Poisoning with paracetamol can cause gastroenteritis within hours and work 1-3 days after taking hepatotoxic. The severity of liver damage after a single acute overdose can be predicted based on the serum concentration of Paracetalmol. Treatment with N-acetylcysteine ??to prevent hepatotoxicity or minimized.
Acetaminophen is contained in> 100 counter products, including many preparations for children in liquid, tablet or capsule form, many preparations for coughs and colds. Also, some prescription drugs containing acetaminophen. Therefore, the overdose of paracetamol is common.
Poisoning with paracetamol can cause gastroenteritis within hours and work 1-3 days after taking hepatotoxic. The severity of liver damage after a single acute overdose can be predicted based on the serum concentration of Paracetalmol. Treatment with N-acetylcysteine ??to prevent hepatotoxicity or minimized. Acetaminophen is contained in> 100 counter products, including many preparations for children in liquid, tablet or capsule form, many preparations for coughs and colds. Also, some prescription drugs containing acetaminophen. Therefore, the overdose of paracetamol is common. The pathophysiology toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine (NAPQI), is produced via the hepatic cytochrome P-450 enzyme system; Glutathionvorräte in the liver can detoxify these metabolites. Acute overdosage of acetaminophen results in a reduction of Glutathionvorräten in the liver. This leads to the accumulation of NAPQI that causes turn to cell necrosis and possibly damage to other organs (eg., Kidney, pancreas). Theoretically, alcoholic liver disease or malnutrition may increase the risk of toxicity because malnutrition (which is also commonly found among alcoholics) reduces the hepatic Glutathionvorräte. However, therapeutic doses of paracetamol are not related to liver damage associated with alcoholic patients. Acute Paracetamolvergiftungen To relevant toxicity to cause acute overdose must exceed ? 150 mg / kg within 24 h (ca. 7.5 g in adults). Intravenous acetaminophen One i.v. Preparation of paracetamol, which was intended for use in hospitals and in patients> 2 years, has been brought several hundred reportedly with overdoses and several dozen deaths, three in children in association. Most of these adverse events were the result of dosage errors because the drug doses in milligrams, but was administered in milliliters. Since these overdoses are iatrogenic, have reliable information about time and total dose available. The Rumack-Matthew nomogram (Rumack-Matthew nomogram in acute poisoning by acetaminophen without accompanying preparations) has therefore been used successfully to predict the toxicity. It is unlikely that overdoses <150 mg / kg lead to toxicity. However, there are no recommendations for treatment i.v. Paracetamol overdose, and consultation with a toxicologist oser a poison control center is recommended symptoms and complaints Slight poisoning may remain asymptomatic, symptoms of acute paracetamol poisoning h usually up to ? 48 after taking small symptoms that occur in four stages (see table: phases of acute paracetamol poisoning) include loss of appetite, nausea, vomiting and pain in the upper right abdominal quadrant. Renal failure and pancreatitis may occur, sometimes even without a liver failure. Usually it comes after 5 days either to a recovery of liver damage, or it goes into a multi-organ failure on that can be fatal. Phases of acute paracetamol poisoning phase time after taking Description I 0-24 h anorexia, nausea, vomiting II 24-72 h Pressing pain in the right upper Abdomenquadranten is frequent. AST, ALT, and - in severe poisoning - even bilirubin and PT (usually reported as INR) may be increased. III 72-96 h vomiting and symptoms of liver failure peak values ??of AST, ALT, bilirubin and INR Sometimes renal failure and pancreatitis IV> 5 days usually occur after 5 days either to a recovery of liver damage, or this turns into a multi-organ failure, the deadly may end. Diagnostic serum concentration of paracetamol Rumack-Matthew nomogram A paracetamol overdose should in all patients with suspected intentional overdose (suicide attempt) should be considered and in children because oral preparations containing paracetamol are more common in such overdoses, as reports might guess. One reason may be that paracetamol often causes only minor symptoms in the early stages of poisoning, potentially fatal, but is treatable. A Paracetamolüberdosierung should also be considered in all cases of accidental ingestion into consideration. Tips and risks to an unknown paracetamol should be considered in all patients with a drug revenue. The likelihood and severity of hepatotoxicity in an acute situation can be described by the occupied volume, but more accurately predict by the serum concentration of paracetamol. If the administration time unknown, on the nomogram does not help. If the time of ingestion is known for estimating the probability of liver damage, the used Rumack-Mathew nomogram (Rumack-Matthew nomogram in acute poisoning by acetaminophen without accompanying preparations). In the case of a single acute overdose with conventional paracetamol formulations or fast acting paracetamol preparations (which are absorbed within 7-8 min), the mirrors are ? 4 h after intake are measured and entered in the nomogram. A Paracetamolkonzentration ? 150 ug / ml (? 990 .mu.mol / l) and the absence of signs of poisoning suggest that hepatotoxicity is very unlikely. Higher concentrations indicate a potential hepatotoxic risk. In acute acetaminophen-Monointoxikationen with slow release acetaminophen preparations (with two peak serum concentrations within 4 hours) the serum acetaminophen concentration ? should be determined 4 hours after administration, and after a further 4 hours; if one of these values ??above the Rumack-Matthew toxicity curve lies, treatment should be done. Rumack-Matthew nomogram in acute poisoning by acetaminophen without accompanying preparations Semilogarithmic representation of paracetamol Plasmakonzenrationsmaspiegel versus time. Notes for the use of this nomogram: The time coordinates refer to time of ingestion. Serum concen rations below 4 h not represent the highest values ??in general. The graph should be used only in the case of a single acute ingestion. The lower solid line 25% below the Standardnomogramm was included in order to make possible errors in the paracetamol Konzentationsbestimmung and the estimated time of ingestion recognizable. Adapted from Rumack BH, Matthew H: acetaminophen poisoning and toxicity. Pediatrics 55 (6): 871-876, 1975; courtesy of Pediatrics. Clinical Calculator: acetaminophen (paracetamol) poisoning -Toxizitätsbewertung When a confirmed or highly probable, or if the time of intake is unclear or unknown, additional tests are displayed. It made liver function tests, and it is measured at suspected of serious poisoning the prothrombin time. AST and ALT levels correlate with the degree of poisoning (see Table: phases of acute acetaminophen poisoning). AST levels> 1000 I.E./l are more likely due to a paracetamol poisoning than by chronic hepatitis or alcoholic liver damage. In severe poisoning, bilirubin and INR may be increased. Small increases in transaminases (eg., Up to 2 or 3 times the upper limit of normal) may occur in adults taking therapeutic doses of paracetamol over days or weeks. These increases appear to be temporary; normalize or decrease usually (even with continued use of paracetamol) and are clinically asymptomatic and probably insignificant in general. Paracetamol / cysteine-protein adducts are newly developed biomarkers and are marketed as indicators of paracetamol-induced hepatotoxicity. Although the biomarker may indicate exposure to paracetamol, they give no compelling insight into paracetamolinduzierte Hepatotoxizität.Prognose If adequate treatment is carried out, a fatal outcome is unusual. Poor prognostic indicators 24-48 h after ingestion are: pH <7.3 after resuscitation INR> 3 serum creatinine> 2.6 Hepatic encephalopathy grade III (confusion and sleepiness) or grade IV (stupor and coma) hypoglycemia Acute thrombocytopenia Paracetamol toxicity is not a risk factor for the development of an oral or iv Leberzirrhose.Therapie N-acetylcysteine ??may activated carbon charcoal is administered when paracetamol is still a high probability in the gastrointestinal tract. N-acetylcysteine ??(NAC) is considered the antidote for paracetamol poisoning. This drug is a Glutathionvorläuferprodukt that the paracetamol toxicity decreased by increasing the hepatic Glutathionvorräte; may have also other mechanisms of action of NAC. It helps to prevent liver toxicity by inactivating the toxic paracetamol metabolites NAPQI before it can cause damage to liver cells. However, it can not do damage to the liver cells reversed that has already taken place. In case of acute acetaminophen poisoning N-acetylcysteine ??is administered when an hepatotoxicity is likely occupied by the dose or by determination of serum concentration. The substance is most effective when it is added within 8 hours after acetaminophen ingestion. After 24 h, the advantage of the antidote is questionable, but it should be given. If the degree of toxicity is uncertain, N-acetylcysteine ??should be given until toxicity can be excluded. N-acetylcysteine ??is at i.v. or oral administration is approximately equal effective. I.v. Dose is administered as a continuous infusion. A starting dose of 150 mg / kg in 200 ml of 5% glucose is administered over 60 minutes, followed by a maintenance dose of 50 mg / kg in 500 ml of 5% glucose for 4 hours, to which a third dosage of 100 mg to / kg followed in 1000 ml of 5% glucose for 16 hours. In children, the dosage may need to be adjusted in order to keep the total liquid volume low. For this, the contact a Poison Control Center is recommended. The oral loading dose of N-acetyl-cysteine ??is 140 mg / kg. This starting dose followed by 17 additional doses of 70 mg / kg every 4 hours. Oral N-acetylcysteine ??is not very tasty. It is in a dilution of 1: 4 administered in carbonated drinks or fruit juices, but can cause vomiting yet. In the event of vomiting emetic may be considered; it comes within one hour after the administered dose nauseam, the gift should be repeated. (D. Talk .: Note. Oral administration is not used in Germany because it is ineffective due to the coal delivery and vomiting.) However, the vomiting can last long and limit oral intake. Allergic reactions are uncommon but have with oral and iv Use occurred. Liver failure is treated supportive. Patients with fulminant hepatic failure may need a Lebertransplantation.Zusammenfassung Because paracetamol is omnipresent and initially asymptomatic, in overdose but treatable, a paracetamol should be considered in all possibly poisoned patients into consideration. The Rumack-Matthew nomogram can throw used when the time of ingestion is known to estimate the risk of liver damage on the basis of paracetamol serum levels. If hepatotoxicity is likely N-acetylcysteine ??may be administered. If acetaminophen is probably still present in the gastrointestinal tract, activated carbon can be useful. If the level of toxicity is uncertain, you can start with the administration of N-acetylcysteine, until more information is available. Chronic paracetamol Excessive chronic use or repeated overdoses can cause hepatotoxicity in some patients. Usually, in cases of chronic overdose not be assumed that self-harm, but rather indicates a pain treatment with high doses inadequate. Symptoms may be absent or include all those that may occur in the context of acute overdoses. Diagnosis AST, ALT and paracetamol serum levels in these cases, the Rumack-Matthew nomogram not be used, but the risk of clinically significant hepatotoxicity can be estimated from AST, ALT and paracetamol serum levels. Unless AST and ALT in the normal range (<50 I.E./l) and the paracetamol levels are <10 ug / ml, a significant hepatotoxicity is very unlikely. Although AST and ALT, acetaminophen concentrations but are ? 10 ug / ml in the normal range, liver damage can not be ruled out. AST and ALT must h be determined again after 24 hours. If these values ??are increased, a significant hepatotoxic effects must be assumed. Unless AST and ALT are repeated in the normal range, a significant liver damage is unlikely. If the initial measured values ??for AST and ALT are elevated, is expected by a significant hepatotoxicity - unanhängig of paracetamol serum concen ration. Therapy Sometimes N-acetylcysteine, the importance of N-acetylcysteine ??in the treatment of chronic paracetamol poisoning also in acute hepatotoxicity is unclear. Theoretically, the antidote may have some advantages, if given> 24 hours after ingestion, when a remainder of non-metabolized acetaminophen is still present. The effectiveness of the following therapeutic approach is not proven but may be attempted if hepatotoxicity is likely (if AST and ALT are normally and the paracetamol levels are first increased), may be N-acetylcysteine ??with a loading dose of 140 mg / kg and then 70 mg / kg every 4 h h be given within the first twenty-fourth Are increases the liver values, they should be re-determined daily and the administration of N-acetylcysteine ??continue until the values ??are within normal limits. If repeated AST and ALT values ??(after 24 hours) within the normal range, the N-Acetylcysteingabe can be stopped. Must be assumed to be hepatotoxicity (especially when the initial measured AST and ALT levels are elevated) must, N-acetylcysteine ??administered following scheme. Prognostic factors are those of an acute paracetamol poisoning comparable (Acute Paracetamolvergiftungen: Forecast).