Olanzapine as a prophylactic antiemetic for preventing postoperative nausea and vomiting after general anesthesia: A systematic review and meta-analysis.

BACKGROUND: The antiemetic effectiveness of olanzapine, as a prophylactic off-label antiemetic drug, for Postoperative Nausea and Vomiting (PONV) is unknown. In this systematic review and meta-analysis, the authors evaluate the efficacy and side effects of olanzapine as a prophylactic antiemetic in adult patients who undergo general anesthesia and assess adverse effects. METHODS: A systematic search was done on electronic bibliographic databases in July 2023. Randomized controlled trials of olanzapine as a prophylactic antiemetic for PONV in adults who underwent general anesthesia were included. The authors excluded non-RCTs and retracted studies. The authors set no date of publication or language limits. The outcomes were the incidence of PONV within 24 h postoperatively and the safety of olanzapine. The risk of bias was assessed according to the tool suggested by the National Heart, Lung, and Blood Institute. RESULTS: Meta-analysis included 446 adult patients. Olanzapine reduced on average 38 % the incidence of PONV. The estimated risk ratio (95 % CI) of olanzapine versus control was 0.62 (0.42-0.90), p = 0.010, I2 = 67 %. In the subgroup meta-analysis, doses of olanzapine (10 mg) reduced on average 49 % of the incidence of PONV (RR = 0.51 [0.34-0.77], p = 0.001, I2 = 31 %). CONCLUSIONS: This systematic review with meta-analysis indicated that olanzapine as a prophylactic antiemetic alone or combined with other antiemetic agents reduced the incidence of postoperative nausea and vomiting. However, this conclusion must be presented with some degree of uncertainty due to the small number of studies included. There was a lack of any evidence to draw conclusions on side effects.

Gaps in our knowledge and future research on the endocannabinoid system and the painful phenomenon / As lacunas do nosso conhecimento e as pesquisas futuras sobre o sistema endocanabinoide e o fenômeno doloroso

ABSTRACT BACKGROUND AND OBJECTIVES: This article aimed to discuss and point out the main gaps and bottlenecks in national and international clinical research regarding medicinal cannabinoid compounds and their respective relevance to pain management practices. Other objectives were to establish standards and regulations for testing the quality, efficacy, and safety of cultivation and manufacturing of cannabis products (similar to biopharmaceutical standards) before prescribing or marketing, and to investigate approaches in order to establish robust guidelines for cannabinoid-influenced driving. CONTENTS: A search with the terms "cannabinoids" and "pain" in the domain www.clinicaltrials.gov, international data platform for registration of clinical research trials, found only two Brazilian studies, on fibromyalgia and chronic headache. The search for the term "cannabinoid" in Plataforma Brasil returned only nine mentions of studies related to pain, most of them being case reports or observational studies, without active intervention or control group. CONCLUSION: There are still few clinical, randomized, controlled trials evaluating effective doses, routes and interval of administration, pharmacological interaction with opioids or among the various cannabinoids, interaction with adjunct analgesics, potential injury in the context of long-term use, and individual factors that predispose to indiscriminate cannabinoid use.

RESUMO JUSTIFICATIVA E OBJETIVOS: O presente artigo teve como objetivo debater e apontar as principais lacunas e gargalos na pesquisa clínica nacional e internacional relativas aos compostos canabinoides de uso medicinal e suas respectivas relevâncias nas práticas relacionadas ao controle da dor. Outros objetivos foram estabelecer padrões e regulamentos para testar a qualidade, eficácia e segurança de cultivo e fabricação de produtos de cannabis (semelhantes aos padrões biofarmacêuticos) antes de prescrever ou comercializar, e investigar abordagens a fim de estabelecer orientações robustas para dirigir sob influência de canabinoides. CONTEÚDO: Uma pesquisa com os termos "canabinoides" e "pain" no domínio do www.clinicaltrials.gov, plataforma internacional de dados de registro de ensaios de pesquisa clínica, cita apenas dois estudos brasileiros, sobre fibromialgia e cefaleia crônica. A busca do termo "canabinoide" na Plataforma Brasil retornou apenas nove menções de estudos relacionados ao tema dor, sendo a maioria relatos de casos ou estudos observacionais, sem intervenção ativa, ou sem grupo controle. CONCLUSÃO: Ainda há poucos estudos clínicos, randomizados e controlados avaliando doses eficazes, vias e intervalo de administração, interação farmacológica com opioides ou entre os diversos canabinoides, interação com analgésicos adjuvantes, lesões potenciais no contexto do uso a longo prazo e fatores individuais que predisponham ao uso indiscriminado dos canabinoides.

Effect of adding clonidine to lidocaine on ocular hemodynamics during sub-Tenon's anesthesia: randomized double-blind study.

INTRODUCTION AND OBJECTIVES: Different regional anesthesia techniques for ophthalmology can have hemodynamic effects on the eye. We assessed the effects of adding clonidine to lidocaine on Intraocular Pressure (IOP), Ocular Pulse Amplitude (OPA), and Ocular Perfusion Pressure (OPP) after the sub-Tenon's technique for cataract surgery. METHODS: The study included 40 patients randomly allocated into two groups: sub-Tenon's blockade with Lidocaine plus Saline Solution (LS) or Lidocaine plus Clonidine (LC). IOP, OPA and OPP were measured before anesthesia, and 1, 5 and 10 minutes after the injection of anesthetic solution. RESULTS: There was no difference between the groups in IOP, OPA, and OPP baseline values. After the injection of the anesthetic solution, the IOP increased in both groups at minute one, with a mean difference of +4.67 mmHg (p = 0.001) and +2.15 mmHg (p = 0.013) at 5 minutes. The increase was lower in the LC group when compared to LS (p = 0.027). OPA decreased in both groups, with a baseline difference, after 1 minute, of -0.85 mmHg (p =  -0.85 mmHg (p = 0.001), and at 5 and 10 minutes with differences of -1.17 (p = 0.001) and -0.89 mmHg (p = 0.001), respectively. The highest decrease was observed in group LC in relation to group LS (p = 0.03). There was no difference in OPP in relation to baseline measurements. CONCLUSIONS: Adding clonidine to lidocaine for sub-Tenon's anesthesia reduced IOP and OPA without significant changes in OPP.

Aprepitant plus palonosetron for the prevention of postoperative nausea and vomiting after breast cancer surgery: a double blind, randomized trial.

OBJECTIVES: To evaluate the addition of a fourth antiemetic intervention in patients at high risk for postoperative nausea and vomiting (PONV). METHODS: High-risk patients (Apfel score 3 or 4) scheduled for unilateral mastectomy were randomly allocated in one of two groups, oral aprepitant (oral aprepitant 80 mg, intravenous dexamethasone 8 mg, and palonosetron 0.075 mg) and oral placebo (oral placebo, intravenous dexamethasone 4 mg, and palonosetron 0.075 mg). Patients and caregivers were blinded to the group assignments. The primary efficacy endpoints included the incidence of nausea and vomiting, and the secondary endpoints included use of rescue antiemetics during a 48-hour postoperative period. ClinicalTrials.gov: NCT02431286. RESULTS: One hundred patients were enrolled in this study and 91 were analyzed, 48 in group A and 43 in group P. No patient presented with nausea or vomiting in the first 2 hours after surgery. From the 2nd to the 6th hour, the incidence of PONV was 8.33% in group A and 9.30% in group P. In the first 24 hours, the incidence of PONV was 27.08% in the group A and 20.93% in group P. From the 24th to the 48th hour, the incidence of PONV was 8.33% in group A and 13.95% in group P. There were no statistically significant differences in PONV between groups. CONCLUSION: The addition of aprepitant as a third antiemetic resulted in no significant reduction in the incidence of PONV in this population. However, the incidence of PONV was reduced in relation to the general population.

Aprepitant plus palonosetron for the prevention of postoperative nausea and vomiting after breast cancer surgery: a double blind, randomized trial

OBJECTIVES: To evaluate the addition of a fourth antiemetic intervention in patients at high risk for postoperative nausea and vomiting (PONV). METHODS: High-risk patients (Apfel score 3 or 4) scheduled for unilateral mastectomy were randomly allocated in one of two groups, oral aprepitant (oral aprepitant 80 mg, intravenous dexamethasone 8 mg, and palonosetron 0.075 mg) and oral placebo (oral placebo, intravenous dexamethasone 4 mg, and palonosetron 0.075 mg). Patients and caregivers were blinded to the group assignments. The primary efficacy endpoints included the incidence of nausea and vomiting, and the secondary endpoints included use of rescue antiemetics during a 48-hour postoperative period. ClinicalTrials.gov: NCT02431286. RESULTS: One hundred patients were enrolled in this study and 91 were analyzed, 48 in group A and 43 in group P. No patient presented with nausea or vomiting in the first 2 hours after surgery. From the 2nd to the 6th hour, the incidence of PONV was 8.33% in group A and 9.30% in group P. In the first 24 hours, the incidence of PONV was 27.08% in the group A and 20.93% in group P. From the 24th to the 48th hour, the incidence of PONV was 8.33% in group A and 13.95% in group P. There were no statistically significant differences in PONV between groups. CONCLUSION: The addition of aprepitant as a third antiemetic resulted in no significant reduction in the incidence of PONV in this population. However, the incidence of PONV was reduced in relation to the general population.

[Development of a multivariable predictive model for postoperative nausea and vomiting after cancer surgery in adults]. / Desenvolvimento de um modelo preditivo multivariado para náusea e vômito no pós­operatório de cirurgia oncológica em adultos.

BACKGROUND AND OBJECTIVES: Predicting postoperative nausea and vomiting risk is the cornerstone for deciding prophylaxis. Apfel's score does not define how long a person must be abstinent from smoking to be considered a non-smoker, and the use of intraoperative spinal opioids as a risk factor for predicting postoperative nausea and vomiting is also not addressed. The aim of this study was to quantify predicting postoperative nausea and vomiting risk by an ordinal smoking status and the use of intraoperative opioids (systemic or neuraxial), and to develop a new predictive model. METHODS: Patients scheduled for cancer surgery were prospectively evaluated for predicting postoperative nausea and vomiting in the first 24h after surgery. RESULTS: Of 2014 initially included patients, 185 participants were excluded. Smoking status classification was associated with predicting postoperative nausea and vomiting incidence rates of 14.1%, 18.1%, 24.7%, 29.4% and 33.9% for smokers, patients who stopped smoking up to 1 month prior to surgery, one to 6 months prior, more than 6 months prior or patients who never smoked, respectively, which was significant in the multiple comparisons analysis (adjusted p=0.015). The multiple comparisons-adjusted hypothesis tests for association with predicting postoperative nausea and vomiting for sex, age, previous predicting postoperative nausea and vomiting, chemotherapy-induced nausea, and ordinal smoking status had p-values of <0.001. The type of surgery (p=0.04), total fentanyl consumption (p=0.04), both intraoperative and postoperative, were significant predictors. A new model was developed and showed higher discriminative power than Apfel's score (AUC 67.9% vs. 63.7%, p<0.001). CONCLUSION: Smoking status showed a significant and linear impact on predicting postoperative nausea and vomiting incidence, and we developed a new model that uses unambiguous smoking and opioid predictors.

Development of a multivariable predictive model for postoperative nausea and vomiting after cancer surgery in adults / Desenvolvimento de um modelo preditivo multivariado para náusea e vômito no pós-operatório de cirurgia oncológica em adultos

Abstract Background and objectives Predicting postoperative nausea and vomiting risk is the cornerstone for deciding prophylaxis. Apfel's score does not define how long a person must be abstinent from smoking to be considered a non-smoker, and the use of intraoperative spinal opioids as a risk factor for predicting postoperative nausea and vomiting is also not addressed. The aim of this study was to quantify predicting postoperative nausea and vomiting risk by an ordinal smoking status and the use of intraoperative opioids (systemic or neuraxial), and to develop a new predictive model. Methods Patients scheduled for cancer surgery were prospectively evaluated for predicting postoperative nausea and vomiting in the first 24 h after surgery. Results Of 2014 initially included patients, 185 participants were excluded. Smoking status classification was associated with predicting postoperative nausea and vomiting incidence rates of 14.1%, 18.1%, 24.7%, 29.4% and 33.9% for smokers, patients who stopped smoking up to 1 month prior to surgery, one to 6 months prior, more than 6 months prior or patients who never smoked, respectively, which was significant in the multiple comparisons analysis (adjusted p = 0.015). The multiple comparisons-adjusted hypothesis tests for association with predicting postoperative nausea and vomiting for sex, age, previous predicting postoperative nausea and vomiting, chemotherapy-induced nausea, and ordinal smoking status had p-values of <0.001. The type of surgery (p = 0.04), total fentanyl consumption (p = 0.04), both intraoperative and postoperative, were significant predictors. A new model was developed and showed higher discriminative power than Apfel's score (AUC 67.9% vs. 63.7%, p < 0.001). Conclusion Smoking status showed a significant and linear impact on predicting postoperative nausea and vomiting incidence, and we developed a new model that uses unambiguous smoking and opioid predictors.

Resumo Justificativa e objetivos A previsão do risco de náusea e vômito no pós-operatório é a base para a decisão da profilaxia. O escore de Apfel não define por quanto tempo uma pessoa deve se abster de fumar para ser considerada não fumante, e o uso de opioide espinhal intraoperatório como fator de risco para náusea e vômito também não é abordado. Nosso objetivo foi quantificar o risco de náusea e vômito no pós-operatório por um estado tabagístico ordinal e o uso de opioides intraoperatórios (sistêmicos ou neuraxiais) e desenvolver um novo modelo preditivo. Métodos Pacientes agendados para cirurgia oncológica foram prospectivamente avaliados para náusea e vômito nas primeiras 24 horas após a cirurgia. Resultados De 2.014 pacientes inicialmente incluídos, 185 foram excluídos. A classificação de tabagismo foi associada a taxas de incidência de náusea e vômito no pós-operatório de 14,1%, 18,1%, 24,7%, 29,4% e 33,9% para fumantes, pacientes que pararam de fumar até um mês antes da cirurgia, de um a seis meses antes da cirurgia, mais de seis meses antes da cirurgia ou pacientes que nunca fumaram, respectivamente, o que foi significativo na análise de comparações múltiplas (p = 0,015 ajustado). Os testes de hipóteses foram ajustadas para múltiplas comparações para associação com náusea e vômito no pós-operatório para sexo, idade, náusea e vômito no pós-operatório anterior, náusea induzida por quimioterapia e estado tabagístico ordinal apresentaram valores de p < 0,001. Tipo de cirurgia (p = 0,04), consumo total de fentanil (p = 0,04) e períodos intraoperatório e pós-operatório foram preditivos significativos. Um novo modelo foi desenvolvido e apresentou um poder discriminativo maior do que o escore de Apfel (AUC 67,9% vs. 63,7%, p < 0,001). Conclusão O estado tabagístico mostrou um impacto significativo e linear sobre a incidência de náusea e vômito no pós-operatório e desenvolveu-se um novo modelo que usa preditores não ambíguos de tabagismo e opioides.

Clinical evidence on visceral pain. Systematic review / Evidência clínica sobre dor visceral. Revisão sistemática

ABSTRACT BACKGROUND AND OBJECTIVES: Visceral pain is induced by abnormalities of organs such as stomach, kidneys, bladder, gallbladder, intestines and others and includes distension, ischemia, inflammation and mesenteric traction. It is responsible for physical and psychic incapacity, absenteeism and poor quality of life. This study aimed at discussing major aspects of visceral pain with regard to prevalence, etiology and diagnosis. CONTENTS: According to Evidence-Based Medicine concepts, visceral pain etiology, diagnosis and prognosis were reviewed in LILACS, EMBASE and Pubmed databases. Therapeutic studies were not selected. The following terms were used as search strategy: ("visceral pain"[MeSH Terms] OR ("visceral"[All Fields] AND "pain"[All Fields]) OR "visceral pain"[All Fields]). Only studies published in Portuguese, English or Spanish were included. Narrative reviews with opinionated content and specific therapeutic procedures of medical specialties were excluded. Studies on visceral pain related to heart, cancer and musculoskeletal diseases and pregnancy were also excluded. CONCLUSION: Visceral pain is a heterogeneous condition where most frequent presentation is abdominal pain in the course of irritable bowel syndrome. Other diseases induce visceral pain and adequate diagnosis is critical for effective treatment.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor visceral é causada por anormalidades de órgãos como o estômago, rim, bexiga, vesícula biliar, intestinos ou outros e inclui distensão, isquemia, inflamação e tração do mesentério. É responsável por incapacidade física e psíquica, absenteísmo do trabalho e má qualidade de vida. O objetivo deste estudo foi discutir os principais aspectos da dor visceral relacionados a prevalência, etiologia e diagnóstico. CONTEÚDO: Foram revisados segundo os preceitos da Medicina Baseada em Evidência os enfoques etiológicos, diagnóstico e prognóstico da dor visceral nas bases de indexações biomédicas, LILACS, EMBASE e Pubmed. Não foram selecionados os estudos terapêuticos. Utilizou-se como estratégia de busca os termos: ("visceral pain"[MeSH Terms] OR ("visceral"[All Fields] AND "pain"[All Fields]) OR "visceral pain"[All Fields]). Somente foram incluídos os estudos publicados em português, inglês ou espanhol. Foram excluídas as revisões narrativas de conteúdo opinativo e procedimentos terapêuticos específicos das especialidades médicas. Também foram excluídos os estudos sobre dor visceral relacionada às doenças do coração, neoplásicas, musculoesqueléticas e a gestação. CONCLUSÃO: A dor visceral é uma condição heterogênea, cuja apresentação mais frequente é de dor abdominal no curso de síndrome do intestino irritável. Outras doenças cursam com dor visceral e o diagnóstico adequado é fundamental para o tratamento eficaz.

Tramadol wound infiltration is not different from intravenous tramadol in children: a randomized controlled trial.

STUDY OBJECTIVE: The purpose of this trial was to assess if tramadol wound infiltration is superior to intravenous (IV) tramadol after minor surgical procedures in children because tramadol seems to have local anesthetic-like effect. DESIGN: Randomized double-blind controlled trial. SETTING: Postanesthesia care unit. PATIENTS: Forty children, American Society of Anesthesiologists physical status I or II, scheduled to elective inguinal hernia repair. INTERVENTIONS: Children were randomly distributed in 1 of 2 groups: IV tramadol (group 1) or subcutaneous infiltration with tramadol (group 2). At the end of the surgery, group 1 received 2 mg/kg tramadol (3 mL) by IV route and 3-mL saline into the surgical wound; group 2 received 2 mg/kg tramadol (3 mL) into the surgical wound and 3-mL saline by IV route. MEASUREMENTS: In the postanesthesia care unit, patients were evaluated for pain intensity, nausea and vomiting, time to first rescue medication, and total rescue morphine and dipyrone consumption. MAIN RESULTS: Pain scores measured during the postanesthesia recovery time were similar between groups. Time to first rescue medication was shorter, but not statistically significant in the IV group. The total dose of rescue morphine and dipyrone was also similar between groups. CONCLUSIONS: We concluded that tramadol was effective in reducing postoperative pain in children, and there was no difference in pain intensity, nausea and vomiting, or somnolence regarding IV route or wound infiltration.

Experimental models for the study of neuropathic pain / Modelos experimentais para o estudo da dor neuropática

ABSTRACT BACKGROUND AND OBJECTIVES: Ideal models should reproduce just sensory deficits, such as alodynia, hyperalgesia and spontaneous pain for short periods. There are different types of animal models to evaluate different neuropathic pain etiologies and manifestations. Some models study neuropathic pain peripheral mechanisms and other study its central mechanisms. This review focuses on animal models most commonly used for neuropathic pain research. CONTENTS: Animal models based on peripheral nerves ligation which are more commonly used are described. From all models described in this review, spared nerve injury is that producing more reproducible behavioral abnormalities for a longer period, while chronic sciatic nerve compression produces behavioral signs of less predictable painful neuropathies. Spinal hemisection and cytokines-induced spinal injury are the models of choice for the study of central pain mechanisms. Other specific models are used for the study of the specific etiology of pain. CONCLUSION: Since neuropathic pain is multifactorial, different neuropathic pain animal models were developed throughout the years, which have been critical for the study of neuropathic pain, since much of current knowledge comes from studies with rats and mice. Current animal models need to be further refined and more efforts should be made to determine which animal models may be more predictive, with less biases and more complex and objective analysis parameters.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os modelos ideais deveriam reproduzir apenas déficits sensitivos, como alodínea, hiperalgesia e dor espontânea por curtos períodos de tempo. Existem diversos tipos de modelos animais, que avaliam as diversas etiologias e manifestações da dor neuropática. Alguns modelos estudam os mecanismos periféricos e outros estudam mecanismos centrais da dor neuropática. Esta revisão enfoca os modelos animais mais comumente utilizados para pesquisa em dor neuropática. CONTEÚDO: São descritos modelos animais baseados em ligadura de nervos periféricos que são mais comumente empregados. De todos os modelos descritos nesta revisão, a lesão poupadora de nervo é aquela que produz anormalidades comportamentais mais reprodutíveis, por um período mais longo, ao passo que a constrição crônica do ciático produz sinais comportamentais de neuropatia dolorosas menos previsíveis. Hemisecção espinhal e lesão espinhal induzida por citocinas são os modelos de escolha para estudar mecanismos de dor central. Outros modelos específicos são utilizados para estudo da etiologia específica da condição dolorosa. CONCLUSÃO: Como a dor neuropática é multifatorial, diferentes modelos animais de dor neuropática foram desenvolvidos ao longo dos anos que têm sido fundamentais para o estudo da dor neuropática, uma vez que muito do conhecimento atual provém de estudos em ratos e camundongos. São necessários maiores refinamentos nos modelos animais atualmente empregados e mais esforços para determinar quais modelos animais podem ser mais preditivos, com menos vieses e com parâmetros de análises mais complexos e objetivos.

Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats / O efeito analgésico de tramadol não é mediado por receptores opioides na dor de ratos no pós-operatório imediato / El efecto analgésico del tramadol no está mediado por receptores opiáceos en el dolor en ratones en el postoperatorio inmediato

BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5 mg, naloxone 200 µg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors. .

JUSTIFICATIVA E OBJETIVOS: Tramadol é conhecido como um fármaco analgésico de ação central, usado para o tratamento de dor moderada a grave. O efeito analgésico local foi demonstrado, em parte devido ao efeito semelhante ao anestésico local, mas outros mecanismos permanecem obscuros. O papel dos receptores opioides periféricos no efeito analgésico local não é conhecido. Neste estudo, examinamos o papel dos receptores opioides periféricos no efeito analgésico local de tramadol em modelo de incisão plantar. MÉTODOS: Ratos Wistar, jovens e machos, foram divididos em sete grupos: controle, tramadol intraplantar, tramadol intravenoso, tramadol intraplantar-naloxona intravenosa, tramadol intraplantar-naloxona intraplantar, tramadol intravenoso-naloxona intravenosa e naloxona intravenosa. Após receber os medicamentos designados (5 mg de tramadol, 200 mg de naloxona ou NaCl a 0,9%, os ratos foram submetidos à incisão plantar e os limiares de retirada após estímulos mecânicos com filamentos de von Frey foram avaliados no início do estudo e nos minutos 10, 15, 30, 45 e 60 após a incisão. RESULTADOS: A incisão plantar levou à hiperalgesia mecânica acentuada durante todo o período de observação no grupo controle; hiperalgesia mecânica não foi observada nos grupos tramadol intraplantar, tramadol intraplantar-naloxona intraplantar e tramadol intraplantar-naloxona intravenosa. No grupo tramadol intravenoso, um aumento tardio do limiar de retirada (após 45 minutos) foi observado. Os grupos tramadol intravenoso-naloxona intravenosa e naloxona intravenosa permaneceram hiperalgésicos durante todo o período. CONCLUSÕES: Tramadol apresentou efeito analgésico local inicial e diminuiu a hiperalgesia mecânica induzida pela incisão plantar. Esse efeito analgésico não foi mediado por receptores opioides periféricos. .

JUSTIFICACIÓN Y OBJETIVOS: Al tramadol se le conoce como un medicamento analgésico de acción central usado para el tratamiento del dolor moderado a intenso. El efecto analgésico local quedó demostrado, en parte, a causa del efecto similar al del anestésico local, pero otros mecanismos permanecen sin clarificar. El rol de los receptores opiáceos periféricos en el efecto analgésico local no se conoce. En este estudio, examinamos el papel de los receptores opiáceos periféricos en el efecto analgésico local del tramadol en un modelo de incisión plantar. MÉTODOS: Ratones Wistar, jóvenes y machos, fueron divididos en 7 grupos: control, tramadol intraplantar, tramadol intravenoso, tramadol intraplantar-naloxona intravenosa, tramadol intraplantar-naloxona intraplantar, tramadol intravenoso-naloxona intravenosa, y naloxona intravenosa. Después de recibir los medicamentos designados (5 mg de tramadol, 200 µg de naloxona o NaCl al 0,9%), los ratones fueron sometidos a la incisión plantar, y los umbrales de retirada de la pata posteriores a los estímulos mecánicos con filamentos de von Frey fueron evaluados al inicio del estudio y en los minutos 10, 15, 30, 45 y 60 después de la incisión. RESULTADOS: La incisión plantar conllevó hiperalgesia mecánica acentuada durante todo el período de observación en el grupo control; la hiperalgesia mecánica no fue observada en los grupos tramadol intraplantar, tramadol intraplantar-naloxona intraplantar, y tramadol intraplantar-naloxona intravenosa. En el grupo tramadol intravenoso, fue observado un aumento tardío del umbral de retirada (después de 45 min); los grupos tramadol intravenoso-naloxona intravenosa y naloxona intravenosa permanecieron hiperalgésicos durante todo el período. CONCLUSIONES: El tramadol presentó un efecto analgésico local inicial, disminuyendo la hiperalgesia mecánica inducida por la incisión plantar. Ese efecto analgésico no fue mediado por receptores opiáceos periféricos. .

Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats.

BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5mg, naloxone 200 µg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors.

[Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats]. / O efeito analgésico de tramadol não é mediado por receptores opioides na dor de ratos no pós-operatório imediato.

BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5mg, naloxone 200µg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors.

Safety profile of intravenous patient-controlled analgesia for breakthrough pain in cancer patients: a case series study.

PURPOSE: The WHO analgesic ladder supports medication choice according to pain intensity. The use of the analgesic ladder in an inverse way, has the advantage of using the same principles of the original ladder to treat crisis of pain in cancer patients. The purpose of this study is to describe the use of intravenous patient-controlled analgesia (IV-PCA) technique in patients admitted to an oncological Hospital. METHODS: This is a case series study. Patients assigned to receive IV-PCA between March 2011 and May 2012 were selected for the study. Medical records were reviewed, patients stratified according to the Karnofsky Performance Score (KPS). The primary outcome was to verify if different IV-PCA opioid solutions could be equally effective providing pain relief. Secondary outcomes were the incidence of clinical side effects that can be associated to IV-PCA infusions. RESULTS: A total of 95 medical records were reviewed. Most patients used IV-PCA with morphine (42.1 %), fentanyl (42.1 %) or methadone (15.7 %) to treat exacerbation periods of cancer pain. IV-PCA used as supplementary therapy successfully improved pain control in 78.9 % of the patients, without any difference related to opioid solution. KPS <40 was related to higher rate of pain relief, without any difference in side effects in this group of patients. The most common side effects were sedation (10.5 %) followed by constipation (9.4 %) and nausea (4.2 %). Morphine presented a higher risk than fentanyl for sedation. Analgesia-related delirium or respiratory depression were not reported in this case series study. CONCLUSIONS: IV-PCA provided timely, safe and useful analgesia for patients with severe breakthrough pain and may be useful to help titration of opioids, weaning to oral analgesia and to decide for interventional procedures.

Avaliação da adição do tramadol sobre o tempo de regressão do bloqueio motor induzido pela lidocaína: estudo experimental em ratos / Evaluation of the addition of tramadol on lidocaine-induced motor block regression time: experimental study in rats

JUSTIFICATIVA E OBJETIVOS: O tramadol bloqueia potenciais somatossensitivos in vitro e pode ser associado a anestésicos locais com o intuito de melhorar a qualidade da analgesia. O objetivo deste estudo foi avaliar se o tramadol altera o tempo de regressão do bloqueio motor da lidocaína em duas diferentes concentrações. MÉTODO: Ratos machos da linhagem Wistar, pesando de 250 a 300 g, foram submetidos a bloqueio de nervo ciático guiado por neuroestimulação percutânea. Os animais foram distribuídos em quatro grupos (n = 5 por grupo): lidocaína a 2% (GI), lidocaína a 0,5% (GII), lidocaína a 2% / tramadol 1,25 mg (GIII), e lidocaína a 0,5% / tramadol 1,25 mg (GIV). Foram avaliados tempo de regressão parcial e tempo de regressão completa do bloqueio motor. RESULTADOS: Todos os animais apresentavam bloqueio motor completo no momento do despertar da anestesia, que regrediu completamente durante o período de observação. O tempo de regressão completa do efeito da lidocaína a 2% foi 41 ± 1,71 minutos, lidocaína a 0,5% foi 25,26 ± 0,83 minutos, lidocaína a 2% / tramadol foi 46,06 ± 0,88 minutos e lidocaína a 0,5% / tramadol foi 36,15 ± 1,18 minutos. A associação da lidocaína a 0,5% ao tramadol 1,25 mg foi mais eficaz que lidocaína a 0,5% isoladamente. Os dados são apresentados como média ± erro padrão da média (epm). Considerou-se significativo p < 0,05 usando a ANOVA seguido do teste de Tukey. CONCLUSÃO: Tramadol possui efeitos semelhantes a anestésicos locais e, quando usado como adjuvante da lidocaína, prolonga a duração do bloqueio motor em ratos.

BACKGROUND AND OBJECTIVES: Tramadol blocks somatosensory potentials in vitro and may be associated to local anesthetics to improve analgesic quality. This study aimed at evaluating whether tramadol changes lidocaine motor block regression in two different concentrations. METHOD: Male Wistar rats weighing 250 to 300 g were submitted to sciatic nerve block guided by percutaneous nerve stimulation. Animals were distributed in four groups (n = 5 per group): 2% lidocaine (GI), 0.5% lidocaine (GII), 2% lidocaine/1.25 mg tramadol (GIII), 0.5% lidocaine/1.25 mg tramadol (GIV). Partial and total motor block regression times were evaluated. RESULTS: Al animals had total motor block when awakening from anesthesia, which has totally regressed during the observation period. Total regression time of 2% lidocaine was 41 ± 1.71 minutes, 0.5% lidocaine was 25.26 ± 0.83 minutes, 2% lidocaine/tramadol was 46.06 ± 0.88 minutes and 0.5% lidocaine/tramadol was 36.15 ± 1.18 minutes. The association of 0.5% lidocaine and 1.25 mg tramadol was more effective as compared to 0.5% lidocaine alone. Data are presented in mean ± mean standard error (mse), considering significant p < 0.05 using ANOVA followed by Tukey test. CONCLUSION: Tramadol has effects similar to local anesthetics and, when used as adjuvant of lidocaine, prolongs motor block duration in rats.

Bloqueio do sistema nervoso simpático para tratamento de dor do membro fantasma: relato de caso / Sympathetic nervous system block to control phantom limb pain: case report

JUSTIFICATIVA E OBJETIVOS: A sensação do membro fantasma é um fenômeno que acomete pacientes submetidos à amputação de qualquer um dos membros, e essa sensação pode ser acompanhada ou não de dor. Este relato teve por objetivo apresentar um caso no qual o bloqueio do sistema nervoso simpático foi utilizado como adjuvante no tratamento da dor do membro fantasma. RELATO DO CASO: Paciente portador de carcinoma epidermoide de punho que evoluiu com dor do membro fantasma após amputação do antebraço esquerdo. Foi submetido a tratamento conservador e de reabilitação física, porém a analgesia obtida com terapia farmacológica foi insuficiente e o paciente evoluiu com dor do coto de amputação e dor mediada pelo sistema nervoso simpático. Finalmente, o paciente foi submetido a bloqueio simpático venoso seguido de bloqueio diagnóstico da cadeia simpática torácica com redução significativa da dor. CONCLUSÃO: Nesse caso foi utilizado o bloqueio do sistema nervoso simpático por meio de infusão venosa de lidocaína, seguido de bloqueio da cadeia simpática torácica como opção terapêutica para dor do membro fantasma. Nessa sequência, foi obtido alívio da dor, sem surgimento de efeitos adversos.

BACKGROUND AND OBJECTIVES: Phantom limb sensation is a phenomenon affecting patients submitted to amputation of any limb and this sensation may or may not be followed by pain. This report aimed at presenting a case where sympathetic nervous system block was used as adjuvant to control phantom limb pain. CASE REPORT: Patient with wrist epidermoid carcinoma, who evolved with phantom limb pain after left forearm amputation. Patient was submitted to conservative treatment and physical rehabilitation, however drug therapy analgesia was insufficient and patient evolved with pain in the amputation stump and sympathetic nervous system-mediated pain. Ultimately, patient was submitted to sympathetic venous block followed by diagnostic chest sympathetic chain block with significant pain decrease. CONCLUSION: Sympathetic nervous system block in this case was induced with venous lidocaine infusion, followed by chest sympathetic chain block as therapeutic option for phantom limb pain. This sequence has provided pain relief without adverse effects.

Bloqueio neurolítico subaracnoideo em paciente com dor oncológica refratária: relato de caso / Subarachnoid neurolytic blockade in patient with refractory cancer pain: case report

JUSTIFICATIVA E OBJETIVOS: O uso de bloqueio neurolítico subaracnoideo no controle de dor tem diminuído nos últimos anos devido à introdução de novas técnicas, mas ainda tem importância no controle de dor oncológica refratária. O objetivo deste estudo foi apresentar um caso de dor oncológica, em que esta técnica foi utilizada para controle da dor. RELATO DO CASO: Paciente do sexo masculino, 45 anos, diagnosticado com carcinoma espinocelular de canal anal localmente avançado e lesão ulcerada em região perineal com presença de fístula retovesical e infecção local. O paciente apresentava dor intensa com escala verbal numérica (EVN) =10 e recebia tratamento farmacológico com doses altas de opioide e adjuvantes sem boa resposta. Foi realizado bloqueio neurolítico subaracnoideo com fenol a 5% e após realização do bloqueio houve melhora significativa do quadro doloroso, tendo paciente referindo alívio de 80% após 20 minutos do procedimento. A melhora permaneceu até o 21º dia após bloqueio quando o paciente foi a óbito devido complicações infecciosas. CONCLUSÃO: O caso ilustrou o uso do bloqueio subaracnoideo com fenol a 5% para controle de dor oncológica. Conclui-se que para casos selecionados, onde a expectativa de vida é limitada, esta técnica pode ser empregada com sucesso.

BACKGROUND AND OBJECTIVES: The use of subarachnoid neurolytic blockade to control pain has decreased in recent years due to the introduction of new techniques, but it is still important to control refractory cancer pain. This study aimed at presenting a case of cancer pain where this technique was used to control pain. CASE REPORT: Male patient, 45 years old, with locally advanced anal canal scamous cell carcinoma and ulcerated lesion in perineal region with enterovesical fistula and local infection. Patient had severe pain with numerical verbal scale (NVS) = 10 and was being pharmacologically treated with high opioid doses and adjuvants without good response. Subarachnoid neurolytic blockade was induced with 5% phenol with significant pain relief; 20 minutes after the procedure patient has referred 80% relief. Improvement has remained for 21 days when patient died due to infectious complications. CONCLUSION: This case has illustrated the use of subarachnoid blockade with 5% phenol to control cancer pain. The conclusion is that for selected cases, where life expectation is limited, this technique may be successfully used.

Dor retal persistente após retossigmoidectomia: relato de caso / Persistent rectal pain after rectosimoidectomy: case report

JUSTIFICATIVA E OBJETIVOS: Dor abdominal crônica após intervenção cirúrgica possui fisiopatologia ainda pouco estudada, sendo descrita após cesariana, hérnia inguinal, videolaparoscopia e colecistectomia. No andar inferior do abdômen, a proctalgia crônica tem sido descrita após hemorroidectomia sendo caracterizada por dor à evacuação acompanhada de urgência para defecar. A dor crônica pós-operatória persistente após retossigmoidectomia videolaparoscópica é pouco frequente. O objetivo deste estudo foi relatar um caso de dor pós-operatória persistente após retossigmoidectomia videolaparoscópica, controlada com bloqueio anestésico bilateral do plexo hipogástrico. RELATO DO CASO: Paciente do sexo feminino, 54 anos, submetida à retossigmoidectomia com anastomose em cólon transverso-retal, por videolaparoscopia. No pós-operatório imediato evoluiu com dor retal em tenesmo, contínua, de forte intensidade, com queimação ocasional. Analgésicos não opioides não aliviavam a dor. Investigação do quadro não evidenciou complicações cirúrgicas, sendo encaminhada para a equipe de controle de dor. Foi realizado bloqueio diagnóstico bilateral de plexo hipogástrico superior com 4 mL de lidocaína a 1%, (sem vasoconstritor) por via transdiscal em L5/S1 guiado por radioscopia, que produziu alívio importante da dor. Permaneceu sem dor durante dois meses, sendo realizado novo bloqueio bilateral hipogástrico superior com 5 mL de lidocaína a 2% (sem vasoconstritor) por via transdiscal em L5/S1 guiado por radioscopia, com remissão importante da dor, atualmente controlada com uso ocasional de gabapentina (300 mg). CONCLUSÃO: A dor retal pós-operatória persistente foi controlada com o bloqueio anestésico bilateral do plexo hipogástrico e a duração do alívio da dor foi prolongada, muito além da meia-vida do anestésico local.

BACKGROUND AND OBJECTIVES: Postoperative chronic abdominal pain still lacks pathophysiological studies, being described after Cesarean section, inguinal hernia, videolaparoscopy and cholecystectomy. In lower abdomen, chronic proctalgia has been described after hemorrhoidectomy and is characterized as pain at evacuation followed by urgency to defecate. Persistent postoperative pain after videolaparoscopic rectosigmoidectomy is uncommon. This study aimed at reporting a case of persistent postoperative pain after videolaparoscopic rectosigmoidectomy, controlled with bilateral anesthetic block of the hypogastric plexus. CASE REPORT: Female patient, 54 years old, submitted to videolaparoscopic rectosigmoidectomy with transverse-rectal colon anastomosis. In the immediate postoperative period she evolved with tenesmus, continuous and severe pain with occasional burning. Non-steroid analgesics would not relieve pain. Evaluation has not shown surgical complications and she was referred to the pain control team. Radioscopy-guided transdiscal bilateral diagnostic blockade of upper hypogastric plexus was induced with 4 mL of 1% lidocaine (without vasoconstrictor) in L5/S1 which has induced major pain relief. Patient remained pain-free for two months when a new radioscopy-guided transdiscal bilateral upper hypogastric block was induced with 5 mL of 2% lidocaine (without vasoconstrictor) with major pain remission. Currently pain is controlled with occasional gabapentin (300 mg). CONCLUSION: Persistent rectal postoperative pain was controlled with bilateral anesthetic hypogastric plexus block with prolonged pain relief, well beyond local anesthetic half life.