Comparison of dexmedetomidine and opioids as local anesthetic adjuvants in patient controlled epidural analgesia: a meta-analysis.

BACKGROUND: Data on the efficacy and incidence of adverse effects associated with dexmedetomidine (DEX) as a local anesthetic adjuvant for patient-controlled epidural analgesia (PCEA) are inconclusive. This meta-analysis assessed the efficacy and risks of DEX for PCEA using opioids as a reference. METHODS: Two researchers independently searched PubMed, Embase, Cochrane Library, and China Biology Medicine for randomized controlled trials comparing DEX and opioids as local anesthetic adjuvants in PCEA. RESULTS: In total, 636 patients from seven studies were included in this meta-analysis. Postoperative patients who received DEX had lower visual analog scale (VAS) scores than those who received opioids at 4-8 h (mean difference [MD]: 0.61, 95% CI [0.45, 0.76], P < 0.001, I2 = 0%), 12 h (MD: 0.85, 95% CI [0.61, 1.09], P < 0.001, I2 = 0%), 24 h (MD: 0.59, 95% CI [0.06, 1.12], P = 0.030, I2 = 82%), and 48 h (MD: 0.54, 95% CI [0.05, 1.02], P = 0.030, I2 = 91%). Additionally, patients who received DEX had a lower incidence of itching (odds ratio [OR]: 2.86, 95% CI [1.18, 6.95], P = 0.020, I2 = 0%) and nausea and vomiting (OR: 6.83, 95% CI [3.63, 12.84], P < 0.001, I2 = 24%). In labor analgesia, no significant differences in neonatal (pH and PaO2 of cord blood, fetal heart rate) or maternal outcomes (duration of labor stage, mode of delivery) were found between the DEX and opioid groups. CONCLUSIONS: Compared with opioids, using DEX as a local anesthetic adjuvant in PCEA improved postoperative analgesia and reduced the incidence of itching and nausea and vomiting without increasing the incidence of adverse events.

Dexamethasone and dexmedetomidine as adjuvants to ropivacaine do not prolong analgesia in wound infiltration for lumbar spinal fusion: a prospective randomized controlled study.

BACKGROUND AND OBJECTIVES: Local anesthetics (LAs) are widely used to infiltrate into surgical wounds for postoperative analgesia. Different adjuvants like dexamethasone and dexmedetomidine, when added to LA agents, could improve and prolong analgesia. The aim of this trial was to evaluate the analgesic efficacy and opioid-sparing properties of dexamethasone and dexmedetomidine when added to ropivacaine for wound infiltration in transforaminal lumbar interbody fusion (TLIF). METHODS: We conducted a controlled study among 68 adult patients undergoing TLIF, which was prospective, randomized and double-blind in nature. The participants were divided into four equal groups at random. Group R was given 150 mg of 1% ropivacaine (15 mL) and 15 mL of normal saline. Group R + DXM received 150 mg of 1% ropivacaine (15 mL) and 10 mg of dexamethasone (15 mL). Group R + DEX received 150 mg of 1% ropivacaine (15 mL) and 1 µg/kg of dexmedetomidine (15 mL). Lastly, group R + DXM + DEX was given 150 mg of 1% ropivacaine (15 mL), 10 mg of dexamethasone and 1 µg/kg of dexmedetomidine (15 mL). The primary focus was on the length of pain relief provided. Additionally, secondary evaluations included the amount of hydromorphone taken after surgery, the numerical rating scale and safety assessments within 48 h after the operation. RESULTS: Based on the p value (P > 0.05), there was no significant variance in the duration of pain relief or the total usage of hydromorphone after surgery across the four groups. Similarly, the numerical rating scale scores at rest and during activity at 6-, 12-, 24- and 48-h post-surgery for all four groups showed no difference (P > 0.05). However, the incidence of delayed anesthesia recovery was slightly higher in group R + DEX and group R + DXM + DEX when compared to group R or group R + DXM. Furthermore, there were no significant differences between the four groups in terms of vomiting, nausea, dizziness or delayed anesthesia recovery. CONCLUSION: For wound infiltration in TLIF, the addition of dexamethasone and dexmedetomidine to ropivacaine did not result in any clinically significant reduction in pain or opioid consumption and could prompt some side effects.

Comparison of Caudal Dexmedetomidine and Midazolam as an Adjuvant to Ropivacaine for Postoperative Pain Relief in Children Undergoing Infra-Umbilical Surgeries: A Randomized Controlled Trial.

BACKGROUND: We explored the analgesic efficacy of two non-opioid adjuvants (midazolam and dexmedetomidine) with ropivacaine in children undergoing infraumbilical surgeries. METHODS: In this parallel group randomized controlled trial, 135 children aged between 2 and 8 years were recruited. Children were randomly allocated to one of three groups: RD received 1 mL/kg of ropivacaine (0.2%) with dexmedetomidine 1 µg/kg, RM received 1 mL/kg of ropivacaine (0.2%) with midazolam 30 µg/kg, and R received 1 mL/kg of ropivacaine (0.2%) with 1 mL normal saline. The primary outcome of the present study was to determine the duration of postoperative analgesia. Secondary outcomes were assessing postoperative face, leg, activity, cry, consolability (FLACC) pain score, rescue analgesics, hemodynamics, sedation scores, and adverse effects. RESULTS: The analgesia duration was significantly prolonged in the RD and RM group (600.0 [480.0-720.0] minutes and 600.0 [480.0-720.0] minutes, respectively) compared to the R group 360.0 (300.0-480.0) minutes (P < 0.001). The FLACC score was comparatively higher in the R group compared to the RD and RM groups postoperatively. Time for the first rescue analgesia was more prolonged in RD and RM groups when compared with the R group. Postoperative sedation was higher in the RM group up to 120 minutes postoperatively compared to the RD and R groups. CONCLUSION: The combination of dexmedetomidine or midazolam with local anesthetics significantly increases the analgesia duration while minimizing adverse effects.

Effects of anesthetic adjunctive agents on postoperative cognitive dysfunction in elderly patients undergoing noncardiac surgery: A Bayesian network meta-analysis.

BACKGROUND: Elderly patients are prone to postoperative cognitive dysfunction (POCD). The comparison of the effects of anesthetic adjuvant drugs on POCD in elderly patients undergoing noncardiac surgery remains controversial. METHODS: The final search took place on June 10, 2023. Randomized controlled trials including ketamine, ulinastatin, dexmedetomidine, parecoxib, and midazolam on the prevention and treatment of POCD in elderly undergoing noncardiac surgery were collected. A Bayesian network meta-analysis was performed to quantitatively combine the evidence. RESULTS: A total of 35 randomized trials were finally included in this systematic review, and the overall risk of bias is Allocation concealment. These anesthetic adjuvant drugs did not show significant differences in preventing POCD on postoperative days 1 and 7 compared with each other, but ulinastatin may be more effective in preventing POCD than dexmedetomidine [odds ratio (OR) = 0.28, 95% confidence interval (CI) = (0.10, 0.71)] and parecoxib [OR = 0.3, 95% CI = (0.10, 0.82 on postoperative day 3. The efficiency ranking results also find that ulinastatin and ketamine might provide better effects regarding POCD prevention. CONCLUSIONS: Ketamine and ulinastatin might have better effects in preventing POCD in elderly patients undergoing noncardiac surgery. Our meta-analysis provided evidence for the use of ulinastatin and ketamine in the prevention of POCD in elderly patients undergoing noncardiac surgery.

Comparison of intravenous and perineural dexmedetomidine in prolongation of analgesia for peripheral nerve block: a meta-analysis and systematic review.

OBJECTIVE: We conducted a meta-analysis and systematic review to compare the efficacy of perineural vs. intravenous dexmedetomidine as local anesthetic adjuvant. MATERIALS AND METHODS: Two researchers searched MEDLINE, OVID, PubMed, Embase, Cochrane Central, Web of Science and Wanfang data for randomized controlled trials comparing the effect of intravenous vs. perineural injection of dexmedetomidine as a local anesthetic adjuvant in prolongation of analgesia for peripheral nerve block, without any language restrictions. RESULTS: We identified 14 randomized controlled trials. The results revealed that the duration of analgesia [Standard mean difference (SMD): -0.55, 95% CI, (-1.05, -0.05) p=0.032, I2=85.4%] and the duration of sensory block [SMD: -2.68, 95% CI, (-4.53, -0.83) p=0.004, I2=97.3%], were significantly longer, the onset time of motor block [SMD: 0.65, 95% CI, (0.02, 1.27) p=0.043, I2=85.0%] was shorter in the perineural dexmedetomidine group, when compared with the systematic dexmedetomidine group. There was no significant difference in the duration of motor block [SMD: -0.32, 95% CI, (-1.11, -0.46) p=0.416, I2=89.8%] and the onset time of sensory block [SMD: 0.09, 95% CI, (-0.33, 0.52) p=0.668, I2=59.9%] between the two groups. Meanwhile, perineural dexmedetomidine reduced analgesic consumption in 24 hours [SMD: 0.43, 95% CI, (0.06, 0.80) p=0.022, I2=58.7%] compared with the intravenous dexmedetomidine group. CONCLUSIONS: Our meta-analysis currently generates the evidence that perineural dexmedetomidine administration offers advantages not only in prolonging the duration of analgesia and sensory block, but also in shortening the onset time of motor block, when compared with the intravenous administration.

α-2 agonists vs. fentanyl as adjuvants for spinal anesthesia in elective cesarean section: a meta-analysis.

INTRODUCTION: Elective cesarean section (CS) is usually performed using spinal anesthesia (SA), which requires the use of local anesthetic (LA) agents, commonly combined with adjuvant drugs. We performed a systematic review and meta-analysis aimed at studying the advantages of α-2 agonists as compared to fentanyl during SA for CS. EVIDENCE ACQUISITION: We screened PubMed and EMBASE for randomized controlled trials (RCTs). We calculated the mean difference (MD) for continuous outcomes, and the relative risk for dichotomous outcomes, using a random-effect model with 95% confidence interval (CI). We performed a Trial Sequential Analysis (TSA) assuming an alpha risk of 5%. The primary outcome was the time to first rescue analgesia. EVIDENCE SYNTHESIS: Eight RCTs were included. Time to first rescue analgesia was significantly longer when the α-2 agonists were used (MD 85.9 min [95% CI: 23.8, 147.9]; P=0.007). Duration of sensory block was also longer in the α-2 group (MD 40.5 [95% CI: 20.21,60.7]; P<0.0001), while no differences were found for onset of sensory block and onset and duration of motor block. Rates of shivering and nausea or vomiting were significantly lower in the α-2 agonist group, while risk of hypotension or respiratory depression were not different. The TSA on the primary outcome suggests the need of further research before drawing conclusions. CONCLUSIONS: α2-agonists seem to increase the time to first rescue analgesia and to prolong the duration of sensory block when used as adjuvants to LA in CS patients compared to fentanyl. Also, α2-agonists may reduce the incidence of shivering and nausea or vomiting.

Anestesia multimodal para ressecção de tumor cerebral com monitorização eletroneurofisiológica: relato de caso / Multimodal anesthesia for brain tumor resection with electroneurophysiological monitoring: case report

Introdução: O monitoramento neurofisiológico intraoperatório (MNIO) é uma técnica valiosa, empregada durante procedimentos neurocirúrgicos complexos. Ao monitorar continuamente as vias neurais, o MNIO fornece feedback em tempo real aos cirurgiões durante o procedimento, permitindo tomada de decisões críticas e redução do risco de déficits neurológicos. O papel do anestesiologista na identificação e correção dos fatores de risco modificáveis é fundamental para a prevenção de lesões neurológicas e otimização dos resultados. Sendo assim, a compreensão das limitações do MNIO e das evidências que orientam seu uso é de fundamental importância. Objetivo: Descrever o manejo de uma anestesia multimodal, realizada em conjunto com a equipe de neurofisiologia, para ressecção de um tumor cerebral recidivante e o seu desfecho clinico. Método: Trata-se de relato de caso atendido no Hospital do Servidor Público Municipal de São Paulo. Os dados para realização deste trabalho foram coletados durante a cirurgia, sendo a coleta autorizada pelo paciente por meio da assinatura de termo de consentimento livre e esclarecido. Relato do Caso: Paciente, sexo masculino, 64 anos, ASA II, hipertenso, com história prévia de meningioma atípico, submetido a neurocirurgia e radioterapia em 2021, em uso de anticonvulsivante oral para profilaxia de crises convulsivas. Apresenta lesão tumoral cerebral recidivante em região frontal bilateral. Após a indução anestésica, foi realizada passagem de acesso venoso central em veia jugular interna direita com auxílio de ultrassonografia, monitoração da pressão arterial invasiva após cateterização de artéria radial direita, sondagem vesical de demora, termômetro esofágico, otimização do posicionamento na mesa cirúrgica, índice bispectral e Scalp Block com 20 ml de ropicavaína a 0,375%. Realizou- se manutenção da anestesia com propofol (4-6 mg/kg/h) e remifentanil (0,1 mcg/kg/min) em infusão contínua associado a dexmedetomidina (0,2-0,6 mcg/kg/h) mantendo valores do índice bispectral entre 40-60. As respostas dos potenciais evocados foram obtidas nas extremidades superiores e inferiores durante todo o procedimento pela equipe de neurofisiologia. Durante a manipulação tumoral, foi detectada queda superior a 40% do potencial evocado motor em dimídio corporal esquerdo, e emitido o alerta à equipe cirúrgica. Nenhuma outra intercorrência foi registrada durante o procedimento. Conclusões: Propofol, dexmedetomidina, lidocaína, opioides e anestésicos voláteis potentes de baixa dosagem (menos de 0,5 CAM) associado a técnicas de bloqueios periféricos, fornecem condições compatíveis com monitoramento neurofisiológico intraoperatório. O MNIO contínuo é um complemento indispensável no período perioperatório para pacientes com alto risco de desenvolver complicações neurológicas. Os anestesistas devem fornecer um meio fisiológico e anestésico estável para facilitar a interpretação significativa das mudanças de sinal e precisa orientação cirúrgica. Palavras-chave: Adjuvantes Anestésicos. Potenciais Evocados. Neurocirurgia. Monitorização Neurofisiológica Intraoperatória.

A Review of the Biological Mechanisms of Dexmedetomidine for Postoperative Neurocognitive Disorders.

Postoperative neurocognitive disorders are common neurological complications following surgery that are generally characterized by varying degrees of cognitive impairment. Postoperative neurocognitive disorders can exhibit as short-term postoperative delirium and/or long-term postoperative cognitive dysfunction. In addition, postoperative neurocognitive disorders may result in poor outcomes in patients, and are a leading cause of postoperative morbidity and mortality, particularly in elderly patients. Recently, there has been a heightened interest in mechanisms and clinical treatments for postoperative neurocognitive disorders. Though some influencing factors and mechanisms of postoperative neurocognitive disorders have been revealed, they remain troublesome problems in clinical departments. Dexmedetomidine is a commonly used anesthetic adjuvant that may help improve postoperative cognitive impairment, especially the conditions of a postoperative acute event (postoperative delirium, within 1 week after operation) and delayed neurocognitive recovery (postoperative cognitive dysfunction, up to 30 days). In the recent literature, dexmedetomidine has been shown to exert positive effects on cognitive impairment in clinical and animal studies, especially for postoperative neurocognitive disorders. However, not all clinical findings support this efficacy. Though some mechanisms of dexmedetomidine on postoperative neurocognitive disorders have been proposed, such as signaling pathways associated with inflammation and apoptosis, this evidence is fragmentary and disputed in the literature. Therefore, this article aims to review the potential biological mechanisms underlying dexmedetomidine's effects on postoperative neurocognitive disorders, providing a reference for future studies.

Review of benefits and adverse effects of the most commonly used local anesthetic adjuvants in peripheral nerve blocks.

Recently, peripheral nerve blocks are extensively applied for many patients undergoing surgical or nonsurgical analgesia. However, the effectiveness is limited by the duration of action of local anesthetics. Therefore, the application of adding local anesthetic adjuvants is evolved to prolong the duration of analgesia and decrease the concentration of local anesthetics in peripheral nerve blocks. There are many local anesthetic adjuvants available such as morphine, fentanyl, sufentanil, hydromorphone, and buprenorphine, dexmedetomidine, dexamethasone, midazolam, and magnesium sulfate. Most of them are safe and possess little adverse effects, while none of them is acknowledged by the food and drug administration. Therefore, this review is aimed to delineate benefits and adverse effects for clinical anesthesia.

Characterizing the Heart Rate Effects From Administration of Sugammadex to Reverse Neuromuscular Blockade: An Observational Study in Patients.

BACKGROUND: Reversal of neuromuscular blockade (NMB) with sugammadex can cause marked bradycardia and asystole. Administration of sugammadex typically occurs in a dynamic period when anesthetic adjuvants and gas concentrations are being titrated to achieve emergence. This evaluation examined the heart rate (HR) responses to sugammadex to reverse moderate to deep NMB during a steady-state period and sought mechanisms for HR changes. METHODS: Patients with normal sinus rhythm, who were undergoing elective surgery that included rocuronium for NMB, were evaluated. After surgery, while at steady-state surgical depth anesthesia with sevoflurane and mechanical ventilation, patients received either placebo or 2 or 4 mg/kg of sugammadex to reverse moderate to deep NMB. Study personnel involved in data analysis were blinded to treatment. Continuous electrocardiogram (ECG) was recorded from the 5 minutes before and 5 minutes after sugammadex/placebo administration. R-R intervals were converted to HR and averaged in 1-minute increments. The maximum prolongation of an R-R interval after sugammadex was converted to an instantaneous HR. RESULTS: A total of 63 patients were evaluated: 8 received placebo, and 38 and 17 received 2 and 4 mg/kg sugammadex. Age, body mass index, and patient factors were similar in groups. Placebo did not elicit HR changes, whereas sugammadex caused maximum instantaneous HR slowing (calculated from the longest R-R interval), ranging from 2 to 19 beats/min. There were 7 patients with maximum HR slowing >10 beats/min. The average HR change and 95% confidence interval (CI) during the 5 minutes after 2 mg/kg sugammadex were 3.1 (CI, 2.3-4.1) beats/min, and this was not different from the 4 mg/kg sugammadex group (4.1 beats/min [CI, 2.5-5.6]). HR variability derived from the standard deviation of consecutive R-R intervals increased after sugammadex. CONCLUSIONS: Sugammadex to reverse moderate and deep NMB resulted in a fast onset and variable magnitude of HR slowing in patients. A difference in HR slowing as a function of dose did not achieve statistical significance. The observational nature of the investigation prevented a full understanding of the mechanism(s) of the HR slowing.

A Comprehensive Review of the Use of Alpha 2 Agonists in Spinal Anesthetics.

BACKGROUND: Spinal Anesthesia was the first regional anesthetic technique to be performed. It was performed by Dr. August Bier, known for the Bier block, and his colleagues on August 16, 1898. Dr. Bier opted for, what he referred to at the time as "cocainization of the spinal cord" by introducing 15 mg of cocaine intrathecally prior to the operation. The surgery was largely uneventful and painless. The patient only experienced some vomiting and a headache postoperatively. Dr. Bier's use of neuraxial anesthesia aimed to directly inject local anesthetics in and around the central nervous system (CNS) for more direct control of pain and anesthesia. Local anesthetics were an important discovery in anesthesiology. However, since the advent of local anesthetics and spinal anesthesia as an alternative technique to general anesthesia, much has been learned about both the benefits and adverse effects of local anesthetics. It was quickly learned that use of local anesthetics would be limited by their potential for life-threatening toxic effects. For this reason, there was a push towards development of novel local anesthetics that had a larger therapeutic window with less likelihood of serious side effects. In addition to developing newer local anesthetics, the idea of adding adjuvants provided an opportunity to potentially limit the life-threatening events. These adjuvants would include medications such as epinephrine and alpha-2 agonists, such as clonidine and dexmedetomidine. Other adjuvants include opioids, glucocorticoids, and mineralocorticoids. OBJECTIVES: In this review, we will delve further into the indications, contraindications, uses, mechanisms, and future of spinal anesthesia and its adjuvants. STUDY DESIGN: A literature review of recent publications in the field of alpha 2 agonists used in spinal anesthetics was carried out from 2015 to present day. Consensus opinions were formulated in various areas. SETTING: This literature review was carried out at various medical universities throughout the nation and Europe. LIMITATIONS: As research has only just begun in this field data is limited at this time. CONCLUSIONS: The use of spinal anesthesia provides a reliable dermatome blockade to facilitate many different surgical procedures. The combination of local anesthetics with opioid medications within the subarachnoid space has been the standard of care. Adjuvant medications like alpha 2 agonists may play a significant role in prolonging spinal blockade as well as limiting cardiovascular complications such as hypotension and bradycardia. The use of alpha 2 agonists instead of opioid medications intrathecally decreases pruritus and delayed respiratory depression. Animal models have demonstrated the synergistic effects of utilizing alpha 2 agonists with opioids in the subarachnoid space. The addition of clonidine to fentanyl and local anesthetic demonstrated a shorter time to neural blockade, but no significant change in duration of the spinal. Interestingly alpha 2 agonists with local anesthetics showed increase block duration compared to opioid with local anesthetics. Further human trials need to be undertaken to analyze the effectiveness of alpha 2 agonists in the intrathecal space, but preliminary data does indicate it is an exemplary alternative to opioids.

Evaluation of the Efficacy of Dexmedetomidine as a Local Anesthetic Adjuvant in Children: A Meta-Analysis of Randomized Controlled Trials.

Dexmedetomidine has been identified as a useful adjunct to improve the effect of nerve blocks in adults; however, its effect for children has not yet been fully investigated. This meta-analysis aimed to evaluate the reliability and efficacy of dexmedetomidine as a local anesthetic adjunct for pediatric surgeries. Eligible studies were searched in Cochrane, Embase, PubMed, and CBM. RevMan 5.4 was used to assess the risk of bias of each study and perform statistical analysis. Stata 15.0 was used to evaluate the publication bias of primary outcomes. Thirteen randomized controlled trial (RCTs) involving 722 patients aged 6 months to 12 years were harvested. Statistical analysis showed that dexmedetomidine resulted in: a significantly longer duration of analgesia (standardized mean difference [SMD], 7.16; 95% confidence interval [95%CI], 4.88 to 9.43; P < .001; I2  = 98%); a reduction in the 1-hour pain score (mean difference [MD], -0.27; 95%CI, -0.47 to -0.06; P = .01; I2  = 28%); cumulative doses of rescue analgesic required of 2 doses (risk ratio [RR], 0.26; 95%CI, 0.14 to 0.49; P < .001; I2  = 0) or 3 doses (RR, 0.04; 95%CI, 0.01 to 0.16; P < .001; I2  = 4%); the frequency of emergence agitation (RR, 0.44; 95%CI, 0.22 to 0.91; P = .03; I2  = 0); and a reduction in the onset time of blocks (mean difference -3.56; 95%CI, -6.39 to -0.74; P = .01; I2  = 90%). However, the incidence of some side effects, including hypotension, bradycardia, nausea and vomiting, pruritis, urinary retention, and respiratory depression, did not significantly differ between the dexmedetomidine group and the placebo group. Therefore, dexmedetomidine is a reliable and efficient adjunct to local anesthetics in children.

Patient and Caregiver Experiences With and Perceptions of Risk Evaluation and Mitigation Strategy Programs With Elements to Assure Safe Use.

Importance: The US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to impose safety requirements on drugs with important risks, such as prescriber certification or routine laboratory testing, to ensure that the benefits of use outweighed the risks. However, little is known about patient and caregiver experiences with these Risk Evaluation and Mitigation Strategy (REMS) programs with Elements to Assure Safe Use (ETASU). Objective: To understand patient and caregiver experiences with and perceptions of REMS programs with ETASU. Design, Setting, and Participants: This qualitative study included semistructured qualitative phone interviews conducted between 2016 and 2017, with initial analysis performed in 2017 and reanalysis performed in 2021. Adult patients prescribed natalizumab or sodium oxybate, adult patients or caregivers of adult patients prescribed vigabatrin, and adult female patients of reproductive age prescribed riociguat were included. Main Outcomes and Measures: Assessment of knowledge, decision-making, medication access, and perceptions of medical privacy. Results: Among 63 participants, 46 (73%) were female. Twenty-five participants (40%) had taken natalizumab, 10 (16%) riociguat, 15 (24%) sodium oxybate, and 10 (16%) vigabatrin. One participant had taken both natalizumab and vigabatrin; 4 (6%) were caregivers of patients using vigabatrin. Most participants expressed knowledge of REMS program requirements, but many lacked the insight that these requirements were part of an FDA-mandated special safety program and expressed difficulty understanding program education materials. REMS requirements made some participants more likely to initiate treatment. However, many reported burdens accessing medication, including the need to travel to certified prescribers or pharmacies. Manufacturer access to personal health information was also controversial, although some participants expressed an altruistic desire to assist others. Conclusions and Relevance: This qualitative study found that REMS programs with ETASU reassured patients and their caregivers about drug safety and helped support medication initiation. However, steps are needed to improve the quality of REMS educational materials, promote efficient medication access, and protect patient privacy.

Efficacy of Nalbuphine as a Local Anesthetic Adjuvant for Brachial Plexus Block: A Systematic Review and Meta-analysis.

BACKGROUND: Nalbuphine has been increasingly used as a local anesthetic adjuvant to extend the duration of analgesia in brachial plexus block (BPB). OBJECTIVES: To systematically and firstly evaluate the available evidence on the efficacy of nalbuphine as an adjuvant to local anesthetics in BPB. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Cochrane Central Register of Controlled Clinical Trials, Cochrane Database of Systematic Reviews, Medline, Embase, Scopus, Web of Science, EBSCO, PubMed, and additional databases were searched. Randomized controlled trials comparing combination of perineural nalbuphine with local anesthetics to local anesthetics alone in BPB for upper extremity surgical procedures were eligible for inclusion. RESULTS: Nineteen randomized controlled trials involving 1,355 patients met the inclusion criteria. Perineural use of nalbuphine prolonged the duration of analgesia in BPB (mean difference [MD], 162.5; 95% confidence interval [CI], 119.0 to 205.9; P < 0.00001; very low quality of evidence). The duration of sensory block was also extended (MD, 141.6; 95% CI, 100.3 to 182.9; P < 0.00001; very low quality of evidence). Furthermore, nalbuphine shortened the onset time of sensory block (MD, -2.6; 95% CI, -3.6 to -1.5; P < 0.00001; very low quality of evidence). There were no significant differences in side effect-related outcomes, including nausea (risk radio [RR], 1.56; 95% CI, 0.82 to 2.59; P = 0.17; moderate quality of evidence) and vomiting (RR, 1.41; 95%  CI, 0.66 to 3.02; P = 0.38; moderate quality of evidence). LIMITATIONS: The study was limited by substantial heterogeneity, a relatively small sample size and difference-in-differences in how outcomes of interest were described and assessed. CONCLUSIONS: Perineural use of nalbuphine in BPB is an effective strategy for analgesia in adult patients undergoing upper extremity surgery.

Prospective real-time evaluation of the QTc interval variation after low-dose droperidol among emergency department patients.

OBJECTIVE: To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the emergency department. METHODS: Prospective cohort study of patients aged ≥12 years of age who received low-dose droperidol (≤ 2.5 mg) for indications other than acute behavioral disturbances. QTc intervals were monitored in real-time during pre-specified observation periods in the ED. Primary outcome was variation of QTc interval after droperidol administration, defined as the maximum delta (change) of QTc interval. Other outcomes included proportion of patients with a QTc ≥ 500 ms after droperidol, delta ≥ +60 ms, and incidence of clinical adverse events. Patients were monitored up to 30 min after IV bolus and up to 46 min after infusion. RESULTS: A total of 68 patients were included (mean age 42.1 years, 66.2% females). The median dose of droperidol was 1.875 mg (range 0.625 mg, 2.5 mg) and 94.1% received droperidol for headache management. Most patients received droperidol as a 2-min bolus (n = 41, 60.3%). The mean maximum delta of QTc interval after droperidol across all 68 patients was +29.9 ms (SD 15). A total of 12 patients (17.6%) experienced a QTc interval ≥ 500 ms during the observation period after droperidol, and 3 patients (4.4%) had a delta QTc ≥ +60 ms. There were no serious arrhythmias, such as TdP, or deaths among the 68 participants in this study (0/68). However, 13.2% (n = 9) had at least one non-serious adverse event including restlessness and/or anxiety. CONCLUSION: The QTc interval slightly increased after droperidol administration, but these prolongations were brief, mostly below 500 msec and did not lead to serious arrhythmias. The yield of continuous cardiac monitoring in patients receiving low doses of droperidol is likely low.

Cardiac Output Assessments in Anesthetized Children: Dynamic Capnography Versus Esophageal Doppler.

BACKGROUND: The objective of this study was to compare esophageal Doppler cardiac output (COEDM) against the reference method effective pulmonary blood flow cardiac output (COEPBF), for agreement of absolute values and ability to detect change in cardiac output (CO) in pediatric surgical patients. Furthermore, the relationship between these 2 methods and noninvasive blood pressure (NIBP) parameters was evaluated. METHODS: Fifteen children American Society of Anesthesiology (ASA) I and II (median age, 8 months; median weight, 9 kg) scheduled for surgery were investigated in this prospective observational cohort study. Baseline COEPBF/COEDM/NIBP measurements were made at positive end-expiratory pressure (PEEP) 3 cm H2O. PEEP was increased to 10 cm H2O and COEPBF/COEDM/NIBP was recorded after 1 and 3 minutes. PEEP was then lowered to 3 cm H2O, and all measurements were repeated after 3 minutes. Finally, 20-µg kg-1 intravenous atropine was given with the intent to increase CO, and all measurements were recorded again after 5 minutes. Paired recordings of COEDM and COEPBF were examined for agreement and trending ability, and all parameters were analyzed for their responses to the hemodynamic challenges. RESULTS: Bias between COEDM and COEPBF (COEDM - COEPBF) was -17 mL kg-1 min-1 (limits of agreement, -67 to +33 mL kg-1 min-1) with a mean percentage error of 32% (95% confidence interval [CI], 25-37) and a concordance rate of 71% (95% CI, 63-80). The hemodynamic interventions caused by PEEP manipulations resulted in significant decrease in COEPBF absolute numbers (155 mL kg-1 min-1 [95% CI, 151-159] to 127 mL kg-1 min-1 [95% CI, 113-141]) and a corresponding relative decrease of 18% (95% CI, 14-22) 3 minutes after application of PEEP 10. No corresponding decreases were detected by COEDM. Mean arterial pressure showed a relative decrease with 5 (95% CI, 2-8) and 6% (95% CI, 2-10) 1 and 3 minutes after the application of PEEP 10, respectively. Systolic arterial pressure showed a relative decrease of 5% (95% CI, 2-10) 3 minutes after application of PEEP 10. None of the recorded parameters responded to atropine administration except for heart rate that showed a 4% relative increase (95% CI, 1-7, P = .02) 5 minutes after atropine. CONCLUSIONS: COEDM was unable to detect the reduction of CO cause by increased PEEP, whereas COEPBF and to a minimal extent NIBP detected these changes in CO. The ability of COEPBF to react to minor reductions in CO, before noticeable changes in NIBP are seen, suggests that COEPBF may be a potentially useful tool for hemodynamic monitoring in mechanically ventilated children.

Comparison of Two Experimental Mouse Dry Eye Models through Inflammatory Gene Set Enrichment Analysis Based on a Multiplexed Transcriptomic Approach.

The goal of this study was to explore the specific signaling pathways related to inflammation in two experimental mouse dry eye (EDE) models. Female C57BL/6 mice housed for 10 days in a controlled desiccative environment were either treated with scopolamine (EDE-1; n = 18) or subjected to extraorbital lacrimal gland excision bilaterally (EDE-2; n = 10). Non-induced mice (n = 20) served as healthy controls. A corneal fluorescein staining (CFS) scoring was used at baseline through to day (D) 10 to evaluate epitheliopathy. At D10, corneas and conjunctivas were collected for multiplexed transcriptomic analysis with the NanoString® mouse inflammatory CodeSet. Both EDE-1 and EDE-2 mice presented a change in corneal integrity, with a significant increase in CFS scores at D10. More gene transcripts were identified in EDE-2 compared with EDE-1 (116 vs. 96, respectively), and only a few were common to both models, 13 for the cornea and 6 for the conjunctiva. The gene functional annotation analysis revealed that the same inflammatory pathways were involved in both models. Comparative profiling of gene expression in the two EDE models leads to the identification of various targets and signaling pathways, which can be extrapolated to and confirmed in human disease.

Comparison of epidural, spinal, and saddle block for holmium laser enucleation of prostate (HoLEP): A prospective randomized, comparative study.

BACKGROUND: Holmium laser enucleation of the prostate (HoLEP) has become an important treatment modality for benign prostate hypertrophy. The aim of the present study was to compare regional anesthesia methods for HoLEP operation and to determine the optimal technique. METHODS: Sixty patients with American Society of Anesthesiologists scores of I-III were randomly allocated into 3 groups. Patients in group E received an epidural block with 75 mg of bupivacaine plus 50 µg of fentanyl. In group S, 15 mg of bupivacaine and 50 µg fentanyl were used for spinal anesthesia. In group SA, patients received saddle block with 15 mg of bupivacaine and 50 µg of fentanyl. RESULTS: Time to T10 dermatome block and to maximal level block were longest in group E (P < .05), and maximal sensorial block level was higher in group E than group SA (P < .05). There was a significant difference in postoperative motor block, but no difference in systolic blood pressure and heart rate. CONCLUSION: Among 3 techniques, saddle block might be preferable in HoLEP because an adequate sensorial level was achieved with lower motor block and stable hemodynamics.