Multimodal Regimen Research Articles

Intraoperative Methadone in Spine Surgery ERAS Protocols: A Systematic Review of the Literature.

Systematic review. To systematically review the use of intraoperative methadone in spine surgery and examine its effects on postoperative opioid use, pain, length of stay, and operative time. Spine surgery patients commonly have a history of chronic pain and opioid use, and as a result, they are at an increased risk of severe postoperative pain. While pure mu opioids remain the standard for acute surgical pain management, they are associated with significant short-term and long-term adverse events. Methadone presents an alternative to pure mu opioids which may improve postoperative management of pain following intraoperative use. A systematic review of MEDLINE, Embase, and Web of Science databases was conducted to review existing literature detailing operating time, postoperative pain, opioid usage, and hospital length of stay (LOS) following intraoperative methadone administration in spine surgery. Following screening of 994 articles and application of inclusion criteria, 8 articles were included, 4 of which were retrospective. Conventional spine surgery intraoperative analgesic strategies used as comparators for intraoperative methadone included hydromorphone, ketamine, and sufentanil. Considering patient outcomes, included studies observed that patients treated with intraoperative methadone had statistically similar or significantly reduced pain scores, opioid usage, and LOS compared with comparator analgesics. However, one study observed that intraoperative methadone used in a multimodal analgesia regimen strategy with ketamine resulted in a shortened LOS compared with the use of intraoperative methadone alone. Differences in operating time between cases that used intraoperative methadone and cases that used comparator analgesics were not statistically significant among included studies. Methadone may present an alternative option for both intraoperative and postoperative analgesia in spine surgery recovery protocols and may reduce postoperative pain, opioid use, and LOS while maintaining consistent operating time and reduced side effects of pure mu opioids. Level II.

Multimodal analgesics after adult cardiac surgery; a systematic review

Abstract Background Moderate to severe pain is frequently reported during the acute recovery phase following adult cardiac surgery. Multimodal analgesics are recommended for adult patients post cardiac surgery, but the optimal combination of multimodal analgesics is unknown. Purpose To synthesise the best available evidence about the effectiveness of multimodal analgesics on pain after adult cardiac surgery. Methods A systematic review was conducted according to the PRISMA-P statement and the published review protocol. Inclusion criteria were full-text papers or abstracts with adequate reporting, in any language, of randomised controlled trials (RCTs) in adult patients undergoing cardiac surgery that investigated the effect of multimodal postoperative analgesic regimens, compared to a control group. The highest mean level of patient self-reported pain intensity at rest, captured using a validated pain assessment tool, was the primary outcome measure. Results Of 3754 citations identified in the initial search to the 12th of December 2022, there were 1605 duplicates leaving 2149 citations for title and abstract screening, of which 2027 were irrelevant. There were 122 full-text papers assessed and 29 included in the review. Data were independently extracted by 2 reviewers in Covidence®. Participants (N = 2360), aged 59.5 + 8.2 years, were primarily male (N = 1561, 66.1%), weighing 78.1 +9.2 kilograms. Risk of bias was high and reporting quality was poor. Pain at rest reported in 18 (62%) studies was 3.5 (SD 1.2) in the control and 2.7 (SD 0.9) in the intervention groups respectively. Nurse-led versus patient-controlled analgesic administration was tested in 14 (48.3%) trials. All trials tested different analgesic combinations, none of which compared a combination of non-opioids, opioid agonist-antagonist agents, or full opioid agonists. Conclusions Poorly managed pain is associated with postoperative complications, unplanned readmissions, and the development of chronic pain. Robust RCTs are urgently needed to inform optimal combinations of multimodal analgesics to optimise patient recovery after adult cardiac surgery.Risk of Bias

The analgesic benefit of rectus sheath block in robotic gynecologic surgery: A retrospective study.

With the growing adoption of robotic techniques in gynecologic surgery, the advantages of minimally invasive procedures over traditional open surgery, such as reduced postoperative pain and quicker recovery, are clear. Yet, establishing an effective multimodal analgesic regimen remains a challenge. This retrospective study from a tertiary care center aimed to assess the analgesic efficacy of the rectus sheath block (RSB) on postoperative pain and opioid consumption after robotic gynecologic surgery. Between June 2022 and March 2023, 20 patients who underwent robotic gynecologic surgery were evaluated. Key parameters included postoperative visual analog scale scores, opioid consumption, and postoperative nausea/vomiting instances. Anesthesia protocols were standardized, with postsurgical pain management involving RSB and a patient-controlled analgesia device filled with morphine. Patients showed an average morphine intake of 8.2 ± 5.09 mg over the initial 24 hours postsurgery. During mobilization, average pain scores were consistently low, with no correlation identified between opioid consumption and age or body mass index. 40% of patients reported postoperative nausea on the first day, and no complications linked to the RSB were observed. The study underlines the potential of integrating RSB in a multimodal analgesic regimen after robotic gynecologic surgery. Its application may lead to reduced opioid consumption and more efficient postoperative pain management. Further randomized controlled trials are recommended to validate these findings.

Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain

Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain

Multimode light generation in an injection semiconductor laser based on a chiral AlAs/(Al, Ga)As/GaAs microcavity

Experimental investigations of chiral injection AlAs/(Al, Ga)As/GaAs vertical-cavity surface-emitting lasers in the multimode generation regime are performed. A high circular polarization degree 70% of different generation modes measured with a high spectral resolution, is demonstrated. Detailed maps of spatial and angular distribution of laser radiation intensity were constructed.

Flurbiprofen axetil is involved in basal-like breast cancer metastasis via suppressing the MEK/ERK signaling pathway.

Flurbiprofen axetil is commonly utilized in clinical practice as one of the nonsteroidal anti-inflammatory drugs (NSAIDs) and is included in multimodal analgesia regimens postbreast cancer surgery. Numerous NSAIDs have been studied for their potential to both promote and inhibit cancer. Given the variability in their effects on tumors, further investigation into the specific role of flurbiprofen axetil is warranted. Therefore, the primary objective of this study was to assess the impact of flurbiprofen axetil on basal-like breast cancer (BLBC) metastasis and elucidate the underlying molecular mechanisms involved. The BLBC metastasis mouse model was established by caudal vein injection of tumor cells. The lung metastasis of breast cancer in mice and the effect of flurbiprofen axetil were assessed by in vivo bioluminescence imaging, hematoxylin and eosin staining and immunohistochemistry. In vitro, the results of flurbiprofen axetil on the proliferation, migration, and invasion of MDA-MB-231 human breast cancer cells and BT-549 human breast cancer cells were assessed by colony formation assay and transwell assay. The effects of flurbiprofen axetil on several tumor metastasis-related signaling pathway proteins were examined by western blot, and the reversal extent of the flurbiprofen axetil effect by Ro 67-7476 (ERK phosphorylation agonist) was detected by transwell assay. The results showed that flurbiprofen axetil significantly inhibited BLBC lung metastasis in mice. Flurbiprofen axetil similarly inhibited breast cancer cell migration and invasion in vitro but did not affect their proliferation. Mechanistic investigations have revealed that flurbiprofen axetil exerts a noteworthy inhibitory influence on the MEK/ERK pathway while exhibiting no significant alteration in the expression of other pathway proteins intricately associated with epithelial-mesenchymal transition. In conclusion, the inhibitory effect of flurbiprofen axetil on BLBC metastasis is characterized by its selectivity in targeting the MEK/ERK signaling pathway rather than exerting a broad impact on the global signaling pathway.

Local Sustained Dinutuximab Delivery and Release From Methacrylated Chondroitin Sulfate.

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. High-risk NB is a subset of the disease that has poor prognosis and requires multimodal treatment regimens, with a 50% rate of recurrence despite intervention. There is a need for improved treatment strategies to reduce high-risk patient mortality. Dinutuximab is an anti-GD2 antibody ideal for targeting GD2 expressing NB cells, but binding of the antibody to peripheral nerve fibers leads to severe pain during systemic administration. Intratumoral delivery of the anti-GD2 antibody would allow for increased local antibody concentration, without increasing systemic toxicity. Chondroitin Sulfate (CS) is a biocompatible glycosaminoglycan that can be methacrylated to form CSMA, a photocrosslinkable hydrogel that can be loaded with therapeutic agents. The methacrylation reaction time can be varied to achieve different degrees of substitution, resulting in different release and degradation profiles. In this work, 4 and 24 h reacted CSMA was used to create hydrogels at 10% and 20% CSMA. Sustained in vitro release of dinutuximab from these formulations was observed over a 24-day period, and 4 h reacted 10% CSMA hydrogels had the highest overall dinutuximab release over time. An orthotropic mouse model was used to evaluate in vivo response to dinutuximab loaded 4 h methacrylated 10% CSMA hydrogels as compared to bolus tail vein injections. Tumor growth was monitored, and there was a statistically significant increase in the days to reach specific tumor size for tumors treated with intratumoral dinutuximab-loaded hydrogel compared to those treated with dinutuximab solution through tail vein injection. This supports the concept that locally delivering dinutuximab within the hydrogel formulation slowed tumor growth. The CSMA hydrogel-only treatment slowed tumor growth as well, an interesting effect that may indicate interactions between the CSMA and cell adhesion molecules in the tumor microenvironment. These findings demonstrate a potential avenue for local sustained delivery of dinutuximab for improved anti-tumoral response in high-risk NB.

Opioids and Cannabinoids in Neurology Practice.

Opioid and cannabinoid therapies for chronic pain conditions including neuropathic pain are controversial. Understanding patient and prescribing factors contributing to risks and implementing risk mitigation strategies optimizes outcomes. The ongoing transformation from a biomedical model of pain care toward a biopsychosocial model has been accompanied by a shift away from opioid therapy for pain, in particular for chronic pain. Opioid overdose deaths and opioid use disorder have greatly increased in the last several decades, initially because of increases in opioid prescribing and more recently associated with illicit drug use, in particular fentanyl derivatives. Opioid risk mitigation strategies may reduce risks related to opioid prescribing and tapering or discontinuation. Opioid therapy guidelines from the Centers for Disease Control and Prevention have become the consensus best practice for opioid therapy. Regulatory agencies and licensing medical boards have implemented restrictions and other mandates regarding opioid therapy. Meanwhile, interest in and use of cannabinoids for chronic pain has grown in the United States. Opioid therapy is generally not recommended for the chronic treatment of neuropathic pain conditions. Opioids may be considered for temporary use in patients with severe pain related to selected neuropathic pain conditions (such as postherpetic neuralgia), and only as part of a multimodal treatment regimen. Opioid risk mitigation strategies include careful patient selection and evaluation, patient education and informed consent, querying the state prescription drug monitoring programs, urine drug testing, and issuance of naloxone as potential rescue medication. Close follow-up when initiating or adjusting opioid therapy and frequent reevaluation during long-term opioid therapy is required. There is evidence for the efficacy of cannabinoids for neuropathic pain, with meaningful response rates in select patient populations.

Early Postoperative Pain is Similar after Arthroscopic Rotator Cuff Repair versus Short-Stay Shoulder Arthroplasty: A Prospective Study.

IntroductionOne of the barriers to counseling patients for shoulder arthroplasty (SA) is the anticipated pain after surgery. This can be contrasted with the common perception of arthroscopic rotator cuff repair (RCR) surgery being less painful due to the less invasive nature of the procedure. We conducted a prospective study comparing postoperative pain levels and narcotic consumption after SA compared to those after RCR. MethodsThis prospective study enrolled 102 patients undergoing short-stay SA and RCR at a single hospital. 50 patients underwent RCR and 52 underwent SA. All participants received a multimodal pain regimen consisting of an interscalene block with liposomal bupivacaine and one of two oral pain medication regimens. Patients were provided a daily pain diary to be completed for 14 postoperative days that tracked pain levels, narcotic consumption, and pain location. Patients were excluded for age <40, revision surgery, SA for fracture, history of chronic opioid use, or an inability to adhere to study protocol. Demographics, visual analogue scale (VAS) scores, and pain sensitivity questionnaires (PSQ) were collected preoperatively. Primary study outcomes were daily VAS pain scores and narcotic consumption during the 14 days after surgery. ResultsRCR patients were younger (60.6 vs. 68.9 years; p<0.01) but other demographics, preoperative pain, and PSQ scores were similar between groups. Peak mean VAS pain levels for RCR and SA each occurred on postoperative (POD) 2 and were 4.4 ± 3.1 and 5.1 ± 2.7 respectively (p=0.214). There was no significant difference in VAS pain during the 14-day postoperative period between RCR and SA patients (p>0.05) or between anatomic SA and reverse SA (p>0.05). Narcotic usage was greater for RCR patients at POD 7 (0.5 vs. 0.2 tablets; p=0.039) and 8 (0.5 vs. 0.2 tablets; p=0.015) compared to SA patients. ConclusionsOur study demonstrated that postoperative pain levels do not significantly differ between RCR and short-stay SA, with greater narcotic usage observed for RCR at one week after surgery. These findings support the notion that despite the increased invasiveness of SA, early postoperative pain is comparable with early pain after RCR.

Management Strategies for Patients with Non-Infectious Cystitis: A Review of the Literature.

The management of noninfectious cystitis continues to evolve as new treatments continue to be developed and investigated. This review aims to synthesize the most recent data regarding management strategies for noninfectious cystitis focused on non-ulcerative, ulcerative, eosinophilic, and ketamine-induced cystitis. Several novel treatments have shown promise as management options including combination antihistamine therapy, phosphodiesterase 5 inhibitors, alpha lipoic acid supplements, and onabotulinumtoxin A. Recent studies have also found pentosan polysulfate sodium to have adverse ophthalmologic effects. For patients with ulcerative cystitis, recent research has shown that fulguration with or without triamcinolone injections should not be delayed. The treatment of noninfectious cystitis should be patient specific based on factors including etiology and symptom profile. Multimodal regimens are often the most effective. Treatment should be started with conservative options and escalated as necessary to oral treatments, intravesical options, or procedural management.

Effect of low-volume ropivacaine in ultrasound-guided superior trunk block on diaphragmatic movement in patients undergoing shoulder arthroscopy: a randomized controlled trial

ObjectivesThe incidence of hemidiaphragmatic paresis (HDP) in superior trunk block (STB) usually depends on the dose of local anesthetic. This study aimed to further evaluate the impact of a lower volume (10 mL) of the same low concentration (0.25%) ropivacaine compared to a conventional volume (15 mL), on diaphragmatic function and analgesic efficacy under a multimodal analgesia regimen for shoulder arthroscopy.MethodsPatients scheduled to undergo shoulder arthroscopy were randomized allocated to receive either 10 mL or 15 mL of 0.25% ropivacaine in the STB under ultrasound guidance prior to general anesthesia. The primary outcome was the percentage reduction in diaphragm excursion (ΔDE) between baseline and 30 min after block. Secondary outcomes included DE and diaphragm thickening fraction (DTF) before and after block, incidence of HDP, onset of sensory/motor block, duration of analgesia/motor block, dermatomal coverage area of the block, postoperative pain severity, pre- and post-block respiratory function and intraoperative hemodynamic parameters, the use of other anesthetic and analgesic drugs, post-block complications, and adverse events post-surgery.ResultsCompared with 15 mL volume, 10 mL ropivacaine significantly reduced the incidence of post-block HDP (as measured by ΔDE: 39.47% vs. 64.10%; and by post-block DTF: 13.16% vs. 33.33%). There was no significant difference in onset of sensory block, duration of analgesia/motor block, dermatomal coverage area of the block, postoperative pain severity between the two groups, except that the onset of motor block was significantly slower in the 10 mL group than in the 15 mL group. Pre- and post-block respiratory function and intraoperative hemodynamic parameters, the use of other anesthetic and analgesic drugs, post-block complications, or postoperative adverse events were not significantly different between the two groups.ConclusionIn shoulder arthroscopy, STB with 10 mL of ropivacaine can reduce the incidence of HDP with no significant difference in analgesic effects under a multimodal analgesia regimen compared with 15 mL.Trial registration: We registered the study at chictr.org (ChiCTR2200057543 , 14/03/2022.https://www.chictr.ogr.cn

Subcutaneous and orally self-administered high-dose carprofen shows favorable pharmacokinetic and tolerability profiles in male and female C57BL/6J mice.

Surgical interventions in mice require appropriate pain relief to ensure animal welfare and to avoid influence of pain on research findings. Carprofen is a non-steroidal anti-inflammatory drug commonly used as an analgesic for interventions inducing mild to moderate pain in laboratory rodents. Despite its frequent use, species-specific data on pharmacokinetics (PK), side effects, and potential impact on behavioral pain indicators are limited. We determined PK and tolerability profiles of carprofen in healthy male and female C57BL/6J mice (n = 42), administered at highest recommended doses via single subcutaneous (s.c.) injection (20 mg/kg) and oral self-administration (25 mg/kg/24 h) per drinking water (d.w.) for 5 days. Plasma concentrations were measured at various time points after the start of the treatment (n = 6 per time point), and side effects were evaluated using a modified Irwin test battery, hematology, and histopathology. Additionally, potential interference with cage-side behaviors commonly used for pain assessment, such as the mouse grimace scale, wheel running, burrowing, nesting, and grooming activity, was investigated. Maximum plasma concentrations of 133.4 ± 11.3 μg/ml were reached 1 h after single s.c. injection with an elimination half-life of 8.52 h. Intake from d.w. resulted in a steady state within 24 h after the start of the treatment with plasma levels of around 60 μg/ml over 5 days in both sexes. The medicated water was well-accepted, and increased d.w. intake was observed in the first 24 h after exposure (p < 0.0001). The Irwin test revealed only minor influence on tested behavior and physiological functions. However, during treatment via d.w., an increase in body temperature (p < 0.0001) was observed, as well as a reduction in voluntary wheel running activity by 49-70% in male mice. Moreover, grooming behavior was slightly affected. Hematology and histopathology were without pathological findings that could be attributed to carprofen treatment. High-dose carprofen can be considered safe and of favorable PK for both administration routes assessed in healthy C57BL/6J mice of both sexes. Further efficacy evaluation of carprofen as monoanalgesic or component of multimodal post-surgical regimens is clearly encouraged; however, the impact on behavioral markers used for pain assessment should be considered in this context.

Effects of Serratus Anterior Plane Block on Early Recovery from Thoracoscopic Lung Resection: A Randomized, Blinded, Placebo-Controlled Trial.

The efficacy of serratus anterior plane block (SAPB) for treatment of pain after minimally invasive thoracic surgery remains unclear. This trial assesses the impact of SAPB on postoperative opioid consumption and on measures of early recovery after thoracoscopic lung resection. Patients undergoing minimally invasive anatomic lung resection at a single center were randomized to undergo SAPB with 40 mL of injectate containing bupivacaine 0.25%, clonidine 100 mcg, and dexamethasone 4 mg (SAPB group) or sham block with 40 mL of normal saline (placebo group) at the conclusion of surgery. The primary outcome was cumulative intravenous morphine equivalents during the first 24 h postoperatively. Secondary outcomes were intravenous morphine equivalents, pain scores at rest and with cough, inspiratory volume on incentive spirometry, and incidence of nausea/vomiting during the first 48 h postoperatively; Quality of Recovery-15 score on postoperative day 7; and length of stay. Using the protocol-specified intention-to-treat analysis, the median (interquartile range, IQR) intravenous morphine equivalents was 10.6 (5.0 to 27.1) mg in SAPB patients (n=46) versus 18.8 (9.9 to 29.6) mg in placebo patients (n=46) (32% reduction; ratio=0.68 [95% CI, 0.44 to 1.06]; P=0.085). Of the secondary outcomes, only the composite pain with cough scores differed significantly in the SAPB group by a coefficient of -0.41 (95% CI, -0.81 to -0.01; P=0.044). A sensitivity as-treated analysis reported median (IQR) intravenous morphine equivalents of 10.0 (5.0 to 27.2) mg in SAPB patients (n=44) versus 19.9 (10.4 to 29.0) mg in placebo patients (n=48) (36% reduction; ratio=0.64 [95% CI, 0.41 to 1.00]; P=0.048). The protocol-specified intention-to-treat analysis demonstrated that SAPB did not result in a significant reduction in opioid consumption when added to a multimodal analgesic regimen after thoracoscopic anatomic lung resection. The sensitivity as-treated analysis showed a significant and modest clinical reduction in the primary outcome that warrants further investigation.

Development and Testing of a Helicon Plasma Thruster Based on a Magnetically Enhanced Inductively Coupled Plasma Reactor Operating in a Multi-Mode Regime

A disruptive Electric Propulsion system is proposed for next-generation Low-Earth-Orbit (LEO) small satellite constellations, utilizing an RF-powered Helicon Plasma Thruster (HPT). This system is built around a Magnetically Enhanced Inductively Coupled Plasma (MEICP) reactor, which enables acceleration of quasi-neutral plasma through a magnetic nozzle. The MEICP reactor features an innovative design with a multi-dipole magnetic confinement system, generated by neodymium iron boron (NdFeB) permanent magnets, combined with an azimuthally asymmetric half-wavelength right (HWRH) antenna and a variable-section ionization chamber. The plasma reactor is followed by a solenoid-free magnetic nozzle (MN), which facilitates the formation of an ambipolar potential drop, enabling the conversion of electron thermal energy into ion beam energy. This study explores the impact of an inhomogeneous magnetic field on the heating mechanism of the HPT and highlights its multi-mode operation within a pulsed power range of 200 to 500 W of RF. The discharge state, characterized by high-energy electron-excited ions and low-energy excited neutral particles in the plasma plume, was analyzed using optical emission spectroscopy (OES). The experimental testing campaign, conducted under pulsed power excitation, reveals that, as RF input power increases, the MEICP reactor transitions from inductive (H-mode) to wave coupling (W-mode) discharge modes. Spectrograms, electron temperature, and plasma density measurements were obtained for the Helicon Plasma Thruster within its operational envelope. Based on OES data, the ideal specific impulse was estimated to exceed 1000 s, highlighting the significant potential of this technology for future LEO/VLEO space missions.

A narrative review on advances in neoadjuvant immunotherapy for esophageal cancer: Molecular biomarkers and future directions.

Esophageal cancer has a poor prognosis and survival rate due to its high incidence in Asia, lack of early symptoms and limited treatment options. In recent years, many clinical trials have demonstrated that immunotherapy has greatly improved the survival of patients with esophageal cancer. In addition, the combination of neoadjuvant immunotherapy with other popular therapeutic regimens has shown good efficacy and safety. In this review, we summarize the progress of clinical trials and some breakthroughs in neoadjuvant immunotherapy for esophageal cancer in recent years and suggest the possibility of multimodal neoadjuvant immunotherapy regimens, as well as directions for future development.

Comparison of thoracic epidural catheter and continuous peripheral infusion for management of traumatic rib fracture pain.

Thoracic epidural catheters (TECs) are useful adjuncts to multimodal pain regimens in traumatic rib fractures. However, TEC placement is limited by contraindications, patient risk profile, and provider availability. Continuous peripheral infusion of ketamine and/or lidocaine is an alternative that has a modest risk profile and few contraindications. We hypothesized that patients with multiple traumatic rib fractures receiving TECs would have better pain control, in terms of daily morphine milligram equivalents (MMEs) and mean pain scores (MPSs) when compared with continuous peripheral infusions of ketamine and/or lidocaine. We retrospectively analyzed traumatic rib fracture admissions to a level 1 trauma center between January 2018 and December 2020. We evaluated two treatment groups: TEC only and continuous infusion only (drip only). A linear mixed-effects model evaluated the association of MME with treatment group. An interaction term of treatment group by time (days 1-7) was included to allow estimating potential time-dependent treatment effect on MME. A zero-inflated Poisson mixed-effects model evaluated the association of treatment with MPS. Both models adjusted for confounders. A total of 1,647 patients were included. After multivariable analysis, a significant, time-varying dose-response relationship between treatment group and MME was found, indicating an opioid-sparing effect favoring the TEC-only group. The opioid-sparing benefit for TEC-only therapy was most prominent at day 3 (27.4 vs 36.5 MME) and day 4 (27.3 vs 36.2 MME) (p < 0.01). The drip-only group had 1.21 times greater MPS than patients with TEC only (p < 0.001). Drip-only analgesia is associated with higher daily MME use and MPS, compared with TEC only. The maximal benefit of TEC therapy appears to be on days 3 and 4. Prospective, randomized comparison between groups is necessary to evaluate the magnitude of the treatment effect. Therapeutic/Care Management; Level III.

Adverse Effects Associated With Multimodal Analgesic Regimens in Critically Ill, Nonintubated Patients: A Systematic Review and Meta-Analysis

Objective: To evaluate the safety of utilizing multimodal analgesic regimens in critically ill, nonintubated patients. Data Sources: A systematic review was conducted using Embase, MEDLINE, Cochrane, SciELO, Web of Science, and the Korean Journal Index. Clinical trials of critically ill, nonintubated patients that contained complete safety outcomes date, including the incidence of specific adverse drug effects (ADE) associated with a multimodal analgesic medication or regimen, were included. Study Selection and Data Extraction: The primary outcome was the incidence of adverse drug effects associated with multimodal analgesics in comparison to standard-of-care analgesic strategies in our patient population. The secondary outcome was a subgroup analysis of adverse drug effect by type and by medication. Data Synthesis: 10 trials were included in this systematic review, of which 6 were randomized control trials that were evaluated in the meta-analysis. There was no statistically significant difference with respect to the primary outcome (mean difference = −0.11, P = 0.31, 95% CI = [−0.35, 0.13]). The subgroup analysis, which was conducted on randomized clinical control trials that documented a single adjunctive analgesic rather than a multimodal regimen, was stratified by the type of adverse effect encountered and the medication in question. There were no statistically significant findings regarding the incidence of specific ADE. Nonrandomized data included in this study support these findings. Conclusions: While concerns of the additive deleterious adverse effects commonly encountered in polypharmacy are valid, our findings support the use of multimodal analgesic regimens in the provision of analgesic in critically ill, nonintubated patients.

The Combined Effects of Endurance and Strength Training on Exercise Tolerance and Quality of Life in Patients with COPD

Chronic Obstructive Pulmonary Disease (COPD) significantly impairs exercise tolerance and quality of life due to respiratory and systemic effects. Exercise training, including endurance and strength modalities, is a cornerstone of pulmonary rehabilitation, yet the combined effects of these training methods remain underexplored. This study aimed to evaluate the combined effects of endurance and strength training on exercise tolerance and quality of life in COPD patients. A randomized controlled trial was conducted involving 100 COPD patients assigned to four groups: Endurance Training, Strength Training, Combined Training, and Control. The interventions were implemented over 12 weeks, with outcomes assessed pre- and post-intervention, including the six-minute walk test (6MWT) for exercise tolerance and the St. George’s Respiratory Questionnaire (SGRQ) for quality of life. Statistical analyses included ANOVA and post-hoc comparisons to determine group differences. The Combined Training group demonstrated the most significant improvement in exercise tolerance, with a mean increase of 72.4 meters in 6MWT distance, compared to 48.7 meters in the Endurance group and 34.2 meters in the Strength group. Quality of life, measured by SGRQ, improved significantly across all intervention groups, with the greatest reduction in total SGRQ scores observed in the Combined Training group (12.6 points), indicating enhanced physical and psychological well-being. Additional improvements in muscle strength and endurance capacity were also most pronounced in the Combined Training group. Combined endurance and strength training provide superior benefits in enhancing exercise tolerance, muscle strength, and quality of life in COPD patients compared to either modality alone. These findings support the integration of multimodal exercise regimens in pulmonary rehabilitation programs to optimize outcomes for COPD patients.

Effects of opioid-sparing general anesthesia on postoperative nausea and vomiting in laparoscopic gynecological surgery.

In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery. Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day (POD) 1. A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups. OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.

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

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. 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. Retrospective observational study. Tertiary care paediatric hospital. Children 1 year up till 18 years. Intranasal (IN) sufentanil (S), intranasal s-ketamine (K) or the free combination of the two drugs (SK). The frequency of adverse events including serious adverse events reported by intervention. 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. 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.