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. 2022 May 26;2022(5):CD013506. doi: 10.1002/14651858.CD013506.pub2

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.