Successful and Rapid Reduction in Neurosedative and Analgesic Medications in Complex Infants with Severe Bronchopulmonary Dysplasia After Tracheostomy Placement: Experience with 24-hour Propofol Infusions.

Infants with severe bronchopulmonary dysplasia may require high doses of neurosedative medications to ensure pain control and stability following tracheostomy placement. Subsequent weaning of these medications safely and rapidly is a challenge. We describe a 24-hour propofol infusion to reduce neurosedative medications in 3 high-risk infants following tracheostomy placement.

Oral and topical analgesia in pediatric electrodiagnostic studies.

INTRODUCTION/AIMS: Electrodiagnostic examinations, such as nerve conduction studies (NCS) and needle electromyography (EMG), are perceived as painful by children and their parents/guardians. Methods to reduce peri-procedural pain improve compliance and have neurocognitive and neuropsychiatric benefits. This study aimed to assess the efficacy of combined oral and topical analgesics (COTA), oral analgesics (OA), and placebo in reducing pain during NCS/EMG in children. METHODS: We performed a double-blind, randomized, placebo-controlled trial on children presenting to our neurophysiology lab. Patients were stratified into two age groups (6M-6Y and 7Y-18Y) and randomized into three arms: COTA, OA, and placebo. Pain scores post-NCS/EMG were assessed using the Modified Behavioral Pain Scale (MBPS) and Faces Pain Scale-Revised (FPS-R). RESULTS: One hundred thirteen participants were enrolled. A comparison of participants from both age groups combined revealed no significant differences in guardian FPS-R scores across all arms for NCS and EMG. A significant difference in the distribution of post-NCS FPS-R score severities in children aged 7Y-18Y was noted between OA and placebo (p = .007). EMG was more painful than NCS across all arms (p < .05). In children aged 6M-6Y undergoing at least 10 muscle samplings during EMG, those receiving COTA had significantly lower pain scores (p = .014). DISCUSSION: This study reveals the complexity of pediatric pain perception during NCS/EMG and highlights that other methods to reduce experienced pain are required. Our findings suggest that procedural characteristics, such as number of muscles sampled, may influence the effectiveness of analgesia and serve as a foundation for future research aimed at optimizing pain management strategies.

Effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection: A prospective randomized, double-blind, placebo-controlled study.

AIMS: Esketamine may reduce acute postoperative pain in several settings. However, the effects of low-dose esketamine on postoperative pain after vestibular schwannoma (VS) resection with propofol/remifentanil total intravenous anaesthesia (TIVA) are unclear. The aim of this study is to observe the effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection. METHODS: This single-centre, randomized, placebo-controlled, double-blind trial included 90 adults undergoing VS resection via the retrosigmoid approach with TIVA. The patients were randomly allocated to two groups: esketamine or control (n = 45 in each group). Patients received low-dose esketamine (0.2 mg/kg) or a similar volume of normal saline after dural closure. The primary outcome was the pain score during movement (gentle head movement) at 24 h postoperatively. Secondary outcomes included recovery time, bispectral index (BIS) values and haemodynamic profiles during the first 30 min after esketamine administration, and adverse effects. RESULTS: Low-dose esketamine did not reduce pain scores at rest (P > .05) or with movement (P > .05) within the first 24 h after surgery. Esketamine moderately increased BIS values for at least 30 min after administration (P < .0001) but did not affect heart rate (P = .992) or mean arterial blood pressure (P = .994). Esketamine prolonged extubation time (P = .042, 95% confidence interval: 0.08 to 4.42) and decreased the effect-site concentration of remifentanil at extubation (P = .001, 95% confidence interval: -0.53 to -0.15) but did not affect the time to resumption of spatial orientation. Postoperative nausea and vomiting rates did not differ between groups, and no hallucinations or excessive sedation was observed. CONCLUSION: Intraoperative low-dose esketamine did not significantly reduce acute pain after VS resection with propofol/remifentanil TIVA. However, BIS values increased for at least 30 min after esketamine administration.

The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis.

OBJECTIVES: To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. BACKGROUND: Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear. METHODS: Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096). RESULTS: A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics. CONCLUSIONS: Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.

Functional impairment of chronic migraine with medication overuse: Secondary analysis from the Medication Overuse Treatment Strategy (MOTS) trial.

BACKGROUND: Chronic migraine exerts substantial negative impacts on daily functioning. Efforts to manage impaired functioning may result in medication overuse, which contributes to the worsening profile and chronification of migraine. The Migraine Functional Impact Questionnaire (MFIQ) is a recently developed measure assessing the impact of migraine on physical, social, and emotional function. OBJECTIVE: The objective of this analysis was to assess changes in MFIQ scores following initiation or modification of migraine preventive medication and determine if changes in function are associated with changes in other aspects of migraine burden, such as headache frequency, headache intensity, and symptoms of anxiety and depression. METHODS: This is a secondary analysis of data from the Medication Overuse Treatment Strategy (MOTS) trial, a prospective pragmatic clinical trial that investigated two treatment strategies for those with chronic migraine and medication overuse. Data from both treatment arms were pooled and analyzed using a pre-post design. Prior to and 12 weeks following initiation or modification of migraine preventive medication, participants completed a series of questionnaires that captured migraine characteristics, medication use, migraine-related physical impairment (MFIQ), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire 9 [PHQ-9]) symptoms. Changes from baseline in all measures were assessed using the paired t-test. Relationships between changes in MFIQ scores and other measures were assessed using linear regression. Multivariable modeling was performed to determine which additional variables contributed to the change in MFIQ beyond that already explained by an individual variable. Model terms were selected by using elastic net regularization. Only those participants who completed the baseline and 12-week MFIQ were included in this analysis. RESULTS: Of the 537 patients, 88.2% were female, and the average age was 45 years (standard deviation 13). The mean frequency of days with moderate-to-severe headache improved 39.2% from 13.5 per 30 days at baseline to 8.1 per 30 days at week 12. The mean MFIQ Usual Activities Global score improved by 15.0 points (on a 100-point scale). All five domains (Usual Activities Global, Usual Activities, Social Function, Emotional Function, Physical Function) of the MFIQ improved by a mean of at least 13.0 points. Changes in PHQ-9 score, followed by changes in headache frequency, had the strongest associations with change in all domains of the MFIQ. CONCLUSIONS: The negative impact of chronic migraine with medication overuse on physical, social, and emotional functioning substantially lessened following initiation or modification of migraine preventive medication. Improved functioning, as measured by the MFIQ, was most strongly associated with reductions in depression scores and headache frequency, highlighting the importance of recognizing and monitoring changes in depressive symptoms, in addition to headache frequency and functional impairment, when evaluating response to preventive medications.

Comparison of Nebulized Ketamine to Intravenous Subdissociative Dose Ketamine for Treating Acute Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind, Double-Dummy Controlled Trial.

STUDY OBJECTIVE: We aimed to assess and compare the analgesic efficacy and adverse effects of intravenous subdissociative-dose ketamine to nebulized ketamine in emergency department (ED) patients with acute painful conditions. METHODS: We conducted a prospective, randomized, double-blind, double-dummy clinical trial in adult patients (ages 18 and older) with a numerical rating scale pain score of ≥5. We randomized subjects to receive either a single dose of 0.3 mg/kg of intravenous (IV) ketamine or 0.75 mg/kg of nebulized ketamine through a breath-actuated nebulizer. Primary outcome was the difference in pain scores on the numerical rating scale between groups at 30 minutes postmedication administration. The secondary outcomes included the need for rescue analgesia, occurrences of adverse events in each group, and the difference in pain scores at 15, 30, 60, 90, and 120 minutes. We calculated a 95% confidence interval (CI) for a mean difference at 30 minutes, with a minimum clinically important difference set at 1.3 points. RESULTS: We enrolled 150 subjects (75 per group). Mean pain scores through numerical rating scale were 8.2 for both groups at baseline, which decreased to 3.6 and 3.8 at 30 minutes, yielding a mean difference of 0.23 (95% CI -1.32 to 0.857). We observed no clinically concerning changes in vital signs. No serious adverse events occurred in any of the groups throughout the study period. CONCLUSION: We found no difference between the administration of IV and nebulized ketamine for the short-term treatment of moderate to severe acute pain in the ED, with both treatments providing a clinically meaningful reduction in pain scores at 30 minutes.

Out-of-Hospital Intranasal Ketamine as an Adjunct to Fentanyl for the Treatment of Acute Traumatic Pain: A Randomized Clinical Trial.

STUDY OBJECTIVE: To evaluate if out-of-hospital administration of fentanyl and intranasal ketamine, compared to fentanyl alone, improves early pain control after injury. METHODS: We conducted an out-of-hospital randomized, placebo-controlled, blinded, parallel group clinical trial from October 2017 to December 2021. Participants were male, aged 18 to 65 years, receiving fentanyl to treat acute traumatic pain prior to hospital arrival, treated by an urban fire-based emergency medical services agency, and transported to the region's only adult Level I trauma center. Participants randomly received 50 mg intranasal ketamine or placebo. The primary outcome was the proportion with a minimum 2-point reduction in self-described pain on the verbal numerical rating scale 30 minutes after study drug administration assessed by 95% confidence interval overlap. Secondary outcomes were side effects, pain ratings, and additional pain medications through the first 3 hours of care. RESULTS: Among the 192 participants enrolled, 89 (46%) were White, (median age, 36 years; interquartile range, 27 to 53 years), with 103 receiving ketamine and 89 receiving placebo. There was no difference in the proportion experiencing improved pain 30 minutes after treatment (46/103 [44.7%] ketamine versus 32/89 [36.0%] placebo; difference in proportions, 8.7%; 95% confidence interval, -5.1% to 22.5%; P=.22) or at any time point through 3 hours. There was no difference in secondary outcomes or side effects. CONCLUSION: In our sample, we did not detect an analgesic benefit of adding 50 mg intranasal ketamine to fentanyl in out-of-hospital trauma patients.

Effectiveness of pain medication tapering in chronic pain patients: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to inventory all outcome measures that are affected by tapering in chronic noncancer pain and to investigate the effectiveness of tapering. METHODS: A literature search was conducted from inception to April 2024 in MEDLINE via PubMed, Web of Science, SCOPUS, EMBASE, and PsycINFO. RESULTS: The initial database search identified 3969 articles, which were screened by two independent reviewers. Studies evaluating pain medication tapering in adults with chronic noncancer pain were eligible for inclusion. In total, 57 and 34 articles were included in the systematic review and meta-analysis, respectively. Risk of bias assessment demonstrated poor, fair, and good quality in 30, 24, and three studies, respectively. Pain intensity was the most reported outcome measure, as reported in 28 studies. Furthermore, a random-effect three-level meta-analysis was performed. An overall effect size of 0.917 (95% confidence interval 0.61-1.22; P<0.001) was found, indicating a beneficial effect of tapering. In addition, a statistically significant improvement was demonstrated after tapering for pain intensity, headache disability, the number of headache days per month, anxiety, depression, the number of pills consumed per month, the number of days with medication intake per month, pain catastrophising, and pain interference. No statistically significant effect was observed for physical functioning, mental health-related quality of life, opioid use, pain self-efficacy, and physical health-related quality of life. CONCLUSIONS: This systematic review revealed a broad range of outcome measures affected by tapering. Owing to the high risk of bias of the included articles, the results of this meta-analysis must be interpreted with caution. SYSTEMATIC REVIEW PROTOCOL: CRD42023416343 (PROSPERO).

Use of electronic health record data to examine administrations of pro re nata analgesics during hip fracture post-acute care.

PURPOSE: Medications prescribed to older adults in US skilled nursing facilities (SNF) and administrations of pro re nata (PRN) "as needed" medications are unobservable in Medicare insurance claims. There is an ongoing deficit in our understanding of medication use during post-acute care. Using SNF electronic health record (EHR) datasets, including medication orders and barcode medication administration records, we described patterns of PRN analgesic prescribing and administrations among SNF residents with hip fracture. METHODS: Eligible participants resided in SNFs owned by 11 chains, had a diagnosis of hip fracture between January 1, 2018 to August 2, 2021, and received at least one administration of an analgesic medication in the 100 days after the hip fracture. We described the scheduling of analgesics, the proportion of available PRN doses administered, and the proportion of days with at least one PRN analgesic administration. RESULTS: Among 24 038 residents, 57.3% had orders for PRN acetaminophen, 67.4% PRN opioids, 4.2% PRN non-steroidal anti-inflammatory drugs, and 18.6% PRN combination products. The median proportion of available PRN doses administered per drug was 3%-50% and the median proportion of days where one or more doses of an ordered PRN analgesic was administered was 25%-75%. Results differed by analgesic class and the number of administrations ordered per day. CONCLUSIONS: EHRs can be leveraged to ascertain precise analgesic exposures during SNF stays. Future pharmacoepidemiology studies should consider linking SNF EHRs to insurance claims to construct a longitudinal history of medication use and healthcare utilization prior to and during episodes of SNF care.

Pain Medication and Pain Intensity Following Hip Fractures-Analyses Based on the ProFem Cohort Study.

PURPOSE: Pain is a common symptom following proximal femoral fractures (PFF), however, information on its treatment in terms of agents and type of use (scheduled vs. pro re nata [PRN]) is scarce. The main objective of this study was to examine pain medication regimens according to pain intensity following PFF. Furthermore, we explored the utilization of medication plans. METHODS: The "ProFem"-study on healthcare provision, functional ability, and quality of life after PFF is a German population-based prospective cohort study based on statutory health insurance data and individually linked survey data from different time points including information on the currently used medication. This present analysis refers to the participants' baseline interviews (about 3 months following PFF) conducted from 2018 to 2019 in the participants' private surroundings. RESULTS: The study population comprised 444 participants (mean age: 81.2 years, 71.0% female). Half of them reported high intensity pain, and the mean value for the EuroQol visual analogue scale was 50.8. Most commonly used analgesics were metamizole and tilidine/naloxone. Among participants with high intensity pain, 21.9% received only PRN pain medication and 17.2% no pain medication at all. Overall, 61.5% of participants presented any (printed) medication plan and only 25.2% a "federal standardized medication plan" (BMP). CONCLUSION: As a substantial number of patients reports high intensity pain about 3 months following a PFF, the large proportion of those receiving no or only PRN pain medication raises questions regarding the appropriateness of the therapy. The overall low utilization of the BMP indicates potential for improvement.

Optimizing medication guidance support for patients with cancer pain: development and evaluation of a pharmaceutical care system for healthcare professionals.

BACKGROUND: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists. METHODS: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires. RESULTS: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens. CONCLUSION: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.

Evaluation of thoracic sympathetic ganglion block as a predictor for response to ketamine infusion therapy and spinal cord stimulation in patients with chronic upper extremity pain.

OBJECTIVE: To investigate the predictive value of thoracic sympathetic ganglion block (TSGB) in response to ketamine infusion therapy (KIT) and spinal-cord stimulation (SCS) in patients with chronic upper-extremity pain including complex regional pain syndrome (CRPS). DESIGN: Retrospective. SETTING: Tertiary hospital single-center. SUBJECTS: Patients who underwent TSGB receiving KIT or SCS within a 3-year window. METHODS: Positive TSGB outcomes were defined as ≥2 0-10 Numerical Rating Scale (NRS) score reduction at 2 weeks post-procedure. Positive KIT and SCS outcomes were determined by ≥2 NRS score reduction at 2-4 weeks post-KIT and ≥4 NRS score reduction at 2-4 weeks post-SCS implantation, respectively. RESULTS: Among 207 patients who underwent TSGB, 38 received KIT and 34 underwent SCS implantation within 3 years post-TSGB; 33 patients receiving KIT and 32 patients receiving SCS were included. Among 33 patients who received KIT, 60.6% (n = 20) reported a ≥ 2 0-10 NRS pain-score reduction. Positive response to TSGB occurred in 70.0% (n = 14) KIT responders, significantly higher than that in 30.8% (n = 4) KIT non-responders. Multivariable analysis revealed a positive association between positive responses to TSGB and KIT (OR 7.004, 95% CI 1.26-39.02). Among 32 patients who underwent SCS implantation, 68.8% (n = 22) experienced short-term effectiveness. Positive response to TSGB was significantly higher in SCS responders (45.5%, n = 10) than in non-responders (0.0%). However, there were no associations between pain reduction post-TSGB and that post-KIT or post-SCS. CONCLUSIONS: A positive response to TSGB is a potential predictor for positive KIT and SCS outcomes among patients with chronic upper-extremity pain, including CRPS.

Intravenous patient-controlled analgesia with esketamine improves early depressive symptoms in patients with postherpetic neuralgia: a single-center retrospective cohort study.

OBJECTIVE: Patients with Postherpetic Neuralgia (PHN) often exhibit depressive-like symptoms, significantly impacting their quality of life. Esketamine, known for its analgesic properties, has also been recognized for its rapid antidepressant effects. However, its efficacy in the treatment of PHN requires further exploration. This study aims to evaluate the impact of intravenous patient-controlled analgesia(PICA) with esketamine on depressive mood in PHN patients. METHODS: This retrospective study analyzed PHN patients hospitalized and treated at the affiliated hospital of Southwest Medical University from June 2021 to March 2023. Patients were divided into the esketamine group (E group) and the sufentanil group (S group) based on their treatment regimens. Primary outcomes included pain numerical rating scale(NRS), depression patient health questionaire-9(PHQ-9), and anxiety generalized anxiety disorder-7(GAD-7) scores measured before treatment, and at 3 days, 7 days, 1 month, 2 months, and 3 months post-treatment. RESULTS: A total of 83 patients were included in the analysis. Before treatment, there were no statistically significant differences in pain NRS, depression PHQ-9, and anxiety GAD-7 scores between the two groups (P > 0.05). Compared to before treatment, significant reductions in pain NRS scores were observed at all post-treatment time points in both groups (P < 0.05), with no differences between groups (P > 0.05). The E group exhibited significantly lower depression PHQ-9 scores than the S group at 3 days and 7 days post-treatment (P < 0.05), but no significant differences were observed at 1 month, 2 months, and 3 months (P > 0.05). Anxiety GAD-7 scores were significantly lower in the E group compared to the S group at 3 days, 7 days post-treatment (P < 0.05), with no statistical differences at 1 month, 2 months, and 3 months post-treatment (P > 0.05). CONCLUSION: Both PICA with esketamine and sufentanil alleviated pain equally in PHN patients. However, PICA with esketamine specifically improved early symptoms of anxiety and depression.

Inhaled analgesics for the treatment of prehospital acute pain-A systematic review.

BACKGROUND: Many prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents. METHODS: As part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs. RESULTS: We included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N2O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N2O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs. CONCLUSION: We found low-quality evidence suggesting that both MF and N2O are safe and may have a role in the management of pain in the prehospital setting. There is low-quality evidence to support MF as a short-acting single analgesic or as a bridge to IV access and the administration of other analgesics. There may be occupational health issues regarding the prehospital use of N2O.

The use of intranasal sufentanil and/or s-ketamine for treatment of procedural pain in children in an ambulatory setting: A retrospective observational study.

BACKGROUND: Minor but painful medical procedures are often handled at the operating room. If safe and effective treatment options are available many procedures may be performed outside of the operating room. OBJECTIVE(S): The objective of this study is to assess the adverse events of intranasal s-ketamine and/or sufentanil alone or as part of a multimodal analgesic regime for medical procedures outside of the operating room. Secondary outcomes included analgesic effect, doses and indications for use. DESIGN: Retrospective observational study. SETTING: Tertiary care paediatric hospital. PATIENTS: Children 1 year up till 18 years. INTERVENTION(S): Intranasal (IN) sufentanil (S), intranasal s-ketamine (K) or the free combination of the two drugs (SK). MAIN OUTCOME MEASURE(S): The frequency of adverse events including serious adverse events reported by intervention. RESULTS: Between 2004 and 2014, 2185 medical procedures were registered, including 652 procedures with IN SK, 1469 procedures with IN S and 64 procedures with IN K. The children's median age was 5.6 years (range 1.0-17.9). Medical procedures with at least one adverse event were 18% with IN SK, 25% with IN K and 18% with IN S. Common adverse events included episodes of vomiting (9%), nausea (8%) and dizziness (3%). In two patients receiving IN S, serious adverse events occurred. One patient had respiratory depression and bronchospasm and another patient with cerebral palsy had a seizure. Both were handled immediately and did not result in any sequelae. The median doses of intranasal sufentanil were 38% lower when combined with s-ketamine (IN SK free combination: sufentanil dose 0.5 µg/kg (range 0.2-1.3) and s-ketamine dose 0.5 mg/kg (range 0.2-1.5). IN S monotherapy, sufentanil dose 0.8 µg/kg (range 0.2-2.7)). Similar analgesic effect was reported for S and SK. CONCLUSIONS: Intranasal sufentanil and/or s-ketamine are feasible for the treatment of procedural pain in an ambulatory setting with appropriate per- and post-procedural observations and trained staff.

Fu'cupping Physical Permeation-Enhancing Technique Enhances the Therapeutic Efficacy of Corydalis yanhusuo Gel Plaster.

Corydalis yanhusuo, a traditional Chinese medicine, is widely used to treat various pains, and its active ingredients are alkaloids. This study aimed to develop a new type of transdermal gel plaster containing the extract of C. yanhusuo. Studies have shown that Fu'cupping physical permeation-enhancing technique can promote the penetration of alkaloids and improve the efficacy of drugs. A transdermal gel plaster containing the extract of C. yanhusuo was prepared and optimized using an orthogonal experimental design. The skin permeation ability of the gel plaster was studied in vitro, while the anti-inflammatory and analgesic effects of the prepared patch alone or with Fu'cupping physical permeation-enhancing technique were evaluated in a rat model. The formulation of a gel plaster containing C. yanhusuo extract was successfully prepared with an optimized composition consisting of glycerin (15 g), sodium polyacrylate (2 g), silicon dioxide (0.3 g), ethanol (2 g), aluminum oxide (0.1 g), citric acid (0.05 g), the C. yanhusuo extract (3 g), and water (15 g). The cumulative transdermal permeation of dehydrocorydaline, corypalmine, tetrahydropalmatine, and corydaline in 24 h was estimated to be 569.7 ± 63.2, 74.5 ± 13.7, 82.4 ± 17.2, and 38.9 ± 8.1 µg/cm2, respectively. The in vitro diffusion of dehydrocorydaline and corydaline followed the zero-order kinetics profile, while that of corypalmine and tetrahydropalmatine followed a Higuchi equation. The prepared gel plaster significantly reduced paw swelling, downregulated inflammatory cytokines, and mitigated pain induced by mechanical or chemical stimuli. The Fu'cupping physical permeation-enhancing technique further improved the anti-inflammatory and analgesic effects of the patch. The combined application of the Fu'cupping physical permeation-enhancing technique and the alkaloid gel plaster may be effective against inflammation and pain.

Emerging Medications and Strategies in Acute Pain Management: Evolving Role of Novel Sodium and Calcium Channel Blockers, Peptide-Based Pharmacologic Drugs, and Non-Medicinal Methods.

PURPOSE OF REVIEW: The present investigation evaluated integration of novel medication technology to enhance treatment options, while improving patient outcomes in acute pain management. In this regard, we focused on determining the role of development and utilization of cutting-edge pharmaceutical advancements, such as targeted drug delivery systems, as well as non-pharmacologic interventions in addressing acute pain states. Further research in this area is warranted related to the need for increased patient comfort and reduced adverse effects. RECENT FINDINGS: Recent innovations and techniques are discussed including pharmacologic drugs targeting sodium and calcium channels, peptide-based pharmacologic drugs, and non-medicinal methods of alleviating pain such as soothing music or virtual reality. The present investigation included review of current literature on the application of these innovative technologies, analyzing mechanisms of action, pharmacokinetics, and clinical effectiveness. Our study also investigated the potential benefits in terms of pain relief, reduced side effects, and improved patient adherence. The research critically examines the challenges and considerations associated with implementing these technologies in acute pain management, considering factors like cost, accessibility, and regulatory aspects. Additionally, case studies and clinical trials are highlighted which demonstrate practical implications of these novel medication technologies in real-world scenarios. The findings aim to provide healthcare professionals with a comprehensive understanding of the evolving landscape in acute pain management while guiding future research and clinical practices toward optimizing their use in enhancing patient care.

Adjuvant Analgesics in Acute Pain - Evaluation of Efficacy.

PURPOSE OF THE REVIEW: Acute postoperative pain impacts a significant number of patients and is associated with various complications, such as a higher occurrence of chronic postsurgical pain as well as increased morbidity and mortality. RECENT FINDINGS: Opioids are often used to manage severe pain, but they come with serious adverse effects, such as sedation, respiratory depression, postoperative nausea and vomiting, and impaired bowel function. Therefore, most enhanced recovery after surgery protocols promote multimodal analgesia, which includes adjuvant analgesics, to provide optimal pain control. In this article, we aim to offer a comprehensive review of the contemporary literature on adjuvant analgesics in the management of acute pain, especially in the perioperative setting. Adjuvant analgesics have proven efficacy in treating postoperative pain and reducing need for opioids. While ketamine is an established option for opioid-dependent patients, magnesium and α2-agonists have, in addition to their analgetic effect, the potential to attenuate hemodynamic responses, which make them especially useful in painful laparoscopic procedures. Furthermore, α2-agonists and dexamethasone can extend the analgesic effect of regional anesthesia techniques. However, findings for lidocaine remain inconclusive.

Acupuncture Versus Oral Medications for Acute/Subacute Non-Specific Low Back Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Pharmacologic intervention do not always achieve benefits in the treatment of acute/subacute non-specific low back pain (NSLBP). We assessed efficacy and safety of acupuncture for acute/subacute NSLBP as alternative treatment. RECENT FINDINGS: We searched PubMed, Web of Science, Embase, Cochrane Library, Scopus, Epistemonikos, CNKI, Wan Fang Database, VIP database, CBMLD, CSTJ, clinical trials, EUCTR, World WHO ICTRP, and ChiCTR for randomized controlled trials, cross-over studies, and cohort studies of NSLBP treated by acupuncture versus oral medication from inception to 23th April 2022. A total of 6 784 records were identified, and 14 studies were included 1 263 participants in this review. The results of the meta-analysis indicated that acupuncture therapy was slightly more effective than oral medication in improving pain (P < 0.00001, I2 = 92%, MD = -1.17, 95% CI [-1.61, -0.72]). According to the results of the meta-analysis, acupuncture therapy exhibited a significant advantage over oral medication with a substantial effect (P < 0.00001, I2 = 90%, SMD = -1.42, 95% CI [-2.22, -0.62]). Based on the results of the meta-analysis, acupuncture therapy was associated with a 12% improvement rate compared to oral medication in patients with acute/subacute NSLBP (P < 0.0001, I2 = 54%, RR = 1.11, 95% CI [1.05, 1.18]). Acupuncture is more effective and safer than oral medication in treating acute/subacute NSLBP. This systematic review is poised to offer valuable guidance to clinicians treating acute/subacute NSLBP and potentially benefit the afflicted patients. REGISTRATION: This review was registered in PROSPERO ( http://www.crd.york.ac.uk/prospero ) with registration number CRD42021278346.

The effect of exercise referral schemes and self-management strategies on use of prescription analgesics among community-dwelling older adults: registry linkage with randomised controlled trials.

BACKGROUND AND OBJECTIVE: Exercise referral schemes and self-management strategies have shown positive effects on patient-reported and objectively measured outcomes, such as increased functional capacity and physical activity level. However, the impact of these interventions on analgesic use remains uncertain. We hypothesised that exercise referral schemes, either utilised alone or in combination with self-management strategies, is more effective in reducing use of prescription analgesics compared with a self-management strategy only. SUBJECTS AND METHODS: We utilised data from two completed randomised controlled trials, namely The Welfare Innovation in Primary Prevention (n = 121) and The SITLESS project (n = 338), and information from the national Danish health registries, including the National Prescription Registry. The two trials have investigated the effectiveness of interventions, which include exercise referral schemes and self-management strategies, on various aspects such as physical function and levels of physical activity among community-dwelling older adults. The studies were conducted in the period 2015-2020 and comprised older adults aged 65+ years, living in three different Danish municipalities. Participants were recruited through nationally regulated preventive home-visits. To estimate changes in use of prescription analgesics over time, a linear fixed effects regression model was applied. The outcome measure was the mean total yearly defined daily dose of analgesics. RESULTS: All intervention groups showed a within-group increase in overall analgesic use, though not statistically significantly different from zero. There were no differences in estimated changes in mean total yearly defined daily dose when comparing the intervention groups to the group receiving the least extensive intervention (self-management strategies/control). The findings indicated that exercise referral schemes and self-management strategies, whether administrated individually or in combination, did not result in a reduction in analgesic use over time.