Article, Emergency Medicine

Side effects from opioids used for acute pain after emergency department discharge

a b s t r a c t

Objective: Opioid side effects are common when treating chronic pain. However, the frequency of opioid side ef- fects has rarely been examined in acute pain conditions, particularly in a post emergency department (ED) set- ting. The objective of this study was to evaluate the short-term incidence of opioid-induced side effects (constipation, nausea/vomiting, dizziness, drowsiness, sweating, and weakness) in patients discharged from the ED with an Opioid prescription.

Methods: This is a prospective cohort study of patients aged >=18 years who visited the ED for an acute pain con- dition (<=2 weeks) and were discharged with an opioid prescription. Patients completed a 14-day diary assessing daily pain medication use and side effects.

Results: We recruited 386 patients with a median age of 54 years (IQR:43-66); 50% were women. During the 2- week follow-up, 80% of patients consumed opioids. Among the patients who used opioids, 79% (95%CI:75-83) reported side effects compared to 38% (95%CI:27-49) for non-users. Adjusting for age, sex, and pain condition, patients who used opioids were more likely to report constipation (OR:7.5; 95%CI:3.1-17.9), nausea/vomiting (OR:4.1; 95%CI:1.8-9.5), dizziness (OR:5.4; 95%CI: 2.2-13.2), drowsiness (OR:4.6; 95%CI:2.5-8.7), and weakness (OR:4.2; 95%CI:1.6-11.0) compared to non-users. A dose-response trend was observed for constipation but not for the other side effects. Nausea/vomiting (OR:2.0; 95%CI:1.1-3.6) and dizziness (OR:1.9; 95%CI:1.1-3.4) were more often associated with oxycodone than with morphine.

Conclusion: As observed for chronic pain treatment, side effects are highly prevalent during short-term opioid treatment for acute pain. Physicians should inform patients about those side effects and should consider prescrib- ing laxatives.

(C) 2019

Introduction

Opioids are frequently used for the treatment of acute and chronic non-cancer pain. However, their use is frequently associated with side effects that can affect daily functioning and quality of life [1,2]. Some disabling side effects can result in the interruption of opioid treatment for a portion of patients, leaving them with unresolved pain [3]. A side effect is an undesired effect occurring with medication use that is most often anticipated by the physician and an informed patient. Gener- ally side effects resolve over time. Side effects most frequently reported with opioids include nausea/vomiting, dizziness, constipation, drowsi- ness, increased sweating/hot flashes, pruritus, and fatigue [4].

* Corresponding author at: Emergency Department, Hopital du Sacre-Coeur de Montreal, 5400 Gouin Blvd. West, Montreal, QC H4J 1C5, Canada.

E-mail address: [email protected] (R. Daoust).

Most studies evaluating opioid side effects have focused on chronic non-cancer pain patients. In that population, 78% of patients experi- enced at least one side effect, the most prevalent being nausea (21%) [4]. In the acute pain context, a study performed in older adults showed that 66% of patients reported any side effects during the first week of oral opioid treatment for acute Musculoskeletal pain [3]. Pollack et al. also showed that the rate of side effects of opioids was higher than that of nonsteroidal anti-inflammatory drugs (NSAIDs) during a 4-day post emergency department (ED) discharge follow-up [5].

Contrary to other side effects, opioid-induced constipation is typi- cally associated with repeated opioid doses and does not subside with time, occurring in 40% to 64% of patients with chronic non-cancer pain [6-10]. However, it can also arise with a single dose of morphine [11]. Hunold et al. observed an incidence of opioid-induced constipation of 21% compared to 3% for patients using NSAIDs during one week after ED discharge [3]. However, that study was performed on older adults

https://doi.org/10.1016/j.ajem.2019.06.001

0735-6757/(C) 2019

(>=65) and was limited to musculoskeletal pain. There is a need for reli- able data on side effects occurring during short-term opioid use in a larger population with different pain conditions to provide suitable rec- ommendations and treatments for these patients.

The main objective of this study was to evaluate the short-term inci- dence of opioid-induced side effects in patients discharged from an ED with an opioid prescription for acute pain management. Secondary ob- jectives were to assess the dose-effect relationship and type of opioids associated with side effects. We hypothesized that patients discharged from an ED who consumed an opioid for an acute pain condition will show higher rates of side effects (including constipation) during a 14- day follow-up compared to those who did not consume opioids.

Methods

Study design

This was a prospective cohort study conducted in the ED of a tertiary care level-1 trauma centre of an academic urban hospital with an affili- ated emergency medicine residency program and an annual census of approximately 65,000 ED visits (mostly adults). This research is a planned analysis of a cohort created to evaluate acute pain management in patients who received an opioid prescription for acute pain after an ED visit [12]. Approval was obtained from the local institutional ethics review board.

Selection of participants

Patients aged 18 years or older treated in the ED from June 2016 to July 2017 were identified by ED physicians in a seven days a week around the clock manner. We included patients with an acute pain con- dition present for b2 weeks and discharged from the ED with an opioid prescription. All ED physicians referred these patients to research nurses; who then verified inclusion and exclusion criteria, explained the study, and obtained informed consent. The selection of patients who received an opioid prescription was not predetermined; pain man- agement was left to the treating physician’s preference. This was a con- venience sample as we were unable to reliably determine the number of patients missed by ED physicians (no electronic Tracking system for out- patient prescriptions). We only excluded patients who did not speak French or English, were using opioid medication prior to the ED visit (last two weeks), stayed in the ED for N48 h, or were suffering from can- cer or chronic pain.

Data collection and processing

Patients’ demographic information, pain intensity at triage on a 11-point numerical rating scale (NRS), Arrival mode, triage priority, and length of ED stay were extracted from our computerized medical system. ED physicians recorded the final diagnosis, pain intensity at dis- charge (11-point NRS), and which pain medications were prescribed. Patients received a 14-day diary in which they recorded the quantity, time, and name of all the pain medication consumed daily. They were also asked to report any side effects experienced throughout each day. A list of possible opioid side effects was provided; this included nau- sea/vomiting, dizziness, constipation, drowsiness, sweating, weakness, other, and none. A research assistant contacted patients by phone after the first week to evaluate if patients were filling out the diary, to answer any of their questions, and to remind them of the importance of mailing it back to us. We chose a two-week follow-up period since it is the usual acute pain time frame definition [13] and it was also dur- ing this period that the need for pain medication was significantly re- solved in a majority of patients (88%) in our pilot study [14]. Study data were entered and managed using REDCap (Research Electronic Data Capture), a secure, web-based application hosted in the hospital [15].

To assess the effect of the dose and the type of opioids on observed side effects, each opioid was transformed into an oral morphine 5 mg pill equivalent [16], using Gammaitoni et al. [17] method (the various opioid doses cannot be analyzed directly due to the particular potency of different types of opioids). A dose of 3.33 mg of oxycodone and

1.25 mg of hydromorphone were considered equipotent to 5 mg of morphine. For example, 5 mg of oxycodone and 2 mg of hydromorphone would be equivalent to 7.5 mg and 8 mg of morphine, respectively. To compare opioid-using to non-using patients, NSAIDs were converted to 1000 mg naproxen pill equivalent as described by Dougados et al. [18] A dose of 1000 mg of naproxen was considered equivalent to 2400 mg of ibuprofen, 150 mg of indometacin, and 400 mg of celecoxib. Finally, acetaminophen was converted to 500 mg pill equivalent (no combinations with opioids were used). We also grouped pain conditions into five categories most frequently reported in the ED [19];, fracture, other musculoskeletal, renal colic, abdominal pain and other (e.g., abscess, burn, tooth pain, etc.) pain complaints.

Data analysis and statistics

The main outcome was the presence of opioid side effects. Each opi- oid side effect was considered present when reported by patients at least once during the 14-day follow-up and occurred after the consump- tion of an opioid regardless of the delay between the two events.

Baseline characteristics of patients included in the study, those who refused to participate, and those who did not return the diary are pre- sented with descriptive statistics. We calculated differences in the me- dians and in proportions (with associated 95% confidence intervals) for included patients compared to the other two groups. Hodges- Lehman estimates were used to calculate the 95% confidence intervals of median differences. The same statistics were used to compare base- line characteristics between patients who consumed opioids and those who did not during the 14-day follow-up. Univariate and multivariate logistic regressions were used to report association between opioid use and side effects controlling for age, sex, and pain conditions. The same analyses were performed to evaluate the effect of the dose of opi- oids on side effects. Dose of opioids were grouped into five categories according to their quintile distribution (0, 0.1-5, 5.1-10, 10.1-20, and N20 mg Morphine equivalents). To evaluate the effect of the type of opi- oids (oxycodone, hydrocodone, morphine) on side effects, univariate and multivariate logistic regressions were also used controlling for age, sex, pain conditions, and quantity of opioids consumed. All analyses were performed using SPSS version 23 (IBM, Somers, NY).

Results

Description of study cohort

During our recruitment period, a total of 1315 patients meeting the inclusion criteria were initially contacted. Of these, 29% had exclusion criteria, 13% declined to participate, and half of the included patients did not return the diary, leaving 386 participants (Fig. 1). Non- participating and included patients were similar on baseline character- istics, except for age and NSAIDs prescriptions at ED discharge (Table 1). Patients lost to follow-up were significantly younger and received more NSAIDs prescriptions at ED discharge than included patients. Included patients’ median age was 54 years, half were women, and pain intensity at triage was severe, decreasing to moderate at ED discharge. The me- dian number of 5 mg morphine equivalent pills prescribed at ED dis- charge was 30.

During the 2-week follow-up, 80% of patients consumed at least one opioid pill, 72% consumed acetaminophen, and 46% consumed NSAIDs. Patients who used opioids had more other musculoskeletal and less renal colic pain conditions, had higher pain intensity at ED discharge, had a slightly higher median quantity of opioids prescribed, and con- sumed more often acetaminophen compared to those who did not use

Fig. 1. Flow chart of patients’ enrollment in the study.

opioids (Table 2). They also consumed a median number of 10 (IQR = 15) 5 mg morphine equivalent pills during the two-week follow-up.

Opioid side effects

Among the patients who used opioids, almost 80% of them reported a side effect compared to 38% for those who did not use opioids: the most prevalent side effect was drowsiness (51%) and the least prevalent was sweating (13%) (Table 3). Adjusting for age, sex, and pain condition, patients who used opioids were significantly more likely to report con- stipation, nausea/vomiting, dizziness, drowsiness, weakness, and any side effect compared to those who did not use opioids during the 14- day follow-up; constipation having the highest odds compared to the other side effects. Patients 65 and older were more likely to report con- stipation (AOR: 1.9; 95CI: 1.1-3.1) than younger patients and women reported significantly more often nausea/vomiting (AOR: 2.4; 95CI: 1.4-4.1), weakness (AOR: 2.6; 95CI: 1.4-4.5), and dizziness (AOR: 2.1; 95CI: 1.3-3.4) than men.

Effect of dose and types of opioids on side effects

A dose-response trend was observed for constipation: the higher the dose of opioid, the more likely the presence of this side effect. This dose- response effect was less apparent for dizziness and drowsiness and ab- sent for nausea/vomiting and weakness (Table 4). As for the effect of the type of opioids, oxycodone was more often associated with nausea/ vomiting and dizziness than was morphine (Table 5). No other signifi- cant association between types of opioids and side effects was observed.

Discussion

In agreement with our main hypothesis, our prospective study showed that opioid side effects are highly prevalent during short-term acute pain treatments. Furthermore, we observed a dose-response rela- tionship for constipation and showed that certain types of opioids are associated with increased incidences of nausea/vomiting and dizziness. Finally, we noted that age and sex were associated with specific side effects.

The incidence of observed opioid side effects in our study (79%) is very similar to the rate observed in the Cochrane review for chronic non-cancer pain (78%) [4]. However, the latter review on non-cancer chronic pain included more types of side effects (ex: anorexia, head- ache, diarrhea, xeostomia) and serious adverse events (e.g.: death) than did our study; these side effects may not have been included by pa- tients in the “other” category. Nevertheless, except for nausea/vomiting which was similar, the incidences of dizziness, drowsiness, excessive sweating, and weakness observed in our study were higher than those reported in the chronic pain review [4]. For example, we reported a drowsiness rate of 51% compared to 10% in the chronic pain study [4], suggesting that some side effects tend to resolve with chronic opioid use. It may also mean that chronic pain patients, with the repeated use of opioids, have favored an opioid which gave them fewer side ef- fects. The important rate of drowsiness observed in the present study could have important clinical implications, notably on driving or tasks requiring attention.

We observed a slightly higher side effects rate in our population, compared to the only other study reporting rates of side effects in an

Table 1

Baseline characteristics of patients included in the study, those who refused to participate, and those who did not return the diary (lost to follow-up).

Baseline characteristics

Included (N = 386)

Refused to participate (N = 176)

Lost to follow-up (N

= 375)

Difference (95% CI) included

vs refused

Difference (95% CI)

included vs lost

Age, median, (IQR, range), y

54 (43-66,

53 (39-66, 18-91)

44 (34-56, 18-92)

1 (-2 to 5)

10 (8 to 12)

18-95)

Sex, no. (%), men

193 (50)

82 (47)

210 (56)

3 (-6 to 12)

-6 (-13 to 1)

ED arrival mode, no. (%)

By self

317 (82)

134 (76)

289 (77)

6 (-1 to 13)

5 (-1 to 11)

By ambulance

69 (18)

42 (24)

85 (23)

High (levels 1 or 2) triage priority, no. (%)

163 (42)

79 (45)

165 (44)

-3 (-12 to 6)

-2 (-9 to 5)

Pain intensity at triage, median, (IQR)

8 (7-9)

8 (7-10)

8 (7-10)

0 (0 to 0)

0 (0 to 0)

ED treatment section, no. (%)

Ambulatory

256 (66)

110 (63)

237 (63)

3 (-6 to 12)

3 (-4 to 10)

On stretcher

130 (34)

66 (37)

137 (37)

type of pain conditions, no. (%) Fracture

72 (19)

41 (23)

68 (18)

-4 (-11 to 3)

1 (-5 to 7)

Other musculoskeletal

195 (50)

83 (47)

174 (46)

3 (-6 to 12)

4 (-3 to 11)

Fracture

65 (17)

33 (19)

63 (17)

-2 (-9 to 5)

0 (-5 to 5)

Renal colic

23 (6)

8 (5)

26 (7)

1 (-3 to 5)

-1 (-4 to 2)

Abdominal pain

31 (8)

11 (6)

44 (12)

2 (-2 to 6)

-4 (-8 to 0)

Other

Acetaminophen? prescriptions at ED discharge, no. (%)

277 (72)

122 (69)

268 (72)

3 (-5 to 11)

0 (-6 to 6)

NSAID prescriptions at ED discharge, no. (%)

158 (41)

75 (43)

201 (54)

-2 (-11 to 7)

-13 (-20 to -6)

Opioid prescription types at ED discharge, no. (%)

Morphine

167 (43)

74 (42)

164 (44)

1 (-8 to 10)

-1 (-8 to 6)

Oxycodone

151(39)

63 (36)

153 (41)

3 (-6 to 12)

-2 (-9 to 5)

Hydromorphone

68 (18)

38 (22)

56 (15)

-4 (-11 to 5)

3 (-2 to 8)

No. of morphine 5 mg equivalent pills prescribed, median,

30 (20-45)

30 (20-45)

30 (20-48)

0 (-1 to 3)

0 (-2 to 1)

(IQR)

ED stay duration, median, (IQR), h

5 (4-8)

6 (4-8)

5 (4-8)

-1 (-1 to 0)

0 (-1 to 0)

Pain intensity at ED discharge, median, (IQR)

5 (2-7)

5 (2-7)

5 (2-7)

0 (0 to 1)

0 (-1 to 0)

IQR: interquartile range; NSAID: nonsteroidal anti-inflammatory drug; ?: acetaminophen was always prescribed or verbally suggested separately from opioids (no combinations).

acute context [3]. However, this could be explained by the fact that both studies differed on the side effects examined, the age of patients studied (older adults vs all adults), the pain conditions involved (only musculo- skeletal pain vs all acute pain conditions), and the reporting methods (phone call at 4-7 days vs 14-day diary). The rate of side effect for pa- tients who did not use opioids was high (38%). Reported side effects

could be higher due to the Hawthorne effect; being observed and having a list of side effects might have motivated patient to detect them. Pain by itself could cause side effects and 44% of patients who did not use opi- oids consumed NSAIDs which can also cause side effects [3,20].

Constipation differs from other opioids side effects because it does not normally resolve with time. Furthermore, it is the only side effect

Table 2

Baseline characteristics for opioid users and non-users during the 14-day follow-up.

Baseline characteristics

Opioid use (N = 310)

No opioid use (N = 76)

Difference (95% CI)

Age, median, (IQR, range), y

55 (44-67, 19-95)

52 (42-65, 18-86)

3 (-1 to 7)

Sex, no. (%), men

152 (49)

41 (54)

-5 (-17 to 7)

ED arrival mode, no. (%)

By own means

257 (83)

60 (79)

4 (-6 to 14)

By ambulance

53 (17)

16 (21)

High (levels 1 or 2) triage priority, no. (%)

126 (41)

37 (49)

-8 (-20 to 4)

Pain intensity at triage, median, (IQR)

8 (7-10)

8 (7-9)

0 (0 to 0)

ED treatment section, no. (%)

Ambulatory

215 (69)

41 (54)

15 (3 to 27)

On stretcher

95 (31)

35 (46)

Type of pain conditions, no. (%) Fracture

59 (19)

13 (17)

2 (-7 to 11)

Other musculoskeletal

164 (53)

31 (41)

12 (0 to 24)

Renal colic

43 (14)

22 (29)

-15 (-26 to -4)

Abdominal pain

18 (6)

5 (7)

-1 (-7 to 5)

Other

26 (8)

5 (7)

1 (-5 to 7)

Patients who consumed acetaminophen, no. (%)

237 (77)

42 (55)

22 (10 to 34)

Patients who consumed NSAID, no. (%)

143 (46)

33 (44)

2 (-10 to 14)

Opioid prescription types at ED discharge, no. (%)

Morphine

131 (42)

36 (47)

-5 (-17 to 7)

Oxycodone

121 (39)

30 (40)

-1 (-13 to 12)

Hydromorphone

58 (19)

10 (13)

6 (-3 to 15)

No. of morphine 5 mg equivalent pills prescribed, median, (IQR)

30 (20-48)

24 (15-38)

6 (1 to 11)

ED stay duration, median, (IQR), h

5 (3-7)

6 (4-8)

-1 (-2 to 0)

Pain intensity at ED discharge, median, (IQR)

5 (3-7)

3 (0-6)

2 (1 to 3)

IQR: interquartile range; NSAID: nonsteroidal anti-inflammatory drug.

Table 3

Side effects reported for opioid users and non-users during the two-week follow-up.

Side effect

Opioid use (N = 310) % (95%CI)

No opioid use (N = 76) % (95%CI)

OR (95%CI)

AOR (95%CI)

Constipation

38 (33-43)

8 (2-14)

7.2 (3.0-17.0)

7.5 (3.1-17.9)

Nausea/vomiting

27 (22-32)

9 (3-15)

3.5 (1.6-8.0)

4.1 (1.8-9.5)

Dizziness

30 (25-35)

8 (2-14)

5.0 (2.1-11.9)

5.4 (2.2-13.2)

Drowsiness

51 (45-57)

18 (9-27)

4.7 (2.5-8.7)

4.6 (2.5-8.7)

Sweating

13 (9-17)

4 (0-8)

3.6 (1.1-12.0)

3.3 (0.99-11.2)

Weakness

21 (16-26)

7 (2-12)

3.7 (1.4-9.5)

4.2 (1.6-11.0)

Other side effect

16 (12-20)

15 (7-23)

1.1 (0.6-2.3)

1.0 (0.5-2.1)

Any side effect

79 (75-83)

38 (27-49)

6.1 (3.6-10.5)

6.4 (3.7-11.1)

OR: odds ratio; 95%CI: 95% confidence interval; AOR: adjusted odds ratio for age, sex, and pain condition; other side effects: skin rash, diarrhea, headache, dry mouth, numbness.

with a strong dose-response trend. The prevalence observed in our study (almost 40%) is at the lower range of what was observed in chronic pain patients (40-64%) [6-10]. We also found a significant effect of age on constipation, which is not surprising since older patients are generally more likely to be constipated [21-23]. Such a high constipa- tion rate for a short-term opioid use could justify the systematic pre- scription of laxatives in acute pain situations similarly to what is done for chronic pain.

Women using opioids reported nausea/vomiting more often than men in our study, a finding also observed in other studies [24-28]. The underlying mechanism is unknown. We also observed more nausea/ vomiting in patients consuming oxycodone compared to morphine; a trend also reported in a retrospective study of ED patients [28].

opioid drugs can be an effective therapy for patients with moderate to severe acute pain; however, patients should be informed of the high probability of experiencing at least one side effect, even in short-term use. Patients should be particularly warned about the high rate of drowsiness and its potential impact on performing certain tasks. Physi- cians should also consider systematically prescribing laxatives in con- junction with opioids, considering the large proportion of patients who will probably suffer from constipation despite short treatment times. A multicenter study with a larger sample size would help support these findings.

Limitations

This study was done at a single site, carried out in an urban, aca- demic, tertiary care hospital and the findings may not generalize to other health settings. As patients were not randomized to “opioid” or “no opioid” groups, a selection bias could exist. However, except for having higher pain intensity and slightly higher quantities of opi- oid prescribed at ED discharge, patients who consumed opioids were relatively similar to those who did not. The low diary return rate (51%) and the convenience sample could also bias the representa- tiveness of our sample. Nevertheless, we did not find clinically signif- icant differences between patients who completed the study and those who did not. It is also possible that patients lost to follow-up did not return the diary because they did not experience any side ef- fect, thus inflating our side effect rate. However, even in the best case scenario where lost to follow-up patients would not experience side effects, the rate would still be around 40% for any side effects and about 20% for constipation. Furthermore, patients were re- cruited seven days a week around the clock, and consecutive recruit- ment was limited only by the fact that the investigators could not determine the number of patients missed by ED physicians (no electronic tracking system for outpatient prescriptions). In addition, self-reported opioid use could be biased by social desirability issues.

Table 4

Effect of opioid quantity consumed on reported side effects.

Side effect

Opioid consumed (M5E)

OR (95%CI)

AOR (95%CI)

Constipation

0 (Reference)

0.1-5

3.9 (1.5-10.2)

4.2 (1.6-10.9)

5.1-10

6.7 (2.5-17.9)

6.7 (2.5-18.2)

10.1-20

8.0 (3.1-20.8)

9.0 (3.4-23.7)

N20

13.0 (5.0-33.4)

13.3 (5.0-35.1)

Nausea/vomiting

0 (Reference)

0.1-5

4.3 (1.8-10.6)

4.8 (1.9-12.1)

5.1-10

3.1 (1.2-8.1)

3.3 (1.2-9.0)

10.1-20

3.3 (1.3-8.4)

4.0 (1.5-10.5)

N20

3.3 (1.3-8.4)

4.0 (1.5-10.8)

Dizziness

0 (Reference)

0.1-5

4.6 (1.8-11.9)

4.5 (1.7-11.8)

5.1-10

3.3 (1.2-9.3)

3.6 (1.3-10.2)

10.1-20

6.8 (2.6-17.7)

7.8 (2.9-20.7)

N20

5.4 (2.1-14.1)

7.2 (2.6-19.7)

Drowsiness

0 (Reference)

0.1-5

4.5 (2.2-9.2)

4.5 (2.2-9.2)

5.1-10

2.7 (1.3-5.9)

2.6 (1.2-5.8)

10.1-20

5.2 (2.5-10.8)

5.2 (2.4-10.9)

N20

6.8 (3.2-14.2)

7.4 (3.5-16.0)

Weakness

0 (Reference)

0.1-5

4.5 (1.6-12.6)

5.1 (1.8-14.5)

5.1-10

2.7 (0.9-8.3)

2.8 (0.9-8.8)

10.1-20

3.8 (1.3-10.9)

4.4 (1.5-13.0)

N20

3.5 (1.2-10.2)

4.2 (1.4-12.9)

OR: odds ratio; 95%CI: 95% confidence interval; reference is no opioid consumption; AOR: adjusted odds ratio for age, sex, and pain condition; M5E: 5 mg morphine equivalent pills.

Table 5

Effect of the type of opioid on side effects.

Side effect

Type of opioid [1]

% (95%CI)

OR (95%CI)

AOR (95%CI)

Constipation

Oxycodone

33 (25-41)

0.7 (0.4-1.9)

0.6 (0.4-1.1)

Hydromorphone

35 (23-47)

0.7 (0.4-1.3)

0.7 (0.3-1.3)

Morphine

44 (36-52)

Reference

Reference

Nausea/vomiting

Oxycodone

33 (25-41)

1.7 (0.9-3.0)

2.0 (1.1-3.6)

Hydromorphone

25 (14-36)

1.2 (0.6-2.4)

1.3 (0.6-2.7)

Morphine

22 (15-29)

Reference

Reference

Dizziness

Oxycodone

37 (28-46)

1.8 (1.0-3.0)

1.9 (1.1-3.3)

Hydromorphone

28 (17-39)

1.2 (0.6-2.4)

1.3 (0.6-2.7)

Morphine

25 (18-32)

Reference

Reference

Drowsiness

Oxycodone

57 (48-65)

1.5 (0.9-2.5)

1.5 (0.9-2.5)

Hydromorphone

56 (43-69)

1.6 (0.9-2.9)

1.7 (0.9-3.1)

Morphine

45 (37-53)

Reference

Reference

Weakness

Oxycodone

26 (18-34)

1.3 (0.7-2.3)

1.3 (0.7-2.5)

Hydromorphone

10 (2-18)

0.4 (0.2-1.1)

0.4 (0.2-1.1)

Morphine

21 (14-28)

Reference

Reference

OR: odds ratio; 95%CI: 95% confidence interval; AOR: adjusted odds ratio for age, sex, pain condition, and quantity of opioids [1]: number of patients for Oxycodone was 117, 60 for Hydromorphone, and 133 for Morphine.

Nonetheless, studies have shown that self-reports of illicit sub- stance use to be valid relative to urine drug screening [29-31]. Finally, the lack of a dose-response effect for some side effects could be explained by the short delay between first use and the occurrence of side effect that could prompt patients to stop the medication.

Conclusions

In summary, oral opioid side effects are frequent during the short-term treatment of acute pain in ED discharged patients. During a short 14-day follow-up, almost 80% of patients experienced at least one side effect; half of them had drowsiness and nearly 40% reported constipation. Physicians should inform patients of the high short- term prevalence of these side effects and should consider prescribing laxatives, especially for elderly patients.

Financial support

This study was supported by the <>.

Clinical trial registration number

NCT02799004, ClinicalTrials.gov PRS.

Author contributions

R.D. and J.M.C conceived the study and obtained research funding. All authors contributed to the final protocol and Data interpretation.

J.P. was responsible for data management and statistical analysis.

R.D. drafted the manuscript, and A.C., E.P., J.M., J.L., V.C., and D.W. contributed substantially to its revision. All authors approved the final manuscript as submitted and have agreed to be accountable for all aspects of the work.

Declaration of Competing Interest

There is no financial benefit or conflict of interests to report from any of the authors.

Acknowledgments

The authors would like to thank Martin Marquis and Dominique Petit for their contributions to manuscript revision.

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