WO1984000894A1

WO1984000894A1 - Programmable drug infusion device

Info

Publication number: WO1984000894A1
Application number: PCT/SE1983/000320
Authority: WO
Inventors: Anders Tamsen
Original assignee: Anders Tamsen
Priority date: 1982-09-10
Filing date: 1983-09-09
Publication date: 1984-03-15
Also published as: IT1169806B; EP0118525A1; AU2030683A; IT8322832A0; SE8205181D0; SE432054B; JPS59501698A

Abstract

Programmable injection and infusion apparatus, comprising a motor-driven syringe connected to an injection needle. This apparatus is characterized by comprising a microprocessor (CPU) for controlling the administration of drugs, a program memory (ROM) for storing the program from which the microprocessor (CPU) featches its instructions, a parameter memory (RAM) for storing of parameters that characterize the desired administration process, and a keyboard (TG) and a display (D) for inputting of the parameters into the parameter memory and display of necessary information.

Description

PROGRAMMABLE DRUG INFUSION DEVICE

The present invention relates to a programmable infusion device for the administration of pharmaceutical drugs. More specifically, the invention consists of an apparatus which makes it possible to, on the one hand, institute controlled drug administration to patients and, on the other hand-, for specific purposes allow the patient to exert an influence on the number of infusions administered to him by patient control over the start function of the device.

The medical background to the present invention is as follows: During the last decades there has been a substantial increase in our knowledge regarding the process of absorption, distribution, metabolism and exertion of drugs from the body. It is now possible to take drug kinetics into account when planning drug treatment. In order to establish a therapeutic blood concentration as quickly as possible and to maintain this concentration for the desired period of treatment, it is often advantageous to give the drug intravenously. Initially, all of the drug is in the blood and the well vascularized tissues. There is a large concentration gradient between the blood and the less vascularized tissues, resulting in a rapid absorption of drug into the tissues. As the drug is absorbed ihto the tissues, the concentration gradient will fall and eventually a dynamic equilibrium state between blood and the tissues arises. Thereafter the drug will be eliminated from the blood and tissues at equal rates due to metabolism and/or excretion.

In connection with intravenous drug administration for prolonged therapy it is therefore preferable to give an initial, large dose in order to saturate the tissue

OMPI depots rapidly. Thereafter the drug should be administered more slowly in order to maintain or only slowly increase the blood and tissue concentrations. This principle has been used for a long period as regards antiarythmic drugs, anticonvulsants and occasionally also antiasthmatic drugs.

The present invention is the first device known to us that can be programmed to give both loading and maintenance infusions automatically without the need for intervention as the switch over from one rate to another is made.

A second theoretical consideration relevant to the present invention is the following: The therapeutic effect of a drug usually varies directly with the alterations in drug concentration in the biophase - that locus in the organism where the drug has its point of action. On the other hand, the concentration in the biophase depends on the blood concentration since the blood is the vehicle of transportation from absorption site to the biophase. Potent drugs often have a narrow therapeutic blood concentration interval. When the drug concentration lies within the limits of this interval the relationship between wanted and unwanted effects is favorable. However, if the blood concentration falls below this level the desired effects may disappear completely, while an increasing number of adverse effects are encountered if the concentration rises substantially above the therapeutic concentration range.

In clinical practice it is seldom possible to measure the blood concentration of drugs other than retrospectively, the therapeutic dose has to be determined from the drug effects obtained. Where it is possible to assess the effect response frequently, it is also possible to let the effect response control the treatment as in a feed¬ back loop: Suboptimal effect leads to an increase in dose whilst unwanted toxic effects lead to a decrease in dose. If this effect response can be measured with sufficient frequency and in a way that is relevant to the objectives of the therapy, it is possible to give an optimal pharmacological therapy.

This principle lies behind a therapeutic strategy which is termed patient-controlled analgesia (PCA). This analgesic regiven implies that patients with acute pain are allowed to self-administer small doses of a potent analgesic intravenously- with the aid of a programmable infusion device. In its simplest form the device is a motor syringe, which can be activated by the patient using a pushbutton switch. The syringe will then issue a preset dose as an intravenous bolus. The total amount of drug available to the patient is limited by the size of the preset dose and the preset minimum time .interval lock. The advantage of PCA over conventional methods of pain control stems from the obvious fact that only the patient himself knows when significant pain is present and, conversely, when pain relief~ is effective PCA is necessitated by the clinically well established fact that pain sensitivity and analgesic drug requirements vary .enormously.

Thus, the patient's own perception of pain and of the effectiveness of the therapy will control drug administration as in a feed-back system, with certain restrictions imposed for reasons of safety.

An overview of marketed technology for PCA shows the following situation:

OM A logic controlled motor syringe, "The Cardiff Palliator", is manufactured by Graseby Dynamics, Bushey, Herts., England. This device is designed for bolus injections only and lacks the features under the claims for the present invention.

Demanalg is a syringe pump controller manufactured by KP Enterprises Ltd, Canada. This device lacks a pump driver mechanism altogether and therefore must be supplemented with a conventional motor syringe or pump.

Finally, Janssen Pharmaceutica, Beerse, Belgium, markets a microprocessor controlled Infusion pump for PCA with that company's own drug "fentanyl". This apparatus operates with bolus doses and background infusions but lacks the flexibility of the present invention and has none of the features under the present claims.

The present invention does not have the limitations of previously known devices but .constitutes a programmable infusion device that is designed to accomplish both interactive, dosi etric and volumetric control over drug administration.

The features that characterize the invention are disclosed in the attached patent claims.

The invention will now be described in detail with reference to the accompanying drawings, on which

Fig. 1 shows a perspective view of a presently preferred embodiment of the programmable infusion apparatus in accordance with the present invention;

Fig.2 shows a perspective view of the drive mechanism in the apparatus; and - -

^• Fig. 3 shows a block diagram of the electronic control circuit of the apparatus .

The programmable infusion apparatus 1 in accordance with the invention comprises a syringe assembly 2 (shown in detail in Fig. 2). The syringe assembly 2 comprises an injection syringe 3. The movable piston of the injection ^• syringe 3 is connected to a. push rod 5, which can be inserted into a co-operating recess 6 in a syringe piston driver 7. Injection syringe 3. is detachably mounted in the assembly 2, which is mounted on a mounting plate 8. The driving mechanism of the syringe piston driver, which is mounted under the mounting plate 8, has a carriage 9 that is connected to the syringe piston driver 7 and moves in a slot provided in mounting plate 8 and upon activation drives piston 4 of syringe 3 the desired distance. Syringe piston driver 7 is connected to carriage 9, which comprises an inner taped hole 10, through which a driving screw 11 extends. Driving screw 11, which is journalled in blocks 12 with ball-bearings, is driven to rotate by the aid of a stepping motor 13 over a gear unit 15 and an intermediate clutch 16. Stepping motor 13 is mounted in a suitable mounting block 14. A more compact version of the syringe assembly shown in Fig. 2 is obtained if screw 11 is reversed so that the stepping motor is located immediately under syringe 3.

Finally the syringe assembly 2 described above is surrounded by a transparent, plastic cover 17 that can be opened for service purposes.

The infusion apparatus 1 in accordance with the present invention further comprises a handle H by the aid of which the patient himself has the means of controlling the injection of the drug in the syringe by pushing a button that is provided on handle H. Furthermore, the

O PI apparatus 1 comprises a display D and a keyboard, which preferably is somewhat tilted in relation to the vertical plane to facilitate input of dosing data.

The keyboard comprises the following keys. The key MODE SEL is used to select a mode of -operation. If, for instance, the key is pushed the interactive mode will be active. The next time the key is pushed the dosimetric mode will be chosen. If the key is pushed once more the volumetric mode will be chosen. Upon pushing the key still another time the apparatus will return to the interactive mode. These three modes will be described in detail below. Furthermore, the keyboard comprises a key ENTER/SHOW, abbreviated to E/S below. With this key and the numeric keys 0 - 9 parameter values relating to dilution, dosing, etc. for all the operating modes of apparatus 1 are entered. When these data have been entered the infusion or injection process is started by pushing the key START. By pushing the key STOP the process is stopped. Furthermore, the keyboard comprises a key[Ϋ] and a key _ by the aid of which the syringe plunger holder can be moved to both of its end positions. If desirable the apparatus 1- can also be provided with a printer (not shown) for registration of essential data, for instance times, doses, etc. The printer preferably is provided under the keyboard. For the operation of this printer the keyboard comprises a key PRINT and a key LINE FEED. In addition to the keys described above the keyboard can also comprise two light emitting diodes 20 indicating which mode (interactive, dosimetric, volumetric) that is active.

The described keyboard is preferably covered by a protective foil of a transparent plastic to protect the keys against moisture and dirt. This foil should be elastic to permit pushing of the keys. Display D is preferably provided above the keyboard and¬ ean in the preferred embodiment display a line consisting of 16 characters.

Above the display an on/off-button 21 is provided. This button is also preferably covered by a protective foil.

The whole apparatus 1 is preferably portable in a handle 22. Furthermore, the apparatus can be mounted on for instance a frame by the aid of a mounting screw 23 that sideways reaches into a vertical slot on the back of the. apparatus (not shown). With this design it is even possible to mount the apparatus directly on a bed post of a hospital bed.

The electronic part of the apparatus 1 will now be described with reference to Fig. 3.

The heart of the system is a microprocessor CPU, for instance of type 8085 from Intel. This processor is controlled by a crystal oscillator K-, with a frequency of for instance 6.144 MHz. The processor is over its bus connected to a ROM memory, for instance an EPROM of type 2716 and containing 8 kbytes. This ROM memory stors the program that controls the apparatus 1. Furthermore, in order to^' store data the processor is connected to a RAM memory, for instance of type 2114 and containing 1 kbyte. The processor is also preferably connected to a real time clock T, which is controlled by a crystal oscillator K2 with a frequency of for instance 32 KHz. This real time clock is used for time measurement in order to guarantee that the proper measures are performed at the right time during the injection or infusion^•process. Real time clock T is preferably driven by accumulators, for instance rechargeable nickel-cadmium-accumulators of 12V. These are automatically loaded while the apparatus 1 is on and then drive clock T even when the power has been turned off. _, ^'

For communication with peripherals the processor CPU is connected to two l/θ-circuits , for instance of type 8155. Of these circuits one is connected to input means while the other is connected to output means. Thus , one i /O- circuit is connected to keyboard TG and to patient handle H. The other l/θ-circuit can for instance be provided to activate different alarm functions A, for instance a stop in the administration from the syringe due to clumping or the like, air in the hose from the syringe, that the accumulator has to be recharged, etc. Furthermore, this circuit controls dif ferent indicators 1/ for instance lamps, light emitting diodes and an acoustical alarm. If the apparatus 1 is provided with a printer this can also be controlled by said l/θ-circuit. Suitable printers are a "Micro Dot Printer" from the firm Epson that prints 16 characters per row in a character matrix of 5 . 7 points .

The processor CPU is furthermore over a buffer B, for instance of type 74 LS 241, connected to display D, which for instance can comprise four elements of type DL-2416 each consisting of 4 characters , that is a total of 16 characters.

In order to control stepping motor 13 the processor CPU is also over a current regulator connected to said stepping motor. Stepping motor 13 and this current regulator are in Fig. 3 des ignated with the common designation M.

Below the operation of the apparatus 1 in its three modes of operation (interactive, dosimetric, volumetric) will now be described. When the apparatus 1 is turned on by pushing button 21 the apparatus can be driven in three modes depending on the setting of the key MODE SEL. In the following discussion it is assumed that this key has been operated in such a way that the lamp 20 indicating volumetric mode is activated. The apparatus will now on display D ask for the infusion rate (ml per hour) and thereafter for the total volume (ml). After entering each of these parameters with the numerical keys 0 - 9 the key marked

E/S is pushed. This will enter the value in question into the RAM memory. As regards the parameter total volume there are two possibilities. Either a value specifying the total volume is entered, . which means that during the subsequent program execution the syringe will be controlled until this volume has been consumed. The other alternative is to ■ enter no value but to indicate an unspecified volume by directly pushing the key E/S. In this case the administration will progress with the specified rate until the program is stopped manually or the syringe is empty.

When the parameters for the. volumetric mode have been entered the display will show READY. _ The apparatus is now ready to execute the program stored in the ROM memory. The execution is started by pushing the START-key.

If desirable it is possible by pushing the E/S-key either before pushing the START-key or during program execution to examine the values of the inputted parameters or the volume that has been accumulated in the patient. Thus, the key E/S has a double-function. The first function is to input (Enter) the keyed-in values in the RAM memory, while the second function is to display (Show) the values of the parameters and relevant data that presently are stored in the RAM memory. During this display (Show) it is also possible to change the values of the parameters stored in the RAM memory by keying- in new values. Thus, if it is desirable to change the parameter that presently is displayed on display D one keys in a new value with keys 0 - 9 and thereafter pushes the E/S-key. Thereby the new value will replace the old value and subsequently the next parameter will be displayed on display D. What has been said above regarding the E/S-key is true in volumetric, dosimetric as well as interactive mode.

By combining ENTER and SHOW in the above way an essential simplification is obtained both as regards the programming procedure and checking the . programmed data settings.

In the dosimetric mode values relating to the parameters concentration, infusion rate and dose are entered by operation of the numeric keys 0 - 9 and the E/S-key in the same way as in the volumetric mode.. If dose = 0 is keyed in (by pushing the key E/S without a preceding input of any value) the apparatus is ready (READY) for program execution. In this case the administration will proceed with the entered rate and concentration after pushing the START-key. If a dose parameter which is not zero is entered it is also possible to set a second dose with a different infusion rate to follow after the first dose. It is then possible to give the patient an initial, rather high dose during a certain time period and thereafter a second dose by a slower infusion rate during a second time period. The second dose and rate are optional, and can be by-passed by entering the value 0 in response to the display question "2. RATE?".^'

In the interactive mode values relating to the parameters concentration, amount of drug to be infused over a certain time period, for instance one minute, and optionally a minimum time between doses and also optionally a second dose are inputted by operation of the numeric keys 0 - 9 and the E/S-key in the same way as described above. By entering a minimum time interval between injections it is possible to let the patient himself start up the administration by pushing the button in handle H when the patient so wishes. The minimum time interval prevents the patient from taking too frequent doses. In interactive mode the program execution is started either by pushing the START-key or by pushing the button in handle H.

Thus, it can be seen that in each mode of operation answers to a specific set of questions are needed to make the apparatus operational. For -each question displayed, the answer is entered from the numerical keyboard and entered into the computer by pressing the E/S-key.

Below are listed examples of specific questions in each mode. Some of the questions pertain to optional settings which can be left out simply by bypassing the question with the E/S-key.

OMPI DISPLAY EXPLANATION

Interactive mode

CONC /ml concentration of drug (amount per ml)

BOLUS /l min ■ amount of drug to be infused over 1 minute

TIME LOCK min (optional) minimum time between doses (0 - 99 min)

2. DOSE /l h — (optinoal) amount of drug to be infused ofer 1 hour following the bolus dose.

Dosimetric mode

CONC /ml concentration of drug (amount per ml)

1. RATE ml/h — infusion rate (initial rate) 1. DOSE (optional) amount of drug to be infused by the above rate (initial dose)

2. RATE ml/h (optional) infusion rate following the termination the initial dose

2. DOSE (optional) amount of drug to be infused by the above rate (terminal dose)

Volumetric mode

INFUSION RATE ml/h — rate of infusion (0.1 - 99.9 ml per hour) :

FINAL VOL ml (optional) volume to be infused

OMPI From the above specification it^* can be seen that the apparatus in accordance with the present invention is very flexible and can be adjusted to different demands by simple entering of parameters. Thus, the apparatus can give both single injections over short time periods and/or slow injections over long time periods

(infusions). Since the apparatus in accordance with the invention can give injections and/or infusions of predetermined amounts of drugs with a predetermined rate it is possible to utilize pharmacokinetic principles in quite a different way from what has hitherto been possible in treatment of a number of disease states, such as epileptic seizures, cardiac arythmias, postoperative pain, asthma, etc. By a simple programming procedure the equipment can be made to give both a loading dose as well as a maintenance dose that maintains the blood concentration on a constant level. The equipment can be activated from a remote location by a simple pushbutton or the like. Thus, the apparatus in accordance with the present invention can be used in the following ways.

A pre-set dose of for instance 1 - 99 mg can be given after reception of a remote signal (for instance when the patient pushes a handle button).

The dose can be given with any chosen injection rate, for instance 0.1 - 99.9 ml per hour.

The volume that is to be injected can be computed from information regarding dilution of the drug and the desired dosis. ^*

An additional pre-set dose can be given in addition to the first dose by another, slower injection rate. This second injection (called "infusion") follows immediately after the first dose and its injection rate can be chosen independently of the injection rate of the first dose. The infus ion can be given with any chos en rate, for instance 0. 1 - 99.9 ml per hour .

An acoustic alarm is provided in case a pre-set dose is exceeded. Furthermore, an acoustic alarm is provided for an emptied syringe.

The piston of the syringe can be moved fast forward or reverse with the aid of special control keys ^*tj |_ΨJ .

The apparatus can be pre— set with a time limit against too frequent dos es . This is set to 0 - 99 minutes and operates in such a way that this time limit is only influences by the f irst rapid bolus dose but not the second, slow infusion dose.

An optical signal can be provided on the apparatus and on the. possible remote alarm, indicating that the dose has been administered and when the apparatus can be made to administer another bolus dose.

The printer unit provided in the apparatus will register ^' for instance each given dose and the time and s ize of the dose.

If desired an optical sensor . for an optional valve device can be provided. When the valve is properly pos itioned inside the sensor the apparatus can be set to deliver volumes exceeding the internal volume of the syringe. As the syringe is emptied, the drive mechanism will then automatically reverse and aspirate fluid from a container attached to a s ide port 24 of the valve 25. In another embodiment of the invention the syringe can be made with a one-way valve and with a hol low piston provided with another one-way valve at one end thereof . It is then

OMPI possible to connect the container directly with the syringe piston. In this case the sensor can also be mounted at the top of the syringe drive mechanism.

Preferably, cover 17 is provided with a mechanical and electronic lock. The mechanical lock will prevent access to the syringe during operation of the apparatus. The electronic lock will prevent manipulation of the keyboard by deactivation of its keys.

The apparatus in accordance with the invention is very flexible and makes possible treatment with' a number of different drugs in accordance with the latest pharmacokinetic principles and can be made to operate both independently as well as triggered by the patient himself. The apparatus should be especially useful for intensive care units in hospitals. It should also be useful on adult and pediatric wards for treatment of asthma, cardiac arythmias, diabetic ckoma and several other emergency states in addition to acute pain states.

Claims

1. Programmable injection and infusion apparatus, comprising a motor-driven syringe connected to an injection needle, ch a r a c t e r i z e d in a micro¬ processor (CPU) for controlling of the drug administration, a program memory (ROM) for storing the program from which the microprocessor (CPU) fetches its instructions, a parameter memory (RAM) for storing parameters characterizing the desired administration process, and a keyboard (TG) and a display (D) for entering necessary parameters into the parameter memory and displaying necessary information, respectively.

2. The apparatus of claim 1, c h a r a c t e r i z e d in that three different modes of operation (interactive, dosimetric,. volumetric) are stored as program pieces in said program memory (ROM), and that the desired mode of operation is selected by pressing a key (MODE SEL) on- the key board.

3. The apparatus of claim 2, c h a r a c t e r i z e d in that each mode of operation is specified by specifying the desired parameters in accordance with a sequence of questions stored in the program memory and shown on the display, which questions are answered from the keyboard.

4. The apparatus of claim 3, c h a r a c t e r i z e d in that the keyboard comprises a key (ENTER/SHOW) having on one hand the function to store entered parameters in the parameter memory when pushed and thereby stepping forward in the program, and on the other hand has the function to show the values of the parameters in the parameter memory one after the other on the display (D) when pushed without a preceding input of any parameter values .

5. The apparatus in accordance with claim 3, c h a r a c t e r i z e d in a mechanical and electronic lock that locks a transparent cover which covers the syringe and which deactivates the keyboard in such a way that only a display function and a stop function^' can be activated from the keyboard when the lock is locked.

6. The apparatus of claim 3, c h a r a c t e r i z e d in an optical sensor for detection of a one-way valve, whereby doses greater. than the volume of the syringe can be administrated by filling the syringe with drugs from a container through an aspiration movement when the syringe has been empted, and an optical sensor for detection of air bubbles.

7. The apparatus of claim 3, c h a r a c t e r i z e d by having a printer for registration of necessary dose and time data.

8. The apparatus of claim 3, c h a r a c t e r i z e d in an acoustical alarm indicating apparatus failure, for instance infusion, line, obstruction, empty syringe, air bubbles, low battery charge, etc.