We agree with Dr. Goucher et al. that low-dose dexmedetomidine infusion did not restore the normal sleep architecture because stage 3 non–rapid eye movement sleep and rapid eye movement (REM) sleep remained significantly decreased or absent in our patients.1 This is also the case when dexmedetomidine was administered for sedation in mechanically ventilated patients.2,3 It should be noted that the target subjects were patients in the intensive care unit (ICU) after major surgery in our study1 or receiving mechanical ventilation in another previous study.3 It is well known that significant sleep disturbances such as fragmented sleep, decreased sleep efficiency, increased stage 1 non-REM sleep, and decreased or absent stage 3 non-REM and REM sleep are often present in those patients. Dexmedetomidine partially improved “sleep architecture” through increasing the percentage of stage 2 non-REM sleep (and decreasing the percentage of stage 1 non-REM sleep), a unique property that has also been demonstrated in other clinical studies previously.4
Considering the importance of sleep for ICU recovery and the lack of effective pharmacologic interventions to improve sleep,5 prophylactic low-dose dexmedetomidine may be a choice, although not the best. Clinical effectiveness was demonstrated in our previous trial in 700 patients admitted to the ICU after noncardiac surgery, in which low-dose dexmedetomidine infusion reduced the incidence of delirium during the first 7 days after surgery (9% compared with 23% with placebo) and also decreased the incidence of nondelirium complications and increased early hospital discharge.6 We cannot establish a causal relationship between delirium reduction and improved sleep in patients from these two independent trials.1,6
It is true that hemodynamic disturbances are major concerns when using dexmedetomidine in ICU patients. Indeed, dexmedetomidine at such a low dose (0.1 µg kg−1 h−1) slightly increased the occurrence of hypotension, although not statistically significantly,6 indicating that close monitoring is necessary whenever dexmedetomidine is on-board. Last but not least, whether delirium prevention by dexmedetomidine ultimately improves patients’ long-term outcome remains unknown and warrants further study.
Regarding the question of Dr. Reade, herein we confirm that these two studies1,6 are completely independent trials in which each has an individual registration (Chinese Clinical Trial Registry [Chengdu, Sichuan, China; www.chictr.org.cn] Nos. ChiCTR-TRC-10000802 and ChiCTR-TRC-12002567). Patients who were recruited in one study were not enrolled the other one.
Support provided by Wu Jieping Medical Foundation (Beijing, China). Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co., Ltd. (Jiangsu, China). The sponsors have no role in the study design and conduct; the collection, management, analysis, and interpretation of the data; or the preparation and approval of the manuscript.
Dr. Wang reports that he has received lecture fees and travel expenses for lectures given at domestic academic meetings from Jiangsu Hengrui Medicine Co., Ltd. (Jiangsu, China). The other author reports no competing interests.