Managing fluid levels in patient and associated devices, systems and methods

Abstract

To provide management of fluid levels in a patient and associated devices, systems and methods.SOLUTION: Devices, systems, and methods for delivering fluid therapy to a patient are disclosed herein. An exemplary method can comprise the steps of: obtaining a urine output rate from a patient; causing a diuretic to be provided to the patient at a dosage rate, where the dosage rate is increased over a period of time such that the urine output rate increases to be above a predetermined threshold within the period of time; and causing a hydration fluid to be provided to the patient at a hydration rate. The hydration rate can be set based on the urine output rate to drive net fluid loss from the patient.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 945,058, filed December 6, 2019, the disclosure of which is incorporated herein by reference in its entirety.

[0002] The present disclosure relates to methods, devices, systems, and algorithms for managing patient fluid levels and, in certain embodiments, for treating fluid overload conditions in patients with heart failure. [Background technology]

[0003] The human physiological system naturally strives to maintain a balance between fluid intake and fluid excretion. When there is a fluid imbalance, a patient may suffer from fluid overload, in which an excessive amount of fluid is retained. A patient may be in a fluid overload condition due to acute decompensated heart failure (ADHF), chronic heart failure (CHF), or other conditions in which insufficient fluid is excreted to avoid fluid overload in the body. A patient in fluid overload may suffer from shortness of breath (called dyspnea), edema, high blood pressure, and other undesirable medical conditions that are symptoms of fluid overload.

[0004] To treat fluid overload, patients are typically treated with diuretics, which induce and / or enhance urine production. Producing and excreting urine reduces the amount of fluid and sodium in the body, thus treating fluid overload conditions. Diuretics can be given orally as tablets or as an IV (intravenous) injection. IV diuretics are typically used when oral diuretics are no longer effective or cannot be absorbed. When referring to "diuretics," authors are primarily referring to IV diuretics. Common loop diuretics are diuretics that act on the ascending limb of the loop of Henle in the kidney. Examples of loop diuretics include bumetanide (Bumex®), ethacrynic acid (Edecrin®), furosemide (Lasix®), and torsemide (Demadex®).

[0005] The short-term effects of diuretics on urine production are not sufficiently predictable to allow for the administration of high doses in the early stages of treatment. For example, one patient may produce much less urine than expected for a given dose of diuretic, while another patient receiving the same dose may produce an excessive amount of urine. This raises concerns about hypotension (low blood pressure) and vital organ damage in patients. As a result, it is difficult to predict which patients will respond to a certain dose of diuretic by excreting no or too little urine, and which patients will respond by excreting excessive amounts of urine.

[0006] The potential for substantially different responses and therapeutic outcomes in response to the same diuretic dose creates uncertainty for physicians, such that safe and correct diuretic dosing for an individual patient requires monitoring the patient's clinical signs and symptoms over a period of time. Because of these uncertainties, physicians may initially prescribe a conservative (low) diuretic dose and wait several hours before considering whether to increase the dose. A conservative low-dose approach begins with a low diuretic dose and slowly and piecemeal increases the dose until the patient's urination reaches a threshold level, e.g., rate. Slowly increasing the diuretic dose avoids causing excessive urination, which can lead to hypovolemia and other undesirable conditions.

[0007] The current standard practice for treating fluid overload in ADHF and CHF uses a conservative, low-dose approach that allows for prolonged treatment time to alleviate the fluid overload condition in patients. Typically, physicians increase diuretic doses at 6- to 12-hour intervals. These long intervals are often necessary to allow the patient to respond to the new diuretic dose level and produce urine at the rate induced by the new diuretic level. At the end of each interval, the physician determines whether the diuretic dose should be changed, e.g., increased, to bring the patient to the desired level of urine production. Because these intervals are typically several hours in length, it may take 6 hours, 12 hours, a day, or longer to determine a safe and effective diuretic dose level. For example, in patients who have not previously received loop diuretic therapy, an initial IV furosemide dose of 20 to 40 mg is reasonable. The maximum diuretic dose recommended by regulatory guidelines is a 40 to 80 mg furosemide-equivalent IV bolus. The dose can then be titrated up to a maximum intravenous dose of 80 to 100 mg of furosemide as urinary output increases. Patients who develop any tolerance to diuretics may need to have their dose increased.

[0008] One aspect of this conservative approach to reducing fluid overload is that it may prolong a patient's symptoms associated with fluid overload while a physician determines and administers a safe and effective diuretic dosage to achieve a desired urination rate. One drawback of this delay is that the clinical condition underlying the fluid overload condition may worsen due to the prolonged fluid overload condition. For example, a delay of many hours or days may occur before urination reaches a desired level that causes significant fluid loss and alleviates the patient's fluid overload condition. Another drawback is that the patient may be hospitalized for several days (e.g., 4-5 days), which is costly. In addition, even after receiving conventional treatment to reduce fluid overload, approximately 23% of patients are re-admitted for fluid overload within 30 days. Consequently, there is a long-felt need to reduce the time required to increase urination in patients using diuretics and to allow patients to more rapidly excrete sufficient urine to reduce the fluid overload condition.

[0009] Another concern with using diuretics to treat fluid overload conditions arises when a patient's urine flow reaches a high rate. While a high urine flow rate is beneficial in rapidly reducing fluid overload conditions, a high urine flow rate carries the risk of excessively reducing the blood volume in the vascular system and increasing electrolyte excretion. Rapid removal of electrolytes can lead to electrolyte imbalance (e.g., potassium loss), which can further worsen the patient's clinical condition. These risks and side effects of IV diuretics, often referred to as hypovolemia and hypokalemia, are known and unnecessary risks, and an unmet clinical need exists for this necessary and commonly used therapy.

[0010] Excessive urinary flow, for example, greater than 2.5 liters per day, can lead to hypovolemia, hypokalemia, and other undesirable medical conditions. The risk of excessive urinary flow caused by conventional fluid overload treatments, such as by using diuretics, is traditionally mitigated by limiting the rate at which urinary flow is induced. Limiting urinary flow tends to increase the duration required to reduce fluid overload conditions in a patient.

[0011] To avoid these drawbacks, the approved dosages of certain diuretics have been limited to at least partially avoid or reduce the risk of hypovolemia, hypokalemia, and other such undesirable medical conditions associated with excessively low intravascular blood volume. For example, in patients not previously exposed to loop diuretics (diuretic-naive), furosemide diuretic is recommended to be administered intravenously (IV) at an initial dose of 20 milligrams per hour (mg / hr) and can be increased only every 6 to 12 hours. In heart failure patients who routinely take oral diuretics, the initial dose and incremental dose increases must be adjusted by significant amounts, further complicating therapy titration.

[0012] Conventional practice dictates that dosage levels are not increased once a certain level of urination is reached. Other commonly prescribed diuretics, such as loop diuretics such as bumetanide and torsemide, thiazide diuretics such as hydrochlorothiazide and metolazone, potassium-sparing diuretics such as spironolactone, and carbonic anhydrase inhibitors such as acetazolamide, are similarly believed to have regulatory dosage limits to prevent excessive urine flow and the potential side effects of these drugs. Summary of the Invention [Problem to be solved by the invention]

[0013] The primary purpose of hospitalization in heart failure patients is to remove excess fluid. However, in the United States, for the majority of hospitalized heart failure patients, total fluid loss is less than 5 pounds (2.3 kilograms), and this loss generally does not achieve effective relief from the fluid overload condition. Therefore, there remains a need to improve conventional fluid management techniques to achieve greater net fluid loss from patients within a shorter time frame. [Means for solving the problem]

[0014] Embodiments of the present technology address the need for improved advances in patient fluid management, for example, by creating an at least partially automated system that enables safe diuretic administration, high diuretic efficacy, and at least mild diuretic tolerance while preserving valuable hospital resources and patient comfort. As described herein, clinical trials of embodiments of the present technology have resulted in rapid decongestion, removal of excess fluid, and increased sodium excretion, each with improved efficacy and / or speed. For example, whereas conventional systems and methods for treating fluid overload require hospitalization for more than several days (e.g., 4-5 days), embodiments of the present technology can diagnose and / or alleviate fluid overload conditions within 1-2 days.

[0015] The present technology relates to methods, devices, systems, and algorithms for reducing fluid levels in fluid-overloaded patients, e.g., patients suffering from ADHF, CHF, or other conditions that result in fluid overload. In some embodiments, an exemplary method includes a diuretic treatment regimen having multiple phases, including Phases I, II, and III. Phase I can include determining an appropriate patient-specific diuretic dosage, which can be performed iteratively. For example, in some embodiments, during the first iteration of Phase I, an initial diuretic dosage is delivered to the patient, possibly automatically. The dosage is increased during Phase I in incremental steps, e.g., piecewise incrementally, and / or in an exponential manner. For example, the dosage can be increased in steps every two to three minutes. The dosage can be increased until the patient reaches a desired urination level or rate or until an upper threshold is reached. The initial diuretic dosage provided to the patient is at the beginning of treatment, and subsequent dosages can be responsive to urination decreasing below the threshold and / or falling outside the threshold range. The threshold can define a maximum (eg, total) amount of diuretic given to the patient, a maximum rate at which diuretic is given to the patient, or a maximum duration for Phase I, such as 1 hour.

[0016] Phase II is optional and can wait for the patient to respond to the diuretic dose given during Phase I. After urination reaches a desired level during Phase I, Phase II can involve delivering a diuretic to the patient at a constant maintenance dose level for an extended period of time (e.g., at least 1 hour, at least 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, or 36 hours). The maintenance dose level is calculated based on the diuretic dose in Phase I that resulted in urination higher than the desired level of urination.

[0017] Phase III is optional and can proceed simultaneously with Phase II. During Phase III, diuretic administration continues, and the net fluid level in the patient (e.g., a patient producing above a threshold urine level in response to Phase I) can be rapidly reduced by infusing hydration fluid or a hydration solution (e.g., saline) into the patient. The hydration fluid infused into the patient during Phase III can be automatically adjusted (i) to match urination during relatively low urine rates, (ii) to reduce hydration fluid to less than urination (e.g., to at least 10%, 20%, 30%, 40%, or 50% of urination) during a range of higher urine rates, and / or (iii) to maintain a substantially constant hydration fluid rate (e.g., in the range of 10% to 20% of the maximum hydration fluid rate) while urination exceeds the upper urinary threshold. During Phase III, the maintenance dose of diuretic can be adjusted by resuming Phase I and initiating diuretic re-titration (e.g., in an exponential manner). Phase I can be resumed by continuing where it was last stopped, or by repeating Phase I from the initial starting point.

[0018] Concurrent with the diuretic regimen described above, the amount or rate of hydration solution given to the patient can be related to the amount or rate of urination. For example, the amount or rate of hydration solution delivered to the patient can be lower than the amount or rate of urination at higher urination levels. The rate of hydration solution infusion can be adjusted to match the urination rate over a specific period of time (e.g., the first hour of therapy) and / or for a threshold volumetric amount (e.g., at least 250 milliliters (ml) of urine produced). The rate of hydration solution infusion can remain constant while the urine rate exceeds a threshold high urine rate.

[0019] The maintenance diuretic dose for Phases II and III can be calculated based on a percentage (e.g., 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%), such as in the range of 100% to 10%, of the maximum dose of diuretic given during Phase I. The percentage reduction in the maximum continuous maintenance dose can be the ratio of the diuretic dose (amount or rate) reached during Phase I that resulted in urination higher than the desired level of excretion to the upper threshold maximum diuretic dose or maximum diuretic rate during Phase I.

[0020] If urination reaches an upper threshold (e.g., the total amount of diuretic delivered to the patient) before reaching a desired output during Phase I, the patient can be diagnosed with diuretic resistance and a different diuretic or treatment can be administered to the patient. Such treatment can include ultrafiltration and / or the use of an artificial pump (e.g., an intravenous pump) to allow the kidneys to produce more urine. If urination falls below the lower urinary threshold for a predetermined period of time during Phase III, the regimen can repeat Phase I to induce more urination and identify a more effective diuretic dosage level (e.g., a higher diuretic dosage).

[0021] Phase I can be resumed if urination (e.g., rate or volume) falls below the micturition threshold during Phase I, II, or III. Phase I can be resumed at the diuretic administration rate given at the end of the previous iteration of Phase I if continued from where it was last stopped. At the end of each iteration of Phase I, a maintenance diuretic dose can be calculated based on the total amount of diuretic given during all iterations of Phase I.

[0022] Phases I and III can be applied as independent treatments. For example, an operator (e.g., a physician, healthcare professional, or nurse) can determine an initial diuretic dosage in a conventional manner and then treat the patient using the Phase III portion of the regimen. Similarly, the operator can quickly determine an effective diuretic dosage to achieve a desired urination rate using the Phase I portion of the regimen and then choose not to adjust the maintenance diuretic dosage or not to infuse hydration fluid into the patient, or can choose a different relationship between diuretic administration, urination, and hydration fluid solution infusion than that proposed in Phase III. Furthermore, Phase II is optional and can begin immediately after Phase I.

[0023] The present technology can include a method of treating a patient suffering from fluid overload, including, for example, automatically administering a diuretic to the patient to increase the patient's urination; determining urination by the patient during administration of the diuretic; infusing hydration fluid into the patient; and automatically adjusting the rate of hydration fluid infused into the patient to achieve a desired net fluid loss in the patient. In some embodiments, the method can include automatically adjusting the rate of hydration fluid based on the difference between urination and the desired net fluid loss. The automatic adjustment of the hydration fluid rate can be calculated based on a current increase in the rate of urination, such that the increase in the rate of hydration fluid is reduced in response to urination being higher than a first threshold output, e.g., the current urination rate. Additionally or alternatively, the automatic adjustment of the hydration fluid rate can include increasing the hydration fluid rate to a rate within 10% of the current urination rate until the current urination rate reaches the first threshold output. The first threshold output can be a urination rate or equivalent urination volume within 200 ml / hr to 240 ml / hr. The rate of hydration fluid infusion can be limited to a maximum limit for hydration fluid while the current urination rate is above a second threshold, above 500 ml / hr, above 700 ml / hr, or above 1020 ml / hr.

[0024] In some embodiments, the method may include limiting the rate of hydration fluid infusion to a maximum limit for the hydration fluid, maintaining the hydration fluid infusion rate at a maximum limit while urination exceeds a maximum threshold urination rate, terminating therapy when net fluid loss reaches a desired amount therefor, automatically adjusting the diuretic administered to the patient based on urination, increasing the rate of diuretic being administered until urination reaches a desired minimum urination value that is a minimum urination rate, and / or automatically adjusting the diuretic by increasing the diuretic level at intervals of 5 minutes or less, e.g., 2 to 3 minutes, until urination reaches a desired minimum urination value. In some embodiments, for example, each increase in diuretic level during the diuretic dosage determination phase or ramp can be a greater increase than the immediately preceding increase.

[0025] In some embodiments, the method can include determining a low diuretic administration rate in response to urination reaching a desired minimum urine volume or urine rate. The low diuretic administration rate is lower than the diuretic administration rate at which urination reaches the desired minimum urine volume or urine rate. The diuretic can be administered at a low rate for a period of at least one hour, e.g., a two-, three-, or four-hour period. This low diuretic administration rate can include reducing the diuretic infusion rate to a very low rate until the measured urine rate falls below a desired threshold or until a period of time, e.g., one hour, has elapsed. The diuretic administration rate can then be calculated based on the time required for the urine rate to fall to the desired threshold, or can be reduced by a predetermined percentage (such as 25%) if urination remains above the threshold when the very low infusion rate period is complete.

[0026] In some embodiments, a method of treatment or automated regimen for managing or optimizing net fluid volume removal and / or improving the quality of urine removed includes an initial personalized diuretic dosage determination phase, followed by a fluid reduction phase. During the diuretic dosage determination phase, the patient's urinary response to a diuretic administered at increasing levels within a predetermined time period is evaluated to establish the diuretic dosage to be used in subsequent phases and / or to assess whether the patient is diuretic resistant. During the fluid reduction phase, a diuretic is infused at the established diuretic dosage, replacing a portion of urine production with hydration fluid, for example, to maintain intravascular volume and / or to halt salt and water retention mechanisms to optimize net volume removal. Urine output is continuously monitored throughout fluid therapy. Diuretic dosage can be adjusted based on urination rate. For example, very low urination (e.g., below 25 ml / hr averaged over the previous 15 minutes) may indicate a malfunction or improper setting of the device, and a warning can be provided to the user. As another example, low urination (e.g., low urination can be defined as less than 325 ml / hr averaged over the previous three hours or by an integral debt function where the debt is greater than 150 ml over the previous three hours) can indicate that a higher diuretic dose may be warranted and the diuretic dose may be re-established. For example, the user may choose to re-enter the diuretic dose determination phase or manually increase the dose. As another example, high urination (e.g., greater than 625 ml / hr averaged over the previous three hours) may indicate that too much diuretic is being infused, and the infused diuretic may be reduced over a period of time (e.g., to 0-0.4 ml / hr over 50 minutes or until urination drops below 525 ml / hr), and a new diuretic dose may be established. For example, the new dose may be a fraction of the previous dose based on how rapidly urination has decreased during this period, or by re-entering the dose determination phase. Additionally, hydration fluid can be infused throughout the fluid reduction phase based on urination.

[0027] The technology of the present invention can be embodied as a fluid management system comprising a hydration fluid pump configured to pump hydration fluid into a patient; a diuretic pump configured to pump a diuretic into the patient; a measurement device configured to measure the patient's urine output; and a computer executing an algorithm configured to determine the amount or rate of the patient's urine output, automatically inject the diuretic into the patient by controlling the diuretic pump to deliver the diuretic at an administration rate determined by the algorithm, automatically infuse hydration fluid into the patient by controlling the hydration fluid pump, and automatically adjust the rate or amount of hydration fluid infused into the patient to achieve a desired level or rate of net fluid loss or net sodium loss in the patient.

[0028] The algorithm can be configured to determine automatic adjustment of the hydration fluid rate based on the difference between urination and the desired net fluid change, and / or to limit the hydration fluid infusion rate to a maximum limit for the hydration fluid, and / or to maintain the hydration fluid infusion rate at a maximum limit while urination exceeds a maximum threshold urination rate, and / or to stop administration of a diuretic when net fluid loss reaches a desired amount. Additionally or alternatively, the computer algorithm can be configured to automatically adjust the diuretic administered to the patient based on urination. Automatic adjustment of the diuretic can include increasing the rate of the diuretic being administered until urination reaches a desired minimum urinary value, such as a minimum urination rate. Adjustment of the diuretic can include automatically increasing the level of the diuretic at intervals of 5 minutes or less until urination reaches the desired minimum urinary value, with at least one of these increases in the diuretic level being greater than the immediately preceding increase. Each increase in the diuretic level is greater than the immediately preceding increase. The automatic adjustment of the diuretic may include, in response to urination reaching a desired minimum urine value or minimum urine rate, calculating a lower rate for diuretic administration that is lower than or based on the value of the diuretic administered when urination reached the desired minimum urine value or minimum urine rate, and administering the diuretic at the lower rate for a period of at least one hour.

[0029] The features, aspects, and advantages of the techniques of the present disclosure may be better understood in connection with the following drawings. [Brief explanation of the drawings]

[0030] [Figure 1] FIG. 1 is a schematic diagram of a patient hydration system configured to monitor urination and control fluid infusion into a patient in accordance with an embodiment of the present technology. [Figure 2A] FIG. 1 is a graphical representation showing a timeline of diuretic doses dispensed by a fluid management system during a treatment regimen in accordance with an embodiment of the present technology. [Figure 2B] FIG. 2B is a graphical representation showing a timeline of urine flow achieved by diuretics dispensed by the fluid management system during the treatment regimen of FIG. 2A. [Figure 3] FIG. 10 is a graphical representation showing the relationship between urination, hydration fluid infusion, and net fluid loss in accordance with an embodiment of the present technology. [Figure 4A] 1 is a flow diagram for controlling diuretic dosage during a diuretic dosage determination phase according to an embodiment of the present technology. [Figure 4B] FIG. 10 is a graphical representation illustrating the relationship between diuretic administration rate and total diuretic delivered in accordance with an embodiment of the present technology. [Figure 5] 1 is a flow diagram of a continuous injection phase or a fluid reduction phase according to an embodiment of the present technology. [Figure 6] FIG. 1 is a graphical representation of diuretic administration rate and corresponding urination rate in accordance with an embodiment of the present technology. [Figure 7] 1 is a flow chart illustrating tapering or decreasing a diuretic administration rate according to an embodiment of the present technology. [Figure 8] FIG. 1 is a graphical representation of the steps of tapering or reducing a diuretic administration rate according to an embodiment of the present technology. [Figure 9] FIG. 10 is a graphical representation of the relationship between urination rate, hydration fluid infusion rate, and net fluid balance in accordance with an embodiment of the present technology. [Figure 10] 1 is a flow diagram of a method for causing net fluid loss from a patient according to an embodiment of the present technology. [Figure 11] 1 is a flow diagram of a method for causing net fluid loss from a patient according to an embodiment of the present technology.

[0031] Those skilled in the art will appreciate that the features shown in the drawings are for illustrative purposes and that variations are possible, including different and / or additional features and arrangements thereof. DETAILED DESCRIPTION OF THE INVENTION

[0032] I. Overview of Devices, Systems, and Related Methods for Managing Fluid Levels Disclosed herein are devices, systems, and related methods for managing patient fluid levels. Compared to current fluid management systems, embodiments of the present technology can improve the effectiveness, safety, and quality of fluid management treatments, improve resource management within hospitals, rapidly assess whether a patient has diuretic resistance, and / or increase diuretic efficiency. Diuretic efficiency can be defined as the amount of urine and / or excreted sodium obtained over a given time period per milligram of diuretic infused intravenously. One expected result of the present technology is that diuretic efficiency can be increased by intravenous infusion of a hydration fluid containing sodium and / or chloride. This is counterintuitive, since the goal of fluid therapy is the net removal of salts (e.g., sodium and chloride) and fluid. As described herein, embodiments of the present technology can increase the net removal of fluid and sodium while also increasing the rate of hydration and the rate of both urine excretion or urination, and in some embodiments, increasing the urine excretion rate more than the rate of hydration fluid infusion. Increasing diuretic efficiency, as opposed to increasing diuretic dosage, as achieved by embodiments of the present technology is a clinically appropriate and beneficial therapy because it allows for the treatment of fluid overload conditions in a more efficient manner (e.g., shorter time frames, higher net fluid loss, and / or higher net sodium loss). Furthermore, embodiments of the present technology increase diuretic efficiency while simultaneously preventing hypotension, for example, by automatically maintaining net fluid loss above a set fluid loss limit (e.g., at least 50 ml / hr, 100 ml / hr, 150 ml / hr, or 200 ml / hr). As described elsewhere herein, net fluid loss can be controlled by adjusting diuretic administration rate and / or hydration fluid infusion rate relative to urination rate or, more specifically, based on whether urination rate is above or below several different thresholds.

[0033] 1 illustrates a patient fluid management system 10 including a urine collection and monitoring system 12 ("urine system 12") and an automatic diuretic infusion system 14 ("diuretic system 14"). In some embodiments, the fluid management system 10 may further include an automatic hydration fluid infusion system 16 ("hydration fluid system 16"). The urine system 12, diuretic system 14, and hydration fluid system 16 may be connected to the patient P by tubing lines (e.g., intravenous (IV) lines) 15, 23 to the diuretic system 14 and hydration fluid system 16, respectively, and by a catheter line 32 (e.g., a Foley catheter, a Texan Condom catheter, a PureWick catheter, etc.) to the urine system 12. The fluid management system 10 may include a console 18 that includes one or more pump or electric motor actuators 22, 26, a computer (e.g., a controller or microprocessor) 19, a user input device 40 (e.g., a keypad) and a user output device 42 (e.g., a display), and communicates with the urine system 12, the diuretic system 14, and / or the hydration fluid system 16. The controller includes electronic programmable memory and accepts inputs from various sensors (e.g., urine monitors, hydration fluid monitors, weight scales, flow meters, optical sensors, fluid level meters, ultrasonic flow meters, pump speed or actuator movement feedback sensors, pressure sensors, blood pressure sensors, air detectors, etc.) and / or user interfaces. The controller is configured to automatically control the actuators, for example, to infuse hydration fluid and diuretic to facilitate safe and effective diuresis in the patient.

[0034] The diuretic system 14 includes or is in fluid communication with a source of diuretic 20. The diuretic 20 may include bumetanide (Bumex®), ethacrynic acid (Edecrin®), furosemide (Lasix®), torsemide (Demadex®), and / or other diuretics known in the art, each of which may be part of a fluid solution (e.g., a mixture of saline and a diuretic or other drug). The diuretic 20 may be infused into the patient using a separate IV tube inserted into an appropriate peripheral vein of the patient, or may be added to the hydration fluid prior to infusion.

[0035] In some embodiments, the diuretic 20 is contained in a syringe barrel (not shown) or other container (e.g., a bag) and can be injected intravenously through an IV needle. The diuretic system 14 can include multiple syringes or containers of the diuretic 20, each available for use, such that if a first syringe or container is used, the supply of the diuretic 20 can continue (e.g., without substantial interruption) via a second (or third) syringe or container. As an example, the diuretic system 14 can be designed so that two independent syringe pumps are available for use, each fluidly coupled to its own syringe filled with the diuretic 20. Note that such syringes can only be filled by a pharmacist or other medical personnel and therefore cannot be replaced immediately (e.g., within a few hours). When the diuretic system 14 detects that the first syringe is empty, the diuretic supply can be initiated (e.g., automatically or manually) to dispense the diuretic 20 from the second syringe. In some embodiments, this delivery may require stopping a first syringe pump, which is now fluidly coupled to the used first syringe, and starting a second syringe pump, which is fluidly coupled to the second syringe. Additionally or alternatively, if only a single pump is utilized, switching between the first and second syringes may include operating one or more valves so that the pump is delivered from the second syringe. After manually or automatically switching to the second syringe, an operator alert may be generated to notify the operator that the first syringe should be replaced with a new, full syringe.

[0036] Additionally or alternatively, diuretic system 14 can anticipate when diuretic 20 is nearly empty (e.g., empty in one hour) and alert the user and / or automatically switch to the second syringe or ask the user to manually confirm switching to the second syringe. In some embodiments, for example, regulatory considerations may require manual switching to ensure that diuretic system 14 does not automatically inject large amounts of diuretic 20 without user confirmation. Additionally or alternatively, the system can be designed with only one syringe pump, and the system can alert the operator in anticipation of the first syringe becoming empty, and the operator can temporarily stop the syringe pump so that the operator can remove the first, nearly empty syringe and replace it with a second, full syringe and restart the pump to continue dispensing diuretic.

[0037] By having a second (or third, fourth, etc.) syringe, or more generally a backup, administering diuretic 20 can proceed uninterrupted throughout the entire fluid therapy session. As described elsewhere herein, the lack of interruptions can help ensure that the fluid therapy described with reference to the disclosed embodiments of the present invention is highly effective and reduce or prevent unnecessary delays. More specifically, an interruption in therapy, even if only for a short period of time, may require a potential reduction in urination rate and / or re-implementation of the diuretic ramp (described elsewhere herein). Embodiments of the present technology utilizing a backup source of diuretic 20, as well as other redundancies described herein (e.g., with respect to hydration fluid sources, urine collection, etc.), can thus avoid such interruptions, enabling more effective therapy.

[0038] The pump 22 can be a peristaltic pump, a syringe pump, a metering pump, or another device suitable for controllable injection of an IV therapeutic agent. In such embodiments including a syringe pump, the pump 22 can include a mechanical syringe operably coupled to the computer 19 such that the computer 19 effects syringe movement to transfer the diuretic 20 from the source to the patient. The actuator can be a mechanical actuator under electric motor control via a rotary motor, a linear motor, or a series of electrically actuated solenoids configured to propel the fluid through the IV delivery tubing toward the patient. The pump 22 or actuator delivers the diuretic 20 at a controlled continuous rate and / or in controlled boluses delivered into the patient through the IV line 23 at regular intervals. The pump 22 or actuator is controlled by the computer 19, which can have executable instructions or software algorithms embedded within the console. The computer 19 or associated algorithms are configured to determine the pumping rate of the diuretic 20 and / or associated solution to achieve a desired dosage of the diuretic 20. The computer 19 controls, for example, a pump 22 or actuator to deliver a dose of diuretic 20 based on a treatment regimen prescribed by an operator and managed by the computer 19. The control logic of the computer 19 can be software or firmware embedded within the computer 19 that controls the infusion of the diuretic based on a programmed time profile, user input, and / or input from various sensors.

[0039] The diuretic system 14 can include reusable motors, actuators, and control electronics, and one or more reusable or disposable components connectable thereto. The reusable or disposable components can include a container or reservoir (e.g., a plastic syringe, a plastic bag, etc.) of a medicinal agent (e.g., a medication or a diuretic), an IV tubing set, and an IV needle. In some embodiments, the reusable and disposable components described herein are attached using an attachment scheme that is relatively easy to engage and disconnect, for example, in a one-step procedure (e.g., a snap connection).

[0040] In some embodiments, the diuretic system 14 can include one or more syringe pumps. Each of these syringe pumps can be designed to accommodate attachment of a needle, tubing, and other accessories, and can include a plunger attached to a shaft to force fluid from a reservoir. The reservoir can be a tubular structure with a port at one end to allow the plunger to force (i.e., dispense) fluid from the syringe pump. The syringe pump can be coupled to an actuator that mechanically drives the plunger to control the delivery of fluid to the patient. This linear actuator can include, for example, a nut to rotate a lead screw that drives the plunger through the medication reservoir. The syringe pump can be equipped with plunger position sensors, air bubble detectors, and other embedded electronics required to provide feedback signals to a controller. In some embodiments, a syringe pump for administering medication to a patient includes a housing, a lead screw, and a sliding block assembly. The sliding block assembly can include a threaded portion that can engage and disconnect from the lead screw and a latching mechanism for rapid engagement and disconnection of the syringe, thereby enabling rapid exchange of an empty syringe with a full syringe. In some embodiments, a syringe pump for administering a diuretic to a patient includes a housing. Within the housing can be a motor, a gearbox operably connected thereto, a means for sensing rotation of the motor (e.g., a tachometer or optical encoder), a controller (e.g., a microcontroller) that controls operation of the motor and functions to monitor the amount of diuretic delivered to the patient, and a pump assembly. In some cases, the plunger includes a fluid-contacting surface fabricated from a resilient material such as silicone rubber or urethane. In some cases, the reusable part forms a void space to receive the lead screw when the lead screw is retracted from the reservoir.

[0041] In some embodiments, a combination of two or more medicinal agents may be required for optimal and / or effective diuresis in a patient. To accomplish this, in some embodiments, the disposable component may further include a second reservoir for containing a supplemental fluidic agent, a second plunger for driving the supplemental fluidic agent out of the second reservoir, a second lead screw attached to the second plunger, and a second nut operable to displace the second lead screw, thereby coupling with the drive component when the reusable and disposable components are attached. In some embodiments, controlling the device to deliver the fluidic agent includes driving both the first and second plungers simultaneously (e.g., at the same or different speeds). In other cases, controlling the device to deliver the fluidic agent includes independently driving the first and second plungers (e.g., continuously and / or intermittently).

[0042] In some embodiments, the pump can be a syringe pump or a peristaltic pump. While these two types of pumps are mechanically different in design, both can be thought of as computer-controlled, electrically actuated mechanical devices for the precise, controlled propulsion of a liquid (i.e., a solution containing an optimal diuretic or combination of diuretic, electrolytes, and other active and inactive ingredients) for injection into a patient's bloodstream through an appropriate vein.

[0043] In embodiments including a peristaltic pump, the diuretic-containing liquid solution can be supplied in a disposable container, which can be a plastic bag with attachments to plastic tubing, and the reusable part can be a peristaltic pump that can engage the plastic tubing and propel the fluid from the bag into the patient under precise control from an electronic controller. In such embodiments, the reusable component can incorporate an electric motor-operated actuator, which can be a roller pump having compression rollers that cyclically engage the tubing or a linear peristaltic pump to continuously engage, compress, and release the tubing, thereby propelling the fluid bolus forward toward the patient.

[0044] As shown in FIG. 1 , diuretic 20 can be stored in a container (e.g., a bag). The container can contain a solution (e.g., saline) having a predetermined concentration of diuretic. The concentration of the diuretic can be entered into computer 19, such as through user input device 40, which can include a scanner that reads a bar code on such container, thereby indicating the type and concentration of the diuretic. Alternatively, the connection between the container and console 18 can be configured to accept only certain containers that computer 19 knows to store a predetermined concentration of diuretic.

[0045] In some embodiments, the hydration fluid system 16 includes or is connectable to a fluid source 24, such as a saline bag containing a saline solution (which may or may not be the same saline solution described above mixed with a diuretic), a hydration fluid infusion pump 26 (e.g., a peristaltic pump) that is optionally attached to the console 18 and capable of receiving an IV line 15. The IV line 15 is coupled to or connectable to the fluid source 24 and an intravenous (IV) needle 28 for insertion into a patient's vein. The amount or rate of hydration fluid flowing from the source 24 into the patient can be measured by a flow, volume, or other sensor downstream of the pump 26, or by the pumping speed or RPM of the infusion pump 26. This amount or rate can be input into an algorithm or computer 19, for example. As described elsewhere herein, the pumping rate of the hydration fluid can be increased or decreased by the computer 19 or associated algorithm based at least in part on urination and an electronically stored relationship between urination and hydration fluid infusion. Computer 19 can monitor the amount or change of hydration fluid in source 24, for example, using input from a weigh scale 38 that weighs source 24. The amount of hydration fluid or the rate of change of hydration fluid can be measured by other means, such as a fluid level monitor, a liquid level sensor, an optical sensor, a drip counter, a flow measurement sensor, etc.

[0046] In some embodiments, the hydration fluid system 16 can include multiple (e.g., redundant) fluid sources 24, for example, to ensure that the supply of hydration fluid can continue uninterrupted throughout a therapy session. As an example of such an embodiment, when the system or computer 19 detects that a first source container is empty or nearly empty (e.g., by measuring container weight, a reduced flow rate, etc.), flow from the first source can be stopped and flow from a second source can be initiated. For example, supply can be switched from the first source to the second source by closing a first valve (e.g., a pinch valve applied to the exterior of the fluid supply tubing) and opening a second valve that allows flow from the second container. An alert can then be issued to the operator informing them that the first source container should be replaced with a new, full container. Additionally or alternatively, the hydration fluid system 16 can predict when a fluid source is nearly empty (e.g., within 15 minutes), alert the user, and / or automatically switch to the second fluid source. In some embodiments, for example, regulatory considerations may require manual switching to ensure that the hydration fluid system 14 does not automatically infuse hydration fluid without user confirmation. Having a second (or third, fourth, etc.) hydration fluid source, or more generally, a backup, allows the infusing of hydration fluid to proceed uninterrupted throughout a fluid therapy session. As described elsewhere herein, the lack of interruptions can help ensure that the fluid therapy is highly effective, for example, by alleviating fluid overload conditions as quickly and safely as possible. In other words, an interruption in therapy, even if only for a short period of time, may require the possibility of slowing down the urination rate and / or re-implementing the diuretic ramp (described elsewhere herein). Embodiments of the present technology utilizing a backup source of diuretic 20, as well as other redundancies described herein (e.g., with respect to diuretics, urine collection, etc.), can avoid such interruptions, thereby enabling more effective therapy.

[0047] The urinary system 12 includes or is connectable to a disposable catheter 30 (e.g., a Foley catheter) for placement within the patient's bladder and disposable tubing 32 connecting it to a urine collection device (e.g., a disposable bag) 34. The amount of urine collected in the bag 34 can be monitored by a weigh scale 36 or other urine flow device in communication with the computer 19. For example, the amount or rate of urine flow can be determined by a urine measurement device, a fluid level monitor, a liquid level sensor, an optical sensor, a drip counter, or a flow measurement sensor. The amount or rate of urine collected can be monitored or calculated in real time by the computer 19. Similarly, the amount of fluid or diuretic 20 can be measured, for example, by a weigh scale 38 and monitored by the computer 19. Alternatively, the weigh scales 36, 38 can be a single weigh scale that measures the combined change in urination by the patient and fluid inflow to the patient. The combined change in urination and fluid inflow indicates the net fluid change by the patient.

[0048] In some embodiments, the urinary system 12 can include multiple (e.g., redundant) independent urine collection devices 34 to ensure that fluid therapy does not have to be stopped or interrupted due to a full collection device. As an example of such an embodiment, when the system or computer 19 detects that a first urine collection device is full (e.g., by sensing the weight of the collection device, calculating the total collected volume using a flow sensor, etc.), urine flow from the patient can be rerouted to a second collection device. An alert can then be issued to the operator to guide the operator to empty the first urine collection device and to indicate replacement of the first urine collection device in the system. In some embodiments, the urine drainage tubing leading from the patient can be connected (e.g., through a "Y" splice) to two flexible tubing lines, each serving one of the available urine collection devices. Flow to each collection device can be controlled using pinch valves that compress the tubing from the outside, thus allowing flow through the tubing when the pinch valve is opened. When the first pinch valve is open and the second is closed, urine flow is directed to the first collection device rather than the second collection device. When the first collection device is detected by computer 19 to be full, the first pinch valve can be closed and the second pinch valve can be opened, thereby diverting urine flow to the second collection device and allowing the first collection device to be taken offline and removed.

[0049] In some embodiments, the fluid management system 10 is comparable to or similar to the Reprieve Cardiovascular® system developed and clinically tested by Reprieve Cardiovascular, Inc. of Milford, Massachusetts, USA.

[0050] The computer 19 may include a processor and tangible, non-transitory memory configured to store program instructions, settings for the patient fluid management system 10, and data collected and calculated by the computer 19. The data may include historical treatment data for the patient, such as the diuretic dose delivered to the patient, the volume or rate of urine output, the amount of hydration fluid infused into the patient, the patient's weight or change therein at various times during the diuretic infusion, an index of the patient's renal function (e.g., estimated glomerular filtration rate (eGFR)), and / or the time it took to treat the patient with the patient fluid management system 10.

[0051] As mentioned above, the console 18 and / or computer 19 may have a user input device 40, such as a keypad, and a user output device 42, such as a computer display. A user may interact with the computer 19 through the input device 40, which may be used to input certain parameters of a treatment session, such as the desired fluid balance level, the desired urination level, the duration of the inflow balance level or urination level regimen, the type of diuretic, and the minimum and maximum diuretic doses. Other inputs may be patient-related (e.g., gender, weight, dry weight, age, target fluid removal volume, renal function, etc.). These inputs may be used by the computer 19 to look up certain parameters, such as the maximum diuretic dose, maximum continuous diuretic dose, and minimum desired urine rate, from tables or other data stored in the computer 19. The computer 19 may display recommended initial and maximum diuretic levels for the operator to select and program into the computer settings. Another input may be the amount of fluid the patient receives during a treatment session through means other than the diuretic 20, such as ingested fluids or other injected medications. For example, the input device 44 may be configured to accept an input indicating an amount of diuretic to be injected into the patient, such as from the diuretic pump 22 or diuretic source 20 .

[0052] 2A and 2B are graphical representations of an exemplary treatment regimen, where FIG. 2A shows a diuretic dose rate 58 (e.g., diuretic mass per hour) dispensed over a period of time, and FIG. 2B shows a corresponding urination rate 62 (e.g., urine volume per hour). In accordance with embodiments of the present technology, the treatment regimen shown and described in FIGS. 2A and 2B can enable a patient to reach and maintain a desired urination rate within a predetermined period of time. Cross-referenced between FIGS. 2A and 2B, diuretic dose 58 and urine flow rate 62 are shown on the graphical representation over a period of approximately six hours, including an initial period referred to as Phase I or the "diuretic dose determination phase," a subsequent period referred to as Phase II or the "continuous diuretic dose phase," and a final period referred to as Phase III. As shown in FIG. 2A, Phase I is approximately one hour, Phase II is approximately three hours, and Phase III is approximately two hours. In other embodiments, these periods may be different and longer or shorter than the time spans shown in FIG. 2A. For example, Phase III may comprise the majority of the therapy session and thus may be 1 to 36 hours.

[0053] In Phase I, a diuretic administration rate and / or dosage that is effective and safe to cause the patient to produce urine at or above the threshold level 56 is determined, e.g., within the shortest possible time. For example, to rapidly increase the urination rate 62 within less than 30, 60, 90, or 120 minutes, the diuretic administration rate 58 can be intentionally significantly higher than the administration rate subsequently applied to maintain the patient at or above the threshold urine rate level or another urine rate level. That is, the maximum diuretic administration rate 58 administered in Phase I can be intentionally higher (100% higher, 200% higher, 300% higher, 400% higher, 500% higher, 600% higher, or within 100-600% of) the expected diuretic administration rate 58 required to produce a urination rate 62 above the threshold level 56 (shown in Phase II).

[0054] During Phase I, the diuretic administration rate 58 can be set to an initial dose 60 that can be prescribed by an operator who enters the dose through a user input device 42 on the console (e.g., console 18 of FIG. 1). The initial administration rate 60 is a non-zero value and can be at least 50 mg / hr, 75 mg / hr, 100 mg / hr, 125 mg / hr, 150 mg / hr, or in the range of 50-150 mg / hr (or any value therebetween). In some embodiments, the initial administration rate 60 can be determined by the system and set as a default initial administration rate or based on other input data unique to the patient (e.g., the patient's weight, excess fluid weight, or other parameters). The operator can input other parameters of the treatment regimen, such as the maximum tolerable diuretic dose (maximum total diuretic dose and / or maximum diuretic administration rate) 59, the minimum 56 and / or maximum 78 desired urination (total urination volume and / or total urination rate), and / or the duration for Phases I, II, and III. The initial diuretic dose 60 can be selected to be conservative and lower than that required to cause the patient to produce urine. For some patients, the initial dose rate can be sufficient to facilitate a rate of urination up to above the threshold 56.

[0055] A computer or controller (e.g., computer 19 of FIG. 1) can monitor and track urination rate 62. Monitoring of urination rate can begin before or when the initial low diuretic administration rate 60 is administered to the patient. The urination rate can be monitored or calculated in real time or at regular intervals, such as every 30 seconds, every minute, or every multiple minutes. In some embodiments, the initial urination is expected to be lower than the minimum desired urination rate 56. If the initial urination rate is higher than the minimum desired urination rate 56, the operator can consider increasing the minimum desired urination rate or modifying the amount and / or rate of diuretic administered. In some embodiments, the computer automatically increases the administration rate of the diuretic during Phase I until the urination rate is at or above the minimum desired urine rate 56. The diuretic administration rate can be automatically increased by the computer adjusting the operation of a diuretic pump (e.g., diuretic pump 22 of FIG. 1). The computer can be programmed to increase the administration rate in an exponential manner, or to increase the administration rate at a linear rate, or to determine the administration rate increase based on another computer-implemented algorithm for increasing the dose. The computer or algorithm utilized by it can limit the diuretic administration rate to no greater than a maximum diuretic administration rate 59 entered by the operator or stored in the computer. In some embodiments, the diuretic administration rate is increased in steps from an initial administration rate 60 in Phase I to a peak diuretic administration rate 64, with each step increasing (e.g., doubling) the increase made in the previous step by, for example, at least 50% or 100% (or a value therebetween). In such embodiments, the rate of increase in the administration rate (i.e., the slope of the diuretic administration) can be successively increased with each step until the maximum dose 64 is reached. The endpoint 66 of Phase I can be a preset period of time, can be determined based on when the peak diuretic administration rate 64 is reached, or can be a certain period of time after the peak diuretic administration rate 64 is reached (e.g., at least 2 minutes, 5 minutes, 10 minutes, or in the range of 2 to 10 minutes).

[0056] The diuretic administration rate 58 can be increased continuously after set intervals (e.g., every 2, 3, 4, or 5 minutes) during Phase I, with each dose increase being higher than the previous increase. In some embodiments, the increase can be exponential and / or achieve a doubling of the diuretic administration rate every 15 minutes. The algorithm is: f(x)=a where f(x) is an exponential function, a is a constant, b is a positive real number, and x is the exponent. * b * The a, b, and x values ​​can be derived by fitting a series of step increases to an exponential curve defined by x. The values ​​for a, b, and x can be determined experimentally and / or by a physician and can be tailored specifically for each patient. The values ​​for a, b, and x can be set into an algorithm stored on a computer. Additionally or alternatively, such values ​​can be based on patient-specific inputs (e.g., the patient's weight, excess fluid weight, home dose of oral diuretic, or other parameters).

[0057] As the diuretic administration rate 58 is increased during Phase I, the computer monitors the urine rate 62. The computer can automatically increase the diuretic administration rate 58 according to an algorithm for increasing the diuretic administration rate that it implements. The increase in the diuretic administration rate can continue until the urination rate 62 reaches or exceeds the desired minimum urine rate 56. Once the computer determines that the urination rate 62 has reached the minimum desired urination rate 56, the diuretic administration rate 58 is not further increased, thus corresponding to the peak diuretic administration rate 64. In some embodiments, the computer can be programmed to prevent the diuretic administration rate 58 from being greater than the maximum diuretic administration rate 59, regardless of whether urination has reached the minimum desired urination rate 56.

[0058] In some patients, the urination rate 62 may increase rapidly, sometimes significantly exceeding the minimum desired urine rate due to a relatively high diuretic administration rate 64. As discussed elsewhere herein, patients with high urination rates may require simultaneous infusion of hydration fluid and optional downward titration of diuretic administration if the urination rate becomes too high, both of which can be controlled by a computer algorithm.

[0059] Phase I can also end if a specified period 66 for this phase elapses before the urination rate reaches a desired minimum urine rate. The period 66 can be determined based on the maximum diuretic administration rate 59, such as 5 minutes, 10 minutes, 15 minutes, or 30 minutes (or another value therebetween) after the maximum diuretic administration rate 59 is reached. Phase I can range from 1 hour, 45 to 90 minutes, or 30 to 120 minutes. If the period of Phase I has elapsed, the computer can generate an alert (e.g., from the user output device 42 of FIG. 1 ) indicating that (i) Phase I ended due to time rather than reaching the maximum diuretic administration rate 59, which may indicate a lower than desired urine rate; (ii) the patient is diuretic resistant; (iii) the patient can be given a different diuretic and Phase I can be restarted; and / or (iv) the patient should be provided with an alternative fluid-reducing therapy, such as ultrafiltration or intravenous pumping. Compared to current methods of administering diuretics to generate urine output, embodiments of the present technology can increase urination rate at a more rapid pace, thereby enabling rapid decongestion, rapid symptom (e.g., dyspnea) relief, increased fluid removal, increased sodium excretion, and / or weight loss in a shorter period of time. As discussed above, prior art techniques often employ a conservative approach, slowly increasing the diuretic administration rate in an attempt to maintain greater control over urination. However, doing so can result in delays of several hours or even days, thereby further exacerbating the underlying fluid overload condition. Unlike these prior art techniques, the relatively rapid pace of the present technology can be beneficial within a shorter time frame for patients suffering from fluid overload or pulmonary edema, as the rapid increase in diuretic administration rate, and therefore urine production, can reduce the volume of fluid in the patient's extravascular space within just a few hours, drawing the fluid back into the intravascular space. Furthermore, as described in detail elsewhere herein, in some embodiments, a rapid diuretic ramp can be paired with a corresponding hydration fluid infusion to optimize net fluid loss while also maintaining a sufficient amount of intravascular volume to maintain adequate renal function.

[0060] 2A and 2B, a regimen or method of the present invention can automatically transition to Phase II after a peak diuretic administration rate 64 is reached or the duration of Phase I 66 has expired. Phase II can continue until the end of fluid therapy and can be configured to maintain the diuretic administration rate 58 at a constant rate or dosage level for an extended period of time 71, such as at least 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, or other set interval. In some embodiments, Phase II is intended to allow the patient's body to adapt to the diuretic administration rate 58 and produce (i) a urination rate at or above the desired minimum urination rate 56, and / or (ii) a urination rate that is maintained within a specified range throughout the duration of Phase II.

[0061] During Phase II, the diuretic administration rate 58 can be set to a continuous dose level (e.g., a maintenance administration rate) 70 that can remain constant during all or most of Phase II. The maintenance administration rate 70 can be the same as the peak administration rate 64 achieved during Phase I, or a predetermined percentage of the peak administration rate 64, such as 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, or a range between 90% and 10% of the peak administration rate 64. In some embodiments, the diuretic maintenance dose 70 is set based on a diuretic administration level 72 that corresponds to the desired minimum urine rate 56 in Phase I or the administration rate required to reach the total amount of diuretic needed during Phase I. For example, in some embodiments, diuretic maintenance infusion rate 70 has a value that is a percentage (e.g., 15%, 20%, 30%, 40%, 50%, or a range of 15-50%) of the value of the total or cumulative dose (e.g., by mass or volume) delivered in Phase I. For example, if the total dose of diuretic delivered in Phase I is 100 mg, diuretic maintenance infusion rate 70 may be 20 mg / hr. Additionally or alternatively, in embodiments in which Phase II begins due to the expiration of Phase I, diuretic maintenance infusion rate 70 may be limited to a maximum rate (e.g., 40 mg / hr, 35 mg / hr, 30 mg / hr, or less). The maintenance infusion rate 70 provided in Phase II may be selected by an operator and entered into the computer. In some embodiments, maximum diuretic maintenance infusion rate 72 may be stored in the computer, such as in a table.

[0062] The regimen or method of the present invention can automatically transition to Phase III at the end of Phase II. Phase III can continue until the treatment regimen is complete, which can occur when the net fluid removed from the patient reaches a predetermined volume or weight (e.g., determined automatically or by an operator) or after a predetermined period of time (e.g., 1, 2, or 3 days). Net fluid removal refers to the difference between the amount of fluid excreted by the patient (which can correspond to urination) and the amount of fluid ingested by the patient.

[0063] During Phase III, the computer can adjust the diuretic administration rate 76, for example, (i) to maintain the urination rate 62 within a desired range 77, (ii) to maintain the urination rate 62 above a desired minimum urination rate 56, and / or (iii) to maintain the urination rate 62 below a maximum urination rate 78. The desired range 77 can be automatically calculated based on the average urination rate during Phase II, such as a range from 80% to 120% of the average urination rate during Phase II. The desired range 77 can be, for example, a range centered around 525 ml / hr, with a low end of the range at 475 ml / hr and an high end at 575 ml / hr. Alternatively, the desired range or the desired minimum and maximum urination rates can be parameters entered into the computer by the operator or can be stored in the computer. The diuretic administration rate for Phase III can be kept the same as the continuous administration rate 70 for Phase II so that Phases II and III operate in a similar manner. Furthermore, if the urination level 62 falls below a desired minimum urination level (which may or may not be the same level as Phase I), the computer can automatically restart Phase I or issue an alert or report suggesting that Phase I be restarted, for example, to determine a more optimal diuretic maintenance administration rate. For example, if the urine rate falls below 325 ml / hr for a three-hour period, the computer can restart Phase I. Similarly, if the urination rate repeatedly fluctuates between below 325 ml / hr and above 325 ml / hr, thereby effectively causing the net fluid loss to be too low, the computer can restart Phase I. To determine whether the net fluid loss is too low, the software can calculate a "debt" value, defined as the area below 325 ml / hr for a given period, such as three hours, that is higher than the current urination rate. For example, if the urination rate was 300 ml / hr for 1 hour, the "debt" would be considered to be 25 ml (325 minus 300).If the "debt" exceeds a set value for a set amount of time, e.g., a debt of 150 ml for 3 hours, the computer may automatically restart Phase I or issue an alert or report on the user output device 42 suggesting that Phase I be restarted.

[0064] If the urination rate exceeds a high threshold level during Phase III, the computer can automatically reduce the diuretic dosage by 20%, 35%, 55%, 75%, or more of the current administration rate. If the urination rate remains excessively high, e.g., above a threshold level, after a predetermined period, such as one hour, after reducing the diuretic administration rate, the computer can automatically stop or taper down the diuretic infusion for a period of time. For example, if the urination rate exceeds 625 ml / hr for one hour, the computer can automatically stop the diuretic infusion for a defined period of time (e.g., 50 minutes to one hour) or reduce the diuretic administration rate to a minimum administration rate. If the urination rate drops below a set threshold in response to the reduction in the diuretic administration rate, the computer can continue the continuous diuretic infusion at a percentage of the previous continuous administration rate. This reduction can be based on the duration of diuretic administration rate cessation that has elapsed when the urination rate drops below a threshold level. If a predetermined period of time has elapsed and the urination rate remains above the threshold level, the continuous administration rate can continue at a rate reduced by a predetermined amount, such as a 25 percent reduction from the continuous administration rate prior to cessation of injection.

[0065] In addition to controlling the diuretic administration rate, the computer can execute a program for controlling the infusion of hydration fluid into the patient from hydration fluid source 24. The computer can control the infusion of hydration fluid by controlling an infusion pump (e.g., infusion pump 26 of FIG. 1) based on an algorithm to achieve a desired net fluid reduction in the patient.

[0066] 3 is a graphical representation illustrating the relationship between urination, hydration fluid infusion, and net fluid loss in accordance with an embodiment of the present technology. In other words, FIG. 3 shows an exemplary representation of how an embodiment of the present technology automatically controls hydration fluid infusion rate 80 based on urination rate 82 to achieve a net fluid change rate 84 in a patient. Control of hydration fluid infusion rate 80 can be performed simultaneously with control of diuretic dosage during Phases I, II, and / or III.

[0067] It is expected that the urination rate 82 will initially increase during Phase I, thereby resulting in an increased net fluid loss rate. In some embodiments, the hydration fluid infusion rate 80 can match the urination rate 82 until a predetermined volume (e.g., at least 150 ml, 200 ml, 250 ml, 300 ml, 400 ml, 500 ml, or in the range of 150-500 ml) is measured or until a certain period of time (e.g., at least 60 minutes) has elapsed. In some embodiments, the net fluid loss rate 84 may be substantially equal to the urination rate 82 until hydration fluid is infused into the patient. The computer can determine that hydration fluid is to be added if or when the net fluid loss rate 84 falls below a threshold minimum value 86 or when the urination rate 82 exceeds a threshold urination rate 88. These thresholds can be entered by the physician into the user input device 40 or stored (as defaults) in the computer. These thresholds need not occur simultaneously as shown in FIG. 3, but are related and therefore likely to occur approximately simultaneously. Alternatively, the computer can infuse hydration fluid at approximately the same time that it begins infusing the diuretic, including when it performs (e.g., re-performs) Phase I or the diuretic dose determination phase. When one or both of thresholds 86, 88 are reached, the computer can automatically initiate infusion of hydration fluid 80 by activating an infusion pump (e.g., hydration fluid infusion pump 26 of FIG. 1 ) that pumps hydration fluid from a fluid source (e.g., fluid source 24 of FIG. 1 ) into the patient. The rate of infusion of hydration fluid 80 can be calculated or determined by the computer based, for example, on the difference between the current urination rate and the desired net fluid balance rate 90. For example, if the desired net fluid reduction rate is 200 ml / hr and the urination rate is 400 ml / hr, the computer can automatically control the infusion of hydration fluid to a rate of 200 ml / hr.

[0068] The computer can adjust the field infusion rate 80 to maintain a desired net fluid reduction rate 84, such as a net fluid balance rate 84 that is constant, between a specified range, or below (i.e., more negative than) a threshold value. During the initial phase or period 85, hydration fluid can be infused until one hour has elapsed or a predetermined amount of hydration fluid (e.g., at least 500 ml) has been infused, whichever occurs first. During the initial phase 85, the computer can match the rate of increase in urination 82 with the rate of increase in hydration fluid infusion 80. Increasing the hydration fluid at the same rate as the rate of increase in urination results in infusing a significant amount of hydration fluid into the vasculature. Hydration fluid contains relatively high concentrations of sodium and / or chloride compared to the typical sodium and chloride concentrations in urine; therefore, infusing hydration fluid into the vasculature increases blood sodium and / or chloride levels even when the patient is excreting urine. Similarly, hydration fluid can add potassium to the blood at a rate greater than potassium is released from urine. By doing so, the initial period 85 allows for artificially increased levels of sodium, chloride, and / or potassium in the blood, which provides a safeguard against sodium, chloride, and / or potassium depletion in the patient if blood volume drops to a relatively low level during treatment.

[0069] After the initial period 85, the computer may increase the hydration fluid rate 80 at a rate 94 that is lower than the current rate increase 96 of the urination rate 82 (e.g., approximately 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or in the range of 10%-95% of the current rate increase 96). Alternatively, the computer may reduce the rate of increase 94 for the hydration fluid in response to the urination rate 82 exceeding a first threshold 92 (e.g., 400 ml / hr, 420 ml / hr, 440 ml / hr, or in the range of 400-440 ml / hr) above which the hydration fluid rate 80 will not be further increased. If or while the urination rate 82 exceeds the first threshold 92, the computer may further reduce the rate of increase 94 of the hydration fluid 80 to a point significantly lower than the current rate of increase 96 of the urination 82. For example, while the urination rate 82 remains above the first threshold 92, a further rate of increase 96 in the urination rate 82 will be balanced by a further rate of increase 94 in the hydration fluid infusion rate 80 that increases by only half or a quarter to three-quarters the rate. At the same time, the rate of decrease 102 in the net fluid reduction 84 increases due to the higher rate of increase in urination compared to the lower rate of increase in hydration fluid. As described elsewhere herein, by adjusting (e.g., increasing or decreasing) the hydration fluid rate (or rate of increase in hydration fluid rate) less than the urination rate, net fluid removal of salts, as well as net fluid loss, from the patient's body can be achieved.

[0070] If the urination rate 82 continues to increase and exceeds a second threshold 98 (e.g., at least 500 ml / hr, 1020 ml / hr, or in the range of 500-1020 ml / hr), the computer can automatically discontinue further increases in the hydration fluid rate 80. While the urination rate 82 remains above the second threshold 98, the computer can maintain the hydration fluid rate 80 at a constant rate 100 (e.g., 200 ml / hr) regardless of further increases in the urination rate 82. Furthermore, increasing the net fluid reduction rate 84 has the advantage of shortening the period required to reach the desired total net fluid reduction. The rate of net fluid reduction 104 increases due to the increasing urination rate 82 and the constant hydration fluid rate 80.

[0071] Setting a threshold 98 for maximum urination, above which hydration fluid is not further increased, is based in part on the desire to avoid excessive sodium levels in the patient. Although the sodium concentration in urine can vary as the patient's physiological state changes throughout treatment, it is lower (approximately half) than the sodium concentration of the saline solution expected to be used as a hydration fluid. At high hydration fluid infusion rates, the net sodium gain to the patient may become excessive over the course of an hour or more of treatment. To reduce the sodium added to the patient, an upper limit of 100 is applied to the hydration fluid rate 80. This limit can be imposed indirectly by setting a threshold maximum urination rate 98 above which the hydration fluid rate 80 will not increase.

[0072] As described above, the computer can automatically provide the ability to reduce high urination rates by reducing the diuretic dosage above thresholds 92 and / or 98, etc. The diuretic dosage can be increased to dosage levels previously considered inappropriate for fluid reduction therapy. Embodiments of the present technology can administer diuretics at these higher levels due to (i) automatic reduction of the diuretic dosage in response to urination rate 82 being above thresholds 92, 98, and / or (ii) direct injection of hydration fluid into the patient's vasculature. The injection of hydration fluid reduces the risk that blood volume in the patient will become excessively low due to a high diuretic dosage. Thus, the diuretic dosage levels 64, 70, 76 described with reference to FIG. 2A can be significantly higher than maximum dosage levels previously considered appropriate and approved.

[0073] The computer can store certain limits for therapy, such as a default fluid balance rate and a maximum net fluid loss. The default net fluid balance rate can be negative 220 ml / hr or can range from 150 ml / hr to 260 ml / hr. The maximum net fluid loss limit can be 5 liters (5,000 ml), at which point the computer can issue a report or alarm and at least temporarily halt the diuretic injection phase. The operator can respond to the alarm by entering a higher maximum net fluid loss limit, such as in 1 liter increments. In response to the higher maximum net fluid loss limit, the computer can continue with Phase III.

[0074] Clinical studies utilizing embodiments of the present technology consistently reduced fluid volume in patients more rapidly than conventional standard of care. In previous studies of this patient population, only 47% of patients receiving standard of care achieved the goal of removing 4 to 5 liters of fluid volume, which typically required five days of hospitalization. In comparison, embodiments of the present technology resulted in the removal of 4 to 5 liters of fluid volume in 24 hours or less. Urinary sodium data from this study confirms that, in addition to a net reduction in fluid volume, embodiments of the present technology also remove significant amounts of salt from patients through hypernatremia. Patients receiving conventional standard of care only remove substantially hypotonic urine (e.g., 60-70 mmol sodium). The greater salt removal achieved by embodiments of the present technology results in less patient propensity to re-accumulate fluid after release, resulting in a significant reduction in hospital readmission rates.

[0075] In addition to automating the delivery of diuretics and hydration fluids based on urine output, embodiments of the present technology can optimize net fluid volume removal, shortening the time required to achieve a desired net fluid reduction by allowing physicians to use higher doses or administration rates earlier in treatment compared to standard care, avoiding or reducing the risk of adverse events such as overdiuresis, dehydration, or intravascular depletion, rapidly assessing whether a patient is diuretic resistant, and providing treatment data recording. Embodiments of the present technology aim to achieve an average net fluid reduction rate (average rate of urine output minus average rate of hydration fluid introduced) of at least 225 ml / hr, achieving a net fluid volume removal of 3.4 liters per day based on introducing 2 liters of fluid per day orally or via IV infusion. This rate of fluid removal while replacing sodium can enable a reduction in length of stay (LOS) and improved decongestion.

[0076] To achieve these goals, embodiments of the present technology include a short diuretic dose determination phase to determine an appropriate continuous diuretic infusion rate, which is then used in a fluid reduction phase to continuously monitor urination and use it to assess whether the diuretic infusion rate remains appropriate and adjust the diuretic infusion rate accordingly. Simultaneously, an algorithm controls the infusion of hydration fluid to replace a portion of the sodium and fluid removed. The hydration fluid infusion rate is at least partially a function of the urine rate.

[0077] FIG. 4A illustrates a method 400 for controlling the diuretic infusion rate during a diuretic dose determination phase (processing portion 402). Method 400 may be part of an algorithm described elsewhere herein. The diuretic dose determination phase may correspond in whole or in part to the diuretic dose determination phase described with reference to FIG. 2. The diuretic dose determination phase may correspond to the beginning of a fluid management therapy or may be triggered when one or more of a set of conditions are met (e.g., urination drops below a threshold). The start of the diuretic dose determination phase may be manually triggered by a user, for example, if the user believes that the diuretic infusion rate or urination is too low and wishes to reevaluate the diuretic dose. In this regard, a patient's underlying physiological condition often changes during inpatient fluid therapy, and therefore, the diuretic dose required to produce a desired urination rate may need to be adjusted by repeating the diuretic dose determination phase.

[0078] As shown in FIG. 4A, the diuretic dosage determination phase can begin by setting a diuretic administration rate (processing portion 404). The initial diuretic administration rate can be set relatively low (e.g., 60 mg / hr, 80 mg / hr, 100 mg / hr, 120 mg / hr, or a range of 60-120 mg / hr or less) and / or can be set based on patient-specific factors (e.g., gender, age, weight, medical history, etc.). Once the diuretic administration rate is determined, the system (e.g., the fluid management system 10, the diuretic system 14, and / or any of their subsystems) can check whether the urine rate exceeds a predetermined threshold (processing portion 406). The predetermined threshold can be 200 ml / hr, 300 ml / hr, 400 ml / hr, 450 ml / hr, 500 ml / hr, 525 ml / hr, 550 ml / hr, or a range of 200-550 ml / hr. If the urine rate does not exceed the predetermined threshold, the system may check whether a predetermined amount of time (e.g., ramp time) has elapsed (processing portion 408). The ramp time may be 40, 50, 60, 70, or 80 minutes, or a range of 40-80 minutes or less. If the ramp time has elapsed without the urine rate being higher than the predetermined threshold, the system may adjust the diuretic administration rate repeatedly after intervals (e.g., every 2 minutes, every 3 minutes, every 4 minutes, or other set intervals). The adjusted diuretic administration rate may increase in a linear or exponential manner until either the urination rate is higher than the predetermined threshold or the ramp time has elapsed. The diuretic administration rate over a given number of minutes t is calculated as A = B + C ... * (2^(t *The ramp time can be calculated using the formula: B)) + C). In some embodiments, an exponential increase can optimize the rate at which an appropriate administration rate is safely found, whereas a slower increase (e.g., a linear increase) can function to find an appropriate administration rate but may consume more time. In some embodiments, each incremental step is higher than the previous step, so that the diuretic administration rate doubles over a period of time (e.g., every 5 minutes, every 10 minutes, every 15 minutes, every 20 minutes, or within 5 to 20 minutes). Doing so allows the system to increase the urine rate in an efficient and rapid manner, which allows excess fluid to be removed from the patient as quickly as possible and / or whether the patient has a condition (e.g., diuretic resistance) as quickly as possible. In some embodiments, the diuretic can be limited to a maximum dosage (e.g., 200 mg for furosemide) over the ramp time. In this regard, the system can be configured to only provide diuretic doses that are within healthcare regulations and can be delivered safely.

[0079] If the urine rate is higher than a predetermined threshold in response to a high diuretic dose, the value of the adjusted administration rate (e.g., the initial rate for the subsequent continuous infusion phase) is set to a predetermined percentage (e.g., 10%, 15%, 20%, 25%, 30%, or in a range of 10-30%) of the value of the total dose delivered to the patient at this point (processing portion 412). For example, if the total dose delivered was 100 mg and the predetermined percentage was 20%, the adjusted administration rate could be 20 mg / hr. Similarly, if the ramp time has elapsed before the urine rate is higher than the predetermined threshold, the value of the administration rate can be set to a predetermined percentage of the value of the total dose delivered to the patient at this point (processing portion 414). This percentage can be based on the pharmacokinetic properties of the particular diuretic being infused. For example, if the diuretic is furosemide, this fraction can be 20%, such that if 50 mg of furosemide is infused within 60 minutes, the calculated continuous diuretic infusion rate can be 10 mg / hr. This concept is explained in more detail with reference to FIG. 4B. Rapidly reducing the diuretic infusion rate to a percentage of the total dose delivered and / or to a point lower than the immediately preceding infusion rate or the average infusion rate over the previous 5-10 minutes can allow the urine rate to decrease its rate of increase (e.g., approaching zero slope) without actually reducing urination itself. Additionally or alternatively, such a diuretic dose reduction can allow the urine rate to be maintained at a predetermined rate and / or within a predetermined range.

[0080] Once the administration rate is set by processing portion 412, the system can determine whether the average urine rate over a predetermined duration (e.g., 5 minutes, 10 minutes, 15 minutes) is higher than a predetermined threshold (processing portion 416). Processing portion 416 can serve as an additional verification that the urine rate is high enough to proceed to another operational phase. For example, if the urine rate peaks above a predetermined threshold for a period of time but does not consistently exceed this predetermined threshold, processing portion 416 could provide an alert and / or prevent the system from proceeding to a subsequent operational phase. If the average urine rate exceeds a predetermined threshold, the system can proceed to another operational phase, such as a continuous infusion phase (e.g., as described with reference to FIG. 5). If the average urine rate is not higher than the predetermined threshold, the system can set the diuretic administration rate to the previous rate (processing portion 418) and then return to processing portion 406, e.g., re-titrate the diuretic administration rate to increase the urine rate.

[0081] The diuretic dose determination phase allows the diuretic dose rate to be ramped to a higher rate more rapidly than current systems and methods, thereby allowing the patient's urine rate to be rapidly increased above a minimum threshold. Unlike current systems and methods that do not ramp diuretic doses rapidly but instead increase them slowly to err on the side of caution (to avoid overdiuresis), embodiments of the present technology allow the diuretic dose rate to be ramped relatively rapidly, mitigating the risk of diuresis or related problems through, for example, the ability of these embodiments to automatically reduce the diuretic dose rate after reaching a predetermined urination rate and / or control hydration fluid infusion. By doing so, embodiments of the present technology can efficiently achieve net fluid loss from the patient while also setting a net fluid loss limit (e.g., 100 ml / hr) to ensure that an adequate amount of intravascular volume is maintained by the patient. This net fluid loss limit limits the decline in cardiac output and renal perfusion that is often seen in heart failure patients when urination rates approach high levels.

[0082] FIG. 4B is a graphical representation 450 illustrating the relationship between diuretic administration rate 460 and total diuretic delivered 470 in accordance with an embodiment of the present technology. The concepts illustrated and described in FIG. 4B can be applied to other aspects of the present technology relating to diuretic dose determination phases, diuretic ramps, and related features. As shown in FIG. 4B, the diuretic administration rate 460 can be ramped from an initial rate of approximately 75 mg / hr to a final rate of approximately 447 mg / hr within a 60-minute interval. Thus, the diuretic administration rate 460 can increase by approximately 500% over this period. As also shown, the diuretic administration rate 460 can effectively double within approximately a 20-minute interval.

[0083] Total diuretic delivered 470 (mg) corresponds to the cumulative amount of diuretic delivered to date. As discussed above (e.g., with reference to FIG. 4A), the value of total diuretic delivered 470 can be used to determine the value or setpoint for diuretic after the patient's urination rate reaches a predetermined threshold. For example, when the urination rate reaches a predetermined threshold (400 ml / hr, 450 ml / hr, 500 ml / hr, 525 ml / hr, 550 ml / hr, or a range of 400-550 ml / hr), the diuretic delivery rate can be set to a percentage (e.g., 20%) of the current total diuretic delivered 470 value. As shown in FIG. 4B, diuretic delivery rate setpoint 480 corresponds to 20% of the total diuretic delivered 470 value. Note that the values ​​shown in FIG. 4B can be used for furosemide diuretic. The use of other diuretics may require different administration rates, but similar basic principles to those described herein would apply.

[0084] II. Re-ramping or rapid increase in diuretic administration rate FIG. 5 is a flow diagram 500 of a continuous diuretic delivery phase or another phase (e.g., a fluid reduction phase) according to an embodiment of the present technology. As described elsewhere herein, the continuous delivery phase 502 can occur after the diuretic dose determination phase, or more specifically, after the urination rate has already exceeded a predetermined threshold. A continuous infusion phase can occur simultaneously with the fluid reduction phase, during which hydration fluid is infused at a rate lower than the urination rate, thereby causing net fluid loss. During the continuous delivery phase, the urine rate is tested and / or acquired periodically (e.g., every minute) to ensure that the urine rate is at an expected level and that the diuretic dose is compliant (processing portion 504). As part of this testing, the system can determine whether the average urination over the previous duration (e.g., the previous 10, 15, or 20 minutes) is higher than a first threshold amount (e.g., 20 ml, 25 ml, 30 ml, or 40 ml) (processing portion 506). If the average urine output is not higher than the first threshold, an alert message can be provided (e.g., displayed on user output device 42 of FIG. 1 ) informing the user of a very low urine rate and the risk of a Foley catheter blockage or other equipment malfunction (processing portion 508). The average urine rate can then be checked against a set of conditions to determine whether the urine rate is low (processing portion 510) and / or whether ramping (e.g., re-ramping) of the diuretic dose is warranted. If any one of the set of conditions is met, and thus the urine output is determined to be low, the system can proceed to ramp or re-ramp the diuretic dose to establish or re-establish a urine rate above the minimum threshold (e.g., by returning to the diuretic dose determination phase). If the urine rate was not low, the system can loop to continuously monitor the urine rate.

[0085] The condition set can include determining whether (i) the average urine rate is below a predetermined threshold rate (e.g., 250 ml / hr, 300 ml / hr, 325 ml / hr, 350 ml / hr, 400 ml / hr, or a range of 250-400 ml / hr) over a predetermined period of time (e.g., 2 hours, 2.5 hours, 3 hours, or a range of 2-3 hours), or (ii) whether a debt higher than a predetermined amount (e.g., 100 ml, 125 ml, 150 ml, 175 ml, or a range of 100-175 ml / hr) has accumulated over this period of time. The "debt" can be defined as the area between the urination rate and a set rate (e.g., 325 ml / hr) on the plot, essentially representing how high and for how long the urination rate was below the set rate. The debt can accumulate unless the associated counter is reset. For example, if a patient urinates at a constant rate of 300 ml / hr for three hours, the debt will be 75 ml at a set rate of 325 ml / hr. The lower the urination rate, the greater the debt. If the urination rate increases above the set rate, the debt is not accumulated, but continues to be considered until a predetermined amount of time (e.g., three hours) has passed since the debt accumulated. By calculating the debt in such a manner, embodiments of the present technology can respond to low urination rates more quickly than if debt calculation were not utilized.

[0086] If any one of the condition sets is satisfied, and therefore the average urine rate is too low, the user may be prompted to confirm that a re-ramping or diuretic dose determination phase will be implemented (processing portion 514). Regulations may require user confirmation before re-ramping begins. If the user does not agree to re-ramping, the counter for the condition set may be reset; that is, the accumulated debt and the time period used to calculate whether the urine rate is below a predetermined threshold may be reset to zero. If the user agrees to re-ramping, the ramp may begin at the previous diuretic dose rate, e.g., where the previous ramp completed (processing portion 518). In such an embodiment, the diuretic dose rate begins at the final rate of the previous ramp, and the total elapsed ramp time is integrated with the total elapsed ramp time of the previous ramp. This concept is shown in more detail with reference to FIG. 6 and described below. After initiating the ramp, the system determines whether the urine rate is above a predetermined threshold (400 ml / hr, 450 ml / hr, 500 ml / hr, 525 ml / hr, 550 ml / hr, or in the range of 400-550 ml / hr) or whether a predetermined amount of time (e.g., ramp time) has elapsed (processing portion 520). If the determination is negative, the system may adjust the diuretic administration rate after the interval time as described elsewhere herein (processing portion 524). If the urine rate is above the predetermined threshold, the diuretic administration rate may be set to a predetermined percentage (e.g., 10%, 15%, 20%, 25%, 30%, or in the range of 10-30%) of the total dose currently delivered to the patient (processing portion 522). Thereafter, the counter for the condition set is reset (processing portion 516), and the system may return to processing portion 504.

[0087] In some embodiments, the user can check with the device and manually adjust the continuous diuretic administration rate or trigger re-entry into the diuretic dose determination phase. If re-entry is manually triggered, the patient can receive a total elapsed dose time of up to 60 minutes, which may be the highest continuous dose allowed by regulatory authorities. Therefore, there may be little benefit to re-entering the ramp if the total elapsed dose time is longer than 55 minutes. In such an embodiment, the 3-hour average urination rate is reset, the urinary debt is set to 0, and the algorithm returns to processing portion 504. However, if the total elapsed dose time is less than or equal to 55 minutes, the user can be prompted to confirm re-entering the ramp (processing portion 514).

[0088] 6 is a graphical representation 600 of a diuretic administration rate 605 and corresponding urine output rate 610 in accordance with an embodiment of the present technology. Graphical representation 600 generally illustrates the embodiment described with reference to FIG. 5. Initially, diuretic administration rate 605 is increased or ramped until urine rate 610 reaches a predetermined threshold, which in this case is approximately 525 ml / hr. Once the predetermined threshold is reached, ramping of diuretic administration rate 605 ceases (e.g., at time 620) and diuretic administration rate 605 is set to a predetermined percentage (e.g., 10%, 15%, 20%, 25%, 30%, or in a range of 10-30%) of the total dose delivered to the patient to date. 6, the ramp of the diuretic administration rate 605 is completed at time 620 after 50 mg of diuretic has been delivered, after which the diuretic administration rate 605 is set to 10 mg / hr or 20% of the total diuretic infused to date. A lower diuretic administration rate 605 may then be provided at a continuous rate of 10 mg / hr until the system adjusts the administration rate 605, for example, in response to the urine rate dropping and / or regulatory limits being met.

[0089] As shown by line 624, the urine rate 610 may decrease to a lower urine rate shown by line 626. This drop in urine rate 610 may be due to a change in the patient's response to the diuretic or other medical condition. Although the urine rate after line 624 is now below the predetermined threshold of 525 ml / hr, the diuretic administration rate may not be adjusted immediately. Instead of immediate adjustment, as described elsewhere herein (e.g., with reference to FIG. 5), the diuretic administration rate 605 may be adjusted only after either (i) the urine rate falls below another predetermined threshold (e.g., a second predetermined threshold) (e.g., 250 ml / hr, 300 ml / hr, 325 ml / hr, 350 ml / hr, 400 ml / hr, or 250-400 ml / hr) for a predetermined period of time (e.g., 2 hours, 2.5 hours, or 3 hours), or (ii) a debt of more than a predetermined amount (e.g., 100 ml, 125 ml, 150 ml, 175 ml) accumulates over a second period of time. Using these time-weighted average measurements of urine rate, rather than a momentary drop below a first predetermined threshold, to initiate re-ramping of the diuretic dose can prevent unnecessary re-ramping, for example, when the drop in urine rate 610 is due solely to a Foley catheter blockage, a temporary sensor failure, or other related short-term treatment. At time 628, the system determines that the average urine rate has fallen below the second predetermined threshold for three hours. As a result, re-ramping of the diuretic administration rate 605 is initiated, and the administration rate is set to the rate at which the previous ramp was discontinued (shown at time 630), in this case approximately 180 mg / hr. The diuretic administration rate 605 is then ramped according to the same conditions described elsewhere herein (e.g., with reference to FIGS. 2A-4). In some embodiments, the initial diuretic administration rate 605 for re-ramping can be set to a rate lower (e.g., 10%, 20%, 30%, or 10-30% lower) than the rate at which the previous ramp was discontinued. When the urination rate reaches a predetermined threshold, the ramping of the diuretic administration rate 605 ceases (i.e., at time 632) and the diuretic administration rate 605 is set to a percentage of the total diuretic dose delivered to the characteristic to date, in this case 20%.6, the ramp of the diuretic administration rate 605 is completed at time 632 after 50 mg of diuretic has been delivered by the second ramp, or after a total of 100 mg of diuretic (i.e., the 50 mg from the second ramp and the 50 mg already delivered to the patient during the previous ramp that ended at time 620), after which the diuretic administration rate 605 is set to 20 mg / hr or 20% of the total diuretic infused to date. A low diuretic administration rate 605 can then be provided at a continuous rate of 20 mg / hr until the system adjusts the administration rate 605.

[0090] III. Downward tapering or reduction of diuretic administration rate FIG. 7 is a flow chart 700 illustrating the downward tapering of a diuretic administration rate according to embodiments of the present technology. Fluid removal from a patient can often lead to physiological changes that can result in a high response to diuretic administration. In such cases, the urine rate may remain higher than clinically desirable, and this high urine rate, if left untreated for an extended period of time, may result in electrolyte loss and / or hypotension. Furthermore, in such cases, it may be desirable not to simply discontinue providing diuretic to the patient, as this would require unnecessary resumption of fluid therapy and thus potentially extend the overall time required to remove the net amount of excess fluid. To mitigate such problems, embodiments of the present technology may include techniques for downward tapering (i.e., reducing) the diuretic administration rate without setting it to zero.

[0091] As shown in FIG. 7, flow chart 700 begins by providing a diuretic to a patient at a dosage rate (processing portion 702), as described elsewhere herein. The system then determines whether each of a set of conditions is met and, if so, tapers the diuretic dosage downward. The set of conditions may include determining whether the average urine rate is higher than a predetermined rate over a first period of time (e.g., 2 hours, 3 hours, 4 hours, or a range of 2-4 hours) (processing portion 704). The predetermined rate may be based on whether a hydration fluid is being infused to the patient. If a hydration fluid is being infused to the patient, the predetermined rate may be 900 ml / hr, 950 ml / hr, 1025 ml / hr, 1100 ml / hr, or in the range of 900-1100 ml / hr. When no hydration fluid is being infused into the patient, the predetermined rate can be 400 ml / hr, 450 ml / hr, 525 ml / hr, 600 ml / hr, or in the range of 400-600 ml / hr. The condition set can be a condition where the average rate of increase (e.g., positive slope) of urine rate exceeds a predetermined rate of change (e.g., 30 ml / hr) over a second period (e.g., 1 hour, 2 hours, 3 hours, or in the range of 1-3 hours). 2 , 40ml / hr 2 , 50ml / hr 2 , 60ml / hr 2 , 70ml / hr 2 , or 30 to 70 ml / hr 2The set of conditions may further include determining whether the diuretic administration rate is higher than a predetermined administration rate (e.g., 8 mg / hr, 10 mg / hr, 12 mg / hr, or a range of 8-12 mg / hr) (processing portion 706). The set of conditions may further include determining whether the diuretic administration rate is higher than a predetermined administration rate (e.g., 8 mg / hr, 10 mg / hr, 12 mg / hr, or a range of 8-12 mg / hr) (processing portion 708). In some embodiments, if none of the set of conditions are met, the system will not taper the diuretic administration rate downward and will return to processing portion 702. If each of the set of conditions is met, the system will proceed to reduce the diuretic administration rate by a predetermined value. In some embodiments, the system may proceed to reduce the diuretic administration rate via processing portion 710 if two of the three conditions are met.

[0092] In some embodiments, by requiring that all or most of the set of conditions be satisfied, the system can avoid unnecessarily reducing the diuretic administration rate, thereby preventing the urine rate from remaining high and fluid therapy from being unnecessarily interrupted. For example, while other techniques may interrupt fluid therapy and reduce the diuretic administration rate when the urine rate barely exceeds a predetermined threshold, embodiments of the present technology may only reduce the administration rate (via processing portion 710) when the urine rate is high and increasing. In other words, such techniques can prevent unnecessarily reducing the diuretic administration rate when the urine rate is temporarily high (e.g., higher than a predetermined rate) but trending downward and ultimately below the predetermined rate. By doing so, embodiments of the present technology can prevent or reduce overdiuresis or excessive fluid and / or electrolyte loss, and further limit the patient's unnecessary exposure to additional pharmaceutical agents. Additionally or alternatively, tapering the diuretic infusion rate downward rather than discontinuing it can be beneficial by allowing fluid therapy to continue (albeit at a lower urine rate) without having to fully resume. Additionally or alternatively, there may be additional regulatory benefits to having a tapering technique by mitigating the potential risk of diuretic overdosing (e.g., when ramping the diuretic during the titration phase) and limiting patient overexposure to the diuretic.

[0093] If the set of conditions is satisfied, the system can reduce the diuretic administration rate by a predetermined percentage (e.g., 20%, 25%, 30%, or a range of 20-30%) over a third period of time (e.g., 2 hours, 3 hours, 4 hours, or a range of 2-4 hours). After reducing the diuretic administration rate, the system checks whether the third period of time has elapsed (processing portion 712) and, if so, resets a counter for the set of conditions (processing portion 714). In such an embodiment, the diuretic administration rate can remain at the downward tapering level or can be adjusted based on subsequent operating phases of therapy. If the third period of time has not elapsed, the system can determine whether the average urine rate is higher than a downward tapering threshold (processing portion 720). The downward tapering threshold can be based on a predetermined rate used in processing portion 704. For example, the downward tapering threshold can be 100 ml / hr lower than the predetermined rate. In such embodiments, the downward taper threshold may be 800 ml / hr, 850 ml / hr, 925 ml / hr, 1000 ml / hr, or in the range of 800-1000 ml / hr when hydration fluid is being infused, and 300 ml / hr, 350 ml / hr, 425 ml / hr, 500 ml / hr, or in the range of 300-500 ml / hr when hydration fluid is not being infused. If the average urine rate is lower than the downward taper threshold, the diuretic administration rate may be adjusted (e.g., increased) based on the current duration. In some embodiments, the predetermined percentage by which the processing portion 710 reduces the diuretic administration rate is reduced by a fraction of the third period that has elapsed. For example, assume the predetermined percentage was 25%, and if the diuretic administration rate drops below the downward tapering threshold 90 minutes after downward tapering began (i.e., halfway through the 180-minute third period), the diuretic administration rate would be increased by only half the predetermined percentage, or 12.5%. After the diuretic administration rate is adjusted by processing portion 720, the system can reset the counter for the condition set as described above (processing portion 714).

[0094] Figure 8 is a graphical representation 800 of tapering a diuretic administration rate 805 downward in accordance with an embodiment of the present technology. Graphical representation 800 generally illustrates the embodiment described with reference to Figure 7. As shown in Figure 8, the diuretic administration rate 805 is initially steady at a rate of approximately 20 mg / hr, and the urine rate 810 is 50 ml / hr. 2 At about time 820, urination is greater than 1025 ml / hr. At time 822, each of the sets of conditions described with reference to FIG. 7 are satisfied: (i) the average urine rate 810 is not greater than a predetermined rate of 1025 ml / hr over the first period of three hours, and (ii) the average rate of change in urine rate is 50 ml / hr. 2 and (iii) the diuretic administration rate is greater than the predetermined administration rate of 10 mg / hr. Thus, the diuretic administration rate at time 822 is reduced by a predetermined percentage, in this case 25%, over a period of time, in this case 3 hours, from 20 mg / hr to 15 mg / hr.

[0095] The step of reducing the diuretic administration rate 805 causes the urine rate to drop, as indicated by portion 824. When urination reaches the downward tapering threshold of 925 ml / hr at time point 826, the diuretic administration rate is increased. Because the downward tapering threshold was reached one hour after the downward tapering event (i.e., one-third of the three-hour period), the diuretic administration rate is then set to a one-third (33%) reduction of the original 25%, or 8.3% lower than the original diuretic administration rate of 20 mg / hr. Thus, the diuretic administration rate is set to approximately 18.3 mg / hr. Time point 828 corresponds to a three-hour duration from the downward tapering event, and thus, at this point the downward tapering check is re-entered. In other words, the downward tapering feature is disabled for a period of time after the downward tapering event occurs, in this case, three hours.

[0096] FIG. 9 is a graphical representation 900 of the relationship between urine output rate 905, hydration fluid infusion rate 910, and net fluid balance 915 in accordance with embodiments of the present technology. As described elsewhere herein, embodiments of the present technology allow for a rapid increase in a patient's urine rate 905 by increasing the administration rate of a diuretic provided to the patient relatively rapidly, e.g., in an exponential manner (as described elsewhere herein), during the diuretic dosage determination phase. Simultaneously, hydration fluid can be infused at a rate equal to or lower than the diuretic administration rate, thereby allowing for net fluid balance over time. For example, hydration fluid infusion during the diuretic dosage determination phase can be performed to "jumpstart" the patient's urinary response. In some embodiments, an initial hydration fluid infusion can cause the patient to respond more rapidly to the diuretic; therefore, without being bound by theory, an initial hydration fluid can be infused to reduce intravascular depletion and, further, reduce the decline in cardiac output and renal perfusion. As described elsewhere herein, in some embodiments, the algorithm can control the hydration fluid infusion rate to substantially match (e.g., at least 90% or 100%) the urination rate during either the initial urination volume (e.g., at least the initial 150 ml, 200 ml, 250 ml, 300 ml, 400 ml, 500 ml, or in the range of 150-500 ml) or the initial period (e.g., the first 1, 2, or 3 hours), whichever occurs first. Note that the need for an initial hydration fluid infusion can be determined by the desire to achieve a more vigorous patient response to diuretics rather than reducing the salinity of fluid levels, which may be necessary with subsequent hydration fluid infusions during the operating phase. For example, hydration fluid infusion during the fluid reduction phase or continuous infusion phase can be performed to optimize net fluid reduction while also avoiding safety risks, e.g., by maintaining safe blood pressure and sodium levels. That is, the goal of infusing hydration fluid is to maximize net fluid reduction while avoiding adding back too much sodium and / or otherwise increasing the likelihood of achieving a hypotensive state.

[0097] As shown in FIG. 9, urine rates can be classified into various regions, including a first region (I), a second region (II), a third region (III), and a fourth region (IV), with each subsequent region corresponding to a higher urination rate 905. The first region (I) can correspond to urine rates below a first threshold (e.g., 175 ml / hr, 225 ml / hr, 275 ml / hr, or a range of 175-275 ml / hr). The second region (II) can correspond to urine rates between the first and second thresholds (e.g., 375 ml / hr, 425 ml / hr, 500 ml / hr, or a range of 375-500 ml / hr). The third region (III) can correspond to urine rates between the second and third thresholds (e.g., 975 ml / hr, 1025 ml / hr, 1100 ml / hr, or a range of 975-1100 ml / hr). The fourth region (IV) can correspond to urine rates above the third threshold. As shown in FIG. 9, as urine rate 905 increases, hydration rate 910 also increases approximately, but at a lower rate than urine rate 905. Doing so decreases the net fluid balance 915 (i.e., becomes more negative) and increases the net fluid loss. The urination rate is calculated continuously throughout treatment to allow the algorithm to respond quickly to changes. For example, flow rate, weight, volume, and / or other characteristics indicative of urine volume rate changes can be measured every minute, and the urination rate 905 can be calculated every minute based on the previous period (e.g., 5 minutes, 10 minutes, 20 minutes, or a range of 5-20 minutes). An assessment of how much hydration fluid to infuse can occur every minute.

[0098] As shown in FIG. 9 , when the urine rate 905 is within a first region (I) below a first threshold, the hydration fluid infusion rate 910 can be zero or a minimum amount (e.g., 10 ml / hr) (referred to as an open vein hold (KVO) rate) to keep the veins pressurized and open. Because urination is low within the first region, little or no rehydration is required. Similarly, because the overall goal is to maximize net fluid loss, no hydration fluid infusion may be provided when the urine rate 905 is within the first region (I). As mentioned above, in some embodiments, the hydration fluid infusion rate 910 can match the urine rate 905 for a first period of time or until a minimum amount of hydration fluid has been infused.

[0099] When the urine rate 905 is within the second region (II), substantially all (e.g., at least 90% or 100%) of the urine volume within the second region (II) (i.e., between the first and second thresholds) is replaced with hydration fluid to ensure the kidneys have sufficient fluid and salt and to prevent a hypotensive state.

[0100] When the urine rate 905 is within the third region (III), substantially all (e.g., at least 90% or 100%) of the urine volume in the second region (II) between the first and second thresholds can be replaced with hydration fluid, with 40%, 45%, 50%, or a range of 40-50% of the urine volume in the third region (III) and above the second threshold being replaced. By replacing only a portion of the urine rate above the second threshold, net fluid balance and salinity can be reduced. Urine has a sodium concentration lower than that of blood or normal saline, which is approximately 154 mmol / L. Therefore, replacing urine with an equal amount of hydration fluid may result in high or undesirable sodium levels. In some embodiments, delivering saline or hydration fluid at a rate greater than 50% of the urine rate may increase the risk of providing the patient with more sodium than they are emitting. Thus, limiting the hydration fluid rate to 50% can protect patients with hyponatriuria while also allowing patients with hypernatriuria to enjoy a faster net reduction in fluid and sodium. A urination rate within the third region (III) can serve as an indication that the kidneys are functioning well, the patient is not in a hypotensive state, and therefore a lower hydration fluid rate is fully acceptable.

[0101] When the urine rate 905 is within the fourth region (IV), substantially all (e.g., at least 90% or 100%) of the urine volume in the second region (II) between the first and second thresholds can be replaced with hydration fluid, 40%, 45%, 50%, or a range of 40-50% of the urine volume in the third region (III) between the second and third thresholds can be replaced, and none of the urine volume in the fourth region (IV) above the third threshold can be replaced, thereby further reducing the net fluid balance.

[0102] Previously, removing excessive fluid volumes (e.g., greater than 5 L) within 24 hours using conventional therapy was thought to be dangerous and potentially result in hypotension. However, embodiments of the present technology demonstrate that even with relatively high urine rates (e.g., urine rates in the third or fourth range), removing at least 5 L of excess fluid volume per day (e.g., by infusing 50% replacement hydration fluid) can be safely performed with little or no risk of renal failure.

[0103] In some embodiments, the net fluid loss limit can be set based on the urine rate at the time and / or in the region, with the net fluid loss limit increasing in each subsequent region. For example, the net fluid loss limit can be (i) 80 ml / hr, 90 ml / hr, 100 ml / hr, or in the range of 80-100 ml / hr in a first region (I), (ii) 100 ml / hr, 130 ml / hr, 160 ml / hr, or in the range of 100-160 ml / hr in a second region (II), (iii) 250 ml / hr, 400 ml / hr, 500 ml / hr, or in the range of 250-500 ml / hr in a third region (III), and (iv) 500 ml / hr, 750 ml / hr, 900 ml / hr, or in the range of 500-1000 ml / hr in a fourth region (IV).

[0104] IV. Methods for Inducing Net Fluid Loss from a Patient 10 is a flow diagram of a method 1000 for causing net fluid loss from a patient according to an embodiment of the present technology. Method 1000 may be implemented by a computer, a controller, and / or on an executable tangible non-transitory computer-readable medium. For example, method 1000 may correspond to executable instructions executed by one or more processors that are part of a console or related device.

[0105] The method 1000 may obtain a urination rate from the patient by accepting input from, for example, a flow sensor, a volume sensor, a weight sensor, an optical sensor, or other sensor for determining flow rate (processing portion 1002). The urination rate may be an average rate measured over the previous 5 or 10 minutes and may be updated continuously or repeatedly (e.g., every 30 seconds, every minute, every 2 minutes, etc.).

[0106] Method 1000 can include providing a diuretic to the patient at an administration rate (processing portion 1004). The diuretic can include furosemide, bumetanide, ethacrynic acid, torsemide, and / or other diuretics known in the art and can be part of a solution including saline or other hydration fluid mixed therewith. The diuretic can be provided to the patient as part of a diuretic dosage determination phase, as described elsewhere herein (e.g., with reference to FIGS. 2A-4B). For example, the diuretic can be delivered at an initial dose and then rapidly increased. In some embodiments, the diuretic administration rate can be increased in an exponential manner and / or in a manner that doubles the diuretic administration rate or total diuretic dose within a period of time (e.g., 10 minutes, 15 minutes, 20 minutes, or a range of 10-20 minutes).

[0107] Method 1000 can include providing hydration fluid to the patient at a hydration rate no greater than the urination rate (processing portion 1006). The hydration fluid can comprise saline or other fluids containing sodium. The hydration fluid can be provided to the patient based on the corresponding urine rate. For example, as described elsewhere herein, the hydration fluid rate can be determined based on whether the urine rate is above or below several different thresholds (e.g., first, second, and third thresholds described with reference to FIG. 9), with the difference between the urine rate and each threshold increasing as the urine rate increases. In some embodiments, the hydration fluid can substantially match the initial volume of urine provided to the patient (e.g., at least an initial 150 ml, 200 ml, or 250 ml) and / or the urine rate over an initial period (e.g., the first hour, two hours, or three hours).

[0108] The method 1000 may adjust at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid, thereby causing a net fluid loss from the patient (processing portion 1008). In this regard, the difference between the diuretic administration rate and the hydration rate may be increased by increasing the diuretic administration rate, increasing the diuretic administration rate relative to the hydration fluid, and / or decreasing the hydration fluid. As described elsewhere, adjusting one or both of the diuretic administration rate and the hydration fluid rate may be performed while still requiring a minimum fluid loss limit.

[0109] In some embodiments, adjusting the administration rate of the diuretic can include ramping or re-ramping the diuretic dosage. Determining whether re-ramping is initiated can be based on a set of conditions (such as those described with reference to processing portion 510 in FIG. 5). For example, a trigger for re-ramping may involve determining whether (i) the average urine rate has fallen below a predetermined threshold rate (e.g., 250 ml / hr, 300 ml / hr, 325 ml / hr, 350 ml / hr, or 400 ml / hr) for a predetermined period of time (e.g., 2 hours, 2.5 hours, or 3 hours), and / or (ii) whether a debt of more than a predetermined amount (e.g., 100 ml, 125 ml, 150 ml, 175 ml) has accumulated over a period of time. As mentioned above, debt can be defined as an area below a threshold (e.g., 250 ml / hr, 275 ml / hr, 325 ml / hr, or a range of 250-325 ml / hr) and above the current urine rate for a given period of time. If one of these conditions is met, re-ramp can be initiated.

[0110] Re-ramping can occur in response to the urine rate dropping below a threshold after an initial diuretic ramp (e.g., during the diuretic dose determination phase). For example, as described above with reference to Figures 5 and 6, if the urine rate (e.g., average urine rate) is determined to be low based on a set of conditions, the system can begin re-ramping the diuretic dose rate, for example, after receiving confirmation from the patient approving re-ramping of the diuretic dose rate. Re-ramping can be performed in a manner similar to the diuretic dose determination phase in that the diuretic dose rate is rapidly increased until a period of time has elapsed and / or until the patient's urine rate increases above a predetermined threshold. For example, in such an embodiment, the diuretic dose is increased piecewise in an exponential manner so that each diuretic dose rate is higher than the previous diuretic dose rate, e.g., by at least 50%, 75%, 100%, or in the range of 50-100%. In such embodiments, the diuretic administration rate can effectively double one or more times throughout a particular ramp or diuretic dosage phase. At the point at which the ramp is discontinued due to the lapse of that period or the urine rate increasing above a predetermined threshold, the diuretic administration rate can be further adjusted, for example, by setting the diuretic dose to be a percentage of the total amount of diuretic delivered to date. The total amount of diuretic delivered can include the amount delivered during the re-ramp and the amount delivered during any previous ramps, if applicable.

[0111] The ramp and re-ramp features of embodiments of the present technology can be beneficial to the user and to fluid therapy in general by allowing a patient's urine rate to be increased as rapidly as possible (e.g., by infusing hydration fluid) while also maintaining safe intravascular volume levels to minimize the risk of hypotension and reduced cardiac output and renal perfusion. Additionally or alternatively, the ramp and re-ramp features, in combination with other features of embodiments of the present technology, can allow the patient, the operator, or the system itself to treat the patient and rapidly reverse fluid overload conditions. That is, embodiments of the present technology have been shown to remove fluid volumes greater than 7.5 L over a period of less than 24 hours. Furthermore, because embodiments of the present technology are configured to rapidly increase a patient's urine rate within a relatively short period of time, the system can automatically determine whether the patient is not responding adequately to a particular fluid therapy. That is, if a patient's urine rate does not increase in an expected manner after providing a diuretic according to the ramp or diuretic dosing phase described herein, this can indicate that the patient is diuretic resistant or that there is another problem that requires further investigation. Thus, embodiments of the present technology may allow problems such as diuretic resistance to be identified and subsequently treated or addressed within a shorter period of time than other conventional techniques.

[0112] 11 is a flow diagram of a method 1100 for causing net fluid loss from a patient in accordance with an embodiment of the present technology. Method 1100 may be implemented by a computer, a controller, and / or on an executable, tangible, non-transitory computer-readable medium. For example, method 1100 may correspond to executable instructions executed by one or more processors that are part of a console or related device. Method 1100 may include processing portions 1002, 1004, 1006 described with reference to FIG. 10.

[0113] Method 1100 may include determining whether any one of a set of predetermined conditions is satisfied (processing portion 1108), for example, to determine whether the urine rate is excessively high. The set of conditions may correspond to those described with reference to FIG. 7 (e.g., processing portions 704, 706, 708) and FIG. 8. For example, the set of conditions may include determining whether the average urine rate is higher than a predetermined rate over a first period of time (e.g., 2 hours, 3 hours, 4 hours, or in the range of 2-4 hours). The predetermined rate may depend on whether a hydration fluid is being infused into the patient. If a hydration fluid is being infused into the patient, the predetermined rate may be 900 ml / hr, 950 ml / hr, 1025 ml / hr, 1100 ml / hr, or in the range of 900-1100 ml / hr. The predetermined rate can be 400 ml / hr, 450 ml / hr, 525 ml / hr, 600 ml / hr, or in the range of 400-600 ml / hr when no hydration fluid is being infused into the patient. The condition set can be a condition where the average rate of change (i.e., slope) of the urine rate exceeds a predetermined rate of change (e.g., 30 ml / hr) over a second period (e.g., 1 hour, 2 hours, 3 hours, or in the range of 1-3 hours). 2 , 40ml / hr 2 , 50ml / hr 2 , 60ml / hr 2 , 70ml / hr 2 , or 30 to 70 ml / hr 2 The set of conditions can further include determining whether the diuretic administration rate is higher than a predetermined administration rate (e.g., 8 mg / hr, 10 mg / hr, 12 mg / hr, or a range of 8-12 mg / hr).

[0114] Method 1100 can include reducing the diuretic administration rate by a predetermined amount if at least two of a set of conditions are satisfied. That is, the administration rate can be reduced if two or three of the following conditions are satisfied: (i) the average urine rate is higher than a predetermined rate over a first period of time; (ii) the average rate of change in urine rate is higher than a predetermined rate; and (iii) the diuretic administration rate is higher than a predetermined administration rate. In some embodiments, each of the set of conditions must be satisfied in order to reduce the diuretic administration rate by a predetermined amount. By requiring all or most of the set of conditions to be satisfied, the system avoids unnecessary reductions in the diuretic administration rate, thereby allowing the urine rate to remain high and preventing fluid therapy from being unnecessarily interrupted. For example, whereas other techniques may simply interrupt fluid therapy and reduce the diuretic administration rate when the urine rate is too high, the present technique can reduce the administration rate (by processing portion 1110) only when the urine rate is high and increasing. In other words, such technology can prevent unnecessary reductions in diuretic administration rates when the urine rate is temporarily high (e.g., higher than a predetermined rate) but trending downward and ultimately below the predetermined rate. By doing so, embodiments of the present technology can prevent or reduce overdiuresis or excessive fluid and / or electrolyte loss, further limiting the patient's unnecessary exposure to additional diuretic. Additionally or alternatively, tapering the diuretic administration rate downward rather than discontinuing it can be beneficial because it can be continued (albeit at a lower urine rate) without requiring a full resumption. This allows the net fluid balance to continue increasing even during a tapering event, rather than discontinuing fluid therapy and thereby halting the increase in net fluid loss. Additionally or alternatively, there may be additional regulatory benefits to having tapering technology by mitigating the potential risk of diuretic overdosing (e.g., when ramping diuretic during the titration phase) and limiting the patient's overexposure to diuretic.

[0115] Reducing the diuretic administration rate by a predetermined amount can correspond to the downward tapering techniques described elsewhere herein with reference to FIG. 7 (e.g., processing portions 710, 712, 714, 716, 720) and FIG. 8. For example, reducing the diuretic administration rate can reduce the diuretic dosage by a predetermined percentage (e.g., 20%, 25%, 30%, or in a range of 20-30%) over a period of time (e.g., 2 hours, 3 hours, 4 hours, or in a range of 2-4 hours). In some embodiments, once the period of time has elapsed after reducing the diuretic dosage, a counter for the set of conditions can be reset. In such embodiments, the diuretic dosage can remain at the downward tapering level or can be adjusted based on subsequent operating phases of therapy. If the third period of time has not elapsed and the average urine rate has fallen below the downward tapering threshold, the diuretic administration rate can be adjusted (e.g., increased) based on the amount of time that has now elapsed. In some embodiments, the predetermined percentage by which the diuretic administration rate is reduced is reduced by a fraction of the elapsed time period. For example, assuming a predetermined percentage of 25% and a three-hour time period, if the diuretic administration rate drops below the downward taper threshold 90 minutes after the downward taper begins, the diuretic administration rate would be increased by half the predetermined percentage, or 12.5%. After the diuretic administration rate is adjusted by processing portion 1110, the counter for the condition set can be reset as described above.

[0116] V. Example: Fluid Overload Therapy Using Diuretics and Hydration Fluids The following examples are included to further illustrate some aspects of the present technology and should not be used to limit the scope of the invention.

[0117] Clinical data relating to embodiments of the present technology were obtained from patient trials conducted at the Tbilisi Heart and Vascular Center in Tbilisi, Georgia, USA. Fifteen patients received fluid therapy in which a diuretic and hydration fluid were administered via the Reprieve Cardiovascular® Second Generation System according to the methods described herein (the "treatment group"). As described below, the data obtained from these trials demonstrate that the resulting levels of net fluid loss and net sodium loss correspond to significant improvements over conventional methods for treating fluid overload conditions, and generally demonstrate that embodiments of the present technology achieve improved diuresis and renal safety.

[0118] Table 1 below shows the total urination, net fluid loss (not including ingested fluids), net fluid loss (including ingested fluids), net sodium balance, and average diuretic (Lasix) administration rate measured over the therapy period for each patient in the treatment group. As shown in Table 1, the average net fluid loss (not including oral fluid intake) for patients in the treatment group was approximately 7 liters (L) over the average therapy period of 31 hours. When normalized over a 24-hour period for each patient, the average net fluid loss was approximately 5.4 L. Compared to patients receiving conventional fluid therapy treatment (i.e., diuretics administered without replacement hydration fluid) (the "control group"), who experienced an average net fluid loss of 1.75 L over the normalized 24-hour period, the treatment group demonstrated a greater than 200% increase in net fluid loss. Furthermore, the average therapy period for the treatment group was 31 hours, compared to the average therapy period for standard of care therapies in this literature, which was approximately 5 days. Thus, combined fluid therapy with diuretics and hydration fluids was able to achieve significantly greater net fluid loss and shorter overall therapy time compared to conventional therapy. During treatment, patients in the treatment group further demonstrated an average weight loss of 6.8 kilograms (kg) at discharge and 5.7 kg after 30 days. Over the 30-day period, none of the patients in the treatment group regained the weight lost during therapy or were readmitted for additional treatment.

[0119] Table 1: Clinical data for patients in the treatment groups JPEG2025161822000002.jpg114142

[0120] As also shown in Table 1, the average diuretic administration rate was approximately 40 mg / hr, corresponding to a daily dose of approximately 950 mg. This diuretic administration rate and dose was significantly higher than the corresponding administration rates and doses for conventional therapies, thus contributing to the relatively high therapeutic efficacy of embodiments of the present technology.

[0121] As also shown in Table 1, the mean net sodium balance for all patients within the treatment group decreased by nearly 800 millimoles (mmol) over the course of therapy. When normalized over a 24-hour period, the mean and median net sodium balance were -14 grams (g) and -15 g, respectively. Compared to conventional therapy, which showed a median net sodium balance of -3.63 g over a normalized 24-hour period, these values ​​correspond to an improvement of 11 g, or more than 300%.

[0122] Estimated glomerular filtration rate (eGFR) is a measure of kidney function and the stage of kidney disease and is based on blood creatinine and patient factors, including the patient's age, body size, and sex. Patients in the treatment group demonstrated a mean creatinine increase of 0.11 mg / dL (deciliter) over the 30-day period, with a modest mean decrease of 1.6 eGFR. Such modest eGFR changes indicate that patients tolerated fluid therapy fairly well, particularly given the amount and rate of net fluid loss, and that post-therapy kidney function remained near pre-treatment levels.

[0123] Blood pressure measurements of patients within the treatment group serve as another indication of the patient's acceptance of fluid therapy. For example, the patient's mean arterial pressure (MAP) decreased from 90.1 mmHg to 88.2 mmHg at discharge and then to 87.2 mmHg 30 days later. Furthermore, the patient's mean systolic pressure decreased from 121 mmHg to 119 mmHg at discharge and then to 117 mmHg 30 days later. Such modest changes in MAP and systolic pressure indicate that the patient tolerated fluid therapy fairly well, especially given the amount and rate of net fluid loss.

[0124] VI. Exemplary Functional Requirements of Embodiments of the Present Technology User Interface display The software shall display the urine production rate reported by the urine monitor device. The software is (desired fluid equilibrium) * Shall display the Net Target defined as (-1) + (Urine Buffer Range) (Note: The default desired fluid balance is -225 and the default urine buffer range is 100, therefore the default Net Target is 325). The software should display the total urine volume over the previous hour ("Last Hour Urine"). The software should display the total urine volume over the previous two hours ("Last 2 Hour Urine"). The software should display the total urine volume over the previous three hours ("Last 3 Hour Urine"). The software will display the total "debt" defined as the area below the "Net Target" and above the "Urine Production Rate" over the previous three hours. If the urine production rate is not greater than the "Net Target", no "debt" will be added or removed. The software shall display the average urine rate over the previous hour. The software shall display the time in current mode. The software shall display the total diuretic dose during the previous ramp. The software shall display the total urine volume measured by the urine monitor device during the previous lamp. The software shall display the time the previous lamp exceeded the target urine rate (Note: the default target urine rate is 525 ml / hr). The software shall display the total amount of diuretic infused from the start of therapy. The software shall display the total amount of diuretic infused during the previous 24 hours. The software shall display the current diuretic infusion rate. The software shall display the total amount of saline infused from the start of therapy as reported by the hydration fluid infusion device. The software shall display the total measured urine volume from the start of therapy as reported by the urine monitoring device. The software shall display the net fluid balance ("volume removed") measured from the start of therapy based on the difference between total voided and total volume of hydration fluid infused. The software shall display the current fluid balance target. The software may plot the urine rate and display the urine rate as an average rate over one or more time periods, such as 15 minutes, 1 hour, and / or 3 hours. The software shall plot the diuretic infusion rate on the same plot as the urine rate. The software shall provide the user with the ability to adjust the time scale and y-axis of the urine plot. The software is intended to indicate that a diuretic infusion device, a urine monitoring device, and / or a hydration fluid source are connected to a console housing a computer control system. The software will indicate that a diuretic dispensing device, for example an injection syringe for dispensing a diuretic, is connected. key The software shall provide a button that allows the user to initiate therapy. The software shall provide a button that allows the user to stop the therapy. The software shall provide a button that allows the user to pause the injection. The software shall provide a button that allows the user to stop the ramp and proceed to continuous infusion. The software shall provide a button that allows the user to enable manual control of the diuretic infusion rate. The software shall provide a control that allows the user to adjust the diuretic pump rate in milliliters / hr. The software shall provide a means to allow the user to view error messages. The software shall provide a means to allow the user to reset the serial port to the syringe injection system. The software shall provide a means for allowing a user to reset one or more serial ports on a console housing the computer system, the ports being connected to one or more of a urine monitor device, a diuretic dispensing device, and a hydration fluid supply or hydration fluid dispensing device. The software shall provide a means to allow the user to initiate lamp mode. The software shall provide a means to allow the user to download event records from the computer system. setting The software shall allow the user to set the following parameters: Urine buffer range (ml / hr) - used as target "desired fluid balance" * Higher speed than (-1) Default value: 100ml / hr Urine Rate Target (ml / hr) - Urine rate target during the ramp phase Default value: 525ml / hr Debt threshold (ml / hr) - urine rate below which debt is calculated Default value: 325ml / hr Mode Control Lamp Mode: The software shall provide a ramp mode that begins when the user initiates diuretic administration. If no file input is selected by the user at the start of the diuretic infusion, the IV diuretic infusion shall follow a log base 2 curve from 0 and ramp exponentially to the maximum rate required to infuse 200 mg of furosemide given 60 minutes. If a file input is selected by the user, the IV infusion shall follow the specified profile. The described IV infusion shall be stopped when: a) 60 minutes have passed since the start of the ramp without reaching the target urine rate. or b) When the urine production rate measured by the console is greater than or equal to the user-adjustable target urine rate (default 525 ml / hr). In this case, the software shall wait 10 minutes and monitor the urine output rate. During this time, the software shall set the diuretic pump rate to 20% of the currently delivered dose. If the urine output rate remains above 525 ml / hr, the software shall enter continuous infusion mode, and if the urine rate falls below 525 ml / hr, the ramp shall continue for at least 5 minutes. or c) At the user's request. Once the ramp is complete, the software shall enter continuous injection. pause : During the ramp phase, the user shall be provided with the option to pause the IV infusion. Upon request to continue the IV infusion, the IV infusion shall commence at the rate at which it was paused and follow the selected IV infusion pattern for the time remaining until the completion of 60 minutes. Continuous infusion : Once the ramp is complete, the system shall continue to administer a continuous diuretic IV infusion rate based on the following formula: Infusion rate (mg / hr)=0.2 * (Total amount in mg of diuretic infused during the ramp phase corresponding to the number of minutes of the ramp completed) If the infusion rate calculated in the previous step was lower than 4 mg / hr, the infusion rate will be set to 4 mg / hr. During the continuous infusion mode, the system monitors the patient's urination to determine if the ramp mode criteria or the downward tapering mode criteria have been met. The software shall enter downward taper mode if urination has been steadily above 625 ml / hr for three hours and the slope of the urine rate over the previous two hours predicts that urination will be higher than 625 ml / hr within three hours. The software shall re-enter ramp mode if average urination falls below the urine buffer range + net target (default 325 ml / hr) for three hours or if the accumulated debt over the previous three hours exceeds 150 ml. Debt shall be defined as the area below the debt threshold and above the urine rate when the urine rate is below the debt threshold (default value 325 ml / hr). Ramp mode shall continue for the number of minutes corresponding to the current infusion rate during the ramp phase (Ramp Total = Infusion Rate / 0.2). If the amount of urine output in the previous 15 minutes is less than 25 ml (100 ml / hr), the device will not enter lamp mode. Ramp mode shall not be entered if the current infusion rate corresponds to a ramp of 55 minutes or more. Gradual decrease downward : When the tapering down mode is initiated, the software shall set the pump rate to 0.4 ml / hr for a maximum of 50 minutes. If the 50 minutes expires without the urine rate dropping below 525 ml / hr, the software shall continue the continuous infusion at 75% of the rate before the downward taper began (a 25% rate reduction). If during this 50 minute period urine output falls below 525 ml / hr, the software will continue the infusion at a rate calculated as follows: New injection rate = previous injection rate * (1-0.25 * (minutes urine rate falls below 525) / 50) Re-lamp : The software shall provide a means for the user to resume lamp mode. The ramp, when restarted, shall last for at least five minutes. When the ramp restarts, it shall continue to restart at the fractional point in the ramp that corresponds to the current continuous infusion rate (e.g., the ramp shall restart at the fractional point in the ramp whose end would achieve the currently set continuous infusion rate). The ramp shall be an initial ramp followed by an exponential ramp. When the urine production rate reaches the target urine rate (525 ml / hr), the software shall switch to the continuous infusion rate corresponding to the current minute of the total ramp (i.e., if the re-ramp begins at the 25 minute mark and runs for 10 minutes, the continuous infusion rate shall be set to the same rate as if the initial ramp had run for 35 minutes). When the ramp is restarted, the debt shall be reset to 0 and the 3-hour average urine rate timer shall be reset. manual : The software shall provide a mode that allows the user to set the diuretic infusion rate. The unit of diuretic infusion setting is ml / hr. The increment of diuretic infusion setting is 0.1 ml / hr. The minimum is 0.4 ml / hr. The maximum is 4.0 ml / hr. The user shall have the option to enable and disable the control algorithm from operating while in manual mode. off: The software shall provide an "off" mode in which diuretic administration is stopped and the diuretic dispensing device, eg, a Gaseby® infusion syringe, is deactivated. When the user restarts diuretic management, control shall continue where it was before entering "off" mode. Monitor / protect function The software shall notify the user if there is an alarm in the diuretic dispensing device, for example, a Gaseby® injection syringe. The software shall notify the user if the diuretic dispensing device, for example, a Gaseby® infusion syringe pump, is disconnected. The software shall notify the user if the system is not in run mode. The software shall notify the user if the urine rate over the previous 15 minutes falls below an enabled limit. When a diuretic dispensing device, e.g., a Gaseby® infusion syringe pump, enters alarm mode, the application shall wait until the alarm is manually resolved and set the pump infusion rate to the previous value and mode according to this resolution. When an infusion rate of a diuretic dispensing device, e.g., a Gaseby® infusion syringe pump, other than that requested by the application is detected, the application shall stop the pump and notify the user. Exemplary software code for the hydration fluid control component of the algorithm is as follows: Static void calcNetGain( float period_urine_delta ) { float setting= 0.0; float netGain_mlphr; / / float maxFluidLossRate; / / float excessUrineOutput; / / urine output over and above the max loss rate, in ml / hr float pMatchSetting; / / float urine_rate_exceeding_net_gain; float percent_match_adjustment_to_target; float fullMatchLimit, urine_rate_exceeding_full_match_limit; float fullMatchRange ; / / float initalBalanceVolume; / / float kvo_setting; float desired_fluid_loss_rate; float fluid_match_rate; netGain_mlphr = getUserSetting( DESIRED_BALANCE_SETTING ); pMatchSetting = getUserSetting( PERCENT_MATCH_SETTING ); fullMatchRange = getUserSetting( PCT100_MATCH_RANGE_SETTING ); initalBalanceVolume = getUserSetting( INITIAL_FLUID_MATCH_SETTING ); maxHourlyInfusion = getUserSetting( HOURLY_INFUSION_LIMIT_SETTING ); if ( netGain_mlphr >= 0 ) { setting = ( float ) ( ( ( double ) netGain_mlphr * ( double ) FlowControlInterval ) / 3600.0 ); / / convert from ml / hr to ml / s if ( (pMatchSetting >= 0) && (pMatchSetting < 100)) / / apply percent match if it's set and negative net gain is not { setting-= period_urine_delta * ( (100-pMatchSetting) / 100 ); } fluid_match_rate = LightUrineRate + (setting)*3600.0 / ( double )FlowControlInterval; if ( fluid_match_rate > maxHourlyInfusion) / / if the current setting exceeds the current max hourly rate, clip it to the max hourly rate { desired_fluid_loss_rate = (-1.0)*(LightUrineRate - maxHourlyInfusion); / / rate of fluid loss in ml / hr setting = ((desired_fluid_loss_rate* ( double ) FlowControlInterval ) / 3600.0 ); / / convert from ml / hr to ml / s } } else if( (control_data.accumulated_urine_weight > initalBalanceVolume ) || ( GetRunModeTime() > 3600 ) ) / / only use negative net gain if 500 ml volume reached or 60 minutes { fullMatchLimit = abs( netGain_mlphr ) + fullMatchRange; / / calculate rate where percent match begins if ( LightUrineRate > abs( netGain_mlphr ) ) / / urine rate if above the max net gain { if ( LightUrineRate < fullMatchLimit ) / / if in full match range, take off net gain, but nothing else { setting = ( float ) ( ( ( double ) ( netGain_mlphr ) * ( double ) FlowControlInterval ) / 3600.0 ); / / convert from ml / hr to ml / s } else { urine_rate_exceeding_full_match_limit = LightUrineRate - fullMatchLimit; / / calculate the amount of urine exceeding full match limit percent_match_adjustment_to_target = urine_rate_exceeding_full_match_limit * ( (100-pMatchSetting) / 100 ); setting = ( float ) ( ( ( double ) ( netGain_mlphr - percent_match_adjustment_to_target ) * ( double ) FlowControlInterval ) / 3600.0 ); / / convert from ml / hr to ml / s } fluid_match_rate = LightUrineRate + (setting)*3600.0 / ( double )FlowControlInterval; / / setting is negative- calculate rate of replacement with current setting if ( fluid_match_rate > maxHourlyInfusion) / / if the current setting exceeds the current max hourly rate, clip it to the max hourly rate { desired_fluid_loss_rate = (-1.0)*(LightUrineRate - maxHourlyInfusion); / / rate of fluid loss in ml / hr setting = ((desired_fluid_loss_rate* ( double ) FlowControlInterval ) / 3600.0 ); / / convert from ml / hr to ml / s } } else { / / if urine rate is below desired fluid balance, take the urine rate off of the target setting = -( ( ( double ) LightUrineRate * ( double ) FlowControlInterval ) / 3600.0 ); / / convert from ml / hr to ml / s } / / increment get gain by the user setting for this interval } control_data.net_gain_target += setting; } / / end func calcNetGain()

[0125] VII. Conclusion It will be apparent to those skilled in the art that changes can be made to the details of the above-described embodiments without departing from the underlying principles of the present technology. In some instances, well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of embodiments of the present technology. While method steps may be presented herein in a particular order, alternative embodiments may perform these steps in a different order. Similarly, certain aspects of the present technology that are disclosed in the context of particular embodiments may be combined or eliminated in other embodiments. Furthermore, while advantages associated with certain embodiments of the present technology may be disclosed in the context of those embodiments, other embodiments may also provide such advantages, and it is not necessary for all embodiments to provide such advantages or other advantages that are disclosed herein and fall within the scope of the present technology. Therefore, the present disclosure and related technology may encompass other embodiments not explicitly shown or described herein, and the present invention is not limited except as by the appended claims.

[0126] Throughout this disclosure, "a," "an," and "the" include singular and plural referents unless the context clearly dictates otherwise. Similarly, unless the word "or" is expressly limited in reference to a list consisting of two or more items to mean only a single item to the exclusion of other items, the use of "or" in such a list shall be interpreted to include (a) any single item in the list, (b) all of the items in the list, or (c) any combination of items in the list. In addition, the terms "comprise," "include," and "have" shall be interpreted to mean including at least the recited features, such that any greater number of the same features and / or other features of additional types are not excluded.

[0127] References herein to "one embodiment," "embodiments," "some embodiments," or similar descriptions mean that a particular feature, structure, operation, or characteristic described in connection with that embodiment can be included in at least one embodiment of the present technology. That is, appearances of such phrases or descriptions herein do not necessarily all refer to the same embodiment. Furthermore, various particular features, structures, operations, or characteristics can be combined in any suitable manner in one or more embodiments.

[0128] Unless otherwise indicated, all numbers expressing concentration, shear strength, and other numerical values ​​used in the specification and claims are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that may vary depending on the desired properties sought to be obtained by the inventive technology. At the very least, and without intending to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed, at least, in light of the number of significant digits disclosed and by applying ordinary rounding techniques. In addition, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a range of "1 to 10" includes any and all subranges between (and including) a minimum value of 1 and a maximum value of 10, i.e., any and all subranges having a minimum value equal to or greater than 1 and a maximum value equal to or less than 10, e.g., 5.5 to 10.

[0129] The above-recited disclosure should not be interpreted as reflecting an intention that any claim require more features than are expressly recited in that claim. Rather, the following claims reflect that aspects of the invention lie in the combination of fewer than all of the features of any single above-disclosed embodiment. Accordingly, the claims following this specification are expressly incorporated herein, with each claim standing on its own as a separate embodiment. The present disclosure includes all permutations of independent claims and their dependent claims.

[0130] The present technology is exemplified, for example, according to various aspects described below. Various embodiments of aspects of the present technology are described as numbered embodiments (1, 2, 3, etc.) for convenience. These are provided as examples and do not limit the present technology. Note that any of the dependent embodiments can be combined in any combination within each independent embodiment. Other embodiments can be presented in a similar manner.

[0131] 1. A system for removing fluid from a patient comprising: a console housing a computer controller; a urination device for measuring the rate or volume of urine production of the patient; a first infusion pump configured to pump a hydration fluid into the patient; and a second infusion pump configured to pump a diuretic therapy into the patient, wherein the controller is configured to accept urination data from the urination device, control the first infusion pump to deliver a first desired infusion rate of hydration fluid to the patient, and simultaneously control the second infusion pump to incrementally increase the dosage of the diuretic therapy; determine a second desired infusion rate of hydration fluid that is lower than the first desired infusion rate and dependent on the rate and / or volume of urine production, and control the first infusion pump to deliver the hydration fluid at the second desired infusion rate, and simultaneously control the second infusion pump to infuse a substantially constant dosage of the diuretic therapy. 2. The system of clause 1, wherein the controller is further configured to progressively increase the dosage of the diuretic therapeutic agent in periodic steps, each step being a greater dosage increase than the previous step. 3. The system of clause 1 or 2, wherein the controller is further configured to progressively increase the dosage of the diuretic therapeutic agent according to a linear mathematical function. 4. The system of clause 1 or 2, wherein the controller is further configured to progressively increase the dosage of the diuretic therapeutic agent according to an exponential mathematical function. 5. The system of clause 4 in which the mathematical function is an exponential function of degree 1. 6. The system of any of the preceding clauses, wherein the controller is further configured to determine a fixed dose of the diuretic therapy based on the total amount of the diuretic therapy administered while controlling the second infusion pump to incrementally increase the dose of the diuretic therapy. 7. A system configured to administer a diuretic and hydration fluid comprising: a console housing a computer controller; a urination device for measuring the rate or volume of urine production of a patient; a first infusion pump configured to pump a hydration fluid into the patient; and a second infusion pump configured to pump a diuretic therapeutic into the patient, wherein the controller is configured to control the second infusion pump to infuse the diuretic into the patient, control the first infusion pump to pump a hydration fluid containing sodium chloride into the patient, and monitor urination by the patient, wherein control of the first infusion pump automatically adjusts the rate of hydration fluid infused into the patient in response to changes in urination by the patient. 8. The system of clause 7, wherein the automatic adjustment of the rate of hydration fluid includes adjusting the rate of hydration fluid to be substantially proportional to urination while urination is below the first threshold, and to be less than urination while urination is above the first threshold. 9. The system of clause 8, wherein the first threshold is within 5% of at least one of the following ranges: 350 ml / hr to 550 ml / hr, 375 ml / hr to 475 ml / hr, 400 ml / hr to 450 ml / hr, or 425 ml / hr. 10. The system of clause 8 or 9, wherein the automatic adjustment of hydration fluid includes setting the hydration fluid at a fraction of the current rate of urination while urination is above the first threshold, the fraction being within a range of 70% to 30%, 60% to 40%, or 45% to 55% of the current rate of urination. 11. The system of any of clauses 7 to 10, wherein the automatic adjustment of the rate of hydration fluid includes adjusting the rate of hydration fluid to a substantially constant hydration fluid rate while urination exceeds the second threshold. 12. The system of clause 10, wherein the second threshold is greater than at least one of 800 ml / hr, 900 ml / hr, 1000 ml / hr, 1025 ml / hr, 1100 ml / hr, or 1200 ml / hr. 13. The system of any of clauses 7 to 12, further comprising automatically adjusting a rate of infusion of a diuretic into the patient during at least one period during which urination is below a third threshold. 14. A method of treating a patient suffering from fluid overload, comprising administering a diuretic to a patient to increase the patient's urination; determining urination by the patient while administering the diuretic; infusing a hydration fluid into the patient; and automatically adjusting a rate of the hydration fluid infused into the patient to achieve a desired net fluid loss in the patient. 15. The method of clause 14, wherein automatic adjustment of the rate of hydration fluid is calculated based on the difference between urination and desired net fluid loss. 16. The method of clause 14 or 15, wherein the automatic adjustment of the rate of hydration fluid is calculated based on the current rate increase of urination. 17. The method of any of clauses 14-16, wherein the automatic regulation of the rate of hydration fluid reduces the rate or rate of increase of hydration fluid in response to urination being above a first threshold output. 18. The method of clause 16, wherein the first threshold output is a rate of urination. 19. The method of any of clauses 14-18, wherein the automatic adjustment of the rate of hydration fluid includes increasing the rate of hydration fluid to a rate within ten percent (10%) of the current urination rate until the current urination rate reaches a first threshold output. 20. The method of clause 19, wherein the first threshold output is a urination rate in the range of 200 ml / hr to 240 ml / hr. 21. Any of the methods of clauses 14 to 20, further comprising limiting the rate of hydration fluid infusion to a maximum limit value for hydration fluid while the current urination rate is above a second threshold, above 500 ml / hr, above 700 ml / hr, or above 1020 ml / hr. 22. The method of any of clauses 14 to 21, further comprising the step of stopping the method when the net fluid loss reaches a desired amount for net fluid loss, such as 5 liters, 8 liters, or 10 liters. 23. The method of any of clauses 14 to 22, further comprising automatically adjusting the diuretic administered to the patient based on urination. 24. The method of clause 23, wherein the autoregulation of the diuretic comprises increasing the rate of administration of the diuretic until urination reaches a desired minimum urine output. 25. The method of clause 24, wherein the minimum urine value is the minimum urination rate. 26. The method of any of clauses 23 to 25, wherein adjusting the diuretic includes automatically increasing the level of diuretic at intervals of 5 minutes or less until urination reaches a desired minimum urine output. 27. The method of clause 26, wherein at least one of the increases in diuretic level is an increase that is greater than the immediately preceding increase. 28. The method of clause 26 or 27, wherein each increase in diuretic level is greater than the immediately preceding increase. 29. The method of any of clauses 14 to 28, wherein the automatic adjustment of the diuretic includes, in response to urination reaching a desired minimum urine value or minimum urine rate, calculating a lower rate for the diuretic that is lower than or based on the value of the diuretic administered when urination reached the desired minimum urine value or minimum urine rate, and administering the diuretic at the lower rate for a period of at least one hour. 30. A fluid management system comprising: a hydration fluid pump configured to pump hydration fluid into a patient; a diuretic pump configured to pump a diuretic into the patient; a measurement device configured to measure the patient's urine output; and a computer configured to determine the amount or rate of the patient's urine output, automatically inject the diuretic into the patient by controlling the diuretic pump to deliver the diuretic at an administration rate determined by the computer, automatically infuse a quantity or rate of hydration fluid into the patient by controlling the hydration fluid pump, and automatically adjust the rate or amount of hydration fluid infused into the patient to achieve a desired amount or rate of net fluid loss in the patient. 31. The fluid management system of clause 30, wherein the computer is configured to determine automatic adjustment of the amount or rate of hydration fluid based on the difference between the amount or rate of urination and the desired net fluid loss, respectively. 32. The fluid management system of clause 30 or 31, wherein the automatic adjustment of the rate of hydration fluid is calculated based on the current rate increase of urination. 33. The fluid management system of any of clauses 30 to 32, wherein the automatic adjustment of the rate of hydration fluid reduces the increase in the rate of hydration fluid in response to urination being above a first threshold output. 34. The fluid management system of any of clauses 30 to 33, wherein the threshold output is a rate of urination. 35. The fluid management system of any of clauses 30-34, wherein the automatic adjustment of the rate of hydration fluid includes increasing the rate of hydration fluid to a rate within ten percent (10%) of the current urination rate until the current urination rate reaches a first threshold output. 36. The fluid management system of any of clauses 30 to 35, wherein the first threshold output is a urination rate in the range of 200 ml / hr to 240 ml / hr. 37. The fluid management system of any of clauses 30 to 36, further comprising limiting the rate of hydration fluid infusion to a maximum limit value for hydration fluid while the current urination rate is above a second threshold, above 500 ml / hr, above 700 ml / hr, or above 1020 ml / hr. 38. The fluid management system of clause 37, wherein the computer is further configured to maintain the rate of hydration fluid infusion at a maximum limit while urination exceeds a maximum threshold urination rate. 39. The fluid management system of any of clauses 30 to 38, further comprising the step of ceasing the step of automatically injecting the diuretic when the net fluid loss reaches a desired amount relative to the net fluid loss, such as 5 liters, 8 liters, or 10 liters. 40. The fluid management system of any of clauses 30 to 39, wherein the computer is further configured to stop administration of the diuretic when fluid loss reaches a desired amount relative to net fluid loss. 41. The fluid management system of any of clauses 30 to 40, wherein the computer is configured to automatically adjust the diuretic administered to the patient based on urination. 42. The fluid management system of any of clauses 30 to 41, wherein the automatic adjustment of the diuretic includes increasing the rate of the diuretic being administered until urination reaches a desired minimum urine output. 43. The fluid management system of any of clauses 30 to 42, wherein the minimum urine value is a minimum urination rate. 44. The fluid management system of any of clauses 30 to 43, wherein adjusting the diuretic includes automatically increasing the level of diuretic at intervals of 5 minutes or less until urination reaches a desired minimum urine output. 45. The fluid management system of clause 44, wherein at least one of the increases in diuretic level is an increase that is greater than the immediately preceding increase. 46. ​​The fluid management system of clause 44 or 45, wherein each increase in diuretic level is greater than the immediately preceding increase. 47. The fluid management system of any of clauses 30 to 46, wherein the automatic adjustment of the diuretic includes, in response to urination reaching a desired minimum urine value or minimum urine rate, calculating a lower rate for the diuretic that is lower than or based on the value of the diuretic administered when urination reached the desired minimum urine value or minimum urine rate, and administering the diuretic at the lower rate for a period of at least one hour. 48. A method of providing fluid therapy comprising obtaining a urine output rate from a patient; providing a diuretic to the patient at an administration rate; providing a hydration fluid to the patient at a hydration rate no greater than the urine output; and adjusting at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid, thereby causing a net fluid loss from the patient. 49. The method of any one of the preceding clauses, wherein adjusting the diuretic administration rate comprises increasing the administration rate until (i) a predetermined period of time has elapsed, (ii) the urination rate is greater than a first predetermined threshold, (iii) the total amount of diuretic delivered is greater than a second predetermined threshold, and / or (iv) the administration rate is greater than a third predetermined threshold. 50. The method of clause 49, wherein the first predetermined threshold is at least 150 ml / hr, 200 ml / hr, 250 ml / hr, 300 ml / hr, 350 ml / hr, 400 ml / hr, 450 ml / hr, 500 ml / hr, or 525 ml / hr. 51. The method of any of clauses 49 or 50, wherein the second predetermined threshold is at least 100 mg, 150 mg, 200 mg, or 250 mg. 52. The method of any of clauses 49-51, wherein the third predetermined threshold is at least 20 mg / hr, 30 mg / hr, 40 mg / hr, or 50 mg / hr. 53. Any of the methods of clauses 49 to 52, wherein the predetermined period is at least 20 minutes, 30 minutes, 40 minutes, or 60 minutes. 54. The method of any one of the preceding clauses, wherein providing the diuretic comprises providing the diuretic in incremental doses, each dose being higher than the immediately preceding dose. 55. The method of any one of the preceding clauses, wherein providing the diuretic comprises providing the diuretic in repeated and increasing doses such that the rate of administration is doubled within a period of 20 minutes, 15 minutes, or 10 minutes. 56. The method of any one of the preceding clauses, wherein the step of providing the diuretic comprises increasing the rate of administration of the diuretic in an exponential manner. 57. The method of any one of the preceding clauses, wherein providing the diuretic comprises providing the diuretic in successively increasing doses until at least one of a predetermined period of time has elapsed and a threshold urine rate is exceeded. 58. The method of any one of the preceding clauses 1, wherein the step of providing the diuretic comprises the step of repeatedly increasing the administration rate so that the rate or amount of diuretic provided to the patient increases by at least 50%, 100%, or 150% compared to the previous administration rate after set intervals of no more than 15, 20, or 30 minutes. 59. The method of any one of the preceding clauses, wherein the step of providing a diuretic to the patient comprises increasing the administration rate of the diuretic so that the urination rate is above a predetermined threshold, and the step of adjusting the administration rate comprises decreasing the administration rate so that the value of the reduced administration rate is a percentage of the value of the total amount of diuretic provided to the patient. 60. The method of any one of the preceding clauses, wherein the step of providing the diuretic comprises providing the diuretic such that the urination rate is above a predetermined threshold, and the method further comprises, after providing the diuretic, determining that the urination rate is below the predetermined threshold, and requesting confirmation from the user or patient to increase the diuretic rate. 61. The method of clause 60., further comprising the steps of receiving confirmation from the user or patient to increase the diuretic rate, and increasing the administration rate only after receiving the confirmation. 62. The method of clause 61, wherein increasing the administration rate comprises increasing the administration rate until the urination rate is greater than a predetermined threshold. 63. The method of any one of the preceding clauses, wherein the step of providing the diuretic comprises providing the diuretic such that the urination rate is above a predetermined threshold, and the method further comprises, after providing the diuretic, determining that the average urination rate over a period of at least one hour is below a desired threshold of at least 300 ml / hr, and increasing the administration rate until the urination rate is above the predetermined threshold. 64. The method of any one of the preceding clauses, wherein providing the hydration fluid to the patient at a hydration rate includes providing a hydration rate such that the hydration rate substantially matches the urination rate at least until a first amount of hydration fluid, the first amount being at least 200 ml or 250 ml, has been infused. 65. The method of any one of the preceding clauses, wherein providing the hydration fluid to the patient at a hydration rate includes providing the hydration rate such that the hydration rate substantially matches the urination rate over an initial infusion period of at least 60 minutes. 66. The method of any one of the preceding clauses 1, wherein the step of adjusting at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid comprises increasing the administration rate of the diuretic and increasing the hydration rate of the hydration fluid, and the step of increasing the hydration rate comprises setting the hydration rate of the hydration fluid based on the urination rate, such that if the urination rate is below a first threshold, the hydration rate is set to zero or less than 20 ml / hr, and if the urination rate is between a second threshold and the first threshold, the hydration rate is set to 75% to 125% of the urination rate that is between the second threshold and the first threshold. 67. The method of any one of the preceding clauses, wherein adjusting at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid comprises increasing the administration rate of the diuretic and increasing the hydration rate of the hydration fluid, wherein increasing the hydration rate comprises setting the hydration rate of the hydration fluid based on the urination rate such that if the urination rate is below a first threshold, the hydration rate is set to zero or less than 20 ml / hr; if the urination rate is between a second threshold and the first threshold, the hydration rate is set to a first rate equal to 100% or 75% to 125% of the urination rate between the second threshold and the first threshold; and if the urination rate is between a third threshold and the second threshold, the hydration rate is set to the sum of (i) the first rate and (ii) 50% or 25% to 75% of the urination rate between the third threshold and the second threshold. 68. The step of adjusting at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid comprises increasing the administration rate of the diuretic and increasing the hydration rate of the hydration fluid, wherein the step of increasing the hydration rate includes setting the hydration rate of the hydration fluid to zero or less than 20 ml / hr when the urination rate is below a first threshold, and setting the hydration rate to 100% of the urination rate between the second threshold and the first threshold when the urination rate is between a second threshold and the first threshold. or 75% to 125% of the urination rate, and if the urination rate is between a third threshold and the second threshold, set the hydration rate to the sum of (i) the first rate and (ii) a second rate equal to 50% or 25% to 75% of the urination rate that is between the third threshold and the second threshold; and if the urination rate is higher than the third threshold, set the hydration rate to the sum of the first rate and the second rate. 69. The method of any one of the preceding clauses, wherein the first threshold is not higher than 100 ml / hr, 125 ml / hr, 150 ml / hr, 175 ml / hr, 200 ml / hr, 225 ml / hr, or 250 ml / hr. 70. The method of any one of the preceding clauses, wherein the second threshold is not higher than 300 ml / hr, 325 ml / hr, 350 ml / hr, 375 ml / hr, 400 ml / hr, 425 ml / hr, or 450 ml / hr. 71. The method of any one of the preceding clauses, wherein the third threshold is not higher than 800 ml / hr, 850 ml / hr, 900 ml / hr, 950 ml / hr, 1000 ml / hr, 1025 ml / hr, or 1050 ml / hr. 72. The method of any one of the preceding clauses, further comprising reducing the administration rate of the diuretic based on a downward tapering algorithm if the urination rate exceeds a urination threshold of at least 500 ml / hr, 525 ml / hr, 550 ml / hr, 1000 ml / hr, 1025 ml / hr, or 1050 ml / hr for a predetermined period of at least 2 hours, 3 hours, or 4 hours. 73. The method of any one of the preceding clauses, further comprising the step of reducing the diuretic administration rate by a percentage that is at least 10%, 25%, or 40% when the urination rate exceeds a urination threshold that is at least 500 ml / hr, 525 ml / hr, 550 ml / hr, 1000 ml / hr, 1025 ml / hr, or 1050 ml / hr for a predetermined period of at least 2 hours, 3 hours, or 4 hours. 74. The method of any one of clauses 72 or 73, wherein reducing the administration rate comprises reducing the administration rate of the diuretic until the urination rate is equal to or less than a downward taper threshold that is at least 50 ml, 100 ml, 150 ml, or 200 ml below the urination threshold. 75. The step of adjusting at least one of the administration rates includes: a urination rate exceeding a predetermined rate of at least 500 ml / hr, 750 ml / hr, or 1000 ml / hr for a predetermined period of at least 1 hour, 2 hours, or 3 hours; a rate of change in urination rate of at least 30 ml / hr; 2 , 40ml / hr 2 , or 50 ml / hr 2the diuretic administration rate is greater than a predetermined rate of at least 5 mg / hr, 10 mg / hr, or 15 mg / hr; and 76. The method of any one of the preceding clauses, wherein the average net fluid loss rate from the patient is at least 50 ml / hr, 75 ml / hr, 100 ml / hr, 125 ml / hr, 150 ml / hr, 175 ml / hr, or 200 ml / hr. 77. The method of any one of the preceding clauses, wherein the average net fluid loss from the patient over a 1-day period is at least 3 L, 4 L, or 5 L. 78. The method of any one of the preceding clauses, further comprising the steps of: determining that the urination rate is lower than a desired threshold after providing the diuretic; and, after determining that the urination rate is lower than the desired threshold, determining whether the patient's blood pressure is below a first predetermined threshold and / or whether the patient's electrolyte levels are below a second predetermined threshold. 79. The method of any one of the preceding clauses, wherein the diuretic is a first diuretic, and the method further comprises determining that the urination rate is lower than a desired threshold after providing the first diuretic, and providing the patient with a second diuretic different from the first diuretic. 80. The method of any one of the preceding clauses, wherein obtaining a urination rate comprises determining urination based on at least one of an optical sensor, an ultrasonic sensor, or a thermistor. 81. The method of any one of the preceding clauses, wherein adjusting at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid is based on the conductivity, potassium concentration, and / or magnesium concentration of urine from the patient. 82. The method of any one of the preceding clauses, wherein providing the patient with a hydration fluid at a hydration rate increases the patient's urinary salt concentration, and adjusting at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid reduces the patient's urinary salt concentration. 83. The method of any one of the preceding clauses, wherein providing the patient with a hydration fluid at a hydration rate increases the patient's salinity, and adjusting at least one of the administration rate of the diuretic or the hydration rate of the hydration fluid reduces the patient's salinity. 84. The method of any one of the preceding clauses, further comprising determining whether the patient has diuretic resistance. 85. A method of providing fluid therapy comprising obtaining a urination rate from a patient; providing a diuretic to the patient at an administration rate such that the urination rate is greater than a predetermined threshold; providing a hydration fluid to the patient at a hydration rate not greater than the urination; determining whether any one of a set of predetermined conditions is satisfied; and reducing the administration rate of the diuretic by a predetermined amount if at least one of the set of conditions is satisfied. 86. The method of any one of the preceding clauses, wherein the predetermined amount is at least 15%, 20%, or 25%, or between 10 and 40%. 87. The method of any one of the preceding clauses, wherein reducing the rate of administration of the diuretic comprises reducing the rate of administration of the diuretic by a predetermined amount over a predetermined period of at least 1 hour, 2 hours, or 3 hours. 88. The method of any one of the preceding clauses, further comprising the step of setting the administration rate of the diuretic after reducing the administration rate based on an algorithm. 89. The method of any one of the preceding clauses, wherein the step of determining whether any one of a set of predetermined conditions is satisfied comprises determining whether the urination rate exceeds a predetermined rate of at least 500 ml / hr, 750 ml / hr, 1000 ml / hr for a predetermined period of at least 1 hour, 2 hours, or 3 hours. 90. The step of determining whether any one of a set of predetermined conditions is satisfied comprises determining whether the rate of change in urination rate is at least 30 ml / hr. 2 , 40ml / hr 2 , or 50 ml / hr 2 10. The method of any one of the preceding clauses, comprising determining whether a predetermined rate of at least 1, 2, or 3 hours has been exceeded. 91. The method of any one of the preceding clauses, wherein the step of determining whether any one of a set of predetermined conditions is satisfied comprises determining whether the administration rate of the diuretic exceeds a predetermined rate that is at least 5 mg / hr, 10 mg / hr, or 15 mg / hr. 92. A tangible, non-transitory computer-readable medium having instructions that, when executed by one or more processors, cause a computing device to perform operations comprising the method of any one of the clauses herein. 93. A fluid therapy system comprising: a urine measurement device configured to measure urine output from a patient; a pump fluidly coupled to a urine medication source and configured to provide a diuretic to the patient; one or more processors; and a tangible, non-transitory computer-readable medium having instructions that, when executed by the one or more processors, cause the fluid therapy system to perform operations comprising: obtaining a urine output rate from the urine measurement device; and providing diuretic to the patient through the pump at an administration rate that increases the administration volume over a period of 120 minutes or less, the end of the period being based at least in part on the urine output rate being greater than a predetermined threshold. 94. The fluid therapy system of any one of the clauses herein, wherein the operation further comprises setting the administration rate of the diuretic after providing the diuretic to be a predetermined percentage of the current administration rate. 95. The fluid therapy system of any one of the clauses herein, wherein operation further comprises determining that the urination rate is higher than a predetermined threshold, and setting the diuretic administration rate to be a predetermined percentage of the total amount of diuretic delivered at the time the urination rate is determined to be higher than the predetermined threshold. 96. The fluid therapy system of any one of the clauses herein, wherein the operation further comprises determining that an average urination rate measured over a preset period of time is higher than a predetermined threshold, and reducing the rate of administration of the diuretic by a predetermined percentage in response to the determination. 97. A fluid therapy system according to any one of the clauses herein, the operation of which further comprises determining that one or more of the following set of conditions exist: (i) the average urination rate measured over a first preset period is higher than a first predetermined threshold; (ii) the urination rate measured over a second preset period is increasing at a rate greater than a predetermined increase rate; and (iii) the administration rate is higher than a second predetermined threshold; and reducing the administration rate of the diuretic by a predetermined percentage in response to determining that one or more of the set of conditions exist. 98. The first predetermined threshold is at least 500 mL / hr and the predetermined rate of increase is at least 30 mL / hr. 2 and the second predetermined threshold is at least 5 mg / hr. 99. The fluid therapy system of any one of the clauses herein, wherein the diuretic is delivered such that the rate of administration increases by at least 200% over a period of time. 100. The fluid therapy system of any one of the clauses herein, wherein the step of providing the diuretic comprises the step of iteratively increasing the administration rate in an exponential manner. 101. The fluid therapy system of any one of the clauses herein, wherein operation further comprises determining that an average urination rate measured over a preset period of time has fallen below a predetermined threshold, and iteratively increasing the rate of administration of the diuretic in an exponential manner in response to the determination. 102. A fluid therapy system of any one of the clauses herein, wherein the pump is a first pump, and the system further comprises a second pump operatively coupled to a source of hydration fluid and configured to provide hydration fluid to the patient, and the operation further comprises providing hydration fluid to the patient through the second pump at a hydration rate no higher than a urination rate. 103. A fluid therapy system of any one of the clauses herein, wherein hydration fluid is provided to the patient such that the hydration rate substantially meets or is within a predetermined percentage of the urination rate until at least one of the following occurs: (i) a predetermined period of time has elapsed; or (ii) a predetermined amount of hydration fluid has been infused. 104. The fluid therapy system of any one of the clauses herein, wherein the hydration rate is based on the urination rate such that if the urination rate is below a first threshold, the hydration rate is set to a first rate, and if the urination rate is higher than the first threshold, the hydration rate is set to a second rate equal to the sum of the first rate and a predetermined percentage of the urination rate higher than the first threshold. 105. A fluid therapy system according to any one of the clauses herein, wherein the first threshold is not higher than 200 mL / hr, the second threshold is not higher than 450 mL / hr, and the predetermined percentage is within the range of 25 to 75%. 106. A fluid therapy system according to any one of the clauses herein, wherein the hydration rate is set so that when the urination rate increases, the difference between the hydration rate and the urination rate increases, thereby inducing a net fluid loss from the patient. 107. A fluid therapy system according to any one of the clauses herein, wherein the net fluid loss is at least 200 mL / hr. 108. A console for providing fluid therapy to a patient comprising: a controller having one or more processors, the controller being in communication with a urine measurement device configured to measure urine output from the patient, a first pump configured to provide a diuretic to the patient, and a second pump configured to provide a hydration fluid to the patient; and a tangible, non-transitory, computer-readable medium having instructions that when executed by the one or more processors cause a fluid therapy system to perform operations comprising obtaining a urine output rate from the urine measurement device, providing diuretic to the patient through the first pump at a dosing rate such that the dosing volume increases over a period of time, and providing hydration fluid to the patient through the second pump at a hydration rate no greater than the urine output rate, thereby promoting net fluid loss from the patient. 109. The console of any one of the clauses herein, wherein the operation further comprises setting the administration rate of the diuretic after providing the diuretic to be a predetermined percentage of the current administration rate. 110. The console of any one of the clauses herein, wherein the operations further comprise determining that the average urination rate measured over a preset period of time is higher than a predetermined threshold, and reducing the administration rate of the diuretic by a predetermined percentage in response to the determination. 111. The console of any one of the clauses herein, the operation further comprising determining that an average urination rate measured over a preset period of time has fallen below a predetermined threshold, and increasing the rate of administration of the diuretic in response to the determination. 112. A console according to any one of the clauses herein, wherein hydration fluid is provided to a patient such that the hydration rate substantially meets or is within a predetermined percentage of the urination rate until at least one of the following occurs: (i) a predetermined period of time has elapsed; or (ii) a predetermined amount of hydration fluid has been infused. 113. A console according to any one of the clauses herein, wherein the hydration rate is set so that when the urination rate increases, the difference between the hydration rate and the urination rate increases, thereby inducing a net fluid loss from the patient. 114. The console of any one of the clauses herein, wherein the hydration rate is based on the urination rate such that if the urination rate is below a first threshold, the hydration rate is set to a first rate, and if the urination rate is higher than the first threshold, the hydration rate is set to a second rate equal to the sum of the first rate and a predetermined percentage of the urination rate higher than the first threshold. 115. The console of any one of the clauses herein, wherein providing the diuretic comprises providing the diuretic at an exponentially increasing rate of administration. 116. A method of fluid therapy for promoting net fluid loss from a patient, comprising the steps of obtaining a urination rate from the patient; providing the patient with a diuretic at an administration rate, the administration rate increasing over a period of time such that the urination rate increases until the urination rate is above a predetermined threshold within the period of time; setting the administration rate of the diuretic to be a predetermined percentage of the current administration rate after the urination rate has increased above the predetermined threshold; and providing a hydration fluid to the patient at a hydration rate. 117. The method of any one of the clauses herein, wherein setting the diuretic administration rate comprises setting the diuretic administration rate to be a predetermined percentage of the total amount of diuretic delivered to the patient. 118. The method of any one of the clauses herein, wherein providing the diuretic comprises providing the diuretic at an administration rate that increases recursively in an exponential manner. 119. The method of any one of the clauses herein, wherein the administration rate is increased repeatedly in an exponential manner over a period of 60 minutes or less. 120. The method of any one of the clauses herein, further comprising determining that the average urination rate measured over a preset period of time has fallen below a predetermined threshold, and iteratively increasing the administration rate of the diuretic in an exponential manner in response to the determination. 121. The method of any one of the clauses herein, wherein the hydration fluid is provided to the patient such that the hydration rate substantially meets or is within a predetermined percentage of the urination rate until at least one of the following occurs: (i) a predetermined period of time has elapsed; or (ii) a predetermined amount of hydration fluid has been infused. 122. The method of any one of the clauses herein, wherein the hydration rate is based on the urination rate such that if the urination rate is below a first threshold, the hydration rate is set to a first rate, and if the urination rate is higher than the first threshold, the hydration rate is set to a second rate equal to the sum of the first rate and a predetermined percentage of the urination rate higher than the first threshold. 123. The method of any one of the clauses herein, wherein the hydration rate is set such that when the urination rate increases, the difference between the hydration rate and the urination rate increases, thereby inducing a net fluid loss from the patient. [Explanation of symbols]

[0132] 10. Patient Fluid Management System 12 Urine Collection and Monitoring System (Urine System) 14 Automatic diuretic injection system (diuretic system) 20 Diuretic Sources P patient

Claims

1. 1. A fluid therapy system comprising: a urine measurement device configured to measure urine output from a patient; a pump configured to provide a diuretic to the patient; one or more processors; When executed by the one or more processors, obtaining a urination rate from the urine measurement device; and providing the diuretic through the pump to the patient at an infusion rate such that a cumulative diuretic dose volume is increased over a period of no longer than 120 minutes, the end of which period being based at least in part on the urination rate being greater than a predetermined threshold; a tangible, non-transitory computer-readable medium having instructions for causing the fluid therapy system to perform operations comprising: A fluid therapy system comprising:

2. 10. The fluid therapy system of claim 1, wherein the operations further comprise, after the step of delivering the diuretic, setting the administration rate of the diuretic to be a predetermined percentage of a current administration rate.

3. The operation is determining that the urination rate is greater than the predetermined threshold; after said determining, setting said administration rate of said diuretic to be a predetermined percentage of the total amount of said diuretic delivered at the time of determining that said urination rate is greater than said predetermined threshold; Further comprising: The fluid therapy system of claim 1 .

4. The operation is determining that an average urination rate measured over a preset period of time is greater than said predetermined threshold; In response to said determining, reducing said administration rate of said diuretic by a predetermined percentage; Further comprising: The fluid therapy system of claim 1 .

5. The predetermined threshold is a first predetermined threshold, and the action is: (i) an average urination rate measured over a first preset period of time is greater than said first predetermined threshold; (ii) the urination rate measured over a second preset period of time increases at a rate greater than a predetermined rate of increase; (iii) the administration rate is greater than a second predetermined threshold; determining that one or more of a set of conditions is true; reducing the administration rate of the diuretic by a predetermined percentage in response to determining that one or more of the set of conditions are met; 10. The fluid therapy system of claim 1, further comprising:

6. The first predetermined threshold is at least 500 mL / hr and the predetermined rate of increase is at least 30 mL / hr. 2 6. The fluid therapy system of claim 5, wherein the second predetermined threshold is at least 5 mg / hr.

7. 10. The fluid therapy system of claim 1, wherein providing the diuretic comprises providing the diuretic such that the administration rate increases by at least 200% over the period of time.

8. 10. The fluid therapy system of claim 1, wherein the step of providing the diuretic comprises repeatedly increasing the administration rate in an exponential manner.

9. The operation is determining that an average urination rate measured over a preset period of time is less than said predetermined threshold; responsive to said determining, iteratively increasing said administration rate of said diuretic in an exponential manner; Further comprising: The fluid therapy system of claim 1 .

10. The pump is a first pump, and the system further comprises a second pump operatively coupled to a hydration fluid and configured to provide the hydration fluid to the patient, the operation comprising: providing the hydration fluid to the patient through the second pump at a hydration rate no greater than the urination rate; 10. The fluid therapy system of claim 1, further comprising:

11. 11. The fluid therapy system of claim 10, wherein the hydration fluid is provided to the patient such that the hydration rate substantially meets or is within a predetermined percentage of the urination rate until at least one of: (i) a predetermined period of time has elapsed; or (ii) a predetermined amount of hydration fluid has been infused.

12. The hydration rate is if the urination rate is less than a first threshold, the hydration rate is set to a first rate; and If the urination rate is higher than the first threshold, the hydration rate is set to a second rate that is (i) different from the first rate and (ii) equal to the first rate plus a predetermined percentage of the urination rate higher than the first threshold. based on the urination rate, 11. The fluid therapy system of claim 10.

13. 13. The fluid therapy system of claim 12, wherein the first threshold is no greater than 200 mL / hr, the second threshold is no greater than 450 mL / hr, and the predetermined percentage is within the range of 25-75%.

14. 11. The fluid therapy system of claim 10, wherein the hydration rate is set so that the difference between the hydration rate and the urination rate increases as the urination rate increases, thereby inducing a net fluid loss from the patient.

15. 15. The fluid therapy system of claim 14, wherein the net fluid loss rate is at least 200 mL / hr.

16. 1. A console for providing fluid therapy to a patient, comprising: has one or more processors, and a urine measurement device configured to measure urine output from a patient; a first pump configured to provide a diuretic to the patient; a second pump configured to provide hydration fluid to the patient; a controller in communication with the When executed by the one or more processors, obtaining a urination rate from the urine measurement device; providing the diuretic through the first pump to the patient at an administration rate such that a cumulative diuretic dose volume is increased over a period of time; and providing the hydration fluid through the second pump to the patient at a hydration rate no greater than the urination rate, thereby promoting net fluid loss from the patient; a tangible, non-transitory computer-readable medium having instructions for causing a fluid therapy system to perform operations comprising: A console comprising:

17. 17. The console of claim 16, wherein the operations further comprise, after the step of delivering the diuretic, setting the administration rate of the diuretic to be a predetermined percentage of a current administration rate.

18. The operation is determining that an average urination rate measured over a preset period of time is greater than a predetermined threshold; reducing the administration rate of the diuretic by a predetermined percentage in response to said determining; Further comprising:

17. The console of claim 16.

19. The operation is determining that an average urination rate measured over a preset period of time is below a predetermined threshold; increasing the administration rate of the diuretic in response to said determination; Further comprising:

17. The console of claim 16.

20. 17. The console of claim 16, wherein the hydration fluid is provided to the patient such that the hydration rate substantially meets or is within a predetermined percentage of the urination rate until at least one of: (i) a predetermined period of time has elapsed; or (ii) a predetermined amount of hydration fluid has been infused.

21. 17. The console of claim 16, wherein the hydration rate is set such that as the urination rate increases, the difference between the hydration rate and the urination rate increases, thereby inducing a net fluid loss from the patient.

22. The hydration rate is if the urination rate is less than a first threshold, the hydration rate is set to a first rate; and If the urination rate is higher than the first threshold, the hydration rate is set to a second rate higher than the first rate. based on the urination rate, 17. The console of claim 16.

23. 17. The console of claim 16, wherein providing the diuretic comprises providing the diuretic such that the administration rate is increased repetitively in an exponential manner.

24. 1. A fluid therapy method for promoting net fluid loss from a patient, comprising: obtaining a urination rate from the patient; providing a diuretic to the patient at an administration rate, wherein a cumulative diuretic dose volume is increased over a period of time, thereby increasing the urination rate above a predetermined threshold within the period of time; setting the administration rate of the diuretic to be a predetermined percentage of the current administration rate after the urination rate increases above the predetermined threshold; providing a hydration fluid to the patient at a hydration rate; A fluid treatment method comprising:

25. 25. The method of claim 24, wherein setting the administration rate of the diuretic comprises setting the administration rate of the diuretic to be the predetermined percentage of the total amount of the diuretic delivered to the patient.

26. 25. The method of claim 24, wherein providing the diuretic comprises providing the diuretic such that the administration rate is increased repetitively in an exponential manner.

27. determining that an average urination rate measured over a preset period of time is less than said predetermined threshold; iteratively increasing the administration rate of the diuretic in an exponential manner in response to said determining; 25. The method of claim 24 further comprising:

28. 25. The method of claim 24, wherein the hydration fluid is provided to the patient such that the hydration rate substantially meets or is within a predetermined percentage of the urination rate until at least one of: (i) a predetermined period of time has elapsed; or (ii) a predetermined amount of hydration fluid has been infused.

29. The hydration rate is if the urination rate is less than a first threshold, the hydration rate is set to a first rate; and if the urination rate is greater than the first threshold, then the hydration rate is set to a second rate equal to the sum of the first rate and a predetermined percentage of the urination rate greater than the first threshold. based on the urination rate, 25. The method of claim 24.

30. 25. The method of claim 24, wherein the hydration rate is set such that the difference between the hydration rate and the urination rate increases as the urination rate increases, thereby inducing a net fluid loss from the patient.

Images