Cardiogenic oscillations to detect intratidal derecruitment and overdistension in a porcine model of healthy and atelectatic lungs.

BACKGROUND: Low positive end-expiratory pressure (PEEP) can result in alveolar derecruitment, and high PEEP or high tidal volume (VT) in lung overdistension. We investigated cardiogenic oscillations (COS) in the airway pressure signal to investigate whether these oscillations can assess unfavourable intratidal events. COS induce short instantaneous compliance increases within the pressure-volume curve, and consequently in the compliance-volume curve. We hypothesised that increases in COS-induced compliance reflect non-linear intratidal respiratory system mechanics. METHODS: In mechanically ventilated anaesthetised pigs with healthy (n=13) or atelectatic (n=12) lungs, pressure-volume relationships and the ECG were acquired at a PEEP of 0, 5, 10, and 15 cm H2O. During inspiration, the peak compliance of successive COS (CCOS) was compared with intratidal respiratory system compliance (CRS) within incremental volume steps up to the full VT of 12 ml kg-1. We analysed whether CCOS variation corresponded with systolic arterial pressure variation. RESULTS: CCOS-volume curves showed characteristic intratidal patterns depending on the PEEP level and on atelectasis. Increasing CRS- or CCOS-volume patterns were associated with intratidal derecruitment with low PEEP, and decreasing patterns above 6 ml kg-1 and high PEEP showed overdistension. CCOS was not associated with systolic arterial pressure variations. CONCLUSIONS: Heartbeat-induced oscillations within the course of the inspiratory pressure-volume curve reflect non-linear intratidal respiratory system mechanics. The analysis of these cardiogenic oscillations can be used to detect intratidal derecruitment and overdistension and, hence, to guide PEEP and VT settings that are optimal for respiratory system mechanics.

Intraoperative positive end-expiratory pressure evaluation using the intratidal compliance-volume profile.

BACKGROUND: Lung-protective mechanical ventilation during general surgery including the application of PEEP can reduce postoperative pulmonary complications. In a prospective clinical observation study, we evaluated volume-dependent respiratory system compliance in adult patients undergoing ear-nose-throat surgery with ventilation settings chosen empirically by the attending anaesthetist. METHODS: In 40 patients, we measured the respiratory variables during intraoperative mechanical ventilation. All measurements were subdivided into 5 min intervals. Dynamic compliance (CRS) and the intratidal volume-dependent CRS curve was calculated for each interval and classified into one of the six specific compliance profiles indicating intratidal recruitment/derecruitment, overdistension or all. We retrospectively compared the occurrences of the respective compliance profiles at PEEP levels of 5 cm H2O and at higher levels. RESULTS: The attending anaesthetists set the PEEP level initially to 5 cm H2O in 29 patients (83%), to 7 cm H2O in 5 patients (14%), and to 8 cm H2O in 2 patients (6%). Across all measurements the mean CRS was 61 (11) ml cm H2O(-1) (40-86 ml cm H2O(-1)) and decreased continuously during the procedure. At PEEP of 5 cm H2O the compliance profile indicating strong intratidal recruitment/derecruitment occurred more often (18.6%) compared with higher PEEP levels (5.5%, P<0.01). Overdistension was practically never observed. CONCLUSIONS: In most patients, a PEEP of 5 cm H2O during intraoperative mechanical ventilation is too low to prevent intratidal recruitment/derecruitment. The analysis of the intratidal compliance profile provides the rationale to individually titrate a PEEP level that stabilizes the alveolar recruitment status of the lung during intraoperative mechanical ventilation. TRIAL REGISTRATION NUMBER: DRKS00004286.

Flow-controlled expiration: a novel ventilation mode to attenuate experimental porcine lung injury.

BACKGROUND: Whereas the effects of various inspiratory ventilatory modifications in lung injury have extensively been studied, those of expiratory ventilatory modifications are less well known. We hypothesized that the newly developed flow-controlled expiration (FLEX) mode provides a means of attenuating experimental lung injury. METHODS: Experimental acute respiratory distress syndrome was induced by i.v. injection of oleic acid in 15 anaesthetized and mechanically ventilated pigs. After established lung injury ([Formula: see text]ratio <27 kPa), animals were randomized to either a control group receiving volume-controlled ventilation (VCV) or a treatment group receiving VCV with additional FLEX (VCV+FLEX). At predefined times, lung mechanics and oxygenation were assessed. At the end of the experiment, the pigs were killed, and bronchoalveolar fluid and lung biopsies were taken. Expression of inflammatory cytokines was analysed in lung tissue and bronchoalveolar fluid. Lung injury score was determined on the basis of stained tissue samples. RESULTS: Compared with the control group (VCV; n=8), the VCV+FLEX group (n=7) demonstrated greater dynamic lung compliance and required less PEEP at comparable [Formula: see text] (both P<0.05), had lower regional lung wet-to-dry ratios and lung injury scores (both P<0.001), and showed less thickening of alveolar walls (an indicator of interstitial oedema) and de novo migration of macrophages into lung tissue (both P<0.001). CONCLUSIONS: The newly developed FLEX mode is able to attenuate experimental lung injury. FLEX could provide a novel means of lung-protective ventilation.

Monitoring of intratidal lung mechanics: a Graphical User Interface for a model-based decision support system for PEEP-titration in mechanical ventilation.

In mechanical ventilation, a careful setting of the ventilation parameters in accordance with the current individual state of the lung is crucial to minimize ventilator induced lung injury. Positive end-expiratory pressure (PEEP) has to be set to prevent collapse of the alveoli, however at the same time overdistension should be avoided. Classic approaches of analyzing static respiratory system mechanics fail in particular if lung injury already prevails. A new approach of analyzing dynamic respiratory system mechanics to set PEEP uses the intratidal, volume-dependent compliance which is believed to stay relatively constant during one breath only if neither atelectasis nor overdistension occurs. To test the success of this dynamic approach systematically at bedside or in an animal study, automation of the computing steps is necessary. A decision support system for optimizing PEEP in form of a Graphical User Interface (GUI) was targeted. Respiratory system mechanics were analyzed using the gliding SLICE method. The resulting shapes of the intratidal compliance-volume curve were classified into one of six categories, each associated with a PEEP-suggestion. The GUI should include a graphical representation of the results as well as a quality check to judge the reliability of the suggestion. The implementation of a user-friendly GUI was successfully realized. The agreement between modelled and measured pressure data [expressed as root-mean-square (RMS)] tested during the implementation phase with real respiratory data from two patient studies was below 0.2 mbar for data taken in volume controlled mode and below 0.4 mbar for data taken in pressure controlled mode except for two cases with RMS < 0.6 mbar. Visual inspections showed, that good and medium quality data could be reliably identified. The new GUI allows visualization of intratidal compliance-volume curves on a breath-by-breath basis. The automatic categorisation of curve shape into one of six shape-categories provides the rational decision-making model for PEEP-titration.

Determination of respiratory system mechanics during inspiration and expiration by FLow-controlled EXpiration (FLEX): a pilot study in anesthetized pigs.

BACKGROUND: Differences between inspiratory and expiratory lung mechanics result in the hysteresis of the pressure volume-loop. While hysteresis area is a global parameter describing the difference between inspiration and expiration in mechanics under quasi-static conditions, a detailed analysis of this difference under the dynamic conditions of mechanical ventilation is feasible once inspiratory and expiratory compliance (Cin/Cex) are determined separately. This requires uncoupling of expiratory flow rate and volume (V). METHODS: Five piglets were mechanically ventilated at positive end-expiratory pressure (PEEP) levels ranging from 0 to 15 cmH2O. Expiratory flow rate was linearized by a computer-controlled resistor (flow-controlled expiration). The volume-dependent Cin(V) and Cex(V) profiles were calculated from the tracheal pressure volume-loops. RESULTS: The intratidal curve-progression of Cex(V) was altogether higher with a steeper slope compared to Cin(V). With increasing positive end-expiratory pressure (PEEP) dynamic hysteresis area decreased and Cex(V) tended to run more parallel to Cin(V). CONCLUSION: The relation between inspiratory and expiratory compliance profiles is associated with the hysteresis area and behaves PEEP dependent. Analysing the Cin-Cex-relation might therefore potentially offer a new approach to titrate PEEP and tidal volume.

Electrical impedance tomography for verification of correct endotracheal tube placement in paediatric patients: a feasibility study.

BACKGROUND: Endotracheal tubes (ETTs) are frequently used in paediatric anaesthesia. Correct placement is crucial. The aim of this study was to evaluate electrical impedance tomography (EIT) for guiding and confirmation of paediatric ETT placement. In a retrospective analysis of stored EIT data, distribution of ventilation between left and right lung was used to verify correct paediatric ETT placement. METHODS: Left and right lung ventilation was studied by EIT in 18 paediatric patients (median age: 53 months) requiring anaesthesia and endotracheal intubation. EIT was recorded before induction of anaesthesia, during mask ventilation, during ETT placement (including deliberate mainstem intubation), and after ETT repositioning according to the formula: ETT intubation depth (cm) = 3× ETT internal diameter (mm) or the mainstem intubation method (withdrawing the ETT 2 cm). Final ETT position was confirmed by fluoroscopy. RESULTS: Following deliberate mainstem intubation, distribution of ventilation to the right lung was unequivocally demonstrated by EIT. Homogeneous distribution of ventilation between left and right lung monitored with EIT correlated in each patient with correct endotracheal ETT placement. The distribution of left and right lung ventilation differed significantly (P < 0.05) between the initial two-lung ventilation and subsequent right one-lung ventilation, and between right one-lung and subsequent two-lung ventilation according to auscultation and the final ETT position, respectively. In one patient, ETT was misplaced within the oesophagus which was also obvious from the EIT record. CONCLUSION: This study demonstrates that EIT enables non-invasive recognition of correct ETT placement. Homogeneous right-left-lung ventilation is an indicator for correct ETT placement.

Cardiogenic oscillations in spontaneous breathing airway signal reflect respiratory system mechanics.

BACKGROUND: Heartbeat-related pressure oscillations appear at the airway opening. We investigated whether these cardiogenic oscillations (COS) - extracted from spontaneous breathing signals - reflect the compliance of the respiratory system. METHODS: Fifteen volunteers breathed spontaneously at normal or reduced chest wall compliance, i.e. with and without thorax strapping, and at normal or reduced lung compliance, induced by positive end-expiratory pressure (PEEP). COS-related signals were extracted by averaging the flow and pressure curve sections, temporally aligned to the electrocardiogram signal. RESULTS: COS-related airway pressure and flow curves correlated closely for each subject (r(2) =0.97 ± 0.02, P<0.0001). At the unstrapped thorax, the oscillation's amplitudes were 0.07 ± 0.03 cm H(2) O (pressure) and 22 ± 10 ml/s (flow). COS-related pressure amplitudes correlated closely with the ratio of tidal volume divided by pressure amplitude (r(2) =0.88, P<0.001) and furthermore increased with either thorax strapping (P<0.001) or with increasing PEEP (P=0.049). CONCLUSION: We conclude that COS extracted from the pressure and flow signal reflect the compliance of the respiratory system and could potentially allow estimating respiratory system mechanics during spontaneous breathing.

Neutron computed tomography of rat lungs.

Using conventional methods, three-dimensional imaging of the lung is challenging because of the low contrast between air and tissue and the large differences in dimensions between various pulmonary structures. The small distal airway structures and the high air-to-tissue ratio of lung tissue require an imaging technique which reliably discriminates between air and water. The objective of this study was to assess whether neutron computed tomography would satisfy such a requirement. This method utilizes the unique characteristic of neutrons of directly interacting with the atomic nucleus rather than being scattered by the atomic shell. Neutron computed tomography was tested in rats and allowed differentiation of larger lung structures (e.g., lobes) and distal airways. Airways could be identified reliably down to the sixth bronchial generation, in some cases even down to the tenth generation. The lung could be stabilized for sufficiently long exposure times to achieve an image resolution of 50-60 µm, which is the current physical resolution limit of the neutron computed tomography facility. Neutron computed tomography allowed excellent lung imaging without the need for additional tissue preparation or contrast media. The enhanced structural resolution obtained by applying this new research technique may improve understanding of lung physiology and respiratory therapy.

Automated mechanical ventilation: adapting decision making to different disease states.

The purpose of the present study is to introduce a novel methodology for adapting and upgrading decision-making strategies concerning mechanical ventilation with respect to different disease states into our fuzzy-based expert system, AUTOPILOT-BT. The special features are: (1) Extraction of clinical knowledge in analogy to the daily routine. (2) An automated process to obtain the required information and to create fuzzy sets. (3) The controller employs the derived fuzzy rules to achieve the desired ventilation status. For demonstration this study focuses exclusively on the control of arterial CO(2) partial pressure (p(a)CO(2)). Clinical knowledge from 61 anesthesiologists was acquired using a questionnaire from which different disease-specific fuzzy sets were generated to control p(a)CO(2). For both, patients with healthy lung and with acute respiratory distress syndrome (ARDS) the fuzzy sets show different shapes. The fuzzy set "normal", i.e., "target p(a)CO(2) area", ranges from 35 to 39 mmHg for healthy lungs and from 39 to 43 mmHg for ARDS lungs. With the new fuzzy sets our AUTOPILOT-BT reaches the target p(a)CO(2) within maximal three consecutive changes of ventilator settings. Thus, clinical knowledge can be extended, updated, and the resulting mechanical ventilation therapies can be individually adapted, analyzed, and evaluated.

Biaxial distension of precision-cut lung slices.

The mechanical forces acting on lung parenchyma during (mechanical) ventilation and its (patho)physiological consequences are currently under intense scrutiny. Several in vivo and cell culture models have been developed to study the pulmonary responses to mechanical stretch. While providing extremely useful information, these models do also suffer from limitations in being either too complex for detailed mechanical or mechanistic studies, or in being devoid of the full complexity present in vivo (e.g., different cell types and interstitial matrix). Therefore in the present study it was our aim to develop a new model, based on the biaxial stretching of precision-cut lung slices (PCLS). Single PCLS were mounted on a thin and flexible carrier membrane of polydimethylsiloxane (PDMS) in a bioreactor, and the membrane was stretched by applying varying pressures under static conditions. Distension of the membrane-PCLS construct was modeled via finite element simulation. According to this analysis, lung tissue was stretched by up to 38% in the latitudinal and by up to 44% in the longitudinal direction, resulting in alveolar distension similar to what has been described in intact lungs. Stretch for 5 min led to increased cellular calcium levels. Lung slices were stretched dynamically with a frequency of 15/min for 4 h without causing cell injury {3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test; live/dead straining}. These findings suggest that stretching of PCLS on PDMS-membranes may represent a useful model to investigate lung stretch in intact lung tissue in vitro for several hours.

Electrical impedance tomography to confirm correct placement of double-lumen tube: a feasibility study.

BACKGROUND: Double-lumen tubes (DLTs) are frequently used to establish one-lung ventilation (OLV). Their correct placement is crucial. We hypothesized that electrical impedance tomography (EIT) reliably displays distribution of ventilation between left and right lung and may thus be used to verify correct DLT placement online. METHODS: Regional ventilation was studied by EIT in 40 patients requiring insertion of left-sided DLTs for OLV during thoracic surgery. EIT was recorded during two-lung ventilation before induction of anaesthesia and after DLT placement, and during OLV in the supine and subsequently in the lateral position. EIT measurements were made before and after verification of correct DLT placement by fibreoptic bronchoscopy (FOB). RESULTS: EIT accurately displayed distribution of ventilation between left and right lung online. All cases (n=5) of initially misplaced DLTs in the contralateral right main bronchus were detected by EIT. However, EIT did not allow prediction of FOB-detected endobronchial cuff misplacement requiring DLT repositioning. Furthermore, after DLT repositioning, distribution of ventilation, as assessed by EIT, did not change significantly (all P>0.5). CONCLUSIONS: This study demonstrates that EIT enables accurate display of left and right lung ventilation and, thus, non-invasive online recognition of misplacement of left-sided DLTs in the contralateral main bronchus. However, as distribution of ventilation did not correlate with endobronchial cuff placement, EIT cannot replace FOB in the routine control of DLT position.

AUTOPILOT-BT: a system for knowledge and model based mechanical ventilation.

A closed-loop system (AUTOPILOT-BT) for the control of mechanical ventilation was designed to: 1) autonomously achieve goals specified by the clinician, 2) optimize the ventilator settings with respect to the underlying disease and 3) automatically adapt to the individual properties and specific disease status of the patient. The current realization focuses on arterial oxygen saturation (SpO(2)), end-tidal CO(2) pressure (P(et)CO(2)), and positive end-expiratory pressure (PEEP) maximizing respiratory system compliance (C(rs)). The "AUTOPILOT-BT" incorporates two different knowledge sources: a fuzzy logic control reflecting expert knowledge and a mathematical model based system that provides individualized patient specific information. A first evaluation test with respect to desired end-tidal-CO(2)-level was accomplished using an experimental setup to simulate three different metabolic CO(2) production rates by means of a physical lung simulator. The outcome of ventilator settings made by the "AUTOPILOT-BT" system was compared to those produced by clinicians. The model based control system proved to be superior to the clinicians as well as to a pure fuzzy logic based control with respect to precision and required settling time into the optimal ventilation state.

[Acute obstruction of the endotracheal tube]. / Akute Obstruktion des endotrachealen Tubus.

Acute occlusion of an endotracheal tube (ETT) is a feared, potentially life-threatening complication of mechanical ventilation. In the presence of a thoracic trauma, a blood clot needs to be taken into consideration as the cause of airway obstruction. This report describes a case of sudden ventilation failure due to acute ETT obstruction by a blood clot caused by intrapulmonary haemorrhaging in a child following multiple trauma accompanied by blunt thoracic trauma in the absence of dyspnoe or haemoptysis.

Respiratory system inertance corresponds to extravascular lung water in surfactant-deficient piglets.

In various cardio-pulmonary diseases lung mass is considerably increased due to intrapulmonary fluid accumulation, i.e. extravascular lung water (EVLW). Generally, inertance is a physical system parameter that is mass-dependent. We hypothesized that changes in lung mass influence the inertive behavior of the respiratory system. EVLW and intrathoracic blood volume (ITBV) were compared with respiratory system inertance (I(rs)) in four piglets before and after broncho-alveolar lavage (BAL) that induced surfactant deficiency with interstitial edema. EVLW and ITBV were determined using the double-indicator dilution technique, I(rs) by multiple linear regression analysis. Measurements were taken before, and 1 and 2 h after BAL. EVLW increased threefold (from 6.2+/-0.8 mL/kg at baseline to 17.7+/-0.9 mL/kg (p < 0.001) after BAL). I(rs) increased by 35% (from 0.17+/-0.02 to 0.23+/-0.04 cmH(2)O s(2)/L (p = 0.036) after BAL) and was tightly correlated to EVLW (r(2) = 0.95, p < 0.023). ITBV did not change significantly after BAL. We conclude that I(rs) reflects actual changes in lung mass and thus hints at fluid accumulation within the lung.

Moisturizing and mechanical characteristics of a new counter-flow type heated humidifier.

BACKGROUND: During mechanical ventilation effective conditioning of inspired air is important. In this respect, conventional humidifiers do not perform optimally. By design, a counter-flow-type humidifier should improve humidification and heating, but may increase resistance. METHODS: We investigated mechanical impedance and work of breathing (using pressure-flow characteristics and additional pressure-time product) of a new counter-flow-type humidifier, a conventional heated humidifier, and a passive heat and moisture exchanger (HME) in physical models of the respiratory system. We investigated moisturizing performance (amount of vaporized water at different air flows and ventilatory frequencies) of the two heated humidifiers. Ease of breathing through both heated humidifiers was investigated in 12 healthy volunteers blinded to the type of humidifier. RESULTS: Moisturizing performance of the conventional heated humidifier was flow-independent (approximately 32.5 mg vaporized water per breath at inspiratory flow rates of 30-120 litre min (- 1); P > 0.05) but decreased (10%; P < 0.0001) with increasing ventilatory rates (12-20 min (- 1)). In contrast, moisturizing performance of the counter-flow-type humidifier (approximately 33.5 mg vaporized water per breath) was both flow- and rate-independent (P = 0.75). In addition, the counter-flow humidifier caused less physical work (approximately 25%) and resistance (approximately 50%) (both P < 0.05) than the other two devices. The passive HME displayed the least favourable mechanical characteristics. Ten of 12 volunteers felt breathing through the counter-flow humidifier easier than through the heated humidifier (P < 0.05). CONCLUSION: Compared with a conventional humidifier, the new counter-flow-type humidifier displayed improved air conditioning and mechanical characteristics. Its lower resistance, particularly at low airflows, should be of clinical benefit during spontaneous breathing and triggered assisted ventilation.