Thomas Strøm1. 1. Department of Anaesthesiology and Intensive Care, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. t.s@dadlnet.dk
Abstract
BACKGROUND: Standard treatment of critically ill patients undergoingmechanical ventilation is continuous sedation. This standard treatment to all patients has been greatly challenged over the last decade. At the general intensive care department at Odense University hospital the standard treatment has been no sedation. The general impression has been that this reduces time in mechanical ventilation and reduces complications such as acute renal failure. It has not been the impression that this treatment increased the risk of long term psychological problems compared to standard treatment with sedation. The "no-sedation" method has however never been described in the literature or tested in a prospective randomized trial. HYPOTHESIS: The main hypothesis was that a no sedation strategy reduces the time patients receive mechanical ventilation, decrease intensive care and total length of hospital stay. Secondary endpoints were: a no sedation strategy would reduce secondary organ failure such as kidney injury and would not increase the risk of post-traumatic stress disorder after hospital discharge. METHODS: We randomized 140 critically ill patients in need of mechanical ventilation. The intervention group received only bolus doses of morphine or haloperidol if delirium was suspected. The control group received standard infusion of sedatives to RAMSAY 3-4 and sedatives were interrupted on a daily basis. Both groups received morphine as intravenous bolus doses (2.5 to 5 mg). The primary outcome was days without mechanical ventilation, days in the ICU and total length of hospital stay. We conducted a post-hoc analysis of the data with kidney function expressed in urine output and RIFLE classification as the primary outcome. After hospital discharge all patients were invited to an interview with a neuropsychologist to assess Post Traumatic Stress Disorder (PTSD), depression and general psychological and physical health. RESULTS:27 patients died or were successfully weaned from mechanical ventilation within 48 hours and were excluded from further analysis. Patients from the awake intervention group (n=55) had 4.2 more days without mechanical ventilation compared to the sedated control group (n=58) (P=0.0191). Also ICU length of stay was reduced in the awake intervention group by 9.7 days (P=0.0316) and total hospital length of stay was reduced 24 days (P=0.0039) compared to the sedated control group. An increased urine output was seen in the group receiving no sedation compared to the sedated control group (1.15 ml/kg/hour vs. 0.88 ml/kg/hour, P=0.03), also more patients from the sedated control group were classified with renal impairment (41 (76%)) according to the RIFLE classification compared to the awake intervention group (25 (51%), P=0.012). 26 patients were interviewed approximately 2 years after randomization, 13 from each group. No difference was seen between the groups with respects to Post Traumatic Stress Disorder, depression and general psychological and physical health. CONCLUSION: A strategy of no sedation to critically ill patients undergoingmechanical ventilation resulted in fewer days in mechanical ventilation, shorter ICU and hospital length of stay compared to a standard strategy with sedation. Also the risk of acute renal impairment seems to be reduced with the use of no sedation. The no sedation strategy does not seem to alter long term psychological outcome.
RCT Entities:
BACKGROUND: Standard treatment of critically illpatients undergoing mechanical ventilation is continuous sedation. This standard treatment to all patients has been greatly challenged over the last decade. At the general intensive care department at Odense University hospital the standard treatment has been no sedation. The general impression has been that this reduces time in mechanical ventilation and reduces complications such as acute renal failure. It has not been the impression that this treatment increased the risk of long term psychological problems compared to standard treatment with sedation. The "no-sedation" method has however never been described in the literature or tested in a prospective randomized trial. HYPOTHESIS: The main hypothesis was that a no sedation strategy reduces the time patients receive mechanical ventilation, decrease intensive care and total length of hospital stay. Secondary endpoints were: a no sedation strategy would reduce secondary organ failure such as kidney injury and would not increase the risk of post-traumatic stress disorder after hospital discharge. METHODS: We randomized 140 critically illpatients in need of mechanical ventilation. The intervention group received only bolus doses of morphine or haloperidol if delirium was suspected. The control group received standard infusion of sedatives to RAMSAY 3-4 and sedatives were interrupted on a daily basis. Both groups received morphine as intravenous bolus doses (2.5 to 5 mg). The primary outcome was days without mechanical ventilation, days in the ICU and total length of hospital stay. We conducted a post-hoc analysis of the data with kidney function expressed in urine output and RIFLE classification as the primary outcome. After hospital discharge all patients were invited to an interview with a neuropsychologist to assess Post Traumatic Stress Disorder (PTSD), depression and general psychological and physical health. RESULTS: 27 patients died or were successfully weaned from mechanical ventilation within 48 hours and were excluded from further analysis. Patients from the awake intervention group (n=55) had 4.2 more days without mechanical ventilation compared to the sedated control group (n=58) (P=0.0191). Also ICU length of stay was reduced in the awake intervention group by 9.7 days (P=0.0316) and total hospital length of stay was reduced 24 days (P=0.0039) compared to the sedated control group. An increased urine output was seen in the group receiving no sedation compared to the sedated control group (1.15 ml/kg/hour vs. 0.88 ml/kg/hour, P=0.03), also more patients from the sedated control group were classified with renal impairment (41 (76%)) according to the RIFLE classification compared to the awake intervention group (25 (51%), P=0.012). 26 patients were interviewed approximately 2 years after randomization, 13 from each group. No difference was seen between the groups with respects to Post Traumatic Stress Disorder, depression and general psychological and physical health. CONCLUSION: A strategy of no sedation to critically illpatients undergoing mechanical ventilation resulted in fewer days in mechanical ventilation, shorter ICU and hospital length of stay compared to a standard strategy with sedation. Also the risk of acute renal impairment seems to be reduced with the use of no sedation. The no sedation strategy does not seem to alter long term psychological outcome.