Penicillin encephalopathy
Penicillin encephalopathy is a rare central nervous system toxic reaction of penicillin, in which a large amount of the drug rapidly enters the brain tissue when the dose is too large and the drip rate is too fast, i.e. the concentration of the drug in the blood and cerebrospinal fluid increases, interfering with normal neurological function and causing a severe central nervous system reaction.
Penicillin encephalopathy is a kind of rare central nervous system toxic reaction of penicillin. Usually, only a small amount of penicillin passes the blood-brain barrier, but when the dose is too large and the IV rate is too fast, a large amount of drug rapidly enters the brain tissue, i.e. the concentration of the drug in the blood and cerebrospinal fluid increases and interferes with the normal neurological function causing severe central nervous system reactions, such as hyperreflexia, perceptual disorders, hallucinations, convulsions, lethargy, etc. It is called “Penicillin encephalopathy”.
Penicillin and other broad-spectrum penicillins, with prolonged half-life, due to diminished renal function in the elderly? For example, penicillin G sedation, half-life is 0.55 hours in 25-year-old youth, while in 70-year-old elderly half-life is 1.0 hours; procaine penicillin half-life is 10 hours in 25-year-old youth, and 18 hours in 70-year-old elderly; diclofenac penicillin half-life is 0.88 hours in less than 30-year-old youth, and in greater than 65-year-old elderly 3.97 hours; the half-life of hydroxybenzyl penicillin by sedation is 1 hour to 1.5 hours in young people and 2.67 hours in 89-year-olds. At the same time, because of the reduced production of plasma albumin in the elderly, only 3.7% in those over 75 years of age, the absorbed antibiotic in a bound state in the blood is correspondingly reduced, and its free fraction is elevated in the blood and tissues. When high doses of penicillin G and benzylpenicillin are applied to the elderly, neurological and psychiatric symptoms may occur, such as hyperreflexia, perceptual disturbances, hallucinations, convulsions, lethargy, etc. Temporary psychiatric disorders may also occur, which can easily lead to “penicillin encephalopathy”.
Due to the immaturity of blood-brain barrier function and renal function in pediatric patients, high dose of penicillin can increase the concentration of cerebrospinal fluid significantly and produce toxic effects on the center, leading to the occurrence of penicillin encephalopathy. In addition, one million penicillin G sodium contains 39mg of Na+ and one million penicillin G potassium contains 66mg of V1+, so attention should be paid to the retention of K+ and Na+ in the body when large amounts are injected. It is also easy to form “penicillin encephalopathy”.
When the systemic dose of penicillin, especially penicillin G, is too large or the intravenous drip is too fast, the concentration of penicillin in cerebrospinal fluid exceeds 8U/ml, which can directly stimulate the cerebral cortex and cause serious reactions such as spasms, convulsions, epilepsy and even coma. It usually appears within 24-72h after drug administration. It often occurs in newborns, children and the elderly because the drug easily crosses the blood-brain barrier. It is also likely to occur in patients with reduced renal function or renal failure due to impaired drug excretion.
Severe disease: The main manifestations are sudden onset of convulsions, dehydration, hypoxia, shortness of breath and blood chemistry changes (e.g. hypoglycemia, hyponatremia, acidemia), hypertension, rapid heart rate, hallucinations, convulsions, coma and respiratory failure based on the original disease. The mechanism of this reaction is unknown. Some children may also develop limb paralysis, bulging fontanelle in children with unclosed fontanelle, and a few children may develop motor incoordination. Most of the above symptoms appear 1 to 2 weeks after the original illness.
Longer periods of coma may leave serious sequelae. Sequelae may include dullness, blindness, deafness, and paralysis. A small number of patients may die from the severity of the disease.
Penicillin encephalopathy treatment
1.Discontinue penicillin If penicillin encephalopathy occurs, discontinue penicillin promptly.
2.Immediately inhale oxygen. In comatose patients, sputum should also be aspirated to keep the respiration unobstructed, and oxygen should be supplied in a timely manner and continue for a longer period of time to promote the decreasing of cerebral edema. If necessary, tracheotomy and artificial respiration should be performed.
3, anticonvulsant, use sedative, antipsychotic drugs luminal sodium, Valium, etc.
4.Adrenocorticotropic hormone. Such as hydrocortisone, prednisone, dexamethasone, all have rapid anti-inflammatory and anti-edema effect, should be used for a short period of time, generally not more than a week.
5, anti-cerebral edema drugs 20% mannitol intravenous push. For repeated cases of increased cranial pressure should be repeatedly applied to prevent brain herniation. At the same time, a rapid diuretic can be added to enhance the effect of dehydrating agents.
6.Strengthen dialysis and cooperate with blood perfusion, blood purification, etc.
7.Appropriate treatment for hyperthermia, dehydration, and blood chemistry changes (such as hypoglycemia, hyponatremia, acidemia) and respiratory failure.
8.Accelerate drug clearance, which can reduce mental symptoms.
9.Energy support treatment. Toxicity can be metabolized in a few hours and tens of hours, but the poisoned nerves are still out of paralysis and shock. If early treatment is not provided to activate and nourish the nerve excitation of paralysis and shock, the affected nerves will be difficult to recover due to prolonged ischemic pathological changes, which is called delayed neurological damage in medicine.
10, the majority of patients with this disease have a good prognosis, the symptoms disappear within 24 hours after appropriate treatment, no sequelae. If the coma lasts for several days to weeks, it may cause serious sequelae such as incomplete intelligence, blindness, deafness, limb ankylosis or paralysis in children. In a few cases, death may occur within a relatively short period of time due to respiratory failure.
Penicillin encephalopathy precautions
1. Among the side effects of penicillin, anaphylaxis is fatal and often draws attention, while the neurotoxic effects manifested as encephalopathy and peripheral nerve damage are easily ignored. It is important to dispel the previous notion that penicillin is rarely toxic as long as there is no allergy, never abuse penicillin (including other antibiotics) in large doses, and when it must be used, use intravenous infusion as little as possible, the elderly and children should be used with caution; in addition, it must also be noted that penicillin and ampicillin combined, more likely to cause the occurrence of penicillin encephalopathy.
2, penicillin is originally a highly effective and low toxicity antibiotic, in the history of human anti-infection has made a great success, the reputation has not diminished. It may be because of this that in recent years there has been a trend for penicillin to be used more and more widely and in increasing doses. There are a few health care workers who give patients a large amount of penicillin intravenously, especially intravenous infusion of more than 8 million units of dosage, and some even several times a day, and several days of continuous use of drugs. This not only leads to high concentration of penicillin in blood, but also makes the concentration of penicillin in cerebrospinal fluid also increase, when the concentration in cerebrospinal fluid > 8 units/ml, it will stimulate the brain nerve and then appear hyperreflexia, perceptual disorders, hallucinations, convulsions, coma and other symptoms of encephalopathy, but also can lead to transient mental disorders, especially the renal insufficiency, the elderly and children are more likely to induce this disease.
3, due to renal hypofunction and plasma albumin reduction, causing an increase in blood concentration and cerebrospinal fluid drug concentration, thus producing the cause of central nervous system toxic reactions. Therefore, when applying antibiotics in the elderly, the dose should be adjusted according to the renal function, in order to prevent the occurrence of “penicillin encephalopathy”, the dose of these drugs should not be too large, if the condition requires a large dose, it is appropriate to give the daily dose in three to four times. By the way, many antibiotics such as cephalosporins, vancomycin, tetracycline, nalidixic acid, etc. can be increased due to decreased renal function and increased serum concentrations, resulting in increased toxic side effects. Some drugs can be applied in reduced doses, and some are best used instead of other antibiotics.
4, can cause damage to the central nervous system of a wide range of antibiotics such as penicillin, cephalosporins, Tylenol, aminoglycosides, macrolides, chloramphenicol, polymyxin E, sulfonamide, quinolone, anti-TB drug isoniazid, antiviral drugs (acyclovir, ganciclovir) and other types of drugs can cause neurological damage to varying degrees, a variety of brain symptoms.