Therapeutic Effects Of Hypertonic Sodium Chloride Hydroxyethyl Starch 40 Injection (HSH) On Acute Intracranial Hypertension Complicated Hemorrhagic Shock Dog

Brain injury is one of the most serious traumatic, Intracranial hypertension complicated shock is the leading cause of death. Therefore, control of brain edema and intracranial hypertension is not only important measure in neurosurgery perioperative treatment, but also one of the key factor in the prognosis of patients. Large quantities of liquid used to treat patient with shock can increase cerebral edema , and cause secondary brain damage, conventional drug of dehydration to treat patient with intracranial hypertension will reduce blood circulation, increase shock level to further reduce cerebral blood flow, cause deeper cerebral edema, forming a vicious circle . Mannitol is used to lower intracranial pressure drug, but rebound phenomenon, and there is a potential kidney toxicity. Diuretics such as furosemide habitation result in side effects ,such as electrolyte imbalance, and the drugs can decrease blood pressure, unfit for traumatic brain injury patients with shock. Much of the basic research and clinical trial evidence that different concentration of hypertonic saline solution can effectively recovery hemorrhagic shock, significantly reduce intracranial pressure, and can treat head injury patient with or without shock. But some literature report hypertonic salt reduce intracranial pressure shorter, cause rebound edema, and hypernatremia. In the past literature, Nacl concentration from 7.5% to 23% different is reported ,but less than 7.5% hypertonic salt or add colloidal hypertonic salt used in intracranial hypertension with shock is reported less.In the experiment, using the inflation of the epidural balloon with saline and arterial blood withdrawal rapidly replication acute intracranial hypertension complicated hemorrhagic shock model of dog, then use hydroxyethyl starch 40 hypertonic sodium chloride injection (HSH) to recovery, observe the effect on the brain edema and hemodynamic,explore the therapeutic effect and mechanism of HSH on acute intracranial hypertension complicated hemorrhagic shock model of dog, confirm HSH the feasibility of the application in neurosurgery, and further guidance Perioperative fluid management in traumatic brain injury patients with shock.Materials and methods1. Experimental animals30 adult healthy dogs, female or male, body weight 10-20 kilograms, were provided by the experiment anmimal center of southern medical university affiliated southern hospital.2.Anesthesia implentationAnesthesia adminutesistered by intravenous injection of pentobarbital sodium 3% solution (1ml/kg),after tracheal intubation , animal's breathing is controlled by ventilator, intravenous infusion of vecuronium (0.08mg·kg-1·h-1), 1% isoflurane and pure oxygen is inhalated in for the maintenance of anesthesia.3.Establish intracranial hypertension with acute hemorrhagic shock model:Cut right jugular vein , insert venous catheter (18G) to monitor central venous pressure(CVP). left femoral vein is cuted and insert 18G venous catheter for intravenous infusion. cut left femoral artery , insert 20G hepatin catheter to monitor mean arterial pressure(MAP) and pulse(P). cut hair on the top of head of dog, median longitudinal incision was made on the head skin, expose parietal bone. Drill the left parietal bone ,diameter (6-10) mm, a water balloon is placed to epidural, fix balloon. Drill the right parietal to place tube to ventricle, and connect L-type pressure measurement to monitor intracranial cerebral pressure(ICP). Both side of the skull defects is closed with bone wax in order to ensure the reliability of pressure. Inject water to the bulloon, making the intracranial cerebral pressure 10 mmHg higher than the basic pressure and maintain the pressure, withdrawal blood rapidly through right femoral attery in 15 minutes, reduce to MAP (40±5)mmHg, and adjust the volume to maintain blood pressure, continuing the status for 60 minutes , the model of intracranial hypertension associated with hemorrhagic shock is completed.4.Experiment group and treatment factors:Dogs were randomly divided into six groups, each with five, groups and factors are:①7.5% sodium chloride group (HS) 6 ml/ kg HS②Ringer's solution group (RL), three times the amount of blood loss③hydroxyethyl starch group (HES), equivalent to the amount of blood loss④4 ml / kg HSH group (HSH4) 4 ml / kg HSH⑤8 ml / kg HSH group (HSH4) 8 ml / kg HSH⑥12 ml / kg HSH group (HSH4) 12 ml / kg HSH. All liquid must be infused within 20 minutes.5.Indicators observation and specimens collection:Mean arterial pressure, central venous pressure, intracranial cerebral pressure and pulse were recorded before the experiment (T1), after making model (T2), 20 minutes after resuscitation (T3), 40 minutes after resuscitation (T4), 1 h after resuscitation (T5), and 2 h after resuscitation (T6), 3 h after resuscitation ( T7), 4 h after resuscitation (T8),and calculated cerebral perfusion pressure(CPP=MAP-ICP). collected blood to test plasma Na~+ and plasma osmotic pressure (OSM) before experiment(T1), after making model(T2), 30 minutes after resuscitation(T30),1h after resuscitation (T60) ,4 h after resuscitation(T240).6.Cerebral water content measurement:After the end of experiment,Animals in each group were rapid craniotomy brain, and cut dura, then the brain will be departed into two half uniform ,filter drain liquid surface, weight the two wet hemispheres. Then brain tissue was putted in the electric incubators (100±2℃) at 48 h drying to constant weight, lastly weight the dry two hemispheres. By Elliot formula cerebral water content (%),cerebral water content = (wet weight - dry weight) / wet weight×100%.7. Statistical analysis.All data are reported as the mean±standard deviation( (x|-)±s). Test of homogeneity of variances was analyzed firstly, then analysis of one-way-anova was used to evaluate the basic status data such as body weight, water balloon, volume of blood loss, baseline intracranial pressure, intracranial pressure after balloon inflation . Two-way ANOVA was used to analyze cerebral water content and paired t-test to test for different within-groups., Analysis of variance of repeated measure data was used to analyze the repeated measures data. Post Hocmultiple comparisons were analyzed by using SNK test. SPSS 13.0 were used to analyze the data. P values of≤0.05 were accepted as significant.Result:1. The baseline dataThere is no statistic significance between body weight, water balloon, volume of blood loss, baseline intracranial pressure, intracranial pressure after balloon inflation . (P>0.05).2.Pulse There is statistic significance with pulse during different time in the test of within-subjects effect (F = 59.272, P = 0.000) , increased evidently after model was made and recovered after the recovery.there is no difference between-subjects effect (F = 0.372, P = 0.863).3. Central venous pressureThere is statistic significance with central venous pressure before and after the recovery time in the test of within-subjects effect (F = 156.821, P = 0.001) , cvp dropped after shock and increased after recovery significantly.between-subjects effect, no difference (F = 2.297, P = 0.077), from all time points, except recovery after 2 h HS group was significantly lower than the other groups (P <0.01), other groups had no statistic significance (P> 0.05).4.Mean arterial pressureThere is statistic significance with mean arterial pressure before and after the recovery time in the test of within-subjects effect (F = 133.096, P = 0.000) , MAP increased significantly after resuscitation, but it responded fastestly in group HSH, and reached the level of before shock after 20 minutes;between-subjects effect, no difference (F = 2.041, P = 0.109), from all time points, except recovery after 2 h group HS was significantly lower than the other groups (P <0.01), other groups had no statistic significance ( P> 0.05), and recovery time between the liquid interactive effect (F = 2.727, P = 0.001).5.Intracranial cerebral pressureThere is statistic significance with intracranial cerebral pressure before and after the recovery time in the test of within-subjects effect (F = 148.719, P = 0.000) , and between-subjects effect, significantly difference (F = 61.446, P = 0.000), group RL and HES increased ICP after the recovery time , and reached peak at 1h and 3h separately, from the time point of view, group HSH8, HSH12 and HS lowered ICP no statistic significance (P> 0.05), were stronger than group HSH4 (P <0.01), and recovery time between the liquid interactive effect (F= 45.957, P = 0.000).6. Cerebral perfusion pressureThere is statistic significance with cerebral perfusion pressure before and after the recovery time in the test of within-subjects effect (F = 170.186, P = 0.000), and between-subjects effect, statistic significance (F = 4.267, P = 0.006),all group rose cpp after the recovery, reached the peak at 1 h and declined slowly . group HSH12 and HSH8 improve CPP no statistic significance (P> 0.05). 4 h after resuscitation, group HS was significantly lower than the other groups (P <0.01 ); recovery time and interaction between the liquid effect (F= 2.976, P = 0.000).7.Cerebral water contentCerebral water content of the groups is significantly different (F = 23.265, P = 0.000), cerebral water content of group RL, HES, HS, HSH4, HSH8, HSH12 are as follows: 0.82±0.04,0.79±0.03,0.75±0.04 , 0.74 ,±0.02, 0.68±0.05, 0.68±0.03; group HSH8 and group HSH12 no statistic significance in cerebral water content (P = 0.860), were lower than the other groups (P <0.01); group RL and HES no difference in cerebral water content (P = 0.105 ), were higher than the other groups (P = 0.000); there is no statistic significance in the cerebral water content between injury side and the normal side (F = 0.724, P = 0.399).8.Blood Na~+There is statistic significance with blood Na~+ before and after the recovery time in the test of within-subjects effect(F = 49.075, P = 0.000), and between-subjects effect, significantly difference (F = 12.654, P = 0.000), except group HES did not change significantly(F = 2.049, P = 0.191), the other groups rose and reached the peak at 30 minutes after resuscitation, gradually restored after 4 h. in three groups HSH blood Na~+ is solubility positive relations with the dosage . 9 .Plasma osmotic pressureThere is statistic significance with plasma osmotic pressure before and after the recovery time in the test of within-subjects effect (F = 166.906, P = 0.000), and between-subjects effect, significantly difference (F = 6.080, P = 0.001), except group RL fell down, the other groups rose and reached the peak at 30 minutes after resuscitation, gradually restored after 4 h. in three groups HSH plasma osmotic pressure is solubility positive relations with the dosage .Conclusion:1. In acute intracranial hypertension complicated hemorrhagic shock model of dog, HSH can effectively correct shock and reduce intracranial pressure,but also can improve cerebral perfusion pressure and maintain longer time, 8 ml / kg dose is suitable.2. HSH can reduce cerebral water content and dehydrate no statistic significance in the brain water content between injury side and the normal side3. HSH lower ICP associated with plasma osm .