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Almost 70% of hospitalized patients require a peripheral intravenous catheter (PIV), yet up to 69% of PIVs fail prior to completion of therapy.To identify risk factors associated with PIV failure.A single center, prospective, cohort study.Medical and surgical wards of a tertiary hospital located in Queensland, Australia.Adult patients requiring a PIV.Demographic, clinical, and potential PIV risk factors were collected. Failure occurred if the catheter had complications at removal.We recruited 1000 patients. Catheter failure occurred in 512 (32%) of 1578 PIVs. Occlusion/infiltration risk factors included intravenous (IV) flucloxacillin (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.19-3.31), 22-gauge PIVs (HR, 1.43; 95% CI, 1.02-2.00), and female patients (HR, 1.48; 95% CI, 1.10-2.00). Phlebitis was associated with female patients (HR, 1.81; 95% CI, 1.40-2.35), bruised insertion sites (HR, 2.16; 95% CI, 1.26-3.71), IV flucloxacillin (HR, 2.01; 95% CI, 1.26-3.21), and dominant side insertion (HR, 1.39; 95% CI, 1.09-1.77). Dislodgement risks were a paramedic insertion (HR, 1.78; 95% CI, 1.03-3.06). Each increase by 1 in the average number of daily PIV accesses was associated (HR 1.11, 95% CI 1.03-1.20)-(HR 1.14, 95% CI 1.08-1.21) with occlusion/infiltration, phlebitis and dislodgement. Additional securement products were associated with less (HR 0.32, 95% CI 0.22-0.46)-(HR 0.63, 95% CI 0.48-0.82) occlusion/infiltration, phlebitis and dislodgement.Modifiable risk factors should inform education and inserter skill development to reduce the currently high rate of PIV failure.