1 Department of Anaesthesia, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium. 2 Research and Development, and 3 Product Management, Business Unit Anesthesia, Dräger Medical, Lübeck, Germany
* Corresponding author. E-mail: michel.struys{at}ugent.be
Accepted for publication October 22, 2004.
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Abstract |
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Methods. Using an artificial test lung, sevoflurane and desflurane time-course and consumption were compared when using the Zeus® apparatus (Dräger, Lübeck, Germany) with direct injection of inhaled anaesthetics or the Primus® apparatus (Dräger, Lübeck, Germany) using a classical out-of-circle vaporizer. Anaesthetics were targeted at 1 and 2 MAC end-tidal during 15 min. For both apparatus, out-of-circle high and low fresh gas control (FGC) and for Zeus®, auto-control (AC) modes (fixed fresh gas flow at 6 and 1 litre min1 and uptake mode) were compared. Time to reach target, initial overshoot and stability at target, and wash-out times were compared.
Results. In FGC, an initial overshoot in end-tidal drug concentration is seen when using 6 litre min1 fresh gas flow and a slower time course is observed when using only 1 litre min1 in both apparatus. In auto-control mode, the time course of both sevoflurane and desflurane was very fast and not influenced by the changes in fresh gas flow. No overshoot at target was seen. At all settings, the wash-out times were faster when using Zeus® than Primus®. Inhaled anaesthetic consumption was lowest with the Zeus® ventilator in uptake AC mode.
Conclusion. A combination of the fastest time course and lowest consumption of sevoflurane and desflurane was found when using the Zeus® apparatus in AC uptake mode.
Keywords: anaesthetics, volatile ; equipment, ventilators ; ventilation, fresh gas flow
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Introduction |
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Classically applied out-of-circle vaporizer setting implies that a fast adjustment of inhaled agent concentration is only feasible by vastly increasing the FGF resulting in a possible overshoot in inhaled agent concentrations and increased consumption.2 3 Using a principle where an agent is directly delivered into the breathing circle system independent of FGF theoretically allows fastest alteration of agent concentration. By uncoupling agent delivery and FGF, the conflict between anaesthetic agent concentration and minimal consumption will be resolved.4
Various experimental systems have been described in the literature seeking these criteria of agent control and delivery while using closed-circuit technology together with in-circle agent delivery.57 Many disadvantages810 have limited their introduction into clinical practice. Recently, a new anaesthesia machine (Zeus®, Dräger, Lübeck, Germany) was developed and commercialized aimed at resolving the disadvantages from the experimental generation of closed-circuit machines. This system uses a newly designed, blower-driven ventilator and a servo-controlled valve system to control various ventilation modes. Anaesthetic and fresh gas delivery is feedback-controlled by using direct injection into the breathing circle, making it possible to realize closed-circuit ventilation.
The aim of this study was to investigate the time course and consumption of inhaled anaesthetic in vitro when using the Zeus® anaesthesia machine in various drug delivery modes and to compare it with a classical anaesthesia machine using an out-of-circle vaporizer in high and low FGF conditions.
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Materials and methods |
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The Direct Injection of Volatile Anaesthetics (DIVA) anaesthetic metering unit meters volatile anaesthetics and FGF, as schematically presented in Figure 2. It comprises the non-anaesthetic-specific supply unit and up to two plug-in, anaesthetic-specific metering units (Fig. 3). The metering unit stores a quantity of anaesthetic liquid. The selected volatile anaesthetic is injected into a heated vaporizing chamber using a pulsed liquid injection valve. The anaesthetic vapour is delivered to the breathing system via the supply unit using a heated pipe. Depending on the ventilator control mode (see below), the supply unit either directly injects (auto-control (AC) mode) the saturated agent vapour into the breathing system or mixes it with the fresh gas first (fresh gas control (FGC) mode).
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The main sensor system contains various oxygen and infrared analysers to continuously monitor the ventilation and agent delivery systems (see Appendix 1).
The Zeus® apparatus is multifunctional in both administration modes for inhaled anaesthetics and fresh gas, as shown in Table 1, and in ventilation modes. Some of the modes require closed-loop feedback systems, which are explained in detail in Appendix 2. For drug delivery, two control modes are possible, FGC and AC. In FGC mode, a classical ventilator with capacity for low-flow and an out-of-circle vaporizer is emulated and no automated system is active. FGF and oxygen concentration are set manually, emulating the use of classical rotameters. The set concentration (vol %) of inhaled anaesthetics is set at a specific emulated vaporizer concentration. In AC mode, multiple computerized closed-loop feedback systems can be turned on. In the AC mode with minimal FGF (e.g. 1 litre min1), the clinician sets a targeted end-tidal concentration of inhaled anaesthetic and the volatile anaesthetic feedback control will obtain and maintain this targeted end-tidal concentration as accurate as possible, thereby initially overshooting the inspiratory concentration. The oxygen concentration in the breathing circuit is targeted towards a set inspiratory oxygen concentration using the oxygen closed-loop feedback control. In full AC mode, also called uptake mode, anaesthetic delivery, inspiratory oxygen concentration, and FGF are feedback-controlled. FGF is therefore minimized towards closed-circuit conditions and will only add the required quanta of oxygen, nitrous oxide or air to maintain a given set gas mixture.
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The Primus® apparatus
The Primus® Anesthesia Workstation consists of an electrical piston-driven ventilator, an electronic mixed gas control unit and out-of-circle vaporizers to deliver the volatile anaesthetic. The breathing system of the Primus® apparatus is a classical rebreathing system (circle system).
In vitro testing
To simulate clinical conditions, an artificial test lung (Lungensimulator LS8000, Dräger, Lübeck, Germany) was used, into which 0.2 litre min1 carbon dioxide was introduced, aiming for an end-tidal carbon dioxide partial pressure () of
5.3 kPa. A continuous flow of 0.2 litre min1 (simulating oxygen consumption) was sampled to a stand-alone S/5 monitor system (Datex-Ohmeda, Helsinki, Finland) and not returned to the system. Using this, human oxygen consumption and carbon dioxide production was simulated. Additionally, the gas sample line from the Zeus® or Primus® apparatus (depending on the study group) was connected at the Y-piece of the breathing circle for obligatory gas sampling. These gas samples are returned into the breathing system resulting in no gas loss. The artificial lung model is already described and used elsewhere.11
For each test-run, carbon dioxide absorbent (Drägersorb 800, Dräger, Lübeck, Germany) was renewed. Only oxygen and air was used in the breathing system. The ventilatory frequency was set at 12 bpm and the tidal volume at 0.49 litre. After checking the air tightness of the ventilator (this is part of the installation procedure), it was connected to the artificial lung. In FGC (Primus® and Zeus®), the fresh gas was set at oxygen 50% in nitrogen. In AC (Zeus® only), the inspiratory oxygen was set at 50% in nitrogen. First, the lung was ventilated until a stable profile of capnography and inspiratory oxygen concentration was attained, simulating adequate preoxygenation. Thereafter, the test was started.
Each test-run consists of three stages: at time 0, the aim is to achieve and maintain an end-tidal concentration of 1 MAC (i.e. 2% for sevoflurane and 6% for desflurane). Thereafter, at time 15 min, the ventilator is reset to achieve and maintain an end-tidal concentration of 2 MAC (i.e. 4% for sevoflurane and 12% for desflurane); and finally, at time 30 min, the volatile anaesthetic administration was stopped and agent is blown-off. Recording stopped when end-tidal level fell below 0.2 MAC. During each test-run, ventilator settings were maintained unchanged; only the fresh-gas percentage (FGC) or the set end-tidal percentage (AC) of volatile anaesthetic were adjusted.
As summarized in Table 2, using the Zeus® apparatus, five different settings were used for each agent (sevoflurane and desflurane): FGC 1 litre FGF; FGC 6 litre FGF; AC 1 litre FGF; AC 6 litre FGF; and AC uptake mode, in which FGF equals consumption. Using the Primus® apparatus, only the two FGC modes were used. In FGC, the anaesthetist manually titrated the vaporizer towards the targeted level. This was done by first setting the vaporizer at a maximum concentration (8% for sevoflurane and 18% for desflurane) until the target end-tidal inhaled anaesthetic concentration was reached. Vaporizer settings were then titrated in step changes of 0.30.5 vol % in order to maintain the targeted end-tidal inhaled anaesthetic concentration. In AC mode (Zeus® only), drug administration needed to reach and maintain the targeted end-tidal concentration was performed automatically. Each setting was repeated five times.
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Performance measures and statistical comparison
Different end-points were analysed and compared:
Statistical analysis was performed using repeated-measures ANOVA, followed by Tukey-Kramer multiple comparison test if required. Significance level was set at P<0.05. All statistics were performed using Graphpad Instat 3.0 for Windows (GraphPad Software, San Diego, CA, USA).
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Results |
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The consumption of inhaled anaesthetic at all settings were calculated using a precision balance (Table 5).
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Discussion |
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In this study, a new closed-circuit anaesthesia apparatus with direct injection of volatile anaesthetic and carrier gas into the breathing system has been compared with a classical anaesthesia machine. To address safety issues, we decided to test the characteristics of this new device using a validated in vitro setting simulating inhaled anaesthetic uptake and carbon dioxide production.11 When comparing the time course of sevoflurane or desflurane end-tidal concentrations in FGC mode from the Zeus® apparatus with the classical Primus® system, we found that the time to reach 90% of the targeted end-tidal gas concentration was shortest when using high FGF. Therefore, the Primus® apparatus, using a classical out-of circle vaporizer, required less time to reach target than the Zeus® apparatus, using a direct injection system. In both anaesthesia machines, this mode resulted in the largest initial overshoot in end-tidal concentration. In contrast, the onset times when using low FGF (1 litre min1) resulted in the longest times to reach target in both anaesthesia machines. Less overshoot was seen than when using low FGF. As already known when using classical out-of-circle vaporizers, the consumption of liquid sevoflurane or desflurane parallels and is influenced by the applied FGF. This was also revealed in this study as seen in Table 5. When comparing the time course for end-tidal concentration in 1 litre min1 and 6 litre min1 FGC mode for both anaesthesia machines, the times to reach 0.9 and 1.9 MAC were always shorter when using the Primus® vs the Zeus® apparatus. This is attributable to the fact that in the Primus®, because there is no blower, fresh gas partly goes directly to the patient, while in Zeus®, fresh gas is extensively mixed within the circle volume before reaching the patient.
For the Zeus® apparatus, the results in FGC were compared with various settings in AC mode. In the full automated mode, the apparatus reaches closed-circuit conditions. In a closed-circuit, the FGF equals the patient's uptake. Closed-circuit conditions have been defined by Baum14 in either non-quantitative anaesthesia, whereby consistency of gas volume but not necessarily of anaesthetic gas composition is obtained in the breathing circuit, and in quantitative anaesthesia, whereby both of these factors are constant during the entire anaesthetic period. The latter is only possible if both aspects are controlled electronically by closed-loop feedback.15 In the Zeus® apparatus, when using uptake AC mode, both fresh gas volume and oxygen concentration are feedback-controlled. Additional fresh gas (oxygen, nitrous oxide/air) will only be delivered when the measured concentrations are lower than the target or when the pressure in the rebreathing bag is <1 mbar.
Previously published, experimental closed-circuit anaesthesia systems used a leak-free classical valve circuit whereby the fresh gas flow was reduced to equal the patient's uptake. Several disadvantages were described with these systems. Accumulation of non-anaesthetic gases like methane, acetone and nitrogen was found.16 17 Recently, Versichelen and colleagues18 described higher absorbent temperatures resulting in higher compound A formation during closed-circuit sevoflurane administration using a classic valve circuit than when using a high-flow valveless closed-circuit system (Physioflex® apparatus, Dräger, Lübeck, Germany).19 In the newly developed Zeus® apparatus, a dynamically driven blower is used to both generate a circuit flow and to generate a breathing pressure in combination with the proportional valve located in the expiratory limb, when required. In contrast to previous systems, no other hardware is required to build up the ventilator.
For patient groups with increased fractions of foreign and trace gases in the exhalation, a fresh gas flow <1 litre1 min is contraindicated.20 Therefore, an AC mode with minimal fresh gas flow was installed into the Zeus® apparatus. In this mode, equivalent to uptake mode, the inhaled anaesthetic and the oxygen delivery are feedback-controlled as described below.
When closed-circuit techniques are used in conjunction with a conventional out-of-circle vaporizer, it is impossible to deliver enough inhaled anaesthetic agent safely into the circuit within a reasonable time.21 Therefore, methods using direct injection of anaesthetic agent into the breathing system have some definitive advantages when compared with the plenum vaporizers. This injection is totally independent from the FGF,22 so even in closed-circuit conditions, rapid changes in concentrations are possible. In our study, when comparing the uptake AC mode with the two fixed-FGF AC modes, no differences in the time course of the end-tidal concentrations were observed (Figs 4B and 5B) for both sevoflurane and desflurane. The consumption of inhaled anaesthetics was only dependent on the set FGF. When using the Zeus® apparatus in uptake AC mode only very small quantities of inhaled anaesthetics are used. This is in contrast to the out-of-circle vaporizers (or FGC when using the Zeus®) where low fresh gas flow will delay changes in inhaled anaesthetic concentrations. When comparing the stability at equilibrium for all modes (Tables 3 and 4), results are excellent except for the 1 litre min1 FGF during FGC mode for both anaesthesia machines. This is largely attributable to its slow response to changes in operator settings. One can conclude that low-flow FGC is not adequate when a swift change in agent is desired. Remarkably, low-flow and uptake conditions in AC are responsive to rapid adjustments of agent concentration.
Although calculated fixed-rate administration of direct injected inhaled anaesthetics using an uptake formula has been described,7 8 23 adaptive control of direct injection of inhaled anaesthetics has become state-of-the-art. Therefore, the feedback controller measures the end-tidal inhaled anaesthetic concentration and titrates the direct anaesthetic injection to reach and maintain the targeted end-tidal concentration as soon and accurate as possible. This facilitates and secures inhaled anaesthetic drug administration as seen when using the Zeus® ventilator. Only a few steps were required to guide drug administration, in contrast to the manually controlled FGC mode where continuous changes in agent titration are required to reach and maintain a targeted concentration. Though stability is satisfactory in all modes, one must consider this to be an in vitro study, where operator attention exclusively goes to the ventilator settings. In daily practice, there are many other responsibilities requiring attention. While stability in AC mode will not alter when the operator is distracted from the ventilator settings, in FGC it can do so dramatically.
Time to washout, again, is highly comparable within the three AC settings of the Zeus® apparatus. Because the ventilator automatically maximizes FGF to enhance flushing of the breathing system until a new set value is reached, the AC mode is always faster in decreasing agent content of the system than fresh gas control mode. Interestingly in AC, washout at 1 litre min1 FGF is faster than at 6 litre min1 FGF and uptake mode, although differences are small. Emergence times may be expected to be much shorter when working in AC than in FGF. Only when vastly increasing FGF, will emergence times approximate those in AC. Times to washout in FGC mode with Zeus® were faster than with Primus®.
In conclusion, when investigating the time course and consumption of inhaled anaesthetic drug concentration during in vitro conditions using the Zeus® apparatus in various drug delivery modes and when comparing it with a classical anaesthesia machine using an out-of-circle vaporizer in high and low FGF conditions, we found that the ability of the Zeus® apparatus to provide AC allows the operator to have a very fast and reliable induction of volatile agent anaesthesia with minimal overshoot. It also allows a stable profile of desired end-tidal agent concentrations with minimal or no operator intervention. Moreover, because elimination of the inhaled agent is optimized when using the Zeus® apparatus, times to washout were short even in closed-circuit settings. In addition, uptake mode allows minimal consumption of volatile anaesthetic, while not compromising the time course of inhaled agent end-tidal concentrations. Optimizing and harmonizing patient safety, operator comfort and economic and ecologic considerations, this machine may set a new level of quality in ventilation anaesthesia.
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Appendix 1 |
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The ventilator and agent-delivery systems are monitored continuously by a protection system that is not only monitoring but also has means to switch the system into a safe operating mode. The system uses additional redundant sensors and computers, so that common mode failures are prevented. The most important protection tasks are:
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Appendix 2 |
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The following measurements are taken to determine the agent concentration in the breathing system and the agent concentration in the patient lung: (i) the inspiratory agent concentration (insp_agent) is measured for safety reasons inside the breathing system and at the Y-piece; and (ii) the end-tidal agent concentration (exp_agent), which corresponds to the agent concentration inside the patient lung, is measured at the Y-piece. For safety reasons the value is only valid, if a valid carbon dioxide-signal is detected. If no carbon dioxide breathing cycles are detected, the end-tidal agent concentration will be replaced by the inspiratory agent concentration, which leads to less feedback control performance.
The output of the feedback controller consists of the following parts:
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To ensure, that the inspiratory agent concentration will not rise above the maximum inspiratory set value (set_inspmax_agent) the total flow:
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If a FGF is set by the user, the oxygen feedback-controller or the oxygen uptake controller, the disturbance is minimized by giving an additional proportional agent flow:
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If the controller detects that the actual expiratory concentration is higher than the set value, the system is flushed with a high FGF and thus washed out to the scavenging system. This is the case at the end of a procedure where the required concentration is decreased.
Oxygen feedback control
The oxygen supply system is based on the measurement of the concentration in the system and the comparison of measured and set values. A robust model-based feedback-controller is used to achieve the set inspiratory oxygen concentration. Provided that a circuit flow of 12 litre min1 leads to a homogeneous gas concentration in the breathing system, the design can be reduced to a simple continuous flow model considering the circuit flow (Fcirc) and the minute ventilation flow (AMV).
The following measurements are taken to determine the oxygen concentration in the breathing system as the input values of the feedback controller: (i) the inspiratory oxygen concentration (insp_oxygen) is measured for safety reasons inside the breathing system and at the Y-piece; and (ii) the end-tidal oxygen concentration (exp_oxygen), which is, from the feedback controller's point of view, a disturbance to the concentration in the breathing system, measured at the Y-piece. For safety reasons, the value is only valid if a valid carbon dioxide signal is detected. If no carbon dioxide breathing cycles are detected, the end-tidal oxygen concentration will be replaced by the inspiratory oxygen concentration, which leads to less feedback-control performance.
The output of the feedback-controller is the amount of FGF, which consists of the following parts:
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The oxygen concentration (oxygenconc_sum_FGF) of the FGF calculated by the oxygen feedback-control is always either 21 or 100 vol % depending on the following criteria:
Regardless of the chosen carrier gas (nitrous oxide or air) the oxygen concentration of the FGF will never be <21 vol %.
Considering the diversity of the gain depending on the target oxygen concentration, this leads to the total flow (total_FGF), which is limited to a maximum flow of 12 litre min1:
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Therefore, it is assumed, that owing to the circuit flow of around 12 litre min1 a fresh gas flow of 12 litre min1 is optimum, and a flow of >12 litre min1 increases the wastage of fresh gas more than the speed of the concentration change.
When choosing a minimum flow (Fmin) above uptake, the FGF is downwardly limited to the set minimum flow. The oxygen concentration of the resulting FGF is calculated as:
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Volume feedback control
If the minimal flow setting is set to uptake and the oxygen concentration is 3 vol % above or below the set value, the feedback-controller switches its priority from oxygen to volume feedback control.
In a balanced closed breathing system, the fresh gas including anaesthetic vapour is equal to the gas uptake of the patient and leakage loss. This is obtained by measuring the pressure of the breathing bag from breath to breath at the end of expiration. A feedback-controller delivers a FGF to the system in order to keep the end-expiratory pressure in the breathing bag constant at 1 mbar. This way, the volume of the breathing system remains consant and the system is balanced.
Using the signal of the oxygen analyser, the computer calculates the required oxygen partition in the delivered fresh gas as described above. Both control algorithms together determine the required amount of oxygen. In a continuous process these two algorithms keep the system volume and the inspiratory oxygen concentration stable.
Only when there is no leak, no gas wash-out or agent wash-in, does oxygen flow reflect the patient's oxygen uptake. When nitrogen is washed out from the patient or when agent is washed into the patient, the oxygen concentration will drop. If the oxygen concentration drops >3 vol % below the set concentration, the system valves will no longer stay closed and the priority is switched back to oxygen concentration. However, the trend of the oxygen flow is stored and can give information about changes in patient uptake. Besides the estimation of oxygen uptake, the uptake mode leads to less agent consumption.
Owing to the concept used to measure the pressure of the breathing bag volume, feedback control is not available in manual spontaneous ventilation.
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Appendix 3 |
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However, during the inspiration phase, the amount of the circuit flow that could be measured with the expiratory flow sensor is negligible in mandatory controlled ventilation whether pressure- or volume-controlled.
Pressure-controlled ventilation
From its nature, the Zeus® is designed for pressure-controlled, and pressure-augmented, ventilation modes (e.g. pressure support). The blower, as the key component of the ventilator, is a pressure source with a breathing-through resistance of 23 mbar litre1 s1. The maximum set value for the inspiratory pressure is 50 mbar, which is generated by the blower at a speed of about 30 000 r.p.m. Although the blower has a low breathing-through resistance, it is feedback-controlled by the expiratory pressure sensor during the inspiration phase to overcome the inspiratory breathing resistances of the absorber, the blower and the inspiratory hoses. During the expiratory phase, the primary task of the blower is to guarantee a circuit flow of
18 litre1 min. Therefore, it is feedback-controlled by the inspiratory flow sensor, whereas the PEEP-valve guarantees the set PEEP value.
Flow/volume-controlled ventilation
The ventilator offers two different volume-controlled ventilation modes. In both modes, the tidal volume is feedback-controlled by the inspiratory flow sensor. The preferred volume controlled ventilation mode in Zeus® should be AutoFlow with a pressure/flow waveform equivalent to pressure-controlled ventilation. Therefore, the inspiratory pressure level is calculated in a breath-by-breath feedback control loop from the set tidal volume and the inspiratory tidal volume measured by the internal inspiratory flow sensor. As such, AutoFlow guarantees the application of the adjusted volume by gradual adaptation of the mechanical inspiration pressure to the lung conditions. Spontaneous breathing is possible at any time also on the inspiratory pressure levelas in pressure-controlled ventilation.
The other controlled ventilation mode is emulating classical volume-controlled ventilation with a constant inspiratory flow and a plateau phase. In this ventilation mode, a feedback-controller, based on the signal of the inspiratory flow sensor, enables the blower to act like a piston-driven ventilator.
The expiratory phase in both volume-controlled ventilation modes is equivalent to that in pressure-controlled ventilation.
Manual/spontaneous ventilation
The Zeus® apparatus is able to assure a PEEP during manual/spontaneous ventilation, which differs from conventional anaesthesia machines. Therefore, the PEEP valve is set to the desired CPAP level and the blower is feedback-controlled by the internal flow sensors. To assure a superposed circuit flow the blower is feedback-controlled by the expiratory flow sensor during inspiration and it is feedback-controlled by the inspiratory flow sensor during expiration.
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Footnotes |
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References |
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