Manifestaciones clínicas post supresión de sedoanalgesia en pacientes adultos de una terapia intensiva / Clinical manifestations after suppression of sedoanalgesia in adult patients in intensive care

Introducción: en la unidad de cuidados intensivos (UCI), las personas asistidas con patologías relevantes se encuentran bajo sedación, una vez que estas se encuentran bajo los principios de supresión de la sedación, es importante identificar cuáles son las manifestaciones que presentan, propias de las sedaciones. Objetivo: describir las manifestaciones clínicas del síndrome de supresión de la sedoanalgesia presentes en pacientes asistidos en un Hospital Público de la Ciudad de Corrientes de enero a diciembre del 2022. Metodología: estudio cuantitativo, descriptivo, transversal y observacional. La muestra incluyó pacientes adultos de UCI. El cálculo del tamaño muestral se realizó a través del método probabilístico aleatorio simple resultando de éste una muestra de 100 historias clínicas. Para la recolección de datos se utilizó la observación y como instrumento un formulario semiestructurado, de carácter anónimo. Cada formulario contenía datos específicos donde se categorizan las variables en estudio como ser edad, sexo, comorbilidades, tiempo de sedoanalgesia, tipo de sedación, sedoanalgesia utilizada, agitación, confusión, alucinación, diaforesis, taquicardia. Resultados: en cuanto a la edad se obtuvo un promedio de 49 años, el sexo predominante fue el masculino con 52%, en cuanto a las comorbilidades más frecuentes, el 20% presentó Insuficiencia Respiratoria Aguda y el 16% Insuficiencia renal. El motivo de ingreso a UCI en mayor medida con el 33% fue por dificultad respiratoria y Post Quirúrgicos complicados 32%. Los fármacos de mayor elección fueron midazolam 94%, seguido del fentanilo 80%. En cuanto al tiempo de sedación de los pacientes, se encontró una media de 1265 horas. Las manifestaciones clínicas que se observaron en la muestra en mayor medida corresponden a taquicardia 70%, agitación 52%, un 37% confusión e hipertensión y un 24% alucinación. Conclusión: las manifestaciones que se presentaron con mayor frecuencia fueron taquicardia, agitación, confusión, hipertensión y con menor frecuencia alucinación[AU]

Introduction: in the intensive care unit (ICU), people treated with relevant pathologies are under sedation. Once they are under the principles of sedation suppression, it is important to identify the manifestations they present, typical of sedations. Objective: To describe the clinical manifestations of sedation suppression syndrome present in patients treated at a Public Hospital in the City of Corrientes from January to December 2022. Methodology: quantitative, descriptive, cross-sectional and observational study. The sample included adult ICU patients. The calculation of the sample size was carried out through the simple random probabilistic method, resulting in a sample of 100 medical records. Manifestaciones clínicas post supresión de sedoanalgesia en pacientes adultos de una terapia intensiva. Observation was used to collect data and a semi-structured, anonymous form was used as an instrument. Each form contained specific data where the variables under study were categorized, such as age, sex, comorbidities, sedation time, type of sedation, sedation used, agitation, confusion, hallucination, diaphoresis, tachycardia. Results: regarding age, an average of 49 years was obtained, the predominant sex was male with 52%, regarding the most frequent comorbidities, 20% presented Acute Respiratory Failure and 16% Renal failure. The reason for admission to the ICU to a greater extent with 33% was due to respiratory difficulty and complicated Post-Surgeries 32%. The drugs of greatest choice were midazolam 94%, followed by fentanyl 80%. Regarding the sedation time of the patients, an average of 1265 hours was found. The clinical manifestations that were observed in the sample to a greater extent correspond to tachycardia 70%, agitation 52%, confusion and hypertension 37% and hallucination 24%. Conclusion: the manifestations that occurred most frequently were tachycardia, agitation, confusion, hypertension and, less frequently, hallucination[AU]

Introdução: na unidade de terapia intensiva (UTI), as pessoas tratadas com patologias relevantes estão sob sedação. Uma vez sob os princípios da supressão da sedação, é importante identificar as manifestações que apresentam, típicas das sedações. Objetivo: Descrever as manifestações clínicas da síndrome de supressão da sedação presentes em pacientes atendidos em um Hospital Público da Cidade de Corrientes no período de janeiro a dezembro de 2022. Metodologia: estudo quantitativo, descritivo, transversal e observacional. A amostra incluiu pacientes adultos internados em UTI. O cálculo do tamanho amostral foi realizado pelo método probabilístico aleatório simples, resultando em uma amostra de 100 prontuários. A observação foi utilizada para a coleta de dados e um formulário semiestruturado e anônimo foi utilizado como instrumento. Cada formulário continha dados específicos onde foram categorizadas as variáveis em estudo, como idade, sexo, comorbidades, tempo de sedação, tipo de sedação, sedação utilizada, agitação, confusão, alucinação, sudorese, taquicardia. Resultados: em relação à idade obteve-se uma média de 49 anos, o sexo predominante foi o masculino com 52%, quanto às comorbidades mais frequentes, 20% apresentavam Insuficiência Respiratória Aguda e 16% Insuficiência Renal. O motivo de internação na UTI em maior proporção com 33% foi por dificuldade respiratória e pós-cirúrgicos complicados 32%. Os medicamentos de maior escolha foram midazolam 94%, seguido de fentanil 80%. Quanto ao tempo de sedação dos pacientes, foi encontrada uma média de 1265 horas. As manifestações clínicas mais observadas na amostra correspondem a taquicardia 70%, agitação 52%, confusão e hipertensão 37% e alucinação 24%. Conclusão: as manifestações que ocorreram com maior frequência foram taquicardia, agitação, confusão, hipertensão e, menos frequentemente, alucinação[AU]

Effect of oxycodone versus fentanyl for patient-controlled intravenous analgesia after laparoscopic hysteromyomectomy: a single-blind, randomized controlled trial.

A single-blind, randomized controlled trial comparing oxycodone and fentanyl for patient-controlled intravenous analgesia (PCIA) after laparoscopic hysteromyomectomy found comparable pain relief between the two groups. The study included 60 participants, with NRS scores for pain at rest and when moving showing no significant differences between oxycodone and fentanyl groups at various time points postoperatively. Self-rating depression scale scores were also similar between the groups at 48 h. However, patients' satisfaction with PCIA was higher in the oxycodone group, with 73.3% reporting being very satisfied compared to 36.7% in the fentanyl group. Additionally, the oxycodone group had fewer incidences of headaches within 48 h postoperatively compared to the fentanyl group. These findings suggest that oxycodone may offer comparable pain relief, higher patient satisfaction, and fewer headaches for patients undergoing laparoscopic hysteromyomectomy compared to fentanyl, making it a suitable option for postoperative pain management in this population.Clinical trial registration number The study was registered with CHICTR.org, ChiCTR2100051924.

Efficacy and safety of fentanyl inhalant for the treatment of breakthrough cancer pain: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25µg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. METHODS: The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). RESULTS: A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. CONCLUSION: Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.

Ketamine-assisted buprenorphine initiation: a pilot case series.

BACKGROUND: Many people with opioid use disorder who stand to benefit from buprenorphine treatment are unwilling to initiate it due to experience with or fear of both spontaneous and buprenorphine-precipitated opioid withdrawal (BPOW). An effective means of minimizing withdrawal symptoms would reduce patient apprehensiveness, lowering the barrier to buprenorphine initiation. Ketamine, approved by the FDA as a dissociative anesthetic, completely resolved BPOW in case reports when infused at a sub-anesthetic dose range in which dissociative symptoms are common. However, most patients attempt buprenorphine initiation in the outpatient setting where altered mental status is undesirable. We explored the potential of short-term use of ketamine, self-administered sublingually at a lower, sub-dissociative dose to assist ambulatory patients undergoing transition to buprenorphine from fentanyl and methadone. METHODS: Patients prescribed ketamine were either (1) seeking transition to buprenorphine from illicit fentanyl and highly apprehensive of BPOW or (2) undergoing transition to buprenorphine from illicit fentanyl or methadone and experiencing BPOW. We prescribed 4-8 doses of sublingual ketamine 16 mg (each dose bioequivalent to 3-6% of an anesthetic dose), monitored patients daily or near-daily, and adjusted buprenorphine and ketamine dosing based on patient response and prescriber experience. RESULTS: Over a period of 14 months, 37 patients were prescribed ketamine. Buprenorphine initiation was completed by 16 patients, representing 43% of the 37 patients prescribed ketamine, and 67% of the 24 who reported trying it. Of the last 12 patients who completed buprenorphine initiation, 11 (92%) achieved 30-day retention in treatment. Most of the patients who tried ketamine reported reduction or elimination of spontaneous opioid withdrawal symptoms. Some patients reported avoidance of severe BPOW when used prophylactically or as treatment of established BPOW. We developed a ketamine protocol that allowed four of the last patients to complete buprenorphine initiation over four days reporting only mild withdrawal symptoms. Two patients described cognitive changes from ketamine at a dose that exceeded the effective dose range for the other patients. CONCLUSIONS: Ketamine at a sub-dissociative dose allowed completion of buprenorphine initiation in the outpatient setting in the majority of patients who reported trying it. Further research is warranted to confirm these results and develop reliable protocols for a range of treatment settings.

Opioid Administration Practice Patterns in Patients With Acute Respiratory Failure Who Undergo Invasive Mechanical Ventilation.

IMPORTANCE: The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES: To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES: We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS: We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3-11%) and 39% (95% CI, 28-49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129-1341 µg) in the KPNC cohort and 200 µg (IQR, 0-1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1-7%) and 20% (95% CI, 15-26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE: In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals' analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.

Extended-Release Injection vs Sublingual Buprenorphine for Opioid Use Disorder With Fentanyl Use: A Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited. Objective: To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use. Design, Setting, and Participants: Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023. Intervention: Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone. Main Outcomes and Measures: Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales. Results: Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups. Conclusions and Relevance: In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use. Trial Registration: ClinicalTrials.gov Identifier: NCT02651584.

What is the Evidence for Using Intranasal Medicine in the Prehospital Setting? A Systematic Review.

OBJECTIVES: Intranasal (IN) medications offer a safe non-invasive way to rapidly deliver drugs in situations where intravenous (IV) access and intramuscular (IM) administration is challenging or not feasible. In the prehospital setting, this can be an essential alternative in time critical situations including trauma management, seizures, and agitated patients. However, there is a paucity of evidence summarizing its efficacy in this environment. This systematic review aims to assess the current evidence supporting the use of IN medicine (midazolam, ketamine, fentanyl, morphine, glucagon, and naloxone) in the prehospital setting alone. METHODS: A systematic literature search (PROSPERO CRD42023440713) of PubMed, Web of Science, OVID Medline, "Cochrane Central Register of Controlled Trials," Cochrane reviews and Embase was performed from inception to June 2023 to identify studies where IN medications were administered to patients in the prehospital setting. All randomized controlled trials, observational cohort studies, case series, and case reports were included. Papers not written in English, review articles, abstracts, and non-published data (including letters to the editor) were excluded. The methodological quality of the included studies was interpreted using the Cochrane risk of bias tool and rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. No funding was received. RESULTS: From 4818 studies, 39 were included (seven for midazolam, five for ketamine, twelve for fentanyl, one for diamorphine, two for glucagon, and twelve for naloxone). A total of 24,097 patients were treated with IN medications across all the studies. There were five moderate quality, four low quality, and thirty very low quality studies. The potential efficacy of IN fentanyl and ketamine was demonstrated consistently throughout the studies with less clear evidence for midazolam, morphine, glucagon, and naloxone. This review was severely limited by the study quality, with most studies demonstrating "high concerns" for bias. CONCLUSIONS: Prehospital IN medication administration has wide-ranging potential, particularly for administering analgesia. There are likely to be certain populations, for example, pediatrics, that will benefit the most, although conclusions are limited by the quality of evidence currently available. We encourage additional research in this area, particularly with robust prospective double-blind RCTs.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

How side effects can improve treatment efficacy: a randomized trial.

While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. In this pre-registered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (inert). After the first session, participants were randomized to two groups and underwent functional MRI. One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief. Our results revealed that nasal sprays with a side effect lead to lower pain than inert nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. Functional MRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects. In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo.

Perioperative analgesic effects of the erector spinae plane block with bupivacaine or bupivacaine-dexmedetomidine in dogs undergoing hemilaminectomy: A randomized controlled trial.

Objective: To compare the perioperative opioid requirements among dogs receiving an erector spinae plane (ESP) block with bupivacaine, with or without dexmedetomidine, and a control group. Animals and procedure: Thirty client-owned, healthy adult dogs undergoing hemilaminectomy were included in this randomized, prospective, blinded clinical study. Dogs were randomly assigned to 1 of 3 treatment groups: Group B, ESP block with bupivacaine; Group BD, ESP block with bupivacaine and dexmedetomidine; and Group C, control. Rescue intra- and postoperative analgesia consisted of fentanyl and methadone, respectively. Postoperative pain was evaluated using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF). Results: In Group BD, 0/10 dogs required intraoperative fentanyl, compared to 9/10 in Group C (P < 0.001), whereas 1/10 required postoperative methadone, compared to 9/10 in Group B (P = 0.003) and 10/10 in Group C (P < 0.001). The total amount of intraoperative fentanyl (µg/kg) was 0 (0 to 4) in Group B and 0 (0 to 0) in BD, compared to 6 (0 to 8) in C (P = 0.004 and P < 0.001, respectively). Postoperative methadone (mg/kg) required during the first 12 h was 0.5 (0 to 1.4) in Group B (P = 0.003) and 0 (0 to 0) in BD (P < 0.001), compared to C (P = 0.003 and P < 0.001, respectively). Conclusion: An ESP block with bupivacaine, with or without dexmedetomidine, was associated with a reduction in perioperative opioid consumption and provided effective acute pain control.

Effets analgésiques périopératoires du bloc des érecteurs du rachis avec de la bupivacaïne ou de la bupivacaïne-dexmédétomidine chez les chiens subissant une hémilaminectomie: un essai contrôlé randomisé. Objectif: Comparer les besoins périopératoires en opioïdes chez les chiens recevant un bloc des érecteurs de la colonne vertébrale (ESP) avec de la bupivacaïne, avec ou sans dexmédétomidine, et un groupe témoin. Animaux et procédure: Trente chiens adultes en bonne santé appartenant à des clients subissant une hémilaminectomie ont été inclus dans cette étude clinique randomisée, prospective et en aveugle. Les chiens ont été répartis au hasard dans 1 des 3 groupes de traitement: groupe B, bloc ESP avec bupivacaïne; groupe BD, bloc ESP avec bupivacaïne et dexmédétomidine; et groupe C, témoin. L'analgésie de secours peropératoire et postopératoire consistait respectivement en fentanyl et en méthadone. La douleur postopératoire a été évaluée à l'aide du formulaire abrégé de l'échelle de mesure de la douleur de Glasgow (CMPS-SF). Résultats: Dans le groupe BD, 0/10 chiens ont eu besoin de fentanyl peropératoire, contre 9/10 dans le groupe C (P < 0,001), tandis que 1/10 ont eu besoin de méthadone postopératoire, contre 9/10 dans le groupe B (P = 0,003) et 10/10 dans le groupe C (P < 0,001). La quantité totale de fentanyl peropératoire (µg/kg) était de 0 (0 à 4) dans le groupe B et de 0 (0 à 0) dans le groupe BD, contre 6 (0 à 8) dans le groupe C (P = 0,004 et P < 0,001, respectivement). La méthadone postopératoire (mg/kg) nécessaire au cours des 12 premières heures était de 0,5 (0 à 1,4) dans le groupe B (P = 0,003) et de 0 (0 à 0) dans le groupe BD (P < 0,001), par rapport au groupe C (P = 0,003). et P < 0,001, respectivement). Conclusion: Un bloc ESP avec de la bupivacaïne, avec ou sans dexmédétomidine, a été associé à une réduction de la consommation peropératoire d'opioïdes et a permis un contrôle efficace de la douleur aiguë.(Traduit par Dr Serge Messier).

Vaccines as Immunotherapies for Substance Use Disorders.

Substance use disorders (SUD) present a worldwide challenge with few effective therapies except for the relative efficacy of opioid pharmacotherapies, despite limited treatment access. However, the proliferation of illicit fentanyl use initiated a dramatic and cascading epidemic of lethal overdoses. This rise in fentanyl overdoses regenerated an interest in vaccine immunotherapy, which, despite an optimistic start in animal models over the past 50 years, yielded disappointing results in human clinical trials of vaccines against nicotine, stimulants (cocaine and methamphetamine), and opioids. After a brief review of clinical and selected preclinical vaccine studies, the "lessons learned" from the previous vaccine clinical trials are summarized, and then the newest challenge of a vaccine against fentanyl and its analogs is explored. Animal studies have made significant advances in vaccine technology for SUD treatment over the past 50 years, and the resulting anti-fentanyl vaccines show remarkable promise for ending this epidemic of fentanyl deaths.

Comparison of sequential and mixture injections of opioids and hyperbaric bupivacaine for subarachnoid block for lower segment caesarean section: a randomised controlled study.

INTRODUCTION: Opioids are commonly added to local anaesthetic for subarachnoid block for caesarean section due to their synergistic effects. The physiochemical characteristics of opioids suggest premixing with hyperbaric bupivacaine may limit their distribution within the CSF. We studied the effect of a separate injection with a combination of bupivacaine, morphine and fentanyl on block characteristics, haemodynamic changes, postoperative pain and patient satisfaction. METHOD: Following ethical approval and informed consent, a prospective double-blinded randomised controlled trial was performed in a university hospital. A total of 126 patients undergoing caesarean section were randomised to two groups. In group M, the premixed group, patients received 12 mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 100 mcg of morphine injected as a single mixture. In group S, the separate injection group, patients received the same drugs in separate injections. Measurements included haemodynamics, block distribution, intra- and postoperative pain, as well as patient satisfaction. RESULTS: Patients in both groups had similar block height, time to maximum sensory block, time to block regression and motor block. However, haemodynamics were different between the groups. The proportion of systolic hypotension episodes was greater in group S [159/1320 (12.05%)] than group M [113/1452 (7.78%)], with P = 0.0002. Moreover, a greater amount of ephedrine was administered in group S than group M, with values 12.09 (8.1) and 9.09 (8.5) mg respectively (P = 0.001). Additionally, postoperative pain, as measured by the Visual Analogue Scale (VAS), was greater in group M, with a VAS of 4.6 (1.7), vs. group S, which recorded a VAS of 3.8 (2.0) (P = 0.017). CONCLUSION: Sequential injection of intrathecal opioids and hyperbaric bupivacaine resulted in greater early haemodynamic instability and slightly better postoperative analgesia without any difference in block height or patient satisfaction. CLINICAL TRIAL REGISTRATION: NCT04403724.

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.

Triage-initiated intranasal fentanyl for hip fractures in an Emergency Department - Results from introduction of an analgesic guideline.

BACKGROUND: Pain relief is a priority for patients with hip fractures who present to Emergency Departments (EDs). Intranasal fentanyl (INF) is an ideal option for nurse initiated analgesia as it does not require intravenous access and can expedite care prior to examination by a physician. LOCAL PROBLEM: Pain relief in patients with hip fractures is delayed during episodes of ED crowding. METHODS: A retrospective medical record review was conducted following introduction of an INF guideline in an adult ED in 2018. Patients were included over a 4-month period during which the guideline was introduced. Historical and concurrent control groups receiving usual care were compared to patients receiving INF. INTERVENTIONS: This quality improvement initiative investigated whether an INF analgesia at triage guideline would decrease time to analgesic administration in adults with hip fracture in ED. RESULTS: This study included 112 patients diagnosed with fractured hips of which 16 patients received INF. Background characteristics were similar between groups. Mean time to analgesic administration (53 v 110 minutes), time to x-ray (46 v 75 minutes), and ED length of stay (234 v 298 minutes) were significantly decreased in the intervention group. Inadequate documentation was a limiting factor in determining improved efficacy of analgesia. CONCLUSION: Use of triage-initiated INF significantly decreased time to analgesic administration, time to imaging and overall length of stay in ED.

Caring for Hospitalized Adults With Opioid Use Disorder in the Era of Fentanyl: A Review.

Importance: The rise of fentanyl and other high-potency synthetic opioids across US and Canada has been associated with increasing hospitalizations and unprecedented overdose deaths. Hospitalization is a critical touchpoint to engage patients and offer life-saving opioid use disorder (OUD) care when admitted for OUD or other medical conditions. Observations: Clinical best practices include managing acute withdrawal and pain, initiating medication for OUD, integrating harm reduction principles and practices, addressing in-hospital substance use, and supporting hospital-to-community care transitions. Fentanyl complicates hospital OUD care. Fentanyl's high potency intensifies pain, withdrawal, and cravings and increases the risk for overdose and other harms. Fentanyl's unique pharmacology has rendered traditional techniques for managing opioid withdrawal and initiating buprenorphine and methadone inadequate for some patients, necessitating novel strategies. Further, co-use of opioids with stimulants drugs is common, and the opioid supply is unpredictable and can be contaminated with benzodiazepines, xylazine, and other substances. To address these challenges, clinicians are increasingly relying on emerging practices, such as low-dose buprenorphine initiation with opioid continuation, rapid methadone titration, and the use of alternative opioid agonists. Hospitals must also reconsider conventional approaches to in-hospital substance use and expand clinicians' understanding and embrace of harm reduction, which is a philosophy and set of practical strategies that supports people who use drugs to be safer and healthier without judgment, coercion, or discrimination. Hospital-to-community care transitions should ensure uninterrupted access to OUD care after discharge, which requires special consideration and coordination. Finally, improving hospital-based addiction care requires dedicated infrastructure and expertise. Preparing hospitals across the US and Canada to deliver OUD best practices requires investments in clinical champions, staff education, leadership commitment, community partnerships, quality metrics, and financing. Conclusions and Relevance: The findings of this review indicate that fentanyl creates increased urgency and new challenges for hospital OUD care. Hospital clinicians and systems have a central role in addressing the current drug crisis.

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.

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.

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.

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.