Fentanyl is a fully synthetic opioid with analgesic and anesthetic properties. It has become a primary driver of the deadliest opioid crisis in the United States and elsewhere, consequently imposing devastating social, economic, and health burdens worldwide. However, the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown, and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are scarce. This review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action, including neural circuit dysfunction and neuroinflammation. We discuss recent progress in the development of pharmacological interventions, anti-fentanyl vaccines, anti-fentanyl/heroin conjugate vaccines, and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory depression. However, translational studies and clinical trials are still lacking. Considering the present opioid crisis, the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.
Humans ; Fentanyl/therapeutic use* ; Opioid-Related Disorders/drug therapy* ; Drug Overdose/prevention & control* ; Analgesics, Opioid/adverse effects* ; Vaccines/therapeutic use* ; Brain

When facing the worldwide abuse of opioid substance, one of the effective responses is opioid substitution therapy (OST). However, different OST service patterns may affect the therapeutic outcome. Using the System Engineering Initiative for Patient Safety (SEIPS) model, we can analyze the factors that affecting the outcomes of patients from the perspective work system. In this paper, SEIPS model is used to describe the existing OST service model. According to the operation mechanism of the methadone maintenance treatment in China and the existing OST service model, some suggestions are put forward to carry out effective OST service in the country.
Analgesics, Opioid/adverse effects* ; China ; Delivery of Health Care ; Humans ; Methadone/therapeutic use* ; Opiate Substitution Treatment ; Opioid-Related Disorders/therapy* ; Treatment Outcome

Analgesics, Opioid ; adverse effects ; therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Clinical Trials as Topic ; Disease Management ; Humans ; Pain, Intractable ; drug therapy ; physiopathology

BACKGROUND: Patients commonly develop postoperative pain after total knee arthroplasty (TKA). Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals. OBJECTIVE: To examine the effect of low-level laser acupuncture (LA) in reducing postoperative pain, pain-related interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A single-blind randomized placebo-controlled trial was conducted. Patients (N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao (SP6), Taixi (KI3), Kunlun (BL60), Fengshi (GB31), Futu (ST32) and Neiguan (PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output. MAIN OUTCOME MEASURES: The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain, postoperative pain-related interference in daily life and morphine consumption, were measured at hours 24, 48 and 72 after TKA. RESULTS: Generalized estimating equations revealed significant between-group differences in pain intensity (P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72 (P < 0.05) and morphine consumption at hours 48 and 72 (P < 0.05). The changes in pain-related interference in daily life were significant (P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood, and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24 (P < 0.05). CONCLUSION: Low-level LA gradually reduced older patients' postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care. TRIAL REGISTRATION ClinicalTrials.gov registration number NCT03995446.
Acupuncture Therapy ; Aged ; Analgesics, Opioid/therapeutic use* ; Arthroplasty, Replacement, Knee/adverse effects* ; Double-Blind Method ; Humans ; Morphine/therapeutic use* ; Pain, Postoperative/drug therapy* ; Single-Blind Method

PURPOSE: We evaluated the incidence and risk factors of postoperative nausea and vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type 3 (5 HT3)-receptor antagonist after the general anesthesia. MATERIALS AND METHODS: In this retrospective study, incidence and risk factors for PONV were evaluated with fentanyl IV-PCA during postoperative 48 hours after various surgeries. RESULTS: Four hundred-forty patients (23%) of 1878 had showed PONV. PCA was discontinued temporarily in 268 patients (14%), mostly due to PONV (88% of 268 patients). In multivariate analysis, female, non-smoker, history of motion sickness or PONV, long duration of anesthesia (>180 min), use of desflurane and intraoperative remifentanil infusion were independent risk factors for PONV. If one, two, three, four, five, or six of these risk factors were present, the incidences of PONV were 18%, 19%, 22%, 31%, 42%, or 50%. Laparoscopic surgery and higher dose of fentanyl were not risk factors for PONV. CONCLUSION: Despite antiemetic prophylaxis with 5 HT3-receptor antagonist, 23% of patients with fentanyl-based IV-PCA after general anesthesia showed PONV. Long duration of anesthesia and use of desflurane were identified as risk factors, in addition to risk factors of Apfel's score (female, non-smoker, history of motion sickness or PONV). Also, intraoperative remifentanil infusion was risk factor independent of postoperative opioid use. As the incidence of PONV was up to 50% according to the number of risk factors, risk-adapted, multimodal or combination therapy should be applied.
Adult ; Aged ; Analgesia, Patient-Controlled/*adverse effects ; Analgesics, Opioid/*adverse effects/therapeutic use ; Antiemetics/administration & dosage/therapeutic use ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Incidence ; Isoflurane/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Piperidines/*adverse effects/therapeutic use ; Postoperative Nausea and Vomiting/chemically induced/*epidemiology ; Retrospective Studies ; Risk Factors

OBJECTIVETo compare the preemptive analgesia efficacy between two cycloxygenase-2 inhibitors, rofecoxib and etoricoxib in the ambulatory uterine evacuation patients.

METHODSIn this randomized, double-blinded, placebo-controlled trial 60 patients were randomly divided into three groups and received a single dose of placebo, rofecoxib 50 mg, or etoricoxib 120 mg, respectively, before operation. Patient's visual analogue score (VAS) was rated postoperatively at 15 min, 30 min, 60 min, time-to-discharge, 6 h and 24 h. Fentanyl (in post-anesthesia care unit) and paracetamol (at home) were supplementary analgesics and the dosage was also recorded. Patient's satisfaction score was rated at 24 h postoperatively.

RESULTSEtoricoxib 120 mg and rofecoxib 50 mg were significantly superior to placebo at 6 h postoperatively (P < 0.05) while there was no significant differences of VAS at other time points. The amounts of Fentanyl used in post-anesthesia care unit were similar in three groups, but paracetamol taken at home was much less in rofecoxib group and etoricoxib group than in placebo group (P < 0.01). Compared to rofecoxib, etoricoxib provided better pain relief after discharge (P < 0.05). The overall pain management satisfaction score was significantly higher in etoricoxib group (96 +/- 7) than in other groups (P < 0.01).

CONCLUSIONPreemptive rofecoxib 50 mg and etoricoxib 120 mg may significantly decrease VAS at 6 h postoperatively, and reduce the usage of analgesics in ambulatory uterine evacuation patients. Etoricoxib 120 mg offeres better pain relief at home compared with rofecoxib 50 mg.

Abortion, Induced ; adverse effects ; Acetaminophen ; therapeutic use ; Adolescent ; Adult ; Ambulatory Surgical Procedures ; Analgesics, Non-Narcotic ; therapeutic use ; Analgesics, Opioid ; therapeutic use ; Cyclooxygenase Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Fentanyl ; therapeutic use ; Humans ; Lactones ; therapeutic use ; Pain Measurement ; Pain, Postoperative ; prevention & control ; Preoperative Care ; Pyridines ; therapeutic use ; Sulfones ; therapeutic use

The use of opioids for the treatment of chronic non-cancer pain has become more widespread recently. Available data support the short-term use of opioids in clearly defined nociceptive and neuropathic pain states. Their use in 'pathological' pain states without a clear diagnosis, such as chronic low back pain, is more contentious. A decision to initiate opioid treatment in these conditions requires careful consideration of benefits and risks; the latter include not only commonly considered adverse effects such as constipation, but also opioid-induced hyperalgesia, abuse, addiction and diversion. Ideally, treatment goals should not only be relief of pain, but also improvement of function. Opioid treatment of chronic non-cancer pain requires informed consent by, and preferably a treatment contract with, the patient. Treatment should be initiated by a trial period with defined endpoints using slow-release or transdermal opioids. Ongoing management of the patient requires ideally a multi-disciplinary setting. Treatment should not be regarded as life-long and can be discontinued by tapering the dose.
Analgesics, Opioid ; adverse effects ; therapeutic use ; Humans ; Hyperalgesia ; chemically induced ; Low Back Pain ; drug therapy ; Pain, Intractable ; drug therapy ; Substance-Related Disorders ; prevention & control

PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. RESULTS: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
Aged ; Aged, 80 and over ; Analgesics, Opioid/*adverse effects/therapeutic use ; Disease Progression ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/*drug therapy/radiography ; Osteoarthritis, Knee/*drug therapy/radiography ; Pain/drug therapy

PURPOSE: The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. MATERIALS AND METHODS: Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n=30), 0.5 microgram/kg remifentanil (Group II, n=30) or 1 microgram/kg remifentanil (Group III, n=30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. RESULTS: The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. CONCLUSION: The pretreatment with 0.5 and 1.0 microgram/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation.
Adult ; Aged ; Analgesics, Opioid/administration & dosage/therapeutic use ; Androstanols/administration & dosage/*adverse effects ; Female ; Humans ; Injections, Intravenous/adverse effects ; Middle Aged ; Pain/etiology/*prevention & control ; Piperidines/administration & dosage/*therapeutic use

PURPOSE: In this randomized, double-blind study, we investigated the analgesic efficacy and side effects of continuous constant-dose infusions of remifentanil after total abdominal hysterectomy and compared it to fentanyl. MATERIALS AND METHODS: Fifty-six adult female patients scheduled for elective total abdominal hysterectomy were enrolled in this study. Patients were randomly assigned to two groups according to fentanyl (group F, n=28) or remifentanil (group R, n=28) for postoperative analgesia. Patients in group F were given fentanyl intravenously with an infusion rate of fentanyl 0.5 microgram/kg/hr; group R was given remifentanil with an infusion rate of remifentanil 0.05 microgram/kg/min for 2 days. Pain intensity at rest, occurrence of postoperative nausea and vomiting (PONV), dizziness, pruritus, and respiratory depression were assessed 1 hr after arrival at the post-anesthesia care unit, at 6; 12; 24; and 48 hr post-operation and 6 hr post-infusion of the study drug. Pain was evaluated by using visual analogue scale (VAS; 0-10). The time that patients first requested analgesics was recorded as well as additional analgesics and antiemetics. RESULTS: There were no significant differences in VAS, time to first postoperative analgesics, and additional analgesics between the 2 groups. The incidences and severities of PONV and opioid related side effects were not different between the groups; however, there were 3 episodes (10.7%) of serious respiratory depression in group R. CONCLUSION: Continuous infusion technique of remifentanil did not reveal any benefits compared to fentanyl. Furthermore, it is not safe for postoperative analgesia in the general ward.
Adolescent ; Adult ; Aged ; Analgesics, Opioid/administration & dosage/therapeutic use ; Drug Administration Schedule ; Female ; Fentanyl/administration & dosage/*therapeutic use ; Humans ; Hysterectomy/*adverse effects ; Infusions, Intravenous ; Middle Aged ; Pain, Postoperative/*drug therapy/etiology ; Piperidines/administration & dosage/*therapeutic use ; Treatment Outcome