Patients in long-term coma are in a state of “unable to die, unable to live”, which brings serious economic burden and pressure to families. With the deepening of basic research and clinical work, some new understanding of patients in long-term coma has been achieved in recent years, and some new progress has been made in treatment, which has improved the level and quality of wake-promoting treatment. The following is a comprehensive introduction for reference. Principles of treatment】 1.Etiology treatment. Active etiological treatment is the first priority. Otherwise, it will aggravate the degree of coma and affect the patient’s awakening. 2, brain protective agent treatment. The nerve cells of patients in long-term coma will undergo pathophysiological changes such as brain metabolism disorder, ischemia and hypoxia, free radical damage, etc. Therefore, early and adequate use of neurotrophic drugs to protect brain nerve cells can prevent further damage to brain cells. 3. Keep the respiratory tract unobstructed to ensure oxygen supply. As the cough reflex and swallowing reflex of comatose patients become shallow or disappear, it is difficult to effectively discharge the secretions from the respiratory tract, which can easily lead to respiratory obstruction and aspiration pneumonia. In addition to strengthening the care of aspiration, tracheotomy should be performed in time if necessary to facilitate breathing, oxygenation and aspiration. 4. Prevention and control of infection. Comatose patients have low resistance and are prone to lung and urinary tract infections. Therefore, broad-spectrum antibiotics should be used to maximize the antibacterial effect and minimize toxicity; at the same time, immune-enhancing drug therapy should be added to improve the efficacy. 5. Prevention and control of hyperthermia. Patients with hypothalamic thermoregulation disorder or infection-induced hyperthermia have serious damage to the brain nerves and are detrimental to the recovery of consciousness, so physical cooling, drug cooling or a combination should be used. 6, prevention and control of epilepsy. Brain injury is very likely to trigger epilepsy, and epilepsy, especially grand mal seizures, can aggravate ischemia and hypoxia of nerve cells. Therefore, epilepsy should be prevented and treated as early as possible. However, anti-epileptic drugs have a central sedative effect, long-term use of a large number of patients will exacerbate the impairment of consciousness, so should use smaller doses and less impact on the impairment of consciousness drugs is better. 7, strengthen nutrition. The energy consumption of comatose patients is 140%-250% of normal people, sufficient nutritional support is the basic condition for recovery of comatose patients, and adequate amounts of multivitamins and trace elements should be given. 8. Prevention and control of complications. For example, strengthen regular turning and skin care to prevent pressure sores, use gastric mucosal protective agent to prevent stress gastric ulcers, and perform ventricular (or vertebral) – abdominal shunt to treat hydrocephalus, etc. Drug therapy to promote awakening】 At present, there are mainly catecholamine agonists, cholinergic agonists (including anticholinesterase inhibitors) and some other drugs. 1.Catecholamine agonists. Brain injury can cause the destruction of central dopamine neurons and their pathways, resulting in the reduction of dopamine synthesis and the blockage of catecholamine nerve impulse conduction. Catecholamine agonists reduce brain inhibition and elevate CNS excitability, cerebral perfusion pressure, and cerebral blood flow. The rationale is that levodopa such as methyldopa can be converted to dopamine and norepinephrine in the body to supplement the normal transmitters. Agonists such as Tysudar and bromocriptan act selectively on the postsynaptic membrane of dopamine receptors to enhance their sensitivity to dopamine and enhance the efficacy of dopamine. 2. Cholinergic agonists. Staphylin A (Haberin) is a highly effective and reversible cholinesterase inhibitor recently isolated from our Staphylinidae plant millipedium. Tacrine (whose metabolite is vinacrine) is another new reversible central cholinesterase inhibitor, which can enter the central nervous system after oral administration and has a long retention time. Both of these 2 drugs can be taken orally and have significant effects on improving cognition, memory and behavior. Cytarabine is a commonly used cholinergic agonist, which can be injected intravenously or intramuscularly in larger doses; it can enhance the function of the relevant reticular structures, and can also play an excitatory role on the pyramidal tract, so that the impaired motor function can be restored; it can also dilate the vascular bed and increase cerebral blood flow. 3.Naloxone hydrochloride (Kingeran). Its chemical structure is similar to morphine, and its affinity for opioid receptors is greater than morphine, and it can prevent morphine-like substances (endorphins) from binding to opioid receptors, so it becomes an opioid antidote. It can be injected intramuscularly or intravenously. 4.Other drugs. Such as nerve growth factor, ganglioside, cerebrofacial, brain activator, adenosine cobalamin, edaravone, ketamine, cloride awakening, cytochrome C, ATP, nimodipine, ginkgo biloba preparations, etc., have their positive effect on the prognosis of patients in long-term coma, but such drugs have been often used in the comprehensive treatment. Hyperbaric oxygen chamber treatment for waking up] is a treatment method of intermittent inhalation of 100% oxygen in a hyperbaric chamber with a pressure greater than 1 standard atmosphere. Clinical practice has confirmed that hyperbaric oxygen can: 1. correct cerebral hypoxia and maintain the energy supply of nerve cells. 2. 2. Reduce intracranial pressure and cerebral edema. 3.Improve cerebral microcirculation. 4, improve the function of brainstem reticular activation system, so it has the effect of promoting coma awakening. At present, it is believed that the earlier hyperbaric oxygen therapy is started, the better the effect. Ultraviolet irradiation and oxygen-filled autologous blood therapy to promote awakening] A therapy of drawing 200ml~400ml of venous blood from a patient at a time and giving it back to the patient immediately after 10 minutes of ultraviolet irradiation and oxygen-filled by a certain wavelength. Once a day or every other day, 10 times for a course of treatment. It can obviously increase the blood oxygen content, strengthen the body, promote the nerve and immune function, and play a supplementary role in promoting wakefulness. This therapy is faster, safer and cheaper than hyperbaric oxygen chamber treatment. Hydrogen injection therapy for wakefulness】 Through subcutaneous injection of high-purity (99.9999%) hydrogen 1oml1~2 times/day, or intravertebral canal injection once every other day, 10 days as a course of treatment. It has the obvious effect of scavenging free radicals and anti-infection, while playing an auxiliary role in promoting wakefulness. Electrical stimulation therapy for waking up】 Electrical stimulation includes spinal cord electrical stimulation, deep brain stimulation (commonly known as “brain pacemaker”), peripheral nerve stimulation (including median nerve stimulation, vagus nerve stimulation, etc.). At present, it is considered to be effective in promoting awakening of patients in long-term coma, and it is worth trying as long as the condition requires and allows. Acupuncture treatment to promote awakening] Once the condition is stable and the condition allows, the treatment can be given due consideration, and it is said to have an auxiliary effect on promoting awakening. Other treatments to promote awakening] such as: ① music therapy, ② passive movement therapy, ③ massage therapy, ④ visual, auditory, olfactory, taste stimulation therapy and ⑤ physical therapy (heat therapy, hydrotherapy), etc., are also commonly used as auxiliary therapy to promote awakening. Although there are many treatment methods for patients in long-term coma at home and abroad, so far there is no specific therapy that can clearly accelerate the recovery of consciousness and perception of patients in long-term coma. Therefore, it is not enough to rely solely on one kind of treatment for patients in long-term coma, and it is better to actively implement comprehensive treatment at an early stage. The individual variability in the efficacy of wakefulness promotion for patients in long-term coma is great and requires a certain amount of time to achieve the goal of turning a small victory into a big one. For this reason, it is important not to prematurely declare the promotion of wakefulness ineffective in the clinical consultation.