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Paracetamol poisoning: reduction of adverse effects from a 12 h modified Acetylcysteine regimen

Paracetamol ( Acetaminophen ) poisoning is common worldwide. It is treated with intravenous Acetylcysteine, but the standard regimen is complex and associated with frequent adverse effects related to concentration, which can cause treatment interruption.
The aim of a study was to ascertain whether adverse effects could be reduced with either a shorter modified Acetylcysteine schedule, antiemetic pretreatment, or both.

Researchers undertook a double-blind, randomised factorial study at three UK hospitals, during the period 2010-2012.
Patients with acute Paracetamol overdose were randomly allocated to either the standard intravenous Acetylcysteine regimen ( duration 20.25 h ) or a shorter ( 12 h ) modified protocol, with or without intravenous Ondansetron ( Zofran ) pretreatment ( 4 mg ).
Masking was achieved by infusion of 5% Dextrose ( during Acetylcysteine delivery ) or saline ( for antiemetic pretreatment ).

The primary outcome was absence of vomiting, retching, or need for rescue antiemetic treatment at 2 h.
Prespecified secondary outcomes included a greater than 50% increase in alanine aminotransferase activity over the admission value.

Analysis was by intention to treat.

Of 222 patients who underwent randomisation, 217 were assessable 2 h after the start of Acetylcysteine treatment. Vomiting, retching, or need for rescue antiemetic treatment at 2 h was reported in 39 of 108 patients assigned to the shorter modified protocol compared with 71 of 109 allocated to the standard Acetylcysteine regimen ( adjusted odds ratio, OR=0.26; p less than 0.0001 ), and in 45 of 109 patients who received Ondansetron compared with 65 of 108 allocated placebo ( OR=0.41; p=0.003 ).

Severe anaphylactoid reactions were recorded in five patients assigned to the shorter modified Acetylcysteine regimen versus 31 who were allocated to the standard protocol ( adjusted common odds ratio, OR=0.23; p less than 0.0001 ).

The proportion of patients with a 50% increase in alanine aminotransferase activity did not differ between the standard ( 9/110 ) and shorter modified ( 13/112 ) regimens ( adjusted odds ratio, OR=0.60 ); however, the proportion was higher with Ondansetron ( 16/111 ) than with placebo ( 6/111; OR=3.30; p=0.024 ).

In patients with Paracetamol poisoning, a 12 h modified Acetylcysteine regimen resulted in less vomiting, fewer anaphylactoid reactions, and reduced need for treatment interruption. T
his study was not powered to detect non-inferiority of the shorter protocol versus the standard approach; therefore, further research is needed to confirm the efficacy of the 12 h modified Acetylcysteine regimen. ( Xagena )

Bateman N et al, The Lancet 2014; 383: 697-704