Traumatic cerebral edema and elevated intracranial pressure are common complications in craniocerebral injuries caused by various reasons, and are also important causes of death in patients with craniocerebral injuries.HTS (Hypertonic Saline) refers to sodium chloride solution with a concentration of more than 0.9%, i.e., hypertonic saline, animal experiments and human experiments have suggested that HTS has its own unique role in the treatment of craniocerebral injuries caused by various reasons. Now we would like to make a review on the research progress of HTS in craniocerebral injury. In the past 30 years, osmotic therapy has been used as a basic treatment for cerebral edema and intracranial hypertension secondary to craniocerebral injury. The mechanism of osmotic agents in the treatment of traumatic cerebral edema and intracranial hypertension is to cause an effective osmotic gradient between plasma and brain tissue and between plasma and cerebrospinal fluid, so that the water of brain tissue and cerebrospinal fluid can enter into the bloodstream, thus reducing cerebral edema and intracranial pressure. It has been proved in animal experiments that osmotic agent can make normal brain tissue dehydrated, but it can’t play an obvious role in the brain edema area where the blood-brain barrier is damaged. 2, commonly used osmotic agents have been used in the treatment of traumatic brain edema and increased intracranial pressure osmotic agents are urea, glycerol, sorbitol, mannitol, and recently reintroduced HTS. urea, glycerol, sorbitol has serious side effects. Mannitol has been used as an effective intracranial pressure-lowering drug in the treatment of traumatic cerebral edema for a long time since it was applied to neurology clinics by Wise et al. in 1963, and it has obvious effects both in dehydration and brain tissue protection. However, with the wide application of mannitol in clinics, its various adverse effects on the organism have also received more and more attention, and its side effects include renal failure, hypovolemic Hypotension, ICP rebound, etc. In recent years, HTS has attracted wide attention from scholars because of its fast onset, obvious effect and long-lasting effect. 3, the mechanism of HTS in the treatment of craniocerebral injury Clinical experiments have reported that the concentration of HTS used ranges from 1.6% to 30%, and the role of HTS in craniocerebral injury may have the following mechanisms. 3.1 Osmotic effect HTS can increase the intravascular osmotic concentration so as to counteract the abnormally high extravascular osmotic concentration, thus absorbing the water between brain tissues, reducing the edema of brain tissues, and reducing the generation of cerebrospinal fluid. 3.2 Improvement of brain tissue perfusion (1) HTS increases MAP; (2) HIS improves brain microcirculation. 3.3 Regulate neurochemicals (1) inhibit the toxic effect of glutamate and reduce intracellular Ca2+ hyper; (2) reduce serum AVP. 3.4 Inhibit immune-monoinflammatory response (1) maintain the balance of T lymphocytes; (2) inhibit the activation of polymorphonuclear neutrophil (PNM); (3) reduce inflammatory reaction. 4, HTS application history and current situation In 1919, Weed and Mckibben first described the beneficial effects of intravenous infusion of HTS on the brain after brain injury, and since then it has attracted people’s attention to its clinical application.In the early 1980s, HTS was mainly used for the treatment of hemorrhagic shock; it was found that volume resuscitation with HTS could significantly improve the circulatory physiological indexes of patients with severe blood loss, and the blood loss of patients with severe blood loss was also improved by the use of HTS, and the blood loss of patients with severe blood loss was also improved by the use of HTS. In 1988, Worthley et al. reported that HTS was used in the treatment of 2 patients with refractory intracranial hypertension and achieved good results; in the experiment, after rapid infusion of 30% HTS, the patient’s elevated intracranial pressure was significantly reduced, and at the same time, the cerebral perfusion was significantly improved. In recent years, a large number of experiments have shown that HTS can play a protective role against brain injury by reducing intracranial pressure and preventing and reducing the occurrence of cerebral edema. Although it has been widely recognized that HTS can control intracranial pressure, more clinical trials are needed to fully understand it before a decision can be made to recommend it for routine clinical use, and the small clinical sample data available for HTS limits clinical dissemination, with the lack of a control population to some extent as well as the fact that many of the findings are case studies or small prospective studies. According to Cooper et al. in a recent study, HTS for prehospital treatment of patients with craniocerebral injuries was not substantially different from placebo; therefore, clinicians need to be cautious when applying HTS. 5.Research results of HTS in animal experiments A large number of animal experiments have shown that HTS can play a significant osmotic therapeutic role in a variety of brain injury models, and a large amount of experimental data obtained have supported its application in brain injury. The areas of research include the effects of HTS on brain water content, ICP, CPP, MAP, CBF and brain oxygen content. In recent years, the resuscitation of severe hemorrhagic shock with small volumes of HTS and its complexes has been demonstrated in experimental studies. In animal experiments, many scholars have found that HTS complexes have the effect of increasing CPP, CBF decreasing ICP and thus maintaining hemodynamic stability when resuscitating hemorrhagic shock with or without craniocerebral injury. Compared with mannitol, under isotonic concentration, the effect of HTS lasts longer and stronger. 6.Results of HTS in clinical trials Based on the osmotic therapeutic effects of HTS in various animal brain injury models, a series of clinical trials have been conducted, and the results have confirmed the protective effects of HTS in the treatment of cerebral edema, the lowering of intracranial pressure, and in other forms of brain injury. There are data suggesting that HTS may have use in the treatment of refractory intracranial hypertension. There are also preliminary pediatric data suggesting that HTS has a role as an osmotic therapy and may be used as an alternative to mannitol.HTS has been shown to reduce increased intracranial pressure caused by non-traumatic brain edema, such as SAH, acute liver failure and stroke. 7, the side effects of HTS (1) renal failure: Huang et al. in burn patients applying HTS for resuscitation found that its damage to renal function is significantly increased compared with Ringer’s solution, but there is no corresponding report in other animal experiments and clinical experiments. (2) Osmotic demyelination syndrome (ODS): acute demyelinating lesions are generally seen in animal models of craniocerebral injury or in clinical practice during sodium supplementation for the treatment of chronic diseases. The pontine brain is more sensitive to hypertonic states, and it is possible that acute demyelination syndromes may occur during treatment with HTS. However, its occurrence can be avoided as long as the daily increase in blood Na does not exceed 1O-20 mmol/L. Khanna et al. treated neurologic disorders with hypertonic saline with a mean peak blood Na of 170 mmol/L, but no acute demyelinating lesions occurred in 1 case. (3) ICP rebound: ICP rebound has been reported in mannitol use, but there is no convincing evidence in HTS use. (4) Systemic complications: coagulation disorders, dilatation with HTS may lead to hemodilution and coagulation disorders, but there is no inevitable connection between the two in a large number of animal experiments and clinical trials; hemolysis, HTS may lead to hemolysis caused by erythrocyte crumpling. (5) Electrolyte and acid-base balance disorders: the application of HTS may lead to hypernatremia, hypokalemia and hyperchloremia. 8.Comparison of HTS and mannitol HTS has faster onset of action than mannitol, more lasting effect, comparable effectiveness, and diuretic effect is weak, not easy to crystallize, the advantages are: (1) HTS in the pre-hospital emergency, the dosage is smaller, more practical and effective; (2) Mannitol can cause acute renal failure, potassium reduction, hypotension, and ICP rebound, and HTS according to the current study without these side effects (3) When plasma osmolality exceeds 320mOsm/L, due to the increase of side effects, it limits the application of mannitol in craniocerebral injuries; (4) For some high intracranial pressure that cannot be controlled by mannitol, HTS can also be effective; (5) And in recent years, it is found that there is a general low-sodium state after craniocerebral injuries, and HTS has a function of elevating the blood sodium. 9.The reason of low blood Na in craniocerebral injury (1) After craniocerebral injury, high intracranial pressure, applying dehydrating agent to reduce cranial pressure (such as 20% mannitol, furosemide), and limiting salt and fluid replenishment, if applying for a long period of time, there may be low blood Na. (2) Craniocerebral injury directly or indirectly affects the function of the hypothalamus and the occurrence of excessive secretion of antidiuretic hormone (ADH), the imbalance of the balance of ADH/ACTH, and the emergence of the The syndrome of inappropriate secretion of antidiuretic hormone (SIADH), i.e., low blood Na (<130 mmol/L), low blood osmolality (<270 mOsmkg-1H2O-1), and high urinary Na (>780 mmol/24h urine). This cause of low blood Na should theoretically occur early after injury, but because of the effects of early application of high doses of dehydrating agents, laboratory tests for blood Na are often normal. Another study showed that the lower thalamus and other places of neural tissue cells can produce atrial natriuretic peptide (ANP), ANP mainly through the inhibition of Na reabsorption in the collecting ducts up to the diuretic, diuretic effect of sodium, excessive secretion of ANP can be made to increase the urinary Na by 30 times, the urine volume increased by 10 times, this kind of low blood Na is also known as cerebral salt-wasting syndrome. This cause of low blood Na is often combined with central dysuria, and this low blood Na is not easy to correct quickly. (3) Post-injury vomiting, poor appetite and low salt intake. 10, the impact of low blood Na on craniocerebral injury Decrease in blood Na concentration, extracellular fluid hypotonic, water from the extracellular to intracellular transfer, resulting in intracellular edema, and the brain tissue, that is, brain cell edema, increased intracranial pressure, and craniocerebral injuries, the most common, the most serious secondary injuries is cerebral edema, if the combination of low blood Na, cerebral edema aggravation, resulting in aggravation of the condition. The difference between the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), cerebral salt-wasting syndrome (CSWS) and other types of hyponatremia in terms of recovery time and cure rate is not statistically significant, and the prognosis has a close relationship with the severity of the disease, the more severe the disease is, i.e., the lower the score on the Glasgow Coma Scale (Glassgow Comascale (GCS)) is, the higher the incidence of hyponatremia is The more severe the hyponatremia, the higher the mortality rate. 11, the basis for the use of HTS after craniocerebral trauma For many years, maintaining a normal or slightly higher serum Na concentration has been shown to be beneficial to patients with craniocerebral injury. At present, most scholars agree with the view that the use of dehydrating agents in conjunction with the treatment of traumatic brain injury should not emphasize the restriction of sodium intake, but should supplement electrolytes to ensure that the blood pressure and cerebral perfusion pressure is within the normal range, to prevent secondary cerebral damage caused by cerebral ischemia and hypoxia. According to the pharmacological properties and mechanism of action of HTS, the basis for its routine use in clinical practice has been laid. Some scholars may worry that the clinical use of HTS may cause hypernatremia, resulting in electrolyte disorders and other adverse reactions. Some scholars believe that as long as people strengthen the monitoring of electrolytes in clinical use, and eliminate the effect of high blood sodium on the function of the body in time, the best therapeutic effect will be achieved. However, how to use the best way to apply the best concentration and dose of HTS for the treatment of cerebral edema and intracranial hypertension caused by craniocerebral injury to avoid the occurrence of its side effects needs to be further studied. 12. Summary: A large number of animal experiments and clinical studies have confirmed that HTS is effective in neurosurgical clinical practice. It can increase mean arterial pressure (mean arterial pressure, MAP), improve microcirculation, increase cerebral tissue perfusion, improve oxygen supply, reduce cerebral edema, HTS can inhibit the toxic effect of glutamate, reduce intracellular Ca2+ overload, reduce serum arginine vasopressin (arginine vasopressin, AVP) and inhibit immune response to reduce brain injury. An inflammatory response attenuates brain damage. Currently, the concentration of HTS used in animal experiments and clinical studies ranges from 1.6% to 30%, due to different study designs, administration methods (continuous intravenous infusion, repeated intravenous infusion, one-time intravenous infusion), and dosages (1.4-4 ml ?????? The available data on small clinical samples of HTS limit clinical dissemination, and to some extent there is a lack of control populations as well as many of the study results are case studies or small prospective studies, which still require a large number of animal experiments and clinical studies with large number of cases to clarify the optimal HTS drug concentration, mode of administration, and dosage, in order to guide the effective application of HTS in the clinic. The results of these studies are summarized in the following table.