Every year, the hopeless task of keeping up with the medical literature grows even more unattainable. Will our Sisyphean burden be replaced with AI? (Read this month’s Skeptics’ Guide to Emergency Medicine for that answer.) Will we be microchipped with peripheral PubMed brains? Will we finally wake up from the Matrix and be freed? Not yet!

So, in the meantime, here’s a host of articles of more than just passing interest from the past year, not already covered in ACEP Now.

New Developments in Forced Air

A few years ago, the vogue debate was rocuronium versus succinylcholine. Then, it was video laryngoscopy versus direct … bougie or stylet. Now, the next debate to be settled is the ideal method for preoxygenation before intubation. The PREOXI trial compared oxygen mask pre-oxygenation versus noninvasive positive-pressure ventilation (NIPPV) in patients requiring intubation in emergency departments (EDs) and intensive care units.¹ The primary outcome was the frequency of observed hypoxemia, defined as any pulse oximetry reading below 85 percent. The obvious winner was NIPPV, whose 9.1 percent incidence of hypoxemia was half that of the oxygen mask cohort. Serious patient-oriented outcomes such as cardiac arrest were rare, but almost all occurred in the oxygen mask cohort. As such, it’s fair to say, whenever conditions allow, pre-oxygenation with positive-pressure ventilation (PPV) is likely superior.

The HAPPEN trial is another one with results that may be worth watching.² This was not an ED trial but was performed in stable patients on the inpatient wards. This trial tested “high-intensity” PPV in patients with type II respiratory failure due to exacerbations of chronic obstructive pulmonary disease. With study results and outcomes best described as “complicated,” the high-intensity PPV improved physiologic normalization of respiratory parameters and decreased need for endotracheal intubation, as compared with typical NIPPV. It remains to be seen whether higher inspiratory pressures find their way into future trials of ED bilevel positive airway pressure ventilation.

Sepsis Robots or Sepsis Humans

The proliferation of “sepsis” alerts in the ED has reached levels best described as “obscene.” The common refrain from trained clinicians: We are smarter than any computer or simple scoring system, and we can rapidly and accurately identify sepsis by ourselves, thank you very much. The claim has obvious face validity, but supporting evidence is always welcome. In a prospective study comparing clinician gestalt against systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA), quick SOFA, Modified Early Warning Score (MEWS), and a logistic regression machine learning model using Least Absolute Shrinkage and Selection Operator (LASSO), the obvious winner was the clinician.³ The machine learning model trailed just behind. My fellow humans, enjoy what may be our short-lived superiority over the robots.

On the flip side, the evidence is better, if still mixed, regarding the utility of early warning scores for deterioration on the inpatient side. Although such scores have been associated with improved inpatient mortality at Kaiser, mixed results have been published in this past year.⁴ On one hand, a retrospective evaluation f the commonly-deployed Epic Deterioration Index (EDI) showed a decrease in unplanned escalations in care without evidence of deleterious effects on mortality.⁵ Conversely, an evaluation comparing several early warning tools found little difference between the EDI and common bedside tools such as the MEWS and National Early Warning Score (NEWS/NEWS2).⁶ The true answer as to what value any electronic deterioration tool may or may not add to your institution will depend greatly on existing culture, workflow, and tools already in use.

Best Protection for Brains

Among many types of critical illness, evidence supports the noninferiority of “restrictive” transfusion strategies. The transfusion cut-offs vary, but it frequently appears reasonable to permit hemoglobin levels to drop, rather than proactively transfuse to prevent severe anemia. The brain is an entirely different organ system, however. The TRAIN trial evaluated whether a liberal or restrictive strategy was preferred in patients suffering traumatic brain injury, subarachnoid hemorrhage, or intracerebral hemorrhage.⁷ Considering the general sensitivity of the brain to hypoxemic and ischemic insults, it is not terribly surprising to find that liberal transfusion strategy was superior.

One of the paradoxical oddities of treatment for acute stroke is the reversal of anticoagulation to enable treatment with thrombolysis. In common practice, this usually involves using idarucizumab to bind dabigatran prior to further acute treatment. In a retrospective, registry-based study and systematic review, the authors reported generally favorable outcomes with few complications to this exceptional practice.⁸ However, the nature of these retrospective studies only serves to amplify the selection biases at work in current practice, demonstrating the baseline superior prognosis of those selected for treatment, rather than any value or safety of the treatment itself. Randomized, controlled trials remain necessary to ultimately determine the efficacy and safety of this practice.

Finally, in what serves as a bit of idle academic curiosity, a re-examination of the rate of intracranial hemorrhage after thrombolysis found starkly different statistics than those typically used in discussions with patients.⁹ In a re-analysis of the ENCHANTED study, the authors reported the incidence and outcomes of patients suffering asymptomatic intracranial hemorrhage (aICH), rather than just the typical symptomatic intracranial hemorrhage (sICH). The rates of sICH were consistent with the typical one percent to two percent generally quoted during informed consent, whereas rates of aICH were ten times this number. As expected, odds ratios for poor outcomes and death for those with sICH were in the 20-60 range, but aICH was certainly not benign, with odds ratios around two. Although there may be net chance of benefit to thrombolysis, the proportion harmed by treatment may approach 20 percent, vastly higher than appreciated.

Use of Bones

Although the topic hardly rises to the level of serious controversy, the best protocol for vascular access in the context of out-of-hospital cardiac arrest is an ongoing unanswered question. Proponents of the intraosseous route highlight the ease of rapid access. In contrast, concerns remain over the relative efficacy of drugs infused through intraosseous sites, contraindications, and the cost of devices.

Two trials were published together on this topic, PARAMEDIC-3 and IVIO.^10,11 The primary outcomes of these trials differed: survival at 30 days in PARAMEDIC-3 and sustained return of spontaneous circulation in IVIO; however, despite differences in both primary outcomes and study procedures, neither access strategy separated itself from its peer. There will always be individual circumstances and clinical indications in which one access strategy may be preferable, but the net result was a wash.

Potpourri!

An amusingly named SENIOR-RITA trial tested whether elderly patients suffering non-ST segment myocardial infarction ought to undergo an invasive strategy versus a conservative, medical management strategy.¹² Although this question may seem a bit odd to some in the U.S., baseline frailty and life expectancy are common considerations during acute care in many health systems. In the frail elderly enrolled in this trial, invasive strategies reduced downstream nonfatal myocardial infarction, but had no effect on cardiovascular death or the overall composite outcome.

The glib dogma “GCS 8, intubate” may seem the perfect combination of clinical indication and clever rhyme, but the Glasgow Coma Scale (GCS) was never designed to predict airway complications in the heterogenous population of patients with diminished levels of consciousness. As it turns out, common sense likely rules the day when presented with patients whose low GCS is the result of a self-limited overdose toxidrome. In a randomized trial of initial preferred management of, primarily, alcohol-and benzodiazepine-intoxicated patients, fewer required mechanical ventilation or intensive care unit admission when an observation-first strategy was employed.¹³ Although intubation certainly has its place, it should not be considered a benign intervention and must be weighed against the risks of the specific presenting syndrome, rather than a blanket rule based on GCS.

In a setting where the ED is frequently described as the “front door” to the hospital, a very reasonable question to ask is: Why? If an inpatient ward is the ultimate intended endpoint, an ED encounter may not add any value, while contributing to long wait times and increased patient costs. The alternative would be direct admission, bypassing the ED, and it sounds so sensible that it rather boggles the mind that it isn’t more robustly utilized. Authors of one study clearly felt the same way and implemented a direct admission program across three pediatric health systems.¹⁴ Uptake was uncommon, but in those who were directly admitted to the ward, no adverse consequences occurred, and appropriate treatment was initiated more quickly. From a patient-oriented standpoint, the advantages of direct admission should encourage health systems to expand such appropriate offerings when the resources of an ED are not acutely required.

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. Gibbs KW, Semler MW, Driver BE, et al. Noninvasive ventilation for preoxygenation during emergency intubation. N Engl J Med. 2024;390(23):2165-2177.
2. Luo Z, Li Y, Li W, et al. Effect of high-intensity vs low-intensity noninvasive positive pressure ventilation on the need for endotracheal intubation in patients with an acute exacerbation of chronic obstructive pulmonary disease: the HAPPEN randomized clinical trial. JAMA. 2024:e2415815.
3. Knack SKS, Scott N, Driver BE, et al. Early physician gestalt versus usual screening tools for the prediction of sepsis in critically ill emergency patients. Ann Emerg Med. 2024;84(3):246-258.
4. Escobar GJ, Liu VX, Schuler A, et al. Automated identification of adults at risk for in-hospital clinical deterioration. N Engl J Med. 2020;383(20):1951-1960.
5. Gallo RJ, Shieh L, Smith M, et al. Effectiveness of an artificial intelligence–enabled intervention for detecting clinical deterioration. JAMA Intern Med. 2024;184(5):557-562.
6. Edelson DP, Churpek MM, Carey KA, et al. Early warning scores with and without artificial intelligence. JAMA Netw Open. 2024;7(10):e2438986.
7. Taccone FS, Bittencourt CR, Møller K, et al. Restrictive vs liberal transfusion strategy in patients with acute brain injury: the train randomized clinical trial. JAMA. 2024;332(19):1623-1633.
8. Theodorou A, Melanis K, Bakola E, et al. Thrombolysis after dabigatran reversal for acute ischemic stroke: a national registry-based study and meta-analysis. Neurology. 2024;103(7):e209862.
9. Wang Y, Maeda T, You S, et al. Patterns and clinical implications of hemorrhagic transformation after thrombolysis in acute ischemic stroke: results from the ENCHANTED study. Neurology. 2024;103(11):e210020.
10. Couper K, Ji C, Deakin CD, et al. A randomized trial of drug route in out-of-hospital cardiac arrest. N Engl J Med. [published online ahead of print October 31, 2024].
11. Vallentin MF, Granfeldt A, Klitgaard TL, et al. Intraosseous or intravenous vascular access for out-of-hospital cardiac arrest. N Engl J Med. [published online ahead of October 31, 2024].
12. Kunadian V, Mossop H, Shields C, et al. Invasive treatment strategy for older patients with myocardial infarction. N Engl J Med. 2024;391(18):1673-1684.
13. 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):2267-2274.
14. Leyenaar JK, Acquilano SC, Freyleue SD, et al. Effectiveness of direct admission compared to admission through the emergency department: a stepped-wedge cluster-randomized trial. Pediatrics. 2024;154(4):e2024065776.