Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

Bloqueo en el plano del músculo erector de la columna frente a anestesia local infiltrativa para discectomía endoscópica percutánea transforaminal: ensayo controlado aleatorizado prospectivo / Erector spine plane block versus local infiltration anaesthesia for transforaminal percutaneous endoscopic discectomy: Prospective randomise controlled trial

Antecedentes: Casi el 60-80% de la población padece de dolor de espalda, lo cual convierte a esta situación en una de las causas más comunes de consulta. Uno de los tratamientos más efectivos para el dolor lumbar es la discectomía endoscópica percutánea transforaminal, que requiere diferentes opciones anestésicas. Nuestro objetivo primario fue probar la hipótesis de si el bloqueo en el plano del músculo erector de la columna (ESP) bilateral con sedación es similar a la infiltración tradicional local de anestésico con sedación. Materiales y métodos: Se asignó aleatoriamente a cincuenta y dos pacientes sometidos a discectomía endoscópica percutánea transforaminal a dos grupos: el G1 recibió sedación intravenosa con anestesia local infiltrativa; G2 recibió sedación intravenosa con ESP bilateral. Resultado primario: cantidad de fentanilo y propofol durante la cirugía. Resultados secundarios: episodios adversos durante la sedación utilizando la herramienta de reporte sobre episodios adversos de la sedación de la Society of Intravenous Anaesthesia (SIVA), nivel de sedación postoperatoria utilizando la escala Richmond Agitation-Sedation Scale (RASS), intensidad del dolor tras la cirugía utilizando la escala visual analógica (EVA), umbral del dolor mecánico (MPT) utilizando microfilamentos de von Frey, medido en ambas extremidades inferiores, y satisfacción con la analgesia aplicando la escala Likert de 5 puntos. Resultados: La cantidad de fentanilo, propofol y el nivel de sedación postoperatoria fueron significativamente menores en G2 (p<0,001). No se produjo diferencia en cuanto a intensidad del dolor, satisfacción con la analgesia y umbral del dolor mecánico tras la cirugía en ambos grupos. No se produjeron episodios adversos en el grupo G2 en comparación con G1 (2 pacientes descriptores del riesgo mínimo, 5 descriptores del riesgo menor y 1 descriptor del riesgo centinela) que requirieron medicación adicional o ventilación de rescate...(AU)

Background: About 60% to 80% of the population suffers from back pain, making it one of the most common health complaints. One of an effective treatments of low back pain is transforaminal percutaneous endoscopic discectomy (TPED) which requires different options for anaesthesia. Our primary objective was to test the hypothesis if the bilateral erector spine plane block (ESP) with sedation is similar to traditional infiltrative local anaesthesia with sedation. Materials and methods: Fifty-two patients that underwent TPED were randomly assigned in two groups: G1 received intravenous sedation with infiltrative local anaesthesia; G2 received intravenous sedation with bilateral ESP. Primary outcome: amount of fentanyl and propofol during surgery. Secondary outcomes: adverse events during sedation employing World Society of Intravenous Anaesthesia (SIVA) adverse sedation event reporting tool, level of postoperative sedation with Richmond Agitation-Sedation Scale (RASS), intensity of pain after surgery engaging a visual analogue scale (EVA), the mechanical pain threshold (MPT) with von Frey monofilaments measured on both lower extremities, satisfaction with analgesia applying 5-point Likert scale. Results: Amount of fentanyl, propofol and level of postoperative sedation was significantly lower in G2 (p<0.001). There was no difference in intensity of pain, satisfaction with analgesia, and the mechanical pain threshold after surgery in both groups. There were no adverse events in G2 group in contradistinction to G1 (2 patients minimal risk descriptors, 5 minor risk descriptors and 1 sentinel risk descriptors) which required additional medication or rescue ventilation...(AU)

Perceptions of fentanyl among African Americans who misuse opioids: implications for risk reduction.

BACKGROUND: Fentanyl is a powerful synthetic opioid that is 50 times more powerful than heroin and has become ubiquitous in the illicit drug supply in the USA. Studies show that among people who use drugs, fentanyl is sometimes viewed as a desirable substance due to its high potency and low cost, while others have an unfavorable perception because of its association with overdose. Unfortunately, studies on the perceptions of fentanyl are relatively rare and existing studies tend to rely on samples with little African American representation. The objective of this study, therefore, was to identify and describe perceptions of fentanyl among African Americans who misuse opioids, while capturing their motivations for seeking out or avoiding fentanyl. METHODS: In-depth interviews (n = 30) were conducted with a sample of African American adults who misuse opioids in Southwest Florida between August 2021 and February 2022. Audiotapes of interviews were transcribed, coded, and thematically analyzed. RESULTS: Analyses revealed the presence of three subtypes of fentanyl-related perceptions: (1) fentanyl as an avoided adulterant, (2) fentanyl as a tolerated adulterant, and (3) fentanyl as a drug of choice. CONCLUSIONS: These findings show that African Americans' perceptions of fentanyl are not monolithic and suggest the distribution of fentanyl test strips and naloxone may be an effective risk reduction strategy. Given that most studies on fentanyl rely on quantitative data from drug seizures and death certificates, this study uniquely contributes to the literature by capturing the voices of African Americans who use drugs.

Continuous fentanyl administration and spontaneous withdrawal decreases home cage wheel running in rats with and without hindpaw inflammation.

Fentanyl is a potent analgesic with a rapid onset and short half-life that make it a useful treatment for pain and a lethal drug of abuse. The present study used voluntary home cage wheel running to assess the effect of hindpaw inflammation, fentanyl administration, and spontaneous fentanyl withdrawal. Fentanyl (0.32 or 1.0 mg/kg/day) or placebo osmotic pumps were implanted subcutaneously and rats received an intraplantar injection of Complete Freund's Adjuvant (CFA) or saline. Rats with hindpaw inflammation caused by CFA administration were less active than rats injected with saline into the hindpaw. The antinociceptive effect of 0.32 mg/kg/day of fentanyl was evident as a recovery of wheel running in these rats. Administration of 1 mg/kg/day of fentanyl almost completely inhibited wheel running during the first day in rats with and without hindpaw inflammation. Wheel running increased each subsequent day until the pumps were surgically removed after day 3. Withdrawal from 0.32 or 1 mg/kg/day of fentanyl caused a decrease in wheel running that lasted 2 days in rats without hindpaw inflammation. In contrast, withdrawal was only evident following termination of 1 mg/kg/day of fentanyl in rats with hindpaw inflammation. This decrease in running seemed to persist beyond the 3 days of assessment. These data demonstrate that fentanyl can either depress or restore activity depending on the dose and pain condition. Moreover, termination of 3 days of continuous fentanyl administration resulted in a dose and time dependent decrease in wheel running consistent with opioid withdrawal.

Put It in the Air? Nebulized Opioids in the Emergency Department.

The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners.

The motives and methods of methamphetamine and 'heroin' co-use in West Virginia.

BACKGROUND: Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose death rates since at least 2013 and rising co-use of methamphetamine with opioids has played a greater role in deaths over the last 5 years. METHODS: This study used rapid ethnography to examine methods and motivations behind opioids and methamphetamine co-use from the viewpoint of their consumers. Participants (n = 30) were people who injected heroin/fentanyl also using methamphetamine who participated in semi-structured interviews. RESULTS: We found multiple methods of co-using opioids and methamphetamine, whether alternately or simultaneously and in varying order. Most prioritized opioids, with motives for using methamphetamine forming three thematic categories: 'intrinsic use', encompassing both inherent pleasure of combined use greater than using both drugs separately or for self-medication of particular conditions; 'opioid assisting use' in which methamphetamine helped people manage their existing heroin/fentanyl use; and 'reluctant or indifferent use' for social participation, reflecting methamphetamine's low cost and easy availability. CONCLUSIONS: Methamphetamine serves multiple functions among people using opioids in WV. Beliefs persist that methamphetamine can play a role in preventing and reversing opioid overdose, including some arguments for sequential use being protective of overdose. 'Reluctant' uptake attests to methamphetamine's social use and the influence of supply. The impact on overdose risk of the many varied co-use patterns needs further investigation.

Efficacy of reconstituted intravenous fentanyl to sublingual solution versus oral morphine syrup for breakthrough pain among patients with chronic gynecologic cancer pain: A randomized, double-blind, placebo-controlled trial.

Rapid-acting fentanyl formulations are superior to oral morphine (OM) syrup in controlling breakthrough pain among patients with cancer, but they are expensive and unavailable in many countries. OBJECTIVE: To evaluate the efficacy of reconstituted intravenous fentanyl to sublingual solution (IFS) in relieving breakthrough pain as compared with OM. METHODS: In this randomized, double-blind, double-dummy, placebo-controlled trial, patients with gynecologic cancer aged ≥18 years experiencing chronic cancer pain with breakthrough pain were enrolled. Patients were randomly allocated (1:1) to receive either 50 µg IFS or 5 mg OM. Pain intensity level was assessed at 5, 15, 30, 45, 60, and 120 min after treatment. The primary outcome was the reduction in pain intensity at 15 min in the intention-to-treat population (ClinicalTrials.gov, NCT05037539). RESULTS: Between June 15, 2021 and December 30, 2021, 40 participants were equally and randomly assigned to receive IFS or OM. The primary outcome was significantly higher in the IFS group (4.25 vs. 1.05, p < 0.0001). The secondary outcomes also showed higher reduction in pain intensity at 5 min in the IFS group. Subsequent breakthrough pain did not differ between the two groups. However, the reduction in pain was lower in the IFS group at 45, 60, and 120 min, where pain was classified as mild. No severe adverse effects were observed in both groups. Burning sensation without noticeable lesion was found in 20% of the IFS group. CONCLUSION: IFS can reduce early breakthrough pain. IFS may be considered for breakthrough pain when rapid-acting fentanyl formulations are unavailable.

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

There is comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD), perhaps because PTSD-like stressful experiences early in life alter the hypothalamic-pituitary-adrenal stress axis to increase the risk for OUD. The present study determined if the glucocorticoid receptor antagonist PT150 reduces the escalation of fentanyl intake in rats exposed to a "two-hit" model of early-life stress (isolation rearing and acute stress). Male and female rats were raised during adolescence in either isolated or social housing and then were given either a single acute stress (restraint and cold-water swim) or control treatment in young adulthood. Rats were then treated daily with PT150 (50 mg/kg, oral) or placebo and were tested for acquisition of fentanyl self-administration in 1-hr sessions, followed by escalation across 6-hr sessions. Regardless of PT150 treatment or sex, acquisition of fentanyl self-administration in 1-hr sessions was greater in isolate-housed rats compared to social-housed rats; the acute stress manipulation did not have an effect on self-administration even though it transiently increased plasma corticosterone levels. During the 6-hr sessions, escalation of fentanyl was observed across all treatment groups; however, there was a significant PT150 Treatment × Sex interaction. While males self-administered more than females overall, PT150 decreased intake in males and increased intake in females, thus negating the sex difference. Although PT150 may serve as an effective treatment for reducing the risk of OUD following early-life stress in males, further work is needed to determine the mechanism underlying the differential effects of PT150 in males and females. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Perfil de pacientes grandes consumidores de fentanilo de liberación rápida en un área sanitaria de Córdoba / Profile of patients with abusive consumption of quick-release fentanyl in a health area of Cordoba

Objetivo: Describir el tipo de pacientes que superan la dosis diaria definida (DDD) de fentanilo de liberación inmediata en un área sanitaria.Material y métodos: Estudio observacional, descriptivo, realizado en un área sanitaria de 256.807 habitantes en el que se incluyeron todos los pacientes que superaban la DDD de fentanilo de liberación inmediata en diciembre de 2019.Resultados: Se detectaron 29 pacientes, 58,6% mujeres, con una mediana de edad de 59 (31-87) años, que superaban una media de 3 (1,1-10) veces la DDD de fentanilo de liberación inmediata, en sus distintas presentaciones, siendo la indicación en el 69% de los casos dolor crónico no oncológico (DCNO). La mayoría de los pacientes tomaba benzodiacepinas (79,3%) y el mayor porcentaje de primeras prescripciones de fentanilo de liberación rápida procedía de atención primaria (38%).Conclusiones: En nuestro estudio el uso inadecuado o posible abuso de fentanilo de liberación inmediata se da en mayor proporción en pacientes con DCNO, y en la mayoría de los casos la primera prescripción se realizó en atención primaria. No observamos relación clara con patología psiquiátrica ni otras adicciones. (AU)

Objective: To describe the type of patients that exceed the defined daily dose (DDD) of immediate-release fentanyl in a health area.Material and methods: Observational, descriptive study, carried out in a health area of ​​256,807 inhabitants, which included all patients who passed the immediate-release fentanyl DDD in December 2019.Results: 29 patients were detected, 58.6% female, with a median age of 59 (31-87) years, who exceeded an average of 3 (1.1-10) times the immediate-release fentanyl DDD, in its different presentations, being the indication in 69% of cases chronic non-cancer pain (CNCP). The majority of patients took benzodiazepines (79.3%) and the highest percentage of first-prescriptions for inmediate-release fentanyl came from primary care (38%).Conclusions: In our study, the inappropriate use or possible abuse of immediate-release fentanyl occurs in a greater proportion in patients with CNCP, and in most cases the first prescription was made in primary care. We did not observe a clear relationship with psychiatric pathology or other addictions. (AU)

Intraoperative Neuromonitoring for Spinal Surgery in a Pregnant Patient: Case Report and Literature Review.

We report the strategy of anesthesia and intraoperative neurophysiological monitoring (IONM) in a 29-year-old, 22 weeks pregnant patient posted for surgery for aggressive vertebral body hemangioma. We used propofol and fentanyl-based anesthesia for IONM. Motor-evoked potentials (MEP) and somatosensory-evoked potentials (SSEP) were used to monitor the neural tracts during surgery. Fetal heart rate monitoring was done preoperatively and postoperatively. Train of 8, 75 µs duration pulse, 250-500 Hz stimulus was used for MEP and 30 mA, 200-400 µs, 3-5 Hz was used for SSEP. No new motor or somatosensory deficits appeared. Our findings suggest that IONM can be safely done in pregnant women.

Nebulized fentanyl for respiratory symptoms in patients with COVID-19 (ventanyl trial).

ABSTRACT: Patients with coronavirus disease (COVID-19) commonly experience distressing and challenging respiratory symptoms. Interventions such as oxygen therapy, oral opiates, and traditional nebulizers like ipratropium bromide and salbutamol are variable in their efficacy, and therapy responses in patients are difficult to predict. The purpose of this study is to investigate the efficacy of nebulized fentanyl citrate on dyspnea, cough, and throat pain in patients with COVID-19 and evaluate the safety with any potential adverse events.In COVID-19, about 59% of patients will exhibit cough, 35% generalized body ache and sore throat, and 31% dyspnea. Some methods such as nebulized lidocaine, magnesium sulfate, and systemic opioids have been used to manage the respiratory symptoms. It has been previously shown that fentanyl nebulizer has beneficial effect in improving shortness of breath in patients with chronic obstructive pulmonary disease. The proposed theory behind that was that fentanyl decreased the rate of spontaneous respiratory rate, diminished the brain stem chemoreceptor response to hypoxia and hypercarbia, in addition to exhibiting a modulating effect on the brain stem. Therefore, we hypothesize that nebulized fentanyl has superior effect in improving shortness of breath and relieving cough compared to normal saline, in addition to its advantageous throat pain relief, while exhibiting fewer side effects in patients with COVID 19 infection. Therefore, this phase-III, randomized, comparative, parallel assignment, single-blinded clinical trial aims at assessing the efficacy and safety of nebulized fentanyl to suppress cough, improve breathlessness, and relieve throat pain in patients with COVID-19.

Association between fentanyl treatment for acute pain in the emergency department and opioid use two weeks after discharge.

BACKGROUND: Analgesia with fentanyl can be associated with hyperalgesia (higher sensitivity to pain) and can contribute to escalating opioid use. Our objective was to assess the relationship between emergency department (ED) acute pain management with fentanyl compared to other opioids, and the quantity of opioids consumed two-week after discharge. We hypothesized that the quantity of opioids consumed would be higher for patients treated with fentanyl compared to those treated with other opioids. METHODS: Patients were selected from two prospective cohorts assessing opioids consumed after ED discharge. Patients ≥18 years treated with an opioid in the ED for an acute pain condition (≤2 weeks) and discharged with an opioid prescription were included. Patients completed a 14-day paper or electronic diary of pain medication use. Quantity of 5 mg morphine equivalent tablets consumed during a 14-day follow-up by patients treated with fentanyl compared to those treated with other opioids during their ED stay were analyzed using a multiple linear regression and propensity scores. RESULTS: We included 707 patients (mean age ± SD: 50 ± 15 years, 47% women) in this study. During follow-up, patients treated with fentanyl (N = 91) during their ED stay consumed a median (IQR) of 5.8 (14) 5 mg morphine equivalent pills compared to 7.0 (14) for those treated with other opioids (p = 0.05). Results were similar using propensity score sensitivity analysis. However, after adjusting for confounding variables, ED fentanyl treatment showed a trend, but not a statistically significant association with a decreased opioid consumption during the 14-day follow-up (B = -2.4; 95%CI = -5.3 to 0.4; p = 0.09). CONCLUSIONS: Patients treated with fentanyl during ED stay did not consume more opioids after ED discharge, compared to those treated with other opioids. If fentanyl does cause more hyperalgesia compared to other opioids, it does not seem to have a significant impact on opioid consumption after ED discharge.

Fentanyl transdermal patches: Extraction and evaluation of a novel disposal method using NarcX®.

Currently, there is no known commercially available product for disposing of used fentanyl transdermal patches. To eliminate the potential for harm and abuse, a proper disposal method is needed-one that neutralizes the dangerous amount of residual fentanyl that remains after therapeutic use of the fentanyl patch. The patent-pending liquid solution of activated carbon, known as NarcX® , was investigated as a potential fentanyl adsorbing agent. In order to determine the amount of fentanyl remaining after a patch is treated with NarcX® , here, we utilized hexanes to first dissolve the patch adhesive and then followed with liquid-liquid extraction with methanol to recover the fentanyl. Using liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS), the extracts obtained with this method yielded between 85% and 117% recovery of fentanyl from new and unused patches. Further optimization of this method allowed for a quantitative evaluation of NarcX® -treated fentanyl patches. 100 µg/h Apotex brand fentanyl patches were exposed to NarcX® for 1, 24, 48, and 72 h. NarcX® was shown to adsorb fentanyl from the patches with varying degrees of success, demonstrating an average of 66.98 ± 0.75% fentanyl adsorption after 72 h. These findings suggest that more work is needed to successfully neutralize the fentanyl patches in their entirety using NarcX® ; however, this work does demonstrate proof of concept.

Low-dose fentanyl reduces pain perception, muscle sympathetic nerve activity responses, and blood pressure responses during the cold pressor test.

Our knowledge about how low-dose (analgesic) fentanyl affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose fentanyl influences human autonomic cardiovascular responses during painful stimuli in humans. Therefore, we tested the hypothesis that low-dose fentanyl reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-three adults (10 females/13 males; 27 ± 7 yr; 26 ± 3 kg·m-2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and 5 min after drug/placebo administration (75 µg fentanyl or saline). We compared pain perception (100-mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography, 11 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo timepoints) using paired, two-tailed t tests. Before drug/placebo administration, perceived pain (P = 0.8287), ΔMSNA burst frequency (P = 0.7587), and Δmean BP (P = 0.8649) during the CPT were not different between trials. After the drug/placebo administration, fentanyl attenuated perceived pain (36 vs. 66 mm, P < 0.0001), ΔMSNA burst frequency (9 vs. 17 bursts/min, P = 0.0054), and Δmean BP (7 vs. 13 mmHg, P = 0.0174) during the CPT compared with placebo. Fentanyl-induced reductions in pain perception and Δmean BP were moderately related (r = 0.40, P = 0.0641). These data provide valuable information regarding how low-dose fentanyl reduces autonomic cardiovascular responses during an experimental painful stimulus.

Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia.

Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.

Transmuscular quadratus lumborum block for postoperative pain and recovery after laparoscopic adrenalectomy: a randomized controlled trial.

BACKGROUND: To investigate the role of transmuscular quadratus lumborum block (TMQLB) for postoperative pain control, patient satisfaction and recovery in laparoscopic adrenalectomy. METHODS: Seventy-two patients aged between 18 and 70 years with an ASA I-II and scheduled for laparoscopic adrenalectomy were randomized to receive a single-shot TMQLB with 0.4 ml/kg 0.5 % ropivacaine or 0.4 ml/kg 0.9 % saline as placebo. The primary endpoint was pain on movement at 12 h after surgery evaluated by the numeric rating scale (NRS, 0-10). P-values < 0.05 was considered statistically significant. The secondary outcomes included pain at rest and pain on movement evaluated by the NRS, and postoperative recovery related parameters. RESULTS: NRS on movement at 12 h after surgery was lower in the TMQLB group compared with the control (median 2 vs. 3, p = 0.024). Intraoperative fentanyl consumption was lower in the TMQLB group (247.08 ± 63.54 vs. 285.44 ± 74.70, p = 0.022). The rate of using postoperative rescue tramadol was also lower in the TMQLB group (5.6 vs. 27.8 %, p = 0.027). Similar incidences of nausea and vomiting were observed (11.1 vs. 25 %, p = 0.220). Patient satisfaction of pain service was better in the TMQLB group (83.3 vs. 25 %, p < 0.001) with shorter time to ambulation (16.5 vs. 21 h, p = 0.004) and flatus (18.5 vs. 23.5 h, p = 0.006). CONCLUSIONS: TMQLB showed better control of postoperative pain on movement for laparoscopic adrenalectomy with improved patients' satisfaction of anesthesia, shorter time to ambulation and flatus. TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov ( NCT03942237 ; registration date: 08/05/2019; enrollment date: 10/05/2019).

The association between intrapartum opioid fentanyl and early breastfeeding: A prospective observational study.

INTRODUCTION: Intrapartum opioids in labor may interfere with the early breastfeeding phase and cause breastfeeding difficulties. This study examines the effects of intrapartum fentanyl given intravenously (IV) or through epidural analgesia (EDA) on early breastfeeding. MATERIAL AND METHODS: This is a prospective observational study conducted in a regional maternity unit. We included 1101 healthy mothers of term singleton babies in vertex presentation born between 2016 and 2018 (468 nulliparous and 633 multiparous). The main data were collected prospectively, and additional data were retrieved from hospital records. The main outcome measures were exclusive breastfeeding at discharge, spontaneous suckling, and breastfeeding problems after birth. We assessed the outcomes in four groups categorized by intrapartum opioid exposure: none, IV fentanyl, EDA fentanyl and IV+EDA fentanyl. We also analyzed the dose-response relation of fentanyl administered by epidural or IV and early breastfeeding. Ultimately, we dichotomized the IV fentanyl group into two groups (≤200 µg and >200 µg) to further study the effect on early breastfeeding. RESULTS: The odds of non-exclusive breastfeeding were doubled with EDA fentanyl (odds ratio [OR] 2.45, 95% CI 1.34-4.48, p = 0.004) and four times higher with IV+EDA fentanyl (OR 4.20, 95% CI 2.49-7.09, p < 0.001) compared with no opioid exposure. Spontaneous suckling was negatively associated with intrapartum fentanyl use (p < 0.001) irrespective of mode of administration. When the IV fentanyl doses exceeded 200 µg compared with less than 200 µg, we found a reduction in exclusive breastfeeding (81% vs. 89%; p = 0.014) and spontaneous suckling (68% vs. 83%; p < 0.001) and an increase in breastfeeding problems (41% vs. 27%; p = 0.004). CONCLUSIONS: Fentanyl in labor is associated with breastfeeding difficulties. However, IV fentanyl in low doses (≤200 µg) seems to affect breastfeeding less than EDA fentanyl and is therefore a viable alternative when labor analgesia is needed. This could be most relevant for multiparous women, where a shorter labor is expected. More research is needed to determine the optimal dose and route of administration of fentanyl for labor analgesia.

Influence of ketamine versus fentanyl on pain relief for pediatric orthopedic emergencies: A meta-analysis of randomized controlled studies.

INTRODUCTION: The comparison of ketamine with fentanyl for pain control of pediatric orthopedic emergencies remains controversial. We conduct a systematic review and meta-analysis to explore the influence of ketamine versus fentanyl on pain management among pediatric orthopedic emergencies. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2020 for randomized controlled trials assessing the effect of ketamine versus fentanyl on pain management for pediatric orthopedic emergencies. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with fentanyl for pediatric orthopedic emergencies, ketamine led to similar change in pain scores at 15 to 20 minutes (standard mean difference = -0.05; 95% confidence interval [CI] = -0.38 to 0.28; P = .77) and 30 minutes (standard mean difference = 0.11; 95% CI = -0.20 to 0.42; P = .49), as well as rescue analgesia (RR = 0.90; 95% CI = 0.54 to 1.51; P = .69), but revealed the increase in nausea/vomiting (RR = 2.65; 95% CI = 1.13 to 6.18; P = .02) and dizziness (RR = 3.83; 95% CI = 1.38 to 10.60; P = .01). CONCLUSIONS: Ketamine may be similar to fentanyl in terms of the analgesic efficacy for pediatric orthopedic emergencies.