any increment of external-PEEP caused a decrease in isovolume-expiratory flows, with evident overinflation. In the paradoxic response, a drop in functional residual capacity during external-PEEP application (when compared to zero-external-PEEP) was commonly accompanied by decreased plateau pressures and total-PEEP, with increased isovolume-expiratory flows. The paradoxic response was observed in five of the eight patients (three with asthma and two with chronic obstructive pulmonary disease) during at least one ventilator pattern.
External-PEEP application may relieve overinflation in selected patients with airway obstruction during controlled mechanical ventilation. No a priori information about disease, mechanics, or ventilatory settings was predictive of the response. An empirical PEEP trial investigating plateau pressure response in these patients appears to be a reasonable strategy with minimal side effects.
To review as best the critical care clinicians can recruit the acute respiratory distress syndrome (ARDS) lungs and keep the lungs opened, assuring homogeneous ventilation, and to present the ...experimental and clinical results of these mechanical ventilation strategies, along with possible improvements in patient outcome based on selected published medical literature from 1972 to 2004 (highlighting the period from June 2003 to June 2004 and recent results of the authors' group research).
In the experimental setting, repeated derecruitments accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate lung injury. In the clinical setting, recruitment maneuvers improve short-term oxygenation in ARDS patients. A recent prospective clinical trial showed that low versus intermediate positive end-expiratory pressure (PEEP) levels (8 vs 13 cm H2O) associated with low tidal ventilation had the same effect on ARDS patient survival. Nevertheless, both conventional and electrical impedance thoracic tomography studies indicate that stepwise PEEP recruitment maneuvers increase lung volume and the recruitment percentage of lung tissue, and higher levels of PEEP (18-26 cm H2O) are necessary to keep the ARDS lungs opened and assure a more homogeneous low tidal ventilation.
Stepwise PEEP recruitment maneuvers can open collapsed ARDS lungs. Higher levels of PEEP are necessary to maintain the lungs open and assure homogenous ventilation in ARDS. In the near future, thoracic CT associated with high-performance monitoring of regional ventilation (electrical impedance tomography) may be used at the bedside to determine the optimal mechanical ventilation of ARDS patients.
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