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Standard clinical practice recommends minimal doses of vasoactive drugs during weaning of patients from mechanical ventilation. However, there are currently no clinical data to inform clinicians about whether the use of noradrenaline during weaning predisposes to weaning failure. The objective of this study was to evaluate whether the necessity of the vasopressor noradrenaline in mechanically ventilated patients recovering from septic shock changed the extubation outcome. A total of 656 patients recovering from septic shock on mechanical ventilation were selected from intensive care units in two university hospitals. Patients receiving noradrenaline at the time of weaning and case-controls not taking noradrenaline were matched for age, gender, haemodynamic and ventilatory parameters, aetiology of respiratory failure and APACHE II score. One hundred and forty-five patients who successfully tolerated a spontaneous breathing trial were extubated while on noradrenaline therapy and the reintubation rate was measured. In the noradrenaline group, the mean dose of noradrenaline during initial shock treatment was 0.52±0.29 μg/kg/min and 0.12±0.10 μg/kg/min during weaning. The reintubation rate was 12/63 (19%) in the noradrenaline group and 15/82 (18.3%) in the control group (P=1.00). Intensive care unit mortality was also similar in both groups (10/63, 15.9%) for noradrenaline patients and (11/82, 13.4%) for control patients (P=0.81). Arterial blood gases and ventilatory and haemodynamic parameters were similar in all patients regardless of weaning success. We did not find that the use of noradrenaline at the time of weaning was associated with extubation failure. Low doses of noradrenaline may not preclude weaning from mechanical ventilation.