Background

Background: Patients with fluid refractory septic shock should be treated with vasoactive medications to improve perfusion. It has become widely accepted in recent years to use norepinephrine as the first-line vasopressor in adults with septic shock. In children, however, there is little research to guide our choice of agent. Dopamine has been used as the first-line agent in children though it has fallen out of favor in adults. Myocardial dysfunction is common in children with septic shock and so the use of a drug with both vasopressor and inotropic properties has potential benefits. Epinephrine and dopamine both have these combined effects.

The American Heart Association recommends dopamine be the 1st line pressor in normotensive pediatric septic shock, norepinephrine in hypotensive, “warm” shock (those with good cardiac function) and epinephrine in hypotensive “cold” shock (those with cardiac depression). However, it is unclear what data these recommendations are based upon.

Clinical Question

In children with septic shock, is there an advantage to using epinephrine or dopamine as the first-line vasoactive agent?

Population

Children aged 1 month to 15 years of age with fluid-refractroy septic shock.

Intervention

Dopamine (5-10 mcg/kg/min) or epinephrine (0.1 – 0.3 mcg/kg/min)

Control

No placebo group

Outcomes

Outcome (Primary): 28-day mortality
Outcome (Secondary): Rate of healthcare-associated infection, the need for other vasoactive drugs and the multiple organ dysfunction score.

Design

Double-blind, prospective, randomized controlled trial

Excluded

Patients already receiving vasoactive drugs prior to hospital admission, known cardiac disease, recurrent presentation during study period, active DNR orders or participation refusal.

Primary Results

Critical Findings

  • Primary outcome: 28-day mortality
    • Dopamine group 20.6% vs. Epinephrine group 7% (p = 0.033)
  • Overall 28-day mortality: 14.2%
  • OR death (Dopamine/Epinephrine): 6.5 (95% CI: 1.1 – 37.8)

Primary Results

  • 120 patients enrolled (dopamine = 63, epinephrine = 57)
  • Baseline characteristics (Table 1) were similar
  • Healthcare-associated infection in dopamine group OR 67.7 (5.0 – 910.8)

Strengths

  • Prospective and randomized enrolling consecutive patients with minimal exclusion criteria
  • Blinding to study medication well done
  • Important, patient-centered primary outcome (mortality)

Limitations

  • Single-center nature limits external validity
  • Overwhelming source of sepsis determined to be respiratory
  • Patients receiving dopamine were more likely to be in “cold” shock (88.3 vs. 70.2%) though this was not statistically significant
  • The dose of dopamine may have been too low
  • Study stopped early for harm (see below for further details)

Discussion

  • The research team planned to collect 180 patients to provide 80% power to detect a 15% absolute reduction in mortality at 28 days based on an estimated baseline mortality of 25% in the dopamine group. The study had planned interim analyses at enrollment of 60 and 120 patients. Interim analysis after 120 patients were collected showed increased mortality in the dopamine group leading to the protocol being stopped. However, the difference in mortality (13.6%) did not meet the preplanned target reduction.

Author's Conclusions

“Dopamine was associated with an increased risk of death and healthcare–associated infection. Early administration of peripheral or intraosseous epinephrine was associated with increased survival in this population. Limitations should be observed while interpreting these results.”

Our Conclusions

Although this is only a single study performed in a single hospital, the authors show a marked increase in mortality in children with septic shock who are given dopamine instead of epinephrine as the first-line vasoactive agent. This is a high-quality study and the best available evidence on the topic to date. These results should be reproduced in other hospitals.

Potential Impact To Current Practice

These results could lead to a pardigm shift from dopamine to epinephrine as the vasoactive agent of choice in pediatric septic shock.

Bottom Line

Providers should strongly consider using epinephrine over dopamine as their first-line vasoactive agent in pediatric septic shock.