CA2283430C - Elimination of vapour anaesthetics from patients after surgical procedures - Google Patents
Elimination of vapour anaesthetics from patients after surgical procedures Download PDFInfo
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- CA2283430C CA2283430C CA002283430A CA2283430A CA2283430C CA 2283430 C CA2283430 C CA 2283430C CA 002283430 A CA002283430 A CA 002283430A CA 2283430 A CA2283430 A CA 2283430A CA 2283430 C CA2283430 C CA 2283430C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/10—Preparation of respiratory gases or vapours
- A61M16/12—Preparation of respiratory gases or vapours by mixing different gases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
- A61M16/0009—Accessories therefor, e.g. sensors, vibrators, negative pressure with sub-atmospheric pressure, e.g. during expiration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/021—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes operated by electrical means
- A61M16/022—Control means therefor
- A61M16/024—Control means therefor including calculation means, e.g. using a processor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/20—Valves specially adapted to medical respiratory devices
- A61M16/208—Non-controlled one-way valves, e.g. exhalation, check, pop-off non-rebreathing valves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/20—Valves specially adapted to medical respiratory devices
- A61M16/208—Non-controlled one-way valves, e.g. exhalation, check, pop-off non-rebreathing valves
- A61M16/209—Relief valves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/22—Carbon dioxide-absorbing devices ; Other means for removing carbon dioxide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/02—Gases
- A61M2202/0225—Carbon oxides, e.g. Carbon dioxide
Abstract
A method of treatment of an animal to recover from vapour anaesthetics administration is provided, the method comprising delivering to a patient gases which do not contain CO2 at a specified rate, and gases containing CO2 to maintain the same PCO2 in the animal independent of the rate of ventilation, at the rate of ventilation of the animal which exceeds the rate of administration of the gases which do not contain CO2.
Description
TTTLE OF INVENTION
Elimination of vapour anaesthetics from patients after surgical procedures FIELD OF INVENTION
r 5 The purpose of this invention is to provide a simple breathing circuit that can, for example, be added to a standard circle anaesthetic circuit known to persons skilled in the art to hasten recovery of patients administered vapour anaesthetics prior to an operation.
This invention also relates to the use of the breathing circuit in hastening the recovery of patients who have been administered vapour anaesthetics prior to a surgical operation.
This invention also relates to methods of treatment of patients to hasten their recovery from administration of the vapour anaesthetics to them prior to surgical procedures.
BACKGROUND OF THE INVENTION
Ph~siolow Venous blood returns to the heart from the muscles and organs depleted of oxygen (~) and full of carbon dioxide (~). Blood from various parts of the body is mixed in the heart (mixed venous blood) and pumped to the lungs. In the lungs the blood vessels break up into a net of small vessels surrounding tiny lung sacs (alveoli). The net of vessels surrounding the alveoli provides a large surface area for the exchange of gases by diffusion along their concentration gradients. A concentration gradient exists between the partial pressure of C02 (PC02) in the mixed venous blood (PvCO~) and the alveolar PC02. The C02 diffuses into the alveoli from the mixed venous blood from the beginning of inspiration until an equilibrium is reached between the PvC02 and the alveolar PC02 at some time during the breath. When the subject exhales, the end of his exhalation is considered to have come from the alveoli and reflect the equilibrium concentration between the capillaries and the alveoli; the PC02 in this gas is called end-tidal PCO~ (PE'rCO~ ).
When the blood passes the alveoli and is pumped by the heart to the arteries it is known as the arterial PCO~ (Pa ). The arterial blood has a PC02 equal to the PC02 at equilibrium between the capillaries and alveoli. With each breath some C02 is eliminated and fresh air containing little C02 {assumed to be O) is inhaled and dilutes the residual alveolar PC02, establishing a new gradient for C02 to diffuse out of the mixed venous blood into the alveoli. The rate of breathing, or ventilation (V), usually expressed in L/min, is exactly that required to eliminate the C02 brought to the lungs and maintain an equilibrium PC02 (and PaC02 ) of approximately 40 mmHg (in normal humans). V1/hen one produces more C02 ( e.g. as a result of fever or exercise), more C02 is produced and carried to the lungs. One then has to breathe harder (h~nerventilate) to wash out the extra C02 from the alveoli, and thus maintain the same equilibrium PaC02. But if the C02 production stays normal, and one hyperventilates, then the PaC02 falls.
It is important to note that not all V contributes to blowing off C02 .
Some V goes to the air passages (trachea and bronchi) and alveoli with little blood perfusing them, and thus doesn't contribute to blowing off C02. That portion of V that goes to well perfused alveoli and participates in gas exchange is called the alveolar ventilation (VA).
There are a number of circumstances in therapeutic medicine and research where we want the subject to breathe harder but not change his PaC02 (see Table 1).
..... .. r . . .,. .. . . ..... ....,m.,. . ....... . .... .
i Table 1 Type of Investigation Reference Method of Source of C02 adjustment Respiratory muscle fatigue 5 M R
Respiratory muscle training 2 M R
Increased V during 6 M R
anaesthesia Carotid chemoreceptor 8 M E
function 1 M E
Effect of hypoxia on 10 M E
sympathetic response 4 M E
Control of respiration 9 A E
Tracheobronchialtone 11 M E
Table 1:
Title: Summary of previous studies attempting to maintain constant PETC02 during hyperpnea Legend: Method of adjustment of inspired PC02 : M = manual; A =
automated. Source of C02: R = rebreathing; E = external.
1. Angell-James, J.E., Clarke, J.A., de Burgh Daly, M. and Taton, A., Carotid chemoreceptor function and structure in the atherosclerotic rabbit: respiratory and cardiovascular responses to hyperoxia and hypercapnia. Cardiovascular Research 23{6): 541-53, 1989.
2. Belman, M.J. and C. Mittman. Ventilatory muscle training improves exercise capacity in chronic obstructive pulmonary disease patients. Am. Rev. Respir. Dis. 121:273-280, 1980.
Elimination of vapour anaesthetics from patients after surgical procedures FIELD OF INVENTION
r 5 The purpose of this invention is to provide a simple breathing circuit that can, for example, be added to a standard circle anaesthetic circuit known to persons skilled in the art to hasten recovery of patients administered vapour anaesthetics prior to an operation.
This invention also relates to the use of the breathing circuit in hastening the recovery of patients who have been administered vapour anaesthetics prior to a surgical operation.
This invention also relates to methods of treatment of patients to hasten their recovery from administration of the vapour anaesthetics to them prior to surgical procedures.
BACKGROUND OF THE INVENTION
Ph~siolow Venous blood returns to the heart from the muscles and organs depleted of oxygen (~) and full of carbon dioxide (~). Blood from various parts of the body is mixed in the heart (mixed venous blood) and pumped to the lungs. In the lungs the blood vessels break up into a net of small vessels surrounding tiny lung sacs (alveoli). The net of vessels surrounding the alveoli provides a large surface area for the exchange of gases by diffusion along their concentration gradients. A concentration gradient exists between the partial pressure of C02 (PC02) in the mixed venous blood (PvCO~) and the alveolar PC02. The C02 diffuses into the alveoli from the mixed venous blood from the beginning of inspiration until an equilibrium is reached between the PvC02 and the alveolar PC02 at some time during the breath. When the subject exhales, the end of his exhalation is considered to have come from the alveoli and reflect the equilibrium concentration between the capillaries and the alveoli; the PC02 in this gas is called end-tidal PCO~ (PE'rCO~ ).
When the blood passes the alveoli and is pumped by the heart to the arteries it is known as the arterial PCO~ (Pa ). The arterial blood has a PC02 equal to the PC02 at equilibrium between the capillaries and alveoli. With each breath some C02 is eliminated and fresh air containing little C02 {assumed to be O) is inhaled and dilutes the residual alveolar PC02, establishing a new gradient for C02 to diffuse out of the mixed venous blood into the alveoli. The rate of breathing, or ventilation (V), usually expressed in L/min, is exactly that required to eliminate the C02 brought to the lungs and maintain an equilibrium PC02 (and PaC02 ) of approximately 40 mmHg (in normal humans). V1/hen one produces more C02 ( e.g. as a result of fever or exercise), more C02 is produced and carried to the lungs. One then has to breathe harder (h~nerventilate) to wash out the extra C02 from the alveoli, and thus maintain the same equilibrium PaC02. But if the C02 production stays normal, and one hyperventilates, then the PaC02 falls.
It is important to note that not all V contributes to blowing off C02 .
Some V goes to the air passages (trachea and bronchi) and alveoli with little blood perfusing them, and thus doesn't contribute to blowing off C02. That portion of V that goes to well perfused alveoli and participates in gas exchange is called the alveolar ventilation (VA).
There are a number of circumstances in therapeutic medicine and research where we want the subject to breathe harder but not change his PaC02 (see Table 1).
..... .. r . . .,. .. . . ..... ....,m.,. . ....... . .... .
i Table 1 Type of Investigation Reference Method of Source of C02 adjustment Respiratory muscle fatigue 5 M R
Respiratory muscle training 2 M R
Increased V during 6 M R
anaesthesia Carotid chemoreceptor 8 M E
function 1 M E
Effect of hypoxia on 10 M E
sympathetic response 4 M E
Control of respiration 9 A E
Tracheobronchialtone 11 M E
Table 1:
Title: Summary of previous studies attempting to maintain constant PETC02 during hyperpnea Legend: Method of adjustment of inspired PC02 : M = manual; A =
automated. Source of C02: R = rebreathing; E = external.
1. Angell-James, J.E., Clarke, J.A., de Burgh Daly, M. and Taton, A., Carotid chemoreceptor function and structure in the atherosclerotic rabbit: respiratory and cardiovascular responses to hyperoxia and hypercapnia. Cardiovascular Research 23{6): 541-53, 1989.
2. Belman, M.J. and C. Mittman. Ventilatory muscle training improves exercise capacity in chronic obstructive pulmonary disease patients. Am. Rev. Respir. Dis. 121:273-280, 1980.
3. Bradley, M.E. and Leith, D.E. Ventilatory muscle training and the oxygen cost of sustained hyperpnea. J. Appl. Physiol. 45(6}:885-892,1978.
4. Busija, D.W., Orr, J.A., Rankin, J.G.H., Liang, H.K. and Wagerle, L.C., Cerebral blood flow during normocapnic hyperoxia in the unanaesthetized pony. J. Apple. Physiol. 48(1):10-15, 1980.
4. Busija, D.W., Orr, J.A., Rankin, J.G.H., Liang, H.K. and Wagerle, L.C., Cerebral blood flow during normocapnic hyperoxia in the unanaesthetized pony. J. Apple. Physiol. 48(1):10-15, 1980.
5. Jonsson, L.O. Predictable PaC02 with two different flow settings using the Mapleson D. system. Acta Anaesthesiol Scand. 34:237-240, 1990.
6. McKerrow, C.B., and Otis, A.B. Oxygen cost of hyperventilation. J.
Apple. Physiol. 9:375-79, 1956.
Apple. Physiol. 9:375-79, 1956.
7. Bobbins, P.A., Swanson, G.D. and Howson, M.G. A prediction-correction scheme for forcing alveolar gases along certain time courses. J. Apple. Physiol. 52(5):1353-1357, 1982.
8. Smith, D.M., Mercer, R.R. and Eldridge, F.L., Servo control of end-tidal C02 in paralyzed animals. J. Apple. Physiol. 45(1):133-136, 1978.
9. Somers, V.K., Mark, A.L., Zavaia, D.C. and Abboud, F.M. Influence of ventilation of hypocapnia on sympathetic nerve responses to hypoxia in normal humans. J. Appl. Physiol. 67(5):2095-2100, 1989.
10. Sorkness, R. and Vidruk, E. Reflex effects of isocapnic changes in ventilation of tracheal tone in awake dogs. Respir. PhysioI. 69:161-172,1987.
11. Tenney, S.M. and Reese, R.E. The ability to sustain great breathing efforts. Respir. Physiol. 5:287-201, 1968.
12. Wahba, R.W.M. and Tessler, M.J. Misleading end-tidal COZ
tensions. Can. J. Anaesth. 43(8):862-6, 1996.
This requires compensating for excess ventilation by inhaling COZ
either from exhaled gas or some external source. The amount of C02 required to be inhaled needs to be adjusted manually or by an automated servo-controlled mechanism, depending on how fine the control of PaCOz is required. The input signal is the PETC02 . Stability of PaC02 depends on the variability of C02 production and ventilation on the one hand, and the ability of a system to compensate for this variability on the other.
The termination of the anaesthetic effects of intravenously administered drugs depends on metabolism and redistribution. The recovery time from anaesthesia is therefore determined by the drug's pharmacology and cannot be accelerated.
This is not so for inhaled anaesthetic vapours. The uptake and elimination of anaesthetic vapours is predominantly through the lungs.
The partial pressure of an anaesthetic vapour in the blood going to the brain is dependent upon the equilibration of vapour between the blood and the lungs. The concentration of vapour in the lungs in turn is dependent on the concentration of vapour in the inhaled gas, the rate of breathing, and the rate of transfer of gas between the lung and the blood.
The newer anaesthetic agents desflurane and sevoflurane have very low blood solubility. Therefore the amount of drug transferred between the lungs and the blood is small and can, for discussion purposes, be ignored.
Thus, for a patient waking up from a vapour anaesthetic, the greater the rate of breathing, the more vapour is eliminated from the lungs.
However, in anaesthetized patients breathing spontaneously, ventilation is often depressed as a result of combined effects of residual intravenously administered anaesthetic drugs, pain relieving drugs (i.e. narcotics), the effects of surgery, as well as the respiratory depressant effect of the residual anaesthetic vapour itself Practically, there has been limited scope for intervention to hasten the process of eliminating vapour from the lung and thus hastening the rate of emergence from the effects of vapour anaesthesia.
Provosals in Prior Art 1. Artificial ventilation Manually or mechanically hyperventilating patients at the end of surgery is generally ineffective in shortening the time of recovery from anaesthesia.
a) High ventilation using the circle anaesthetic circuit results in rebreathing of exhaled gases. These gases contain anaesthetic vapour as well as C02 . The C02 is eliminated by the C02 absorber in the circuit, but the exhaled anaesthetic vapour is returned to the patient.
b) The attempts at hyperventilation will result in a decrease in arterial PC02. The low arterial PC02 removes the stimulus to breathe, which in turn delays elimination of vapour (and may also prevent adequate oxygenation of the blood).
This is seldom practised.
2. Flushing the circuit:
High fresh gas flows in the circuit are inefficient in washing out the vapour from the circuits. The circle anaesthetic circuits have volumes of approximately 8 L (not counting the patient's lung volume of approximately 2.5 L). At the maximum fresh gas flows on the oxygen flow meter of 10 L/min, it would take about 4 minutes to wash out the anaesthetic vapour from the circuit alone!
3. Stimulate breathing In the past, some anaesthetists tried to stimulate the patient's breathing by adding C02 to the breathing circuit. The rationale was to increase the C02 concentration in the circuit, stimulate the patient to breathe harder until he managed to ventilate off the C02 and some of the vapour as well. This has largely been abandoned and has been labeled a wasteful and dangerous practice.
a) It is wasteful for the reasons enumerated in 1a and 1b (vide supra}. As well, the practice is wasteful in that extra C02 absorbing crystals are consumed.
b) The technique may put a patient at risk if the patient cannot respond to the extra C02 by increasing their ventilation.
They will absorb it and develop a high blood C02 concentration which can be detrimental. The high C02 in the patient also causes them a good deal of distress on waking up as it makes them feel like they are not getting enough air to breathe.
4. Increase ventilation, keeping PC02 constant To increase the ventilation without lowering PC02 requires adding C02 to the circuit. This can be supplied from an external source or from the subject's exhaled gas. All the presently described systems depend on a servo-controlled system, or feedback loop to regulate the amount of C02 supplied to the patient. These devices are complex, cumbersome and expensive. No such device has been reported used for hastening the elimination of anaesthetic vapour during recovery from anaesthesia.
With respect to 4 above, there are considerable limitations of servo-controlled methods, both manual or automatic. These may be discussed _w _... ~ .. .. ..
WO 98/41266 - ,~ - PCTICA97100186 as follows:
1. Input signal Whereas the parameter that we want to keep constant is the arterial PC02, feedback systems use the C02 concentration in the expired gas, the so called end tidal PC02 (PETC02) as the input signal and endpoint. The PETC02 can be very different from the arterial PC02 in many circumstances. Furthermore, changes in PETC02 may not correlate with those in arterial PCO2. This will result in PETC02 being an inappropriate input for the control of arterial PC02. For example, a smaller than usual breath decreases PETC02 (tending to increase arterial PCOZ), causing a servo-controller to respond with an inappropriate increase in inspired C02.
2. Gain If, in an attempt to obtain fine control, the gain in a servo-control system is set too high, the response becomes unstable and may result in oscillation of the control variable. Conversely, if the gain is set too low, compensation lags. Over-damping of the signal results in a the response never reaching the target. To address these problems, servo-controllers require complex algorithms and expensive equipment.
3. Inherent limitation Servo-control systems work on the principle of detecting, and subsequently attempting to correct for, changes in PETC02. Even under ideal conditions, no such system can predict the size of an impending VT in a spontaneously breathing subject and thus deliver the appropriate C02 load.
As is apparent, people have tried to hasten the recovery of patients who have been anaesthetized and have made substantial efforts in this regard. However, they have been, for the most part, as seen above, unsuccessful. The reason for the attempts is that the benefits of faster return to consciousness, the less the need for recovery care and the less risk of nausea and post-operative respiratory complications. Thus the health care system will save substantial dollars. In this regard, the cost to the health care system of operating room and recovery area time is approximately $5.00 (Canadian Dollars) and $2.00 (Canadian Dollars) ~r_ minute respectively. The total number of anaesthetics given in North _ g _ America is approximately 35,000,000/year (3.5 million and about 30 million in the United States), a conservative estimate with as high as about 50,000,000/year. The North American estimate does not include Mexico or countries in Central America. A modest average decrease in recovery time in the operating time and in the recovery room of 5 minutes each can potentially result in billions of dollars savings per year worldwide. In North America alone, the expectation of saving 5 minutes In eacn or the operanng room ana recovery area can amount to $1,000,000,000 in savings.
It is therefore an object of this invention to provide an improved breathing circuit or circuit components that can be added to a standard circle anaesthetic circuit to be used to hasten recovery of patients who have been administered vapour anaesthetics.
It is a further object of the invention to provide methods of treatment using the said circuit and the use of the said circuit during the administration of vapour anaesthetics to hasten recovery of the said patients.
Further and other objects of the invention will be realized by those skilled in the art reading the following summary of the invention and detailed description of embodiments thereof.
SUMMARY OF THE INVENTION
According to one aspect of the invention, there is provided a new breathing circuit and components thereof that can, for example, be added to a standard circle anaesthetic circuit for hastening the recovery of patients administered vapour anaesthetics.
In accordance with the invention, the said circuit and components thereof, when combined with the general anaesthetic circle circuit cause the administration of carbon dioxide gas to the patient to maintain the same PC02 in the patient independent of the rate of ventilation (so long as the said rate of ventilation is greater than a control rate of ventilation) but permit the rate of anaesthetic vapour elimination from the lungs of the patient to vary directly as the total ventilation by the patient, whether the patient is breathing normally or is hyperventilating. Thus, the vapour anaesthetic is eliminated from the lungs. However, the carbon dioxide is not eliminated from the lungs at a rate greater than the resting rate of the patient or a predetermined control rate. (The predetermined rate of .__~.~.w..__.~ w... , , .
elimination of C02 may be set based on the rate of administration of the fresh gas into the circuit as discussed below.) Thus, according to another aspect of the invention, the simple breathing circuit comprises components which together form the simple circuit and comprise (a) an exit port from which the gases exit from the circuit to the patient, (b) a non-rebreathing valve which constitutes a one-way valve permitting gases to be delivered to the exit port to be delivered to the patient but which non-breathing valve when the patient breathes into the exit port does not permit the gases to pass the non-rebreathing valve into the portion of the circuit from which the gases are delivered but passes them to ambient or elsewhere, (c) a source of gas (which may be oxygen or air or other gases but does not contain C02 (air contains physiologically insignificant amounts of C02) in communication with the non-breathing valve to be delivered through the valve to the patient, (d) a fresh gas reservoir in communication with the source of fresh gas flow for receiving excess gas not breathed by the patient from the source of gas and for storing same and when the patient breathes and withdraws amounts of gas from the source of gas flow also enables the patient to receive gas from the fresh gas reservoir in which the gases have been stored, (e) a reserve gas supply containing C02 and other gases (usually oxygen) wherein the partial pressure of the C02 is approximately equal to the partial pressure of the C02 in the patient's mixed venous blood, for being delivered to the non-rebreathing valve as required by the patient to make up that amount of gas required by the patient when breathing that is not fulfilled from the gases delivered from the source of gas_ flow and fresh gas reservoir, the said source of gas and fresh gas reservoir and reserve gas supply being disposed on the side of the valve remote from the exit port.
Preferably a pressure relief valve is in communication with the fresh gas reservoir, in the event that the fresh gas reservoir overfills with gas so that the fresh gas reservoir does not break, rupture or become damaged in any way.
The reserve gas supply preferably includes a demand valve regulator so that where the additional gas is required, the demand valve regulator opens the communication of the reserve gas supply to the non-rebreathing valve for delivery of the gas to the non-breathing valve and where not required the demand valve regulator is closed and only fresh gas flows from the source of fresh gas and from the fresh gas reservoir to the non-rebreathing valve. The source of fresh gas is set to supply fresh gas (non-C02-containing gas) at a rate equal to the desired alveolar ventilation for the elimination of C02.
The basic concept underlying my approach is that when breathing increases, the rate of flow of fresh gas (inspired PC02 = 0} from the fresh gas flow contributing to elimination of C02 is kept constant. The remainder of the gas inhaled by the subject (from the reserve gas supply}
has a PC02 equal to that of mixed venous blood, does not contribute to a C02 concentration gradient between mixed venous blood and alveolar gas, and thus does not contribute to elimination of C02. If there is access to mixed venous blood (such as if a catheter is present in the pulmonary artery, the mixed venous PC02 can be measured directly. If there is no possibility of measuring, then an estimation can be made from PETCO2.
PETCO2 is determined by measuring the PC02 of expired using a capnograph usually present or easily available in an operating facility by persons skilled in the art.
In effect, the device passively, precisely and continuously matches the amount of C02 breathed in by the patient to the amount of total breathing, thereby preventing any perturbation of the arterial PC02. This is opposed to servo-controllers which are always attempting to compensate for changes. Persons skilled in the art, however, may automate the circuit by using a servo-controller or computer to monitor and deliver the amounts from the reserve gas supply.
According to another aspect of the invention, the new simple breathing circuit is used to treat a patient to enable the patient to recover more quickly from, and to hasten the recovery of the patient after, vapour anaesthetic administration.
According to another aspect of the invention, the use of the said circuit is made in the manufacture of a device to hasten the recovery of patients from administration of vapour anaesthetics.
According to another aspect of the invention, the use of the said circuit is made to hasten the recovery of patients from vapour anaesthetics administration.
According to another aspect of the invention, a method of treatment of an animal (for example, a person) is provided (such as to enable such animal to recover from vapour anaesthetics administration), the method comprising delivering to a patient gases which do not contain C02 at a specified rate, and gases containing C02 to maintain the same PCO2 in the animal independent of the rate of ventilation, at the rate of ventilation of the animal which exceeds the rate of administration of the gases which do not contain C02.
Therefore, when the rate of ventilation of the animal exceeds the rate of delivery to the animal of non-C02-containing gases inhaled by the animal, the C02-containing gases inhaled by the animal maintain the PC02 in the animal constant.
Thus, with respect to the use of the invention to eliminate anaesthetic vapour from the lungs, the total ventilation of combined gases which includes the C02-containing, and non-C02 containing, gases act to eliminate vapour from the Iungs.
25 This circuit and methods of treatment can also be used for any circumstance where one wants to dissociate the minute ventilation from elimination of carbon dioxide such as respiratory muscle training, investigation of the role of pulmonary stretch receptors, tracheobronchial tone, expand the lung to prevent atelectasis, and control of respiration and other uses as would be understood by those skilled in the art.
The circuit and methods of treatment may also be used by deep sea divers and astronauts to eliminate nitrogen from the body. It can also be used to treat carbon monoxide poisoning under normal baric or hyper baric conditions. The fresh gas will contain 100% oxygen, and the reserve gas will contain approximately 6% C02 and approximately 94% oxygen.
Neither the fresh gas nor the reserve gas supply will, in this case, contain nitrogen.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 illustrates schematically the nature of the simple breathing circuit and components which enable the patient to recover more quickly from vapour anaesthetics administration. The said device shown enables the PC02 to remain constant despite increase in minute ventilation which thereby permits faster elimination of the vapour anaesthetic.
Figure 2 illustrates schematically portions of a standard circle anaesthetic circuit generally known to persons skilled in the art.
Figure 3 illustrates schematically the simple breathing circuit in one embodiment added to the portions of the circle anaesthetic circuit shown schematically in Figure 2, illustrating modifications of the circuit shown schematically in Figure 1 for use with the generally known circuit shown in Figure 2. (It would be clear to persons skilled in the art that depending upon the circuit used as the circle anaesthetic circuit, different modifications on the basic circuit shown in Figure 1 will be made.}
Figure 4A illustrates the structure shown in Figure 3, now combined with the general structure shown in Figure 2. (Figure 3 shows the modifications made specifically to the structure of Figure 1 to combine it with the structure in Figure 2 which is now shown in Figure 4A.) Figures 4B and 4C illustrate schematically close up portions of one portion of the structure shown in Figure 4A in different positions.
Figure 5 graphs the VT (Tidal Volume} and PETC02.
Figure 6 graphs traces of airway PC02 and VT.
Figures 7A, 7B and 8A and 8B graphically depict changes in PaC02 and PETC02.
DETAILED DESCRIPTION OF EMBODIMENTS
The circuit (Figure 1) consists of a non-rebreathing valve (A) connected distally to two ports (C and D). The first port is connected in parallel to a source of fresh gas (E) (which does not contain C02) and a fresh gas reservoir (F). A one-way pressure relief valve (G) prevents overfilling of the reservoir (F} by venting excess fresh gas. The second port (D} is connected via a one-way valve (H), to a source of gas (containing C02) whose PC02 is equal approximately to that of the mixed venous PC02 . We call this the "reserve gas" (I). Non-rebreathing valve A is connected to exit port J (from which the patient breathes).
Functional analysis of circuit maintaining constant PC02 with hyperventilation When the minute ventilation "V" is less tYtan or equal to the fresh gas flow "FGF" from (E), the subject inhales only fresh gas (non-C02-containing gas). When V exceeds FGF, the reservoir (F) containing fresh non-C02-containing gas empties first and the balance of inhaled gas is drawn from the reserve gas (I) which contains C02. The reserve gas is considered not to participate in COz exchange ensuring that the actual ventilation provided is limited by FGF. If the rate of FGF is 5L/minute and the patient breathes at 5L/minute or less, then the patient will inhale ..
tensions. Can. J. Anaesth. 43(8):862-6, 1996.
This requires compensating for excess ventilation by inhaling COZ
either from exhaled gas or some external source. The amount of C02 required to be inhaled needs to be adjusted manually or by an automated servo-controlled mechanism, depending on how fine the control of PaCOz is required. The input signal is the PETC02 . Stability of PaC02 depends on the variability of C02 production and ventilation on the one hand, and the ability of a system to compensate for this variability on the other.
The termination of the anaesthetic effects of intravenously administered drugs depends on metabolism and redistribution. The recovery time from anaesthesia is therefore determined by the drug's pharmacology and cannot be accelerated.
This is not so for inhaled anaesthetic vapours. The uptake and elimination of anaesthetic vapours is predominantly through the lungs.
The partial pressure of an anaesthetic vapour in the blood going to the brain is dependent upon the equilibration of vapour between the blood and the lungs. The concentration of vapour in the lungs in turn is dependent on the concentration of vapour in the inhaled gas, the rate of breathing, and the rate of transfer of gas between the lung and the blood.
The newer anaesthetic agents desflurane and sevoflurane have very low blood solubility. Therefore the amount of drug transferred between the lungs and the blood is small and can, for discussion purposes, be ignored.
Thus, for a patient waking up from a vapour anaesthetic, the greater the rate of breathing, the more vapour is eliminated from the lungs.
However, in anaesthetized patients breathing spontaneously, ventilation is often depressed as a result of combined effects of residual intravenously administered anaesthetic drugs, pain relieving drugs (i.e. narcotics), the effects of surgery, as well as the respiratory depressant effect of the residual anaesthetic vapour itself Practically, there has been limited scope for intervention to hasten the process of eliminating vapour from the lung and thus hastening the rate of emergence from the effects of vapour anaesthesia.
Provosals in Prior Art 1. Artificial ventilation Manually or mechanically hyperventilating patients at the end of surgery is generally ineffective in shortening the time of recovery from anaesthesia.
a) High ventilation using the circle anaesthetic circuit results in rebreathing of exhaled gases. These gases contain anaesthetic vapour as well as C02 . The C02 is eliminated by the C02 absorber in the circuit, but the exhaled anaesthetic vapour is returned to the patient.
b) The attempts at hyperventilation will result in a decrease in arterial PC02. The low arterial PC02 removes the stimulus to breathe, which in turn delays elimination of vapour (and may also prevent adequate oxygenation of the blood).
This is seldom practised.
2. Flushing the circuit:
High fresh gas flows in the circuit are inefficient in washing out the vapour from the circuits. The circle anaesthetic circuits have volumes of approximately 8 L (not counting the patient's lung volume of approximately 2.5 L). At the maximum fresh gas flows on the oxygen flow meter of 10 L/min, it would take about 4 minutes to wash out the anaesthetic vapour from the circuit alone!
3. Stimulate breathing In the past, some anaesthetists tried to stimulate the patient's breathing by adding C02 to the breathing circuit. The rationale was to increase the C02 concentration in the circuit, stimulate the patient to breathe harder until he managed to ventilate off the C02 and some of the vapour as well. This has largely been abandoned and has been labeled a wasteful and dangerous practice.
a) It is wasteful for the reasons enumerated in 1a and 1b (vide supra}. As well, the practice is wasteful in that extra C02 absorbing crystals are consumed.
b) The technique may put a patient at risk if the patient cannot respond to the extra C02 by increasing their ventilation.
They will absorb it and develop a high blood C02 concentration which can be detrimental. The high C02 in the patient also causes them a good deal of distress on waking up as it makes them feel like they are not getting enough air to breathe.
4. Increase ventilation, keeping PC02 constant To increase the ventilation without lowering PC02 requires adding C02 to the circuit. This can be supplied from an external source or from the subject's exhaled gas. All the presently described systems depend on a servo-controlled system, or feedback loop to regulate the amount of C02 supplied to the patient. These devices are complex, cumbersome and expensive. No such device has been reported used for hastening the elimination of anaesthetic vapour during recovery from anaesthesia.
With respect to 4 above, there are considerable limitations of servo-controlled methods, both manual or automatic. These may be discussed _w _... ~ .. .. ..
WO 98/41266 - ,~ - PCTICA97100186 as follows:
1. Input signal Whereas the parameter that we want to keep constant is the arterial PC02, feedback systems use the C02 concentration in the expired gas, the so called end tidal PC02 (PETC02) as the input signal and endpoint. The PETC02 can be very different from the arterial PC02 in many circumstances. Furthermore, changes in PETC02 may not correlate with those in arterial PCO2. This will result in PETC02 being an inappropriate input for the control of arterial PC02. For example, a smaller than usual breath decreases PETC02 (tending to increase arterial PCOZ), causing a servo-controller to respond with an inappropriate increase in inspired C02.
2. Gain If, in an attempt to obtain fine control, the gain in a servo-control system is set too high, the response becomes unstable and may result in oscillation of the control variable. Conversely, if the gain is set too low, compensation lags. Over-damping of the signal results in a the response never reaching the target. To address these problems, servo-controllers require complex algorithms and expensive equipment.
3. Inherent limitation Servo-control systems work on the principle of detecting, and subsequently attempting to correct for, changes in PETC02. Even under ideal conditions, no such system can predict the size of an impending VT in a spontaneously breathing subject and thus deliver the appropriate C02 load.
As is apparent, people have tried to hasten the recovery of patients who have been anaesthetized and have made substantial efforts in this regard. However, they have been, for the most part, as seen above, unsuccessful. The reason for the attempts is that the benefits of faster return to consciousness, the less the need for recovery care and the less risk of nausea and post-operative respiratory complications. Thus the health care system will save substantial dollars. In this regard, the cost to the health care system of operating room and recovery area time is approximately $5.00 (Canadian Dollars) and $2.00 (Canadian Dollars) ~r_ minute respectively. The total number of anaesthetics given in North _ g _ America is approximately 35,000,000/year (3.5 million and about 30 million in the United States), a conservative estimate with as high as about 50,000,000/year. The North American estimate does not include Mexico or countries in Central America. A modest average decrease in recovery time in the operating time and in the recovery room of 5 minutes each can potentially result in billions of dollars savings per year worldwide. In North America alone, the expectation of saving 5 minutes In eacn or the operanng room ana recovery area can amount to $1,000,000,000 in savings.
It is therefore an object of this invention to provide an improved breathing circuit or circuit components that can be added to a standard circle anaesthetic circuit to be used to hasten recovery of patients who have been administered vapour anaesthetics.
It is a further object of the invention to provide methods of treatment using the said circuit and the use of the said circuit during the administration of vapour anaesthetics to hasten recovery of the said patients.
Further and other objects of the invention will be realized by those skilled in the art reading the following summary of the invention and detailed description of embodiments thereof.
SUMMARY OF THE INVENTION
According to one aspect of the invention, there is provided a new breathing circuit and components thereof that can, for example, be added to a standard circle anaesthetic circuit for hastening the recovery of patients administered vapour anaesthetics.
In accordance with the invention, the said circuit and components thereof, when combined with the general anaesthetic circle circuit cause the administration of carbon dioxide gas to the patient to maintain the same PC02 in the patient independent of the rate of ventilation (so long as the said rate of ventilation is greater than a control rate of ventilation) but permit the rate of anaesthetic vapour elimination from the lungs of the patient to vary directly as the total ventilation by the patient, whether the patient is breathing normally or is hyperventilating. Thus, the vapour anaesthetic is eliminated from the lungs. However, the carbon dioxide is not eliminated from the lungs at a rate greater than the resting rate of the patient or a predetermined control rate. (The predetermined rate of .__~.~.w..__.~ w... , , .
elimination of C02 may be set based on the rate of administration of the fresh gas into the circuit as discussed below.) Thus, according to another aspect of the invention, the simple breathing circuit comprises components which together form the simple circuit and comprise (a) an exit port from which the gases exit from the circuit to the patient, (b) a non-rebreathing valve which constitutes a one-way valve permitting gases to be delivered to the exit port to be delivered to the patient but which non-breathing valve when the patient breathes into the exit port does not permit the gases to pass the non-rebreathing valve into the portion of the circuit from which the gases are delivered but passes them to ambient or elsewhere, (c) a source of gas (which may be oxygen or air or other gases but does not contain C02 (air contains physiologically insignificant amounts of C02) in communication with the non-breathing valve to be delivered through the valve to the patient, (d) a fresh gas reservoir in communication with the source of fresh gas flow for receiving excess gas not breathed by the patient from the source of gas and for storing same and when the patient breathes and withdraws amounts of gas from the source of gas flow also enables the patient to receive gas from the fresh gas reservoir in which the gases have been stored, (e) a reserve gas supply containing C02 and other gases (usually oxygen) wherein the partial pressure of the C02 is approximately equal to the partial pressure of the C02 in the patient's mixed venous blood, for being delivered to the non-rebreathing valve as required by the patient to make up that amount of gas required by the patient when breathing that is not fulfilled from the gases delivered from the source of gas_ flow and fresh gas reservoir, the said source of gas and fresh gas reservoir and reserve gas supply being disposed on the side of the valve remote from the exit port.
Preferably a pressure relief valve is in communication with the fresh gas reservoir, in the event that the fresh gas reservoir overfills with gas so that the fresh gas reservoir does not break, rupture or become damaged in any way.
The reserve gas supply preferably includes a demand valve regulator so that where the additional gas is required, the demand valve regulator opens the communication of the reserve gas supply to the non-rebreathing valve for delivery of the gas to the non-breathing valve and where not required the demand valve regulator is closed and only fresh gas flows from the source of fresh gas and from the fresh gas reservoir to the non-rebreathing valve. The source of fresh gas is set to supply fresh gas (non-C02-containing gas) at a rate equal to the desired alveolar ventilation for the elimination of C02.
The basic concept underlying my approach is that when breathing increases, the rate of flow of fresh gas (inspired PC02 = 0} from the fresh gas flow contributing to elimination of C02 is kept constant. The remainder of the gas inhaled by the subject (from the reserve gas supply}
has a PC02 equal to that of mixed venous blood, does not contribute to a C02 concentration gradient between mixed venous blood and alveolar gas, and thus does not contribute to elimination of C02. If there is access to mixed venous blood (such as if a catheter is present in the pulmonary artery, the mixed venous PC02 can be measured directly. If there is no possibility of measuring, then an estimation can be made from PETCO2.
PETCO2 is determined by measuring the PC02 of expired using a capnograph usually present or easily available in an operating facility by persons skilled in the art.
In effect, the device passively, precisely and continuously matches the amount of C02 breathed in by the patient to the amount of total breathing, thereby preventing any perturbation of the arterial PC02. This is opposed to servo-controllers which are always attempting to compensate for changes. Persons skilled in the art, however, may automate the circuit by using a servo-controller or computer to monitor and deliver the amounts from the reserve gas supply.
According to another aspect of the invention, the new simple breathing circuit is used to treat a patient to enable the patient to recover more quickly from, and to hasten the recovery of the patient after, vapour anaesthetic administration.
According to another aspect of the invention, the use of the said circuit is made in the manufacture of a device to hasten the recovery of patients from administration of vapour anaesthetics.
According to another aspect of the invention, the use of the said circuit is made to hasten the recovery of patients from vapour anaesthetics administration.
According to another aspect of the invention, a method of treatment of an animal (for example, a person) is provided (such as to enable such animal to recover from vapour anaesthetics administration), the method comprising delivering to a patient gases which do not contain C02 at a specified rate, and gases containing C02 to maintain the same PCO2 in the animal independent of the rate of ventilation, at the rate of ventilation of the animal which exceeds the rate of administration of the gases which do not contain C02.
Therefore, when the rate of ventilation of the animal exceeds the rate of delivery to the animal of non-C02-containing gases inhaled by the animal, the C02-containing gases inhaled by the animal maintain the PC02 in the animal constant.
Thus, with respect to the use of the invention to eliminate anaesthetic vapour from the lungs, the total ventilation of combined gases which includes the C02-containing, and non-C02 containing, gases act to eliminate vapour from the Iungs.
25 This circuit and methods of treatment can also be used for any circumstance where one wants to dissociate the minute ventilation from elimination of carbon dioxide such as respiratory muscle training, investigation of the role of pulmonary stretch receptors, tracheobronchial tone, expand the lung to prevent atelectasis, and control of respiration and other uses as would be understood by those skilled in the art.
The circuit and methods of treatment may also be used by deep sea divers and astronauts to eliminate nitrogen from the body. It can also be used to treat carbon monoxide poisoning under normal baric or hyper baric conditions. The fresh gas will contain 100% oxygen, and the reserve gas will contain approximately 6% C02 and approximately 94% oxygen.
Neither the fresh gas nor the reserve gas supply will, in this case, contain nitrogen.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 illustrates schematically the nature of the simple breathing circuit and components which enable the patient to recover more quickly from vapour anaesthetics administration. The said device shown enables the PC02 to remain constant despite increase in minute ventilation which thereby permits faster elimination of the vapour anaesthetic.
Figure 2 illustrates schematically portions of a standard circle anaesthetic circuit generally known to persons skilled in the art.
Figure 3 illustrates schematically the simple breathing circuit in one embodiment added to the portions of the circle anaesthetic circuit shown schematically in Figure 2, illustrating modifications of the circuit shown schematically in Figure 1 for use with the generally known circuit shown in Figure 2. (It would be clear to persons skilled in the art that depending upon the circuit used as the circle anaesthetic circuit, different modifications on the basic circuit shown in Figure 1 will be made.}
Figure 4A illustrates the structure shown in Figure 3, now combined with the general structure shown in Figure 2. (Figure 3 shows the modifications made specifically to the structure of Figure 1 to combine it with the structure in Figure 2 which is now shown in Figure 4A.) Figures 4B and 4C illustrate schematically close up portions of one portion of the structure shown in Figure 4A in different positions.
Figure 5 graphs the VT (Tidal Volume} and PETC02.
Figure 6 graphs traces of airway PC02 and VT.
Figures 7A, 7B and 8A and 8B graphically depict changes in PaC02 and PETC02.
DETAILED DESCRIPTION OF EMBODIMENTS
The circuit (Figure 1) consists of a non-rebreathing valve (A) connected distally to two ports (C and D). The first port is connected in parallel to a source of fresh gas (E) (which does not contain C02) and a fresh gas reservoir (F). A one-way pressure relief valve (G) prevents overfilling of the reservoir (F} by venting excess fresh gas. The second port (D} is connected via a one-way valve (H), to a source of gas (containing C02) whose PC02 is equal approximately to that of the mixed venous PC02 . We call this the "reserve gas" (I). Non-rebreathing valve A is connected to exit port J (from which the patient breathes).
Functional analysis of circuit maintaining constant PC02 with hyperventilation When the minute ventilation "V" is less tYtan or equal to the fresh gas flow "FGF" from (E), the subject inhales only fresh gas (non-C02-containing gas). When V exceeds FGF, the reservoir (F) containing fresh non-C02-containing gas empties first and the balance of inhaled gas is drawn from the reserve gas (I) which contains C02. The reserve gas is considered not to participate in COz exchange ensuring that the actual ventilation provided is limited by FGF. If the rate of FGF is 5L/minute and the patient breathes at 5L/minute or less, then the patient will inhale ..
only non-C02-containing gas that comes from fresh gas flow sources (E
and F). If minute ventilation exceeds FGF, the difference between minute ventilation and fresh gas flow is made up from gas from reserve gas (I) which contains C02 at a concentration that does not provide a gradient for elimination of C02 in the patient.
Ayylication of circuit to anaesthesia circle circuit The schematic of the standard anaesthetic circle circuit, spontaneous ventilation (Figure 2) When the patient exhales, the inspiratory valve (1) closes, the expiratory valve (2) opens and gas flows through the corrugated tubing making up the expiratory limb of the circuit (3) into the rebreathing bag {4). When the rebreathing bag is full, the airway pressure-limiting (APL) valve (5) opens and the balance of expired gas exits through the APL valve into a gas scavenger (not shown). When the patient inhales, the negative pressure in the circuit closes the expiratory valve (2), opens the inspiratory valve (1), and directs gas to flow through the corrugated tube making up the inspiratory limb of the circuit (6). Inspiration draws all of the gas from the fresh gas hose (7) and makes up the balance of the volume of the breath by drawing gas from the rebreathing bag (4). The gas from the rebreathing bag contains expired gas with C02 in it. This C02 is extracted as the gas passes through the C02 absorber (8) and thus is delivered to the patient (P) without C02, (but still containing exhaled anaesthetic vapour, if any).
Modification of the circuit (Figure 3) to allow hyperventilation of patients under anaesthesia The modified circuit consists of 1. a circuit which acts functionally like a standard self inflating bag (such as made by Laerdal ) consisting of a) a non rebreathing valve, such as valve #560200 made by Laerdal, that functions during spontaneous breathing as well as manually assisted breathing (9);
b) an expired gas manifold, such as the Expiratory Deviator #850500, to collect expired gas (10) and direct it to a gas scavenger system (not shown) or to the expiratory limb of the anaesthetic circuit {figure 4);
c) a self inflating bag (11) whose entrance is guarded by a one WO 98/41266 _ 14 _ PCT/CA97/00186 way valve directing gas into the self inflating bag (12).
2. a source of fresh gas, (i.e. not containing vapour) e.g. oxygen or oxygen plus nitrous oxide (13) with a flow meter (22).
3. a manifold (24} with 4 ports:
a) a port (15} for input of fresh gas (13);
b) a port (16) for a fresh gas reservoir bag (17);
c) a port to which is attached a one way inflow valve that opens when the pressure inside the manifold is 5cm H20 less than atmospheric pressure, such as Livingston Health Care Services catalog part #9005, (18) (assuring that all of the fresh gas is utilized before opening);
d} a bag of gas (19) whose PC02 is equal approximately to that of the mixed venous PCOZ connected to inflow valve (18)(Alternatively, the valve and gas reservoir bag can be replaced by a demand regulator, such as Lifetronix MX91120012, similar to that used in SCUBA diving, and a cylinder of compressed gas);
e) a port to which is attached a one way outflow valve (20), such as Livingston Health Care Services catalog part #9005, that allows release of gas from the manifold to atmosphere when the pressure in the manifold is greater than 5cm H20.
Method of operation in an anaesthetic circuit (Figure 4A) The distal end of the nonrebreathing valve (Laerdal type) (9), is attached to the patient.
The proximal port of the nonrebreathing valve is attached to a 3 way respiratory valve (21) which can direct inspiratory gas either from the circle anaesthetic circuit (Figure 4B) or from the new circuit (Figure 4C).
The expiratory manifold (10) of the self inflating bag's non rebreathing valve is attached to the expiratory limb of the anaesthetic circuit (3).
Regardless of the source of inspired gas, exhalation is directed into the expiratory limb of the anaesthetic circuit.
To maximize the elimination of anaesthetic vapour from the patient's lungs, the 3-way respiratory stopcock is turned such that patient inspiration is from the new circuit (Figure 4C). Thus inspired gas from the very first breath after turning the 3-way valve onward contains no vapour, providing the maximum gradient for anaesthetic vapour _m..__.~w., w. . . T , .
WO 98!41266 - 15 - PCT/CA97/00186 elimination.
An increased breathing rate will further enhance the elimination of vapour from the lung. If breathing spontaneously, the patient can be stimulated to increase his minute ventilation by lowering the FGF (22) thereby allowing the PC02 to rise. Using this approach the PC02 will rise and plateau independent of the rate of breathing, resulting in a constant breathing stimulus. All of the ventilation is effective in eliminating vapour.
If the patient is undergoing controlled ventilation, he can also be hyperventilated with the self-inflating bag (11). In either case, the patient's PC02 will be determined by the FGF (22). As long as the FGF
remains constant, the PC02 will remain constant independent of the minute ventilation.
To illustrate the effectiveness of the circuit we performed a number of tests with respect to humans and dogs. The humans were breathing spontaneously and the dogs were mechanically ventilated.
Human subjects After obtaining institutional ethics board approval and informed consent, four healthy subjects aged 19 - 25 y breathed through the circuit by means of a mouth piece while wearing nose clips. During normal breathing, the FGF was set equal to V by adjusting the FGF such that the bag containing fresh gas just emptied at the end of each inhalation.
Subjects were then instructed to breathe maximally ("breathe as hard as you can") for 3 min. Flows were recorded by means of a Pitot tube (Voltek Enterprises, Willowdale Canada) and the signal integrated to obtain volume. C02 was sampled continuously at the mouthpiece (Medical Gas Analyzer LB-2, Sensormedics Corp., Anaheim California). Analog signals were digitized at 60 samples~s 1 and recorded using data acquisition software (WINDAQ/200, DATAQ instruments, Inc. Akron Ohio).
Studies in dogs Following institutional ethics board approval, 6 mongrel dogs of either sex weighing 20-25kg were anaesthetized with methohexital (5-7 mg~kg-1 for induction followed by 150-300 mg~kg l~miri 1) and intubated.
Adequacy of anaesthetic depth was deduced from the eye lash reflex, lack of spontaneous movements, and stable heart rate and blood pressure. A
catheter was placed in the femoral artery for monitoring blood pressure and periodic sampling of blood for gas analysis., The dogs were ventilated with a conventional mechanical piston ventilator (Harvard Apparatus model 618, South Natick, MA). For each dog, an inflation volume (VT} of 400 ml and a frequency (f) of 10 miri 1 (duty cycle, 0.5) were used. All dogs were ventilated to just below their apneic thresholds (by increasing VT
about 50 mL) so that they made no respiratory efforts. Tidal C02 was sampled continuously (Ametek, Thermox Instruments Division, Pittsburgh, PA) at the proximal end of the endotracheal tube. Flow was measured with a pneumotachograph (Vertek series 47303A, Hewlett-Packard) and the signal integrated to obtain volume. Analog signals were digitized at 17 samples~s 1 and recorded using the same data acquisition software as that used in studies on human subjects.
Because of differences in initial PaC02s among dogs (reflecting individual sensitivities to C02, differences in anaesthetic levels, or differences in VT/body weight ratio), the C02 concentration in the reserve gas was arbitrarily adjusted for each dog to 1.5 ~ 0.5% above its FetC02 to approximate the mixed venous PC02 (PvC02) (see Table II}. To allow greater flexibility in setting the concentration of C02 in the reserve gas, the circuit was modified by replacing the demand valve with a one-way PEEP
(positive end expiratory pressure) valve and the cylinder with a bag containing premixed gas. This circuit is functionally identical to that used in studies on humans. The circuit was connected to the intake port of the ventilator. Under control conditions, FGF was adjusted so that the fresh gas reservoir just emptied during each ventilator cycle; this end point was confirmed by a slight rise in FICOz above zero. After a steady-state had been reached (difference < 1.5 mm Hg in two successive PaC02's taken 5 minutes apart), VT was increased at 5 minute intervals from 400 to 600 to 900 to 1200 mL. In a second trial at a fixed VT (approximately 400 mL} and fixed FGF, f was increased at 5 minute intervals from 10 to 14 to 18 to 22 min-1. A blood sample for the determination of blood gases was drawn from the femoral artery at the beginning and end of each 5 min interval.
All data are expressed as means ~ standard deviation. We tested for significant differences using one- or two-way ANOVA with post hoc analysis where appropriate. A p value Iess than 0.05 was considered significant.
_,.~... ~ , , WO 98/41266 _ l,~ _ PCT/CA97100186 Results:
Human subjects Figure 5 presents the VT and PETCOz of subject 1 during 3 min of maximal ventilatory effort. Results for all subjects are summarized in Table III; data represent average values for 10 breaths at 0 (the onset of hyperventilation), 2.5 and 3 min. PETCOZ did not change significantly from control values throughout the course of hyperventilation (p = 0.08, ANOVA). There was considerable variability in V and breathing patterns between subjects but individual subjects tended to sustain a particular breathing pattern throughout the run.
Dogs Figure 6 presents traces of airway PC02 and VT for dog #5 during changes in f or VT. Figures 7 and 8 show the changes in PaC02 and the PETC02 in all dogs during changes in f or VT. Increases in f did not significantly affect mean PaC02 or PETCOz (p=0.28 and p=0.11, respectively;
ANOVA). Increases in VT decreased mean PaC02 from control only at VT
of 1200 mL (p=0.01); in contrast, changes in VT did not affect mean PETCOz (p=0.25). The mean absolute change in PaC02 between control and the highest ventilation was 2.2 ~ 1.8 mmHg (range 0.4 to 4.8) for f and 3.4 ~ 2.3 mmHg (range 0.4 to 5.6) for VT.
COMMENTARY
The system minimized decreases in PETCOz over a wide range of ventilation (56 to 131 L miri') and breathing patterns, in hyperventilating human subjects and in mechanically hyperventilated dogs (4 to 12 L
min'). The variability in PaCOz in the hyperventilated dogs, although small, may have been due to a) imprecise matching of reserve gas PCOZ to the dog's PvCO2s; b) prolonged duration of the maneuver in dogs (> 15 min versus 3 min for human subjects) and c) the extent of hyperventilation (see below). In addition, the different levels of ventilation may have induced changes in systemic and pulmonary blood flow (ventilation-perfusion matching, physiological and anatomical dead space), thereby affecting PaC02 and PvC02. Despite these sources of variability, the range over which PaC02 varied in my studies in dogs was similar to those reported in studies utilizing more complex equipment (see Table 1).
Conventional servo-controlled techniques designed to prevent changes in PCO~ with hyperpnea are less affected by changes in CO
production than the circuit; however, they have other limitations. The assumption that detected changes in PETCOz are due to a change in PaC02 is not always warranted (14). Small changes in ventilatory pattern can 'uncouple' PETCOz from PaCO~, resulting in PETCO~ being an inappropriate input for the control of PaCOz. For example, a smaller VT decreases VA
(which tends to increase PaCOZ) but will also decrease PETCO~, causing a servo-controller to respond with an inappropriate increase in inspired CO, Even under ideal conditions, a servo-controlled system attempting to correct for changes in PETCOZ cannot predict the size of an impending VT
in a spontaneously breathing subject and thus deliver the appropriate CO~
load. If in an attempt to obtain fine control the gain in a servo-control system is set too high, the response becomes unstable and may result in oscillation of the control variable (11). Conversely, if the gain is set too low, compensation lags (9). Over-damping of the signal results in a the response never reaching the target. To address these problems, servo-controllers require complex algorithms (16) and expensive equipment.
When CO~ production is constant, the circuit has the theoretical advantage over servo-controlled systems in that it provides passive compensation for changes in V. This minimizes changes in VA, pre empting the need for subsequent compensation. Maintenance of a nearly constant VA occurs even during irregular breathing, including brief periods when V is less than the FGF. Under this circumstance, excess FGF
is stored in the fresh gas reservoir and subsequently contributes to VA
when ventilation exceeds FGF.
When COZ production increases during hyperventilation, as would occur with increased work of breathing or exercise, my method requires modification. To compensate, additional VA can be provided either by increasing FGF or by lowering the PCOZ of the reserve gas below the PvCOZ, as expressed in the following equation:
VA = FGF + (V-FGF) (PvC02 - reserve gas PCOz)/PvC02 Because spontaneously breathing subjects had such variable V
during hyperventilation, compensating for the COZ production by modifying FGF would have required constant adjustment. We therefore chose to decrease the PCOZ of the reserve gas to establish a concentration ~A~~NDE.D SI-kE-~T
:y i WO 98/412bb PCT/CA97/00186 gradient between the PCOZ of the reserve gas and the PvC02; when this gradient is constant, Vr~ is a function of V. We found that, over the wide range of V exhibited by the subjects, a concentration of 5.5% C02 in the reserve gas (instead of 6.5% which corresponds to a PvC02 of 46 mrnHg) provided the optimal gradient to compensate for increases in C02 production resulting from increased work of breathing.
I therefore have described a simple circuit that disassociates VA
from V. It passively minimizes increases in Vr~ that would normally accompany hyperventilation when COZ production is constant. It can be modified to compensate for increases in COZ production. The circuit may form the basis for a simple and inexpensive alternative to servo-controlled systems for research and may have therapeutic applications.
TABLE II
Dog # Weight Initial FETCOZ Bag FC02 (kg) (%) (%) 1 22 5.3 7.0 2 20 4.6 6.6 3 20 7.1 9.0 4 24 7.3 9.0 5 25 5.5 6.9 6 20 6.0 7.2 WO 98/41266 _ 20 - PCT/CA97/0018G
TABLE III
End Tidal PC(~2(mmHg) Frequency (ruin-1) Time Subject Control0 1.5 3 Subject # 0 1.5 3 #
1 40.3 33.6 34.935.6 1 57 50 47 2 36.6 30.9 28.128.0 2 89 87 88 3 42.0 42.5 43.242.7 3 31 30 30 4 41.0 34.5 38.838.8 4 149 130 127 Tidal Volume Minute Ve ntilation min-I) (L) (L
Time Time Subject 0 1.5 3 Subject # 0 1.5 3 #
1 2.30 2.49 2.58 1 131 124 118 2 0.85 0.72 0.63 2 75 63 56 3 2.60 2.64 2.26 3 80 78 68 4 0.78 0.62 0.60 4 117 80 76 While the foregoing provides a detailed description of a preferred embodiment of the invention, it is to be understood that this description is illustrative only of the principles of the invention and not limitative.
Furthermore, as many changes can be made to the invention without departing from the scope of the invention, it is intended that all material contained herein be interpreted as illustrative of the invention and not in a limiting sense.
_, _ ... _ ...
and F). If minute ventilation exceeds FGF, the difference between minute ventilation and fresh gas flow is made up from gas from reserve gas (I) which contains C02 at a concentration that does not provide a gradient for elimination of C02 in the patient.
Ayylication of circuit to anaesthesia circle circuit The schematic of the standard anaesthetic circle circuit, spontaneous ventilation (Figure 2) When the patient exhales, the inspiratory valve (1) closes, the expiratory valve (2) opens and gas flows through the corrugated tubing making up the expiratory limb of the circuit (3) into the rebreathing bag {4). When the rebreathing bag is full, the airway pressure-limiting (APL) valve (5) opens and the balance of expired gas exits through the APL valve into a gas scavenger (not shown). When the patient inhales, the negative pressure in the circuit closes the expiratory valve (2), opens the inspiratory valve (1), and directs gas to flow through the corrugated tube making up the inspiratory limb of the circuit (6). Inspiration draws all of the gas from the fresh gas hose (7) and makes up the balance of the volume of the breath by drawing gas from the rebreathing bag (4). The gas from the rebreathing bag contains expired gas with C02 in it. This C02 is extracted as the gas passes through the C02 absorber (8) and thus is delivered to the patient (P) without C02, (but still containing exhaled anaesthetic vapour, if any).
Modification of the circuit (Figure 3) to allow hyperventilation of patients under anaesthesia The modified circuit consists of 1. a circuit which acts functionally like a standard self inflating bag (such as made by Laerdal ) consisting of a) a non rebreathing valve, such as valve #560200 made by Laerdal, that functions during spontaneous breathing as well as manually assisted breathing (9);
b) an expired gas manifold, such as the Expiratory Deviator #850500, to collect expired gas (10) and direct it to a gas scavenger system (not shown) or to the expiratory limb of the anaesthetic circuit {figure 4);
c) a self inflating bag (11) whose entrance is guarded by a one WO 98/41266 _ 14 _ PCT/CA97/00186 way valve directing gas into the self inflating bag (12).
2. a source of fresh gas, (i.e. not containing vapour) e.g. oxygen or oxygen plus nitrous oxide (13) with a flow meter (22).
3. a manifold (24} with 4 ports:
a) a port (15} for input of fresh gas (13);
b) a port (16) for a fresh gas reservoir bag (17);
c) a port to which is attached a one way inflow valve that opens when the pressure inside the manifold is 5cm H20 less than atmospheric pressure, such as Livingston Health Care Services catalog part #9005, (18) (assuring that all of the fresh gas is utilized before opening);
d} a bag of gas (19) whose PC02 is equal approximately to that of the mixed venous PCOZ connected to inflow valve (18)(Alternatively, the valve and gas reservoir bag can be replaced by a demand regulator, such as Lifetronix MX91120012, similar to that used in SCUBA diving, and a cylinder of compressed gas);
e) a port to which is attached a one way outflow valve (20), such as Livingston Health Care Services catalog part #9005, that allows release of gas from the manifold to atmosphere when the pressure in the manifold is greater than 5cm H20.
Method of operation in an anaesthetic circuit (Figure 4A) The distal end of the nonrebreathing valve (Laerdal type) (9), is attached to the patient.
The proximal port of the nonrebreathing valve is attached to a 3 way respiratory valve (21) which can direct inspiratory gas either from the circle anaesthetic circuit (Figure 4B) or from the new circuit (Figure 4C).
The expiratory manifold (10) of the self inflating bag's non rebreathing valve is attached to the expiratory limb of the anaesthetic circuit (3).
Regardless of the source of inspired gas, exhalation is directed into the expiratory limb of the anaesthetic circuit.
To maximize the elimination of anaesthetic vapour from the patient's lungs, the 3-way respiratory stopcock is turned such that patient inspiration is from the new circuit (Figure 4C). Thus inspired gas from the very first breath after turning the 3-way valve onward contains no vapour, providing the maximum gradient for anaesthetic vapour _m..__.~w., w. . . T , .
WO 98!41266 - 15 - PCT/CA97/00186 elimination.
An increased breathing rate will further enhance the elimination of vapour from the lung. If breathing spontaneously, the patient can be stimulated to increase his minute ventilation by lowering the FGF (22) thereby allowing the PC02 to rise. Using this approach the PC02 will rise and plateau independent of the rate of breathing, resulting in a constant breathing stimulus. All of the ventilation is effective in eliminating vapour.
If the patient is undergoing controlled ventilation, he can also be hyperventilated with the self-inflating bag (11). In either case, the patient's PC02 will be determined by the FGF (22). As long as the FGF
remains constant, the PC02 will remain constant independent of the minute ventilation.
To illustrate the effectiveness of the circuit we performed a number of tests with respect to humans and dogs. The humans were breathing spontaneously and the dogs were mechanically ventilated.
Human subjects After obtaining institutional ethics board approval and informed consent, four healthy subjects aged 19 - 25 y breathed through the circuit by means of a mouth piece while wearing nose clips. During normal breathing, the FGF was set equal to V by adjusting the FGF such that the bag containing fresh gas just emptied at the end of each inhalation.
Subjects were then instructed to breathe maximally ("breathe as hard as you can") for 3 min. Flows were recorded by means of a Pitot tube (Voltek Enterprises, Willowdale Canada) and the signal integrated to obtain volume. C02 was sampled continuously at the mouthpiece (Medical Gas Analyzer LB-2, Sensormedics Corp., Anaheim California). Analog signals were digitized at 60 samples~s 1 and recorded using data acquisition software (WINDAQ/200, DATAQ instruments, Inc. Akron Ohio).
Studies in dogs Following institutional ethics board approval, 6 mongrel dogs of either sex weighing 20-25kg were anaesthetized with methohexital (5-7 mg~kg-1 for induction followed by 150-300 mg~kg l~miri 1) and intubated.
Adequacy of anaesthetic depth was deduced from the eye lash reflex, lack of spontaneous movements, and stable heart rate and blood pressure. A
catheter was placed in the femoral artery for monitoring blood pressure and periodic sampling of blood for gas analysis., The dogs were ventilated with a conventional mechanical piston ventilator (Harvard Apparatus model 618, South Natick, MA). For each dog, an inflation volume (VT} of 400 ml and a frequency (f) of 10 miri 1 (duty cycle, 0.5) were used. All dogs were ventilated to just below their apneic thresholds (by increasing VT
about 50 mL) so that they made no respiratory efforts. Tidal C02 was sampled continuously (Ametek, Thermox Instruments Division, Pittsburgh, PA) at the proximal end of the endotracheal tube. Flow was measured with a pneumotachograph (Vertek series 47303A, Hewlett-Packard) and the signal integrated to obtain volume. Analog signals were digitized at 17 samples~s 1 and recorded using the same data acquisition software as that used in studies on human subjects.
Because of differences in initial PaC02s among dogs (reflecting individual sensitivities to C02, differences in anaesthetic levels, or differences in VT/body weight ratio), the C02 concentration in the reserve gas was arbitrarily adjusted for each dog to 1.5 ~ 0.5% above its FetC02 to approximate the mixed venous PC02 (PvC02) (see Table II}. To allow greater flexibility in setting the concentration of C02 in the reserve gas, the circuit was modified by replacing the demand valve with a one-way PEEP
(positive end expiratory pressure) valve and the cylinder with a bag containing premixed gas. This circuit is functionally identical to that used in studies on humans. The circuit was connected to the intake port of the ventilator. Under control conditions, FGF was adjusted so that the fresh gas reservoir just emptied during each ventilator cycle; this end point was confirmed by a slight rise in FICOz above zero. After a steady-state had been reached (difference < 1.5 mm Hg in two successive PaC02's taken 5 minutes apart), VT was increased at 5 minute intervals from 400 to 600 to 900 to 1200 mL. In a second trial at a fixed VT (approximately 400 mL} and fixed FGF, f was increased at 5 minute intervals from 10 to 14 to 18 to 22 min-1. A blood sample for the determination of blood gases was drawn from the femoral artery at the beginning and end of each 5 min interval.
All data are expressed as means ~ standard deviation. We tested for significant differences using one- or two-way ANOVA with post hoc analysis where appropriate. A p value Iess than 0.05 was considered significant.
_,.~... ~ , , WO 98/41266 _ l,~ _ PCT/CA97100186 Results:
Human subjects Figure 5 presents the VT and PETCOz of subject 1 during 3 min of maximal ventilatory effort. Results for all subjects are summarized in Table III; data represent average values for 10 breaths at 0 (the onset of hyperventilation), 2.5 and 3 min. PETCOZ did not change significantly from control values throughout the course of hyperventilation (p = 0.08, ANOVA). There was considerable variability in V and breathing patterns between subjects but individual subjects tended to sustain a particular breathing pattern throughout the run.
Dogs Figure 6 presents traces of airway PC02 and VT for dog #5 during changes in f or VT. Figures 7 and 8 show the changes in PaC02 and the PETC02 in all dogs during changes in f or VT. Increases in f did not significantly affect mean PaC02 or PETCOz (p=0.28 and p=0.11, respectively;
ANOVA). Increases in VT decreased mean PaC02 from control only at VT
of 1200 mL (p=0.01); in contrast, changes in VT did not affect mean PETCOz (p=0.25). The mean absolute change in PaC02 between control and the highest ventilation was 2.2 ~ 1.8 mmHg (range 0.4 to 4.8) for f and 3.4 ~ 2.3 mmHg (range 0.4 to 5.6) for VT.
COMMENTARY
The system minimized decreases in PETCOz over a wide range of ventilation (56 to 131 L miri') and breathing patterns, in hyperventilating human subjects and in mechanically hyperventilated dogs (4 to 12 L
min'). The variability in PaCOz in the hyperventilated dogs, although small, may have been due to a) imprecise matching of reserve gas PCOZ to the dog's PvCO2s; b) prolonged duration of the maneuver in dogs (> 15 min versus 3 min for human subjects) and c) the extent of hyperventilation (see below). In addition, the different levels of ventilation may have induced changes in systemic and pulmonary blood flow (ventilation-perfusion matching, physiological and anatomical dead space), thereby affecting PaC02 and PvC02. Despite these sources of variability, the range over which PaC02 varied in my studies in dogs was similar to those reported in studies utilizing more complex equipment (see Table 1).
Conventional servo-controlled techniques designed to prevent changes in PCO~ with hyperpnea are less affected by changes in CO
production than the circuit; however, they have other limitations. The assumption that detected changes in PETCOz are due to a change in PaC02 is not always warranted (14). Small changes in ventilatory pattern can 'uncouple' PETCOz from PaCO~, resulting in PETCO~ being an inappropriate input for the control of PaCOz. For example, a smaller VT decreases VA
(which tends to increase PaCOZ) but will also decrease PETCO~, causing a servo-controller to respond with an inappropriate increase in inspired CO, Even under ideal conditions, a servo-controlled system attempting to correct for changes in PETCOZ cannot predict the size of an impending VT
in a spontaneously breathing subject and thus deliver the appropriate CO~
load. If in an attempt to obtain fine control the gain in a servo-control system is set too high, the response becomes unstable and may result in oscillation of the control variable (11). Conversely, if the gain is set too low, compensation lags (9). Over-damping of the signal results in a the response never reaching the target. To address these problems, servo-controllers require complex algorithms (16) and expensive equipment.
When CO~ production is constant, the circuit has the theoretical advantage over servo-controlled systems in that it provides passive compensation for changes in V. This minimizes changes in VA, pre empting the need for subsequent compensation. Maintenance of a nearly constant VA occurs even during irregular breathing, including brief periods when V is less than the FGF. Under this circumstance, excess FGF
is stored in the fresh gas reservoir and subsequently contributes to VA
when ventilation exceeds FGF.
When COZ production increases during hyperventilation, as would occur with increased work of breathing or exercise, my method requires modification. To compensate, additional VA can be provided either by increasing FGF or by lowering the PCOZ of the reserve gas below the PvCOZ, as expressed in the following equation:
VA = FGF + (V-FGF) (PvC02 - reserve gas PCOz)/PvC02 Because spontaneously breathing subjects had such variable V
during hyperventilation, compensating for the COZ production by modifying FGF would have required constant adjustment. We therefore chose to decrease the PCOZ of the reserve gas to establish a concentration ~A~~NDE.D SI-kE-~T
:y i WO 98/412bb PCT/CA97/00186 gradient between the PCOZ of the reserve gas and the PvC02; when this gradient is constant, Vr~ is a function of V. We found that, over the wide range of V exhibited by the subjects, a concentration of 5.5% C02 in the reserve gas (instead of 6.5% which corresponds to a PvC02 of 46 mrnHg) provided the optimal gradient to compensate for increases in C02 production resulting from increased work of breathing.
I therefore have described a simple circuit that disassociates VA
from V. It passively minimizes increases in Vr~ that would normally accompany hyperventilation when COZ production is constant. It can be modified to compensate for increases in COZ production. The circuit may form the basis for a simple and inexpensive alternative to servo-controlled systems for research and may have therapeutic applications.
TABLE II
Dog # Weight Initial FETCOZ Bag FC02 (kg) (%) (%) 1 22 5.3 7.0 2 20 4.6 6.6 3 20 7.1 9.0 4 24 7.3 9.0 5 25 5.5 6.9 6 20 6.0 7.2 WO 98/41266 _ 20 - PCT/CA97/0018G
TABLE III
End Tidal PC(~2(mmHg) Frequency (ruin-1) Time Subject Control0 1.5 3 Subject # 0 1.5 3 #
1 40.3 33.6 34.935.6 1 57 50 47 2 36.6 30.9 28.128.0 2 89 87 88 3 42.0 42.5 43.242.7 3 31 30 30 4 41.0 34.5 38.838.8 4 149 130 127 Tidal Volume Minute Ve ntilation min-I) (L) (L
Time Time Subject 0 1.5 3 Subject # 0 1.5 3 #
1 2.30 2.49 2.58 1 131 124 118 2 0.85 0.72 0.63 2 75 63 56 3 2.60 2.64 2.26 3 80 78 68 4 0.78 0.62 0.60 4 117 80 76 While the foregoing provides a detailed description of a preferred embodiment of the invention, it is to be understood that this description is illustrative only of the principles of the invention and not limitative.
Furthermore, as many changes can be made to the invention without departing from the scope of the invention, it is intended that all material contained herein be interpreted as illustrative of the invention and not in a limiting sense.
_, _ ... _ ...
Claims (24)
OR PRIVILEGE IS CLAIMED ARE AS FOLLOWS:
1. A breathing circuit system for ventilating an anesthetized patient, the system comprising:
a) a standard primary circle anaesthetic circuit comprising a one-way inspiratory limb for delivering re-breathed gas and a one-way expiratory limb for accepting expired gas;
b) a supplementary respiratory circuit solely supplying non-rebreathed gas and comprising a source of non-rebreathed substantially carbon dioxide-free gas, a non-rebreathed fresh gas reservoir for storing fresh gas, a source of non-rebreathed reserve gas containing carbon dioxide whose PCO2 value is selectable, and a gas delivery conduit;
c) a non-rebreathing valve disposed in communication with the inspiratory limb;
and d) a three-way respiratory valve disposed in communication with both the inspiratory limb and the delivery conduit for selectively permitting passage of gas from the inspiratory limb or from the delivery conduit.
a) a standard primary circle anaesthetic circuit comprising a one-way inspiratory limb for delivering re-breathed gas and a one-way expiratory limb for accepting expired gas;
b) a supplementary respiratory circuit solely supplying non-rebreathed gas and comprising a source of non-rebreathed substantially carbon dioxide-free gas, a non-rebreathed fresh gas reservoir for storing fresh gas, a source of non-rebreathed reserve gas containing carbon dioxide whose PCO2 value is selectable, and a gas delivery conduit;
c) a non-rebreathing valve disposed in communication with the inspiratory limb;
and d) a three-way respiratory valve disposed in communication with both the inspiratory limb and the delivery conduit for selectively permitting passage of gas from the inspiratory limb or from the delivery conduit.
2. A breathing circuit system as claimed in claim 1 additionally comprising a pressure relief valve in communication with the fresh gas reservoir.
3. A breathing circuit system as claimed in claim 2 additionally comprising a demand valve in communication with the source of reserve gas for permitting delivery upon demand of said reserve gas.
4. A breathing circuit system as claimed in claim 1 additionally comprising a demand valve in communication with the source of reserve gas for permitting delivery upon demand of said reserve gas.
5. A circuit for ventilating a patient to recover from exposure to vapours, the circuit comprising:
.cndot. a standard circle anaesthetic circuit comprising a one-way inspiratory limb for delivering rebreathed gas, and a one-way expiratory limb for accepting expired gas;
.cndot. a supplementary respiratory circuit for solely supplying non-rebreathed gas, and comprising a source of fresh gas substantially free from a significant amount of CO2, and a gas delivery conduit; characterized in that said supplementary respiratory circuit further comprises a fresh gas reservoir for storing fresh gas, a source of non-rebreathed reserve gas for supplementing, as required, the fresh gas, the reserve gas containing a predetermined amount of CO2 whose PCO2 is substantially equal to that of mixed venous blood, said circuit for ventilating a patient further comprising .cndot. a non-rebreathing valve disposed for communication with the patient;
and .cndot. a three-way respiratory valve disposed in communication with the non-breathing valve and both the inspiratory limb and the gas delivery conduit for selectively permitting passage of either rebreathed gas from the inspiratory limb or non-rebreathed gas from the gas delivery conduit to the non-rebreathing valve.
.cndot. a standard circle anaesthetic circuit comprising a one-way inspiratory limb for delivering rebreathed gas, and a one-way expiratory limb for accepting expired gas;
.cndot. a supplementary respiratory circuit for solely supplying non-rebreathed gas, and comprising a source of fresh gas substantially free from a significant amount of CO2, and a gas delivery conduit; characterized in that said supplementary respiratory circuit further comprises a fresh gas reservoir for storing fresh gas, a source of non-rebreathed reserve gas for supplementing, as required, the fresh gas, the reserve gas containing a predetermined amount of CO2 whose PCO2 is substantially equal to that of mixed venous blood, said circuit for ventilating a patient further comprising .cndot. a non-rebreathing valve disposed for communication with the patient;
and .cndot. a three-way respiratory valve disposed in communication with the non-breathing valve and both the inspiratory limb and the gas delivery conduit for selectively permitting passage of either rebreathed gas from the inspiratory limb or non-rebreathed gas from the gas delivery conduit to the non-rebreathing valve.
6. The circuit of Claim 5 further comprising means to automate the supplementary respiratory circuit for monitoring, mixing and delivering fresh gas and reserve gas.
7. The circuit of Claim 5, further comprising a pressure relief valve in communication with the fresh gas reservoir , in the event that should the fresh gas reservoir overfill with gas, the presence of the pressure relief valve will prevent the fresh gas reservoir from breaking, rupturing or become damaged in any way.
8. The circuit of Claim 6, further comprising a pressure relief valve in communication with the fresh gas reservoir, in the event that should the fresh gas reservoir overfill with gas, the presence of the pressure relief valve will prevent the fresh gas reservoir from breaking, rupturing or become damaged in any way.
9. The circuit of any of Claims 5, 6, 7, or 8, wherein the source of reserve gas comprises a demand valve regulator so that when additional gas is required, the demand valve regulator opens the communication of the source of reserve gas and when not required the demand valve regulator is closed and only fresh gas flows from the source of fresh gas and the fresh gas reservoir to the non-rebreathing valve.
10. The use of the circuit of any claims 1 to 9 in a device to hasten the recovery of patients from administration of vapour anaesthetics.
11. The use of the circuit of any of claims 5 to 9 for: respiratory muscle training, investigation of the rate of pulmonary stretch receptors, tracheobronchial tone, expanding the lung to prevent atelectasis, and control of respiration.
12. The use of the circuit of any of claims 5 to 9 for deep sea divers and astronauts to eliminate nitrogen in the body.
13. The use of the circuit of claims 5 to 9 to treat carbon monoxide poisoning under normal baric or hyper baric conditions.
14. The use of a non-rebreathing circuit during recovery for ventilating a patient to recover from exposure to undesirable gases, said circuit comprising:
(i) a source of fresh gas being substantially free from a significant amount of CO2 incorporated into a primary circuit for delivering said gas to a patient at a specified rate through an inspiratory limb;
(ii) a source of reserve gas available to the patient through a supplementary circuit when required at a rate of ventilation equal to that amount exceeding the consumption of fresh gas, said supplementary circuit being in communication with said inspiratory limb of said primary circuit, and said reserve gas containing a predetermined amount of CO2 whose PCO2 is substantially equal to that of mixed venous blood, whereby the level of PCO2 is maintained in the patient regardless of the rate of ventilation providing for maximum gradient for elimination of the undesirable gases.
(i) a source of fresh gas being substantially free from a significant amount of CO2 incorporated into a primary circuit for delivering said gas to a patient at a specified rate through an inspiratory limb;
(ii) a source of reserve gas available to the patient through a supplementary circuit when required at a rate of ventilation equal to that amount exceeding the consumption of fresh gas, said supplementary circuit being in communication with said inspiratory limb of said primary circuit, and said reserve gas containing a predetermined amount of CO2 whose PCO2 is substantially equal to that of mixed venous blood, whereby the level of PCO2 is maintained in the patient regardless of the rate of ventilation providing for maximum gradient for elimination of the undesirable gases.
15. The use of claim 14 wherein the patient is a person.
16. The use of claim 14 or 15 for: respiratory muscle training, investigation of the rate of pulmonary stretch receptors, tracheobronchial tone, expanding the lung to prevent atelectasis, and control of respiration.
17. The use of claim 14 or 15 for deep sea divers and astronauts to eliminate nitrogen in the body.
18. The use of claim 14 or 15 to treat carbon monoxide poisoning under normal baric or hyper baric conditions.
19. A circuit for ventilating a patient to recover from exposure to undesirable gases comprising:
(i) a primary circuit including a one-way inspiratory limb and a one-way expiratory limb for supplying gas from a source of fresh gas and delivered to the patient at a specified rate through the inspiratory limb, said fresh gas containing an insignificant amount of CO2;
(ii) a supplementary circuit for supplying gas from a source of reserve gas in communication with the inspiratory limb and delivered to the patient through a three way respiratory valve when required at a rate of ventilation supplementing the delivery of fresh gas, said reserve gas containing a predetermined amount of CO2 whose PCO2 is substantially equal to that of mixed venous blood, whereby the level of PCO2 is maintained in the patient regardless of the rate of ventilation providing for maximum gradient for elimination of undesirable gases.
(i) a primary circuit including a one-way inspiratory limb and a one-way expiratory limb for supplying gas from a source of fresh gas and delivered to the patient at a specified rate through the inspiratory limb, said fresh gas containing an insignificant amount of CO2;
(ii) a supplementary circuit for supplying gas from a source of reserve gas in communication with the inspiratory limb and delivered to the patient through a three way respiratory valve when required at a rate of ventilation supplementing the delivery of fresh gas, said reserve gas containing a predetermined amount of CO2 whose PCO2 is substantially equal to that of mixed venous blood, whereby the level of PCO2 is maintained in the patient regardless of the rate of ventilation providing for maximum gradient for elimination of undesirable gases.
20. The use of the circuit of claim 19 for: respiratory muscle training, investigation of the rate of pulmonary stretch receptors, tracheobronchial tone, expanding the lung to prevent atelectasis, and control of respiration.
21. The use of the circuit of claim 19 for deep sea divers and astronauts to eliminate nitrogen in the body.
22. The use of the circuit of claim 19 to treat carbon monoxide poisoning under normal baric or hyper baric conditions.
23. The use of claims 20 to 22 further comprising means to automate the circuit for monitoring , mixing and delivering fresh gas and reserve gas.
24. The circuit of claim 1, 5 or 19 further comprising means to automate the circuit for monitoring , mixing and delivering fresh gas and reserve gas.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/CA1997/000186 WO1998041266A1 (en) | 1997-03-19 | 1997-03-19 | Elimination of vapour anaesthetics from patients after surgical procedures |
Publications (2)
Publication Number | Publication Date |
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CA2283430A1 CA2283430A1 (en) | 1998-09-24 |
CA2283430C true CA2283430C (en) | 2006-05-23 |
Family
ID=4173205
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Application Number | Title | Priority Date | Filing Date |
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CA002283430A Expired - Fee Related CA2283430C (en) | 1997-03-19 | 1997-03-19 | Elimination of vapour anaesthetics from patients after surgical procedures |
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US (2) | US6354292B1 (en) |
EP (1) | EP0973572B1 (en) |
JP (1) | JP3822647B2 (en) |
KR (1) | KR100481207B1 (en) |
AT (1) | ATE252402T1 (en) |
AU (1) | AU1919197A (en) |
CA (1) | CA2283430C (en) |
DE (1) | DE69725759T2 (en) |
ES (1) | ES2212078T3 (en) |
HK (1) | HK1027047A1 (en) |
WO (1) | WO1998041266A1 (en) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE252402T1 (en) | 1997-03-19 | 2003-11-15 | Joseph Arnold Fisher | DEVICE FOR REMOVAL OF ANESTHETIC VAPOR FROM A PATIENT AFTER A SURGICAL PROCEDURE |
CA2304292C (en) * | 2000-03-31 | 2009-01-13 | Joseph Fisher | An improved rebreathing circuit to set and stabalize end tidal and arterial pco2 despite varying levels of minute ventilation |
CA2346517A1 (en) * | 2001-05-04 | 2002-11-04 | Joseph Fisher | Improved method of maintaining constant arterial pco2 during increased minute ventilation and measurement of anatomic and alveolar dead space |
SE0100064D0 (en) * | 2001-01-10 | 2001-01-10 | Siemens Elema Ab | Anaesthetic filter arrangement |
WO2002072185A1 (en) | 2001-03-12 | 2002-09-19 | Fisher Joseph A | Rebreathing circuit |
ATE328629T1 (en) * | 2001-09-24 | 2006-06-15 | Atsuo F Fukunaga | BREATHING CIRCUIT WITH UNCONVENTIONAL BREATHING LINES AND SYSTEMS AND METHODS FOR OPTIMIZING THE USE OF FRESH GASES |
US7717109B2 (en) * | 2001-09-24 | 2010-05-18 | F-Concepts Llc | Breathing systems with post-inspiratory valve fresh gas flow input, components for implementing same, and methods of use |
FR2829942A1 (en) * | 2001-09-27 | 2003-03-28 | Taema | Measurement of flow rates in an artificial respirator for medical use with only a single respiratory branch, whereby a differential pressure is measured and related to the inspiration or expiration mass flow rate |
CA2379353C (en) * | 2002-03-28 | 2012-07-31 | Joseph Fisher | A new method for continuous measurement of flux of gases in the lungs during breathing |
US20040084048A1 (en) * | 2002-09-27 | 2004-05-06 | Alex Stenzler | High FIO2 oxygen mask with a sequential dilution feature and filter |
US7353825B2 (en) * | 2003-05-01 | 2008-04-08 | Axon Medical, Inc. | Apparatus and techniques for reducing the effects of general anesthetics |
US7621272B2 (en) * | 2003-05-01 | 2009-11-24 | Anecare Laboratories, Inc. | Apparatus and techniques for reducing the effects of general anesthetics |
DE102004017403B4 (en) * | 2004-04-08 | 2010-03-25 | Dräger Medical AG & Co. KG | Measuring device for measuring the volume flow of a gas whose flow direction can reverse |
CA2605950C (en) * | 2004-04-23 | 2013-06-11 | Stephan Boehm | Method and apparatus for changing the concentration of a target gas at the blood compartment of a patient's lung during artificial ventilation |
DE102004040740A1 (en) * | 2004-08-21 | 2006-02-23 | Viasys Healthcare Gmbh | Gas reservoir bag, distributor housing, respiratory mask and ventilation method |
US20090173348A1 (en) * | 2005-02-25 | 2009-07-09 | Fisher Joseph A | Method And Apparatus For Inducing And Controlling Hypoxia |
AU2012244252B2 (en) * | 2005-05-06 | 2013-09-12 | Anecare Laboratories, Inc. | Apparatus and techniques for reducing the effects of general anesthetics |
US7900626B2 (en) * | 2006-04-17 | 2011-03-08 | Daly Robert W | Method and system for controlling breathing |
US8381732B2 (en) * | 2008-03-21 | 2013-02-26 | The Periodic Breathing Foundation, Llc | Nasal interface device |
FR2906710B1 (en) * | 2006-10-05 | 2008-12-12 | Equip Veterinaire Minerve Sa | SAFETY ANESTHESIA DEVICE FOR MEDICAL SAMPLES CARRIED OUT WITH HIGH CADENCE ON SMALL LABORATORY ANIMALS |
US20080302365A1 (en) * | 2007-06-08 | 2008-12-11 | Cohen Eric D | Respiratory Mask |
US20100192947A1 (en) * | 2009-02-04 | 2010-08-05 | Jeff Mandel | Anesthetic delivery system and methods of use |
US9168045B2 (en) | 2009-09-11 | 2015-10-27 | Tbi Innovations, Llc | Device to reduce SLOSH energy absorption and its damaging effects through the reduction of the flow of one or more outflow vessels of the cranium |
US8985120B2 (en) * | 2009-09-11 | 2015-03-24 | Tbi Innovations, Llc | Method to reduce SLOSH energy absorption and its damaging effects through the reduction of inelastic collisions in an organism |
US11696766B2 (en) | 2009-09-11 | 2023-07-11 | Tbi Innovations, Llc | Methods and devices to reduce damaging effects of concussive or blast forces on a subject |
US10842502B2 (en) | 2009-09-11 | 2020-11-24 | Tbi Innovations, Llc | Devices and systems to mitigate traumatic brain and other injuries caused by concussive or blast forces |
US9173660B2 (en) | 2009-09-11 | 2015-11-03 | Tbi Innovations, Llc | Methods and devices to reduce the likelihood of injury from concussive or blast forces |
US10004515B2 (en) | 2009-09-11 | 2018-06-26 | Tbi Innovations, Llc | Methods and devices to reduce damaging effects of concussive or blast forces on a subject |
NL1037372C2 (en) * | 2009-10-07 | 2011-04-11 | Alcmair Partners B V | METHOD AND DEVICE FOR BREATHING PATIENTS. |
US20140163397A1 (en) * | 2012-12-07 | 2014-06-12 | Shape Medical Systems, LLC | Gas Exchange Testing and Auxiliary Gas Delivery Apparatus |
US8900169B2 (en) | 2013-03-15 | 2014-12-02 | Tbi Innovations, Llc | Methods and devices to reduce the likelihood of injury from concussive or blast forces |
CN104214373A (en) * | 2013-06-05 | 2014-12-17 | 北京谊安医疗系统股份有限公司 | Air source module and anesthesia machine provided with same |
US10758700B2 (en) * | 2013-09-30 | 2020-09-01 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Home-based heliox system with carbon dioxide removal |
US9649466B2 (en) | 2014-02-18 | 2017-05-16 | The Board Of Regents Of The University Of Texas System | Systems and methods for gas mixture delivery to humans inside an MRI scanner |
HUP1400421A2 (en) * | 2014-09-10 | 2016-03-29 | Gyarmathy Agnes Dr Pomozine | Instrument for adjusting and/or controlling co2 content of inhaled air |
EP3376970A4 (en) | 2015-11-16 | 2019-07-31 | Q30 Sports Science, LLC | Traumatic brain injury protection devices |
WO2023153940A1 (en) * | 2022-02-11 | 2023-08-17 | Fisher & Paykel Healthcare Limited | Positive pressure breathing circuit |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3921628A (en) * | 1971-08-19 | 1975-11-25 | Philips Corp | Medical ventilators |
US3901230A (en) * | 1972-01-17 | 1975-08-26 | Henkin Melvyn Lane | Anesthesia rebreathing apparatus including improved reservoir means |
US4188946A (en) * | 1977-10-07 | 1980-02-19 | Rayburn Robert L | Controllable partial rebreathing anesthesia circuit and respiratory assist device |
US4991576A (en) * | 1988-10-11 | 1991-02-12 | Henkin Melvyn Lane | Anesthesia rebreathing system |
US5320093A (en) * | 1990-12-21 | 1994-06-14 | Brigham And Women's Hospital | Rapid anesthesia emergence system using closed-loop PCO2 control |
US5398675A (en) * | 1992-10-14 | 1995-03-21 | Henkin; Melvyn L. | Anesthesia rebreathing system |
SE9400992L (en) * | 1994-03-24 | 1995-05-02 | Siemens Elema Ab | Respiratory gas system with a pressure transmitting selector between the breathing circuit and the propellant apparatus |
SE9402537L (en) * | 1994-07-20 | 1996-01-21 | Siemens Elema Ab | Anesthesia System |
SE506727C2 (en) * | 1995-05-15 | 1998-02-02 | Jacob & Allard Ab | Shunt valve in a circulation-type breathing system |
DE19606470C2 (en) * | 1996-02-21 | 2001-03-15 | Mpo Ges Fuer Medizintechnische | Procedure for determining the functional residual capacity (FRC) |
US5662099A (en) * | 1996-03-29 | 1997-09-02 | Ohmeda Inc. | Detection of bellows collapsed condition in medical ventilator |
ATE252402T1 (en) | 1997-03-19 | 2003-11-15 | Joseph Arnold Fisher | DEVICE FOR REMOVAL OF ANESTHETIC VAPOR FROM A PATIENT AFTER A SURGICAL PROCEDURE |
US6131571A (en) * | 1997-04-30 | 2000-10-17 | University Of Florida | Ventilation apparatus and anesthesia delivery system |
US5857458A (en) * | 1997-09-26 | 1999-01-12 | Ohmeda Inc. | Automatic bellows refill |
US6125848A (en) * | 1997-09-26 | 2000-10-03 | Datex-Ohmeda, Inc. | Distal volume monitoring |
US6216690B1 (en) * | 1997-10-15 | 2001-04-17 | Datex-Ohmeda, Inc. | Method and apparatus for rapid control of set inspired gas concentration in anesthesia delivery systems |
US6152131A (en) * | 1998-08-26 | 2000-11-28 | Instrumentarium Corp. | Method and apparatus for detecting an empty breathing gas compartment in a patient ventilator |
SE9803684D0 (en) * | 1998-10-27 | 1998-10-27 | Siemens Elema Ab | Anesthesia apparatus |
-
1997
- 1997-03-19 AT AT97906959T patent/ATE252402T1/en not_active IP Right Cessation
- 1997-03-19 AU AU19191/97A patent/AU1919197A/en not_active Abandoned
- 1997-03-19 JP JP53996698A patent/JP3822647B2/en not_active Expired - Fee Related
- 1997-03-19 CA CA002283430A patent/CA2283430C/en not_active Expired - Fee Related
- 1997-03-19 US US09/380,705 patent/US6354292B1/en not_active Expired - Lifetime
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- 1997-03-19 WO PCT/CA1997/000186 patent/WO1998041266A1/en active IP Right Grant
- 1997-03-19 EP EP97906959A patent/EP0973572B1/en not_active Expired - Lifetime
- 1997-03-19 DE DE69725759T patent/DE69725759T2/en not_active Expired - Lifetime
- 1997-03-19 KR KR10-1999-7008559A patent/KR100481207B1/en not_active IP Right Cessation
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2000
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2002
- 2002-01-16 US US10/050,392 patent/US6708689B2/en not_active Expired - Fee Related
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ATE252402T1 (en) | 2003-11-15 |
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CA2283430A1 (en) | 1998-09-24 |
KR20010005502A (en) | 2001-01-15 |
US20030047187A1 (en) | 2003-03-13 |
KR100481207B1 (en) | 2005-04-07 |
WO1998041266A1 (en) | 1998-09-24 |
US6354292B1 (en) | 2002-03-12 |
EP0973572A1 (en) | 2000-01-26 |
JP3822647B2 (en) | 2006-09-20 |
EP0973572B1 (en) | 2003-10-22 |
AU1919197A (en) | 1998-10-12 |
DE69725759T2 (en) | 2004-08-05 |
ES2212078T3 (en) | 2004-07-16 |
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