Authors: Haley Goucher Miranda, M.D. et al
Anesthesiology 8 2017, Vol.127, 397-398.
To the Editor:
In November 2016’s issue of Anesthesiology, Wu et al., in their article “Low-dose Dexmedetomidine Improves Sleep Quality Pattern in Elderly Patients after Noncardiac Surgery in the Intensive Care Unit: A Pilot Randomized Controlled Trial,”1 demonstrated polysomnographic improvement in sleep in patients treated with low-dose (0.1 µg kg−1 h−1) prophylactic dexmedetomidine. Although many nonpharmacologic strategies have been proposed to improve sleep quality in the intensive care unit (ICU), nocturnal infusions of the α-2 agonist and sedative dexmedetomidine have been increasingly utilized in nonintubated ICU patients in efforts to reduce the incidence or duration of delirium, which affects 20 to 80% of ICU patients and is associated with prolonged lengths of stay and possibility increased mortality.2 Because the efficacy of the treatments of delirium have been disappointingly limited, increasing enthusiasm has been placed on preventative techniques, such as ensuring that ICU patients achieve adequate durations of sleep.3 A pathophysiologic rationale for this therapy comes from observational polysomnographic studies that demonstrated a dramatic reduction in both restorative rapid eye movement (REM) and slow-wave (stages 3 and 4) sleep in ICU patients.4,5 Dexmedetomidine infusions generate an electroencephalogram pattern that resembles stage 2 non-REM sleep in treated patients, which is the basis of its usage in the ICU to promote sleep.4,5 However, in these polysomnographic studies, treated subjects also demonstrated severely disrupted overall sleep architecture, with few achieving slow-wave sleep or REM sleep of any significant duration.4,5 In addition, an animal study demonstrated a complete loss of REM sleep with dexmedetomidine infusions, with treated rats requiring significant posttreatment rebound in both non-REM and REM sleep need.6 In the study by Wu et al.,1 there was no significant difference in the occurrence of stage 3 non-REM sleep, and REM sleep remained absent in the two groups. Although they demonstrated an improvement in sleep efficiency or the ratio of total sleep time to total monitoring time, this metric does not account for sleep architecture. Importantly, there was also no observed difference in delirium, a predefined secondary outcome. In addition, the authors noted a decreased ICU length of stay but an increased hospital length of stay in dexmedetomidine patients.
Further well-powered studies evaluating patient-oriented outcomes are needed before supporting the routine usage of prophylactic nocturnal dexmedetomidine infusions as a sleep aid, particularly given the two- to threefold increased incidence of bradycardia and hypotension seen in treated patients in this trial and in other studies.7 In an ICU population, such a high incidence of unfavorable hemodynamic disturbances may outweigh the minimal demonstrated treatment effect.
Because access to dexmedetomidine will continue to increase as the generic formulation becomes widely available, indications beyond just sedation of the mechanically ventilated patient are increasingly explored. Although there are suggestions of potential efficacy, many unanswered questions about the drug remain. First, although it has been consistently demonstrated that nocturnal dexmedetomidine infusion increases duration of a stage 2 non-REM sleep-like electroencephalogram pattern, it is unclear whether this shift in sleep architecture, even if total sleep time is increased, yields a restorative effect. Second, the risks of utilizing dexmedetomidine in nonintubated, critically ill patients, including the possibility of increasing delirium secondary to its sedative effects, have yet to be fully elucidated. Third, and perhaps most importantly, current studies of nocturnal dexmedetomidine infusions have focused primary outcomes on polysomnographic data and have either not evaluated or failed to demonstrate significant clinical benefit. Perhaps enthusiasm for the off-label use of dexmedetomidine as a prophylactic sleep adjunct in nonintubated patients without refractory hyperactive delirium should be tempered until prospective, randomized data are able to adequately define the risks and benefits.
Haley Goucher Miranda, M.D., Andrew D. Krystal, M.D., Michael A. Fierro, M.D. Kansas University Medical Center, Kansas City, Kansas (H.G.M.).
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