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 classical music on light-plane anaesthesia and analgesia in dogs subjected to surgical nociceptive stimuli.

The objectives of this prospective, randomized, blinded, crossover, experimental study were to detect the potential anaesthetic- and analgesic-sparing effects of classical music provided to dogs undergoing skin surgery, and to investigate the role of substance P as an intraoperative pain indicator. Twenty dogs were included, each subjected to three different treatments: Chopin music, Mozart music and no music. They were premedicated with acepromazine, butorphanol and meloxicam and anaesthetized with propofol and isoflurane. Fentanyl was used as rescue analgesia. The anaesthetic depth was monitored by using the bispectral index along with standard anaesthetic monitoring, and autonomic nervous system responses were used to monitor the adequacy of analgesia. Furthermore, measurements of substance P serum concentration were carried out. Dogs exposed to music required less isoflurane and fentanyl. Furthermore, a statistically significant effect of time on substance P concentration was observed regardless of exposure to music, and there was a significant interaction effect between different timepoints and the type of acoustic stimulus. Classical music seems to have an isoflurane and fentanyl sparing effect on dogs undergoing minor surgery. Following surgical stimulation, the serum substance P concentration increases rapidly, and thus appears to be a potentially useful pain indicator.

Comparison of different concentrations of ropivacaine in epidural anesthesia for percutaneous transforaminal endoscopic discectomy: a randomized controlled trial.

BACKGROUND: This study investigated the optimal concentration of ropivacaine epidural anesthesia for clinical use in percutaneous transforaminal endoscopic discectomy (PTED) by comparing the effects of different concentrations. METHODS: Seventy patients scheduled for their first PTED procedure were enrolled in this randomized controlled trial. Patients were randomized to receive ropivacaine at varying concentrations (0.3% or 0.4%). Primary outcome measures included the numeric rating scale (NRS) and hip extension level (HEL). Secondary outcome measures included intraoperative fentanyl dosage and postoperative complications. RESULTS: One patient withdrew due to severe postoperative complications. The remaining 69 patients were allocated to the 0.3% (n = 34) and 0.4% (n = 35) groups, respectively. Baseline characteristics showed no significant differences between the two groups (P > 0.05). The NRS score was significantly lower in the 0.4% group than in the 0.3% group (P < 0.01), whereas the HEL score was significantly higher (P < 0.001). The average fentanyl dose in the 0.4% group was significantly lower than that in the 0.3% group (P < 0.01). Postoperative complications occurred in five and two patients in the 0.3% and 0.4% groups, respectively. CONCLUSION: Although 0.4% ropivacaine (20 mL) impacts muscle strength, it does not impede PTED surgery. Given its effective analgesic properties and few postoperative complications, 0.4% ropivacaine can be considered a preferred dose for PTED. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trials Registry (Registration number: ChiCTR2200060364; Registration Date: 29/5/2022) and on chictr.org.cn ( https://www.chictr.org.cn/showproj.html?proj=171002 ).

Reported Xylazine Use Among Adults Aged ≥18 Years Evaluated for Substance Use Treatment - United States, July 2022-September 2023.

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.

Opioid-sparing effect of erector spinae plane block and intravenous dexmedetomidine for obese patients with obstructive sleep apnea: A randomized controlled trial.

OBJECTIVE: This study assessed the impact of erector spinae plane block (ESPB) and intravenous (IV) dexmedetomidine in reduction of perioperative opioid consumption following bariatric surgery and their impact on post-operative recovery, analgesia, and pulmonary functions. DESIGN: A randomized controlled trial. SETTING: Tanta University Hospitals, Tanta, Gharboa, Egypt. PATIENTS: Forty obese patients with obstructive sleep apnea syndrome (OSAS), aged 20-55 years, and eligible for bariatric surgery were included. INTERVENTIONS: Patients randomized into group I (received general anesthesia [GA] with opioid, sham ESPB, and IV normal saline) or group II (received GA [without opioid], ESPB [at T7 level] using 20 mL bupivacaine 0.25 percent and bolus IV dexmedetomidine 1 µg/kg and then 0.25 µg/kg/h). MAIN OUTCOME MEASURES: Fentanyl consumption (primary outcome), sevoflurane consumption, recovery time, Visual Analog Scale (VAS), and pulmonary functions (secondary outcomes) were recorded. RESULTS: Perioperative fentanyl (intraoperative, post-operative, and total) consumption and sevoflurane consumption were substantially lower in group II compared to group I (p = 0.010, <0.001, <0.001, and <0.001, respectively). Moreover, recovery time was shorter in group II (p < 0.001). At 2, 4, 8, and 24 hours after surgery, group I patients had VAS values considerably higher. Relative to preoperative values, pulmonary function did not significantly alter after surgery. Oxygen desaturation was significantly lower in group II (p = 0.001). CONCLUSIONS: The ESPB with IV dexmedetomidine is advantageous for OSAS patients having bariatric surgery as it provides anesthesia and opioid-sparing effect with short recovery, adequate analgesia, and nonsignificant complications. Yet, it had no effect on post-operative pulmonary function.

Exploring the thermally-controlled fentanyl transdermal therapy to provide constant drug delivery by physics-based digital twins.

Transdermal drug delivery is suitable for low-molecular-weight drugs with specific lipophilicity, like fentanyl, which is widely used for cancer-induced pain management. However, fentanyl's transdermal therapy displays high intra-individual variability. Factors like skin characteristics at application sites and ambient temperature contribute to this variation. In this study, we developed a physics-based digital twin of the human body to cope with this variability and propose better adapted setups. This twin includes an in-silico skin model for drug penetration, a pharmacokinetic model, and a pharmacodynamic model. Based on the results of our simulations, applying the patch on the flank (side abdominal area) showed a 15.3 % higher maximum fentanyl concentration in the plasma than on the chest. Additionally, the time to reach this maximum concentration when delivered through the flank was 19.8 h, which was 10.3 h earlier than via the upper arm. Finally, this variation led to an 18 % lower minimum pain intensity for delivery via the flank than the chest. Moreover, the impact of seasonal changes on ambient temperature and skin temperature by considering the activity level was investigated. Based on our result, the fentanyl uptake flux by capillaries increased by up to 11.8 % from an inactive state in winter to an active state in summer. We also evaluated the effect of controlling fentanyl delivery by adjusting the temperature of the patch to alleviate the pain to reach a mild pain intensity (rated three on the VAS scale). By implementing this strategy, the average pain intensity decreased by 1.1 points, and the standard deviation for fentanyl concentration in plasma and average pain intensity reduced by 37.5 % and 33.3 %, respectively. Therefore, our digital twin demonstrated the efficacy of controlled drug release through temperature regulation, ensuring the therapy toward the intended target outcome and reducing therapy outcome variability. This holds promise as a potentially useful tool for physicians.

Effects of dexmedetomidine, fentanyl and magnesium sulfate added to ropivacaine on sensory and motor blocks in lower abdominal surgery: a randomized clinical trial.

This study aimed to compare the effects of intrathecal dexmedetomidine, fentanyl and magnesium sulfate added to ropivacaine on the onset and duration of sensory and motor blocks in lower abdominal surgery. This double-blind randomized clinical trial included 90 patients scheduled for lower abdominal surgery at Vali-Asr Hospital in Arak, Iran. The enrolled patients were randomly divided into three equal groups and then underwent spinal anesthesia. The first group received 10 µg of dexmedetomidine, the second group received 50 µg of fentanyl, and the third group received 200 mg of 20% magnesium sulfate intrathecally in addition to 15 mg of 0.5% ropivacaine. In the dexmedetomidine group, the mean arterial blood pressure was lower than the other two groups (P = 0.001). Moreover, the time to onset of sensory block (P = 0.001) and the mean duration of sensory block (P = 0.001) were shorter and longer, respectively, in the dexmedetomidine group than in the other two groups. In the dexmedetomidine group, the mean time to onset of motor block (P = 0.001) and the mean duration of motor block (P = 0.001) were lower and higher than in the other two groups, respectively. There was no significant difference in visual analog scale score, heart rate, administered opioid, and drug side effects among the three groups. Dexmedetomidine caused early sensory and motor blocks while prolonging the duration of sensory and motor blocks compared with the other two groups. In addition, dexmedetomidine reduced mean arterial blood pressure in patients. Based on the findings of this study, it is recommended that dexmedetomidine can be used in order to enhance the quality of sensory and motor block in patients.

Impact of general anesthesia on postoperative complications in orthognathic surgery: a retrospective comparison of total intravenous anesthesia versus volatile anesthesia.

Orthognathic surgery has a high incidence of postoperative nausea (PON) and vomiting (POV), delaying mobility initiation and postoperative recovery. Bleeding is another risk associated with this surgical procedure. We aimed to compare total intravenous anesthesia (TIVA) and volatile anesthesia in patients undergoing orthognathic surgery in terms of postoperative nausea and vomiting (PONV) incidence and hemodynamic changes. This retrospective study included 82 patients who underwent bilateral sagittal split ramus osteotomies at Saga University Hospital between April 2016 and April 2021. We compared the effects of TIVA and volatile anesthesia on PONV onset after surgery, acute postoperative hemodynamic changes (blood pressure and heart rate), and factors contributing to PONV. PON was significantly lower in the TIVA group than in the volatile anesthesia group. The total dose of fentanyl contributed to the onset of POV, while the onset of PON was associated with low volumes of fluid infusion and urine in the TIVA and volatile anesthesia groups, respectively. Furthermore, post-extubation hemodynamic change was significantly smaller in the TIVA group than in the volatile anesthesia group. Therefore, TIVA could have a reduced risk of PONV and hemodynamic changes in patients undergoing orthognathic surgery. Employing TIVA could mitigate perioperative complications and enhance patient safety.

Comparison of Fentanyl, Ketamine, and Lidocaine Combined with Propofol Anesthesia in Patients with Crohn Disease Undergoing Colonoscopy.

BACKGROUND Colonoscopy is the predominant invasive procedure for Crohn disease (CD) patients. Opioids and propofol carry risks of respiratory and cardiovascular complications. This study aimed to evaluate whether substituting fentanyl with ketamine or lidocaine could diminish propofol usage and minimize adverse events. MATERIAL AND METHODS In total, 146 patients with CD scheduled for elective colonoscopy were assigned to anesthesia with fentanyl (n=47), ketamine (n=47), or lidocaine (n=55). Propofol was administered to achieve sufficient anesthesia. Measured outcomes in each group included propofol consumption, hypotension and desaturation incidents, adverse event types, consciousness recovery time, abdominal pain intensity, Aldrete scale, and Post Anaesthetic Discharge Scoring System (PADSS). RESULTS Patients administered fentanyl needed significantly more propofol (P=0.017) than those on ketamine, with lidocaine showing no notable difference (P=0.28). Desaturation was significantly less common in the ketamine and lidocaine groups than fentanyl group (P<0.001). The ketamine group experienced milder reductions in mean arterial (P=0.018) and systolic blood pressure (P<0.001). Recovery metrics (Aldrete and PADSS scores) were lower for fentanyl (P<0.001), although satisfaction and pain levels were consistent across all groups (P=0.797). Dizziness occurred less frequently with lidocaine than fentanyl (17.2%, P=0.018) and ketamine (15.1%, P=0.019), while metallic taste incidents were more prevalent in the lidocaine group (13.5%, P=0.04) than fentanyl group. CONCLUSIONS Using ketamine or lidocaine instead of fentanyl in anesthesia for colonoscopy in patients with CD significantly lowers propofol use, reduces desaturation events, maintains blood pressure more effectively, without increasing hypotension risk, and accelerates recovery, without negatively impacting adverse events or patient satisfaction.

ED50 and ED95 of Remimazolam Tosilate Combined with Different Doses of Fentanyl in Elderly Patients for Painless Gastroscopy.

Background: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy. Methods: Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate. Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups. Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.

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 .

Dexmedetomidine-ketamine combination versus fentanyl-midazolam for patient sedation during flexible bronchoscopy: a prospective, single-blind, randomized controlled trial.

BACKGROUND: Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB. METHODS: Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction. RESULTS: The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033). CONCLUSION: DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.

Total intravenous anesthesia with Ketofol in rabbits: a comparison of the effects of constant rate infusion of midazolam, fentanyl or dexmedetomidine.

BACKGROUND: When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg- 1 minute- 1 [0.3 mg kg- 1 minute- 1 of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min. RESULTS: Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg- 1 and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression. CONCLUSIONS: At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used.

Prospective Pilot Study: Tolerability of Outpatient Penile Plication Under Nursing-Administered Conscious Sedation vs Anesthesiologist-Administered Deep Sedation.

INTRODUCTION: Penile plication is commonly performed for Peyronie's disease under general or spinal anesthesia. Conscious sedation (CS) offers decreased anesthetic risks, cost-effectiveness, and the ability to perform the procedure in outpatient settings with shorter wait times. We sought to compare tolerability of penile plication under deep intravenous sedation (DIS) administered by anesthesiologists and nursing-administered CS (NACS). METHODS: Tolerability for penile plication was prospectively evaluated, excluding revision surgeries and those with hourglass or hinge deformities. DIS included midazolam and ketamine with infusion of propofol and remifentanil. NACS consisted of midazolam and fentanyl. Baseline characteristics, procedural information, and patient- and surgeon-reported pain assessments were collected. Patients were administered a standardized tolerability questionnaire on follow-up. RESULTS: Forty patients were enrolled (23 DIS; 17 NACS) with similar baseline characteristics. Median curvature of the DIS cohort was 55° (interquartile range = 43.75-76.25) and 45° (interquartile range = 45-60) in NACS. There was a 100% success rate with no procedure abortion or conversion to general anesthetic. On follow-up, all patients had functional curvature (<20°), and 100% of patients in the DIS and NACS cohorts reported that they would recommend CS to others. Over 93% of patients in both cohorts would choose CS over general anesthetic in the future, with no differences in perioperative and postoperative pain between groups. CONCLUSIONS: Penile plication with CS, whether administered by an anesthesiologist or nursing, is well tolerated with no differences in pain or complications. This indicates that outpatient penile plication with trained nursing staff administering CS can safely reduce costs, risks, and wait times.

Ultrasound-guided suprainguinal fascia iliaca block to position the patient for neuraxial anaesthesia in acetabular surgery - a randomized controlled pilot study.

INTRODUCTION: Neuraxial anaesthesia is a common choice for most hip and lower limb operations. Pain associated with positioning is often a deterrent, and the vast literature suggests different regional blocks and opioids for these patients. Patients with acetabular fractures may experience increased pain, and thus are more difficult to position for the neuraxial block. We conducted a randomized controlled pilot study to assess and compare the analgesic efficacy of ultrasound-guided suprainguinal fascia iliaca block (SFICB) versus systemic fentanyl to facilitate positioning for combined spinal epidural (CSE) anaesthesia in patients undergoing acetabular fracture surgery. MATERIAL AND METHODS: Twenty patients referred for surgical repair of acetabular fractures were randomly assigned to receive either ultrasound-guided SFICB (group B) or intravenous fentanyl (group F). Changes in visual analogue scale (VAS) scores in supine and sitting position, improvement in sitting angle (SA), positioning quality, rescue analgesic requirement, total opioid consumption, comfort VAS scores, and complications were noted to compare both groups. RESULTS: The post-intervention VAS score in the sitting position was significantly lower in group B than in group F (5.9 ± 2.1 vs. 3.5 ± 1.5, P = 0.01). Group B also had more significant improvement in SA (27.5° (20.75-36.5°), in comparison to group F (10 (5-18.75), P = 0.006). The positioning quality was better in group B, with 70% of patients achieving an optimal position compared to only 10% in group F ( P = 0.02). CONCLUSIONS: Ultrasound-guided SFICB, as compared to systemic fentanyl, provided better analgesia and helped to achieve a better and more comfortable position to perform the neuraxial block.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020-2023.

BACKGROUND: Amidst an increasingly toxic drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking opioids and methamphetamine among a cohort of people who inject drugs from San Diego, California. METHODS: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting. Multivariable Poisson regression via generalized estimating equations was used to examine time trends. RESULTS: Of 362 participants, median age was 40 years; a minority were female (29%), Hispanic/Latinx/Mexican (45%), and housed (33%). Among this cohort, of whom 100% injected (and 84% injected and smoked) in period one (October 2020-April 2021), by period five (November 2022-April 2023), 34% only smoked, 59% injected and smoked, and 7% only injected. By period five, the adjusted relative risk (aRR) of injecting opioids was 0.41 (95% Confidence Interval [CI]: 0.33, 0.51) and the aRR for injecting methamphetamine was 0.50 (95% CI: 0.39, 0.63) compared to period one. Risks for smoking fentanyl rose significantly during period three (aRR=1.44, 95% CI: 1.06, 1.94), four (aRR=1.65, 95% CI: 1.24, 2.20) and five (aRR=1.90, 95% CI: 1.43, 2.53) compared to period one. Risks for smoking heroin and methamphetamine more frequently than injecting these drugs increased across all periods. CONCLUSIONS: Opioid and methamphetamine injection declined precipitously, with notable increases in smoking these drugs. Research is needed to understand the health consequences of these trends.

Bedside urine testing for fentanyl in self-reported heroin users in a tertiary Brisbane emergency department.

OBJECTIVE: To determine if patients presenting to our toxicology unit following self-reported heroin use had positive urine immunoassay testing for fentanyl or its analogues. METHODS: Urine samples from consenting patients were tested at the bedside for the presence of opiates or fentanyl and its analogues. RESULTS: Over a 30-month period, 58 patients were recruited. All samples tested positive for opiates, but none tested positive for fentanyl or its analogues. CONCLUSION: In patients presenting to our toxicology unit in Brisbane, we did not find any cases where the urine of patients self-reporting heroin exposure tested positive for fentanyl or its analogues.

Ultrasound guided quadratus lumborum block versus interlaminar epidural block for analgesia in pediatric abdominal surgery: a randomized controlled trial.

BACKGROUND: Although the efficacy and safety of epidural block (EB) are fairly high, complications such as inadvertent dural puncture may limit its use. Ultrasound-guided quadratus lumborum block (QLB) is a relatively new regional technique that provides perioperative somatic and visceral analgesia for pediatric patients. This trial compared the quality of pain relief in pediatric patients undergoing abdominal surgery who received either QLB or EB. METHODS: Patients were randomly allocated into two equal groups: Group E(n = 29): received EB; Group QL(n = 29): received QLB. Both groups were injected with 0.25% bupivacaine (0.5 ml/kg). Assessment of total analgesia consumption was the primary outcome measure, whereas the secondary outcome measures were assessment of postoperative analgesic effect by Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and time of first analgesic request. RESULTS: Our study showed that the mean total fentanyl consumption was comparable between both groups(38.67 ± 5.02 and 36.47 ± 5.13 µg in the E and QL groups, respectively, P = 0.246). Only five patients did not require rescue analgesia (3 in the E group,2 in the QL group, P = 0.378). The mean duration of analgesia showed no significant difference between the two groups (9.9 ± 1.58 and 11.02 ± 1.74 h in the E and QL groups, respectively, P = 0.212). Evaluation of CHEOPS score values immediately in PACU and for the initial 24 h following operation showed no significant difference between the two study groups(P > 0.05). CONCLUSION: QLB can achieve analgesic effects comparable to those of EB as a crucial part of multimodal analgesia in children undergoing abdominal surgeries. CLINICAL TRIAL REGISTRATION NUMBER: PACTR202203906027106.

Innovation and adaptation: The rise of a fentanyl smoking culture in San Francisco.

BACKGROUND: Illicitly manufactured fentanyls and stimulants are implicated in the escalating US mortality from drug overdose. San Francisco, California (SF) has seen declining fentanyl injection while smoking has increased. Beliefs and behaviors surrounding this development are not well understood. METHODS: The study used rapid ethnography to explore fentanyl and methamphetamine use in SF. The team conducted semi-structured interviews (n = 34) with participants recruited from syringe service programs. Video-recorded smoking sequences (n = 12), photography and daily field notes supplemented interview data. RESULTS: Difficulty injecting and fear of overdose motivated transitions from injecting to smoking. Fentanyl was extremely cheap-$10/gram-with variability in quality. Foil was the most commonly used smoking material but glass bubbles, bongs and dabbing devices were also popular. No reliable visible methods for determining fentanyl quality existed, however, participants could gauge potency upon inhalation, and developed techniques to regulate dosage. Several participants reported at least hourly use, some reporting one or more grams of daily fentanyl consumption. Smoking was also very social, with people sharing equipment, drugs and information. Participants raised concerns about hygiene and overdose risk to others arising from shared equipment. Reportedly potent fentanyl 'residue' accumulated on smoking materials and was commonly shared/traded/stolen or consumed accidentally with diverse preferences for its use. CONCLUSION: Our data highlight fentanyl residue as a new overdose risk with potential mismatch between the potency of the residual drug and the recipient's tolerance. Further, large doses of fentanyl are being consumed (estimated at approximately 50 mg of pure fentanyl/day). Smoking fentanyl has potential health benefits over injecting and may be protective against overdose, but substantial uncertainty exists. However, SF overdose mortality hit a record high in 2023. Recommendations to reduce fentanyl smoking overdose risks through pacing, greater awareness of dosages consumed and checking tolerance of residue recipients are potentially viable interventions deserving further exploration.

Mitigating Medication Tampering and Diversion via Real-Time Intravenous Opioid Quantification.

Opioid tampering and diversion pose a serious problem for hospital patients with potentially life-threatening consequences. The ongoing opioid crisis has resulted in medications used for pain management and anesthesia, such as fentanyl and morphine, being stolen, substituted with a different substance, and abused. This work aims to mitigate tampering and diversion through analytical verification of the administered drug before it enters the patient. We present an electrochemical-based sensor and miniaturized wireless potentiostat that enable real-time intravenous (IV) monitoring of opioids, specifically fentanyl and morphine. The proposed system is connected to an IV drip system during surgery or post-operation recovery. Measurement results of two opioids are presented, including calibration curves and data on the sensor performance concerning pH, temperature, interference, reproducibility, and long-term stability. Finally, we demonstrate real-time fluidic measurements connected to a flow cell to simulate IV administration and a blind study classified using a machine-learning algorithm. The system achieves limits of detection (LODs) of 1.26 µg/mL and 2.75 µg/mL for fentanyl and morphine, respectively, while operating with >1-month battery lifetime due to an optimized ultra-low power 36 µA sleep mode.