| Hemorrhagic shock (HS) is a critical pathological process that is caused by massive blood loss with an acute reduction in circulating blood volume, and serious insufficient microcirculatory perfusion of tissues and organs, and cellular metabolic disorders and functional impairment, and vital organs functional disturbance and metabolic dysfunction. In World War Ⅱ, the mortality rate of US Army caused by wound HS was up to65%. It was predicted that in the high-techlocal wars the incidence of shock might be up to40%of the total injured, and death caused by the wound HS would amounted to32.6～59.5%. The experts predicted that by2020the total amount of death in the world caused by trauma will reach8.4million, and the death caused by HS will account for1/3.HS features reduction of the central venous pressure and the blood less, and low blood pressure resulting from the reduction of the cardiac output, the most effective treatment measures are timely and effective fluid resuscitation. However, the traditional resuscitation method is combined with artificial drip infusion timely, rapid, and resuscitation strategy, as soon as possible to improve homodynamic goal, which often causes inadequate organ perfusion after resuscitation, systemic inflammatory response syndrome even the development of multiple organ dysfunction syndrome (MODS). Especially in the disaster, war, and major accidents, large quantities of patients/the wounded with blood loss, limited treatment power and medical resources caused that effective fluid resuscitation can’t be implemented with traditional resuscitation method, which led to the success rate of resuscitation is not high, and later morbidity and mortality rates are on the high side.In recent years, based on the automatic control of the closed-loop resuscitation (CLR) has become the research focus of the shock fluid resuscitation at home and abroad. Resuscitation of closed-loop control of the "quantity" and "speed" in the early expansion of the treatment for shock and resuscitation methods has the absolute advantage compared with traditional method, which can avoid clinical over resuscitation or under resuscitation occurred through monitoring of human physiological signals and adjusting the infusion rate and infusion volume in real time. On the other hand, it will play an important role in pre-hospital emergency or continuous evacuation treatment when encountering large-quantity patients and relative lack of medical resources because that self-adjustment or closed-loop control can be done by feedback of the physiological state without needing any professional medical staff. US Army have proposed early the study of automated critical care life support system aiming at providing automated computer-based closed-loop control, fluid resuscitation and drug administration based on computer closed-loop control.Nowadays the CLR of shock based on the control principle can be divided into the following two categories:the first category is mainly based on linear control system of the PID controller, real-time blood pressure for the system input, adjust the infusion rate of linear approximation to the target blood pressure with good accuracy; the second category is based on the intelligent controller of nonlinear control systems, including fuzzy control systems based fuzzy controller (FC) and computer closed-loop system based decision-making table, as opposed to linear control systems, both control systems are to optimize the resuscitation strategy is more intelligent, more stable. However, the ultimate purpose of the CLR is to achieve the desired resuscitation endpoint with most effective way (at least the liquid, the best outcome). Despite many animal studies have confirmed the superiority of the CLR in terms of fluid management, but not yet sufficient data on the utility of CLR in improved patient outcomes and improve survival rates. The reasons are as follows:(1) Physiological monitoring technologies are limited. General clinical resuscitation in patients with HS advocated that the priority is rapid resuscitation of homodynamic indicators. Hypotensive resuscitation is taken for non-controlled HS to maintain the body can withstand the most hypotension with a minimum volume fluid, and positive resuscitation is taken controlled HS. Arterial blood pressure (ABP) is still the most widely used and most effective for the CLR guide fluid resuscitation. Most clinical non-invasive blood pressure measurement methods for the cuff pressure method, but the technology in patients with hypovolemic measurement accuracy is poor, and a longer measurement period does not meet the demand for closed-loop control. In addition, the shock fluid resuscitation is mainly used in pre-hospital, clinical homodynamic and oxygen metabolism in detection technology have some limitations, which restricted them used as the control variables of the resuscitation guidance.(2) Hemorrhage severity is difficult to be recognized. It is difficult to precisely establish a scientific model, in order to achieve real-time identification and assessment of patients with blood loss or resuscitation of the state, and provide effective evidence-based closed-loop control the basis of medical decision-making. In recent years, studies have shown that blood pressure for the resuscitation of the end of the treatment of patients with HS can rapidly restore the body’s circulating blood volume, but in fact the cells of the body is still in a hypoxic state, has not been effective tissue perfusion. Thus, the microcirculation and organ perfusion is considered to be important indicators to evaluate the effect of fluid resuscitation and prognosis. Arterial blood lactate, base excess/deficit (BE/BD) may not fully reflect every organ blood flow of the vascular bed. Gastric mucosa pH have certain limitations. Organ carbon dioxide partial pressure (PCO2) as monitoring indicators of tissue hypoxia, tissue perfusion failure prediction is of great significance. The latest reported in the literature, buccal mucosal PCO2(PbuCO2) can achieve a continuous, noninvasive monitoring and PbuCO2and cardiac output (CO) has a good correlation in the monitoring of clinical shock, has a certain value.(3) Resuscitation outcome can not be guaranteed. The CLR used in HS resuscitation strategy based on ABP and other hemodynamic indexes in guiding resuscitation, but only under the supervision of the target blood pressure, fluid resuscitation, many cases can’t make the microcirculation and organizations and organ perfusion is easy to cause a lot of clinical complications. Shock occurs and the early expansion of the treatment of shock monitoring and shock degree of real-time identification is very important to effectively guide the optimization of the resuscitation decision-making and timely adjustment of the resuscitation strategy, especially the infusion rate and infusion volume. For these two reasons, both based on the PID controller, FC and the decision-making table, CLR system in accordance with the existing principles of resuscitation, the resuscitation objectives and resuscitation of liquid closed resuscitation were not taking into account the resuscitation of circulating blood volume and improve tissue perfusion resuscitation decision-making capacity and therefore can’t ensure that the good effect of the CLR on the prognosis of patients with shock.In summary, the subject combined with fluid resuscitation theory and intelligent control theory, the shock of recognition-resuscitation decision-making-the treatment of CLR of timing as the main line, divided into three stages of the CLR of key algorithms in HS. Firstly, to carry out a large sample of animal hemorrhagic model experiments, the study reflects the non-invasive detection techniques for monitoring indicators of tissue perfusion and oxygen metabolism. Secondly, to establish the mathematical model of the shock degree of recognition ollowed by statistical analysis based on experimental data, the development of different levels HS, evaluation methods, a prerequisite for the resuscitation decision-making. Thirdly, to study the mechanism of PbuCO2and MAP guidance of fluid resuscitation and to improve the prognosis, the shock degree of recognition algorithms and fuzzy rules based on FC to optimize the resuscitation decision-making, and intelligent control of shock and fluid resuscitation. The key algorithms include:(1) Continuous noninvasive measurement of tissue PCO2. We defined PbuCO2as a continuns and non-invasive indicators to monitoring organ PCO2, and improved PbuCO2detection device based on the detection methods of PCO2to reduce interference applied in the oral environment, including the baseline calibration, the temperature correction and optimization of the support structure. We studied the correlation of the PbuCO2HS, including hemodynamics and oxygen metabolism indicators.(2) Identification and evaluation of the severity of HS. We used ABP, PbuCO2, ECG, RES and CT and other physiological signals, consecutive non-invasive detection technology for studying on HS and resuscitation pathophysiological mechanisms, the establishment of a fuzzy model of HS. The microcirculation is the most commonly used Laser Doppler technology to monitor perfusion, thus reflecting the dynamic changes and spatial differences of the microcirculation in shock process. Hypovolemic shock resuscitation guidelines (2007) in the quantity and speed the body’s blood volume is lost, mainly to identify and evaluate the occurrence and the severity of HS. (3) FCS-based resuscitation strategy optimization. Based on the FCS-based CLR system platform, we optimized resuscitation decision-making by combining with the modern resuscitation theory and the recognition technology. We provided tow target blood pressure (60or90mmHg) for non-controlled and controlled HS, to CLR from the shock of the pre-hospital first aid extended to the hospital. PbuCO2was as a secondary control to monitor feedback microcirculation and tissue perfusion in the resuscitation process. The recognition of shock degree was focusing on the fuzzy decision to use the principle of least rehydration capacity of microcirculation and tissue perfusion, computational fluid capacity and rate of infusion.In order to verify the validity and reliability of algorithms of CLR, experimental design and clinical trials were implemented based on animal models.(1) Correlation between PbuCO2and the severity of HS. The analysis of dynamics indicators of25%,30%,35%and40%blood loss group PbuCO2after the baseline level of blood loss and blood loss and blood flow, oxygen metabolism indicators. After30min, some animals with an estimated40%blood loss died. In the remaining animals, ABP, CO, ECG, RES, blood gas and electrolytes among animals with35%,30%, and25%blood loss were not significantly different. Compared with all the above physiological parameters, only within15min, PbuCO2manifested notable significance (P<0.01). Analysis of correlation revealed that PbuCO2and CO, PbuCO2and PaCO2were well correlated (R2=0.85,0.74). In this experiment, we found that mild hemorrhagic When PbuCO2less than70mmHg; moderate blood loss When PbuCO2is between70-90mmHg; the When PbuCO2more than90mmHg, indicating severe, blood loss, must be compulsory intervention.(2) Closed-loop fluid resuscitation experiments based on FCS.25%,30%,35%and40%blood loss group before and after resuscitation of the continuous monitoring of the systemic microcirculation blood flow perfusion, and blood gas analysis and survival statistics, results showed that each group animal perfusion of the percentage change was statistically significant, all animals survived.MAP, PbuCO2of25%,30%,35%and40%blood loss group were continuous monitored for feedback regulation of infusion rate. PU of local skin microcirculation blood flow were continuous monitored at baseline, before and after resuscitation, and the minimum time and minimum capacity of fliud were caculated during CLR, and survival rate. The results showed that at baseline, MAP and PbuCO2in each group was not statistically significant; PU values were chest280～310PU, brain130～140PU and upper limb40～50PU; chest and brain PU in different blood loss group s were not statistically significant, only the upper limbs showed statistically significant (P<0.01). After30min, PbuCO2, brain, chest and upper limbs PU in different blood loss groups was statistically significant (P<0.05). For30min after blood loss, only40%of blood loss group some animals were death (mortality20%), and other animals all survived. At the beginning of CLR, PbuCO2were decreased,25%of blood loss group have been up to the target blood pressure. During CLR, the increase rate of PbuCO2was slower than MAP. After1hour of CLR, all animals survived, the minimum time and minimum capacity of CLR suggested a growing trendency in25%,30%,35%and40%of blood loss group, and showed obviously statistical significance (P<0.01). Each group of animals chest percentage change was positive, but the percentage changes of upper limb PU was negative value. Only25%blood loss group the percentage change of brain PU was positive value, and other animals were negative value.(3) The evaluation of hemolysis during CLR for HS. Control experiments confirmed FHb detection method has good accuracy and precision. The CV of inter-day variability and intraday variability was less than3.6%and6%. The method is applied the quantitative detection of FHb concentration in before and after blood transfusion. The results showed that, FHb values of animals in each group were statistically significant (P<001) before and after blood transfusion. To compare FHb concentrations between before and after resuscitation (AFHb<2mg/dl), it shown that hemolysis was not statistically significant during CLR. Blood gas analysis shown that pH levels were corrected for1h. Stepwise regression suggested that a good correlation FHb concentration and pH were correlated (r=0.905, P<0.01).The clinical study results show that1) PbuCO2not only is able to detect changes in tissue perfusion after blood loss, but also provides more consistency, accuracy and sensitivity than ABP, CO, blood gases and electrolytes to discriminate between different blood loss. PbuCO2consecutive non-invasive monitoring methods can be used as measurable indicators of wounded classification, clinical diagnosis and the severity of HS, especially in the absence of human intervention as a predictor of early lethal factor in the identification of indicators;2) the closed-loop control system based on the FCS in the fluid management of HS can effectively improve microcirculation and tissue perfusion, and has great significance to the survival of animals;3) the FCS-based closed-loop control system has good quality control for red blood cells hemolysis in whole blood or blood products, which can not only be applied to deal with a lot of liquid infusion can also be used for the transfusion of whole blood or blood products in the pre-hospital. |
