| Management of shock remains a difficult problem in surgery development. Early treatment of wound and traumatic shock is critically important to improve survival of trauma victims. The mortality of shock and morbidity of acute renal failure after shock have decreased markedly since isotonic crystalloid solutions were applied to shock resuscitation. But as for uncontrolled hemorrhagic shock, early aggressive resuscitation with the purpose of obtaining normotension may increase blood losses because of thrombus dislodgement and hemodilution, and accelerate death or increase mortality. Therefore early resuscitation of uncontrolled hemorrhagic shock has become a prominent problem in the treatment shock. In recent years, several animal experiments showed that appropriate hypotensive resuscitation may obtain increased survival compared with nonresuscitated control or normotensive resuscitation in uncontrolled hemorrhagic shock animals. But what pressure level should be maintain to gain better resuscitation effects and how long could hypotension be maintained without evidently increased mortality remains unclear. Much disputation exists about shock resuscitation with colloid or crystalloid solutions. Which kind of resuscitative fluid could obtain better effects in early hypotensive resuscitation of uncontrolled hemorrhagic shock remains ambiguous. In recent years, some experimental studies showed that controlled mild or moderate hypothermia could protect organ function and prolong survival time of hemorrhagic shock animals. Whether controlled hypothermia could be applied to the treatment of uncontrolled hemorrhagic shock, and how can we combine hypothermia and hypotensive resuscitation deserves more studies. In the present study, uncontrolled hemorrhagic shock model of rats and swine were used to simulate the clinical scenario to investigate optimal early fluid resuscitation scheme, including the kinds of resuscitative fluid, optimal resuscitative pressure and permissive hypotensive duration and the application of hypothermia, with the purpose of providing experimental evidence for the treatment of uncontrolled hemorrhagic shock.The main methods and results: 1. A rat model of uncontrolled hemorrhagic shock was used to compare the effects of different molecular weight of hydroxyethyl-starch (HES) 40, HES130 and HES200 in early hypotensive resuscitation. The results showed that compared to nonresuscitated control, early hypotensive resuscitation with HES markedly prolonged survival time of rats with uncontrolled hemorrhagic shock. HES with different molecular weight obtained different early resuscitative effects in rats with uncontrolled hemorrhagic shock. Compared to HES40, HES130 and HES200 could improve the hemodynamic parameters and survival of shock rats with less fluid requirement and less blood loss.2. A rat model of uncontrolled hemorrhagic shock was used to compare the effects of 6 kinds of different fluid formulation [normal saline, Lactated Ringer's (LR), Dextran40, LR/Dextran40, HES200 and LR/HES200] in early hypotensive resuscitation. The results showed that among several fluids which are often used in shock resuscitation, LR plus HES200 achieved a relatively optimal early resuscitative effects. They resulted in a less blood loss, a lower fluid requirement, and a good improving effects on hemodynamics and survival time.3. A rat model of uncontrolled hemorrhagic shock was used to compare the effects of different resuscitative pressure (40, 50, 60, 70 and 80 mmHg) in early resuscitation. The results showed that the bleeding rate in all resuscitation groups was higher than in the nonresuscitated control group, but the survival time in hypotensive groups was longer than in the nonresuscitated control group. Bleeding rate in 50 mmHg group was less than in 60 to 80 mmHg groups. Hematocrit in 50mmHg group was significantly higher than in 70 and 80mmHg groups. Hepatic biochemical parameters in 40mmHg group were significantly higher than in 50, 60 and 70 mmHg groups. Survival time in 50 mmHg group was significantly longer than in nonresuscitated control and 80 mmHg groups. These results implicated that appropriate hypotensive resuscitation [maintaining mean arterial pressure (MAP) at 50~60mmHg] could obviously decrease blood loss, alleviate hemodilution and improve survival of shock animals, when compared with normotensive resuscitation (maintaining MAP at 80 mmHg).4. A rat model of uncontrolled hemorrhagic shock was used to compare the effects of duration of hypotension (60min, 90min and 120min) in early resuscitation. The results showed that along with the prolongation of hypotension, the fluid requirement and blood loss increased and the survival time decreased, implicating the duration of hypotension should not be too long, and effective intervention should be taken as soon as possible to control bleeding for uncontrolled hemorrhagic shock.5. A rat model of uncontrolled hemorrhagic shock was used to compare the effects of controlled hypothermia in early hypotensive resuscitation. The results showed that the survival time in mild or moderate hypothermia groups was longer than in profound hypothermia group; after shock and resuscitation, pH value and base excess in mild hypothermia group were both higher than in normothermia and profound hypothermia groups; hemodynamic parameters in mild or moderate hypothermia groups were better than in profound hypothermia group. These results indicated that controlled mild or moderate hypothermia can better improve the early resuscitation effect for uncontrolled hemorrhagic shock.6. A swine model was used to investigate the effects of hypotensive resuscitation combined with controlled hypothermia on early resuscitation in large animal with uncontrolled hemorrhagic shock. The results showed that on the basis of application of controlled mild hypothermia, the survival rate in 60 mmHg group was significantly higher than in 40 and 50 mmHg groups, and pH value and base excess in 60 mmHg group were both significantly higher than in 40 and 50 mmHg groups, indicating that on the basis of controlled mild hypothermia, maintaining MAP at 60 mmHg in early resuscitation is relatively appropriate.7. A rat model of uncontrolled hemorrhagic shock was used to investigate the effect of hypotensive resuscitation and controlled mild hypothermia on organ function of shock animals and its mechanism. The results showed that after shock and resuscitation, plasma total-bilirubin in 70 mmHg/normothermia group was significantly higher than the normal value; MB isoenzyme of creatine kinase (CKMB) in 70 mmHg/normothermia group was significantly higher than the normal value and in 50 mmHg/hypothermia group; the respiratory control rate (RCR) of hepatic cell mitochondria in 50 mmHg/normothermia, 70mmHg/hypothermia and 70 mmHg/normothermia groups was significantly lower than the normal value, but no significant difference was observed between 50 mmHg/hypothermia group and the normal value in RCR; the RCR in 70 mmHg/normothermia group was significantly lower than in 50 mmHg/hypothermia group; plasma D-lactic acid in 70 mmHg/hypothermia and 70 mmHg/normothermia groups were significantly higher than the normal value and in 50 mmHg/hypothermia group. These results indicated that appropriate hypotensive resuscitation and controlled mild hypothermia can both protect organ function of uncontrolled hemorrhagic shock animals, and the combination of hypotension and hypothermia obtained the best protective effects. The mechanism of the protective effects could be related to alleviation of mitochondria impairment and protection of the intestinal mucosa barrier function.Conclusions:1. HES with different molecular weight obtained different resuscitative effects in uncontrolled hemorrhagic shock, the effects of HES 130 and HES 200 were better than that of HES 40. Among several solutions which are often used in shock resuscitation, LR plus HES 200 achieved a relatively optimal resuscitative effects.2. As for uncontrolled hemorrhagic shock, hypotensive resuscitation before definitive operative intervention to control hemorrhage could significantly prolong the survival time of shock animal. Appropriate hypotensive resuscitation (MAP 50~60mmHg) could obviously decrease the blood loss, lower the fluid requirement, alleviate hemodilution and increase the survival time and rate of shock animals, when compared with normotensive resuscitation (MAP 80 mmHg). But too low pressure restrains cardiac function and aggravates liver damage.3. As for uncontrolled hemorrhagic shock, application of mild or moderate hypothermia in hypotensive phase could evidently improve hemodynamics, alleviate acidosis and prolong survival time of shock animals. In swine model of uncontrolled hemorrhagic shock, on the basis of mild hypothermia, the appropriate early resuscitative pressure is maintaining MAP at 60 mmHg.4. Appropriate hypotensive resuscitation and mild hypothermia can both protect organ function of uncontrolled hemorrhagic shock animals. The mechanism of the protective effects could be related to alleviation of mitochondria impairment and protection of the intestinal mucosa barrier function.
|
PDF Full Text Request