Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals

Abstract

EDITOR’S PERSPECTIVE What We Already Know about This Topic The prevalence of patients prescribed buprenorphine for treatment of opioid use disorder is increasing Managing acute pain in buprenorphine-maintained individuals can be challenging What This Article Tells Us That Is New Large doses of intravenous hydromorphone can provide analgesia in buprenorphine-maintained individuals However, the use of hydromorphone for analgesia in buprenorphine-maintained individuals confers greater abuse liability and side effects than does supplemental intravenous buprenorphine Background Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone. Methods Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events. Results A significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting. Conclusions In this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.

Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use

“…8 The efficacy of full agonist opioids (ie, hydromorphone or fentanyl) to treat BPOW is limited by buprenorphine's high-affinity blockade at μORs. 11 Successfully overcoming the opioid activation deficit driving BPOW requires surmounting this blockade and may require full agonist doses far outside the range of common clinical practice (eg, 32 mg intravenous [IV] hydromorphone). 12 The clinical limitations of these existing treatment options is evidenced by the continued report of BPOW leading to potentially life-threatening critical illness.…”

“…Administration of additional buprenorphine is limited by both the current Federal Drug Agency recommendations that no more than 12 mg SL buprenorphine be administered on day 1 of induction and the ceiling effect resulting from buprenorphine’s partial agonism (low intrinsic efficacy) at μORs 8 . The efficacy of full agonist opioids (ie, hydromorphone or fentanyl) to treat BPOW is limited by buprenorphine’s high-affinity blockade at μORs 11 . Successfully overcoming the opioid activation deficit driving BPOW requires surmounting this blockade and may require full agonist doses far outside the range of common clinical practice (eg, 32 mg intravenous [IV] hydromorphone) 12 .…”

ASAM Clinical Considerations: Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids

“…After most MORs are bound with buprenorphine, opioid agonism is optimized 14 . The ceiling for many agonist effects is unknown, 15 whereas the ceiling effect for respiratory depression has been well demonstrated 15 . Nevertheless, in patients with advanced age, acute medical illness, chronic lung disease, and those already sedated due to other drugs or medications, the risk of worsening sedation and/or respiratory depression should be considered.…”

Reply to Blatt

“…First, we agree with Dr. Blatt that little work has been conducted on the subjective effects of opioids among patients with chronic pain who are prescribed long-term opioid therapy. The bulk of work on opioid subjective effects (eg, hedonic effects) has been conducted in other populations, such as recreational (ie, illicit) opioid users 6,8,12,23,28 or pain-free healthy volunteers 29,30 tested under laboratory conditions. In his letter, Dr. Blatt described a study in which patients with chronic pain were asked to retrospectively recall the hedonic (ie, euphoric) effects experienced shortly after being exposed to opioids for the first time.…”