Every year, the volume of published research continues to outpace capacity to consume. “Gotta catch ‘em all!” may be an appealing mantra, however it is impracticable to achieve with the medical literature. The Sisyphean task remains to try to keep up—and, in that vein—here is a light round of the emergency medicine literature from 2023.

How Best to Stop the Bleeding in Trauma?

All bleeding stops. The delicate trick is to stop the bleeding before the patient dies, while also simultaneously not tilting the coagulation cascade too far in the direction of excessive clotting.

The past decade has seen the ubiquitous rise of tranexamic acid (TXA), for use in nearly all types of bleeding. Many of the trials testing TXA, however, have been performed in low-resource settings, potentially limiting generalizability. The PATCH-Trauma trial took a critical look at TXA in major trauma in the advanced trauma systems of Australia and found a mixed result: a slightly greater number of patients were still alive six months following TXA administration, but there was no difference in survival with a good functional outcome.¹ Yet another typically narrow result to add to the body of evidence surrounding TXA.

Asking the question, “Wouldn’t it be better to get ahead of the curve, rather constantly play catch-up to replete factor derangement associated with major bleeding?” A trial tested whether it would be fruitful to pre-emptively infuse four-factor prothrombin concentrate complexes (PCCs).² The brief answer from the “PROAG” trial in France is “no.” Empiric PCC infusion was associated only with increased pro-thrombotic events without corresponding witnessed benefits. In a similar vein, “CRYOSTAT-2” tested whether routinely adding cryoprecipitate to massive transfusion protocols improved all-cause mortality.³ In this instance, there was neither benefit nor harm.

What’s New in Stroke Care?

Adding further to the body of literature telling us tenecteplase is an entirely valid alternative to alteplase, we have “TRACE-2.”⁴ Repeated trials have not shown alteplase to have any signal of better outcomes, nor tenecteplase to have an association with increased adverse events. TRACE-2 continues to demonstrate these observations. The simplicity of tenecteplase administration makes its use likely the preferred agent for treating acute ischemic stroke.

Tackling the age-old question: “we can administer thrombolytics to everyone, right?” the “ARAMIS” trial throws up another red flag for patients suffering mild stroke.⁵ In this randomized controlled trial enrolling patients with non-disabling stroke, dual antiplatelet therapy provided better outcomes for patients than thrombolytics, while avoiding excess symptomatic intracranial hemorrhage. These results do not generalize to mild, disabling stroke.

In contrast, more is almost certainly better when treating devastating large-vessel occlusions (LVO). Early trials testing endovascular treatment of LVO enrolled primarily patients with very small core infarcts surrounded by large viable penumbra. The “SELECT-2” trial looked at occlusions of the internal carotid and proximal middle cerebral artery resulting in larger core infarcts.⁶ The outcomes were dismal whether treated with endovascular therapy or conservative medical care, but 20 percent achieved a modified Rankin score of 0 to 2 with the former, compared with only seven percent of the latter.

The Right Way to Airway

Video largyngoscopy (VL) is simply, in most situations, the better tool for the job. Expertise with direct visualization is still necessary, but the “DEVICE” trial adds another feather to the cap favoring VL.⁷ The operators involved in the trial were mostly emergency medicine residents or critical care fellows, but this fact does not diminish the generalizability of these observations. Many clinicians staffing emergency departments intubate infrequently, as well, and these results are likely applicable to a wide scope of practice.

More commonly asked than how to intubate, the more challenging question is whether to intubate. It may be conveniently glib to base clinical practice on the charming rhyme of “less than eight, intubate,” but accumulated wisdom teaches many patients with depressed Glasgow coma scores (GCS) improve spontaneously without adverse consequences. Now, a randomized, controlled trial clearly demonstrates some patients with low GCS are far more likely to be harmed by an aggressive approach to airway management.⁸ Enrolling patients with depressed GCS thought to be from substance abuse and misuse, including nearly a quarter in each cohort with GCS 3, a conservative approach to airway management avoided both intubation-related risks and intensive care unit admissions.

Finally, the “EXACT” trial examined whether, in patients with return of spontaneous circulation after an out of hospital cardiac arrest, a peripheral oxygenation target of 90–94 percent conferred a survival benefit, as compared with the typical 98–100 percent.⁹ Unfortunately, this trial can be added to the heap of things ruined by the COVID-19 pandemic, as the arrival of COVID necessitated early termination. Only 425 of the planned 1,416 were enrolled, leaving the primary and secondary outcomes grossly imprecise. Survival to hospital discharge favored the “standard care” group, 47.9 percent to 38.3 percent, leaving little chance the lower oxygen target would have become a preferred strategy.

A Myriad of Infectious Disease Papers

The use of steroids in severe sepsis remains challenging, primarily as proper patient selection is necessary to tease out those with the greatest likelihood of benefit. One consistent signal for potential benefit has been community-acquired pneumonia, and the “CAPE COD” trial very clearly identifies those patients admitted to the intensive care unit as candidates for steroids.¹⁰ The trial was stopped due to superiority due to both its overall mortality benefit, as well as a reduction in the need for mechanical ventilation.

As much as we rely upon life-saving antibiotics, we must heed the stewardship nannies and their ever-important mission of harm reduction. Unfortunately, when the prevailing interest is preventing poor acute patient outcomes, prudent antibiotic prescribing falls by the wayside. A randomized controlled trial from the primary care literature attempts to gently reduce excess prescribing with personalized feedback and peer comparison—and fails.¹¹ It is absolutely possible to change physician behavior, but the means of doing so are likely more Draconian than most would find palatable.

There are some low-hanging stewardship fruit, however, addressed by trials such as “SCOUT,” looking at the duration required for antibiotics.¹² In this trial, children with a urinary tract infection were randomized to either five or 10 days of oral antibotics. Nearly every child improved and treatment failures were rare, but they were clearly more common in those receiving short-courses of antibiotics. It is likely the most appropriate strategy for prescribing is to start with a short course, but to remain adaptable to the occasional need for longer-course therapy.

In a bit of an odd trial attempting to tease out the best candidates for antibiotic therapy in those children with acute sinusitis, a trial explored clinical and microbiological predictors of treatment outcomes.¹³ The most interesting finding is the failure of the “color of nasal discharge” finding used by many to guide clinical management. This clinical manifestation was not shown to correlate with the presence of underlying pathogenic bacteria. While this trial was “positive” in the sense amoxicillin/clavulanic acid treatment was a bit better than placebo, the mean symptoms scores improved rapidly in both arms. Any benefit to antibiotics was restricted to the fraction whose testing proved presence of pathogenic bacteria. The most prudent strategy for mild acute sinusitis in children is almost assuredly still watchful waiting.

A Closing Treasure

Medicine is littered with perverse incentives to do “more” instead of “less.” Because of this, each gem in which an established dogma is challenged is greatly appreciated. The so-called “NINJA” trial evaluates whether children with nail and nailbed injuries benefit from replacement of the nail into the nail fold, or whether cosmesis and function are retained if the nail is simply discarded.¹⁴ While anatomic re-approximation sounds good in theory, these authors do not report any advantage to doing so. It turns out humans have at least some small remaining regenerative power, and the nail will grow back without any additional deleterious effect.

Dr. Radecki (@emlitofnote) is an emergency physician and informatician with Christchurch Hospital in Christchurch, New Zealand. He is the Annals of Emergency Medicine podcast co-host and Journal Club editor.

References

1. The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital tranexamic acid for severe trauma. N Engl J Med. 2023;389(2):127-136.
2. Bouzat P, Charbit J, Abback PS, et al. Efficacy and safety of early administration of 4-factor prothrombin complex concentrate in patients with trauma at risk of massive transfusion: the procoag randomized clinical trial. JAMA. 2023;329(16):1367.
3. Davenport R, Curry N, Fox EE, et al. Early and empirical high-dose cryoprecipitate for hemorrhage after traumatic injury: the cryostat-2 randomized clinical trial. JAMA. 2023;330(19):1882.
4. Wang Y, Li S, Pan Y, et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial. The Lancet. 2023;401(10377):645-654.
5. Chen HS, Cui Y, Zhou ZH, et al. Dual antiplatelet therapy vs alteplase for patients with minor non-disabling acute ischemic stroke: the aramis randomized clinical trial. JAMA. 2023;329(24):2135.
6. Sarraj A, Hassan AE, Abraham MG, et al. Trial of endovascular thrombectomy for large ischemic strokes. N Engl J Med. 2023;388(14):1259-1271.
7. Prekker ME, Driver BE, Trent SA, et al. Video versus direct laryngoscopy for tracheal intubation of critically ill adults. N Engl J Med. 2023;389(5):418-429.
8. Freund Y, Viglino D, Cachanado M, et al. Effect of noninvasive airway management of comatose patients with acute poisoning: a randomized clinical trial. JAMA. 2023;330(23):2267.
9. Bernard SA, Bray JE, Smith K, et al. Effect of lower vs higher oxygen saturation targets on survival to hospital discharge among patients resuscitated after out-of-hospital cardiac arrest: the exact randomized clinical trial. JAMA. 2022;328(18):1818.
10. Dequin PF, Meziani F, Quenot JP, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(21):1931-1941.
11. Aghlmandi S, Halbeisen FS, Saccilotto R, et al. Effect of antibiotic prescription audit and feedback on antibiotic prescribing in primary care: a randomized clinical trial. JAMA Intern Med. 2023;183(3):213.
12. Zaoutis T, Shaikh N, Fisher BT, et al. Short-course therapy for urinary tract infections in children: the scout randomized clinical trial. JAMA Pediatr.2023;177(8):782.
13. Shaikh N, Hoberman A, Shope TR, et al. Identifying children likely to benefit from antibiotics for acute sinusitis: a randomized clinical trial. JAMA. 2023;330(4):349.
14. Jain A, Greig AVH, Jones A, et al. Effectiveness of nail bed repair in children with or without replacing the fingernail: NINJA multicentre randomized clinical trial. British Journal of Surgery. 2023;110(4):432-438.