Daily MME Meta Analysis

Objective: To assess, we identified daily MME definitions from published literature and digital clinical tools. We quantified the proportion of patients considered “high dose” across four definitional variants.

Design: Observational cohort from July to September 2018

Setting: Population-based records of all outpatient opioid analgesic prescriptions (n=9,436,640) from electronic prescription drug monitoring programs in California and Florida

Participants: 3,916,461 adult residents dispensed opioid analgesics

Exposures: In continuous models of MME per day, patients were stratified by immediate-release and long-acting opioid status

Main Outcomes: Proportion of adult opioid analgesic patients considered “high dose” (greater than 90 daily MME). Meta-analytic technique quantified heterogeneity attributable to definition. Sensitivity analysis explored the 90 milligram inclusion boundary.

Results: In Florida, patients considered “high dose” were 5.9% or 9.2% or 6.5% or 14.2% of opioid recipients because of definitional variation; in California 3.5% or 5.8% or 3.6% or 10.3%. While Florida had relatively more “high dose” patients, but quantification was inconclusive: 60% or 54% or 79% or 34% more. Average MME per day was 17 to 52 milligrams in California, and 23 to 65 milligrams in Florida. Among patients on opioids for chronic pain, the mean MME difference between states varied by definition: 8.8 (8.3 to 9.3) milligrams to 17.2 (15.1 to 19.3) milligrams. Meta-analyses revealed strong heterogeneity (I2 range: 86% to 99%) based solely on how MME was calculated, impacting immediate-release and extended-release opioids differentially. Including 90.0-90.9 milligrams in the “high dose” boundary increased patients by 15.4% (15.2% to 15.7%).

Conclusions: No single definition appears ideally suited for all clinical settings. While 90 MME may have cautionary mnemonic benefits, without harmonisation the contrivance holds limited clinical value and raises the specter of harm. As the CDC Guideline is revised, it is critically important to reassess the evidence base, lest we promulgate a definitional artifact into mandate.