Table 1 Study characteristics of randomized controlled trials from eligible systematic reviews and meta-analyses
First author, year, country (ref) | Study design | Sample size, intervention/placebo, Mean age, critical illness types | Intervention (s): first and following dose | Comparison (s) | APACHE or SAPS or SOFA score, intervention/placebo | Follow-up duration | Outcomes |
|---|---|---|---|---|---|---|---|
Andrew, 2011, UK [45] | A double-blinded randomized parallel trial | 127/125, 64.5 years, GI bleeding | Intravenous sodium selenite 500 μg/day for 7 day | Selenium ≤ 50 μg /day | APACHE II: 20/20 | 14 day | Infection, adverse events, LOS hospital, LOS ICU, mortality by duration (28 days), mortality |
Angstwurm, 2007, Germany [46] | Prospective randomized, placebo-controlled, multiple-center trial | 122/124, 64.6 years, SIRS, sepsis, and septic shock | Bolus and continuous intravenous sodium selenite bolus 1000 μg/day, followed by a continuous dose of 1000 μg/day | Placebo | APACHE III: 92.2/91.2 | 28 days | Mortality, mortality by duration (28 days), infection, adverse events, pneumonia, LOS ICU |
Angstwurm, 1999, Germany [47] | Prospective open-label pilot RCT | 21/21, 56 years, SIRS | Continuous intravenous sodium selenite, 535 μg/day for 3 days then 285 μg/day for 3 days then 155 μg/day for 3 days then 35 μg/day for the remainder of the total treatment time | Placebo | APACHE II: ≥ 15/≥ 15 | Until discharge | Adverse event, LOS hospital, LOS ICU, renal failure length of ventilation, mortality by duration (28 days), mortality |
Bloos, 2016, Germany [48] | Placebo-controlled trial, multi-center | 543/546, 65.7 years, mixed ICU patients with severe sepsis or septic shock in last 24 h | Sodium selenite, IV loading dose of 1000 μg/day followed by a continuous 1000 μg/day | Placebo | APACHE II: 24.7/24.4 | 90 days | Infection, adverse events, LOS ICU, mortality by duration (28 days), mortality |
Brodska, 2015, Czech Republic [60] | Prospective, randomized, open-label single center | 75/75, 60 years, SIRS/sepsis | Intravenous sodium selenite, 1000 μg/day on the first day, 500 μg/day on subsequent days in the form of Na selenite pentahydrate | Standard selenium dose (< 75 μg/day) | APACHE II: 30/28 | Until discharge | Mortality by duration (28 days) |
Berger, 2001, Switzerland [7] | Prospective couple blind RCT | 9/12, 42 years trauma patients | Slow intravenous selenium 500 μg/day | Placebo | APACHE II: 13/11 | 20 days | Infection, LOS ICU, days on ventilation, mortality by duration (28 days), mortality |
Chelkeba, 2017, Iran [49] | Prospective RCT | 29/25, 38 years, septic patients | Intravenous selenium selenite, high‑dose parenteral sodium selenite (2 μg/day intravenous bolus, followed by 1.5 μg/day IV continuous infusion plus standard therapy | Standard therapy | APACHE II: 17/16.4 | 90 days | LOS ICU, LOS hospital, days on ventilation, renal failure, mortality, mortality by duration (28 days) |
Forcevill, 2007, France [50] | Double-blind, phase II RCT | 31/29, 67.5 years, severe septic shock patients with documented infection and mechanically ventilated | Intravenous sodium selenite, 400 μg/day (in 192 mL saline) over 24 h, then 1000 μg/da (in 48 mL saline) over 24 h for 9 days | Placebo | NR | 208 days | Infection, pneumonia, adverse event, LOS ICU, LOS hospital, days of ventilation, renal failure, mortality by duration (28 days), mortality |
Gartner, 1983, Germany [61] | Double-blind parallel RCT | 21/21, SIRS/sepsis | Intravenous sodium selenite, 500 μg/day, 250 μg/day, and 125 μg/day, each amount for 3 days | 35 μg/day sodium selenite during the whole treatment period | APACHE II: 17/19 | 48 days | Renal failure, mortality by duration (28 days) |
Janka, 2013, Slovak Republic [51] | Prospective observational trial | 35/37, 53 years, septic patients | Continuous intravenous sodium selenite pentahydrate at 750 μg/day | Placebo | APACHE II: 24/34 | 28 days | Mortality by duration (28 days), mortality |
Khalili, 2017, Iran [62] | Clinical trial | 125/182, 35.5 years, traumatic brain injury | Sodium selenate pentahydrate intravenously, 1000 μg/day for the first 5 days, followed by 500 μg/day for an additional 5 days | No treatment | NR | 96 days | Mortality by duration (28 days), LOS hospital, LOS ICU |
Kuklinski, 1991, Germany [52] | RCT | 8/9, 46.5 years, acute pancreatic necrosis | Intravenous 500 μg/day sodium selenite | No treatment | NR | NR | Mortality, mortality by duration (28 days) |
Lindner, 2004, Germany [53] | Prospective randomized trial | 35/35, 51 years, severe acute pancreatitis | Intravenous sodium selenite day 1, 2000 μg/day, days 2–5, 1000 μg/day, day 6 until discharged 300 μg/day | Placebo | NR | 90 days | Mortality, infection |
Mahmoodpoor, 2018, Iran [63] | clinical trial | 20/20, 54.7 years, acute respiratory distress syndrome | Intravenous sodium selenite, 3000 μg/day in as an initial bolus during the first 3 h of first day followed by 1500 μg/day at the same hourly interval on days 2–10 | Normal saline | APACHE II: 21/23 | NR | Mortality by duration (28 days), infection, LOS hospital, days on ventilation |
Moghaddam, 2017, Iran [65] | Double-blinded controlled trial | 57/56, 41.5 years, traumatic brain injury | Intravenous sodium selenite, 500 μg/day for 30 min and then 500 μg/day se during 24 h continuously | Standard care | APACHE III: 49.91/49.34 | 32 days | Days of ventilation, LOS ICU, LOS hospital, Mortality by duration (28 days) |
Manzanares, 2011, Uruguay [54] | Prospective, placebo-controlled, randomized, single-blinded phase II study | 15/16, 58 years, SIRS | Intravenous selenium bolus loading 2000 μg/day then 1600 μg/day for10 days | 0.9% NaCl only for 10 days | APACHE II: 21/23 | 28 days | Mortality, renal failure, days of ventilation, LOS ICU, infection, pneumonia, adverse events |
Manzanares, 2010, Uruguay [64] | Prospective, placebo-controlled, randomized, single-blinded phase II study | 10/10, 42.5 years, SIRS/sepsis | Intravenous selenium, 2000 μg/day (as selenious acid) bolus loading dose over 2 h thereafter 1600 μg/day for 10 days | Loading dose of selenium selenite 1200 μg over 2 h and thereafter 800 μg as a continuous intravenous infusion | APACHE II: 21/23 | NR | Mortality by duration (28 days), infection, renal failure, LOS ICU |
Montoya, 2009, Mexico {56] | Prospective, randomized, double-blind trial | 34/34, 66 years, sepsis | Selenium 1000 μg/day IV on day 1 then 500 μg/day on day 2 then 200 μg/day for 7 day | 100 μg/day selenium up to the end of the trial | APACHE II: 17.6/19.8 | NR | Mortality, LOS hospital, days of ventilation |
Mishra, 2007, UK [55] | Double-blind controlled trial | 18/22, 66 years, sepsis | Intravenous selenium, 470 μg/day for 3 days, then 320 μg/day for 3 days, then 160 μg/day for 3 days, and 30 μg/day thereafter | 30 μg/day selenium | APACHE II: 17.6/19.8 | 28 days | Mortality, mortality by duration (28 days), adverse events, renal failure, LOS ICU |
Reisinger, 2009, Austria [66] | Double-blind, placebo-controlled, randomized trial | 124/102, 65 years, cardiac arrest after CPR | Intravenous sodium selenite, infusion of 200 to 1000 μg/day over 30 min | Placebo | SAPSIII:59/59 | 96 days | Mortality by duration (28 days) |
Schmidt, 2018, Switzerland [67] | Randomized,placebo-controlled, double-blinded clinical trial | 206/205, 67 years, elective cardiac surgery | Intravenous bolus of 4000 μg/day sodium selenite and then 1000 μg/day | Placebo | SAPSII: 28/29 | NR | LOS ICU, LOS hospital, renal failure, mortality by duration (28 days) |
Valenta, 2011, Czech Republic [57] | Prospective randomized, open-label, single-center clinical trial | 93/89, 28 years, SIRS/sepsis | Na selenite, 1000 μg/day on the first day, 500 μg/day on days 2–14 via a central venous catheter | Standard Selenium dose (< 75 μg/day) | APACHE II: 30/28 | 28 days | Mortality, mortality by duration (28 days) |
Woth, 2014, Hungary [58] | RCT | 23/17, 20 years, severe septic | Intravenous sodium selenite, bolus for 30 min on the first day, the treatment group received 1000 µg/day continuous infusion for 14 days | NR | SOFA score > 2 | 7 days | Mortality, mortality by duration (28 days) |
Zimmerman, 1997, Germany [59] | A prospective randomized study | 20/20, SIRS | Intravenous Na-Selenite, 1000 μg/day bolus then 1000 μg/day as a continuous infusion | Standard therapy | APACHE II: 15/15 | 28 days | Mortality, mortality by duration (28 days) |