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Published on: December 6, 2016
A randomized controlled trial of daily sedation interruption in critically ill children
Nienke J Vet1,2, Saskia N de Wildt3,4, Carin W M Verlaat5
1Intensive Care, Erasmus MC - Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. n.vet@erasmusmc.nl.
Insights
Daily sedation interruption in critically ill children did not improve outcomes and was linked to higher mortality. Protocolized sedation alone is a safer approach for pediatric intensive care units.
Area of Science:
- Pediatric Critical Care Medicine
- Pharmacology
- Clinical Trials
Background:
- Sedation management is crucial for mechanically ventilated children.
- Daily interruption of sedation aims to reduce sedation duration and improve outcomes.
- Evidence for the efficacy and safety of daily sedation interruption in pediatric populations is limited.
Purpose of the Study:
- To compare the efficacy and safety of daily sedation interruption plus protocolized sedation (DSI + PS) versus protocolized sedation only (PS) in critically ill children.
- To evaluate the impact on ventilator-free days and other clinical outcomes.
Main Methods:
- A multicenter randomized controlled trial involving mechanically ventilated children requiring sedation.
- Participants were randomized to either DSI + PS or PS only groups.
- The primary endpoint was ventilator-free days at day 28; secondary endpoints included length of stay and mortality.
Main Results:
- The study was terminated early due to slow recruitment.
- No significant difference was observed in ventilator-free days between the DSI + PS and PS groups (median 24.0 days in both).
- Mortality at 30 days was higher in the DSI + PS group (6/66) compared to the PS group (0/63), though causality was not established.
Conclusions:
- Daily sedation interruption in addition to protocolized sedation did not improve clinical outcomes in critically ill children.
- The DSI + PS approach was associated with increased mortality compared to protocolized sedation alone.
- Protocolized sedation alone appears to be a safer strategy for this patient population.
Purpose:
To compare daily sedation interruption plus protocolized sedation (DSI + PS) to protocolized sedation only (PS) in critically ill children.
Methods:
In this multicenter randomized controlled trial in three pediatric intensive care units in the Netherlands, mechanically ventilated critically ill children with need for sedative drugs were included. They were randomly assigned to either DSI + PS or PS only. Children in both study arms received sedation adjusted on the basis of validated sedation scores. Provided a safety screen was passed, children in the DSI + PS group received daily blinded infusions of saline; children in the PS group received blinded infusions of the previous sedatives/analgesics. If a patient's sedation score indicated distress, the blinded infusions were discontinued, a bolus dose of midazolam was given and the 'open' infusions were resumed: DSI + PS at half of infusion rate, PS at previous infusion rate. The primary endpoint was the number of ventilator-free days at day 28. Data were analyzed by intention to treat.
Results:
From October 2009 to August 2014, 129 children were randomly assigned to DSI + PS (n = 66) or PS (n = 63). The study was terminated prematurely due to slow recruitment rates. Median number of ventilator-free days did not differ: DSI + PS 24.0 days (IQR 21.6-25.8) versus PS 24.0 days (IQR 20.6-26.0); median difference 0.02 days (95 % CI -0.91 to 1.09), p = 0.90. Median ICU and hospital length of stay were similar in both groups: DSI + PS 6.9 days (IQR 5.2-11.0) versus PS 7.4 days (IQR 5.3-12.8), p = 0.47, and DSI + PS 13.3 days (IQR 8.6-26.7) versus PS 15.7 days (IQR 9.3-33.2), p = 0.19, respectively. Mortality at 30 days was higher in the DSI + PS group than in the PS group (6/66 versus 0/63, p = 0.03), though no causal relationship to the intervention could be established. Median cumulative midazolam dose did not differ: DSI + PS 14.1 mg/kg (IQR 7.6-22.6) versus PS 17.0 mg/kg (IQR 8.2-39.8), p = 0.11.
Conclusion:
In critically ill children, daily sedation interruption in addition to protocolized sedation did not improve clinical outcome and was associated with increased mortality compared with protocolized sedation only.
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