Infections, Septic Shock, Severe Sepsis
Conditions
Keywords
Catecholamines, Septic shock
Brief summary
Catecholamines infusion is a major component of septic shock management. International guidelines recommend that norepinephrine should be preferred to epinephrine, though phase III trials are lacking. The present study aimed at comparing the efficacy and safety of norepinephrine plus dobutamine to that of epinephrine in adults with septic shock.
Detailed description
The french Conference on Consensus on catecholamines use in septic shock has underlined the importance of carrying out a clinical trial to clarify the use of epinephrine, norepinephrine and dobutamine in the management of multiple organ failure associated with severe sepsis. The main objective of the study was therefore to compare the effects of the combination of dobutamine and norepinephrine to those of epinephrine alone in patients with septic shock. In this purpose, patients were randomly assigned to receive either epinephrine or norepinephrine plus dobutamine and drugs were titrated to maintain blood pressure over 70 mmHg. Main outcome was 28-day mortality.
Interventions
DRUGnorepinephrine and dobutamine
continuous infusion of norepinephrine titrated to maintain a mean arterial pressure at 70mmHg or more and dobutamine could be added as a continuous infusion when cardiac index was of less than 2.5 liters per squared meter of body surface
DRUGepinephrine plus placebo of dobutamine
epinephrine was titrated to maintain a mean arterial pressure at 70mmHg or more and placebo of dobutamine was titrated in case of a cardiac index lower than 2.5 liters per squared meters of body surface
Sponsors
Assistance Publique - Hôpitaux de Paris
University of Versailles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults over 18 years * Informed consent Presenting from less than 7 days : * One or more infectious site * At least 2 of the following criteria: temperature \> 38°C or \< 36.5°C, respiratory rate \> 20 breaths per min or PaCO2 \< 32 mmHg or mechanical ventilation, heart rate \> 90 beats/min, white blood cell count \> 12,000/mm3 or \< 4,000/mm3 * At least 2 of the following criteria: PaO2/FiO2 ratio \<280 mmHg (if mechanical ventilation, urinary output of less than 0.5 mL/kg of body weight or \< 30 mL/h at least 1 hour, plasma lactate \> 2 mmol/L, platelet count \< 100,000 /mm3 And presenting from at least 24 hours: * Systolic blood pressure \< 90 mmHg or mean blood pressure \< 70 mmHg (for at least 30 min); * 1000 mL fluid replacement or pulmonary capillary wedge pressure \> 12 mmHg * Dopamine infusion at 15 µg/kg/min for at least 1 hour, or epinephrine or norepinephrine in first intention
Exclusion criteria
* Pregnant woman * Obstructive cardiomyopathy * Acute coronary disease * Non infectious shock * Care limitation * White blood cell count \< 500 /mm3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28 Day mortality | 28 Day |
Secondary
| Measure | Time frame |
|---|---|
| -Survival rate at days 14, 28, 90, 6 months and 1 year. | one year |
| -Rate of patients with secondary care limitation | one year |
| -Organ failure between randomization and day 28. | Day 28 |
| -Serious adverse events between randomization and exit of intensive care unit. | one year |
| -28-day survival distribution | Day 28 |
| -Time on vasopressors | Day 90 |
| -Time in intensive care unit | one year |
| -Time in hospital | one year |
| -Costs | Day 90 |
| -Onset of a reversible clinical event between randomization and exit of intensive care unit (bronchospasm, cutaneous rash, tachycardia) | one year |
Countries
France
Outcome results
None listed