- 1 Clinical Question
- 2 Bottom Line
- 3 Major Points
- 4 Guidelines
- 5 Design
- 6 Population
- 7 Interventions
- 8 Outcomes
- 9 Criticisms
- 10 Funding
- 11 Further Reading
Among patients with shock, how does dopamine compare to norepinephrine in decreasing mortality?
In the treatment of shock, norepinephrine and dopamine compare similarly with respect to 28-day mortality, but dopamine is associated with an increased risk of arrhythmias.
Dopamine and norepinephrine had long been considered equivalent first-line agents for the treatment of shock, but the first SOAP trial suggested that dopamine was an independent predictor of increased mortality in shock. A related 2004 Cochrane meta-analysis, was limited in its ability to inform clinical practice as it only included 62 patients.
The 2010 Sepsis Occurrence in Acutely Ill Patients (SOAP) II trial randomized 1,679 patients with mostly septic shock to norepinephrine or dopamine. At 28 days, there was no difference in all-cause mortality though there was a significantly higher rate of arrhythmias in the dopamine group (24.1% vs. 12.4%; NNH 9). As such, sepsis guidelines now recommend norepinephrine as the first-line vasopressor in shock.
Surviving Sepsis Campaign severe sepsis and septic shock (2016, adapted)
- During the initial resuscitation, target MAP of 65 mm Hg in patients with septic shock needing vasopressors
- Recommend norepinephrine as first-line vasopressor (strong recommendation, moderate quality of evidence)
- Can add vasopressin up to 0.03 U/min (weak recommendation, moderate quality of evidence) or epinephrine (weak recommendation, low quality of evidence) to norepinephrine to achieve MAP targets
- Can add vasopressin up to 0.03 U/min to decrease norepinephrine dose (weak recommendation, low quality of evidence)
- Recommend against using low-dose dopamine for renal protection (strong recommendation, high quality of evidence)
- Suggest using dobutamine in patients with persistent hypoperfusion despite adequate fluid loading and vasopressor agent use (weak recommendation, low quality of evidence)
- Multicenter, double-blinded, parallel-group, randomized controlled trial
- Dopamine (n=858)
- Norepinephrine (n=821)
- Setting: 8 centers in Belgium, Austria, and Spain
- Enrollment: December 2003 to October 2007
- Analysis: Intention-to-treat
- Follow-up: 28 days
- Primary outcome: All-cause mortality
- Age ≥18 years
- Shock requiring a vasopressor agent
- Shock defined as MAP <70 mmHg or systolic BP <100 despite adequate fluids (1L crystalloid or 500mL colloids)
- Unless CVP >12 or PCWP >14
- Signs of tissue hypoperfusion
- Receipt of vasopressor agent >4 hours prior to enrollment
- Serious arrhythmia (rapid atrial fibrillation >160 bpm, VT)
- Brain death
Comparisons are dopamine vs. norepinephrine.
- Septic shock 62%
- Cardiogenic shock 17%
- Hypovolemic shock 16%
- Hydrocortisone administered: 40.1% vs. 39.7%
- Activated protein C administered: 18.8% vs. 19.1%
- Patients randomized to dopamine or norepinephrine
- Doses adjusted to target BP decided by treating physician
- Dopamine max 20 mcg/kg/min
- Norepinephrine max 0.19 mcg/kg/min
- If max doses reached, open-label norepinephrine was added
- Open-label dopamine not allowed
- Epinephrine and vasopressin only as rescue agents
- Inotropes allowed as needed for cardiac output
- If adverse events occurred, treating physician could withdraw patient and change to open-label vasopressor
Comparisons are dopamine vs. norepinephrine.
- All-cause mortality at 28 days
- 52.5% vs. 48.5% (OR 1.17; 95% CI 0.97-1.42; P=0.10)
- ICU death
- 50.2% vs. 45.9% (OR 1.19; 95% CI 0.98-1.44; P=0.07)
- Inpatient mortality
- 59.4% vs. 56.6% (OR 1.12; 95% CI 0.92-1.37; P=0.24)
- 6-month mortality
- 63.8% vs. 62.9% (OR 1.06; 95% CI 0.86-1.31; P=0.71)
- 12-month mortality
- 65.9% vs. 64.0% (OR 1.15; 95% 0.91-1.46; P=0.34)
- 28-day mortality among patients with cardiogenic shock
- Increased in dopamine group compared with norepinephrine (P=0.03)
- Mortality among those with septic and hypovolemic shock
- No significant difference
- 24.1% vs. 12.4% (P<0.001; NNH 9)
- Open label norepinephrine was given if maximum dose of dopamine or noriphinephrine was used
- Unclear if the underlying cause of shock was treated appropriately
- Unclear how frequent supportive interventions (eg, intraaortic balloon pumps) were used
- Unclear what doses of norepinephrine were given
Funding provided by the European Critical Care Research Network.
- Sakr Y, et al. "Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study." Critical Care Medicine. 2006;34:589-597
- Mullner M, et al. "Vasopressors for shock." Cochrane Database System Reviews. 2004;3:CD003709-CD003709.
- Rhodes A, et al. "Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016." Critical Care Medicine. 2017;45(3)1-67.
- Multiple authors. "Correspondence: Comparison of dopamine and norepinephrine in shock." The New England Journal of Medicine. 2010;362:2328-2331.