Efficacy and Safety of Dopamine versus ...

Shock, Publish Ahead of Print DOI: 10.1097/SHK.0b013e3181c6ba6f

Efficacy and Safety of Dopamine versus Norepinephrine in the Management of Septic Shock

Gourang P. Patel, Jaime Simon Grahe, Mathew Sperry, Sunit Singla, Ellen Elpern, Omar Lateef, Robert A. Balk

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Division of Pulmonary and Critical Care Medicine, Department of Medicine, Rush University Medical Center and Rush Medical College, Chicago, IL.

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Send Correspondence and Reprint Requests To: Robert A. Balk, M.D. Division of Pulmonary and Critical Care Medicine 1653 West Congress Parkway Chicago, Il 60612 T- 312-942-5132 F- 312-563-2157 Email – [email protected]

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Copyright © 2008 by the Shock Society. Unauthorized reproduction of this article is prohibited.

Abstract Background: The optimum septic shock vasopressor support strategy is currently debated. This study was performed to evaluate the efficacy and safety of norepinephrine and dopamine as the initial vasopressor in septic shock patients who were managed with a specific treatment protocol.

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Methods: Prospective, randomized, open-label, clinical trial in a medical intensive care unit comparing dopamine to norepinephrine as the initial vasopressor in fluid

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resuscitated 252 adult patients with septic shock. If the maximum dose of the initial vasopressor was unable to maintain the hemodynamic goal, then fixed dose vasopressin was added to each regimen. If additional vasopressor support was

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needed to achieve the hemodynamic goal, then phenylephrine was added. Results: The primary efficacy endpoint was all cause 28-day mortality. Secondary endpoints included organ dysfunction, hospital and ICU length of stay, and safety (primarily occurrence of arrhythmias). The 28-day mortality rate was 50% (67/134)

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with dopamine as the initial vasopressor compared to 43% (51/118) for norepinephrine treatment (p=0.282). There was a significantly greater incidence of

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sinus tachycardia with dopamine [27.5% (33/120)] than norepinephrine [5.3% (7/132)] and arrhythmias noted with dopamine treatment [23.3% (18/120)] compared

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to norepinephrine treatment [5.3% (7/132)] (p 90 mmHg

Add Vasopressin (0.04 units/min)

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Phenylephrine (25-200 mcg/min)

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Figure 3. Kaplan-Meier Survival Curve

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p=0.213*

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* p-value calculated based on log-rank test

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Table 1. Inclusion and Exclusion Criteria

Inclusion Criteria Greater than or equal to 18 years of age

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Admission to MICU

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Diagnosis of Septic Shock requiring vasopressor therapy after adequate fluid

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Exclusion Criteria •

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resuscitation (clinical exam and/or CVP > 8 mmHg)

Lack of infectious etiology of shock (e.g. hypovolemic, hemorrhagic,

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cardiogenic, anaphylactic, and/or obstructive shock) Noninfectious etiology of the SIRS response

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Allergy to dopamine or norepinephrine

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Vasopressor therapy for > 6 hours.

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•

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Table 2. Demographics and Baseline Characteristics Significance p value

70 28+6.7

66 27+6.1

0.557 0.548

12+3.3

12+3.2

0.754

5435+2084

5643+2304

0.452

53 42

52 43

0.468 0.441

46 41 28 23 54 19

36 43 20

0.518 0.326 0.426

27 50 16

0.328 0.798 0.887

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Female (n) APACHE II (mean+SD) SOFA (mean+SD) Fluids (ml) First 6 hours (mean+SD) Cancer (n) Corticosteroids (n) Infection Gram + bacteria (n) Gram - bacteria (n) Culture Negative (n) Site of Infection Respiratory Tract (n) Blood Stream (n) Urine (n)

NE n= 118 52

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Male (n)

DA n= 134 64

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Category

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Table 3. Outcome Data utcome DA NE Mortality 50% (67/134) 43% (51/118) ICU Length of stay 6.8 + 7.3 7.5 + 7.6 (days + SD ) Hospital Length of stay (days + SD) Incidence of Arrhythmias

p value 0.282 0.469

14.2 + 16.3

13.5 + 13.3

0.695

38% (51/134)

11.8% (14/118)

< 0.0001

RR (95% CI) 1.16 (0.886-1.51)

3.21 (1.88-5.49)

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Note: RR is relative risk with 95% Confidence Interval (CI)

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Table 4. Vasopressor Requirements DA NE Vasopressin 23 28 Vasopressin and 32 23 Phenylephrine Change Secondary 32 8 to Arrhythmia

p value 0.110 0.400

RR (95% CI)