Analgesic and Opioid Use for Patients Discharged from the Emergency Department with Ureteral Stones

Background

In the United States, urinary stone disease affects nearly 1 in 11 people over a lifetime, with an estimated annual medical cost of $5 billion. ¹ The prevalence and rate of emergency department (ED) visits for urinary stone disease have nearly doubled over the past fifteen years. ^{2 –4} It is the standard of care to prescribe either opioid or nonopioid analgesics for patients with urinary stone disease who are discharged from the ED. The negative consequences associated with opioid use have been well described in the medical literature and the lay press. ⁵ Clinicians seek to balance the benefit of providing relief for a painful condition with the risk of taking analgesics. ⁶ The individual patient and stone characteristics associated with prescribing of opioids and the duration of opioid use are unknown. The objective of this analysis was to describe the use and duration of analgesics, including opioids, for patients discharged from the ED with renal colic and to determine the factors associated with their use.

Methods

After an initial phase assessing feasibility, participants were enrolled in the second phase of the Study of Tamsulosin for Urolithiasis in the Emergency Department conducted from 2013 to 2016 in six ED recruiting sites at U.S. academic centers. ⁷ Eligibility criteria for both phases of the study have been previously published in detail. ⁷ Briefly, adults (at least 18 years of age) were eligible if they presented to the ED with a symptomatic stone determined by CT scan to be less than 9 mm in diameter and located in the ureter and did not require immediate admission or surgical intervention. Stone size was measured as the largest dimension on the axial view of the CT scan. Eligible patients were randomized to take either oral tamsulosin or a matching placebo for 28 days. For this analysis, the treatment groups were combined. Prescribing an analgesic at discharge was considered to be standard of care at all sites, but it was up to the treating physician to determine the type, dosage, and amount of analgesic for each participant. All participants were contacted after randomization on days 2, 7, 15, 20, and 29. At each contact, the participants reported analgesic use since the last contact and whether they had visualized or captured a stone (the study definition of stone passage). As part of each contact, the participant was asked specifically if they were currently taking analgesics. Analgesics were subsequently classified as opioid or nonopioid by investigators. For any contacts with missing information regarding analgesics or opioids, data were imputed if the subject had given the same response at the contacts directly before and after. For example, if data for a day 7 call were missing, but opioid use was reported on days 2 and 15, then the participant was considered to be taking opioids on day 7. In addition, participants were asked if they underwent outpatient ureteroscopic surgery.

Results

Of the 403 participants in the multicenter study, 314 (78%) took analgesics and 199 (49%) took opioid analgesics after discharge from the ED. Characteristics of participants who used an analgesic at any time were compared with those of participants who did not use analgesics (Table 1). Those who took analgesics were not different in baseline characteristics than those who did not take them. However, opioid use was more common in younger patients (p = 0.04) and in those with a family history of stones (p = 0.003). The use of pain medication was analyzed in relation to tamsulosin use, stone size, stone location, and time to expel the stone (Table 2). In patients who used opioids, 62 (31.2%) had a personal history of kidney stones, and in patients who did not use opioids, 54 (26.5%) had a personal history of kidney stones (p = 0.30). Tamsulosin and stone size were not associated with analgesic use. Stone location and time to expel the stone were associated with increased analgesic and opioid use. Analgesics were used in 96% of participants with a stone in the upper ureter that took 4 or more days to pass, compared with only 62% of participants who had a stone in the lower ureter that passed within one day of randomization (Table 3). For those who did not expel a stone, 81% took analgesics and 55% took opioids at any time from day 0 to day 29. For those who did expel a stone, 56% took analgesics at any time before the stone was expelled and 31% continued to take analgesics at some time after passage. Regarding opioids specifically, 32% took opioids before passage and 16% at any time after passage. In general, the use of opioids and other analgesics decreased about the time of stone passage (Fig. 1). Those who required surgery were included in this analysis. In 2% of participants, ureteroscopic surgery was required after discharge.

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FIG. 1.

Days on all analgesics, opioids alone, and time to stone passage. Color images are available online.

Discussion

Urinary stone disease is the diagnosis associated with the greatest proportion of patients who receive prescriptions for opioids. In a national survey from 2006 to 2012, 62% of patients with urinary stone disease received opioid prescriptions. ⁸ In addition, there is evidence that urinary stones may be a risk factor for long-term opioid use and for conversion to persistent opioid use after a new ED prescription. ^9,10

There is considerable debate about the optimal method for pain control for urinary stones. ^11,12 In this analysis, from a multicenter, randomized clinical trial, we identified factors associated with the use of analgesic medication in patients discharged from the ED with a ureteral stone. We found that younger patients, patients with a family history of stone disease, those who took longer to pass a stone, and those with a proximal stone had an association with opioid use. We did not find an association between the size of the stone and the use of analgesics.

Surprisingly, many participants continued to use an analgesic (31%) or an opioid (16%) after reported stone passage. Patients may have continued to experience ureteral spasms after the stone had passed. However, it is also possible that these patients continued to take opioid analgesics for other reasons related to the addictive nature of these medications. A prior study showed that ∼9% of previous opioid-naive patients were still taking opioid analgesics months after the initial stone event. ¹³ This study followed patients for 30 days, but a longer follow-up would be needed to determine if an opioid use disorder had developed. The potential public health implications of persistent opioid use for a disease as common as renal colic should not be minimized.

This analysis found that a stone that took longer to pass was associated with increased use of analgesics. While this finding is logical, it is an important piece of information to communicate to patients who may be at high risk of opioid use disorder. Patients at high risk of opioid disorder might include patients with previous issues of substance use disorders or mental health disease. For these patients and others, the risk of watchful waiting and increased use of analgesics might outweigh the risk of early surgical intervention. Data from this study might allow the clinician to have a more evidenced-based discussion with the patient regarding the options for care.

Since this study was completed, there has been a trend toward relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and other nonopioid analgesics such as acetaminophen for pain control in patients with renal colic. This trend has been supported by evidence that these other options may be as effective as opioids. ^{14 –16} One double-blinded, randomized controlled trial showed that NSAIDs were superior to morphine. ¹⁷ Some EDs have applied a variety of opioid reduction initiatives to the treatment of renal colic. ^18,19 It should be noted that enrollment for this study began in 2013 and coincided with a rise in synthetic opioid overdose deaths and an increasing awareness of the dangers of opioid use among both clinicians and patients. ²⁰ Rates of prescribing opioid analgesia are likely lower now than they were when this study was conducted. ²¹ In this study, we did analyze opioid use by date of enrollment and found a slight, but not dramatic, trend toward lower use of opioids as time went on (from 59% in 2013 to 49% in 2016) (p = 0.327).

Our study has several strengths. First, we recruited participants from six EDs located in four different geographic locations. Second, we had a diverse sample with respect to race (23% nonwhite) and ethnicity (7% Hispanic), making our results generalizable. Third, we followed participants across multiple time points following ED discharge to assess analgesic use. Fourth, since we did not create uniform prescription templates, this study represents a real-world description of analgesic use by patients with ureteral stones after ED discharge. Finally, to increase the generalizability of our study, we did not limit the inclusion to a specific location in the ureter, but included patients who had stones in any part of the ureter.

Our study has a few limitations. First, for participants who passed the stone before the first contact, we did not have information on analgesic use before expulsion. Second, the use of opioids and other analgesics was only captured as to whether the participant was currently taking the medication. Third, data on the use of analgesia were participant reported, as well as stone passage status, which a prior study showed may also not be completely reliable. ²² Fourth, we did not use standardized prescriptions at discharge, but left the amount and dose of the prescribed analgesic to the treating physician's discretion. Fifth, we did not collect data on medical comorbidities in participants with the exception of a history of kidney stones, which was seen in 29.7% of participants. Finally, our participants were not blinded to the characteristics of their stone and may have taken more or less medication depending on the size and location of the stone.

In conclusion, we found several significant factors, including younger patients, patients with a family history of stone disease, patients who took longer to pass a stone, and those with a proximal stone, to be associated with analgesic use after discharge from the ED. Future randomized control trials should focus on comparing opioid and nonopioid management of pain due to urinary stone disease and the variation in prescribing patterns among individual physicians. This study adds important information on the use of analgesics after ED discharge for urinary stone disease and may help guide clinicians who prescribe analgesics for these patients.