The Effect Of Oxygen Therapy On High Altitude Hemorrhagic Shock

Introduction In China, about 17 percent of total areas are above the altitude of 3000 meters. In high altitude the most important factor affecting body is low partial pressure of oxygen. After hemorrhagic shock, hypoxia and blood loss can make shock more severe and the related treatment more difficult, which will result in short survival time and less survival rate. Therefore, in the treatment of high altitude hemorrhagic shock(HAHS), oxygen therapy is very important besides countershock therapy. According to the overseas and domestic literature, the investigation on HAHS focused on blood volume expansion or application of drug. The research on oxygen therapy in HAHS was not sufficient with divergent standpoints. Zheng Bihai reported that inhaling 100% oxygen (O2) could decrease the pulmonary arterial pressure of animals with acute hypoxia at high altitude. Zhang Litang suggested 40-50 %O2 should be applied intermittently in the treatment of HAHS. But most researchers maintained that 30-40% O2 could be administered continuously when HAHS occurred. So which concentration of oxygen is ideal in the treatment of HAHS has not been determined. Now it's believed that during the phase Ⅲof shock, the intestines will suffer ischemia and anoxia severely, then the function of intestinal mucosal barrier will be depressed, which can cause the intestinal bacteria and lipopolysaccharide(LPS) to shift into blood and cause inflammatory cells to be activated. Thereby all kinds of inflammatory medium will be excreted, which can result in an irreversible shock. The intestines are the main source of endotoxemia after shock, and the translocation of intestinal LPS correlate closely with the functional lesion of organs and the prognosi of shock. Moreover, most evaluation of oxygen therapy focused on hemodynamics and oxygen metabolism in tissue. While the effect of oxygen therapy on intestinal barrier has not been reported in HAHS. We hypothesized that in the hemorrhagic shock animal model, rapidly exposed to high altitude, applying various fraction of inspired oxygen (FiO2) based on simple countershock, would produce one ideal FiO2, the inhalation of which would improve hemodynamics and tissue oxygenation, and this ideal oxygen therapy might also increase long-term survival rate by mitigating visceral hypoxia and thereby reducing the injury of gut barrier function. During resuscitation and reoxygenation, the elevation of partial pressure of oxygen in artery (PaO2) could also become detrimental, so we should evaluate the safety of this FiO2. In this way, we could provide feasible methods for raising the survival rate of HAHS and improving the nursing intervention in clinic. Objective: This study is designed to determine one ideal FiO2 in the treatment of HAHS. Then, to investigate the therapeutic effect of oxygen on HAHS in respect to not only hemodynamics and tissue oxygenation, but gut barrier function as well. Last, to evaluate the safety of such oxygen therapy. Methods: 1. Thirty rabbits were exposed to a simulated 3500m high altitude in a hypobaric chamber and randomly divided into five groups: Ⅰ(80% FiO2+countershock),Ⅱ(50% FiO2+countershock), Ⅲ(30% FiO2+countershock), Ⅳ(simple countershock), Ⅴ(blank control). Each group had 6 rabbits. Then hemorrhagic shock was induced through bleeding to 5.33Kpa of mean arterial pressure (MAP). After 1 hour, the rabbits were resuscitated with balanced saline. Then the changes of hemodynamics and arterial blood gas were recorded at different stages, as well as the survival time of rabbits. 2. The safety of the determined oxygen concentration applied to the rabbits rapidly exposed to high altitude was evaluated. On the spot of high altitude, 24 rabbits from the plain were divided into four groups: before oxygenation,Ⅰ(80% FiO2, 8h),Ⅱ(80% FiO2, 3d), Ⅲ(80% FiO2, 5d). Each group had 6 rabbits. Then the pathologic changes of lung were observed, and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in plasm were investigated. 3. Fifteen rabbits were exposed to a simulated 4000m high altitude in a hypobaric chamber and randomly divided into two groups of trial and control. Then hemorrhagic shock was induced through bleeding to 5.33Kpa of mean arterial pressure (MAP). After 1 hour, the rabbits were resuscitated with blood and balanced saline. In addition, the trial group was administered with oxygen therapy of 80% FiO2, while the control was not. (1) Hemodynamics was monitored with PowerLab/8sp physiological recorder at various phases, including MAP, the pressure of left ventricle and pulmonary artery, et al. Meanwhile, the survival number after 8 hours'treatment in each group was recorded. (2) The tissue oxygenation was detected by withdrawing arterial blood at various phases, which involved arterial blood gas and lactate concentration in plasma.(3) The pathologic changes of small intestinal mucous membrane were observed, after 8 hours'treatment, with light microscopy. The level of LPS in plasma was detected by kinetic turbidi-metric limulus test; the expression of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) mRNA in the total white blood cells were measured by RT-PCR. (4) The pathologic changes of lung were observed, after 8 hours'treatment, with light microscopy. The levels of MDA and SOD were investigated respectively by thibabituric acid (TBA) and hydroxylamine assays. Results: 1. The hemorrhagic shock model of animals rapidly exposed to high altitude was established. After bleeding, the MAP of the five groups was all maintained at 40mmHg, and their CVP decreased. Compared with group Ⅴ, there were no significance among every group. After shock, the survival time of group Ⅴ(138±55.03min), the shortest one, was significantly less than that of group Ⅳ(238.33±69.18 min). 2. The ideal FiO2 in the treatment of HAHS has been determined. GroupⅠ(80% FiO2+countershock) survived longer than any other group,with remarkablely decreased respiratory rate and slighter metabolic acidosis.The MAP, CVP and PaO2 of GroupⅠwere significantly higher than those of groups Ⅱ, Ⅲand Ⅳrespectively. 3. The safety of 80% FiO2 applied to animals rapidly exposed to high altitude was illustrated. On the spot of high altitude, after 80% FiO2 had been inhaling for 8 hours, the alveolars were dilated, and the alveolar cells were intac. With the time going on, pulmonary alveolus was obviously dilated, without edema of lung interstitial and pathologic changes of the alveolar cells. The changes of MDA and SOD were always parallel and coordinate. 4. The oxygen therapy of 80% FiO2 exerted a therapeutic effect on HAHS animals. (1) Compared with the control group, the MAP, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and the left ventricular maximal rates of pressure rising and dropping (±dp/dtmax) in the trial group increased significantly after 4 hours'or 8 hours'treatment, and the mean pulmonary artery pessure (mPAP) decreased significantly. (2) The PaO2, SaO2, HCO3 ?, PaCO2 of the trial group rose higher than those of the control group after treatment. While the lactate concentration in plasma was lower than that of the control. (3) The histologic damage of the small intestinal mucous membrane in the trial group was milder than that in the control, but the plasma LPS levels in the trial were significantlylower after treatment. The expression of TNF-a and IL-6 mRNA in the total white blood cells of the trial group were suppressed significantly in comparison with the control after treatment 4h, 8h respectively. (4) The survival rate after 8 hours'treatment was achieved by 7 of 7 in the trial group, by 3 of 8 in the control group. (5) After 8 hours'treatment, the pulmonary alveolus of the trial group was dilated without edema, and there were no proliferation or destruction of alveolar epithelium cells. There was no significant difference in the changes of MDA, SOD between the two groups. Conclusion: 1. In the simulated hypobaric chamber, according to Wiggers, the hemorrhagic shock model of animals rapidly exposed to high altitude was successfully established and proved to be credible and stable. 2. The oxygen therapy of 80% FiO2 was prior to those of 50% FiO2 and 30% FiO2 respectively in the treatment of HAHS, based on simple application of balanced saline. 3. On the spot of high altitude, continuous inhalation of 80% FiO2 for 8h, 3d and 5d was safe for animals rapidly exposed to high altitude. During the given time, oxygen toxicity was not found. 4. The oxygen therapy of 80% FiO2 could exert a therapeutic effect on the HAHS animals based on countershock. There were possibly three mechanisms as follows: (1) Oxygen therapy could promote the hemodynamics and restore cardiac function by increasing the oxygen supply to the myocardium, restoring its energy metabolism, which might enhance the myocardial contractile and diastolic performance. (2) Oxygen therapy could elevate the dissolved oxygen in blood and the oxygen delivery to tissue, so that the metabolic acidosis was delayed and tissue oxygenation was well improved. (3) Oxygen therapy could protect the gut barrier from badly injured, so as to reduce the translocation of LPS, and then systemic inflammatory response and multiple organ failure were relieved. 5. The oxygen therapy of 80% FiO2 might be feasible and practible, because there were no obviouse unwanted and poisonous effects within 8 hours'treatment in HAHS.