CORR Insights®: Preoperative Exposure to Benzodiazepines or Sedative/hypnotics Increases the Risk of Greater Filled Opioid Prescriptions After Surgery

Where Are We Now?

Opioid abuse is a global issue, but one that is concentrated in the United States. Although the United States is only 5% of the world’s population, Americans consume 80% of the global supply of opioids [4]. One study found that surgeons prescribe two to five times more opioids than their patients consume [1]. A separate, population-based study suggested that nearly 9% of patients receiving opioids had indicators of inappropriate prescribing, such as opioid prescriptions with at least one overlap of 7 days or more, overlapping opioid and benzodiazepine prescriptions, long-acting/extended-release opioid prescriptions for acute pain, and daily opioid doses of 100 morphine milligram equivalent or higher [10]. This can be partially attributed to the lack of standardized procedures surrounding opioid prescription. The variety of factors associated with prolonged use makes it difficult to establish standards that accommodate the individual needs of patients.

Preoperative indicators of prolonged opioid use following surgery include (but are not limited to) prior exposure to opioids, benzodiazepines, sedative/hypnotics, depression, baseline alcohol use, tobacco use, and larger prescriptions (in oral morphine equivalents) at discharge [2, 3]. Another recent study emphasized this, and found that discharge prescription amount was the leading factor of prolonged opioid use, suggesting that protocols based on this factor could result in meaningful improvements in this important problem [4]. The consequences of abusing any or all of these opioids are dire. The concurrent use of benzodiazepines, sedative/hypnotics, and opioids has been linked to substantially higher risk of overdose death; the concomitant use of sedative-hypnotic drugs with opioids was associated with increased the risk of death 6.4 fold, and when opioids were combined with benzodiazepines and muscle relaxants, the associated risk increased 12.6 fold [5].

In the current study, Hozack and colleagues [6] performed a prospective analysis of the effects of preoperative exposure to controlled substances on extended opioid use after hand surgery and found that benzodiazepines, sedative/hypnotics, preoperative opioid exposure, smoking history, and mood disorders were associated with more filled opioid prescriptions. Additionally, patients using a combination of controlled substances filled more opioid prescriptions than those using only one. These findings not only extend our body of knowledge on identifying significant risk factors for prolonged use, but also warrant consideration when developing systematic approaches to opioid prescription.

Where Do We Need To Go?

Despite the frequent use of opioids to treat pain after surgery, research does not link sustained opioid use with decreased pain scores at postoperative followup visits or increased patient satisfaction. In fact, multiple studies show that patients using more opioids communicate greater pain intensity and lower satisfaction with pain control [2, 7, 8]. An evaluation of systems imposing greater restrictions on prescriptions reported no increase in postoperative pain, complications, or refill requests [7]. Few institutions have such systems in place, and these systems differ widely across institutions. The presence of distinct systems presents an opportunity to address important questions regarding their efficacy. Which systems show the most promise in addressing prolonged opioid use? What elements do successful systems share?

Preoperative benzodiazepine antagonizes the analgesic effect of postoperative opioids by enhancing the action of gamma-aminobutyric acid receptors [9]. This decrease in potency of opioids immediately following surgery could lead to increased patient perception of dosage needed for pain relief. The extent to which benzodiazepines and sedative/hypnotics antagonize opioid efficacy merits further investigation as it relates to prolonged opioid use. We also need: (1) Evidence-based protocols for the prescription of postoperative opioids; (2) guidelines specific to various specialties and subsets of operations that also account for established preoperative risk factors [11]; and (3) further studies to identify risk factors for prolonged opioid use and to evaluate the efficacy of prescription protocols.

How Do We Get There?

Attempts to limit consumption of postoperative opioids have all helped to varying degrees, but lowering dosage limits does little to address indicators for greater postop usage [7, 8]. Systems tailored to type of operation have already shown success, with one study reporting decreases in prescriptions ranging from 97.8% to 176% [8]. This study used a tiered system of opioid limitation categorizing common orthopaedic operations and setting consensus limits using past prescribing data [8]. The extent to which prescription amounts were decreased without an increase in secondary prescriptions suggests that models using similar methods should be tested moving forward.

Given what we know, I suggest the following steps for reducing prolonged postoperative opioid use:

1. Institute evidence-based protocols for the prescription of postoperative opioids. Though attempts have been made to address prolonged opioid use, few have addressed specific risk factors implicated in the relevant literature. More targeted protocols could potentially be of use in reducing prolonged consumption.

2. Generate guidelines specific to various specialties and subsets of operations that also account for established preoperative risk factors [8, 11]. The success of protocols accounting for distinctions in operation indicates that a more tailored approach to postoperative opioid prescription is an avenue warranting further exploration. This concept can be extended to include preoperative risk factors.

3. Develop studies evaluating the efficacy of prescription protocols in relation to the risk factors they address. As protocols are developed to address a greater variety of factors associated with prolonged opioid use, studies are needed to determine which aspects of these protocols are responsible for the results they produce. One such study could follow protocols that adjust prescribing limits to account for preoperative benzodiazepine use. The results of this study could then be compared to a separate study of protocols that adjusted for preoperative opioid use. In this manner, one could evaluate which factors yield the greatest decrease in prolonged use.

4. Begin investigating the extent to which benzodiazepine and sedative/hypnotic antagonism of opioid efficacy relates to prolonged opioid use. Given the antagonistic effect of benzodiazepines and their association with prolonged opioid use, studies are needed to understand how this temporary antagonism translates to prolonged opioid use. These studies should aim to determine the correlation between preoperative consumption of benzodiazepines and sedative/hypnotics and initial perceived pain relief of postop opioids. If the association is noteworthy, the connection between patients’ initial perceived pain relief and their long-term perceived dosage needed for pain relief should be analyzed to understand the possible effect on prolonged opioid use.