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. 2014 Jan 30:348:g445.
doi: 10.1136/bmj.g445.

Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study

Magnus P Ekström  1 , Anna Bornefalk-Hermansson, Amy P Abernethy, David C Currow
Affiliations

Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study

Magnus P Ekström et al. BMJ. .

Abstract

Objective: To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).

Design: Population based longitudinal consecutive cohort study.

Setting: Centres prescribing long term oxygen therapy in Sweden.

Patients: 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register.

Main outcome measures: Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs.

Results: 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤ 30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia.

Conclusions: Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work..

Figures

None
Adjusted hazard ratios with 95% confidence intervals. Rates of hospital admission rates adjusted for WHO performance status, number of previous admissions, number of cardiovascular diagnoses, diabetes mellitus, osteoporosis, and treatment with oral glucocorticoids. Mortality adjusted for age, sex, PaO2 air, PaCO2 air, WHO performance status, BMI, anaemia, number of cardiovascular diagnoses, renal failure, and oral glucocorticoids. DDD=defined daily dose
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