WO2018042376A1 - Method and system for the detection of the respiratory profile of a patient undergoing non invasive respiratory assistance by nasal cannulas or other interface - Google Patents

Abstract

System and method for monitoring respiratory quantities during the administration of oxygen at various concentrations by nasal cannulas, in particular by means of an HFNC (High Flow Nasal Cannula) apparatus (100) or a CPAP (Continuous Positive Airway Pressure) apparatus (200), which system and method provide the use of: - a first flow detector (21 or 1021, DPT-A) configured to measure a delivered flow (Φ_{HFNC_PNT-A} or Φ_{ΟΡΑΡ_ΙΠ_ΡΝΤ-Α}) of oxygen at different concentrations administered upstream the nasal cannulas (105 or 205); - a second flow detector (22 or 1022, DPT-B) configured to measure a residual flow (Φ_{Mask_PNT-B} or Φ_{ΟΡΑΡ_out_ΡΝΤ-Β}) that crosses an oro-nasal mask (3) worn above the nasal cannulas (105) of an HFNC apparatus (100) or expiratory branch (206) of the ventilation circuit in the case of a CPAP apparatus (200); - a pharyngeal catheter (4) associated with a pressure transducer (DPT-D) for measuring pharyngeal pressure (Pphar); - an esophagus-gastric catheter (5) associated with two pressure transducers (DPT-E, DPT-F) for measuring the esophageal pressure (P_Es) and gastric pressure (P_Ga); - a catheter associated with a pressure transducer (DPT-C) configured to measure the internal pressure of the oro-nasal mask (3) (P_Mask) or a circuit catheter (1006) associated with a pressure transducer (DPT-C ) configured to measure the pressure inside the ventilation circuit near the nasal cannulas (205) (P_Circ); - an oscilloscope (7); - a processing unit (10 or 1010) for the determination of parameters representative of respiration and/or pulmonary mechanics.

Description

METHOD AND SYSTEM FOR THE DETECTION OF THE RESPIRATORY PROFILE OF A PATIENT UNDERGOING NON INVASIVE RESPIRATORY ASSISTANCE BY NASAL CANNULAS OR OTHER INTERFACE

DESCRIPTION

Technical field of the invention

The present invention relates to a method and a system for the detection and the monitoring of the respiratory profile of a patient undergoing high-flow oxygen therapy by nasal cannulas or assisted by apparatuses that apply continuous positive pressure to the airways by nasal cannulas or other interface, for example a nasal mask.

Background of the invention

In patients with various types of pulmonary disease, a progressive deterioration of respiratory function may occur, which, if not rapidly and effectively treated, may lead to the need for intubation and mechanical ventilation.

Among the support devices that are used in initial cases of respiratory failure, those most used are bidirectional flow systems that use a circuit equipped with an inspiratory branch that goes from the apparatus to the patient, an interface (nasal cannulas, NC), from which the patient inhale a fraction of the flow (respiratory flow), and an expiratory branch, in which the residual flow runs, which from the patient returns to the apparatus. Among these, nasal CPAP ("Continuous Positive Airway Pressure") systems are known, which maintain a positive pressure in the airways throughout the respiratory cycle.

More recently, unidirectional flow (from the apparatus to the patient) apparatuses, that deliver high flow of humidified and heated oxygen and air, have been developed. These oxygen therapy apparatuses interface with the patient by nasal cannulas and are generally identified by the HFNC ("High-Flow Nasal Cannula") acronym.

Both of these apparatuses are able to improve oxygenation and reduce breathing work in many respiratory failure conditions. HFNC apparatuses have been designed to deliver oxygen at different concentrations at a higher flow with respect to the patient's Peak Inspiratory Flow (PIF) so that the patient should not have to inspire additional air from the environment to adapt the inhaled flow to his PIF, as in low-flow systems. When this condition is met, the oxygen inhaled by the patient comes exclusively from the NCs and therefore the oxygen fraction set on the HFNC (Fi02) apparatus coincides with the one inhaled by the subject. In addition, if the flow of the HFNC apparatus is adequate to the PIF, a continuous flow of fresh gas from the nose to the mouth is obtained, resulting in a consequent reduction of the anatomic dead space. Other effects resulting from inhalation of flows higher than the PIF are the reduction of inspiratory strengths and an increased pressure at pharyngeal level.

Unlike common ventilation system and also because of the easiness of use with which they were conceived, HFNC and CPAP apparatuses are both not equipped with a system for measuring and/or monitoring physiological parameters associated with respiratory flow (current volume or other), nor the parameters of respiratory mechanics, such as compliance, resistances or respiratory work. This represents an important drawback of known systems, as these parameters could guide the clinician in optimum HFNC and nasal CPAP setting.

In addition, neither HFNC apparatuses nor the one for nasal CPAC, have a device for monitoring pressure inside airways. This deficiency is another major drawback of known systems because it is not possible to detect an increase in pharyngeal pressure, that is a potential cause of pulmonary hyperinflation and pneumothorax.

Flow setting in HFNC apparatuses plays a crucial role as it affects the levels of FiO₂ and the respiratory mechanics parameters mainly through a change in pharyngeal pressure. Equally important is the setting of the pressure levels in CPAP apparatuses. However, currently, these settings can only be done empirically on the basis of the clinical response, heart and respiratory rate, and of the peripheral oxygen or blood gasses saturation. Clinical response is indicative of the efficacy of treatment, but is not objective because it changes on the basis of the observer's experience and therefore may not coincide with the actual values of the respiratory stress of the patient.

In particular, the current flow setting in HFNC systems, starts from an initial value of 1 L/kg/min + 1 , to reach 2 L/kg/min or 3 L/kg/min if no clinical signs of respiratory stress disappear or physiological parameters do not improve. As mentioned, this graduation of the flow levels is independent of the pathophysiological mechanism of the underlying respiratory problem and is based only on clinical parameters. Therefore, another major drawback of known systems is that, if the delivered flow is not adequately proportioned to the subject's needs, there may also be a worsening of respiratory function over time.

In attempting to solve some of the aforementioned drawbacks, some methods that would allow us to evaluate respiratory function in patients undergoing treatments with HFNC or nasal CPAP apparatuses have been proposed. Some of these methods are not invasive, such as: inductance respiratory plethysmography, which estimates chest and abdominal volume variations by thoraco-abdominal bands; electrical impedance tomography, which allows to produce tomographic images of the spatial distribution of electrical impedance within the thoraco-abdominal area from which the variations in the pulmonary volume can be deduced; and optoelectronic plethysmography, which is able to continuously provide accurate measurement of thoraco-abdominal volume and of changes in lung volume. However, these techniques have the disadvantage of requiring initial calibration by measuring the current volume, which measurement cannot currently be practiced in patients treated with an HFNC or CPAP apparatus.

Other respiratory monitoring techniques, more invasive but more accurate than the previous ones, require the detection of the esophageal pressure by a balloon catheter. To evaluate respiratory mechanics through esophageal pressure it is essential to identify, in the signal of the esophageal pressure, the beginning and the end of the inspiration (respiratory timing). To do this, the most correct way would be to acquire the respiratory flow signal by differential spirometry that measures the difference between the flow delivered by the apparatus and the residual flow from the patient. However, this is not currently practicable during HFNC treatment due to gas leakages from the nose and the mouth, which are inevitable in a unidirectional flow system, and which cannot be completely intercepted by a monitoring interface (mask or other device) because of the non-perfect adherence of this to the patient's face.

Also for nasal CPAP, the correct acquisition of respiratory flow could be achieved by differential spirometry too, i.e. by subtracting from the flow running through the inspiratory branch, the one running through the expiratory branch of the ventilation circuit. However, even in this case, the accuracy of the measurement would depend on the absence of leakages or on the possibility of calculating them and summing them to the respiratory flow. An attempt has been made in the past by a group of German researchers who have calculated the leakage flow from the respiratory tracts of the subject using a particular algorithm and have used this result to correct the respiratory flow obtained by differential spirometry. However, this algorithm can be applied up to flow losses of 30%, a value that greatly limits the clinical application. The currently used formula to determine the respiratory flow taking into account the losses is (Foitzik B. et al., "Leak measurement in spontaneous breathing of premature newborns by using the flow-through technique", J. Appl. Physiol. (1985). 1998 Sep;85 (3): 1 187-93):

V'_diff^*(f) = [V'diff (t) + V'pTo (t) ^■ leak] ^■ [1 / (1 - leak)] = V'_pat(f).

Wherein V'diff* and V'_pat represent the correct respiratory flow of the patient (the apex " ' " represents the mathematical derivative with respect to time); V'diff (t) the incorrect breathing flow; V'_PTo the flow which arrives to the subject (background flow); and leak represents the loss coefficient.

To overcome the above-mentioned problems, methods alternative to respiratory flow were used, such as transdiaphragmatic pressure variations, which are more invasive than respiratory flow measurement. These methods, while allowing to identify the respiratory timing and therefore to calculate some parameters of the pulmonary mechanics, do not allow to determine the respiratory flow and thus the current volume, which is essential to determine the most important parameters of pulmonary mechanics and the adequacy of the flow set on the HFNC apparatus or of the pressure in case of nasal CPAP.

Summary of the invention

The technical problem placed and solved by the present invention is therefore to provide a method and a system for the detection of the respiratory flow, the parameters associated therewith, and the respiratory mechanics in patients undergoing treatment with HFNC (High-Flow Nasal Cannula) apparatuses or nasal CPAP (Continuous Positive Airway Pressure), which allow to overcome the drawbacks mentioned above with reference to the prior art.

Such problem is solved by a method according to claim 1 1 and a system according to claim 1 .

Preferred features of the present invention are subject of the depending claims.

The method and the system of the present invention allow the detection and the monitoring of physiological parameters characteristic of the respiratory flow and the respiratory mechanical parameters in a patient during the use of a HFNC apparatus or a nasal CPAP apparatus.

Specifically, the method and the system of the invention allow the detection of the patient's actual respiratory flow based on the measurement of the difference between the flow delivered by the ventilation apparatus and the residual flow from the patient, mathematically corrected for any leakage coming from the monitoring device of the respiratory flow of the patient (the oro-nasal mask) or from the patient itself. As regarding the flow difference, it is obtained by positioning a first sensor at the ventilation output, typically after a humidifier, and a second sensor on the collector of the flow coming from the patient. In HFNC systems, the second sensor is inserted into a mask that covers the nose and the mouth of the subject and that collects the residual ventilation flow while the subject breathes, instead in case of CPAP systems the second sensor is inserted into the expiratory branch of the ventilation circuit.

The method and the system of the invention also allow to determine the losses between the two flow sensors occurring, in the case of HFNC systems, predominantly at the edge of the oro-nasal mask, while in the CPAP case from the mouth or around the nasal cannulas. These losses are then returned to the previously calculated respiratory flow. Thanks to a method or algorithm that measures leaks, it is no longer necessary for HFNC systems to use a dedicated mask that has a perfect pneumatic seal with the patient, and, in the case of nasal CPAP, that the nasal cannulas are airtight and that the patient keeps the mouth shut during the measurements.

Starting from the quantities obtainable from the respiratory flow and pharyngeal and esophageal pressures, it is possible to set and adapt the flow values delivered by the HFNC apparatus, or pressure in the CPAP case, so that they are adapted to the patient's needs and to his respiratory response to the treatment.

The above-mentioned advantages are achieved through a system based on an effective set-up and at the same time simple to implement.

Other advantages, features and used modes of the present invention will result evident from the following detailed description of some embodiments, shown by way of example and not for limitative purposes.

Brief description of the drawings

The Figures of the enclosed drawings will be referred to, wherein:

^■ Figure 1 shows a HFNC apparatus employable to be used in association with the system of the invention, in a configuration in which it is connected to a patient;

^■ Figure 2 shows, in an exemplary manner, a preferred embodiment of a monitoring system according to the present invention, represented in conjunction with the HFNC apparatus of Figure 1 ;

^■ Figure 3 shows a schematic representation of a fluid dynamic circuit of a physical model that can be adopted for the system of Figure 2;

^■ Figure 4 shows a schematic representation of an electrical equivalent circuit of the fluid-dynamic circuit of Figure 3;

^■ Figure 5 shows schematically a possible configuration of a device that allows to measure the pharyngeal pressure (Pp_har) and, at the same time, to unblock the catheter used for its measurement (Figure 2), that being a fundamental condition for its operation;

^■ Figure 6 shows a possible implementation of the method of the present invention applied by the system of Figure 2;

^■ Figure 7 shows a CPAP apparatus employable in association with the system of the invention, in a configuration in which it is connected to a patient;

^■ Figure 8 shows, in an exemplary manner, a preferred embodiment of a monitoring system according to the present invention, represented in conjunction with the CPAP apparatus of Figure 7;

^■ Figure 9 shows a schematic representation of a fluid dynamics circuit of a physical model that can be adopted for the system of Figure 8; and

^■ Figure 1 0 shows a schematic representation of an electrical equivalent circuit of the fluid-dynamic circuit of Figure 9.

Detailed description of preferred embodiments

Figure 1 provides a schematic representation of a possible embodiment of a so- called HFNC (High-Flow Nasal Cannula) apparatus, denoted as a whole with 1 00.

The HFNC system 100 mainly comprises:

- a flow meter 1 01 that measures the flow delivered, that typically varies in a range of 0.25-70 l/min and is denoted by HFNC_PNT-A;

- a blender, or mixer, 102 which blends air and oxygen, typically with a Fi0₂ that varies between 0.21 and 1 ;

- a system of humidification and heating of gases, or humidifier, 103; and

- a ventilation circuit 1 04 connected on one side to the humidifier 103 and on the other to the nasal cannulas, here denoted by 1 05. Figure 2 shows a schematic representation, in terms of functional units, of a system of determination and/or monitoring of respiratory quantities and of pulmonary mechanics parameters according to a preferred embodiment of the invention. This system is hereby denoted as a whole by 1 .

The monitoring system 1 is intended to be applied in conjunction with an HFNC apparatus 1 00 as described above, in a spontaneous breathing subject.

In the present embodiment, the monitoring system 1 mainly comprises:

- a first flow detector 21 , in particular a pneumotachograph (denoted with PNT-A in FIG. 2), in series with the ventilation circuit 1 04 of the HFNC apparatus 1 00, downstream of the humidifier 1 03 and upstream of the nasal cannulas 1 05; detector 21 allows the flow measurement from the HFNC apparatus 100 during treatment ( HFNC_PNT-A) and includes, or is associated with, a corresponding differential pressure transducer (denoted with DPT-A in Figure 2);

- an oro-nasal monitoring mask 3 (mask) worn above the nasal cannulas 1 05 and without any apertures for the passage of the latters;

- a second flow detector 22, in particular a pneumotachograph (PNT-B), connected to the oro-nasal mask 3, preferably at the main opening thereof; the detector 22 allows the measurement of the flow running through the mask (<t½ask_PNT-B) and includes, or is associated with/, a corresponding differential pressure transducer (denoted with DPT-B in Figure 2);

- a pharyngeal catheter 4 for the measurement of pharyngeal pressure

(Pphar);

- a balloon esophagus-gastric catheter 5 with a proximal and a distal end, positioned respectively in the esophagus for the measurement of the esophageal pressure (P_Es) and in the stomach for gastric pressure (PG₃);

- a mask catheter 6, connected to or associated with mask 3 to measure the pressure inside the mask (Piviask);

- a plurality of differential pressure transducers (DPT), six in the present example, for the measurement of the following flows and pressures, some already introduced above: OHFNC_PNT-A (DPT-A), 0Mask_PNT-B (DPT- B), Pp_har (DPT-D), PE_S (DPT-E), P_Ga (DPT-F), P_MaSk (DPT-C); ^"

- an oscilloscope 7 for detecting, monitoring and capturing the signals generated by the six DPTs;

- a processing unit 1 0, such as a laptop or other electronic processor, for processing the signals stored by the oscilloscope 7. The use of the monitoring system 1 provides the following procedure:

- insertion the nasal cannulas 105 into the patient and setting of the flow of the HFNC apparatus 100 by comparison with the flow meter 101 included therein;

- insertion of the esophagus-gastric catheter 5;

- insertion of the pharyngeal catheter 4;

- positioning the gold-nasal mask 3 on the patient's face, overlapping the cannulas 105.

The monitoring system 1 also allows the determination of pharyngeal pressure during the use of the HFNC apparatus 100, as illustrated below.

The monitoring system 1 , allows therefore the determination of the respiratory flow and of other physiological respiratory parameters during the application of the HFNC apparatus 100, by means of a dedicated algorithm and in the following manner.

The system also allows the determination of parameters representative of the respiratory mechanics, as explained below.

The monitoring system 1 also allows the determination of pharyngeal pressure during application of the HFNC apparatus 100, as illustrated below.

Another important aspect of system 1 is that it allows to verify in real time the patient's HFNC_PNT-A> PIF (Peak Inspiratory Flow) condition, as illustrated below.

_{* * *}

Determination of the respiratory flow in the case of a HFNC system

When a subject is assisted with the HFNC system 100, the respiratory flow rate of the patient is more complex than the patient's spontaneous breath because of the flow delivered by the system itself and because of the leakages from the nose and the mouth. In fact, it is not enough to use only one flow detector connected to the mask, but two detectors are needed. As illustrated above, one of these detectors (21 or PNT-A) is inserted in series with respect to the ventilation circuit 104 which terminates with the nasal cannulas 105 and continuously monitors the flow from the HFNC apparatus 100. Another detector (22 or PNT-B) is directly connected to the oro-nasal mask 3 and continuously monitors the flow fraction that runs through the mask, in input to and in out of from the mask.

If the mask 3 was fully airtight and able to intercept all the flow going to and coming from the patient, the respiratory flow of the patient would be equal to the difference between the flow through the two flow detectors 21 and 22.

However, since no oro-nasal mask 3 can be considered fully airtight - because of the rigidity of the shape of the mask with respect to the variability of the face conformation as well as the interference with the nasal cannulas 105 - a fraction of said flow continuously crosses the edges of the mask. To determine the leakage flow from the mask, the system 100 implements, at level of unit 10, a leakages calculation algorithm.

A preferred implementation of this algorithm that determines the respiratory flow of the patient (0R_esp) in the presence of a leakage flow from mask 3 (<t½ask_Leak) is described below.

As illustrated in Figure 3, a physical model composed of a fluid-dynamic circuit (FC) which includes the HFNC apparatus 100, the aforementioned oro-nasal mask (Mask) 3, the PNT-A (21 ), the PNT-B (22), and the mask catheter 6 (shown in Figure 2), is used to determine the respiratory flow of the patient (<t>Resp) during treatment with HFNC apparatus 100. This allows us to evaluate the flows (Φ) of afferent and efferent gases to or from the patient as well as the pressure inside the mask 3 (Piviask)-

The behavior of the fluid dynamics circuit during treatment with the HFNC apparatus 100 can be efficiently studied and solved via the equivalent electrical circuit (CEE) shown in Figure 4.

In this context, the application of the equivalent electrical circuit is "correct" and "justified" on the basis of the following reasons. The "correctness" derives from the well-known equivalence of behaviour between the electric circuits and the fluid-dynamic circuits: the difference in electrical potential, electrical current, electric charge, electrical resistance, electrical capacity, and electrical inductance can be replaced with pressure, flow, volume, fluid dynamics, elastic compliance, and fluid-dynamic/elastic inertia. In this case, the electric inductance does not appear in the equivalent electric circuit because both the inertia of the flows that run through the airways and the one of the tissue that constitute the airways, the lungs, the chest, and the abdomen are both negligible at low respiratory frequencies (typically <10 Hz). The "justification" derives from the possibility to apply well-known theorems and available methods to solve the problems associated with electric circuits and, in particular, the Kirchhoff's laws.

The quantities characterizing the fluid-dynamic circuit of Figure 3 and the equivalent electric circuit of Figure 4, already partly cited above, are defined below.

Regarding pressure quantities:

- pressure inside mask 3 (PMask);

- pressure outside the mask 3 or atmospheric pressure (PAtm), which, as is known, is considered zero.

Regarding flow quantities:

- flow delivered from the HFNC apparatus 100 to the patient and monitored by the first flow detector 21 (OHFNC_ PNT-A);

- flow running through the oropharynx cavity ( phar);

- flow running through the nostrils externally to the nasal cannulas 105

(Φΐη-ouLNose)^',

- flow running through the mouth (Φΐη-outjviouth);

- ln-Out_Nose and ln-Out_Mouth Total Flow (ΦΙ_Π-OULNM);

- fraction of ΦΙ_Π-_OULNM intercepted by the oro-nasal mask 3 and monitored by the second flow detector 22 (ΦΜ₃₅Ι<_ΡΝΤ-Β);

- leakage flow from mask edge 3 (0Mask_Leak);

- respiratory flow of the patient (0R_esp).

The arrows shown in Figure 3 and Figure 4 indicate the direction of each specific flow (Φ) that can be unidirectional (single arrow) or bidirectional (double arrow).

From Figure 3 (or Figure 4), applying the continuity law (or Kirchhoff's first law) at junction 1 and junction 2, it is possible to write the following two equations:

phar = <t HFNC_ PNT-A " <t>ln-out_Nose GunCtlOn 1 ) (2)

Φρ-esp = <t>Phar " Φΐη-outJVIouth GunCtlOn 2) (3)

By substituting (2) in (3), the following equations are obtained:

^Resp ⁼ (Φ|ΗΡΝΟ_ΡΝΤ-Α ^" Φΐη-οι Ιοεθ) " Φΐη-outJVIouth (4)

^Resp ⁼ Φ|ΗΡΝΟ_ΡΝΤ-Α ^" ^ln-out_Nose + Φΐη-outJVIouth) (5)

By applying the Kirchhoff's first law at junction 3, it is possible to write the following equation:

Φΐη-ouLNM = ln-out_Nose + Φ|η-οιιΙ_Μοιιϋι (junction 3) (6)

By applying the continuity law (or Kirchhoff's first law) at junction 4, we can write the following equation:

Φΐη-οι ΐΜ =

(junction 4) (7) Finally, by substituting (6) and (7) in (5), the followin e uation is obtained:

Φρ-esp ⁼ ΦΗΡΝΟ_ΡΝΤ-Α ^"

(8)

From (8) it is clear that in order to determine the R_esp signal, we need to know the signals of all the following quantities: Φ_ΗΡΝΟ_ΡΝΤ-Α, ΦΜ₃₅Κ_ΡΝΤ-Β and <l>Mask_Leak-

The signals ΦΗΡΝΟ_ΡΝΤ-Α and ΦΜ₃₅Ι<_ΡΝΤ-Β are obtained, respectively, from flow sensors 21 (PNT-A) and 22 (PNT-B). As already shown in Figure 2, the flow sensors 21 (PNT-A) and 22 (PNT-B) have respective terminals connected, for example through tubes, to respective terminals of two differential pressure transducers (DPT-A and DPT-B).

To determine 0Mask_Leak, which is not known by the state of the art, it is possible to proceed as follows.

As shown in Figure 4, pressure at the ends of branch 1 (PMask and P_Atm) coincides with the one on the branch 2 (PMask and PAtm)- Consequently, the difference in pressure at the ends of both the branches (PMask - PAtm) coincides (parallel connection). Considering that P_At_m = 0 and applying Kirchhoff's second law to both branches, it is possible to write the following equation:

PlVlask ^" PAtm ⁼ PlVlask ⁼ RlVlask PNT-B * ΦMask PNT-B ⁼ RlVlask Leak * ΦMask Leak (9) wherein

and RMaskj_eak are respectively the fluid-dynamic resistance of the detector 22 (PNT-B) and the one of the equivalent loss channel (shown in Figure 4 and corresponding to a flow loss channel from the edge of the mask) through which ΦMask_Leak is established. RMask_PNT-B depends on the geometric characteristics of the detector 22 (PNT-B), which are indicated by the constructor, and on the value of ΦΜ₃₅^ΡΝΤ-Β- The value of RMask_PNT-B can still be verified by applying (9) by means of the measurement of PMask and ΦΜ₃₅^ΡΝΤ-Β-

A primary approach to the determination of ΦMask_Leak is based on the

equivalence between the second and fourth members of (9), from which the following equations can be derived:

PlVlask RlVlask Leak (10) R|Vlask_Leak = PlVlask / ΦMask_Leak (1 1 )

The measurement of PMask is obtainable through a tube (catheter to mask 6 in Figure 2) that connects the inside of the mask 3 with one of the two terminals of a DPT transducer (DPT-C in Figure 2). To get Ri iask_Leak, assuming that its value remains constant in any condition, it is necessary to identify the specific condition in which 0Mask_i_eak is directly measurable.

A first method for this measurement is the so-called apnea.

The specific condition in which 0Mask_i_eak is directly measurable is represented by the patient's apnea state, which can be defined by the following equation:

During apnea, (1 2), (8) and ( 1 1 ) assume the followin expression:

^<i^)AMask_Leak = Φ^ΑΗΡΝΟ_ΡΝΤ-Α "

(1 3) R^AMask_Leak = P^AMask / ^<i^)AMask_Leak (1 4) wherein the symbol ^Λ denotes the value assumed by the relative quantities during apnea.

By substituting (1 3) in (1 4), the followin equation is obtained:

R^AMask_Leak

( 1 5)

The (1 5) allows to determine the value of R^AMask_i_eak, that is the resistance of the equivalent loss channel during apnea, which, on the basis of the hypothesis previously mentioned, is considered equal to the one supposed during respiratory activity of the patient, in accordance with the following condition:

RlVlask Leak ⁼ R^AMask Leak (1 6)

During the respiratory activity of the patient (0R_eSp ≠ 0), considering (1 6), from 1 0) and (1 5) the following equation may be deduced:

/ P^AMask] * PlVlask ( 1 7)

The equation (1 7) provides a first solution to the problem of the determination of By substituting (1 7) in (8), the following equation is obtained:

ΦResp⁼ΦHFNC_PNT-A-ΦMask_PNT-B-[(Φ^AHFNC_PNT-A-Φ^AMask_PNT-ByP^AMask]*PMask ( 1 8)

The above approach assumes the possibility of identifying an apnea phase between the respiratory cycles of the patient, in which it's possible to measure the values of Φ^ΑΗΡΝΟ_ΡΝΤ-Α, Φ^ΑΜ₃₅^ΡΝΤ-Β, P^AMask- This approach is easily practicable with a collaborating patient, while it is more complicated in early childhood patients who cannot voluntarily retain their breath (apnea).

A second method for the determination of RMask_Leak consists in the detection of the equilibrium value associated with ΦΗΡΝΟ_ΡΝΤ-Α, wiask.PNT-B and PMask by computing the mean value of these quantities, calculated in the time interval corresponding to n consecutive respiratory acts. This mean value, being associated with the equilibrium value, coincides with the value assumed during apnea. Unlike the apnea method, this solution is applicable to patients of all ages, even to non-collaborating patients.

Secondary approach to the determination of t sk i ?.ak

A different (secondary) method for determinating 0Mask_i_eak is based on the equivalence between the second and the third member of (9), which gives the following equation:

PlVlask = R|viask_PNT-B * l las^PNT-B ( 9)

By applying (19) to the state of apnea, the following equation is obtained:

P^AMask = R^AMask_PNT-B * ^as^PNT-B (20)

If it is assumed that the resistance of the detector 22 (PNT-B) during respiratory activity of the patient is the same as the one during apnea, in accordance with the following condition:

R|Vlask_PNT-B ⁼ R^AMask_PNT-B (21 ) by substituting (19), (20) and (21 ) in (17), the following equation is obtained:

^<i⁾Mask_Leak = [(Φ^ΑΗΡΝΟ_ΡΝΤ-Α ^"

* Mask_PNT-B (22)

The equation (22) provides a second solution to the problem of determining

By substituting (22) in (8), the following equation is obtained:

Φρ-esp = HFNC_PNT-A " Mask_PNT-B ^" [(Φ^ΑΗΡΝΟ_ΡΝΤ-Α ^"

*

Thanks to simple mathematical steps, (23) assumes the following equation:

Φρ-esp

(24)

In summary, from the comparison between the primary approach and the secondary approach the following considerations can be made.

By adopting the secondary approach, it is not necessary to monitor PMask, nor to find the equilibrium value of the latter (P^AMask), since the determination of 0R_esp require the continuous monitoring of only ΦΗΡΝΟ_ΡΝΤ-Α and ΦΜ₃₅^ΡΝΤ-Β- This advantage can be partially canceled by the need to consider the further hypothesis that the resistor of detector 22 (Riviask_PNT-B), during respiratory activity of the patient, is the same as during apnea (R^AMask_PNT-B)- Thus, although the secondary approach is based on a simpler procedure with respect to the primary approach, since it includes an additional hypothesis, it may be less effective in adapting to possible variations of the characteristics of the system. Therefore, if the PMask signal, including its equilibrium value (P^AMask), can be monitored without interruption, the primary approach is preferred. Determination and monitoring of the HFNC threshold value

The HFNC apparatus 100 exerts its clinical benefits thanks to the fact that the flow delivered by the machine is always higher than the respiratory flow of the patient (0R_eSp), according to the following condition:

HFNC_PNT-A > ^Resp (27) or, equally:

ΦΗΡΝΟ_ΡΝΤ-Α - ^Resp > 0 (28)

Since the following equation is obtained from (8):

ΦΗΡΝΟ_ΡΝΤ-Α - Resp

⁺ Mask_Leak (29) in accordance with (29), (28) assumes the following expression:

lVlaskJ'NT-B + Mask_Leak > 0 (30)

By substituting (17), obtained with the primary approach, in (30), the following expression is obtained:

l las^PNT-B + {[(Φ^ΑΗΡΝΟ_ΡΝΤ-Α " ^askJ^NT-B) / P^AMask] * PlVlask} > 0 (31 )

The signal of the quantity that appears on the first member of (31 ) can be monitored in real time, and it is therefore possible to ascertain whether the HFNC's operating criterion is satisfied, in accordance with (27).

Alternatively, by substituting the (22) obtained with the secondary approach in (30), the following expression is obtained:

Mask_PNT-B ⁺ {[(Φ^ΑΗΡΝΟ_ΡΝΤ-Α ^{" A}Mask_PNT-B)

* Mask_PNT-B} > 0 (32)

The signal of the quantity that appears on the first member of (32) can be monitored in real time too, and as for (31 ), it is possible to verify that the HFNC application criterion is satisfied.

_{* * *}

Figure 7 provides a schematic representation of a possible form of a so-called "Continuous Positive Airway Pressure" (CPAP) device, denoted as a whole with 200.

The CPAP system 200 mainly comprises:

- a flow meter 201 that measures the delivered flow denoted by ΦΟΡΑΡ_ΙΠ_ΡΝΤ-Α;

- a blender, or mixer, 202 which blends air and oxygen, typically with a Fi0₂ variable between 0.21 and 1 ;

- a system of humidification and heating of gases, or humidifier, 203; and - a ventilation circuit 208 provided with an inspiratory branch 204 connected to the CPAP system 200 and to the nasal cannulas 205, with a humidifier 203 interposed;

- an expiratory branch 206 connected to the CPAP system 200 and the nasal cannulas, the latters here referred to as 205.

Figure 8 shows a schematic representation, in terms of functional units, of a system of determination and/or monitoring of respiratory quantities and parameters of pulmonary mechanics according to another preferred embodiment of the invention. This system is here denoted as a whole with 1000.

The monitoring system 1000 is intended to be applied in conjunction with a CPAP apparatus 200 as described above, in a spontaneous breathing subject.

In the present embodiment, the monitoring system 1000 comprises mainly:

- a first flow detector 1021 , in particular a pneumotachograph (denoted with PNT-A in FIG. 8), inserted into the inspiratory branch 204 of the ventilation circuit of the CPAP apparatus 200, downstream of the humidifier 203 and upstream of the nasal cannulas 205; detector 1021 allows flow measurement from the CPAP apparatus 200 during treatment (ΦΟΡΑΡ_ΙΠ_ΡΝΤ-Α) and includes, or is associated with, a corresponding differential pressure transducer (denoted with DPT-A in Figure 8);

- a second flow detector 1022, in particular a pneumotachograph (PNT-B), inserted into the expiratory branch 206 of the ventilation circuit of the CPAP apparatus 200; the detector 1022 allows the flow measurement to flow in the expiratory branch of the circuit (ΦΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β) and includes, or is associated with, a corresponding differential pressure transducer (denoted with DPT-B in Figure 8);

- a pharyngeal catheter 4 for the measurement of pharyngeal pressure

(Pphar);

- a balloon esophagus-gastric catheter 5, with a proximal end and a distal end positioned respectively in the esophagus for the measurement of the esophageal pressure (P_Es) and in the stomach for the measurement of the gastric pressure (PG₃);

- a circuit catheter 1006 connected to the ventilation circuit near the nasal cannulas 205 for measuring the internal circuit pressure (Pc -c);

- a plurality of differential pressure transducers (DPTs), six in the present example, for the measurement of the following flows and pressures, some already introduced above ΦΟΡΑΡ_ΙΠ_ΡΝΤ-Α (DPT-A), ΦΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β (DPT-B),

Pp_har (DPT-D), PES (DPT-E), P_Ga ^"(DPT-F), P_Circ (DPT-C);^" - an oscilloscope 7 for detecting, monitoring and capturing the signals generated by the six DPTs;

- a processing unit 1010, such as a laptop or other electronic processor, for processing the signals stored by the oscilloscope 7.

The use of the monitoring system 1000 presume the following procedure:

- insertion of the nasal cannulas 205 into the patient and setting the flow and pressure level in the circuit of the CPAP apparatus 200 by comparison with the flow meter 201 and a variable resistor 207 which adjusts the CPAP set level;

- insertion of esophagus-gastric catheter 5;

- insertion of pharyngeal catheter 4.

- the monitoring system 1000 allows the determination of respiratory flow and other physiological respiratory parameters during the use of the CPAP apparatus 200, using a dedicated algorithm and in the following manner.

The monitoring system 1000 also allows the determination of pharyngeal pressure during the use of the CPAP apparatus 200, as illustrated below.

_{* * *}

Determination of respiratory flow in the case of a nasal CPAP system

When a subject is treated with a CPAP system 200, the respiratory flow measurement of the patient requires, as for the HFNC case, the insertion of two flow detectors in the ventilation circuit. As illustrated above, one of these detectors (1021 or PNT-A) is inserted in series into the ventilation circuit in the inspiratory branch 204 ending with the nasal cannulas 205 and continuously monitors the flow from the CPAP apparatus. The second detector (1022 or PNT-B) is inserted into the breathing branch 206 of the ventilation circuit and continuously monitors the residual flow. As reported for HFNC systems, in the absence of leakages (which in the case of CPAP mainly occurs in the patient's airways), the respiratory flow of the patient would be equal to the difference between the signals obtained from the two flow detectors (1021 and 1022). To determine the airway leakage flow, the system 200 implements, at level of unit 1010, an algorithm for calculating leakage.

As shown in Figure 9, to determine the respiratory flow of the patient (0_Resp) during CPAP 200 treatment, a physical model is adopted. This physical model is formed by a fluid-dynamic circuit (FC) which includes the CPAP apparatus 200, the inspiratory branch of the CPAP circuit 204, the expiratory branch 206, PNT-A (1021 ), PNT-B (1022), and the circuit catheter 1006 (shown in Figure 8), and that to evaluate afferent and efferent flows (Φ) to and from the patient, as well as the internal pressure of circuit 208 (Pc -c)-

The behavior of the fluid dynamics circuit during treatment with the CPAP apparatus 200 can be efficiently studied and solved via the equivalent electrical circuit (CEE) shown in Figure 1 0.

In this context, the application of the equivalent electrical circuit is justified according to the reasons already expressed for HFNC systems.

The quantities that characterize the fluid-dynamic circuit of Figure 9 and the equivalent electrical circuit of Figure 1 0, already partly cited above, are defined below.

Regarding pressure quantities:

- internal pressure inside circuit 208 (Pcirc);

- outside patient pressure or atmospheric pressure (PAtm), which, as is known, is considered zero.

P_Atm = 0 (1 )

Regarding flow quantities:

- flow flowing in the inspiratory branch of the CPAP apparatus 200 and monitored by the first flow detector 1 021 (QCPAPJ^PNT-A);

- nasal cannulas flow (QNC) ;

- flow through the oropharynx cavity (Pphar);

- flow through the nostrils externally to the nasal cannulas 205 ( i_n-out_Nose);

- flow through the mouth (Φΐη-outjviouth);

- total ln-out_Nose and ln-Out_Mouth (ΦΙΠ-OULNM);

- total loss flow (0i_eak_pat) which coincides with ln-out_Nose and In- out_Mouth (ΦΙΠ-OULNM) ;

- respiratory flow of the patient (0R_esp)-

The arrows shown in Figure 9 and Figure 1 0 indicate the direction of each specific flow (Φ) that can be unidirectional (single arrow) or bidirectional (double arrow).

From Figure 9 (or Figure 1 0), applying the continuity law (or Kirchhoff's first law) to junction 1 and junction 2, it's possible to write the following two equations:

ΦΝΟ = ΦθΡΑΡ in PNT-A " ΦθΡΑΡ out PNT-B Gunction l ) (1 02)

Pphar = ΝΟ - Φΐη-ouLNose GunCtlOn 2) (1 03)

By substituting (2) in (3), the following equation is obtained:

Pphar ⁼ ΦθΡΑΡ_ίη_ΡΝΤ-Α " ΦθΡΑΡ_οιιΙ_ΡΝΤ-Β " Φΐη-οι Ιοδβ G^uncti°ⁿ 2) (1 04) By applying the continuity law (or Kirchhoff's first law) to junction 3, it's possible to write the following equation:

<t>Resp = Pphar - Φΐη-outJVIouth GunCtlOn 3) (105)

By substituting (104) in (105) the following equation is obtained:

^Resp ⁼ ΦθΡΑΡ_ίη_ΡΝΤ-Α " ΦθΡΑΡ_οιιΙ_ΡΝΤ-Β " ^ln-ouLNose " Φΐη-outJVIouth (106)

Considering that the total loss flow (0i_eak_pat) coincides with the overall flow ln_Out_Nose and ln_Out_Mouth (ΦΙ_Π-_OULNM) which represents the sum of the flow that runs through the nostrils around the nasal cannulas (Oi_n-out_Nose) with the flow through the mouth (Φΐη-outjviouth), from (106) it is possible to write the following two equations:

^Resp ⁼ ΦθΡΑΡ_ίη_ΡΝΤ-Α " ΦθΡΑΡ_οιιΙ_ΡΝΤ-Β " Φ|η-οιιΙ_ΝΜ (107) Resp ⁼ ΦθΡΑΡ_ίη_ΡΝΤ-Α " ΦθΡΑΡ_οιιΙ_ΡΝΤ-Β " ^Leak Pai (108)

From (108) it is evident that to determine the signal 0R_esp it is necessary to know the signals of all three of the following quantities: ΦΟΡΑΡ__ΙΠ_ΡΝΤ-Α,

ΦθΡΑΡ_οιιΙ_ΡΝΤ-Β © ^Leak Pat

The signals of ΦΟΡΑΡ__ΙΠ_ΡΝΤ-Α and ΦΟΡΑΡ_Ο_ΙΙΙ_ΡΝΤ-Β are obtained, respectively, from flow detectors 1021 (PNT-A) and 1022 (PNT-B). As shown in Figure 8, the flow sensors 1021 (PNT-A) and 1022 (PNT-B) have respective terminals connected, for example, through the tubes, to respective terminals of two differential pressure transducers (DPT-A and DPT-B).

For the determination of Φι_₆₃ι<_Ρ3ΐ, not known by the state of the art, it is possible to proceed as follows.

As can be seen from Figure 9, pressures at the ends of branch 1 and branch 2 are equal. Consequently, the difference of pressure between the two branches (Pcirc - PAtm) coincides (parallel connection). So, taking into account that P_At_m = 0, and applying Kirchhoff's second law to both branches, it's possible to write the following equation:

Pcirc - PAtm = Pcirc = RcPAP_out_PNT-B * ΦθΡΑΡ_οιιΙ_ΡΝΤ-Β = R|_eak_Pat * ^Leak Pai (109) wherein, RCPAP_OULPNT-B e Ri_eak_Pat are respectively the fluid-dynamic resistance equal to the sum of the resistance of the detector 1022 (PNT-B) with the expiratory flow resistance of the ventilation circuit and the fluid dynamic resistance of the equivalent loss channel through which

is established. RcpAP_out_PNT-B depends on the geometric characteristics of the detector 1022 (PNT-B) and the resistance at the end of the expiratory branch to adjust the value set for CPAP, both of which are provided by the constructor, and on the value of ΦΟΡΑΡ_Ο_ΙΙΙ_ΡΝΤ-Β- The value of RCPAP_OULPNT-B can still be verified by applying (109) the measurement of Pol and of ΦΟΡΑΡ_Ο_ΙΙΙ_ΡΝΤ-Β-

Primary approach to the determination of Φι _Rak p_at A primary approach to the determination of 0i_eak_pat is based on the equivalence between the second and fourth members of (109), from which the following equations can be derived:

^Leak Pai ⁼ Pcirc R|_eak_Pat (1 10) R|_eak_Pat = Pcirc / ^Leak Pai (1 1 1 )

The Pcirc measurement is obtainable through a tube (circuit catheter 1006 in Figure 8) that connects the inside of circuit 208 to one of the two terminals of a DPT transducer (DPT-C in Figure 8).

To obtain Ri_eak_pat, assuming that its value remains constant in any condition, it is necessary to identify the specific condition during which Ri_eak_p_at is directly measurable.

A first method for such measurement is the so-called apnea.

The specific condition during which Ri_eak_Pat is directly measurable is represented by the patient's apnea state, which can be defined by the following equation:

Equations (1 12), (108) and (1 1 1 ), during apnea, assume the following equation:

^Leak Pai ⁼ Φ^ΑΟΡΑΡ_ίη_ΡΝΤ-Α " Φ^ΑΟΡΑΡ_οιιΙ_ΡΝΤ-Β (1 13) R^ALeak_Pat = P ^ACirc /

(1 14) where the symbol ^Λ denotes the value assumed by the relative quantities during apnea.

By substituting (1 13) in (1 14), the following equation is obtained:

R^ALeak_Pat ⁼ P^ACirc (Φ^ΑΟΡΑΡ_ίη_ΡΝΤ-Α ^" Φ^ΑΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β) (1 15)

Equation (1 15) allows to determines the value of

that is the resistance of the equivalent loss channel during apnea, which, on the basis of the previously mentioned hypothesis, is considered to be equal to the one taken during the respiratory activity of the patient, in accordance with the following condition:

R|_eak Pat ⁼ R^A|_eak Pat (1 16)

During the respiratory activity of the patient (0R_eSp≠ 0) then, considering (1 16), from (1 10) and (1 15) it is possible to deduce the following equation:

$Leak_Pat ⁼ Pcirc R^A|_eak_Pat ⁼ [(Φ^ΑΟΡΑΡ_ίη_ΡΝΤ-Α ^" Φ^ΑΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β) P^ACirc] * Pcirc

(1 17)

The (1 17) provides a first solution to the problem of the determination of Leak_Pat-

By substituting (1 17) in (108), the following equation is obtained:

^Resp ⁼ΦθΡΑΡ_ίη_ΡΝΤ-Α-ΦθΡΑΡ_ουΙ_ΡΝΤ-Β-[(Φ^ΑΟΡΑΡ_ίη_ΡΝΤ-Α-Φ^ΑΟΡΑΡ_ουΙ_ΡΝΤ- B)/P^ACirc]^*Pcirc (1 18) This approach assumes the possibility of identifying an apnea phase between the respiratory cycles of the patient, in which it is possible to measure the

Values Of Φ^Α ₀ΡΑΡ_ίη_ΡΝΤ-Α, <t>^ACPAP_out_PNT-B, ^d P^Acirc-

This is easily practicable with the collaborating patient, while it is more complicated in early childhood patients who cannot voluntarily retain their breath (apnea).

A second method for determining Ri_eak_Pat consists in the detection of the equilibrium value associated with ΦΟΡΑΡ_ΙΠ_ΡΝΤ-Α, ΦΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β and P_Ci_rc by computing the mean value of these quantities, calculated in the time interval corresponding to n consecutive respiratory acts. This mean value, being associated with the equilibrium value, coincides with the value assumed during apnea. Unlike the apnea method, the latter solution is applicable to patients of all ages, even non-collaborators.

Secondary approach to the determination of Φι _Rak pat

A different (secondary) approach to the determination of Φι_₆₃ι<_Ρ3ΐ is based on equivalence between the second and third members of (109), which gives the following equation:

Pcirc ⁼ RcPAP_out_PNT-B * ΦθΡΑΡ_οιιι_ΡΝΤ-Β (1 19)

By applying (1 19) to the state of apnea, the following equation is obtained:

P^ACirc = R^ACPAP_out_PNT-B ^* Φ^ΑΟΡΑΡ_οιιι_ΡΝΤ-Β (120)

If it is assumed that the resistance of the detector 1022 (PNT-B) and the resistance at the end of the expiratory branch that allows to adjust the CPAP value during respiratory activity of the patient is the same as during the apnea, in accordance with the following condition:

RcPAP_out_PNT-B = R^ACPAP_out_PNT-B (121 ).

By substituting (1 19), (120) and (121 ) in (1 17), the following equation is obtained:

^Leak Pa^ [(Φ^ΑΟΡΑΡ_ίη_ΡΝΤ-Α ^" Φ^ΑΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β) Φ^ΑΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β]* ΦθΡΑΡ_οιιι_ΡΝΤ-Β

(122)

Thus (122) provides a second solution to the problem of the determination of

$Leak_Pat-

By substituting (122) in (108), the following equation is obtained:

Φρ-esp ⁼ ΦθΡΑΡ_ίη_ΡΝΤ-Α ^" ΦθΡΑΡ_οιιι_ΡΝΤ-Β " [(Φ^ΑΟΡΑΡ_ίη_ΡΝΤ-Α ^" Φ^ΑΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β) Φ^ΑΟΡΑΡ_ΟΙΙΙ_ΡΝΤ-Β] * ΦθΡΑΡ_οιιι_ΡΝΤ-Β (123)

Thanks to simple mathematical steps, (123) assumes the following equation:

Φρ85ρ⁼ΦθΡΑΡ_ίη_ΡΝΤ-Α-(Φ^ΑΟΡΑΡ_ίη_ΡΝΤ-Α/Φ^ΑΟΡΑΡ_ουΙ_ΡΝΤ-Β)*ΦθΡΑΡ_ουΙ_ΡΝΤ-Β (124) In summary, from the comparison between the primary approach and the secondary approach, the following considerations can be drawn.

By adopting the secondary approach, there is no need to monitor Pc -c, nor find the equilibrium value of the latter (P^Acirc), since the determination of 0R_esp assumes continuous monitoring of only ΟΡΑΡ__ΙΠ_ΡΝΤ-Α and CPAP_OUI_PNT-B- This advantage can be partially canceled by the need to consider the further hypothesis that the sum between the resistance of the detector 1022 and the resistance at the end of the expiratory branch to adjust the CPAP (RCPAP_OULPNT- B) value during n respiratory activity of the patient is the same as during apnea (R^ACPAP_OULPNT-B)- Thus, although the secondary approach is based on a simpler procedure than the primary approach, since it includes an additional hypothesis, it may be less effective in adapting to possible variations in system characteristics. Therefore, if the Pc -c signal, including its equilibrium value (P^Acirc), can be monitored without interruption, the primary approach is preferred.

* * *

Determination of pharyngeal pressure

Pharyngeal pressure (Pphar) determination, valid for both HFNC systems and CPAP systems, requires the introduction of the already mentioned catheter 4, preferably of small caliber, with a single terminal hole, with the end positioned immediately above the epiglottis. The catheter 4 can be introduced either through a nostril or through the mouth.

As shown in Figure 5, in order to avoid the occlusion of the catheter by pharyngeal secretions, it is preferably grafted onto a T-joint so that it is connected to the already mentioned DPT-D pressure transducer on one side and to a device 1 1 from which it receives a flushing flow (0Fi_UShing) on the other side.

The aforementioned device preferably comprises three units: a pressure generator (PG), a flow regulator (FR), and a flow meter (FM). The presence of continuous gas flow in the pharyngeal catheter 4 results in a differential pressure (ΔΡ) between the T-joint and the catheter terminal located in the pharynx due to the catheter's resistance. As a result of this ΔΡ, the pressure detected by DPT-D (PDPT-D) is greater than the one found in the pharynx (Pphar)- The ΔΡ can be derived from the following equation:

ΔΡ = (PDPT-D - Pphar) = Rcat_phar * FIushing (25) wherein Rc_at__Phar is the resistance of the catheter tract between the T-joint and the catheter terminal and crushing is the flow that passes therethrough. From (25) it's possible to derive P_Phar follows: Pphar - PDPT-D "

(26)

Therefore, from (26) results that to determine P_Phar it is necessary to know P_DPT- D, Rcat_phar and Opiushing. PDPT-D and Opiushing are provided respectively by the DPT-D and the flowmeter (FM) included in the device 1 1 . Then Rc_at__Phar remains to be determined. This determination can be carried out in advance by performing vacuum measurements (with the catheter in the air) and obtaining the curve related to the functional dependence between ΔΡ and crushing through (25) by replacing P_Atm with Pphar-

_{* * *}

Determination of respiratory mechanics

Once 0Res_P is determined, it is possible to derive real-time key respiratory physiological parameters for the evaluation of respiratory mechanics. This opportunity allows to verify not only if the initial setting of the HFNC apparatus 100 or the CPAP apparatus (200) is correct, but also to modify it at any time depending on the evolution of respiratory disease more objectively with respect to the variation of clinical signs.

In addition to the 0R_esp signal and in synchronous mode with respect to it, pharyngeal pressure (Pphar), esophageal pressure (PES), and gastric pressure (PG₃) signals are required for the determination of respiratory mechanics. The monitoring of pressure signals (Pphar, PES, and P_Ga) is performed by connecting their respective catheters to a DPT terminal via a tube.

If it is not possible to obtain 0R_esp, however, it is still possible to determine respiratory timing by using an acquisition of OHFNC-PNT-A (or ΦΟΡΑΡ_ΙΠ_ΡΝΤ-Α) or <t½ask_PNT-B (or CPAP_OUI_PNT-B) in Alternating Current (AC) mode.

Specifically, as it is well known, oscilloscopes can be set in such a way as to monitor only the alternate signal component. Using this modality it's possible to obtain a signal that intersects the zero flow line at the beginning and end of the intake. This method can also be applied to provide an inspirational trigger signal for use in fans that provide synchronized ventilation modes.

List of key respiratory parameters that can be detected

Below is a list of the main parameters that can be calculated by processing the signals obtained with monitoring systems 1 (HFNC) and 1000 (CPAP) as described above:

- Start of inspiration time (Tstaruns);

- End of inspiration time (T_End_ins);

- Inspiration time (Tj); - Expiration time (T_e);

- Ratio between Tj and T_e (Tj_/T_e);

- Duration of respiratory period (T_Tot);

- Respiration rate (RF);

- Inspiratory current volume (VCj);

- Expiratory current volume (VC_e);

- Volume per minute (Vmin);

- Ratio VCi/Ti (VCi/Ti);

- Ratio VCi/Te (VCi/Te);

- Inspiratory effort start time (T_Dro_P_Pes);

- Time interval between Tstaitjns and T_Dr0p__Pes (T_deia_y);

- Positive pressure at the end of intrinsic expiration (PEEPj);

- Inspiratory variation of the esophageal pressure (APes);

- Maximum variation of the esophageal pressure (APes_max);

- Transpulmonary pressure at the end of inspiration (Pt_P_end_ins_P);

- Thoracic resistance (R_t);

- Pulmonary resistance (R_p);

- Total respiratory resistance (R_resp_tot);

- Thoracic compliance (C_t);

- Pulmonary compliance (C_p);

- Dynamic pulmonary compliance (C_p__din);

- Thoracic compliance in relaxation (Ct__reiax);

- Resistive component of the inspiratory effort (Pressure Time Product) (iPTPres);

- Elastic component (pulmonary expansion) of inspiratory PTP

(iPTP_e|as_pulm),

- Elastic component (thoracic expansion) of inspiratory PTP

(iPTPeiaS-thorac),

- Elastic component linked to PEEPi of inspiratory PTP (iPTP_PEEPi);

- Total elastic component of inspiratory PTP (iPTP_eias_tot);

- Total inspiratory PTP (iPTP_tot);

- PTP_tot per minute (iPTPtot_min);

- Resistive component of inspiratory work (Work of Breathing, WOB) (iWOBres);

- Elastic component (pulmonary expansion) of inspiratory WOB (iWOB_ei_as_ pulm), Elastic component (thoracic expansion) of inspiratory

(iWOBeiasJhorac);

Elastic component linked to PEEPi of inspiratory WOB (iWOB_PEEPi) Total elastic component of inspiratory WOB (iWOB_ei_as_tot);

Total inspiratory WOB (iWOB_tot);

WOBJot per minute (iWOB__tot_min);

WOBJot per litre (iWOB_{tot N}t).

It will be appreciated that the invention allows to determine the respiratory flow of the subject (0R_esp) according to an equation such that:

wherein:

^Leak ⁼ PNode I R^ALeak ⁼ [^^pparatusJ^NT-A " ^<t^)AResidual_PNT-B) P^ANode] * PNode or

<t>Leak = [( ^Α Apparatus_PNT-A " ^<J^)AResidual_PNT-B) / ^<J^)AResidual_PNT-B] * ^Residual_PNT-B wherein 0R_esp is the respiratory flow of the patient, <t>Apparatus_PNT-A is the flow delivered by the HFNC (100) o CPAP (200) apparatus, <t>Residuai_PNT-B is the residual flow from the patient which runs through the PNT-B, 0i_eak is the leakage flow of the oro-nasal mask in case of HFNC systems (100) or the leakage flow from the airways of the patient in case of systems CPAP (200), PNode is the pressure inside the mask (3) in case of HFNC systems (100) or inside the ventilation circuit in proximity of nasal cannulas (205) in case of CPAP systems (200),

is the fluidic-dynamic resistance of the equivalent leakage canal by means of which 0i_eak is established in apnea conditions, <t>^AApparatus_PNT-A is the flow delivered by the apparatus under apnea conditions, ⁽I^)AResiduaLPNT-B is the residual flow in apnea conditions, P^ANode is the pressure inside the mask (3) or inside the ventilation circuit in proximity of nasal cannulas, under apnea conditions. It will be appreciated that the parameter <t>Apparato_PNT-A corresponds to the above mentioned parameters OHFNC_PNT-A and ΦΟΡΑΡ__ΙΠ_ΡΝΤ-Α respectively for the HFNC and the CPAP system. Similarly: the parameter <t>Residuai_PNT-B corresponds to <t½ask_PNT-B and CPAP_OUI_PNT-B; the parameter 0_Leak corresponds to 0_Mask_Leak and 0_Leak_Paz; PNode corresponds to P_MaSk and to P_Ci_rc;

corresponds to AMask_Leak and

P^ANode corresponds to P^A _Mask and to P^Acir_C;

Corresponds tO ^AHFNC_PNT-A and Φ^Λ0ΡΑΡ_ίη_ΡΝΤ-Α; ^<i^)AResidual_PNT-B corresponds to Φ^Λ _Μ35^ΡΝΤ-Β and 4>^aCPAP_OUL PNT-B-

_***

Once the respiratory physiological parameters and pulmonary mechanics data are known, the setting of HFNC 100 can be adjusted according to the flow chart of Figure 6. The latter shows a recursive adaptation mode of the flow delivered by the HFNC device 100.

An analogue diagram applies to a CPAP apparatus.

_{* * *}

The present invention has been herein described with reference to preferred embodiments. It is to be understood that other embodiments of the same inventive core may exist, as defined by the scope of protection of the claims below.

Claims

1 . A monitoring system (1 ; 1000) of respiratory quantities during the administration of oxygen at various concentrations by nasal cannulas (105, 205) or equivalent interfaces, in particular with an apparatus of H FNC {High Flow Nasal Cannulas) type (100), or of CPAP (Continuous Positive Airway Pressure) type, which monitoring system (1 ; 1000) comprises:

- a first flow detector (21 ; 1021 ; DPT-A), configured to measure, upstream of nasal cannulas (105; 205), a delivered flow (<|)Apparatus_PNT-A) of air and oxygen from the ventilation apparatus (H FNC or CPAP);

- a second flow detector (22; 1022; DPT-B), configured to measure a residual flow (<|)ResiduaLPNT-B) from the patient, combined with an oro-nasal mask (3) worn over the nasal cannulas (105), in the case of unidirectional systems, like H FNC (100), or inserted in the expiratory branch of the circuit in the case of bidirectional systems like CPAC (200);

- detection means of the pharyngeal pressure (Pphar), in particular a pharyngeal catheter (4) associated to a pressure transducer (DPT-D);

- detection means of the esophageal pressure (P_Es) and gastric pressure (P_Ga), in particular an esophagus-gastric catheter (5) associated to respective pressure transducers (DPT-E, DPT-F);

- detection means of a node pressure which can be configured as pressure inside the oro-nasal mask (PMask) (3), in particular a mask catheter (6) associated to a pressure transducer (DPT-C) in the case of H FNC systems, or as pressure inside the circuit in proximity of the nasal cannulas (Pare), in particular a circuit catheter (1006) associated to a pressure transducer (DPT-C) in the case of CPAC system; and

- a processing unit (10; 1010), in communication with said detection means and configured for the determination of parameters representative of the respiration and/or pulmonary mechanics,

wherein said processing unit (10; 1010) is configured to determine a respiratory flow of the sub ect (0R_esp) according to the formula:

,

wherein:

^Leak ⁼ Puode I F^\A|_eak ⁼ [(^Apparatus.PNT-A - ^AResidual_PNT-B) P^ANode] * PNode or

Apparatus_PNT-A " ^<J^)AResidual_PNT-B) / ^<J^)AResidual_PNT-B] ^{* <}J⁾Residual_PNT-B wherein <t>Apparatus_PNT-A is the flow delivered by the HFNC or CPAP apparatus, ResiduaLPNT-B is the residual flow from the patient, ^AR_esiduai_PNT-B is the residual flow under apnea conditions, 0i_eak is a leak flow of the oro-nasal mask (3) in the case of HFNC systems (100) or the leak flow of the airways of the patient in the case of CPAC systems (200), P_N0de is the pressure inside the mask (3) in the case of HFNC systems (100) or inside the ventilation circuit in proximity of the nasal cannulas (205) in the case of CPAP systems (200), P^ANode is the pressure inside the mask (3) or inside the ventilation circuit near the nasal cannulas, under apnea conditions, R^Ai_eak is the flow resistance of the equivalent loss channel in which 0i_eak is established under apnea condition, and ^AA_PParatus_PNT- A is the flow delivered by the apparatus under apnea condition.

2. The monitoring system (1 ) according to the preceding claim, wherein said rocessing unit (10) is configured to verif that

⁺ {[(Φ^ΑΗΡΝΟ_ΡΝΤ-Α " Φ ^AMask_PNT-B] * Φ Mask_PNT-B} > 0,

Wherein ΦΜ₃₅^ΡΝΤ-Β is the residual flow, Φ^ΑΗΡΝΟ_ΡΝΤ-Α is the flow delivered under apnea conditions, PMask is the pressure inside the mask (3), Φ^ΑΜ₃₅^ΡΝΤ-Β is the residual flow under apnea conditions, P^AMask is the pressure inside the mask (3) under apnea conditions; PMask is the pressure inside the mask (3).

3. The monitoring system (1 ) according to any of the preceding claims, comprising a device (1 1 ) connected to said pharyngeal catheter (4) and configured to dispense a flushing flow (⁽^lushing) therethrough.

4. The monitoring system (1 ; 1000) according to the preceding claim, wherein said processing unit (10; 1010) is configured to determine the phar ngeal pressure (Pphar according to the formula:

Pphar

wherein P_Phar is the pharyngeal pressure, PDPT-D is the pressure detected by said pharyngeal pressure transducer (DPT-D), Rcat__Phar is the flow resistance of said pharyngeal catheter (4) and ΦΡΙ^Μ_Γ^ is the dispensed flushing flow.

5. The monitoring system (1 ; 1000) according to any of the preceding claims, further comprising an oscilloscope (7) in communication with one or more of said detection means and with said processing unit (10; 1010) and arranged upstream of the latter.

6. The monitoring system (1 ) according to any of the preceding claims, comprising said oro-nasal mask (3) wearable above the nasal cannulas (105).

7. The monitoring system (1 ; 1000) according to any of the preceding claims, comprising an oscilloscope (7) interposed between said detection means and said processing unit (10, 1010) and in communication with the latter.

8. The monitoring system (1 ; 1000) according to any of the preceding claims, wherein said processing unit (10; 1010) is configured to determine one or more of the following parameters of respiratory mechanics: Start of inspiration time (Tstaitjns); End of inspiration time (T_End_ins); Inspiration time (Tj); Expiration time (T_e); Ratio between Tj and T_e (Tj_/T_e); Duration of respiratory period (T_Tot); Respiration rate (RF); Inspiratory current volume (VC,); Expiratory current volume (VC_e); Volume per minute (V_min); Ratio between VC, and Tj (VCi/Tj); Ratio between VC_e and T_e (VC_e/T_e); Inspiratory effort start time (T_Dro_P_Pes); Time interval between Tstartjns and T_Dro_P_Pes (T_deia_y); Positive pressure at the end of intrinsic expiration (PEEPj); Inspiratory variation of the esophageal pressure (APes); Maximum variation of the esophageal pressure (APes_max); Transpulmonary pressure at the end of inspiration (Pt_P_end_ins_P); Thoracic resistance (R_t); Pulmonary resistance (R_p); Total respiratory resistance (Rrespjot); Thoracic compliance (C_t); Pulmonary compliance (C_p); Dynamic pulmonary compliance (C_p__din); Thoracic compliance in relaxation (C_t__reiax); Resistive component of the inspiratory effort (Pressure Time Product, PTP) (iPTPpes); Elastic component (pulmonary expansion) of inspiratory PTP (iPTPeias_puim); Elastic component (thoracic expansion) of inspiratory PTP (iPTPeiasjhorac); Elastic component linked to PEEPi of inspiratory PTP (iPTPpEEPi); Total elastic component of inspiratory PTP (iPTP_eias_tot); Total inspiratory PTP (iPTP_tot); PTPtot per minute (iPTP_tot_min); Resistive component of inspiratory work (Work of Breathing, WOB) (iWOB_res); Elastic component (pulmonary expansion) of inspiratory WOB (iWOB_ei_as_puim); Elastic component (thoracic expansion) of inspiratory WOB (iWOB_ei_as_thorac); Elastic component linked to PEEPi of inspiratory WOB (iWOB_PEEPi); Total elastic component of inspiratory WOB (iWOB_eiast_tot); Total inspiratory WOB (iWOB_tot); iWOB_tot per minute (WOB__tot_min); iWOB_tot per litre (WOB_totjit).

9. An administration apparatus of an oxygen flow at various concentrations through nasal cannulas (105; 205) or other interface, comprising a monitoring system (1 ; 1000) according to any of the preceding claims.

10. An apparatus for applying a positive airway pressure comprising a monitoring system (1000) according to any one of the preceding claims.

1 1 . A method of monitoring respiratory quantities during the administration of air and oxygen through nasal cannulas (105; 205) or equivalent interfaces, in particular with an apparatus of HFNC (High Flow Nasal Cannulas) type (100), or of CPAP (Continuous Positive Airway Pressure) type (200), which monitoring method provides:

^■ a detection of supplied air and oxygen flow (<|)Apparatus_PNT-A) upstream of nasal cannulas (105, 205);

^■ a detection of residual flow (<|)ResiduaLPNT-B) running through an oro-nasal mask (3) worn over the nasal cannulas (105) in the case of unidirectional systems, like HFNC, or inserted in the expiratory branch of the circuit in the case of bidirectional systems like CPAP; ^■ a detection of pharyngeal pressure (Pphar), in particular by means of a pharyngeal catheter (4) associated to a pressure transducer (DPT-D);

^■ a detection of esophageal pressure (P_Es) and gastric pressure (PGa), in particular by means of an esophagus-gastric catheter (5) associated to respective pressure transducers (DPT-E, DPT-F);

^■ a detection of node pressure (PNode) inside the oro-nasal mask (3) in the case of HFNC system or inside the ventilation circuit in proximity of the nasal cannulas (205) in the case of CPAP systems, in particular by means of a mask catheter (6) or a circuit catheter (1006) associated to a pressure transducer (DPT-C);

^■ a determination of parameters representative of respiration and/or pulmonary mechanics on the basis of said detections

which provides the determination of a respiratory flow of the subject (<|>Resp) accordin to the formula:

,

wherein:

^Leak ⁼ PNode F^\A|_eak ⁼ [(^Apparatus_.PNT-A - ^AResidual_PNT-B) P^ANode] * PNode or

Apparatus_PNT-A ^{" <}J^)AResidual_PNT-B) / ^<J^)AResidual_PNT-B] * ^<J⁾Residual_PNT-B wherein <t>Ap_Paratus_PNT-A is the flow delivered from the HFNC or CPAP apparatus, ResiduaL PNT-B is the residual flow of the patient, ^AR_eSiduai_PNT-B is the residual flow under apnea conditions, 0i_eak is a leak flow of the oro-nasal mask (3) in the case of HFNC system or the leak flow of the patient's airways in the case of CPAP systems, P_N0de is the pressure inside the mask (3) in the case of HFNC system (100) or inside the ventilation circuit near the nasal cannulas (205) in the case of CPAP systems (200), P^ANode is the pressure inside the mask (3) or inside the ventilation circuit in proximity of the nasal cannulas under apnea conditions,

is the flow resistance of the equivalent loss channel in which 0i_eak is established under apnea condition, and ^AA_PParatus_PNT-A is the flow delivered by the apparatus under apnea condition.

12. The monitoring method according to claim 1 1 , which provides dispensing a flushing flow (crus_hing) through said pharyngeal catheter (4).

13. The monitoring method according to the preceding claim, which provides the determination of haryngeal pressure (Pphar) according to the formula:

Pphar

* FIushing)

wherein P_Phar is the pharyngeal pressure, PDPT-D is the pressure detected by said pharyngeal pressure transducer (DPT-D), Rc_at__Phar is the flow resistance of said pharyngeal catheter (4) and crus_hing is the dispensed flushing flow.

14. The monitoring method according to any of claims 1 1 to 13, which provides the determination of the respiratory timing by means of acquisition of dispensed flow (<t>A_Pparatus_PNT-A) or residual flow (<t>Residuai_PNT-B) in an Alternating Current (AC) mode. Said method could also be applied for obtaining a signal of inspiratory trigger to be used in fans which provide synchronized ventilation modes.

15. The monitoring method according to any of claims 1 1 to 14, which provides the determination of one or more of the following parameters of respiratory mechanics: Start of inspiration time (Tstait_jns); End of inspiration time (Tendjns); Inspiration time (Tj); Expiration time (T_e); Ratio between Tj and T_e (Tj_/T_e); Duration of respiratory period (T_Tot); Respiration rate (RF); Inspiratory current volume (VCj); Expiratory current volume (VC_e); Volume per minute ( min); Ratio between VCj and Tj (VCj/Tj); Ratio between VC_e and T_e (VC_e/T_e); Inspiratory effort start time (T_Dro_P_Pes); Time interval between Tstaitjns and TDro_P_Pes (Tdeiay); Positive pressure at the end of intrinsic expiration (PEEPj); Inspiratory variation of the esophageal pressure (A_Pes); Maximum variation of the esophageal pressure (Ap_es_max); Transpulmonary pressure at the end of inspiration (Pt_P_end_ins_P); Thoracic resistance (R_t); Pulmonary resistance (R_p); Total respiratory resistance (R_resp_tot); Thoracic compliance (C_t); Pulmonary compliance (C_p); Dynamic pulmonary compliance (C_p__din); Thoracic compliance in relaxation (C_t__reiax); Resistive component of the inspiratory effort (Pressure Time Product) (iPTP_res); Elastic component (pulmonary expansion) of inspiratory PTP (iPTP_eias__Puim); Elastic component (thoracic expansion) of inspiratory PTP (iPTP_ei_as_thorac); Elastic component linked to PEEPi of inspiratory PTP (iPTPp_EEPi); Total elastic component of inspiratory PTP (PTP_ei_as_tot); Total inspiratory PTP (PTP_tot); PTP_tot per minute (PTP_tot_min); Resistive component of inspiratory work (Work of Breathing, WOB) (iWOB_res); Elastic component (pulmonary expansion) of inspiratory WOB (iWOB_eias_puim); Elastic component (thoracic expansion) of inspiratory WOB (iWOB_eias_thorac); Elastic component linked to PEEPi of inspiratory WOB (IWOBPEEP ; Total elastic component of inspiratory WOB (iWOB_eias_tot); Total inspiratory WOB (iWOB_tot); WOBJot per minute (iWOB__tot_min); WOBJot per litre (iWOB_tot_iit)-