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

Drug

Onset and Duration

Precautions

for Use

CYP

Substrate

(major)

Usual Dose

Significant

Adverse

Effects

Propofol

Onset: 1 min

Duration: 
short term:

0.5–1 hr; long term

> 7 days: variable;

25–50 hr has been

observed (depends

on depth and time on

sedation)

Hypotension,

bradycardia,

hepatic/

renal failure,

pancreatitis

2B6

5–50 mcg/kg/

min; 0.3–3 mg/

kg/hr

Hypotension,

pancreatitis,

respiratory

depression,

bradycardia,

PRIS

Dexmedetomidine

Onset: 5–10 min

(with LD)
1–2 hr

(without LD)

Duration: 1–2 hr

Hepatic failure;

symptomatic

bradycardia

2A6

LD: 0.5–1 mcg/

kg (optional)

MD: 0.2–0.7

mcg/kg/hr

Hypo/hyper-

tension,

bradycardia,

pyrexia

Lorazepam

Onset: 5–20 min

Duration: 4–8 hr;

prolonged with

continuous infusion

Delirium, renal

failure

N/A

Intermittent:

1–4 mg IV

every 4–6 hr

Oversedation,

propylene

glycol toxicity

Midazolam

Onset: 3–5 min

Duration: 2–6 hr,

prolonged with

continuous infusion

Hepatic failure,

end-stage

renal failure

or dialysis,

delirium

3A4

(active

metabolite)

0.02–0.1 mg/

kg/hr

Oversedation

CI = continuous infusion; IV = intravenously; LD = loading dose; MD = maintenance dose; N/A = not applicable; PRIS = propofol-related infusion syndrome.

suggest using either propofol or dexmedetomidine over benzodiazepines [midazolam or lorazepam] for

sedation in critically ill, mechanically ventilated adults” and those after cardiac surgery. SCCM states

that “benzodiazepine use may be a risk factor for the development of delirium in adult ICU patients.” Two

randomized studies evaluated the differences in clinical outcomes while adult ICU patients were receiving

sedation with either a benzodiazepine or a non-benzodiazepine strategy. Heterogeneity occurred among the

findings of these two studies (see No. 1 and No. 2 below), which may be partly because of differences in study

design.

The MENDS study compared the sedative effects of lorazepam and dexmedetomidine in medical and

surgical adult ICU patients (n=103). Dexmedetomidine had more “delirium-free + coma-free” days

than lorazepam (7 vs. 3 days, p=0.01), and the prevalence of “delirium or coma” was lower in the

dexmedetomidine group (87% vs. 98%, p=0.03). The assessment of “delirium-free + coma-free” was

a more appropriate outcome to evaluate than “delirium without coma,” given that delirium cannot

be assessed in patients with coma. More patients were within 1 point of their RASS goal with

dexmedetomidine (67%) than with lorazepam (55%), p=0.008, but there was no difference in mechanical

ventilator–free days, ICU length of stay, or 28-day mortality. This study has been criticized because

both groups received continuous infusions of sedatives without additional bolusing, whereas in clinical

practice, most practitioners would bolus lorazepam before increasing the infusion rate. In addition,