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1.
Med Sci Monit ; 30: e944116, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822518

RESUMO

BACKGROUND Colonoscopy is the predominant invasive procedure for Crohn disease (CD) patients. Opioids and propofol carry risks of respiratory and cardiovascular complications. This study aimed to evaluate whether substituting fentanyl with ketamine or lidocaine could diminish propofol usage and minimize adverse events. MATERIAL AND METHODS In total, 146 patients with CD scheduled for elective colonoscopy were assigned to anesthesia with fentanyl (n=47), ketamine (n=47), or lidocaine (n=55). Propofol was administered to achieve sufficient anesthesia. Measured outcomes in each group included propofol consumption, hypotension and desaturation incidents, adverse event types, consciousness recovery time, abdominal pain intensity, Aldrete scale, and Post Anaesthetic Discharge Scoring System (PADSS). RESULTS Patients administered fentanyl needed significantly more propofol (P=0.017) than those on ketamine, with lidocaine showing no notable difference (P=0.28). Desaturation was significantly less common in the ketamine and lidocaine groups than fentanyl group (P<0.001). The ketamine group experienced milder reductions in mean arterial (P=0.018) and systolic blood pressure (P<0.001). Recovery metrics (Aldrete and PADSS scores) were lower for fentanyl (P<0.001), although satisfaction and pain levels were consistent across all groups (P=0.797). Dizziness occurred less frequently with lidocaine than fentanyl (17.2%, P=0.018) and ketamine (15.1%, P=0.019), while metallic taste incidents were more prevalent in the lidocaine group (13.5%, P=0.04) than fentanyl group. CONCLUSIONS Using ketamine or lidocaine instead of fentanyl in anesthesia for colonoscopy in patients with CD significantly lowers propofol use, reduces desaturation events, maintains blood pressure more effectively, without increasing hypotension risk, and accelerates recovery, without negatively impacting adverse events or patient satisfaction.


Assuntos
Colonoscopia , Doença de Crohn , Fentanila , Ketamina , Lidocaína , Propofol , Humanos , Ketamina/efeitos adversos , Ketamina/administração & dosagem , Fentanila/efeitos adversos , Fentanila/administração & dosagem , Propofol/efeitos adversos , Propofol/administração & dosagem , Lidocaína/efeitos adversos , Lidocaína/administração & dosagem , Masculino , Feminino , Colonoscopia/métodos , Adulto , Pessoa de Meia-Idade , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Anestesia/métodos , Anestesia/efeitos adversos
2.
BMJ Open ; 14(6): e079984, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830745

RESUMO

INTRODUCTION: Intraoperative opioids have been used for decades to reduce negative responses to nociception. However, opioids may have several, and sometimes serious, adverse effects. Cardiac surgery exposes patients to a high risk of postoperative complications, some of which are common to those caused by opioids: acute respiratory failure, postoperative cognitive dysfunction, postoperative ileus (POI) or death. An opioid-free anaesthesia (OFA) strategy, based on the use of dexmedetomidine and lidocaine, may limit these adverse effects, but no randomised trials on this issue have been published in cardiac surgery.We hypothesised that OFA versus opioid-based anaesthesia (OBA) may reduce the incidence of major opioid-related complications after cardiac surgery. METHODS AND ANALYSIS: Multicentre, randomised, parallel and single-blinded clinical trial in four cardiac surgical centres in France, including 268 patients scheduled for coronary artery bypass grafting under cardiac bypass, with or without aortic valve replacement. Patients will be randomised to either a control OBA protocol using remifentanil or an OFA protocol using dexmedetomidine/lidocaine. The primary composite endpoint is the occurrence of at least one of the following: (1) postoperative cognitive disorder evaluated by the Confusion Assessment Method for the Intensive Care Unit test, (2) POI, (3) acute respiratory distress or (4) death within the first 48 postoperative hours. Secondary endpoints are postoperative pain, morphine consumption, nausea-vomiting, shock, acute kidney injury, atrioventricular block, pneumonia and length of hospital stay. ETHICS AND DISSEMINATION: This trial has been approved by an independent ethics committee (Comité de Protection des Personnes Ouest III-Angers on 23 February 2021). Results will be submitted in international journals for peer reviewing. TRIAL REGISTRATION NUMBER: NCT04940689, EudraCT 2020-002126-90.


Assuntos
Analgésicos Opioides , Procedimentos Cirúrgicos Cardíacos , Dexmedetomidina , Lidocaína , Remifentanil , Humanos , Dexmedetomidina/uso terapêutico , Lidocaína/uso terapêutico , Remifentanil/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Método Simples-Cego , Analgésicos Opioides/uso terapêutico , França , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle
3.
Minerva Anestesiol ; 90(6): 561-572, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38869266

RESUMO

INTRODUCTION: The full extent of intravenous lidocaine's effectiveness in alleviating postoperative pain and enhancing gastrointestinal function recovery remains uncertain. EVIDENCE ACQUISITION: We conducted an exhaustive search of databases to identify randomized controlled trials that compared intravenous lidocaine infusion's efficacy to that of a placebo or routine care in patients undergoing gastrointestinal surgery. The primary outcome measure was resting pain scores 24 h postoperatively. We utilized a random-effects model based on the intention-to-treat principle for the overall results. EVIDENCE SYNTHESIS: This study included twenty-four trials with 1533 patients. Intravenous lidocaine significantly reduced resting pain scores 24 h after gastrointestinal surgery (twenty trials, SMD -0.67, 95% CI -1.09 to -0.24, P=0.002, I2 = 90%). This finding was consistent in subgroup analyses and sensitivity analyses. The benefit was also observed at other resting and moving time points (1, 2, 4, and 12 h) postoperatively. Intravenous lidocaine significantly decreased opioid consumption within 24 h after surgery (eleven trials, SMD: -1.19; 95% CI: -1.99 to -0.39; P=0.003). Intravenous lidocaine also shortened the time to bowel sound (MD: -8.51; 95% CI: -14.59 to -2.44; P=0.006), time to first flatus (MD: -6.00; 95% CI: -9.87 to -2.13; P=0.002), and time to first defecation (MD: -9.77; 95% CI: -17.19 to -2.36; P=0.01). CONCLUSIONS: Perioperative intravenous lidocaine can alleviate acute pain and expedite gastrointestinal function recovery in patients undergoing gastrointestinal surgery. However, the results should be interpreted with caution due to substantial heterogeneity. Further large-scale studies are necessary to validate these findings.


Assuntos
Anestésicos Locais , Procedimentos Cirúrgicos do Sistema Digestório , Lidocaína , Dor Pós-Operatória , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Infusões Intravenosas , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Gen Hosp Psychiatry ; 89: 84-92, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38838608

RESUMO

OBJECTIVE: This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. METHOD: 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. RESULTS: The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 µg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. CONCLUSIONS: This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3-2021-0295) and registered at ClinicalTrials.gov (NCT05076903).


Assuntos
Analgésicos Opioides , Dexmedetomidina , Gastrectomia , Lidocaína , Dor Pós-Operatória , Remifentanil , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Analgésicos Opioides/administração & dosagem , Idoso , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Remifentanil/administração & dosagem , Remifentanil/farmacologia , Laparoscopia , Catastrofização , Adulto , Limiar da Dor/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia
5.
Clin Pharmacokinet ; 63(5): 623-643, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38703307

RESUMO

BACKGROUND: The establishment of optimal dosing regimens for intravenous (IV) lidocaine in the perioperative setting, aiming to balance effective pain relief with minimisation of potential side effects, is a topic of ongoing debate. This discussion stems from the significant variability in lidocaine's pharmacokinetic (PK) parameters and its relatively narrow safety margin. Population pharmacokinetic (popPK) modelling has emerged as a valuable tool for understanding the factors contributing to this observed variability in drug kinetics. OBJECTIVES: This systematic review compiles the existing knowledge on lidocaine's PK properties and published popPK models, with a focus on significant covariates. METHODS: A systematic search on Cochrane CENTRAL, Medline, and EMBASE was performed from inception to June 2023. Original clinical studies that administered IV lidocaine to adults and performed PK analyses using a nonlinear mixed effects modelling approach were included. The quality of the included studies was assessed by compliance with the Clinical Pharmacokinetics (ClinPK) statement checklist. RESULTS: Seven studies were included, which involved a diverse adult population, including both volunteers and patients with various comorbidities. Lidocaine PK was primarily characterised by a two- or three-compartment model. The volume of distribution at steady state ranged from 66 to 194 L, and the total clearance ranged from 22 to 49 L/h. Despite adjusting for significant covariates like heart failure status, alpha-1-acid glycoprotein, duration of lidocaine infusion, and body weight, each study revealed substantial variability in PK parameters. The potential impact of hepatic or renal function biomarkers on these PK parameters calls for further investigation. Incomplete reporting of key aspects of developed models may hinder the models' reliability and clinical application. CONCLUSION: The findings emphasise the importance of tailoring drug dosage to ensure the safe and effective use of intravenous lidocaine. Optimal design methodologies may be incorporated for a more efficient identification of important covariates. Utilising contemporary model evaluation methods like visual predictive checks and bootstrapping would enhance the robustness of popPK models and the reliability of their predictions. This comprehensive review advances our understanding of lidocaine's pharmacokinetics and lays the groundwork for further research in this critical area of perioperative pain management. Review protocol registered on 25 August 2023 in PROSPERO (CRD42023441113). This work was supported by the Fundamental Research Grant Scheme, the Ministry of Higher Education, Malaysia (FRGS/1/2020/SKK01/UM/02/2).


Assuntos
Administração Intravenosa , Anestésicos Locais , Lidocaína , Modelos Biológicos , Humanos , Lidocaína/farmacocinética , Lidocaína/administração & dosagem , Anestésicos Locais/farmacocinética , Anestésicos Locais/administração & dosagem , Adulto , Infusões Intravenosas
6.
Basic Clin Pharmacol Toxicol ; 135(1): 98-108, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38784974

RESUMO

Adenosine, lidocaine and Mg2+ (ALM) solution is an emerging therapy that reduces secondary injury after intravenous administration in experimental models of traumatic brain injury (TBI). Intranasal delivery of ALM may offer an alternative route for rapid, point-of-care management of TBI. As a preliminary safety screen, we evaluated whether ALM exerts cytotoxic or inflammatory effects on primary human nasal epithelial cells (pHNEC) in vitro. Submerged monolayers and air-liquid interface cultures of pHNEC were exposed to media only, normal saline only, therapeutic ALM or supratherapeutic ALM for 15 or 60 min. Safety was measured through viability, cytotoxicity, apoptosis, cellular and mitochondrial stress, and inflammatory mediator secretion assays. No differences were found in viability or cytotoxicity in cultures exposed to saline or ALM for up to 60 min, with no evidence of apoptosis after exposure to supratherapeutic ALM concentrations. Despite comparable inflammatory cytokine secretion profiles and mitochondrial activity, cellular stress responses were significantly lower in cultures exposed to ALM than saline. In summary, data show ALM therapy has neither adverse toxic nor inflammatory effects on human nasal epithelial cells, setting the stage for in vivo toxicity studies and possible clinical translation of intranasal ALM therapy for TBI treatment.


Assuntos
Adenosina , Administração Intranasal , Apoptose , Sobrevivência Celular , Células Epiteliais , Lidocaína , Mucosa Nasal , Humanos , Lidocaína/administração & dosagem , Lidocaína/toxicidade , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Adenosina/administração & dosagem , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Magnésio/administração & dosagem , Citocinas/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
7.
Minerva Anestesiol ; 90(5): 397-408, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38771164

RESUMO

BACKGROUND: We assessed the efficiency of intravenous adjuvants in decreasing opioid intake and pain scores after spine fusion surgery. METHODS: This study included 120 patients aged 18-60 listed for spine fusion surgery under general anesthesia. Patients were randomly assigned to four groups: Group (Lidocaine): received IV lidocaine 4 mg/kg in 50 mL volume over 30 min. Group (Magnesium): received IV magnesium sulfate 30mg/kg in 50 mL volume over 30 min. Group (combined Lidocaine and Magnesium): received IV lidocaine 4 mg/kg in 50 mL volume over 30 min.+IV magnesium sulfate 30mg/kg in 50 mL volume over 30 min. Group (Control): received IV saline 50 mL. The time to the first request analgesia, the postoperative pain score, total analgesic use, patient satisfaction, anxiety, depression, mental state, quality of life, and side effects were measured. RESULTS: The combined group had more extended time for the first analgesic request and fewer rescue analgesia doses than the other groups. NRS scores at rest or movement were statistically significantly lower in the lidocaine group and the combined group compared to the control group (P1, P3<0.05) at almost all times. This combination reduces anxiety and depression and improves overall health up to three months after a single infusion. The combined group had higher patient satisfaction. CONCLUSIONS: A synergistic effect of a combination of lidocaine and magnesium sulfate on perioperative pain was found. It reduces analgesic consumption, depression, and anxiety and improves overall health up to three months after a single infusion dose.


Assuntos
Lidocaína , Sulfato de Magnésio , Dor Pós-Operatória , Qualidade de Vida , Fusão Vertebral , Humanos , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/uso terapêutico , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Masculino , Feminino , Dor Pós-Operatória/tratamento farmacológico , Adulto , Pessoa de Meia-Idade , Infusões Intravenosas , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Emoções , Adulto Jovem , Adolescente , Método Duplo-Cego
8.
Trials ; 25(1): 337, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38773653

RESUMO

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).


Assuntos
Anestésicos Locais , Neoplasias da Mama , Lidocaína , Mastectomia , Estudos Multicêntricos como Assunto , Dor Pós-Operatória , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Neoplasias da Mama/cirurgia , Feminino , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/diagnóstico , Mastectomia/efeitos adversos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Infusões Intravenosas , Resultado do Tratamento , Medição da Dor , Qualidade de Vida , Dor Crônica/prevenção & controle , Dor Crônica/etiologia , Mastectomia Segmentar/efeitos adversos , Fatores de Tempo , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/efeitos adversos , Análise Custo-Benefício
9.
Discov Med ; 36(184): 992-1001, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798258

RESUMO

BACKGROUND: Diabetic neuropathic pain (DNP) is a complication of diabetes mellitus (DM). Hyperbaric lidocaine (HL), a local anesthetics drug, has neurotoxicity. The present study aims to study the effect and molecular mechanisms of HL on spinal nerve injury in DNP. METHODS: The DNP rat model was established through a high-fat-glucose diet in combination with Streptozotocin (STZ) administration. SB203580 and PD98059 were utilized to inhibit p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK). The mechanical paw withdrawal threshold (PWT) and the thermal paw withdrawal latency (PWL) were tested to evaluate rats' mechanical allodynia and thermal hyperalgesia. Hematoxylin-eosin (H&E) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end Labeling (TUNEL) staining were performed to evaluate the pathological changes and neuron apoptosis in spinal cord tissues of L4-5. Western blotting analysis and reverse transcription-polymerase chain reaction (RT-qPCR) assay were used to measure the levels of proteins and mRNAs, respectively. RESULTS: PWT and PWL were decreased in DNP rats with serious spinal nerve injury. HL administration downregulated the PWT and PWL and aggravated spinal nerve injury in DNP rats, but isobaric lidocaine had no effects on these changes. Meanwhile, p38 MAPK/ERK signaling and PTEN-induced kinase 1 (PINK1)-mediated mitophagy were activated in DNP, which was enhanced by HL but not isobaric lidocaine. Blocking p38 MAPK/ERK signaling could effectively attenuate HL-induced spinal nerve injury and inhibit mitophagy. CONCLUSION: In summary, HL can aggravate spinal cord tissue damage in DNP rats by inducing PINK1-mediated mitophagy via activating p38 MAPK/ERK signaling. Our data provide a novel insight that supports the potential role of p38 MAPK/ERK signaling in acting as a therapeutic target for HL-induced neurotoxicity.


Assuntos
Neuropatias Diabéticas , Lidocaína , Mitofagia , Proteínas Quinases , Ratos Sprague-Dawley , Ubiquitina-Proteína Ligases , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Lidocaína/farmacologia , Ratos , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/etiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Mitofagia/efeitos dos fármacos , Masculino , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
11.
Medicine (Baltimore) ; 103(21): e38253, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787976

RESUMO

BACKGROUND: This study investigated the outcomes up to 12 weeks after serial lidocaine infusion for early-onset peripheral neuropathic pain. METHODS: This pilot double-blind, randomized, 2-arm placebo-controlled trial recruited 50 participants with onset of peripheral neuropathic pain within the past 6 months and randomized them to either receive lidocaine (3 mg/kg) in normal saline (50 mL) intravenous infusion over 1 hour (lidocaine group) once a week for 4 weeks or 50 mL of normal saline infusion (placebo group) once a week for 4 weeks. Twenty-nine participants completed the protocol; 15 participants were assigned to the lidocaine group and 14 to the placebo group. The outcomes were pain intensity assessed using a numerical rating scale (NRS), quality of life assessed using EuroQol-Five Dimensions-Five Levels questionnaire (EQ-5D-5L), psychological function using the Thai version of the 21-item Depression Anxiety Stress Scales (DASS-21), pain medication use, and adverse effects, all assessed at baseline (BL) and again at 4, 8, and 12 weeks following randomization. RESULTS: The reported tramadol use at 8 and 12 weeks following the first infusion was significantly lower in the lidocaine group (P = .023). No other significant between-group differences were observed at any time point or for any other outcome, and no serious adverse events were observed. CONCLUSION: Multiple lidocaine infusions of 3 mg/kg once a week for 4 weeks in participants with recent onset of peripheral neuropathic pain demonstrated no significant benefits in pain intensity, quality of life, or psychological outcomes. At most, this treatment may result in less tramadol use.


Assuntos
Anestésicos Locais , Lidocaína , Neuralgia , Medição da Dor , Qualidade de Vida , Humanos , Lidocaína/administração & dosagem , Método Duplo-Cego , Feminino , Masculino , Projetos Piloto , Neuralgia/tratamento farmacológico , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Pessoa de Meia-Idade , Infusões Intravenosas , Resultado do Tratamento , Adulto , Tramadol/administração & dosagem , Tramadol/uso terapêutico , Idoso
12.
J Pain Palliat Care Pharmacother ; 38(2): 153-156, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718037

RESUMO

This report describes the use of subcutaneous lidocaine infusion to manage complex pain associated with checkpoint inhibitor inflammatory arthritis. In addition, the safe administration of lidocaine in the home setting is described. A 49-year-old man with metastatic melanoma to lung, right axilla and posterior chest wall on regular pembrolizumab developed checkpoint inhibitor inflammatory arthritis. Pain associated with this was unresponsive to simple analgesia, escalating opioids and adjuvant analgesics. Lidocaine infusion was used on separate occasions (inpatient unit and home setting) to gain rapid and sustained control of inflammatory pain. Inflammatory pain responded well to 2 mg/kg/h lidocaine infusion over 4 days with sustained response between infusions of up to 6 wk. Resulting in improved mobility, functional status, and overall quality of life. Lidocaine infusion should be considered as an option for analgesic management of checkpoint inhibitor inflammatory arthritis in patients for whom usual treatment is ineffective, and as an opioid-sparing intervention.


Assuntos
Inibidores de Checkpoint Imunológico , Lidocaína , Melanoma , Humanos , Masculino , Pessoa de Meia-Idade , Lidocaína/administração & dosagem , Inibidores de Checkpoint Imunológico/administração & dosagem , Melanoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite/tratamento farmacológico , Anestésicos Locais/administração & dosagem , Infusões Subcutâneas , Qualidade de Vida
13.
J Biomed Sci ; 31(1): 57, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38811967

RESUMO

Severe infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy and multiple organ dysfunction. Males appear to have a higher risk of mortality than females. Currently, there are few or no effective drug therapies to protect the brain, maintain the blood brain barrier, resolve excessive inflammation and reduce secondary injury in other vital organs. We propose a major reason for lack of progress is a consequence of the treat-as-you-go, single-nodal target approach, rather than a more integrated, systems-based approach. A new revolution is required to better understand how the body responds to an infection, identify new markers to detect its progression and discover new system-acting drugs to treat it. In this review, we present a brief history of sepsis followed by its pathophysiology from a systems' perspective and future opportunities. We argue that targeting the body's early immune-driven CNS-response may improve patient outcomes. If the barrage of PAMPs and DAMPs can be reduced early, we propose the multiple CNS-organ circuits (or axes) will be preserved and secondary injury will be reduced. We have been developing a systems-based, small-volume, fluid therapy comprising adenosine, lidocaine and magnesium (ALM) to treat sepsis and endotoxemia. Our early studies indicate that ALM therapy shifts the CNS from sympathetic to parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces inflammation, corrects coagulopathy, and maintains tissue O2 supply. Future research will investigate the potential translation to humans.


Assuntos
Sepse , Humanos , Sepse/terapia , Adenosina/metabolismo , Lidocaína/uso terapêutico , Magnésio/uso terapêutico , Hidratação/métodos
14.
Int J Pharm ; 658: 124210, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38718972

RESUMO

The objective of this present work was to develop and optimize oil-in-water (O/W) emulsion-based gels, namely emulgels that allow maximum topical drug delivery while having desired microstructure and acceptable physical stability. Emulgels containing 2.0 wt% lidocaine were prepared using various concentrations (0.75-5.0 wt%) of Sepineo P600. Their droplet size distribution, physical stability, rheological behaviors, in vitro drug release, and skin permeation profiles were evaluated. Results show that the concentration of Sepineo P600 significantly influenced the microstructure, rheology, and physical stability of the emulgel formulations. The physico-chemical properties also reveals that at least 1.0 wt% Sepineo P600 was needed to produce stable emulgel formulations. All formulations exhibited non-Newtonian shear-thinning properties which are desirable for topical applications. Both the release and permeation rates decreased with increasing viscosity and rigidity of the formulation. The lower the complex modulus of the emulgels, the higher the steady-state flux of the drug through the skin. Adding Sepineo P600 to emulgel systems resulted in increased rheological properties, which in turn slowed the diffusion of the drug for in vitro release. Although as expected skin permeation was rate limiting since in vitro release was 3 to 4 log-fold faster than skin flux. However, an interesting finding was that the derived skin/vehicle partition coefficient suggested the ionic interaction between lidocaine and Sepineo polymer reducing the free drug, i.e., thermodynamic activity and hence the flux with increasing Sepineo P600 concentration. Overall, this study has provided us with valuable insights into understanding the relationship between the microstructure (rheology), physical stability and skin drug delivery properties which will help to design and optimize topical emulgel formulations.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emulsões , Géis , Lidocaína , Reologia , Absorção Cutânea , Absorção Cutânea/efeitos dos fármacos , Lidocaína/administração & dosagem , Lidocaína/química , Lidocaína/farmacocinética , Animais , Viscosidade , Pele/metabolismo , Estabilidade de Medicamentos , Suínos , Química Farmacêutica/métodos , Administração Tópica
15.
Sci Rep ; 14(1): 11759, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782997

RESUMO

In this randomized controlled trial, 74 patients scheduled for gynecological laparoscopic surgery (American Society of Anesthesiologists grade I/II) were enrolled and randomly divided into two study groups: (i) Group C (control), received sufentanil (0.3 µg/kg) and saline, followed by sufentanil (0.1 µg/kg∙h) and saline; and (ii) Group F (OFA), received esketamine (0.15 mg/kg) and lidocaine (2 mg/kg), followed by esketamine (0.1 mg/kg∙h) and lidocaine (1.5 mg/kg∙h). The primary outcome was the 48-h time-weighted average (TWA) of postoperative pain scores. Secondary outcomes included time to extubation, adverse effects, and postoperative sedation score, pain scores at different time points, analgesic consumption at 48 h, and gastrointestinal functional recovery. The 48-h TWAs of pain scores were 1.32 (0.78) (95% CI 1.06-1.58) and 1.09 (0.70) (95% CI 0.87-1.33) for Groups F and C, respectively. The estimated difference between Groups F and C was - 0.23 (95% CI - 0.58 - 0.12; P = 0.195). No differences were found in any of the secondary outcomes and no severe adverse effects were observed in either group. Balanced OFA with lidocaine and esketamine achieved similar effects to balanced anesthesia with sufentanil in patients undergoing elective gynecological laparoscopic surgery, without severe adverse effects.Clinical Trial Registration: ChiCTR2300067951, www.chictr.org.cn 01 February, 2023.


Assuntos
Analgésicos Opioides , Procedimentos Cirúrgicos em Ginecologia , Ketamina , Lidocaína , Dor Pós-Operatória , Sufentanil , Humanos , Sufentanil/administração & dosagem , Sufentanil/efeitos adversos , Feminino , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Adulto , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Pessoa de Meia-Idade , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Anestesia/métodos , Anestesia/efeitos adversos , Anestésicos Locais/administração & dosagem , Medição da Dor
16.
Skin Res Technol ; 30(5): e13723, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38696233

RESUMO

BACKGROUND: Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP. AIMS: We sought to comprehensively evaluate the role of procedural treatments for NP. METHODS: We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included. RESULTS: Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non-pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first-line choice or an alternative in refractory cases. CONCLUSION: Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.


Assuntos
Prurido , Humanos , Prurido/terapia , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Parestesia/terapia , Parestesia/fisiopatologia , Hiperpigmentação/terapia , Modalidades de Fisioterapia , Terapia por Acupuntura/métodos , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/uso terapêutico , Anestésicos Locais/administração & dosagem , Terapia por Exercício/métodos , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Agulhamento Seco/métodos
17.
BMC Anesthesiol ; 24(1): 170, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714924

RESUMO

BACKGROUND: Dynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical procedures blood pressure is usually measured in equal intervals allowing to assess its intraoperative variability, which significance for peri and post-operative period is still under debate. Lidocaine has positive cardiovascular effects, which may go beyond its antiarrhythmic activity. The aim of the study was to verify whether the use of intravenous lidocaine may affect intraoperative BPV in patients undergoing major vascular procedures. METHODS: We performed a post-hoc analysis of the data collected during the previous randomized clinical trial by Gajniak et al. In the original study patients undergoing elective abdominal aorta and/or iliac arteries open surgery were randomized into two groups to receive intravenous infusion of 1% lidocaine or placebo at the same infusion rate based on ideal body weight, in concomitance with general anesthesia. We analyzed systolic (SBP), diastolic (DBP) and mean arterial blood (MAP) pressure recorded in 5-minute intervals (from the first measurement before induction of general anaesthesia until the last after emergence from anaesthesia). Blood pressure variability was then calculated for SBP and MAP, and expressed as: standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and coefficient of hemodynamic stability (C10%), and compared between both groups. RESULTS: All calculated indexes were comparable between groups. In the lidocaine and placebo groups systolic blood pressure SD, CV, AVR and C10% were 20.17 vs. 19.28, 16.40 vs. 15.64, 14.74 vs. 14.08 and 0.45 vs. 0.45 respectively. No differences were observed regarding type of surgery, operating and anaesthetic time, administration of vasoactive agents and intravenous fluids, including blood products. CONCLUSION: In high-risk vascular surgery performed under general anesthesia, lidocaine infusion had no effect on arterial blood pressure variability. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04691726 post-hoc analysis; date of registration 31/12/2020.


Assuntos
Anestésicos Locais , Pressão Sanguínea , Lidocaína , Procedimentos Cirúrgicos Vasculares , Humanos , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Masculino , Feminino , Pressão Sanguínea/efeitos dos fármacos , Idoso , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Procedimentos Cirúrgicos Vasculares/métodos , Pessoa de Meia-Idade , Método Duplo-Cego , Infusões Intravenosas , Anestesia Geral/métodos , Monitorização Intraoperatória/métodos
18.
Eur J Pharm Biopharm ; 200: 114329, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761870

RESUMO

Therapeutic deep eutectic solvents (THEDES) have been attracting increasing attention in the pharmaceutical literature as a promising enabling technology capable of improving physicochemical and biopharmaceutical properties for difficult-to-deliver drug compounds. The current literature has explored amide local anaesthetics and carboxylic acid nonsteroidal anti-inflammatories (NSAIDs) as commonly used THEDES formers for their active hydrogen-bonding functionality. However, little is known about what happens within the "deep eutectic" region where a range of binary compositions present simply as a liquid with no melting events detectable across experimentally achievable conditions. There is also very limited understanding of how parent compounds' physicochemical properties could impact upon the formation, interaction mechanism, and stability of the formed liquid systems, despite the significance of these information in dose adjustment, industrial handling, and scaling-up of these liquids. In the current work, we probed the "deep eutectic" phenomenon by investigating the formation and physicochemical behaviours of some chosen lidocaine-NSAID systems across a wide range of composition ratios. Our data revealed that successfully formed THEDES exhibited composition dependent Tg variations with strong positive deviations from predicted Tg values using the Gordon-Taylor theory, suggesting substantial interactions within the formed supramolecular structure. Interestingly, it was found that the parent compound's glass forming ability had a noticeable impact upon such profound interaction and hence could dictate the success of THEDES formation. It has also been confirmed that all successful systems were formed based on charge-assisted hydrogen bonding within their THEDES network, affirming the significant role of partial protonisation on achieving a profound melting point depression. More importantly, the work found that within the "deep eutectic" region there was still an ideal, or thermodynamically preferrable "THEDES point", which would exhibit excellent stability upon exposure to stress storage conditions. The discoveries of this study bring the literature one step closer to fully understanding the "therapeutic deep eutectic" phenomenon. Through correlation between parent reagents' physicochemical properties and the synthesised products' characteristics, we establish a more educated process for the prediction and engineering of THEDES.


Assuntos
Anti-Inflamatórios não Esteroides , Lidocaína , Lidocaína/química , Lidocaína/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Solventes/química , Anestésicos Locais/administração & dosagem , Anestésicos Locais/química , Ligação de Hidrogênio , Química Farmacêutica/métodos , Estabilidade de Medicamentos
19.
Eur J Radiol ; 176: 111529, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810440

RESUMO

PURPOSE: This study investigated strategies to reduce pneumothorax risk in CT-guided lung biopsy. The approach involved administering 10 ml of 1 % lidocaine fluid in the subpleural or pleural space before lung puncture and utilizing the gravitational effect of pleural pressure with specific patient positioning. METHOD: We retrospectively analyzed 72 percutaneous CT-guided lung biopsies performed at a single center between January 2020 and April 2023. These were grouped based on fluid administration during the biopsy and whether the biopsies were conducted in dependent or non-dependent lung regions. Confounding factors like patient demographics, lesion characteristics, and procedural details were assessed. Patient characteristics and the occurrence of pneumothoraces were compared using a Kurskal-Wallis test for continuous variables and a Fisher's exact test for categorical variables. Multivariable logistic regression was used to identify potential confounders. RESULTS: Subpleural or pleural fluid administration and performing biopsies in dependent lung areas were significantly linked to lower peri-interventional pneumothorax incidence (n = 15; 65 % without fluid in non-dependent areas, n = 5; 42 % without fluid in dependent areas, n = 5; 36 % with fluid in non-dependent areas,n = 0; 0 % with fluid in dependent areas; p = .001). Even after adjusting for various factors, biopsy in dependent areas and fluid administration remained independently associated with reduced pneumothorax risk (OR 0.071, p<=.01 for lesions with fluid administration; OR 0.077, p = .016 for lesions in dependent areas). CONCLUSIONS: Pre-puncture fluid administration to the pleura and consideration of gravitational effects during patient positioning can effectively decrease pneumothorax occurrences in CT-guided lung biopsy.


Assuntos
Biópsia Guiada por Imagem , Pleura , Pneumotórax , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Pneumotórax/prevenção & controle , Pneumotórax/etiologia , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Pleura/patologia , Pleura/diagnóstico por imagem , Idoso , Pulmão/patologia , Pulmão/diagnóstico por imagem , Radiografia Intervencionista/métodos , Gravitação , Lidocaína/administração & dosagem , Posicionamento do Paciente/métodos , Adulto , Pressão , Punções
20.
Vet Anaesth Analg ; 51(4): 381-390, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38744657

RESUMO

OBJECTIVE: To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A total of 29 female dogs with mammary tumors. METHODS: Premedication consisted of intramuscular acepromazine and morphine. General anesthesia was induced with intravenous propofol and maintained with sevoflurane. Dogs were randomized to be administered intravenous DLK [dexmedetomidine 1 µg kg-1 loading dose (LD) and 1 µg kg-1 hour-1; lidocaine 2 mg kg-1 LD and 3 mg kg-1 hour-1; ketamine 1 mg kg-1 LD and 0.6 mg kg-1 hour-1; n = 14] or FLK (fentanyl 5 µg kg-1 LD and 9 µg kg-1 hour-1; same doses of lidocaine and ketamine; n = 15) during anesthesia. Cardiorespiratory variables and end-tidal sevoflurane (Fe'Sevo) were recorded during surgery. The number of dogs administered ephedrine to treat arterial hypotension [mean arterial pressure (MAP) < 60 mmHg] was recorded. Meloxicam was administered to both groups. Postoperative pain and rescue analgesia requirement were assessed for 24 hours using the short form of the Glasgow Composite Measure Pain Scale. Data were compared using a mixed effects model or a Mann-Whitney test. RESULTS: More dogs required ephedrine in FLK than in DLK (67% versus 7%). Heart rate was not significantly different between groups, whereas lower values of MAP (p ≤ 0.01) and Fe'Sevo (p = 0.018) were observed in FLK than in DLK. Rescue analgesia was administered to 2/15 dogs in FLK and 0/14 dogs in DLK. CONCLUSIONS AND CLINICAL RELEVANCE: Based on the cardiovascular response during surgery, intraoperative infusions of FLK and DLK provided adequate antinociception. Infusion of DLK provided greater stability of blood pressure. Both protocols resulted in minimal need for additional analgesia within 24 hours postoperatively.


Assuntos
Dexmedetomidina , Doenças do Cão , Fentanila , Ketamina , Lidocaína , Mastectomia , Dor Pós-Operatória , Sevoflurano , Animais , Cães/cirurgia , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Feminino , Ketamina/administração & dosagem , Ketamina/farmacologia , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Mastectomia/veterinária , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Fentanila/administração & dosagem , Fentanila/farmacologia , Doenças do Cão/cirurgia , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/farmacologia , Infusões Intravenosas/veterinária , Neoplasias Mamárias Animais/cirurgia , Estudos Prospectivos , Anestésicos Inalatórios/administração & dosagem
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