1.Concept
A syndrome caused by partial or complete hypoxia, reduced or suspended cerebral blood flow due to various causes, resulting in brain damage and a series of neuropsychiatric abnormalities, is called ischemic-hypoxic encephalopathy (HIE). In severe cases, it can cause permanent neurological impairment.
2.Etiology
There is no major difference between ischemic-hypoxic encephalopathy and hypoxic encephalopathy, the basic cause of which is hypoxia. It is mainly divided into.
(1) hypoxic hypoxia: characterized by a decrease in CaO2 and a decrease in PaO2. It is commonly seen in obstruction of the whistle tract, emphysema, drowning, whistle muscle paralysis, central inhibition of whistle, anesthesia accident, and altitude sickness.
(2) Anemic hypoxia: mainly seen in massive blood loss, anemia, carboxyhemoglobinemia (carbon monoxide poisoning), normohemoglobinemia (nicotinic acid poisoning, etc.).
(3) Circulatory disorder hypoxia (ischemic-hypoxic encephalopathy Ischemic-HypoxicEncephalopathy): commonly seen in shock, heart failure, cardiac arrest, etc.
(4) Tissue toxic hypoxia: caused by the disruption of cellular oxidation processes and the inability of brain tissue to utilize blood oxygen, commonly seen in oxidative toxicity, etc.
(5) Excessive oxygen consumption hypoxia: such as hyperthermia or convulsions, etc.
3.Pathogenesis
The brain is the most unbearable organ in the human body and is most sensitive to ischemia and hypoxia. Adult brain mass accounts for only 2% of body weight, but at rest it receives 15% of cardiac blood volume, and oxygen consumption accounts for 20% of total body oxygen consumption; there is basically no oxygen and nutrient substrate reserve in brain tissue, once cerebral blood flow stops, available oxygen reserve is depleted within 10s, and aerobic metabolism stops; 15s can fall into coma; 2-4 min anaerobic metabolism also stops, and ATP is no longer produced; 4-5 min ATP is depleted, and all energetic reactions stop; 4-4 min ATP is depleted, and all energetic reactions stop. All energy-demanding reactions stop; 4-6
After 4-6 min, irreversible damage to brain cells occurs.
(1) Cerebral blood flow changes: In hypoxia and hypercapnia, cerebrovascular autoregulation is impaired and “pressure passive cerebral blood flow” occurs.
(1) In mild or chronic hypoxia, the blood flow is redistributed to ensure the blood supply to the heart and brain.
(2) When the duration of hypoxia is prolonged, a second redistribution occurs to ensure adequate blood flow to the basal ganglia, brainstem, thalamus, and cerebellum. The parsagittal area of the cerebral cortex (the watershed area, the limbic zone of the anterior, middle and posterior cerebral arteries) and its subcutaneous white matter are ischemic.
(3) Severe hypoxia causes loss of vascular autoregulation and damage to the deep gray matter (basal ganglia area).
(2) Altered energy metabolism of brain cells: manifested by.
(1) Impaired oxidative metabolism: intracellular oxidative metabolism is impaired in hypoxia, which can only rely on glucose anaerobic enzymolysis to produce energy, while producing large amounts of lactic acid, leading to acidosis and cerebral edema.
②Calcium in-flow: Calcium pump activity is weakened in hypoxia, leading to calcium in-flow. When the intracellular calcium concentration is too high, enzymes regulated by calcium are activated, such as phospholipase, nuclease and protease, producing a series of neuronal cell damage and destructive effects.
③The role of oxygen free radicals: when hypoxia ischemia, ATP is degraded, adenosine is transformed into hypoxanthine, and oxygen free radicals are generated under the action of hypoxanthine oxidase. A large number of oxygen free radicals accumulate in the body, damaging cell membranes, proteins and nucleic acids, resulting in the destruction of cell structure and function, and the structure and integrity of the blood-brain barrier are damaged, forming vasogenic brain edema.
④Neurotoxic effects of excitatory amino acids: energy failure can lead to impaired sodium pump function, accumulation of extracellular potassium ions, continuous depolarization of cell membranes, and release of large amounts of excitatory amino acids (glutamate) from presynaptic neurons, which over-activates postsynaptic glutamate receptors, leading to a series of biochemical chain reactions and causing delayed neuronal death.
⑤ Delayed neuronal death: hypoxia and ischemia can cause two different types of cell death, i.e. necrosis and apoptosis. After hypoxia and ischemia, cell necrosis is caused by acute energy failure, and delayed neuronal death (i.e. apoptosis) occurs several hours later.
4.Clinical manifestations
Clinical manifestations are non-specific and can be manifested as follows
① Disorders of consciousness (excitement, drowsiness, lethargy).
② muscle tone: normal, reduced, flaccid.
(iii) seizures.
④pupillary changes: normal, dilated, narrowed, unequal in size, blunted or absent light reflex.
⑤ Course and prognosis: long duration of symptoms, poor prognosis, high death rate, and many survivors have sequelae. The specific mainly depends on the speed, degree and duration of hypoxia, and the common point is the extensive suppression of CNS function. Those with mild unconsciousness disorder show inattention, decreased judgment and motor incoordination; those with severe disorder show consciousness disorder, coma, vegetative state and brain death.
Three clinical stages of acute hypoxic encephalopathy.
(1) Acute coma phase: different manifestations according to the site and degree of involvement.
(1) Damage to the upper part of the brainstem: decerebrate syndrome: extensional ankylosis of the limbs, moderate dilatation of the pupils, and disappearance of the reflex to light.
(ii) simultaneous damage to the upper and lower brainstem: significant muscle relaxation in the limbs, loss of corneal reflexes, and irregular whistling. It usually lasts for 1~2 weeks, with 3~7 days being the most dangerous.
(2) Decortical state period: subcortical and brainstem functions recover first, while cortical functions remain in a suppressed state. There is no conscious activity, no speech, no language, no movement, no expression, incontinence of urine and feces, no response to whistle and touch pressure, no voluntary movement, and relying on manual feeding. The light reflex, corneal reflex and cough reflex existed. However, the patient often opens his eyes and stares, and most of his perceptions are lost, and he is unaware of his surroundings and himself. There may be unconscious crying and defensive reactions, increased muscle tone in the limbs, flexion and inversion of both upper limbs, and extension and internal rotation of both lower limbs in a de-corticalized tonic state. There is a distinct sleep-wake cycle. Some of them enter recovery period in 1~3 months, some become persistent vegetative state (more than 12 months for trauma, more than 3 months for others), and some die from complications.
(3) Recovery period: conscious activity gradually returns, speech reappears, and intelligence gradually improves. Some of them died from complications, and some of them left dementia, limb paralysis and other sequelae.
5.Imaging-assisted diagnosis of HIE methods
Head CT is sensitive to cerebral hemorrhage and can detect hydrocephalus. MR is the most sensitive imaging method for HIE and shows: diffuse edema in cerebral white matter (cytotoxic edema with vasogenic edema); intracranial hemorrhage; cerebral white matter softening; cerebral lobe cerebral infarction: chequered lesions with loss of gray and white boundaries.
6.Diagnosis
There is no sound diagnostic criteria, and we can refer to the diagnostic criteria of Pediatrics, mainly to exclude other diseases causing the etiology of ischemia and hypoxia.
7.Treatment
Treatment principle: etiological treatment is fundamental, the etiology leading to hypoxia should be rapidly lifted; further stopping the pathophysiology of hypoxia and maximum possible brain protection.
(1) Supportive treatment.
Oxygen administration: ensure PaO2>60-80mmHg, avoid PaO2 too high or PaCO2 too low. Hyperventilation to lower cranial pressure is one of the most common methods of cerebral resuscitation, but so far there is no evidence to support that hyperventilation improves prognosis.
Pay attention to maintaining cerebral and systemic blood perfusion to avoid over- or under-perfusion of the brain. Maintain blood glucose at normal levels.
(2) Control epilepsy treatment
(3) Treatment of cerebral edema: cerebral edema can form a few hours after cerebral hypoxia, peaks in 2-3 d, and begins to gradually subside after 5 d. Apply dehydrating agents as appropriate, and use mannitol, glycerol fructose, diuretics, albumin, etc. according to the situation.
(4) Subcritical treatment: animal experiments have shown that subcritical treatment can reduce neurological damage, and the earlier the start of cryotherapy, the longer the duration of reperfusion, the more pronounced and durable the cryoprotective effect. holzer
M et al. concluded in a meta-analysis of three randomized clinical trials on post-resuscitation hypothermia that subcold temperatures after SCA improve neurological prognosis without significant adverse effects.
In-hospital and out-of-hospital non-VF-induced SCA, as well as in patients who were unconscious but had satisfactory blood pressure after recovery of autonomic circulation. Induced hypothermia is generally not performed in patients with SCA due to drowning, hypothermia, and post-resuscitation hypothermia.
Methods: Intravenous application of hibernation combination; also through intravascular placement of cooling catheters, bladder injection of ice saline, application of ice blankets, ice bags, ice caps, etc., to rapidly reduce the patient’s body temperature to 32-34 ℃ for 12-24h.
(5) Brain protection: Calcium antagonists, glutathione, gangliosides, etc. can be applied. The Chinese medicines Chuanxiongzin and levotetrahydropalmatine have protective effects on cerebral ischemia-reperfusion injury and can be used.
(6) Glucocorticoids: At present, the routine application of corticosteroids is not advocated for brain resuscitation after total cerebral ischemia. In the past, it was thought that high-dose glucocorticoids could stabilize the activity of cell membrane and lysosome, improve the blood-brain crest fluid barrier and cerebral vascular permeability, and accelerate the dissipation of cerebral edema, so they were commonly used in brain resuscitation. However, a large number of controlled studies have found that traditional glucocorticoids do not improve the prognosis of cerebral resuscitation, and may aggravate cerebral ischemic damage by increasing blood glucose and increasing the release of excitatory amino acids.
(7) Hyperbaric oxygen therapy: It may be beneficial to improve the patient’s state of consciousness.