🩺 THIS WEEK IN EM
Acetaminophen Overdose: For Selected Low-Risk Patients, 12 Hours of NAC May Be Enough
Most of us were trained to think of intravenous N-acetylcysteine as a fixed ritual: once you start it, you run the whole course. The newer acetaminophen literature is starting to chip away at that reflex. The key phrase is not "everyone gets less NAC." The key phrase is "selected low-risk patients."
The 2026 NACSTOP 2 trial tested that question directly. Patients who required acetylcysteine for single or staggered paracetamol ingestion were eligible for randomization only if their ALT was below 40 IU/L on presentation and, after 12 hours of treatment, their ALT remained below 40 IU/L and their paracetamol concentration was below 20 mg/L. In other words, this was not a "let's stop early and hope" study. It was a carefully selected group that had already declared itself low risk on serial labs.
Among the 186 patients randomized across six Australian emergency departments, the abbreviated strategy was non-inferior to finishing the standard 20-hour two-bag regimen. Median ALT change at 20 hours was essentially the same in both groups, and no patients developed hepatic injury or hepatotoxicity. That is a meaningful result because it challenges the idea that a clean, improving low-risk overdose patient automatically benefits from the back half of the infusion simply because tradition says so.
The trap is overgeneralizing it. NACSTOP 2 does not give you permission to abbreviate treatment in every overdose. The trial excluded modified-release ingestions, supratherapeutic repeat ingestions, pregnancy, pre-existing liver disease, and patients whose 12-hour labs were not clean. If the ALT is rising, the acetaminophen level is still above 20 mg/L after 12 hours, the history is messy, or the ingestion pattern is not the straightforward low-risk profile studied here, the full course still matters.
Bottom line: NACSTOP 2 suggests that if a patient looks low risk both clinically and biochemically after 12 hours of a two-bag NAC regimen, finishing the full 20-hour infusion may not buy additional benefit — but this should not be extrapolated to modified-release ingestions, repeat supratherapeutic overdoses, abnormal 12-hour labs, or other higher-risk poisonings.
Wong A, McNulty R, Hodgson SE, Gunja N, Graudins A. Early Cessation of Acetylcysteine Treatment After Paracetamol Overdose (NACSTOP 2): A Non-Inferiority Randomised Controlled Trial. Med J Aust. 2026. doi:10.5694/mja2.70114.
TBI Osmotherapy: Better ICP Numbers Are Not the Same as Better Brains
The hypertonic saline versus mannitol argument has been around so long that people often talk about it as if the outcome data are already settled. They are not. What is settled is that both are used to manage intracranial hypertension. What remains unsettled is whether either strategy improves the outcomes families actually care about.
The most important randomized paper in this lane is still COBI. In that 2021 multicenter trial, 370 adults with moderate to severe traumatic brain injury were randomized to continuous 20% hypertonic saline plus standard care or standard care alone. The primary outcome was 6-month neurological status by the Extended Glasgow Outcome Scale. The result was blunt: no significant difference. The adjusted common odds ratio for better neurological outcome was 1.02, and the confidence interval crossed comfortably through no effect.
That matters because it forces a distinction emergency clinicians do not always make cleanly enough. Hyperosmolar therapy can be useful for managing intracranial pressure. It does not follow that it has proven long-term neurological benefit. COBI also was not an ED bolus trial. It studied continuous ICU hypertonic saline infusion, so it does not answer every bedside question about which rescue agent to push first in a crashing herniation patient. But it absolutely does puncture the idea that hypertonic saline has already earned a randomized long-term outcome win.
The practical read is uncomfortable but honest. If your patient is actively herniating, you still treat the ICP problem in front of you. That is not in doubt. But when we talk about hypertonic saline versus mannitol as though one of them is clearly delivering better brains months later, we are saying more than the evidence supports. The physiologic argument is stronger than the outcome argument.
Bottom line: In traumatic brain injury, osmotherapy remains a tool for acute intracranial pressure management, not a therapy with proven randomized long-term neurological benefit — and COBI is the paper that makes that limitation impossible to ignore.
Roquilly A, Moyer JD, Huet O, et al. Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial. JAMA. 2021;325(20):2056-2066. doi:10.1001/jama.2021.5561.
Pediatric Appendicitis: Antibiotics-First Is Real, But Surgery Still Wins
The idea of treating uncomplicated appendicitis in children with antibiotics alone has obvious appeal. Avoid anesthesia, avoid the OR, avoid an operation in a child who might get better without one. The question has never been whether it is possible. The question is whether it performs well enough to replace appendicectomy as the default.
The 2025 Lancet trial by St. Peter and colleagues gave the cleanest answer yet. Across 11 children's hospitals in five countries, 936 children aged 5 to 16 years with suspected non-perforated appendicitis were randomized to antibiotics or appendicectomy. At 12 months, treatment failure occurred in about 34% of the antibiotic group and 7% of the appendicectomy group. With a prespecified 20% non-inferiority margin, antibiotics-first did not make the cut. Surgery remained the more reliable strategy.
That does not mean antibiotics-first is fake or reckless. It means the tradeoff needs to be described honestly. Many children in the antibiotic arm did avoid surgery over the following year. But roughly one in three ultimately failed that strategy, which is too high to pretend antibiotics and appendicectomy are interchangeable. "Non-operative management is an option" is not the same as "non-operative management matches surgery."
For the ED, this is mostly a framing correction. If a well-informed family strongly prefers trying antibiotics first, that conversation is legitimate. But if you are counseling them as though the evidence now shows equivalence, you are overselling it. The best randomized pediatric trial we have says surgery is still the more dependable endpoint.
Bottom line: Antibiotics-first for uncomplicated pediatric appendicitis is a real option, but the strongest randomized pediatric data still favor appendicectomy as the more reliable treatment, with about one-third of children in the antibiotic arm ultimately meeting criteria for failure within a year.
St. Peter SD, Noel-MacDonnell JR, Hall NJ, et al. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial. Lancet. 2025;405(10474):233-240. doi:10.1016/S0140-6736(24)02420-6.
🔭 Next Week
Prehospital whole blood in traumatic hemorrhage: whether the survival advantage is finally real, or whether the enthusiasm is still ahead of the outcome data
Pregnancy pulmonary embolism workup: how much imaging you can safely avoid, and whether D-dimer and ultrasound deserve a bigger role than many EDs give them
Video EMS dispatch: whether letting dispatch actually see the scene changes triage, transport decisions, and who really needs the highest-urgency response
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— The Hallway Consult team