The commercial ventilator was an INSPIRA model 557059 (Harvard Apparatus, MA, USA). The information available on the website of the manufacturer is that the PEEP feature "allows a positive pressure to be maintained between inspirations instead of falling to zero or near zero at the end of the expiratory phase. When the PEEP pressure is reached, the expiration valve closes until the next inspiration cycle begins." The PEEP generated by this ventilator was denominated PEEP-old. A specimen of the INSPIRA ventilator ASVP, serial number B-45397 (Harvard Apparatus, MA, USA) regularly purchased has been used in all tests.
In this work, a prototype PEEP controller was designed, to operate in conjunction with the ventilator INSPIRA. The system includes a miniaturized on-off valve 003-0459-900 (Parker, OH, USA) connected to the exhaust port of the ventilator. To control such valve, two signals, available from the ventilator, were employed: the airways opening pressure (Pao-Inspira) and a binary signal of synchronism (SI-E), in which the logical one indicates the occurrence of the inspiratory cycle and the logical zero, the expiratory cycle. These two signals were acquired at a sampling rate of 1000 Hz by an analog-to-digital (A/D) converter PCM-3718HG (Advantech, CA, US) installed on a personal computer PCM-6898 (AAEON Electronics, NJ, US) running a Simulink model using the Real-Time Windows Target (Mathworks, US). The controller reads Pao-Inspira and SI-E, and computes the duration of the opening of the on-off valve during the expiration, τexp. From SI-E, for the n-th respiratory cycle the controller calculates the total duration of the expiration as reported by the ventilator, Texp(n). Then, from Pao-Inspira and the target PEEP (PEEPT), the controller updates τexp for the n-th respiratory cycle by the law:
where PEEPI is the intrinsic PEEP [3], measured immediately before the beginning of the n-th inspiration while the on-off valve is still closed, and g(PEEPT) has values that depend on PEEPT, equal to 0.08 (0 ≤ PEEPT ≤ 3 cmH2O), 0.03 (3 < PEEPT ≤ 5 cmH2O), 0.01 (5 < PEEPT ≤ 10 cmH2O) and 0.006 (PEEPT > 10 cmH2O). The values of g were adjusted empirically by numerical simulation in order to reduce the settling time as well as the under/overshoot of the response. The values of τexp were limited by software from Texp/12 to Texp. The controller outputs the signal to a driver circuit, switched by a digital output of the A/D card. The PEEP generated by this system is hereafter called PEEP-new.
During tests, the signals of interest were also continuously monitored and digitized at a sampling rate of 1000 Hz by an A/D converter 6008 (National Instruments, TX, US) and stored in a personal computer running a program written in LabVIEW (National Instruments, TX, US).
Performance Tests
In order to test the performance characteristics of the PEEP control system, the following definitions have been applied: for each respiratory cycle, the PEEP was calculated as the mean value of the airways opening pressure for the last 10 ms of the expiratory phase; during a PEEP step change, the steady-state PEEP was calculated as the mean value of the last 20 respiratory cycles of a period with constant PEEP; the settling time was determined as the time after which the difference between the actual PEEP and the steady-state PEEP was less than ± 0.5 cmH2O; the overshoot (undershoot) was found as the highest PEEP deviation from the steady-state PEEP after the rise (fall) time, considered as the period of time of PEEP increasing (decreasing) from the start of a PEEP step change up to the first cross with the new target PEEP.
In vitro tests
Figure 1-a shows the experimental set-up. A physical model of the respiratory system (RS) of a rat has been used for tests. It consisted of a bottle of 500 ml, whose compliance, around 0.5 ml/cmH2O, is within the range of the compliance of a healthy RS of a rat [5]. A Y piece for rats 73-2846 (Harvard Apparatus, Ma, US) was inserted into the compliance model. An additional resistor, representing the airways resistance (Raw), was not included in the model since the cannula of the Y piece presented a resistance in the order of magnitude of the airways resistance of a rat with healthy lungs [6]. The Pao (Pao-monitor) was monitored with a pressure transducer 163PC01D48 (Honeywell, NJ, US) connected to a T piece placed in the expiratory limb, close to the Y piece. In the instances when the PEEP-old was evaluated, tubes and connections were employed as suggested by the manufacturer. When the PEEP-new was tested, the set-up was the same with the inclusion of the on-off valve. The total expiratory circuit resistance from the cannula to the atmosphere including all connecting tubes, the ventilator's on-off valve and the additional on-off valve for PEEP-new control system was of 390 cmH2O.l-1.s-1. The additional on-off valve represented about 50% of the total expiratory circuit resistance.
Both PEEP generators were tested with the same respiratory settings. The ventilator was set in volume control mode with a tidal volume (VT) of 3 ml, a respiratory frequency (RF) of 60 breaths per minute, an inspiratory to expiratory time ratio (I:E) of 1:1, and ventilated with ambient air.
The PEEP-old was tested for the targets of 3, 5 and 10 cmH2O, in increasing as well as decreasing steps. The trials were triplicate. Since the results with PEEP-old showed large deviations from the target PEEP (more than 5 cmH2O), the following test was performed only for the PEEP-new method. Initially, the PEEP was set to zero cmH2O, and sequentially it was changed to 3, 5, 10, 15, 10, 5, 3 and again zero cmH2O. The duration of each PEEP step was of 1 min, controlled by the computer. Again, the trials were repeated three times.
In vivo tests
Figure 1-b shows the in vivo experimental setup. After the results of the in vitro experiments in which the resistances of the Y plus the cannula's revealed to be fairly obstructive (see Results), another, less resistive Y connector was employed. To the common limb of the Y a unicapillary pneumotachometer, designed and calibrated according to Giannella-Neto et al. [7], was connected, together with a small tube with a lateral port for the measurement of Pao-monitor calibrated against a reference instrument Timeter RT-200 (Allied HealthCare Products, Mo, US). A short, low resistive cannula (ID of 1.5 mm, 30 mm long) was placed to fit to the trachea. The flow rate (
), Pao-monitor and ECG were continuously monitored, digitized at 1000 Hz each and stored on hard-disk.
As an in vivo pilot experiment, three Sprague-Dawley rats weighting 220 ± 15 g were mechanically ventilated in a protocol approved by the local Ethical Committee. The animals were sedated, anesthetized and paralyzed. The respiratory settings were the same as the in vitro experiments.
Initially, a baseline condition with PEEP-new of 3 cmH2O was performed. The PEEP-old was tested three times at the levels of 3 and 5 cmH2O. Similarly as the in vitro experiments, it failed to follow the target PEEP. The subsequent protocol was applied only for the PEEP-new, which consisted in decreasing then increasing PEEP in 1-minute steps of 1 cmH2O, starting and ending at a pressure of 9 cmH2O.