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University of Virginia Nutrition Support
E-Journal Club
January 2007


We took a break from our journal club in December since we were dealing with visions of sugarplums and visits with family over the holidays.  Currently we are finalizing our new Weekend Warrior program  (check out the details here: http://www.healthsystem.virginia.edu/pub/digestive-health/nutrition/resources.html) and getting ready for Clinical Nutrition Week in Phoenix.  We are planning a get-together with past trainees and any interested future trainees at Nutrition Week after the DNS meeting on Sunday night-we are meeting there.


January Citation: 

Angstwurm MWA, Engelmann L, Zimmermann T, et al.  Selenium in Intensive Care (SIC) study: Results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.  Crit Care Med 2007;35(1):1.



This was a phase III, multiple-center, double-blind, randomized placebo-controlled trial in 249 ICU patients w/ severe SIRS, sepsis, and septic shock.

The study group received 1000 µg of intravenous sodium-selenite within 30 minutes, followed by a continuous drip of 1000 µg of sodium-selenite/day for 14 days (total dose 15mg).  The control group received 0.9% NaCl in a similar pattern.

Selenium supplementation, up to 100 µg of selenium per day, together with other trace elements during parenteral nutrition, was allowed in all patients.

Patients were followed for 28 days after inclusion, and the primary endpoint of the study was 28-day mortality.


There were multiple secondary endpoints to the study including:

  1. Time of survival after enrollment
  2. Variable part of the APACHE III score-percentage of change between day 1 and last visit
  3. Logistic organ dysfunction system score at all visits or last available visit
  4. Incidence of renal failure within the 28-day survey
  5. Days of dialysis or chronic veno-venous hemofiltration dialysis
  6. Incidence of cardiovascular failure defined as the demand for vasoactive drugs despite volume substitution
  7. Number of days with vasopressor therapy to maintain adequate tissue  perfusion
  8. Days of mechanical ventilation
  9. Incidence of nosocomial pneumonia
  10. Incidence of acute respiratory distress syndrome
  11. Incidence of reinfection
  12. Duration of stay (days) in the intensive care unit for all patients
  13. And, there was a prospectively planned analysis of subgroups (age, gender, severity of illness, number of organ failure, intensive insulin treatment, source of infection, surgical vs. internal).

Inclusion Criteria were:

  • APACHE) III score >=70 and at least two of the following criteria:
    •  Rectal body temperature >38°C or hypothermia <36°C, heart rate >90 beats/min,
  • Respiratory frequency >20' and PaCO2 <32 mm Hg.
  • Leukocytes >12,000/µL or <4 000/µL or >10% immature leukocytes
  • Decrease of platelet count >50% within the first 24 hrs or platelets <150,000/µL at admission
  • Admission into the study after diagnosis within 24 hrs
  • Beginning of treatment within 1 hr after inclusion


Major Results reported by authors:

The authors reported that in the primary outcome of 28-day mortality there was no significant difference the intention-to-treat analysis (n = 238). Forty-six of 116 (40%) of the selenium group and 61 of 122 (50%) of the control patients died (p = 0.109; OR, 0.66; 95% CI, 0.39-1.10). The estimated mean survival time was 20.3 days in selenium group and 17.6 days in control group (p = .098). 

However, in the group that received the full dose and protocol of selenium (189 patients) there was a significant reduction in 28-day mortality.  Thirty-nine of 92 (42%) patients in the selenium group compared with 55 of 97 (57%) in the control group died within 28 days (p = 0.049; OR, 0.56; 95% CI, 0.32-1.00). The absolute reduction in mortality was 14.3%.

The subgroup analysis is a bit lengthy to provide the full details here, so we will summarize.  The following subgroups had a significant improvement in mortality in those supplemented with selenium:

  • APACHE III score >102, N = 54 (p = 0.040; OR, 0.28; 95% CI, 0.08-0.97)
  • More than three organ failures, N = 83 (p = 0.039; OR, 0.40; 95% CI, 0.16-0.96).
  • Sepsis criteria, a continuous decrease in platelet counts below 50,000/µL (indicating disseminated intravascular coagulation), and septic shock, N = 92, (p = 0.018; OR, 0.34; 95% CI, 0.14-0.84).
  • Patients receiving intensified insulin treatment with tight glucose control, N = 54,(p = 0.034; OR, 0.30; 95% CI, 0.10-0.93).

The investigators reported that there were no significant differences in the survival rate of patients identified with pneumonia or peritonitis alone, without other systemic signs of septic shock, or surgical or internal medicine patients.

Also, the incidence of acute respiratory distress syndrome was not significantly different in selenium (5.4%) and controls (4.1%) patients.


Author's Conclusions:

The authors concluded that high-dose sodium selenite reduces mortality rate in patients with severe sepsis or septic shock, and that a larger trial is now needed to confirm the results of this trial.



Our first comment was about the sheer number of secondary study endpoints because when > 7 endpoints are measured, there is a 40% chance of finding at least one statistically significant outcome.

There were some concerns about the description of the intention to treat group versus the per-protocol group.  The authors reported that 249 patients were randomized and enrolled and that 11 patients were lost after randomization, suggesting that there were 238 patients in the intention-to treat analysis.  However, by definition, the intention to treat analysis should include every patient that was randomized.  In the end, the dropping of these 11 patients is a relatively minor concern, because there was no significant difference in the intention to treat analysis either way. 

A much more significant concern was that35 of the 49 patients that were dropped from the per-protocol analysis were those that did not receive the full dose(s), or missed the initial bolus of selenium.  Considering that there was no benefit in the intention to treat analysis, this may affect the efficacy of giving selenium in a real-world clinical setting.  The lack of benefit in the intention to treat group may mean that patients that cannot receive selenium very quickly, or patients that have selenium infusion held at any point greater than 6 hours, may not benefit??

Overall, the randomization appeared to have "worked" with similar patients between selenium and control groups, however, we noted that there was no mention of the numbers of patients that received enteral versus parenteral nutrition, or the amount of nutrition received during the study.

The editorial for this article discusses the limitations of current knowledge regarding the ideal dose of selenium, and suggests that the ideal dose may be closer to 500-750µg/day.  We encourage you to review the details within the editorial (Berger MM, Shenkin A.  Selenium in intensive care: probably not a magic bullet but an important adjuvant therapy.  Crit Care Med. 2007;35(1):306-7).


Take home message: 

Despite our reservations stated above, the group felt that the results of this study were very exciting as well as promising because of the benefits seen in the per-protocol group, and the lack of any known negative effects of short-term selenium supplementation.  There is a need for larger studies to evaluate the optimum dose and timing of selenium, and to determine if there is further benefit when combined with other "antioxidant" micronutrients.  We are currently considering implementing an IV selenium protocol in selected patients with severe sepsis.

If you are interested in data from previous studies, here are some recent reviews of selenium supplementation in critical illness:

  1. 1) Angstwurm MW, Gaertner R. Practicalities of selenium supplementation in critically ill patients. Curr Opin Clin Nutr Metab Care. 2006 May;9(3):233-8.
  2. 2) Geoghegan M, McAuley D, Eaton S, Powell-Tuck J. Selenium in critical illness. Curr Opin Crit Care. 2006 Apr;12(2):136-41.



Other News:

1)     Weekend Warrior Mini-Nutrition Support Traineeship is here! 

When: Weekend of March 10th and 11th, 2007.  Check out our website for details:


2)     Check out the latest Practical Gastroenterology articles/info at:

Scroll down to GI Nutrition on the far left column and click on link
Then scroll down to box with links within the nutrition site
Nutrition Articles in Practical Gastroenterology is in the right column:

December 2006:

1)      Dinga M, Dinga A.  Heart Health and Celiac Disease. Practical Gastroenterology 2006:XXX(12):70.

2)      Lee V.  Liver Dysfunction Associated with Parenteral Nutrition: What Are the Options? Practical Gastroenterology 2006:XXX(12):49.

January 2007: 

3)      Plogsted S. Medications and Celiac Disease - Tips From a Pharmacist.   Practical Gastroenterology 2007;XXXI(1):58.

4)      Loch Michelle, Kahaleh M.  Stents for the Gastrointestinal Tract and Nutritional Implications. Practical Gastroenterology 2007;XXXI(1):48.



Joe Krenitsky MS, RD

Carol Parrish RD, MS


PS - Please feel free to forward this on to friends and colleagues.