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

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

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

The objective of this study was to assess the effect of lidocaine jelly application to chest tubes on the intensity and duration of overall pain, chest tube site pain and the required analgesics for postoperative pain relief in coronary artery bypass graft (CABG) patients. For patients in group L, we applied sterile 2% lidocaine jelly on the chest tubes just before insertion, and for patients in group C, we applied normal saline. Overall visual analogue scale (VAS), maximal pain area with their VAS were documented postoperatively, and the frequency that button of patient-controlled analgesia was pressed (FPB) and total fentanyl consumption were assessed. The number of patients who complained that tube site was the most painful site was significantly higher in group C than in group L (85% vs. 30% at extubation, P<0.001). The overall VAS score was significantly higher in group C than in group L (39.14+/-12.49 vs. 27.74+/-13.76 at extubation, P=0.006). After all of the tubes were removed, the VAS score decreased more in group C (5.74+/-4.77, P<0.001) than in group L (3.05+/-2.48, P<0.001). FPB and total fentanyl consumption were significantly higher in group C than in group L (73.00, 59.00-78.00 vs. 34.00, 31.00-39.25, P<0.001; 2,214.65+/-37.01 vs. 1,720.19+/-361.63, P<0.001, respectively). Lidocaine jelly application is a very simple way to reduce postoperative pain by reducing chest tube site pain after CABG. (Clinical Trials Registry No. ACTRN 12611001215910)
Adolescent ; Adult ; Aged ; Analgesia, Patient-Controlled ; Anesthetics, Local/*therapeutic use ; Cardiac Catheters/adverse effects ; Chest Tubes/*adverse effects ; Coronary Artery Bypass ; Drainage ; Female ; Fentanyl/therapeutic use ; Humans ; Lidocaine/*therapeutic use ; Male ; Middle Aged ; Pain Management/*methods ; Pain Measurement ; Pain, Postoperative/*drug therapy ; Random Allocation ; Young Adult

PURPOSE: This analysis was done to investigate the optimal regimen for fentanyl-based intravenous patient-controlled analgesia (IV-PCA) by finding a safe and effective background infusion rate and assessing the effect of adding adjuvant drugs to the PCA regimen. MATERIALS AND METHODS: Background infusion rate of fentanyl, type of adjuvant analgesic and/or antiemetic that was added to the IV-PCA, and patients that required rescue analgesics and/or antiemetics were retrospectively reviewed in 1827 patients who underwent laparoscopic abdominal surgery at a single tertiary hospital. RESULTS: Upon multivariate analysis, lower background infusion rates, younger age, and IV-PCA without adjuvant analgesics were identified as independent risk factors of rescue analgesic administration. Higher background infusion rates, female gender, and IV-PCA without additional 5HT3 receptor blockers were identified as risk factors of rescue antiemetics administration. A background infusion rate of 0.38 microg/kg/hr [area under the curve (AUC) 0.638] or lower required rescue analgesics in general, whereas, addition of adjuvant analgesics decreased the rate to 0.37 microg/kg/hr (AUC 0.712) or lower. A background infusion rate of 0.36 microg/kg/hr (AUC 0.638) or higher was found to require rescue antiemetics in general, whereas, mixing antiemetics with IV-PCA increased the rate to 0.37 microg/kg/hr (AUC 0.651) or higher. CONCLUSION: Background infusion rates of fentanyl between 0.12 and 0.67 microg/kg/hr may safely be used without any serious side effects for IV-PCA. In order to approach the most reasonable background infusion rate for effective analgesia without increasing postoperative nausea and vomiting, adding an adjuvant analgesic and an antiemetic should always be considered.
Adult ; Aged ; Analgesia, Patient-Controlled/*adverse effects/*methods ; Female ; Fentanyl/administration & dosage/therapeutic use ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sex Factors

PURPOSE: Opioid-based intravenous patient-controlled analgesia (IV PCA) is popular method of postoperative pain control, but many patients suffer from IV PCA-related postoperative nausea and vomiting (PONV). In this retrospective observational study, we have determined independent predictors of IV PCA-related PONV and predictive values of the Apfel's simplified risk score in pursuance of identifying high-risk patients. MATERIALS AND METHODS: We analyzed 7000 patients who received IV PCA with background infusion after elective surgery. Patients who maintained IV PCA for a postoperative period of 48 hr (completion group, n=6128) were compared with those who have discontinued IV PCA within 48 hr of surgery due to intractable PONV (cessation group, n=872). Patients, anesthetics, and surgical factors known for predicting PONV were evaluated by logistic regression analysis to identify independent predictors of IV PCA related intractable PONV. RESULTS: In a stepwise multivariate analysis, weight, background infusion dose of fentanyl, addition of ketolorac to PCA, duration of anesthesia, general anesthesia, head and neck surgery, and Apfel's simplified risk score were revealed as independent risk factors for intractable PONV followed by the cessation of IV PCA. In addition, Apfel's simplified risk score, which demonstrated the highest odds ratio among the predictors, was strongly correlated with the cessation rate of IV PCA. CONCLUSION: Multimodal prophylactic antiemetic strategies and dose reduction of opioids may be considered as strategies for the prevention of PONV with the use of IV PCA, especially in patients with high Apfel's simplified risk scores.
Adult ; Analgesia, Patient-Controlled/*adverse effects ; Anesthetics, Intravenous/administration & dosage/adverse effects/therapeutic use ; Antiemetics/administration & dosage/therapeutic use ; Female ; Fentanyl/administration & dosage/adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Postoperative Nausea and Vomiting/*drug therapy ; Retrospective Studies ; Risk Assessment/methods ; Risk Factors

BACKGROUNDEmergence agitation is a common problem in pediatric anesthesia, especially after sevoflurane induction and maintenance anesthesia. The purpose of this study was to investigate the effect of sufentanil to reduce emergence agitation after sevoflurane anesthesia in children undergoing adenotonsillectomy compared with fentanyl.

METHODSOne hundred and five children, aged 3 - 11 years, were randomly allocated to receive normal saline (control group), sufentanil 0.2 µg/kg (S2) or fentanyl 2 µg/kg (F2) 1 minute after loss of the eyelash reflex. Anesthesia was induced and maintained with sevoflurane. Time to tracheal extubation, recovery time, Paediatric Anesthesia Emergence Delirium (PAED) scale, and emergence behavior were assessed.

RESULTSThe incidence of severe agitation was significantly lower in S2 and F2 groups vs. the control group, 4/32 and 15/34 vs. 24/34 respectively, (P = 0.002, 0.009, respectively). PAED scales were significantly different among three groups (P = 0.007), and lower in the S2 and F2 groups than in the control group (P = 0.007 and P = 0.025, respectively). And the incidence of severe agitation and the PAED scale score was significantly different between the S2 and F2 groups (P = 0.007, P = 0.019, respectively). Time to tracheal extubation and recovery time were similar in all three groups.

CONCLUSIONSAdministration of sufentanil at 0.2 µg/kg after induction of anesthesia reduced emergence agitation in children receiving sevoflurane anesthesia for adenotonsillectomy compared with fentanyl. This was without delaying the recovery time or causing significant hypotension.

Adenoidectomy ; methods ; Anesthesia ; methods ; Child ; Child, Preschool ; Female ; Fentanyl ; therapeutic use ; Humans ; Male ; Methyl Ethers ; adverse effects ; therapeutic use ; Prospective Studies ; Psychomotor Agitation ; drug therapy ; etiology ; Sufentanil ; therapeutic use

BACKGROUNDThe authors found no study to compare the efficacy of bolus dose fentanyl and remifentanil blunting the cardiovascular intubation response in children, so they designed this randomized, double-blind clinical study to assess the effects of remifentanil 2 microg/kg and fentanyl 2 microg/kg by bolus injection on the cardiovascular intubation response in healthy children.

METHODSOne hundred and two children, the American Society of Anesthesiologists (ASA) physical status 1-2 and scheduled for elective plastic surgery under general anesthesia, were randomly divided into one of two groups to receive the following treatments in a double blind manner: remifentanil 2 microg/kg (Group R) and fentanyl 2 microg/kg (Group F) when anesthesia was induced with propofol and vecuronium. The orotracheal intubation was performed using a direct laryngoscope. Blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline values), immediately before intubation, at intubation and every minute for 5 minutes after intubation. The percent changes of systolic blood pressure (SBP) and HR relative to baseline values and the rate pressure product (RPP) at every observing point were calculated. The incidences of SBP and HR percent changes >30% of baseline values and RPP >22,000 during the observation were recorded.

RESULTSThere were no significant differences between groups in the demographic data, baseline values of BP and HR and the intubation time. As compared to baseline values, BP, HR and RPP at intubation and their maximum values during observation increased significantly in Group F, but they all decreased significantly in Group R. BP, HR and RPP at all observed points, and their maximum values during the observation, were significantly different between groups. There were also significant differences between groups in the percent change of SBP and HR relative to baseline values at all observed points and their maximum percent changes during the observation. The incidences of SBP and HR percent increased >30% of the baseline values and RPP >22,000 during the observation, were significantly higher in Group F than in Group R, but the incidences of SBP and HR percent decreased >30% of baseline values were significantly lower in Group F compared with Group R.

CONCLUSIONSWhen used as part of routine anesthesia induction with propofol and vecuronium in children, fentanyl 2 microg/kg by bolus injection fails to effectively depress the cardiovascular intubation response. Remifentanil 2 microg/kg by bolus injection can completely abolish the cardiovascular intubation response, but also cause more adverse complications of temporary significant cardiovascular depression.

Anesthetics, Intravenous ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Child ; Child, Preschool ; Double-Blind Method ; Female ; Fentanyl ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Humans ; Intubation, Intratracheal ; adverse effects ; Male ; Piperidines ; pharmacology ; 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

Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion.
Adult ; Aged ; *Analgesia, Patient-Controlled ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/*adverse ; Case-Control Studies ; Drug Therapy, Combination ; Female ; Fentanyl/administration & dosage/therapeutic use ; Humans ; Injections, Intravenous ; Ketorolac/*administration & dosage/*adverse effects/therapeutic use ; Male ; Middle Aged ; Postoperative Care/*adverse effects ; Research Support, Non-U.S. Gov't ; Retrospective Studies ; *Spinal Fusion/standards ; Treatment Outcome