Postoperative delirium refers to the delirium of patients after surgical operation. Its main characteristics are the disorder of consciousness level and cognitive dysfunction. The condition fluctuates greatly and the course of disease is relatively short. Dexmedetomidine (DEX) is a new type of sedative and hypnotic drug, which has the effects of inhibiting sympathetic nerve, sedation, moderate analgesia, reducing anesthetic dosage, and reducing postoperative delirium.

In recent years, dexmedetomidine is increasingly used in the prevention and treatment of postoperative delirium (POD) in elderly patients. This article summarized the pharmacological characteristics of dexmedetomidine and its application in postoperative delirium in elderly patients. Delirium is a common complication after major surgery. According to the literature, the incidence of postoperative delirium in elderly patients over 65 years old is as high as 54.4%, which is significantly higher than serious postoperative complications such as myocardial infarction and respiratory failure.

Postoperative delirium can cause a series of adverse effects on patients, including prolonged stay in ICU, increased hospitalization costs, increased perioperative complications, and long-term decline in cognitive function. Dextrmedetomidine is highly selective α 2 Receptor agonists can act on the central and peripheral nervous systems respectively, playing a good role in anti anxiety, sedation, hypnosis, moderate analgesia, etc. They are widely used in clinical practice as sedative adjuvants for tracheal intubation, maintenance of anesthesia and mechanical ventilation of ICU patients.

A large number of literatures have confirmed that dexmedetomidine has anti-inflammatory and neuroprotective effects, which can effectively reduce cerebral ischemia reperfusion injury and reduce the occurrence of postoperative delirium. A recent study showed that in a placebo-controlled study of dexmedetomidine and normal saline, the use of dexmedetomidine can reduce the incidence of postoperative delirium in elderly patients undergoing major non cardiac surgery by 50% compared with the control group. This article summarized a series of current related data, summarized the pharmacological characteristics of dexmedetomidine hydrochloride and its application in postoperative delirium of elderly patients, with a view to giving more comprehensive guidance in clinical work.

1. Postoperative delirium

Postoperative delirium is the brain function damage caused by many factors. The elderly, preoperative cognitive function damage, combined with other diseases, and traumatic stress can increase the incidence of postoperative delirium. The main manifestations of postoperative delirium are disturbance of consciousness level, attention disorder and cognitive impairment. Its clinical manifestation has two obvious characteristics, namely, acute onset and fluctuating course. Acute onset refers to the sudden occurrence of symptoms within hours or days.

Disease fluctuation refers to that the symptoms often appear, disappear, worsen or reduce within 24 hours, have obvious fluctuation, and have an intermediate lucid period. The incidence of postoperative delirium in elderly patients is very high, but clinical studies show that 40% of postoperative delirium can be prevented. For patients with postoperative delirium, the principle of early discovery and early treatment should be adhered to, so as to minimize the severity of delirium and shorten the duration of delirium. At present, there is no definite conclusion on the pathogenesis of delirium. There are inflammatory reaction theory, stress response theory, biological rhythm theory and cholinergic theory that are widely studied and recognized by the public.

2. Pharmacological characteristics of dexmedetomidine

Dextrmedetomidine, chemically named 4 - [(1S) - 1 - (2,3-dimethylphenyl) ethyl] - 1H-imidazole, is the dextral enantiomer of medetomidine and a high choice commonly used in clinical practice α Adrenaline receptor agonist, with anti anxiety, sedative, hypnotic and analgesic effects.

2.1 Effect on central nervous system: the sedative and hypnotic effect of dexmedetomidine is shown as the effect of dexmedetomidine on the locus coeruleus of the brain stem α Receptors produce physiological sleep like responses. The analgesic effect of dexmedetomidine is achieved by acting on the locus coeruleus nucleus, spinal cord and peripheral organs α 2 receptors.

A study in brain tumor surgery showed that the sedative and analgesic effects of dexmedetomidine can reduce the cerebral metabolic rate and cerebral blood flow of patients with brain tumors, reduce the intracranial pressure of patients, help to remove the catheter early after surgery, and also reduce the use of anesthetic drugs and opioids. Dextrmedetomidine has some neuroprotective effects on brain nerves in addition to its conventional sedative, hypnotic, anti anxiety and analgesic effects (the mechanism of Dextrmedetomidine's neuroprotective effects will be described in detail below).

2.2 Effect on the respiratory system: Dextrmedetomidine has a slight effect on the respiratory system while playing a sedative and hypnotic role. This sedative hypnosis is similar to physiological sleep, and the changes in ventilation are similar to normal sleep, so respiratory depression is less likely to occur. In a test comparing remifentanil and dexmedetomidine in vivo, the plasma concentration of dexmedetomidine reached 2.4 μ G/L, the inhibitory effect of dexmedetomidine on respiration was still not observed. However, dexmedetomidine can cause airway obstruction by relaxing the tension of pharyngeal muscles. Close observation is still needed in clinical medication to avoid adverse events.

2.3 Effect on cardiovascular system: The effect of dexmedetomidine on cardiovascular system is mainly manifested in slowing down heart rate and decreasing systemic vascular resistance, which leads to decreased cardiac output and hypotension. The effect of dexmedetomidine on blood pressure can be shown as a two-way effect, that is, low concentration of dexmedetomidine can reduce blood pressure, while high concentration of dexmedetomidine can increase hypertension.

The most common adverse reaction of dexmedetomidine is the occurrence of adverse events of cardiovascular system, mainly including hypotension and bradycardia. The main reason is that dexmedetomidine excites the heart α 2 receptor, which inhibits sympathetic nerve and causes reflex bradycardia and hypotension. For the adverse events such as hypotension and bradycardia caused by dexmedetomidine, the treatment methods mainly include slowing down the drug infusion rate or stopping the drug infusion, speeding up fluid infusion, raising the lower limbs, and using vasopressor drugs (such as atropine, gluonium bromide). In addition, the study found that dexmedetomidine also has a certain protective effect on ischemic myocardium after coronary blood flow occlusion.

3. Application and deficiency of traditional drugs in postoperative delirium of elderly patients

3.1 Antipsychotic drugs: Early studies have found that low-dose haloperidol can reduce the incidence of postoperative delirium in elderly patients in ICU. With the development of diagnostic techniques and multicenter and large sample studies, the research results in recent years tend that haloperidol cannot reduce the incidence of delirium in severe elderly patients, nor can it improve the short-term survival rate of elderly patients with postoperative delirium. Haloperidol has adverse reactions of central nervous system and cardiovascular system in use, such as extravertebral system reaction, prolonged QT interval, arrhythmia, hypotension, etc., so it is not recommended to use this drug as a routine drug to prevent delirium.

3.2 Cholinesterase inhibitors: Although many studies have shown that cholinergic deficiency is related to delirium, many studies have shown that cholinesterase inhibitors have no effect on preventing postoperative delirium in elderly patients. At present, it is not advocated to use cholinesterase inhibitors in clinical work to prevent and treat postoperative delirium in elderly patients.

3.3 Benzenediazepines: This drug can be used for delirium caused by alcohol withdrawal or benzodiazepines withdrawal, and it can increase the risk of delirium for general delirium patients or high-risk delirium patients who are not alcohol withdrawal or benzodiazepines withdrawal. Therefore, it is not recommended to use such drugs for the routine treatment of delirium.

4. Application and advantages of dexmedetomidine in postoperative delirium of elderly patients

4.1 Brain nerve protection: As a new type of sedative and hypnotic drug, dexmedetomidine is used more and more widely in clinical practice. Hoffman et al. found for the first time in animal experiments that dexmedetomidine has neuroprotective effects on brain nerves, which can be α Reversal of 2-adrenergic antagonist atemizole. Su et al. found in a randomized double-blind placebo-controlled trial that the prophylactic use of low dose dexmedetomidine (0-1 per hour μ G/kg) can effectively reduce the incidence of delirium in elderly ICU patients 7 days after surgery.

Carrasco et al found that, compared with haloperidol, dexmedetomidine can shorten the stay time of patients in the ICU with non mechanical ventilation and reduce the incidence of delirium. At present, there are many studies on the protective mechanism of dexmedetomidine on brain nerves. A large number of literatures have confirmed that dexmedetomidine mainly plays a neuroprotective role in brain nerves by inhibiting sympathetic nerve activity, reducing catecholamine concentration, inhibiting glutamate release, regulating cell apoptosis and other mechanisms.

4.1.1 Inhibition of sympathetic nerve activity: reduce the concentration of catecholamine: dexmedetomidine can not only inhibit the activity of sympathetic nervous system, but also directly act on the cell bodies and dendrites of monoamine neurons in the brain α 2 receptor, reducing catecholamine release of norepinephrine nerve endings. Dextrmedetomidine can reduce the release of inflammatory factors and cytokines in endotoxin induced shock rats by inhibiting the sympathetic nervous system and reducing the stress response in vivo. Dextrmedetomidine can alleviate the vasospasm caused by subarachnoid hemorrhage in rabbits by inhibiting the release of catecholamine in brain tissue, and has a protective effect on brain injury.

4.1.2 Balanced calcium ion concentration: inhibit the release of glutamate: ischemia and hypoxia will cause the release of excitatory amino acids (such as glutamate) in the brain. High concentration of glutamate will cause excessive excitation of N-methyl-D-aspartate receptor in neurons, make calcium ions flow in, activate calcium dependent proteases, cause cytoskeleton destruction, and produce free radical damage. Dextrmedetomidine can activate the α 2-AR, inhibit N-type voltage gated calcium channel, directly inhibit calcium influx; At the same time, it can also open the outward potassium channel, depolarize the presynaptic membrane, and indirectly inhibit the inward flow of calcium ions, thus inhibiting the release of glutamate.

4.1.3 Regulation of cell apoptosis: cell apoptosis is a multi gene controlled multi cell biological programmed active death, and its process mainly involves caspase-1, caspase-3, etc. An in vitro experiment showed that dexmedetomidine could inhibit the expression of caspase-3, prevent its influence on long-term neurocognitive function, and alleviate the reperfusion injury of lung ischemia in rats.

4.2 Reduce the amount of narcotic drugs: Dextrmedetomidine is often used as an auxiliary anesthetic in clinical practice, which has a synergistic effect with inhalation anesthetics, propofol, midazolam and opioids, and can reduce the amount of other narcotic drugs when used together. It is reported in the literature that inhalation anesthetics such as sevoflurane and isoflurane can increase the permeability of blood brain barrier (BBB), thereby promoting the occurrence and progress of postoperative delirium.

Dextrmedetomidine activates the central nervous system α 2 receptor, which can improve the hyperfunction of the hypothalamic pituitary adrenal axis (HPA), weaken the stress response, and reduce the damage to the sensorimotor system after sevoflurane anesthesia.

4.3 Maintaining the stability of hemodynamics: In elderly patients, especially those with hypertension, coronary heart disease and other diseases, attention should be paid to maintaining the stability of hemodynamics during operation to avoid sharp fluctuations of blood pressure. During craniotomy, strong pain stimulation can activate the sympathetic nervous system, causing a significant increase in blood pressure and intracranial pressure. Sanders and other researchers have shown that the administration of dexmedetomidine to general anesthesia patients undergoing intracranial tumor resection can reduce the violent fluctuations in hemodynamics during operations such as skull sawing and scalp peeling, and can also reduce the amount of antihypertensive drugs.

5. Recommended method and dosage of dexmedetomidine for postoperative delirium in elderly patients

Both studies on intraoperative auxiliary sedation and postoperative ICU sedation with dexmedetomidine have proved that it can reduce the incidence of postoperative delirium in elderly patients and shorten the duration of postoperative delirium. The European Union has approved that dexmedetomidine can be used for sedation in adult patients. The most common adverse reaction of dexmedetomidine infusion is the occurrence of cardiovascular adverse events, mainly including hypotension and bradycardia. During clinical use, it is also necessary to pay close attention to the occurrence of hypotension and bradycardia. Although the incidence of such situations is low in clinical practice, attention should be paid to and prevention should be taken to avoid inducing cardiac arrest. The renal function of the elderly is often reduced. When using dexamethasone which is mainly excreted by the kidney, it is necessary to consider the slow injection load (load 0.5 μ G/kg, infusion for more than 10min) or without load.