Nouira 2014.

Study characteristics
Methods	Study design: randomised, double‐blind, controlled trial Number of study centres and location: 2; Fattouma Bourguiba University Hospital (Monastir, Tunisia) and Tahar Sfar University Hospital (Mahdia, Tunisia) Study setting: emergency department (ED) Withdrawals: stated Date of study: January 2005 and June 2007
Participants	Number screened: 208 Number randomised: 124 Numbers in treatment group: 62 Number in placebo group: 62 Numbers of withdrawals: 2 (magnesium); 2 (ipratropium) Numbers completing trial: 60 (magnesium); 60 (ipratropium) Number included in analysis: 62 (magnesium); 62 (ipratropium) Mean age (years): 69.2 (SD 8.6) (magnesium), 68.9 (SD 7.8) (ipratropium) Gender (male/female): 48/14 (magnesium), 47/15 (ipratropium) Diagnostic criteria: clinical Smoking history: current smokers: 58 (magnesium); 52 (ipratropium) Hospitalisation for COPD within the last year, n (%): 3.6 (2.4) (magnesium); 3.1 (1.7) (ipratropium) Inclusion criteria: 40 years or older; known or suspected COPD based on pulmonary function test, arterial blood gas, clinical history, physical examination, and chest radiograph; have criteria of acute exacerbation as: worsening of dyspnoea within 2 weeks and PaCO2 > 45 mmHg and at least 2 of the following criteria: respiratory rate > 24/min; arterial pH < 7.35; PaO2 < 50 mmHg under room air. Exclusion criteria: hypersensitivity to anticholinergics and to magnesium sulfate; those who received anticholinergics within 6 hours before ED admission; systolic arterial pressure < 90 mmHg or need of vasoactive drugs; those who required immediate endotracheal intubation.
Interventions	Intervention: magnesium sulfate 150 mg in 4 mL of normal saline delivered via aerosol mask at 10 L/min driven by pressurised air plus IV magnesium sulfate 1.5 g in 10 mL, followed by 4 doses of magnesium sulfate with terbutaline at 30 min apart Comparator: ipratropium bromide 0.5 mg in 3 mL of normal saline delivered via aerosol mask at 10 L/min driven by pressurised air plus IV 10 mL of normal saline as placebo, followed by 4 doses of nebulized ipratropium bromide with terbutaline at 30 min apart Concomitant medications: standard treatment consisting of intravenous methylprednisolone, parenteral fluid therapy, antibiotics, and nebulised terbutaline 5 mg in 4 mL of normal saline
Outcomes	Primary outcomes hospital admission need for endotracheal intubation hospital death rates Secondary outcomes improvement in PEFR, dyspnoea score, PaCO2 hospital length of stay incidence of adverse events
Notes	Funding for studies: University of Monastir Conflicts of interest of trial authors: not described; proposal was approved by the Ethic committee Clinical Trials Registry: NCT01136421
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "treatment preparation and allocation were performed by the hospital pharmacy in random sequence using a random table"
Allocation concealment (selection bias)	Unclear risk	Comment: not reported in detail.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "patients were assigned in a randomised double‐blind fashion; treatment preparation performed by the hospital pharmacy were kept identical in their appearance"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: masking includes participant, care provider, investigator and outcomes assessor.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no dropouts from the study arms.
Selective reporting (reporting bias)	Unclear risk	Comment: trial was registered on website; however, outcomes were not provided on the website so unclear if all outcomes were reported as planned.
Other bias	Low risk	Comment: no other apparent biases identified.