Chronic opioid pain treatment converted to buprenorphine: A case series using a 3-step low-dose incremental dosing guideline.

We report a 30-case series from the Pain Management Center at the Massachusetts General Hospital where we have applied a guideline to convert chronic treatment for pain from full agonist opioids (FAO) to buprenorphine (BUP). Of the patients, 24 (80 percent) elected to continue BUP over FAO. Five conversions were stopped for side effects (fatigue) and/or lack of sufficient pain reduction. One patient elected not to participate on the day that the conversion was to begin. There were no major adverse events. We conclude that conversion to BUP should be considered as an alternative to treat patients on chronic opioids for pain.

Substance Use Disorders: Basic Overview for the Anesthesiologist.

Substance use disorders (SUDs) represent a current major public health concern in the United States and around the world. Social and economic stressors secondary to the coronavirus disease 2019 (COVID-19) pandemic have likely led to an increase in SUDs around the world. This chronic, debilitating disease is a prevalent health problem, and yet many clinicians do not have adequate training or clinical experience diagnosing and treating SUDs. Anesthesiologists and other perioperative medical staff frequently encounter patients with co-occurring SUDs. By such, through increased awareness and education, physicians and other health care providers have a unique opportunity to positively impact the lives and improve the perioperative outcomes of patients with SUDs. Understanding commonly used terms, potentially effective perioperative screening tools, diagnostic criteria, basics of treatment, and the perioperative implications of SUDs is essential to providing adequate care to patients experiencing this illness.

Perioperative Management of Extended-Release Buprenorphine: A Narrative Review and Case Series.

BACKGROUND: Perioperative management of formulations of buprenorphine used for the treatment of opioid use disorder and/or pain are common clinical challenges. Care strategies are increasingly recommending continuation of buprenorphine while administering multimodal analgesia including full agonist opioids. While this "simultaneous strategy" is relatively simple for the shorter-acting sublingual buprenorphine formulation, best practices are needed for the increasingly prescribed extended-release buprenorphine (ER-buprenorphine). To our knowledge there are no prospective data to guide perioperative management of patients on ER-buprenorphine. Herein we provide a narrative review, report on the perioperative experiences of a series of patients maintained on ER-buprenorphine, and propose recommendations for perioperative ER-buprenorphine management based on best evidence, clinical experience, and our judgments. CASES: Here we present clinical data describing the perioperative experiences of patients maintained on extended-release buprenorphine who recently underwent a variety of surgeries ranging from outpatient inguinal hernia repair to multiple inpatient surgeries for source control in sepsis, at different medical centers throughout the United States. These patients were identified via an email solicitation to substance use disorder treatment providers throughout a nationwide healthcare system, requesting cases of patients maintained on extended-release buprenorphine who had recently undergone surgery. We report here on all of the cases received. DISCUSSION: Extrapolating from these and recently published case reports, we describe an approach to perioperative management of extended-release buprenorphine.

Perioperative Management of Extended-release Buprenorphine.

Perioperative management of buprenorphine is increasingly characterized by continuation of buprenorphine throughout the perioperative period while coadministering full agonist opioids for analgesia. Although this "simultaneous strategy" is commonly used for the shorter-acting sublingual buprenorphine formulations, there is little to guide management of the extended-release formulations of buprenorphine. Here we report the perioperative experience of an individual maintained on extended-release buprenorphine who successfully underwent major surgeries utilizing a strategy of performing the surgeries at the time of the next scheduled dose.

Perioperative Buprenorphine Management: A Multidisciplinary Approach.

Buprenorphine formulations (including buprenorphine/naloxone) are effective treatments of pain and opioid use disorder (OUD). Historically, perioperative management of patients prescribed buprenorphine involved abstinence from buprenorphine sufficient to allow for unrestricted mu-opioid receptor availability to full agonist opioid (FAO) treatment. Evidence is mounting that a multimodal analgesic strategy, including simultaneous administration of buprenorphine and FAO, nonopioid adjuncts such as acetaminophen and nonsteroidal anti-inflammatory drugs, and regional anesthesia, is a safe and effective perioperative strategy for the patient prescribed long-term buprenorphine treatment of OUD. This strategy will likely simplify management and more seamlessly provide continuous buprenorphine treatment of OUD after hospital discharge.

Facilitating discontinuation of intravenous opioids by -concurrent use of sublingual buprenorphine with rapid microdosing -induction: A pain management case study.

We report a case in which sublingual buprenorphine was used to help transition a patient off intravenous (IV) opioid analgesics medications post-multiple abdominal procedures. Intravenous opioids are commonly used in inpatient surgical pain management for patients with severe pain who are unable to take oral medications. Typically, a short course of IV analgesics is used, followed by transition to oral analgesic regimen. However, in patients with poor gastrointestinal absorption, pain control can be challenging. We present this case to highlight how sublingual buprenorphine can be a useful agent for acute pain management, especially when conventional strategies provide suboptimal responses.

Thiopental Does Not Produce Hyperalgesia: A Laboratory Study Using Two Human Experimental Pain Models.

OBJECTIVE: Past investigations assessing the effects of thiopental on pain are conflicting. Although several studies demonstrate hyperalgesia as a result of barbiturate administration, others show analgesia. Our objective was to assess the effects of an infusion of the GABAA agonist thiopental, compared with placebo, in healthy participants on two subjective experimental pain paradigms: noxious electrical stimulation and intradermal capsaicin. METHODS: For electrical stimulation, the milliamps required to achieve pain threshold and tolerance were recorded, and the percent change from baseline was determined for each infusion condition. In the intradermal capsaicin condition, the area of hyperalgesia was determined by von Frey technique pre- and postinfusion, and the percent change in the area of hyperalgesia was calculated. RESULTS: Though thiopental infusion resulted in an increase in the electrical stimulation current required to elicit pain threshold or reach pain tolerance when compared with baseline, this finding was not statistically significant. In the intradermal capsaicin condition, there was a statistically significant difference in overall pre- and postinfusion pain interpretation, as measured by the McGill Pain Questionnaire (P < 0.05), but there was no significant difference in area of hyperalgesia. CONCLUSIONS: In this human study of thiopental's effects on two experimental pain models, our results show that thiopental does not induce hyperalgesia.

Perioperative Continuation of Buprenorphine at Low-Moderate Doses Was Associated with Lower Postoperative Pain Scores and Decreased Outpatient Opioid Dispensing Compared with Buprenorphine Discontinuation.

OBJECTIVE: An increasing number of individuals are prescribed buprenorphine as medication-assisted treatment for opioid use disorder. Our institution developed guidelines for perioperative buprenorphine continuation with an algorithm for dose reduction based upon the surgical procedure and patient's maintenance dose. The objective of this study was to compare the effects of buprenorphine continuation with those of discontinuation on postoperative pain scores and outpatient opioid dispensing. DESIGN: Retrospective observational study. SUBJECTS: Surgical patients on buprenorphine from March 2018 to October 2018. Patients on buprenorphine for chronic pain and those with minor procedures were excluded from analysis. METHODS: We compared postoperative outpatient opioid dispensing and postanesthesia care unit (PACU) pain scores in patients where buprenorphine was continued compared with held perioperatively, collecting single surgical subspecialty prescriber data on outpatient full mu-opioid agonist prescriptions dispensed, converted into mean morphine equivalents. Buprenorphine formulations were not included in our morphine milligram equivalents (MME) total. RESULTS: There were 55 patients total (38 cont. vs 17 held). There was no difference in postoperative buprenorphine treatment adherence (91% cont. vs 88% held, P = 0.324). The number of opioid prescriptions dispensed was significantly higher with buprenorphine discontinuation (53% cont. vs 82% held, P = 0.011), as was MME dispensed (mean of 229 cont. vs mean of 521 held, P = 0.033). PACU pain scores were higher with buprenorphine discontinuation (mean 2.9 cont. vs mean 7.6 held, P < 0.001). CONCLUSIONS: There was a significant reduction in opioid prescriptions filled, MME dispensed, and PACU pain scores in patients where buprenorphine was continued vs held perioperatively. We provide evidence to support that buprenorphine can be continued perioperatively and that continuation is associated with decreased postoperative pain and decreased outpatient opioid dispensing. These results contribute to the existing literature supporting the perioperative continuation of buprenorphine.

Perioperative Buprenorphine Continuous Maintenance and Administration Simultaneous With Full Opioid Agonist: Patient Priority at the Interface Between Medical Disciplines.

Buprenorphine is a partial-agonist opioid that is prescribed as a medication-assisted treatment (MAT) for opioid use disorder (OUD). Buprenorphine is also a potent analgesic with high opioid-receptor affinity and binding coefficient; when buprenorphine is administered simultaneously with a µ-opioid receptor full agonist ("full agonist opioid" [FAO]), the combination can yield unexpected outcomes depending on dosing and timing. Buprenorphine is sometimes perceived as a powerful competitive opioid blocker that will hamper pharmacologic management that necessitates the use of FAO. When patients receiving buprenorphine-MAT (BUP-MAT) formulations have presented for operative procedures, there has been clinical variance in approach to their BUP-MAT management. Recognizing the risk management challenge from both analgesia and BUP-MAT perspectives, we convened a multidisciplinary group of clinicians who treat BUP-MAT patients and completed a literature review with the goal of generating a guideline for appropriate management of these patients presenting for a broad spectrum of surgical procedures. Our conclusion is that continuous simultaneous administration of buprenorphine products with FAO is safe when accounting for dose and timing, including surgeries that historically produce moderate to severe pain, and may further provide an analgesic advantage, lessen FAO burden, and reduce relapse risk to this group.

Effect of Intravenous Ethanol on Capsaicin-Induced Hyperalgesia in Human Subjects.

BACKGROUND: The objective of this study was to assess ethanol's (EtOH's) effects on capsaicin-induced hyperalgesia in healthy participants. Specifically, we investigated the change in area of capsaicin-induced hyperalgesia following 3 interventions: intravenous EtOH at 2 targeted breath alcohol concentrations (BrAC), or placebo. METHODS: Eighteen participants participated in 3 test days in a randomized order. Each test day, participants received an intradermal capsaicin injection on the volar surface of the forearm, followed by either infusion of high concentration EtOH (targeted BrAC = 0.100 g/dl), low concentration EtOH (targeted BrAC = 0.040 g/dl), or placebo. The area of hyperalgesia was determined by von Frey technique at 2 time points, prior to EtOH infusion, and again when target BrAC was reached. The primary outcome was the percent change in the area of capsaicin-induced hyperalgesia. Additional outcome measures included the visual analogue scale of mood states (VAS), which was administered at each time point. RESULTS: There was a marked 30% reduction in the area of capsaicin-induced hyperalgesia with infusion of a high concentration of EtOH (p < 0.05). Low concentration EtOH produced a 10% reduction in hyperalgesia area, although this finding did not reach significance. Further, participants reported significant feelings of euphoria and drowsiness at high concentrations of EtOH (p < 0.05), as measured by the VAS. CONCLUSIONS: In a human model examining pain phenomena related to central sensitization, this study is the first to demonstrate that capsaicin-induced hyperalgesia is markedly attenuated by EtOH. The capsaicin experimental pain paradigm employed provides a novel approach to evaluate EtOH's effects on pain processing. The antihyperalgesic effects of EtOH observed have important clinical implications for the converging fields of substance abuse and pain medicine and may inform why patients with chronic pain often report alcohol use as a form of self-medication.

Subjective Effects of Thiopental in Young Adults with and without a Family History of Alcoholism.

BACKGROUND: The development of alcohol use disorders is genetically influenced, and may be mediated through differences in the subjective response to alcohol. There is some evidence to suggest that response differences to alcohol could be conveyed by heritable differences in GABAA receptors. The purpose of this study was to investigate whether individuals with a family history positive (FHP) for alcohol dependence would experience alterations in response to the GABAA receptor agonist thiopental, in comparison to family history negative (FHN) subjects. METHODS: 73 subjects (24 FHP and 49 FHN) between the ages of 21 and 30 years were administered sub-anesthetic doses of the GABAA receptor agonist thiopental and placebo on two separate test days. Various alcohol-related measures were administered, including those examining subjective effects, coordination, and cognition. RESULTS: Sub-anesthetic doses of thiopental produced alcohol-like subjective effects, as well as alcohol-like impaired coordination and cognition in healthy subjects. While there were no significant main effects in subjective, coordination, or cognitive effects between FHP and FHN individuals, analysis of peak effects suggested FHP had blunted sedative, but not stimulant effects compared to FHN. CONCLUSION: Thiopental produced alcohol-like effects and perceived similarities to alcohol in healthy individuals. Subtle differences in sedative effects are consistent with reports of blunted FHP response to the negative but not stimulant effects of alcohol. Future studies are needed to better understand how this insight informs our understanding of the heritable risk for alcoholism and the treatment of alcohol use disorders.

Analgesic effects of ethanol are influenced by family history of alcoholism and neuroticism.

BACKGROUND: Although personality factors and family history of substance abuse influence how individuals experience pain and respond to analgesics, the combined effects of those factors have not been extensively studied. The objective of this study was to consider the possible role of personality trait of neuroticism and family history of alcoholism on the experience of pain and their role in the analgesic response to an ethanol challenge. METHODS: Forty-eight healthy subjects participated in this study; thirty-one had a positive family history of alcoholism (FHP), seventeen had a negative family history of alcoholism (FHN). They were also categorized based on their neuroticism (N) scores (low N = 28, and high N = 20). This was a double-blind, placebo-controlled, randomized, within-subject design study of intravenous administration of three doses of ethanol. The testing consisted of 3 separate test days scheduled at least 3 days apart. Test days included a placebo day (saline solution), low-exposure ethanol day (targeted breathalyzer = 0.040 g/dl), and high-exposure ethanol day (targeted breathalyzer = 0.100 g/dl). Noxious electrical stimulation and pain assessments were performed prior to start of infusion and at the 60-minute infusion mark. RESULTS: The analgesic effect of ethanol was mediated by an interaction between the personality trait of neuroticism and family history. Individuals with family history of alcoholism and high N scores reported significantly more analgesia on low dose of ethanol than those with low N scores. There was no difference in the analgesic response to ethanol among FHNs with low and high N scores. CONCLUSION: These findings support the conclusion that neuroticism and family history of alcoholism both influence the analgesic response of alcohol. Individuals with high N scores and FHP have the strongest response to ethanol analgesia particularly on the low exposure to alcohol.

Ethanol and pain sensitivity: effects in healthy subjects using an acute pain paradigm.

BACKGROUND: The primary objective of this study was to determine whether healthy subjects without a history of heavy alcohol use or a family history of alcoholism exhibit a concentration-dependent analgesic effect of ethanol. In a preliminary fashion, we also compared this sample to a group of subjects with a strong positive family history for alcoholism (FHP) to test the secondary hypothesis that FHP individuals will be more sensitive to the analgesic effects of alcohol compared to healthy subjects who are negative for a family history of alcoholism (FHN). METHODS: Forty-one healthy FHN subjects and 19 FHP subjects participated. Test days included an ethanol high concentration (breathalyzer = 0.100 g/dl), ethanol low concentration (breathalyzer = 0.040 g/dl) or placebo. The infusion of ethanol was via computerized pump to achieve a steady-state ("clamp") ethanol concentration. Noxious electrical stimulation and pain assessments were performed prior to start of placebo/ethanol infusion and at the 60-min infusion mark. The applied current was progressively increased until the pain was reported as 5 or higher on an 11-point Verbal Numeric Scale (VNS). Outcome variables included measures of pain threshold and tolerance and Visual Analog Scales of mood states. RESULTS: Among FHN subjects there was a significant ethanol concentration effect on pain tolerance (F = 3.0, p = 0.05). The average change in pain stimuli required to reach a VNS of 5 or greater were (-2.4, -1.0, and 2.2 mAmps respectively) for high concentration, low concentration, and placebo. There were no ethanol concentration related differences in pain threshold. The analgesic effect of ethanol was not correlated with changes in mood states, suggesting an independent analgesic effect of the drug. A comparison of FHP to FHN subjects produced no differences on pain responses. CONCLUSION: The findings support the hypothesis that in healthy subjects intravenous ethanol administration has a concentration effect on pain tolerance but not on pain threshold. Additional studies are planned to further elucidate the mechanisms of ethanol's analgesic effects.