Cardiovascular disease is the leading cause of death in the United States, and approximately one million people die of it annually. For this reason, contrast angiography is today an integral part in the diagnosis and treatment of cardiovascular disease. In the year 2000, U.S. cardiologists performed approximately two million diagnostic and therapeutic angiographic procedures according to data from Health Resources Utilization Branch of Center for Disease Control and Prevention/National Center for Health Statistics.
Also, despite recent advances in non-invasive imaging techniques, angiography remains the gold standard for diagnosis of vascular disease. Angiography as a technique involves the placement of a catheter (a thin plastic tube) into a major blood vessel or the heart (catheterization) through another artery or vein found either in the groin or arm (typically the femoral or radial artery respectively). During angiography, the proximal end of the catheter is connected to either a hand-held syringe or an electrically powered injector; and a radiopaque dye (a contrast medium containing iodine) is injected through the catheter in order to make the blood vessels visible on x-ray images (angiogram) and/or fluoroscopic pictures (or moving x-rays).
Throughout the procedure, injections of contrast medium are repeatedly made in varying volumes (usually 1 to 10 cc/sec) and with varying durations of injection (typically 1 to 5 seconds). The resulting angiogram is obtained solely for diagnostic purposes; and is routinely used during a subsequently performed interventional procedure such as angioplasty or stenting—where a balloon is inserted into the blood vessels and inflated to open a stenosis caused by atherosclerotic plaque buildup. Frequent intermittent injections of the radiopaque contrast medium is required during each of these diagnostic and interventional procedures to obtain various views of the blood vessels and for optimal positioning of catheters, guidewires, balloons and stents at the targeted vessels. Traditionally also, coronary angiography has been performed using a disposable manual syringe attached to a manifold system.
The Commonly Occurring Complications of Catheterization:
Once the dye injection procedures are complete, the catheter is slowly and carefully removed from the blood vessel (or heart); and manual compression is applied over the puncture site for 15 minutes, followed by bed rest for 4-6 hours, in order for blood clotting to take place and the arterial or veinal puncture to reseal itself (hemostasis).
Sometimes however, serious complications take place and occur even during simple diagnostic catheterization procedures. Such major complications include (1) formation of pseudoaneurysm (i.e., formation of a cavity of blood around the artery by continuous leakage of blood through the hole due to failure of spontaneous closure of the puncture hole); (2) creation of a hematoma or pseudoaneurysm formation large enough to compress the adjacent nerves causes paralysis of the leg; and (3) continuous bleeding into the free body spaces (such as the pelvic cavity, abdominal cavity or retroperitoneal space) which can cause rapid loss of blood and subsequent hypotensive shock.
These kinds of major complications are known to be closely related to the size of the puncture hole on the access blood vessels, i.e. the size of the catheters. Therefore, interventional procedures, such as coronary angioplasty, are far more likely to produce major complications at the catheter insertion site of the arteries than diagnostic catheterization procedures, owing to the use of larger sized catheters. These complications occur even after a long duration of direct compression time (10 to 60 minutes) upon removal of the catheter from the patient. Also, a long manual compression time period is inconvenient for the attending physicians and, equally important, can be very painful to the patient. For these reasons, the use of larger sized catheters for coronary angiography (CA) has been generally and routinely discouraged.
The recent technological advances in the manufacture of catheters having a smaller outer diameter and a larger inner diameter (such as 4 French diagnostic catheters) and the availability of lower profile balloons and stents have made it feasible to perform coronary procedures with smaller sized guiding catheters. In interventional procedures, the use of smaller sized guiding catheters (for example, 6 Fr) helps avoid the problems and complications described above with respect to large catheters, and most notably reduces the incidence of access site complications. [See for example: Pande et al., “Coronary Angiography With Four French Catheters”, Am J Cardiol, 1992, 70 (11):1085-1086; Nasser et al., “Peripheral Vascular Complications Following Coronary Interventional Procedures”, Clin Cardiol, 1995; 18:609-614; Muller et al., Am J Cardiol 1992; 69:63-68; Davis et al., Heart Lung, 1997, 26:119-127; and Metz et al., Am Heart J, 1997, 134:131-137].
Conventional Manually Operated Syringes:
The conventional, manually operated syringe (typically 10-12 cc in fluid containing capacity) is in common use and has been adequate for injection of radiopaque contrast medium through the relatively large-bore catheters which range in size from about 6-7 French for diagnostic procedures or from 7-8 French guiding catheter for interventional procedures. The manual syringes conventionally used for the injection of contrast medium are typically made of various plastics such as polypropylene and polycarbonate. These syringes include a barrel having a liquid discharge opening at one end, and a nozzle through which the contrast medium of choice is ejected. The act of fluid ejection is effected by means of a plunger which has a displaceable piston at the distal end of the barrel; and the body of the syringe has either a ring or a grip at the proximal end which can be held by the user's index and third fingers. The displaceable piston can then be actuated by the user's thumb in a forward and backward motion made in response to the coordinated movement of the operator's hand and fingers at the proximal end of the barrel.
As is apparent, an adequate pressure force is needed to operate a syringe. A non-human driving mechanism, such as an electrical motor, provides this quantity of pressure force in automated syringes. Many syringes, however, are operated using only the manual force generated by a human hand. Although typically less sophisticated than automated syringes, manually operated syringes continue to be widely used because they are inexpensive; are easy to use; are disposable; offer excellent operator control; and do not require complex and bulky driving mechanisms.
Pressure Force Problems of Manual Syringes:
One of the disadvantages in performing angiography using a smaller sized diagnostic catheter (such as a 4 to 5 French catheter) and a guiding catheter (such as a 6 French catheter) coaxially and for internally carrying hardware (such as balloon catheter or stent to be positioned inside a blood vessel) is that much higher injection pressures are required to introduce adequate quantities of radiopaque fluids and to produce adequate opacification of coronary flow. For example, force pressures in the range of 300 to 500 psi are needed for delivery of x-ray dye at a rate of 3 to 5 cc/sec for small sized catheters in comparison to a pressure force of less than 150 psi with larger sized catheters. [See Danzi et al., “A Randomized Comparison Of The Use Of 4 And 6 French Diagnostic Catheters And The Limits Of Downsizing”, Int J Cardiol, 2001, 80(1):5-6; Resar et al, “Percutaneous Transluminal Coronary Angioplasty Through 6 F Diagnostic Catheters: A Feasibility Study”, Am Heart J, 1993, 125(6):1591-1596; Saito et al, “Evaluation Of New 4 French Catheters By Comparison To 6 French Coronary Artery Images”, J Invasive Cardiol 1999, 11(1):13-20; Dodge et al, “Coronary Artery Injection Technique: A Quantitative In Vivo Investigation Using Modern Catheters”, Cathet Cardiovasc Dian, 1998, 44 (1):34-39)].
This high force pressure requirement makes the use of manual syringes (previously used in percutaneous coronary procedures with small sized catheters) functionally inadequate—since, with a 10-ml manual syringe, an operator can generally produce a hand pressure force only in the range of about 20-130 psi. The maximum pressure force which can be manually exerted is only about 130 psi; and is thus generally inadequate for injections through small sized catheters. Additionally, with any conventional manual syringe, the amount of pressure force which can be delivered by hand is inconsistent and will vary from person to person. Accordingly therefore, the injection flow rate and the fluid volume able to be delivered is likely to be very variable and the hand-generated pressure force will be somewhat unpredictable. Such undesirable conditions are only further exacerbated by the use of smaller sized catheters. [See for example, Brown et al., “Limitation In Use Of Five French Coronary Catheters”, Int J Card Imaging, 1991, 7(1):43-45; Franken G. and E. Zeitler, Cardiovasc Radiol, 1978, 1:21-26; Ireland et al., Cathet Cardiovasc Diagn, 1989, 16:199-201; Saito et al., “Evaluation Of New 4 French Catheters By Comparison To 6 French Coronary Artery Images”, J Invasive Cardiol 1999, 11(1):13-20; Dodge et al., “Coronary Artery Injection Technique: A Quantitative In Vivo Investigation Using Modern Catheters”, Cathet Cardiovasc Dian, 1998, 44 (1):34-39].
These long-recognized limitations of the conventional manual syringe can and often do result in suboptimal quality of angiographic studies and frequently necessitate repeat injections—which, in turn, lead to toxic effects from contrast overdose such as renal or heart failure [McCullough et al., “Acute Renal Failure After Coronary Intervention: Incidence, Risk Factors, And Relationship To Mortality”, Am J Med, 1997, 103:368-375].
As a consequence, there have been considerable efforts to make the conventional manual syringe more powerful by making various modifications in the shape and the ergonomics of the syringe, such as those disclosed by U.S. Pat. Nos. 4,925,449 and 6,616,634 respectively. Nevertheless, the various modifications developed to date for manual syringes have not been performance sufficient; and the modified syringes' injection flow rates and fluid volume capacities remain functionally inadequate and continue to cause suboptimal imaging results.
In addition, there have been other developments directed towards mechanisms for increasing the actuation force on the manual syringe by utilizing either internal or external springs to displace the plunger of the syringe, such as are described by U.S. Pat. Nos. 5,318,539 and 5,951,517 respectively. However, it remains very difficult to achieve the requisite injection pressure either reliably or in sufficiently high force in order to perform angiography using these spring-based actuated syringes.
Mechanical Power Injectors:
In the past, mechanical power injectors capable of providing higher-pressure fluid delivery have been adapted and used to overcome the disadvantages of the manual syringe during diagnostic and interventional coronary angiographic procedures. This has been especially true when the quality of imaging is hampered by the small size of the diagnostic catheter—as for patients with high coronary resistance or flows (due to hypertension, left ventricular hypertrophy, aortic regurgitation, or cardiomyopathy); and when there are interventional devices within the lumen of the guide catheter [See for example: Angelini P., “Use Of Mechanical Injectors During Percutaneous Transluminal Coronary Angioplasty (PTCA)”, Cathet Cardiovasc Diagn, 1989, 16:193-194; and Goss et al., “Power Injection Of Contrast Media During Percutaneous Transluminal Coronary Artery Angioplasty”, Cathet Cardiovasc Diagn, 1989, 16:195-198]. Nevertheless, mechanical power injectors have not been accepted by the majority of cardiologists because they were found to be cumbersome; to be expensive; and to have a number of other problems which are discussed in greater detail below.
In general, there are three types of mechanical power injectors: electric, hydraulic, or pneumatic (see Abram's Angiography, “Basic Types of Pressure Injectors”, pages 171-175, 4th edition, Little, Brown Company]. Each of these types of power injectors can provide the extra volume and power (between 100-1200 psi.) when a large syringe (65 to 130 ccs) is loaded into the power drive mechanism. Currently, electrically motorized injection devices are the most widely used and constitute a syringe connected to a linear actuator [as described by U.S. Pat. Nos. 4,006,736; 4,854,324; 5,269,762 and 5,322,511 respectively]. When used, the linear actuator is connected to a motor, which is controlled electronically. The operator determines via the electronic control a fixed volume of contrast material to be injected at a fixed rate of injection. The fixed rate of injection provides a specified initial rate of flow increase and a final rate of injection until the entire volume of fluid material (contrast media) is injected.
Mechanical power injectors can deliver a precise volume of contrast medium at higher pressure, resulting in more consistent coronary opacification. Enhanced visualization through power injection may be particularly beneficial in patients in whom opacification by manual syringe injection is difficult, such as patients with hyperdynamic or with high flow states (as may occur with aortic stenosis/insufficiency or hypertensive cardiovascular disease) and those patients with large caliber or dilated atherosclerotic vessels. Power injectors potentially can also enhance visualization when using smaller profile diagnostic and guiding catheters; and is especially important in interventions employing 5 to 6 Fr guides, in which visualizing coronary lesions through its internal annular space around indwelling balloon catheters and stent delivery systems by manual injection may be limited. [See for example: Goldstein et al, “A Novel Automated Injection System For Angiography”, J Invas Cardiol, 2001,14:147-152].
It will be noted and appreciated, however, that these mechanical power injector devices also have some serious deficiencies: There is no interactive control between the operator and machine, except to start or stop the injection. Thus, any change in flow rate can occur only by stopping the machine completely and resetting the operating parameters. This lack of ability to vary the flow rate of fluid injection during the course of the procedure results in a suboptimal quality for angiographic studies because the optimal flow rate of injections typically varies considerably between different patients and different phases of cardiac cycles.
In the cardiovascular system, the rate and volume of contrast medium injection is dependent on the size of patient, the target organ and the blood vessels, as well as upon hemodynamic factors such as blood flow rate and pressure within the chamber or blood vessel being evaluated. In most cases, these parameters/factors are not known precisely and can change rapidly as the patient's condition changes in response to the variables of stress, different drugs, personal illness, or individual physiology. Consequently, the initial injection of contrast medium may be insufficient in flow rate to outline the structure on x-ray imaging, thereby necessitating another injection of medium—which can lead to toxic effects from overdose of contrast medium such as kidney or heart failure. Conversely, an excessive injection rate may injure the blood vessel or heart being evaluated, and also cause the catheter to become internally displaced (from the jet of contrast material exiting the catheter tip)—thereby resulting in severe adverse health outcomes such as life-threatening vascular or cardiac injuries (exemplified by dissection, or perforation of the artery, or cardiac arrhythmia).
In addition, some cardiologist have tried to use mechanical power injectors which were remotely activated using a hand or foot switch [See for example: Goss et al., “Power Injection Of Contrast Media During Percutaneous Transluminal Coronary Angioplasty”, Cathet Cardiovasc Diagn 1989, 16:195-198; and Angelini, P., “Use Of Mechanical Injectors During Percutaneous Transluminal Coronary Angioplasty”, Cathet Cardiovasc Diagn, 1989, 16:193-194]. Others have used a modified hand injector for specific application in percutaneous coronary intervention [See for example: Sanders et al., “Coronary Power Injection During Percutaneous Transluminal Coronary Angioplasty”, Cathet Cardiovasc Diagn, 1984, 10:603-605; Ireland et al., “Safety And Convenience Of A Mechanical Injector Pump For Coronary Angiography”, Cathet Cardiovasc Diagn, 1989, 16(3):199-201; and Weiner, R. I. and Maranhao V., “A Modified Hand Injector For Percutaneous Transluminal Coronary Angioplasty”, Cathet Cardiovasc Diagn, 1987, 13:145-147]. All these attempts to employ mechanical power injectors were found to be cumbersome and clinically unsatisfactory.
More recently, a manually-operated, mechanically-assisted power syringe has been developed [as is disclosed by U.S. Pat. Nos. 5,830,194 and 6,030,368], wherein a syringe is assisted by an attached levered apparatus providing force amplification to the injection. Although providing a mechanically assisted advantage, a major disadvantage of this type of power syringe is its relatively large size and its complete immobility (due to its being fixed on the catheterization procedure table). Another disadvantage of this type of power syringe is the need for a second operator who must press down on a lever in order to actuate the injection action, while a first operator must hold the catheter in the desired position. Furthermore, there is no sense of fine control in either flow rate and/or fluid volume during the activation of lever and the actual injection of contrast medium into the catheter.
For these reasons, despite their having potential advantages, mechanical power injectors are infrequently used for coronary angiography. Operator's resistance to power injection of coronary arteries is based in part on the limitations of presently available motorized injectors, which do not allow the physician immediate control to vary the flow rate during power injection; and often result in insufficient contrast injection or excessive flow [see Goldstein et al, “A Novel Automated Injection System For Angiography”, J Invas Cardiol, 2001, 14:147-152].
Other Relevant Developments:
1. ACIST Medical Systems (Eden Prairie, Minn., USA) has introduced a software-controlled variable rate syringe injector connected to an automated manifold without stopcocks. The ACIST Injection System (as disclosed by U.S. Pat. Nos. 6,221,045 and 6,344,030 respectively) is composed of four integrated components that include a software-controlled syringe injector, a disposable automated manifold without stopcocks, a disposable hand controller, and a touch screen control panel.
The ACIST Medical Systems injection system is mounted on its own wheeled stand; but is optimally utilized when firmly attached (immobilized) to the catheterization table. The touch screen control panel can be mounted on the syringe injector, but alternatively can be separately attached to the catheterization table and positioned in proximity to the operator. The disposable components (syringe body, manifold, check valves, and tubing) are provided in a separate sterile kit. The system setup is directed in a step-by-step maneuver using touch screen monitor prompts. After the initial setup is completed, the operator calibrates the hand controller and selects the injection program. The system is then ready to be connected to the angiographic catheter for angiography [see Goldstein et al, “A Novel Automated Injection System For Angiography”, J. Invas Cardiol, 2001, 14:147-152].
Unfortunately, the ACIST injection system has a number of major disadvantages: The system is cumbersome to setup and load; and it requires additional disposable products to accommodate the complex repetitive steps and multiple connections. Moreover, the system has a very high cost for acquiring the essential equipment, for its operation and maintenance, and for the disposable supplies required for its continued use. Additional disadvantages are the injector's large size, its limited portability and its complexity of operation—all of which tend to lengthen the procedure time and to waste other resources such as staffing and facility. For these reasons, such software controlled injector systems for coronary angiography are not widely used; and presently, most laboratories employ only the manual syringe system for selective coronary angiography.
2. Another approach has been to substitute an electromechanical injector as an improvement upon manually-operated syringes. Examples of such injectors are described in U.S. Pat. Nos. 6,221,045; 5,383,858; 4,854,324; 4,677,980; 5,322,511; and 4,006,736 respectively. These electromechanical injectors are made in the form of a conventional syringe, with the added feature of a force amplification system to overcome the limitations of the conventional manual syringe and power injectors.
3. Some earlier innovations were made in the form of a conventional syringe equipped with force amplications using a liquid gas such as carbon dioxide. In 1956, Gidlund first described a compressed-air injector with a stainless steel syringe that could be placed in a vertical position [Gidlund A., “Development Of Apparatus And Methods For Roentgen Studies In Haemodynamics”, Acta Radiol (Stockh), 1956, 130 (suppl):1]. The vertical position facilitated the addition of a valve for air removal at the top of the syringe.
Later, in 1960, Amplatz described a pneumatic power injector for injection of contrast medium powered by carbon dioxide cartridges. [Amplatz K., “A Vascular Injector With Program Selector”, Radiology, 1960, 75:955]. The Amplatz pneumatic power injectors used compressed gases to transmit pressure to a barrel, which were connected to the injector syringe. The device operates under basic pneumatic and hydraulic principles [see Abram's Angiography, “Basic Types Of Pressure Injectors”, 4th edition, Little, Brown & Company, pages 171-175]. However, a bulky and heavy pressure regulator was one of the essential parts of these injectors. Each pneumatic power injector weighed more than 5 kg and were not practical for use in any clinical setting.
4. Another approach is the Bourdon device (as disclosed by U.S. Pat. No. 4,323,066; the text of which is expressly incorporated herein by reference). The Bourdon device is a modified syringe that allows the operator to regulate the speed at which injection occurs and can alter the flow rate of injected liquid. Functionally, a gas from a pressurized-gas source flows continuously through the device and exits freely into the atmosphere, thereby wasting large quantities of gas needlessly. Also, the amount of gas required for a single injection procedure is much larger than can be stored in a miniature cylinder; and thus a remote source of pressurized-gas is always required in each instance of use.
5. Still another variation is the Smith et al. syringe device (as disclosed by U.S. Pat. No. 4,861,340; the text of which is expressly incorporated herein by reference). The Smith et al. syringe is intended to provide control of contrast flow rate (as in the Bourdon syringe device described above), but has a configuration that addresses the gas-wasting problem. The syringe is designed for injecting contrast media into the vascular system during angiography; and is composed of two main parts: the injection syringe itself and the gas system. The function of the gas system is to deliver regulated pressurized CO2 gas to the injection syringe to assist the forward motion of the piston. The pressurized gas is contained in a CO2 gas tank and is regulated by the operator. This required pressure regulation allows the operator to adjust the pressure to a desired setting.
It will be noted that pressurized gas is conserved in the Smith et al. syringe design by the use of a configured portal system, which allows gas flow from the pressurized-gas source to occur only during contrast medium injection. This, however, markedly reduces the operator's sensation of flow rate control, which is very critical in practice of cardiac catheterization, in terms of both safety and efficacy.
It will be appreciated that within the Smith et al. system design, the marked reduction in the operator's sensation of flow rate control is caused directly by an undesirably large “dead band”. From the operator's perspective, a “dead band” is the difference between the relative motion of the operator's fingers and the displacement of the piston in the syringe barrel. The mechanical distances required to separate axial source ports using O-rings thus dictates the size of the dead band. Increasing or decreasing the contrast flow rate occurs in a step-wise manner as the operator-applied force is varied; and the dead band variances between the steps and the limited number of steps in a practical device markedly reduce the operator's sensation of flow rate control as compared with a conventional manual syringe. The Smith et al. device also requires a pressure regulator, which makes the system cumbersome and difficult to handle. For these reasons, the Smith et al. device was deemed to be clinically impractical and was unfavorably received by medical practitioners shortly after its introduction [see Pande et al., “Randomized Evaluation Of 5 French Catheters For Coronary Angiography With Or Without The CO2 Powered Hercules Syringe”, J Invas Cardiol, 1992, 4:136-138].
Clearly therefore, there remains a well recognized and long standing need for a power-assisted syringe that can overcome the various problems associated with the injection of contrast medium in the different angiographical procedures. Accordingly, were a syringe apparatus capable of delivering contrast fluid on-demand to a patient to be developed which permits the operator to adjust and increase appropriately the force applied to the syringe and provides feedback parameters with tactile and visual components by which to control the flow rate and volume of the fluid in real time, such an improvement would be seen as having substantive medical benefit and be recognized as a major advance and improvement within the technical field.