Method and Apparatus for Mixing a Gas Containing Nitric Oxide With a Gas Containing Oxygen

1. Field of the Invention

The present invention is directed to a method for mixing a gas containing nitric oxide (NO) with a gas containing oxygen, as well as to an apparatus for conducting the method.

2. Description of the Prior Art

In recent years, the use of gaseous nitric oxide (NO) has attracted widespread interest in different kinds of therapy. A number of positive effects has been found when small amounts of gaseous NO are administered to a patient via the airways. For example, NO has a relaxing effect on smooth muscle, thereby improving oxygenation and reducing blood pressure across the lung in patients with severe pulmonary disease. More extensive descriptions of the effects conveyed by NO are provided in e.g. PCT application WO 92/10228 and U.S. Pat. No. 5,427,797.

NO, usually diluted with N.sub.2, is supplied in gas cylinders and is subsequently mixed with a respiratory gas, usually a mixture of air and oxygen (O.sub.2), before the final mixture is delivered to the patient. Examples of known administration systems are described in European Application 0 659 445 and Swedish Application 502 724.

The biggest problem with NO is that it is a highly reactive gas and forms, with O.sub.2, nitrogen dioxide (NO.sub.2)--a highly toxic gas even in small concentrations. Since respiratory gas often contains an elevated concentration of 0.sub.2, typically 50-80% O.sub.2, special measures may be necessary to minimize the amount of NO.sub.2 delivered to the patient.

One approach to minimize the opportunity for NO.sub.2 to form is to supply the gas containing NO closely as possible to the patient, even inside the patient. This has the disadvantage, however, that the NO and respiratory gases may not have time to mix thoroughly, and a heterogeneous gas mixture could be carried into the lungs.

Another option is to mix the two gases continuously as they flow at a constant rate past an inspiratory line, so that the patient then draws a fresh mixture into her/his lungs at every breath. Implementing this option is difficult, however, when the patient is incapable of spontaneous breathing with an adequate volume. Moreover, large amounts of gas would be consumed, and gas containing NO would have to be evacuated to prevent a rise in the level of NO.sub.2 in the room.

Another possibility is to mix the gases in the customary fashion and to install an NO.sub.2 absorber or an NO.sub.2 filter before the patient. A disadvantage here is the difficulty in determining the supplied concentration of NO. An absorber must be monitored to keep it from becoming saturated, thereby losing its ability to absorb NO.sub.2, and a filter must be arranged to keep NO.sub.2 from escaping into the room.

Heretofore, the conversion of NO into NO.sub.2 was believed to occur in proportion to the squared concentration of NO times the level of O.sub.2 times time (k.sub.2 *(NO).sup.2 *O.sub.2 *t). In addition, a small amount Of NO.sub.2 may be present in the O.sub.2 --NO mixture. This amount is proportional to the concentration of NO (k.sub.0 *NO).

Recently conducted experiments have disclosed an additional factor. NO was found to have a property which causes initial formation of NO.sub.2 at the instant of mixture with oxygen, which is proportional only to the square of the NO concentration and the O.sub.2 concentration (k.sub.1 *(NO).sup.2 *O.sub.2).

Thus the final conversion equation, designating the concentration of NO.sub.2, is as follows:

An object of the present invention is to utilize this recently discovered phenomenon in the formation of NO.sub.2 for achieving a method for minimizing the formation of NO.sub.2 when two gases respectively containing NO and O.sub.2 are mixed.

Another object of the invention is to provide a device which is designed to minimize the formation of NO.sub.2 when two gases respectively containing NO and O.sub.2 are mixed.

The above objects are achieved in a method and apparatus according to the invention wherein a first gas, containing nitric oxide, is added to a second gas, containing oxygen, at at least two, and preferably more, mixing points arranged at specified distances from each other.

When gas containing NO is added to gas containing O.sub.2 at a number of mixing points, the contribution to the formation of NO.sub.2, according to the newly discovered conversion expression, can be reduced. Assume e.g. that the first gas contains 1000 ppm of NO in N.sub.2. When it is diluted to form the second gas with a concentration of 100 ppm, k.sub.1 *100.sup.2 ppm of NO.sub.2 are initially formed. If two mixing points are employed, the initial formation (at each point) becomes k.sub.1 *50.sup.2 ppm of NO.sub.2. Total initial formation then becomes 2*(K.sub.1 *50.sup.2) ppm, i.e., a reduction in initial NO.sub.2 by a factor of 2.

FIG. 1 shows a device constructed and operating according to the present invention connected to a ventilator for dosing NO to a patient.

FIG. 2 shows the device of FIG. 1 in greater detail.

A system 2 for administering NO to a patient 14 is shown in FIG. 1. The system 2 includes a device 4 for dosing a gas containing NO from a gas source 6 to an inspiratory line 10 via dosing lines 8.

The inspiratory line 10 is connected to a ventilator 12 and carries a respiratory gas from same to the patient 14. The ventilator 12 can be an existing commercially available ventilator such as the Servo Ventilator 300, Siemens-Elema, Solna, Sweden.

Air expired by the patient 14 is carried back to the ventilator 12 in an expiratory line 16.

As FIG. 2 shows, the device 4 has a gas connector 18, which is coupled to the gas source 6, and a flow regulator 20 for regulating the flow required to achieve a pre-defined concentration of NO in the final mixture supplied to the patient 14. The flow regulator 20 is controlled by a control device 22. As indicated by the arrow in the FIG. 2, the control device 22 receives information about the flow of respiratory gas in the inspiratory line 10 and then controls the flow regulator 20 according to the received flow value and a reference value for the pre-defined concentration. In the known manner, the flow of respiratory gas can be obtained from the ventilator 12 or from a separate flow meter (not shown in the figures).

The dosed flow is carried to a flow divider 24 which distributes this flow via a first mixing point 26A, a second mixing point 26B, a third mixing point 26C and a fourth mixing point 26D, to the inspiratory line 10. The distance between neighboring mixing points within 26A-26D is selected so a homogenous gas mixture is achieved before the next successive mixing point 26B-26D in the direction of respiratory gas flow. The number of mixing points can vary, but two to ten mixing points are appropriate. Too many mixing points 26A-26D could result in needlessly long mixing distances.

Since NO reacts with O.sub.2 to form NO.sub.2 according to the equation

in which k.sub.0, k.sub.1 and k.sub.2 are constants, the first term designates the concentration of NO.sub.2 in the gas source, the second term designates the initial formation of NO.sub.2 in the mixture of gases and the third term designates the time-related formation of NO.sub.2 when the gases have been mixed, it can be seen that subdivision into a number of mixing points reduces the second term, i.e. the initial formation of NO.sub.2.

Assume that NO is to be supplied to an infant, e.g., a premature neonate with respiratory problems, through an 1.5 m long inspiratory tube. A typical flow would then be one 1/min with an oxygen content of 90% and administration of 100 ppm of NO.

With four mixing points, as in FIG. 2, 10 cm apart and the same dosing flow at each mixing point, a concentration of NO of 25 ppm results after the first mixing point 26A, 50 ppm after the second mixing point 26B, 75 ppm after the third mixing point 26C and 100 ppm after the fourth mixing point 26D. When the first mixing point is 1.5 m from the patient (and the others are at 1.4, 1.3 and 1.2 m), respectively 0.43, 0.42, 0.40 and 0.39 ppm of NO.sub.2 are formed at the mixing points. This amounts to a total of 1.63 ppm.

The introduction of 100 ppm of NO at one mixing point at 1.2 m, i.e., the shortest distance, would have resulted in the formation of 4.69 ppm of NO.sub.2. In view of the toxicity of NO.sub.2 the difference is particularly significant.

Introduction does not have to be into the inspiratory line 10 but can be accomplished in a special mixing chamber or the like. The most important thing is for mixing to occur at a number of mixing points and for homogenous mixing to take place before each new mixing point for the very best results to be achieved.

The distance between the mixing points 26A-26D does not need to be constant, but can vary.

Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventors to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within the scope of their contribution to the art.