Association between opioid and benzodiazepine use and clinical deterioration in ward patients
BACKGROUND
Opioids and benzodiazepines are frequently used in hospitals, but little is known about outcomes among ward patients receiving these medications.
OBJECTIVE
To determine the association between opioid and benzodiazepine administration and clinical deterioration.
DESIGN
Observational cohort study.
SETTING
500-bed academic urban tertiary-care hospital.
PATIENTS
All adults hospitalized on the wards from November 2008 to January 2016 were included. Patients who were “comfort care” status, had tracheostomies, sickle-cell disease, and patients at risk for alcohol withdrawal or seizures were excluded.
MEASUREMENTS
The primary outcome was the composite of intensive care unit transfer or ward cardiac arrest. Discrete-time survival analysis was used to calculate the odds of this outcome during exposed time periods compared to unexposed time periods with respect to the medications of interest, with adjustment for patient demographics, comorbidities, severity of illness, and pain score.
RESULTS
In total, 120,518 admissions from 67,097 patients were included, with 67% of admissions involving opioids, and 21% involving benzodiazepines. After adjustment, each equivalent of 15 mg oral morphine was associated with a 1.9% increase in the odds of the primary outcome within 6 hours (odds ratio [OR], 1.019; 95% confidence interval [CI], 1.013-1.026; P < 0.001), and each 1 mg oral lorazepam equivalent was associated with a 29% increase in the odds of the composite outcome within 6 hours (OR, 1.29; CI, 1.16-1.45; P < 0.001).
CONCLUSION
Among ward patients, opioids were associated with increased risk for clinical deterioration in the 6 hours after administration. Benzodiazepines were associated with even higher risk. These results have implications for ward-monitoring strategies. Journal of Hospital Medicine 2017;12:428-434. © 2017 Society of Hospital Medicine
© 2017 Society of Hospital Medicine
Chronic opioid and benzodiazepine use is common and increasing.1-5 Outpatient use of these medications has been associated with hospital readmission and death,6-12 with concurrent use associated with particularly increased risk.13,14 Less is known about outcomes for hospitalized patients receiving these medications.
More than half of hospital inpatients in the United States receive opioids,15 many of which are new prescriptions rather than continuation of chronic therapy.16,17 Less is known about inpatient benzodiazepine administration, but the prevalence may exceed 10% among elderly populations.18 Hospitalized patients often have comorbidities or physiological disturbances that might increase their risk related to use of these medications. Opioids can cause central and obstructive sleep apneas,19-21 and benzodiazepines contribute to respiratory depression and airway relaxation.22 Benzodiazepines also impair psychomotor function and recall,23 which could mediate the recognized risk for delirium and falls in the hospital.24,25 These findings suggest pathways by which these medications might contribute to clinical deterioration.
Most studies in hospitalized patients have been limited to specific populations15,26-28 and have not explicitly controlled for severity of illness over time. It remains unclear whether associations identified within particular groups of patients hold true for the broader population of general ward inpatients. Therefore, we aimed to determine the independent association between opioid and benzodiazepine administration and clinical deterioration in ward patients.
MATERIALS AND METHODS
Setting and Study Population
We performed an observational cohort study at a 500-bed urban academic hospital. Data were obtained from all adults hospitalized on the wards between November 1, 2008, and January 21, 2016. The study protocol was approved by the University of Chicago Institutional Review Board (IRB#15-0195).
Data Collection
The study utilized de-identified data from the electronic health record (EHR; Epic Systems Corporation, Verona, Wisconsin) and administrative databases collected by the University of Chicago Clinical Research Data Warehouse. Patient age, sex, race, body mass index (BMI), and ward admission source (ie, emergency department (ED), transferred from the intensive care unit (ICU), or directly admitted to the wards) were collected. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used to identify Elixhauser Comorbidity Index categories.29,30 Because patients with similar diagnoses (eg, active cancer) are cohorted within particular areas in our hospital, we obtained the ward unit for all patients. Patients who underwent surgery were identified using the hospital’s admission-transfer-discharge database.
