The Hallway Consult Issue #8: Aspirin, Pediatric Fever, and the TBI Intubation

Walk into almost any ED in the country and you'll see it: chest pain patient hits the door, and someone gives them aspirin before the first troponin is back. It's become so reflexive that it barely registers as a decision anymore. But the evidence for that practice is more conditional than the reflex suggests.

The foundational data comes from ISIS-2, the landmark 1988 trial that enrolled over 17,000 patients with suspected acute MI and randomized them to IV streptokinase, oral aspirin 162.5 mg, both, or neither. Aspirin alone reduced 35-day vascular mortality by 23% compared to placebo — one of the most durable treatment effects in cardiology. That result legitimately cemented aspirin as the first drug you think of in acute MI.

The problem is that ISIS-2 enrolled patients with suspected MI, and ISIS-2 was from 1988 — before high-sensitivity troponin, before accelerated diagnostic protocols, before most of the risk stratification infrastructure we now rely on. The 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline recommends aspirin 162–325 mg (chewed, non-enteric) for all patients with suspected ACS without contraindications. That framing matters. The guideline is not saying to give it to everyone with chest pain — it's saying to give it when your clinical gestalt puts ACS at the top of the list. For the patient who already looks like a STEMI or presents with high pretest probability, the recommendation is clear. For the low-risk undifferentiated patient you're about to work up with a 0/2-hour hs-troponin protocol, the expected benefit shrinks considerably, while the risk profile (GI bleed, hemorrhagic stroke) is unchanged.

The practical principle: aspirin in chest pain should still be a decision, not a default. Use it when you think you're treating ACS. Hold it when the diagnosis is genuinely undifferentiated and bleeding risk is meaningful. The old habit of reflexively aspirin-ing every chest pain patient "just in case" oversteps what the evidence actually supports.

Bottom line: Give aspirin early and confidently when the clinical picture suggests ACS. For truly undifferentiated low-pretest-probability chest pain, it's reasonable to wait for your workup before committing.

ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction. Lancet. 1988;2(8607):349–360. | Bhatt DL, Lopes RD, Harrington RA, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. Circulation. 2025;151(13):e785–e878.

Before routine pneumococcal and Hib vaccination, a well-appearing 18-month-old with a temperature of 40°C and no focus had a 3–5% chance of occult bacteremia — usually Streptococcus pneumoniae. That risk number drove an entire generation of protocols: CBC, blood culture, empiric ceftriaxone, close follow-up, high anxiety. For good reason.

That number no longer applies to most of the children you're seeing today. In the routine conjugate-vaccine era, occult bacteremia in fully vaccinated children aged 3 to 36 months with fever without source has fallen to well under 1% in most cohorts. S. pneumoniae used to drive the old calculus, but its incidence has dropped so dramatically that the traditional protocol — reflexively drawing blood cultures and covering empirically — now generates far more false positives, unnecessary admissions, and antibiotic courses than true bacterial saves. UTI is now the most common serious bacterial infection in this age group, not bacteremia.

The 2021 AAP clinical practice guideline restructured how we approach febrile infants under 60 days, using procalcitonin and other inflammatory markers as part of a validated risk-stratification framework rather than defaulting to full septic workups for every febrile baby. For the older well-appearing vaccinated child (3–36 months), the calculus has shifted even further. Blood cultures in this group add minimal yield in the absence of abnormal inflammatory markers, toxic appearance, or immunocompromise. Urine, however, remains a must.

The key mental model update: in the post-PCV era, your febrile well-appearing vaccinated toddler with no source has a primary concern of UTI, not invasive bacterial disease. Adjust your workup accordingly, and reserve empiric antibiotics for the kids who actually look sick, are unvaccinated, or have objective lab findings to support their use.

Bottom line: The rule-out-everything protocol for fever without source in a well-appearing vaccinated 18-month-old is outdated. Think UTI first, set your bacteremia threshold higher, and match your workup intensity to the actual risk.

Pantell RH, Roberts KB, Adams WG, et al. Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics. 2021;148(2):e2021052228. | Greenhow TL, Hung YY, Herz AM. Bacteremia in Children 3 to 36 Months Old After Introduction of Conjugated Pneumococcal Vaccines. Pediatrics. 2017;139(4):e20162098.

For decades, the teaching was clear: avoid ketamine in traumatic brain injury because it raises intracranial pressure. This found its way into protocols, textbooks, and bedside teaching. Some institutions still have it in their RSI guidelines today. The problem is that the original evidence it was based on is essentially worthless.

The concern traces back to case reports and small studies from the 1970s — most involving spontaneously breathing patients with space-occupying intracranial lesions who received ketamine without paralysis and without controlled ventilation. In those conditions, with rising PaCO2 and no airway control, ICP rose. That became the warning label on the drug. What it does not tell you is what happens when ketamine is used in the way we actually use it: as the induction agent in a controlled RSI with succinylcholine or rocuronium, mechanical ventilation immediately after, and normocapnia as a target.

Modern evidence has systematically dismantled the old concern. Systematic reviews of ketamine use in acute brain injury have found no evidence of harm from ketamine in ventilated TBI patients, and several included studies reported stable or decreased ICP after administration. Crucially, ketamine's sympathomimetic properties maintain or increase mean arterial pressure — and in TBI, hypotension kills. Secondary brain injury from a dropped MAP after induction in a hypotensive trauma patient is a real harm. The fear of theoretical ICP elevation from ketamine has pushed clinicians toward agents that may be hemodynamically worse in the patients who can least afford to tank their blood pressure.

The current evidence supports ketamine as a reasonable, and arguably preferred, induction agent in TBI patients undergoing RSI — particularly when hemodynamic instability is present. The old contraindication should be retired from your mental model.

Bottom line: Ketamine does not meaningfully raise ICP when used in a proper RSI with controlled ventilation. In the hemodynamically compromised TBI patient, its ability to maintain MAP makes it the better choice over etomidate. Stop letting a 1970s case report make your drug decisions.

Gregers MCT, Mikkelsen S, Hansen TK, Wetterslev J. Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review. Neurocrit Care. 2020;33(1):273–282. | Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014;21(1):163–173.

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— The Hallway Consult team