SYSTEM AND METHOD FOR DELIVERY OF REGIONAL CITRATE ANTICOAGULATION TO EXTRACORPOREAL BLOOD CIRCUITS

• US 20090221948A1
• Filed: 02/22/2007
• Published: 09/03/2009
• Est. Priority Date: 02/22/2006
• Status: Active Grant

• Current Assignee: Henry Ford Health System
• Original Assignee: Henry Ford Health System
• Inventors: Szamosfalvi, Balazs, Yee, Jerry, Frinak, Stanley
• Granted Patent: US 8,211,048 B2
• Time in Patent Office: Days
• US Class Current: 604/6.70
• CPC Class Codes: A61M 1/342 Adding solutions to the blood, e.g. substitution solutions for preventing coagulation A61M1/3672
• CPC Class Codes: A61M 1/3434 with pre-dilution and post-dilution
• CPC Class Codes: A61M 1/3437 downstream of the filter, e.g. post-dilution with filtrate
• CPC Class Codes: A61M 1/3441 Substitution rate control as a function of the ultrafiltration rate
• CPC Class Codes: A61M 1/3458 having electrolytes not present in the dialysate
• CPC Class Codes: A61M 1/3626 Gas bubble detectors
• CPC Class Codes: A61M 1/3658 Indicating the amount of purified blood recirculating in the fistula or shunt
• CPC Class Codes: A61M 1/3672 Means preventing coagulation
• CPC Class Codes: A61M 1/3675 Deactivation
• CPC Class Codes: A61M 2202/0028 fluid entering a filter
• CPC Class Codes: A61M 2202/0468 non-physiological
• CPC Class Codes: A61M 2205/18 with alarm
• CPC Class Codes: A61M 2205/3306 Optical measuring means
• CPC Class Codes: A61M 2205/7563 with means preventing clogging of filters
• CPC Class Codes: A61M 2230/207 hematocrit
• CPC Class Codes: B01D 2311/12 Addition of chemical agents
• CPC Class Codes: B01D 2311/243 Electrical conductivity control
• CPC Class Codes: B01D 2311/246 Concentration control
• CPC Class Codes: B01D 61/32 Controlling or regulating

Abstract

The present invention includes a comprehensive replacement fluid system and method for the delivery of regional citrate anticoagulation (RCA) to extracorporeal blood circuits, wherein the system may include an online clearance monitor (OCM) and a circuit effluent online sensor system (OSS) for the continuous determination of patient plasma content of ultrafilterable soultes.

Claims

1-145. -145. (canceled)

146. A system for regional citrate anticoagulation in an extracorporeal blood circuit including an arterial blood line arranged to be connected to a vascular access for withdrawing blood from a patient and a venous blood line arranged to be connected to the vascular access for returning blood to the patient, the system comprising:

a hemofilter in fluid communication with the arterial and venous blood lines and having a dialysis-fluid in connector and a dialysis-fluid out connector;

a first pre-filter infusion line and pump having a connection to the arterial blood line upstream from the hemofilter for infusing a first pre-filter infusion solution comprising a citrate anticoagulant-containing solution;

a second pre-filter infusion line and pump capable of a connection to the arterial blood line upstream from the hemofilter for infusing a second pre-filter infusion solution comprising a first bicarbonate-containing solution;

a fresh dialysis fluid line and pump capable of a connection to the hemofilter dialysis-fluid in connection for providing dialysis with a second bicarbonate-containing solution countercurrent to a direction of blood flow in the hemofilter;

a post-filter infusion line and pump capable of a connection to the venous blood line downstream from the hemofilter for infusing a post-filter infusion solution comprising a third bicarbonate-containing solution;

an effluent fluid line and pump connected to the hemofilter dialysis-fluid out connection for receiving filter effluent fluid;

an additional infusion line and pump having a connection to the venous blood line downstream from the connection of the post-filter infusion line for infusing an additional infusion solution comprising a calcium- and magnesium-containing solution; and

a monitor for determining a performance of the hemofilter in removing citrate from the blood.

147. The system according to claim 146, wherein connection of one or more of the second pre-filter infusion line and pump, the fresh dialysis fluid line and pump, and the post-filter infusion line and pump allow for the operational modes of:

isolated pre-dilution hemofiltration when the second pre-filter infusion line and pump is connected to the arterial blood line upstream from the hemofilter;

simultaneous pre-dilution hemodiafiltration when the second pre-filter infusion line and pump is connected to the arterial blood line upstream from the hemofilter and the fresh dialysis fluid line and pump is connected to the hemofilter dialysis-fluid in connector;

simultaneous pre-dilution and post-dilution hemofiltration when the second pre-filter infusion line and pump is connected to the arterial blood line upstream from the hemofilter and the post-filter infusion line and pump is connected to the venous blood line downstream from the hemofilter;

isolated hemodialysis when the fresh dialysis fluid line and pump is connected to the hemofilter dialysis-fluid in connector; and

simultaneous post-dilution hemodiafiltration when the fresh dialysis fluid line and pump is connected to the hemofilter dialysis-fluid in connector and the post-filter infusion line and pump is connected to the venous blood line downstream from the hemofilter.

148. The system according to claim 146, wherein the first pre-filter infusion solution comprises a basic citrate to acid citrate ratio of about 2:

1 to 8;

1.

149. The system according to claim 146, wherein the first pre-filter infusion solution comprises about 150-250 mmol/L sodium chloride and about 50-1000 mmol/L total citrate.

150. The system according to claim 149, wherein the total citrate comprises about 150 mmol/L, including about 133.33 mmol/L basic citrate and about 16.67 mmol/L acid citrate, and sodium chloride comprises about 150 mmol/L.

151. The system according to claim 149, wherein the total citrate comprises about 150 mmol/L, including about 100 mmol/L basic citrate and about 50 mmol/L acid citrate, and sodium chloride comprises about 250 mmol/L.

152. The system according to claim 146, wherein the bicarbonate-containing solutions are provided in ready-to-use, sterile packaging.

153. The system according to claim 146, wherein the bicarbonate-containing solutions are provided by an online fluid generation module using at least one solute source.

154. The system according to claim 153, wherein the online fluid generation module uses a single solute source diluted with water.

155. The system according to claim 153, wherein the online fluid generation module uses a dual acid and base solute source, wherein an acid concentrate from a first container is diluted with water and a base concentrate from a second container is diluted with water according to respective dilution ratios.

156. The system according to claim 155, wherein the base concentrate comprises sodium, bicarbonate, and phosphate, wherein phosphate is provided as a mixture of Na₂HPO₄ and NaH₂PO₄ in a 20:

1 molar ratio.

157. The system according to claim 155, wherein a final 1×

bicarbonate solution comprises about 138 mmol/L sodium, about 4.0 mmol/L potassium, about 114 mmol/L chloride, about 28 mmol/L bicarbonate, about 1.25 mmol/L phosphoric acid, about 5.5 mmol/L dextrose, and is essentially free of calcium and magnesium.

158. The system according to claim 153, wherein at least one of the solute sources for the online fluid generation module is formulated to have a substantially different sodium content from other concentrated solute sources used by the same online fluid generation module in a non-regional citrate anticoagulation-specific fluid generation mode, resulting in an alarm condition if an incorrect solute source is used.

159. The system according to claim 146, wherein at least one of a conductivity and a solute composition of the bicarbonate-containing solutions is monitored by the system.

160. The system according to claim 146, further comprising a citrate concentration sensor operably connected to the effluent fluid line.

161. The system according to claim 146, further comprising a secondary extracorporeal blood treatment device operably connected downstream from the pre-filter infusion connection and upstream from the additional infusion line connection.

162. The system according to claim 146, further comprising at least one arterial hematocrit sensor implemented on an arterial limb of the blood circuit and at least one venous hematocrit sensor implemented on a venous limb of the blood circuit.

163. The system according to claim 162, wherein programmed changes in a flow of at least one of the filter effluent fluid and the bicarbonate-containing solutions result in a programmed change in hematocrit of the blood circuit venous limb, wherein the programmed change in hematocrit is detected by the at least one venous hematocrit sensor, the subsequent change in hematocrit due to blood access recirculation is detected by the at least one arterial hematocrit sensor, and blood access recirculation is calculated from the detected hematocrit changes in an automated manner.

164. The system according to claim 162, wherein the at least one arterial hematocrit sensor includes a first arterial sensor disposed before the pre-filter connection and a second arterial sensor disposed after the pre-filter connection, and the at least one venous hematocrit sensor includes a first venous sensor disposed before the post-filter connection and a second venous sensor disposed after the post-filter connection, wherein a change in hematocrit between the first and second arterial sensors and the first and second venous sensors is detected, and an actual blood flow in the arterial and venous limbs of the blood circuit are calculated from the change in hematocrit between the arterial and venous sensors, respectively, and a rate of infusion of fluids in an automated manner.

165. The system according to claims 146, wherein an initial flow rate of the additional infusion solution is determined by at least one of a plasma flow entering an arterial limb of the blood circuit, a systemic albumin level of the patient, a desired systemic ionized calcium concentration of the patient, a performance of the hemofilter in removing total calcium from plasma entering the blood circuit arterial limb, a predicted systemic plasma citrate concentration of the patient, a systemic plasma total calcium concentration of the patient input by an operator, an hourly net fluid removal goal, and a calcium concentration of the additional infusion solution.

166. The system according to claim 146, further comprising:

sterile solution bags for the pre-filter infusion solution having connectors that only accept a unique end connector on the pre-filter infusion line; and

sterile solution bags for the additional infusion solution having connectors that only accept a unique end connector on the additional infusion line.

167. The system according to claim 146, further comprising a control program for providing a prescription for the hemofilter which ensures that a single pass removal of citrate on the hemofilter from blood into the filter effluent fluid is at least 60% during the operation of the system, monitoring the transfer of citrate from blood into the filter effluent fluid on the hemofilter;

and adjusting a flow rate of the additional infusion solution to maintain target calcium levels in the patient'"'"'s systemic blood.

168. The system according to claim 146, further comprising an online effluent sensor system comprising:

an air-in-fluid detector operably connected to the venous blood line;

at least one line clamp operably connected to at least one of the arterial and venous blood lines;

at least one blood-in-circuit detector operably connected to at least one of the arterial and venous blood lines and the effluent fluid line;

a pressure sensor operably connected to at least one of the arterial and venous blood lines and the effluent fluid line; and

at least one effluent fluid sensor operably connected to the effluent fluid line for determining a change in a concentration of at least one solute in the filter effluent fluid in response to a change in the composition of blood entering the hemofilter caused by a changed in a pumping rate of the pre-filter infusion solution.

169. The system according to claim 168, further comprising a control program with data processing, storage, display, and alarm functions in communication with the at least one effluent fluid sensor, means for determining a performance of the hemofilter in transferring a solute between blood and filter effluent fluid, and means for detecting access recirculation of blood from a venous limb of the blood circuit into an arterial limb of the blood circuit.

170. A system for regional citrate anticoagulation in an extracorporeal blood circuit including an arterial blood line arranged to be connected to a vascular access for withdrawing blood from a patient and a venous blood line arranged to be connected to the vascular access for returning blood to the patient, the system comprising:

a hemofilter in fluid communication with the arterial and venous blood lines and having a dialysis-fluid in connector and a dialysis-fluid out connector;

a pre-filter infusion line and pump having a connection to the arterial blood line upstream from the hemofilter for infusing a pre-filter infusion solution comprising a citrate anticoagulant-containing solution;

a post-filter infusion line and pump having a connection to one of

     1) the hemofilter dialysis-fluid in connector to provide dialysis with a bicarbonate-containing solution countercurrent to blood flow or

     2) the venous blood line downstream from the hemofilter for infusing a post-filter infusion solution comprising a bicarbonate-containing solution;

an effluent fluid line and pump connected to the hemofilter dialysis-fluid out connector for receiving filter effluent fluid;

an additional infusion line and pump having a connection to the venous blood line downstream from the connection of the post-filter infusion line for infusing an additional infusion solution comprising a calcium- and magnesium-containing solution; and

a monitor for determining a performance of the hemofilter in removing citrate from the blood.

171. The system according to claim 170, wherein the pre-filter infusion solution and the post-filter infusion solution are essentially free of calcium, magnesium, and phosphate.

172. The system according to claim 170, wherein the pre-filter infusion solution and the post-filter infusion solution comprise about 1.25 mmol/L phosphate.

173. The system according to claim 170, wherein the pre-filter infusion solution includes a ready-to-use solution comprising about 135-150 mmol/L sodium, about 0-4 mmol/L potassium, about 8-16.67 mmol/L basic citrate, about 0-10 mmol/L acid citrate, about 95-120 mmol/L chloride, about 0-4.0 mmol/L calcium, about 0-2.0 mmol/L magnesium, about 5.5-11.0 mmol/L dextrose, about 0-few mmol/L inulin, about 0-few mmol/L para-amino-hippuric acid, about 0-5.0 mmol/L phosphate, and optionally trace metals.

174. The system according to claim 173, wherein the pre-filter infusion solution comprises about 145 mmol/L sodium, about 2 or 4 mmol/L potassium, about 14 mmol/L basic citrate, about 2 mmol/L acid citrate, about 105 or 107 mmol/L chloride, about 1.25 mmol/L phosphate, and about 5.5 mmol/L dextrose.

175. The system according to claim 170, wherein the post-filter infusion solution includes a ready-to-use solution comprising about 135-150 mmol/L sodium, about 0-4 mmol/L potassium, about 20-60 mmol/L bicarbonate, about 85-120 mmol/L chloride, about 0-4 mmol/L calcium, about 0-2.0 mmol/L magnesium, about 0-5 mmol/L phosphate, and about 5.5-11.0 mmol/L dextrose.

176. The system according to claim 175, wherein the post-filter infusion solution comprises about 140 mmol/L sodium, about 2 or 4 mmol/L potassium, one of about 25 mmol/L bicarbonate and about 113.25 or 115.25 mmol/L chloride or about 50 mmol/L bicarbonate and about 88.25 or 90.25 mmol/L chloride, about 1.25 mmol phosphate, and about 5.5 mmol/L dextrose.

177. The system according to claim 170, wherein the first pre-filter infusion solution and the post-filter infusion solution are each provided in a single chamber bag when a sterilization method other than heat sterilization is used.

178. The system according to claim 170, wherein the additional infusion solution comprises calcium, magnesium, sodium, and chloride, wherein a molar ratio of calcium to magnesium is about 2:

1 to 4;

1, and wherein a conductivity of the additional infusion solution is substantially different from a conductivity of normal human plasma, a conductivity of the pre-filter infusion solution, and a conductivity of the post-filter infusion solution.

179. The system according to claim 178, wherein the additional infusion solution comprises about 50 mmol/L calcium, about 25 mmol/L magnesium, about 150 mmol/L sodium, about 300 mmol/L chloride, and optionally trace metals.

180. The system according to claim 170, further comprising a citrate concentration sensor operably connected to the effluent fluid line.

181. The system according to claims 170, further comprising a secondary extracorporeal blood treatment device operably connected downstream from the pre-filter infusion connection and upstream from the additional infusion line connection.

182. The system according to claim 170, further comprising at least one arterial hematocrit sensor implemented on an arterial limb of the blood circuit and at least one venous hematocrit sensor implemented on a venous limb of the blood circuit.

183. The system according to claim 182, wherein programmed changes in a flow of at least one of the filter effluent fluid and the bicarbonate-containing solutions result in a programmed change in hematocrit of the blood circuit venous limb, wherein the programmed change in hematocrit is detected by the at least one venous hematocrit sensor, the subsequent change in hematocrit due to blood access recirculation is detected by the at least one arterial hematocrit sensor, and blood access recirculation is calculated from the detected hematocrit changes in an automated manner.

184. The system according to claim 182, wherein the at least one arterial hematocrit sensor includes a first arterial sensor disposed before the pre-filter connection and a second arterial sensor disposed after the pre-filter connection, and the at least one venous hematocrit sensor includes a first venous sensor disposed before the post-filter connection and a second venous sensor disposed after the post-filter connection, wherein a change in hematocrit between the first and second arterial sensors and the first and second venous sensors is detected, and an actual blood flow in the arterial and venous limbs of the blood circuit are calculated from the change in hematocrit between the arterial and venous sensors, respectively, and a rate of infusion of fluids in an automated manner.

185. The system according to claims 170, wherein an initial flow rate of the additional infusion solution is determined by at least one of a plasma flow entering an arterial limb of the blood circuit, a systemic albumin level of the patient, a desired systemic ionized calcium concentration of the patient, a performance of the hemofilter in removing total calcium from plasma entering the blood circuit arterial limb, a predicted systemic plasma citrate concentration of the patient, a systemic plasma total calcium concentration of the patient input by an operator, an hourly net fluid removal goal, and a calcium concentration of the additional infusion solution.

186. The system according to claim 170, further comprising:

sterile solution bags for the pre-filter infusion solution having connectors that only accept a unique end connector on the pre-filter infusion line; and

sterile solution bags for the additional infusion solution having connectors that only accept a unique end connector on the additional infusion line.

187. The system according to claim 170, further comprising a control program for providing a prescription for the hemofilter which ensures that a single pass removal of citrate on the hemofilter from blood into the filter effluent fluid is at least 60% during the operation of the system, monitoring the transfer of citrate from blood into the filter effluent fluid on the hemofilter;

and adjusting a flow rate of the additional infusion solution to maintain target calcium levels in the patient'"'"'s systemic blood.

188. The system according to claim 170, further comprising an online effluent sensor system comprising:

an air-in-fluid detector operably connected to the venous blood line;

at least one line clamp operably connected to at least one of the arterial and venous blood lines;

at least one blood-in-circuit detector operably connected to at least one of the arterial and venous blood lines and the effluent fluid line;

a pressure sensor operably connected to at least one of the arterial and venous blood lines and the effluent fluid line; and

at least one effluent fluid sensor operably connected to the effluent fluid line for determining a change in a concentration of at least one solute in the filter effluent fluid in response to a change in the composition of blood entering the hemofilter caused by a changed in a pumping rate of the pre-filter infusion solution.

189. The system according to claim 188, further comprising a control program with data processing, storage, display, and alarm functions in communication with the at least one effluent fluid sensor, means for determining a performance of the hemofilter in transferring a solute between blood and filter effluent fluid, and means for detecting access recirculation of blood from a venous limb of the blood circuit into an arterial limb of the blood circuit.