A Portable Continuous Blood Purification Machine for Emergency Rescue in DisastersHe P.a · Zhou C.b · Li H.a · Yu Y.a · Dong Z.a · Wen Y.a · Li P.c · Tang W.c · Wang X.c
aDepartment of Nephrology, General Hospital of the Navy, bNavy General Hospital, Clinical Medical College, Second Military Medical University, and cBeijing Aojiaishengkang Technology Development Corp. Ltd., Beijing, China Corresponding Author
Background: Continuous renal replacement therapy plays an important role in emergency rescue. Currently, no continuous renal replacement therapy machine can be used under unstable conditions as the fluid flow of these machines is controlled electronically. A novel machine that can provide emergency continuous renal replacement therapy in disaster rescue is therefore needed. Methods: Based on a volumetric metering method, a prototype portable continuous blood purifier based on a volumetric metering method was developed. Basic performance tests, special environmental tests, animal experiments and clinical use of the novel machine were completed to test and verify its performance under unstable conditions. Results: All tests completed showed that the machine met the requirements of the national industry standards with a size reduced to approximately one half of the Baxter Aquarius machine. The clearance of harmful substances by the machine described here was equal to that of the Baxter Aquarius machine and was adequate for clinical purposes. Conclusions: The novel prototype performed well in all situations tested and can aid rescue work on disaster sites.
Copyright © 2012 S. Karger AG, Basel
Continuous blood purification therapy balances electrolytes in the blood, clears harmful substances, such as endogenous myoglobin and inflammatory factors, improves kidney function and maintains a stable internal organ environment. It plays an important role in the treatment of patients in critical conditions [1,2,3,4,5,6,7,8]. In a statistical analysis of Japan's Kobe earthquake (1995, Awaji Island), 2,718 traumatic patients were treated within the first 15 days; 13.8% of the patients suffered from crush syndrome and 7.5% suffered from acute renal failure requiring blood purification treatment . In the Chi-Chi earthquake of Taiwan province (1999), acute renal failure occurred in 46.3% of the crush syndrome patients, 31.6% of whom needed blood purification therapy . Blood purification therapy was also required in 42% of the crush syndrome patients with acute renal failure in the Wenchuan earthquake (2008, China) . Thus, blood purification therapy is in great demand during natural disasters.
Currently, several continuous blood purifiers or dialyzers are available, including the following: Campbell Prisma, Baxter Accura, Asahi Kasei ACH-10, and Fresenius ADM-08. These instruments all use electronic weighing technology to control fluid balance. Electronic weighing technology is currently the most widely used method to control fluid balance. By measuring the changes in fluid weight in the replacement fluid container and the waste fluid container, the rotation speeds of the blood pump, replacement pump and ultrafiltration pump can be controlled to achieve precise ultrafiltration. Because electronic weighing is easily affected by the environment, it cannot function in vibrating, swinging and bumpy conditions. When the ground shakes, the Baxter Aquarius electronic weighing device will also shake, an alarm will sound, and the pump will stop; therefore, the device cannot operate normally under these conditions. To solve this problem, we developed a novel portable mobile continuous blood purification machine in which a new volumetric metering method is applied instead of electronic weighing, thus enabling our machine to be used in unstable conditions. This method precisely measures the amount of liquid that is discharged by a pump with a fixed volume and does not rely on gravity measurement or flow sensors. Additionally, as there are no freely moving parts within the apparatus, it can operate normally in an unstable external environment. All tests and experiments proved that this machine can improve rescue operations on a disaster site.
After solving the issues of accurate flow measurement in an unstable environment, other clinical operation applications were considered. By integrating the technologies of electronic detection, monitoring and networking, the continuous blood purifier becomes useful in clinical settings because its key parameters (e.g. flow, temperature and pressure) can be automatically monitored, alarmed and adjusted. After many tests were conducted at a national authorized medical center, the novel prototype machine was proven to be applicable in rescue work at sea and in ambulances. Its performance also implies a potential role in the clinical treatment of renal failure.
Materials and Methods
|Fig. 1. Scheme of the novel portable continuous blood purifier system. The novel portable continuous blood purifier consists of four main parts: the blood circuit, the replacement fluid circuit, the ultrafiltration circuit and the corresponding control system. The blood circuit is formed by the blood pump, blood tubing, arterial blood pressure monitor, venous pressure monitor, blood filters and air bubble monitor. The replacement fluid circuit is formed by the replacement fluid, piping, air bubbles monitor, infusion pumps, one-way fluid valve, heater, temperature monitor, thermal conductivity monitor, and pyrogen filter. The ultrafiltration circuit consists of the ultrafiltration pump, blood leakage monitor, one-way valve and pressure monitor.|
|Fig. 2. Prototype machine appearance. The size of the machine is 50 × 50 × 23.8 cm, and its weight is 30.5 kg.|
When blood filtration treatment is performed, blood is pumped out of the body into a small chamber known as the arterial bubble collector. Blood then flows into the arterial port of a blood filtration device in which material exchange takes place by a process of fluid dispersion and convection. Thereafter, the blood exits the venous port of the filter and passes a chamber-like venous bubble collector before finally returning to the body. The replacement fluid is pumped into the heater through a one-way valve. As the fluid temperature reaches the set point, it is driven into the venous bubble collector (functional valve is off), where the blood and replacement fluid are mixed together. After a process of blood dialysis filtration, the harmful substances in the blood are transferred away from the membrane. Driven by the ultrafiltration pump, the liquid containing harmful substances is pumped out of the replacement fluid while the blood leakage is monitored. It is very important that the infusion pumps and dehydration pumps work in concert to ensure accurate fluid balance. To meet the demands of rescue crews during disasters and ensure the safety of the treatment, the purifier utilizes three vital technologies: high-precision volume measurement, precise control of blood pump flow and highly efficient active heating temperature control.
We used amplifier separation technology to separate the pre- and post-stage power, and the entire power system was sealed using insulated materials. Therefore, the power supply could not contact the machine case and human body, which prevents the leakage of electric current and, consequently, the patient's risk of electric shock. This machine uses a variety of self-monitoring and feedback systems to ensure treatment safety. The central processing unit (CPU) controls the blood pump, the replacement fluid pump and the ultrafiltration pump, and it can automatically adjust the rotation speeds of these devices to ensure fine control of the output flows according to treatment requirements. The machine can heat the replacement fluid in real time to control the replacement fluid temperature within the required range. During treatment, the CPU continuously detects the arterial and venous pressures, ultrafiltration pressure, blood leakage, and the liquid level of the infusion fluid chamber. When the monitored items are out of range, the system uses light and sound alarms to alert healthcare personnel and automatically cut off the circulation of blood and dialysis solution as a safety measure.
High-Precision Volume Measurement
Precise control of the replacement fluid flow and dehydration are important indicators that reflect the purifier's performance. The novel portable continuous blood purifier replaces the traditional weight measurement with volume measurement for continuous blood without any reduction in accuracy. To achieve high precision, a pump with a very small volume is chosen in which a single complete movement can pump 0.6 ml of liquid. Meanwhile, a counter for the pump movements is specially designed to ensure accuracy. When a small error occurs, the reading of the counter can be self-compensated according to the software calculation, and therefore, the precision of replacement fluid flow and dehydration meets the requirements of national industry standards . The principle of the fluid volume measurement is shown in figure 3.
|Fig. 3. Working principle of volume measurement. Counting devices 1 and 2 measure liquid volumes. The chamber is of a certain volume (0.6 ml), and the arrows indicate the direction of liquid flow.|
As shown in figure 3, the liquid volume measurement device is installed at the inlet and outlet of the replacement pump. For each unit (0.6 ml) of volume measurement, the sampling rate is 50/s, and an isolated 3-volt AC input signal is applied to the liquid volume measurement devices. The signal is sampled, amplified and analyzed by the microprocessor CPU at 50 Hz. The results from the CPU analysis are used in the feedback control of the replacement pump to ensure precise fluid flow as detailed in figure 4.
|Fig. 4. Scheme of the feedback control loop for the replacement fluid flow.|
Precise Control of Fluid Flow in the Blood Pump
To ensure patient safety, the blood pump must beginat a low speed and gradually increase over time to reach normal circulation. This process requires that the driver of the blood circulation, a three-phase brushless DC motor, constantly accelerate and reach the set point within a specified time interval. The motor must have good performance in dynamic control systems; it should rapidly adjust the power according to the load and stabilize the speed of the fluid flow within a certain period of time.
High-Efficiency Heating and Temperature Control Technology
In a disaster scene such as a shipwreck or an earthquake, the wounded may suffer hypothermia, and in these cases, it is critical to increase the temperature of the replacement fluids and effectively rewarm the blood as a life-saving procedure. Although there are limits to the size of the overall machine structure, the heating element utilizes a double layer of four successive heating cycles to achieve rapid temperature increases. This design provides a heating area that is four times larger than the traditional design, which makes the novel purifier capable of heating replacement fluids five times faster than traditional machines. The response time was approximately 325 s from an initial replacement fluid temperature of 20-37°C. Meanwhile, robust temperature control is achieved by a feedback loop design with a proportional integral derivative controller (PID) control algorithm. In the temperature control system, the settings of the PID control parameters mostly affect its accuracy, dynamic response and stability. By tuning the PID parameters, the following optimized values are obtained: kp = 3, ki = 3.5 and kd = 0.2. Based on the above design, the setting temperature of the replacement fluid can be raised as needed in the field, and the temperature stability and control accuracy are guaranteed.
To meet the treatment needs on a disaster site, the mobility of the machine must be considered as it needs to be frequently moved within limited space. The structural design must be highly integrated and compact. The design of the current machine significantly reduces the total volume compared with several traditional devices, such as the Baxter Aquarius (size: 60 × 1,700 × 500 mm, weight: 75 kg), the Swedish Campbell PRISMA (size: 300 × 1,620 × 490 mm, weight: 60 kg), the B. Braun (Germany) (volume: 480 × 1,260 × 500 mm, weight: 46 kg) and the Shanwai-shan (China) (volume: 350 × 1,470 × 400 mm, weight: 58 kg). The novel prototype (size: 238 × 500 × 500 mm, weight: 30.5 kg, including the battery) has several advantages: it is small, lightweight, and highly portable. Therefore, this machine can better serve in rescue work on a disaster site.
At a disaster scene, power is mainly provided by temporary generators, which are different from conventional power sources. Therefore, an adaptive power unit is used in the machine, which allows it to be powered by 220 V AC or 12 V and 24 V DC. An assembly of high-capacity batteries is also included. The battery installed in the machine is a rechargeable lithium battery; therefore, when connected to a power supply device, the battery will automatically charge until it reaches full power. Together with the battery-saving program, the machine can provide 5 h of treatment on a disaster site where a power supply is unavailable. The purifier is also configured with an RS232 interface and a CS8900 Ethernet controller, which allow for a network of multiple purifiers to be set up. In this case, such a multi-instrument network could facilitate centralized monitoring and control during a shortage of doctors and/or engineers. A network of purifiers can also facilitate remote medical treatment functions via LAN connections.
Basic Performance Test
A series of rigorous tests of the prototype machines were conducted at China's State Food and Drug Administration, Beijing Medical Device Quality Supervision and Inspection Center. This system is classified as continuous blood purification equipment and therefore must comply with the national standard YY 0645-2008 and the national standard for electronic general medical equipment GB9706.1-2007 .
The machine utilizes a variety of self-monitoring and feedback systems to ensure safe treatment. The CPU controls the initiation of the blood pumps, fluid pumps and the ultrafiltration pump. According to treatment requirements for the flow of the blood and ultrafiltrate, the flow is adjusted by changing the motor speed. To guarantee precise fluid flow, the motor speed can be automatically adjusted based on the feedback signals of the fluid volume.
The infusion pump controls the replacement fluid and implements real-time heating to maintain fluid temperature within a preset range according to the patient's body temperature requirements. Throughout treatment, the CPU monitors all real-time signals, e.g. arterial/vein and ultrafiltration pressure, blood leakage and fluid levels of the infusion port. When any of these signal indicators increase above the critical values, a sound and light alarm system is triggered to alert healthcare staff, and the blood and replacement liquid circuits are automatically turned off to ensure treatment safety.
To test the performance of the machine under extreme circumstances, a series of specially designed environmental tests were completed at a testing center in Beijing. They included four special circumstances: the salt spray test, the tilt and swing test, the vibration test and the electromagnetic compatibility test.
Animal experiments included three parts that were completed separately to simulate earthquakes, disasters at sea and ambulance conditions. Animal experiments were also conducted in a pressurized hyperbaric oxygen cabin.
Animal experiments under simulated earthquake conditions were completed with dogs. Following anesthesia, dogs were intubated, and continuous blood purification treatment was performed for 24 or 72 h with a replacement fluid flow rate of 1 or 2 liters/h. A standard constant temperature concussion apparatus (LH-293-A, Taicang Experimental Instrument Factory) on which our machine was placed was used to simulate earthquakes. The shaking rate was within 0-120 rpm with an amplitude of 20 mm convolutely and reciprocally.
Adaptation experiments were performed at sea according to our previous study . The sea conditions were class 4-6, and the wind forces were class 4-8 with a wave height of 1.5-2.7 m. The sway rate of the ship was 2-7°, and the ship speed was 14-40 knots. Four dogs received continuous blood purification therapy for 5 h with replacement fluid rates of 1 and 2 liters/h.
An adaptation experiment using an ambulance was also performed as shown in figure 5. The wind force was class 3, and the vehicle speed was 80-110 km/h. The routes traveled included expressways, countryside pack-ways, and valley roads, which were uneven with declivities causing the ambulance to bump and shake strongly. During the treatment, the replacement fluid error ranged between 1.33 and 4.55%. The dehydration error ranged between 0.2 and 0.8% (table 3). All alarms were precise and sensitive to guarantee safety. This experiment indicated that the novel portable continuous blood purification machine is suitable for use within ambulances.
|Table 3. Comparisons of the replacement fluid error and dehydration error (mean 8 SD)|
|Fig. 5. Photograph of an animal experiment. The photograph shows that when driving on a muddy gravel road in the wild suburbs, our ambulance was bumping vigorously; however, our machine operated normally.|
To examine the safety of this machine when used in sealed pressurized cabins in aircraft, animal experiments were performed in hyperbaric and hypobaric chambers (manufactured by Shanghai Jiangnan Shipyard Co.). The hypobaric experiment was first performed to simulate the pressure conditions of an aircraft flying at various heights. At altitudes of 2,000, 3,000, and 4,000 m, the corresponding pressure values were approximately 0.8, 0.7, and 0.6 atm. Next, a pressurized test was performed to observe the treatment safety and stability of the machine when the pressure in the cabin was increased to 1.1, 1.2, 1.3, 1.4, or 1.5 atm.
Clinical Uses of the Novel Machine
A crossover design experiment was used to test and verify the application of the novel prototype machine in clinical settings. Thirty-two participants were enrolled in the study (19 men and 13 women). Five patients had acute renal failure, 25 had chronic renal failure and 2 had multi-organ failure. The average age was 51.9 years (range: 26-75 years). Serum creatinine levels before treatment were between 111 and 1470 µmol/l with an average of 712.5 µmol/l. Urea nitrogen assessments were between 8.6 and 53.5 mmol/l with an average of 28.36 mmol/l. Patients were randomly divided into two groups, those first treated with the Aquarius and then the novel purifier and vice versa. The continuous blood purification therapy was performed for 8 h with a blood flow of 150-200 ml/min, replacement fluid flow rate of 3 liters/h, and a variable dehydration rate.
Numbers, means, standard deviations, minimums, maximums, medians, and interquartile ranges were used for descriptions of the continuous data. Continuous data were analyzed with the t test (normally distributed continuous data) or the Wilcoxon test (continuous data not normally distributed). Data were also analyzed with the χ2 test or Fisher's exact test and the ranked data were compared with the Wilcoxon test. Analysis was performed using SAS9.1.3 software, and a value of less than 0.05 (double-sided test) was considered significant. Means and proportions were calculated as appropriate, with 95% conﬁdence intervals (CIs) constructed around proportional estimates. Statistical descriptions were used for the pass rates of performance and safety indicators. Comparisons between the pass rates of the two groups were analyzed with the exact-rate test.
The experimental protocol conforms to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publication No. 85-23, revised 1996) and was approved by the ethics committee of the Navy General Hospital (Beijing, China).
The clinical trial protocol complied with the principles specified in the Declaration of Helsinki (revised in Edinburgh in 2000) and was approved by the Ethics Committee of the General Hospital of the Jinan Military Area (Jinan, China) and the No. 302 Hospital of PLA (Beijing, China). All patients involved in this trial provided informed consent.
The results showed that the machine met the national standard requirements (table 1).
|Table 1. Technical specifications of the novel portable continuous blood purifier|
The results showed that the machine performance and stability met the requirements for special circumstances (table 2).
|Table 2. Environmental test of the novel machine|
In animal experiments with simulated earthquakes, the replacement fluid flow error ranged between 0.5 and 4.2%, and the dehydration error ranged between 0.23 and 0.82% (table 3). Both of these parameters met the requirements of the national industry standards. All alarms were precise and sensitive, thus confirming the safety of the system. This experiment indicated that the novel portable continuous blood purification machine is applicable for use in simulated earthquakes. A more detailed description of the simulated earthquake animal experiments can be found elsewhere .
In animal experiments at sea, the average errors of the replacement fluid and dehydration rate were 2.2 and 0.32%, respectively (table 3). Both of these parameters met the national industry standard requirements. All alarms were precise and sensitive, thus confirming the safety of the system. This experiment indicated that the novel portable continuous blood purification machine is applicable at sea. A more detailed description of the animal experiment at sea can be found elsewhere .
In animal experiments in an ambulance, the replacement fluid error ranged between 1.3 and 4.5%. The dehydration error ranged between 0.21 and 0.78% (table 3). All alarms were precise and sensitive, thus confirming the safety of the system. This experiment indicated that the novel portable continuous blood purification machine is applicable for use in an ambulance.
Under hypobaric and hyperbaric experimental conditions in the cabin, the portable continuous blood purification machine could function normally, all alarms were precise and sensitive, and there were no adverse reactions in the experimental dogs. We found that with the changes in cabin pressure, venous chamber pressure also showed corresponding changes; the machine automatically detected pressure changes, and the alarm sounded promptly to ensure the safety of the treatment.
Clinical Use of the Novel Machine (fig. 6)
The replacement fluid flow of the novel machine ranged between 0.02 and 1.48%, and the dehydration rate ranged between 0.1 and 0.59%. The accuracy of the replacement fluid flow and dehydration rate of the two groups (the novel machine group and the Aquarius group) was not significantly different (p > 0.05) (table 4). The serum creatinine and urea nitrogen of the two groups decreased significantly after treatment (p < 0.001). However, the decreases in serum creatinine and urea nitrogen between the two groups were not significantly different, which indicates that the novel machine is equivalent to the Aquarius in improving renal function.
|Table 4. Comparisons of the replacement fluid error and dehydration error between the two groups|
|Fig. 6. An acute renal failure patient received continuous blood purification treatment using the machine. After treatment for 8 h, the patient's levels of serum potassium, serum creatinine and blood urea nitrogen all decreased significantly; the results are remarkable.|
No obvious changes could be found between the two groups with regard to serum potassium, serum sodium, and serum chlorine after therapy (p > 0.05). The changes between the two groups were not significantly different (p > 0.05). The serum level of calcium and phosphate decreased (p < 0.05), but the difference between the two groups was not significantly (p > 0.05), which indicates that the novel machine is equivalent to Aquarius in adjusting the acid-base and electrolyte balance (table 5). We also observed changes in the levels of myoglobin and CPK during treatment. The results showed that the values of myoglobin and CPK during and after treatment decreased when compared with those before treatment; however, because the number of cases was small, statistical analyses were not performed. No adverse effect was observed during the experiment. The novel continuous blood purification machine has the advantage of handiness, simplicity and ease of use.
|Table 5. Comparisons of renal function between the two groups (medians with interquartile ranges in parentheses), difference and percent difference|
For the first time, we used a volumetric measurement method instead of a liquid weight measurement method to develop a specialized volumetric measurement control device. This machine solves the problem that current continuous blood purification devices cannot be used in swinging, bumpy, or vibrating conditions or for accurate liquid measurement. Combined with an intelligent and efficient heating device, this machine can achieve rapid blood rewarming in wounded patients. Furthermore, by optimizing the liquid-measuring device and other components and designing compact structures, weight reduction and miniaturization of the machine can be achieved, and thus, this instrument can be used in a variety of medical settings. In addition, this purification machine also uses combined electronic detection, monitoring and networking technology to achieve automatic monitoring and alarming, notably of flow, pressure and temperature (fig. 7). These measures increase the reliability and stability of the device and the safety of the treatment. The machine can also achieve centralized monitoring and control of multiple purification instruments through networking and LAN telemedicine.
|Fig. 7. Screen shots. a Operation mode when the machine is started. b Before infusion. c Normal operation. d Alarm when bubbles occur in the blood flow.|
Compared with current existing portable continuous blood purification machines, this novel portable continuous blood purification machine includes the following five advantages: (1) high measurement accuracy; (2) high heating efficiency; (3) smallness, portability and suitability for use in emergency rescue operations during disasters; (4) strong environmental adaptability, which makes this device currently the only continuous blood purification machine that can be used in harsh conditions, such as swinging, vibrating and salt-spraying environments (patent already obtained), and (5) a wide range of applications.
After many measurements and experiments, this novel portable continuous blood purification machine can be used in special disaster situations. Whether on earthquake sites with many aftershocks, rocking ships, or bumpy ambulances or trains, this machine can immediately achieve continuous treatment of the wounded, gain more time for treatment, and save the lives of injured individuals. The use of this novel portable continuous blood purification machine will greatly increase our emergency rescue ability in disasters.
This work was supported by Navy Logistics Scientific Research Projects (No. 07-3308).
The novel continuous blood purification machine has been patented as an invention and utility model in China. Patent No. CN101347644.
Prof. Zhou Chunhua, MD
Navy General Hospital, Clinical Medical College
Second Military Medical University, No.6 Fucheng Road
Haidian District, Beijing 100048 (China)
Tel. +86 10 6695 8151, E-Mail email@example.com
Received: August 12, 2011
Accepted: December 27, 2011
Published online: February 15, 2012
Number of Print Pages : 11
Number of Figures : 7, Number of Tables : 5, Number of References : 15
Vol. 33, No. 4, Year 2012 (Cover Date: June 2012)
Journal Editor: Ronco C. (Vicenza)
ISSN: 0253-5068 (Print), eISSN: 1421-9735 (Online)
For additional information: http://www.karger.com/BPU