Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial.

OBJECTIVES: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. DESIGN: Randomized controlled trial. SETTING: Tertiary mixed ICU. PATIENTS: Adult patients admitted for septic shock within the first 72 hours. INTERVENTIONS: Patients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each session. Twenty-one patients were included. Three died before the second muscle biopsy. Ten patients in the control and eight in the intervention group were analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F-box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the intervention group, but without difference between groups (muscle atrophy F-box: -7.3% ± 138.4% in control vs -56.4% ± 37.4% in intervention group; p = 0.23 and muscle ring finger-1: -30.8% ± 66.9% in control vs -62.7% ± 45.5% in intervention group; p = 0.15). Muscle fiber cross-sectional area (µm) was preserved by exercise (-25.8% ± 21.6% in control vs 12.4% ± 22.5% in intervention group; p = 0.005). Molecular regulations suggest that the excessive activation of autophagy due to septic shock was lower in the intervention group, without being suppressed. Markers of anabolism and inflammation were not modified by the intervention, which was well tolerated by the patients. CONCLUSIONS: Early physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area.

SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study.

PURPOSE: To compare in vivo the total and regional pulmonary deposition of aerosol particles generated by a new system combining a vibrating-mesh nebulizer with a specific valved holding chamber and constant-output jet nebulizer connected to a corrugated tube. METHODS: Cross-over study comparing aerosol delivery to the lungs using two nebulizers in 6 healthy male subjects: a vibrating-mesh nebulizer combined with a valved holding chamber (Aerogen Ultra®, Aerogen Ltd., Galway, Ireland) and a jet nebulizer connected to a corrugated tube (Opti-Mist Plus Nebulizer®, ConvaTec, Bridgewater, NJ). Nebulizers were filled with diethylenetriaminepentaacetic acid labelled with technetium-99 m (99mTc-DTPA, 2 mCi/4 mL). Pulmonary deposition of 99mTc-DTPA was measured by single-photon emission computed tomography combined with a low dose CT-scan (SPECT-CT). RESULTS: Pulmonary aerosol deposition from SPECT-CT analysis was six times increased with the vibrating-mesh nebulizer as compared to the jet nebulizer (34.1 ± 6.0% versus 5.2 ± 1.1%, p < 0.001). However, aerosol penetration expressed as the three-dimensional normalized ratio of the outer and the inner regions of the lungs was similar between both nebulizers. CONCLUSIONS: This study demonstrated the high superiority of the new system combining a vibrating-mesh nebulizer with a valved holding chamber to deliver nebulized particles into the lungs as comparted to a constant-output jet nebulizer with a corrugated tube.

Aerosol delivery during invasive mechanical ventilation: a systematic review.

BACKGROUND: This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in animal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways and the administration technique for aerosol delivery were analyzed. METHODS: In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on a systematic search among four databases. Two investigators independently assessed the eligibility and the risk of bias. RESULTS: Twenty-six clinical and ten experimental studies were included. Between 30% and 43% of nominal drug dose was lost to the circuit in ventilated patients. Whole lung deposition of up to 16% and 38% of nominal dose (proportion of drug charged in the device) were reported with nebulizers and metered-dose inhalers, respectively. A penetration index inferior to 1 observed in scintigraphic studies indicated major proximal deposition. However, substantial concentrations of antibiotics were measured in the epithelial lining fluid (887 (406-12,819) µg/mL of amikacin) of infected patients and in sub-pleural specimens (e.g., 197 µg/g of amikacin) dissected from infected piglets, suggesting a significant distal deposition. The administration technique varied among studies and may explain a degree of the variability of deposition that was observed. CONCLUSIONS: Lung deposition was lower than 20% of nominal dose delivered with nebulizers and mostly occurred in proximal airways. Further studies are needed to link substantial concentrations of antibiotics in infected pulmonary fluids to pulmonary deposition. The administration technique with nebulizers should be improved in ventilated patients in order to ensure an efficient but safe, feasible and reproducible technique.

Effects of Neurally Adjusted Ventilatory Assist (NAVA) levels in non-invasive ventilated patients: titrating NAVA levels with electric diaphragmatic activity and tidal volume matching.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) delivers pressure in proportion to diaphragm electrical activity (Eadi). However, each patient responds differently to NAVA levels. This study aims to examine the matching between tidal volume (Vt) and patients' inspiratory demand (Eadi), and to investigate patient-specific response to various NAVA levels in non-invasively ventilated patients. METHODS: 12 patients were ventilated non-invasively with NAVA using three different NAVA levels. NAVA100 was set according to the manufacturer's recommendation to have similar peak airway pressure as during pressure support. NAVA level was then adjusted ±50% (NAVA50, NAVA150). Airway pressure, flow and Eadi were recorded for 15 minutes at each NAVA level. The matching of Vt and integral of Eadi (ʃEadi) were assessed at the different NAVA levels. A metric, Range90, was defined as the 5-95% range of Vt/ʃEadi ratio to assess matching for each NAVA level. Smaller Range90 values indicated better matching of supply to demand. RESULTS: Patients ventilated at NAVA50 had the lowest Range90 with median 25.6 uVs/ml [Interquartile range (IQR): 15.4-70.4], suggesting that, globally, NAVA50 provided better matching between ʃEadi and Vt than NAVA100 and NAVA150. However, on a per-patient basis, 4 patients had the lowest Range90 values in NAVA100, 1 patient at NAVA150 and 7 patients at NAVA50. Robust coefficient of variation for ʃEadi and Vt were not different between NAVA levels. CONCLUSIONS: The patient-specific matching between ʃEadi and Vt was variable, indicating that to obtain the best possible matching, NAVA level setting should be patient specific. The Range90 concept presented to evaluate Vt/ʃEadi is a physiologic metric that could help in individual titration of NAVA level.

NAVA enhances tidal volume and diaphragmatic electro-myographic activity matching: a Range90 analysis of supply and demand.

Neurally adjusted ventilatory assist (NAVA) is a ventilation assist mode that delivers pressure in proportionality to electrical activity of the diaphragm (Eadi). Compared to pressure support ventilation (PS), it improves patient-ventilator synchrony and should allow a better expression of patient's intrinsic respiratory variability. We hypothesize that NAVA provides better matching in ventilator tidal volume (Vt) to patients inspiratory demand. 22 patients with acute respiratory failure, ventilated with PS were included in the study. A comparative study was carried out between PS and NAVA, with NAVA gain ensuring the same peak airway pressure as PS. Robust coefficients of variation (CVR) for Eadi and Vt were compared for each mode. The integral of Eadi (ʃEadi) was used to represent patient's inspiratory demand. To evaluate tidal volume and patient's demand matching, Range90 = 5-95 % range of the Vt/ʃEadi ratio was calculated, to normalize and compare differences in demand within and between patients and modes. In this study, peak Eadi and ʃEadi are correlated with median correlation of coefficients, R > 0.95. Median ʃEadi, Vt, neural inspiratory time (Ti_ ( Neural )), inspiratory time (Ti) and peak inspiratory pressure (PIP) were similar in PS and NAVA. However, it was found that individual patients have higher or smaller ʃEadi, Vt, Ti_ ( Neural ), Ti and PIP. CVR analysis showed greater Vt variability for NAVA (p < 0.005). Range90 was lower for NAVA than PS for 21 of 22 patients. NAVA provided better matching of Vt to ʃEadi for 21 of 22 patients, and provided greater variability Vt. These results were achieved regardless of differences in ventilatory demand (Eadi) between patients and modes.

Reciprocal influence of refractory hypoxemia and high intracranial pressure on the postoperative management of an urgent neurosurgical procedure.

A 20-year-old man was admitted in the neurology ICU after the drainage of a large frontal hematoma related to the spontaneous bleeding of a recently diagnosed cavernoma. On admission the Glasgow coma score was 4/15, with evidence of sub-falcorial herniation and elevated intracranial pressure. On the 4th postoperative day the patient developed acute lung injury, with an apparently normal bedside chest x-ray examination. Several episodes of critical oxygen desaturation (S(pO(2)) < 75%) occurred, which were not responsive to increasing PEEP and recruitment maneuvers. Hypoxemia was complicated by further increase in intracranial pressure. Ventilation in the prone position was not tolerated. The introduction of inhaled nitric oxide allowed a rapid and sustained improvement of both arterial oxygenation and cerebral hemodynamics. Interactions between acute brain and lung injury are complex. The correction of hypoxemia can usually be achieved by increasing PEEP or by alveolar recruitment maneuvers. Ventilation in the prone position can also be helpful in improving oxygenation, but is not always possible. The potential benefit of inhaled nitric oxide in similar cases has been described, but has still to be further explored.

Acute Effects of Sitting Out of Bed and Exercise on Lung Aeration and Oxygenation in Critically Ill Subjects.

BACKGROUND: Early mobilization during critical illness is safe and has beneficial effects on functional outcomes. However, its impact on pulmonary function has not been thoroughly explored. We hypothesized that a sitting position out of bed coupled with exercise could result in an improvement in oxygenation and lung aeration. METHODS: The study was conducted on a cohort of adult subjects within a week of their admission to an ICU. Subjects were transferred to a chair and undertook a 15-min session of exercise, either active or passive. Subjects in the control group were only transferred to a chair. Electrical impedance tomography, a reliable bedside technique monitoring regional lung aeration and the distribution of ventilation, was continuously performed, and blood gases were assessed at baseline and 20 min post-exercise. RESULTS: The cohort included 40 subjects, 17 of whom were mechanically ventilated and 23 spontaneously breathing. The control group for each modality consisted of 5 mechanically ventilated or 5 spontaneously breathing subjects. Mild hypoxemia was present in 45% of the spontaneously breathing cohort, whereas the mechanically ventilated subjects demonstrated moderate (50%) or severe (12%) hypoxemia. Compared with the control group, early mobilization induced a significant increase in lung aeration. In mechanically ventilated subjects, lung aeration increased, especially in the anterior lung regions (mean impedance [95% CI]: T1 (baseline in bed) = 1,265 [691-1,839]; T2 (chair sitting) = 2,003 [1,042-2,963]; T3 (exercise) = 1,619 [810 2,427]; T4 (post exercise in chair) = 2,320 [1,186-3,455]). In spontaneously breathing subjects, lung aeration increased mainly in the posterior lung regions (mean impedance [95% CI]: T1 = 380 [124-637]; T2 = 655 [226-1,084]; T3 = 621 [335-906]; T4 = 600 [340-860]). [Formula: see text] increased, especially in subjects with lower [Formula: see text] at baseline (< 200) (133 ± 31 to 158 ± 48, P = .041). CONCLUSIONS: For critically ill subjects, a sitting position and exercise increased lung aeration and were associated with an improvement in [Formula: see text] in the more severely hypoxemic subjects.

Incentive spirometry and positive expiratory pressure improve ventilation and recruitment in postoperative recovery: A randomized crossover study.

Introduction: Impairment of global and regional pulmonary ventilations is a well-known consequence of general anesthesia. Positive expiratory pressure (PEP) or incentive spirometry (IS) is commonly prescribed, albeit their efficacy is poorly demonstrated. The aim of this study was to assess the effects of PEP and IS on lung ventilation and recruitment in patients after surgery involving anesthesia using electrical impedance tomography (EIT). Method: Ten male subjects (age = 61.2 ± 16.3 years; BMI = 25.3 ± 3.8 kg/m2), free of pulmonary disease before being anesthetized, were recruited. Two series of manoeuvers (PEP and volume-oriented IS) were randomly performed with quiet breathing interposed between these phases. Pulmonary ventilation (ΔEELVVT (i - e)) and recruitment (ΔEELI) were evaluated continuously in a semi-seated position during all phases by EIT. Comparisons between rest and treatment were performed by Wilcoxon signed rank test. Rest phases were compared by a mixed ANOVA. Bonferroni method was used for post-hoc comparisons. Results: ΔEELVVT (i - e) and ΔEELI were significantly increased by both techniques (+422% [p < 0.001]; +138% [p = 0.040] and +296% [p < 0.001]; +638% [p < 0.001] for PEP and IS, respectively). No difference was observed between both manoeuvers neither on ventilation nor on recruitment. This positive effect disappeared during the quiet breathing phases. Conclusion: IS and PEP improved ventilation and recruitment instantaneously without remnant effect after stopping the exercise.

Effect of continuous positive airway pressure combined to nebulization on lung deposition measured by urinary excretion of amikacin.

UNLABELLED: Continuous positive airway pressure (CPAP) is frequently used in patients attending emergency units. Its combination with nebulization is sometimes necessary in those patients presenting with a CPAP dependency. STUDY OBJECTIVE: To compare lung deposition of amikacin delivered by a classical jet nebulizer (SideStream; Medic-Aid; West Sussex, UK) used alone (SST) or coupled to a CPAP device (Boussignac; Vygon; Belgium). METHOD: Amikacin (1g) was nebulized with both devices in six healthy subjects during 5 min on spontaneous breathing. A 1-week wash-out period between each nebulization was applied. Lung deposition was indirectly assessed by urinary monitoring of excreted amount of amikacin. RESULTS: Total daily amount of amikacin excreted in the urine was significantly lower with CPAP than with SST (1.97% initial dose versus 4.88% initial dose, p<0.001) with a corresponding mean ratio CPAP/SST of 0.41. The residual amount of amikacin in the nebulizer was higher with CPAP than with SST (607 mg versus 541 mg) but the difference was not significant (p=0.35). CONCLUSION: These data suggest that the amount of amikacin delivered to healthy lungs is 2.5-fold lower with CPAP than with SST for the same nebulization time and that the nebulization time when using CPAP should be increased to reach the same amount of drug delivered with a classical jet nebulizer.

Emergency orthopaedic surgery under noninvasive ventilation after refusal for general anaesthesia.

In this observation, we report a novel use of noninvasive positive pressure ventilation in the operating room to support ventilation in an acidotic hypercapnic patient with severe acute chronic respiratory failure refuted for general anaesthesia, operated under spinal anaesthesia for a femoral fracture. The feasibility of noninvasive ventilatory assistance during surgery performed under regional anaesthesia is reported here. In selected cases, noninvasive ventilation can be used in the management of patients with acute or chronic respiratory failure requiring an urgent surgical intervention but in whom the respiratory status excluded a general anaesthesia.

Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission Computed Tomography-Computed Tomography Study.

BACKGROUND: High-flow nasal cannula use is developing in ICUs. The aim of this study was to compare aerosol efficiency by using two nebulizers through a high-flow nasal cannula: the most commonly used jet nebulizer (JN) and a more efficient vibrating-mesh nebulizer (VN). METHODS: Aerosol delivery of diethylenetriaminepentaacetic acid labeled with technetium-99m (4 mCi/4 mL) to the lungs by using a VN (Aerogen Solo®; Aerogen Ltd., Galway, Ireland) and a constant-output JN (Opti-Mist Plus Nebulizer®; ConvaTec, Bridgewater, NJ) through a high-flow nasal cannula (Optiflow®; Fisher & Paykel, New Zealand) was compared in six healthy subjects. Flow rate was set at 30 L/min through the heated humidified circuit. Pulmonary and extrapulmonary deposition was measured by single-photon emission computed tomography combined with a low-dose computed tomographic scan and by planar scintigraphy. RESULTS: Lung deposition was only 3.6 (2.1-4.4) and 1 (0.7-2)% of the nominal dose with the VN and the JN, respectively (p < 0.05). The JN showed higher retained doses than the VN. However, both nebulizers were associated with substantial deposition in the single limb circuit, the humidification chamber, and the nasal cannula [58.2 (51.6-61.6)% of the nominal dose with the VN versus 19.2 (15.8-22.9)% of the nominal dose with the JN, p < 0.05] and in the upper respiratory tract [17.6 (13.4-27.9)% of the nominal dose with the VN and 8.6 (6.0-11.0)% of the nominal dose with the JN, p < 0.05], especially in the nasal cavity. CONCLUSIONS: In the specific conditions of the study, pulmonary drug delivery through the high-flow nasal cannula is about 1%-4% of the initial amount of drugs placed in the nebulizer, despite the higher efficiency of the VN as compared with the JN.

Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study.

OBJECTIVE: To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a "respiratory comfort zone" during noninvasive ventilation (NIV) in patients with acute respiratory failure. DESIGN AND SETTING: Prospective crossover interventional study in an intensive care unit of a university hospital. PATIENTS: Twenty patients. INTERVENTIONS: After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45 min with the automated PS activated. MEASUREMENTS AND RESULTS: During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20+/-3 vs. 25+/-3 bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO(2) decreased significantly from 61+/-9 to 51+/-2 mmHg, and pH increased significantly from 7.31+/-0.05 to 7.35+/-0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention. CONCLUSIONS: The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.

In Vitro Comparison of a Vibrating Mesh Nebulizer Operating in Inspiratory Synchronized and Continuous Nebulization Modes During Noninvasive Ventilation.

UNLABELLED: Backround: Coupling nebulization with noninvasive ventilation (NIV) has been shown to be effective in patients with respiratory diseases. However, a breath-synchronized nebulization option that could potentially improve drug delivery by limiting drug loss during exhalation is currently not available on bilevel ventilators. The aim of this in vitro study was to compare aerosol delivery of amikacin with a vibrating mesh nebulizer coupled to a single-limb circuit bilevel ventilator, using conventional continuous (Conti-Neb) and experimental inspiratory synchronized (Inspi-Neb) nebulization modes. METHODS: Using an adult lung bench model of NIV, we tested a vibrating mesh device coupled with a bilevel ventilator in both nebulization modes. Inspi-Neb delivered aerosol only during the whole inspiratory phase, whereas Conti-Neb delivered aerosol continuously. The nebulizer was charged with amikacin solution (250 mg/3 mL) and placed at two different positions: between the lung and exhalation port and between the ventilator and exhalation port. Inhaled, expiratory wasted and circuit lost doses were assessed by residual gravimetric method. Particle size distribution of aerosol delivered at the outlet of the ventilator circuit during both nebulization modes was measured by laser diffraction method. RESULTS: Regardless of the nebulizer position, Inspi-Neb produced higher inhaled dose (p < 0.01; +6.3% to +16.8% of the nominal dose), lower expiratory wasted dose (p < 0.05; -2.7% to -42.6% of the nominal dose), and greater respirable dose (p < 0.01; +8.4% to +15.2% of the nominal dose) than Conti-Neb. The highest respirable dose was found with the nebulizer placed between the lung and exhalation port (48.7% ± 0.3% of the nominal dose). CONCLUSIONS: During simulated NIV with a single-limb circuit bilevel ventilator, the use of inspiratory synchronized vibrating mesh nebulization improves respirable dose and reduces drug loss of amikacin compared with continuous vibrating mesh nebulization.

Teamwork enables high level of early mobilization in critically ill patients.

BACKGROUND: Early mobilization in critically ill patients has been shown to prevent bed-rest-associated morbidity. Reported reasons for not mobilizing patients, thereby excluding or delaying such intervention, are diverse and comprise safety considerations for high-risk critically ill patients with multiple organ support systems. This study sought to demonstrate that early mobilization performed within the first 24 h of ICU admission proves to be feasible and well tolerated in the vast majority of critically ill patients. RESULTS: General practice data were collected for 171 consecutive admissions to our ICU over a 2-month period according to a local, standardized, early mobilization protocol. The total period covered 731 patient-days, 22 (3 %) of which met our local exclusion criteria for mobilization. Of the remaining 709 patient-days, early mobilization was achieved on 86 % of them, bed-to-chair transfer on 74 %, and at least one physical therapy session on 59 %. Median time interval from ICU admission to the first early mobilization activity was 19 h (IQR = 15-23). In patients on mechanical ventilation (51 %), accounting for 46 % of patient-days, 35 % were administered vasopressors and 11 % continuous renal replacement therapy. Within this group, bed-to-chair transfer was achieved on 68 % of patient-days and at least one early mobilization activity on 80 %. Limiting factors to start early mobilization included restricted staffing capacities, diagnostic or surgical procedures, patients' refusal, as well as severe hemodynamic instability. Hemodynamic parameters were rarely affected during mobilization, causing interruption in only 0.8 % of all activities, primarily due to reversible hypotension or arrhythmia. In general, all activities were well tolerated, while patients were able to self-regulate their active early mobilization. Patients' subjective perception of physical therapy was reported to be enjoyable. CONCLUSIONS: Mobilization within the first 24 h of ICU admission is achievable in the majority of critical ill patients, in spite of mechanical ventilation, vasopressor administration, or renal replacement therapy.

Closed-loop ventilation mode (IntelliVent®-ASV) in intensive care unit: a randomized trial.

BACKGROUND: Closed-loop modes automatically adjust ventilation settings, delivering individualized ventilation over short periods of time. The objective of this randomized controlled trial was to compare safety, efficacy and workload for the health care team between IntelliVent®-ASV and conventional modes over a 48-hour period. METHODS: ICU patients admitted with an expected duration of mechanical ventilation of more than 48 hours were randomized to IntelliVent®-ASV or conventional ventilation modes. All ventilation parameters were recorded breath-by-breath. The number of manual adjustments assesses workload for the healthcare team. Safety and efficacy were assessed by calculating the time spent within previously defined ranges of non-optimal and optimal ventilation, respectively. RESULTS: Eighty patients were analyzed. The median values of ventilation parameters over 48 hours were similar in both groups except for PEEP (7[4] cmH2O versus 6[3] cmH2O with IntelliVent®-ASV and conventional ventilation, respectively, P=0.028) and PETCO2 (36±7 mmHg with IntelliVent®-ASV versus 40±8 mmHg with conventional ventilation, P=0.041). Safety was similar between IntelliVent®-ASV and conventional ventilation for all parameters except for PMAX, which was more often non-optimal with IntelliVent®-ASV (P=0.001). Efficacy was comparable between the 2 ventilation strategies, except for SpO2 and VT, which were more often optimal with IntelliVent®-ASV (P=0.005, P=0.016, respectively). IntelliVent®-ASV required less manual adjustments than conventional ventilation (P<0.001) for a higher total number of adjustments (P<0.001). The coefficient of variation over 48 hours was larger with IntelliVent®-ASV in regard of maximum pressure, inspiratory pressure (PINSP), and PEEP as compared to conventional ventilation. CONCLUSIONS: IntelliVent®-ASV required less manual intervention and delivered more variable PEEP and PINSP, while delivering ventilation safe and effective ventilation in terms of VT, RR, SpO2 and PETCO2.

Aerosol delivery with two ventilation modes during mechanical ventilation: a randomized study.

BACKGROUND: Volume-controlled ventilation has been suggested to optimize lung deposition during nebulization although promoting spontaneous ventilation is targeted to avoid ventilator-induced diaphragmatic dysfunction. Comparing topographic aerosol lung deposition during volume-controlled ventilation and spontaneous ventilation in pressure support has never been performed. The aim of this study was to compare lung deposition of a radiolabeled aerosol generated with a vibrating-mesh nebulizer during invasive mechanical ventilation, with two modes: pressure support ventilation and volume-controlled ventilation. METHODS: Seventeen postoperative neurosurgery patients without pulmonary disease were randomly ventilated in pressure support or volume-controlled ventilation. Diethylenetriaminepentaacetic acid labeled with technetium-99m (2 mCi/3 mL) was administrated using a vibrating-mesh nebulizer (Aerogen Solo(®), provided by Aerogen Ltd, Galway, Ireland) connected to the endotracheal tube. Pulmonary and extrapulmonary particles deposition was analyzed using planar scintigraphy. RESULTS: Lung deposition was 10.5 ± 3.0 and 15.1 ± 5.0 % of the nominal dose during pressure support and volume-controlled ventilation, respectively (p < 0.05). Higher endotracheal tube and tracheal deposition was observed during pressure support ventilation (27.4 ± 6.6 vs. 20.7 ± 6.0 %, p < 0.05). A similar penetration index was observed for the right (p = 0.210) and the left lung (p = 0.211) with both ventilation modes. A high intersubject variability of lung deposition was observed with both modes regarding lung doses, aerosol penetration and distribution between the right and the left lung. CONCLUSIONS: In the specific conditions of the study, volume-controlled ventilation was associated with higher lung deposition of nebulized particles as compared to pressure support ventilation. The clinical benefit of this effect warrants further studies. Clinical trial registration NCT01879488.

Influence of inspiratory flow pattern and nebulizer position on aerosol delivery with a vibrating-mesh nebulizer during invasive mechanical ventilation: an in vitro analysis.

BACKGROUND: Aerosol delivery during invasive mechanical ventilation (IMV) depends on nebulizer type, placement of the nebulizer and ventilator settings. The purpose of this study was to determine the influence of two inspiratory flow patterns on amikacin delivery with a vibrating-mesh nebulizer placed at different positions on an adult lung model of IMV equipped with a proximal flow sensor (PFS). METHODS: IMV was simulated using a ventilator connected to a lung model through an 8-mm inner-diameter endotracheal tube. The impact of a decelerating and a constant flow pattern on aerosol delivery was evaluated in volume-controlled mode (tidal volume 500 mL, 20 breaths/min, inspiratory time of 1 sec, bias flow of 10 L/min). An amikacin solution (250 mg/3 mL) was nebulized with Aeroneb Solo(®) placed at five positions on the ventilator circuit equipped with a PFS: connected to the endotracheal tube (A), to the Y-piece (B), placed at 15 cm (C) and 45 cm upstream of the Y-piece (D), and placed at 15 cm of the inspiratory outlet of the ventilator (E). The four last positions were also tested without PFS. Deposited doses of amikacin were measured using the gravimetric residual method. RESULTS: Amikacin delivery was significantly reduced with a decelerating inspiratory flow pattern compared to a constant flow (p<0.05). With a constant inspiratory flow pattern, connecting the nebulizer to the endotracheal tube enabled similar deposited doses than these obtained when connecting the nebulizer close to the ventilator. The PFS reduced deposited doses only when the nebulizer was connected to the Y-piece with both flow patterns or placed at 15 cm of the Y-piece with a constant inspiratory flow (p<0.01). CONCLUSIONS: Using similar tidal volume and inspiratory time, a constant flow pattern (30 L/min) delivers a higher amount of amikacin through an endotracheal tube compared to a decelerating inspiratory flow pattern (peak inspiratory flow around 60 L/min). The optimal nebulizer position depends on the inspiratory flow pattern and the presence of a PFS.

Volumetric capnography as a screening test for pulmonary embolism in the emergency department.

STUDY OBJECTIVE: To compare the diagnostic performance of volumetric capnography (VCap), which is the plot of the expired CO(2) partial pressure against the expired volume during a single breath, with the PaCO(2) to end-tidal CO(2) (EtCO(2)) gradient, in the case of suspected pulmonary embolism (PE). DESIGN: Single-center, prospective study. SETTING: Emergency department of a teaching hospital. PATIENTS: A total of 45 outpatients with positive enzyme-linked immunosorbent assay d-dimer levels of > 500 ng/mL. The diagnosis of PE was confirmed in 18 outpatients according to a validated procedure based on the ventilation-perfusion lung scan and/or spiral CT scanning. INTERVENTIONS: Curves of VCap were obtained from a compact monitor connected to a computer. A sequence of four to six stable breaths allowed the calculation of the following several variables: alveolar dead space fraction; the ratio of alveolar dead space (VDalv) to airway dead space (VDaw); the VDalv to physiologic dead space (VDphys) fraction; the slope of phase 3; and the late dead space fraction (Fdlate) corresponding to the extrapolation of the capnographic curve to a volume of 15% of the predicted total lung capacity. RESULTS: The mean (+/- SD) PaCO(2)-EtCO(2) gradient was 5.3 +/- 0.7 mm Hg in the PE-positive group and 2.8 +/- 0.7 mm Hg in the PE-negative group (p = 0.019). Four variables of the VCap exhibited a statistical difference between both groups, as follows: the VDalv/VDaw fraction(;) the slope of phase 3; the VDalv/VDphys fraction; and the Fdlate, which was 8.2 +/- 3.3% vs -7.7 +/- 2.8%, respectively (p = 0.000011). The diagnostic performance expressed as the mean area under a receiver operating characteristic curve comparison was 75.9 +/- 7.4% for the PaCO(2)-EtCO(2) gradient and 87.6 +/- 4.9% for the Fdlate (p = 0.02). CONCLUSION: Fdlate, a variable of VCap, had a statistically better diagnostic performance in suspected PE than the PaCO(2)-EtCO(2) gradient. VCap is a promising computer-assisted bedside application of pulmonary pathophysiology. Future research should define the place of this technique in the diagnostic workup of PE, especially in the presence of positive d-dimers.

Volumetric capnography as a bedside monitoring of thrombolysis in major pulmonary embolism.

OBJECTIVE: To describe the use of volumetric capnography, a plot of expired CO(2) concentration against expired volume, in monitoring fibrinolytic treatment of major pulmonary embolism. DESIGN AND SETTING: Two case reports in the emergency department of a teaching hospital. PATIENTS: Two conscious and spontaneously breathing patients (69- and 31-year-old women) with major pulmonary embolism requiring thrombolysis. Decision for thrombolysis was based on the association of right ventricular afterload on echocardiography, with respiratory failure and hypotension in the first patient, and dyspnea and hemodynamically stable parameters in the second one. INTERVENTIONS: Successive capnographic measurements were performed before, during, and after thrombolysis. Curves of volumetric capnography were obtained from a sidestream gas monitor with flow sensor and an arterial blood gas analysis for CO(2) partial pressure. MEASUREMENTS AND RESULTS: We calculated late deadspace fraction, previously suggested as the most effective capnographic parameter in the diagnosis of pulmonary embolism. Late deadspace fraction decreased in the two patients, respectively, from 64.4% to 1.1% and from 25.6% to 5.7% after thrombolysis, with a concomitant disappearance of right heart dysfunction signs on echocardiography. CONCLUSIONS: Volumetric capnography can monitor thrombolysis in major pulmonary embolism. Differences between volumetric capnography technology and the more traditional arterial to end-tidal CO(2) gradient are important to take into account for clinical application.