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Biomedical subjects

Dimitris Georgopoulos

Publications and source records attributed to Dimitris Georgopoulos.

17 recordsLinked to original sources

Modulation and treatment of patient-ventilator dyssynchrony.

PURPOSE OF REVIEW: The coupling between ventilator delivered inspiratory flow and patient's demands both in terms of timing and drive is a challenging task that has become largely feasible in recent years. This review addresses the new advances to modulate and treat patient-ventilator dyssynchrony. RECENT FINDINGS: Patient-ventilator dyssynchrony is a common phenomenon with conventional modes of mechanical ventilation which influence the duration of mechanical ventilation. Inspection of pressure, volume and flow waveforms represents a valuable tool for the physician to recognize and take the appropriate action to improve patient-ventilator synchrony. New developments have been introduced aiming to improve patient ventilator synchrony by modulating the triggering function and the variables that control the flow delivery and the cycling off. SUMMARY: Patient-ventilator dyssynchrony may affect patients' outcome. New modes of assisted mechanical ventilation have been introduced and represent a major step forward in modulating patient-ventilator dyssynchrony.

Critical Care↗

Respiratory load compensation during mechanical ventilation--proportional assist ventilation with load-adjustable gain factors versus pressure support.

RATIONALE: In mechanically ventilated patients respiratory system impedance may vary from time to time, resulting, with pressure modalities of ventilator support, in changes in the level of assistance. Recently, implementation of a closed-loop adjustment to continuously adapt the level of assistance to changes in respiratory mechanics has been designed to operate with proportional assist ventilation (PAV+). OBJECTIVES: The aim of this study was to assess, in critically ill patients, the short-term steady-state response of respiratory motor output to added mechanical respiratory load during PAV+ and during pressure support (PS). PATIENTS AND INTERVENTIONS: In 10 patients respiratory workload was increased and the pattern of respiratory load compensation was examined during both modes of support. MEASUREMENTS AND RESULTS: Airway and transdiaphragmatic pressures, volume and flow were measured breath by breath. Without load, both modes provided an equal support as indicated by a similar pressure-time product of the diaphragm per breath, per minute and per litre of ventilation. With load, these values were significantly lower (p<0.05) with PAV+ than those with PS (5.1+/-3.7 vs 6.1+/-3.4 cmH2O.s, 120.9+/-77.6 vs 165.6+/-77.5 cmH2O.s/min, and 18.7+/-15.1 vs 24.4+/-16.4 cmH2O.s/l, respectively). Contrary to PS, with PAV+ the ratio of tidal volume (VT) to pressure-time product of the diaphragm per breath (an index of neuroventilatory coupling) remained relatively independent of load. With PAV+ the magnitude of load-induced VT reduction and breathing frequency increase was significantly smaller than that during PS. CONCLUSION: In critically ill patients the short-term respiratory load compensation is more efficient during proportional assist ventilation with adjustable gain factors than during pressure support.

Adolescent↗

Effect of the physical properties of isoflurane, sevoflurane, and desflurane on pulmonary resistance in a laboratory lung model.

BACKGROUND: Airway resistance depends not only on an airway's geometry but also on flow rate, and gas density and viscosity. A recent study showed that at clinically relevant concentrations, the mixtures of volatile agents with air and oxygen and oxygen-nitrogen affected the density of the mixture. The goal of the current study was to investigate the effect of different minimum alveolar concentrations (MACs) of three commonly used volatile agents, isoflurane, sevoflurane, and desflurane, on the measurements of airway resistance. METHODS: A two-chamber fixed-resistance test lung was connected to an anesthesia machine using the volume control mode of ventilation. Pulmonary resistance was calculated at baseline (25% oxygen in air); at 1.0, 1.5, and 2.0 MAC; and also at the same concentrations, 1.2% and 4%, of isoflurane, sevoflurane, and desflurane mixtures with 25% oxygen in air. The analysis of variance test for repeated measures and probabilities for post hoc Tukey and least significant difference tests were used. RESULTS: Isoflurane affected pulmonary resistance only at 2 MAC. Sevoflurane caused a significant increase of pulmonary resistance at 1.5 and 2 MAC, whereas desflurane caused the greatest increase in pulmonary resistance at all MAC values used. At 1.2% concentration, no difference from the baseline resistance was observed, whereas at 4%, the three agents produced similar increases of pulmonary resistance. CONCLUSION: High concentrations of volatile agents in 25% oxygen in air increased the density of the gas mixture and the calculated resistance of a test lung model with fixed resistance.

Airway Resistance↗

Short-term cardiorespiratory effects of proportional assist and pressure-support ventilation in patients with acute lung injury/acute respiratory distress syndrome.

BACKGROUND: Recent data indicate that assisted modes of mechanical ventilation improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a new mode of support that amplifies the ventilatory output of the patient effort and improves patient-ventilator synchrony. It is not known whether this mode may be used in patients with ALI/ARDS. The aim of this study was to compare the effects of PAV and pressure-support ventilation on breathing pattern, hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS due to sepsis. METHODS: Twelve mechanically ventilated patients with ALI/ARDS (mean ratio of partial pressure of arterial oxygen to fractional concentration of oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure-support ventilation and PAV in random order for 30 min while maintaining mean airway pressure constant. With both modes, the level of applied positive end-expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the end of each study period, cardiorespiratory data were obtained, and dead space to tidal volume ratio was measured. RESULTS: With both modes, none of the patients exhibited clinical signs of distress. With PAV, breathing frequency and cardiac index were slightly but significantly higher than the corresponding values with pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4 +/- 1.6 vs. 4.1 +/- 1.3 l . min . m, respectively). None of the other parameters differ significantly between modes. CONCLUSIONS: In patients with ALI/ARDS due to sepsis, PAV and pressure-support ventilation both have clinically comparable short-term effects on gas exchange and hemodynamics.

Acute Disease↗

Bedside waveforms interpretation as a tool to identify patient-ventilator asynchronies.

OBJECTIVE: During assisted modes of ventilatory support the ventilatory output is the final expression of the interaction between the ventilator and the patient's controller of breathing. This interaction may lead to patient-ventilator asynchrony, preventing the ventilator from achieving its goals, and may cause patient harm. Flow, volume, and airway pressure signals are significantly affected by patient-ventilator interaction and may serve as a tool to guide the physician to take the appropriate action to improve the synchrony between patient and ventilator. This review discusses the basic waveforms during assisted mechanical ventilation and how their interpretation may influence the management of ventilated patients. The discussion is limited on waveform eye interpretation of the signals without using any intervention which may interrupt the process of mechanical ventilation. DISCUSSION: Flow, volume, and airway pressure may be used to (a) identify the mode of ventilator assistance, triggering delay, ineffective efforts, and autotriggering, (b) estimate qualitatively patient's respiratory efforts, and (c) recognize delayed and premature opening of exhalation valve. These signals may also serve as a tool for gross estimation of respiratory system mechanics and monitor the effects of disease progression and various therapeutic interventions. CONCLUSIONS: Flow, volume, and airway pressure waveforms are valuable real-time tools in identifying various aspects of patient-ventilator interaction.

Data Display↗

Effects of hypoxia and hypercapnia on surfactant protein expression proliferation and apoptosis in A549 alveolar epithelial cells.

UNLABELLED: During lung injury alveolar epithelial cells are directly exposed to changes in PO(2) and PCO(2). Integrity of alveolar epithelial type II cells (AECII) is critical in lung injury but the effect of hypoxia and hypercapnia on AECII function, viability and proliferation has not been clearly investigated. Aim of the present work was to determine the direct effect of hypoxia and hypercapnia on surfactant protein expression, proliferation and apoptosis of lung epithelial cells in vitro. A549 alveolar epithelia cells were subjected to hypoxia (1%O(2)-5% CO(2)) or hypercapnia (21% O(2-) 15% CO(2)) and expression of surfactant protein C was measured and compared to normal conditions (21% O(2)- 5% CO(2)). Cell cycle progression and apoptosis were measured by flow cytometric analysis. RESULTS: A549 alveolar epithelial cells produce surfactant proteins, including surfactant protein C, when cultured under normal conditions, which is reduced under hypoxic conditions. Specifically, pro-SpC expression is moderately decreased after 8 h of culture in hypoxia, and is completely attenuated after 48 h. Hypercapnia decreases pro-SpC expression only after 48 h of exposure. Stimulation with TNF-alpha partly reverses pSPC decrease observed under hypoxic and hypercapnic conditions. Hypoxic culture of A549 cells results in progressive arrest of cells in the G1 phase of the cell cycle and increased apoptosis first observed 4 h following exposure and peaking at 24 h. In contrast hypercapnia has no significant effect on alveolar epithelial cell proliferation or apoptosis. CONCLUSIONS: Taken together we can conclude that hypoxia rapidly and severely affects AECII function and viability while hypercapnia has an inhibitory effect on pro-SpC production only after prolonged exposure.

Apoptosis↗

Recombinant human erythropoietin therapy in critically ill patients: a dose-response study [ISRCTN48523317].

INTRODUCTION: The aim of this study was to assess the efficacy of two dosing schedules of recombinant human erythropoietin (rHuEPO) in increasing haematocrit (Hct) and haemoglobin (Hb) and reducing exposure to allogeneic red blood cell (RBC) transfusion in critically ill patients. METHOD: This was a prospective, randomized, multicentre trial. A total of 13 intensive care units participated, and a total of 148 patients who met eligibility criteria were enrolled. Patients were randomly assigned to receive intravenous iron saccharate alone (control group), intravenous iron saccharate and subcutaneous rHuEPO 40,000 units once per week (group A), or intravenous iron saccharate and subcutaneous rHuEPO 40,000 units three times per week (group B). rHuEPO was given for a minimum of 2 weeks or until discharge from the intensive care unit or death. The maximum duration of therapy was 3 weeks. RESULTS: The cumulative number of RBC units transfused, the average numbers of RBC units transfused per patient and per transfused patient, the average volume of RBCs transfused per day, and the percentage of transfused patients were significantly higher in the control group than in groups A and B. No significant difference was observed between group A and B. The mean increases in Hct and Hb from baseline to final measurement were significantly greater in group B than in the control group. The mean increase in Hct was significantly greater in group B than in group A. The mean increase in Hct in group A was significantly greater than that in control individuals, whereas the mean increase in Hb did not differ significantly between the control group and group A. CONCLUSION: Administration of rHuEPO to critically ill patients significantly reduced the need for RBC transfusion. The magnitude of the reduction did not differ between the two dosing schedules, although there was a dose response for Hct and Hb to rHuEPO in these patients.

Adult↗

New and future developments to improve patient-ventilator interaction.

The new and future developments to improve the patient-ventilator interaction are mainly based on the concept of the tight coupling between neural output and ventilator function. This tight coupling should be present throughout a patient's respiratory cycle, a task that is demanding from a technical point of view. By achieving a tight neuromechanical coupling, the ventilator operates as an external respiratory muscle of high capabilities controlled mainly by the patient. This task, however, necessitates knowledge of respiratory system physiology and pathophysiology and the interaction between patient and ventilator. Although currently sophisticated computer algorithms have been developed, the caregiver is the one who controls the patient-ventilator system. Without indepth knowledge of this system, the algorithms may induce harm rather than benefit.

Humans↗

Patient-ventilator interaction: an overview.

During assisted mechanical ventilation, the total pressure applied to respiratory system is the sum of ventilator and muscle pressure. As a result, the respiratory system is under the influence of two pumps, the ventilator pump (ie, Paw), which is controlled by the physician's brain and the capabilities of the ventilator, and the patient's own respiratory muscle pump (Pmus), which is controlled by the patient's brain. The patient-ventilator interaction is mainly an expression of the function of these two brains, which should be in harmony to promote patient-ventilator synchrony. The achievement of this harmony depends exclusively on the physician, who should be aware that during assisted mechanical ventilation the respiratory system is not a passive structure but reacts to pressure delivered by the ventilator via various feedback systems and, depending on several factors both to the ventilator and patient, may modify the function of the ventilator. Finally, the physician should know that the ventilator imposes significant constraints to the respiratory system, the magnitude of which depends heavily on the triggering variable, the variable that controls the gas delivery and the cycling off criterion.

Humans↗

Determinants of the cuff-leak test: a physiological study.

INTRODUCTION: The cuff-leak test has been proposed as a simple method to predict the occurrence of post-extubation stridor. The test is performed by cuff deflation and measuring the expired tidal volume a few breaths later (VT). The leak is calculated as the difference between VT with and without a deflated cuff. However, because the cuff remains deflated throughout the respiratory cycle a volume of gas may also leak during inspiration and therefore this method (conventional) measures the total leak consisting of an inspiratory and expiratory component. The aims of this physiological study were, first, to examine the effects of various variables on total leak and, second, to compare the total leak with that obtained when the inspiratory component was eliminated, leaving only the expiratory leak. METHODS: In 15 critically ill patients mechanically ventilated on volume control mode, the cuff-leak volume was measured randomly either by the conventional method (Leakconv) or by deflating the cuff at the end of inspiration and measuring the VT of the following expiration (Leakpause). To investigate the effects of respiratory system mechanics and inspiratory flow, cuff-leak volume was studied by using a lung model, varying the cross-sectional area around the endotracheal tube and model mechanics. RESULTS: In patients Leakconv was significantly higher than Leakpause, averaging 188 +/- 159 ml (mean +/- SD) and 61 +/- 75 ml, respectively. In the model study Leakconv increased significantly with decreasing inspiratory flow and model compliance. Leakpause and Leakconv increased slightly with increasing model resistance, the difference being significant only for Leakpause. The difference between Leakconv and Leakpause increased significantly with decreasing inspiratory flow (V'I) and model compliance and increasing cross-sectional area around the tube. CONCLUSION: We conclude that the cross-sectional area around the endotracheal tube is not the only determinant of the cuff-leak test. System compliance and inspiratory flow significantly affect the test, mainly through an effect on the inspiratory component of the total leak. The expiratory component is slightly influenced by respiratory system resistance.

Aged↗

Pattern of lung emptying and expiratory resistance in mechanically ventilated patients with chronic obstructive pulmonary disease.

OBJECTIVES: To study the pattern of lung emptying and expiratory resistance in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD). DESIGN: A prospective physiological study. SETTING: A 12-bed Intensive Care Unit. PATIENTS: Ten patients with acute exacerbation of COPD. INTERVENTIONS: At three levels of positive end-expiratory pressure (PEEP, 0, 5 and 10 cm H(2)O) tracheal (Ptr) and airway pressures, flow (V') and volume (V) were continuously recorded during volume control ventilation and airway occlusions at different time of expiration. MEASUREMENTS AND RESULTS: V-V' curves during passive expiration were obtained, expired volume was divided into five equal volume slices and the time constant (tau) and dynamic deflation compliance (Crs(dyn)) of each slice was calculated by regression analysis of V-V' and post-occlusion V-Ptr relationships, respectively. In each volume slice the existence or not of flow limitation was examined by comparing V-V' curves with and without decreasing Ptr. For a given slice total expiratory resistance was calculated as tau/Crs(dyn), whereas expiratory resistance (Rrs) and time constant (tau(rs)) of the respiratory system were subsequently estimated taken into consideration the presence of flow limitation. At zero PEEP, tau(rs) increased significantly toward the end of expiration due to an increase in Rrs. PEEP significantly decreased Rrs at the end of expiration and resulted in a faster and relatively constant rate of lung emptying. CONCLUSIONS: Patients with COPD exhibit a decrease in the rate of lung emptying toward the end of expiration due to an increase in Rrs. PEEP decreases Rrs, resulting in a faster and uniform rate of lung emptying.

Aged↗

Effects of the flow waveform method of triggering and cycling on patient-ventilator interaction during pressure support.

OBJECTIVE: To examine patient-ventilator interaction during pressure support ventilation in critically ill patients when they were ventilated: (1) by a new system (Vision, Respironics) which uses the flow waveform as a method of triggering and cycling; and (2) by a new generation ventilator (Evita 4, Drager) which uses the traditional flow triggering (2 l/min) and cycling criterion (25% of peak flow). DESIGN: Prospective clinical and bench study. METHODS: Twelve mechanically ventilated patients were studied at three levels of pressure support, applied randomly with both ventilators. The two systems of triggering were further studied at controlled levels of dynamic hyperinflation and respiratory drive using an active lung model. RESULTS: Patients' breathing patterns, respiratory effort, and arterial blood gases were not affected by the type of ventilator. The flow waveform method of triggering was more sensitive to patient effort than the flow triggering, resulting in less ineffective effort but a greater number of auto-triggerings. At controlled levels of dynamic hyperinflation and inspiratory effort the simulated patient effort needed to trigger the ventilator was considerably less with the flow waveform method of triggering than that with the flow triggering. The flow waveform method of cycling resulted in mechanical breaths with similar characteristics to those that used the traditional flow criterion of breath termination. CONCLUSIONS: We conclude that the flow waveform method of triggering improves the ventilator function and decreases the patient effort during the triggering phase. This system is highly sensitive, but under certain circumstances may be unstable.

Adult↗

Effects of theophylline on ventilatory poststimulus potentiation in patients with brain damage.

Patients with brain damage, in contrast to normal subjects, exhibit a significant ventilatory undershoot when brief hypocapnic hypoxia is terminated abruptly by hyperoxia. This has been attributed to an impairment of activation of short-term potentiation, a brain stem mechanism promoting breathing stability. We hypothesized that in these patients theophylline, a drug that stabilizes breathing, may affect short-term potentiation. Eight stable patients with brain damage and 10 normal adults were studied. Activation of short-term potentiation was examined by brief exposure to hypoxia followed by hyperoxia after pretreatment with placebo or theophylline. Both in patients and normal subjects at the end of hypoxia ventilation increased to a similar magnitude with and without theophylline. In normal subjects independent of pretreatment, when hypoxia was terminated abruptly by hyperoxia, ventilation declined slowly to baseline without an undershoot, indicating activation of short-term potentiation. In patients with placebo, ventilation upon switching to hyperoxia exhibited a significant undershoot. This undershoot was significantly attenuated by theophylline, although compared with normal subjects, a slight hypoventilation was observed. We conclude that in patients with brain damage, theophylline largely prevents the hyperoxic drop of ventilation, presumably by affecting the activation of short-term potentiation. This may underlie the beneficial effect of theophylline on breathing stability.

Double-Blind Method↗

Aerosol medications.

Aerosol medications are used commonly in mechanically ventilated patients. Several classes of drugs with different properties and indications may be given by inhalation. In all cases, inhaled therapy's main advantage over the systemic route is that, for a given therapeutic response, the drug dose is several-fold lower, whereas systemic absorption is negligible. Because of this, the side effects are minimized greatly. Additionally, for some medications, the systemic route either causes nonacceptable side effects or results in considerably inferior therapeutic response, rendering the inhaled route the method of choice of drug administration. Bronchodilators, vasoactive drugs, surfactant, antibiotics, and helium are some agents that can be inhaled during mechanical ventilation.

Administration, Inhalation↗

Treatment with aerosols in mechanically ventilated patients: is it worthwhile?

Aerosol medications are commonly used in mechanically ventilated patients. Several classes of drugs with different properties and indications may be given by inhalation. In all cases, compared with the systemic route, the inhaled therapy has the main advantage that for a given therapeutic response, the drug dose is several-fold lower, while the systemic absorption is negligible, thus the side effects are greatly minimized. In addition, for some medications the systemic route either causes non-acceptable side effects or results in considerably inferior therapeutic response, rendering the inhaled route the method of choice of drug administration. Bronchodilators, corticosteroids, vasoactive drugs, surfactants, antibiotics, helium and perfluorocarbons are the medications that can be given by inhalation during mechanical ventilation. Some of those represent part of the standard treatment for various groups of mechanically ventilated patients, while the role of others has not been well established yet.

Journal Article↗