EBQ:SOAP II Trial

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Complete Journal Club Article
De Backer D, et al. "Comparison of dopamine and norepinephrine in the treatment of shock". The New England Journal of Medicine. 2010. 362(9):779-89.
PubMed Full text PDF

Clinical Question

Does dopamine decrease mortality when compared to norepinepherine as a vasopressor when treating shock?

Conclusion

For septic shock, no statistical difference was seen between dopamine and norepinepherine for all cause 28 day mortality. Dopamine was associated with increased arrhythmias.

Major Points

The Sepsis Occurrence in Acutely Ill Patients (SOAP) II trial was a multi-center trial that randomized patients to receive either norepinephrine or dopamine in the treatment of shock. [1]

The 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%; P<0.001). Currently the surviving sepsis campaign recommends norepinephrine as the first line vasopressor therapy.[2]


Design

  • Multicenter, double-blinded, parallel-group, randomized controlled trial
  • N=1,679
    • 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

Population Studied

Inclusion Criteria

  • Age ≥18 years
  • Shock requiring a vasopressor agent
    • Shock defined as MAP <70 mmHg or systolic BP <100 despite adequate fluids (1L crystalloid or 500cc colloids)
    • Unless CVP >12 or PCWP >14
    • Signs of tissue hypoperfusion

Exclusion Criteria

  • Receipt of vasopressor agent >4 hours prior to enrollment
  • Serious arrhythmia (rapid atrial fibrillation >160 bpm, VT)
  • Brain death

Baseline Characteristics

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%

Interventions

  • 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

Outcomes

Comparisons are dopamine vs. norepinephrine.

Primary Outcomes

All-cause mortality at 28 days
52.5% vs. 48.5% (OR 1.17; 95% CI 0.97-1.42; P=0.10)

Secondary Outcomes

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)

Subgroup Analysis

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

Adverse Events

Arrhythmia
24.1% vs. 12.4% (P<0.001)

Current Sepsis Guidelines

Surviving Sepsis Campaign (2012)[2]

  • Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C).
  • Norepinephrine as the first choice vasopressor (grade 1B).
  • Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B).
  • Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage (ungraded).
  • Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) (ungraded).
  • Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (grade 2C).
  • Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine is associated with serious arrhythmias, (b) cardiac output is known to be high and blood pressure persistently low or (c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target (grade 1C).
  • Low-dose dopamine should not be used for renal protection (grade 1A).
  • All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (ungraded).

Funding

Funding provided by the European Critical Care Research Network.

CME

1. You are treating a patient with undifferentiated shock, and after performing all of the usual aspects of care (administration of fluids, which is the first-line therapeutic strategy), you consider using a vasopressor. You are debating between dopamine vs. norepinephrine to restore and maintain blood pressure. True statements about the two pressors in the setting of the treatment of shock include which of the following:

Both of these agents influence alpha-adrenergic and beta-adrenergic receptors, but to different degrees.
In this multicenter, randomized trial, patients with shock were randomized to receive either dopamine or norepinephrine. The primary outcome variable was rate of death. The trial included 1679 patients, and there was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001).
There is no significant difference between the two groups in rate of all-cause death at 29 days, 6 months, or 12 months.
Patients who are treated with norepinephrine are more likely to have an arrhythmia.
Patients with cardiogenic shock have a higher rate of death if treated with dopamine when compared to those who are treated with norpepinephrine.
A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses).
Dopamine is a less potent vasopressor than norepinephrine.

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Further Reading

  1. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. The New England Journal of Medicine. 2010;362(9):779–789. doi:10.1056/NEJMoa0907118.and a subsequent meta-analysis
  2. 2.0 2.1 Dellinter, RP et al. "Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012." Critical Care Medicine. 2013;41(20):580-637.