Patent Description:
Diabetes is a metabolic disorder that afflicts tens of millions of people throughout the world. Diabetes results from the inability of the body to properly utilize and metabolize carbohydrates, particularly glucose. Normally, the finely tuned balance between glucose in the blood and glucose in bodily tissue cells is maintained by insulin, a hormone produced by the pancreas which controls, among other things, the transfer of glucose from blood into body tissue cells. Upsetting this balance causes many complications and pathologies including heart disease, coronary and peripheral artery sclerosis, peripheral neuropathies, retinal damage, cataracts, hypertension, coma, and death from hypoglycemic shock.

In patients with insulin-dependent diabetes the symptoms of the disease can be controlled by administering additional insulin (or other agents that have similar effects) by injection or by external or implantable insulin pumps. The correct insulin dosage is a function of the level of glucose in the blood. Ideally, insulin administration should be continuously readjusted in response to changes in blood glucose level. In diabetes management, insulin enables the uptake of glucose by the body's cells from the blood. Glucagon acts opposite to insulin and causes the liver to release glucose into the blood stream. The basal rate is the rate of continuous supply of insulin provided by an insulin delivery device (pump). The bolus is the specific amount of insulin that is given to raise blood concentration of the insulin to an effective level when needed (as opposed to continuous).

Presently, systems are available for continuously monitoring blood glucose levels by inserting a glucose sensitive probe into the patient's subcutaneous layer or vascular compartment or, alternately, by periodically drawing blood from a vascular access point to a sensor. Such probes measure various properties of blood or other tissues including optical absorption, electrochemical potential, and enzymatic products. The output of such sensors can be communicated to a hand held device that is used to calculate an appropriate dosage of insulin to be delivered into the blood stream in view of several factors such as a patient's present glucose level and rate of change, insulin administration rate, carbohydrates consumed or to be consumed, steroid usage, renal and hepatic status and exercise. These calculations can then be used to control a pump that delivers the insulin either at a controlled basal rate or as a periodic or one-time bolus. When provided as an integrated system the continuous glucose monitor, controller, and pump work together to provide continuous glucose monitoring and insulin pump control.

Such systems at present require intervention by a patient or clinician to calculate and control the amount of insulin to be delivered. However, there may be periods when the patient is not able to adjust insulin delivery. For example, when the patient is sleeping he or she cannot intervene in the delivery of insulin yet control of a patient's glucose level is still necessary. A system capable of integrating and automating the functions of glucose monitoring and controlled insulin delivery would be useful in assisting patients in maintaining their glucose levels, especially during periods of the day when they are unable to intervene.

Alternately, in the hospital environment an optimal glucose management system involves frequent adjustments to insulin delivery rates in response to the variables previously mentioned. However, constant intervention on the part of the clinician is burdensome and most glucose management systems are designed to maximize the time interval between insulin updates. A system capable of safely automating low-risk decisions for insulin delivery would be useful in improving patient insulin therapy and supporting clinician workflow.

Since the year <NUM> at least five continuous or semi-continuous glucose monitors have received regulatory approval. In combination with continuous subcutaneous insulin infusion (CSII), these devices have promoted research toward closed loop systems which deliver insulin according to real time needs as opposed to open loop systems which lack the real time responsiveness to changing glucose levels. A closed loop system, also called the artificial pancreas, consists of three components: a glucose monitoring device such as a continuous glucose monitor (CGM) that measures subcutaneous glucose concentration (SC); a titrating algorithm to compute the amount of analyte such as insulin and/or glucagon to be delivered; and one or more analyte pumps to deliver computed analyte doses subcutaneously. Several prototype systems have been developed, tested, and reported based on evaluation in clinical and simulated home settings. This concerted effort promises accelerated progress toward home testing of closed loop systems.

Similarly, closed loop systems have been proposed for the hospital setting and investigational devices have been developed and tested, primarily through animal studies. In addition, several manufacturers are either in the process of developing or have submitted to the FDA automated glucose measurement systems designed for inpatient testing. Such systems will accelerate the development of fully automated systems for inpatient glucose management.

The primary problem with closed loop control or full automation of insulin therapy is that a computerized system makes decisions that may be high risk in terms of potential consequences if the patient's condition changes or differs from the assumptions behind the computerized decision system. As a result of the automation these high risk decisions are not uncovered until the risk is realized and the patient displays an unacceptable medical condition. Second, in the event of a device failure or medication management system or MMS failure, action is required by the automated system despite the potential lack of information. Third, in scenarios in which frequent glucose measurements are automatically collected but automation is not desired, it is undesirable to update the infusion at the same frequency as glucose measurements are collected. Fourth, when user intervention is required it may be undesirable or difficult for a clinician to respond at the bedside. For example, if the patient is in an isolation room but is observable the clinician may desire to update the infusion rate without entering the room.

<CIT> discloses a system that monitors a closed loop infusion system and detects communication failures, however does not disclose that the infusion is reverted to a backup infusion rate, and to revert to a different channel of the multi infusion system.

Thus, a principle object of the invention is to provide an improved system for monitoring and delivering medication to a patient that makes risk determinations before providing therapy.

Another object of the invention is to provide a system that minimizes patient risk by mapping device failure, patient state and condition, and uncertainty.

Yet another object of the invention is to provide a system for monitoring and delivering medication to a patient that minimizes the risk to a patient.

Another object of the invention is to provide a system for monitoring and delivering medication that is able to selectively request for a user intervention.

These and other objects, features, or advantages of the invention will become apparent from the specification and claims.

A system for monitoring and delivering medication to a patient and the method of using the same. The system has a controller that has an adjustment or control algorithm and an automation risk monitor that monitors the control algorithm. More specifically, the present invention is directed toward a system and method that monitors the risk to a patient of an automated therapy decision and allows a clinician to customize rules that determine whether an automated change in therapy is to be allowed or whether user/clinician intervention should be required based upon the risk of automation and the customized rules. Thus, the risk of potential adverse consequences to the patient if the patient's condition changes or differs from the assumptions behind the computerized or automated decision system can be minimized.

A sensor in communication with the controller monitors a medical condition to provide data to a rule based application in the controller. In addition, the rule based application receives data from the closed loop control and compares the data to predetermined medical information to determine the risk to the patient. When the risk is below a predetermined risk threshold, medication or therapy adjustments are allowed to occur in an automated manner according to a closed loop algorithm. Alternatively, when the risk is above the predetermined risk threshold, the controller triggers a request for user intervention or reduces the degree of automated therapy allowed.

A system monitor in communication with the controller monitors conditions and activity of the system and remote system. Upon detection of a system failure the system monitor provides data to the controller to determine whether to adjust treatment, message a clinician, and send an alarm. Similarly, the system monitor tracks network activity to detect network failures or failures of remote systems such as a clinician messaging system. Depending on the conditions presented an alarm system escalates the alarm sent.

<FIG> provides a system <NUM> for monitoring and delivering medication, such as insulin, to a patient <NUM>. The system <NUM> includes a controller <NUM> that utilizes a control algorithm and an automation risk monitor <NUM> all presented in a closed loop. A sensor <NUM> is in communication with the controller <NUM> and monitors a medical condition of the patient <NUM>. A rule based application <NUM> (see <FIG> for example) in the automation risk monitor of the controller <NUM> receives data from the sensor <NUM> and compares the data to predetermined medical information to determine the risk to the patient <NUM> to automate the delivery of medication.

The rule based application <NUM> can be set to assess the therapy being administered and its criticality. Further, the rule based application <NUM> can assess currently administered drugs and patient <NUM> characteristics such as food intake, fluid intake, and disease state. Patient physiological response variables such as vitals, labs, and cognitive assessments can also be set to be used by the rule based application <NUM> to determine the risk to the patient. The rule based application <NUM> can also be set to include factors related to patient risk parameters such as change in patient state and transitions in therapy such as beginning, continuing, changing, or ending therapy.

The rule based application <NUM> in one embodiment includes physician or clinician entered conditions of when automation is acceptable. Clinician entered conditions can include therapy importance such as critical, life sustaining, supplementary, and benign. Further, the clinician can establish fail-safe, fail-operate, and fail-stop conditions for infusion that are based on strict rules or based on ranges of conditions. The system <NUM> is thus in communication with a clinician messaging system <NUM> that communicates to a clinician when the risk of automation is unacceptable. In a preferred embodiment the messaging system is remote from the system <NUM>.

The rule based application <NUM> in one embodiment can include a risk profile wherein a clinician implements a risk profile according to a metric that may be qualitative (low, medium or high) or quantitative (<NUM>-<NUM> where <NUM> is the highest risk) and a threshold defining when intervention is required. In either case, a quantitative metric is internally calculated and compared to a quantitative threshold. For example, in the case of low, medium or high each qualitative measurement is assigned a quantitative value such as <NUM>, <NUM> and <NUM> respectively. Consequently, a risk scale is specified and a threshold above which intervention is requested. The rule based application <NUM> can also include a risk matrix that is developed to enable a determination of risk. Although the matrix is ultimately stored internally, it can be parameteritized by the user. One example of the risk matrix is shown below:.

Specifically, the second column is the calculated or requested insulin level from the closed loop controller. The table is an example of how the treatment condition is mapped to a risk level. There are numerous other methods for implementing this information which may include continuous mapping functions, fuzzy logic, probability calculations and the like.

A second way to provide this type of system is to employ an insulin/glucose pharmacokinetic/pharmacodynamic model as shown below which predicts the future glucose level. The clinician can then use a predicted value rather than or in addition to glucose level and a derivative. <MAT> <MAT> <MAT> <MAT> <MAT> <MAT> <MAT> <MAT>.

In Equations (<NUM>)-(<NUM>), G(t) [mmol/L] denotes the total plasma glucose concentration, and I(t) [mU/L] is the plasma insulin concentration. The effect of previously infused insulin being utilized over time is represented by Q(t) [mU/L], with k [<NUM>/min] accounting for the effective life of insulin in the system. Exogenous insulin infusion rate is represented by uex(t) [mU/min], whereas P(t) [mmol/L min] is the exogenous glucose infusion rate. Patient's endogenous glucose removal and insulin sensitivity through time are described by pG(t) [<NUM>/min] and SI(t) [L/mU min], respectively. The parameters VI [L] and VG [L] stand for insulin and glucose distribution volumes. n [<NUM>/min] is the first order decay rate of insulin from plasma. Two Michaelis-Menten constants are used to describe saturation, with αI [L/mU] used for the saturation of plasma insulin disappearance, and αG [L/mU] for the saturation of insulin-dependent glucose clearance.

Thus, the rule based application <NUM> determines the risk to a patient <NUM> by determining a predetermined risk threshold. Below the predetermined risk threshold, because low risk is detected, the system <NUM> can move forward in an automated fashion and provide medication as required. If the risk is determined to be above the predetermined risk threshold the controller triggers a request for user intervention by contacting the clinician messaging system <NUM> instead of moving forward with automation.

The system <NUM> can also be used to monitor any form of infusion including anticoagulation monitoring during heparin infusion, respiratory monitoring during pain medication infusion such as morphine, and hemodynamic monitoring during infusion of vasco-active medication for cardio vascular support.

As best understood in view of <FIG>, in an alternative embodiment the system <NUM> includes a system monitor <NUM> that is in communication with the controller <NUM>. In one arrangement the system monitor <NUM> tracks network activity on a network <NUM> to determine whether a network failure has occurred. The system <NUM> also detects interruptions in communication with decision support provided by a remote system <NUM>. Similarly, the system monitor <NUM> tracks network activity to determine whether an interruption has occurred between the system <NUM> and the clinician messaging system <NUM> or other remote system <NUM> that allows for remote operation of the system <NUM> by a clinician or other basis of support such as medical record tracking. In the event that an interruption is detected the system <NUM> is enabled to continue infusion at either a backup infusion rate set by a clinician or the rule based application <NUM>. Alternatively, the system <NUM> can be configured to set an infusion rate based on a default setting that can include a minimum or maximum rate that depends on the physiological state of the patient <NUM> and the therapy being administered.

In another embodiment the system monitor <NUM> detects air in line levels. In this embodiment the system monitor <NUM> determines whether the amount of air present in line is at a critical level that requires stopping the infusion. When air in line is detected the system monitor <NUM> sends data to the controller <NUM> that uses the automation risk monitor <NUM> to determine whether the criticality of treatment is sufficient to allow the system <NUM> to continue to operate. In one arrangement, when air is detected by the system monitor <NUM> an alarm is sent via the clinician messaging system <NUM> or emitted from the system <NUM> locally. The system monitor <NUM> also determines whether the detection of air in line is a false positive and if a false positive is detected the alarm is auto-cleared. The system monitor <NUM> can also be set to not send an alarm if the amount of air present is non-critical.

Additionally, the system monitor <NUM> detects whether an occlusion is present. If an occlusion is detected the system monitor <NUM> sends data to the controller <NUM> to determine whether the occlusion poses a sufficient risk to adjust the infusion rate. Alternatively, if the controller <NUM> determines a sufficient risk is presented by an occlusion an alarm can be triggered or a message can be sent via the clinician messaging system <NUM>. In one arrangement the presence of occlusions is based on occlusion pressure levels.

In the event that the system monitor <NUM> detects a sufficient amount of air or large enough occlusion the system <NUM> can activate a backup system <NUM>. For example, in a life-sustaining situation, a backup system <NUM> would be enabled and the infusion rate set by the controller <NUM>. In one arrangement, the backup system <NUM> maintains infusion parameters set by the system <NUM> so that treatment can be transitioned without interruption.

In another arrangement the system <NUM> includes a multi-channel infusion system <NUM> that allows for multiple treatment paths or channels <NUM>. When the system monitor <NUM> detects that one channel <NUM> has failed the system <NUM> switches to an alternative channel <NUM> to deliver the infusion. In one embodiment the system <NUM> adjusts the infusion rate of a concurrently infused medication to compensate for the failure of a channel <NUM>. For example, if a dextrose infusion fails in a hypoglycemic patient <NUM> the system <NUM> can increase the infusion of nutrition to compensate for the lack of dextrose being infused.

In one embodiment, the system monitor <NUM> tracks whether input is received from clinicians after the clinician is contacted via the clinician monitoring system <NUM> to input or confirm a therapy adjustment. If the clinician fails to respond the system monitor <NUM> sends data to the controller <NUM> to adjust treatment based on information from the automation risk monitor <NUM> as described previously.

An alarm system <NUM> can also be included in the system <NUM>. The alarm system <NUM> determines the appropriate alarm to send depending on the level of patient risk, uncertainty, and predicted outcomes. In this manner, the alarm system <NUM> provides the highest degree of alarm in association with critical events that require immediate attention.

In operation, the system <NUM> monitors a control algorithm of a controller <NUM> to receive data. The controller <NUM> additionally receives continuous data from a sensor <NUM> regarding a medical condition such as a glucose level. The controller <NUM> then compares the data from the control algorithm and the sensor <NUM> to predetermined medical information so that the controller <NUM> can determine a predetermined risk threshold of automating the delivery of medication. Then, based on the data, if a risk is below a predetermined threshold, automation is permitted and a command or request for medication or insulin is provided to the insulin pump. Therefore the insulin delivery rate is automatically updated according to the algorithm model or closed loop controller used. Alternatively, if the risk is at or above a predetermined threshold a request for user intervention is triggered sending a message to the clinician messaging system <NUM> so that a user may intervene to make a determination regarding whether the medication should be provided. The request for intervention is generated and sent directly to the user through a messaging system that is bi-directional. The message system <NUM> provides information and requests a user response. When the response is related to a change in therapy an authentication step is included.

The response to a request is provided by the user directly through the user interface of the system. Alternatively, the response can be returned through an authenticated messaging system involving a unique identifier specific to a positive or negative response. In the event that the clinician fails to respond the therapy may be continued at a lower rate or stopped altogether. Optionally, an alarm can be generated by the alarm system <NUM>.

During the course of normal operation glucose measurements may be received that generate a change in the recommended insulin. However, the change may not be significant enough to provide a therapeutic advantage to the patient versus the burden of requesting confirmation from the nurse. Consequently, a rule based application <NUM> is provided which evaluates therapy changes to trigger a request for an automatic update or nursing intervention. The input to the rule based application <NUM> includes the blood glucose level, the change in glucose, the insulin infusion, the recommended change in insulin infusion, the estimated insulin on board, and the predicted glucose in the future. Rules involving comparisons to thresholds, regression equations, and calculations are created which trigger a therapy update based on the inputs.

In the event that an interruption to the normal operation of the system <NUM>, the remote systems <NUM>, or network <NUM> is detected by the system monitor <NUM>, the system adjusts therapy by altering the infusion rate of the system <NUM> or switching to a backup system <NUM>. Additionally, if an interruption is detected in a system <NUM> using multi-channel infusions <NUM>, the system <NUM> can alter the infusion rate or channel <NUM> used for infusing to compensate for the channel <NUM> failure.

When a command request is made or an interruption to normal operation is detected an alarm system <NUM> determines the appropriate alarm to send. The highest alarm is sent by the alarm system <NUM> based on the most critical failures of the system <NUM> or risks to the patient <NUM>.

Thus, the present system can be used to make determinations of treatment decisions requiring user intervention based upon a diagnostic value, the change in diagnostic value, the current drug infusion rate, the updated drug infusion rate, the treatment target range, network failures, system failures, and clinician inactivity. In addition, the system notifies a clinician that intervention is required and receives the implementing clinician instruction in response to the notification.

An additional advantage is presented because the system <NUM> determines when clinician intervention is necessary and unnecessary. Specifically, system <NUM> is independent of an adaptive control algorithm or a computerized protocol. The system <NUM> functions as a supervisor that watches the performance of the closed loop system. Consequently, data from the closed loop system and diagnostic sensor <NUM> are provided to the rule based application <NUM> that uses a matrix to produce a quantitative level of risk. The level of risk can be expressed as a discrete general level such as the "High", "Low" and "Medium" values expressed in the table above or the level of risk can be a numerical value, score, index or percentage. The risk is compared to a particular risk threshold to either generate and/or provide an "okay" to proceed with therapy or to trigger a request for user intervention.

This operation differs from current systems that do not determine risk of automation. Instead prior art systems allow automation to occur regardless of potential risk and then when sensors indicate a patient is experiencing an unacceptable medical condition a clinician is alerted. Therefore the system <NUM> provides an advantage of preventing the unacceptable medical condition from occurring in the first place as a result of monitoring the automation process and predetermining risks of automation.

Claim 1:
A system (<NUM>) for delivering medication to a patient, the system comprising:
a controller (<NUM>) having a control algorithm and an automation risk monitor (<NUM>) that monitors the control algorithm;
a sensor (<NUM>) in communication with the controller and the automation risk monitor and monitoring a medical condition;
a rule based application (<NUM>) in the automation risk monitor that receives data from the sensor and a closed loop control and compares the data to predetermined medical information to determine risk to a patient, wherein the controller controls a medication delivery device to deliver medication to the patient by infusion based on a comparison of the risk to a predetermined risk threshold; and
a system monitor (<NUM>) in communication with a network (<NUM>), the controller and the automation risk monitor, wherein the system monitor tracks network activity on the network to detect network failures and interruptions between the system and a clinician messaging system (<NUM>) being remote to the system, whereby the infusion continues at a back-up infusion rate set by the rule based application when interruptions are detected, the system further comprising a multi-channel infusion system, wherein when the system monitor detects an interruption between the system and the clinician messaging system the controller transitions medication delivery to a different channel of the multi-channel infusion system.