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Acetaminophen Poisoning

Management of Acetaminophen Toxicity

Acetaminophen or commonly known as Paracetamol, is the most used antipyretic and analgesic in the whole world. It is readily available over-the-counter as a component of common drugs for fever and headache in most parts of the world. The chemical name of paracetamol is N-acetyl-p-aminophenol (APAP). Due to its ubiquitous presence, acetaminophen poisoning is a common and sometimes a debilitating consequence.

Pathophysiology of Acetaminophen Toxicity

The maximum recommended daily dose of acetaminophen is 4 g in adults and 90 mg/kg in children. Acute ingestion of 150 mg/kg or approximately 7-10 g in adults results in toxicity. Acetaminophen is rapidly absorbed from the stomach and small intestine and primarily metabolized by conjugation in the liver to nontoxic, water-soluble compounds that are eliminated in the urine. When there is an overdosage, the conjugation in the liver becomes saturated, and excess APAP is oxidatively metabolized by the cytochrome P enzymes to a reactive metabolite, N-acetyl-p-benzoquinone-imine (NAPOI). This metabolite is rapidly conjugated with glutathione and is excreted by the kidney.

An ensuing cascade of oxidative damage, mitochondrial dysfunction, and the subsequent inflammatory response propagate hepatocellular injury, death, and centrilobular (zone III) liver necrosis. Similar enzymatic reactions occur in extra-hepatic organs, such as the kidney, and can contribute to some degree of extra-hepatic organ dysfunction. Production of APAP’s toxic metabolite, NAPQI, in excess of an adequate store of conjugating glutathione, is associated with hepatocellular damage, necrosis, and hepatic failure

Clinical Features

Four phases mark the course of Acetaminophen toxicity. Hepatic and occasionally renal toxicity is manifest only after 24 to 48 hours postingestion. Patients with significant liver damage subsequently develop  multi-system organ failure including haemorrhage, sepsis, ARDS, and cerebral oedema. Death usually occurs 3-5 days after ingestion.

Phase 1 (0-24 h)

  • Asymptomatic
  • Anorexia
  • Nausea or vomiting
  • Malaise
  • Subclinical rise in serum transaminases levels begins at about 12 hours postingestion

Phase 2 (18-72 h)

  • Right upper quadrant abdominal pain, anorexia, nausea, vomiting
  • Continued rise in serum transaminases levels

Phase 3 (72-96 h)

  • Centrilobular hepatic necrosis with continued abdominal pain
  • Jaundice
  • Coagulopathy
  • Hepatic encephalopathy
  • Nausea and vomiting
  • Renal failure
  • Fatality

Phase 4 (4 d to 3 wk)

  • Complete resolution of symptoms
  • Complete resolution of organ failure

Laboratory Investigations

  • Acetaminophen serum concentration
  • Transaminase levels
  • Measures of hepatic function
  • Serum concentrations of NAPQI-protein adducts
  • Electrolytes and creatinine
  • Human chorionic gonadotropin (HCG) in females of childbearing age: Acetaminophen crosses the placenta, and the fetal liver is able to elaborate NAPQI by 14 weeks of gestation.
  • Urinalysis

Lactate and Arterial blood gas with pH 7.3 is a laboratory component predictive of mortality


  1. Decontamination with activated charcoal if within one hour of ingestion: 1 g/kg PO or 10 times the amount of drug ingested
  2. N-acetylcysteine blocks the production of toxic metabolites and hence acts as an antidote. It should preferably be given within 8 hours of ingestion but it could still be beneficial if given within 24 hours of ingestion. It can be given per oral, intermittent intravenous and continuous intravenous routes. The recommended standard dose is 140 mg/kg PO, then 70 mg/kg q4h x 17 doses. Drug is continued until encephalopathy is resolved and INR.IV administration is mandated for fulminant hepatic failure, patient unable to take orally, high serum levels at or beyond 8 hours post-ingestion, or a pregnant patient (higher placental delivery prior to first pass metabolism).
  3. Antiemetics like metoclopramide or ondansetron
  4. Medical toxicologist, hepatologist and transplant surgeon may be consulted depending on the findings.

Admit the patient in an intensive care unit for continuous monitoring and shift the patient to the ward once the toxicity has settled down. Follow-up in the OPD should be strictly pursued.

Remember, any poisoning case should be treated as medicolegal until proven otherwise!


With aggressive supportive care, the mortality rate for acetaminophen hepatotoxicity is less than 2%. Patients who survive should be expected to have a return of normal hepatic function.


Lipogram: Is it the weight of fat in grams?

English is a funny language. Indeed it is! You must be wondering what “Lipogram” stands for? My first thought when I saw the word was “must be something related to fat”. What else with all the media attention on all things relating to fat. Well, I was wrong to say the least.

What is it then?

Interestingly, a lipogram is a literary composition which omits a certain letter of the alphabet. Imagine omitting the letter ‘e’. That would be a linguistic challenge.

Variation on the lipogram include verses which omit one letter but contain every other letter of the alphabet. A glaring example of such a lipogram is this anonymous poem which omits the letter ‘e’ in each line.

Bold Nassan quits his caravan,
A hazy mountain grot to scan;
Climbs craggy rocks to spy his way,
Both tax his sight, but far doth stray.

Interesting, huh! Another interesting read is the nursery rhyme, “Mary had a Little Lamb”, rewritten without the letter ‘s’

Mary had a little lamb
With fleece a pale white hue,
And everywhere that Mary went
The lamb kept her in view;
To academe he went with her,
Illegal, and quite rare;
It made the children laugh and play
To view a lamb in there.

[box type=”spacer”]Next time, remember that lipogram is not the weight of your fatty parts in grams![/box]Lipogram

Methanol Poisoning

Management of Methyl Alcohol Poisoning

Methanol or Methyl Alcohol is a denaturant. It is a component of varnishes, paint removers, windshield wipers, anti-freeze solutions, copy-machine fluid and as a solvent.

Acute Poisoning

Acute Methanol Poisoning is usually a consequence of ingestion of cheap, adulterated, illicit liquor. Methanol is very toxic and requires as little as 30 ml of 40% solution to be fatal. Poisoning is mostly stratified among the people of lower socioeconomic status. On ingestion, Methanol is metabolized in the liver to formaldehyde and formic acid by alcohol dehydrogenase. Although both are toxic, formic acid is what causes the more serious delayed effects. It is also readily distributed in the liver, gastrointestinal tract, eyes and kidneys.

Clinical Features

Methanol is rapidly absorbed from the gastrointestinal tract, peak levels reaching within 1-2 hours. Onset of clinical manifestations is variable.

Early manifestations such as nausea, vomiting, headache, vertigo and gastritis are primarily caused by Methanol itself. High serum levels of Methanol (>40 mg/dl) is associated with obtundation, convulsions and coma.

Late manifestations such as visual disturbances, severe metabolic acidosis, seizures, coma and death are common after 30 hours after ingestion. The latent period is longer when Ethanol is ingested concurrently. Ocular toxicity is associated with diminished vision, flashing spots, dilated pupils, optic disc hyperemia, retinal edema and ultimately blindness.

Severe poisoning leads to myocardial depression, bradycardia and shock.

Laboratory Investigations

Apart from arterial blood gases which is essential, serum osmolality and anion gap assist in diagnosis. Renal and Liver function tests should be done and blood Methanol levels measured, if possible. CT scan of the brain may show bilateral putamen necrosis. A retrospective diagnosis of Methanol poisoning is sometimes based on this finding. Diagnosis is essentially clinical, but calculation of the osmolal and anion gap can help assess severity where serum methanol levels cannot be estimated.


1. Unabsorbed Methanol should be removed by gastric lavage.

2. Supportive Measures:

  • Correction of Acidosis
  • Control of seizures
  • Maintenance of nutrition
  • Alkalization of urine enhances excretion of formic acid

3. Specific Measures:

  • Administration of Ethanol to saturate alcohol dehydrogenase in the liver, preventing the formation of toxic metabolite, formaldehyde. A 5% solution of Ethanol is prepared and 15 ml/kg is given as loading dose and then 2-3 ml/kg/hour as maintenance dose orally. It can also be given intravenously.
  • Hemodialysis enhances elimination of Methanol and Formic acid and is indicated when Methanol levels exceed 50 mg/dl. In the absence of serum Methanol level measurements, the osmolar gap is useful to assess the indication for and duration of hemodialysis in Methanol-poisoned patients.
  • Folic acid has been used to enhance conversion of formate to carbon dioxide and water. The dose is 50 mg IV 4 hourly for 24 hours.
  • 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, has been successfully used as an alternative to Ethanol and Dialysis.
BP Apparatus

Discovery of Indirect Blood Pressure Measurement

Most medical discoveries have a notable story to tell. So it is with the discovery of Blood Pressure Measurement. This as I feel is one of the most important discoveries in medical science. With the rise in incidence of hypertension, cerebrovascular accidents, and heart failure, it is only apt that I brought out this interesting history about the past.

The Guys who made it possible

Riva Rocci invented the mercury manometer – this led to the dissemination of indirect sphygmomanometry for systolic pressure. Riva Rocci was the pupil of Potain, the great Parisian diagnostician who is attributed with introduction of the sphygmomanometer. Once Korotkoff had discovered the sounds known by his name, for diastolic as well, the history of the discovery of Indirect Blood Pressure Measurement was complete.

Korotkoff was a surgeon in the Czar’s army and not an internist as was believed earlier. Pirogoff, his teacher, had taught him always to auscultate over any area before performing an incision. On one occasion, while auscultating over an artery just as he was releasing a tourniquet, he heard thumping sounds. Abandoning his original scientific problem which was to study posttraumatic arteriovenous fistulas in the surgical dog laboratory, he tried to quantitate the amount of pressure required to make these auscultated sounds appear and disappear. The sounds correlated well with systole and diastole, as could be ascertained by direct inspection of the flow of blood from the distally severed artery of the dog.

Like most revolutionary discoveries, this landmark discovery was no alien to alienation. When Korotkoff first reported his findings in humans, some considered he had gone bonkers! So were many other scientists and innovators.


Irritable Bowel Syndrome – Symptoms, Causes and Treatments

Irritable bowel syndrome is a chronic functional disorder of the intestines which causes abdominal pain, often accompanied by cramping, bloating, diarrhea and constipation. It is also referred to as spastic colon or mucous colitis. Irritable bowel syndrome is more commonly known by its abbreviated term – IBS.

There are three forms of IBS depending on the symptoms — diarrhea-predominant (IBS-D), constipation-predominant (IBS-C) and IBS with alternating stool pattern (IBS-A). Clinical investigations are going on a new IBS subtype, post-infectious IBS (IBS-PI).

Symptoms of IBS

[box]IBS symptoms include: • Abdominal pain • Discomfort associated with changes in bowel habits • Fewer than three bowel movements a week • More than three bowel movements a day • Hard or lumpy stools • Loose or watery stools • Straining during a bowel movement • Urgency (having to rush to have a bowel movement) • Feeling of incomplete bowel movement • Passing mucus (white material) during a bowel movement • Abdominal fullness, bloating, or swelling • Chronic pelvic pain • Mental stress • Fibromyalgia and various mental disorders • Researchers believe that there are neurological and psychological disorders associated with IBS.[/box]

Causes of Irritable Bowel Syndrome

The exact causes of irritable bowel syndrome are unknown, but there are factors that may aggravate the trouble. Dietary factors and stress don’t exactly cause IBS, but they can aggravate it. Various studies and researches have noted an IBS connection to diet. Physicians feel that the correct diet can provide IBS relief.

Common IBS diet advice includes:

• Eat soluble fiber foods and supplements.
• Substitute dairy products for soy or rice products.
• Be careful with fresh fruits and vegetables that are high in insoluble fiber.
• Eat small amounts in regular intervals to lessen the symptoms of IBS.
• Avoid eating red meat, oily or fatty (and fried) products.
• Avoid taking dairy products (especially when lactose intolerance is suspected).
• Avoid solid chocolate, coffee (regular and decaffeinated), alcohol, carbonated beverages and artificial sweeteners.

IBS Treatment

IBS treatment includes dietary advice and medication. Developing good dietary habits may be the best treatment for irritable bowel syndrome.

Medications can provide instant IBS relief. These may include stool softeners and laxatives in constipation-predominant, and antidiarrheal (loperamide) in diarrhea-predominant IBS. The low dosage of tricyclic and SSRI antidepressants has shown to be the most widely prescribed medications for helping to relieve symptoms of visceral sensitivity (pain) and diarrhea or constipation respectively. Other medications include:

• Alosetron: Alosetron is a selective 5-HT3 antagonist for IBS-D. It is only available for women in the United States under a restricted access program, due to severe risks of side effects if taken mistakenly by IBS-A or IBS-C sufferers.

• Cilansetron: Cilansetron is also a selective 5-HT3 antagonist that is undergoing further clinical studies in Europe for IBS-D sufferers.

• Tegaserod: Tegaserod is a selective 5-HT4 antagonist for IBS-C. It has shown to have an excellent safety profile for relieving IBS constipation and chronic idiopathic constipation.