Table 1.
Randomized clinical trials evaluating selenium supplementation in critically ill patients
| Study | Population | Methodology (score) | Intervention |
|---|---|---|---|
| Kuklinski 1991 [38] | Patients with acute pancreatic necrosis | C.Random: not sure | PN + selenium supplementation (500 μg/day) vs. PN without selenium supplementation |
| n = 17 | ITT: no | ||
| Blinding: no | |||
| (4) | |||
| Zimmerman 1997 [39] | Patients with SIRS, sepsis, APACHE II score >15, and multiorgan failure score >6 | C.Random: no | IV selenium as sodium selenite 1000 μg as a bolus and then 1000 μg sodium selenite 24 h as a continuous infusion over 28 days vs. standard |
| n = 40 | ITT: yes | ||
| Blinding: no | |||
| (6) | |||
| Berger 1998 [40] | Burns >30 % TBSA | C.Random: yes | IV copper (40.4 μmol), selenium (159 μg), zinc (406 μmol) + standard trace elements vs. standard trace elements (copper 20 μmol, selenium 32 μg, zinc 100 μmol) from days 0 to 8, all received early EN |
| n = 20 | ITT: yes | ||
| Blinding: double blind | |||
| (12) | |||
| Angstwurm 1999 [41] | Patients with SIRS and sepsis at 11 ICUs | C.Random: not sure | PN with high-dose selenium (535 μg × 3 days, 285 μg × 3 days, 155 μg × 3 days, and 35 μg thereafter) vs. low-dose selenium (35 μg/day for duration of study) |
| n = 42 | ITT: yes | ||
| Blinding: no | |||
| (10) | |||
| Porter 1999 [42] | Surgical ICU penetrating trauma patients with Injury Severity Score ≥25 | C.Random: yes | 50 μg selenium IV every 6 h + 400 IU vitamin E, 100 mg vitamin C every 8 h, and 8 g of N-acetylcysteine every 6 h via nasogastric or oral route from days 0 to 7 vs. none |
| n = 18 | ITT: yes | ||
| Blinding: no | |||
| (9) | |||
| Berger 2001 [43] | Trauma patients, surgical ICU | C.Random: yes | IV selenium supplementation (500 μg/day) vs. placebo (selenium group randomized further to two groups: 500 μg selenium alone vs. 500 μg selenium + 150 mg α-tocopherol + 13 mg zinc) given slowly for first 5 days after injury (all groups received EN) |
| n = 31 | ITT: no | ||
| Blinding: double | |||
| (9) | |||
| Lindner 2004 [44] | Patients with acute pancreatitis admitted to the ICU | C.Random: not sure | IV sodium selenite dose of 2000 μg on day 1, 1000 μg on days 2–5, and 300 μg from day 6 until discharge vs. placebo (isotonic 0.9 % IV NaCl solution) |
| n = 70 | ITT: no | ||
| Blinding: single | |||
| (9) | |||
| Angstwurm 2007 [45] | Multicenter mixed ICUs | C.Random: not sure | 1000 μg selenium IV within 1 h followed by 1000 μg selenium for 14 days vs. NaCl (0.9 %) (all patients received EN or PN) |
| n = 249 | ITT: no | ||
| Blinding: double | |||
| (8) | |||
| Berger 2007 [46] | Burns >20 % TBSA | C.Random: not sure | IV 100 ml of copper (59 μmol) + selenium (375 μg + zinc (574 μmol) vs. NaCl (0.9 %) from admission for 5–15 days |
| n = 21 | ITT: yes | Both groups were on EN | |
| Blinding: no | |||
| (8) | |||
| Forceville 2007 [47] | Septic shock patients | C.Random: not sure | 4000 μg selenium IV on day 1 followed by 1000 μg selenium for 9 days vs. NaCl (0.9 %) (all patients received EN or PN) |
| n = 60 | ITT: no | ||
| Blinding: double | |||
| (8) | |||
| Mishra 2007 [48] | Septic ICU patients | C.Random: not sure | 474 μg selenium IV × 3 days followed by 316 μg × 3 days, 158 μg × 3 days, and 31.6 μg thereafter vs. 31.6 μg selenium (all patients received EN or PN) |
| n = 40 | ITT: yes | ||
| Blinding: double | |||
| (9) | |||
| Berger 2008 [49] | Mixed ICU | C.Random: not sure | IV selenium supplementation loading dose 540 μg/day + zinc (60 mg) + vitamin C 2700 mg + vitamin B 305 mg + vitamin E enteral 600 mg + vitamin E 12.8 mg IV for 2 days followed by half the dose of all vs. standard vitamins |
| n = 200 | ITT: yes | ||
| Blinding: no | All groups received EN or PN | ||
| (10) | |||
| El-Attar 2009 [50] | Patients with COPD | C.Random: yes | IV selenium as sodium selenite 100 μg/day, zinc 2 mg/day, and manganese 0.4 mg/day vs. none |
| n = 80 | ITT: yes | Trace elements were administered during the period on mechanical ventilation | |
| Blinding: yes | |||
| (12) | |||
| Montoya 2009 [51] | Medical/surgical septic | C.Random: yes | Day 1 IV sodium selenite 1000 μg , day 2 sodium selenite 500 μg, and thereafter 200 μg during 7 additional days vs. selenite 100 μg/day |
| ICU patients | ITT: yes | ||
| n = 68 | Blinding: double | ||
| (7) | |||
| Andrews 2011 [52] | Mixed ICU, multicenter | C.Random: yes | 500 μg selenium supplemented PN (12.5 g nitrogen, 2000 kcal) vs. standard PN (12.5 g nitrogen, 2000 kcal) initiated after ICU admission (actual median 2.6 days) for 7 days (actual duration, mean 4.1 days). |
| n = 502 | ITT: yes | ||
| Blinding: double blind | |||
| (13) | |||
| Manzanares 2011 [53] | Septic or trauma patients | C.Random: not sure | IV selenium supplementation loading dose 2000 μg (2 h) on day 1 followed by 1600 μg/day for 10 days vs. NaCl as placebo |
| n = 35 | ITT: no (except mortality) | ||
| Blinding: single blind | |||
| (9) | |||
| Valenta 2011 [54] | Patients with sepsis or SIRS | C.Random: not sure | IV selenium supplementation loading dose 1000 μg on day 1 followed by 500 μg/day for 5–14 days + <75 μg/day of sodium selenite added to PN vs. NaCl + <75 μg/day of sodium selenite added to PN |
| n = 150 | ITT: yes | ||
| Blinding: no | |||
| (8) | |||
| Heyland 2013 [16] | Multicenter mixed ICUs | C.Random: yes | 500 μg selenium via PN + 300 μg selenium, 20 mg zinc, 10 mg β-carotene, 500 mg vitamin E, 1500 mg vitamin C via EN vs. placebo via PN and EN |
| n = 1218 | ITT: yes | ||
| Blinding: double | |||
| (12) | |||
| Woth 2014 [14] | Mixed ICU, severe septic patients with multiorgan failure | C.Random: not sure | 1000-μg/30 minutes loading dose of sodium selenite and 1000-μg/day treatment for a maximum of 14 days vs. control group (not described) |
| n = 40 | ITT: yes | ||
| Blinding: no | |||
| (6) | |||
| Bloos 2016 [17] | Multicenter mixed ICU patients with severe sepsis or septic shock in last 24 h | C.Random: yes | IV loading dose of 1000 μg sodium selenite followed by continuous IV of 1000 μg sodium selenite daily until ICU discharge or for 21 days, whichever comes first vs. placebo (NaCl) |
| ITT: yes | |||
| n = 1089 | Blinding: double | ||
| (12) | |||
| Chelkeba 2015 [15] | Mixed ICU patients with severe sepsis and septic shock | C.Random: yes | IV loading dose of 2000 μg sodium selenite followed by continuous IV of 1500 μg sodium selenite daily until day 14 vs. standard therapy without selenium |
| n = 54 | ITT: no | ||
| Blinding: single | |||
| (11) |
Abbreviations: APACHE Acute Physiology and Chronic Health Evaluation, COPD Chronic obstructive pulmonary disease, C.Random Concealed randomization, D5W Dextrose 5 % in water, EN Enteral nutrition, ICU Intensive care unit, ITT Intention to treat, IV Intravenous, PN Parenteral nutrition, SIRS Systemic inflammatory response syndrome, TBSA Total body surface area