Abstract:
An injection system for the delivery of a gaseous substance to a patient respiratory system is described herein. The injection system includes a control unit and a valve assembly including a valve and a valve actuator allowing partial opening of the valve and controlled by the control unit. The control unit is supplied with gas flow data and controls the valve assembly so that the opening of the valve is a function to the gas flow to thereby enable the control over the concentration of the gaseous substance delivered to the patient.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates to an injection system for delivery of a gaseous substance. More specifically, the present invention relates to an injection system for delivery of a gaseous substance to a patient, where the concentration of the gaseous substance delivered to the patient may be modified during the patient inspiratory phase and may be gradually modified over a predetermined number of patient inspiratory phases.  
       BACKGROUND OF THE INVENTION  
       [0002]     It has been found that various chemical compounds, such as, for example, nitric oxide (NO), administered during a patient inspiratory phase may provide beneficial effects.  
         [0003]     For example, NO presents some lung vasodilator properties that may be helpful for respiratory distress conditions such as respiratory distress syndrome of newborn.  
         [0004]     Apparatus for delivering such gaseous chemical compounds have therefore been designed to deliver the compounds during the patient&#39;s inspiratory phase.  
         [0005]     One such apparatus is described in Canadian Patent Application No. 2,106,696, filed on Sep. 22, 1993 and published on Mar. 25, 1994 and naming Robert Briand and Marie-Hélène Renaudin as inventors. In this document, Briand et al. describe an apparatus for delivering controlled doses of NO to the respiratory system of the patient without conventional pre-mixing of the NO with oxygen supplied by a ventilator device. The apparatus therefore includes means for detecting the beginning of a patient inspiratory phase and to open an electromagnetic valve for a predetermined duration to supply a controlled dose of NO. The duration and the pressure of the NO supplied dose is adjusted so as to obtain the desired NO concentration with respect to the average inhalation volume of the patient. The NO dose supplied is therefore not directly related to the inhalation volume of the patient. Of course, there is no NO injection during the expiration phase.  
         [0006]     A major drawback of the apparatus described by Briand et al. is the automatic opening of the electromagnetic valve for a predetermined duration each time the beginning of an inhalation phase is detected. Indeed, if the patient repetitively draws short breaths, harm may be caused by the high concentration of NO injected to the patient.  
         [0007]     In an article entitled: “Comparison of two administration techniques on inhaled nitric oxide on nitrogen dioxide production”, published in Canadian journal of Anaesthesiology  1995 , Vol. 42: 10, pages 922-927, Dubé et al. describe an injection system for delivering NO during inspiratory phase. In this injection system, an electronic circuit detects the beginning and the end of each inspiration by processing a flow signal supplied by a ventilator. At the beginning of the inspiratory phase, the electronic circuit opens a solenoid valve and NO is injected into the respiratory line. At the end of the inspiratory phase, the electronic circuit closes the solenoid valve and the injection of NO is stopped.  
         [0008]      FIG. 1  of the appended drawings is a graph of the inspiratory gas flow  20  vs time for a conventional ventilator when the ventilator is in a first mode. When it is in this mode, the flow of inspiratory gas is constantly delivered for a predetermined duration (inspiratory phase  22 ) and the patient then expires (expiratory phase  24 ). In the injection system proposed by Dubé et al., when the gas flow reaches a predetermined threshold level  26 , a solenoid valve is open, delivering NO to the patient. The line  28  illustrates the injected flow of NO in the inspiration circuit over time. It is to be noted that the scale is different for the flow of inspiratory gas  20  and the flow  28  of NO. Indeed, line  28  illustrating the flow of NO is shown scaled up for illustrative purposes.  
         [0009]     Since the solenoid valve used by Dubé et al. is of the type fully open/fully closed, the flow  28  of NO is constant when the valve is open. As can be seen from  FIG. 2 , the concentration  29  of NO is essentially constant over time during the inspiratory phases. When the inspiratory gas flow  20  falls below the threshold level  26 , the solenoid valve is closed, stopping the flow of NO.  
         [0010]      FIG. 3  is a graph of the inspiratory gas flow  30  vs time for a conventional ventilator when the ventilator is in a second ventilating mode. When it is in this mode, the flow of gas is not constantly delivered for a predetermined duration but follows a particular curve during the inspiratory phase  32  and the patient then expires (expiratory phase  34 ). In the injection system proposed by Dubé et al., when the gas flow reaches a predetermined threshold level  36 , the solenoid valve is open delivering NO to the patient. The line  38  illustrates the flow of NO over time. Again, it is to be noted that the scale is different for the flow of inspiratory gas and the flow  38  of NO. Indeed, line  38  illustrating the flow of NO is shown scaled up for illustrative purposes.  
         [0011]     Since the solenoid valve used by Dubé et al. is of the type fully open/fully closed, the flow of NO is constant when the valve is open. As can be seen from  FIG. 4 , the concentration of NO (line  39 ) is not constant over time during the inspiratory phases but varies inversely with the flow of gas since the flow of NO is constant. When the inspiratory Gas flow  30  falls below the threshold level  36 , the solenoid valve is closed.  
         [0012]     A drawback of the injection system of Dubé et al. is that, in certain cases, the NO concentration is not constant during the inspiratory phase.  
         [0013]     Canadian patent application No. 2,133,516 filed on Oct. 3, 1994 and naming Bathe et al. as inventors describes a nitric oxide (NO) delivery system monitoring the inspiratory gas flow of a patient and controlling a proportional valve to allow a calculated flow of NO to enter the inspiratory gas flow. The delivery system calculates the flow of NO in order to maintain a constant, user programmable, NO concentration in the inspiratory gas.  
         [0014]     A drawback of the delivery system of Bathe et al. is that, while the delivery system may be programmed so that the concentration of NO in the inspiratory gas flow is constant, there are no provisions to modify the concentration of the NO during a particular inspiratory phase, or to program the variation of the concentration of NO over a number of successive inspiratory phases in view of gradually increasing or decreasing the concentration of NO supplied to the patient.  
       OBJECTS OF THE INVENTION  
       [0015]     An object of the present invention is therefore to provide an improved apparatus for the delivery of gaseous substances.  
       SUMMARY OF THE INVENTION  
       [0016]     More specifically, in accordance with the present invention, there is provided an injection system for the delivery of a gaseous substance from a container to a patient through a conduit coupled to the patient respiratory system; the injection system comprising: 
        a control unit controlling the injection system;     a valve assembly in connection with the conduit to selectively allow the delivery of the gaseous substance from the container to the conduit; the valve assembly including a valve and valve actuating means allowing variable opening of the valve; the valve actuating means being coupled to the control unit to be controlled thereby;     a flowmeter quantitatively measuring inspiratory gas flow in the conduit; the flowmeter being coupled to the control unit to supply inspiratory gas flow data thereto;     the control unit controlling the valve assembly so that the variable opening of the valve is responsive to the inspiratory gas flow in the conduit.        
 
         [0021]     According to another aspect of the present invention, there is provided an injection system for the delivery of a gaseous substance from a container to a patient through a conduit coupled to the patient respiratory system; the respiratory system of the patient being also coupled to a ventilator forcing inspiratory gas therein; the injection system comprising: 
        a control unit controlling the injection system; the control unit receiving inspiratory gas flow data from the ventilator;     a valve assembly in connection with the conduit to selectively allow the delivery of the gaseous substance from the container to the conduit; the valve assembly including a valve and valve actuating means allowing variable opening of the valve; the valve actuating means being coupled to the control unit to be controlled thereby;     the control unit controlling the valve assembly so that the variable opening of the valve is responsive to the inspiratory gas flow supplied to the patient.        
 
         [0025]     A major advantage of the present invention concerns the variable opening of the valve to increase or decrease the quantity of the gaseous substance delivered to the patient. Hence, it is possible to control the opening of the valve so that the variable opening of the valve is responsive to the inspiratory gas flow directed towards the respiratory system of the patient and thereby controlling the concentration of the gaseous substance delivered to the patient.  
         [0026]     Other objects, advantages and features of the present invention will become more apparent upon reading of the following non restrictive description of preferred embodiments thereof, given by way of example only with reference to the accompanying drawings.  
         [0027]     The subject of the present invention was developed at “Le Département de physique biomédicale, Pavillon Notre-Dame, Centre hospitalier de l&#39;Université de Montréal (CHUM)” 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0028]     In the appended drawings:  
         [0029]      FIG. 1 , which is labelled “PRIOR ART”, illustrates a graph of flow vs time for a conventional ventilator when the ventilator is in a first mode;  
         [0030]      FIG. 2 , which is labelled “PRIOR ART”, illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 1 ;  
         [0031]      FIG. 3 , which is labelled “PRIOR ART”, illustrates a graph of flow vs time for a conventional ventilator when the ventilator is in a second mode;  
         [0032]      FIG. 4 , which is labelled “PRIOR ART”, illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 3 ;  
         [0033]      FIG. 5  schematically illustrates an injection system according to an embodiment of the present invention, the injection system being installed to a conventional ventilator;  
         [0034]      FIG. 6  schematically illustrates the injection system of  FIG. 5  when the injection system is not connected to a ventilator;  
         [0035]      FIG. 7 , illustrates a graph of flow vs time for a injection system according to the present invention, the inspiratory phase illustrated could represent a long inspiration;  
         [0036]      FIG. 8  illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 7 ;  
         [0037]      FIG. 9 , illustrates a graph of flow vs time for a injection system according to the present invention, the inspiratory phase illustrated could represent a short inspiration;  
         [0038]      FIG. 10  illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 9 ;  
         [0039]      FIG. 11  illustrates a graph of flow vs time for a injection system according to the present invention, the inspiratory phase illustrated generally representing a long inspiration, the flow of injected gaseous substance being modified during the same inspiration;  
         [0040]      FIG. 12  illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 11 ;  
         [0041]      FIG. 13 , illustrates a graph of flow vs time for a injection system according to the present invention, the inspiratory phase illustrated generally representing a long inspiration, the flow of injected gaseous substance being modified during the same inspiration;  
         [0042]      FIG. 14  illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 13 ;  
         [0043]      FIG. 15  is a block diagram showing the simplified operation of the injection system of  FIG. 5 ;  
         [0044]      FIG. 16  is a block diagram showing the operation of the injection system of  FIG. 5 , including safety features;  
         [0045]      FIG. 17  illustrates a graph of flow vs time for a injection system according to the present invention, the inspiratory phases illustrated generally representing long inspirations, the flow of injected gaseous substance being modified between consecutive inspirations;  
         [0046]      FIG. 18  illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 17 ;  
         [0047]      FIG. 19  illustrates a graph of flow vs time for a injection system according to the present invention, the inspiratory phases illustrated generally representing long inspirations, the flow of injected gaseous substance being modified between consecutive inspirations; and  
         [0048]      FIG. 20  illustrates a graph of nitric oxide concentration vs time corresponding to the graph of  FIG. 19 . 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0049]      FIG. 5  of the appended drawings illustrates an injection system  100  according to an embodiment of the present invention. The injection system  100  includes a user interface unit  101 , a control unit  102 , a temperature and humidity measuring unit  103 , a valve assembly  104  a backup unit  105  an inspiratory gas flowmeter  106  and a gaseous substance flowmeter  107 .  
         [0050]     The injection system  100  is illustrated in  FIG. 5  as being connected to a conventional ventilator  108  through a data cable  110 , to a source of a gaseous substance  112  through a conduit  114  and to a patient  116  through an inspiratory conduit  118 .  
         [0051]     It is to be noted that the following description of the injection system  100  will be given with the particular example of nitric oxide (NO) injection, but that the system  100  could be used to inject other gaseous substance in the respiratory system of a patient.  
         [0052]     The source of gaseous substance (NO)  112  includes a NO container  120 , a pressure reducer  122  connected to the container  120  and a precision flowmeter  124  adjusting the maximum flow rate of NO in the injection system  100  and connected to the pressure reducer  122 . The conduit  114  pneumatically connects the precision flowmeter  124  to a fluid input  126  of the valve assembly  104  and to a fluid input  127  of a backup valve assembly  129  of the backup unit  105  as will be described hereinafter.  
         [0053]     The ventilator  108 , when in operation, repetitively supplies a predetermined quantity of inspiratory gas to the respiratory system of the patient  116  through the inspiratory conduit  118  connected to an endotracheal tube  128 .  
         [0054]     The inspiratory gas supplied to the patient goes through the flowmeter  106 , via conduit  130 , thereby enabling the flowmeter  106  to measure the inspiratory gas flow supplied to the patient  116 . Inspiratory gas flow data is supplied to the control unit  102  via a data cable  132 , interconnecting an inspiratory gas flow data output  134  of the flowmeter  106  and an inspiratory gas flow data input  136  of the control unit  102 . Of course, the inspiratory gas flow data is either in analog or in digital format, compatible with the control unit  102 .  
         [0055]     The data cable  132  is illustrated in dashed line in  FIG. 5  since the data cable  132 , along with the flowmeter  106 , are not essential to the operation of the injection system  100  when the injection system  100  is connected to a conventional ventilator  108  provided with a flow data output. Indeed, the ventilator  108  includes an inspiratory gas flow data output  138  electrically connected to an inspiratory gas flow data input  140  of the control unit  102  through the data cable  110 . The control unit  102  is therefore supplied with inspiratory gas flow data from either the independent flowmeter  106  or the data flow output  138  of the ventilator  108 .  
         [0056]     The control unit  102  includes a control output  142  electrically connected to a control input  144  of the valve assembly  104  via a control cable  146 . The control unit  102  therefore controls the variable opening of the valve assembly  104 . The valve assembly  104  may be a normally closed valve assembly or a normally open valve assembly but is advantageously a normally closed valve assembly for safety reasons. Indeed, it is advantageous that the valve automatically closes upon loss of electrical power.  
         [0057]     The valve assembly  104  also includes a fluid output  148  pneumatically connected a fluid input  149  of the gaseous substance flowmeter  107  through a conduit  150 . The flowmeter  107  includes a fluid output  151  connected to conduit  118  through a conduit  152  and a “Y” junction  153 .  
         [0058]     As can be seen from  FIG. 5 , the ventilator  108  also includes an expiratory gas inlet  154  connected to the conduit  118  through a conduit  156  and a “Y” junction  158 . The patient&#39;s expiration gases is therefore returned to the ventilator  108 .  
         [0059]     The temperature and humidity measuring unit is provided with conventional means to measure relative humidity and temperature and to supply this data to the control unit  102  via a data cable  111 . The measure of both humidity and temperature will enable the control unit  102  to determine the precise flow of the inspiratory gas and subsequently adjust the flow of NO.  
         [0060]     The user interface unit  101  is connected to the control unit  102  via a data cable  113  enabling the user interface unit  101  to supply data pertaining to user&#39;s inputs to the control unit  102  and enabling the control unit  102  to supply data pertaining to information to be displayed on a display portion (not shown) of the user interface unit  101 .  
         [0061]     For example, the user interface unit  101  includes controls operable by the user to determine the desired concentration of NO to be injected, the type of injection (constant or according to a predetermined pattern) and the variation of the NO concentration over time. These two controls will be further described hereinafter.  
         [0062]     The display portion (not shown) of the user interface unit  101  can be used to display the following information: 
        the total amount of NO injected to the patient (mole);     the concentration of inspiratory NO/NO 2  (calculated) (ppm);     the decrease of FiO 2  following the NO injection (%); the flow of NO (cc/min);     the quantity of NO remaining in the container  120  (litres);     the NO flow curve; and     the ventilation flow curve.        
 
         [0069]     It is believed within the skills of one of ordinary skills in the art to design the control unit  102  as to calculate or to obtain the above-mentioned quantities and concentration from the flowmeters and some initial data, and to format them to be displayed on a conventional display device. Or course, other data, such as, for example, the oxygen concentration supplied by the ventilator, is advantageously supplied to the control unit  102  to enable the determination of the FiO 2 . It is also to be noted that models predicting the NO 2  concentration exist and are believed sufficient for the present purpose.  
         [0070]     The valve assembly  104  includes a valve portion  160  including the fluid input  126  and output  148  and a valve actuating portion  162  including the control input  144 . The valve actuating portion  162  advantageously transduces an electric signal supplied to the control input  144  to a mechanical opening of the valve portion  160 .  
         [0071]     As mentioned hereinabove, the injection system  100  includes a backup unit  105  intended to be automatically activated should problems occur with the injection system  100 . Indeed, since NO is a drug, the abrupt stopping of the injection of NO could be armful to a patient. The backup unit  105  is thus provided with a backup valve assembly  129  having a valve portion  137  including the fluid input  127  and a fluid output  131  connected to the conduit  118  via a conduit  133  and a “Y” junction  135 . The backup valve assembly  129  also includes a valve actuating portion  139  connected to the control unit  102  via a data cable  141  to monitor the status of operation of the control unit  102 . The flow of NO through the valve portion  137 , when it is open, is manually adjustable by the user. Therefore, the valve portion  137  automatically supplies a predetermined flow of NO should the injection system  100  fail. It is to be noted that this predetermined flow of NO is generally adjusted so as to be small to prevent injuries to the patient.  
         [0072]     In a most simple embodiment, the valve portion  137  is a normally open valve that is configured manually and that is kept closed by a power signal coming from the control unit  102  via the data cable  141  and the valve actuating portion  139 . If the control circuit  102  fails so that the power signal is no longer present, for example if the electrical power fails, the valve portion  137  reverts to its normally open state. Of course, other types of detection are possible to determine failure of the other elements of the injection system  100 .  
         [0073]     A monitoring unit  161  may also be connected to a monitoring aperture  163  via a conduit  165  when monitoring is necessary. It is to be noted that continuous monitoring is not believed required for the injection system of the present invention. However, monitoring at the beginning of the injection of NO is advantageous since the user may verify that the concentration of NO injected, as determined by the monitoring unit  161 , is equal to the concentration of NO displayed on the user interface unit  101 .  
         [0074]     In operation, when the control unit  102  determines, with the inspiratory gas flow data supplied by either the flowmeter  106  or the ventilator  108 , that the patient enters an inspiratory phase, it generates a control signal, supplied to the valve assembly  104  via the control cable  146 , to cause the opening of the valve assembly  104  that will allow NO to be transferred from the container  120  to the respiratory system of the patient&#39;s through the conduits  114 ,  150 ,  152 ,  118  and endotracheal tube  128 . The opening of the valve assembly  104  is variable and is, in a first mode, a function of the inspiratory gas flow data supplied to the control unit  102 . Therefore, the concentration of NO injected to the patient during the inspiratory phase is essentially constant since the opening of the valve assembly  104  is proportional to the inspiratory gas flow detected. As will be described hereinafter with reference to  FIGS. 11-14 , the concentration of injected NO could be non linear with respect to time.  
         [0075]     Turning now to  FIG. 15 , of the appended drawings, a simplified block diagram  200  of the operation of the injection system will be described. When the system is started (step  202 ) it is initialized (step  203 ). A sample of the inspiratory gas flow (IGF) is then taken (step  204 ), and is converted to a digital value (step  206 ) before being supplied to a comparator (step  208 ). The threshold level (REF, step  210  and numeral  26  in  FIG. 5 ) is also converted to a digital value (step  212 ) before being supplied to the comparator of step  208 .  
         [0076]     The comparator then compares IGF and REF to determine if the inspiratory gas flow is greater than the threshold. If so, the valve assembly  104  is activated (step  214 ) and the opening of the valve  160  by the valve actuating portion  162  is a function of the inspiratory gas flow level (IGF). If not, the valve  160  is deactivated. Of course, as will be described hereinafter, the opening of the valve  160  may be non linear.  
         [0077]      FIG. 6  of the appended drawings illustrates the injection system  100  used without a ventilator. The only major difference in the operation of the injection system  100  when used without a ventilator is that the inspiratory gas flow data is supplied to the control unit by the flowmeter  106  since the ventilator  108  is not present.  
         [0078]     This is a major advantage to be able to use the injection system  100  without a ventilator since the injection of NO may be continued even though the patient  116  does not require a ventilator. The use of the injection system  100  without a ventilator is possible, without danger to the patient, because of the proportional opening of the valve according to the inspiratory gas flow level. Indeed, even if the patient draws short breaths, the concentration of NO with be essentially constant during the inspiratory phases.  
         [0079]      FIG. 7  of the appended drawings is a graph schematically illustrating the flow  300  vs time for unassisted respiration by a patient. During the inspiratory phase  302  the inspiratory gas flow rise and falls to form a semi-sinusoidal curve. The patient then expires (see expiratory phase  304 ). When the injection system  100 , as illustrated in  FIG. 6 , is used to inject NO to the patient during the inspiratory phase  302 , the flow  306  of NO will begin when the inspiratory gas flow reaches a predetermined threshold 308. The rate of NO injection will then follow the inspiratory gas flow. When the inspiratory gas flow falls below the threshold level  308 , the flow of NO is stopped. It is to be noted that the scale is different for the inspiratory gas flow and the flow  306  of NO. Indeed, line  306  illustrating the flow of NO is shown scaled up for illustrative purposes.  
         [0080]     As can be seen from  FIG. 8 , that schematically illustrates the NO concentration  310  vs time, the concentration of NO is constant during the patient&#39;s inspiratory phase.  
         [0081]      FIGS. 9 and 10  are respectively similar to  FIGS. 7 and 8  but illustrate a patient taking a relatively short inspiration. As can be seen from  FIG. 10 , a resulting NO concentration  310 ′ is essentially equal to the NO concentration  310  of  FIG. 8 . Indeed, with the proportional opening of the valve injecting the NO, changes in the inspiratory gas flow does not modify the injected NO concentration.  
         [0082]     As will be readily apparent to one skilled in the art, the inspiratory gas supplied to the patient during the beginning of the inspiratory phase will reach the alveola of the patient, and the inspiratory gas supplied to the patient during the end of the inspiratory phase will stay in the trachea and bronchial tree.  
         [0083]      FIGS. 11 and 12  illustrate the operation of the injection system of  FIG. 5  or  6  when the opening of the valve assembly  104  is not linear but varies in time to deliver a higher concentration  406  of NO during the beginning of the inspiratory phase  402  and to decrease the concentration of NO (see line  408 ) after a predetermined and programmable time period  410 . Indeed, as described hereinabove, the user interface unit  101  includes controls to determine the shape on the NO concentration during each inspiratory phase.  
         [0084]     The NO flow pattern illustrated in  FIG. 12  could be beneficial to a patient who requires a larger concentration of NO in his alveola than in his bronchial tree.  
         [0085]     Similarly,  FIGS. 13 and 14  illustrate the operation of the injection system of  FIG. 5  or  6  when the opening of the valve assembly  104  is not linear but varies in time to deliver a lower concentration  406 ′ of NO during the beginning of the inspiratory phase  402 ′ and to increase the concentration of NO (see line  408 ′) after a predetermined and programmable time period  410 ′. Again, as described hereinabove, the user interface unit  101  includes controls to determine the shape on the NO concentration during each inspiratory phase.  
         [0086]     The NO flow pattern illustrated in  FIG. 14  could be beneficial to a patient who requires a larger concentration of NO in his bronchial tree than in his alveola.  
         [0087]     One skilled in the art will easily be able to modify the configuration of the control unit  102  to achieve the NO concentrations of  FIG. 12  or  14 , or of any other suitable NO concentration.  
         [0088]     Turning now briefly to  FIGS. 17 and 18 , the control unit  102  may also be configured, via the user interface unit  101 , to progressively decrease the NO concentration injected to the patient over a predetermined number of injection phases or over a predetermined time. The flow of NO ( 500   a - 500   d  in  FIG. 17 ) is thus decreased of a minute amount at each inspiratory phase  502   a - 502   e  to yield decreasing NO concentrations  504   a - 504   d  in  FIG. 18 . Of course, many inspiratory phases (not shown) are taken by the patient between adjacent inspiratory phases illustrated.  
         [0089]     Turning now briefly to  FIGS. 19 and 20 , the control unit  102  may also be configured, via the user interface unit  101 , to progressively increase the NO concentration injected to the patient over a predetermined number of injection phases or over a predetermined time. The flow of NO ( 600   b - 600   e  in  FIG. 19 ) is thus increased of a minute amount at each inspiratory phase  602   a - 602   e  to yield decreasing NO concentrations  604   b - 604   e  in  FIG. 20 . Of course, many inspiratory phases (not shown) are taken by the patient between adjacent inspiratory phases illustrated.  
         [0090]      FIG. 16  is a block diagram illustrating an other mode of operation of the injection system  100 . It is to be noted that the mode of operation of  FIG. 16  could be used when the injection system  100  is used in conjunction with a ventilator  108  (see  FIG. 5 ). However, this mode of operation is advantageously used when the injection system  100  is used without a ventilator as can be seen in  FIG. 6 .  
         [0091]     The mode of operation of  FIG. 16  is similar to the mode of operation of  FIG. 15 . The extra steps, described hereinafter, are taken to provide safe operation of the injection system  100 .  
         [0092]     In step  216 ′, a first variable (T inj ), representing the duration of an injection, is reset and a second variable (T bet inj ), representing the duration between injection, in incremented. The formula f(IGF) representing the opening variations of the valve over time is determined using the data supplied by the user via the user interface unit  101  and other data of the system such as, for example, temperature and humidity data supplied by the measuring unit  103 .  
         [0093]     Then, in step  218 , the second variable T bet inj  is compared to a predetermined reference number (Y, steps  220  and  222 ) to activate an alarm and stop the injection system (step  224 ) should T bet inj  be greater than Y. This alarm would indicate that there is a condition preventing the normal injection of NO and that supervision is required.  
         [0094]     Similarly, in step  214 ′, T inj  is incremented and T bet inj  is reset. Then, in step  226 , the second variable T inj  is compared to a predetermined reference number (X, steps  228  and  230 ) to activate an alarm and stop the injection system (step  232 ) should T inj  be greater than X. This alarm would indicate that a malfunction exists in the injection system and that the valve is continuously open.  
         [0095]     Of course, the analog to digital conversion steps  206 ,  212 ,  222  and  230  could be omitted if the data is already in a digital format.  
         [0096]     As will be apparent to one of ordinary skill in the art, the variable opening of the valve assembly  104  is not essentially proportional to the inspiratory gas flow supplied to the patient. Indeed, the opening could be responsive to the inspiratory gas flow in any other suitable manner.  
         [0097]     It is to be noted that the concentration of NO and of NO 2  (or of any other gaseous substance injected and their derivative) could be monitored downstream from the “Y” junction  153  by using an appropriate monitoring system  161  for the gaseous substance injected.  
         [0098]     It is also to be noted that any adequate flowmeter may be used for the flowmeter  106 . However, it has been found advantageous to use a pneumotachometer (PNT) since it is already used in medical application, many models are available through different makers, it is approved by the Food &amp; Drug Administration (FDA), it is sufficiently accurate and is reasonably priced, it is known to users and its performances are well documented since it has been used for years. It is however to be noted that PNT usually do not indicate the mass flow of fluid. As will be apparent to one skilled in the art, the control unit  102  may calculate the mass flow of the inspiratory gas and of the NO since it is supplied with the composition of these gases (via the user interface unit  101 ) and it is supplied with the temperature and relative humidity of the injection system  100  (via the temperature and humidity measuring unit  103 ).  
         [0099]     As it will be easily understood by one skilled in the art, by installing the PNT inside the injection system  100  it is possible to control the condensation on the PNT to prevent a dramatic decrease in precision.  
         [0100]     As will be readily apparent to one skilled in the art, the control unit  102  could include an electronic circuit, a programmable micro controller and/or a microprocessor, to control the operation of the injection system  100 .  
         [0101]     Although the present invention has been described hereinabove by way of preferred embodiments thereof, it can be modified, without departing from the spirit and nature of the subject invention as defined in the appended claims.