Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study.
OBJECTIVE
To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).


METHODS
Population based longitudinal consecutive cohort study.


METHODS
Centres prescribing long term oxygen therapy in Sweden.


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


METHODS
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.
Department of Clinical Sciences, Division of Respiratory Medicine and Allergology, Lund University, SE-221 00 Lund, Sweden.
Magnus P
MP
Ekström
Anna
A
Bornefalk-Hermansson
Amy P
AP
Abernethy
David C
DC
Currow
D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D013548:Sweden / Q000453:epidemiology
D000701:Analgesics, Opioid; D001569:Benzodiazepines