Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption, and Neuromuscular Blockade

Data: SPICE III was an open-label, randomized controlled trial comparing dexmedetomidine as primary

sedation with usual care (propofol, midazolam, or other sedation) in patients receiving less than 12 hours

of mechanical ventilation who are expected to be on the ventilator for at least one additional day. The

target RASS goal was -2 to +1. Death at 90 days occurred in 569 of 1956 (29.1%) of the usual care group

and 566 of 1948 (29.1%) of the dexmedetomidine group (adjusted risk difference 0.0 percentage points;

95% CI, –2.9 to 2.8). In the dexmedetomidine group, 64% of patients additionally received propofol, 3%

received midazolam, and 7% received both during the first 2 days after randomization. Sixty percent

of patients received propofol, 12% received midazolam, and 20% received both in the usual care group.

Given the many sedatives administered in both groups, application of the study results is difficult. In

the dexmedetomidine group, bradycardia and hypotension occurred in 5.1% and 2.7% of patients. A

post hoc analysis of SPICE III included 703 mechanically ventilated patients. Over the first 5 ICU days,

more patients in the dexmedetomidine group had a temperature of 38.3°C or greater (43.3% vs 32.7%,

p=0.004) and 39.0°C or greater (19.4% vs 12.5%, p=0.013). A post hoc subgroup analysis of SPICE III

compared the effect of dexmedetomidine versus usual care on vasopressor requirements in patients

with septic shock. This subroup included 83 patients, of which, 44 (53%) received dexmedetomidine

and 39 (47%) usual care. In the first 48 hours, median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the

dexmedetomidine group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). Patients in

the dexmedetomidine group had a lower NEq/MAP ratio, meaning lower vasopressor requirements to

maintain the target MAP.

difference was found between dexmedetomdine and propofol in the number of days alive and without

delirium of coma (adjusted median 10.7 vs 10.8 days; odds ratio, 0.96; 95% CI 0.74–1.26), ventilator free

days (adjusted median, 23.07 vs. 24 days, odds ratio 0.98; 95% CI, 0.63–1.51), or death at 90 days 38%

vs. 39%; hazard ratio, 1.06; 95% CI 0.74–1.52).

adults. A total of 77 randomized trials were included. Compared with other sedatives, dexmedetomidine

reduced the risk of delirium (RR 0.67; 95% CI, 0.55–0.81; moderate certainty), duration of mechanical

ventilation (mean difference [MD] -1.8 hours; 95% CI, -2.89 to -0.71; low certainty), and ICU length

of stay (MD -0.32 days; 95% CI, -0.42 to -0.22; low certainty). The risk of bradycardia (RR 2.39; 95%

CI, 1.82–3.13; moderate certainty) and hypotension (RR 1.32; 95% CI, 1.07–1.63; low certainty) was

increased with dexmedetomidine.

mechanically ventilated adult patients in the ICU. It suggested use of dexmedetomidine over other

sedative agents if the reduction in delirium was more highly valued than the potential for hypotension

and bradycardia.

generally be avoided in patients with acute decompensated heart failure or advanced heart block

to opiates for sickle cell crisis, adjunct to benzodiazepines or propofol for alcohol withdrawal, bridge to

extubation while tapering off longer-acting sedatives and/or opiates, to provide sedation and anxiolysis

during noninvasive mechanical ventilation

Pharmacokinetics: Benzodiazepine that binds to the postsynaptic GABAA receptor, undergoes hepatic

clearance by conjugation to inactive compounds; moderate to high volume of distribution and high

protein binding. Onset of action is 15–30 minutes, slower than more lipophilic benzodiazepines (e.g.,

midazolam). Duration of action of intermittent dosing is 4–8 hours. As a continuous infusion, clearance

of lorazepam decreases in an unpredictable fashion, and prolonged sedation may occur.