Edwards 2013.

Study characteristics
Methods	Study design: randomised double‐blind placebo‐controlled trial Number of study centres and location: two university hospitals in New Zealand (Wellington Regional Hospital and Hutt Hospital) Study setting: emergency departments Withdrawals: stated Date of study: June 2008 to November 2011
Participants	Number screened: 161 Number randomised: 116 Number allocated in treatment group: 52 Number allocated in placebo group: 64 Numbers of withdrawals: 0 Numbers excluded from analysis: 4 (magnesium); 3 (placebo) Number included in analysis: 109 Number included in analysis: 48 (magnesium): 61 (placebo) Mean age/SD (years): 73.2/9.8 (magnesium); 69.5/11.9 (placebo) Gender (male/female): 27/21 (magnesium); 31/30 (placebo) Diagnostic criteria: clinical diagnosis Baseline lung function: Mean FEV1 at presentation (% of predicted): 28.2 (magnesium); 29.7 (placebo) Mean FEV1 at presentation: 0.69 L (magnesium); 0.72 L (placebo) Smoking history: Mean amount of smoking (pack‐years): 41.3 (magnesium); 45 (placebo) Current smokers: 18 (magnesium); 22 (placebo) Never smokers: 1 (magnesium); 2 (placebo) Average number of hospital admission in last year: 1 (magnesium); 1.3 (placebo) Serum magnesium level (mmol/L) mean/SD: 0.81 (SD 0.08) (magnesium); 0.78 (SD 0.1) (placebo) Inclusion criteria: age ≥ 35 years with a doctor diagnosis of COPD, FEV1/FVC < 70% and an FEV1 ≤ 50% predicted 20 min after initial treatment with 2.5 mg salbutamol and 500 mg ipratropium bromide by nebulisation. Exclusion criteria: those who required intubation or NIV, were unable to perform spirometry or had evidence of pneumothorax, hypotension, any other serious medical condition that would prevent their participation in the trial or were pregnant.
Interventions	Intervention: jet nebulisation 2.5 mg salbutamol (GlaxoSmithKline, London, UK) mixed with 2.5 ml isotonic magnesium sulfate (250 mmol/L, tonicity 289 mosmol; 151 mg per dose) on 3 occasions at 30 min intervals Comparator: jet nebulisation 2.5 mg salbutamol (GlaxoSmithKline, London, UK) mixed with 2.5 mL isotonic saline (placebo) on 3 occasions at 30 min intervals Concomitant medications: Supplemental oxygen via nasal prongs during the nebuliser (1–2 L/min) Standard initial treatment with 2.5 mg salbutamol and 500 mg ipratropium bromide by jet nebulisation and 40 mg prednisone
Outcomes	Primary outcomes FEV1 at 90 min Secondary outcomes FEV1 at 30 and 60 min hospital admission episodes of NIV admission to ICU
Notes	Funding for studies: The Health Research Council of New Zealand. Conflicts of interest of trial authors: Declared "None"; trial registry: ACTRN12608000167369
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The study statistician performed block randomisation with a block size of eight using a computer‐generated random sequence"
Allocation concealment (selection bias)	Low risk	Quote: "Patients were randomly allocated in a double‐blind fashion to receive one of the treatment regimens. This was administered by a third‐party process"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Participants and investigators were unaware of treatment allocation through provision by the hospital pharmacy of pre‐prepared identical syringes containing the study drug or placebo according to random allocation"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 3 (4.9%) from magnesium group and 4 (8.3%) from placebo group were excluded from the analyses, with reasons provided.
Selective reporting (reporting bias)	Unclear risk	Comment: Trial was registered on website and results for most of the outcomes were reported, except for mortality at 30 days.
Other bias	Low risk	Comment: no other apparent biases identified.