. 2020 Nov 3;35(Suppl 3):945–953. doi: 10.1007/s11606-020-06256-5

Table 2.

Findings from Studies with Control Groups

Author, year	Study design Study size Duration Comparison	Population	Acute pain management strategies	Key findings	Quality assessment (high, unclear, or low risk of bias) and major limitations
MacIntyre, 2013¹³	Retrospective cohort N = 51 24 h after surgery Methadone vs buprenorphine groups as well as those who did and did not miss their medications for OUD dose after surgery	Surgical patients (33% orthopedic, 27% abdominal, 16% orofacial, 13% thoracic, and 10% other) on medications for OUD (57% methadone; 43% buprenorphine) who required IV PCA	•Use of medications for OUD: 64% of the buprenorphine group received medications for OUD (mean 13.7 mg) and 79% of the methadone group received medications for OUD (mean 78.9 mg) the day of surgery. Only 50% of the buprenorphine and 76% of the methadone groups received medications for OUD the day after surgery. •Use of opioids: Similar high doses of morphine-equivalent doses given in the postoperative period (mean 200 mg/day for the buprenorphine group vs 221 mg/day for the methadone group); < 1/4 of patients received tramadol. •Use of adjuvant analgesics: Patients received regular paracetamol and varying doses of nonsteroidal anti-inflammatory drug or continuous ketamine infusion; 1/4 of patients received ketamine, 1/8 received clonidine, and 1 patient received remifentanil.	•The methadone and the buprenorphine groups, and those that did and did not receive their medications for OUD dose the day after surgery, were similar in terms of pain, functionality, and adverse events (nausea, vomiting, sedation) the day after surgery. •Buprenorphine patients who were not given their usual medications for OUD dose the day after surgery used significantly more PCA for longer periods of time, and similar trends were seen in PCA amount in methadone patients.	•High risk of bias •Differences between groups at baseline in terms of substance use (alcohol, cannabis, and benzodiazepines) that were not controlled for •Some patients had medications for OUD discontinued and it is unclear why.
Hansen, 2016²³	Retrospective cohort N = 51 27.2 months Those taking OUD medications for OUD vs those not taking OUD medications	17 knee or hip replacement surgical patients on medications for OUD (methadone or buprenorphine/naloxone) were matched to 34 controls not on medications for OUD	•Use of medications for OUD: the medications for OUD group was taking methadone or buprenorphine/naloxone at baseline (median 870 mg/day), but it is not clear whether medications for OUD were continued or discontinued during surgery. •Use of opioids: Medications for the OUD group received 8 times the morphine-equivalent dose of oral opioids at discharge compared to the non-OUD group (mean 793 mg/day vs 109 mg/day). This is a decrease from baseline for the medications for the OUD group and an increase from baseline for the non-OUD group. •Use of adjuvant analgesics: Similar pain management approaches in both groups including regional block and preoperative anesthesia adjunct medications	•Similar pain, functionality, and quality of life at 6 weeks and 1 year, except the medications for the OUD group had worse knee range of motion at 1 year.	•High risk of bias •Unclear if medications for OUD were continued for all, some, or no patients. •No information on which opioids were prescribed at discharge •Different medications for OUD medications grouped together and no subgroup analysis
Hines, 2008¹¹	Retrospective cohort N = 134 7 days Methadone vs no methadone groups	67 with acute or surgical condition taking methadone were matched to 67 controls not taking methadone	•Use of medications for OUD: Patients taking methadone received an average of 82.4 mg methadone at admission; a total of 12% of patients had methadone increased; 16% experienced withdrawal symptoms (of which 18% had methadone dose increased). •Use of opioids: Median morphine-equivalent dose of opioids similar in methadone and nonmethadone groups (5.07 vs 6.67 mg/day, respectively). •Use of adjuvant analgesics: Some patients in both the methadone and nonmethadone groups received a nonopioid analgesic (42% vs 40%, respectively) and very few received nondrug pain relief (8% vs 5%). The methadone group received a higher median dosage of benzodiazepines than the nonmethadone group (5 vs 2.67 mg/day, respectively).	•Patients taking methadone had the same number of pain reports per day as controls. •Patients taking methadone spent a higher median number of days in the hospital, although this difference was not significant when obstetric cases were excluded. •Methadone patients were more likely to have behavioral problems, to discharge themselves against medical advice, and to transfer to another hospital. Methadone patients also had longer hospital stays overall compared to nonmethadone patients.	•High risk of bias •Pain assessments based on how often the word “pain” appears in a patient’s ward notes •Unclear why some patients had methadone dose increased •The authors do not report the source of acute pain or types of surgery.

Author, year

Study design Study size Duration Comparison

Population

Acute pain management strategies

Key findings

Quality assessment (high, unclear, or low risk of bias) and major limitations

MacIntyre, 2013¹³

Retrospective cohort

N = 51

24 h after surgery

Methadone vs buprenorphine groups as well as those who did and did not miss their medications for OUD dose after surgery

Surgical patients (33% orthopedic, 27% abdominal, 16% orofacial, 13% thoracic, and 10% other) on medications for OUD (57% methadone; 43% buprenorphine) who required IV PCA

•Use of medications for OUD: 64% of the buprenorphine group received medications for OUD (mean 13.7 mg) and 79% of the methadone group received medications for OUD (mean 78.9 mg) the day of surgery. Only 50% of the buprenorphine and 76% of the methadone groups received medications for OUD the day after surgery.

•Use of opioids: Similar high doses of morphine-equivalent doses given in the postoperative period (mean 200 mg/day for the buprenorphine group vs 221 mg/day for the methadone group); < 1/4 of patients received tramadol.

•Use of adjuvant analgesics: Patients received regular paracetamol and varying doses of nonsteroidal anti-inflammatory drug or continuous ketamine infusion; 1/4 of patients received ketamine, 1/8 received clonidine, and 1 patient received remifentanil.

•The methadone and the buprenorphine groups, and those that did and did not receive their medications for OUD dose the day after surgery, were similar in terms of pain, functionality, and adverse events (nausea, vomiting, sedation) the day after surgery.

•Buprenorphine patients who were not given their usual medications for OUD dose the day after surgery used significantly more PCA for longer periods of time, and similar trends were seen in PCA amount in methadone patients.

•High risk of bias

•Differences between groups at baseline in terms of substance use (alcohol, cannabis, and benzodiazepines) that were not controlled for

•Some patients had medications for OUD discontinued and it is unclear why.

Hansen, 2016²³

Retrospective cohort

N = 51

27.2 months

Those taking OUD medications for OUD vs those not taking OUD medications

17 knee or hip replacement surgical patients on medications for OUD (methadone or buprenorphine/naloxone) were matched to 34 controls not on medications for OUD

•Use of medications for OUD: the medications for OUD group was taking methadone or buprenorphine/naloxone at baseline (median 870 mg/day), but it is not clear whether medications for OUD were continued or discontinued during surgery.

•Use of opioids: Medications for the OUD group received 8 times the morphine-equivalent dose of oral opioids at discharge compared to the non-OUD group (mean 793 mg/day vs 109 mg/day). This is a decrease from baseline for the medications for the OUD group and an increase from baseline for the non-OUD group.

•Use of adjuvant analgesics: Similar pain management approaches in both groups including regional block and preoperative anesthesia adjunct medications

•Similar pain, functionality, and quality of life at 6 weeks and 1 year, except the medications for the OUD group had worse knee range of motion at 1 year.

•High risk of bias

•Unclear if medications for OUD were continued for all, some, or no patients.

•No information on which opioids were prescribed at discharge

•Different medications for OUD medications grouped together and no subgroup analysis

Hines, 2008¹¹

Retrospective cohort

N = 134

7 days

Methadone vs no methadone groups

67 with acute or surgical condition taking methadone were matched to 67 controls not taking methadone

•Use of medications for OUD: Patients taking methadone received an average of 82.4 mg methadone at admission; a total of 12% of patients had methadone increased; 16% experienced withdrawal symptoms (of which 18% had methadone dose increased).

•Use of opioids: Median morphine-equivalent dose of opioids similar in methadone and nonmethadone groups (5.07 vs 6.67 mg/day, respectively).

•Use of adjuvant analgesics: Some patients in both the methadone and nonmethadone groups received a nonopioid analgesic (42% vs 40%, respectively) and very few received nondrug pain relief (8% vs 5%). The methadone group received a higher median dosage of benzodiazepines than the nonmethadone group (5 vs 2.67 mg/day, respectively).

•Patients taking methadone had the same number of pain reports per day as controls.

•Patients taking methadone spent a higher median number of days in the hospital, although this difference was not significant when obstetric cases were excluded.

•Methadone patients were more likely to have behavioral problems, to discharge themselves against medical advice, and to transfer to another hospital. Methadone patients also had longer hospital stays overall compared to nonmethadone patients.

•High risk of bias

•Pain assessments based on how often the word “pain” appears in a patient’s ward notes

•Unclear why some patients had methadone dose increased

•The authors do not report the source of acute pain or types of surgery.

IV = intravenous; medications for OUD = medication-assisted treatment; PCA = patient-controlled analgesia