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BACKGROUND: Despite the low-risk nature of participation in most clinical anesthesia trials, subject recruitment on the same day as surgery is often restricted due to the concerns of researchers and local research ethics boards that same-day consent may not afford adequate time and opportunity for patients to weigh and make decisions, as well as perceptions of patient vulnerability immediately prior to surgery that could impact the voluntary nature and the rigor of the informed consent process. However, specialties such as anesthesiology, critical care, interventional radiology, and emergency medicine have a varied pattern of practice and patient acquaintance that does not typically afford the luxury of time or, in many cases, advance consent for participation in research. Indeed, the initial encounter between anesthesiologists and patients undergoing elective procedures routinely occurs on the day of surgery. Concerns of coercion related to same-day consent for clinical anesthesia research trials have not been borne out in the literature, and represent a significant obstacle to clinical researchers, as well as to the patients who are denied opportunities for potential benefit through participation in research studies. METHODS: We describe the protocol for a prospective randomized controlled trial examining the voluntariness of patient consent, solicited either in advance of surgery or on the same day, to participate in an anesthesia research study at Women's College Hospital. One hundred fourteen patients scheduled to undergo ambulatory anterior cruciate ligament repair facilitated by general anesthesia with an adductor canal block will be randomized for recruitment either (a) in the pre-operative assessment clinic before the day of surgery or (b) on the day of surgery, to be approached for consent to participate in a fabricated research study of adjunct medications in adductor canal blocks. Regardless of allocation, patients in both groups will receive the same routine standard of care and will complete a post-operative questionnaire to signal perceptions of undue influence in the process of providing informed consent for the fabricated trial. DISCUSSION: This study will inform trial design and practice guidelines surrounding the amount of time patients ought to be afforded in order to make durable decisions to participate (or not) in clinical research studies. This is expected to impact trial recruitment in a variety of clinical settings where researchers have only brief opportunities to interface with patients. TRIAL REGISTRATION: The trial was registered prospectively on the Open Science Framework (OSF), registration #46twc, on 2023-Mar-17.
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Consentimento Livre e Esclarecido , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Estudos Prospectivos , Seleção de Pacientes , Sujeitos da Pesquisa/psicologia , Fatores de Tempo , Feminino , Anestesia GeralRESUMO
During the last 100 years, the role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium and other perioperative neurocognitive disorders. The discovery of the rapid and sustained antidepressant properties of ketamine, and early results suggesting that other general anesthetic drugs (including nitrous oxide, propofol, and isoflurane) have antidepressant properties, has positioned anesthesiologists at a new frontier in the treatment of neuropsychiatric disorders. Moreover, shared interest in understanding the biologic underpinnings of anesthetic drugs as psychotropic agents is eroding traditional academic boundaries between anesthesiology and psychiatry. This article presents a brief overview of anesthetic drugs as novel antidepressants and identifies promising future candidates for the treatment of depression. The authors issue a call to action and outline strategies to foster collaborations between anesthesiologists and psychiatrists as they work toward the common goals of repurposing anesthetic drugs as antidepressants and addressing mood disorders in surgical patients.
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Anestesiologistas , Anestésicos Gerais , Antidepressivos , Reposicionamento de Medicamentos , Humanos , Reposicionamento de Medicamentos/métodos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológicoRESUMO
INTRODUCTION: Transition-related surgery is an effective treatment for gender dysphoria, but the perioperative analgesic management of transgender patients is nuanced and potentially complicated by higher rates of mood and substance use disorders. Regional anesthetic techniques are known to reduce pain severity and opioid requirements; however, little is known regarding the relative analgesic effectiveness of regional anesthesia for transgender patients undergoing transition-related surgery. METHODS: We performed a systematic review of the literature to evaluate original reports characterizing the analgesic effectiveness of regional anesthetic techniques for patients undergoing chest and/or genital transition-related surgery. Our primary outcomes were pain severity and opioid requirements on the first postoperative day. RESULTS: Of the 1863 records identified, 10 met criteria for inclusion and narrative synthesis. These included two randomized controlled trials, three cohort studies, and five case reports/series, comprising 293 patients. Four reports described 243 patients undergoing chest surgery, of whom 86% were transgender men undergoing mastectomy with pectoralis nerve blocks or local anesthetic instillation devices. The remaining six reports comprised 50 patients undergoing genital surgery, of whom 56% were transgender women undergoing vaginoplasty with erector spinae plane blocks or epidural anesthesia. Three studies directly compared regional techniques to parenteral analgesia alone. Two of these studies reported lower pain scores and opioid requirements on the first postoperative day with nerve blocks compared with none while the third study reported no difference between groups. Complications related to regional anesthetic techniques were rare among patients undergoing transition-related surgery. DISCUSSION: Despite the ever-growing demand for transition-related surgery, the relative analgesic effectiveness of regional anesthesia for transgender patients undergoing transition-related surgery is very understudied and insufficient to guide clinical practice. Our systematic review of the literature serves to underscore regional anesthesia for transition-related surgery as a priority area for future research.
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INTRODUCTION: The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. OBJECTIVE: The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. METHODS: This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. RESULTS: A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. CONCLUSION: The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.
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Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Feminino , Humanos , Masculino , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Estudos Transversais , Derivados da Morfina/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor/tratamento farmacológicoRESUMO
BACKGROUND: Hyperbaric oxygen therapy (HBOT) has several hemodynamic effects including increases in afterload (due to vasoconstriction) and decreases in cardiac output. This, along with rare reports of pulmonary edema during emergency treatment, has led providers to consider HBOT relatively contraindicated in patients with reduced left ventricular ejection fraction (LVEF). However, there is limited evidence regarding the safety of elective HBOT in patients with heart failure (HF), and no existing reports of complications among patients with HF and preserved LVEF. We aimed to retrospectively review patients with preexisting diagnoses of HF who underwent elective HBOT, to analyze HBOT-related acute HF complications. METHODS: Research Ethics Board approvals were received to retrospectively review patient charts. Patients with a history of HF with either preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmEF), or reduced ejection fraction (HFrEF) who underwent elective HBOT at two Hyperbaric Centers (Toronto General Hospital, Rouge Valley Hyperbaric Medical Centre) between June 2018 and December 2020 were reviewed. RESULTS: Twenty-three patients with a history of HF underwent HBOT, completing an average of 39 (range 6-62) consecutive sessions at 2.0 atmospheres absolute (ATA) (n = 11) or at 2.4 ATA (n = 12); only two patients received fewer than 10 sessions. Thirteen patients had HFpEF (mean LVEF 55 ± 7%), and seven patients had HFrEF (mean LVEF 35 ± 8%) as well as concomitantly decreased right ventricle function (n = 5), moderate/severe tricuspid regurgitation (n = 3), or pulmonary hypertension (n = 5). The remaining three patients had HFmEF (mean LVEF 44 ± 4%). All but one patient was receiving fluid balance therapy either with loop diuretics or dialysis. Twenty-one patients completed HBOT without complications. We observed symptoms consistent with HBOT-related HF exacerbation in two patients. One patient with HFrEF (LVEF 24%) developed dyspnea attributed to pulmonary edema after the fourth treatment, and later admitted to voluntarily holding his diuretics before the session. He was managed with increased oral diuretics as an outpatient, and ultimately completed a course of 33 HBOT sessions uneventfully. Another patient with HFpEF (LVEF 64%) developed dyspnea and desaturation after six sessions, requiring hospital admission. Acute coronary ischemia and pulmonary embolism were ruled out, and an elevated BNP and normal LVEF on echocardiogram confirmed a diagnosis of pulmonary edema in the context of HFpEF. Symptoms subsided after diuretic treatment and the patient was discharged home in stable condition, but elected not to resume HBOT. CONCLUSIONS: Patients with HF, including HFpEF, may develop HF symptoms during HBOT and warrant ongoing surveillance. However, these patients can receive HBOT safely after optimization of HF therapy and fluid restriction.
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Insuficiência Cardíaca , Oxigenoterapia Hiperbárica , Edema Pulmonar , Disfunção Ventricular Esquerda , Masculino , Humanos , Volume Sistólico , Função Ventricular Esquerda , Estudos Retrospectivos , Oxigenoterapia Hiperbárica/efeitos adversos , Edema Pulmonar/etiologia , Edema Pulmonar/terapia , Prognóstico , Disfunção Ventricular Esquerda/terapia , Diuréticos , Dispneia/terapiaRESUMO
Technological innovation has greatly aided modern medicine, and anaesthesiology in particular, but also contributes to dehumanising influences that promote physician burnout and dissatisfaction among patients. Here we advocate for a profound reaffirmation of humanistic principles-empathy, compassion, and communication-in perioperative medicine. We propose adaptable strategies to bolster humanism in practice, such as curricular offerings, simulation training, role modelling, and recognition. As perioperative technologies continue to evolve, the threat of depersonalisation in anaesthetic care looms, making commitments to humanism a crucial precondition for healing in the communities in which we work and live.
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Anestesiologia , Médicos , Humanos , Humanismo , Comunicação , TecnologiaRESUMO
During endochondral ossification, chondrocytes secrete a proteoglycan (PG)-rich extracellular matrix that can inhibit the process of cartilage maturation, including expression of Ihh and Col10a1. Because bone morphogenetic proteins (BMPs) can promote cartilage maturation, we hypothesized that cartilage PGs normally inhibit BMP signalling. Accordingly, BMP signalling was evaluated in chondrocytes of wild-type and PG mutant (fam20b-/-) zebrafish and inhibited with temporal control using the drug DMH1 or an inducible dominant-negative BMP receptor transgene (dnBMPR). Compared with wild type, phospho-Smad1/5/9, but not phospho-p38, was increased in fam20b-/- chondrocytes, but only after they secreted PGs. Phospho-Smad1/5/9 was decreased in DMH1-treated or dnBMPR-activated wild-type chondrocytes, and DMH1 also decreased phospho-p38 levels. ihha and col10a1a were decreased in DMH1-treated or dnBMPR-activated chondrocytes, and less perichondral bone formed. Finally, early ihha and col10a1a expression and early perichondral bone formation of fam20b mutants were rescued with DMH1 treatment or dnBMPR activation. Therefore, PG inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification, and these results offer hope for the development of growth factor therapies for skeletal defects of PG diseases.
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Osteogênese , Proteoglicanas , Animais , Osteogênese/genética , Proteoglicanas/genética , Proteoglicanas/metabolismo , Peixe-Zebra/genética , Cartilagem/metabolismo , Condrócitos/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismoRESUMO
BACKGROUND/IMPORTANCE: Arachnoiditis is a rare but devastating disorder caused by various insults, one of which is purported to be local anesthetic neurotoxicity following neuraxial blockade. However, the relationship between local anesthetics administered into the neuraxis and the development of arachnoiditis has not been clearly elucidated. OBJECTIVE: We aimed to summarize the existing complex body of literature and characterize both the essential features and strength of any association between neuraxial local anesthetic neurotoxicity and arachnoiditis with a view toward mitigating risk, enhancing prevention, and refining informed consent discussions. EVIDENCE REVIEW: We reviewed all published reports of arachnoiditis attributed to local anesthetic neurotoxicity following perioperative neuraxial anesthesia. This narrative review was based on a systematic search methodology, which included articles published up until December 2022. FINDINGS: Thirty-eight articles were included, comprising 130 patients, over one-half of which were published prior to this century and inconsistent with modern practice. Neuraxial techniques included 78 epidurals, 48 spinals, and 5 combined spinal-epidurals, mostly for obstetrics. Reporting of essential procedural data was generally incomplete. Overall, at least 57% of patients experienced complicated needle/catheter insertion, including paresthesia, pain, or multiple attempts, irrespective of technique. The onset of neurological symptoms ranged from immediate to 8 years after neuraxial blockade, while the pathophysiology of arachnoiditis, if described, was heterogeneous. CONCLUSIONS: The existing literature attributing arachnoiditis to local anesthetic neurotoxicity is largely outdated, incomplete, and/or confounded by other potential causes, and thus insufficient to characterize the features and strength of any association.
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BACKGROUND: Digital therapeutics (DTx), a class of software-based clinical interventions, are promising new technologies that can potentially prevent, manage, or treat a spectrum of medical disorders and diseases as well as deliver unprecedented portability for patients and scalability for health care providers. Their adoption and implementation were accelerated by the need for remote care during the COVID-19 pandemic, and awareness about their utility has rapidly grown among providers, payers, and regulators. Despite this, relatively little is known about the capacity of DTx to provide economic value in care. OBJECTIVE: This study aimed to systematically review and summarize the published evidence regarding the cost-effectiveness of clinical-grade mobile app-based DTx and explore the factors affecting such evaluations. METHODS: A systematic review of economic evaluations of clinical-grade mobile app-based DTx was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Major electronic databases, including PubMed, Cochrane Library, and Web of Science, were searched for eligible studies published from inception to October 28, 2022. Two independent reviewers evaluated the eligibility of all the retrieved articles for inclusion in the review. Methodological quality and risk of bias were assessed for each included study. RESULTS: A total of 18 studies were included in this review. Of the 18 studies, 7 (39%) were nonrandomized study-based economic evaluations, 6 (33%) were model-based evaluations, and 5 (28%) were randomized clinical trial-based evaluations. The DTx intervention subject to assessment was found to be cost-effective in 12 (67%) studies, cost saving in 5 (28%) studies, and cost-effective in 1 (6%) study in only 1 of the 3 countries where it was being deployed in the final study. Qualitative deficiencies in methodology and substantial potential for bias, including risks of performance bias and selection bias in participant recruitment, were identified in several included studies. CONCLUSIONS: This systematic review supports the thesis that DTx interventions offer potential economic benefits. However, DTx economic analyses conducted to date exhibit important methodological shortcomings that must be addressed in future evaluations to reduce the uncertainty surrounding the widespread adoption of DTx interventions. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42022358616; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022358616.
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COVID-19 , Aplicativos Móveis , Humanos , Análise Custo-Benefício , Pandemias , Ensaios Clínicos como AssuntoRESUMO
Background: Neurologic injury is relatively common in the context of spinal surgery, and is often treated with physiotherapy, pharmacotherapy, or surgical intervention. Emerging evidence supports a possible role for hyperbaric oxygen therapy (HBOT) in the treatment of peripheral and spinal nerve injuries. We describe the successful use of HBOT in improving neurologic recovery after complex spine surgery with new-onset postoperative unilateral foot drop. Case Description: A 50-year-old woman was found to have new right-sided foot drop and L2-S1 motor deficits following complex thoracolumbar revision spinal surgery. She received standard conservative management for a provisional diagnosis of acute traumatic nerve ischemia, but demonstrated no neurologic improvement. On postoperative day four, after other avenues of treatment were exhausted, she was referred for HBOT. The patient received a total of twelve sessions of HBOT at 2.0 absolute atmospheres (ATA) of pressure, for 90 minutes (including two air breaks) per session, before transfer to a rehabilitation facility. Conclusions: The patient displayed marked neurologic improvement after the first hyperbaric session, and further recovery thereafter. She concluded therapy with a significantly improved range of motion and lower limb power, ability to ambulate, and pain control. HBOT was associated with a rapid, sustained improvement when applied in this case as a salvage therapy for persistent postoperative neurologic deficit. Mounting evidence supports the consideration of hyperbaric therapy as a standard adjunct treatment for traumatic neurologic injury.
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In many jurisdictions, legal frameworks afford patients the opportunity to make prospective medical decisions or to create directives that contain a special provision forfeiting their own ability to object to those decisions at a future time point, should they lose decision-making capacity. These agreements have been described with widely varying nomenclatures, including Ulysses Contracts, Odysseus Transfers, Psychiatric Advance Directives with Ulysses Clauses, and Powers of Attorney with Special Provisions. As a consequence of this terminological heterogeneity, it is challenging for healthcare providers to understand the terms and uses of these agreements and for ethicists to engage with the nuances of clinical decision-making with such unique provisions surrounding patient autonomy. In theory, prospective self-binding agreements may safeguard patient's "authentic" wishes from future "inauthentic" changes of mind. In practice, it is unclear what may be comprised within these agreements or how-and to what effect-they are used. The primary focus of this integrative review is to curate the existing literature describing Ulysses Contracts (and analogous decisions) used in the clinical arena, in order to empirically synthesize their shared essence and provide insights into the traditional components of these agreements when used in practice, the requirements of their consent processes, and the outcomes of their utilization.
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Transtornos Mentais , Humanos , Transtornos Mentais/psicologia , Autonomia Pessoal , Competência Mental , Estudos Prospectivos , Diretivas Antecipadas , ContratosRESUMO
INTRODUCTION: Phantom limb pain (PLP) refers to pain perceived in a part of the body removed by amputation or trauma. Despite the high prevalence of PLP following amputation and the significant morbidity associated with it, robust therapeutic approaches are currently lacking. Calcitonin, a polypeptide hormone, has recently emerged as a novel analgesic with documented benefits in the treatment of several pain-related conditions. METHODS: We present a systematic review that comprehensively evaluates the analgesic effects of calcitonin for patients with PLP. We searched MEDLINE, OLDMEDLINE, and PubMed Central databases with the key words "calcitonin" "phantom limb pain" and "phantom pain" to identify clinical studies evaluating the efficacy or effectiveness of calcitonin administration, in any form and dose, for the treatment of PLP. Additionally, Google Scholar was searched manually with the search term "calcitonin phantom limb pain". All four databases were searched from inception until 1 December 2022. The methodological quality of each included study was assessed using the Downs and Black checklist and the GRADE criteria were used to assess effect certainty and risk of bias. RESULTS: Our search identified 4108 citations, of which six ultimately met the criteria for inclusion in the synthesis. The included articles described a mix of open-label (n = 2), prospective observational cohort (n = 1), and randomized clinical trials (n = 3). The most common treatment regimen in the current literature is a single intravenous infusion of 200 IU salmon-derived calcitonin. CONCLUSION: The available evidence supported the use of calcitonin as either monotherapy or adjuvant therapy in the treatment of PLP during the acute phase, while the evidence surrounding calcitonin treatment in chronic PLP is heterogeneous. Given the limited treatment options for the management of PLP and calcitonin's relatively wide therapeutic index, further research is warranted to determine the role that calcitonin may play in the treatment of PLP and other pain disorders.
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Calcitonina , Membro Fantasma , Humanos , Amputação Cirúrgica , Estudos Observacionais como Assunto , Membro Fantasma/tratamento farmacológico , Membro Fantasma/epidemiologia , Prevalência , Calcitonina/uso terapêuticoRESUMO
Hyperbaric oxygen therapy (HBOT) is known to be associated with pulmonary oxygen toxicity. However, the effect of modern HBOT protocols on pulmonary function is not completely understood. The present study evaluates pulmonary function test changes in patients undergoing serial HBOT. We prospectively collected data on patients undergoing HBOT from 2016-2021 at a tertiary referral center (protocol registration NCT05088772). Patients underwent pulmonary function testing with a bedside spirometer/pneumotachometer prior to HBOT and after every 20 treatments. HBOT was performed using 100% oxygen at a pressure of 2.0-2.4 atmospheres absolute (203-243 kPa) for 90 minutes, five times per week. Patients' charts were retrospectively reviewed for demographics, comorbidities, medications, HBOT specifications, treatment complications, and spirometry performance. Primary outcomes were defined as change in percent predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75), after 20, 40, and 60 HBOT sessions. Data was analyzed with descriptive statistics and mixed-model linear regression. A total of 86 patients were enrolled with baseline testing, and the analysis included data for 81 patients after 20 treatments, 52 after 40 treatments, and 12 after 60 treatments. There were no significant differences in pulmonary function tests after 20, 40, or 60 HBOT sessions. Similarly, a subgroup analysis stratifying the cohort based on pre-existing respiratory disease, smoking history, and the applied treatment pressure did not identify any significant changes in pulmonary function tests during HBOT. There were no significant longitudinal changes in FEV1, FVC, or FEF25-75 after serial HBOT sessions in patients regardless of pre-existing respiratory disease. Our results suggest that the theoretical risk of pulmonary oxygen toxicity following HBOT is unsubstantiated with modern treatment protocols, and that pulmonary function is preserved even in patients with pre-existing asthma, chronic obstructive lung disease, and interstitial lung disease.
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Oxigenoterapia Hiperbárica , Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Humanos , Oxigenoterapia Hiperbárica/efeitos adversos , Estudos Retrospectivos , Pulmão , Volume Expiratório Forçado , Capacidade Vital , OxigênioRESUMO
Patients with implanted medical devices are increasingly referred for hyperbaric oxygen therapy (HBOT), and the safety of exposing some of these devices to hyperbaric environments has not previously been explored. There is a paucity of evidence surrounding the management of implanted neurological devices such as neurostimulators and intrathecal drug delivery (IDD) pumps in the context of HBOT. However, these devices can be expected to harbor unique risks; for example, vacant space in the reservoir of an implanted IDD pump may change in pressure and volume during the compression and decompression phases of HBOT, resulting in a damaged or dysfunctional device. We present the case of a 27-year-old woman with cerebral palsy referred for HBOT to manage a necrotizing soft tissue infection cultured from a dehiscent abdominal wound at the previous implantation site of an intrathecal baclofen pump. An HBOT protocol was ultimately chosen in partnership with the patient and her family, but treatment was not performed due to a paucity of evidence that the implanted IDD pump could safely withstand hyperbaric exposure. In this review, we have synthesized manufacturer recommendations regarding the management of implanted neurological devices before, during, and after HBOT to inform future decision-making in this setting. Among these recommendations, we highlight that neurostimulators should be switched off for the duration of HBOT and implanted pumps should be refilled prior to each treatment session to minimize empty reservoir space.
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Oxigenoterapia Hiperbárica , Humanos , Feminino , Adulto , Pacientes , Sistemas de Liberação de MedicamentosRESUMO
Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.
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Dor Crônica , Humanos , Dor Crônica/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Analgésicos/uso terapêutico , AmidasRESUMO
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have emerged as an alternative to opioids for optimal postoperative pain management. However, the adoption of NSAIDs in sinonasal surgery has been impeded by a theoretical concern for postoperative bleeding. Our objective is to systematically review the efficacy and safety of NSAIDs for patients undergoing sinonasal surgery. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO International Clinical Trials Registry Platform were searched from inception to January 27, 2022. Randomized controlled trials (RCTs) and comparative observational studies in any language were considered. Screening, data extraction, and risk of bias assessment were performed in duplicate. Our outcomes were postoperative pain scores, requirement for rescue analgesia, and postoperative adverse events (epistaxis, nausea/vomiting). RESULTS: Out of 4661 records, 15 RCTs (enrolling 1210 patients) and two observational studies were included. Following endoscopic sinus surgery, there was no difference in pain scores between NSAIDs and non-NSAIDs groups (standardized mean differences [SMD] 0.44 units better, 95% CI -0.18 to 1.05). Following septorhinoplasty, NSAIDs decreased pain scores compared to non-NSAID regimens (SMD 1.14 units better, 95% CI 0.61 to 1.67 units better). Overall, NSAIDs reduced the need for rescue medication with a relative risk (RR) of 0.45 (95% CI 0.24 to 0.84). In addition, NSAIDs decreased the risk of nausea with an RR of 0.62 (95% CI 0.42 to 0.91) and did not increase the risk of epistaxis (RR 0.72, 95% CI 0.23-2.22). CONCLUSION: Among patients undergoing sinonasal surgery, NSAIDs are beneficial in postoperative pain management and avoidance of postoperative nausea without increasing the risk of postoperative epistaxis.