Gabapentinoids in Chronic Kidney Disease: A Closer Look at Respiratory Risk

In 2019, the Food and Drug Administration issued a warning regarding the risk of respiratory depression with gabapentin use, especially when combined with opioids or other central nervous system depressants. While prior inpatient studies have observed increased respiratory risks in postoperative patients, data are limited in hospitalized patients with renal dysfunction.

The objective of the study is to evaluate the association between gabapentinoid use and respiratory depression in hospitalized patients with chronic kidney disease (CKD).

This single-center retrospective cohort study included adult inpatients receiving a multimodal pain regimen with or without gabapentinoid and CKD stage III, IV, or V. Patients were excluded if they had a history of epilepsy, generalized anxiety disorder, restless leg syndrome, acute respiratory conditions, hepatic disease, or were initially admitted to the intensive care unit. The primary outcome was a composite measure of respiratory depression, including use of high-flow nasal cannula, bilevel positive airway pressure, mechanical ventilation, oxygen escalation, naloxone or flumazenil administration, or rapid response/code activation. Secondary outcomes included altered mental status, falls, and individual components of the primary outcome.

A total of 320 patients were included. In the unadjusted analysis, respiratory depression occurred in 35.6% of gabapentinoid users versus 24.1% of nonusers (P = 0.10). After controlling for confounders, gabapentinoid use was associated with a significantly higher risk of respiratory depression (odds ratio: 1.71; 95% confidence interval: 1.02-2.89). A dose-dependent relationship was observed with respiratory depression: gabapentin >1400 mg/d (83.3%), 800 to 1400 mg/d (42.3 %), and 100 to 700 mg/d (29.7%); pregabalin >150 mg/d (66.7%) and ≤150 mg (26.3%). Secondary outcomes were not significantly different between groups.

Gabapentinoid use in hospitalized CKD patients was associated with respiratory depression. These findings support the need for careful dosing and monitoring of gabapentinoids in this high-risk population.