BURDEN OF

POISONING IN TUTH
ER

&
JUNIOR INTERNS

GROUP B2
PCM POISONING
ROLL: 1783-1789
 OBJECTIVES

• Enlist total amount of poisoning cases and the types in months

of Mangsir to Magh, 2079.

• Discuss epidemiology, pharmacology, manifestations and

management of PCM poisoning.
 TOTAL POISONING AND TYPES

30 28

25
Number of Cases

20
17
15
15
10
10 8
5 5 5 4 4
5 3 2 3
2 1 2 2 2 1 1 2
0 0 0 0 0 0 0 0 0
0
OP Alcohol ZnP AlP PCM CO Others Unknown Total Death
Poisoning
Cases

Types of Poisoning

Mangsir Poush Magh

Proportion of Various Poisonings

12
18

6 5
2 6
5
OP Alcohol ZnP AlP
PCM CO Others Unknown
 PARACETAMOL POISONING

•Acetaminophen, APAP, N-acetyl-p-aminophenol.

•Widespread availability
•Intentional ingestions.
•Repeated supratherapeutic dosing.
•Prescription drug abuse.
•Use by alcoholic patients.
•APAP-Opioid combination products
 LIMITS OF SAFETY

• Maximum total daily dose recommended in adults 1:

• 3900 mg using 325-mg APAP (regular strength)
• 3000 mg using 500-mg APAP (extra strength) preparation.

• Maximum total daily dose recommended in children 1:

• 75 mg/kg
• 10-15mg/kg every 4 to 6 hours as needed.

1
Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 9e Eds. Judith E. Tintinalli, et al. McGraw Hill, 2020.
 LIMITS OF SAFETY

• Single Doses of APAP > 7 to 10 g ( 140 mg/kg body weight in children) :

Liver Injury 2
• Severe Liver Injury (ALT > 1000 U/L) or fatal cases : at least 15 to 25 g 2
INTER-INDIVIDUAL VARIABILITY
• Untreated APAP toxicity 2 :
• Severe Liver Injury in 20%
• Mortality rate of 20% in those with Severe Liver Injury.
2
Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Ed. Feldman et. al., Elsevier, 2021
 LIMITS OF SAFETY

• Heavy Drinker: daily APAP doses of 2-6 g a/w fatal hepatotoxicity. 2

• Concomitant use of Phenobarbitone/Phenytoin/INH/Zidovudine:

increase risk of hepatotoxicity

2
Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Ed. Feldman et. al., Elsevier, 2021
METABOLISM

Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 9e Eds. Judith E. Tintinalli, et al. McGraw Hill, 2020.
PATHOLOGY

Source: Frontiers in Physiology

 THE FOUR STAGES

Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 9e Eds. Judith E. Tintinalli, et al. McGraw Hill, 2020.
 RISK FACTORS FOR APAP-INDUCED
HEPATOTOXICITY
FACTORS RELEVANCE
Age Children more resistant than adults
DOSE Minimal Hepatotoxic dose: 7-10 gm (adults); 150mg/kg in children
Severe Toxicity with dose >15g

Blood Levels of APAP Influenced by dose, time after ingestion, gastric emptying.
Best indicator of risk of hepatotoxicity.

Chronic Excessive Alcohol Ingestion Toxic threshold is lowered; worsens prognosis (also related to related presentation);
nephrotoxicity common.

Fasting Toxic threshold is lowered – therapeutic misadventure

Concomitant medication Toxic threshold is lowered – therapeutic misadventure

Time of Presentation Late presentation or delayed treatment (>16 hrs) predicts worse outcome
THE TREND

Rosen's Emergency Medicine: Concepts and Clinical Practice, 9 th ed. Hockberger et al., Elsevier, 2018
RUMMACK
MATTHEW
NORMOGRAM

Goldfrank’s Toxicological Emergencies, 11th Ed. Nelson

et. al., McGraw Hill, 2019
 ABCs
GI DECONTAMINATION
MANAGEMENT N-ACETYL CYSTEINE
SYMPTOMATIC MANAGEMENT
EXTRACORPOREAL ELIMINATION
LIVER TRANSPLANTATION
N-ACETYL
CYSTEINE

Goldfrank’s Toxicological Emergencies, 11 th Ed. Nelson et. al., McGraw Hill, 2019
MANAGEMENT
ALGORITHM

STANDARD TREATMENT PROTOCOL OF EMERGENCY

HEALTH SERVICE PACKAGE, MoHP.
MANAGEMENT
ALGORITHM

Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 9e Eds. Judith E. Tintinalli, et al. McGraw Hill, 2020.
Rosen's Emergency Medicine: Concepts and Clinical Practice, 9 th ed. Hockberger et al., Elsevier, 2018
 PREDICTORS OF POOR OUTCOMES

Rosen's Emergency Medicine: Concepts and Clinical Practice, 9 th ed. Hockberger et al., Elsevier, 2018
 PREDICTORS OF POOR OUTCOMES

• Grade 4 HE
• Acidosis
• Severe and Sustained impairment of coagulation factor
synthesis
• Falling ALT levels + Worsening PT
• Renal Failure
• Myocardial Injury
• Skin/ Lung involvement in APAP hypersensitivity.
Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Ed. Feldman et. al., Elsevier, 2021
 MORTALITY

• 4-18 days after overdose.

• Cerebral edema and sepsis complicating hepatic and Multiorgan failure.

• Majority recover completely.

2
Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Ed. Feldman et. al., Elsevier, 2021
 TAKE HOME POINTS

• Intentional overdoses or repeated supratherapeutic overdoses.

• APAP Concentration at normogram at 4 hours or more post-ingestion determines NAC therapy.
• IV NAC > PO NAC
• Once it is initiated, NAC is continued until completing the NAC Protocol and there is no
evidence of liver injury and clearance of APAP.
• For max. benefit, NAC not delayed beyond 8 hours after ingestion. If more than 8 hours has
passed since ingestion, treatment started with assessment of amount of ingestion (serial APAP
levels) and likelihood of hepatotoxicity (elevated transaminases, coagulopathy, encephalopathy)
• Late or prolonged NAC is beneficial even with low or absent APAP concentration if
hepatotoxicity is evident.
• NAC safe in pregnancy.
 BIBLIOGRAPHY

• Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 9e Eds. Judith E. Tintinalli, et

al. McGraw Hill, 2020.

• Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Ed. Feldman et. al., Elsevier, 2021.

• Rosen's Emergency Medicine: Concepts and Clinical Practice, 9 th ed. Hockberger et al., Elsevier, 2018

• Goldfrank’s Toxicological Emergencies, 11th Ed. Nelson et. al., McGraw Hill, 2019

• Standard Treatment Protocol Of Emergency Health Service Package, MoHP.

• UpToDate
THANK YOU