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Table 1 Characteristics of included studies

From: Use of dexmedetomidine in patients with sepsis: a systematic review and meta-analysis of randomized-controlled trials

Study author and year

Study design

No. of patients DEX/control

Gender,

Male DEX/control

Mean or median age in years DEX/control

Mean or median APACHE II scores DEX/control

Mean or median SOFA scores DEX/control

Sedation goals

Evaluating pain management

Pain management

Ventilation settings

Usage dose in DEX group

Control group

Sepsis case definition

Relevant outcomes collected

Cai et al., 2019

Single site RCT

30/30

20/19

54 ± 17.55/

58.6 ± 14.95

20.3 ± 4.76/

21.43 ± 4.52

8.67 ± 1.54/

8.8 ± 2.36

RASS score of -2 to 0

not reported

not reported

not reported

loading dose of 1 μg/kg, followed by a maintenance dose of 0.2–1 μg/kg/h

Propofol group: loading dose of 1–3 mg/kg, followed by a maintenance dose of 0.05–3 mg/kg/hr

Sepsis-3

Inflammatory cytokine changes;

overall mortality on day 28

Chen et al., 2018

Single site RCT

80/80

48/46

47.57 ± 4.48/46.21 ± 4.22

17.74 ± 1.19/

17.26 ± 1.12

N/A

RASS score of -1 to 0

score of severe patients with pain assessment table was controlled at 0 ~ 1

Remifentanil

not reported

maintenance dose of

0.2–0.7 μg/kg/h

Propofol group: maintenance dose of 0.3–4 mg/kg/hr

Sepsis-2

Inflammatory cytokine changes

Cioccari et al., 2020

Multisite RCT

44/39

29/28

67.7 ± 12.4/

62.9 ± 16.8

24.9 ± 6.7/

25.3 ± 7.0

6 (5,10)/

9 (5,14)

RASS score of -2 to -4

not reported

not reported

not reported

1.12 (0.06–8.0) μg/kg/d; Duration (days): 0.75 (1.7)

Propofol group: 13.56 (4.25–31.7) mg/kg/d; Duration (days): 3.34 (3.27)

Sepsis-2 and septic shock

Vasopressor requirements in the first 48 h;

Overall mortality day 28;

days of mechanical ventilation;

Length of ICU stay;

Length of hospital stay;

Vasopressor-free at 48 h

Hughes et al., 2021

Multi-center RCT

214/208

121/120

59 (48–68)/

60 (50–68)

27 (21,32)/

27 (22,32)

10 (8,13)/

10 (8,12)

RASS score of -2 to 1

not reported

intermittent opioid boluses or fentanyl infusion

not reported

maintenance dose of

0.2–1.5 μg/kg/h

Propofol group: maintenance dose of 5–50 μg/kg/h

Clinical signs laboratory findings

Overall mortality day 90;

Ventilator-free days;

days of alive without delirium or coma;

Safety end points

Kawazoe et al., 2017

Multisite RCT

100/101

63/64

68(14.9)/

69(13.6)

23 (18,29)/

22 (16,29.5)

8 (6,11)/

9 (5,11)

RASS score of -2 to 0

not reported

DEX group: DEX continuously, and other sedatives

control group: propofol, midazolam, and analgesia without DEX

mechanical ventilation for at least 24 h

m [IQR], mg (in the first week): 81 [11, 154.5] ~ 228 [29, 408.5]

Propofol group: m [IQR], mg (in the first week):0 [0, 200] ~ 600 [0, 1077.5]

Sepsis-1

28-day mortality and ventilator-free days;

Organ Failure Assessment score (days 1, 2, 4, 6, 8); Sedation control;

Occurrence of delirium and coma;

Length of ICU stay;

Renal function;

Inflammation;

Nutrition state

Lei et al., 2016

Single site RCT

29/29

17/16

46.5 ± 18.4/

47.5 ± 15.2

17.9 ± 4.9/

18.3 ± 4.2

N/A

Ramsay score of

2 to 3

not reported

not reported

not reported

loading dose of 1 μg/kg over 10 min, followed by a maintenance dose of 0.2–0.7 μg/kg/h

Propofol group: loading dose of 1–3 mg/kg over 30–60 s, followed by a maintenance dose of 0.5—4 mg/kg/hr

Sepsis-2

Overall mortality day 28;

Length of hospital stays;

Changes of myocardial injury markers before and after sedative use

Liu et al., 2020

Single site RCT

100/100

57/58

57 (31–66) /

54 (35–71)

29 (26,37)/

29 (22,36)

10 (8,13)/

11 (8,12)

RASS score of -2 to 0

not reported

not reported

not reported

loading dose of 1 μg/kg over 10 min, followed by a maintenance dose of 0.2–0.3 μg/kg/h

Propofol group: loading dose of 1 mg/kg over 10 min, followed by a maintenance dose of 1 to 3 mg/kg/hr

septic shock

Inflammatory cytokine changes;

Changes of SCr and BUN;

Overall mortality day 28;

Length of ICU stays

Memiş et al., 2009

Single site RCT

20/20

14/13

60 (31–80)/

54 (25–78)

22 ± 5/

20 ± 8

4.5 ± 2.8/

4.0 ± 2.9

N/A

not reported

Alfentanil infusion

Ventilator setting: volume or pressure-controlled, no alteration during the study period;

only patients with PaO2 80–140 mmHg and PaCO2 35–50 mmHg were included

loading dose of 1 μg/kg over 10 min, followed by a maintenance dose of 0.2–2.5 μg/kg/h

Propofol group: loading dose of 1 mg/kg over 15 min, followed by a maintenance dose of 1 to 3 mg/kg/hr

septic shock

Overall ICU mortality;

Length of ICU stay

Meng et al., 2014

Single site RCT

20/20

13/11

56 ± 18/

51 ± 14

18 ± 4/

19 ± 4

4.2 ± 1.7/

4.1 ± 2.4

Ramsay score of

2 to 3

Behavioral Pain Scale (BPS)

Alfentanil:

1.0–3.0 μg/kg/min

not reported

loading dose of 1 μg/kg over 10 min, followed by a maintenance dose of 0.2–2.5 μg/kg/h

Propofol group: loading dose of one mg/kg over 15 min, followed by a maintenance dose of three mg/kg/hr

Sepsis-1

Inflammatory cytokine changes

Pandharipande et al., 2010

Single site RCT

31/32

18/13

60 (46,65)/

58 (44,66)

30 (26, 34)/

29 (24, 32)

10 (9,13)/

9 (8,12)

RASS score of -4 to -2

changes in vital signs, facial expressions,

limb movement, ventilator synchrony

Fentanyl, intermittent doses

not reported

maximum 1.5 mcg/kg/hr

Lorazepam group: maximum 10 mg/hr

Sepsis-2

Delirium/coma-free days;

Ventilator-free days;

Risk of dying at 28 days;

Reduced the daily risk of delirium

Sigler et al., 2018

Single site RCT

17/19

13/9

62.5/59

19 (13, 20)/

16 (12, 19)

11 (7, 14)/

10 (8, 13)

RASS score of -2 to 2

not reported

Fentanyl infusion, or intermittent opioid boluses

not reported

initiated at 0.2 mcg/kg/hour, titrated every 5 min by 0.1 mcg/kg/hour to a maximum dose of 1.4 mcg/kg/hour

Propofol group: initiated at 5 mcg/kg/minute and titrated every 5 min by 5 mcg/kg/minute

Sepsis-2

Overall mortality day 28;

days of mechanical ventilation,

Length of ICU stay,

Vasopressor infusion

Tasdogan et al., 2009

Single site RCT

20/20

14/11

58 (21–78)/ 50 (19–74)

19 ± 5/ 18 ± 4

4.2 ± 1.8/ 4.0 ± 2.5

N/A

Behavioral Pain Scale (BPS)

Alfentanil, 0.25–1.0 μg/kg/min

Mechanical ventilation setting: DEX/control group Tidal volume (mL/kg):

6.5(6.0–8.6)/6.2(5.8–7.8)

Respiratory rate (breaths/ min): 24(19–26)/22(18–26)

Fi02(%): 55(40–65)/55(45–70)

PEEP (cmH2O): 5(5–8)/6 (5–10)

loading dose of 1 μg/kg over 10 min followed by a maintenance dose of 0.2–2.5 μg/kg/h

Propofol group: loading dose of one mg/kg over 15 min, followed by a maintenance dose of one to three mg/kg/hr

Sepsis-1

Biochemical and hemodynamic parameters;

Cytokine levels;

IAP were recorded before the start of the study and at the 24th and 48th hours

Wang et al., 2016

Single site RCT

28/28

24/24

47.32 ± 14.86/

51.11 ± 15.15

11.21 ± 3.99/

11.86 ± 6.87

10.68 ± 5.15/

11.39 ± 5.19

Ramsay score of

3 to 4

not reported

not reported

not reported

loading dose of 1 μg/kg over 10 min followed by a maintenance dose of 0.2–0.7 μg/kg/h

Propofol group: loading dose of 0.025–1 mg/kg, followed by a maintenance dose of 0.5–4 mg/kg/hr

Sepsis-2

Inflammatory cytokine changes;

Overall mortality;

Length of ICU stay;

Incidence of adverse reactions

Wang et al., 2019

Single site RCT

31/32

17/17

74.13 ± 10.69/

20.97 ± 5.64/20.7 ± 5.85

8.23 ± 1.23/

8.07 ± 1.46

RASS score of -2 to 0

Critical Care Pain Observation Tool (CPOT), goal: CPOT < 3

Butorphanol tartrate 0.5 ~ 1.0 mg as loading dose, 0.10–0.25 mg/h pumping

not reported

loading dose of 1 μg/kg over 10 min followed by a maintenance dose of 0.2–1 μg/kg/h

Propofol group: loading dose of 1–3 mg/kg over 15 min followed by a maintenance dose of 0.5–4 mg/kg/hr

Sepsis-3

Overall ICU mortality;

Length of ICU stay;

days of mechanical ventilation

Wei et al., 2020

Single site RCT

60/59

33/30

43.45 ± 7. 86/

45.21 ± 8. 35

26.43 ± 5.24/

25.12 ± 5.89

12.37 ± 2.82/

11.82 ± 2.53

SAS score of 1 to 2

not reported

not reported

not reported

loading dose of 1 μg/kg over 10 min followed by a maintenance dose of 0.2–0.7 μg/kg/h

Propofol group: loading dose of 1–1.5 mg/kg, followed by a maintenance dose of 50–150 μg/kg/hr

Guidelines for the treatment of severe sepsis/ septic shock in China 2014

Overall mortality day 30;

Incidence of adverse reactions

Wu et al., 2018

Single site RCT

48/48

30/27

47 ± 10/51 ± 8

21.11 ± 3.73/19.96 ± 4.08

3.15 ± 0.86/

4.83 ± 1.07

RASS score of -2 to 1

not reported

not reported

Mechanical ventilation setting: SIMV) + PSV, A/C

Tidal volume 8–10 mL/kg, Respiratory rate 13–18/min

PaCO2 35–50 mmHg, adjust PEEP, FiO2 to SpO2 of 90%

loading dose of 1 μg/kg over 10 min followed by a maintenance dose of 0.2–0.8 μg/kg/h

Midazolam group: loading dose of 0.1 mg/kg over30 seconds followed by a maintenance dose of 0.03–0.15 mg/kg/hr

Sepsis-3

Inflammatory cytokine changes et al

Zhang et al., 2020

Single site RCT

25/25

NA /NA

59.0 ± 4. 8/

58.8 ± 4. 8

21 ± 4/

20 ± 5

8. 8 ± 1. 6/

8. 6 ± 1. 8

N/A

not reported

not reported

not reported

loading dose of 1 μg/kg over 10 min followed by a maintenance dose of 0.2–0.7 μg/kg/h

Propofol group: loading dose of 0.025–1 mg/kg, followed by a maintenance dose of 0.5–4 mg/kg/hr

Clinical signs: neurological dysfunction

Inflammatory cytokine changes;

Overall mortality;

days of mechanical ventilation;

Incidence of adverse reactions

Zheng et al., 2019

Single site RCT

32/30

18/16

46.05 ± 8.52/45. 76 ± 7. 93

14.25 ± 4.81/14.61 ± 4.35

N/A

N/A

not reported

not reported

Tidal volume was set to 6–8 mL/kg, respiration ratio was set to 1:1–1:1.5, respiration rate was set to 12–18 times/min, inhaled oxygen concentration (FiO2) 50–90%, PEEP 8–10

loading dose of 1 μg/kg over 10 min followed by a maintenance dose of 0.2–0.7 μg/kg/h

Midazolam group: loading dose of 0.05 mg/kg over 10 min, followed by a maintenance dose of 0.03–0.2 mg/kg/hr

Sepsis-3

Inflammatory cytokine changes;

Overall mortality day 7;

days of mechanical ventilation

Zhou et al., 2017

Single site RCT

40/40

22/23

48.54 ± 4.79/

48.45 ± 4.82

18.07 ± 4.09/17.89 ± 4.32

N/A

Ramsay score of

2 to 3

not reported

not reported

not reported

loading dose of 1 ug/kg/hr over 10 min followed by a maintenance dose of 0.2–0.7 mg/kg/h

Propofol group: loading dose of 1–3 mg/kg over 30–60 s followed by a maintenance dose of 0.4–5 mg/kg/hr

Sepsis-2

Overall mortality day 28;

Length of hospital stay;

Changes of myocardial injury markers before and after sedative use

  1. DEX dexmedetomidine, N/A not applicable, IAP intraabdominal pressure, APACHE II acute physiology and chronic health evaluation, SOFA sequential organ failure assessment score,FiO2 inhaled oxygen concentration, PaO2 patients with arterial oxygen tension, PaCO2 patients with arterial carbon dioxide tension, PEEP positive end expiratory pressure, SpO2 oxygen saturation,Cr Serum creatinine, BUN blood urea nitrogen
  2. *Mean (SD)