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 10Â mg/hr | Sepsis-2 | Delirium/coma-free days; Ventilator-free days; Risk of dying at 28Â 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 5Â 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 5Â 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 |