Safe Opioid Prescribing for Acute Noncancer Pain in Hospitalized Adults: A Systematic Review of Existing Guidelines

Opioid Selection Considerations, Including Selection of Dose, Duration, and Route of Administration

Three guidelines recommended using the lowest effective dose, supported by expert consensus and observational data in the outpatient setting demonstrating that overdose risk increases with opioid dose.^16-18 Three guidelines recommended using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain based on expert consensus.^16-18 Two guidelines recommended using as-needed rather than scheduled dosing of opioids based on expert recommendation.^{16, 17}

Strategies to Minimize the Risk of Opioid-Related Adverse Events

Several strategies to minimize the risk of opioid-related adverse events were identified, but most were only recommended by a single guideline. Strategies recommended by more than one guideline included using a recognized opioid dose conversion guide when prescribing, reviewing, or changing opioid prescriptions (based on expert consensus);^16,19 avoiding co-administration of parenteral and oral as-needed opioids, and if as-needed opioids from different routes are necessary, providing a clear indication for use of each (based on expert consensus and other guidelines);^17,19 and avoiding/using caution when co-prescribing opioids with other central nervous system depressant medications^16,17 (supported by observational studies demonstrating increased risk in the outpatient setting).

Safe Practices on Discharge

All 4 of the guidelines recommended prescribing a limited duration of opioids for the acute pain episode; however the maximum recommended duration varied widely from one week to 30 days.^16-19 It is important to note that because these guidelines were not focused on hospitalization specifically, these maximum recommended durations of use reflect the entire acute pain episode (ie, not prescribing on discharge specifically). The guideline with the longest maximum recommended duration was from NICE, based in the United Kingdom, while the US-based guideline development groups uniformly recommended 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

This systematic review identified only 4 existing guidelines that included recommendations on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions, specific nonhospital settings, or the intensive care setting. Although 2 of the identified guidelines offered sparse recommendations specific to the hospital setting, we found no guidelines that focused exclusively on the period of hospitalization specifically outside of the perioperative period. Furthermore, the guideline recommendations were largely based on expert opinion. Although these factors limit the confidence with which the recommendations can be applied to the hospital setting, they nonetheless represent the best guidance currently available to standardize and improve the safety of prescribing opioids in the hospital setting.

This paucity of guidance specific to patients hospitalized in general, nonintensive care areas of the hospital is important because pain management in this setting differs in a number of ways from pain management in the ambulatory or intensive care unit settings (including the post-anesthesia care unit). First, there are differences in the monitoring strategies that are available in each of these settings (eg, variability in nurse-to-patient ratios, frequency of measuring vital signs, and availability of continuous pulse oximetry/capnography). Second, there are differences in available/feasible routes of medication administration depending on the setting of care. Finally, there are differences in the patients themselves, including severity of illness, baseline and expected functional status, pain severity, and ability to communicate.

Accordingly, to avoid substantial heterogeneity in recommendations obtained from this review, we chose to focus on guidelines most relevant to clinicians practicing medicine in nonintensive care areas of the hospital. This resulted in the exclusion of 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management and included use of advanced management procedures beyond the scope of practice for general internists,^20,21 and one guideline that focused on management in the intensive care unit.²² Within the set of guidelines included in this review, we did include recommendations designated for the postoperative period that we felt were relevant to the care of hospitalized patients more generally. In fact, the ACOEM guideline, which includes postoperative recommendations, specifically noted that these recommendations are mostly comparable to those for treating acute pain more generally.¹⁶

In addition to the lack of guidance specific to the setting in which most hospitalists practice, most of the recommendations in the existing guidelines are based on expert consensus. Guidelines based on expert opinion typically carry a lower strength of recommendation, and, accordingly, should be applied with some caution and accompanied by diligent tracking of outcome metrics, as these recommendations are applied to local health systems. Recommendations may have unintended consequences that are not necessarily apparent at the outset, and the specific circumstances of each patient must be considered when deciding how best to apply recommendations. Additional research will be necessary to track the impact of the recommended prescribing practices on patient outcomes, particularly given that many states have already begun instituting regulations on safe opioid prescribing despite the limited nature of the evidence. Furthermore, although several studies have identified patient- and prescribing-related risk factors for opioid-related adverse events in surgical patient populations, given the differences in patient characteristics and prescribing patterns in these settings, research to understand the risk factors in hospitalized medical patients specifically is important to inform evidence-based, safe prescribing recommendations in this setting.

Despite the largely expert consensus-based nature of the recommendations, we found substantial overlap in the recommendations between the guidelines, spanning our prespecified topics of interest related to safe prescribing. Most guidelines recommended restricting opioid use to severe pain or pain that has not responded to nonopioid therapy, checking PDMPs, using the lowest effective dose, and using short-acting opioids and/or avoiding use of long-acting/extended-release opioids for acute pain. There was less consensus on risk mitigation strategies, where the majority of recommendations were endorsed by only 1 or 2 guidelines. Finally, all 4 guidelines recommended prescribing a limited duration of opioids for the acute pain episode, with US-based guidelines recommending 1 to 2 weeks as the maximum duration of opioid use, including the period of hospitalization.

There are limitations to our evaluation. As previously noted, in order to avoid substantial heterogeneity in management recommendations, we excluded 2 guidelines intended for anesthesiologists that focused exclusively on perioperative management,^20,21 and one guideline focused on management in the intensive care unit.²² Accordingly, recommendations contained in this review may or may not be applicable to those settings, and readers interested in those settings specifically are directed to those guidelines. Additionally, we decided to exclude guidelines that focused on managing acute pain in specific conditions (eg, sickle cell disease and pancreatitis) because our goal was to identify generalizable principles of safe prescribing of opioids that apply regardless of clinical condition. Despite this goal, it is important to recognize that not all of the recommendations are generalizable to all types of pain; clinicians interested in management principles specific to certain disease states are encouraged to review disease-specific informational material. Finally, although we used rigorous, pre-defined search criteria and registered our protocol on PROSPERO, it is possible that our search strategy missed relevant guidelines.

In conclusion, we identified few guidelines on safe opioid prescribing practices for managing acute, noncancer pain, outside of the context of specific conditions or nonhospital settings, and no guidelines focused on acute pain management in general, nonintensive care areas of the hospital specifically. Nevertheless, the guidelines that we identified make consistent recommendations related to our prespecified topic areas of relevance to the hospital setting, although most recommendations are based exclusively on expert opinion. Our systematic review nonetheless provides guidance in an area where guidance has thus far been limited. Future research should investigate risk factors for opioid-related adverse events in hospitalized, nonsurgical patients, and the effectiveness of interventions designed to reduce their occurrence.