This document summarizes the pathophysiology, clinical features, diagnosis, and management of salicylate and paracetamol poisoning. It describes how salicylates cause respiratory alkalosis by stimulating respiration and how this leads to hypokalemia, dehydration, and other effects. Clinical features range from mild tachycardia with high doses to seizures, coma, and organ failure. Diagnosis involves blood or urine tests and treatment includes gastric lavage, activated charcoal, alkalinization, and hemodialysis if needed. For paracetamol, it explains how toxicity occurs when glutathione is depleted, allowing a toxic metabolite to damage the liver. Symptoms appear within

1. TDM Pointers –
Salicylates Poisoning

2.  Salicylate poisoning is mainly due to ingestion of…
• Aspirin [10-20 g (adults); 3g (children)], or
• LMS (1 ml of 25% LMS = 300 mg salicylate)
 Pathophysiology:
SALICYLATES
Stimulate resp.
centre
Hyperpnoea
(hyperventilation)
Hypocarbia
(Hypocapnoea)
↓ed CO2;
↑ed HCO3
-
↑ed pH
Respiratory
Alkalosis
Body compensates:
Excretes HCO3
-, Na+,
Ca2+; BUT…
Retains Cl-
Hypokalemia and
dehydration

3.  Hypokalemia (mild toxicity); Hyperkalemia (severe toxicity);
 Stimulate metabolism (generally) causing Hyperthermia.
 Damage hepatocytes Renal dysfunction; ↑ed plasma
enzyme activity;
 ↑ed PT time; ↓ed platelet aggregation;
 Interferes w/ Carbohydrates metabolism
↑ed conc. of lactic acid, ketones and inorganic acids
HAGMA: Due to ↑ed conc. of acid in the body
Anion Gap;
High Anion
Gap;
Delta Ratio;
AG formula

4. Clinical Features
Mild Poisoning:
• Tachycardia; Hyperpnoea; Respiratory Alkalosis
• Tinnitus
• Alkaline Urine ( pH > 6)
Severe Poisoning:
• Convulsions; Coma;
• Respiratory and Cardiac Failure; Cerebral and pulmonary
oedema
• AKI; Acidosis;

5.  Salicylates are weak acids that cross cell membranes
relatively easily (they are more toxic when blood pH is
low).
 Dehydration, hyperthermia, and chronic ingestion
increase salicylate toxicity because they result in
greater distribution of salicylates to tissues.
 Excretion of salicylates increases when urine pH
increases.

6. Suspect Salicylate poisoning if patients present with
any of the following
H/o a single acute overdose
Repeated ingestions of therapeutic doses
Unexplained metabolic acidosis
Unexplained confusion and fever (in elderly
patients)
Other findings compatible with sepsis (fever,
hypoxia, non-cardiogenic pulmonary oedema,
dehydration, hypotension)

7.  The symptoms of acute salicylate poisoning may be minimal
initially with severe toxicity not evident until 6-12 hours.
 There is a poor correlation between salicylate concentration
and toxicity (Organs and systems deterioration may still occur
with falling serum concentrations due to rising CNS
concentration).
 In moderate to severe salicylate poisoning, consider
decontamination (activated charcoal) and the early
enhancement of elimination (urinary alkalization with or without
haemodialysis).

8. SALICYLATE DOSAGE CLINICAL EFFECTS
<150mg/kg Minimal symptoms
150-300mg/kg Mild-moderate symptoms:
Tinnitus, vomiting, hyperventilation
>300mg/kg Severe symptoms:
Acidosis, seizures, hyperthermia

9. Ix:
 Positive Ferric Chloride test (blood or urine sample)
 Blood salicylate levels:
• 50-110 mg/dl 6-hrs post-ingestion (mild-moderate intoxication);
• >110 mg/dl 6-hrs post-ingestion (severe intoxication; often fatal);
 Elevated Hct, WBC count, platelet count;
 Hypo- and Hyper- natremia; kalemia;
 Hypoglycemia
 Respiratory alkalosis; Metabolic acidosis;
 Respiratory alkalosis + Metabolic acidosis;
 Prolonged PT time
ABGs

10. Significant salicylate toxicity:
 Serum levels > therapeutic range (10 - 20 mg/dL),
particularly 6 hrs. post-ingestion (when absorption is
usually almost complete),
 Acidemia plus ABG results compatible with salicylate
poisoning.
• Serum levels are helpful in confirming the diagnosis
and may help guide therapy, but levels may be
misleading and should be clinically correlated.

11. ABGs result (usually):
 Primary respiratory alkalosis (during the first few hours
after ingestion);
 Later, they show compensated metabolic acidosis or
mixed metabolic acidosis/respiratory alkalosis.
 As salicylate levels decrease, poorly compensated or
uncompensated metabolic acidosis is the primary
finding.
 If respiratory failure occurs, ABGs suggest combined
metabolic and respiratory acidosis, and CXR shows
diffuse pulmonary infiltrates. Plasma glucose levels
may be normal, low, or high.
 Increased serum CK and urine myoglobin levels
suggest rhabdomyolysis.

12. Management:
 Gastric lavage performed for upto 12 – 24 hrs.
 Activated charcoal:
• Initial dose 1g/kg
• Subsequent doses 25 g Q2H for 3 doses, or
50 g Q4H for 2 doses;
 For dehydration: 0.9% NS and Potassium as indicated;
Correct electrolyte imbalance;
Oxygen and glucose may be required.
 For severe acidosis, treat with bicarbonate (pH < 7.15);

13.  Forced Alkaline Diuresis: Is indicated if/ in case of..
• Salicylate level > 50 mg/dl;
• Very symptomatic patient;
• Patient w/ increasing salicylate levels;
 Forced diuresis can be safely initiated if the urine flow rate is at
least 4 ml/min.
 If not, give IV Frusemide 20 – 40 mg.
 Even after this, if urine flow rate is still < 4 ml/min., abandon
the procedure as renal insufficiency is present.

14.  Regime of IV infusion:
• 500 ml D5% + 50 ml of 8.4% NaHCO3
• 500 ml D5% + 1 g KCl (if no hyperkalemia)
• 500 ml NS + 40 mg frusemide
• Given at a rate of 500 ml/hr.

15.  The above cycle can be repeated for 2-3 times for 24-
48 hrs.
 Monitor the following:
• Urine output (target > 4ml/min.);
• I/O chart
• Urine pH 7-8
• Potassium levels

16.  Monitor for fluid overload in pulmonary and cerebral
oedema cases (mostly among geriatric patients);
 Forced diuresis should be stopped in oliguric patients.
 Serum salicylate levels should be checked regularly
until a consistent downward trend is observed in 2
successive readings.

17. FYI:
 Alkaline diuresis is indicated for patients with any
symptoms of poisoning and should not be delayed until
salicylate levels are determined.
 This intervention is usually safe and exponentially
increases salicylate excretion.
 As hypokalemia may interfere with alkaline
diuresis, patients are given a solution consisting of 1 L
of 5% D/W, three 50-mEq ampules of NaHCO3, and 40
mEq of KCl at 1.5 to 2 times the maintenance IV fluid
rate. Serum K is monitored.
 As fluid overload can result in pulmonary edema,
patients are monitored for respiratory findings.

18. TDM Pointers -
Paracetamol Poisoning

19.  Paracetamol N-acetyl-p-benzoquinoneimine (toxic)
Inactivated
 This interaction is concentration-dependent.
 Large overdose:
• Glutathione is depleted.
• N-acetyl-p-benzoquinoneimine binds to hepatic cell membranes,
causing necrosis.
Glutathione Conjugation
Cyt.P-450

20. Clinical Features:
 1st 24 hrs.: Vomiting; diaphoresis; pts. are usually fully
conscious;
 After 24 hrs.: Hepatic enzymes’ conc. ↑es; peaks at 72-96 hrs.;
Rt. Upper quadrant pain, coagulopathy, jaundice, somnolence,
coma;
 Normally, recovery commences on 4th day post-ingestion, if
hepatic failure does not occur.

21.  Ix:
• If patient presents within 1-4 hrs. post-ingestion, plasma
paracetamol conc. should be estimated within 4 hrs. post-
ingestion.
• If it is ER product, one additional estimation should be done 4-
6 hrs. after the first estimation.
• AST, ALT, Sr. bilirubin, BU, PT time, and Sr. Creatinine levels
should be estimated daily for 3 days.
• Suspected fulminant liver failure cases: Additionally estimate
the Sr. glucose and ABG levels.

22. Management:
 For Pts. presenting within 1 hr.:
• Gastric lavage;
• Activated charcoal (one stat dose of 1 g/kg within 4 hrs. of
ingestion);
 Acetylcysteine (IV or oral) – if paracetamol concs. are above
toxic levels;
 Patients on enzyme-inducing drugs (CBZ, phenobarbitone,
phenytoin, rifampicin, etc.) can develop toxicity at lower
plasma paracetamol concs. They should be administered
acetylcysteine if plasma paracetamol concs. are > 50%
of the std. ref. values.
 For max. hepatoprotective effect, initiate Tx within 8-10
hrs. post-ingestion.

23.  Tx should be stopped if the conc. falls below the treatment line.
 Acetylcysteine IV: Continuous Infusion in D5%
1) 150 mg/kg in 200 ml over 15 mins., followed by
2) 50 mg/kg in 500 ml over 4 hrs., then followed by
3) 100 mg/kg in 1000 ml over 16 hrs.
 Acetylcysteine oral: 140 mg/kg stat, followed by 70 mg/kg Q4H
for 17 additional doses;
 Pts. w/ hepatic failure may require longer duration of admn.
( > 72 hrs.); Oral preparation may be more useful; End points
are clinical improvement and INR < 2.0

24.  Acetylcysteine should be used with caution in asthmatic
patients as it can induce bronchospasm.
Indications for acetylcysteine:
 Pt. ingested > 150 mg/kg paracetamol;
 Pt. has Hx of excessive ingestion of paracetamol.
 Sr. paracetamol cannot be done or is not available within 8 hrs.
 Pt. w/ unknown ingestion time, and Sr. paracetamol level > 10
mcg/ml;
 Lab evidence of hepatotoxicity (AST or ALT > 1000 IU/L);

25. Side effects:
If flushing: Can continue acetylcysteine infusion;
If urticaria: Stop the infusion;
Treat w/ IV antihistamine;
Restart infusion once symptoms resolve;
Hypotension or respiratory symptoms: Switch from
IV form to oral acetylcysteine;

26. Nomogram for paracetamol intoxication

27. THE END