Surgery – Blood drawn and replaced or treated and returned to body
Reissue Patent
1999-10-07
2003-07-22
Sykes, Angela D. (Department: 3762)
Surgery
Blood drawn and replaced or treated and returned to body
C607S106000, C128S898000
Reissue Patent
active
RE038203
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to an apparatus and method for eliminating viruses by means of extracorporeal whole body hyperthermia, and more particularly to an apparatus and method that regulates the blood pH, pCO
2
, and base excess, thereby maintaining a constant CO
2
as the patients body temperature is increased.
BACKGROUND OF THE INVENTION
The use of heat to treat ailments dates back many centuries to ancient Egyptian times, where certain cancers were treated by partial burial of the patient in hot sand. The use of hyperthermia as a treatment has continued into the twentieth century. Hyperthermia presents a unique set of physiologic problems that require careful management in order to achieve success. These problems have plagued soldiers on the battlefield, inner city residents during heat waves, and clinicians trying to treat cancer and AIDS.
In homoiothermal bodies, thermoregulation and maintenance of near normal temperature automatically takes precedence over other homeostatic functions, including electrolyte balance. In order to maintain normal temperatures during external exposure to heat, the body responds through an increase in both cardiac output, and more importantly, respiratory rate well above metabolic needs, thereby ridding the body of excess heat. The bulk of the blood is directed to the cutaneous vessels of the skin through increased cardiac output, while the increase respiratory rate or hyper ventilatory response is akin to the panting of a dog. A negative consequence of hyperventilation is that an increased respiratory rate effectively and drastically reduces the pCO
2
(and total CO
2
) of the circulating blood creating a respiratory alkalosis. This decrease in pCO
2
increases the pH gradient across the cellular membrane. To regain electrical neutrality between intra and extracellular compartments there is a shift of ions between these two spaces, many of which may be lost due to renal excretion. Additionally, cellular function may be impaired as enzyme activity is adversely affected by electrolyte imbalance.
The measurement of intracellular pH has only been reliably performed within the last 25 to 30 years, therefore, most of this knowledge had gone unnoticed until 15 years ago. Researchers studying better methods of myocardial protection during hypthermic/cardioplegia cardiac arrest discovered that alkalotic infusion into the coronary arteries prior to the removal of the aortic cross clamp prevented the so called reperfusion injury.
During normal arterial blood flow, at 37° C. the arterial pH is approximately 7.4, having an arterial carbon dioxide tension of about 40 torr (mmHg). The human body modulates the arterial pCO
2
levels as temperature and the CO
2
content in the blood are altered. It is known that during hypothermic reactions, when the body temperature is decreased, there is a decrease in pCO
2
due to increased solubility, and increases in the blood pH. Generally, the &Dgr;pH/° C.≅−0.015 when the CO
2
content of blood and the [OH
−
]/[H
+
] remain constant. Also, pN is defined as the pH of the neutrality of water where [H
+
]+[OH
−
]=1, that is when ionic balance is achieved. This balance is governed by the ionization constant of water K
w
and varies with temperature. As temperature rises the pN is reduced. Of the three known buffer systems, it is believed that imidazole moiety of a person's blood accounts for this relationship.
Researchers in whole body hyperthermia have used temperature correction of blood gases (pH-stat). During the use of pH-stat, researches have observed electrolyte replacement and metabolic acidosis even with a reduced A—V O
2
difference. One explanation for this is that the use of the pH-stat technique artificially imposes a respiratory alkalosis which in turn affects oxyhemoglobin dissociation, reducing the availability of oxygen to the tissue.
In studies of heterotherms, or cold blooded animals, it was noted that as they were exposed and equilibrated to different temperatures, the pCO
2
values varied as the temperature dependent solubility factor changed, without concomitant alteration of total CO
2
content, which in turn resulted in an inverse change in pH. The misconception of homoiotherm (warm blooded) blood gas regulation insists that normality is based upon the blood pH of 7.40 and a pCO
2
of 40 torr and that changes of temperature do not effect this relationship. Indeed, pioneering work in cardiovascular surgery studied the effects of hypothermia on hibernating animals which maintain those values at lowered temperature. However, in the latter case hormonal and central nervous system intervention has affected the organism in ways which are not yet completely understood. In any case it is not the pH of the blood that is important, it is that of the intracellular space where the chemical reactions of life takes place.
Alpha-stat blood gas management achieved better methods of myocardial protection and was proposed for use during open heart surgery. Later, it was discovered that alpha-stat preserved the mechanisms of cerebral autoregulation, i.e. the appropriate blood flow rate for the metabolic needs of the brain. The practice of adding CO
2
to the blood in the oxygenator to maintain a normal temperature corrected pCO
2
(pH-stat) resulted in a blood flow exceeding demand as the pCO
2
is the controlling factor of cerebral autoregulation. The use of pH-stat regulation during hypothermic treatments produces a notable decrease in plasma phosphorous concentrations. Alternatively, the use of alpha-stat during total body hypothermia, reduces the amount of reduction in plasma phosphorous concentrations. The fact that alpha-stat may have an overall beneficial effect on human physiology, during hyperthermia, has largely gone unnoticed.
The properties of imidazole moiety of protein-bound histidine is described by White et al. in a paper entitled “Carbon Dioxide Transport and Acid-Base Balance During Hypothermia” (Pathophysiology & Techniques of Cardiopulmonary Bypass, 1983; Vol. II: 40-48). White et al. states that imidazole moiety is present in a persons blood in sufficient quantity to account for the pH-temperature relationship. The state of protonization (charged state) of imidazole is expressed as a variable (alpha) equal to the ratio of deprotonated to total imidazole groups. White et al. notes that the maintenance of a constant alpha, referred to as
alpha-star
alpha-
stat
behavior, occurs when carbon dioxide partial pressure (pCO
2
) is appropriately regulated by ventilation. During a decrease in temperature (hypothermia), the maintenance of arterial blood at constant CO
2
content is achieved either by reducing the base excess of the blood or elevating pCO
2
as a function of temperature. Claude B. Kancir and Tommy Madsen in an article entitled Effect of Acid-Base Management With or Without Carbon Dioxide on Plasma Phosphate Concentration During And After Hypothermic Cardiopulmonary Bypass; Scand J Thor Cardiovasc Surg. 151-155, 1992, concluded that “acid-base management may influence phosphate homeostasis during hypothermia for cardiac surgery.”
As recognized in Sites et al. U.S. Pat. No. 5,391,142, hyperthermic treatment of a patient's blood has been well accepted as a cancer treatment. Sites et al. recognized that the hyperthermic treatment of blood could be used to treat for cancer, acquired immune deficiency syndrome (AIDS), collagen vascular diseases such as rheumatoid arthritis and scleroderma, hepatitis, and Epstein-Barr virus. Sites et al. did not, however, recognize the need to regulate the biochemical reactions fundamental to the metabolic welfare of the organisms within a patient's blood while the viruses within the patient's blood are eliminated.
During hyperthermia, pCO
2
varies directly with a change in body temperature. It is desirous to hold the bloods CO
2
content constant during alpha-stat regulation, thereby requiring an inverse relationship between
Bianco Patricia
First Circle Medical, Inc.
Popovich & Wiles, P.A.
Sykes Angela D.
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