Search Results (10)

The search for effective pain management solutions remains a critical challenge, especially amidst growing concerns over the use of conventional opioids. In the US, opioid-related mortality rates have surged to as many as 80 deaths per 100,000 people in some states, with an estimated economic burden of USD 1.5 trillion annually—exceeding the gross domestic product (GDP) of most US industrial sectors. A remarkable breakthrough lies in the discovery that indole and oxindole alkaloids, produced by several genera within the plant Tribe Naucleeae, act on opioid receptors without activating the beta-arrestin-2 pathway, the primary driver of respiratory depression and overdose deaths. This systematic review explores the pharmacological properties, mechanisms of action, dosing considerations, interactions, and long-term effects of mitragynine and corynoxeine, alkaloids from the Southeast Asian plant Mitragyna speciosa (kratom) and others in the Tribe Naucleeae. Mitragynine, a partial opioid receptor agonist, and corynoxeine, known for its anti-inflammatory and neuroprotective effects, demonstrate significant therapeutic potential for managing diverse pain types—including neuropathic, inflammatory, nociceptive, visceral, and central pain syndromes—with a focus on cancer pain. Unlike traditional opioids, these compounds do not recruit beta-arrestin-2, avoiding key adverse effects such as respiratory depression, severe constipation, and rapid tolerance development. Their distinct pharmacological profiles make them innovative candidates for safer, non-lethal pain relief. However, challenges persist, including the unregulated nature of kratom products, inconsistencies in potency due to crude extract variability, potential for misuse, and adverse drug interactions. Addressing these issues requires establishing standardized quality control protocols, such as Good Manufacturing Practices (GMP), to ensure consistent potency and purity. Clear labeling requirements with dosage guidelines and warnings should be mandated to ensure safe use and prevent misuse. Furthermore, the implementation of regulatory oversight to monitor product quality and enforce compliance is essential. This review emphasizes the urgency of focused research to optimize dosing regimens, characterize the pharmacodynamic profiles of these alkaloids, and evaluate long-term safety. By addressing these gaps, the mitragynine- and corynoxeine-related drug classes can transition from promising plant-derived molecules to validated pharmacotherapeutic agents, potentially revolutionizing the field of pain management. Full article

Background/Objectives: Eversion carotid endarterectomy (CEA) in awake patients is performed using cervical plexus blocks (CPBs) with or without carotid artery sheath infiltration (CASI) under ultrasound guidance. Although adequacy of anesthesia (AoA) guidance monitors nociception/antinociception balance, its impact on intraoperative analgesia quality and perioperative outcomes in awake CEA remains unexplored. Existing literature lacks evidence on whether AoA-guided anesthesia enhances clinical outcomes over standard techniques. This study aimed to assess the role of AoA guidance in improving intraoperative analgesia and perioperative outcomes in patients undergoing CEA with CPBs alone or with CASI compared to standard practice. Methods: A randomized controlled trial included 184 patients divided into three groups: CPBs with intravenous rescue fentanyl (IRF) and lidocaine (LID) guided by hemodynamic observation (C group), AoA-guided IRF and LID (AoA group), and AoA-guided IRF, LID, and CASI (AoA-CASI group). Primary outcomes included perioperative adverse events, and secondary outcomes assessed rescue medication demand and hemodynamic stability. Results: Analysis of 172 patients revealed no significant differences between groups in perioperative adverse events or hemodynamic parameters (p > 0.05). However, the AoA-CASI group demonstrated significantly reduced IRF and LID usage compared to the C and AoA groups (p < 0.001). No significant advantage was observed between the AoA and C groups regarding adverse events (p = 0.1). Conclusions: AoA-guided anesthesia with or without CASI does not significantly reduce perioperative adverse events or improve hemodynamic stability in awake CEA. Clinical implications suggest that focusing on surgical technique optimization may yield greater benefits in reducing adverse events compared to advanced anesthetic monitoring. Further studies are warranted to explore alternative approaches to enhance clinical outcomes. Full article

In this paper, we present the development and the validation of a novel index of nociception/anti-nociception (N/AN) based on skin impedance measurement in time and frequency domain with our prototype AnspecPro device. The primary objective of the study was to compare the Anspec-PRO device with two other commercial devices (Medasense, Medstorm). This comparison was designed to be conducted under the same conditions for the three devices. This was carried out during total intravenous anesthesia (TIVA) by investigating its outcomes related to noxious stimulus. In a carefully designed clinical protocol during general anesthesia from induction until emergence, we extract data for estimating individualized causal dynamic models between drug infusion and their monitored effect variables. Specifically, these are Propofol hypnotic drug to Bispectral index of hypnosis level and Remifentanil opioid drug to each of the three aforementioned devices. When compared, statistical analysis of the regions before and during the standardized stimulus shows consistent difference between regions for all devices and for all indices. These results suggest that the proposed methodology for data extraction and processing for AnspecPro delivers the same information as the two commercial devices. Full article

Pain refinement represents an important aspect of animal welfare in laboratory animals. Refining analgesia regimens in mice undergoing craniotomy has been sparsely investigated. Here, we sought to investigate the effect of dexmedetomidine in combination with other analgesic drugs on intraoperative anti-nociceptive effects and cardiorespiratory stability. All mice were anaesthetised with isoflurane and received local lidocaine infiltration at the surgical site. Mice were randomised into treatment groups consisting of either carprofen 5 mg kg⁻¹ or meloxicam 5 mg kg⁻¹ with or without dexmedetomidine 0.1 mg kg⁻¹ administered subcutaneously. Intra-anaesthetic heart rates, breathing rates, isoflurane requirements, and arterial oxygen saturations were continuously monitored. We found that administration of dexmedetomidine significantly improved heart and breathing rate stability during two of four noxious stimuli (skin incision and whisker stimulation) compared to non-dexmedetomidine-treated mice and lowered isoflurane requirements throughout anaesthesia by 5–6%. No significant differences were found between carprofen and meloxicam. These results demonstrate that dexmedetomidine reduces nociception and provides intra-anaesthetic haemodynamic and respiratory stability in mice. In conclusion, the addition of dexmedetomidine to anaesthetic regimes for craniotomy offers a refinement over current practice for laboratory mice. Full article

Background: The monitoring of nociception/antinociception poses a significant challenge during anesthesia, making the incorporation of new tools like the Parasympathetic Tone Activity (PTA) monitor an added value in feline anesthesia. Objectives: To compare the effectiveness and speed of PTA monitoring when compared to heart rate (HR) in detecting surgical stimuli (SS) during the intraoperative period in 49 female cats undergoing ovariectomy (OV). Methods: Instantaneous Parasympathetic Tone Activity (PTAi) values, HR, f_R, and non-invasive SAP and MAP were continuously monitored and systematically assessed. The time required for HR (HR time) and PTAi (PTAi time) to reach their minimum peak values following each surgical stimulus was collected at five points for each anaesthetized cat. Each collected surgical stimulus was categorized into 3 groups for statistical analysis: no nociception detection, no hemodynamic reaction and a PTAi > 50 (Nhre); no hemodynamic reaction and a PTAi < 50 (Nhre < 50); and hemodynamic reaction and PTAi < 50 (Hre < 50). Results: PTAi response demonstrated effectiveness in detecting nociception compared to HR. The SS were categorized as 36.1% in the Nhre group, 50% in the Nhre < 50 group, and only 13.9% in the Hre < 50 group. In the Hre < 50 group, PTAi time and HR time had similar speeds in detecting the SS (p = 0.821); however, PTA time was significantly slower in the Nhre < 50 group when compared to the Hre < 50 group (p = 0.001). Conclusions: PTA monitoring may be a useful tool to complement HR monitoring for detecting nociception. PTA monitoring demonstrated a superior diagnostic value compared to HR for detecting nociception in cats undergoing OV and a similar speed to HR in detecting SS when HR increases above 20%. Future studies are needed to understand in a clinical setting the meaning of sympathetic activation/nociception detected using the PTA monitor when the HR increase is not clinically relevant. Full article

Adequacy of anesthesia concept (AoA) in the guidance of general anesthesia (GA) is based on entropy, and it also reflects the actual depth of anesthesia and the surgical pleth index (SPI). Therefore, this study aimed to analyze the potential existence of relationships between SPI values at certain stages of the AoA-guided GA for vitreoretinal surgeries (VRS) and the incidence of intolerable postoperative pain perception (IPPP). A total of 175 patients were each assigned to one of five groups. In the first, the VRS procedure was performed under GA without premedication; in the second group, patients received metamizole before GA; in the third, patients received acetaminophen before GA; in the fourth group, patients received Alcaine before GA; and, in the peribulbar block group, the patients received a peribulbar block with a mix of the solutions of lignocaine and bupivacaine. Between the patients declaring mild and statistically significant differences in the IPPP in terms of SPI values before induction (52.3 ± 18.8 vs. 63.9 ± 18.1, p < 0.05) and after emergence from GA (51.1 ± 13 vs. 68.1 ± 8.8; p < 0.001), it was observed that the patients postoperatively correlated with heart rate variations despite the group allocation. The current study proves the feasibility that preoperative SPI values help with predicting IPPP immediately after VRS under AoA guidance and discrimination (between mild diagnoses and IPPP when based on postoperative SPI values) as they correlate with heart rate variations. Specifically, this applies when the countermeasures of IPPP and hemodynamic fluctuations are understood to be of importance in reducing unwelcome adverse events. Full article

Postoperative nausea and vomiting (PONV) constitutes an adverse event after endoscopic sinus surgery (ESS) under general anesthesia (GA) with intravenous opioids, such as remifentanil (RMF). Monitoring the nociception/antinociception balance using the surgical pleth index (SPI) or pupillary dilatation reflex (PRD) helps guide intravenous RMF infusion. We aimed to investigate whether their employment could help reduce the incidence of PONV in patients undergoing ESS. The data of 30 patients from the GA group, 31 from the SPI group, and 28 from the PRD group were analyzed. The initial RMF infusion rate of 0.25 µg/kg body weight/minute was increased by 50% when the SPI, PRD, or Boezaart Bleeding Scale (BBS) were elevated by >15, >5%, or >2 points, respectively, until they normalized. PONV was present in 7/89 patients (7.9%): 2/31 patients (6.5%) of the SPI group, 1/30 patients (3.3%) of the GA group, and 4/28 patients (14.3%) of the PRD group. Neither PRD nor SPI guidance for RMF administration reduced the incidence of PONV compared to standard practice. Further studies are required in order to investigate the possibility of PONV eradication in patients undergoing ESS under GA when it is possibly combined with paracetamol/metamizole preventive analgesia, as well as those using antiemetic prophylaxis based on the Apfel Score and premedication with midazolam. Full article

We present a narrative review focusing on the new role of nociception monitor in intraoperative anesthetic management. Higher invasiveness of surgery elicits a higher degree of surgical stress responses including neuroendocrine-metabolic and inflammatory-immune responses, which are associated with the occurrence of major postoperative complications. Conversely, anesthetic management mitigates these responses. Furthermore, improper attenuation of nociceptive input and related autonomic effects may induce increased stress response that may adversely influence outcome even in minimally invasive surgeries. The original role of nociception monitor, which is to assess a balance between nociception caused by surgical trauma and anti-nociception due to anesthesia, may allow an assessment of surgical stress response. The goal of this review is to inform healthcare professionals providing anesthetic management that nociception monitors may provide intraoperative data associated with surgical stress responses, and to inspire new research into the effects of nociception monitor-guided anesthesia on postoperative complications. Full article

Despite acceptance of the surgical pleth index (SPI) for monitoring the intraoperative balance between noxious stimulation and anti-nociception under general anesthesia, its efficacy for predicting postoperative moderate-to-severe pain remains unclear. We searched electronic databases (e.g., Google Scholar, MEDLINE, Cochrane Library, and EMBASE) to identify articles focusing on associations of SPI at the end of surgery with immediate moderate-to-severe pain in the postanesthesia care unit from inception to 7 July 2022. A total of six observational studies involving 756 adults published between 2016 and 2020 were eligible for quantitative syntheses. Pooled results revealed higher values of SPI in patients with moderate-to-severe pain than those without (mean difference: 7.82, 95% CI: 3.69 to 11.95, p = 0.002, I² = 46%). In addition, an elevated SPI at the end of surgery was able to predict moderate-to-severe pain with a sensitivity of 0.71 (95% confidence interval (CI): 0.65–0.77; I² = 29.01%) and a specificity of 0.58 (95% CI: 0.39–0.74; I² = 79.31%). The overall accuracy based on the summary receiver operating characteristic (sROC) curve was 0.72. In conclusion, this meta-analysis highlighted the feasibility of the surgical pleth index to predict postoperative moderate-to-severe pain immediately after surgery. Our results from a limited number of studies warrant further investigations for verification. Full article

The development of general anesthesia techniques and anesthetic substances has opened new horizons for the expansion and improvement of surgical techniques. Nevertheless, more complex surgical procedures have brought a higher complexity and longer duration for general anesthesia, which has led to a series of adverse events such as hemodynamic instability, under- or overdosage of anesthetic drugs, and an increased number of post-anesthetic events. In order to adapt the anesthesia according to the particularities of each patient, the multimodal monitoring of these patients is highly recommended. Classically, general anesthesia monitoring consists of the analysis of vital functions and gas exchange. Multimodal monitoring refers to the concomitant monitoring of the degree of hypnosis and the nociceptive-antinociceptive balance. By titrating anesthetic drugs according to these parameters, clinical benefits can be obtained, such as hemodynamic stabilization, the reduction of awakening times, and the reduction of postoperative complications. Another important aspect is the impact on the status of inflammation and the redox balance. By minimizing inflammatory and oxidative impact, a faster recovery can be achieved that increases patient safety. The purpose of this literature review is to present the most modern multimodal monitoring techniques to discuss the particularities of each technique. Full article