U.S. patent application number 17/215686 was filed with the patent office on 2021-07-15 for systems and methods of administering a pharmaceutical gas to a patient.
This patent application is currently assigned to Mallinckrodt Hospital Products IP Unlimited Company. The applicant listed for this patent is Mallinckrodt Hospital Products IP Unlimited Company. Invention is credited to Duncan P. Bathe, Frederick J. Montgomery.
Application Number | 20210213235 17/215686 |
Document ID | / |
Family ID | 1000005482089 |
Filed Date | 2021-07-15 |
United States Patent
Application |
20210213235 |
Kind Code |
A1 |
Montgomery; Frederick J. ;
et al. |
July 15, 2021 |
Systems And Methods Of Administering A Pharmaceutical Gas To A
Patient
Abstract
Methods and systems for delivering a pharmaceutical gas to a
patient. The methods and systems provide a known desired quantity
of the pharmaceutical gas to the patient independent of the
respiratory pattern of the patient over a plurality of breaths
every n.sup.th breath, where n is greater than or equal to 1. The
pharmaceutical gases include CO and NO, both of which are provided
as a concentration in a carrier gas. The gas control system
determines the delivery of the pharmaceutical gas to the patient to
result in the known desired quantity (e.g. in molecules, milligrams
or other quantified units) of the pharmaceutical gas being
delivered. Upon completion of that known desired quantity of
pharmaceutical gas over a plurality of breaths, the system can
either terminate, continue, activate and alarm, etc.
Inventors: |
Montgomery; Frederick J.;
(Sun Prairie, WI) ; Bathe; Duncan P.; (Fitchburg,
WI) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Mallinckrodt Hospital Products IP Unlimited Company |
Mulhuddart |
|
IE |
|
|
Assignee: |
Mallinckrodt Hospital Products IP
Unlimited Company
Mulhuddart
IE
|
Family ID: |
1000005482089 |
Appl. No.: |
17/215686 |
Filed: |
March 29, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16156453 |
Oct 10, 2018 |
10960169 |
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17215686 |
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14551186 |
Nov 24, 2014 |
10099029 |
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16156453 |
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13331807 |
Dec 20, 2011 |
8893717 |
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14551186 |
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12430220 |
Apr 27, 2009 |
8091549 |
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13331807 |
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13287663 |
Nov 2, 2011 |
8517015 |
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12430220 |
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13284433 |
Oct 28, 2011 |
8397721 |
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13287663 |
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11231554 |
Sep 21, 2005 |
7523752 |
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13284433 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 2016/0027 20130101;
A61M 16/12 20130101; A61M 16/105 20130101; A61M 2205/3334 20130101;
A61M 2202/0233 20130101; A61M 2016/0015 20130101; A61M 16/0666
20130101; A61M 16/0003 20140204; A61M 16/04 20130101; A61M 2205/18
20130101; A61M 2016/0039 20130101; A61M 2205/75 20130101; A61M
2205/50 20130101; A61M 2202/0275 20130101; A61M 16/024 20170801;
A61M 16/0051 20130101; A61M 2016/0021 20130101; A61M 16/201
20140204; A61M 16/107 20140204; A61M 2016/003 20130101 |
International
Class: |
A61M 16/12 20060101
A61M016/12; A61M 16/00 20060101 A61M016/00; A61M 16/20 20060101
A61M016/20; A61M 16/04 20060101 A61M016/04; A61M 16/06 20060101
A61M016/06; A61M 16/10 20060101 A61M016/10 |
Claims
1. A method of administering a pharmaceutical gas to a patient,
wherein the pharmaceutical gas comprises at least one of nitric
oxide or carbon monoxide, the method comprising: delivering a first
quantity of the pharmaceutical gas to the patient in a first
breath; monitoring the patient's respiratory rate or changes in the
patient's respiratory rate; varying the quantity of pharmaceutical
gas delivered to the patient in one or more subsequent breaths
based on the monitored respiratory rate or changes in the patient's
respiratory rate.
2. The method of claim 1, wherein the quantity delivered in the
subsequent breath is greater than the first quantity in response to
a decrease in the patient's respiratory rate.
3. The method of claim 1, wherein the quantity delivered in the
subsequent breath is less than the first quantity in response to an
increase in the patient's respiratory rate.
4. The method of claim 1, wherein varying the quantity of
pharmaceutical gas delivered to the patient avoids high unsafe
doses or doses too low to be effective.
5. The method of claim 1, wherein the pharmaceutical gas is
delivered to the patient every breath.
6. The method of claim 1, wherein the pharmaceutical gas is
delivered to the patient every nth breath, wherein n is 1 or
greater.
7. The method of claim 1, wherein at least one breath is skipped
such that pharmaceutical gas is not administered during the
breath.
8. The method of claim 7, wherein when the breath is skipped, a new
quantity of pharmaceutical gas per nth breath is calculated.
9. The method of claim 1, wherein when the quantity of
pharmaceutical gas to be delivered in a breath is greater than a
maximum quantity of pharmaceutical gas per breath, the maximum
quantity of pharmaceutical gas per breath is administered and the
difference between the quantity of pharmaceutical gas to be
delivered in the breath and the maximum quantity of pharmaceutical
gas per breath is added to one or more subsequent breaths.
10. The method of claim 1, wherein one or more of the first
quantity and the quantity delivered in the subsequent breath is
delivered during the first half of inspiration.
11. A gas delivery system comprising: an inlet to connect to a
source of pharmaceutical gas comprising at least one of nitric
oxide or carbon monoxide; an outlet to connect to a device that
introduces the pharmaceutical gas to a patient; a breath trigger
sensor to measure a patient's respiratory rate; and a gas control
system in communication with the breath trigger sensor that
delivers a varying quantity of pharmaceutical gas to the patient
based on changes in the patient's respiratory rate.
12. The system of claim 11, wherein a quantity delivered in a
subsequent breath is greater than a quantity delivered in a
previous breath in response to a decrease in the patient's
respiratory rate.
13. The system of claim 11, wherein a quantity delivered in a
subsequent breath is less than a quantity delivered in a previous
breath in response to an increase in the patient's respiratory
rate.
14. The system of claim 11, wherein the gas control system delivers
the quantity of pharmaceutical gas during the first half of the
patient's inspiratory cycle.
15. The system of claim 11, wherein the gas control system delivers
the pharmaceutical gas to the patient every breath.
16. The system of claim 11, wherein delivering a varying quantity
of pharmaceutical gas to the patient avoids high unsafe doses or
doses too low to be effective.
17. The system of claim 11, wherein the pharmaceutical gas is
delivered to the patient every nth breath, wherein n is 1 or
greater.
18. The system of claim 11, wherein at least one breath is skipped
such that pharmaceutical gas is not administered during the
breath.
19. The system of claim 18, wherein when the breath is skipped, a
new quantity of pharmaceutical gas per nth breath is
calculated.
20. The system of claim 11, wherein when a quantity of
pharmaceutical gas to be delivered in a breath is greater than a
maximum quantity of pharmaceutical gas per breath, the maximum
quantity of pharmaceutical gas per breath is administered and the
difference between the quantity of pharmaceutical gas to be
delivered in the breath and the maximum quantity of pharmaceutical
gas per breath is added to one or more subsequent breaths.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation under 35 U.S.C. .sctn.
120 of U.S. patent application Ser. No. 16/156,453, filed Oct. 10,
2018, which is a continuation under 35 U.S.C. .sctn. 120 of U.S.
patent application Ser. No. 14/551,186, filed Nov. 24, 2014, now
U.S. Pat. No. 10,099,029, issued Oct. 16, 2018, which is a
continuation under 35 U.S.C. .sctn. 120 of U.S. patent application
Ser. No. 13/331,807, filed Dec. 20, 2011, now U.S. Pat. No.
8,893,717, issued Nov. 25, 2014, which is a continuation-in-part
under 35 U.S.C. .sctn. 120 of U.S. patent application Ser. No.
12/430,220, filed Apr. 27, 2009, now U.S. Pat. No. 8,091,549,
issued Jan. 10, 2012, and U.S. patent application Ser. No.
13/287,663, filed Nov. 2, 2011, now U.S. Pat. No. 8,517,015, issued
Aug. 27, 2013, and U.S. patent application Ser. No. 13/284,433,
filed Oct. 28, 2011, now U.S. Pat. No. 8,397,721, issued Mar. 19,
2013, which are continuations of U.S. patent application Ser. No.
11/231,554, filed Sep. 21, 2005, now U.S. Pat. No. 7,523,752,
issued Apr. 28, 2009, the entire disclosures of which are hereby
incorporated by reference herein.
BACKGROUND
[0002] The present invention relates to methods and systems for
administering a pharmaceutical gas to a patient and, more
particularly, to methods and systems for introducing carbon
monoxide CO or nitric oxide NO to a patient in a predetermined
quantity.
[0003] The normal or conventional way of giving a pharmaceutical
drug to a patient is to prescribe the dose based on the quantity of
drug (usually in weight) per unit weight of the patient (e.g.
mg/Kg) with the dose being specified to be delivered over a period
of time or being repeated at specified intervals of time. This
allows the user to control the quantity of drug and ensures the
quantity of drug being delivered is in proportion to the patient's
size. This is to reduce the patient to patient variability in
response to the drug due to the size of the patient i.e. a 7 Kg
baby will not get the same quantity of drug as a 80 Kg adult.
[0004] In recent times there have been a number of gases which have
been shown to have pharmaceutical action in humans and animals.
Examples include Nitric Oxide (NO) Zapol et al U.S. Pat. No.
5,485,827 and more recently Carbon Monoxide (CO) Otterbein et al
(U.S. Published Patent Application No. 2003/0219496). In the
Otterbein patent application, CO is described as having a
pharmacological action in a number of medical conditions including
ileus and vascular disease.
[0005] In these cases, the carbon monoxide gas needs to be
delivered to the patients' alveoli where it can move across the
alveolar membrane and into the blood stream where its action can
take effect. The current dosing used in these cases is for the
patient to breath at a specified concentration of CO in ppm for a
specified period of time. Accurate dosing of CO for these
treatments is important as CO reacts with the hemoglobin in the
blood to form carboxyhemoglobin which means the hemoglobin is no
longer able to carry oxygen to the tissues of the body. If too much
CO is given, the patient may exhibit the toxic effects of CO for
which it is usually known.
[0006] There is a tight window for CO delivery between the
therapeutic level and the level that causes carboxyhemoglobin above
safe levels. Up until now CO has been delivered as a constant
concentration in the gas breathed by the patient/animal for a
specified period of time. For example in reference 3 of the
Otterbein publication, (Example 2 pg 13) the therapeutic dose
delivered to mice for the treatment of ileus was 250 ppm of CO for
1 hour.
[0007] However, this method of dosing CO can be associated with
large variability in the actual dose being delivered to the
animal/humans alveoli. This variability is because the quantity of
CO being delivered to the animal/patient is dependent on a number
of variables including, but not limited to, the patients tidal
volume, respiratory rate, diffusion rate across the alveolar and
ventilation/perfusion (V/Q) matching.
[0008] The amount of CO delivered into a patient's alveoli can be
determined by the ideal gas law as shown in the following
equation:
N=PV/(R.sub.uT) (1)
Where: N is the number of moles of the gas (mole) P is the absolute
pressure of the gas (joule/m.sup.3) V is the volume of the
particular gas (m.sup.3), R.sub.u is the universal gas constant,
8.315 joule/mole-K and T is the absolute temperature (K).
[0009] If we assume atmospheric pressure (101,315 joule/m.sup.3)
and 20.degree. C. (293 K) as the temperature and we express the
volume in mL (10.sup.-6 m.sup.3), then equation (1) reduces to:
N=4.16.times.10.sup.-5V (moles) (2)
[0010] Equation (2) can be used to calculate the number of moles of
gas delivered to a patient's alveolar volume over a period of time
when given a specified concentration by using the following
equation:
N.sub.CO=RRtC.sub.CO10.sup.-64.16.times.10.sup.-5V.sub.a (3)
Where; C.sub.CO is the concentration of CO (ppm), V.sub.a is the
alveolar volume (mL), RR is the respiratory rate (BPM) and t is the
time in minutes.
[0011] For example, if the CO dose for ileus in humans was 250 ppm
of CO for one hour (60 minutes), the alveolar volume is 300 mL and
the patients respiratory rate is 12 breaths per minute (bpm) then
the amount of CO gas in moles delivered to the patients alveoli
over that period would be:
N.sub.CO=126025010.sup.-64.16.times.10.sup.-5300=2.25.times.10.sup.-3
moles
[0012] This can be converted into the mass of drug delivered
(M.sub.CO) using the gram molecular weight of CO which is 28 as
shown in the following equation:
M.sub.CO=N.sub.CO28=63.times.10.sup.-3 g=63 mg (4)
[0013] However, although this works for a given set of assumptions,
a spontaneous patient's respiratory rate can vary widely from
perhaps 8 to 20 breaths per minute depending on circumstances and
the patient's alveolar volume per breath can also vary
significantly from say 200 to 400 mL depending on the metabolic
need. These variables can have a dramatic effect on the amount of
gaseous drug being delivered to the patient over the same period of
time. For instance, if the patients respiratory rate was 8 bpm and
the alveolar volume was 200 mL, the CO dose delivered to the
patients alveoli would have been 27.8 (mg). Likewise if the
patients respiratory rate was 20 bpm and the alveolar volume was
400 mL, then the dose delivered to the patients alveoli would have
been 139.2 (mg) thus representing a five-fold difference in the
amount of drug being delivered.
[0014] This means, in the example of CO, the quantity of gaseous
drug a patient gets as measured in grams could vary substantially
depending on the patient's ventilation pattern. For a dose based on
constant concentration and time, the effect of these variables
could mean that an individual patient could get significantly
higher or lower doses of CO in grams and this could result in
either high unsafe levels of carboxyhemoglobin or doses too low to
be effective. Although not all the gaseous drug delivered to the
alveoli will be taken up by the body's bloodstream (due to
variables such as cardiac output and the diffusion coefficient of
the gas) controlling the amount delivered to the alveoli takes away
a major source of variability.
[0015] In addition, there is a need to administer NO to a patient
in a predetermined quantity as described in "Cell-free hemoglobin
limits nitric oxide bioavailabllity in sickle-cell disease", Nature
Medicine, Volume 8, Number 12, December 2002, pages 1383 et seq.
This paper describes the use of inhaled NO to react with cell free
hemoglobin to form plasma methemoglobin and so reduce the ability
of the cell free hemoglobin in the plasma to consume endogenously
produced NO (FIG. 5, page 1386). The quantity of NO delivered to
the patient blood needs to be equivalent to the amount of cell free
hemoglobin that is in the patients plasma. The amount of NO
delivered to a sample of sickle cell patients was 80 ppm of NO for
1.5 hours. However, there was variability in the amount of
methemoglobin produced in individual patients as shown by the error
bars on FIG. 4b. So, in a similar way to the CO example, a known
quantity of NO needs to be delivered to a patient to provide the
desired therapeutic effect and again it is important to remove any
variability of delivery because of differences in the individual
patient's respiratory pattern.
[0016] Accordingly, it would be advantageous to have a system and
method of introducing pharmaceutical gases (such as carbon monoxide
and nitric oxide) that allows for the precise control of a known
quantity of the pharmaceutical gas to be delivered to the patients
alveoli and which is not subject to change based on the patients
respiratory patterns.
SUMMARY
[0017] Accordingly, the present invention relates to systems and
methods for administering a pharmaceutical gas, such as carbon
monoxide and nitric oxide, that allows a clinician to determine and
control the desired quantity of the gas to be delivered to the
patient. The methods determine the desired quantity of the
pharmaceutical gas to be administered to the patient and then
administers the desired quantity of the pharmaceutical gas
irrespective of the patients respiratory patterns. If the
prescription is specified as a total quantity of drug, then the
method terminates the administration of the pharmaceutical gas when
the desired total quantity has been administered to the
patient.
[0018] Thus, by the methods of various embodiments of the present
invention, the amount of the pharmaceutical gas is delivered to the
patient as a known desired quantity and that known desired quantity
can be expressed in various units of measurement, such as, but not
limited to, the weight of drug in micrograms (.mu.g), milligrams
(mg), grams (g) etc., the moles of drug in nanomoles (nM),
micromoles (.mu.M), millimoles (mM) moles (M) etc, or the volume of
drug, at a known concentration or partial pressure, in microliters
(.mu.L), milliliters (mL), liters (L) etc. The desired quantity of
the pharmaceutical gas can also be expressed as an amount per unit
of time for a period of time such as mg/hour for 2 hours.
[0019] One or more embodiments of the invention also include
systems for administering a pharmaceutical gas, such as carbon
monoxide or nitric oxide, and the system includes an inlet means
that can be connected to the source of the pharmaceutical gas and
deliver the gas to a patient by means of a patient device. That
patient device can be any device that actually introduces the
pharmaceutical gas into the patient such as a nasal cannula,
endotracheal tube, face mask or the like. There is also a gas
control system that controls the introduction of the quantity of a
pharmaceutical gas from the gas source through the patient device.
Again, therefore, the system provides a known quantity of gas to
the patient.
[0020] As such, embodiments of the present invention allows a user
to set a desired quantity of gaseous drug to be delivered to a
patient's alveoli and for the system to then deliver that gaseous
drug over multiple breaths until the prescribed amount has been
delivered.
[0021] As a further embodiment, the system and method may simply
provide an alarm, visual and/or audible, to alert the user when the
predetermined total quantity of the pharmaceutical gas has been
administered to the patient and not actually terminate that
administration. As such, the user is warned that the total
predetermined desired quantity administered over the plurality of
breaths has now been delivered to the patient so that the user can
take the appropriate action, including a closer monitoring of the
patient.
[0022] These and other features and advantages of the present
invention will become more readily apparent during the following
detailed description taken in conjunction with the drawings
herein.
[0023] One or more embodiments of the invention are directed to
methods of administering a therapy gas to a patient, the therapy
gas being at least one gas selected from CO and NO. The methods
comprise determining a desired total quantity of therapy gas to be
administered to the patient over a period of time over a plurality
of breaths. A quantity of the therapy gas is administered to the
patient during inspiration every n.sup.th breath of the plurality
of breaths, wherein n is 1 or greater. The quantity of the therapy
gas varied per n.sup.th breath to ensure that the desired total
quantity over the period of time is administered independent of the
respiratory pattern of the patient.
[0024] In some embodiments, the quantity of therapy gas per
n.sup.th breath is in the range of a minimum quantity of therapy
gas per breath and a maximum quantity of therapy gas per breath. In
detailed embodiments, the quantity of therapy gas per n.sup.th
breath is a function of one or more of a first respiratory rate, a
first tidal volume of the patient and the patient's ideal body
weight. In specific embodiments, the quantity of therapy gas per
n.sup.th breath to be delivered is greater than the minimum
quantity of therapy gas per breath and less than the maximum
quantity of therapy gas per breath, the quantity of therapy gas per
breath is administered on the n.sup.th breath, or when the quantity
of therapy gas per n.sup.th breath is less than the minimum
quantity of therapy gas per breath, administration of the quantity
of therapy gas per n.sup.th breath is skipped for that n.sup.th
breath, or when the quantity of therapy gas per n.sup.th breath is
greater than the maximum quantity of therapy gas per breath, one or
more of an alarm is triggered or the maximum quantity is delivered
on the n.sup.th breath and a difference between the quantity of
therapy gas per n.sup.th breath to be delivered and the maximum
quantity of therapy gas per breath is carried to one or more
subsequent breaths. In certain embodiments, when the quantity of
therapy gas per n.sup.th breath is skipped, a new quantity of
therapy gas per n.sup.th breath is calculated. In detailed
embodiments, when the quantity of therapy gas per n.sup.th breath
is greater than the maximum quantity of therapy gas per breath, the
maximum quantity of therapy gas per breath is administered on the
n.sup.th breath and the difference between the quantity of therapy
gas per n.sup.th breath and the maximum quantity of therapy gas per
breath is added to one or more subsequent breaths.
[0025] In one or more embodiments, n is 2 or greater and the
therapy gas is delivered during the n.sup.th breath. In some
embodiments, no therapy gas is administered during the breaths that
are not n.sup.th breaths. In detailed embodiments, the quantity of
therapy gas per n.sup.th breath is in the range of a minimum
quantity of therapy gas per breath and a maximum quantity of
therapy gas per breath. In specific embodiments, the quantity of
therapy gas per n.sup.th breath is a function of one or more of a
first respiratory rate, a first tidal volume of the patient and the
patient's ideal body weight.
[0026] In some embodiments, when the quantity of therapy gas per
n.sup.th breath to be delivered is greater than the minimum
quantity of therapy gas per breath and less than the maximum
quantity of therapy gas per breath, the quantity of therapy gas per
n.sup.th breath is administered on the n.sup.th breath, or when the
quantity of therapy gas per n.sup.th breath is less than the
minimum quantity of therapy gas per breath, administration of the
quantity of therapy gas per n.sup.th breath is skipped for that
n.sup.th breath, or when the quantity of therapy gas per n.sup.th
breath is greater than the maximum quantity of therapy gas per
breath, one or more of an alarm is triggered or the maximum
quantity is delivered on the n.sup.th breath and a difference
between the quantity of therapy gas per n.sup.th breath to be
delivered and the maximum quantity of therapy gas per breath is
carried to one or more subsequent breaths. In one or more
embodiments, when the quantity of therapy gas per n.sup.th breath
is skipped, a new quantity of therapy gas per n.sup.th breath is
calculated. Detailed embodiments further comprise repeating the
administration of the therapy gas on one or more subsequent
breaths. In specific embodiments, when the quantity of therapy gas
per n.sup.th breath is greater than the maximum quantity of therapy
gas per breath, the maximum quantity of therapy gas per breath is
administered on the n.sup.th breath and the difference between the
quantity of therapy gas per n.sup.th breath and the maximum
quantity of therapy gas per breath is added to one or more
subsequent breaths. Certain embodiments further comprise repeating
the administration of the therapy gas on one or more subsequent
breaths.
[0027] In some embodiments, when the quantity of therapy gas per
n.sup.th breath is greater than the maximum quantity of therapy gas
per breath, the maximum quantity of therapy gas per breath is
administered on the n.sup.th breath and the difference between the
quantity of therapy gas per n.sup.th breath and the maximum
quantity of therapy gas per breath is administered over one or more
subsequent breaths that are not an n.sup.th breath. In specific
embodiments, the therapy gas is delivered to the patient's alveoli.
In certain embodiments, the therapy gas is delivered to the patient
during the first half of the inspiratory cycle.
[0028] Additional embodiments are directed to methods of
administering a therapy gas to a patient, the therapy gas being at
least one of CO and NO. A desired total quantity of therapy gas to
be administered to the patient over a period of time over a
plurality of breaths is determined. A quantity of therapy gas to be
delivered to the patient per n.sup.th breath is calculated, where
calculating the quantity based on one or more of respiratory rate
and quantity already given to the patient. The quantity of the
therapy gas administered to the patient's alveoli during the first
half of the inspiratory cycle for every n.sup.th breath of the
plurality of breaths, n being greater than 1 averaged over the
period of time. Steps b) and c) are repeated varying the quantity
of the therapy gas per n.sup.th breath to ensure that the desired
total quantity over the period of time is maintained independent of
the respiratory pattern of the patient.
[0029] Some embodiments further comprise comparing the quantity of
therapy gas to be delivered to determine if the quantity is in the
range of a minimum quantity and a maximum quantity. In detailed
embodiments, if the quantity of therapy gas to be delivered is
lower than the minimum quantity, then the quantity of therapy gas
delivered during the breath is zero and the quantity of therapy gas
to be delivered is added to one or more subsequent breaths. In
specific embodiments, wherein if the quantity of therapy gas to be
delivered is greater than the maximum quantity, then performing one
or more of activating an alarm, determining the difference between
the quantity of therapy gas to be delivered and the maximum
quantity, administering the maximum quantity or adding the
difference between the quantity of therapy gas to be delivered and
the maximum quantity to one or more subsequent breaths.
[0030] Further embodiments of the invention are directed to systems
for administering a therapy gas to a patient having a respiratory
pattern, the therapy gas being at least one gas selected from CO
and NO. The system comprises an inlet to connect to a source of
therapy gas, an outlet to connect to a device that introduces the
therapy gas to the patient, a setting control to determine the
desired quantity of therapy gas to be delivered to the patient over
a plurality of breaths, and a gas control system to deliver the
desired quantity of the therapy gas to the patient during
inspiration by the patient over the plurality of breaths
independent of the patient's respiratory pattern. The gas control
system is configured to calculate a quantity of therapy gas to be
delivered to the patient per n.sup.th breath, calculating the
quantity based on one or more of respiratory rate and quantity
already given to the patient, administer the quantity of the
therapy gas to the patient's alveoli during the first half of the
inspiratory cycle for every n.sup.th breath of the plurality of
breaths, n being greater than 1 averaged over the period of time,
and repeat steps a) and b) varying the quantity of the therapy gas
per breath to ensure that the desired total quantity over the
period of time is maintained independent of the respiratory pattern
of the patient.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIGS. 1 and 2 are views of a front panel of an apparatus for
carrying out the present invention showing different user
options;
[0032] FIG. 3 is a schematic view of the present invention used
with a spontaneously breathing patient;
[0033] FIG. 4 is a schematic view of the present invention used
with a patient being breathed by means of a ventilator; and
[0034] FIG. 5 shows a flowchart of an exemplary method of
administering a therapy gas to a patient according to one or more
embodiments of the invention.
DETAILED DESCRIPTION
[0035] In the following detailed description, CO is used as the
pharmaceutical gas but the description can also be valid for NO.
Referring now to FIG. 1, there is shown a front view of an
apparatus that can be used in carrying out the present invention.
As can be seen, there is a front panel 10 that can be a part of the
apparatus and on that panel there are input setting knobs and
displays which allow the user to set and monitor the amount of CO
that is to be delivered to the patient.
[0036] The means for determining the desired quantity of CO to be
delivered is by means of an input setting knob 12 with the set
amount being shown on the setting display 8. The units shown in
FIG. 1 are in milligrams per kilogram that is, the units are
measured in a dosage per kilogram of the patient's ideal body
weight. Along with that input, there is a further input 14 whereby
the user can enter the patient's ideal body weight in kilograms
with the amount also displayed on the setting display 8. With those
inputs, the user can set the quantity of the pharmaceutical gas to
be administered to the patient in proportion to the size of the
patient and which reduces the patient to patient variability in
response to the pharmaceutical gas due to the size of the patient,
i.e. a 7 kilogram baby will not be administered the same quantity
of the pharmaceutical gas as a 80 kilogram adult.
[0037] The front panel 10 also has a monitor display 6 which can
display total dose of CO (mg) to be delivered (shown at 16) as
calculated for multiplying the dosage/kg by the patients ideal body
weight in kg.
[0038] Once the desired quantity of gaseous drug has been set on
the device the system then determines the amount of pharmaceutical
gas that is to be delivered in each breath and the amount of time
and/or the number of breaths that it will take to deliver the total
desired quantity of drug. The monitor display 6 can also display a
running total of the delivered dose of CO (mg) (shown at 17) as it
is delivered to the patient so the user can monitor the progress of
the treatment. This can be updated each breath as more
pharmaceutical gas is delivered.
[0039] As stated, the units illustrated in FIG. 1 are in metric
units, however, it can be seen that other units of mass and volume
could be used in carrying out the present invention i.e. ounces and
cubic inches and other designs of a front panel can be used as will
later be understood.
[0040] Referring to FIG. 2, there is shown a similar front panel 10
for the apparatus as shown in FIG. 1 but illustrating a different
user setting option. The desired quantity of CO to be delivered to
the patient is prescribed as a rate of delivery by means of input
setting knob 13 and is in units of mg/hr of CO to be delivered. In
this option, the device also allows the time duration (in hours) of
treatment to be set by a means of an input setting knob 15. If
required, the input setting by input setting knob 15 could be set
to continuous where the dose per hour would run continuously until
the user changed the setting. With these input settings, the
apparatus can calculate and display the desired quantity of the
pharmaceutical gas to be administered to the patient.
[0041] Also, as in FIG. 1, the front panel 10 also has a monitor
display 6 which can display total dose of CO (mg) to be delivered
(shown at 16) as calculated by multiplying the dosage/hr by the
total time duration (hr.). Once the desired quantity of
pharmaceutical gas has been set on the device, the system then
determines the amount of pharmaceutical gas to be delivered in each
breath and the amount of time and/or the number of breaths that it
will take to deliver the total desired quantity of drug. As before,
the monitor display 6 can display a running total of the delivered
dose of CO (mg) (shown at 17) as it is delivered to the patient so
the user can monitor the progress of the treatment. This can be
updated each breath as more pharmaceutical gas is delivered.
[0042] As can be appreciated, FIGS. 1 and 2 illustrate two of the
many options for setting the desired quantity and duration of
pharmaceutical gas therapy. These options are not meant to be
exhaustive and there are other setting options described or that
can be understood from the detailed descriptions that follow.
[0043] Once the desired quantity of gaseous drug has been set on
the device, the gas control system can then determine the amount of
pharmaceutical gas to be delivered in each breath and the amount of
time and/or the number of breaths that it will take to deliver the
desired quantity of pharmaceutical gas.
[0044] There are a number of different approaches that the gas
control system can use to determine the amount per breath and how
long to deliver that dose so the desired quantity of pharmaceutical
gas is delivered independent of the respiratory pattern of the
patient:
[0045] a) The user can set the quantity of pharmaceutical gas to be
delivered during each breath (M.sub.CO breath) and the gas control
system calculates the number of breaths (n.sub.breaths) which will
be required to deliver the total quantity of pharmaceutical gas
(M.sub.CO) i.e.
n.sub.breaths=M.sub.CO/M.sub.CO breath (5)
[0046] Once the total number of breaths (n.sub.breaths) required
has been determined the value can be displayed on the front panel
12 by means of display 16 to inform the user of the number of
breaths.
[0047] b) The user can set the number of breaths (n.sub.breaths)
that will administer the total quantity of the pharmaceutical gas
and the system calculates the amount per breath (M.sub.CO breath)
to be delivered.
M.sub.CO breath=M.sub.CO/n.sub.breaths (mg) (6)
[0048] Once the amount per breath (M.sub.CO breath) to be delivered
has been determined, the value can be displayed on the front panel
10 to inform the user of the amount.
[0049] (c) The user could set the time duration for which the
treatment is to be delivered over. The amount per breath would then
be determined by calculating the quantity per minute and then, by
monitoring the patients respiration rate in breaths per minute, the
amount of breath can be calculated. This calculation can be
repeated after every breath so any changes in the patients
respiratory rate does not affect the overall quantity of gaseous
drug being delivered.
[0050] d) If the desired quantity of pharmaceutical gas was entered
as a dose per Kg of the patient's ideal body weight (.mu.g/kg)
along with the patient's ideal body weight (Kg) then the amount per
breath (M.sub.CO breath) can be determined as a function of the
patient's ideal body weight (IBW), the set dose per kilogram
(M.sub.kg) and the patient's monitored respiratory rate (RR) or
combinations thereof;
[0051] M.sub.CO breath=f (IBW, M.sub.kg, RR) and the number of
breaths can then be calculated as;
n.sub.breaths=M.sub.CO/M.sub.CO breath (7)
[0052] Once the amount per breath (M.sub.CO breath) and the number
of breaths (n.sub.breaths) required to be delivered has been
determined, the values can be displayed on the front panel 10 to
inform the user of the amounts the device has selected.
[0053] e) Instead of the ideal body weight (IBW) of the patient,
the height and sex of the patient could be entered (which is how
IBW is determined).
[0054] f) If the desired quantity of pharmaceutical gas per unit of
time is entered into the device, then the device can calculate the
quantity per breath to be delivered to the patient based on the
current monitored respiratory breath rate (as determined by the
breath trigger sensor). This quantity per breath can be
recalculated after every breath when new information on the
respiratory rate is available to ensure the quantity per unit of
time is maintained even if the patient respiratory breath pattern
changes over time.
[0055] g) There are also other ways of varying the quantity of
pharmaceutical gas delivered per breath to ensure the quantity per
unit of time is maintained even if the patients respiratory rate
changes. As used in this specification and the appended claims, the
term "varying the quantity" means that the calculated quantity is a
dynamic value capable of being re-evaluated throughout
administration of the therapy gas, not a fixed value. It is
possible that the amount of gas delivered for each of the n.sup.th
breaths is the same, or the amount for nearly every breath is the
same. Varying the quantity does not mean that the amount of therapy
gas delivered on every n.sup.th breath is different from the
previous or subsequent breaths, merely that the value could be
varied to compensate for changes in the patient's breathing
pattern. For example, varying the quantity of therapy gas per
breath may mean that the amount per breath is cut in half when the
respiratory rate of the patient doubles.
[0056] Another example is where the device has two different
amounts of delivery per breath, a high amount and a low amount. The
device chooses which one to use based on the calculated quantity
per unit of time being delivered over the past number of breaths.
If the amount per unit of time is greater than required, it uses
the low amount per breath until the situation corrects itself;
likewise, if the quantity per unit of time is running low, then the
unit switches to the high amount per breath.
[0057] The device can also have programmed limits which restrict
the maximum and minimum values that can be selected for M.sub.CO
breath so that the system doesn't select inappropriately too high
or too low values. These limits can be set to vary based on the
patient's ideal body weight, or other indicator of the patient size
such as the patient's height, or the respiratory rate of the
patient.
[0058] The aforesaid information is sufficient for the system of
the present invention to deliver the dose to the patient and to
determine the amount per breath, time of administration or other
parameter in order to commence the administration of CO and to
terminate that administration when the user set quantity of the
pharmaceutical gas has been delivered to the patient.
[0059] Turning now to FIG. 3, there is shown a schematic of a
system that can be used to carry out the present invention when the
patient is breathing spontaneously. As can be seen, there is a
patient device 18 that delivers the dosage of the pharmaceutical
gas from the gas delivery system 22 to the patient 41 via a gas
conducting conduit 19. As indicated, the patient device 18 can be
any one of a variety of devices that actually directs the
pharmaceutical gas into the patient and may be a nasal cannula, a
mask, an endotracheal tube and the like.
[0060] With the FIG. 3 embodiment, there is a source of the
pharmaceutical gas by means of a gas supply tank 20 containing the
pharmaceutical gas generally in a carrier gas. When the
pharmaceutical gas is carbon monoxide, for example, the
conventional, commercially available carrier gas is air. The supply
of carbon monoxide and air is provided in concentrations of 3000
ppm however, concentrations within the range of 1000 to 5000 ppm of
CO in air are also possible alternatives. In the case of NO as the
pharmaceutical gas, the carrier gas is conventionally nitrogen and
the typical available concentrations range from 100 ppm to 1600
ppm.
[0061] Accordingly, from the supply tank 20, there is a tank
pressure gauge 21 and a regulator 23 to bring the tank pressure
down to the working pressure of the gas delivery system 22. The
pharmaceutical gas enters the gas delivery system 22 through an
inlet 24 that can provide a ready connection between that delivery
system 22 and the supply tank 20 via a conduit. The gas delivery
system 22 has a filter 25 to ensure no contaminants can interfere
with the safe operation of the system and a pressure sensor 27 to
detect if the supply pressure is adequate and thereafter includes a
gas shut off valve 26 as a control of the pharmaceutical gas
entering the delivery system 22 and to provide safety control in
the event the delivery system 22 is over delivering the
pharmaceutical gas to the patient. In the event of such over
delivery, the shut off valve 26 can be immediately closed and an
alarm 42 sounded to alert the user that the gas delivery system has
been disabled. As such, the shut off valve 26 can be a solenoid
operated valve that is operated from signals directed from a
central processing unit including a microprocessor.
[0062] Downstream from the shut off valve 26 is a flow control
system that controls the flow of the pharmaceutical gas to the
patient through the patient device 18. In the embodiment shown, the
flow control system comprises a high flow control valve 28 and a
low control valve 30 and just downstream from the high and low flow
control valves 28, 30, respectively, are a high flow orifice 32 and
a low flow orifice 34 and the purpose and use of the high and low
flow valves 28, 30 and the high and low flow orifices 32, 34 will
be later explained. A gas flow sensor 36 is also located in the
flow of pharmaceutical gas to the patient device 18 and, as shown,
is downstream from the flow control system, however, the gas flow
sensor 36 may alternatively be located upstream of the flow control
system.
[0063] Next, there is a patient trigger sensor 38. When the patient
breathes in during inspiration it creates a small sub atmospheric
pressure in the nose or other area where the patient device 18 is
located, and hence in the patient device 18 itself. The patient
trigger sensor 38 detects this pressure drop and provides a signal
indicative of the start of inspiration of the patient. Similarly,
when the patient breathes out there is a positive pressure in the
patient device 18 and the patient trigger sensor 38 detects that
positive pressure and provides a signal indicative of the beginning
of expiration. This allows the patient trigger sensor 38 to
determine not only the respiratory rate of the patient but also the
inspiratory and expiratory times.
[0064] Finally there is a CPU 40 that communicates with the patient
trigger sensor 38, the high and low flow valves 28, 30, the gas
shut off valve 26 and other components in order to carry out the
purpose and intent of the present invention. The CPU 40 may include
a processing component such as a microprocessor to carry out all of
the solutions to the equations that are used by the gas delivery
system 22 to deliver the predetermined quantity of the
pharmaceutical gas to a patient. The CPU 40 is connected to the
front panel 10 where the user can enter settings and monitor
therapy.
[0065] The use of the delivery system 22 of the present invention
for spontaneous breathing can now be explained. When the delivery
system 22 detects by means of the patient trigger sensor 38 that
inspiration has started, there is a signal that is provided to the
CPU 40 to deliver a dose of a pharmaceutical gas (M.sub.CO breath)
into the patient's inspiratory gas flow, preferably during the
first 1/2 of the inspiratory cycle. This amount per breath has been
determined based on the desired quantity of pharmaceutical gas that
has been set on the system and the calculations made in a) to g)
described earlier.
[0066] The actual volume of gas delivered during the breath depends
on the concentration of the pharmaceutical gas in the carrier gas
that is supplied by the supply tank 20. A typical source
concentration (C.sub.CO) for CO would be 3000 ppm (range 500 to
5000). The volume of source gas (V.sub.d) per breath to provide a
dose per breath (M.sub.CO breath) when the source of CO is 3000 ppm
is given by the following equation, combining equations 2, 3, 4 and
6;
V.sub.d=M.sub.CO breath/(28C.sub.CO4.16.times.10.sup.-11) (8)
[0067] Given that M.sub.CO=60.times.10.sup.-3 (g), C.sub.CO=3000
(ppm), n.sub.breaths=600, then V.sub.d=28.6 (mL).
[0068] To deliver the volume of source gas per breath (V.sub.d),
that is, the pharmaceutical gas and the carrier gas, the delivery
system 22 opens a flow control valve, such as high flow valve 28 or
low flow valve 30 to allow the gas to flow to the patient until the
volume per breath (V.sub.d) has been delivered. The presence of the
high flow orifice 32 and the low flow orifice 36 limits the flow of
gas to a fixed set level during the period that the high or low
flow valves 28, 30 are open so the delivery system 22 can determine
the period of time the high or low flow valves 28, 30 should be
open to deliver the volume per breath (V.sub.d) required. Also, as
another option, the flow can be determined by the gas flow sensor
36 to monitor the gas flow to the patient device 18 and thus to the
patient and can shut off the appropriate high or low flow control
valve 28, 30 when the desired predetermined quantity of
pharmaceutical gas dose has been delivered to the patient.
[0069] As can be seen, to provide enough range to cover all the
possible doses, the use of multiple flow valves, that is, the high
flow valve 28 and the low flow valve 30 along with corresponding
multiple orifices, high flow orifice 32 and low flow orifice 34,
can be used in parallel so as to provide high and low ranges of gas
flow. For instance, the low flow gas flow through the low flow
valve 30 could be set to 1 L/min and the high flow gas flow through
the high flow control valve 28 could be set to 6 L/min. The flow
range of the particular gas flow valve is selected to ensure that
the volume of gas per breath (V.sub.d) can be delivered to the
patient in at least 1/2 the inspiratory time.
[0070] As an example, if the patient was breathing at 12 breaths
per minute and had an I:E ratio of 1:2 then the inspiratory time
would be 1.66 seconds and half that would be 0.83 seconds.
[0071] The time (t) taken to deliver a V.sub.d of 28 mL can be
calculated as follows.
t=V.sub.d60/(Q1000) (secs) (9)
[0072] When Q (the flow of gas when the high flow valve 28 is
open)=6 L/mins t=0.28 (secs).
[0073] That time is therefore well within 1/2 the inspiratory time
allowed of 0.83 seconds.
[0074] The delivery system 22 can also include monitoring and alarm
features to alert the user if the delivery system 22 is not working
correctly. Those alarm conditions can be determined by the CPU 40
and the alarm 42 activated to alert the user to the particular
fault condition. The alarm 42 can be audible, visual or both and
the alarm conditions can be any one or all of the following: no
breath detected, low source gas pressure, inaccurate delivery of
the volume per breath (V.sub.d), over delivery of the volume per
breath (V.sub.d), under delivery of the volume per breath (V.sub.d)
and termination/completion of the delivery program.
[0075] Under certain conditions, such as when the delivery system
22 is over delivering the pharmaceutical gas, the CPU 40 may signal
the gas shut off valve 26 and immediately cease any further
delivery of the pharmaceutical gas and the alarm 42 also
activated.
[0076] The use of the alarm 42 can also be an alternative to
actually shutting off the supply of the pharmaceutical gas to a
patient when the predetermined desired quantity of pharmaceutical
gas has been fully delivered to the patient. In such case, as an
alternative to ceasing the further supply of the pharmaceutical gas
to the patient, the delivery system 22 may, by means of the CPU 40,
activate the alarm 42 to alert the user that the total
predetermined desired quantity of the pharmaceutical gas has been
delivered. The user can then determine whether to manually
deactivate the delivery system 22 or continue the delivery of the
pharmaceutical gas under more watchful control of the patient's
status.
[0077] Turning now to FIG. 4, there is shown a schematic view of a
gas delivery system 44 used in conjunction with a patient being
breathed by a ventilator 46. In the FIG. 4 embodiment, again there
is a supply tank 20 that includes a conventional gas regulator 23
and pressure gauge 21 to supply the pharmaceutical gas along with
the carrier gas to an inlet 24 in the gas delivery system 44.
Briefly summarizing the components of the FIG. 4 embodiment, since
they are basically the same components as described with respect to
the FIG. 3 embodiment, there can be a filter 25 and a pressure
sensor 27 in the gas delivery system 44. Again there is a shut off
valve 26 to control the overall flow of the pharmaceutical gas
through the gas delivery system 44.
[0078] The high and low flow control valves 28 and 30 control the
flow of the pharmaceutical gas through the gas delivery system 44
and, the high and low flow valves 28, 30 operate as described with
respect to the FIG. 3 embodiment with high and low flow orifices
32, 34 located downstream of the flow control valves.
[0079] Again there is a gas flow sensor 36 and a patient trigger
sensor 66, both of which communicate with the CPU 40. With this
embodiment, however, the pharmaceutical gas is carried through an
outlet conduit 70 to a patient device 72 that also receives the
breathing gas from the ventilator 46. As such, the ventilator 46
delivers a flow of gas through the inspiratory limb 74 and gas is
returned to the ventilator 46 through the expiratory limb 76.
[0080] The flow of gas from the ventilator 46 is thus supplemented
by the flow of pharmaceutical gas from the gas delivery system 44
where that gas is mixed at or proximate to the patient device 72
for introduction into the patient 78. Since all of the
pharmaceutical gas is still delivered to the patient over the
plurality of breaths, basically the CPU 40 can carry out the same
determination of flows and the like as explained with respect to
the FIG. 3 embodiment. The main difference between this FIG. 4
embodiment, and that shown in FIG. 3 is that the patient trigger
sensor 66 is designed to operate in a way that works with a
ventilator 46.
[0081] For instance, when the ventilator 46 provides gas flow to a
patient during inspiration, it causes a positive pressure in the
breathing circuit. The positive pressure is conducted through the
outlet conduit 70 and is detected by the patient trigger sensor 66
and is recognized as the start of inspiration. This is the opposite
to the embodiment of FIG. 3 where the patient breathes
spontaneously and a negative pressure is generated during
inspiration in the patient device 18; this negative pressure is
conducted to the patient trigger sensor 38 of FIG. 3 and is
recognized as the start of inspiration. As can be appreciated, the
patient trigger sensor 38 of FIG. 3 and the patient trigger sensor
of FIG. 4 could be the same pressure sensor and the gas delivery
system 44 can be set for work with a ventilator or a spontaneously
breathing patient.
[0082] One or more embodiments of the invention are directed to
methods of administering a therapy gas to a patient. A desired
total quantity of therapy gas to be administered to the patient
over a period of time over a plurality of breaths is determined.
The desired total quantity of therapy gas can be measured in any
suitable units including, but not limited to, mass of therapy gas,
mass of the therapy gas active ingredient and moles of the therapy
gas active ingredient. The desired total quantity of therapy gas to
be administered to the patient can be entered directly into the
device or can be calculated by the device. For example, one or more
of the following parameters may be input to the device: (a) the
desired total quantity of therapy gas; (b) the period of time for
delivery of the therapy gas; (c) the total number of breaths over
which the delivery gas is delivered; and (d) the frequency of
administration, i.e. choose the value of n such that the therapy
gas is delivered every n.sup.th breath, wherein n is 1 or greater.
Treatment may be repeated as necessary. It will be understood by
those skilled in the art that other parameters may be entered.
[0083] The quantity of the therapy gas is delivered to the patient
during inspiration. In one or more embodiments, the therapy gas is
delivered to the patient's alveoli. In specific embodiments,
substantially all of the therapy gas is delivered to the patient's
alveoli. As used in this specification and the appended claims, the
term "substantially all" means that at least about 80%, 85%, 90% or
95% of the therapy gas is delivered to the alveoli. In some
embodiments, "substantially all" means that a sufficient percentage
of therapy gas is delivered to the alveoli so that there is little
or no irritation of the respiratory track.
[0084] Delivery of the therapy gas to the patient happens every
n.sup.th breath during the plurality of breaths. In detailed
embodiments, n is 1 or greater. When n is 1, the therapy gas is
delivered to the patient on each breath. Where n is 2, the therapy
gas is delivered to the patient on every other breath. In various
embodiments, n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. Thus, when n is
2 or greater, conditions of skipped breathing are achieved, meaning
therapy gas is skipped on certain breaths while administered on
certain other breaths. Additionally, the interval between delivery
breaths can vary throughout the delivery of the total quantity
depending on a number of conditions. For example, therapy gas may
be delivered on breaths 1, 3, 5, 8, 10, 12, etc. In detailed
embodiments, the administration of the therapy gas is repeated for
each n.sup.th breath. In various embodiments, the therapy gas is
delivered for 2 out of every 3 breaths, or for 3 out of every 5
breaths, or for 4 out of every 7 breaths, or for 2 out of every 5
breaths, or for 2 out of every 7 breaths, etc.
[0085] Furthermore, certain embodiments provide that the delivery
every n.sup.th breath does not need to follow a specific pattern.
For example, as discussed in more detail below, certain breaths may
be skipped for a variety of reasons, such as an amount to be
delivered in a particular breath being less than a minimum delivery
quantity. Breaths may also be skipped such that the gas is not
delivered on literally every n.sup.th breath, but the therapy gas
is delivered on average every n.sup.th breath. Also, the value of n
may change during administration such that the therapy gas is
delivered is every n.sub.1.sup.th breath for part of the
administration, the therapy gas is delivered is every
n.sub.2.sup.th breath for another part of the administration, the
therapy gas is delivered every n.sub.3.sup.th breath for a third
part of the administration, etc.
[0086] In some embodiments, the quantity of therapy gas provided at
the n.sup.th breath is a function of one or more of a first
respiratory rate, a first tidal volume of the patient and the
patient's ideal body weight. The first respiratory rate and tidal
volume can be measured prior to, at the beginning of, or during the
treatment. One or more of the first respiratory rate and tidal
volume can be used to calculate an initial amount of therapy gas to
be delivered on each n.sup.th breath for a period of time to
deliver the desired total quantity of therapy gas. After this
initial respiratory rate is measured and the initial amount to be
delivered per n.sup.th breath is calculated or determined, changes
in the respiratory rate may occur and the calculated amount may
need to be adjusted. Thus, a subsequent calculation of the amount
of therapy gas to be delivered can be performed. The subsequent
calculation can be done after any or all individual administration
of therapy gas. In one embodiment, the amount of therapy gas to be
delivered during the n.sup.th breath can be recalculated after each
individual delivery. As a result of the recalculations, the total
quantity of therapy gas delivered is independent of the patient's
respiratory rate, and the total quantity of therapy gas can be
controlled to be the desired amount.
[0087] As an example, should the initial amount of therapy gas to
be delivered during the n.sup.th breath be calculated to amount to
100 .mu.L, and after the first breath, the patients respiratory
rate doubles, the subsequent calculated rate would be about 50
.mu.L per n.sup.th breath. In the prior art, which does not
recalculate the amount of therapy gas to be delivered, this
scenario would result in the patient having received about twice
the amount of therapy gas as was originally intended by the end of
the period of time for delivery of the gas. Thus, recalculating the
amount of gas to be delivered throughout the delivery period may
result in a more accurate amount of therapy gas provided to the
patient and can help mitigate potential side effects of too much of
the therapy gas. Accordingly, varying the amount per n.sup.th
breath ensures that the desired total amount of therapy gas is
delivered to the patient over the plurality of breaths.
[0088] The quantity of the therapy gas per n.sup.th breath can be
varied to ensure that the desired total quantity over the period of
time is administered, independent of the respiratory pattern of the
patient. The quantity of therapy gas delivered may be in the range
of a minimum quantity and a maximum quantity. In detailed
embodiments, the minimum quantity and maximum quantity are
functions of the device delivering the therapy gas. The minimum
quantity may be the smallest amount that the device is capable of
providing and the maximum quantity may be the maximum amount that
the device is capable of providing. For example, if the smallest
volume of therapy gas that the device is capable of releasing is 10
.mu.L, then the concentration of the therapy gas multiplied by the
smallest deliverable volume will give the smallest amount of
therapy gas active that can be delivered.
[0089] In some embodiments, when the quantity of therapy gas to be
delivered per n.sup.th breath is greater than the minimum quantity
and less than the maximum quantity, the quantity of therapy gas per
breath is administered on the n.sup.th breath. When the quantity of
therapy gas per n.sup.th breath is less than the minimum, the
therapy gas can be administered in many ways. For example, if the
device is only capable of delivering a minimum of 10 .mu.L, but the
quantity to be delivered is 8 .mu.L, the device can skip the amount
to be delivered during this breath and add the amount (8 .mu.L) to
any of the subsequent breaths, or can divide the amount among two
or more subsequent breaths. Alternatively, the device can deliver
the minimum amount to be delivered (10 .mu.L) and subtract the
difference (2 .mu.L) from a subsequent breath or divided the amount
to be subtracted over two or more subsequent breaths. In detailed
embodiments, the quantity of therapy gas per breath is skipped and
a new quantity of therapy gas per breath is calculated for
subsequent doses. The new quantity can include the skipped amount
in a single breath, or the new quantity can spread the skipped
amount over multiple breaths.
[0090] When the quantity of therapy gas to be delivered for the
n.sup.th breath is greater than the maximum quantity, several
potential courses of action can be taken, including triggering an
alarm. In detailed embodiments, the maximum quantity of therapy gas
per breath is administered and the difference between the
calculated quantity of therapy gas for the n.sup.th breath and the
maximum quantity of therapy gas is carried forward for later
delivery on one or more subsequent breaths. However, where later
delivery is not possible, the system may trigger one of many alarm
conditions or can be set to automatically extend the period of time
for delivery to ensure that the desired total amount of therapy gas
is delivered.
[0091] In some embodiments, n is 1 such that the therapy gas is
administered every breath. However, even if the therapy gas is set
to be administered every breath, some breaths may be skipped if the
amount to be delivered in a given breath is less than the minimum
quantity. As noted above, the quantity that would have been
delivered during this skipped breath may be added to any of the
subsequent breaths or may be divided among two or more subsequent
breaths.
[0092] In some embodiments, the therapy gas is administered every
n.sup.th breath where n is 2 or greater. This means that the
therapy gas is provided in a "skip breathing" regimen. Skip
breathing may be desired as there can be an overall decrease in the
amount and severity of adverse reactions including irritation due
to the therapy gas. In some embodiments, where n is 2 or greater,
the therapy gas is delivered during every other (for n=2) breath,
or greater, and no therapy gas is administered during the other
breaths. During the alternate breaths (i.e., where no therapy gas
is provided) the patient can breathe ambient air, oxygenated air,
pure oxygen, or a different therapy gas, depending on the desired
treatment. In detailed embodiments, the patient breathes ambient
air on inhalations not accompanied by therapy gas.
[0093] In some embodiments, where n is 2 or greater, the
administration of quantities greater than the maximum amount can be
handled differently than when therapy gas is delivered on every
breath. If the amount to be delivered is greater than the maximum,
the device may proceed in one or more of the following manners: (a)
an alarm can be activated; (b) the maximum amount of therapy gas
that can be delivered is delivered to the patient on the n.sup.th
breath; and (c) the difference between the maximum amount and the
quantity to be delivered is carried over to subsequent breaths or
administrations. If the following breath is skipped as part of a
skip breathing protocol, i.e. is not an n.sup.th breath, the
carryover dose could be provided during the skipped breath or
maintained until the next breath scheduled for dosing.
[0094] The amount of therapy gas to be delivered can be calculated
multiple times during the total administration time. The amount can
be recalculated based on the number of breaths, the amount of time
between measurements and after every breath, as desired by the
administration protocol. When the quantity of the therapy gas to be
delivered is skipped, for any reason, a new quantity of therapy gas
per breath is calculated.
[0095] Upon completion of the administration program, one or more
of several actions can be taken by the device. The device can
trigger an alarm, as described earlier. The administration can
continue until manually or programmatically stopped. The delivery
program (i.e., the amount of therapy gas per period of time) can be
repeated for any number of repetitions, or indefinitely. The
administration of the therapy gas can be stopped until manually or
programmatically restarted (i.e., a programmed pause between
executions of the administration protocol). For example, if the
program calls for delivery over a one hour period, the device can
be programmed to wait for a specified period (e.g., 2 hours) after
completion before restarting the administration program.
[0096] Additional embodiments of the invention are directed to
methods of treating pulmonary arterial hypertension (PAH),
including those suffering from chronic obstructive pulmonary
disease (COPD), idiopathic pulmonary fibrosis (IPF), etc. A desired
total quantity of therapy gas to be delivered to a COPD patient
over a period of time over a plurality of breaths is determined.
The quantity is administered to the patient during inspiration
every n.sup.th breath of the plurality of breaths, where n is 2 or
greater. The quantity of therapy gas is varied per breath to ensure
that the desired total quantity delivered over the period of time
is maintained independent of the respiratory pattern of the
patient. In detailed embodiments, varying the quantity of the
therapy gas per breath comprises determining the quantity of
therapy gas to be delivered during the breath based on the
respiratory rate of the patient and the amount of therapy gas
already given to the patient. In other words, the desired total
amount of therapy gas to be delivered to the patient over the
plurality of breaths is ensured by varying the amount delivered per
breath, as required by changes in the breathing pattern of the
patient.
[0097] FIG. 5 shows a flowchart for a detailed method 100 in
accordance with one or more embodiments of the invention. It will
be understood by those skilled in the art that the method outlined
in FIG. 5 is merely a possible methodology and should not be taken
as limiting the scope of the invention. The methods described
provide for ability to manage the total quantity of therapy gas
given over a period of time. Pertinent information related to the
administration of the therapy gas and the program conditions 102
are entered into a device capable of delivering the therapy gas.
The program conditions can explicitly state the necessary
information for delivery, or can provide variables which the device
can use to calculate the necessary information.
[0098] The device determines if the approaching breath is an
n.sup.th breath 104, meaning that the device will administer the
therapy gas on that breath. On a first pass through the process
flow, the answer will likely be yes, leading the device to
determine one or more physiological parameters 106 of the patient
(e.g., respiratory rate and tidal volume). The physiological
parameters can be measured by the device or transferred from
another measuring device or can be manually entered into the
device.
[0099] Based on the measurements of the physiological parameters,
the device can calculate the amount of therapy gas to be delivered
to the patient 108. This can be an initial calculation or a
subsequent calculation. The calculated amount of therapy gas per
breath may be compared 110 to a minimum quantity and a maximum
quantity of deliverable gas. The minimum and maximum quantities, as
described previously, can be functions of the device, functions of
the concentration of the therapy gas source, a function of the
physiological parameters of the patient and combinations thereof.
If the amount of therapy gas to be delivered is between the minimum
and maximum quantities, the dose of therapy gas is delivered 112 to
the patient on the next breath.
[0100] If the comparison in 110 indicated that the amount of
therapy gas to be delivered is less than the minimum deliverable
amount, the device can proceed with any or all of several below
minimum amount options 114. The device can withhold administration
116 of the therapy gas for that breath. The device can carryover
118 the amount not administered to one or more subsequent breaths.
The minimum amount can be administered 120 resulting in an
over-administration for that breath. The amount over-administered
can then be reduced from one or more subsequent breaths. An alarm
condition 122 (e.g., audible, visual, or electronic), as described
earlier, can be activated.
[0101] If the comparison in 110 indicates that the amount of
therapy gas to be delivered is greater than the maximum deliverable
amount, the device can proceed with any or all of several above
maximum amount options 124. The device can trigger an alarm
condition 122 as described above. The device can administer the
maximum amount 126 and either discard the difference or carryover
118 the difference to subsequent breaths. However, depending on the
reason for the quantity to be delivered to be over the maximum and
the administration protocol, carrying over the difference to
subsequent breaths can result in the amount for each n.sup.th
breath to be over the maximum. To avoid this, the device can be
programmed to carryover the amount if, for example, the calculated
amount to be delivered is an outlier or if subsequent breaths are
skipped.
[0102] After the amount of therapy gas is delivered (if
applicable), the device determines if it has reached the end
conditions 128 of the program (e.g., time, amount delivered, number
of breaths). If the end condition has not been reached, the device
can then check to see if the next breath is scheduled to receive a
dose of therapy gas 104. If yes, the method proceeds through one or
more of the steps as previously described. If the following breath
is not supposed to receive therapy gas, the device can determine if
there is carryover from a previous breath 130. If there is
carryover and it is the delivery of therapy gas is allowed on the
alternate breaths, the device can determine the amount of therapy
gas per breath to deliver 108. This can be as simple as delivering
the carried over amount, or holding the amount for further
subsequent breaths. If there are no carry over breaths 130, the
device can do nothing for the breath and restart the method at
evaluating if the next breath is an n.sup.th breath 104.
[0103] When the end conditions 128 have been met, the method and
device can proceed through one or more of various end condition
actions 132. The delivery of the therapy gas can be discontinued
until manually or programmatically restarted 134. An alarm can be
triggered. Administration of the therapy gas can continue 136 under
the same conditions (e.g., restarting the program 138) or with
different conditions.
[0104] Those skilled in the art will readily recognize numerous
adaptations and modifications which can be made to the
pharmaceutical gas delivery system and method of delivering a
pharmaceutical gas of the present invention which will result in an
improved method and system for introducing a known desired quantity
of a pharmaceutical gas into a patient, yet all of which will fall
within the scope and spirit of the present invention as defined in
the following claims. Accordingly, the invention is to be limited
only by the following claims and their equivalents.
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