A new approach to the prevention and treatment of delirium in elderly patients in the intensive care unit

Figures & data

Fig. 1 Flowchart of identification, screening, and review of studies.

Table 1 Comparison of the nine articles

Study, year (reference)	Type	Aim	Patients, n	Avg age	Validated tools used	Comparison medication	Average dose of each medication	Outcomes (dexmedetomidine vs. comparison drug)
Pandharipande et al., 2007 (16)	Double-blind, randomized controlled trial	To determine whether DEX reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam	106	60 (DEX) vs. 59 (L)	RASS CAM-ICU	Lorazepam (L)	DEX (prepared for a final concentration of 0.15 µg/kg per mL) or lorazepam (1 mg/mL). The study drug infusion was started at 1 mL/h (0.15 µg/kg per hour DEX or 1 mg/h lorazepam) and titrated by the bedside nurse to a maximum of 10 mL/h (1.5 µg/kg per hour DEX or 10 mg/h lorazepam)	Days alive without delirium or coma: median days, 7.0 vs. 3.0 (p=0.01). More patients in the DEX group (42% vs. 31%; p=0.61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions.
Riker et al., 2009 (17)	Prospective, double-blind, randomized trial	To compare the efficacy and safety of prolonged sedation with DEX vs. midazolam for mechanically ventilated patients	375	61.5 (DEX) vs. 62.9 (M)	RASS CAM-ICU	Midazolam (M)	0.8 µg/kg per hour for DEX and 0.06 mg/kg per hour for midazolam Patients in either group not adequately sedated by study drug titration could receive open-label midazolam bolus doses of 0.01 to 0.05 mg/kg at 10- to 15-min intervals until adequate sedation	Prevalence of delirium was 54% (132/244) in DEX-treated patients vs. 76.6% (93/122) in midazolam-treated patients (22.6% difference; 95% CI, 14–33%; p=0.001). CAM-ICU–negative at study enrollment: the effect of DEX treatment measured by GEE was a 15.4% decrease (95% CI, 2–29%; p=0.02), with a delirium prevalence of 32.9% (25/76) in DEX-treated patients vs. 55.0% (22/40) in midazolam-treated patients (p=0.03). CAM-ICU–positive at baseline, the DEX treatment effect measured by GEE was a 32.2% reduction (95% CI, 21–43%; p=0.001), with a prevalence of 68.7% (90/131) for DEX-treated patients vs. 95.5% (63/66) for midazolam-treated patients (p 0.001).
Shehabi et al., 2009 (18)	Randomized, double-blind, controlled trial	Assessing the neurobehavioral, hemodynamic, and sedative characteristics of DEX vs. a morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia	299	71	MAAS CAM-ICU	morphine	DEX (0.1–0.7 µg/kg/mL 1) vs. morphine (10–70 μg/kg/mL)	Overall incidence of delirium within 5 days was 11.7% (35 of 299), with 8.6% occurring in the DEX group and 15% in the morphine group (RR 0.571, 95% CI 0.256–1.099, p=0.088). The duration of delirium was significantly less in DEX compared with morphine-treated patients (2 vs. 5 days, 95% CI 1.09–6.67, log rankp=0.0317).
Maldonado et al., 2009 (19)	Open label, prospective, randomized trial	Looking at the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures	90	55 (DEX) vs. 58 (P) vs. 60 (M)	RSS DRS, CAM, CAM-ICU	Midazolam (M), propofol (P)	DEX (loading dose: 0.4 μg/kg, followed by a maintenance drip of 0.2–0.7 μg/kg/hour) propofol drip (25–50 μg/kg/minute) midazolam drip (0.5–2 mg/hour)	The incidence of delirium for patients on DEX was 3% (1/30); for those on propofol, 50% incidence (15/30); for patients receiving midazolam, 50% incidence (15/30). Mean length of delirium days: 2.0 (DEX) vs. 3.0 (P) vs. 5.4 (M).
Reade et al., 2009 (20)	Randomized, open-label, parallel groups pilot trial	To compare the efficacy of haloperidol and DEX in facilitating extubation	20	52 (DEX) vs. 68.5 (H)	RASS ICDSC	Haloperidol (H)	DEX: 0.2–0.7 µg/kg/hour Haloperidol: 0.5–2 mg/hour, preceded by a loading dose of 2.5 mg if desired	Proportion of time with a satisfactory ICDSC score (<4) when assessable, %: median (IQR) DEX 95.5 (51–100) vs. H 31.5 (17–97) p 0.122. Proportion of time with a desirable ICDSC score (<1) when assessable, %: median (IQR) DEX 61.0 (0.0–100.0) vs. H 0.0 (0.0–0.0) p=0.134.
Pandharipande et al., 2010 (21)	Randomized, double-blind, a-priori subgroup	To determine if sedation with DEX vs. lorazepam in septic and non-septic patients affected clinical outcomes, including duration and prevalence of acute brain dysfunction and 28-day mortality	103	60.5 vs. 59	RASS CAM-ICU	Lorazepam (L)	DEX-based (maximum 1.5 µg/kg/h) lorazepam-based (maximum 10 mg/h) sedation for up to 5 days	Septic patients sedated with DEX had a mean (95% CI) of 3.2 (1.1–4.9) more delirium/coma-free days, 1.5 (–0.1 to 2.8) more delirium-free days, and 6 (0.3–11.0) more ventilator-free days than patients receiving lorazepam. Among all patients (regardless of sepsis), DEX-treated patients had 70% lower odds, compared with lorazepam-treated patients, of being delirious on any given day [odds ratio (OR)=0.3, 95% CI=0.1–0.7].
Jakob et al., 2012 (10)	Two phase, 3 multicenter, randomized, double-blind trials	To determine the efficacy of DEX vs. midazolam or propofol in maintaining sedation, reducing duration of mechanical ventilation, and improving patients’ interaction with nursing care	MIDEX=501	65	RASS CAM-ICU	MIDEX=midazolam	DEX 0.450 (0.273–0.756) Midazolam 0.062 (0.041–0.098) (units µg/kg/h or mg/kg/h)	Patients’ interaction (VAS) was improved with DEX (estimated score difference vs. midazolam, 19.7 [95% CI, 15.2–24.2]; p<0.001.
			PRODEX=500	65	RASS CAM-ICU	PRODEX=propofol	DEX 0.925 (0.673–1.170) Propofol 1.752 (1.211–2.424) (units µg/kg/h or mg/kg/h)	Patients receiving DEX were more arousable, more cooperative, and better able to communicate their pain than patients receiving either midazolam or propofol (estimated score difference vs. propofol 11.2 (95% CI, 6.4–15.9), p<0.001.
Park et al., 2014 (22)	Prospective, randomized trial	To investigate the post-operative sedative effects of DEX as compared to remifentanil in patients undergoing open heart surgery with cardiopulmonary bypass	142	51 vs. 54	Modified RSS CAM-ICU	remifentanil	DEX (loading dose, 0.5 µg/kg; maintenance dose, 0.2–0.8 µg/kg/h) Remifentanil (range, 1,000–2,500 μg/h)	Overall incidence of delirium during postoperative first 3 days was 16% (23 of 142), with 8.96% (6 of 67) occurring in the DEX and 22.67% (17 of 75) in the remifentanil group, respectively (p<0.05).
Wanat et al., 2014 (23)	Retrospective, observational trial	To evaluate the efficacy and safety of DEX and propofol for sedation after cardiovascular surgery	352	63 (DEX) vs. 68 (P)	RASS CAM-ICU	Propofol (P)	DEX (µg/kg/h): Average dose 0.489±0.13, Maximum dose 0.602±0.15 Propofol (µg/kg/min):	Incidence delirium (CAM-ICU+): DEX 3 (12.0), propofol 24 (9.0), p=0.747.
							mean 29.50±10.63, maximum 36.38±13.49

DEX, dexmedetomidine; RASS, Richmond Agitation Sedation Scale; CAM, Confusion Assessment Method; CAM-ICU, Confusion Assessment Method for the ICU; MAAS, Motor Activity Assessment Scale; DRS, Delirium Rating Scale; RSS, Ramsay Sedation Scale; ICDSC, Intensive Care Delirium Screening Checklist.

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Park JB, Bang SH, Chee HK, Kim JS, Lee SA, Shin JK. Efficacy and safety of dexmedetomidine for postoperative delirium in adult cardiac surgery. Korean J Thorac Cardiovasc Surg. 2014; 47: 249–54. doi: 10.5090/kjtcs.2014.47.3.249.

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