Corticosteroids for acute ischaemic stroke

Peter AG Sandercock; Tim Soane

doi:10.1002/14651858.CD000064.pub2

Corticosteroides para el accidente cerebrovascular isquémico agudo

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Referencias

References to studies included in this review

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estudios excluidos
otras referencias
otras versiones publicadas

Bauer RB, Tellez H. Dexamethasone as treatment in cerebrovascular disease. 2. A controlled study in acute cerebral infarction. Stroke 1973;4:547‐55.

Gupta RC, Bhatnagar HN, Gambhir MS, Shah DR. Betamethasone therapy in acute cerebrovascular accidents. Journal of the Association of Physicians of India 1978;26:589‐94.

Google Scholar

McQueen EG. Betamethasone in stroke. New Zealand Medical Journal 1978;87:103‐4.

Google Scholar

Mulley G, Wilcox RG, Mitchell JR. Dexamethasone in acute stroke. BMJ 1978;2:994‐6.

Norris JW. Steroid therapy in acute cerebral infarction. Archives of Neurology 1976;33:69‐71.

Norris JW, Hachinski VC. High dose steroid treatment in cerebral infarction. BMJ 1986;292:21‐3.

Ogun SA, Odusote KA. Effectiveness of high dose dexamethasone in the treatment of acute stroke. West African Journal of Medicine 2001;20(1):1‐6.

Patten BM, Mendell J, Bruun B, Curtin W, Carter S. Double‐blind study of the effects of dexamethasone on acute stroke. Neurology 1972;22:377‐83.

References to studies excluded from this review

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estudios incluidos
otras referencias
otras versiones publicadas

Albizzati MG, Candelise L, Capitani E, Colombo A, Spinnler H. Association of stroke to dexamethasone in treatment of stroke patients. Acta Neurologica Scandinavica 1979;60:77‐84.

Barolin GS, Scholz H, Widhalm K, Hemmer W. Cortisone in non‐haemorrhagic stroke. An anterospective comparative study. Münchener Medizinische Wochenschrift 1976;118(36):1117‐20.

Dyken M, White PT. Evaluation of cortisone in the treatment of cerebral infarction. JAMA 1956;162:1531‐5.

Freeman J, Tappin J, Karat AB, Meecham J. Dexamethasone in acute stroke. BMJ 1978;2:1500.

Gahlot SR, Goyal RK, Swaroop AK Mathur RN. Intravenous glycerol versus dexamethasone therapy in the management of acute cerebral oedema in patients with acute cerebral infarction. Journal of the Association of Physicians of India 1982;30:575‐8.

Google Scholar

Gilsanz V, Rebollar JL, Buencuerpo J, Chantres MT. Controlled trial of glycerol versus dexamethazone in the treatment of cerebral oedema in acute cerebral infarction. Lancet 1975;1:1049‐51.

Hasan D, Lindsay KW, Wijdicks EFM, Murray GD, Brouwers PJAM, Bakker WH, et al. Effect of fludrocortisone acetate in patients with subarachnoid haemorrhage. Stroke 1989;20:1156‐61.

Hetzel BS, Lander H, Robson HN. Immediate treatment of apoplexy. BMJ 1957;1:1122.

Kaste M, Fogelholm R, Waltimo O. Combined dexamethasone and low‐molecular‐weight dextran in acute brain infarction: double‐blind study. BMJ 1976;2:1409‐10.

Kumar N, Jain S, Maheshwari MC. Role of dexamethasone in the outcome from acute stroke. Journal of the Association of Physicians of India 1989;3:315‐7.

Google Scholar

Paal G, Grossman W, Leshem D, Coelho‐Velho‐Groneburg P. Dexamethasone and stroke: The results of a clinical, EEG and CT‐study. 12th World Congress of Neurology: Kyoto. 1981.

Google Scholar

Poungvarin N, Bhoopat W, Viriyavejakul A, Rodprasert P, Buranasari P, Sukondhabhant S, et al. Effects of dexamethasone in primary supratentorial intracerebral haemorrhage. New England Journal of Medicine 1987;316:1229‐33.

Rompel C, Kramer W, Umlauf B, Ulm K, Hellhake T. Effect of dexamethasone phosphate in cerebral infarction compared with current standard therapy. Controlled double‐blind method. Die Medizinische Welt 1980;31:1370‐2.

Rubinstein MK. The influence of adrenocortical steroids on severe cerebrovascular accidents. Journal of Nervous and Mental disease 1965;141:291‐9.

Russek HI, Russek AS, Zohman BL. Cortisone in immediate therapy of apoplectic stroke. JAMA 1955;2:102‐5.

Google Scholar

Santambrogio S, Martinotti R, Sardello F, Porro F, Randazzo A. Is there a real treatment for stroke? Clinical and statistical comparison of different treatments in 300 patients. Stroke 1978;9:130‐2.

Tellez H, Rauer B. Dexamethasone as treatment in cerebrovascular disease.1. A controlled study in intracerebral haemorrhage. Stroke 1973;4:541‐54.

Wright WB. High‐dosage dexamethasone in treatment of strokes in the elderly. Gerontologia Clinica 1974;16:88‐91.

Additional references

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estudios incluidos
estudios excluidos
otras versiones publicadas

Battistini N. Oedema in ischemic cerebral lesions, pathophysiology and treatment. In: Loeb C editor(s). Studies in Cerebrovascular Disease. Milano: Mason Italia Editori, 1981:181‐94.

Google Scholar

Chen ZM, Sandercock P, Xie JX, Peto R, Collins R, Liu LS. Hospital management of acute ischaemic stroke in China. Journal of Stroke and Cerebrovascular Diseases 1997;6:361‐7.

CRASH Trial Collaborators. Final results of MRC CRASH, a randomised placebo‐controlled trial of intravenous corticosteroids in adults with head injury ‐ outcomes at 6 months. Lancet 2004;365:1957‐9.

Faulkes MA, Wolf PA, Price TR, Mohr JP, Hier DB. The Stroke Data Bank: design, methods and baseline characteristics. Stroke 1988;19:547‐54.

Gomes JA, Stevens RD, Lewin JJ, Mirski MA, Bhardwaj A. Glucocorticoid therapy in neurologic critical care. Critical Care Medicine 2005;33(6):1214‐24.

Schulz KF, Chalmers I, Hayes RJ, Altman DG. Failure to conceal treatment allocation schedules in controlled trials influences estimates of treatment effects: an analysis of 250 trials in 33 meta‐analyses. Atlanta: Center for Disease control and prevention. JAMA 1995;273:408‐12.

Shapiro HM. Intracranial hypertension: therapeutic and anaesthetic considerations. Anaesthesia 1975;43:445‐71.

Staykov D, Gupta R. Hemicraniectomy in malignant middle cerebral artery infarction. Stroke 2011;42:513‐6.

References to other published versions of this review

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estudios incluidos
estudios excluidos
otras referencias

Qizilbash N, Lewington S, López‐Arrieta J. Corticosteroids for acute ischaemic stroke. Cochrane Database of Systematic Reviews 2002, Issue 3. [DOI: 10.1002/14651858.CD000064]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Bauer 1973

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: 5 (including 1 lost to follow‐up, none included in analysis) Number lost to follow‐up: 1
Participants	USA 54 in total (after exclusions): 30 female, 24 male Mean age: 66 years Time from onset of stroke to enrolment: within 48 hours Method of diagnosis: clinical, lumbar puncture 100% 28 dexamethasone 26 placebo
Interventions	Dexamethasone versus placebo Intervention: dexamethasone 12 mg i.v. stat, 4 mg i.m. 6 hourly for 3 days, 4 mg i.m. 8 hourly for 3 days, 4 mg i.m. 12 hourly for 2 days, 4 mg i.m. 24 hourly for 2 days: total dose: 120 mg dexamethasone Placebo: unspecified All patients: prophylactic ulcer diet and antacid (30 cc Maalox) 4 times a day where oral intake possible Duration: 10 days
Outcomes	Death at 14 days Neurological impairment in the level of consciousness, the motor system and of mentation at 14 days
Notes	Exclusions: more than 300 red blood cells per cc in the cerebrospinal fluid; history of gastro‐intestinal bleeding or symptomatic duodenal ulcer Follow‐up: 14 days
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated, but assumed computer‐generated by Merck, Sharp & Dohme
Allocation concealment (selection bias)	Unclear risk	"randomisation was performed on a consecutive admission basis". Blind until last patient assessed
Blinding (performance bias and detection bias) All outcomes	Low risk	"coded vials which contained either Decadron [dexamethasone] or a similarly appearing placebo"
Incomplete outcome data (attrition bias) All outcomes	Low risk	5 patients withdrawn (3 placebo, 2 dexamethasone). These were not included in analyses
Selective reporting (reporting bias)	Low risk

Gupta 1978

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: not stated Number of losses to follow‐up: not stated
Participants	India 30 patients (sex breakdown and age not stated) Time from onset of stroke to enrolment: less than 24 hours Method of diagnosis: clinical, lumbar puncture to exclude haemorrhage (100%) 13 Betamethasone 17 Placebo
Interventions	Betamethasone versus placebo Intervention: betamethasone 10 mg stat, 10 mg/day in divided doses for 2 days, 8 mg/day in divided doses for 3 days, 6 mg/day in divided doses for 3 days, 4 mg/day for 3 days, 2 mg/day for 10 days: total dose: 94 mg betamethasone Placebo: unspecified Duration: 21 days
Outcomes	Death at 21 days Neurological status (self‐made method) at 1, 2 and 3 days, and at 1, 2 and 3 weeks Cerebrospinal fluid pressures Adverse events not reported
Notes	Exclusions: not stated Follow‐up: 21 days
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) All outcomes	Low risk	"ampoules of the drug and placebo were similar in appearance"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Authors do not indicate if there were any patients excluded or lost to follow‐up prior to analysis

McQueen 1978

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: not stated Number of losses to follow‐up: not stated
Participants	New Zealand 48 in total (sex breakdown and age not stated) Time from onset of stroke to enrolment: not stated Method of diagnosis: clinical diagnosis of cerebral thrombosis, lumbar puncture ?% 24 betamethasone 24 placebo
Interventions	Betamethasone versus placebo Interventions: betamethasone 12 mg i.m. stat, 4 mg i.m. 8 hourly for 1 day, 4 mg i.m. 8 hourly for 9 days, 4 mg i.m. 2 hourly for 2 days, 2 mg i.m. 2 hourly for 2 days: total dose: 345 mg betamethasone Placebo: vitamin C Duration: 14 days
Outcomes	Death at 12 weeks Causes of death Neurological scores (not available) at 14th to 15th day and week 12
Notes	Exclusions: subarachnoid haemorrhage; severe diabetes; pre‐existing steroid treatment; known peptic ulceration Follow‐up: 12 weeks
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated, but probably prepared by outsider to study
Allocation concealment (selection bias)	Unclear risk	"each centre received packages of betamethasone or identical placebo in randomised order within blocks of six. As patients were entered into the trial they were given the medication designated by the next number in the treatment block"
Blinding (performance bias and detection bias) All outcomes	Low risk	"packages of betamethasone or identical placebo"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Authors do not indicate if there were any patients excluded or lost to follow‐up prior to analysis

Mulley 1978

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: 16 (not included in analysis, 5 due to alternative diagnoses (subarachnoid haemorrhage, cerebral tumour, demyelinating disease and ethanol overdose), 5 due to history revealing previous stroke or onset over 48 hours previously, 1 due to developing tuberculosis, and 1 at the request of the admitting physician, treatment allocations not stated) Number lost to follow‐up: 4 (2 dexamethasone, 2 placebo, not included in analysis)
Participants	UK 134 in total (118 included in final analysis) Mean age: 70 years (no breakdown by sex) Time from onset of stroke to enrolment: within 48 hours Method of diagnosis: clinical, lumbar puncture ?% 61 dexamethasone 57 placebo
Interventions	Dexamethasone versus placebo Interventions: dexamethasone 4.2 mg i.m. 6 hourly for 10 days, 4.2 mg i.m. 8 hourly for 1 day, 4.2 mg i.m. 12 hourly for 2 days, 4.2 mg i.m. once for 1 day: total dose: 201.6 mg dexamethasone Placebo: water Duration: 14 days
Outcomes	Death at day 10 and at 3 and 12 months Functional disability (Adams method) at 12 months Adverse effects of treatment Quality of life Duration of hospital stay
Notes	Exclusions: previous stroke; considered to have intracranial tumour, injury or subarachnoid haemorrhage; diabetes mellitus; peptic ulcer; already receiving steroids. Follow‐up: 12 months
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Low risk	"each of the four wards contained a series of sealed envelopes containing randomised treatment instructions ... After entering into the trial the next envelope was opened"
Blinding (performance bias and detection bias) All outcomes	Low risk	"treatment ampoules identified only by a code number", "the treatment code was available to [one of the trial organisers], who did not participate in assessment"
Incomplete outcome data (attrition bias) All outcomes	Low risk	16 patients excluded after randomisation and not included in analysis. 4 patients lost to follow‐up (2 placebo, 2 treatment) not included in analysis

Norris 1976

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: not stated Number of losses to follow‐up: 1 (lost after assessment on day 22, included in analysis)
Participants	Canada 53 in total (including 1 lost to follow‐up): 24 female, 29 male Mean age: 70 years Time from onset of stroke to enrolment: within 24 hours Method of diagnosis: clinical, lumbar puncture 100%, brain scan 100%, angiography ?% 26 dexamethasone 27 placebo
Interventions	Dexamethasone versus placebo. Intervention: dexamethasone 8 mg stat bolus, 4 mg 6 hourly gradually decreased over 12 days: total dose: 140 mg dexamethasone Placebo: unspecified Duration: 12 days
Outcomes	Death at day 29 Cause of death at day 29 Neurological status (self‐made scale) at days 1, 8, 15, 22 and 29 Adverse effects of treatment
Notes	Exclusions: recent peptic ulcer; concurrent infection, psychiatric disturbances Follow‐up: 29 days
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Correspondence with author suggests random number tables
Allocation concealment (selection bias)	Unclear risk	"patients ... were randomly allocated on admission to a placebo or steroid group in a double‐blind manner"
Blinding (performance bias and detection bias) All outcomes	Low risk	"each patient received either dexamethasone or matching placebo"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	1 patient lost to follow‐up but included in analysis, not stated if any patients were excluded after randomisation: "53 patients completed the study"

Norris 1986

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: 13 (6 placebo and 7 dexamethasone due to presumed side effects: diabetes (4 steroid, 0 placebo), infection (0 steroid, 4 placebo), gastrointestinal bleed (3 steroid, 2 placebo)) Number of losses to follow‐up: not stated
Participants	Canada 113 in total: 61 female, 52 male Mean age: 75 years Time from onset of stroke to enrolment: within 48 hours Method of diagnosis: CT used in (not stated but implied) 100% ? 54 dexamethasone 59 placebo
Interventions	Dexamethasone versus placebo Intervention: dexamethasone 24 mg p.o./i.v. 6 hourly with progressive reduction of dose until day 12: total dose: 480 mg dexamethasone Placebo: unspecified Duration: 12 days
Outcomes	Death at day 21 Cause of death at day 21 Neurological impairment (Toronto stroke method) at days 6, 12, 21 Adverse effects of treatment
Notes	Exclusions: cerebral haemorrhage by CT, mild stroke, massive previous stroke, terminal stroke, dementia, diabetes mellitus, concurrent sepsis, gastrointestinal haemorrhage, or cardiac embolic source Follow‐up: 21 days
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number tables
Allocation concealment (selection bias)	Unclear risk	"consecutive patients admitted to the stroke unit were entered into the study", "patients were assigned to receive either dexamethasone or placebo according to random number"
Blinding (performance bias and detection bias) All outcomes	Low risk	"material was supplied in identical‐appearing vials bearing the patients number in the study"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	13 patients excluded after randomisation and not included in analysis. ? patients lost to follow‐up (likely 0)

Ogun 2001

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: 0 Number of losses to follow‐up: 0
Participants	Nigeria 13 in total (cannot determine age and sex breakdown) Time from onset of stroke to enrolment: within 24 hours Method of diagnosis: clinical, using Siriraj stroke score to distinguish haemorrhagic from ischaemic stroke 5 dexamethasone 8 placebo
Interventions	Dexamethasone versus placebo Interventions: dexamethasone 100 mg stat, 16 mg 6 hourly for 2 days: total dose: 228 mg dexamethasone Placebo: water Duration: 2 days
Outcomes	Death at 1 and 6 months Adverse effects of treatment
Notes	Exclusions: presentation after 24 hours; primary subarachnoid haemorrhage; symptoms suggestive of head injury, subdural, tumour; brainstem stroke; diabetes mellitus; peptic ulcer; sepsis; previous stroke in same hemisphere; impairment of consciousness Follow‐up: 6 months
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"by simple ballot"
Allocation concealment (selection bias)	Unclear risk	"patients were sequentially paired and randomised", "the code was broken after the first 20 patients ... by [one author] who was not involved in assessment of patients"
Blinding (performance bias and detection bias) All outcomes	Low risk	"ampoules were prepared by MCA Chemical, Italy and contained either dexamethasone or distilled water ... these were indistinguishable and kept in identically numbered boxes; one box for each patient"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Authors do not state if there were any patients excluded subsequent to randomisation. None were lost to follow‐up

Patten 1972

Methods	Double‐blind, placebo controlled Randomised Number of patients excluded after randomisation: 7 (3 placebo due to alternative diagnosis (subdural haematoma), alternative cause of death (ruptured abdominal aortic aneurysm) and 1 due to concomitant administration of dextran 40; 3 dexamethasone due to exacerbation of diabetes and stopping of steroid, alternative diagnosis (subarachnoid haemorrhage) and 1 due to concomitant administration of anticoagulant therapy; 1 (? allocation) who had not received any treatment due to nursing error) Number of losses to follow‐up: not stated
Participants	USA 31 in total: 15 female, 16 male Mean age: 69 years Time from onset of stroke to enrolment: within 24 hours Method of diagnosis: clinical, lumbar puncture ?%, isotope brain scan ?%, angiography ?% 17 dexamethasone 20 placebo
Interventions	Dexamethasone versus placebo Intervention: dexamethasone 10 mg i.v. stat, 4 mg i.m. 6 hourly for 10 days, dose gradually decreased to 0 over 7 days: total dose: unknown Control: placebo All patients: oral antacid Duration: 17 days
Outcomes	Death at day 17 Motor function (self‐made scoring) at days 3, 6, 10 and 17 Mental function (self‐made scoring) at days 3, 6, 10 and 17 Adverse effects of treatment
Notes	Exclusions: subarachnoid haemorrhage Follow‐up: 17 days
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number tables
Allocation concealment (selection bias)	Low risk	randomisation not broken until end of trial
Blinding (performance bias and detection bias) All outcomes	Low risk	"the material was supplied in identical appearing vials bearing the patients number in the study"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Number lost to follow‐up not stated. The authors provide outcome data on those randomised and subsequently excluded, so that an ITT analysis can be performed
Selective reporting (reporting bias)	Unclear risk	Patient excluded from the analysis due to alternative mechanism of death despite meeting inclusion criteria and receiving treatment

CT: computerised tomography
i.m.: intramuscular
ITT: intention‐to‐treat
i.v.: intravenous
p.o.: per os (by mouth)
stat: immediately

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Albizzati 1979	Glycerol treatment compared with dexamethasone and not placebo
Barolin 1976	Not randomised ‐ alternate allocation
Dyken 1956	Alternate allocation
Freeman 1978	No data on deaths in each treatment group given. Contained haemorrhagic stroke. Dexamethasone plus mannitol versus placebo
Gahlot 1982	Glycerol compared with dexamethasone and not placebo
Gilsanz 1975	Glycerol treatment compared with dexamethasone and not with placebo
Hasan 1989	Subarachnoid haemorrhage only
Hetzel 1957	No information on randomisation procedure or blinding
Kaste 1976	Dexamethasone plus dextran versus placebo
Kumar 1989	Uneven allocation between treatment (25 participants) and control (15 participants) and confounded by the administration of antacids to the treatment group only
Paal 1981	Dexamethasone plus dextran plus aspirin versus placebo
Poungvarin 1987	Haemorrhagic stroke only
Rompel 1980	No data available
Rubinstein 1965	Not randomised ‐ unequal allocation between treatment (21 participants) and placebo (6 participants)
Russek 1955	Open, uncontrolled study
Santambrogio 1978	No data provided on number of deaths
Tellez 1973	Haemorraghic stroke only
Wright 1974	No randomised allocation

Data and analyses

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Comparison 1. Corticosteroids versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All deaths Show forest plot	8	466	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.87 [0.57, 1.34]
Open in figure viewer Analysis 1.1 Comparison 1 Corticosteroids versus placebo, Outcome 1 All deaths.
2 Deaths within one month Show forest plot	8	466	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.97 [0.63, 1.47]
Open in figure viewer Analysis 1.2 Comparison 1 Corticosteroids versus placebo, Outcome 2 Deaths within one month.

Analysis 1.1

Comparison 1 Corticosteroids versus placebo, Outcome 1 All deaths.

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Analysis 1.2

Comparison 1 Corticosteroids versus placebo, Outcome 2 Deaths within one month.

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Comparison 1. Corticosteroids versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All deaths Show forest plot	8	466	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.87 [0.57, 1.34]

2 Deaths within one month Show forest plot	8	466	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.97 [0.63, 1.47]

Comparison 1. Corticosteroids versus placebo

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Referencias

References to studies included in this review

Bauer 1973 {published data only}

Gupta 1978 {published data only}

McQueen 1978 {published and unpublished data}

Mulley 1978 {published and unpublished data}

Norris 1976 {published and unpublished data}

Norris 1986 {published and unpublished data}

Ogun 2001 {published data only}

Patten 1972 {published and unpublished data}

References to studies excluded from this review

Albizzati 1979 {published data only}

Barolin 1976 {published data only}

Dyken 1956 {published data only}

Freeman 1978 {published data only}

Gahlot 1982 {published data only}

Gilsanz 1975 {published data only}

Hasan 1989 {published data only}

Hetzel 1957 {published data only}

Kaste 1976 {published and unpublished data}

Kumar 1989 {published data only}

Paal 1981 {published data only}

Poungvarin 1987 {published and unpublished data}

Rompel 1980 {published data only}

Rubinstein 1965 {published data only}

Russek 1955 {published data only}

Santambrogio 1978 {published data only}

Tellez 1973 {published data only}

Wright 1974 {published data only}

Additional references

Battistini 1981

Chen 1997

CRASH 2005

Faulkes 1988

Gomes 2005

Schulz 1995

Shapiro 1975

Staykov 2011

References to other published versions of this review

Qizilbash 2002

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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