Sepsis remains a major cause of illness and death among children worldwide. Although mortality has decreased due to quality improvement initiatives and clinical guidelines, 4–10% of paediatric sepsis cases still result in death, often due to refractory shock or multiorgan dysfunction.
For children with persistent shock despite fluid resuscitation, vasoactive agents are essential to restore circulation. While dopamine was once the first-line agent, newer studies have shown better outcomes with epinephrine, leading to updated guidelines recommending either epinephrine or norepinephrine. However, no direct comparison between the two has been made in paediatric patients. Both drugs are affordable, widely available, and similarly effective and safe in improving haemodynamic status. A direct comparison could inform optimal treatment and improve outcomes for the many children affected by sepsis each year.
A study was conducted at a single quaternary care children’s hospital to compare outcomes in paediatric patients with septic shock who received either epinephrine or norepinephrine. The study included patients aged 1 month to 18 years who presented to the emergency department, had no known cardiac dysfunction, and began a vasoactive infusion within 24 hours of arrival.
The primary outcome of the study was major adverse kidney events within 30 days (MAKE30). Secondary outcomes included 30-day in-hospital mortality, 3-day mortality, need for kidney replacement therapy or ongoing kidney dysfunction, endotracheal intubation, duration of mechanical ventilation, use of extracorporeal membrane oxygenation (ECMO), and lengths of hospital and ICU stay.
Among 231 paediatric septic shock encounters, the median age was 11.4 years, 54.6% were female, and 61.5% had predisposing medical conditions. 63.6% received epinephrine, while 36.4% received norepinephrine. MAKE30 occurred in 6.1% of the epinephrine group and 3.6% of the norepinephrine group; 30-day mortality was 4.1% with epinephrine and 0% with norepinephrine. After adjusting for treatment differences, there was no significant difference in MAKE30. However, 2:1 propensity matching showed higher 30-day mortality with epinephrine compared to norepinephrine (3.7% vs 0%).
This is the first study to directly compare norepinephrine and epinephrine in paediatric septic shock. While prior meta-analyses hinted at a benefit for norepinephrine, this study found a statistically significant mortality reduction. If confirmed in prospective trials, norepinephrine could become the preferred first-line agent in this population.
Current guidelines do not clearly favour one agent over the other, contributing to wide practice variation. The physiological differences between the drugs—norepinephrine being a stronger vasoconstrictor and epinephrine a stronger inotrope—may influence outcomes. Although no major cardiac side effects were noted, norepinephrine’s favourable impact on preload and systemic perfusion may explain its benefit.
Overall, these findings suggest that in children with septic shock and no known cardiac dysfunction, initial treatment with norepinephrine is associated with lower mortality but similar rates of MAKE30 compared to epinephrine. Further prospective studies are needed to confirm whether norepinephrine should be the preferred first-line vasoactive agent in this population.
Source: JAMA
Image Credit: iStock
