Opioid Resource Center
Opioid Resource Center
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Disclosures: Muzaale reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
May 27, 2020
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Opioid-benzodiazepine combination linked to increased mortality in patients on dialysis

Source/Disclosures
Disclosures: Muzaale reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Patients with kidney failure who were dispensed a short-acting benzodiazepine in combination with opioids had an increased risk for mortality within 1 year of initiating hemodialysis, according to study results.

“Benzodiazepine-related mortality has been identified as a growing concern, particularly among white adults,” Abimereki D. Muzaale, MD, MPH, of Johns Hopkins University School of Medicine, and colleagues wrote. “Although the mortality risk associated with benzodiazepine use in the general population is likely minimal, it is elevated when combined with opioids.”

According to the researchers, the interaction between the drugs may lead to enhanced respiratory depressant effects.

They added that patients with kidney failure are frequently prescribed benzodiazepines to treat a high burden of physical and psychiatric conditions. Further, these patients are prescribed opioids at a rate three times greater than the general population.

In light of this, Muzaale and colleagues included 69,368 adults initiating hemodialysis in a study to examine the mortality risk associated with short- and long-acting benzodiazepines and its interaction with opioids.

Using Medicare claims, researchers determined 16% of the study population were dispensed a short-acting benzodiazepine and 5% were dispensed a long-acting benzodiazepine. Co-dispensing of opioids and short-acting benzodiazepines occurred among 26% patients, while co-dispensing of opioids and long-acting benzodiazepines occurred among 8%.

Researchers found patients with an opioid prescription were more likely to also be dispensed a short-acting benzodiazepine (adjusted HR [aHR]= 1.66) or a long-acting benzodiazepine (aHR = 1.11).

Regarding mortality, the researchers observed that patients dispensed a short-acting benzodiazepine had a 1.45-fold higher mortality risk compared with those without a short-acting benzodiazepine. For those also dispensed an opioid, the risk increased to 1.90-fold.

On the other hand, they noted long-acting benzodiazepine dispensing was inversely associated with mortality (aHR = 0.84) compared with no dispensing of a long-acting benzodiazepine. Risk did not appear to differ with opioid co-dispensing.

The increased mortality risk observed with short-acting benzodiazepines and opioids led the researchers to recommend physicians use their state’s prescription drug monitoring programs to see whether a patient has been prescribed an opioid prior to prescribing a benzodiazepine.

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Patients with kidney failure who used benzodiazepines with opioids had increased mortality risk.
Source: Adobe Stock

“The potential risks associated with short-acting benzodiazepines should always be weighed against their therapeutic benefit, and patients undergoing hemodialysis who are currently undergoing treatment with short-acting benzodiazepines should consider other treatments when clinically appropriate,” they wrote.

“Furthermore,” they added, “providers caring for patients undergoing hemodialysis should be given the tools needed to implement a collaborative, team-based approach for deprescribing short-acting benzodiazepines, particularly for patients who are likely to use opioids.”

In an accompanying commentary, Cher Thomas, a patient with kidney disease and chronic pain for more than 2 decades, wrote that she was concerned with the authors’ argument that “benzodiazepine mortality ha[s] already been identified as a growing concern for white women.”

She argued that her interactions with patients living with similar conditions (kidney disease and chronic pain/depression), have led her to conclude all patients, regardless of race or gender, “live with the same struggles.”

Still, she wrote, “I am encouraged to see the crisis of palliative care being addressed in the kidney population.” – by Melissa J. Webb

Disclosures: Muzaale reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.