Safety and effectiveness of adding fentanyl or sufentanil to spinal anesthesia: systematic review and meta-analysis of randomized controlled trials

Abstract Introduction Spinal infusions of either fentanyl or sufentanil have been reported in international reports, articles, and scientific events worldwide. This study aimed to determine whether intrathecal fentanyl or sufentanil offers safety in mortality and perioperative adverse events. Methods MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane library databases), gray literature, hand-searching, and clinicaltrials.gov were systematically searched. Randomized controlled trials with no language, data, or status restrictions were included, comparing the effectiveness and safety of adding spinal lipophilic opioid to local anesthetics (LAs). Data were pooled using the random-effects models or fixed-effect models based on heterogeneity. Results The initial search retrieved 4469 records; 3241 records were eligible, and 3152 articles were excluded after reading titles and abstracts, with a high agreement rate (98.6%). After reading the full texts, 76 articles remained. Spinal fentanyl and sufentanil significantly reduced postoperative pain and opioid consumption, increased analgesia and pruritus. Fentanyl, but not sufentanil, significantly reduced both postoperative nausea and vomiting, and postoperative shivering; compared to LAs alone. The analyzed studies did not report any case of in-hospital mortality related to spinal lipophilic opioids. The rate of respiratory depression was 0.7% and 0.8% when spinal fentanyl or sufentanil was added and when it was not, respectively. Episodes of respiratory depression were rare, uneventful, occurred intraoperatively, and were easily manageable. Conclusion There is moderate to high quality certainty that there is evidence regarding the safety and effectiveness of adding lipophilic opioids to LAs in spinal anesthesia.

Administración prolongada de morfina intratecal por bomba de infusión implantada, en un caso de dolor crónico no oncológico / Prolonged administration of intratecal morphine by infusion pump implanted in a case of non-oncological chronic pain / Administração prolongada de morfina intratecal por bomba de infusão implantada, em caso de dor crônica não oncológica

Introducción: Se describe la evolución de un paciente que recibe morfina intratecal mediante una bomba de infusión, que le fuera implantada hace 14 años para tratamiento de su dolor lumbar crónico post-laminectomía. Material y método: Requería la administración de 60 mg/día de morfina subcutánea que le provocaban efectos secundarios que no toleraba, y múltiples internaciones para control del dolor. Se le implantó una bomba de infusión continua (Isomed) conectada a un catéter subaracnoideo, que libera 1 ml/día, y requiere ser llenada cada 60 días. Resultados: Se observó una disminución del dolor promedio de 50% al año, y de 75% a los 6 y 14 años. Requirió un aumento progresivo de las dosis de llenado, que pasaron de 30 mg de morfina (0.5 mg/día) al inicio, a 40 mg de morfina (0.66 mg /día) al año, a 70 mg de morfina (1.16 mg/día) a los 6 años, a 140 mg (2.33 mg/día) a los 14 años. No se registraron complicaciones médicas graves. Mantuvo constipación y sudoración durante todo el período, e instaló un hipogonadismo secundario con trastornos de la libido y de la erección que fueron corregidos con la administración de testosterona. No requirió más internaciones por dolor. No se observaron complicaciones relacionadas con el funcionamiento o llenado de la bomba, ni vinculadas al catéter. El paciente manifestó estar satisfecho con el implante. Discusión: A pesar del aumento de las dosis de llenado, expresión del desarrollo de tolerancia, las dosis de morfina/día requeridas son francamente inferiores al límite recomendado. Conclusiones: El balance del riesgo-beneficio del implante resultó positivo, considerando el mejor control del dolor logrado, las menores dosis de morfina utilizadas, así como la ausencia de complicaciones graves y de internaciones para control del dolor.

Introduction: The evolution of a patient receiving intrathecal morphine through an infusion pump that was implanted 14 years ago for the treatment of chronic post-laminectomy low back pain is described. Material and method: It required the administration of 60 mg / day of subcutaneous morphine that caused side effects that did not tolerate, and multiple hospitalizations for pain control. He was implanted with a continuous infusion pump (Isomed) connected to a subarachnoid catheter, which releases 1 ml / day, and needs to be filled every 60 days. Results: An average pain decrease of 50% per year, and 75% at 6 and 12 years was observed. It required a progressive increase in filling doses, which went from 30 mg of morphine (0.5 mg / day) at the beginning, to 40 mg of morphine (0.66 mg / day at the first year, to 70 mg of morphine (1.16 mg / day) at the sixth year, at 140 mg (2.33 mg / day) at the fourteen year. No serious medical complications were recorded, he maintained constipation and sweating throughout the period, and installed secondary hypogonadism with libido and erection disorders, that were corrected with the administration of testosterone. No further hospitalizations were required due to pain. No complications were observed related to the operation or filling of the pump or linked to the catheter. The patient stated that he was satisfied with the implant. Discussion: Despite the increase in filling doses, expression of tolerance development, the required morphine / day doses are frankly below the recommended limit. Conclusions: The risk-benefit balance of the implant was positive, considering the best pain control, the lowest doses used, the absence of serious complications, and the lack of hospitalizations for pain control.

Introdução: Descreve-se a evolução de um paciente que recebeu morfina intratecal através de uma bomba de infusão, implantada há 14 anos para o tratamento de lombalgia crônica pós-laminectomia. Material e método: Necessitou de administração de 60 mg/dia de morfina por via subcutânea, que provocou efeitos colaterais intolerantes, e múltiplas internações para controle da dor. Foi implantada uma bomba de infusão contínua (Isomed) conectada a um cateter subaracnóideo, que libera 1 ml/dia, necessitando de reenchimento a cada 60 dias. Resultados: Observou-se redução média da dor de 50% em um ano e 75% em 6 e 14 anos. Foi necessário um aumento progressivo das doses de enchimento, que passaram de 30 mg de morfina (0,5 mg/dia) no início, para 40 mg de morfina (0,66 mg/dia) por ano, para 70 mg de morfina (1,16 mg/dia) dia) aos 6 anos, para 140 mg (2,33 mg/dia) aos 14 anos. Não foram registradas complicações médicas graves. Manteve constipação e sudorese durante todo o período e desenvolveu hipogonadismo secundário com distúrbios de libido e ereção que foram corrigidos com administração de testosterona. Ele não necessitou de mais hospitalizações por dor. Não foram observadas complicações relacionadas à operação ou enchimento da bomba, ou relacionadas ao cateter. O paciente afirmou estar satisfeito com o implante. Discussão: Apesar do aumento das doses de enchimento, expressão do desenvolvimento da tolerância, as doses necessárias de morfina/dia são francamente inferiores ao limite recomendado. Conclusões: A relação risco-benefício do implante foi positiva, considerando o melhor controle da dor alcançado, as menores doses de morfina utilizadas, bem como a ausência de complicações graves e internações para controle da dor.

Single-center, retrospective study on changes in pain-relieving therapy after bone metastasis detection by bone scintigraphy in prostate cancer patients

Abstract Whole-body bone scintigraphy (WB-BS) is used for detecting and monitoring metastatic spread of prostate cancer (PCa) and to investigate bone pain episodes. To investigate the impact of a positive WB-BS on pain-relieving medicine prescription in PCa patients, a single-center, retrospective cohort study with PCa patients classified as positive for bone metastases (BM) by WB-BS was conducted. Demographic, clinical, and ambulatory pain-relieving medicine prescription data were evaluated. Pain-relieving medicines were categorized according to the WHO 'Analgesic Ladder'. Regimens adopted before and after WB-BS were compared. Differences were considered significant at p<0.05. A total of 180 PCa patients were diagnosed with BM, 64.4% of whom were ≥65 years of age. Thirty-three patients were prescribed analgesics only after WB-BS, mostly including NSAIDs and weak opioids. Pain-relieving prescription changed after WB-BS in patients with prescriptions before and after WB-BS, with a reduction in NSAIDs and adjuvants and an increase in weak and strong opioids. In addition, 40% of patients with WHO analgesic step 1 drugs and 21.7% of patients with WHO step 2 drugs before WB-BS changed to other WHO steps after WB-BS. Pain-relieving prescriptions changed after a positive WB-BS, providing evidence that it could contribute to clinical management of painful metastatic PCa patients.

The future of precision medicine in opioid use disorder: inclusion of patient-important outcomes in clinical trials

Opioid use has reached an epidemic proportion in Canada and the United States that is mostly attributed to excess availability of prescribed opioids for pain. This excess in opioid use led to an increase in the prevalence of opioid use disorder (OUD) requiring treatment. The most common treatment recommendations include medication-assisted treatment (MAT) combined with psychosocial interventions. Clinical trials investigating the effectiveness of MAT, however, have a limited focus on effectiveness measures that overlook patient-important outcomes. Despite MAT, patients with OUD continue to suffer negative consequences of opioid use. Patient goals and personalized medicine are overlooked in clinical trials and guidelines, thus missing an opportunity to improve prognosis of OUD by considering precision medicine in addiction trials. In this mixed-methods study, patients with OUD receiving MAT (n=2,031, mean age 39.1 years [SD 10.7], 44% female) were interviewed to identify patient goals for MAT. The most frequently reported patient-important outcomes were to stop treatment (39%) and to avoid all drugs (25%). These results are inconsistent with treatment recommendations and trial outcome measures. We discuss theses inconsistencies and make recommendations to incorporate these outcomes to achieve patient-centered and personalized treatment strategies.

Abuse of Pharmaceutical Drugs and Its Prevention / 法医学杂志

Abuse of pharmaceutical drugs is a major public health and social problem worldwide. Mostly abused drugs mainly include opioids such as morphine, tramadol, methadone and fentanyl, sedative-hypnotics such as benzodiazepines and non-benzodiazepines, and central stimulants such as Ritalin (methylphenidate), Adderall (amphetamine and dextroamphetamine) and modafinil. Abuse of pharmaceutical drugs not only causes direct damage to multiple systems of the body, but also significantly increases risks of mental and physical diseases, imposing a heavy burden on individuals, families and society. Therefore, the prevention and control of pharmaceutical drug abuse are of vital importance. The Chinese government has taken strict administration measures for pharmaceutical drugs with abuse risk. However, confronting endless new drugs and changing abuse trends, it is necessary to further strengthen management and prevention of pharmaceutical drugs, monitor the trend of abuse, establish rapid response mechanisms, popularize relevant knowledge, and develop specific therapeutic drugs and intervention means, in order to promote prevention and treatment of pharmaceutical drug abuse.

Epidemiological Characteristics of Sedative-Hypnotics and Opioid Painkillers at High-Frequency Exposure / 法医学杂志

Drug poisoning has a high incidence and serious consequences in medical institutions; its epidemiological characteristics also directly affect the changes in national laws and policies and the implementation of local management policies. Chinese statistics on drug-related abnormal death cases generally come from judicial appraisal centers and medical units. However, due to differences in work content and professional restrictions, there are differences in information management forms, which makes it difficult for appraisers to conduct a professional and systematic analysis of drug-related cases. This article focuses on the analysis of epidemiological characteristics of sedative-hypnotics and opioid painkillers and their exposure patterns in cases of poisoning death by analyzing the annual report of the American Association of Poison Control Center, combined with the characteristics of drug exposure in China.

Efectos de los opioides en endocrinología / Opioids effects in endocrinology

El uso de opioides ha aumentado en forma significativa en las últimas décadas, lo que nos ha permitido conocer sus diversos efectos en el sistema endocrino. Estos efectos están sub diagnosticados, en parte porque los síntomas se confunden con los de la misma enfermedad que lleva al uso de opioides y porque no los buscamos de forma dirigida. El hipogonadismo y la insuficiencia suprarrenal son sus efectos más establecidos, sin embargo, otros efectos como los provocados en el tejido óseo requieren de especial atención. La evaluación de los ejes gonadotropo, adrenal y de la salud ósea debe tenerse en consideración en los usuarios crónicos de opioides, particularmente frente a la presencia de síntomas. La suspensión o reducción del uso de opioides es el primer tratamiento del compromiso endocrinológico.

The use of opioids has increased significantly in recent decades, which has allowed us to understand its effects on the endocrine system. These effects are underdiagnosed, the symptoms are confused with those of the same disease that leads to the use of opioids and we do not look for them in a targeted way. Hypogonadism and adrenal insufficiency are its most established effects, however, other effects such as the ones caused on bone tissue require special attention. Evaluation of gonadotropic and adrenal axes as well as bone health should be taken into consideration in chronic opioid users, particularly in the presence of symptoms. Stopping or reducing opioid use is the first treatment for endocrine compromise.

Can eastern wisdom resolve western epidemics? Traditional Chinese medicine therapies and the opioid crisis / 中西医结合学报

The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine (TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large meta-analyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favor non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without life-threatening side effects (e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that: (1) opioid misuse cannot be satisfactorily managed with standard medication; (2) opinion leaders in the United States favor to consider non-opioid and non-pharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions; (3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.

Guiding opioid-free intravenous antinociception with the Analgesia Nociception Index: a case report / Antinocicepção intravenosa sem opioides orientada pelo Índice de Analgesia/Nocicepção: relato de caso

Abstract Background: Opioid-free anesthesia decreases the incidence of opioid adverse events, but its optimal antinociceptive depth has not been clearly defined. Personalizing intraoperative opioid-free infusions with a nociception monitor may be the solution. Case report: We describe the feasibility and potential limitations of titrating opioid-free antinociception during major abdominal surgery using the Analgesia Nociception Index (Mdoloris, Lille, France) in an obese patient. After stabilizing the patient's nociception-antinociception balance intraoperatively we quickly reversed anesthesia and the patient did not require postoperative opioids. Conclusion: Personalizing opioid-free antinociception with a nociception monitor is feasible. It may optimize intraoperative antinociception and improve postoperative comfort.

Resumo Introdução A anestesia sem opioides diminui a incidência de eventos adversos associados aos opioides, mas a profundidade antinociceptiva ideal dessa abordagem não está claramente definida. Personalizar a infusão intraoperatória sem opioides com o uso de monitor de nocicepção pode ser a solução. Relato de caso Descrevemos a viabilidade e as eventuais limitações da titulação da antinocicepção sem opioides por meio do uso do Índice de Analgesia/Nocicepção (Mdoloris, Lille, França) durante cirurgia abdominal de grande porte em paciente com obesidade. Depois de estabilizar o equilíbrio nocicepção-antinocicepção da paciente no intraoperatório, revertemos rapidamente a anestesia e a paciente não precisou de opioides no pós-operatório. Conclusão A personalização da antinocicepção sem opioides por meio do emprego de monitor de nocicepção é factível. A abordagem pode otimizar a antinocicepção intraoperatória e melhorar o conforto pós-operatório.

Experiencia en la práctica clínica real de la efectividad y la tolerabi- lidad de tapentadol de liberación prolongada para el tratamiento de dolor crónico postraumático producido por accidentes de trabajo / Real-world clinical practice experience of the effectiveness and tolerability of pro- longed-release tapentadol for the treatment of chronic post-traumatic pain caused by occupational accidents

Se llevó a cabo un estudio observacional para analizar si tapentadol de liberación prolongada (LP) puede considerarse un tratamiento de primera línea para pacientes con dolor crónico postraumático (DCPT). Métodos: Se presenta una serie de casos de la práctica clínica real de pacientes con DCPT producido por accidentes de trabajo. Antes de ingresar al estudio, todos los pacientes recibían tramadol, que se interrumpió cuando se inició la administración de tapentadol LP. Las evaluaciones de dolor incluyeron una escala de valoración numérica, el cuestionario DN4 y la escala de Impresión Global de Cambio del Paciente (PGIC, Patients' Global Impression of Change). Se recuperaron y registraron los eventos adversos. Resultados: 94 pacientes participaron en el estudio y 77 (82 %) completaron todas las visitas predefinidas. Cerca de la mitad de los pacientes informaron dolor crónico que tenía una duración de al menos 3 años; se observó un componente neuropático en el 87 % de los pacientes. El puntaje de dolor se redujo en 1,5 puntos luego del primer mes de tratamiento con tapentadol LP y en 2,48 puntos luego de 4 meses (p<0,05). También se asoció la administración de tapentadol LP con una reducción del 28,9 % de la dosis concomitante de pregabalina (p<0,01). De acuerdo con el cuestionario PGIC, el 74 % y el 77,9 % de los pacientes informó mejoría luego de uno y cuatro meses de tratamiento, respectivamente. El perfil de seguridad fue consistente con los datos actuales sobre tapentadol LP. Conclusión: El dolor osteomuscular crónico es una enfermedad prevalente que se caracteriza por tener resultados terapéuticos deficientes y se asocia a una mayor discapacidad y una mala calidad de vida. En este estudio de la práctica clínica real en pacientes que trabajan y que cuentan con un componente de dolor neuropático elevado, se observó que tapentadol LP produce efectos beneficiosos en términos del control del DCPT, y se obtuvieron índices altos de eficacia y seguridad.

An observational study was carried out to analyze whether prolonged-release (PR) tapentadol may be considered a first-line treatment for patients with chronic post-traumatic pain (PTD). Methods: A case series of cases of patients with PTFE caused by work accidents in a real clinical practice setting is described. Before entering the study, all patients were receiving tramadol, which was discontinued when PR tapentadol was started. Pain assessments included a numerical rating scale, the DN4 questionnaire, and the Patients' Global Impression of Change (PGIC) scale. Adverse events were retrieved and described. Results: 94 patients participated in the study and 77 (82%) completed all the predefined visits. About half of the patients reported chronic pain that lasted for at least 3 years. A neuropathic component was reported in 87% of patients. The pain score was reduced by 1.5 points after the first month of treatment with PR tapentadol and by 2.48 points after 4 months (p < 0.05). Administration of PR tapentadol was also associated with a concomitant reduction of pregabalin dose of 28.9% (p < 0.01). According to the PGIC questionnaire, 74% and 77.9% of patients reported improvement after one and four months of treatment, respectively. The safety profile was consistent with current data on PR tapentadol. Conclusion: Chronic musculoskeletal pain is a prevalent disease characterized by poor therapeutic results and associated with increased disability and poor quality of life. In our study in a real clinical practice setting with patients with a high neuropathic pain component, PR tapentadol produced beneficial effects in terms of DCPT control, and high efficacy and safety rates were obtained. Keywords: tapentadol, chronic pain, pain caused by work accidents, chronic post-traumatic pain, evidence from real clinical practice.

Transdermal buprenorphine for acute postoperative pain: a systematic review / Uso da buprenorfina transdérmica na dor aguda pós-operatória: revisão sistemática

Background and objectives: Postoperative pain is still a major concern in several surgical procedures. Multimodal analgesia is best for postoperative pain management; however, opioid therapy is still the main treatment for pain after surgical procedures. Transdermal buprenorphine is a partial µ-agonist opioid widely used for chronic pain syndromes, with limited evidence for acute postoperative pain. A systematic review of studies examining transdermal buprenorphine for acute pain management after surgery was conducted. Contents: Data from PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL via EBSCOhost, and LILACS were reviewed, including randomized clinical trials that evaluated total postoperative pain, postoperative analgesic consumption, drug-related side effects and patient satisfaction with analgesia regimen. Data from nine studies (615 patients) were included in this review. Most studies initiated transdermal buprenorphine use 6 to 48 hours before surgery, maintaining use from 1 to 28 days after the procedure. Most studies showed lower or similar postoperative pain scores, postoperative analgesic consumption and patient satisfaction comparing buprenorphine to placebo, tramadol, celecoxib, flurbiprofen and parecoxib. The incidence of side effects varied between studies, with most showing no increase in drug-related side effects with buprenorphine use, except one study, which compared buprenorphine to oral tramadol, and one to transdermal fentanyl. However, most results were derived from evidence with an overall high or unclear risk of bias. Conclusions: Although more studies are necessary, initial results show that transdermal buprenorphine seems to be an effective and safe opioid choice for management of acute postoperative pain

Justificativa e objetivos: A dor pós-operatória ainda é uma queixa importante em vários procedimentos cirúrgicos. A analgesia multimodal é a melhor conduta para a dor pós-operatória, embora a terapia com opioides ainda seja o principal tratamento para a dor após procedimentos cirúrgicos. A buprenorfina transdérmica é um opioide agonista µ amplamente prescrito nas síndromes de dor crônica, mas com limitada evidência do seu uso para dor aguda no pós-operatório. Realizamos revisão sistemática de estudos que examinaram o papel da buprenorfina transdérmica no tratamento da dor aguda pós-operatória. Conteúdo: Revisamos os dados de PubMed, Embase, Registro Central de Ensaios Controlados Cochrane (CENTRAL), CINAHL via EBSCOhost e LILACS, incluindo estudos clínicos randomizados que avaliaram a dor pós-operatória total, consumo de analgésicos pós-operatórios, efeitos colaterais relacionados a medicamentos e satisfação do paciente com esquema de analgesia. Dados de nove estudos (615 pacientes) foram incluídos nesta revisão. A maioria dos estudos iniciou o uso transdérmico de buprenorfina 6 a 48 horas antes da cirurgia, mantendo o uso de 1 a 28 dias após o procedimento. A maioria dos estudos encontrou valores semelhantes ou menores para o escore de dor pós-operatória, consumo pós-operatório de analgésicos e satisfação do paciente quando a buprenorfina foi comparada ao placebo, tramadol, celecoxibe, flurbiprofeno e parecoxibe. A incidência de efeitos colaterais oscilou nos estudos, e a maioria não mostrou aumento de efeito colateral relacionado ao uso de buprenorfina, exceto em dois estudos, um que comparou buprenorfina ao tramadol oral e outro ao fentanil transdérmico. No entanto, a maioria dos resultados foi obtida a partir de evidências com um risco geral alto ou risco de viés impreciso. Conclusões: Embora sejam necessários mais estudos, os resultados iniciais mostram que a buprenorfina transdérmica parece ser uma forma de administração segura e efetiva de opioide no tratamento da dor aguda pós-operatória

Anestesia libre de opioides en hemicolectomía abierta derecha extendida. Reporte de un caso y revisión / Opiod Free Anesthesia (OFA) for Open extended right colectomy. A case report and review

Opioid free anesthesia (OFA) is defined as an anesthesiologic technique where opioids are not used in the intraoperative and postoperative period. Although the mainstay of intra-operative analgesia may be opioids, current challenges are focus on reducing them and preventing the adverse effects of opioids, by rationalizing and even suspending their perioperative use, specifically at risk populations such as Obstructive Sleep Apnea Syndrome (OSAHS), obesity, Chronic Obstructive Pulmonary Disease (COPD) and cancer surgery. We present this case of OFA in a susceptible patient with complications from the use of opioids undergoing an extended right hemicolectomy. Multimodal analgesia was performed with a thoracic peridural and subanesthetic doses of intravenous agents including dexmedetomidine, ketamine and propofol, accompanied by short and long-lasting local periglotic anesthetics. The patient had given an intraand postoperative analgesia without presenting any adverse events, good recovery, early deambulation and extubation.

La anestesia libre de opioides (OFA) es una técnica anestésica donde no hay administración de opioides, tanto en el intraoperatorio como en el postoperatorio. Aunque una de las bases de la analgesia intraoperatoria podrían ser los opioides, los desafíos actuales están enfocados en reducir su uso perioperatorio, previniendo sus efectos adversos, racionalizando y limitando su empleo específicamente en poblaciones de riesgo como síndrome de apnea obstructiva del sueño (SAHOS), obesidad, enfermedad pulmonar obstructiva crónica (EPOC) y cirugía oncológica. Presentamos este caso de OFA en un paciente susceptible de complicaciones por uso de opioides sometido a una hemicolectomía derecha extendida. Se realizó analgesia multimodal con peridural torácica y dosis subanestésicas de agentes endovenosos como dexmedetomidina, ketamina y propofol, acompañado de anestésicos locales periglóticos de corta y larga duración. Se otorgó una adecuada analgesia intra y postoperatoria, el paciente no tuvo eventos adversos, presentando una buena recuperación, deambulación y extubación precoz.

Low dose intrathecal morphine for hip arthroplasty / Dosis baja de morfina intratecal para artroplastía cadera

OBJECTIVES: 100 mcg intrathecal morphine (ITM) for hip arthroplasty provides adequate functional recovery and reduces associated complications but is not exempt from opioid-related adverse effects. We evaluate efficacy of a reduced dose of ITM (80 mcg) in terms of anesthetic quality, postoperative analgesia, complication rates and early recovery. METHODS: Case control study. Patients under hip arthroplasty were treated on a specific protocol, using neuraxial anesthesia with hyperbaric bupivacaine 10.5-13.5 mg plus 80 mcg ITM versus controls with 100 mcg ITM. Demographic variables, intra and perioperative course were extracted from medical records. Pain severity and morphine associated complications were blindly assessed at regular intervals postoperatively. p < 0.01 were considered significant. RESULTS: 82 patients were analyzed. Mean age was 64.21 years, 62.20% women and 70.73% ASA-2. Main endoprosthesis indication was arthrosis (58.53%). No statistically significant differences in demographic and operative data were found between groups, including surgical time, ambulation time, length of stay, and patient satisfaction for pain management. Mean VAS for pain during first 24 hours was 0.24 for the low ITM group and 0.22 for control. Rescue intravenous morphine was the same between groups. Compared to 80 mcg ITM, 100 mcg showed trends for higher complication rates for respiratory depression (OR 2.58, CI 95% 0.4514.54, p = 0.28), nausea without vomiting (OR 1.82, CI 95% 0.82-4.01, p = 0.13), urinary retention (OR 2.02, CI95% 0.88-4.61, p = 0.09) and significantly higher rates of pruritus (OR 3.55, CI 95% 1.61-7.82, p < 0.01). CONCLUSIONS: 80 mcg ITM during spinal anesthesia for hip arthroplasty provided comparable postoperative analgesia and lower incidence of opioid-related adverse effects.

OBJETIVOS: 100 mcg morfina intratecal (ITM), en artroplastía de cadera, proporciona una recuperación funcional adecuada y reduce complicaciones asociadas, pero no está exento de efectos adversos conocidos asociados a opioides. Evaluamos eficacia de reducir dosis (80 mcg ITM) en términos de calidad anestésica, analgesia, complicaciones y recuperación postoperatoria. MÉTODOS: Estudio de casos y controles. Pacientes sometidos a artroplastía de cadera fueron tratados con anestesia espinal con bupivacaína hiperbárica 10,5-13,5 mg más 80 mcg ITM y controles de manera similar, pero con 100 mcg ITM. Variables demográficas, así como intra y perioperatorio, se extrajeron de registros médicos. Severidad del dolor, y complicaciones asociadas a ITM, se evaluaron a ciegas según protocolo. p < 0,01 fue considerado significativo. RESULTADOS: 82 pacientes analizados. Edad promedio fue 64,21 años, 62,20% fueron mujeres y 70,73% ASA-2. Principal indicación de prótesis fue artrosis (58,53%). No se encontraron diferencias estadísticas entre variables demográficas, tiempo quirúrgico, tiempo deambulación, duración hospitalización y satisfacción paciente. EVA promedio dolor, primeras 24 horas, fue 0,24 para grupo 80 mcg ITM y 0,22 para control (100 mcg ITM). Morfina intravenosa de rescate fue similar entre grupos. En comparación con 80 mcg, 100 mcg presentó mayores tasas de complicaciones para depresión respiratoria (OR 2,58, IC 95% 0,45-14,54, p = 0,28), náuseas y vómitos (OR 1,82, CI 95% 0,82-4,01, p = 0,13), retención urinaria (OR 2,02, CI 95% 0,88-4,61, p = 0,09) y prurito (OR 3,55, CI 95% 1,61-7.82, p < 0,01). CONCLUSIONES: 80 mcg ITM, en anestesia espinal para artroplastía cadera, proporciona analgesia postoperatoria comparable a 100 mcg, pero con menor incidencia de efectos adversos relacionados a opioides.

Efecto del fentanilo intratecal en hiperlagesia secundaria posoperatoria de cirugía ligamento cruzado anterior de rodilla / Effect of Intrathecal fentanyl on secondary hyperalgesia, in patients undergoing anterior cruciate ligament repair

BACKGROUND AND OBJECTIVES: Fentanyl addition is a common practice when administering spinal anesthesia. Intrathecal fentanyl has been associated to increased postoperative pain and increase morphine consumption, but considered to be related to acute opioid tolerance. This prospective, randomized, blind study evaluates the effect of intrathecal fentanyl in the development of secondary hyperalgesia, measured with Von Frey filaments, in patients undergoing anterior cruciate ligament repair. METHODS: 46 patients having anterior cruciate ligament repair, received intrathecal hyperbaric bupivacaine 13.5 mg with fentanyl 20 mcg or no fentanyl addition. Light touch pain threshold was measured with von Frey filaments before anesthesia, at 6 and 24 hours post anesthesia in the non-operated thigh and in the forearm. Visual analogue pain scores and morphine consumption were also measured at the same time. RESULTS: Baseline thresholds to mechanical stimuli were similar in both groups. In the forearm, analysis showed a decreased threshold for the non-fentanyl group at 24 h p = 0.036. In the lower extremity, control and treatment group showed lower thresholds (secondary hyperalgesia) p = 0.002 but no difference between them p = 0.795. VAS score and morphine consumption did not differ among groups. CONCLUSIONS: Spinal fentanyl added to hyperbaric bupivacaine showed no evidence of an augmented state of hyperalgesia after ACL repair, neither by pain threshold modification nor clinical outcomes. On the contrary, at 24 h, fentanyl may have a protective effect at levels above the spinal block.

ANTECEDENTES Y OBJETIVOS: El uso de fentanilo es una práctica común en la administración de anestesia espinal. Su aplicación se ha asociado a un aumento del dolor post operatorio y a un aumento en el uso de morfina; por otro lado, se ha vinculado a una tolerancia aguda a opioides. El siguiente estudio prospectivo, randomizado y ciego, evalúa los efectos del fentanilo intratecal en la aparición de hiperalgesia secundaria, medida a través de filamentos Von Frey, en pacientes operados de ligamento cruzado anterior. METODOLOGÍA: Se incluyeron a 46 pacientes operados de ligamento cruzado anterior (LCA) con una dosis intratecal de bupivacaína hiperbárica de 13,5 mg; con y sin la adición de fentanilo de 20 mcg. Se midió el umbral del dolor mecánico, a través de filamentos Von Frey, antes de la anestesia, a las 6 y 24 horas postanestesia en el muslo no operado y en el antebrazo. Al mismo tiempo, se midió la puntuación del dolor en la escala verbal numérica (EVN) y el consumo de morfina. RESULTADOS: Los umbrales basales ante la estimulación mecánica resultaron similares en ambos grupos. En el antebrazo, el análisis mostró una disminución del umbral en el grupo de pacientes sin fentanilo, a las 24 h, p = 0,036 comparado con uso de fentanilo. En el muslo, el grupo control y tratamiento mostró umbrales más bajos (hiperalgesia secundaria) p = 0,002; no obstante, no se mostraron diferencias entre ellos. No se mostraron diferencias entre las puntuaciones de la EVN y el consumo de morfina en los dos grupos. CONCLUSIÓN: No hay evidencia que la adición de fentanilo espinal, a la dosis de bupivacaína hiperbárica, haya contribuido a un aumento en la hiperalgesia tras la reparación del LCA, medido por la modificación del umbral del dolor, ni en los resultados clínicos. Al contrario a las 24 h fentanilo puede tener un efecto protector de la hiperalgesia secundaria sobre el nivel del bloqueo espinal.

Opioid-induced immunosuppression and carcinogenesis promotion theories create the newest trend in acute and chronic pain pharmacotherapy

Opioids are the main group of pharmacological agents used during the perioperative period and provide a sedative and analgesic component. The observations of opioid consumption in West Europe indicate that this group of drugs is widely used in chronic noncancer pain therapy. Nearly 20 years ago, the first publications indicating that opioids, as an element of perioperative pharmacotherapy in oncologic patients, increase the risk of tumor recurrence and affect further prognosis were presented. The actual publications suggest that there are multifactorial, complex mechanisms underlying the immunological impact and carcinogenesis promotion of opioids and that the intensity varies depending on the type of opioid. There are also questions about the immunosuppressive effects among patients receiving opioids in the treatment of chronic noncancer pain. The aim of the review article is to present information about the action of opioids on the immune system in carcinogenic settings and to define the clinical usefulness of this pharmacological phenomenon.

Constipação induzida por opióides em cuidado paliativo: o estado da arte / Opioid-induced constipation in palliative care: state of the art / Presión de vientre induzida por opióides en cuidado paliativo: el estado del arte

Objetivo: Objetivou-se realizar o estado da arte de publicações que relatem estratégias de como minimizar a constipação induzida pelo uso de opioides, de pacientes em cuidado paliativo. Método: Trata-se de um estudo exploratório através de uma revisão integrativa em quatro bases de dados de artigos publicados entre os anos de 2013 a 2017. Resultados: Evidenciaram-se 117 publicações, as quais 17 apresentaram os critérios de inclusão da pesquisa. Conclusão: Apesar das drogas aliviarem a dor, as reações adversas geram desconforto e perda da qualidade de vida. Existem dados limitados referentes ao tratamento da constipação intestinal em cuidado paliativo. Observou-se que poucos autores mencionaram a dieta como auxiliador no quadro, enfatizando o uso de medicamentos. Mais estudos devem ser estimulados no intuito de encontrar o equilíbrio entre analgesia e redução de efeitos adversos causados pelos opioides

Objective: The study's purpose has been to address the state of the art in investigations such as clinical trials, systematic reviews with metaanalysis and case studies, which report how to minimize opioid-induced constipation in patients undergoing palliative care. Methods: This is an exploratory study through an integrative review of four databases addressing published articles from 2013 to 2017. Results: A total of 117 publications were presented, which 17 presented the inclusion criteria. The studies describe the prevalence of constipation rates induced by the use of opioids. Conclusion: Although these drugs alleviate pain, the adverse reactions may generate discomfort and loss of the patient's life quality. There are limited data on the treatment of constipation. It was observed that few authors mentioned diet as a helper on this situation, emphasizing the use of medications. Further studies should be encouraged aiming to find the balance between analgesia and reduction of adverse effects

Objetivo: Se objetivó realizar el estado del arte de publicaciones que relatan estrategias de cómo minimizar el constipación inducida por el uso de opioides, de pacientes en cuidado paliativo. Método: Se trata de un estudio exploratorio a través de una revisión integrativa en cuatro bases de datos de artículos publicados entre los años de 2013 a 2017. Resultados: Se evidenció 117 publicaciones, las cuales 17 presentaron los criterios de inclusión de la investigación. Conclusión: A pesar de las drogas aliviar el dolor, las reacciones adversas generan incomodidad y pérdida de la calidad de vida. Existen datos limitados referentes al tratamiento del estreñimiento intestinal en el cuidado paliativo. Se observó que pocos autores mencionaron la dieta como auxiliador en el cuadro, enfatizando el uso de medicamentos. Más estudios deben ser estimulados con el fin de encontrar el equilibrio entre analgesia y reducción de efectos adversos causados por los opioide

Superficial cervical plexus blockade improves pain control after thyroidectomy: A randomized controlled trial

OJECTIVES: The aim was to evaluate the ability of bilateral superficial cervical plexus blockade to control pain and to reduce the side effects of general anesthesia in patients submitted to thyroidectomy. METHODS: In this randomized controlled trial, we prospectively studied 100 consecutive patients who underwent total thyroidectomy. The simple random patient sample was divided into two groups: 50 patients received general anesthesia alone (group 1 [G1]), and 50 patients received general anesthesia with bilateral superficial cervical plexus blockade (group 2 [G2]). Statistical analyses were performed, and a 5% significance level was adopted. RESULTS: The mean arterial blood pressure and heart rate were 12% lower in G2 patients than in G1 patients 60 minutes after surgery (101 mmHg for G1 vs. 92.3 mmHg for G2; p<0.001). G2 patients reported less pain than G1 patients, and opioid consumption was lower in G2 patients than in G1 patients, not upon postanesthesia care unit arrival, but at 30 minutes (2% vs. 34%; p<0.001, respectively), 45 minutes (0% vs. 16%; p=0.006, respectively), and 4 hours postoperatively (6% vs. 20%; p=0.037, respectively). The incidence of nausea and vomiting was lower in G2 patients than in G1 patients from 45 minutes (0% vs. 16%; p=0.006, respectively) to 8 hours postoperatively (0% vs. 14%; p=0.012, respectively). CONCLUSIONS: The present study demonstrated that the combination of bilateral superficial cervical plexus blockade with general anesthesia for thyroidectomy is feasible, safe, and effective for achieving pain control and improving patient outcomes.

Opioid tapering and weaning protocols in pediatric critical care units: a systematic review

SUMMARY OBJECTIVE: Opioid abstinence syndrome is common in the pediatric intensive care environment because sedation is often needed during the children's treatment. There is no specific guideline regarding the management of these patients; and lately, methadone is an important drug for the prevention of abstinence symptoms during the weaning of opioids. This study gathers the available research to establish the initial dose of methadone, the rate of taper and tools to recognize this syndrome and act promptly. METHODS: A systematic review was made from data of four different databases. Forty-nine articles of observational and experimental studies were selected based on the inclusion criteria (critical pediatric patients in acute use of opioids) and exclusion criteria (previous chronic use of opioids, other medications). The data regarding specific themes were separated in sections: initial dose of methadone, use of protocols in clinical practice, abstinence scales and adjuvant drugs. RESULTS: The articles showed a great heterogeneity of ways to calculate the initial dose of methadone. The pediatric intensive care units of the study had different weaning protocols, with a lower incidence of abstinence when a pre-defined sequence of tapering was used. The Withdrawal Assessment Tool - 1 was the most used scale for tapering the opioids, with good sensitivity and specificity for signs and symptoms. CONCLUSION: There is still little evidence of other medications that can help prevent the abstinence syndrome of opioids. This study tries to promote a better practice during opioid weaning.

RESUMO OBJETIVO: A síndrome de abstinência de opioides é comum no ambiente de terapia intensiva pediátrica porque a sedação é frequentemente necessária durante o tratamento das crianças. Não existe uma diretriz específica sobre o manejo desse paciente e, ultimamente, a metadona tem sido uma droga importante para a prevenção dos sintomas de abstinência durante o desmame dos opioides. Este estudo reúne as pesquisas disponíveis para estabelecer a dose inicial de metadona, taxa de redução e ferramentas para reconhecer essa síndrome e agir prontamente. MÉTODOS: Uma revisão sistemática foi feita a partir de dados de quatro diferentes bases de dados. Quarenta e nove artigos, de estudos observacionais e experimentais, foram selecionados com base nos critérios de inclusão (pacientes críticos pediátricos em uso de opioides agudamente) e critérios de exclusão (uso crônico prévio de opioides, outros medicamentos). Os dados referentes a temas específicos foram separados em seções: dose inicial de metadona, uso de protocolos na prática clínica, escalas de abstinência e drogas adjuvantes. RESULTADOS: Os artigos mostraram uma grande heterogeneidade de formas de calcular a dose inicial de metadona. As unidades de terapia intensiva pediátrica do estudo apresentaram diferentes protocolos de desmame, com menor incidência de abstinência quando foi utilizada uma sequência predefinida de redução gradual. A Ferramenta de Avaliação de Retirada - 1 foi a escala mais utilizada durante a redução dos opioides, com boa sensibilidade e especificidade para sinais e sintomas. CONCLUSÃO: Ainda há poucas evidências de outros medicamentos que possam ajudar a prevenir a síndrome de abstinência dos opioides. Este estudo tenta promover uma prática melhor durante o desmame dos opioides.