September 2019

Authors: Becky Maxwell, Andy Neill, Felipe Dhawahir, Sarah Edwards, Dave McCreary, Anu Mitra / Codes: / Published: 01/09/2019

Clinical Question
– are antiplalet agents or anticoagulation better in treatment of cervical artery dissection

– Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection. The Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results

– Markus, JAMA Neurology 2019

– cervical artery dissections cause about 2% of strokes overall. There’s probably a higher prevalence in young people and those who do weight lifting followed by daily chiropractic sessions
– the disruption in the vessel wall leads to thrombosis and embolism so making the blood a bit thinner probably helps. Up till now it’s been unclear whether to give some antiplatelets or anticogaulants and i’ve seen people use either

– multi centre RCT in UK and Oz
– had to have definite or probably dissection on CT, MR or even by ultrasound
randomised to 3 months treatment. agent used was locally determined though no DOACs were used
– open label
– in person follow up at 3 months (note in the tpa trials this is rarely done…)
– primary outcome was ipsilateral stroke or death at 3 months
– this was a phase 2 trial so there was no power calculation – they just set it at 250 patients

– 250 patients
– mean time at randomisation was 3 days (so probably not a resus room decision…)
– average age of 50 (these are young strokes) with a quarter having some kind of history of trauma to the head or neck in the past month
– reasonably even split between vertebrals and carotids
– vast majority presented with stroke and a few with TIAs and a much smaller number with headache, neck pain and Horner’s syndrome
– interesting that the vast majority had their anticoagulation stopped as soon as the 3 month period was up which gives you a sense of what the pre trial opinion was
– at 3 months (primary outcome) 3 had a stroke in the antiplatelet group and 1 had a stroke in the anticoagulant group.
– nothing really changed as time went on
– a single intracranial extension and bleed on an anticoagulated patient (remember that intracranial dissections are a very different beast to extracranial dissections. The lack of a “media” in the vessel wall make them very likely to bleed and even present with ICH, H/T Frank Gaillard and Radiopaedia).

– the stroke recurrence rate here was much lower than previously reported (good news for patients) so it’s not surprising that there was no difference between the treatment arms.
– antiplatelets on their own are probably fine but whether that’s dual, single and what combination this trial can tell us nothing as the docs did what they wanted here

Interviewee: Mr Felipe Dhawahir-Scala
Interviewer: Sarah Edwards

Mr Felipe Dhawahir-Scala is a Vitroretinal Surgeon and director of Acute Ophthalmic services at Manchester Royal Eye Hospital

In this talk he gives an overview of Emergency ophthalmology including:
The things that ophthalmology are less keen to see
The things that ophthalmology will need to get out of bed for
Along with some tips and tricks along the way


Dave McCreary
Andy Neill

Clinical Question:

Can low-risk paracetamol overdose patients be treated in 12 hours instead of 20?

Title of Paper:

The NACSTOP trial: A multi-centre, cluster-controlled trial of early cessation of acetylcysteine in acetaminophen overdose

Journal and Year:

Hepatology. Feb 2019.

Lead Author:

Anselm Wong


* Paracetamol is a very common drug of overdose

* Anyone at risk of hepatotoxicity following paracetamol overdose gets treated with N-Acetylcysteine 300mg/kg over 21hours

* Previously this was 20 hours but the initial infusion has been slowed from 15 minutes to 1 hour following evidence that it reduced side effects of rapid initial bolts dose

* Currently, once youre on the treatment pathway, youre on it

* Depending on where you work this involves either a short stay unit or more commonly a hospital inpatient admission

* Recent studies have shown patients with normal LFTs at the start of treatment are unlikely to develop hepatotoxcity

* Another study showed that very few patients developed hepatotoxicity when their regime was stopped early given it was: 1) Started within 8 hours of ingestion and 2) at least 200mg/kg had been administered

* The 20 hour regimen was recommended in the 1970s, based on the elimination of paracetamol (5 half-lives) and when level measurement was less readily available in most hospitals

Study Design:

* Multi-centre, cluster-controlled open-label trial

Patients Studied:

* 16 years old

* Acute single or staggered paracetamol ingestion requiring NAC (level >150mg/L at 4 hour treatment nomogram line)

* Normal ALT on presentation at after 12 hours of NAC

* Serum paracetamol level < 20mg/L (upper limit of therapeutic concentration) after 12 hours of NAC

* Normal serum creatinine on presentation and after 12 hours of NAC


* NAC 200mg_kg over 4 hours followed by 6.25mg_kg/hr for 8 hours then 1L Ringers Lactate over 8 hours

* Total of 250mg/kg NAC


* NAC 200mg_kg over 4 hours follow by 6.25mg_kg/hr for 16 hours

* Total of 300mg/kg NAC


* Primary: incidence of hepatic injury at 20 hours post initiation of NAC

* Defined as ALT doubling and peak ALT >100 IU/L

* Secondary:

* Incidence of hepatotoxicity (peak ALT 1000 IU/L), change in ALT, peak INR, adverse reactions to NAC.

Summary of Results:

* 1411 paracetamol overdoses across 6 sites

* 449 got NAC

* 100 subjects enrolled (50 intervention, 50 control)

* Primary: No subjects showed hepatic injury (OR 1.0)

* Secondary:

* No difference in 20-hour ALT

* Median 18 (intervention) vs 16 (control)

* No subject had doubling of ALT

* No difference in 20-hour creatinine

* No subjects developed hepatotoxicity, received a liver transplant or died

* No difference in INR

Authors Conclusion:

An abbreviated 12-hour acetylcysteine regimen is feasible and likely safe in selected patients at low risk of liver injury from acetaminophen overdose based on laboratory testing after 12 hours of treatment.

Clinical Bottom Line:

This is a preliminary trial that will hopefully be used to prove safety and allow a larger RCT to confirm the results, so guidelines arent going to change just yet. Still, I think its interesting to consider the serial testing as a means of predicting which or your patients at 12 hours are most likely to be medically cleared at 24 hours, and at a push this could help decision making with patients who want to self discharge after a shorter NAC course.

Leave a Reply