New aspects of pulmonary mechanics: "slowly" distensible compartments of the respiratory system, identified by a PEEP step maneuver.

OBJECTIVE: The aims of the present study were 1) to evaluate a method for identification of "slowly" distensible compartments of the respiratory system (rs), which are characterized by long mechanical time constants (RC) and 2) to identify "slowly" distensible rs-compartments in mechanically ventilated patients. DESIGN: Prospective study on a physical lung model. SETTING: Intensive Care Unit, University Hospital, Tübingen. PATIENTS AND PARTICIPANTS: 19 patients with severe lung injury (acute respiratory distress syndrome, ARDS) and on 10 patients with mild lung injury. MEASUREMENTS AND RESULTS: Positive end-expiratory pressure (PEEP)-increasing and -decreasing steps of about 5 cmH2O were applied and the breath-by-breath differences of inspiratory and expiratory volumes (delta V) were measured. The sequence of delta Vs were analyzed in terms of volume change in the "fast" compartment (Vfast), the "slow" compartment (Vslow), total change in lung volume (delta VL) and mechanical time constant of the slow compartment (RCslow). Thirty-eight measurements in a lung model revealed a good correlation between the preset Vslow/delta VL and Vslow/delta VL measured: r2 = 0.91. The Vslow/delta VL measured amounted to 0.94 +/- 0.15 of Vslow/delta VL in the lung model. RCslow measured was 0.92 +/- 0.43 of the RCslow reference. Starting from a PEEP level of 11 cmH2O PEEP-increasing and PEEP-decreasing steps were applied to the mechanically ventilated patients. Three out of ten patients with mild lung injury (30%) and 7/19 patients with ARDS (36.8%) revealed "slowly" distensible rs-compartments in a PEEP-increasing step, whereas 15/19 ARDS patients and 1/10 patients with mild lung injury showed "slowly" distensible rs-compartments in a PEEP-decreasing step (78.9% vs 10%, P < 0.002, chi-square test). CONCLUSIONS: The gas distribution properties of the respiratory system can be easily studied by a PEEP-step maneuver. The relative contribution of the "slow" units to the total increase of lung volume following a PEEP step could be adequately assessed. "Slowly" distensible rs-compartments could be detected in patients with severe and mild lung injury, however significantly more ARDS patients revealed "slow" rs-compartments in PEEP-decreasing steps. The influence of "slowly" distensible rs-compartments on pulmonary gas exchange is unknown and has yet to be studied.

Closed-loop control of airway occlusion pressure at 0.1 second (P0.1) applied to pressure-support ventilation: algorithm and application in intubated patients.

OBJECTIVE: Airway occlusion pressure at 0.1 sec (P0.1) is an index of respiratory center output. During pressure-support ventilation, P0.1 correlates with the mechanical output of the inspiratory muscles and has an inverse relationship with the amount of pressure-support ventilation. Based on these observations, we designed a closed-loop control which, by automatically adjusting pressure-support ventilation, stabilizes P0.1, and hence patient inspiratory activity, at a desired target. The purpose of the study was to demonstrate the feasibility of the method, rather than its efficacy or even its influence on patient outcome. DESIGN: Prospective, randomized trial. SETTING: A general intensive care unit of a university hospital in Italy. PATIENTS: Eight stable patients intubated and ventilated with pressure-support ventilation for acute respiratory failure. INTERVENTIONS: Patients were transiently connected to a computer-controlled ventilator on which the algorithm for closed-loop control was implemented. The closed-loop control was based on breath by breath measurement of P0.1, and on comparison with a target set by the user. When actual P0.1 proved to be higher than the target value, the P0.1 controller automatically increased pressure-support ventilation, and decreased it when P0.1 proved to be lower than the target value. For safety, a volume controller was also implemented. Four P0.1 targets (1.5, 2.5, 3.5, and 4.5 cm H2O) were applied at random for 15 mins each. MEASUREMENTS AND MAIN RESULTS: The closed-loop algorithm was able to control P0.1, with a difference from the set targets of 0.59 +/- 0.27 (SD) cm H2O. CONCLUSIONS: The study shows that P0.1 can be automatically controlled by pressure-support ventilation adjustments with a computer. Inspiratory activity can thus be stabilized at a level prescribed by the physician.

The automatic selection of ventilation parameters during the initial phase of mechanical ventilation.

OBJECTIVE: To test a method that allows automatic set-up of the ventilator controls at the onset of ventilation. DESIGN: Prospective randomized crossover study. SETTING: ICUs in one adult and one children's hospital in Switzerland. PATIENTS: Thirty intubated stable, critically ill patients (20 adults and 10 children). INTERVENTIONS: The patients were ventilated during two 20-min periods using a modified Hamilton AMADEUS ventilator. During the control period the ventilator settings were chosen immediately prior to the study. During the other period individual settings were automatically determined by the ventilatior (AutoInit). MEASUREMENTS AND RESULTS: Pressure, flow, and instantaneous CO2 concentration were measured at the airway opening. From these measurements, series dead space (V(DS)), expiratory time constant (RC), tidal volume (VT, total respiratory frequency (f(tot), minute ventilation (MV), and maximal and mean airway pressure (Paw, max and Paw, mean) were calculated. Arterial blood gases were analyzed at the end of each period. Paw, max was significantly less with the AutoInit ventilator settings while f(tot) was significantly greater (P < 0.05). The other values were not statistically significant. CONCLUSIONS: The AutoInit ventilator settings, which were automatically derived, were acceptable for all patients for a period of 20 min and were not found to be inferior to the control ventilator settings. This makes the AutoInit method potentially useful as an automatic start-up procedure for mechanical ventilation.

Simple method to measure total expiratory time constant based on the passive expiratory flow-volume curve.

OBJECTIVE: In intubated, mechanically ventilated patients, inspiration is forced by externally applied positive pressure. In contrast, exhalation is passive and depends on the time constant of the total respiratory system. The expiratory time constant is thus an important determinant of mechanical ventilation. The aim of this study was to evaluate a simple method for measuring the expiratory time constant in ventilated subjects. DESIGN: Prospective study using a lung simulator and ten dogs. SETTING: University hospital. SUBJECTS: Commercially available lung simulator and ten greyhound dogs. INTERVENTIONS: Different expiratory time constants were set on the lung simulator. In the dogs, the endotracheal tube was clamped to increase airways resistance by 22.5 cm H2O/(L/sec) and the lungs were injured with hydrochloric acid to decrease total respiratory compliance by 16 mL/cm H2O. This procedure resulted in a wide range of expiratory time constants. MEASUREMENTS AND MAIN RESULTS: Pneumotachography was used to measure flow and volume. The ratio of exhaled volume and peak flow was calculated from these signals, corrected for the limited exhalation time yielding the "calculated expiratory time constant" and compared with the actual expiratory time constant. The typical error was +/- 0.19 sec for the lung simulator and +/- 0.15 sec for the dogs. CONCLUSIONS: The volume and peak flow corrected for limited exhalation time is a good estimate of the total expiratory time constant in passive subjects and may be useful for the titration of mechanical ventilation.

Automatic weaning from mechanical ventilation using an adaptive lung ventilation controller.

STUDY OBJECTIVE: To evaluate a new method of closed-loop mechanical ventilation using an adaptive lung ventilation (ALV) controller in patients with different pathologic causes of respiratory failure at a time when they first met standard weaning criteria. STUDY DESIGN: Prospective, open, selected case study. SETTING: The 10-bed, multidisciplinary respiratory intensive care unit at Groote Schuur hospital, which is a teaching unit of the University of Cape Town. PATIENTS: Twenty-seven patients (9 patients in each of 3 groups: normal lungs, parenchymal lung disease, and COPD) who required prolonged mechanical ventilation and who met standard weaning criteria were included. Our institutional committee for ethical research approved the study and informed consent was obtained. INTERVENTIONS: The patients were mechanically ventilated and had daily measurements of vital capacity, respiratory rate, and arterial blood gas analysis until they met standard weaning criteria. On the day that each patient met the weaning criteria, a closed loop control algorithm providing ALV was implemented on a modified ventilator (Hamilton AMADEUS) with a PC-based lung function analyzer. After measuring gross alveolar ventilation, patients were placed in ALV and ventilatory and hemodynamic parameters were measured at baseline, 5 min, 30 min, and 2 h. Pertinent parameters measured included airway pressures, pressure support levels, respiratory rates, rapid shallow breathing indices, airway resistance indices, and patient respiratory drive and work indices. MEASUREMENTS AND RESULTS: In 22 patients, ALV reduced pressure support to 5 cm H2O and an intermittent mandatory ventilation rate of 4 breaths/min within 30 min, and all but 1 of these patients were successfully extubated within 24 h. In four patients, pressure support was maintained by ALV at a mean level of 14.6 cm H2O +/- for 2 h and these patients were recorded as having failed to wean. There was a measurable difference in an index of airway resistance relative to muscular activity between the successfully weaned and failed wean patients with COPD during the attempted wean by the ALV controller. CONCLUSIONS: ALV will provide a safe, efficient wean and will respond immediately to inadequate ventilation in patients when standard weaning criteria are met.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

An adaptive lung ventilation controller.

Closed loop control of ventilation is traditionally based on end-tidal or mean expired CO2. The controlled variables are the respiratory rate RR and the tidal volume VT. Neither patient size or lung mechanics were considered in previous approaches. Also the modes were not suitable for spontaneously breathing subjects. This report presents a new approach to closed loop controlled ventilation, called Adaptive Lung Ventilation (ALV). ALV is based on a pressure controlled ventilation mode suitable for paralyzed, as well as spontaneously breathing, subjects. The clinician enters a desired gross alveolar ventilation (V'gA in l/min), and the ALV controller tries to achieve this goal by automatic adjustment of mechanical rate and inspiratory pressure level. The adjustments are based on measurements of the patient's lung mechanics and series dead space. The ALV controller was tested on a physical lung model with adjustable mechanical properties. Three different lung pathologies were simulated on the lung model to test the controller for rise time (T90), overshoot (Ym), and steady state performance (delta max). The pathologies corresponded to restrictive lung disease (similar to ARDS), a "normal" lung, and obstructive lung disease (such as asthma). Furthermore, feasibility tests were done in 6 patients undergoing surgical procedures in total intravenous anesthesia. In the model studies, the controller responded to step changes between 48 seconds and 81 seconds. It did exhibit an overshoot between 5.5% and 7.9% of the setpoint after the step change.(ABSTRACT TRUNCATED AT 250 WORDS)

The mitogenic effects of sera from psoriatic subjects on normal dermal fibroblasts: an absence of correlation with the clinical activity of psoriasis.

Serum was obtained from 21 normal and 22 psoriatic subjects, and the severity of skin disease in the psoriatic patients was recorded using the PASI score. The scores ranged from 1.8 to 51.0. The growth stimulatory effect of the sera on normal dermal fibroblasts in cell culture was assessed by measuring [3H]-thymidine uptake. Each serum was assessed at four concentrations (2,5, 10,20%). The psoriatic sera were more growth stimulatory than normal sera, but this difference was statistically significant (P less than 0.02) only at 20% serum concentration. Eleven of the 22 psoriatic serum samples had a mitogenic effect greater than the mean +/- SEM of all the normal sera; these sera were then from patients with PASI scores of 4.5-51.0. Six of these psoriatic subjects were recalled after 5 months; their PASI scores were reassessed, and the mitogenic effect of new serum samples was compared with that of the initial samples. All of these patients displayed a change in serum mitogenic effect, but this was not consistent with the change in severity of skin disease over the corresponding time period. In one subject, the severity of the psoriasis had increased marginally over the 5 months, while the mitogenic effect of her serum decreased significantly (mean counts of 43808 vs. 32660; P = 0.0029).