WO2008067245A2

WO2008067245A2 - Determining insulin pump rate for tight glycemic control

Info

Publication number: WO2008067245A2
Application number: PCT/US2007/085518
Authority: WO
Inventors: Vinay Vaidya; Carl Barton Shanholtz
Original assignee: University Of Maryland, Baltimore
Priority date: 2006-11-29
Filing date: 2007-11-26
Publication date: 2008-06-05
Also published as: WO2008067245A3

Abstract

A method for controlling a patient's blood glucose includes receiving target selection data that indicates a particular target glucose level for a patient among multiple target glucose levels. Current glucose data and previous glucose data that indicate blood glucose levels for a particular patient are also received. Current insulin data that indicates a rate at which insulin is currently being administered intravenously to the particular patient is also received. Based on the target selection data, the current glucose data and the previous glucose data, recommended insulin data is determined. The recommended insulin data indicates a rate at which insulin should be administered to the particular patient to achieve the particular target glucose level. In some embodiments, recommended measurement data that indicates a time at which to make a next measurement of blood glucose level for the particular patient is also determined.

Description

DETERMINING INSULIN PUMP RATE FOR TIGHT GLYCEMIC CONTROL

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit of United States Provisional Appln. 60/867,759, filed November 29, 2006, under 35 U.S.C. §119(e).

BACKGROUND OF THE INVENTION

1. Field of the Invention

[0002] The present invention relates to providing tight glycemic control in intensive care unit patients and in particular to automated techniques for determining insulin pump rates based on measured blood glucose levels.

2. Description of the Related Art

[0003] In has been established that controlling blood glucose levels within strict, near-normal limits in intensive care unit (ICU) patients improves mortality and morbidity (i.e., reduces death and illness rates). Such strict control is called tight glycemic control (TGC). It is well known that glucose levels in patients requiring intravenous glucose, such as ICU patients can be controlled using administration of insulin. One technique for such administration of insulin is by insulin infusion into intravenous (IV) tubes feeding the patient. The rate of insulin infusion can be regulated, either automatically or manually. The rate of infusion is often expressed in terms of standard units of insulin per hour. In pediatric cases, the rate is adjusted to the weight of the patient and the rate is expressed as standard units per hour per kilogram of patient weight. [0004] Protocols have been developed to regulate insulin infusion rate based on one or more measurements of glucose level in the patient' s blood. Glucose measurements are typically performed as manual procedures at discrete moments in time. A blood sample is taken and supplied to a glucometer that outputs a numerical value that indicates blood glucose level. Blood glucose levels are expressed in units of glucose mass per unit volume of blood, e.g., milligrams (mg, 1 mg = 10^"3 grams,) per deciliter (dl, 1 dl = 0.1 liter), and milli-Mole (mmole, 1 mmole = 10^"3 Mole, 1 Mole is Avogadro's Number of molecules, Avagadro's Number is the number of carbon-12 atoms in 12 grams of unbound carbon-12 in its rest-energy electronic state) per liter (L). [0005] For example, a protocol proposed by the University of North Carolina attempts to maintain glucose levels under 100 mg/dl. Another example protocol from the University of Pittsburgh attempts to maintain glucose levels between 80 and 100 mg/dl. Another protocol provided in the Cleveland Journal of Medicine, vol. 71, no. 10, at 805 (October 2004) attempts to maintain the glucose level between 80 and 110 mg/dl for ICU patients. A protocol from the Diabetes Roundtable attempts to control the glucose level via administration of insulin to between 75 and 100 mg/dl. Another example protocol from the Ottawa Hospital attempts to control the glucose level via insulin administration to between 81 and 108 mg/dl. Some of these protocols have been estimated to reduce mortality rates in ICU patients by as much as 30 to 40 percent. [0006] A problem with many such protocols is they are implemented as written procedures and decision trees to be implemented manually. These procedures are tedious and difficult to learn. This difficulty can lead to errors, especially when applied repeatedly and frequently among multiple patients in a regular hospital ward. Errors can result in sickness and even loss of life due to incorrect or untimely glucose level control. [0007] To simplify the protocol complexity, some protocols have been implemented as software instructions executed on computer processors that depend on manually input data, such as one or more measured blood glucose levels. See, for example, Davidson PC, Steed RD, Bode BW, "Glucommander: a computer-directed intravenous insulin system shown to be safe, simple, and effective in 120,618 h of operation," Diabetes Care, v.28 (#10), pp2418-23, Oct 2005 (hereinafter Davidson); and Vogelzang M, Zijlstra F, Nijsten MW, "Design and implementation of GRIP: a computerized glucose control system at a surgical intensive care unit," BMC Med Inform Decis Mak, v.5 (#38). Dec 19 2005 (hereinafter Vogelzang).

[0008] While suitable for many purposes, the computerized protocols still suffer some deficiencies. For example, both Davidson and Vogelzang require manual blood glucose input that itself is prone to human error. Vogelzang uses built in target glucose levels or ranges that are not amenable to user changes. Both Davidson and Vogelzang specify absolute insulin rate as an output that does not allow for different units or dose per kilogram as desirable for pediatric cases. Neither Davidson nor Vogelzang specify procedures for transitioning onto or off intravenous insulin infusion. Neither Davidson nor Vogelzang suggest circumstances in which the user is directed to involve a physician

-?- in determining whether to implement a recommended insulin rate. Furthermore, Davidson teaches regular, closely-timed glucose measurements that are a burden on both patient and caregiver.

[0009] The approaches described in this section could be pursued, but are not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated herein, the approaches described in this section are not to be considered prior art to the claims in this application merely due to the presence of these approaches in this background section

SUMMARY OF THE INVENTION

[0010] In a first set of embodiments of the invention, a method for determining insulin drip rate for a patient, includes receiving target selection data that indicates a particular target glucose level for a patient among a plurality of target glucose levels for a patient. Current glucose data is received, which indicates a most recent measurement of blood glucose level for a particular patient. Previous glucose data is received, which indicates blood glucose level for the particular patient at a time before the most recent measurement of blood glucose level for the particular patient by more than about fifteen minutes. Current insulin data is received, which indicates a rate at which insulin is currently being administered intravenously to the particular patient. Based on the target selection data and the current glucose data and the previous glucose data and the current insulin data, recommended insulin data is determined, which indicates a rate at which insulin should be administered to the particular patient to achieve the particular target glucose level.

[0011] In another set of embodiments, a method for determining insulin drip rate for a patient, includes receiving BGcurrent that indicates a most recent measurement of blood glucose level for a particular patient. BGprevious is also received, which indicates a blood glucose level for the particular patient at a time before the most recent measurement of blood glucose level for the particular patient by more than about fifteen minutes. Iprevious is received, which indicates a rate at which insulin is currently being administered intravenously to the particular patient. A new insulin rate, Inew, is determined as directly proportional to the quantity Iprevious * (BGcurrent/BGprevious)². [0012] In another set of embodiments, an apparatus includes a glucometer configured to receive a blood sample and to output glucose data that indicates a blood glucose level. The apparatus also includes computer readable medium configured to store glucose data; and logic encoded in one or more tangible media for execution. When executed, the encoded logic is operable to receive from the computer readable medium current glucose data that indicates a most recent measurement of blood glucose level for a particular patient and receiving from the computer readable medium previous glucose data that indicates a blood glucose level for the particular patient at a time before the most recent measurement of blood glucose level for the particular patient by more than about fifteen minutes. The encoded logic is further operable for determining, based on the current glucose data and the previous glucose data, recommended insulin data that indicates a rate at which insulin should be administered to the particular patient.

[0013] In various other sets of embodiments, logic encoded in a tangible medium or an apparatus performs one or more steps of the above methods.

BRIEF DESCRIPTION OF THE DRAWINGS

[00010] The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements and in which:

[0014] FIG. 1 is a block diagram that illustrates an example IV insulin infusion system in a patient care facility, according to an embodiment:

[0015] FIG. 2A is a flow diagram that illustrates at a high level a method for implementing tight glycemic control according to an embodiment;

[0016] FIG. 2B is a flow diagram that illustrates an initiation step of the method of

FIG. 2A according to an embodiment;

[0017] FIG. 2C is a flow diagram that illustrates a manual input step of the method of

FIG. 2A according to an embodiment;

[0018] FIG. 2D is a flow diagram that illustrates an insulin determination step of the method of FIG. 2A according to an embodiment;

[0019] FIG. 3 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a target range for a step of the flow diagram of FIG. 2D, according to an embodiment;

[0020] FIG. 4 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a first range above the target range for a step of the flow diagram of FIG. 2D, according to an embodiment;

[0021] FIG. 5 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a second range above the first range for a step of the flow diagram of FIG. 2D, according to an embodiment;

[0022] FIG. 6 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a third range above the second range for a step of the flow diagram of FIG. 2D, according to an embodiment; and

[0023] FIG. 7 illustrates a computer system upon which an embodiment of the invention may be implemented. DESCRIPTION OF EXAMPLE EMBODIMENTS

[0024] A method and apparatus for determining insulin rate are described. In the following description, for the purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It will be apparent, however, to one skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known structures and devices are shown in block diagram form in order to avoid unnecessarily obscuring the present invention.

[0025] Some embodiments of the invention are described in the context of tight glycemic control (TGC) for a human non-diabetic patient in an intensive care unit (ICU) with manually controlled insulin infusion pumps. However, the invention is not limited to this context. In various other embodiments, the patient is a diabetic or non-diabetic human or non-human patient in an ICU, a non-ICU hospital facility, or outside a hospital, using an automatic or manual intravenous (IV) insulin infusion device for TGC or non- TGC glucose control.

1.0 STRUCTURAL OVERVIEW

[0026] FIG. 1 is a block diagram that illustrates an example IV insulin infusion system 100 in a patient care facility, according to an embodiment. In the illustrated embodiment, the system includes a patient support 120, such as a hospital bed or gurney, an IV support 130, such as a fixed or mobile pole, an IV delivery system 110, a computer system 150 and a glucose measurement device 140. Also depicted in FIG. 1 for illustrative purposes, as a broken line oval shape, is a patient 190 who is treated by the system 100; however the patient 190 is not part of the system 100. [0027] The IV delivery system 110 includes an insulin infusion pump 114, a dextrose infusion pump 116 and IV tubes 112 that connect the pumps 114, 116 to a vein of patient 190 so that fluid pumped by pumps 114, 116 enters a reservoir that leads to the vein of patient 190.

[0028] Computer system 150 includes an IV control process 152 that automatically adjusts the rate of infusion by pump 114 and pump 116. Control signals that represent a pump infusion rate are sent over wires 154 from computer system 150 to pump 114 and pump 116 of IV delivery system 110. In some embodiments that use manually controlled pump 114 and pump 116, process 152 and wires 154 are omitted. In some embodiments, an automated infusion pump system includes computer system 150 as part of an integrated device. Hardware that constitutes computer system 150 is described in a later section with reference to FIG. 7.

[0029] According to some embodiments, computer system 150 includes insulin rate recommendation process 160. The steps performed by insulin rate recommendation process 160 are described in more detail below with reference to the flow diagrams of FIG. 2A, FIG. 2B, FIG. 2C, FIG. 2D, FIG. 3, FIG. 4, FIG. 5, and FIG. 6. In some such embodiments, an insulin rate determined by the insulin rate recommendation process 160 is automatically input into the IV control process 152 to control IV delivery system 110. In some embodiments, an insulin rate determined by the insulin rate recommendation process 160 is presented to a user, who provides that rate manually as input into the IV delivery system 110.

[0030] According to another embodiment, insulin rate recommendation process 160 is included in a glucose measurement device 140. In some such embodiments, a blood glucose level determined by a glucometer is automatically input into the insulin rate recommendation process 160 and presented to a user. The user then provides that rate manually as input into the IV delivery system 110. In some such embodiments, a blood glucose level determined by the glucometer is automatically input into the insulin rate recommendation process 160 and automatically controls IV delivery system 110 without user intervention.

2.0 METHOD FOR DETERMINING INSULIN RATE

[0031] A method for determining insulin rate to maintain blood glucose levels in a patient improves on one or more features of prior art approaches. For example, in some embodiments, multiple selectable target ranges are allowed for patient blood glucose levels and a caregiver is allowed to select one, and even allowed to change the selection during the course of IV insulin administration. This allows the process to be adjusted as medical best practice evolves or as the patient progresses through treatment. In some embodiments, one or more manual input data is presented to the user, such as a caregiver, so that such entries may be confirmed. Such confirmation is included to reduce error rates in manually input data. In addition, in some embodiments, alerts are presented when input values indicate dangerous conditions, such as hypoglycemia. In some embodiments, arbitrary units may be used for insulin rate by a user, such as units per hour and units per hour per kilogram, and the approach automatically adjusts insulin rate in the chosen units without additional input by the user. In various embodiments, special steps are introduced for initiation of IV insulin infusion, or to transition off IV insulin infusion, or both. In some embodiments, less frequent invasive blood glucose level measurements are required than in some prior art approaches.

[0032] FIG. 2A is a flow diagram that illustrates at a high level a method 200 for implementing tight glycemic control according to an embodiment that incorporates all these features. Although steps are shown in FIG. 2A and subsequent flow diagrams in a particular order for purposes of illustration, in other embodiments one or more steps may be performed in a different order or overlapping in time by one or more persons or processors executing in series or in parallel, or one or more steps may be omitted, or some combination of changes may be made.

[0033] In step 202, a prompt is issued to a user to receive and present initiation orders and transition orders using any insulin units. During step 202 a user is prompted for any special instructions from a physician or other caregiver, guided through the decision to start a patient on IV insulin infusion, and given instructions on how to prepare the patient for IV insulin infusion. For example, the user is prompted for a minimum insulin infusion rate in any units and prompted to take an initial measurement of the patient's blood glucose level. It is assumed for purposes of illustration that the user responds with a minimum insulin infusion rate of 0.02 units per hour per kilogram. In another example embodiment, it is assumed for purposes of illustration that the user responds with a minimum insulin infusion rate of 1 unit per hour. The user is also provided with an initial insulin infusion rate in terms of a multiple of the minimum infusion rate based either on a default value or on the initial measurement of blood glucose level. [0034] In some embodiments, step 202 includes the steps depicted in FIG. 2B, and described in more detail in the next subsection.

[0035] In step 204, data is received that indicates a particular target blood glucose range among a plurality of ranges. In some embodiments, the user is prompted for the target range during step 202 and that response is received during step 204. In some embodiments, step 204 is performed before step 202. In some embodiments, step 204 is performed both before and after step 202. [0036] Multiple target blood glucose ranges are useful for a variety of reasons. For example, best medical practice for TGC may evolve as the result of research findings. The best practice target blood glucose range (hereinafter, simply, target range) is still a topic of ongoing research at the time of this writing. Furthermore, the target range may depend on individual characteristics of a patient, such as disease, age, genetic markers and other health status. In addition, the target range may change during the course of treatment. In some embodiments, the target range is a single value, i.e., the upper and lower limits of the range are the same.

[0037] In an illustrated embodiment, four target ranges for a patient are made available to a user. Table 1 lists the four target ranges in the illustrated embodiment in units of mg/dl. Table 1. Example selectable blood glucose ranges.

[0038] In step 206 multiple glucose thresholds for decisions are determined based on the selected target range. Any method may be used to define the thresholds. In the illustrated embodiment, there are five glucose thresholds outside the target range used to make decisions. The five thresholds are named the hypoglycemic threshold, the high threshold, the higher threshold, the highest threshold and the diabetic ketoacidosis (DKA) threshold. In some embodiments, one or more of these glucose thresholds are multiples of the upper or lower limits of the target range. In the illustrated embodiment, these thresholds are defined in a list associated with each target range. The thresholds associated with each target range for the illustrated embodiment are given in Table 2 in order of increasing blood glucose level.

Table 2. Example blood glucose thresholds associated with target ranges.

[0039] In some embodiments, decisions are based on a formula rather than blood glucose thresholds and some or all of step 206 is omitted.

[0040] In step 210, data is received that indicates current measured blood glucose level (i.e., a current glucose reading), a previous measured blood glucose level and the current insulin infusion rate. For simplicity hereinafter, the IV insulin infusion rate is simply called the insulin rate. The user is also prompted for any of this data that is input manually. For example, in the illustrated embodiment, the user is prompted for all three data items. In some embodiments, some of the data is retrieved from data storage. In some embodiments, the current blood glucose level is received automatically from a glucometer to which a blood sample has been introduced. In some embodiments, step 210 includes the steps depicted in FIG. 2C, and described in more detail in a later subsection.

[0041] In step 220, the user is prompted for confirmation of critical, manually-input data. For example, the current and previous blood glucose levels are presented to the user and the user is prompted to confirm, yes or no, that the presented values are correct. In some embodiments, step 220 includes colors, symbols or other visual cues, alone or in some combination, to highlight the significance of the data being confirmed. For example, the presentation of current and previous blood glucose readings includes a red upward arrow when the data indicates the blood glucose is rising above the target range, a green downward arrow when the data indicates the blood glucose is falling above the target range. Similarly, the presentation of current and previous blood glucose readings includes a red downward arrow when the data indicates the blood glucose is falling below the target range, a green upward arrow when the data indicates the blood glucose is rising below the target range. In a current embodiment, a red upward arrow indicates that the current blood glucose is rising and a blue downward arrow indicates that the current blood glucose is falling. As a further example, the user is presented with the current insulin infusion rate that is yellow when the rate is zero and red when the rate is above 10 times the minimum infusion rate.

[0042] In step 222, it is determined whether the data has been confirmed. If not, then control flows to step 224. In step 224, an alert is issued such as an alert to enter manual data again or check for corruption in the database. In some embodiments, step 224 is omitted and control simply flows directly back to step 210 to receive inputs and prompt for any manually input data.

[0043] If it is determined, in step 222, that the data has been confirmed, then control flows to step 226. In step 226, it is determined whether the patient is to be transitioned off IV insulin infusion. Any method may be used. For example, the user inputs data that indicates a physician has ordered the patient off IV insulin infusion, either in response to a prompt or unprompted. If it is determined in step 226 that the patient is to be transitioned off IV insulin infusion, then control passes to step 228.

[0044] In step 228, the user is presented with transition orders. In various embodiments, the transition orders are based on data input during step 202 or default values. For example, the user is directed to perform the following steps:

1] Administer subcutaneously Glargine insulin in an amount that is four times the total amount of insulin administered to the particular patient in the previous four hours.

2] Continue IV insulin infusion at the current rate, but not to exceed three units per hour.

3] Stop IV insulin infusion after 2 hours.

4] Administer subcutaneously 3 times the minimum insulin infusion rate multiplied by one hour with meals.

5] Make a measurement of the patient's blood glucose level after IV insulin infusion is stopped and every 6 hours thereafter and before meals and at bedtime.

6] Input the measured blood glucose level and receive a recommended dose of subcutaneous regular insulin or dextrose.

7] Administer subcutaneously the recommended dose of regular insulin or dextrose. [0045] During step 6 of step 228, a recommended dose of regular insulin is computed based on the input measured blood glucose level. For example, the recommended dose is computed based on Table 3.

Table 3. Example recommended dose of subcutaneous regular insulin or IV dextrose.

[0046] If it is determined in step 226 that the patient is not to be transitioned off IV insulin infusion, control passes to step 230. In step 230 an IV insulin infusion rate change is determined based on the target range, current glucose, previous glucose and current insulin rate. In the illustrated embodiment, dextrose doses and glucose measurement times are also determined during step 230. In the illustrated embodiment, if the current insulin rate is zero, then the change is expressed in terms of the minimum insulin rate; otherwise in the illustrated embodiment, the change is expressed as a percent change of the current insulin rate. An advantage of this approach is that any insulin rate units may be used, such as units per hour per kilogram utilized for pediatric cases. In some embodiments, step 230 includes the steps depicted in FIG. 2D, and described in more detail in a later subsection. In some embodiments, a formula replaces one or more steps depicted in FIG. 2D. One embodiment of such a formula is described in subsection 2.4, below.

[0047] In step 290, insulin or dextrose is administered to the patient based on the percent change. In the illustrated embodiment, the dextrose dose or percent change (or both) is presented to the user (either separately or combined with the current insulin rate to give a recommended insulin rate) and the user manually adjusts the IV delivery system 110. In some embodiments, the dextrose dose or percent change (or both) is presented to the IV control process 152 (either separately or combined with the current insulin rate to give a recommended insulin rate) and the IV control process 152 sends control signals over wires 154 to control the IV delivery system 110.

[0048] In the illustrated embodiment, control passes back to step 204 to receive data that indicates the current selection among multiple target ranges. It is expected that the data indicating the selection does not change during IV insulin administration in most cases. Steps 204, 206, 210, 220, 222, 226, 230 and 290 are performed repeatedly until it is determined in step 226 that the patient is to be transitioned off IV insulin infusion.

2.1 INITIATION PHASE

[0049] FIG. 2B is a flow diagram that illustrates an initiation step 202 of the method of FIG. 2A according to an embodiment. In other embodiments step 202 includes one or more different or fewer steps from those depicted in FIG. 2B. For purposes of illustration it is assumed that the selected target range is target B, 80 to 120 mg/dl. [0050] In step 270, prompts are presented to a user to input special physician orders for minimum dose, target range and initial glucose measurement times. In some embodiments, a prompt for an initial insulin rate is also presented. [0051] In step 272, it is determined whether the response to prompts indicate any physician inputs. If not, control passes to step 273. In step 273, default values are used. For example, default values includes target range B, minimum insulin infusion rate of 1 unit per hour of 150 regular insulin units in 150 ml of normal saline. Default initiation instructions include discontinuing all subcutaneous insulin, discontinue all antidiabetics, initial insulin rate of 2 times the minimum insulin rate, and measurements of blood glucose level at start of IV insulin infusion and at one hour after start of IV insulin infusion. Default insulin infusion instructions include reducing insulin by 50% and notify physician if the patient needs to be transported from ICU or there is a sudden reduction in intake of dextrose. Control then passes to step 276. It is assumed for purposes of illustration that no special physician input is provided and that the default values are used, including Target B (from 80 to 120 mg/dl) as the current target range. [0052] If it is determined, in step 272, that the response to prompts indicates any physician inputs, control passes to step 274 to replace default values with physician provided values. Control then passes to step 276. [0053] In step 276 and 278, it is determined whether the patient is subject to insulin infusion. For example, in step 276, the user is presented with a question that asks whether the patient is expected to stay in the ICU more than 12 hours. The response is also received during step 276. In step 278, it is determined whether the response is negative or affirmative. If negative, control passes to step 279 and IV infusion of insulin is not used. No further action is taken. If the response is affirmative, control passes to step 280. [0054] In step 280, it is determined whether there is an initial blood glucose level measurement available. If not, control passes to step 281 to prompt the user to measure blood glucose level and input the initial blood glucose level measurement. Control then passes to step 282. If it is determined, in step 280, that there is an initial blood glucose level measurement available, then control passes to step 282 directly. [0055] In step 282, it is determined whether the initial glucose level is greater than the high threshold associated with the current (or default) target range, such as listed in Table 2. The high threshold associated with Target B in Table 2 is 150 mg/dl. Thus in this example, it is determined during step 282 whether the initial blood glucose level is greater than 150 mg/dl.

[0056] If it is determined in step 282 that the initial blood glucose level is not greater than the high threshold, then control passes to step 283. For example, if the initial blood glucose level is not greater than 150 mg/dl, then control passes to step 283. [0057] In step 283, it is determined whether the two most recent blood glucose measurements are greater than the target range. For example, if the initial blood glucose level is greater than the target range, then the user is prompted for a second blood glucose level measurement after a certain time. If this second blood glucose level measurement is also greater than the target range, then it is determined during step 283 that two glucose levels are greater than the target range. If not, then control passes to step 204 of FIG. 2A, and nothing further is done as part of the initiation step 202. For example, if the initial blood glucose level is not greater than 120, then control passes to step 204. [0058] If it is determined, in step 283, that the two most recent blood glucose measurements are greater than the target range, then control passes to step 289. In step 289 an initial insulin rate is set at the minimum insulin rate. For example, using default values, the initial insulin rate is set at 0.02 units per hour per kilogram. In default non- pediatric cases, the initial insulin rate is set at 1 unit per hour. Control then passes to step 204 of FIG. 2A, and nothing further is done as part of the initiation step 202. [0059] If it is determined in step 282 that the initial blood glucose level is greater than the high threshold, then control passes to step 284. For example, if the initial blood glucose level is greater than 150 mg/dl, then control passes to step 284. In step 284, it is determined whether the initial blood glucose level is greater than the higher threshold associated with the current (or default) target range, such as listed in Table 2. The higher threshold associated with Target B in Table 2 is 250 mg/dl. Thus in this example, it is determined during step 284 whether the initial blood glucose level is greater than 250 mg/dl.

[0060] If it is determined, in step 284, that the initial blood glucose level is not greater than the higher threshold, then control passes to step 285. In step 285, an initial insulin rate is set at twice the minimum insulin rate. For example, using default values, the initial insulin rate is set at 0.04 units per hour per kilogram. In default non-pediatric cases, the initial insulin rate is set at 2 units per hour. Control then passes to step 204 of FIG. 2A, and nothing further is done as part of the initiation step 202.

[0061] If it is determined in step 284 that the initial blood glucose level is greater than the higher threshold, then control passes to step 286. For example, if the initial blood glucose level is greater than 250 mg/dl, then control passes to step 286. In step 286, it is determined whether the initial blood glucose level is greater than the highest threshold associated with the current (or default) target range, such as listed in Table 2. The highest threshold associated with Target B in Table 2 is 300 mg/dl. Thus in this example, it is determined during step 286 whether the initial blood glucose level is greater than 300 mg/dl.

[0062] If it is determined, in step 286, that the initial blood glucose level is not greater than the highest threshold, then control passes to step 287. In step 287, an initial insulin rate is set at three times the minimum insulin rate. For example, using default values, the initial insulin rate is set at 0.06 units per hour per kilogram. In default non-pediatric cases, the initial insulin rate is set at 3 units per hour. Control then passes to step 204 of FIG. 2A, and nothing further is done as part of the initiation step 202. [0063] If it is determined, in step 286, that the initial blood glucose level is greater than the highest threshold, then control passes to step 288. In step 288, an initial insulin rate is set at four times the minimum insulin rate. For example, using default values, the initial insulin rate is set at 0.08 units per hour per kilogram. In default non-pediatric cases, the initial insulin rate is set at 4 units per hour. Control then passes to step 204 of FIG. 2A, and nothing further is done as part of the initiation step 202.

2.2 MANUAL INPUT

[0064] FIG. 2C is a flow diagram that illustrates a manual input step 210 of the method of FIG. 2 A, according to an embodiment. In other embodiments step 210 includes one or more different or fewer steps from those depicted in FIG. 2C. Control passes to step 210 from step 206, as shown in FIG. 2A. In some embodiments with no manual input, step 210 is omitted.

[0065] In step 211, the user is prompted for the current glucose reading, i.e., the current blood glucose level measurement. In some embodiments, the method 200 is implemented in a glucometer 140 so that the current glucose reading is automatically input during step 210, and step 211 is omitted.

[0066] In step 212, the current glucose reading is received. For example, in some embodiments, the current glucose reading is received based on manual input in response to the prompt of step 211. In some embodiments, the current glucose reading is received automatically from a glucometer.

[0067] In step 214, it is determined whether the current glucose reading is greater than the DKA threshold associated with the current (or default) target range, such as listed in Table 2. The DKA threshold associated with Target B in Table 2 is 350 mg/dl. Thus in this example, it is determined during step 214 whether the initial blood glucose level is greater than 350 mg/dl.

[0068] If it is determined, in step 214, that the current glucose reading is greater than the DKA threshold, then control passes to step 215. In step 215 an alert is issued, such as text and colored icons to get the attention of the user that the patient may be suffering from DKA and to obtain the immediate advice of a physician. In some embodiments, a physician is automatically paged. Control then passes to step 218. In step 218 it is determined whether to proceed with IV insulin infusion. For example, the user is prompted to input data that indicates whether the patient will be removed from IV insulin infusion, and that input is used to determine whether to proceed. If it is determined in step 218 that the patient will not proceed with IV insulin infusion, control passes to step 219 to end the method. In some embodiments, step 219 includes passing control to step 228 to present transition orders. If it is determined in step 218 that the patient will proceed with IV insulin infusion, control passes to step 260. If it is determined, in step 214, that the current glucose reading is not greater than the DKA threshold, then control passes directly to step 260.

[0069] In step 260, the user is prompted for the previous glucose reading, e.g., the blood glucose level measurement that immediately precedes in time the current glucose reading. In some embodiments, the previous glucose reading is stored locally or on a network device and automatically retrieved from storage when needed, and step 260 is omitted.

[0070] In step 262, the previous glucose reading is received. For example, in some embodiments, the previous glucose reading is received based on manual input in response to the prompt of step 260. In some embodiments, the previous glucose reading is received automatically from local or network storage.

[0071] In step 264, the user is prompted for the current insulin rate. In some embodiments, the current insulin rate is stored locally or on a network device or read from the insulin infusion pump 114 and automatically retrieved when needed, and step 264 is omitted.

[0072] In step 266, the current insulin rate is received. For example, in some embodiments, the current insulin rate is received based on manual input in response to the prompt of step 264. In some embodiments, the current insulin rate is received automatically from local or network storage or from the insulin infusion pump 114. [0073] Control then passes to step 220 of FIG. 2A to prompt for confirmation of manually input data. In some embodiments, no data is manually input; and control passes directly to step 226.

2.3 DETERMINING INSULIN RATE IN ARBITRARY UNITS

[0074] FIG. 2D is a flow diagram that illustrates an insulin determination step 230' of the method of FIG. 2A according to an embodiment. The method 230' is one specific embodiment of step 230. In other embodiments, step 230 includes one or more different or fewer steps from those depicted in FIG. 2C. Control passes to step 230' from step 226, as shown in FIG. 2A. For purposes of illustration it is assumed that the selected target range is target B, 80 to 120 mg/dl. [0075] In step 231, it is determined whether the current glucose reading (i.e., the current blood glucose level measurement) is less than the hypoglycemic threshold associated with the current (or default) target range, such as listed in Table 2. The hypoglycemic threshold associated with Target B in Table 2 is 60 mg/dl. Thus in this example, it is determined during step 231 whether the current glucose reading is less than 60 mg/dl.

[0076] If it is determined, in step 231, that the initial blood glucose level is less than the hypoglycemic threshold, then control passes to step 232. In step 232, insulin infusion is temporarily stopped, i.e., the insulin rate is reduced by 100%; extra glucose is administered according to the physician-specified or default values received during step 202 (e.g., 25 ml 50% dextrose solution by weight through infusion pump 116); the user is prompted to notify a physician and the next two blood glucose level measurements are scheduled for 15 minutes and 30 minutes after the time of the current glucose reading. Control then passes to step 204 of FIG. 2A, to make the next measurements. [0077] If it is determined, in step 231, that the initial blood glucose level is not less than the hypoglycemic threshold, then control passes to step 240. For example, if the current glucose reading is greater than 60 mg/dl, then control passes to step 240. In step 240, it is determined whether the current glucose reading is less than the current (or default) target range, such as listed in Table 2. The target range of Target B in Table 2 is 80 to 120 mg/dl. Thus in this example, it is determined during step 240 whether the current glucose reading is less than 80 mg/dl.

[0078] If it is determined, in step 240, that the current glucose reading is less than the target range, then control passes to step 242. In step 242, insulin infusion is temporarily stopped, i.e., the insulin rate is reduced by 100%; and the next blood glucose level measurement is scheduled for 30 minutes after the time of the current glucose reading. Control then passes to step 204 of FIG. 2A, to make the next measurements. [0079] If it is determined in step 240 that the current glucose reading is not less than the target range, then control passes to step 250. For example, if the current glucose reading is greater than 80 mg/dl, then control passes to step 250. In step 250, it is determined whether the current glucose reading is within the current (or default) target range, such as listed in Table 2. The Target B range in Table 2 is 80 to 120 mg/dl. Thus in this example, it is determined during step 250 whether the current glucose reading is within the range from 80 to 120 mg/dl.

[0080] If it is determined, in step 250, that the current glucose reading is within the target range, then control passes to step 300. In step 300, insulin rate is adjusted based on rate of change of glucose from the previous measurement, as described in more detail below with reference to FIG. 3. During step 300, control is eventually returned to step 290 of FIG. 2A to administer insulin according to the adjusted insulin rate. [0081] If it is determined in step 250 that the current glucose reading is not within the target range, then control passes to step 252. For example, if the current glucose reading is greater than 120 mg/dl, then control passes to step 252. In step 252, it is determined whether the current glucose reading is greater than the high threshold associated with the current (or default) target range, such as listed in Table 2. The high threshold associated with Target B in Table 2 is 150 mg/dl. Thus in this example, it is determined during step 252 whether the current glucose reading is greater than 150 mg/dl. [0082] If it is determined, in step 252, that the current glucose reading is not greater than the high threshold, then control passes to step 400. In step 400, insulin rate is adjusted based on rate of change of glucose from the previous measurement, as described in more detail below with reference to FIG. 4. During step 400, control is eventually returned to step 290 of FIG. 2A to administer insulin according to the adjusted insulin rate.

[0083] If it is determined in step 252 that the current glucose reading is greater than the high threshold, then control passes to step 254. For example, if the current glucose reading is greater than 150 mg/dl, then control passes to step 254. In step 254, it is determined whether the current glucose reading is greater than the higher threshold associated with the current (or default) target range, such as listed in Table 2. The higher threshold associated with Target B in Table 2 is 250 mg/dl. Thus in this example, it is determined during step 254 whether the current glucose reading is greater than 250 mg/dl. [0084] If it is determined, in step 252, that the current glucose reading is not greater than the higher threshold, then control passes to step 500. In step 500, insulin rate is adjusted based on rate of change of glucose from the previous measurement, as described in more detail below with reference to FIG. 5. During step 500, control is eventually returned to step 290 of FIG. 2A to administer insulin according to the adjusted insulin rate.

[0085] If it is determined, in step 252, that the current glucose reading is greater than the higher threshold, then control passes to step 600. In step 600, insulin rate is adjusted based on rate of change of glucose from the previous measurement, as described in more detail below with reference to FIG. 6. During step 600, control is eventually returned to step 290 of FIG. 2A to administer insulin according to the adjusted insulin rate. [0086] FIG. 3 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a target range for step 300 of the flow diagram of FIG. 2D, according to an embodiment. In other embodiments, step 300 includes one or more different or fewer steps from those depicted in FIG. 3. Control passes to step 300 from step 250, as shown in FIG. 2D.

[0087] In step 310, it is determined whether the previous glucose reading is less than the current (or default) target range, such as listed in Table 2. The Target B range in Table 2 is 80 to 120 mg/dl. Thus in this example, it is determined during step 310 whether the previous glucose reading is less than the range from 80 to 120 mg/dl. [0088] If it is determined, in step 310, that the previous glucose reading is less than the target range, then control passes to step 311. In step 311, it is determined whether the current insulin rate is zero, such that a percentage change in insulin rate is meaningless. If so, control passes to step 312. In step 312 it is determined whether the current glucose reading is below the middle of the current (or default) target range. The middle of the target range for Target B is 100 mg/dl. Thus in this example, it is determined during step 312 whether the current glucose reading is less than 100 mg/dl.

[0089] If it is determined, in step 312, that the current glucose reading is below the middle of the target range, then control passes to step 314. In step 314 the adjusted insulin rate is set equal to the minimum insulin rate. For example, using the default values, the adjusted insulin rate is set to 0.02 units per hour per kilogram. For non- pediatric cases, the adjusted insulin rate is set to 1 unit per hour. Control then passes to step 318.

[0090] If it is determined, in step 312, that the current glucose reading is not below the middle of the target range, then control passes to step 316. In step 316 the adjusted insulin rate is set equal to twice the minimum insulin rate. For example, using the default values, the adjusted insulin rate is set to 0.04 units per hour per kilogram. For non- pediatric cases, the adjusted insulin rate is set to 2 units per hour. Because the adjusted insulin rate is expressed as a multiple of the minimum rate, any insulin infusion units may be used. Control then passes to step 318.

[0091] In step 318, the time for the next blood glucose level measurement (called hereinafter the next reading time) is set to be 30 minutes after the time of the current glucose reading (called hereinafter the current reading time). Control then passes to step

290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

[0092] If it is determined in step 310 that the previous glucose reading is not less than the current (or default) target range, or if it is determined in step 311 that the previous glucose reading is less than the current (or default) target range but the current insulin rate is not zero, then control passes to step 320. In step 320, it is determined whether the current glucose reading represents a glucose drop of more than 75 mg/dl from the previous glucose reading. If so, control passes to step 322.

[0093] In step 322, the current insulin rate is decreased by 50% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step

318, described above to determine the next reading time and return control to step 290.

[0094] If it is determined, in step 320, that the current glucose reading does not represent a glucose drop of more than 75 mg/dl from the previous glucose reading, then control passes to step 330. In step 330, it is determined whether the current glucose reading represents a glucose drop of more than 10 mg/dl from the previous glucose reading.

[0095] If so, then control passes to step 332. In step 332, the current insulin rate is decreased by 25% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step 338.

[0096] In step 338, the time for the next reading time is set to be 60 minutes after the current reading time. Control then passes to step 290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

-99- [0097] If it is determined, in step 330, that the current glucose reading does not represent a glucose drop of more than 10 mg/dl from the previous glucose reading, then there has been a small decrease or an increase in glucose, and control passes to step 334. In step 334, the current insulin rate is maintained (i.e., decreased by 0%) to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step 338, described above, to set the next reading time and return control to step 290. [0098] FIG. 4 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a first range above the target range for step 400 of the flow diagram of FIG. 2D, according to an embodiment. In other embodiments step 400 includes one or more different or fewer steps from those depicted in FIG. 4. Control passes to step 300 from step 252, as shown in FIG. 2D.

[0099] In step 410, it is determined whether the current insulin rate is zero, such that a percentage change in insulin rate is meaningless. If so, then control passes to step 416. In step 416 the adjusted insulin rate is set equal to twice the minimum insulin rate. For example, using the default values, the adjusted insulin rate is set to 0.04 units per hour per kilogram. For non-pediatric cases, the adjusted insulin rate is set to 2 units per hour. Because the adjusted insulin rate is expressed as a multiple of the minimum rate, any insulin infusion units may be used. Control then passes to step 418. [0100] In step 418, the next reading time is set to be 30 minutes after the current reading time. Control then passes to step 290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

[0101] If it is determined in step 410 that the current insulin rate is not zero, then control passes to step 420. In step 420, it is determined whether the current glucose reading represents a glucose drop of more than 75 mg/dl from the previous glucose reading. If so, control passes to step 422.

[0102] In step 422, the current insulin rate is decreased by 50% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step 418, described above to determine the next reading time and return control to step 290. [0103] If it is determined, in step 420, that the current glucose reading does not represent a glucose drop of more than 75 mg/dl from the previous glucose reading, then control passes to step 430. In step 430, it is determined whether the current glucose reading represents a glucose drop of more than 30 mg/dl from the previous glucose reading.

[0104] If so, then control passes to step 432. In step 432, the current insulin rate is decreased by 30% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step 438.

[0105] In step 438, the time for the next reading time is set to be 60 minutes after the current reading time. Control then passes to step 290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

[0106] If it is determined, in step 430, that the current glucose reading does not represent a glucose drop of more than 30 mg/dl from the previous glucose reading, then there has been a small decrease or an increase in glucose, and control passes to step 434.

In step 434, the insulin rate is increased by the greater of 10% or the minimum insulin rate to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate or the minimum insulin rate, any insulin infusion units may be used. Control then passes to step 438, described above, to set the next reading time and return control to step 290.

[0107] FIG. 5 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a second range above the first range for step 500 of the flow diagram of FIG. 2D, according to an embodiment. In other embodiments step 500 includes one or more different or fewer steps from those depicted in FIG. 5. Control passes to step 500 from step 254, as shown in FIG. 2D.

[0108] In step 510, it is determined whether the current insulin rate is zero, such that a percentage change in insulin rate is meaningless. If so, then control passes to step 516.

In step 516 the adjusted insulin rate is set equal to three times the minimum insulin rate.

For example, using the default values, the adjusted insulin rate is set to 0.06 units per hour per kilogram. For non-pediatric cases, the adjusted insulin rate is set to 3 units per hour. Because the adjusted insulin rate is expressed as a multiple of the minimum rate, any insulin infusion units may be used. Control then passes to step 518. [0109] In step 518, the next reading time is set to be 30 minutes after the current reading time. Control then passes to step 290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

[0110] If it is determined in step 510 that the current insulin rate is not zero, then control passes to step 520. In step 520, it is determined whether the current glucose reading represents a glucose drop of more than 75 mg/dl from the previous glucose reading. If so, control passes to step 522.

[0111] In step 522, the current insulin rate is decreased by 50% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step

538.

[0112] In step 538, the next reading time is set to be 60 minutes after the current reading time. Control then passes to step 290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

[0113] If it is determined, in step 520, that the current glucose reading does not represent a glucose drop of more than 75 mg/dl from the previous glucose reading, then control passes to step 530. In step 530, it is determined whether the current glucose reading represents a glucose drop of more than 50 mg/dl from the previous glucose reading.

[0114] If so, then control passes to step 532. In step 532, the current insulin rate is decreased by 20% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step 538, described above, to set the next reading time and return control to step 290.

[0115] If it is determined, in step 530, that the current glucose reading does not represent a glucose drop of more than 50 mg/dl from the previous glucose reading, then there has been a small decrease or an increase in glucose, and control passes to step 534.

In step 534, the insulin rate is increased by at least 20% to determine the adjusted insulin rate. If 20% increase brings the adjusted insulin rate to less than 1.5 times the minimum rate, then the adjusted insulin rate is set to 1.5 times the minimum insulin rate. Thus, the adjusted rate is set to the greater of a 20% increase and 1.5 times the minimum insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate or a multiple of a minimum insulin rate, any insulin infusion units may be used.

Control then passes to step 538, described above, to set the next reading time and return control to step 290.

[0116] FIG. 6 is a flow diagram that illustrates a method to determine insulin rate when blood glucose is in a third range above the second range for a step 600 of the flow diagram of FIG. 2D, according to an embodiment. In other embodiments step 600 includes one or more different or fewer steps from those depicted in FIG. 6. Control passes to step 600 from step 254, as shown in FIG. 2D.

[0117] In step 610, it is determined whether the current insulin rate is zero, such that a percentage change in insulin rate is meaningless. If so, then control passes to step 616.

In step 616 the adjusted insulin rate is set equal to four times the minimum insulin rate.

For example, using the default values, the adjusted insulin rate is set to 0.08 units per hour per kilogram. For non-pediatric cases, the adjusted insulin rate is set to 4 units per hour. Because the adjusted insulin rate is expressed as a multiple of the minimum rate, any insulin infusion units may be used. Control then passes to step 618.

[0118] In step 618, the next reading time is set to be 30 minutes after the current reading time. Control then passes to step 290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

[0119] If it is determined in step 610 that the current insulin rate is not zero, then control passes to step 620. In step 620, it is determined whether the current glucose reading represents a glucose drop of more than 100 mg/dl from the previous glucose reading. If so, control passes to step 622.

[0120] In step 622, the current insulin rate is decreased by 50% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step

638.

[0121] In step 638, the next reading time is set to be 60 minutes after the current reading time. Control then passes to step 290 to administer insulin at the adjusted rate and take the next glucose reading at the next reading time.

[0122] If it is determined, in step 620, that the current glucose reading does not represent a glucose drop of more than 100 mg/dl from the previous glucose reading, then control passes to step 630. In step 630, it is determined whether the current glucose reading represents a glucose drop of more than 75 mg/dl from the previous glucose reading.

[0123] If so, then control passes to step 632. In step 632, the current insulin rate is decreased by 30% to determine the adjusted insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate, any insulin infusion units may be used. Control then passes to step 638, described above, to set the next reading time and return control to step 290.

[0124] If it is determined, in step 630, that the current glucose reading does not represent a glucose drop of more than 75 mg/dl from the previous glucose reading, then there has been a small decrease or an increase in glucose, and control passes to step 634. In step 634, the insulin rate is increased by at least 30% to determine the adjusted insulin rate. If 30% increase brings the adjusted insulin rate to less than twice the minimum rate, then the adjusted insulin rate is set to 2 times the minimum insulin rate. Thus, the adjusted rate is set to the greater of a 30% increase and 2 times the minimum insulin rate. Because the adjusted insulin rate is expressed as a percentage of the current insulin rate or a multiple of a minimum insulin rate, any insulin infusion units may be used. Control then passes to step 638, described above, to set the next reading time and return control to step 290.

2.4 DETERMINING INSULIN RATE IN ARBITRARY UNITS BY ALGORITHM [0125] In another embodiment of step 230, the insulin rate is determined using Equation 1, below. For example, in some embodiments, Equation 1 is used instead of step 250 and following steps of the decision tree of method 230' . In an illustrated embodiment, step 231 , step 232 and step 240 are still used to determine a response, should the patient's glucose level be below the target range. In some embodiments, the threshold steps in step 250 and following are used to determine next measurement time. In some embodiments, a next measurement time is based on the percent change of insulin rate. A change of more than a particular percentage causes the next glucose measurement time to be 30 minutes later. A smaller percentage change in insulin rate generates a next measurement time that is 60 minutes later or more.

[0126] In an illustrated embodiment, control passes from the "no" branch of step 240 to a substitute step to compute the insulin rate using Equation 1.

Inew = IRCnew * B Gcurrent² ( 1 ) where Inew is the new insulin rate, BGcurrent is the current blood glucose measurement and IRCnew is a newly computed Insulin resistance coefficient (IRC) that accounts for observed blood glucose responses to previous insulin rates in the particular patient being treated. IRCnew is computed based on Equations 2a through Equation 2c.

IRCprevious = Iprevious / (BGprevious) (2a)

CF = min(2, 1 + (BGcurrent - BGprevious) / BGprevious) (2b)

IRCnew = IRCprevious * CF (2c)

Where Iprevious is the previous insulin rate applied in the time interval immediately preceding the measurement of the current blood glucose (BGcurrent), and BGprevious is the previous blood glucose measurement, and CF is a correction factor. Any units may be used for Iprevious; Inew will be in the same units automatically as Iprevious. The notation min(a,b) indicates a function that selects the minimum value of a and b. Thus the maximum value of the correction factor, CF, is 2. Equation 1 is not used when Iprevious is zero, e.g., when the initiation procedure does not include an initial insulin rate and only two BG measurements are available. In that case, Inew = Imin, where Imin is the minimum insulin rate, described above. Equation 1, Equation 2a and Equation 2c can be combined into Equation 3.

Inew = CF * Iprevious * (BGcurrent/BGprevious)² (3)

Where CF is defined in Equation 2b.

[0127] It is assumed for purposes of illustration that Iprevious is 4 (arbitrary units), BGprevious is 123 mg/dl, BGcurrent is 143 mg/dl and that insulin rates are expressed only in whole units. Clearly, blood glucose has risen by 16% and the previous insulin rate is inadequate. An increased insulin rate is desired. According to Equation 2a, IRCprevious is 0.000264. According to Equation 2b, CF is 1.162602. A CF greater than one indicates that insulin resistance is greater than previously used. According to Equation 2c, IRCnew is increased to 0.000307. Then, according to Equation 1, Inew = 6.28 which is rounded to the minimum increments of whole insulin units, which is 6. [0128] In other embodiments, other variations of the Equation 1 and Equation 2a through Equation 2c are used. For example, in some embodiments IRCprevious is based on BGcurrent rather than on BGprevious in Equation 2a; or is based on insulin rate before the measurement of BGprevious, rather than on the insulin rate before the measurement of BGcurrent. 3.0 IMPLEMENTATION MECHANISMS -- HARDWARE OVERVIEW [0129] FIG. 7 illustrates a computer system 700 upon which an embodiment of the invention may be implemented. Computer system 700 includes a communication mechanism such as a bus 710 for passing information between other internal and external components of the computer system 700. Information is represented as physical signals of a measurable phenomenon, typically electric voltages, but including, in other embodiments, such phenomena as magnetic, electromagnetic, pressure, chemical, molecular atomic and quantum interactions. For example, north and south magnetic fields, or a zero and non-zero electric voltage, represent two states (0, 1) of a binary digit (bit). A sequence of binary digits constitutes digital data that is used to represent a number or code for a character. A bus 710 includes many parallel conductors of information so that information is transferred quickly among devices coupled to the bus 710. One or more processors 702 for processing information are coupled with the bus 710. A processor 702 performs a set of operations on information. The set of operations include bringing information in from the bus 710 and placing information on the bus 710. The set of operations also typically include comparing two or more units of information, shifting positions of units of information, and combining two or more units of information, such as by addition or multiplication. A sequence of operations to be executed by the processor 702 constitute computer instructions.

[0130] Computer system 700 also includes a memory 704 coupled to bus 710. The memory 704, such as a random access memory (RAM) or other dynamic storage device, stores information including computer instructions. Dynamic memory allows information stored therein to be changed by the computer system 700. RAM allows a unit of information stored at a location called a memory address to be stored and retrieved independently of information at neighboring addresses. The memory 704 is also used by the processor 702 to store temporary values during execution of computer instructions. The computer system 700 also includes a read only memory (ROM) 706 or other static storage device coupled to the bus 710 for storing static information, including instructions, that is not changed by the computer system 700. Also coupled to bus 710 is a non-volatile (persistent) storage device 708, such as a magnetic disk or optical disk, for storing information, including instructions, that persists even when the computer system 700 is turned off or otherwise loses power. [0131] Information, including instructions, is provided to the bus 710 for use by the processor from an external input device 712, such as a keyboard containing alphanumeric keys operated by a human user, or a sensor. A sensor detects conditions in its vicinity and transforms those detections into signals compatible with the signals used to represent information in computer system 700. Other external devices coupled to bus 710, used primarily for interacting with humans, include a display device 714, such as a cathode ray tube (CRT) or a liquid crystal display (LCD), for presenting images, and a pointing device 716, such as a mouse or a trackball or cursor direction keys, for controlling a position of a small cursor image presented on the display 714 and issuing commands associated with graphical elements presented on the display 714. [0132] In the illustrated embodiment, special purpose hardware, such as an application specific integrated circuit (IC) 720, is coupled to bus 710. The special purpose hardware is configured to perform operations not performed by processor 702 quickly enough for special purposes. Examples of application specific ICs include graphics accelerator cards for generating images for display 714, cryptographic boards for encrypting and decrypting messages sent over a network, speech recognition, and interfaces to special external devices, such as robotic arms and medical scanning equipment that repeatedly perform some complex sequence of operations that are more efficiently implemented in hardware. Logic encoded in one or more tangible media includes one or both of computer instructions and special purpose hardware [0133] Computer system 700 also includes one or more instances of a communications interface 770 coupled to bus 710. Communication interface 770 provides a two-way communication coupling to a variety of external devices that operate with their own processors, such as printers, scanners and external disks. In general the coupling is with a network link 778 that is connected to a local network 780 to which a variety of external devices with their own processors are connected. For example, communication interface 770 may be a parallel port or a serial port or a universal serial bus (USB) port on a personal computer. In some embodiments, communications interface 770 is an integrated services digital network (ISDN) card or a digital subscriber line (DSL) card or a telephone modem that provides an information communication connection to a corresponding type of telephone line. In some embodiments, a communication interface 770 is a cable modem that converts signals on bus 710 into signals for a communication connection over a coaxial cable or into optical signals for a communication connection over a fiber optic cable. As another example, communications interface 770 may be a local area network (LAN) card to provide a data communication connection to a compatible LAN, such as Ethernet. Wireless links may also be implemented. For wireless links, the communications interface 770 sends and receives electrical, acoustic or electromagnetic signals, including infrared and optical signals, that carry information streams, such as digital data. Such signals are examples of carrier waves.

[0134] The term computer-readable medium is used herein to refer to any medium that participates in providing information to processor 702, including instructions for execution. Such a medium may take many forms, including, but not limited to, nonvolatile media, volatile media and transmission media. Non- volatile media include, for example, optical or magnetic disks, such as storage device 708. Volatile media include, for example, dynamic memory 704. Transmission media include, for example, coaxial cables, copper wire, fiber optic cables, and waves that travel through space without wires or cables, such as acoustic waves and electromagnetic waves, including radio, optical and infrared waves. Signals that are transmitted over transmission media are herein called carrier waves.

[0135] Common forms of computer-readable media include, for example, a floppy disk, a flexible disk, a hard disk, a magnetic tape, or any other magnetic medium, a compact disk ROM (CD-ROM), a digital video disk (DVD) or any other optical medium, punch cards, paper tape, or any other physical medium with patterns of holes, a RAM, a programmable ROM (PROM), an erasable PROM (EPROM), a FLASH-EPROM, or any other memory chip or cartridge, a carrier wave, or any other medium from which a computer can read.

[0136] Network link 778 typically provides information communication through one or more networks to other devices that use or process the information. For example, network link 778 may provide a connection through local network 780 to a host computer 782 or to equipment 784 operated by an Internet Service Provider (ISP). ISP equipment 784 in turn provides data communication services through the public, world-wide packet- switching communication network of networks now commonly referred to as the Internet 790. A computer called a server 792 connected to the Internet provides a service in response to information received over the Internet. For example, server 792 provides information representing video data for presentation at display 714. [0137] The invention is related to the use of computer system 700 for implementing the techniques described herein. According to one embodiment of the invention, those techniques are performed by computer system 700 in response to processor 702 executing one or more sequences of one or more instructions contained in memory 704. Such instructions, also called software and program code, may be read into memory 704 from another computer-readable medium such as storage device 708. Execution of the sequences of instructions contained in memory 704 causes processor 702 to perform the method steps described herein. In alternative embodiments, hardware, such as application specific integrated circuit 720, may be used in place of or in combination with software to implement the invention. Thus, embodiments of the invention are not limited to any specific combination of hardware and software.

[0138] The signals transmitted over network link 778 and other networks through communications interface 770, which carry information to and from computer system 700, are example forms of carrier waves. Computer system 700 can send and receive information, including program code, through the networks 780, 790 among others, through network link 778 and communications interface 770. In an example using the Internet 790, a server 792 transmits program code for a particular application, requested by a message sent from computer 700, through Internet 790, ISP equipment 784, local network 780 and communications interface 770. The received code may be executed by processor 702 as it is received, or may be stored in storage device 708 or other nonvolatile storage for later execution, or both. In this manner, computer system 700 may obtain application program code in the form of a carrier wave.

[0139] Various forms of computer readable media may be involved in carrying one or more sequence of instructions or data or both to processor 702 for execution. For example, instructions and data may initially be carried on a magnetic disk of a remote computer such as host 782. The remote computer loads the instructions and data into its dynamic memory and sends the instructions and data over a telephone line using a modem. A modem local to the computer system 700 receives the instructions and data on a telephone line and uses an infra-red transmitter to convert the instructions and data to an infra-red signal, a carrier wave serving as the network link 778. An infrared detector serving as communications interface 770 receives the instructions and data carried in the infrared signal and places information representing the instructions and data onto bus 710. Bus 710 carries the information to memory 704 from which processor 702 retrieves and executes the instructions using some of the data sent with the instructions. The instructions and data received in memory 704 may optionally be stored on storage device 708, either before or after execution by the processor 702.

4.0 EXTENSIONS AND ALTERNATIVES

[0140] In the foregoing specification, the invention has been described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.

Claims

CLAIMSWhat is claimed is:

1. A method for determining insulin drip rate for a patient, comprising: receiving target selection data that indicates a particular target glucose level for a patient among a plurality of target glucose levels for a patient; receiving current glucose data that indicates a most recent measurement of blood glucose level for a particular patient; receiving previous glucose data that indicates a blood glucose level for the particular patient at a time before the most recent measurement of blood glucose level for the particular patient by more than about fifteen minutes; receiving current insulin data that indicates a rate at which insulin is currently being administered intravenously to the particular patient; and determining, based on the target selection data and the current glucose data and the previous glucose data and the current insulin data, recommended insulin data that indicates a rate at which insulin should be administered to the particular patient to achieve the particular target glucose level.

2. A method as recited in Claim 1, further comprising determining, based on the current glucose data and the previous glucose data, recommended measurement data that indicates a time at which to make a next measurement of blood glucose level for the particular patient.

3. A method as recited in Claim 1, said step of determining recommended insulin data further comprising determining a corrected insulin resistance coefficient based on the current insulin data and a change in measured blood glucose level based on the current glucose data and the previous glucose data.

4. A method as recited in Claim 1, said step of determining recommended insulin data further comprising determining recommended insulin data that indicates a percentage change in the current insulin data, whereby insulin rate may be expressed in any units including units per hour per kilogram used in pediatric care.

5. A method as recited in Claim 1, said step of determining recommended insulin data further comprising determining recommended insulin data that indicates a multiple of a minimum insulin rate when the current insulin data indicates that no insulin is currently administered to the particular patient, whereby insulin rate may be expressed in any units including units per hour per kilogram used in pediatric care.

6. A method as recited in Claim 1 , wherein: the method further comprises presenting a first prompt to a user for a current blood glucose level of a patient, presenting a second prompt to a user to confirm the current glucose data, in response to presenting the second prompt, receiving glucose confirmation data that indicates whether the current glucose data is correct, and determining whether the current glucose data is correct based on the glucose confirmation data; said step of receiving current glucose data is performed in response to presenting the first prompt; and said step of determining recommended insulin data is performed only if it is determined that the current glucose data is correct.

7. A method as recited in Claim 6, further comprising, if it is determined that the current glucose data is not correct, then returning to said step of presenting the first prompt to the user for the current blood glucose level of a patient:

8. A method as recited in Claim 7, further comprising, if it is determined that the current glucose data is not correct, then presenting an alert to the user to warn of dangerous conditions.

9. A method as recited in Claim 6, said step of presenting the second prompt to the user to confirm the current glucose data further comprising presenting an alert to the user to warn of dangerous conditions.

10. A method as recited in Claim 1, further comprising: determining whether the current glucose data indicates hypoglycemic conditions in the particular patient, and if it is determined that the current glucose data indicates hypoglycemic conditions in the particular patient, then presenting recommended dextrose data that indicates an extra amount of dextrose to be administered intravenously to the particular patient.

11. A method as recited in Claim 1 , further comprising before said step of receiving the current glucose data performing the steps of: prompting a user to obtain and input initiation orders that include an initial time for starting intravenous administration of insulin to the particular patient, initial insulin data that indicates a rate at which insulin is administered intravenously to the particular patient, and initial measurement data that indicates a time to make a first blood glucose measurement after starting intravenous administration of insulin to the particular patient; receiving initial glucose data that indicates a first blood glucose measurement after starting intravenous administration of insulin to the particular patient; and determining, based on the initial glucose data, recommended insulin data that indicates a rate at which insulin should be administered intravenously to the particular patient and recommended measurement data that indicates a time at which to make a next measurement of blood glucose level for the particular patient.

12. A method as recited in Claim 11, further comprising: determining whether the initial glucose data indicates hypoglycemic conditions in the particular patient, and if it is determined that the initial glucose data indicates hypoglycemic conditions in the particular patient, then presenting recommended dextrose data that indicates an extra amount of dextrose to be administered intravenously to the particular patient.

13. A method as recited in Claim 1, further comprising the steps of: receiving data that indicates the particular patient is to transition from intravenous administration of insulin to subcutaneous administration of insulin; and in response to receiving data that indicates the particular patient is to transition from intravenous administration of insulin to subcutaneous administration of insulin, then performing the steps of: prompting the user to administer a first dose of insulin subcutaneously; presenting final recommended insulin data that indicates a rate at which insulin should be administered intravenously to the particular patient after administering the first dose of insulin subcutaneously, and presenting transition time data that indicates a time to terminate intravenous administration of insulin, and presenting recommended measurement data that indicates a time at which to make a measurement of blood glucose level for the particular patient after the time to terminate intravenous administration of insulin.

14. Logic encoded in one or more tangible media for execution and, when executed, operable to perform the steps of: receiving target selection data that indicates a particular target glucose level for a patient among a plurality of target glucose levels for a patient; receiving current glucose data that indicates a most recent measurement of blood glucose level for a particular patient; receiving previous glucose data that indicates a blood glucose level for the particular patient at a time before the most recent measurement of blood glucose level for the particular patient by more than about fifteen minutes; receiving current insulin data that indicates a rate at which insulin is currently being administered intravenously to the particular patient; and determining, based on the target selection data and the current glucose data and the previous glucose data, recommended insulin data that indicates a rate at which insulin should be administered to the particular patient to achieve the particular target glucose level.

15. An apparatus comprising: a glucometer configured to receive a blood sample and to output glucose data that indicates a blood glucose level; computer readable medium configured to store glucose data; and logic encoded in one or more tangible media for execution and, when executed, operable to perform the steps of: receiving from the computer readable medium current glucose data that indicates a most recent measurement of blood glucose level for a particular patient; receiving from the computer readable medium previous glucose data that indicates a blood glucose level for the particular patient at a time before the most recent measurement of blood glucose level for the particular patient by more than about fifteen minutes; and determining, based on the current glucose data and the previous glucose data, recommended insulin data that indicates a rate at which insulin should be administered to the particular patient.

16. A method for determining insulin drip rate for a patient, comprising: receiving BGcurrent that indicates a most recent measurement of blood glucose level for a particular patient; receiving BGprevious that indicates a blood glucose level for the particular patient at a time before the most recent measurement of blood glucose level for the particular patient by more than about fifteen minutes; receiving Iprevious that indicates a rate at which insulin is currently being administered intravenously to the particular patient; and determining a new insulin rate, Inew, as directly proportional to the quantity Iprevious * (BGcurrent/BGprevious)² .

17. A method as recited in Claim 16, said step of determining a new insulin rate, Inew, further comprising determining Inew according to Inew = CF * Iprevious * (BGcurrent/BGprevious)², wherein CF = 1 + (BGcurrent - BGprevious)/BGprevious.