**8. Acetaminophen poisoning**

First time acetaminophen had been clinically used was in 1950 and since that time acetaminophen become most common over-the-counter antipyretic and analgesic used in public. Acetaminophen is the most common cause of acute liver failure in the United States [9, 10].

#### **8.1. Mechanism of action**

Acetaminophen metabolized in the liver and converted to nontoxic metabolites via glucuronidation (40–67%) and sulfation (20–46%). In therapeutic doses of acetaminophen, the small amount of NAPQI formed which detoxified by conjugation with reduced glutathione (GSH). Glutathione is an important tripeptide which is reduced in a NADPH dependent reaction, and used to reduce oxidants (such as NAPQI).

In large overdoses of APAP, the usual pharmacokinetic pathways are overwhelmed and saturation of the nontoxic pathways occurs. Endogenous glutathione is depleted and NAPQI cannot be detoxified. Leaving excess NAPQI to bind to intracellular proteins, cause cell death [11].

#### **8.2. Clinical features**

Symptoms are frequently nonspecific or absent in early Acetaminophen toxicity.


**8.3. Treatment**

hepatic failure.

**Figure 1.** Rumack-Matthew nomogram.

**Figure 2.** ECG changes in TCA toxicity.

After initial support of airway, breathing and circulation, the clinician should consider gastrointestinal (GI) decontamination by activated charcoal. The cornerstone of acetaminophen overdose is N-acetylcysteine (NAC). NAC serves as a precursor to glutathione and may also directly reduce NAPQI. Clinical data suggest that if therapy is initiated within 8 h of ingestion, NAC is completely effective in preventing hepatotoxicity. Although NAC decreases in efficacy after 8 h, the drug has a benefit at all points in time, even for patients with fulminant

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N-acetylcysteine should only be given to patients with hepatotoxicity or risk of developing hepatotoxicity. The Rumack-Matthew nomogram is a tool for determining potential hepatotoxicity based on Acetaminophen level and time after ingestion. The nomogram is used to determine the risk for APAP hepatotoxicity for patients who present within 24 h of an acute ingestion. Risk determination of hepatotoxicity becomes more difficult

**Table 1.** Antidote.

Clinical presentation of Acetaminophen toxicity divided into four stages:


#### **8.3. Treatment**

After initial support of airway, breathing and circulation, the clinician should consider gastrointestinal (GI) decontamination by activated charcoal. The cornerstone of acetaminophen overdose is N-acetylcysteine (NAC). NAC serves as a precursor to glutathione and may also directly reduce NAPQI. Clinical data suggest that if therapy is initiated within 8 h of ingestion, NAC is completely effective in preventing hepatotoxicity. Although NAC decreases in efficacy after 8 h, the drug has a benefit at all points in time, even for patients with fulminant hepatic failure.

N-acetylcysteine should only be given to patients with hepatotoxicity or risk of developing hepatotoxicity. The Rumack-Matthew nomogram is a tool for determining potential hepatotoxicity based on Acetaminophen level and time after ingestion. The nomogram is used to determine the risk for APAP hepatotoxicity for patients who present within 24 h of an acute ingestion. Risk determination of hepatotoxicity becomes more difficult

**Figure 1.** Rumack-Matthew nomogram.

Clinical presentation of Acetaminophen toxicity divided into four stages:

into thousands.

**Table 1.** Antidote.

sepsis and cerebral oedema.

**Toxin Antidote**

254 Essentials of Accident and Emergency Medicine

β-Blockers Glucagon 3–10 mg

Digoxin Digoxin Fab 5–10 vials

Tricyclic antidepressants Sodium bicarbonate

Cyanide Amyl nitrite

Calcium channel blockers Calcium gluconate 10% 10–30 mL IV

Narcotics Naloxone 0.1–0.4 mg, may repeated

Cholinergic (organophosphates,

carbamates)

• Stage I (first 24 h): Patients may present nausea, vomiting, malaise, anorexia, or may be asymptomatic. Also hypokalaemia and metabolic acidosis can be found in blood test. • -Stage II (Days 2–3): patients develop nausea, vomiting, right upper quadrant abdominal pain and laboratory evidence of hepatotoxicity. Aminotransferases (AST and ALT) elevate

methaemoglobinaemia Methylene Blue 1–2 mg/kg (0.1–0.2 mL/kg of 1% solution) IV slowly over

local anaesthetics Intravenous lipid emulsion 1–1.5 mL/kg 20% IV bolus over 1 min Repeat

Then Infuse 0.25 mL/kg/min

bolus at 3–5 min

Acetaminophen N-acetylcysteine 150 mg/kg dextrose IV over 15–60 min then50 mg/kg

Anticholinesterases Physostigmine 0.5–1 mg IV as a slow push over 5 min and repeat every

Sodium thiosulfate

Methanol, ethylene glycol Ethanol Loading 8 mL/kg of 10% ethanol then 1–2 mL/kg/h of 10%

Vitamin B12

Isoniazid Pyridoxine (vitamin B6) 70 mg/kg IV (maximum 5 gm)

ethanol

iron Desferrioxamine IV infusion dose of 15 mg/kg/h

5 min

Sodium nitrite (3% solution)

10 min Benzodiazepines Flumazenil 0.2 Mg repeated max dose 2 mg

NAC IV over 4 h. Then 100 mg/kg NAC IV over 16 h.

Fomepizole Loading: 15 mg/kg in 100 mL IV over 30 min Maintenance: 10 mg/kg IV over 30 min every 12 h for 48 h

1–2 mEq/kg IV bolus followed by 2 mEq/kg per h IV infusion

Atropine 1–2 mg every 2–3 mins, until there is drying of secretions Pralidoxime (2-PAM) 70 mg/kg IV then infusion at 500 mg/h

• -Stage III (3–4 days) defined by maximum hepatotoxicity, Patients exhibit coma, encephalopathy, coagulopathy, renal failure, Jaundice, acute respiratory distress syndrome (ARDS),

• -Stage IV (7–8 d): recovery or deterioration to multi-organ failure and death [12, 13].

**Figure 2.** ECG changes in TCA toxicity.

when the nomogram is not applicable. Examples of such cases would be when the time of ingestion is unknown, when patients present more than 24 h after the ingestion and following ingestions that occur over many hours. In all of these cases NAC should be administered immediately. If aminotransferases (ALT, AST) are normal and APAP concentration is undetectable, the NAC may be discontinued. Otherwise, treatment with NAC should be continued.

**9.6. Inhibition sodium channel block**

**9.7. Inhibition potassium channel block**

**9.9. ECG changes in cyclic antidepressant poisoning**

• Sinus tachycardia, most common

and a negative S wave in lead I)

• Brugada pattern is seen 10–15%

• Prolongation QT, PR

and Flumazenil [22, 23].

**9.10. Treatment**

of the QRS complex [19].

**9.8. Clinical features**

seizures [20, 21].

This effect produces decreased conduction velocity, increases the duration of repolarization and depressed myocardial contractility which lead to heart blocks, bradycardia and widening

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This effect produces QT interval prolongation and rarely torsades de pointes can be seen [19].

Symptoms occur typically within 2 h of ingestion, which varies from mild antimuscarinic symptoms to severe cardio-toxicity. Patient may present with drowsiness, confusion, slurred speech, ataxia, sinus tachycardia, urinary retention, myoclonus and hyperreflexia. Serious toxicity is almost seen within 6 h of ingestion and patient present with: coma, cardiac conduction delays, supraventricular tachycardia, hypotension, respiratory depression, ventricular tachycardia and

• Right axis deviation of the terminal 40 milliseconds positive terminal R wave in lead aVR

Treatment starts with supportive management securing airway, bolus i.v fluid in case of

Add vasopressors if hypotensive refractory to IV normal saline. Cardiac conduction abnormalities, ventricular dysrhythmias, or hypotension refractory to IV fluid are indicated to start blood alkalization by Sodium bicarbonate Keep blood pH 7.50–7.55. Seizures, treat with Benzodiazepines if seizure refractory use Phenobarbital 10–15 mg/kg, The medication contraindication in CA toxicity are: Class I antiarrhythmic (lidocaine, phenytoin, and flecainide), Class III antiarrhythmic (amiodarone, sotalol), Β-blockers, Ca channel blockers, Physostigmine

hypotension, GI decontamination with activated charcoal within 1 h of ingestion.

• Prolongation of QRS,(risk of seizures increases if the QRS complex is >100 milliseconds)

N-acetylcysteine dose Oral 140 mg/kg loading dose 70 mg/kg q4 h × 17 doses or Intravenous 150 mg/kg loading dose 50 mg/kg over 4 h 100 mg/kg over 16 h [14–16] (**Figures 1** and **2**).
