Abstract:
Nitric oxide delivery devices comprise a chamber ( 33 ) carrying a gas transfer member ( 40 ). An interior chamber ( 44 ) of the gas transfer member ( 40 ) is in fluid communication with a gas source ( 60, 62 ) and the outer wall surface of the gas transfer member ( 40 ) is in fluid communication with blood flowing through the chamber ( 33 ). The gas transfer member ( 40 ) permits the gas to pass through or diffuse through the member from the interior chamber ( 44 ) to the chamber ( 33 ) carrying the blood so that the blood becomes infused with the gas. Nitric oxide and oxygen can be diffused through the same gas transfer member. Alternatively, nitric oxide can first be passed through a first gas transfer member and into the blood followed by oxygen being passed through a second gas transfer member and into the blood. Alternatively, oxygen can first be infused into the blood followed by nitric oxide.

Description:
BACKGROUND 
       [0001]    1. Field of Invention 
         [0002]    The invention is directed to medical devices and systems for delivering nitric oxide to a patient&#39;s blood, and in particular, medical devices for delivery of nitric oxide to a patient&#39;s blood as it circulates through an extracorporeal circulation system such that may be established during surgery. 
         [0003]    2. Description of Art 
         [0004]    Cardiac surgery requiring cardiopulmonary bypass (“CPB”) generally requires establishment of a circulation system outside of the body to facilitate circulation of blood through the patient, as well as oxygenation of the blood. Such systems are known in the art and are generally referred to as cardiopulmonary bypass machines that are operated by trained technicians referred to as perfusionists. In addition to monitoring the oxygen levels in the blood, the perfusionist can also monitor other blood chemistry and blood temperature and modify both as desired or necessary to assist in the surgery. Modification of the blood chemistry can be accomplished by devices, such as an oxygenator, that deliver oxygen to the blood. 
       SUMMARY OF INVENTION 
       [0005]    Broadly, the medical devices or systems and methods disclosed herein are directed to nitric oxide delivery devices having a chamber carrying a gas transfer member. An interior of the gas transfer member is in fluid communication with a gas source and the outer wall surface of the gas transfer member is in fluid communication with blood flowing through a chamber. The gas transfer member permits the gas to pass through or diffuse through the gas transfer member from the interior chamber to the chamber carrying the blood so that the blood becomes infused with the gas. 
         [0006]    In one specific embodiment, one gas transfer member is in fluid communication with both a nitric oxide source and an oxygen source so that both nitric oxide and oxygen are diffused into the chamber carrying the blood. 
         [0007]    In other specific embodiments, the nitric oxide delivery device includes two gas transfer members. In one such embodiment having two gas transfer members, nitric oxide is the first gas to be diffused into the blood through a first gas transfer member and oxygen is the second gas to be diffused into the blood through a second gas transfer member. In an alternative embodiment, oxygen is the first gas to be diffused into the blood through a first gas transfer member and nitric oxide is the second gas to be diffused into the blood through a second gas transfer member. 
         [0008]    It is believed that the present devices will effectively deliver nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery to result in a significantly shortened duration of mechanical ventilation [8.4+7.6 hours vs. 16.3+6.5 hours (p&lt;0.05)] and intensive care unit length of stay [53.8+19.7 hours vs. 79.4+37.7 hours (p&lt;0.05)] as compared to a patient who does not receiving nitric oxide during surgery. In addition, it is believed that delivery of nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery also can lower troponin levels at 12, 24, and 48 hours (p&lt;0.05), lower B-type natriuretic peptide levels at 12 and 24 hours (p&lt;0.05), and lower the use of diuretics. Further, it is believed that delivery of nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery also can result in the patient having a higher mean hemoglobin at 48 hours despite no differences in chest tube output, PRBC transfusion, platelet counts or transfusion, FFP transfusion, or pT/pTT in the first 48 hours after surgery. Accordingly, it is believed that delivery of nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery will result in myocardial protection, improved fluid balance, and improved postoperative ICU course. It is to be understood, however, that the effects and results of the nitric oxide delivery devices disclosed herein are dependent upon the skill and training of the operators and surgeons. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0009]      FIG. 1  is a partial cross-sectional/partial schematic view of one specific embodiment of a nitric oxide delivery device disclosed herein. 
           [0010]      FIG. 2  is a partial cross-sectional/partial schematic view of another specific embodiment of a nitric oxide delivery device disclosed herein. 
           [0011]      FIG. 3  is a partial cross-sectional/partial schematic view of an additional specific embodiment of a nitric oxide delivery device disclosed herein. 
       
    
    
       [0012]    While the invention will be described in connection with the preferred embodiments, it will be understood that it is not intended to limit the invention to that embodiment. On the contrary, it is intended to cover all alternatives, modifications, and equivalents, as may be included within the spirit and scope of the invention as defined by the appended claims. 
       DETAILED DESCRIPTION OF INVENTION 
       [0013]    Referring now to Figures, nitric oxide delivery devices are designed to deliver nitric oxide to blood flowing through an extracorporeal circulation system. In one embodiment illustrated in  FIG. 1 , nitric oxide delivery device  20  comprises housing  25  defining chamber  27  having disposed therein blood flow housing  30 . Blood flow housing  30  include inlet  31 , outlet  32  and chamber  33 . Disposed within chamber  33  is gas transfer member  40  having one or more walls  42  defining interior chamber  44 . As shown in  FIG. 1 , gas transfer member  40  is a rectangular-shaped member having four walls  42 . It is to be understood, however, that gas transfer member  40  can be spherical-shaped or any other shape having as few as one wall such as in the case of a sphere, or any other number of walls depending on the shape of gas transfer member  40 . 
         [0014]    Gas transfer member  40  can be any device capable of allowing gases such as nitric oxide, oxygen and the like to pass through wall(s)  42  of gas transfer member  40 , but prevent blood (not shown) from flowing through wall(s)  42  of gas transfer member  40 . In the embodiment of  FIG. 1 , gas transfer member  40  comprises two inlets  52 ,  54 , and one outlet  56 . 
         [0015]    Inlet  52  is in fluid communication with interior chamber  44  and tubing  53  which is in fluid communication with nitric oxide source  60 . Thus, inlet  52  delivers nitric oxide to interior chamber  44  of gas transfer member  40  so that it can then diffuse through wall(s)  42  of gas transfer member  40  and combine with blood (not shown) flowing through chamber  33  of blood flow housing  30 . Nitric oxide source  60  can be any type of nitric oxide source known in the art and can include additional components, such as a regulator, a monitor, and/or a titration component, to facilitate delivery of the desired amount of nitric oxide to interior chamber  44 . 
         [0016]    Inlet  54  is in fluid communication with interior chamber  44  and tubing  55  which is in fluid communication with oxygen source  62 . Thus, inlet  54  delivers oxygen to interior chamber  44  of gas transfer member  40  so that it can then diffuse through wall(s)  42  of gas transfer member  40  and combine with blood (not shown) flowing through chamber  33  of blood flow housing  30 . Oxygen source  62  can be any type of oxygen source known in the art and can include additional components, such as a regulator, a monitor, and/or a titration component, to facilitate delivery of the desired amount of oxygen to interior chamber  44 . 
         [0017]    Outlet  56  is in fluid communication with interior chamber  44  and tubing  57  which is in fluid communication with venting device  64  to facilitate removal of excess nitric oxide and/or oxygen from interior chamber  44 . Venting device  64  can be any type of gas collection system. 
         [0018]    Although the embodiment of  FIG. 1  shows a single outlet  56 , it is to be understood that more than one outlet  56  can be included as desired or necessary to remove excess oxygen or nitric oxide from interior chamber  44  of gas transfer member  40 . Similarly, one or more additional inlets can be included as desired or necessary to deliver oxygen and/or nitric oxide to interior chamber  44  of gas transfer member  40 . Moreover, a single inlet can deliver both oxygen and nitric oxide to interior chamber  44  in the embodiment of  FIG. 1 . 
         [0019]    In operation of the embodiment of  FIG. 1 , an extracorporeal circulation system is established by having blood from a patient flow from the body, through the system, and back into the patient&#39;s body. As noted above, such systems are known in the art and generally involve use of a pump or other device operated by a perfusionist. As the blood flows through the extracorporeal circulation system, the blood flows into inlet  31 , into chamber  33 , and out of outlet  32 . As the blood flows through chamber  33  it is infused with nitric oxide and oxygen flowing through walls  42  of gas transfer member  40  as a result of both gases flowing from their respective sources  60 ,  62 . As a result, in this embodiment, the blood from the patient is infused with both nitric oxide and oxygen within chamber  33 . Excess nitric oxide and oxygen flow out of outlet  56 , through tubing  57 , and into venting device  64 . 
         [0020]    Referring now to  FIGS. 2-3 , in two other specific embodiments, nitric oxide delivery device  120  comprises housing  125  defining chamber  127  having disposed therein blood flow housing  130 . Blood flow housing  130  include inlet  131 , outlet  132  and first chamber  133 , second chamber  135 , and passage  137  placing first chamber  133  in fluid communication with second chamber  135 . Disposed within chamber  133  is first gas transfer member  140  having one or more walls  142 , and disposed within chamber  135  is second gas transfer member  145  having one or more walls  148 . 
         [0021]    As shown in  FIG. 2 , gas transfer members  140 ,  145  are rectangular-shaped members having four walls  142 ,  148 , respectively. It is to be understood, however, that gas transfer members  140 ,  145  can be spherical-shaped or any other shape having as few as one wall such as in the case of a sphere, or any other number of walls depending on the shape of gas transfer members  140 ,  145 . In addition, gas transfer members  140 ,  145  can be any device capable of allowing gases such as nitric oxide, oxygen and the like to pass through wall(s)  142 ,  148 , but prevent blood (not shown) from flowing through wall(s)  142 ,  148 . 
         [0022]    With respect to the embodiment of  FIG. 2 , gas transfer member  140  comprises inlet  152  and outlet  156 . Inlet  152  is in fluid communication with interior chamber  144  and tubing  153  which is in fluid communication with nitric oxide source  160 . Thus, inlet  152  delivers nitric oxide to interior chamber  144  of gas transfer member  140  so that it can then diffuse through wall(s)  142  of gas transfer member  140  and combine with blood (not shown) flowing through chamber  133  of blood flow housing  130 . Nitric oxide source  160  can be any type of nitric oxide source known in the art and can include additional components, such as a regulator, a monitor, and/or a titration component, to facilitate delivery of the desired amount of nitric oxide to interior chamber  144 . 
         [0023]    Outlet  156  is in fluid communication with interior chamber  144  and tubing  157  which is in fluid communication with venting device  164 . Venting device  164  can be any type of gas collection system. 
         [0024]    Inlet  154  is in fluid communication with interior chamber  146  and tubing  155  which is in fluid communication with oxygen source  162 . Thus, inlet  154  delivers oxygen to interior chamber  146  of gas transfer member  145  so that it can then diffuse through wall(s)  148  of gas transfer member  145  and combine with blood (not shown) flowing through chamber  135  of blood flow housing  130 . Oxygen source  160  can be any type of oxygen source known in the art and can include additional components, such as a regulator, a monitor, and/or a titration component, to facilitate delivery of the desired amount of oxygen to interior chamber  146 . 
         [0025]    Outlet  158  is in fluid communication with interior chamber  146  and tubing  159  which is in fluid communication with venting device  166  to facilitate removal of excess oxygen from interior chamber  146 . Venting device  166  can be any type of gas collection system. 
         [0026]    In operation of the embodiment of  FIG. 2 , an extracorporeal circulation system is established by having blood from a patient flow from the body, through the system, and back into the patient&#39;s body. As the blood flows through the extracorporeal circulation system, the blood flows into inlet  131 , into chamber  133 , through passage  137 , into chamber  135 , and out of outlet  132 . As the blood flows through chamber  133  it is infused with nitric oxide flowing through walls  142  of gas transfer member  140  as a result of nitric oxide flowing from nitric oxide source  160 . Excess nitric oxide flows out of outlet  156 , through tubing  157 , and into venting device  164 . Therefore, in this embodiment, the blood from the patient is first infused with nitric oxide within chamber  133 . 
         [0027]    After being infused with nitric oxide in chamber  133 , the blood then flows through passage  137  and into chamber  135 . As the blood flows through chamber  135  it is infused with oxygen flowing through walls  148  of gas transfer member  145  as a result of oxygen flowing from oxygen source  162 . Excess oxygen flows out of outlet  158 , through tubing  159  and into venting device  166 . Therefore, in this embodiment, the blood from the patient is infused with oxygen within chamber  135  after being infused with nitric oxide within chamber  133 . The blood then flows out of outlet  135  so that can be carried back to the patient. 
         [0028]    Referring now to the embodiment of  FIG. 3  which is substantially similar to the embodiment of  FIG. 2  and, therefore, includes like reference numerals, gas transfer member  140  comprises interior chamber  144  in fluid communication with inlet  152 , tubing  153 , outlet  156 , and tubing  157  similar to the embodiment of  FIG. 2 . In the embodiment of  FIG. 3 , however, oxygen source  262  is in fluid communication with tubing  153 , inlet  152 , and, thus, interior chamber  144 . Accordingly, inlet  152  delivers oxygen to interior chamber  144  of gas transfer member  140  so that it can then diffuse through wall(s)  142  of gas transfer member  140  and combine with blood (not shown) flowing through chamber  133  of blood flow housing  130 . Oxygen source  262  can be any type of oxygen source known in the art and can include additional components, such as a regulator, a monitor, and/or a titration component, to facilitate delivery of the desired amount of oxygen to interior chamber  144 . 
         [0029]    Outlet  156  is in fluid communication with venting device  266  by tubing  157  to facilitate removal of excess oxygen from interior chamber  144 . Venting device  266  can be any type of gas collection system. 
         [0030]    Similar to the embodiment of  FIG. 2 , inlet  154  and tubing  155  are in fluid communication interior chamber  146  of gas transfer member  145 ; however, instead of being in fluid communication with an oxygen source as shown in  FIG. 2 , inlet  154  and tubing  155  and, therefore, interior chamber  146 , are in fluid communication with nitric oxide source  260 . Accordingly, inlet  154  delivers nitric oxide to interior chamber  146  of gas transfer member  145  so that it can then diffuse through wall(s)  148  of gas transfer member  145  and combine with blood (not shown) flowing through chamber  135  of blood flow housing  130 . Nitric oxide source  260  can be any type of nitric oxide source known in the art and can include additional components, such as a regulator, a monitor, and/or a titration component, to facilitate delivery of the desired amount of nitric oxide to interior chamber  146 . 
         [0031]    Outlet  158  is in fluid communication with venting device  264  by tubing  159  to facilitate removal of excess nitric oxide from interior chamber  146 . Venting device  264  can be any type of gas collection system. 
         [0032]    In operation of the embodiment of  FIG. 3 , the blood is infused with oxygen prior to being infused with nitric oxide. Thus, in the embodiment of  FIG. 3 , as the blood flows through chamber  133  it is infused with oxygen flowing through walls  142  of gas transfer member  140  as a result of oxygen flowing from oxygen source  262 . Excess oxygen flows out of outlet  156 , through tubing  157 , and into venting device  266 . Therefore, in this embodiment, the blood from the patient is first infused with oxygen within chamber  133 . 
         [0033]    After being infused with oxygen in chamber  133 , the blood then flows through passage  137  and into chamber  135 . As the blood flows through chamber  135  it is infused with nitric oxide flowing through walls  148  of gas transfer member  145  as a result of nitric oxide flowing from nitric oxide source  260 . Excess nitric oxide flows out of outlet  158 , through tubing  159 , and into venting device  264 . Therefore, in this embodiment, the blood from the patient is infused with nitric oxide within chamber  135  after being infused with oxygen within chamber  133 . The blood then flows out of outlet  135  so that can be carried back to the patient. 
         [0034]    Infusion of nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery has been found by the inventors to result in a significantly shortened duration of mechanical ventilation [8.4+7.6 hours vs. 16.3+6.5 hours (p&lt;0.05)] and intensive care unit length of stay [53.8+19.7 hours vs. 79.4+37.7 hours (p&lt;0.05)] as compared to a patient not receiving nitric oxide during surgery. The inventors have also observed that delivery of nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery can lower troponin levels at 12, 24, and 48 hours (p&lt;0.05), lower B-type natriuretic peptide levels at 12 and 24 hours (p&lt;0.05), and lower the use of diuretics. In addition, the inventors have found that delivery of nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery also can result in the patient having a higher mean hemoglobin at 48 hours despite no differences in chest tube output, PRBC transfusion, platelet counts or transfusion, FFP transfusion, or pT/pTT in the first 48 hours after surgery. Accordingly, the inventors believe that delivery of nitric oxide to a patient&#39;s blood during cardiopulmonary bypass surgery will result in myocardial protection, improved fluid balance, and improved postoperative ICU course. 
         [0035]    It is to be understood that the invention is not limited to the exact details of construction, operation, exact materials, or embodiments shown and described, as modifications and equivalents will be apparent to one skilled in the art. For example, inlets  52  and  54  can be combined into a single inlet. Moreover, the shapes and sizes of the housing, chambers, and gas transfer members can be any shape or size desired or necessary to facilitate the infusion of nitric oxide and oxygen to the blood flowing through the devices. In addition, in the embodiments of  FIGS. 2 and 3 , passage  137  is not required, but instead chambers  133 ,  135  can be separated by a wall instead of passage  137 . Alternatively, the gas transfer members  140 ,  145  can be disposed in series in the same chamber. Moreover, although the embodiments of  FIGS. 2-3  are shown as having first and second chambers  133 ,  135 , and passage  137 , it is to be understood that all of first chamber  133 , second chamber  135 , and passage  137  can comprise a single chamber having two separate portions separated by a passage. Additionally, the devices of  FIGS. 1-3  are not required to include housing  25 ,  125 . Further, luer locks or other connectors can be included to facilitate connection of inlets  31 ,  131  and outlets  32 ,  132  of housings  30 ,  130  to additional components making up the extracorporeal circulation system. Similarly, luer locks or other connections can be used to facilitate connection of the sources of nitric oxide and oxygen to the nitric oxide delivery devices. Accordingly, the invention is therefore to be limited only by the scope of the appended claims.