Daily Anesthesiology Research Analysis
Three impactful studies span mechanistic anesthesia science, perioperative pain therapy, and thoracic anesthesia practice. Orexinergic activation in the nucleus accumbens promotes arousal and restores NAc–frontal cortex communication under isoflurane. A meta-analysis of 56 RCTs shows platelet-rich plasma provides medium-term analgesic benefit for several chronic pain conditions, while a meta-analysis of 19 RCTs suggests non-intubated VATS may reduce PPCs, PONV, and sore throat but with more intr
Summary
Three impactful studies span mechanistic anesthesia science, perioperative pain therapy, and thoracic anesthesia practice. Orexinergic activation in the nucleus accumbens promotes arousal and restores NAc–frontal cortex communication under isoflurane. A meta-analysis of 56 RCTs shows platelet-rich plasma provides medium-term analgesic benefit for several chronic pain conditions, while a meta-analysis of 19 RCTs suggests non-intubated VATS may reduce PPCs, PONV, and sore throat but with more intraoperative hypoxemia risk than intubated VATS.
Research Themes
- Neural circuits of anesthesia and arousal
- Biologic therapies for chronic pain (PRP)
- Non-intubated anesthesia strategies in thoracic surgery
Selected Articles
1. Orexin signalling in the nucleus accumbens promotes arousal from isoflurane anaesthesia and restores communication between the nucleus accumbens and frontal cortex.
In mice, orexinergic inputs to the nucleus accumbens are wake-active during isoflurane anesthesia and arousal. Optogenetic activation of NAc orexin terminals reduced burst suppression, delayed induction, accelerated emergence, and orexin-A microinjection promoted arousal; effects involved OX1R on D1R-positive neurons and restored NAc–frontal cortex communication.
Impact: This mechanistic study delineates a specific striatal circuit and receptor mechanism by which orexin modulates emergence from anesthesia, advancing our understanding of consciousness control under anesthesia.
Clinical Implications: Targeting orexin–NAc pathways or OX1R on D1R-positive neurons could inspire pharmacologic strategies to hasten emergence or mitigate EEG burst suppression, pending translational safety and efficacy data.
Key Findings
- Orexinergic afferents in NAc are wake-active during isoflurane anesthesia and arousal.
- Optogenetic activation of NAc orexin terminals reduced burst suppression ratio from 67.4% to 14.5% at 1.4 vol% isoflurane (n=6, P<0.001), delayed induction, and shortened emergence.
- NAc microinjection of orexin-A promoted arousal; OX1R predominantly on D1R-positive neurons mediated effects and restored NAc–frontal cortex communication.
Methodological Strengths
- Multi-modal mechanistic approach combining fibre photometry, optogenetics, neuropharmacology, and in vivo electrophysiology
- Clear, quantifiable EEG endpoints (burst suppression ratio) under controlled anesthetic concentration
Limitations
- Preclinical rodent model; human translatability and safety are unknown
- Findings are specific to isoflurane and may not generalize across anesthetic agents
Future Directions: Test orexinergic modulators in large-animal models and early-phase clinical trials to evaluate emergence profiles, EEG dynamics, cognition, and safety; assess agent-specific generalizability.
BACKGROUND: Orexin can induce arousal from general anaesthesia; however, the underlying mechanisms are not fully understood. Nucleus accumbens (NAc), a downstream target of orexinergic neurones, plays a role in regulating consciousness. We aimed to clarify whether and how the NAc mediates the arousal effects of orexin. METHODS: Fibre photometry was used to track changes of orexinergic afferent activity during isoflurane anaesthesia and arousal from anaesthesia. Optogenetics was used to study the effects of orexinergic afferents to the NAc. Neuropharmacology approaches were used to assess receptor mechanisms. Optogenetics and in vivo electrophysiology were used to assess the influence of orexin on NAc neuronal firing and communication between the NAc and the frontal cortex. RESULTS: Orexinergic afferents in the NAc were wake-active during isoflurane anaesthesia and the arousal process. Optogenetic activation of orexinergic terminals in the NAc prolonged the time to induction, shortened time to emergence, and reduced the burst suppression ratio (from 67.4% [2.5%] to 14.5% [1.0%]; n=6, P<0.001) during 1.4 vol% isoflurane anaesthesia. Microinjection of orexin-A into the NAc promoted arousal from isoflurane anaesthesia. Orexin-1 receptors were primarily expressed in NAc D1 receptor-positive (D1R
2. Platelet-Rich Plasma for Treating Chronic Noncancer Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Across 56 RCTs (7142 patients), PRP modestly reduced pain overall vs placebo/active controls, with clinically meaningful benefits emerging at ≥3 months. PRP outperformed corticosteroid and hyaluronic acid injections and was beneficial in knee osteoarthritis and rotator cuff tendinopathy/tear, but not in plantar fasciitis.
Impact: This is the most comprehensive RCT-based synthesis to date indicating condition-specific and time-dependent analgesic benefits of PRP, informing evidence-based integration of PRP into pain practice.
Clinical Implications: Consider PRP as a longer-term analgesic option particularly for knee osteoarthritis and rotator cuff disorders, with realistic counseling that benefits are unlikely within 3 months and may be absent for plantar fasciitis.
Key Findings
- Included 56 RCTs (7142 patients); overall pain reduction vs controls (SMD -0.37; p=0.001).
- No significant effect <3 months (SMD 0.12), but moderate benefit at ≥3 months (SMD -0.69; p<0.001).
- Condition-specific efficacy: knee osteoarthritis (SMD -0.59) and rotator cuff tendinopathy/tear (SMD -0.60) favored PRP; no benefit in plantar fasciitis.
- PRP outperformed corticosteroid (SMD -0.53) and hyaluronic acid (SMD -0.55) injections.
Methodological Strengths
- PRISMA-compliant meta-analysis with PROSPERO registration (CRD42023441115)
- Risk of bias (RoB 2) and GRADE appraisal; random-effects modeling for heterogeneity
Limitations
- High heterogeneity and variability in PRP preparation, dosing, and protocols across trials
- Condition-specific evidence uneven; some subgroups (e.g., plantar fasciitis) underpowered or inconsistent
Future Directions: Standardize PRP preparation/administration and conduct head-to-head RCTs with longer follow-up to define optimal indications, dosing, and durability.
INTRODUCTION: Chronic noncancer pain represents a significant global health challenge, contributing to disability, lost productivity, diminished quality of life, and substantial socioeconomic burden. Platelet-rich plasma (PRP) has emerged as a promising therapeutic option for managing chronic pain. However, a comprehensive assessment of its efficacy and the evidence supporting its use remains limited. This study aimed to systematically evaluate the analgesic effectiveness of PRP compared with placebo or active drug treatments across a wide range of chronic noncancer pain conditions using a rigorous meta-analytic approach. The goal is to provide evidence-based insights to inform clinical decision-making and improve patient outcomes. METHODS: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted in the PubMed, Embase, MEDLINE, and Cochrane Library databases to identify randomized controlled trials (RCTs). Studies were screened according to predefined inclusion and exclusion criteria. A random-effects model was applied to account for heterogeneity among studies. The primary outcome, pain scores in patients with chronic noncancer pain, was assessed using the standardized mean difference (SMD). The risk of bias of the included studies was evaluated using the Revised Cochrane Risk-of-Bias Tool (RoB 2). The quality of evidence was rated by the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: A total of 691 RCTs were screened, and 56 studies (comprising 103 comparisons and 7142 patients) were eligible for analysis. PRP was associated with a statistically significant reduction in pain scores compared with both active drug treatments and placebo (SMD = -0.37, 95% confidence interval (CI) -0.59 to -0.15, p = 0.001). No significant differences were observed in pain scores for follow-up periods shorter than 3 months (SMD = 0.12, 95% CI -0.16 to 0.40, p > 0.05). A statistically significant and moderate reduction in pain score was found for follow-up durations of at least 3 months (SMD = -0.69, 95% CI -0.98 to -0.40, p < 0.001). Meta-analyses of subgroups revealed statistically significant and moderate pain reduction in favor of PRP versus active drug treatments for osteoarthritic knee pain (SMD = -0.59, 95% CI -1.01 to -0.17, p = 0.009) and rotator cuff tendinopathy/tear (SMD = -0.60, 95% CI -1.01 to -0.19, p = 0.01), but no significant differences for plantar fasciitis (SMD = 0.03, 95% CI -0.98 to 1.04, p > 0.05). PRP was associated with moderate pain reduction when compared with corticosteroid (SMD = -0.53, 95% CI -0.98 to -0.08, p = 0.02) and hyaluronic acid injection (SMD = -0.55, 95% CI -0.89 to -0.21, p = 0.004). CONCLUSIONS: PRP injections appear to effectively reduce pain in various chronic noncancer pain conditions and show superior analgesic efficacy compared with corticosteroid and hyaluronic acid injections. These findings suggest that PRP may be a preferred treatment option for managing chronic noncancer pain, offering a more sustainable alternative for long-term pain relief. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023441115.
3. Comparison of non-intubated and intubated video-assisted thoracoscopic surgery for perioperative complications-a systematic review and meta-analysis.
In 19 RCTs, NIVATS reduced hospital length of stay, time to feeding, and chest-tube duration, and lowered risks of PPCs, PONV, and sore throat compared with IVATS. However, intraoperative hypoxemia occurred less frequently with IVATS, underscoring the need for careful patient selection and intraoperative monitoring when using NIVATS.
Impact: Synthesizes RCT evidence clarifying benefits and trade-offs of NIVATS, directly informing anesthetic strategy and perioperative risk management in thoracic surgery.
Clinical Implications: NIVATS may be preferred for selected patients to reduce PPCs and enhance recovery, but teams should have protocols for managing hypoxemia and conversion to intubation.
Key Findings
- Meta-analysis of 19 RCTs comparing NIVATS vs IVATS.
- NIVATS reduced length of stay, time to feeding, and chest-tube duration.
- NIVATS lowered postoperative pulmonary complications, PONV, and sore throat vs IVATS.
- Hypoxemia incidence was lower in IVATS groups; no significant differences in perioperative cough or arrhythmias.
Methodological Strengths
- Restriction to randomized controlled trials across multiple databases
- Assessment of bias risk and synthesis of clinically meaningful outcomes
Limitations
- Variability in surgical indications, anesthetic techniques, and NIVATS protocols across trials
- Potential publication bias and limited reporting on conversion and rescue strategies
Future Directions: Standardize NIVATS protocols and identify risk stratification criteria for hypoxemia; pragmatic RCTs with predefined conversion algorithms and cardiopulmonary endpoints.
BACKGROUND: Non-intubated video-assisted thoracic surgery (NIVATS) avoids lung injury and intubation-related complications from mechanical ventilation, but the intraoperative safety and postoperative recovery quality of NIVATS remain controversial. Consequently, we systematically assessed the viability and safety of non-intubated video-assisted thoracic surgery (NIVATS) in comparison to intubated video-assisted thoracic surgery (IVATS). These findings provide evidence for optimizing anesthetic and surgical decision-making. METHODS: PubMed, Web of Science, Embase, Cochrane Library, OVID, and Google Scholar were queried from their establishment until October 2024. We included eligible studies that compared non-intubated anesthesia with intubated anesthesia for video-assisted thoracoscopic surgery for thoracic conditions. Following the evaluation of bias risk in these randomized controlled trials (RCTs), a meta-analysis was conducted using Review Manager (Manager 5.4). RESULTS: Nineteen randomized controlled trials were incorporated into the study. NIVATS demonstrated a reduced length of hospital stay, feeding time, and chest-tube dwell time compared to intubated methods. IVATS groups, hypoxemia exhibited a reduced incidence, but perioperative cough and perioperative arrhythmias revealed no statistically significant differences between IVATS and NIVATS groups. The NIVATS groups exhibited a significantly reduced risk compared to the IVATS groups for postoperative pulmonary complications (PPCs), postoperative nausea and vomiting (PONV), and sore throat. CONCLUSIONS: NIVATS avoid complications associated with intubation and are able to accelerate patient recovery to a certain extent. Although NIVATS carries intraoperative safety risks, careful patient selection can mitigate these risks.