PCM Poisoning or Paracetamol Poisoning: Causes, Risk Factors, Symptoms, Signs, Treatment, Diagnosis, Prevention

PCM poisoning, is also known as paracetamol poisoning or acetaminophen toxicity or acetaminophen overdose or Tylenol toxicity, is quite a common condition that can occur in any age group due to the overdose of the drug paracetamol. Paracetamol is a demethylated active metabolite of phenacetin, which is an antipyretic (used in fever) and an analgesic drug (used to reduce pain). Paracetamol was introduced in last century in 1950 and is a widely used and the most accepted drug by common people and practitioners of medicine. Paracetamol is well absorbed orally, only about one fourth is protein bound in plasma and it is uniformly distributed in the body. Its metabolism mainly occurs by conjugation of the glucuronic acid and sulphate. Its remaining metabolites are excreted in the urine very rapidly. Plasma half-life of paracetamol is two to three hours; and its effect after an oral dose lasts for about three to five hours. Well, paracetamol poisoning is theacute type of poisoning as it has a sudden onset and is usually progressive in nature if not treated in time. Death rate or mortality rate with PCM Poisoning or Paracetamol Poisoning is not that that severe. Due to a severe rise in cases of paracetamol poisoning in 1980’s and 1990’s, the system of prescription and purchase over the counter for paracetamol was reduced and stopped in many countries. But in India, paracetamol is much easily available and is healthily sold over the counter and can be easily obtained by getting a prescription from a qualified doctor or any medical practitioners.

Causes of PCM poisoning or paracetamol poisoning can be elaborated as following:

• PCM poisoning can occur due to the accidental ingestion of huge amount of paracetamol.
• Sometimes people of suicidal tendencies tend to take PCM overdose to harm themselves.
• PCM Poisoning or Paracetamol Poisoning usually occurs in small children who have low glucuronide conjugation ability.
• In premature infants, paracetamol poisoning can occur at a dose of fewer than two kilograms (<2kg) and dose more than this can lead to hepatotoxicity.
• In adults, paracetamol toxicity occurs when there is an overdose of more than 150 milligrams per kilogram of body weight (>150mg/kg) or more than 10 grams per day (>10gm/day). This much amount of dose can lead to serious PCM Poisoning or Paracetamol Poisoning.
• Paracetamol poisoning can turn fatal, if the dose in more than 250 milligrams per kilogram of body weight (>250/kg).
• In adults, if more than six grams of paracetamol is given per day for forty-eight hours, then it can also lead to PCM Poisoning or Paracetamol Poisoning.
• In rare cases, paracetamol poisoning can occur by the use of this drug at normal doses and this usually occurs due to the difference in expression and activity of certain enzymes and various metabolites that are synthesized in our body. This can also occur due to alteration in pathways and variations in body metabolism and responses.
• Any other mutational variation can also lead to PCM Poisoning or Paracetamol Poisoning.

Various conditions and factors can be associated and lead to PCM poisoning or paracetamol poisoning in people and these are:

Alcohol Consumption: Chronic alcoholism is considered as one of the risk factors and conditions that can lead to PCM Poisoning or Paracetamol Poisoning. The topic is yet debatable. According to a research, it is said that alcohol consumption leads to induction of CYP2E1 enzymes in our body, which increases an individual’s susceptibility and chances of having paracetamol poisoning. In chronic alcoholic people, 5 to 6 gram of paracetamol dosage can also result in hepatotoxicity and degeneration of the liver.

Use of Other Drugs: Various drugs that induce our bodies CYP mechanism can increase a person’s chances or susceptibity for developing paracetamol poisoning. These include drugs like carbamazepine, phenytoin, barbiturates etc.

Diet Restriction: A person who is on a diet restriction or diet control or fasting can develop PCM Poisoning or Paracetamol Poisoning quite easily. The mechanism of the above process is quite unclear, but according to some scientific papers, there is a decrease in liver enzymes like glutathione or glucuronides, which induces CYP receptors and thus act as a risk factor.

When paracetamol is taken in normal doses, it acts as an effective analgesic and antipyretic drug; however, the following mechanism takes place and can lead to toxic side effects or PCM poisoning or paracetamol poisoning:

NAPQI or N-acetyl-p-benzoquinone imine is a highly reactive. This metabolite generally or normally gets detoxified by conjugation (binds) with glutathione that is present and secreted by theliver; but when a person has ingested a large amount of paracetamol, the ability of NAPQI to bind with glutathione is reduced as there occurs saturation of glutathione. Explaining in normal terms of ingestion of heavy amount of paracetamol, there occurs massive production of the metabolite NAPQI, but the amount of glutathione remains limited hence all the NAPQI metabolite does not bind to glutathione. This causes accumulation of the metabolite which is NAPQI in our body. Now the remaining metabolite starts binding to the liver proteins and renal cells and tubules. This leads to degeneration and death of liver tissue and renal tissues. This metabolite can also be induced or increased in chronic alcoholics, as alcohol acts as a good booster or a buffer to NAPQI metabolite.

As soon as the dose is ingested early manifestations set in and include:

• Extreme nausea.
• Recurrent vomiting.
• Restlessness.
• Dyspnea.
• Anxiety.
• Sweating.
• Temperature fluctuation.
• There is a sudden dull aching pain in the abdomen which intensifies with time.
• The patient develops pain and tenderness over the right hypochondrium, which is the right upper part of the abdomen.
• In severely overdosed patients, there may occur loss of consciousness and mental impairment.

After twelve to twenty-four hours of paracetamol poisoning, the patient develops the following symptoms:

Liver Pathology

There is occurenence of liver damage and liver cell death, usually involvings the central lobe of the liver first. There is abnormal increased in the amount of transaminase aspartate and transmarine lysine.

Kidney Pathology

The patient starts developing reduction in glomerular filtration rate, which increases the PCM toxicity, as paracetamol is mainly excreted in urine. Damage to kidney cells, tissues and tubules start and this leads to reduction and damage of kidney function. The patient may land up into acute kidney failure. The patient also tends to develop metabolic acidosis and alkalosis.

After four to five days of PCM ingestion, the following symptoms start developing:

• Due to massive destruction of kidney and liver, patient ends up having hepatorenal syndrome.
• The patient suffers from fulminant liver which is end stage of liver degeneration and usually ends up in liver necrosis.
• There is also increased collection of a number of toxic metabolites in our body.
• The patient starts suffering from coagulation defects, as the liver is the main site of production of coagulation factors.
• With further increase in duration, there occurs hepatic encephalopathy, and this further leads to brain swelling. The body also develops septicemia.
• With further prevalence of the condition, patient has multi-organ dysfunction or multi-organ failure.
• When worse comes to worse, death of the patient can occur.

If the patient survives PCM Poisoning or Paracetamol Poisoning for more than the above time, then the body starts to heal on its own and develops a mechanism to restore back its normal function. The kidney and liver start regaining their normal function. The toxic metabolites are excreted out of the person’s body. However, liver necrosis, if once started, continues to keep worsening over time. It can only be slowed down, but can never be healed or stopped completely.

Other than the clinical manifestations, signs and symptoms of PCM poisoning, there are various diagnostic tests available for checking and confirming the suspicion of PCM poisoning or paracetamol poisoning. This includes the following:

• A drug nomogram is done to estimate the risk of toxic effects and spread of PCM toxicity in our body. This test tells about the concentration of paracetamol in one’s body even after hours of ingestion.
• Due to various liver symptoms there is elevated AST and ALT in the body.
• There is also an increase in the level of serum bilirubin.
• There is increase in the amount of prothrombin time.

Paracetamol can be easily detected in one’s body fluids and this can be detected by various methods like automated calorimetric techniques, gas chromatography and liquid chromatography etc.

Once the patient suffers from PCM poisoning or paracetamol poisoning, the following steps need to be undertaken to prevent any fatal condition and treat the patient:

• The patient should be made to induce vomiting immediately and should be brought to the hospital or emergency as soon as possible.
• No other intervention or drugs should be given to the patient suspected to suffer from PCM Poisoning or Paracetamol Poisoning.
• Gastric lavage, that is emptying the contents of the bowel from the mouth by Ryles tube should be carried out immediately on reaching the hospital.
• Activated charcoal (more preferred as it is aspirated less than gastric lavage) is given to the person, as it the most commonly used method and helps in reducing the contamination by absorption the gastric content and paracetamol present in the stomach.
• The acetylcysteine drug can normally be given in some patients. This leads to decrease in the number of harmful metabolites that get accumulated in our bodies. It is very effective in cases where the poisoning is only six to seven hours old.
• Intravenous acetylcysteine is given to the patient at the rate of 300 milligrams per kilogram (300 mg/kg)
• 150 mg of acetylcysteine that is MUCOMIX, ANTIGEN 200 can be given intravenous for 15 minutes and can be infused followed by the same dose for the next 20 hours.
• The dose is altered to 75 mg/kg body weight and may be given orally for every four to six hours for next three days. This helps to replenish glutathione and reduce toxic metabolites.
• Liver transplantation is considered as an option in patients who have suffered severe liver necrosis and hepatotoxicity or have landed up in liver failure.
  Fluid resuscitation can be done in the patient and the serum creatinine brought to normal.
• Kidney transplantation is also done in severe cases of kidney failure and necrosis or degeneration of kidney.

Some patients are kept on immune system suppressing drugs, so that the liver or kidney from a donor can be accepted by the patient’s body. Later these drugs are withdrawn to restore and check the normal function of liver and kidney.

Various practices and methods can be adapted in our society to reduce the chances of PCM poisoning or paracetamol poisoning. These include the following:

• Replacement of paracetamol with other drugs like ibuprofen, calcitriol etc. can be done, which have less toxic side effects.
• The easy availability of paracetamol should be reduced and should be monitored over the counter. Any misuse of paracetamol and large-scale purchase should be cross-checked.
• Ideally, paracetamol should not be given without any authorized medical prescription. This practice has been started by many European countries and is strictly adhered to.
• Any suspected or reported case of PCM poisoning should be immediately brought to the hospital without any delay.
• Paracetamol can be combined with other drugs that can help reduce its toxic effects and cause less harm in the long run to the patient.