Standardized Citrate Solutions for CRRT Metabolic Control

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Solution Overview

Problem

Current CRRT protocols using citrate as an anticoagulant face complications such as metabolic alkalosis, citrate toxicity, and require customization of solutions based on individual patient needs, leading to increased costs, pharmacy resource strain, and risk of errors in preparation and administration.

Innovation Solution

A standardized citrate replacement fluid solution and dialysate solution are used, comprising 0.67% or 0.5% trisodium citrate and a bicarbonate-based dialysate, which provide effective regional anticoagulation and metabolic control without the need for customization, using only three types of solutions to minimize errors and costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If customized citrate solutions are prepared for each patient based on individual needs, then effective anticoagulation and metabolic control are achieved, but pharmacy resource strain increases and risk of errors in preparation and administration rises

Engineering Contradiction:
Improveeffective anticoagulationVSAvoidsolution customization complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the concentration parameter of citrate solutions to create standardized options (0.67% and 0.5%) that can be selectively used based on patient needs without requiring custom compounding. This maintains effective anticoagulation while eliminating the complexity of individualized solution preparation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates universal standardized citrate solutions that can be used across multiple patients with different clinical conditions. The 0.67% and 0.5% solutions serve as multi-functional alternatives that replace the need for customized formulations, reducing pharmacy workload and preparation errors.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Reliability

If customized solutions are prepared for each patient, then individualized metabolic control is achieved, but costs and pharmacy resource strain increase

Engineering Contradiction:
Improvemetabolic controlVSAvoidsolution preparation ease
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent establishes standardized citrate concentrations (0.67% and 0.5%) as manufacturable parameters that balance individualized metabolic control needs with ease of preparation. These standardized concentrations can be manufactured in advance and stored, eliminating the need for complex custom compounding while maintaining metabolic control effectiveness.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If high ultrafiltration rates are used in CRRT, then patient survival improves, but fluid and solute removal requirements increase

Engineering Contradiction:
Improvepatient survival rateVSAvoidfluid and solute removal volume
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent utilizes standardized citrate solutions that enable sustained high ultrafiltration rates by providing consistent anticoagulation and metabolic support. The standardized formulations ensure stable performance during high-rate CRRT, allowing patients to receive higher ultrafiltration doses for improved survival without compromising fluid and solute removal efficiency.

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The standardized solutions achieve high solute clearance, effective anticoagulation, and metabolic control, reducing the risk of citrate toxicity and metabolic complications, while simplifying the preparation and administration process, thereby improving patient outcomes and reducing healthcare costs.

Implementation Method 1

Citrate affects anticoagulation by binding with calcium and rendering calcium unavailable to the clotting cascade. Since several steps of the clotting cascade are dependent on calcium, the absence of calcium prevents clotting.

Methodology Applied
Scientific EffectChelation:

Implementation Method 2

When CRRT was first developed, the major indications for use were fluid and solute removal associated with renal failure

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP3061456B1Process for metabolic control and high solute clearance and solutions for use therein
Publication Date: 2020.07.22 THE UAB RESEARCH FOUNDATION INC
  • EP3061456B1 patent drawingFigure 1A~1B
  • EP3061456B1 patent drawingFigure 2A~2B
  • EP3061456B1 patent drawingFigure 3

AI summary

The present disclosure describes novel standardized citrate replacement fluid solutions and a standardized dialysate solution for use with CRRT methods. The standardized citrate replacement fluid solutions and standardized dialysate solutions do not require modification based on the clinical status of the individual patients. The use of the standardized solutions described herein offers significant advantages over the prior art solutions used in CRRT. The present disclosure describes superior metabolic and electrolyte control and significantly increased dialyzer patency in: (a) 24 intensive care unit (ICU) patients with ARF using a 0.67% trisodium citrate replacement fluid solution, and (b) 32 ICU patients with ARF using a 0.5% trisodium citrate replacement fluid solution. Both groups were treated with Bicarbonate-25 dialysate and achieved effluent rates of 35 mL/kg/hr.