Fifteen-minute update: International normalised ratio as the treatment end point in children with acute paracetamol poisoning

2021 ◽  
pp. edpract-2020-320190
Author(s):  
Kavinda Dayasiri ◽  
Sahana Rao
Keyword(s):  
Alanine Transaminase ◽  
Paracetamol Poisoning ◽  
Clotting Factors ◽  
Hepatocellular Damage ◽  
Asymptomatic Children ◽  
International Normalised Ratio ◽  
Acetyl Cysteine ◽  
The Uk ◽  
Reduced Activity ◽  
Persistent Elevation

Paracetamol is one of the most frequent reasons for poisonings across the UK with an estimated 90,000 patients and 150 deaths annually. International normalised ratio (INR) may be elevated due to hepatocellular damage and is frequently used to monitor progress on N-acetyl cysteine. N-acetyl cysteine is associated with reduced activity of vitamin K dependent clotting factors leading to a benign elevation of INR. In asymptomatic children with normal aspartate transaminase/alanine transaminase, isolated borderline elevation of INR following paracetamol overdose should be reviewed for possible N-acetyl cysteine induced elevation of INR. Due to these factors, in those with borderline persistent elevation of INR, N-acetyl cysteine can be safety stopped if INR is falling on two or more consecutive tests and is <3.0.

Thromboplastin Related Differences in the Determination of International Normalised Ratio: A Cause for Concern?

1994 ◽  
Vol 72 (03) ◽  
pp. 426-429 ◽  
Author(s):  
S Kitchen ◽  
I D Walker ◽  
T A L Woods ◽  
F E Preston
Keyword(s):  
Patient Management ◽  
External Quality Assessment ◽  
Oral Anticoagulant Therapy ◽  
Warfarin Dosage ◽  
External Quality ◽  
External Quality Assessment Scheme ◽  
International Normalised Ratio ◽  
The Uk ◽  
The Relationship

SummaryWhen the International Normalised Ratio (INR) is used for control of oral anticoagulant therapy the same result should be obtained irrespective of the laboratory reagent used. However, in the UK National External Quality Assessment Scheme (NEQAS) for Blood Coagulation INRs determined using different reagents have been significantly different.For 18 NEQAS samples Manchester Reagent (MR) was associated with significantly lower INRs than those obtained using Diagen Activated (DA, p = 0.0004) or Instrumentation Laboratory PT-Fib HS (IL, p = 0.0001). Mean INRs for this group were 3.15, 3.61, and 3.65 for MR, DA, and IL respectively. For 61 fresh samples from warfarin-ised patients with INRs of greater than 3.0 the relationship between thromboplastins in respect of INR was similar to that observed for NEQAS data. Thus INRs obtained with MR were significantly lower than with DA or IL (p <0.0001). Mean INRs for this group were 4.01, 4.40, and 4.59 for MR, DA, and IL respectively.We conclude that the differences between INRs measured with the thromboplastins studied here are sufficiently great to influence patient management through warfarin dosage schedules, particularly in the upper therapeutic range of INR. There is clearly a need to address the issues responsible for the observed discrepancies.

Prothrombin time prolongation in paracetamol poisoning: a relevant marker of hepatic failure?

2003 ◽  
Vol 22 (11) ◽  
pp. 617-621 ◽  
Author(s):  
C Payen ◽  
A Dachraoui ◽  
C Pulce ◽  
J Descotes
Keyword(s):  
Liver Failure ◽  
Prothrombin Time ◽  
Vitamin K ◽  
Hepatic Failure ◽  
Paracetamol Overdose ◽  
Paracetamol Poisoning ◽  
Clotting Factors ◽  
Prolonged Prothrombin Time ◽  
Few Data

The association between paracetamol overdose and prolonged prothrombin time due to hepatic failure is well recognized. However, little is known of the possibility that paracetamol overdose can prolong the prothrombin time without overt hepatic failure. The few data from the literature suggest this is either due to a reduction in the functional levels of the vitamin K-dependent clotting factors by elevated doses of paracetamol, or a consequence of the administration of the antidote N-acetylcystein. The three reported cases provide further evidence that paracetamol overdose can be associated with a prolongation in the prothrombin time without overt hepatic failure. Even though the prothrombin time provides useful prognosis information, decisions regarding the management of these patients should not solely be based on this endpoint to avoid misinterpretation of the accuracy and the severity of liver failure.

Epidemiology of Analgesic Overdose in England and Wales

1984 ◽  
Vol 3 (1_suppl) ◽  
pp. 61s-74S ◽  
Author(s):  
T.J. Meredith ◽  
J.A. Vale
Keyword(s):  
Carbon Monoxide ◽  
Northern Ireland ◽  
Hospital Admissions ◽  
Acute Poisoning ◽  
Paracetamol Poisoning ◽  
England And Wales ◽  
Analgesic Drugs ◽  
Salicylate Intoxication ◽  
The Uk ◽  
Hospital Use

1 The number of deaths from acute poisoning in England and Wales has remained constant at approximately 4000 per annum for the last 10 years despite major changes in the agents responsible. Deaths due to carbon monoxide and barbiturate and non-barbiturate hypnotics have fallen, while those due to psychotropic and analgesic drugs have risen. 2 The number of hospital admissions in England and Wales due to analgesics taken in overdose has risen from 15 940 in 1968 to 24 930 in 1980, with aspirin and paracetamol being the preparations most commonly ingested. Currently, the mortality from salicylate intoxication is falling while that due to paracetamol is rising. In 1980, the Office of Population Censuses and Surveys recorded 790 deaths from analgesic poisoning, of which 181 were due to salicylates and 152 to paracetamol alone. A further 269 deaths were attributed to paracetamol and dextropropoxyphene, and an additional 132 deaths were thought to be due to paracetamol in combination with other drugs. 3 An important factor in the changing mortality from salicylate and paracetamol poisoning is the trend observed in the sales and usage of these agents. Since 1979, the number of analgesic tablets containing aspirin sold in the UK (except Northern Ireland), excluding hospital use, has fallen by 326 x 106, while sales of those containing paracetamol have increased by 395 × 106 tablets.

Effect of paracetamol poisoning on international normalised ratio

The Lancet ◽  
2003 ◽  
Vol 361 (9355) ◽  
pp. 429-430 ◽  
Author(s):  
Lars E Schmidt ◽  
Tore Tveit Knudsen ◽  
Kim Dalhoff ◽  
Flemming Bendtsen
Keyword(s):  
Paracetamol Poisoning ◽  
International Normalised Ratio

Isolated persistent elevation of alanine transaminase for early diagnosis of pre-symptomatic Wilson’s disease in Chinese children

2013 ◽  
Vol 9 (4) ◽  
pp. 361-364 ◽  
Author(s):  
Joannie Hui ◽  
Yuet-Ping Yuen ◽  
Chung-Mo Chow ◽  
Josephine Chong ◽  
Grace Chiang ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Alanine Transaminase ◽  
Chinese Children ◽  
Persistent Elevation

Improvements in the packaging of drugs and chemicals may reduce the likelihood of severe intentional poisonings in adults

2000 ◽  
Vol 19 (7) ◽  
pp. 387-391 ◽  
Author(s):  
T YK Chan
Keyword(s):  
Methyl Salicylate ◽  
Marked Decrease ◽  
Rapid Onset ◽  
Pulmonary Aspiration ◽  
Paracetamol Poisoning ◽  
Severe Liver ◽  
Salicylate Poisoning ◽  
Severe Liver Damage ◽  
Time Required ◽  
The Uk

Because of the inconvenience and longer time required to punch out the tablets, strip packaging may reduce the number of tablets that can be readily swallowed by adults with self-poisonings. In fact, hospital-based studies of paracetamol poisoning in the U.K. and Hong Kong have shown that blister packs were associated with fewer tablets being ingested and large overdoses were mostly from loose preparations. In Australia, following the change in packa-ging for carbamazepine from bottles of tablets to blister packs, a marked decrease in the reported number of tablets ingested by patients was seen. Reducing the maximum number of tablets that can be available in individual preparations or prescriptions may also reduce the likelihood of severe poisonings. In France, but not in the UK, the content of each pack of paracetamol has been legally limited to 8 g. This was thought to be one reason why severe liver damage and deaths after paracetamol poisonings are less common in France than in the UK. Medicated oils containing methyl salicylate pose the threat of rapid-onset, severe salicylate poisoning if swallowed. To reduce the amount of methyl salicylate that can be readily swallowed, the methyl salicylate content and the size of the bottle and its opening should be restricted. In adults with Dettol poisoning, serious complications such as pulmonary aspiration are more likely if a large amount is ingested. Similarly, the risk may be reduced by restricting the size of bottle and its opening.

scholarly journals Effect of the UK 's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment

2014 ◽  
Vol 78 (3) ◽  
pp. 610-618 ◽  
Author(s):  
D. Nicholas Bateman ◽  
Robert Carroll ◽  
Janice Pettie ◽  
Takahiro Yamamoto ◽  
Muhammad E. M. O. Elamin ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Paracetamol Poisoning ◽  
Management Guidelines ◽  
Costs Of Treatment ◽  
The Uk

MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose

2019 ◽  
Vol 38 (6) ◽  
pp. 646-654 ◽  
Author(s):  
A Wong ◽  
C Nejad ◽  
M Gantier ◽  
KW Choy ◽  
James Doery ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Alanine Transaminase ◽  
Paracetamol Overdose ◽  
Paracetamol Poisoning ◽  
Control Groups ◽  
Treatment Groups ◽  
Significant Difference ◽  
Risk Patients ◽  
And Control

Paracetamol overdose is common and microRNA (miR)-122 expression is increased with liver injury. We aimed to measure miR-122 in the setting of an abbreviated paracetamol overdose treatment regimen. We compared miRNA expression in patients treated for paracetamol poisoning with an abbreviated 12-h intravenous acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) or a 20-h regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) (NACSTOP trial). miR-122 expression is increased (decreased cycle threshold (Ct) values) with paracetamol liver injury. We assessed miR-122 expression in patients receiving the two acetylcysteine regimens and in a separate group with acute liver injury (ALI). We examined 121 blood samples in 38 patients. After 20 h of acetylcysteine, median alanine transaminase (ALT) was 12 U/L (18, 14) versus 16 U/L (11, 21) ( p = 0.17) and median miR-122 Ct was 30.1 (interquartile range (IQR): 28.9, 33.3) versus 31.4 (28.9, 33.9) ( p = 0.7) in the NACSTOP abbreviated and control groups, respectively. Median normalized miR-122 Ct after 20 h of acetylcysteine was 2.2 (IQR 1.9, 6.4), 1.1 (0.7, 2.9), 63.9 (2.5, 168), 123.2 (40.9, 207.8) in the NACSTOP-abbreviated, NACSTOP-control, ALI and hepatotoxicity groups, respectively. There was no significant difference in ALT or miRNA between NACSTOP treatment groups and no signal of increased liver injury from an abbreviated 12-h acetylcysteine regimen. These findings suggest that an abbreviated acetylcysteine regimen in low-risk patients who have overdosed on paracetamol is safe. Further study is required to validate this finding utilizing miRNA as a comparative biomarker.

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