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Suplementos de selenio en adultos gravemente enfermos

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Referencias

Referencias de los estudios incluidos en esta revisión

Ir a:

Angstwurm 1999 {published data only}

Angstwurm MWA, Schopohl J, Gaertner R. Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients. European Journal of Endocrinology 2004;151:47‐54. [MEDLINE: PMID: 15248821]
Angstwurm MWA, Schottdorf J, Schopohl J, Gaertner R. Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Critical Care Medicine 1999;27:1807‐13. [MEDLINE: PMID: 10507602]
Gärtner R, Angstwurm MWA, Schopohl J. Selenium replacement in patients with SIRS improves clinical outcome. Clinical Nutrition 2002;21(Suppl 1):66.
Gärtner R, Angstwurm MWA, Schottdorf J. Selenium substitution in critical ill patients [Selensubstitution bei sepsispatienten]. Medizinische Klinik 1997;92(Suppl III):12‐4.

Angstwurm 2007 {published data only}

Angsturm MWA, Gaertner R. Selenium substitution in severe sepsis as useful additive? Preliminary results of the SIC study. Intensive Care Medicine 2005;31(Suppl 1):S84.
Angstwurm M, Gärtner R. Selenium in Intensive Care (SIC) study: the XX files are still unresolved. Critical Care Medicine 2007;35(3):995‐6.
Angstwurm MW, Englemann L, Zimmermann T, Lehmann C, Spes CH, Abel P, et al. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo‐controlled, multiple‐center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Critical Care Medicine 2007;35(1):118‐26.
Gaertner R. Sodium selenite as an adjunctive therapy for sepsis ‐ clinical data from a multi‐centre intervention study (SIC Study). DIVI Congress, Hamburg, Symposium 'Adjunctive therapy in spesis: what has been confirmed?'. 4th December 2004.

Berger 2001 {published data only}

Berger MM, Baines M, Chioléro RL, Wardle CA, Cayeux C, Shenkin A. Influence of early trace element and vitamin E supplements on antioxidant status after major trauma: a controlled trial. Nutrition Research 2001;21:41‐54.
Berger MM, Reymond MJ, Shenkin A, Rey F, Wardle C, Cayeux C, et al. Influence of selenium supplements on the post‐traumatic alterations of the thyroid axis: a placebo‐controlled trial. Intensive Care Medicine 2001;27:91‐100. [MEDLINE: PMID: 11280679]

Kuklinski 1991 {published data only}

Kuklinski B, Buchner M, Schweder R, Nagel R. Acute pancreatitis ‐ a "free radical disease". Decrease of lethality by sodium selenite (Na2SeO3) therapy [Akute pankreatitis ‐ eine "free radical disease". Letalitatssenkung durch natriumselenit (Na2SeO3)‐therapie]. Zeitschrift fur die Gesamte Innere Medizin und Ihre Grenzgebiete 1991;46:S145‐9. [MEDLINE: PMID: 1648849]

Lindner 2004 {published data only}

Lindner D, Lindner J, Baumann G, Dawczynski H, Bauch K. Investigation of antioxidant therapy with sodium selenite in acute pancreatitis. A prospective randomized blind trial [Untersuchung zur antioxidativen therapie mit natriumselenit bei akuter pankreatitis. Eine prospektive, randomisierte blindstudie]. Medizinische Klinik 2004;99(12):708‐12. [MEDLINE: PMID: 15599680]

Mishra 2007 {published data only}

Mishra V, Baines M, Perry S, McLaughlin J, Carson J, Wenstone R, Shenkin A, Mostafa SM. Selenium supplementation and outcome in septic ICU patients. Clinica Chimica Acta 2005;355(Suppl 1):S45.
Mishra V, Baines M, Perry SE, McLaughlin PJ, Carson J, Wenstone R, et al. Effect of selenium supplementation on biochemical markers and outcome in critically ill patients. Clinical Nutrition 2007;26:41‐50.
Mishra V, Perry S, Baines M, McLaughlin J, Carson J, Wenstone R, Shenkin A, Mostafa SM. Selenium replacement, HLA‐DR expression and outcome in septic ICU patients. Intensive Care Medicine 2004;30(Suppl 1):110.

Ogawa 1999 {published data only}

Ogawa A, Yoshimoto T, Kikuchi H, Sano K, Saito I, Yamaguchi T et al for the Ebselen Study Group. Ebselen in acute middle cerebral artery occlusion: a placebo‐controlled, double‐blind clinical trial. Cerebrovascular Diseases 1999;9:112‐8. [MEDLINE: PMID: 9973655]

Saito 1998 {published data only}

Asano T, Takakura K, Sano K. Comparative analysis of the clinical effects of water‐soluble (AVS) and ‐insoluble (ebselen) antioxidants on the delayed ischemic neurological deficits after aneurysmal subarachnoid hemorrhage. Journal of Stroke and Cerebrovascular Diseases 1996;6(Suppl 1):188‐92.
Saito I, Abe H, Yoshimoto T, Asano T, Takakura K, Ohta T, et al. Multicentre randomised clinical trial of ebselen with aneurysmal subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism 1995;15(Suppl 1):162.
Saito I, Asano T, Sano K, Takakura K, Abe H, Yoshimoto T, et al. Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage. Neurosurgery 1998;42:269‐78. [MEDLINE: PMID: 9482177]

Yamaguchi 1998 {published data only}

Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T et al for the Ebselen Study Group. Ebselen in acute ischemic stroke. A placebo‐controlled, double‐blind clinical trial. Stroke 1998;29:12‐7. [MEDLINE: PMID: 9445321]

Zimmermann 1997 {published data only}

Zimmermann T, Albrecht S, Kühne H, Vogelsang U, Grützmann R, Kopprasch S. Selenium administration in patients with sepsis syndrome. A prospective randomized study [Selensubstitution bei sepsispatienten. Eine prospektiv randomisierte studie]. Medizinische Klinik 1997;92(Suppl III):3‐4. [MEDLINE: PMID: 9417494]
Zimmermann T, Albrecht S, von Gagern G. Molecular‐biological investigations of the multicenter stage‐III study (SIC‐study) [Molekularbiologische untersuchungen zur multizentrischen phase‐III‐studie (SIC‐studie)]. Medizinische Klinik 1999;94(Suppl III):58‐61.

Referencias de los estudios excluidos de esta revisión

Ir a:

Berger 1998 {published data only}

Berger MM, Spertini F, Shenkin A, Wardle C, Wiesner L, Schindler C, Chiolero RL. Trace element supplementation modulates pulmonary infection rates after major burns: a double‐blind, placebo‐controlled trial. American Journal of Clinical Nutrition 1998;68:365‐71. [MEDLINE: PMID: 9701195]

Berger 2004a {published data only}

Berger M, Binnert C, Baines M, Raffoul W, Cayeux M, Chiolero R, Tappy L, Shenkin A. Trace element supplements influence protein metabolism and tissue levels after major burns. Intensive Care Medicine 2004;30(Suppl 1):61.

Berger 2004b {published data only}

Berger M, Soguel L, Schindler C, Revelly J, Chiolero R. Antioxidant micronutrients after complex cardiac surgery and clinical evolution? Preliminary data. Intensive Care Medicine 2004;30(Suppl 1):175.

Berger 2005a {published data only}

Berger MM, Eggimann P, Revelly JP, Raffoul W, Shenkin A, Chiolero R. Trace element supplements are associated with fewer nosocomial pneumonia after major burns. Intensive Care Medicine 2005;31(Suppl 1):77.
Berger MM, Eggimann P, Revelly JP, Raffoul W, Shenkin A, Chiolero RL. Selenium supplements reduce the incidence of nosocomial pneumonia after major burns. Clinical Nutrition 2005;24:614.

Berger 2005b {published data only}

Berger MM, Soguel L, Pinget C, Revelly JP, Schindler C, Chiolero RL. Antioxidant supplements modulate clinical course after complex cardiac surgery, and major trauma. Intensive Care Medicine 2005;31(Suppl 1):32.
Berger MM, Soguel L, Pinget C, Revelly JP, Schindler C, Chiolero RL. Antioxidant supplements modulate clinical course after complex cardiac surgery, major trauma, and subarachnoid haemorrhage. Clinical Nutrition 2005;24(4):616.

Börner 1997 {published data only}

Börner J, Zimmermann T, Albrecht S, Roesner D. Selenium administration in severe inflammatory surgical diseases and burns in childhood [Selensubstitution bei schweren entzündlichen chirurgischen krankheitsbildern sowie verbrennungen un verbrühungen in kindesalter]. Medizinische Klinik 1997;92(Suppl III):17‐9. [MEDLINE: PMID: 9417488]

Porter 1999 {published data only}

Porter JM, Ivatury RR, Azimuddin K, Swami R. Antioxidant therapy in the prevention of organ dysfunction syndrome and infectious complications after trauma: early results of a prospective randomized study. American Surgeon 1999;65:478‐83 (Erratum in American Surgeon 1999; 65:902). [MEDLINE: PMID: 10231223]

Thiele 1997 {published data only}

Thiele R, Wagner D, Gassel M, Winnefeld K, Pleissner J, Pfeifer R. Selenium substitution in acute myocardial infarct [Selensubstitution bei akutem myokardinfarkt]. Medizinische Klinik 1997;92(Suppl III):26‐8. [MEDLINE: PMID: 9417492]

Uden 1990 {published data only}

Uden S, Bilton D, Nathan L, Hunt LP, Main C, Braganza JM. Antioxidant therapy for recurrent pancreatitis: placebo‐controlled trial. Alimentary Pharmacology and Therapeutics 1990;4:357‐71. [MEDLINE: PMID: 2103755]

Watters 2002 {published data only}

Watters JM, Vallerand A, Kirkpatrick SM, Abbott HE, Norris S, Wells G, et al. Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneursymectomy. Clinical Nutrition 2002;21:321‐7. [MEDLINE: PMID: 12135593]

Wollschläger 1997 {published data only}

Wollschläger S, Ludwig K, Meissner D, Porst H. Effect of selenium administration on various laboratory parameters in patients with acute pancreatitis [Einfluß einer selensubstitution auf verschiedene laborparameter bei patienten mit akuter pankreatitis]. Medizinische Klinik 1997;92(Suppl III):22‐4. [MEDLINE: PMID: 9417490]

Referencias de los estudios en espera de evaluación

Ir a:

Forceville 2006 {published data only}

Forceville X, Bellissant E. Selenium, as sodium selenite, in the treatment of septic shock. http://clinicaltrials.gov/show/NCT00207844. Accessed 8th August 2006.
Forceville X, Lavoille B, Annane D, Vitoux D, Bleichner G, Korach JM, et al. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo‐controlled, randomized, double‐blind, phase II study. Critical Care 2007;11:R73.

Kiessling 2006 {published data only}

Kiessling AH, Isgro F, Skuras JA, Kammerer I, Lehmann A, Saggau W. Selenium application in intensive care medicine. Intensive Care Medicine 2006;32(Suppl 1):89.

Andrews 2004 {published data only}

The SIGNET Trial. https://www.charttrials.abdn.ac.uk/signet/ Accessed 9th August 2006.

Yamaguchi 2003 {published data only}

Yamaguchi T, for Ebselen Study Group. Phase III trial of Ebselen (abstract). The American Stroke Association 28th International Stroke Conference, February 13th‐15th 2003, Phoenix, Arizona. 2003.

Angstwurm 2006a

Angstwurm MW, Gaertner R. Practicalities of selenium supplementation in critically ill patients. Current Opinion in Clinical Nutrition and Metabolic Care 2006;9:233‐8.

Berger 1998a

Berger MM, Spertini F, Shenkin A, Wardle C, Wiesner L, Schindler C, et al. Trace element supplementation modulates pulmonary infection rates after major burns: a double‐blind, placebo‐controlled trial. American Journal of Clinical Nutrition 1998;68:365‐71. [MEDLINE: PMID: 9701195]

Bulger 2001

Bulger EM, Maier RV. Antioxidants in critical illness. Archives of Surgery 2001;136:1201‐7. [MEDLINE: PMID: 11585516]

Geoghegan 2006

Geoghegan M, McAuley D, Eaton, Powell‐Tuck J. Selenium in critical illness. Current Opinion in Critical Care 2006;12:136‐41.

Heyland 1998

Heyland DK, MacDonald S, Keefe L, Drover JW. Total parenteral nutrition in the critically ill patient. A meta‐analysis. JAMA 1998;280:2013‐9. [MEDLINE: PMID: 9863853]

Heyland 2005

Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Mediicine 2005;31:327‐37. [MEDLINE: 15605227]

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analysis. BMJ 2003;327:557‐60. [MEDLINE: 12958120]

Higgins 2005

Higgins JPT, Green S, editors. Highly sensitive search strategies for identifying reports of randomized controlled trials in MEDLINE. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]; Appendix 5b. In: The Cochrane Library, Issue 4, 2005. Chichester, UK: John Wiley & Sons, Ltd.

Jennett 1975

Jennett B, Bond M. Assessment of outcome after severe brain damage. A practical scale. Lancet 1975;1:480‐4. [MEDLINE: PMID: 46957]

Moher 2001

Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel‐group randomised trials. Lancet 2001;357:1191‐4. [MEDLINE: PMID: 11323066]

Parnham 2000

Parnham M, Sies H. Ebselen: prospective therapy for cerebral ischaemia. Expert Opinion on Investigational Drugs 2000;9:607‐19. [MEDLINE: PMID: 11060699]

Porter 1999a

Porter JM, Ivatury RR, Azimuddin K, Swami R. Antioxidant therapy in the prevention of organ dysfunction syndrome after trauma: early results of a prospective randomized trial. American Surgeon 1999;65:478‐83. Erratum in: American Surgeon 1999 Sep;65:902. [MEDLINE: PMID: 10231223]

Rayman 2000

Rayman MP. The importance of selenium to human health. Lancet 2000;356:233‐41. [MEDLINE: PMID: 10963212]

Sattar 1997

Sattar N, Eatock F, Fell GS, O'Reilly D. Selenium: an acute‐phase reactant?. Annals of Clinical Biochemistry 1997;34:437‐9. [MEDLINE: PMID: 9247681]

Shah 1989

Shah S, Vanclay F, Cooper B. Predicting discharge status at commencement of stroke rehabilitation. Stroke 1989;20:766‐9. [MEDLINE: PMID: 2728043]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Angstwurm 1999

Methods

Method of randomization: states stratified randomization only
Assessor blinding: states open label
Intention to treat: carried out
Lost to follow up: none

Participants

Location: intensive care unit, Klinikum Innenstadt, University of Munich, Germany
Period of study: recruitment March 1995 to August 1996
42 patients
Inclusion criteria: APACHE score greater or equal to 15, and clinical and laboratory signs of new systemic inflammatory response syndrome (SIRS) according to sepsis criteria (American College of Chest Physicians/Society of Critical Care Medicine), first 24 hours after admission
Exclusion criteria: age < 18 years, pregnancy, after cardiopulmonary resuscitation, severe gastrointestinal bleeding, trauma, surgery, chronic renal failure, refusal to participate
Sex: 29 males, 13 females
Age: mean age 56 years (range 18 to 83 years)

Interventions

Timing of intervention: from day of admission to intensive care for additional supplementation for nine days
a: continuous intravenous sodium selenite (535 mcg selenium for 3 days, 285 mcg selenium for 3 days, 155 mcg selenium for 3 days, 35 mcg selenium for remainder of total treatment time; and standard parenteral nutrition including glutamine 20 g/L
b: continuous placebo of saline and intravenous 35 mcg selenium as sodium selenite, and standard parenteral nutrition including glutamine 20 g/L
Allocated: 21/21
Assessed: 21/21

Outcomes

Length of follow up: until discharge
Main outcomes:
Mortality
Other outcomes:
Number of days on a ventilator
Length of hospital stay

Notes

Request for further details of interventions sent 24th October 2003, reply received 17th November 2003.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Angstwurm 2007

Methods

Method of randomisation: states randomised but no further details
Assessor blinding: carried out
Intention to treat: not carried out
Lost to follow up: reported

Participants

Location: 11 independent German intensive care units
Period of study: enrolment December 1999 to October 2004
249 patients
Inclusion criteria: men and women > 18 years with APACHE III score (22) > 70 and at least two of the following criteria: rectal body temperature > 38 °C or hypothermia < 36 °C, heart rate > 90 per minute, respiratory frequency > 20 per minute and PaCO2 < 32 mmHg (< 4.3 kPa), leucocytes > 12 000/µl or < 4 000/µl or > 10 % immature leucocytes, decrease of platelet count > 50 % within the first 24 h or platelets < 150 000/µl at admission; admission into the study after diagnosis within 24 h; beginning of treatment within 1h after inclusion.
Exclusion criteria: pregnancy; missing informed consent of patient or relative/intimate friend; withdrawal of informed consent after inclusion into study; participation in any clinical trial within last 30 days; prior participation in this clinical trial; cerebral injury due to hypoxia after cardiopulmonary resuscitation; primary concomitant disease with expected high mortality within 2 months; not for resuscitation; malignant primary disease as cause of systemic inflammatory response syndrome or sepsis, e.g. agranulocytosis as result of chemotherapy or idiopathic bone marrow aplasia; haemorrhagic ‐ necrotising pancreatitis without infectious complications.
Sex: 162 males, 76 females
Age: 64.6 years (SD 14.0)

Interventions

Timing of intervention: admission into study after diagnosis within 24 hours, study treatment beginning within 1 hour after inclusion
a: 48 ml vial as bolus intravenous injection over 30 minutes of sodium selenite providing 1000 mcg selenium, followed by continuous infusion of 2 ml/hour over 24 hours for 14 days, total dose 15,000 mcg selenium. Allowed selenium from other preparations of up to 100 mcg/day.
b: Matching placebo of 0.9% sodium chloride give as same regimen. Allowed selenium from other preparations of up to 100 mcg/day.
Allocated: ???/???
Assessed: 116/122

Outcomes

Length of follow up: 28 days
Main outcomes:
28 day mortality
Participants with new infections
Other outcomes:
Number of hours on a ventilator
Length of ICU stay
Participants with adverse events

Notes

Emailed 8th August 2006 asking for further details on participants with all infections, length of ventilation, total numbers randomised to each group, and further details of the randomisation process.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Berger 2001

Methods

Method of randomization: concealed
Assessor blinding: states double‐blind but no further details
Intention to treat: carried out
Lost to follow up: none

Participants

Location: surgical intensive care unit (ICU) of the Central Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Period of study: before 2000
21 patients
Inclusion criteria: severe multiple injury (injury Severity Score, ISS, > 15) involving at least two body systems, pathophysiological changes requiring ICU support, age 18 to 75 years, admission within 24 hours of injury
Exclusion criteria: pre‐existing renal or hepatic failure, foreseeable imminent death, no informed consent, documented hypothyroidism prior to accident
Sex: 15 males, 6 females
Age: age range 18 to 74 years

Interventions

Timing of intervention: from day of admission for five days
a: slow intravenous infusion over 24 hours of 500 mcg selenium as sodium selenite/day
b: infusion vehicle over 24 hours
c: slow intravenous infusion over 24 hours of 500 mcg selenium/day and 13 mg zinc/day, 150 mg alpha‐tocopherol in 5 ml 10% lipid emulsion (Lipovenös, Fresenius, Stans, Switzerland) as slow injection once daily upon initiation of intravenous infusion (data for this group not used in this review)
Allocated: 9/12/11
Assessed: 9/12/11

Outcomes

Length of follow up: appears followed up until died or left hospital, maximum length of stay 249 days
Main outcomes:
Mortality
Numbers of patients with infection (defined as requiring antibiotics)
Other outcomes:
Number of days on a ventilator
Length of intensive care unit stay
Length of hospital stay

Notes

Intention to treat data taken from paper in Nutrition Research.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate
Kuklinski 1991

Methods

Method of randomization: states randomized but no further details
Assessor blinding: not reported
Intention to treat: carried out
Lost to follow up: none

Participants

Location: hospital, Rostock, Germany
Period of study: before 1991
17 patients
Inclusion criteria: contrast CT scan showed pancreatic necrosis, less than 72 hours since onset of pancreatitis
Exclusion criteria: mild pancreatitis
Sex: all male
Age: range 28 ‐ 65 years

Interventions

Timing of intervention: unclear ?8 days
a: intravenous 500 mcg sodium selenite daily duration unclear (Selenase pro injectione, GN PHARM, Arzneimittel GmbH, Stuttgart)
b: no treatment
Allocated: 8/9
Assessed: 8/9

Outcomes

Length of follow up:
Main outcome:
Mortality

Notes

Request for further details on dose of selenium given sent 20th October 2003. Letter returned as author no longer at address in publication.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Lindner 2004

Methods

Method of randomisation: states randomised but no further details
Assessor blinding: not reported
Intention to treat: not reported
Lost to follow up: details provided

Participants

Location: medical centre, Chemnitz, Germany
Period of study: enrolment January 1997 to November 1998
70 patients
Inclusion criteria: severe acute pancreatitis managed on medical wards, severe abdominal pain, 3 fold increase of amylase and lipase, onset within 72 hours
Exclusion criteria: none given
Sex: 39 males, 28 females (completers)
Age: median 50‐52 years

Interventions

Timing of intervention: start unclear, given until discharged
a: day 1 2000 mcg selenium as sodium selenite, days 2‐5 1000 mcg/d, day 6 until discharged 300 mcg/d
b: 0.9% sodium chloride placebo,
Allocated: 35/35
Assessed: 32/35

Outcomes

Length of follow up: until discharge
Main outcomes:
Mortality
Number of patients with infectious complications (sepsis)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Mishra 2007

Methods

Method of randomisation: states randomised but no further details
Assessor blinding: states double‐blind
Intention to treat: not reported
Lost to follow up: no details provided

Participants

Location: intensive care unit, Liverpool, UK
Period of study: before 2005
40 patients
Inclusion criteria: APACHE II score > 15, clinical suspicion of infection and > 1 organ dysfunction
Exclusion criteria: chronic renal failure, alcoholic liver disease, immunodeficiency
Sex: 19 males, 21 females
Age: mean age 66 years

Interventions

Timing of intervention: within 24 hours of admission to intensive care and within 72 hours since diagnosis of sepsis, given until discharged
a: intravenous selenium 470 mcg/d for 3 days, then 320 mcg/d for 3 days, then 160 mcg/d for 3 days, and 30 mcg/d thereafter
b: 30 mcg/d
Allocated: 18/22
Assessed: 18/22 for mortality

Outcomes

Length of follow up: 28 days
Main outcomes:
Mortality at 28 days
Infections
Other outcomes:
Length of intensive care unit stay
Renal replacement therapy

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Ogawa 1999

Methods

Method of randomization: states randomized list but no further details
Assessor blinding: states double‐blind but no further details
Intention to treat: ITT for mortality only
Lost to follow up: none

Participants

Location: 28 Japanese neurosurgical and neurological units
Period of study: recruitment June 1994 to November 1996
105 patients
Inclusion criteria: acute stroke with complete occlusion of the M1 (M2) portion of the middle cerebral artery (MCA) on cerebral angiography and no low‐density area (LDA) in the MCA territory on computed tomography (CT), could start drug treatment within 12 hours of stroke
Exclusion criteria: distinct fresh LDA in the MCA territory on CT scans; stenosis or occlusion of trunk arteries, other than MCA; haemorrhagic stroke including subarachnoid haemorrhage; pregnancy; severe hepatorenal or metabolic disease
Sex: 67 males, 32 females
Age: mean age 66 years

Interventions

Timing of intervention: started within 12 hours of middle cerebral artery occlusion, given for 14 days
a: oral ebselen 150 mg twice daily given enterally as fine granules dispersed in water, gastric tube if disturbed consciousness
b: oral placebo granules twice daily given enterally as fine granules dispersed in water, gastric tube if disturbed consciousness
Allocated: 48/57
Assessed: 48/57 for mortality

Outcomes

Length of follow up:
Main outcomes:
Mortality
Numbers of patients with infection
Other outcomes:
Quality of life ‐ Glasgow Outcome Scale,

Notes

Request for further details of denominators and infections sent October 22nd 2003, no reply received.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Saito 1998

Methods

Method of randomization: states randomized lists but no further details
Assessor blinding: states double‐blind and blinded outcome assessment
Intention to treat: carried out
Lost to follow up: none

Participants

Location: 84 Japanese neurosurgical units
Period of study: enrolled November 1992 to April 1994
286 patients
Inclusion criteria: subarachnoid haemorrhage (SAH) from aneurysmal rupture within previous 96 hours, and SAH Hunt and Kosnik grade II to IV or World Federation of Neurosurgical Surgeons grade I to IV at admission
Exclusion criteria: pregnancy; age < 20 years or > 71 years; major cardiopulmonary, hepatorenal or metabolic disease; large intracerebral or intraventricular clots
Sex: 112 males, 174 females
Age: mean age 56 years

Interventions

Timing of intervention: started within 96 hours of subarachnoid haemorrhage, given for 14 days
a: oral ebselen 150 mg twice daily given enterally as fine granules dispersed in water, gastric tube if disturbed consciousness
b: oral placebo granules twice daily given enterally as fine granules dispersed in water, gastric tube if disturbed consciousness
Allocated: 145/141
Assessed: 145/141

Outcomes

Length of follow up: 3 months
Main outcomes:
Mortality
Numbers of patients with meningitis, respiratory infection
Other outcomes:
Quality of life ‐ Glasgow Outcome Scale

Notes

Request for further details of unpublished trial mentioned in main trial report, and numbers of patients with infections sent 21st October 2003, no reply received.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Yamaguchi 1998

Methods

Method of randomization: states randomized lists but no further details
Assessor blinding: states double‐blind but no further details
Intention to treat: not carried out
Lost to follow up: not complete, two patients excluded

Participants

Location: 68 Japanese neurological and neurosurgical units
Period of study: recruitment June 1994 to December 1996
302 patients
Inclusion criteria: acute ischaemic stroke, including thrombosis and embolism, by symptoms and CT scan; could receive drug treatment within 48 hours of onset
Exclusion criteria: transient ischaemic attacks; pregnancy; surgery interfering with the assessment of neurological function; previous stroke with residual neurological impairment; major cardiopulmonary, hepatic, renal or metabolic disease; haemorrhagic stroke
Sex: 189 males, 111 females
Age: mean age 65 years, range 22 to 85 years

Interventions

Timing of intervention: started within 48 hours of stroke, given for 14 days
a: oral ebselen 150 mg twice daily given enterally as fine granules dispersed in water, gastric tube if disturbed consciousness
b: oral placebo granules twice daily given enterally as fine granules dispersed in water, gastric tube if disturbed consciousness
Allocated: 152/150
Assessed: 151/149

Outcomes

Length of follow up: 3 months
Main outcomes:
Mortality
Numbers of patients with respiratory infection
Other outcomes:
Quality of life ‐ Glasgow Outcome Scale, modified Barthel Index

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Zimmermann 1997

Methods

Method of randomization: states randomized but no further details
Assessor blinding: not reported
Intention to treat: not reported
Lost to follow up: not reported

Participants

Location: university hospital, Dresden, Germany
Period of study: before 1997
40 patients
Inclusion criteria: systemic inflammatory response syndrome and organ failure
Exclusion criteria: none given
Sex: not given
Age: not given

Interventions

Timing of intervention: start unclear, given for 28 days
a: 1000 mcg bolus of sodium selenite, thereafter 1000 mcg/24 hours as continuous intravenous infusion, for 28 days
b: no treatment
Allocated: 20/20
Assessed: ?20/?20

Outcomes

Length of follow up: 28 days
Main outcome:
Mortality

Notes

Request for details of denominators and infections sent 21st October 2003, no reply received.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Berger 1998

Randomized trial in adults with burns; selenium part of trace element supplement evaluated, which also contained copper and zinc

Berger 2004a

Randomized trial in adults with burns; selenium part of trace element supplement evaluated, which also contained copper and zinc

Berger 2004b

Randomized trial in adults with cardiac surgery; selenium part of antioxidant supplement evaluated.

Berger 2005a

Combined results of Berger 2004 and Berger 1998

Berger 2005b

Randomized trial in adults with cardiac surgery, myocardial infarction, trauma or subarachnoid haemorrhage; selenium part of antioxidant supplement evaluated.

Börner 1997

Not randomized trial, not adults

Porter 1999

Randomized trial of antioxidant therapy (including selenium) versus placebo in trauma patients

Thiele 1997

Not randomized trial, not critical care

Uden 1990

Randomized, crossover trial of antioxidant therapy (including selenium) versus placebo in the prevention of recurrence of pancreatitis

Watters 2002

Randomized trial of micronutrients (including selenium) versus placebo in patients undergoing elective aneurysmectomy

Wollschläger 1997

Not randomized trial, selenium supplementation in acute pancreatitis

Characteristics of ongoing studies [ordered by study ID]

Ir a:

Andrews 2004

Trial name or title

SIGNET trial (Scottish multicentre trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients)

Methods

Participants

500 patients, on intensive care units, requiring at least half nutritional requirements by parenteral route, aged 16 years and over

Interventions

Factorial design with glutamine containing versus non‐glutamine containing parenteral nutrition for 7 days, with or without 500 mcg/d selenium as sodium selenite for 7 days

Outcomes

Participants with new infections, length of stay in intensive care, mortality, infections, days of antibiotic use, duration of parenteral nutrition, alive ventilator‐free days, acute hospital length of stay, quality of life, economic evaluation

Starting date

June 2004, recruitment due to finish August 2008

Contact information

Dr Peter Andrews; Anaesthetics, Intensive Care and Pain Medicine; University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH24 2XU, UK

Notes
Yamaguchi 2003

Trial name or title

Forty centre, double‐blind, placebo‐controlled trial

Methods

Participants

394 patients with acute non‐lacunar stroke (cardio‐embolic or atherothrombotic infarction < 24 hours)

Interventions

Ebselen 150 mg twice daily or placebo started within 24 hours of onset for 14 days

Outcomes

Glasgow Outcome Scale three months post stroke, National Institute of Health Stroke Scale and Barthel Index scores at one and three months

Starting date

March 2000, recruitment finished September 2002

Contact information

Takanori Yamaguchi, for the Ebselen Study Group, National Cardiovascular Center, Osaka, Japan

Notes

Letter requesting further details sent 20th October 2003. Reply received 3rd November 2003, giving further details of inclusion criteria and trial intervention from Dr T Motohashi, Daiichi Pharmaceutical Co Ltd. Email sent to Dr Motohashi requesting results of trial 12th June 2006, reply received 19th June 2006 stating that publication is still planned.

Data and analyses

Open in table viewer
Comparison 1. Selenium versus no selenium

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by duration (sodium selenite) Show forest plot

7

476

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.53, 1.06]
Analysis 1.1
Comparison 1 Selenium versus no selenium, Outcome 1 Mortality by duration (sodium selenite).

Comparison 1 Selenium versus no selenium, Outcome 1 Mortality by duration (sodium selenite).

1.1 Selenium 28 day

5

364

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.43, 1.17]

1.2 Selenium 90 day

2

112

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.35, 2.14]

2 Selenium mortality ICU and pancreatitis (sodium selenite) Show forest plot

7

476

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.53, 1.06]
Analysis 1.2
Comparison 1 Selenium versus no selenium, Outcome 2 Selenium mortality ICU and pancreatitis (sodium selenite).

Comparison 1 Selenium versus no selenium, Outcome 2 Selenium mortality ICU and pancreatitis (sodium selenite).

2.1 General intensive care patients

5

389

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.59, 0.96]

2.2 Acute pancreatitis

2

87

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.01, 12.30]

3 Mortality by duration (ebselen) Show forest plot

3

693

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.51, 1.35]
Analysis 1.3
Comparison 1 Selenium versus no selenium, Outcome 3 Mortality by duration (ebselen).

Comparison 1 Selenium versus no selenium, Outcome 3 Mortality by duration (ebselen).

3.1 Ebselen 30 day

1

105

Risk Ratio (M‐H, Random, 95% CI)

1.78 [0.53, 5.95]

3.2 Ebselen 3 month

2

588

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.42, 1.22]
Open in table viewer
Comparison 2. Selenium versus no selenium

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of infected participants Show forest plot

6

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 2.1
Comparison 2 Selenium versus no selenium, Outcome 1 Number of infected participants.

Comparison 2 Selenium versus no selenium, Outcome 1 Number of infected participants.

1.1 Selenium

3

337

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.67, 2.23]

1.2 Ebselen

3

685

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.36, 1.02]
Open in table viewer
Comparison 3. Selenium versus no selenium

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants with adverse event Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 3.1
Comparison 3 Selenium versus no selenium, Outcome 1 Number of participants with adverse event.

Comparison 3 Selenium versus no selenium, Outcome 1 Number of participants with adverse event.

1.1 Selenium

3

328

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.40, 1.43]

1.2 Ebselen

2

588

Risk Ratio (M‐H, Random, 95% CI)

1.16 [0.40, 3.36]

Comparison 1 Selenium versus no selenium, Outcome 1 Mortality by duration (sodium selenite).
Figuras y tablas -
Analysis 1.1

Comparison 1 Selenium versus no selenium, Outcome 1 Mortality by duration (sodium selenite).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Selenium versus no selenium, Outcome 2 Selenium mortality ICU and pancreatitis (sodium selenite).
Figuras y tablas -
Analysis 1.2

Comparison 1 Selenium versus no selenium, Outcome 2 Selenium mortality ICU and pancreatitis (sodium selenite).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Selenium versus no selenium, Outcome 3 Mortality by duration (ebselen).
Figuras y tablas -
Analysis 1.3

Comparison 1 Selenium versus no selenium, Outcome 3 Mortality by duration (ebselen).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 2 Selenium versus no selenium, Outcome 1 Number of infected participants.
Figuras y tablas -
Analysis 2.1

Comparison 2 Selenium versus no selenium, Outcome 1 Number of infected participants.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 3 Selenium versus no selenium, Outcome 1 Number of participants with adverse event.
Figuras y tablas -
Analysis 3.1

Comparison 3 Selenium versus no selenium, Outcome 1 Number of participants with adverse event.

Ir a la figura de la revisiónAbrir en una pestaña nueva
Comparison 1. Selenium versus no selenium

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality by duration (sodium selenite) Show forest plot

7

476

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.53, 1.06]

1.1 Selenium 28 day

5

364

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.43, 1.17]

1.2 Selenium 90 day

2

112

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.35, 2.14]

2 Selenium mortality ICU and pancreatitis (sodium selenite) Show forest plot

7

476

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.53, 1.06]

2.1 General intensive care patients

5

389

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.59, 0.96]

2.2 Acute pancreatitis

2

87

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.01, 12.30]

3 Mortality by duration (ebselen) Show forest plot

3

693

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.51, 1.35]

3.1 Ebselen 30 day

1

105

Risk Ratio (M‐H, Random, 95% CI)

1.78 [0.53, 5.95]

3.2 Ebselen 3 month

2

588

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.42, 1.22]
Figuras y tablas -
Comparison 1. Selenium versus no selenium
Ir a la tabla de la revisión
Comparison 2. Selenium versus no selenium

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of infected participants Show forest plot

6

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Selenium

3

337

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.67, 2.23]

1.2 Ebselen

3

685

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.36, 1.02]
Figuras y tablas -
Comparison 2. Selenium versus no selenium
Ir a la tabla de la revisión
Comparison 3. Selenium versus no selenium

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants with adverse event Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Selenium

3

328

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.40, 1.43]

1.2 Ebselen

2

588

Risk Ratio (M‐H, Random, 95% CI)

1.16 [0.40, 3.36]
Figuras y tablas -
Comparison 3. Selenium versus no selenium
Ir a la tabla de la revisión