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PURPOSE OF REVIEW: Identification of biomarkers for immunotherapy treatment in triple negative breast cancer remains crucial for improving outcomes and optimising regimes, particularly in the perioperative setting. There is a need to conduct a scoping review to provide an overview of current research, explore the wider context, and highlight future research considerations in this field. RECENT FINDINGS: The most commonly assessed biomarkers are PD-L1, TILs and CD8 + cells with correlation to outcomes mainly focused on survival. There is a growing interest in evaluating genetic markers. Conclusions are currently limited by knowledge gaps around contextual factors. Important areas of focus for future research include a greater understanding of complex cellular, genetic and metabolic interactions in the perioperative tumour microenvironment, including patient-specific immune profiles. An important challenge remains elucidating the clinical significance of the immunological effects of interventions at each stage of the perioperative period, including the use of anaesthetic agents.
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Adequate management of acute pain in the older population is crucial. However, it is inherently complex because of multiple physiological changes that significantly impact both the pharmacokinetics and pharmacodynamics of medications. Current guidelines promote paracetamol as the first-line analgesic for acute pain in older adults, whereas opioids are advised cautiously for moderate to severe acute pain. However, opioids come with a significant array of side effects, which can be more pronounced in older individuals. Ketamine administered via intranasal (IN) and nebulised inhalation in the emergency department for managing acute pain in older patients shows promising potential for improving pain management and reducing opioid reliance Kampan, Thong-on, Sri-on (2024, Age Ageing, 53, afad255). Nebulised ketamine appears superior in terms of adverse event incidence. However, the adoption of IN or nebulised ketamine in older adult acute pain management remains unclear because of the lack of definitive conclusions and clear guidelines. Nevertheless, these modalities can be valuable options for patients where opioid analgesics are contraindicated or when intravenous morphine titration is impractical or contraindicated. Here, we review these concepts, the latest evidence and propose avenues for research.
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Dor Aguda , Ketamina , Dor Musculoesquelética , Humanos , Idoso , Ketamina/efeitos adversos , Ketamina/administração & dosagem , Morfina/administração & dosagem , Morfina/efeitos adversos , Manejo da Dor/efeitos adversos , Dor Aguda/diagnóstico , Dor Aguda/tratamento farmacológico , Dor Aguda/induzido quimicamente , Dor Musculoesquelética/induzido quimicamente , Dor Musculoesquelética/tratamento farmacológico , Analgésicos/efeitos adversos , Analgésicos Opioides/efeitos adversos , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: The African Surgical Outcomes Study (ASOS) found that maternal mortality following cesarean delivery in Africa is 50 times higher than in high-income countries, and associated with obstetric hemorrhage and anesthesia complications. Mothers who died were more likely to receive general anesthesia (GA). The associations between GA versus spinal anesthesia (SA) and preoperative risk factors, maternal anesthesia complications, and neonatal outcomes following cesarean delivery in Africa are unknown. METHODS: This is a secondary explanatory analysis of 3792 patients undergoing cesarean delivery in ASOS, a prospective observational cohort study, across 22 African countries. The primary aim was to estimate the association between preoperative risk factors and the outcome of the method of anesthesia delivered. Secondary aims were to estimate the association between the method of anesthesia and the outcomes (1) maternal intraoperative hypotension, (2) severe maternal anesthesia complications, and (3) neonatal mortality. Generalized linear mixed models adjusting for obstetric gravidity and gestation, American Society of Anesthesiologists (ASA) category, urgency of surgery, maternal comorbidities, fetal distress, and level of anesthesia provider were used. RESULTS: Of 3709 patients, SA was performed in 2968 (80%) and GA in 741 (20%). Preoperative factors independently associated with GA for cesarean delivery were gestational age (adjusted odds ratio [aOR], 1.093; 95% confidence interval [CI], 1.052-1.135), ASA categories III (aOR, 11.84; 95% CI, 2.93-46.31) and IV (aOR, 11.48; 95% CI, 2.93-44.93), eclampsia (aOR, 3.92; 95% CI, 2.18-7.06), placental abruption (aOR, 6.23; 95% CI, 3.36-11.54), and ruptured uterus (aOR, 3.61; 95% CI, 1.36-9.63). SA was administered to 48 of 94 (51.1%) patients with eclampsia, 12 of 28 (42.9%) with cardiac disease, 14 of 19 (73.7%) with preoperative sepsis, 48 of 76 (63.2%) with antepartum hemorrhage, 30 of 55 (54.5%) with placenta previa, 33 of 78 (42.3%) with placental abruption, and 12 of 29 (41.4%) with a ruptured uterus. The composite maternal outcome "all anesthesia complications" was more frequent in GA than SA (9/741 [1.2%] vs 3/2968 [0.1%], P < .001). The unadjusted neonatal mortality was higher with GA than SA (65/662 [9.8%] vs 73/2669 [2.7%], P < .001). The adjusted analyses demonstrated no association between method of anesthesia and (1) intraoperative maternal hypotension and (2) neonatal mortality. CONCLUSIONS: Analysis of patients undergoing anesthesia for cesarean delivery in Africa indicated patients more likely to receive GA. Anesthesia complications and neonatal mortality were more frequent following GA. SA was often administered to high-risk patients, including those with eclampsia or obstetric hemorrhage. Training in the principles of selection of method of anesthesia, and the skills of safe GA and neonatal resuscitation, is recommended.
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Anestesia Geral , Anestesia Obstétrica , Cesárea , Mortalidade Infantil , Humanos , Feminino , Cesárea/efeitos adversos , Cesárea/mortalidade , Gravidez , Estudos Prospectivos , Fatores de Risco , Adulto , Recém-Nascido , Anestesia Obstétrica/efeitos adversos , Anestesia Obstétrica/mortalidade , Mortalidade Infantil/tendências , Anestesia Geral/efeitos adversos , Anestesia Geral/mortalidade , África/epidemiologia , Mortalidade Materna/tendências , Raquianestesia/efeitos adversos , Raquianestesia/mortalidade , Lactente , Adulto Jovem , Estudos de CoortesRESUMO
BACKGROUND: Opioids play an important role in peri-operative pain management. However, opioid use is challenging for healthcare practitioners and patients because of concerns related to opioid crises, addiction and side effects. OBJECTIVE: This review aimed to identify and synthesise the existing evidence related to adults' experiences of opioid use in postoperative pain management. DESIGN: Systematic scoping review of qualitative studies. Inductive content analysis and the Theoretical Domains Framework (TDF) were applied to analyse and report the findings and to identify unexplored gaps in the literature. DATA SOURCES: Ovid MEDLINE, PsycInfo, Embase, CINAHL (EBSCO), Cochrane Library and Google Scholar. ELIGIBILITY CRITERIA: All qualitative and mixed-method studies, in English, that not only used a qualitative approach that explored adults' opinions or concerns about opioids and/or opioid reduction, and adults' experience related to opioid use for postoperative pain control, including satisfaction, but also aspects of overall quality of a person's life (physical, mental and social well being). RESULTS: Ten studies were included; nine were qualitative ( n â=â9) and one used mixed methods. The studies were primarily conducted in Europe and North America. Concerns about opioid dependence, adverse effects, stigmatisation, gender roles, trust and shared decision-making between clinicians and patients appeared repeatedly throughout the studies. The TDF analysis showed that many peri-operative factors formed people's perceptions and experiences of opioids, driven by the following eight domains: Knowledge, Emotion, Beliefs about consequences, Beliefs about capabilities, Self-confidence, Environmental Context and Resources, Social influences and Decision Processes/Goals. Adults have diverse pain management goals, which can be categorised as proactive and positive goals, such as individualised pain management care, as well as avoidance goals, aimed at sidestepping issues such as addiction and opioid-related side effects. CONCLUSION: It is desirable to understand the complexity of adults' experiences of pain management especially with opioid use and to support adults in achieving their pain management goals by implementing an individualised approach, effective communication and patient-clinician relationships. However, there is a dearth of studies that examine patients' experiences of postoperative opioid use and their involvement in opioid usage decision-making. A summary is provided regarding adults' experiences of peri-operative opioid use, which may inform future researchers, healthcare providers and guideline development by considering these factors when improving patient care and experiences.
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Analgésicos Opioides , Manejo da Dor , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Adulto , Manejo da Dor/métodos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/etiologiaRESUMO
Pain is widely studied and is considered a major clinical, social, and economic problem worldwide, although it remains poorly understood. For disaster victims, the complex picture, biologically, psychologically, and socially, only makes the situation even more complicated. This narrative review aims to describe specific aspects of pain and pain management in disaster victims. We reviewed relevant literature, both on pain management and selected specific data related to conflict victims. We discuss the complexity of the picture, its different aspects, and mechanisms. We discuss the limitations of current approaches and propose a simple strategy, including mitigation plans, all illustrated by a case study based on a personal experience in the Gaza Strip in 2022. The vulnerability factors are well known, as well as the tangle of intense acute pain and the persistence of pain in the subacute and chronic phase. However, the management of acute pain is, in a disaster context, more constrained than chosen. Empirical evidence suggests a focus on modifiable risk factors as well as the evaluation of strategies guiding future management. This management may depend on obstacles and barriers, linked to the context of the disaster, the availability of medicines, techniques, skills as well as linguistic and cultural barriers. Our proposal includes systematic assessment and, in a later phase, tailored and personalized treatment. In the chronic phase of rehabilitation and follow-ups, the essential place for management of psychological and social aspects become predominant. In disaster areas, including during and after conflict, the management, and recommendations for the management of acute and chronic pain are complex, distinct but interdependent. Acute pain must be systematically assessed and treated while personalized care pathways are desirable at a later stage. Psychological and social considerations are essential. Data collection should be systematically considered.
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Manejo da Dor , Humanos , Manejo da Dor/métodos , Desastres , Vítimas de Desastres/psicologia , DorRESUMO
Background: Chronic conditions, especially pain conditions, have a very significant impact on quality of life and on workplaces. Workplace interventions for chronic conditions are heterogenous, multidimensional, and sometimes poorly evidenced. The Joint Action for Chronic Disease Plus (CHRODIS Plus), including The CHRODIS Plus Workbox on Employment and Chronic Conditions (CPWEC), aimed to combat this, prevent chronic disease and multimorbidity, and influence policy in Europe. However, the supporting evidence behind CHRODIS Plus has not been formally assessed. Methods: A scoping review was carried out; Embase, MEDLINE, and CINAHL were searched for literature related to CHRODIS Plus and pain. Title and abstract and full-text screening were carried out in duplicate and independently. Additionally, CHRODIS Plus authors were approached for unpublished data. Secondly, the search was broadened to CHRODIS Plus and pain-causing conditions. Grey literature was also searched. Appropriateness appraisal was derived from the Trial Forge Guidance. Systematic reviews, on which CPWEC was based, were appraised using the A Measurement Tool to Assess systematic Reviews (AMSTAR) 2 tool. Results: The initial search yielded two results, of which zero were suitable to be included in the scoping review. The second, broader search revealed 14 results; however, none were deemed suitable for inclusion. AMSTAR 2 scores revealed that the three systematic reviews influencing CPWEC were of varying quality (from critically low to moderate). Conclusions: CPWEC is based on heterogenous reviews of varying quality. However, comparable tools are designed using alternative forms of evidence. Further research evaluating the post-implementation efficacy of the tool is needed.
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BACKGROUND: Although the challenges of living with chronic pain are widely documented within existing literature, to our knowledge, the acceptability of pain for people living with persistent pain, has not been fully explored. The current study aims to explore what 'acceptable pain' means to adults living with chronic non-cancer pain (CPCP). METHODS: A total of 117 participants (aged 21 to 77 years) worldwide were recruited using opportunity sampling. Participants completed an online qualitative survey. Qualitative analysis of the data used inductive reflexive thematic analysis. RESULTS: Two themes were generated. The first theme-'I grin and bear it', described participants' desire and drive to push through their pain to live their daily lives to the best of their ability. Contrastingly, the second theme-'Thriving versus surviving', placed greater importance on leading meaningful and happy lives despite living with chronic pain. The acceptability of pain was found to be influenced by various factors including, but not limited to, pain severity, mental health, functionality, productivity and quality of life. CONCLUSIONS: It can be difficult to identify when a clinically significant change in pain has occurred from numerical pain rating scales. We have identified two themes and a number of factors influencing the acceptability of pain. Understanding individuals' unique perceptions of what constitutes 'acceptable pain' is crucial for clinicians when assessing and managing chronic pain. Pain is a highly subjective experience, and what one person considers acceptable may differ significantly from another person's perspective. Recommendations to improve healthcare services for adults living with CNCP are proposed and directions for future research are explored. SIGNIFICANCE: Adults with CNCP have unique experiences of living with and managing their chronic pain. CNCP was found to affect biological, psychological, and social aspects of an individual's life. The acceptability of pain exists on a continuum where adjacent parts are not noticeably different from each other, but the extremes of the continuum appear very distinct. The acceptability of pain is determined by the different factors that influence an individuals' ability to function on a day-to-day basis as well as their quality of life. While acceptable pain and manageable pain represent distinct aspects of the pain experience, the relationship between them is complex and plays a crucial role in how individuals cope with and adapt to chronic pain.
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Dor Crônica , Pesquisa Qualitativa , Qualidade de Vida , Humanos , Dor Crônica/psicologia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Qualidade de Vida/psicologia , Adulto Jovem , Percepção da Dor , Medição da Dor/métodosRESUMO
Consumption of fava beans in a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency, also called favism, can lead to a haemolytic crisis. We report the case of a 69-year-old patient of Iranian origin admitted to the emergency department following syncope. The patient's comprehensive interview and blood analysis revealed that the patient presented a haemolytic crisis triggered by fava beans consumption, due to previously undiagnosed G6PD deficiency. The pathophysiology of favism is complex and clinical presentations of G6PD deficiency are numerous due to multiple genetic variants. Indirect signs, such as the presence of methemoglobinaemia and hemighosts on the blood smear, can aid in the diagnosis. This case highlights the importance of considering G6PD deficiency as a potential diagnosis in case of haemolytic crisis, even in elderly patients.
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ABSTRACT: The 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11) aims at improving the lives of persons with the lived experience of chronic pain by providing clearly defined and clinically useful diagnoses that can reduce stigma, facilitate communication, and improve access to pain management, among others. The aim of this study was to assess the perspective of people with chronic pain on these diagnoses. An international web-based survey was distributed among persons with the lived experience of chronic pain. After having seen an information video, participants rated the diagnoses on 8 endorsement scales (eg, diagnostic fit, stigma) that ranged from -5 to +5 with 0 representing the neutral point of no expected change. Overall ratings and differences between participants with chronic primary pain (CPP) and chronic secondary pain (CSP) were analyzed. N = 690 participants were included in the data analysis. The ratings on all endorsement scales were significantly higher than the neutral point of 0. The highest ratings were obtained for "openness" (2.95 ± 1.93) and "overall opinion" (1.87 ± 1.98). Participants with CPP and CSP did not differ in their ratings; however, those with CSP indicated an improved diagnostic fit of the new diagnoses, whereas participants with CPP rated the diagnostic fit of the new diagnoses similar to the fit of their current diagnoses. These results show that persons with the lived experience of chronic pain accept and endorse the new diagnoses. This endorsement is an important indicator of the diagnoses' clinical utility and can contribute to implementation and advocacy.
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Chronic postoperative pain (CPSP) is a major issue after surgery, which may impact on patient's quality of life. Traditionally, CPSP is believed to rely on maladaptive hyperalgesia and risk factors have been identified that predispose to CPSP, including acute postoperative pain. Despite new models of prediction are emerging, acute pain is still a modifiable factor that can be challenged with perioperative analgesic strategies. In this review we present the issue of CPSP, focusing on molecular mechanism underlying the development of acute and chronic hyperalgesia. Also, we focus on how perioperative strategies can impact directly or indirectly (by reducing postoperative pain intensity) on the development of CPSP.
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Dor Crônica , Hiperalgesia , Humanos , Hiperalgesia/complicações , Qualidade de Vida , Analgésicos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/complicações , Dor Pós-Operatória/prevenção & controle , Sistema Nervoso CentralRESUMO
Opioid-free anesthesia (OFA) represents an innovative approach that prioritizes patient safety, reduces the risks associated with opioid use, and seeks to enhance recovery. Few descriptions regarding the practical and implementation aspects exist. This review serves as a practical guide on OFA teaching and application. We briefly discuss the historical use of opioids in anesthesia, side effects and their consequences. We discuss pedagogical avenues and challenges, as well as implementation of OFA in less experienced settings. Opioid use in anesthesia originally coexisted with OFA. During the last decades, the advent of multimodal analgesia has resulted in decreased opioid dosages both before and after surgery. Recently, OFA increased in popularity, supported by meta-analyses, due to reduced nausea and vomiting, with a potential, even if limited, impact on pain. OFA, as part of rational prescribing, may contribute to a more patient-centered approach. Different strategies for OFA implementation coexist. Educational aspects, leadership, guidelines, local guidance, and training are all important. We propose a framework for OFA implementation with concrete options, including patient preparation, choice of OFA pharmacological agents (according to type of surgery and patient), and postoperative care. Whilst opioids still have an important place in pain management, they have brought harms that we cannot ignore. Evidence for using opioid-sparing and OFA techniques continues to emerge and there is a need to personalize more approaches. In this review, we provide evidence-based, relatively simple methods that can be used in implementing and delivering OFA.
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Analgésicos Opioides , Anestesiologia , Humanos , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Anestesia/métodos , Anestesiologia/educaçãoRESUMO
Research has been conducted investigating the neuronal pathways responsible for the generation of chronic neuropathic pain, including the components of it in conditions such as chronic post-surgical pain, phantom limb pain, and cluster headaches. Forming part of the management of such conditions, capsaicin as a molecule has proven effective. This review has investigated the central nervous system modifications exhibited in such conditions and the pharmacological mechanisms of capsaicin relevant to this. The current paradigm for explaining topical capsaicin-induced analgesia is that TRPV1-mediated calcium ion influx induces calpain, in turn causing axonal ablation and functional defunctionalisation in the PNS (Peripheral Nervous System). Demonstrated through the analysis of existing data, this review demonstrates the changes seen in the CNS (Central Nervous System) in chronic neuropathic pain, as well as some of the evidence for capsaicin modulation on the CNS. Further supporting this, the specific molecular mechanisms of capsaicin-induced analgesia will also be explored, including the action of TRPV1, as well as discussing the further need for clinical research into this area of uncertainty due to the limited specific data with suitable parameters. Further research this review identified as potentially useful in this field included fMRI (functional Magnetic Resonance Imaging) studies, though more specific observational studies of patients who have already been administered capsaicin as a current treatment may prove helpful in studying the modification of the CNS in the long term.
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Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics' impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature.
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INTRODUCTION: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. MATERIALS AND METHODS: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. RESULTS: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. CONCLUSION: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.
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Background: Although cancer is a significant issue in sub-Saharan Africa, and cancer pain is prevalent, there is insufficient data and research on the barriers to cancer pain management. Even in countries where evidence exists, few studies explore the links between these barriers, which makes it difficult to implement system-wide approaches to address them. Methods: The search strategy was developed and conducted on databases including MEDLINE, Embase and Web of Science to identify peer-reviewed studies. Then, these retrieved studies were screened systematically to select papers that had met pre-specified criteria. The barriers were categorised into patient-, health professional- and health system-level domains. Then, the quality of the included papers was assessed using the mixed methods appraisal tool. Finally, a narrative synthesis was utilised to summarise the findings. Results: Fourteen relevant articles from 19 sub-Saharan African countries were included in the scoping review. All the studies highlighted barriers to optimal cancer pain management. Healthcare system-related domains had the most frequently reported barriers. Approximately half of the included studies met 100% of the methodological quality criteria in the critical appraisal. Conclusion: Improving pain management for cancer patients in sub-Saharan Africa requires further high-level research evidence on regulatory policies and interventional strategies, especially at the health system level, as most barriers to cancer pain treatment essentially stem from the healthcare system.
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Despite the potential benefits of intrathecal morphine (ITM), the precise role and dosing of ITM in robotic assisted surgery (RAS) remains unclear. This systematic review explores real-world evidence to evaluate the efficacy and outcomes of ITM in patients undergoing RAS. In accordance with PRISMA guidelines, a comprehensive search was conducted on four databases: MEDLINE, Embase, Cochrane Library and APA PsycInfo. Primary outcomes included pain scores at rest and on exertion at 24- and 48-h time intervals, and secondary outcomes aimed to explore the side effects of ITM. A meta-analysis was conducted to determine mean differences. A risk of bias assessment was conducted via the Cochrane Risk of Bias 2 tool. A total of 9 RCTs involving 619 patients were included in this review, of which 298 patients were administered ITM. Significant pain score reductions were observed both at rest (MD = -27.15; 95% CI [-43.97, -10.33]; I2 = 95%; p = 0.002) and on exertion (MD = -25.88; 95% CI [-37.03, -14.72]; I2 = 79%; p = 0.0003) 24 h postoperatively in the ITM groups, accompanied by a notable decrease in postoperative IV morphine equivalent consumption at 24 h (MD = -20.13; 95% CI [-30.74, -9.52]; I2 = 77%; p = 0.0002). ITM improved pain scores both at rest and on exertion at 24 and 48 h intervals, concurrently reducing the need for postoperative opioid consumption, but at the cost of an increased incidence of adverse events.