Comparative study between remifentanil (or fentanyl) and dexmedetomidine for the analgesia of rhinoplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: Remifentanil (or fentanyl) and dexmedetomidine may have some potential to improve the analgesia of rhinoplasty, and this meta-analysis aims to compare their efficacy for the analgesia of rhinoplasty. METHODS: PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the analgesic effect of remifentanil (or fentanyl) versus dexmedetomidine for rhinoplasty. RESULTS: Four RCTs were finally included in the meta-analysis. In patients undergoing rhinoplasty, remifentanil (or fentanyl) infusion and dexmedetomidine infusion resulted in similar good patient satisfaction (odd ratio [OR] = 2.71; 95% confidence interval [CI] = 0.63 to 11.64; P = .18), good surgeon satisfaction (OR = 1.68; 95% CI = 0.02 to 181.40; P = .83), extubation time (mean difference [MD] = 7.56; 95% CI = -11.00 to 26.12; P = .42), recovery time (MD = -2.25; 95% CI = -23.41 to 18.91; P = .83), additional analgesic requirement (OR = 0.16; 95% CI = 0 to 8.65; P = .37) and adverse events (OR = 8.50; 95% CI = 0.47 to 153.30; P = .15). CONCLUSIONS: Remifentanil (or fentanyl) and dexmedetomidine may have comparable analgesia for patients undergoing rhinoplasty.

Fentanyl abuse proportion in methadone maintenance treatment, and patients' knowledge about its risks.

INTRODUCTION: Fentanyl is not yet routinely monitored among methadone maintenance treatment (MMT) patients in Israel. We aimed 1. to evaluate urine fentanyl proportion changes over 3 years and characterize patients' characteristics 2. To study patients' self-report on fentanyl usage, and compare knowledge about fentanyl risk, before and following brief educational intervention. METHODS: Fentanyl in the urine of all current MMT patients was tested every 3 months year between 2021 and 2023, and patients with positive urine fentanyl were characterized. Current patients were interviewed using a fentanyl knowledge questionnaire (effects, indications, and risks) before and following an explanation session. RESULTS: Proportion of fentanyl ranged between 9.8 and 15.1%, and patients with urine positive for fentanyl (September 2023) were characterized as having positive urine for pregabalin, cocaine, and benzodiazepine (logistic regression). Of the current 260 patients (87% compliance), 78(30%) self-reported of fentanyl lifetime use ("Ever"), and 182 "never" use. The "Ever" group had higher Knowledge scores than the "Never", both groups improved following the explanatory session (repeated measure). The "Ever" group patients were found with urine positive for cannabis and benzodiazepine on admission to MMT, they were younger, did not manage to gain take-home dose privileges and had a higher fentanyl knowledge score (logistic regression). CONCLUSIONS: In the absence of routine fentanyl tests, a high knowledge score, shorter duration in MMT, benzodiazepine usage on admission, and current cannabis usage, may hint of the possibility of fentanyl abuse.

Fact vs. fiction: naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids.

Opioid-induced respiratory depression (OIRD) deaths are ~80,000 a year in the US and are a major public health issue. Approximately 90% of fatal opioid-related deaths are due to synthetic opioids such as fentanyl, most of which is illicitly manufactured and distributed either on its own or as an adulterant to other drugs of abuse such as cocaine or methamphetamine. Other potent opioids such as nitazenes are also increasingly present in the illicit drug supply, and xylazine, a veterinary tranquilizer, is a prevalent additive to opioids and other drugs of abuse. Naloxone is the main treatment used to reverse OIRD and is available as nasal sprays, prefilled naloxone injection devices, and generic naloxone for injection. An overdose needs to be treated as soon as possible to avoid death, and synthetic opioids such as fentanyl are up to 50 times more potent than heroin, so the availability of new, higher-dose, 5-mg prefilled injection or 8-mg intranasal spray naloxone preparations are important additions for emergency treatment of OIRDs, especially by lay people in the community. Higher naloxone doses are expected to reverse a synthetic overdose more rapidly and the current formulations are ideal for use by untrained lay people in the community. There are potential concerns about severe withdrawal symptoms, or pulmonary edema from treatment with high-dose naloxone. However, from the perspective of first responders, the balance of risks would point to administration of naloxone at the dose required to combat the overdose where the risk of death is very high. The presence of xylazines as an adulterant complicates the treatment of OIRDs, as naloxone is probably ineffective, although it will reverse the respiratory depression due to the opioid. For these patients, hospitalization is particularly vital. Education about the benefits of naloxone remains important not only in informing people about how to treat emergency OIRDs but also how to obtain naloxone. A call to emergency services is also essential after administering naloxone because, although the patient may revive, they may overdose again later because of the short half-life of naloxone and the long-lasting potency of fentanyl and its analogs.

Melatonin attenuates fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice.

Melatonin is a neurohormone synthesized by the pineal gland to regulate the circadian rhythms and has proven to be effective in treating drug addiction and dependence. However, the effects of melatonin to modulate the drug-seeking behavior of fentanyl and its underlying molecular mechanism is elusive. This study was designed to investigate the effects of melatonin on fentanyl - induced behavioral sensitization and circadian rhythm disorders in mice. The accompanying changes in the expression of Brain and Muscle Arnt-Like (BMAL1), tyrosine hydroxylase (TH), and monoamine oxidase A (MAO-A) in relevant brain regions including the suprachiasmatic nucleus (SCN), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus (Hip) were investigated by western blot assays to dissect the mechanism by which melatonin modulates fentanyl - induced behavioral sensitization and circadian rhythm disorders. The present study suggest that fentanyl (0.05, 0.1 and 0.2 mg/kg) could induce behavioral sensitization and melatonin (30.0 mg/kg) could attenuate the behavioral sensitization and circadian rhythm disorders in mice. Fentanyl treatment reduced the expression of BMAL1 and MAO-A and increased that of TH in relevant brain regions. Furthermore, melatonin treatment could reverse the expression levels of BMAL1, MAO-A, and TH. In conclusion, our study demonstrate for the first time that melatonin has therapeutic potential for fentanyl addiction.

Lower extremity peripheral nerve block for total knee arthroplasty in a patient with chronic inflammatory demyelinating polyneuropathy: A case report.

RATIONALE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder that affects the peripheral nerves, leading to weakness and sensory symptoms. CIDP is a rare disease, and few studies have reported on anesthetic management in patients with this condition, especially the peripheral nerve block (PNB). Therefore, a safe and standardized anesthetic approach remains to be established. This case report aims to address this gap in evidence by documenting our experience with PNB in a patient with CIDP undergoing surgery. It contributes significantly to expanding the range of anesthetic options and enhancing perioperative outcomes for patients with CIDP. PATIENT CONCERNS: A 58-year-old woman diagnosed with CIDP was scheduled to undergo left total knee arthroplasty due to osteonecrosis. We anticipated postoperative pain and aggravation of neurological symptoms. DIAGNOSIS: CIDP. INTERVENTIONS: To manage the postoperative pain, we planned a combination of general anesthesia (GA) and lower extremity PNBs, viz. the tibial and femoral nerve blocks, supplemented with intravenous patient-controlled analgesia. An initial dose of fentanyl 50 µg was administered as analgesia. The tibial and femoral nerves were identified using a peripheral nerve stimulator in conjunction with an ultrasonic echo device while the patient was conscious, to minimize the risk of nerve injury. The tibial and femoral nerve blocks were performed with 20 mL of ropivacaine (0.25%) and dexamethasone 2.2 mg, respectively. Subsequently, we administered fentanyl and ketamine and initiated continuous infusion of remifentanil. Thereafter, propofol 120 mg was administered intravenously over a span of 1 minute, followed by continuous infusion at 4 mg/kg/h. Upon confirming loss of consciousness, we induced GA using a supraglottic airway device without using muscle relaxants. For postoperative analgesia, we administered acetaminophen 1000 mg. OUTCOMES: The patient experienced no pain immediately after surgery, and good analgesia was achieved subsequently without worsening of sensory symptoms during rehabilitation. LESSONS: We achieved effective anesthetic management in a patient with CIDP by combining GA with nerve stimulation and ultrasound-guided PNB. It is crucial to devise a personalized anesthesia plan that focuses on the patients' safety and comfort while minimizing risk in patients with CIDP.

Analgesic Efficacy of Epidural Patient-Controlled Analgesia on Cancer Pain: A Retrospective Observational Study.

BACKGROUND: In patients with severe cancer pain, systemic analgesics are often refractory or have limited application due to the side effects of opioids. In these cases, epidural analgesia may be effective. However, data on the effects of epidural patient-controlled analgesia (PCA) on cancer pain are limited. OBJECTIVES: To evaluate the analgesic efficacy of epidural PCA in patients with cancer pain through a retrospective chart review. STUDY DESIGN: Retrospective analysis. SETTING: A single academic center in Daegu, South Korea. METHODS: The analgesic efficacy of epidural PCA on cancer pain was analyzed in patients who underwent epidural PCA using a disposable balloon pump with a flow regulator between 2012 and 2021. The pump was filled with a 600-mL mixture of 6 ampoules of 0.2% ropivacaine, 1 mg fentanyl, and normal saline. For the first use of epidural PCA, the basal rate, bolus dose, and lockout time were set as 4 mL/h, 2 mL, and 15 min, respectively. The basal rate was increased and decreased depending on the degree of pain relief effect and occurrence of side effects, respectively. To increase the usage time of epidural PCA and reduce the patient's cost burden, the fentanyl dose was increased by 1 mg when the disposable balloon pump was replaced with a new one after exhaustion of the drug if no side effects from the previous dose were observed. Analgesic efficacy was confirmed by comparing the number of types and the total amount of opioids used in patients before and after epidural PCA application in terms of the equivalent dose of oral morphine. RESULTS: Epidural catheterization was performed 105 times, and PCA was refilled 257 times in 88 patients. On average, epidural catheterization was performed 1.2 ± 0.4 (1-3) times, and epidural PCA was refilled 3.2 ± 2.3 (1-11) times per patient. The mean duration of PCA use was 15.6 ± 13.4 (1-82) days. The mean number of opioid types used the day before the procedure and the mean smallest number of opioids used per day up to 5 days after the procedure were 3.4 ± 1.2 and 2.4 ± 1.4, respectively (P < 0.05). The total amount of opioids used the day before the procedure and the smallest total amount of opioids used per day up to 5 days after the procedure were converted into oral morphine equivalent doses, respectively, and the mean doses were 449.5 ± 555.9 and 331.9 ± 462.8 mg, respectively (P < 0.05). LIMITATIONS: The study results are the author's observations from a single center. Epidural PCA was performed only on hospitalized patients. Individual differences were not considered in the composition of drugs for PCA. Transmucosal immediate-release fentanyl was not accurately converted to oral morphine; thus, it was excluded from the analysis of the total amount used, and the effect of adjuvant analgesics could not be considered. CONCLUSION: Epidural PCA using subcutaneous tunneling is a useful cancer pain control method. Furthermore, it can be safely used for a longer duration owing to its low infection risk.

Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

Deaths From Drug Overdoses What School Nurses Need to Know.

Drug overdose deaths in pre-teen and adolescent students have risen over the past several years, causing increasing concerns in our society, along with concerns over the rise in availability of more counterfeit pills and illegally manufactured fentanyl. School nurses interface regularly with pre-teen and adolescent students and therefore are in a position to recognize students at risk for illicit drug use and provide important education to students, staff, parents, and the community. The purpose of this article is to briefly discuss risk factors for opioid misuse and to provide recommendations for interventions school nurses can use, including collaboration with other school and community leaders, to help prevent opioid overdose and death in pre-teen and adolescence.

Open-label investigation of rapid initiation of extended-release buprenorphine in patients using fentanyl and fentanyl analogs.

BACKGROUND AND OBJECTIVES: Synthetic opioids, including fentanyl and fentanyl analogs, account for over 70,000 annual overdose deaths in the United States, but there is limited information examining methods of induction and maintenance outcomes for buprenorphine treatment of patients with opioid use disorder (OUD) using these opioids. METHODS: A secondary analysis of results grouped by fentanyl use status was completed for an open-label study with rapid induction of extended-release buprenorphine in the inpatient research unit. Eligible participants received a single 4 mg dose of transmucosal buprenorphine (BUP-TM) followed by an extended-release buprenorphine 300 mg injection ([BUP-XR]) after approximately 1 h. An extension study continued follow-up up to 6 months (6 monthly injections). RESULTS: Among participants with fentanyl-positive urine samples (FEN+; n = 19), all received BUP-TM, 17 received BUP-XR, 13 elected to receive a second BUP-XR injection, and 10 received all six scheduled injections. Among participants with fentanyl-negative samples (FEN-; n = 7), all received BUP-TM and BUP-XR, four elected to receive a second injection, and two participants received all six scheduled injections. Induction day clinical opioid withdrawal scale (COWS) scores were similar for FEN+ and FEN- groups. In the FEN+ group, mean COWS scores fell to below 5 within 24 h of BUP-XR injection. DISCUSSION AND CONCLUSIONS: The treatment of individuals with OUD using fentanyl with a rapid 1-day induction to BUP-XR 300 mg injection is feasible and well-tolerated. SCIENTIFIC SIGNIFICANCE: A prospective trial of participants grouped by fentanyl use status at induction demonstrates comparable patient retention and clinical response following single-day induction of BUP-XR in participants who are FEN+ and FEN-.

Finding predictors for successful opioid response in cancer patients: An analysis of data from four randomized controlled trials.

CONTEXT: There is no consensus on which "strong" (or step 3 WHO analgesic ladder) opioid to prescribe to a particular patient with cancer-related pain. A better understanding of opioid and patient characteristics on treatment response will contribute to a more personalized opioid treatment. OBJECTIVES: Assessment of potential predictors for successful opioid treatment response in patients with cancer pain. METHODS: An international partnership between four cancer pain research groups resulted in a combined individual-level database from four relevant randomized controlled trials (RCTs; n = 881). Together, these RCTs investigated the short-term (1 week) and medium-term (4 or 5 weeks) treatment responses for morphine, buprenorphine, methadone, oxycodone, and fentanyl. Candidate predictors for treatment response were sex, age, pain type, pain duration, depression, anxiety, Karnofsky performance score, opioid type, and use of anti-neuropathic drug. RESULTS: Opioid type and pain type were found statistically significant predictors of short-term treatment success. Sex, age, pain type, anxiety, and opioid type were statistically, significantly associated with medium-term treatment success. However, these models showed low discriminative power. CONCLUSION: Fentanyl and methadone, and mixed pain were found to be statistically significant predictors of treatment success in patients with cancer-related pain. With the predictors currently assessed our data did not allow for the creation of a clinical prediction model with good discriminative power. Additional - unrevealed - predictors are necessary to develop a future prediction model.

A randomized controlled trial of propofol-remifentanil total intravenous anesthesia and sevoflurane-fentanyl anesthesia on early postoperative fatigue in patients undergoing laparoscopic colorectal surgery.

PURPOSE: Even after uncomplicated surgery, postoperative fatigue prevalence has been reported to be 30-80% for various surgeries. We evaluated postoperative fatigue according to anesthetic technique in patients who underwent colorectal surgery. METHODS: One hundred thirty patients who underwent colorectal surgery were randomly assigned to either propofol-remifentanil total intravenous anesthesia (propofol-remifentanil group, n = 65) or sevoflurane-fentanyl anesthesia (sevoflurane-fentanyl group, n = 65). The primary outcome was the prevalence of postoperative fatigue, as defined by the Chalder Fatigue Questionnaire (total score ≥ 16), at 24 h postoperatively. Secondary outcomes were early postoperative complications during hospitalization and laboratory examination. RESULTS: The final analyses included 127 patients. The prevalence of postoperative fatigue on the 1st postoperative day was lower in the propofol-remifentanil group than the sevoflurane-fentanyl group: 56.3% (36/64) in the propofol-remifentanil group and 73.0% (46/63) in the sevoflurane-fentanyl group (relative risk [RR] = 0.77, 95% confidence interval [CI] 0.59-1.00; P = 0.048). However, there was no difference between the two groups in postoperative fatigue at postoperative day 3. Other postoperative outcomes including the severity of pain and the incidence of nausea/vomiting were not different between the two groups, but postoperative atelectasis on chest X-ray was higher in the sevoflurane-fentanyl group (2/64 [3.1%] vs. 9/63 [14.3%], P = 0.025). C-reactive protein change from preoperative to postoperative day 1 and 5 was significantly lower in the propofol-remifentanil group (P = 0.044). CONCLUSION: Propofol-remifentanil total intravenous anesthesia was associated with reduced postoperative fatigue at the 1st postoperative day compared with sevoflurane-fentanyl anesthesia. Clinical trial The Korean Clinical Research Registry (study identifier: KCT0006917, principal investigator's name: MiHye Park, date of registration: January 12, 2022).

Comparison of the Effects of OPRM1 A118G Polymorphism Using Different Opioids: A Prospective Study.

CONTEXT: µ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of µ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited. OBJECTIVE: To compare the impact of A118G polymorphism on the efficacy of various opioids. METHODS: This prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups. RESULTS: Overall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001). CONCLUSION: Tapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.

Opioid Use Disorder, Adolescents, and the Importance of Treatment in the Emergency Department.

ABSTRACT: Deaths from opiate overdoses are climbing every year, especially from fentanyl. Adolescents are particularly vulnerable to the acute and chronic harms associated with drug use, addiction, and overdose. Providers in the acute care setting have a unique opportunity to address a population of adolescents with opioid use disorder who are at the highest risk of harm and who may be more receptive to help. It is critical that providers are familiar with the tools that are available to assist and have some facility with their application.

Safety and efficacy of remimazolam tosilate combined with low-dose fentanyl for procedural sedation in obese patients undergoing gastroscopy: study protocol for a single-centre, double-blind, randomised controlled trial.

INTRODUCTION: Obese patients are susceptible to hypoxaemia during procedural sedation. Propofol combined with low-dose opioids is commonly used as a sedation strategy, but it can exacerbate hypoxaemia by causing cardiopulmonary depression and airway obstruction, especially in obese patients. Remimazolam, a novel ultra-short-acting benzodiazepine, has minimal accumulative effects and less cardiorespiratory depression. This study aims to evaluate the safety and efficacy of combining remimazolam tosilate with low-dose fentanyl as an alternative option for procedural sedation in obese patients undergoing gastroscopy. METHODS AND ANALYSIS: This randomised controlled trial (RCT) will be conducted in the Endoscopy Centre of the First Affiliated Hospital of Xiamen University, recruiting 174 participants scheduled for painless gastroscopy with a body mass index of 30-39.9 kg×m-2. All patients will be randomly divided into two groups in a 1:1 ratio. The sedation strategy of the intervention group is remimazolam tosilate combined with fentanyl, while the control group is propofol combined with fentanyl. The primary outcome is the incidence of hypoxaemia and the secondary outcomes include the time to ambulation, need for airway manoeuvres and rescue sedation, sleep quality, the incidence of sedation failure, adverse events and the cost of sedatives. All statistical tests will be performed using IBM SPSS V.20.0 statistical software. A p value<0.05 is considered statistically significant. ETHICS AND DISSEMINATION: This RCT was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Xiamen University (Scientific Research Ethics Review 2022, No.093). The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2200067076.

Low-dose buprenorphine initiation in the era of fentanyl and fentanyl analogs: A case series of outpatient inductions.

Buprenorphine, a partial opioid agonist, is a Food and Drug Administration-approved medication for the treatment of opioid use disorder (OUD). However, due to its high binding affinity, precipitated withdrawal may occur if initiated in the presence of other opioids. The growing literature demonstrates promise for alternative induction model of low-dose initiation of buprenorphine for the treatment of OUD, specifically targeting patients averse to withdrawal or using fentanyl. In this case series, we present four clinical cases of outpatient inductions, in which three out of four successfully transitioned from fentanyl to buprenorphine, and one patient transitioned from methadone to buprenorphine using a low-dose induction method.

Intravenous acetaminophen for postoperative pain in the neonatal intensive care unit: A protocol for a pilot randomized controlled trial (IVA POP).

BACKGROUND: In neonates, uncontrolled pain and opioid exposure are both correlated with short- and long-term adverse events. Therefore, managing pain using opioid-sparing approaches is critical in neonatal populations. Multimodal pain control offers the opportunity to manage pain while reducing short- and long-term opioid-related adverse events. Intravenous (IV) acetaminophen may represent an appropriate adjunct to opioid-based postoperative pain control regimes. However, no trials assess this drug in patients less than 36 weeks post-conceptual age or weighing less than 1500 g. OBJECTIVE: The proposed study aims to determine the feasibility of conducting a randomized control trial to compare IV acetaminophen and fentanyl to a saline placebo and fentanyl for patients admitted to the neonatal intensive care unit (NICU) undergoing major abdominal or thoracic surgery. METHODS AND DESIGN: This protocol is for a single-centre, external pilot randomized controlled trial (RCT). Infants in the NICU who have undergone major thoracic or abdominal surgery will be enrolled. Sixty participants will undergo 1:1 randomization to receive intravenous acetaminophen and fentanyl or saline placebo and fentanyl. After surgery, IV acetaminophen or placebo will be given routinely for eight days (192 hours). Appropriate dosing will be determined based on the participant's gestational age. Patients will be followed for eight days after surgery and will undergo a chart review at 90 days. Primarily feasibility outcomes include recruitment rate, follow-up rate, compliance, and blinding index. Secondary clinical outcomes will be collected as well. CONCLUSION: This external pilot RCT will assess the feasibility of performing a multicenter RCT comparing IV acetaminophen and fentanyl to a saline placebo and fentanyl in NICU patients following major abdominal and thoracic surgery. The results will inform the design of a multicenter RCT, which will have the appropriate power to determine the efficacy of this treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05678244, Registered December 6, 2022.

The United States opioid crisis: Big pharma alone is not to blame."

OBJECTIVE: The opioid crisis in the United States continues essentially unabated, fueled by fentanyl contamination of the heroin supply and resulting in 79,770 reported opioid-involved overdose deaths in the calendar year 2022. To prevent another such crisis emerging, it is necessary to fully identify its root causes. METHODS: Despite the well-recognized role the pharmaceutical industry played in facilitating the crisis via the aggressive marketing of prescription opioids, several other less appreciated but perhaps more influential factors were also contributors, and the overall goal of this review is to ensure that these are not be lost to history in a concerted effort to blame opioid manufacturers and distributors. Presented is a historical review of research and regulatory documents beginning with the loosening of opioid prescription for chronic pain through current thought and practice today. Beginning with a necessary decoupling of the current opioid crisis from the increased use of opioids to treat chronic pain, this review will examine these contributing factors. RESULTS: Clinical concerns about under- or untreated pain, practice guidelines from standard-setting organizations and government entities, and a health system-wide move away from specialty interdisciplinary pain programs together set the stage for an over-reliance on opioids in chronic pain care. CONCLUSIONS: This review reminds the health care community that despite the deep pockets of the pharmaceutical industry and highly the organized efforts of the drug cartels, additional self-reflection is warranted to fully understand the true root causes of the current epidemic and ways to prevent similar epidemics in the future.

[Electrophysiological appropriateness technique based on TCM meridian theory for postoperative pain after urethral reconstruction: A real-world study].

OBJECTIVE: To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery. METHODS: Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients. RESULTS: The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls. CONCLUSION: Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.

"Safer Drug Supply" Measures in Canada to Reduce the Drug Overdose Fatality Toll: Clarifying Concepts, Practices and Evidence Within a Public Health Intervention Framework.

North America has been home to an unprecedented crisis of drug overdose deaths, driven largely by drug users' exposure to highly potent and toxic, illicit opioid drugs (e.g., fentanyl). Although a large and diverse menu of interventions (e.g., targeted prevention or treatment measures) has been implemented or expanded in Canada, these have not effectively managed to revert and reduce this excessive death toll. Given the fact that these interventions do not directly aim to address toxic drug exposure as the primary vector and cause of acute overdose deaths, public health-oriented "safer drug supply" measures have been initiated in local settings across Canada. These safer supply initiatives provide users with prescribed, pharmaceutical-grade drug supply with the aim of reducing overdose and death risks. These measures have been criticized but also misconstrued from several angles, e.g., as representing inadequate medical or even unethical and harmful practice. Related concerns regarding "diversion" have been raised. In this Perspective, we briefly address some of these issues and clarify selected issues of elementary concepts, practices, and evidence related to safer supply measures within a public health-oriented intervention framework. These measures are also discussed in reference to other, comparable types of public health-oriented emergency health or survival care standards, while considering the extreme contexts of an ongoing, acute drug death crisis in Canada.

The efficacy of intradermal sterile water application in severe renal colic: a randomised clinical trial.

It is important to do a fast and effective treatment for patients with renal colic pain in emergency departments for both patients' comfort and clinicians' patient management. In this study, we aimed primarily to test the efficacy of intradermal sterile water application as a rapid and effective treatment in severe renal colic. This is a single-centre, prospective, randomised controlled trial. Study group consists of patients with severe renal colic related to urolithiasis. Patients were randomly divided into three groups. The first group received only intramuscular diclofenac sodium, the second group received intramuscular diclofenac sodium and intradermal sterile water, and the third group received intramuscular diclofenac sodium together with intravenous fentanyl. Numerical Rating Scale was used to determine the level of pain before and after the treatment at the 1st, 5th, 15th, 30th, 60th and 120th minutes. 95 out of 201 patients with severe renal colic pain randomly divided into 3 groups. The pre-treatment pain severity of the groups was similar (p = 0.228). We found that the decrease in pain intensity was significantly faster in the intradermal sterile water group than the other groups even in the first minute. Percentages of patients who had 50% pain reduction, which is considered as successful treatment, was higher in the intradermal sterile water group (which had 75.9% success rate) in the first 5 min compared to the IM diclofenac sodium group (which had 7.1% success rate) and IV fentanyl group (which had 25% success rate) (p < 0.001). According to the results, pain control was achieved much faster than the other methods with intradermal sterile water injection. All methods were found to be effective in relieving the pain of the patients.