Surgery – Respiratory method or device
Reexamination Certificate
2000-09-22
2004-02-24
Lewis, Aaron J. (Department: 3761)
Surgery
Respiratory method or device
C128S203120, C128S204230
Reexamination Certificate
active
06694969
ABSTRACT:
BACKGROUND OF THE INVENTION
Human and animal body metabolism uses oxygen and produces carbon dioxide. The required oxygen is received from the atmospheric air during respiration, in the course of which waste carbon dioxide is released. The gas exchange between the body and the environment takes place in the lung alveoli, where pulmonary blood capillaries are separated from the gas space in the lung in communication with the atmospheric air by only a thin membrane permeable for gases. The pulmonary blood flow passing through the alveoli equilibrates in gas partial pressure with the alveolar gas, resulting in blood oxygen uptake and carbon dioxide release. During each breath the alveolar blood gas concentration is changed as a result of the oxygen supplement and carbon dioxide removal. The blood transports the oxygen from the lungs to the sites of consumption and waste carbon dioxide from the sites of metabolism back to the lungs.
Blood flow rates through the lungs and perfusion pressure are regulated by the smooth muscle tension of the pulmonary capillaries. This regulation is mediated by endothelium derived nitric oxide. Insufficient local NO production increases smooth muscle tone. This results in pulmonary vasoconstriction and impaired blood flow or, alternatively, elevated pulmonary artery pressure. Pulmonary hypertension is present in various circumstances, such as pneumonia, traumatic injury, aspiration or inhalation injury, fat embolism in the lung, acidosis, inflammation of the lung, adult respiratory distress syndrome, acute pulmonary edema, acute mountain sickness, post cardiac surgery, acute pulmonary hypertension, persistent pulmonary hypertension of the newborn, prenatal aspiration syndrome, hyaline membrane disease, acute pulmonary embolism, heparinprotamine reactions, sepsis, or hypoxia (including that which may occur during one-lung anesthesia), as well as those cases of chronic pulmonary vasoconstriction which have a reversible component, such may result from chronic pulmonary hypertension, bronchopulmonary dysplasia, chronic pulmonary embolism, idiopathic or primary pulmonary hypertension, or chronic hypoxia due to chronic obstructive lung disease.
U.S. Pat. No. 5,485,827 discloses a method using inhaled nitric oxide (NO) useful for preventing or reversing acute pulmonary vasoconstriction, such as that arising from the foregoing injuries. A method for using NO gas also to achieve bronchodilatation and thereby improve the distribution of other agents administered by inhalation is also disclosed.
A special advantage of inhaled NO as a pulmonary vasodilator is its selectivity. NO is rapidly bound with blood hemoglobin, thus the free NO needed for mediating the vasodilatation is available selectively for the smooth muscles of the pulmonary capillaries only, and even more specifically, for the pulmonary capillaries adjacent ventilated alveoli. The pulmonary blood for alveoli which are not ventilated form a pulmonary shunt flow, since the non-ventilated alveoli are rapidly equilibrated with the pulmonary artery blood gases and no further gas exchange will take place. The pulmonary blood flow not participating in the gas exchange is thus called shunt flow. One reason for using inhaled NO therapy is to reduce the alveolar-arterial oxygen partial pressure difference for better oxygenation. The mechanism for this is reduction of the shunt. Administration of NO to ventilated alveoli dilates the pulmonary capillaries carrying blood for gas exchange. Capillaries in communication with the non-ventilated alveoli are constricted due to the low NO concentration. This results in blood perfusion redistribution towards the ventilated lung areas. When the portion of the pulmonary perfusion participating in the blood flow increases, the arterial oxygen partial pressure will increase, improving oxygenation.
Despite this well known mechanism, the published research results of inhaled NO for improving oxygenation have been limited. Examples of studies of oxygenation improvements are e.g. Gerlach et al.: “
Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome
”, Intensive Care Med (1993) 19:443-449; Gerlach et al.: “
Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome
”, Euro J. of Clinical Investigation (1993) 23: 449-502:, Benzing et al.: “
Hypoxic pulmonary vasoconstriction in non-verlated lung areas contributes to diff ences in hemodynamic and gas exchange responses to inhalation of nitric oxide
”, Anesthesiology (1997) 86:1254-61. In all these, and other, published studies, NO has been administered to patients having a diagnosis of lung disease.
The NO delivery rate for improving oxygenation has both minimum and maximum limits making the oxygenation improvement clinically challenging. The loss of the oxygenation effect with increased doses is most likely traced back to the smooth muscle sensitivity. With increasing delivery, more NO diffuses to non- or poorly ventilated alveoli causing dilatation. This impairs the improvement in oxygenation seen prior to increasing the dose, as discussed by Gerlach in “Time-course . . . ” The balance between improved and impaired gas exchange depends on lung status and is, therefore, individual for each patient. When the ventilation or lung performance is changing, most likely this balance is also affected.
Pulmonary shunt variation is very commonly present in healthy and sick lungs in various daily life and treatment conditions. Atelectasis, areas of the lung not participating in the gas exchange due to collapse of the alveoli, prevent normal oxygen delivery, and increases the pulmonary shunt. It has been pointed out that atelectasis is present during almost every anaesthesia (A. Strandberg et al: “
Atelectasis during anaesthesia and in the postoperative period
”, Acta Anaesthesiol. Scand. (Feb. 1986) 30:2,154-8); L. Tokic et al: “
Lung collapse and gas exchange during general anesthesia: effects of spontaneous breathing, muscle paralysis, and positive end expiratory pressure
”, Anesthesiology (Feb. 1997) 66:2, 157-67). In normal healthy subjects this atelectasis is not very significant due to the oxygenation reserve.
The severity of atelectasis will increase along with decrement of the oxygenation reserve. During artificial ventilation in anaesthesia and intensive care it is possible to increase the inhaled oxygen fraction and thereby increase the oxygenation reserve. In extensive collapse of lung, aeration with even 100% oxygen in the inhaled gases may not be sufficient. An example where the oxygenation reserve is endangered is horses experiencing anaesthesia in the unnatural supine position. The lungs, anatomically suited for the standing position, will be compressed by the body mass in the supine position. The lung volume can be reduced by as much as 50% and cause a pulmonary perfusion shunt of 20-50%. NO delivered to the inspired gas ca distribute the blood flow to ventilated areas and improve oxygenation.
Similar problems, which may in the worst case be chronic in nature, are encountered by humans having morbid obesity, i.e. twice the normal body weight, or 50 kg over the normal, or a body mass index over 40. In the supine position the lung functional residual capacity, FRC, is markedly reduced by the tissue mass restricting the lung volume. This may lead to impaired oxygenation and pulmonary shunt without any diagnosis of lung disease especially when sleeping when the lungs are squeezed by the body mass. Even worse, the diaphragm of obese people tends to assume a position which can be described as elevated when a person is standing, leading to a decrease in lung volume and increase in shunt. This may cause oxygenation problems even in normal daily life. The problem also occurs in anaesthesia or intensive care, and extends also to postoperative care where the restoration of normal pulmonary functions may take 4-5 hours (Brodsky: “
Heinonen Erkki
Högman Marieann
Meriläinen Pekka
Nyman Görel
Instrumentarium Corp.
Lewis Aaron J.
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