Paracetamol poisoning is an acute drug intoxication provoked by taking this drug at a dose exceeding the maximum permissible. The main symptoms include weakness, nausea, vomiting, drowsiness, tinnitus, abdominalgia, jaundice. Acute liver failure may develop. The diagnosis is made on the basis of data obtained as a result of a survey of the patient and his relatives, a toxicochemical examination of blood and urine, auxiliary methods for assessing the state of the body. The main directions of therapy: active detoxification, administration of antidotes, correction of emerging somatic disorders.
ICD 10
T39.1 Poisoning with 4-aminophenol derivatives
General information
Paracetamol poisoning is common among residents of Denmark, France, Great Britain, Norway. Today, the share of drug poisoning with antipyretic substances accounts for about 12% of the total number of hospitalizations. The risk group is children, people with reduced liver function, patients who prefer to avoid visiting a doctor and taking medications on their own, adolescents who are prone to suicidal attempts.
Causes
The most common mechanism of pathology is the deliberate use of the drug in a dose many times higher than the therapeutic one. This becomes possible in the following cases:
- Suicide attempts. Paracetamol poisoning as a way of voluntary retirement is usually chosen by teenagers, young women, and middle-aged men. In elderly people, para-aminophenol intoxication is rarely diagnosed.
- Self-medication. Symptoms occur when using more than 2 tablets (1000 mg) at a time or more than 8 tablets (4 grams) per day. Pathology also develops in patients who do not observe the minimum required interval between doses of the drug, which should be equal to four hours. Such exotoxicoses occur relatively easily and do not lead to serious consequences.
- Liver diseases. A decrease in the functional capabilities of the organ, which arose as a result of disease or treatment with inducers of liver enzymes, leads to a slowdown in the metabolism of paracetamol and its accumulation. When the medication is taken for more than 2-3 days, its concentration in the body becomes toxic (150-250 mcg / ml). If the signs of pathology were noticed in a timely manner, it does not go beyond a mild degree.
- An erroneous reception. Sometimes paracetamol poisoning occurs as a result of mistakenly drinking the drug. Elderly people and patients with mental disorders are able to confuse the drug with those medications that they take constantly. It is also necessary to take into account the risk of accidental ingestion of tablets by children if the drug is stored in the public domain.
Pathogenesis
The effect of paracetamol is predominantly hepatotoxic. The active metabolites of the drug form covalent bonds with hepatocyte proteins, which provokes the denaturation of the latter. In addition, there is a change in the structure of cell membranes due to lipid degradation. Areas of centrolobular necrosis are formed in the liver. Deterioration of the urinary and cardiovascular system develops indirectly due to hypovolemia, hemodynamic disorders, hypokalemia.
The defeat of the nervous system is associated with transformations in the activity of excretion devices. At the initial stage of the disease, asthenia and somnolence are noted. Hepatic encephalopathy may develop – a reversible violation of brain function caused by the accumulation of ammonia. The half-life of the drug increases in proportion to its amount in the body. The destruction of hepatocytes begins if the peak concentration of paracetamol is maintained for 4 hours. Its increase to 12 hours causes partial failure of neurotransmitter mechanisms.
Classification
Paracetamol poisoning is divided by the type of penetration of a toxic agent (oral, intravenous), for reasons (accidental, suicidal, iatrogenic), by severity (mild, moderate, severe, extremely severe), by the predominance of a particular syndrome (with predominant damage to the liver, kidneys, intestines). The classification according to the stage of pathology development is of the greatest clinical importance:
- Initial stage. It is not accompanied by symptoms or is manifested by moderate signs of damage to the central nervous system, intestines. Occurs 2-24 hours after taking the medication. If the amount of the drug consumed only slightly exceeds the permissible dosage, there is no further progression of pathology. The patient’s condition corresponds to a mild degree of exotoxicosis.
- Cytolytic hepatitis. The development period is 24-48 hours from the time of taking the toxic substance. It is manifested by signs of liver damage. It is more common against the background of chronic diseases of the hepatobiliary system, alcoholism. In order for such changes to occur in a healthy person, multiple exceeding of the recommended dose is required.
- Liver failure. It appears on the 3-6 day of the disease. There is a violation of excretory and metabolizing function, there is damage to the kidneys, heart and other body systems. Metabolic acidosis, electrolyte failures are formed. With an unfavorable course, the death of the patient occurs after 4-18 days.
Symptoms
Poisoning with paracetamol at the initial stage leads to the appearance of drowsiness, weakness, pain in the epigastric region and the projection of the intestine in the patient. Appetite is absent or sharply reduced. Complaints of nausea, vomiting, headache and other general toxic signs are presented. A specific symptom is tinnitus. The clinical picture is observed for 1-2 days, the intensity of manifestations in mild poisoning gradually decreases. Sometimes the patient reveals a residual decrease in hearing acuity, which is difficult to treat.
With the development of cytolytic hepatitis, the symptoms become more vivid. Abdominalgia increases, the pain is localized in the right hypochondrium. Nausea increases, vomiting occurs at intervals of 3-4 times per hour. The content of bilirubin, creatinine, AlAT, AsAT increases. During the examination, an increase in the size of the liver is detected due to its edema. Jaundice occurs in 65% of cases. Transformations are considered reversible. With a successful outcome, the functional state of the hepatobiliary apparatus is fully restored in a few weeks.
Liver failure is the cause of a sharp deterioration of the condition. The phenomena of encephalopathy are almost always noted. The patient is inadequate, there is psychomotor agitation or sopor. Coagulopathy develops, which is accompanied by the appearance of hemorrhagic rash on the skin, internal bleeding. Blood pressure decreases, arrhythmias occur. Body temperature is below normal. The skin is pale or marbled. Vomiting persists, severe pain syndrome.
Complications
Poisoning with paracetamol in 15-17% of cases leads to the formation of a hepatic coma. After leaving it, the victim may have some cognitive impairments for life. 5-10% of patients with severe poisoning are exposed to the development of shock conditions that sharply worsen the prognosis. Internal bleeding associated with a weakening of the blood clotting ability occurs in 7-8% of people. At the same time, both the course of the underlying disease and the dysfunction of the organ where the hemorrhage occurred are aggravated.
Another possible complication is kidney failure (PN). The frequency of its development does not exceed 1-2% of the total number of hospitalized patients. Kidney damage is a negative prognostic factor that significantly complicates the course of the disease. Complete restoration of the urinary system occurs in no more than 83% of cases, even against the background of ongoing treatment. People with chronic PN need lifelong hemodialysis.
Diagnostics
The primary diagnosis is made by the doctor of the ambulance team that arrived at the scene. It is based on information received from the patient’s relatives, the patient himself, as well as as a result of an analysis of the environment (blisters from pills, suicide notes). Finally, the type of poisoning is determined by toxicologists of a specialized center or resuscitators of a multidisciplinary clinic where the victim was taken. Additionally, a consultation with a psychiatrist, a hepatologist is required. Survey methods:
- Physical. Mental depression is noted, the patient is depressed, drowsy. With the development of encephalopathy – psychomotor agitation. Blood pressure is reduced by 10-30 units relative to the usual indicators, the pulse is faster. There may be a yellow coloration of the skin, the whites of the eyes. With severe intoxication, the skin is pale, the pressure is sharply reduced, with respiratory disorders, diffuse cyanosis is present.
- Laboratory. The results of the toxicochemical study determine the presence of paracetamol. Concentrations of 10-500 mg/l are of clinical significance. Blood test allows to detect an increase in the activity of hepatic transaminases (AlAT above 30 IU/ l, AsAT above 40 IU/ l). There are some electrolyte disturbances, pH shift below 7.3, and a decrease in the amount of total protein.
- Hardware. They are required only for severe poisoning. Imaging methods (ultrasound, MRI of the liver) allow to identify areas of necrosis in the area of large heptral veins, the impregnation of surrounding tissues with blood. Massive collagen degradation zones and inflammatory infiltrates can be detected. In almost all cases, there is fatty degeneration of the affected organ.
A lesion with the described symptoms occurs not only in poisoning with para-aminophenols. Therefore, the patient is shown mandatory differential diagnosis with intoxication with salicylates, dichloroethane, carbon tetrachloride, pale toadstool and other hepatotoxic substances. Suspicion of viral hepatitis B occurs if a person has recently undergone a blood transfusion or had sexual contact with a carrier of the infection.
Treatment
Paracetamol poisoning, regardless of the severity, requires hospitalization of the patient. People with signs of cytolytic hepatitis or liver failure are placed in the ICU. The initial stage of intoxication can be eliminated in the conditions of the hospital department. In any case, the patient is shown careful monitoring of the condition, dynamic monitoring of the indicators of biochemical activity of the liver.
First aid
The basis of first aid at the prehospital stage is gastric lavage. During the first hour after taking the pills, it can be implemented by a non-probe method. To do this, the victim must drink up to 1 liter of water, then induce vomiting. The manipulation is repeated 4-6 times, until a clean washing liquid is obtained. If more than an hour has passed since the use of the toxicant, a probe method is used. After the procedure is completed, 80-100 grams of crushed activated carbon in the form of an aqueous suspension is injected into the stomach.
The antidote of paracetamol is acetylcysteine. The drug should be administered intravenously, since its oral use simultaneously with the sorbent significantly reduces the effectiveness of therapy. The dose of the drug is 150 mg / kg of weight in a 5% glucose solution. ACC plays the role of a donor of SH-groups, which ensures the synthesis of glutathione and reduces the damaging effect of hepatotoxic metabolites. Against the background of its use, the rate of excretion of the toxic substance is doubled.
Planned treatment
In general departments, the technique of forced diuresis is used to accelerate the elimination of paracetamol. To create a liquid load, saline infusion solutions in the amount of 2-5 liters / day are used. After that, the person receives loop diuretics. The treatment started at the pre-hospital stage is also continuing. The patient is given activated charcoal 1 tablet per 10 kg of weight 1 time per day, AСC 140 mg / kg every 4 hours. The intake of sorbents and antidote should be spaced by time so that the interval between them is at least 2 hours. The total duration of the course of antidote therapy is 72 hours.
Resuscitation allowance
Extracorporeal detoxification (hemodialysis) can be performed in intensive care units. Forced diuresis is carried out with an increased water load, which reaches 10-12 liters / day. The dose of diuretics is 80-100 mg. Strict control of the liquid balance is shown. Another way to remove the drug is intestinal lavage. The essence of the technique is the introduction of 5-7 liters of saline enteral solution into the stomach, which leads to a complete cleansing of the intestines in a natural way.
Symptomatic therapy is indicated. Patients with respiratory insufficiency are transferred to artificial respiratory support, in case of hemodynamic disorders they receive inotropic agents. Psychomotor agitation requires the use of sedatives. Essential phospholipids are injected to maintain liver function. Antispasmodics, vitamins, glucocorticosteroids, antiemetics are prescribed. Parenteral nutrition, solutions of amino acids, lipids. The need for carbohydrates is met by intravenous infusion of dextrose.
Prognosis and prevention
Mild to moderate paracetamol poisoning has a life-friendly prognosis. With the early onset of antidote and antitoxic therapy, complete or almost complete restoration of impaired functions can be achieved in 90% of cases. Severe intoxication is often accompanied by acute hepatic or multiple organ failure, which reduces the likelihood of convalescence. Approximately 30% of patients recover without consequences, with moderate residual changes – 55%. The mortality rate according to various data is 15-25%.
Prevention of drug poisoning consists in strict adherence to dosages, refusal of self-medication, seeking medical help for diseases requiring nonsteroidal anti-inflammatory drugs. At home, drugs should be stored inside factory packages, outside the access zone of children, the elderly with signs of age-related decline in intelligence, people suffering from mental disorders and suicidal. Taking into account the possibility of medical errors, it is recommended to compare the prescribed doses of medicines with the maximum permissible ones indicated in the official annotation.