Widely Used Heart Drug Fails to Protect Newborns During Intubation, Landmark Study Finds

One of the most routine drugs in the neonatal intensive care unit may not be doing what doctors have long assumed. Atropine, a medication given to tens of thousands of newborns every year before breathing tubes are inserted, does not appear to reduce the risk of cardiac arrest during the procedure, according to a large new analysis from the National Emergency Airway Registry for Neonates, known as NEAR4NEOS. The findings, published in the Journal of Perinatology, are prompting a fresh look at a practice that has been embedded in neonatal care guidelines for decades.

Tracheal intubation, the placement of a tube into the windpipe to secure an infant’s airway, is among the highest-stakes procedures performed on newborns. It requires a clinician to thread a tube through the vocal cords of a patient who may weigh less than a kilogram, often while that patient is critically ill. The procedure is known to carry a substantial burden of adverse events, including oxygen desaturation, bradycardia, and in rare but devastating cases, cardiac arrest. Because newborns have a predominantly parasympathetic cardiovascular system, their hearts are especially vulnerable to vagal stimulation, which can be triggered by laryngoscopy and airway manipulation, slowing the heart rate dangerously.

Atropine works by blocking acetylcholine receptors at the muscarinic sites of the heart, effectively dampening the vagal reflexes that can cause the heart to slow. The logic behind its use during intubation has been straightforward: if airway manipulation can provoke reflex bradycardia, and if severe bradycardia can cascade into cardiac arrest, then preemptively blunting that reflex should protect the infant. That reasoning, drawn largely from pediatric anesthesia and emergency medicine, has made atropine a standard component of premedication regimens in neonatal units around the world, alongside sedatives and, in some centers, neuromuscular blocking agents.

To test that assumption at scale, a team led by Taylor Sawyer of the University of Washington School of Medicine and including co-senior authors Elizabeth Foglia and Akira Nishisaki turned to the NEAR4NEOS registry, an international collaborative that prospectively collects standardized data on every intubation attempt at participating neonatal units. The researchers analyzed 13,085 neonatal tracheal intubations performed between 2014 and 2023, making this one of the largest datasets ever assembled to examine the safety of neonatal airway management. Atropine was administered in 8,189 of those procedures, or 62.6 percent, underscoring just how deeply entrenched the practice is.

The team used multivariable logistic regression to compare outcomes between intubations in which atropine was given and those in which it was not, adjusting for confounding factors such as patient characteristics and clinical context. The primary outcome was cardiac arrest during the procedure. The result was striking: atropine use was not associated with reduced odds of cardiac arrest, with an adjusted odds ratio of 0.52 and a confidence interval spanning from 0.25 to 1.09, a range that crosses the threshold of statistical significance. In other words, the data could not demonstrate that the drug prevents the very complication it is most often given to avert.

The secondary findings were equally revealing. Atropine did deliver on one of its promised effects: it was associated with substantially lower odds of severe bradycardia, with an adjusted odds ratio of 0.33, meaning the drug cut the risk of dangerous heart rate slowing by roughly two-thirds. But that cardiac benefit came with trade-offs. Infants who received atropine had higher odds of oxygen desaturation during the procedure, with an adjusted odds ratio of 1.35, and lower odds of success on the first intubation attempt, with an adjusted odds ratio of 0.76. First-attempt success matters enormously in neonatal care, because repeated attempts prolong airway manipulation, increase physiological stress, and compound the risk of harm.

The desaturation finding has a plausible physiological explanation. Atropine increases heart rate and cardiac output, which can accelerate the consumption of oxygen reserves in an infant whose lungs are being ventilated intermittently or not at all during the attempt. A faster heart rate in a tiny preterm baby may burn through the limited oxygen buffer more quickly, causing saturation levels to fall sooner. Meanwhile, the mechanism behind the reduced first-attempt success is less clear. It may reflect confounding by indication, since clinicians may reach for atropine in sicker, more fragile infants in whom intubation is intrinsically harder, or it may reflect a genuine drug-related effect that further research will need to disentangle.

The study arrives amid a growing body of evidence questioning routine atropine in neonates. A randomized clinical trial published in The Journal of Pediatrics in 2025 by Afifi, El-Naggar, Narvey and colleagues compared atropine with placebo for nonemergent neonatal intubation and found the drug offered no clear advantage, an accompanying commentary asking pointedly whether routine pre-intubation atropine does more harm than good. Earlier work in pediatric critical care, including studies by Jones and colleagues on more than three hundred critical care intubations, had likewise suggested that atropine’s effects on rhythm disturbances during intubation are more complicated than the simple reflex-blocking model implies, and that mortality benefits observed in some pediatric cohorts appeared unrelated to the drug’s influence on bradycardia.

For clinicians, the new findings do not amount to an immediate call to abandon atropine, but they do challenge the reflexive use of the drug in every neonatal intubation. The authors themselves conclude that the association between atropine and increased desaturation and lower first-attempt success warrants further study, and the observational design of the registry analysis means that unmeasured differences between patients who received the drug and those who did not could still influence the results. Randomized trials, such as the recent placebo-controlled study, will remain essential for establishing causation. In the meantime, the results give neonatologists something they have lacked: large-scale data suggesting that the most common cardiac premedication in the NICU may not prevent the worst outcome, and may carry costs of its own.

The broader significance of the study lies in what it says about how neonatal practice evolves. Many interventions in the NICU were adopted on physiological reasoning and small studies rather than rigorous outcome data, and the NEAR4NEOS registry has become a powerful instrument for auditing those practices across hundreds of thousands of recorded procedures. Previous reports from the same collaboration have shown that premedication with sedation and neuromuscular blockade is associated with fewer adverse events, that team stress correlates with complications, and that training level affects success rates. This latest analysis adds a crucial nuance to that picture, suggesting that the individual components of premedication regimens deserve scrutiny on their own terms. As the authors and their international collaborators continue to accumulate data, the question is shifting from whether atropine blunts a reflex, which it clearly does, to whether blunting that reflex, at the cost of faster desaturation and more attempts, actually serves the smallest patients best.

Subject of Research: Atropine use and adverse events during neonatal tracheal intubation

Article Title: Association of atropine use during neonatal intubation with cardiac arrest, severe bradycardia, and other adverse events: a report from NEAR4NEOS

Article References: Sawyer, T., Narvey, M., Tyler, M. D., Abou Mehrem, A., Iben, S., DeMartino, C., Tingay, D., Hodgson, K., Kim, J., Herrick, H., Unrau, J., Puia-Dumitrescu, M., Shay, R., DeMeo, S., Assaad, M.-A., O’Shea, J., Brajkovic, I., Quek, B. H., Glass, K., … DeMartino, C. (2026). Association of atropine use during neonatal intubation with cardiac arrest, severe bradycardia, and other adverse events: a report from NEAR4NEOS. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02916-2

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02916-2

Keywords: atropine, neonatal intubation, cardiac arrest, bradycardia, oxygen desaturation, NEAR4NEOS, premedication, neonatology, NICU, patient safety, Journal of Perinatology, registry study