Drug delivery system for conscious sedation

(12) PATENT DESCRIPTION (19) PL (11) 206780 (13) B1 (21) Application number: 369032 (51) Int.Cl.

(22) Filing date: 17/10/2002 A61M 15/00 (2006.01)

A61M 16/00 (2006.01) (86) Date and number of the international application:

2002-10-17, PCT / US02 / 033190 (87) International application publication date and number:

April 24, 2003, WO03 / 033048 (54)

System for delivering gas to a patient (73) The patent holder:

(30) Priority:

October 17, 2001, US, 60 / 330,063 (43) Application announced:

April 18, 2005 BUP 08/05

MINRAD INC., Buffalo, US (72) Inventor (s):

WILLIAM H. JR BURNS, Orchard Park, US JOHN C. MCNEIRNEY, Fairburn, US ROSS C. TERRELL, Phillipsburg, US (45) The grant of the patent was announced as:

30.09.2010 WUP 09/10 (74) Plenipotentiary:

item. stalemate. Kowal Elżbieta POLSERVICE KANCELARIA OF PATENT ATTORS, limited liability company

PL 206 780 B1

Description of the invention

The present invention relates to a system for delivering a gas to a patient.

Since the mid-18th century, sedation / anesthesia has been used to relieve pain in hospitals and pre-hospital stays. Nitrous oxide (N2O) was the primary inhalant in this regard. Sedative hypnotics such as diazepam and midazolam have been used as alternatives to many barbitutes, opioids, and agonist / antagonist agents.

Oral dentistry and surgery were the first medical applications of nitrous oxide to calm consciousness and gained widespread acceptance after successful use on Queen Victoria. Subsequently, the use of sedation spread to hospitals, emergency rooms, ambulances, and other doctor's offices.

Calming awareness is a pain blocking technique that allows the patient to remain partially alert during an invasive procedure. Anesthesia is achieved but, unlike with anesthesia, the patient remains conscious and able to recall. Specifically, the method is unique in that patients feel no pain, but retain defensive reflexes, keep their airways working independently, and respond in response to stimuli. Thus, the risk of low or constricted breathing accompanying anesthesia is reduced.

The use of nitrous oxide to sedate consciousness in recent years has decreased, primarily as a consequence of reports on the safety profile of gases, including those given above, but also due to their effects on methionine synthesis during prolonged use. These factors are particularly relevant to healthcare professionals of childbearing age who face an increased risk of spontaneous abortion due to the teratogenic profile of nitrous oxide.

Nitrous oxide (N2O) causes a relative weakening of the ability to perform vital functions. As illustrated in the following description of the invention, this inability imposes strict limits on the percentage of N2O in the inspired mix to ensure that the patient receives a sufficient amount of oxygen. The oxygen content of the atmosphere is approximately 21%. Consequently, most international regulatory agencies, including the United States Food and Drug Administration (FDA), have established guidelines for the administration of oxygen to avoid organ and tissue hypoxia. The most common ratio is 70% N2O / 30% oxygen, although some delivery systems maintain 50% oxygen. With a 70% mixture of nitrous oxide N2O, sedation of consciousness occurs in most patients. A mixture of 70% N2O / 30% oxygen, on a sustained base in the administration level, provides a Minimum Alveolar Content ("MAC") of 0.636 MAC.

Six inhaled ethers are currently used: halothane, methoxyflurane, enflurane, isoflurane, sevoflurane, and desflurane (Terrell, Airco, Inc., synthesized enflurane, isoflurane, and desflurane). Research and development has been carried out on these ingredients due to their effectiveness, rapid action after administration, cardiovascular stability and their non-inflammatory and non-addictive properties. Traditionally, these products are packaged in 100 ml and 250 ml brown glass bottles and volatilized using a special refrigerant in an even temperature system.

These drugs were developed for the needs of anesthesia. No research and development has been carried out on any of the inhaled ethers as an inhaled analgesic. This reflects the perception of these drugs by the industry that either there was no need for inhaled analgesics or there was no cost-effective specialized instrumentation for administering these drugs as analgesic drugs. The instrumentation used increasingly in hospital installations for pharmacological anesthesia has been both fancy and expensive, often valued at over $ 100,000. The combination of these factors actually eliminated the use of these drugs as a calming agent, especially outside the hospital.

US Publication No. 5,771,882 discloses a solution in which a liquid anesthetic is contained in a reservoir.

A system for delivering a gas to a patient according to the invention for producing anesthesia in a patient, comprising an oxygen source connected to an anesthetic reservoir and a distributor having an outlet and a pair of inputs connected to the oxygen source and the reservoir, respectively, the distributor being a means for providing a mixture of oxygen and generating agent. anesthesia without loss of consciousness, and the system includes elements connected to the outlet of the distributor

Conveying the mixture from the output of the divider to the patient, and the reservoir contains a liquid anesthetic agent, the agent being a halogenated material from the group consisting of halogenated ethers and halothane, characterized in that supplying a mixture of oxygen and generating agent anesthesia with a splitter is carried out by measuring the liquid halogen material to oxygen with a flow meter, the mixture comprising halogenated material limited to no more than 0.636 MAC to produce anesthesia without unconsciousness in a patient undergoing a medical or dental procedure or treatment.

The manifold includes a pressure regulator and a flow meter in fluid communication, the flow meter in fluid communication with the output of the manifold.

The manifold inlet connected to the oxygen source is in fluid communication with the pressure regulator and the manifold inlet connected to the anesthetic-generating gas reservoir is in fluid communication with the flow meter.

The system includes heating elements technically coupled with an anesthesia-generating gas reservoir and ambient temperature measuring elements in a regulating relationship with the heating elements to ensure compensation of changes in environmental temperature conditions.

An oxygen drainage system is functionally located between the oxygen source and the patient. The oxygen source contains cylinders. The gas tank contains cylinders. The gas tank has a selection index. The pressure regulator is digital. The pressure regulator is analog.

The system includes a unit that cleans the gas exhaled by the patient from the anesthetic generating agent.

The halogenated material is haloton.

The halogenated material is enflurane.

The halogenated material is isoflurane.

The halogenated material is sevoflurane.

The halogenated material is desflurane.

There are many benefits to calming awareness. In particular, medical procedures are easier to bear for patients and medical operators as calming the consciousness reduces the patient's tension and reluctance to be treated. Further, the technique has the potential for expansive applications. Research shows success with patient-controlled anesthesia.

Inhaled halogenated ethers offer many advantages in important application categories compared to calming the consciousness with nitrous oxide or calming the message with sedative hypnotics. An example of a few compared with these measures is shown in Table 1.

Table 1

<td colspan="5">Sedative hypnotics</td>

<td>Properties</td><td>Halogenated ethers</td><td>Nitrous oxide</td><td>IV Diazepam</td><td>IV Midazolam</td>

<td>The beginning of action</td><td>Lightning fast</td><td>Lightning fast</td><td>Moderate</td><td>Moderate</td>

<td>Security profile</td><td>Tall</td><td>Teratogenic and blood damage</td><td>Moderate</td><td>Moderate</td>

<td>Served with high concentration O2</td><td>Yes</td><td>No</td><td>Freely</td><td>Freely</td>

<td>Potentially overdosage</td><td>No</td><td>Relaxing</td><td>Substance requiring control</td><td>Substance requiring control</td>

<td>Convenience of use</td><td>Yes</td><td>Yes</td><td>Restoring agent required</td><td>Restoring agent required</td>

<td>Ability to restore the initial state</td><td>Yes</td><td>Yes</td><td>Reasonably</td><td>Reasonably</td>

<td>Rapid return for activity</td><td>Yes</td><td>Yes</td><td>Possible long weakness</td><td>Possible moderate weakness</td>

PL 206 780 B1

The combination of these characteristics makes the halogenated ethers attractive agents for calming consciousness. However, there is also a need for a safe, accurate and economical delivery system.

The clinical application of the sedation system is possible in a wide range of procedures, including, but not limited to, dental and oral surgical procedures, surgical debridement of a burn wound, reduction of pain in emergencies and trauma situations, use of medications in intensive care units, cardiac care, or in cooperation with devices used in critical conditions, for testing or working in end-use medical applications including pediatric, delivery and puerperal procedures, in individual cases to reduce anxiety related to the fear of needle insertion and where prolonged property status would be difficult to obtain without sedation.

Additionally, the invention has the following features. The invention increases blood oxygenation, which is an important feature for individual patients with poor oxygenation of the heart muscle or the brain. The invention enhances occupational safety when the analgesic drugs described herein are introduced as substitutes for nitrous oxide, which is essential for women of childbearing age. The invention may reduce the anxiety associated with claustrophobia and may reduce pain in patients forced to a prolonged period of inactivity, such as during visualization with a nuclear magnetic resonance (MRI) machine when used with the MR safe (1.5 Tesla) version of the delivery system. Likewise, the invention may be used for sedation in Intensive Care Units ("ICU"), Critical Care Units "CCU", or during cardiac catheterization, defibrillator implantation or pacemaker regulation and generally reducing pain. The device may be developed in alternative configurations, such as with a station or a method of continuous patient monitoring, including the integration of monitors into the system. Additionally, the device may be equipped with a regulator system that controls the inhalation depth of the patient to enable safe and controlled anesthesia of the patient's pain sensation.

Research and development works have been carried out on inhaled anesthetics to obtain many properties, including their rapid onset of action and rapid recovery of the patient's activity, ease of control and an ideally broad safety profile. The effectiveness of these agents is measured by their ability to produce narcosis (analgesia, amnesia and unconsciousness) along with other desirable properties. The present invention focuses on the drug dosage level at which pain analgesia occurs, but amnesia or unconsciousness do not. Additionally, to determine a dosage level at which pain is greatly reduced or eliminated but awareness remains, an delivery system for the safe and efficient administration of the agent is described.

Fig. 1 shows a block diagram of an embodiment of the invention, Fig. 2 shows a perspective view of another embodiment of the invention, Fig. 3 shows a perspective view of an embodiment of the invention similar to that of Fig. 2, but rotated by 180 °.

Halogenated ethers are modern inhalants. Generally, they are characterized by specific gravity between 1.0 and 2.0, low molecular weights (165.0-200.0), low boiling point (22 ° C to 104 ° C) and significant potency at concentrations ranging from 0. 16% -7.8% oxygen agent, which causes 99% of adults to anesthetize. These particular variables are important in characterizing the invention because drugs are changed from a liquid to a gaseous state and administered with a float gas - usually oxygen, but sometimes with a combination of oxygen and another gas or gases containing oxygen, nitrous oxide and / or air.

However, the measures differ in a number of important features. Some agents containing methoxyflurane, halothane and sevoflurane are known to interact with metals. To some extent, the same agents decompose in the presence of "soda lime" (calcium hydroxide) and / or in the presence of UV radiation. To a greater or lesser extent, all halogenated agents are solvents. The delivery system of the sedative drugs must be compatible with the administration of the agent that is used.

Anesthetic strength is measured by the minimum concentration in the alveoli of anesthetic causing immobility in 50% of patients, defined as 39-year-old men, undergoing a surgical incision ("MAC"). MAC of Strong Inhaled Agents

The PL 206 780 B1 varies significantly. In the case of nitrous oxide, the leading inhaled drug for calming consciousness, the MAC index can only be determined under unusual temperature and pressure conditions, such as in a hyperbaric chamber, where additional doses can be delivered without inducing organ and tissue hypoxia. Research proposes a MAC index of nitrous oxide of 110%. Thus, to induce anesthesia most patients would suffocate. Conversely, the MAC rate of methoxyflurane, an early halogenated ether, is only 0.16%. In the current system of calming consciousness by inhaled agents, nitrous oxide is administered in conjunction with at least 30% oxygen to enable the patient to maintain a sufficient level of oxygen. In the United States of America, the Food and Drug Administration ("FDA") has set the limit for nitrous oxide at 70% in calming devices. For this description, the MAC rate equivalent of 70% nitrous oxide will be used for comparison with other inhalants as shown in Table 2.

Table 2

<td>Bow</td><td>MOTHER*</td><td>Level of sedative administered consciousness</td><td>Equivalent MOTHER</td><td>Inhaled oxygen</td>

<td>Nitrous oxide</td><td> 110,00%</td><td> 70,00%</td><td> 0,636</td><td> 30,00%</td>

<td colspan="5">Existing inhalation drugs</td>

<td>Methoxyflurane</td><td> 0,16%</td><td> 0,11%</td><td></td><td> 99,89%</td>

<td>Halothan</td><td> 0,75%</td><td> 0,48%</td><td></td><td> 99,52%</td>

<td>Isoflurane</td><td> 1,15%</td><td> 0,73%</td><td></td><td> 99,27%</td>

<td>Enfluran</td><td> 1,68%</td><td> 1,07%</td><td></td><td> 99,93%</td>

<td>Sevoflurane</td><td> 2,00%</td><td> 1,27%</td><td></td><td> 99,73%</td>

<td>Desflurane</td><td> 6,00%</td><td> 3,82%</td><td></td><td> 99,18%</td>

* MAC is shown at 100% oxygen for middle aged men. MAC varies with age and individual habits, including alcohol and medication intake

For patients who would benefit from a higher concentration of oxygen, but not limited to those with Coronary Artery Disease CAD, replacement of nitrous oxide with inhaled anesthetics could provide an improvement in myocardial oxygenation.

To give the concentration of an appropriate agent that induces anesthesia but not a loss of alertness (or amnesia or loss of consciousness), an instrument with a precision calibration is required through which the agent can flow with little risk of overdosing or administering a hypoxic mixture (Figure 1) .

In practice, for extracorporeal installations, the device must be cost effective, preferably costing less than anesthetic machines which currently cost $ 100,000 or more. Compared to hypnotic sedatives, barbituts, opioids, and agonist / antagonist agents that can also be used for sedation, the invention offers a faster onset and recovery, and a lower risk of possible overdose. Therefore, the invention comprises an oxygen supply mechanism or an O2 oxygen cylinder (s) and / or an oxygen store manifold ("Source

ABOUT₂") 16 and anesthetic reservoir 12, for example, but not limited to, a cylinder adapted to contain anesthetic.

Further, the invention includes a heating element 14 attached to an anesthetic reservoir, for example, but not limited to, a heating plate connected to an ambient temperature sensor to allow environmental temperature and pressure compensation. The heating of the anesthetic reservoir 12 by the heating element 14 allows the pressure of the anesthetic in the reservoir to be adjusted such that the flow of the anesthetic can be properly regulated despite changing ambient temperature.

The reservoir system includes a selection index system 10 to ensure that only said anesthetic can be introduced into the reservoir and, when filled, can be associated with the delivery system indicated for that anesthetic. Oxygen from the source O₂ 16 passes by

Through a manifold system 22 including a sensitive pressure regulator 18 to either an analog or electronic flow meter 20, where it is mixed in exact proportions with the anesthetic from the reservoir 12 and the dose of the anesthetic is accurately metered to an accuracy of ± 0.1% gas flow or less. While the anesthetic may be transferred directly to the flow meter 20, it may also flow through the manifold 22 to regulate the flow and ensure that, should the oxygen flow be cut off or defined as insufficient, safety devices including, but not limited to, an automatic agent shutoff system. anesthetic, they will react. The oxygen trigger assembly 24 enables the operator to rapidly inflate the patient's lungs and force the residual anesthetic to exhale.

The system is designed such that when trigger assembly 24 is actuated, the flow of pain medication is automatically stopped because trigger assembly 24 is connected to anesthetic reservoir 12 by means of a three-way valve 25 such that when trigger assembly 24 is connected, the reservoir is 12 anesthetic is disconnected and vice versa. The mixing head and / or flow meter assembly allow the user to regulate the flow of anesthetic and its concentration to the limits for sedation of consciousness established by the appropriate competent authority and are sufficiently accurate in calibration to allow the flowing anesthetic to achieve the required level of sedation. Additionally, the adjustable heating element 14 and flow meter 20 may be co-operated with a relationship therebetween to regulate the flow of anesthetic.

As shown in Figs. 2 and 3, an embodiment of the invention is an independent self-contained unit for a doctor's office. Fig. 2 shows heating element 14, mixing head 28, oxygen pressure regulator 42, steam pressure regulator 44, oxygen trigger regulator 46, nasal cannula outlet port 48, inhaler outlet port 50, oxygen pressure sensor 52, vapor pressure sensor 54, optional monitor 56, regulator flow rate 58, anesthetic concentration controller 60, selector switch 62 nasal / shutoff / inhalation outlet and on / off controller 64.

Figure 3 shows an oxygen source 10, an anesthetic reservoir 12, a heating element 14, a mixing head 28, an electrical outlet 30, an additional air cylinder 32, and an electrical conduit 40. These components may be coupled with other components, including, but not limited to, modifying the device to be portable in emergency or military applications, modifying the device for patient controlled analgesia (PCA); attaching a purging unit to recover the exhaled agent and removing it from the environment, enabling or adapting the device to work with systems for continuous observation and recording of physiological body activities, including but not limited to oximetry, ECG, blood pressure, carbon dioxide tracking and depth of consciousness, cooperation in at least one configuration with diagnostic visualization devices, including but not limited to, for nuclear magnetic resonance devices ("MRI's") to enable the administration of a painkiller to a patient who needs sedation or pain relief during visualization with a nuclear magnetic resonance device.

While the preferred embodiments of the invention have been described herein, the invention is not limited thereto. The claims which follow apply to the invention and are intended for describing the invention, but their literal wording should not limit the scope of the invention.