Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey

ABSTRACT Introduction: Intrathecal chemotherapy is a mainstay component of acute lymphoblastic leukemia treatment. In Mexico, there is a considerable practice variability in aspects, such as the manner of preparation and the administration technique. Objective: Our objective was to describe the different techniques used for the application of ITC and review the existing recommendations in the literature. Method: A cross-sectional, nationwide survey study was conducted by an electronic questionnaire sent to hematologists and oncologists in Mexico. We collected demographic data, personal experience, intrathecal chemotherapy techniques, drug preparation and postprocedural conduct. Results: We received 173 responses. Twenty percent had an anesthesiologist administering sedation and pain management. The platelet count considered safe was 50 × 109/L in 48% of the participants. In 77% (n = 133) of the cases, the conventional needle with stylet used was, 49% did not receive any added diluent in the intrathecal chemotherapy and only 42% were recommended to rest in a horizontal position for more than 30 min. Conclusion: We identified a considerable variation in the administration of intrathecal chemotherapy across the hematologists in Mexico. We discuss the implications and opportunities in reducing the variation in our setting, highlighting the unmet need to establish guidelines that should be evaluated by the Mexican professional society to produce a position paper regarding practice standardization.

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.

Subarachnoid lavage following inadvertent intrathecal injection of tranexamic acid

Tranexamic acid (TXA) is a commonly used antifibrinolytic drug during surgical procedures to reduce blood loss. An Inadvertent intrathecal injection of TXAmay lead to serious side effects including seizures and ventricular fibrillation with reported fatalities. We report a case of an inadvertentintrathecal injection of TXAwhich occurred as a result of similarities in appearance between TXAand heavy bupivacaine ampoules. The patient had subarachnoid lavage after experiencing back pain, systemic hypertension followed by generalized tonic clonic seizures

Effects of intrathecal injection of ropivacaine on spinal cord in rats based on genomics / 中南大学学报(医学版)

OBJECTIVES@#There are clinical reports of nerve injury caused by ropivacaine. The mechanism for nerve injury induced by ropivacaine has not been fully clarified. This study aims to investigate the changes of pain threshold and L3 spinal cord genomics at 6 h and 24 h after intrathecal injection of 0.5% and 1.0% ropivacaine, and to explore the underlying mechanisms for nerve injury caused by ropivacaine.@*METHODS@#A total of 30 male Sprague Dawley rats weighing 220-260 g were successfully implanted with microspinal catheter. The rats were randomly divided into 5 groups (each n=6): a control group (given saline), a ropivacaine group 1 and a ropivacaine group 2 (both given 1% ropivacaine), a ropivacaine group 3 and a ropivacaine group 4 (both given 0.5% ropivacaine). The rats received continuous intrathecal injection of corresponding drugs at 8.3 μL/h for 24 h via an implanted intrathecal catheter followed by 24 h-pause of injection for the ropivacaine group 2, the ropivacaine group 4 and the control group, 6 h-pause of injection for the ropivacaine group 1 and the ropivacaine group 3. For each group, the observation of behavioral change and the paw withdrawal mechanical threshold (PWMT) was conducted immediately after the injection and again after the pause of injection. After the PWMT observation, the rats were dissected to acquire L3 spinal cords. Illumina sequencing was applied to construct gene libraries. Then the statistical methods were used to find out differentially expressed genes between the groups. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were conducted for those genes. Real-time RT-PCR was used to determine different expressions of some of those genes.@*RESULTS@#Compared with control group, the PWMT got higher in the ropivacaine group 1-4 and was positively correlated with concentration, negatively correlated with discontinuation duration. Compared with control group, the ropivacaine group 1 had 488 differentially expressed genes, of which 456 were up-regulated and 32 were down-regulated; the ropivacaine group 2 had 1 194 differentially expressed genes, of which 1 092 were up-regulated and 102 were down-regulated; the ropivacaine group 3 had 518 differentially expressed genes, of which 384 were up-regulated and 134 were down-regulated; and the ropivacaine group 4 had 68 differentially expressed genes, of which 46 were up-regulated and 22 were down-regulated. GO enrichment analysis and KEGG signaling pathway analysis showed that most of these differentially expressed genes were related to signaling pathways of inflammatory response.@*CONCLUSIONS@#After intrathecal injection of 0.5% ropivacaine and 1.0% ropivacaine for 24 h, the differentially expressed genes in L3 spinal cord of rats are mainly related to signaling pathways of inflammatory response.

Inyección intratecal inadvertida de ácido tranexámico / Inadverted intrathecal injection of tranexamic acid / Injeção intratecal inadvertida de ácido tranexâmico

Resumen: Se realiza una revisión descriptiva sobre la inyección de ácido tranexámico en el espacio subaracnoideo. Se destaca que un error puede tener consecuencias catastróficas sobre el paciente, con un alto porcentaje de mortalidad. Se analizan las posibles causas que pueden llevar a la inyección errónea. Se advierte sobre la existencia de preparaciones de ácido tranexámico de similar apariencia a las de la bupivacaína de uso intratecal. Se describe el cuadro clínico de la complicación, el mecanismo de toxicidad, los tratamientos utilizados, y la evolución de los casos relatados en las referencias encontradas. Se discuten estrategias para evitar la complicación, señalando que la seguridad no debe basarse en la perfección humana, sino en medidas que dificulten cometer errores.

Summary: A descriptive review of tranexamic acid injection in the subarachnoid space is performed. A point is made that this error may have catastrophic consequences on the patient with a high percentage of mortality. Possible causes that can lead to an erroneous injection are analyzed. A warning is made about tranexamic acid preparations being similar in appearance to those of bupivacaine for intrathecal use. The study describes the clinical manifestation of this complication, the toxicity mechanism, treatments used, and the evolution of the cases reported in the references found. Strategies to avoid complications are discussed, pointing out that safety should not be based on human perfection, but on measures that make it difficult for humans to make mistakes.

Resumo: Faz-se uma revisão descritiva sobre a injeção de ácido tranexâmico no espaço subaracnóideo. Ressalta-se que é um erro que pode ter consequências catastróficas para o paciente com um elevado percentual de mortalidade. Faz-se uma análise das possíveis causas que podem levar ao uso equivocado de ácido tranexâmico devido a existência de preparações semelhantes em aparência às da bupivacaína para uso intratecal. Descreve-se o quadro clínico da complicação, o mecanismo de toxicidade, os tratamentos utilizados e a evolução dos casos relatados nas referências encontradas. Discute-se estratégias para evitar complicações, ressaltando que a segurança não deve ser baseada na perfeição humana, mas em medidas que dificultem o erro do ser humano.

Comparison among subarachnoid opioid mix for cesarean section - An observational study / Comparación de mezcla de Opioides subaracnoideos para cesárea. Estudio observacional

Abstract Introduction Classically, the local anesthetic (LA) has been combined with one lipophilic and another hydrophilic opioid for neuraxial anesthesia in cesarean section. In Colombia, the practice has been the use of morphine hydrochloride with fentanyl, but the occasional shortage of the former triggered an interest in new options. In response to the shortage of morphine in 2017-2018, a contingency plan was developed at the SES Hospital in Caldas, prefilling syringes at the hospital compounding central, with: bupivacaine, morphine and fentanyl (BMF); bupivacaine, fentanyl and hydromorphone (BFH); and bupivacaine and hydromorphone (BH). Hydromorphone has a rapid onset of action, long-lasting effect and is indicated for spinal administration in the safety data sheet; therefore, the advantages of adding fentanyl to this mix are questionable. Objective To compare the clinical analgesic efficacy at the time of the incision and during the first 12 hours after surgery. Methods An observational, analytical study was conducted, using the mixtures BMF, BFH and BH in patients receiving subarachnoid anesthesia for cesarean section. Pain was assessed at the time of the incision, as well as any adverse effects and the pain visual analogue scale over the following 12 hours. Results Of the 71 patients participating in the study, 40.9 % received BMF; 22.5 %, BFH; and 36.6 %, BH. None of the patients experienced pain at the time of the incision. There was no difference in terms of adverse effects among the three groups. The mean difference in the visual analogue scale (VAS) for postoperative pain at 3, 6 and 12 hours was lower in the groups in which hydromorphone was used. Conclusion BFH and BH combinations are comparable to the original preparation in terms of adverse effects, with the advantage of being more effective in controlling postoperative pain.

Resumen Introducción Para anestesia neuroaxial en cesárea, se ha combinado clásicamente el anestésico local (AL) con un opioide lipofílico y otro hidrofílico. En Colombia se ha usado clorhidrato de morfina con fentanilo, pero el ocasional desabastecimiento del primero despertó el interés por nuevas alternativas. En SES Hospital de Caldas se generó un plan de contingencia frente a la escasez de morfina en 2017-2018, pre llenando jeringas en su central de mezclas con: bupivacaína, morfina y fentanilo (BMF); bupivacaína, fentanilo e hidromorfona (BHF); y bupivacaína e hidromorfona (BH). La hidromorfona tiene inicio rápido de acción, efecto prolongado e indicación en ficha técnica por vía espinal, por lo tanto, las ventajas que pudiera generar la adición del fentanilo a esta mezcla son cuestionables. Objetivo Comparar la eficacia analgésica clínica al momento de la incisión y en las primeras 12 horas postoperatorias. Métodos Se realizó un estudio observacional analítico, empleando las mezclas BMF, BHF y BH en pacientes que recibieron anestesia subaracnoidea para cesárea. Se evaluó el dolor a la incisión, los efectos adversos y la escala visual análoga de dolor en las 12 horas siguientes. Resultados De las 71 pacientes del estudio, 40,9 % recibieron BMF; 22,5 %, BHF; y 36,6 %, BH. En ninguna paciente se observó dolor a la incisión. No hubo diferencia en efectos adversos entre los 3 grupos. La diferencia de medias de la escala visual analógica (EVA) para dolor postoperatorio a las 3, 6 y 12 horas, fue menor en los grupos en los que se usó hidromorfona. Conclusiones Las mezclas BHF y BH son equiparables a la preparación tradicional en cuanto a efectos adversos, con la ventaja de ser más efectivas para el control del dolor postoperatorio.

Anestesia para colocación de nusinersen intratecal en pacientes con atrofia muscular espinal / Anesthesia for instillation of intratecal nusinersen in patients for muscular atrophy

We present a series of four patients diagnosed with Spinal Muscular Atrophy (SMA), 2 type II, 2 type III, for placement of spinal nusinersen/Spinraza under general anesthesia with propofol. This new treatment can improve the quality of life of these patients. Its management represents a challenge for anesthesiologists as they try to provide not only adequate general anesthesia but containment to adolescent or young patients. In particular, patients that need to enter into the operating room several times a year.

Presentamos una serie de 4 pacientes con diagnóstico de atrofia muscular espinal (AME) 2 tipo II y 2 tipo III, para colocación de nusinersen/Spinraza raquídeo bajo anestesia general con propofol. Este nuevo tratamiento puede mejorar la calidad de vida de los pacientes. Su manejo representa un desafío para los anestesiólogos que intentamos brindar no solo una adecuada anestesia general sino contención a pacientes adolescentes o jóvenes que necesitan ingresar al quirófano varias veces al año.

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.

Analgesic and side effects of intravenous recombinant Phα1ß

Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1ß exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1ß in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1ß using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1ß toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1ß may be feasible for drug-induced analgesia, without causing any severe side effects.(AU)

Anesthesia management in cesarean section for a patient with coronavirus disease 2019 / 浙江大学学报·医学版

Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.

Anesthesia management in cesarean section for patient with COVID-19: a case report / 浙江大学学报·医学版

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.

Quimioterapia intratecal: percepções e significados atribuídos por pacientes com câncer hematológico / Intrathecal chemotherapy: perceptions and meanings attributed by patients with hematological cancer / Quimioterapia intratecal: percepciones y signficados atribuidos por pacientes com cáncer hematológico

Objetivo: analisar os significados e as percepções dos pacientes submetidos à quimioterapia intratecal sobre esse tratamento. Método: estudo descritivo de abordagem quantiqualitativa, desenvolvida com 13 participantes atendidos em uma central de quimioterapia de um hospital universitário do interior de Minas Gerais, entre os anos de 2015 a 2016, cujos dados, obtidos por meio de entrevistas, foram submetidos à análise do discurso do sujeito coletivo. Aprovado pelo Comitê de Ética em Pesquisa da instituição campo do estudo. Resultados: dos dados codificados emergiram cinco discursos: desconhecimento do tratamento, dor, ansiedade, fé e esperança. Conclusão: a quimioterapia intratecal é desconhecida pelos pacientes em tratamento, causando ansiedade, dor e reações adversas as quais trazem prejuízo para a qualidade de vida desses indivíduos. Com isso criam-se mecanismos de enfrentamento da doença por meio da fé e da esperança.

Objective: analyze the meanings and perceptions of patients undergoing intrathecal chemotherapy about this treatment Method: qualitative and descriptive study carried out with 13 participants attended at a Chemotherapy Center of a University Hospital in the interior of Minas Gerais, from 2015 to 2016, whose data were submitted to the analysis of the collective subject discourse. Approved by the Research Ethics Committee of the study development institution. Results: the information obtained through the interviews was coded and five discourses emerged: lack of treatment, pain, anxiety, faith and hope. Conclusion: intrathecal chemotherapy is unknown to patients undergoing treatment, causing anxiety, pain and adverse reactions that impair their quality of life. This creates mechanisms for coping with the disease through faith and hope.

Objetivo: analizar los significados y las percepciones de los pacientes sometidos a quimioterapia intratecal sobre este tratamiento. Método: estudio de enfoque cuantitativo y descriptivo desarrollado con 13 participantes atendidos en un Centro de Quimioterapia de un Hospital Universitario en el interior de Minas Gerais, entre 2015 y 2016, cuyos datos fueron sometidos al análisis del discurso del sujeto colectivo. Aprobado por el Comité de Ética en Investigación de la institución de desarrollo del estudio. Resultados: la información obtenida a través de las entrevistas fue codificada y surgieron cinco discursos: falta de tratamiento, dolor, ansiedad, fe y Esperanza. Conclusión: la quimioterapia intratecal es desconocida para los pacientes sometidos a tratamiento, lo que causa ansiedad, dolor y reacciones adversas que deterioran su calidad de vida. Esto crea mecanismos para hacer frente a la enfermedad a través de la fe y la esperanza.

Effect of bupivacaine versus bupivacaine plus intrathecal dexmedetomidine in postoperative pain

Background: Pain is defined as "unpleasant sensory and sensory experience", associated with actual or potential tissue domage or described in terms of such damage. Objetive: To assess the effect of bupivacaine versus bupivacaine plus intrathecal dexmedetomidine in postoperative pain. Patients and method: An experimental design was made of a controlled clinical trial type, in patients scheduled for lower abdomen surgery or lower extremities. A sample of 60 patients was studied during the period from October 1 to december 15, 2018, who agreed to participate in the study through of signing consent under information. Results: It was observed that the time of the rescue analgesia was prolonged in more than 120 min in the case of dexmedetomidine when compared with bupivacaine (p<0.0001); also VAS scores at the time of analgesia rescue for the group with dexmedetomidine were 3.71 ± 1.27 and in the bupivacaine group of 5.7 ± 1.59, the difference of two pints of the VAS (p= <0.001) was significant, which demonstrates that dexmedetomidine is effective for prolong postoperative analgesia and decrease the analgesia requirements. Conclusions: Dexmedetomidine at a dose of 5 ug associated with bupivacaine administered intrathecally is more Effective in postoperative analgesia compared with this substance alone in abdominal surgery inferior and lower extremities (AU)

Evaluation of the neurotoxic effects of intrathecal administration of (S)-(+)-Ketoprofen on rat spinal cords: randomized controlled experimental study / Avaliação dos efeitos neurotóxicos da administração intratecal do (S)-(+)-cetoprofeno em medula espinhal de rato: estudo experimental randômico e controlado

Abstract Background and objectives Intrathecal administration of non-steroidal anti-inflammatory drugs is more efficacious for post-operative pain management. Cyclooxygenase inhibiting non-steroidal anti-inflammatory drugs like (S)-(+)-Ketoprofen, may be effective at lower intrathecal doses than parenteral ones. Preclinical safety regarding possible neurotoxicity associated with the intrathecal (S)-(+)-Ketoprofen was not evaluated. Here we analysed the neurotoxicity of intrathecally administered (S)-(+)-Ketoprofen in rats. Methods A randomized placebo-controlled experimental study was conducted. Sprague-Dawley rats (250-300 g) aged 12-16 weeks were randomly divided into 2 treatments [100 and 800 µg (S)-(+)-Ketoprofen] and control (sterile water) groups. Intrathecal catheters were placed via the atlantoaxial space in anesthetized rats. Pinch-toe tests, motor function evaluations and histopathological examinations of the spinal cord and nerve roots were performed at days 3, 7 and 21. Spinal cord sections were evaluated by light microscopy for the dorsal axonal funiculus vacuolation, axonal myelin loss, neuronal chromatolysis, neuritis, meningeal inflammation, adhesions, and fibrosis. Results Rats in all the groups exhibited normal pinch-toe testing response (score = 0) and normal gait at each observed time (motor function evaluation score = 1). Neurotoxicity was higher with treatments on days 3 and 7 than that on day 21 (2, 3, 0, p = 0.044; 2, 5, 0, p = 0.029, respectively). On day 7, the total scores reflecting neuronal damage were higher in the 800 µg group than those in the 100 µg and Control Groups (5, 3, 0, p = 0.048, respectively). Conclusion Intrathecal (S)-(+)-Ketoprofen caused dose-dependent neurohistopathological changes in rats on days 3 and 7 after injection, suggesting that (S)-(+)-Ketoprofen should not be intrathecally administered.

Resumo Justificativa e objetivos A administração intratecal de anti-inflamatórios não esteroides é mais eficaz no tratamento da dor pós-operatória. Anti-inflamatórios não esteroides, como o (S)-(+)-cetoprofeno, pode ser eficaz em doses intratecais inferiores às parenterais. A segurança pré-clínica relativa à possível neurotoxicidade associada ao (S)-(+)-cetoprofeno intratecal não foi avaliada. Neste estudo avaliamos a neurotoxicidade do (S)-(+)-cetoprofeno administrado por via intratecal em ratos. Métodos Conduzimos um estudo experimental randomizado e controlado por placebo em ratos Sprague-Dawley (250-300 g) com idades entre 12 e 16 semanas. Eles foram randomicamente divididos em dois grupos de tratamento [100 e 800 µg de (S)-(+)-cetoprofeno] e um de controle (água estéril). Cateteres intratecais foram colocados através do espaço atlantoaxial nos ratos anestesiados. Testes de pinça, avaliações da função motora e exames histopatológicos da medula espinhal e das raízes nervosas foram realizados nos dias 3, 7 e 21 do estudo. Os cortes da medula espinhal foram avaliados por microscopia de luz para vacuolização do funículo axonal dorsal, perda de mielina axonal, cromatólise neuronal, neurite, inflamação, aderências e fibrose das meninges. Resultados Em todos os grupos, os ratos exibiram resposta normal ao teste de pinça (pontuação = 0) e marcha normal em cada tempo observado (escore de avaliação da função motora = 1). A neurotoxicidade foi maior com os tratamentos nos dias 3 e 7 do que no dia 21 (2, 3, 0, p = 0,044; 2, 5, 0, p = 0,029, respectivamente). No dia 7, os escores totais refletindo o dano neuronal foram maiores no grupo com 800 µg que nos grupos com 100 µg e controle (5, 3, 0, p = 0,048, respectivamente). Conclusão A administração intratecal de (S)-(+)-cetoprofeno causou alterações neuro-histopatológicas dose-dependentes em ratos nos dias 3 e 7 após a aplicação e sugerindo que o (S)-(+)-cetoprofeno não deve ser administrado por via intratecal.

Feasibility of Ultrasound-Guided Lumbar and S1 Nerve Root Block: A Cadaver Study

OBJECTIVE: This study evaluated the feasibility of ultrasound-guided lumbar nerve root block (LNRB) and S1 nerve root block by identifying spread patterns via fluoroscopy in cadavers.METHOD: A total of 48 ultrasound-guided injections were performed in 4 fresh cadavers from L1 to S1 roots. The target point of LNRB was the midpoint between the lower border of the transverse process and the facet joint at each level. The target point of S1 nerve root block was the S1 foramen, which can be visualized between the median sacral crest and the posterior superior iliac spine, below the L5-S1 facet joint. The injection was performed via an in-plane approach under real-time axial view ultrasound guidance. Fluoroscopic validation was performed after the injection of 2 cc of contrast agent.RESULTS: The needle placements were correct in all injections. Fluoroscopy confirmed an intra-foraminal contrast spreading pattern following 41 of the 48 injections (85.4%). The other 7 injections (14.6%) yielded typical neurograms, but also resulted in extra-foraminal patterns that occurred evenly in each nerve root, including S1.CONCLUSION: Ultrasound-guided injection may be an option for the delivery of injectate into the S1 nerve root, as well as lumbar nerve root area.

The Evidence for Nonoperative Treatment of Lumbar Spinal Diseases / 대한척추외과학회지

STUDY DESIGN: Review article.OBJECTIVES: To assess the evidence for nonoperative treatment of various degenerative spinal degenerative diseases.SUMMARY OF LITERATURE REVIEW: No study has yet evaluated the evidence for preoperative nonoperative treatment of lumbar spinal diseases.METHODS: The evidence regarding nonoperative treatment for each disease was reviewed through NASS guidelines, and the treatment effect compared to surgical treatment was reviewed through the SPORT series. The efficacy of nonoperative treatment according to disease severity and certain special conditions was investigated through corresponding individual articles.RESULTS: No kind of nonoperative treatment could change the fundamental progression of degenerative spinal disease. The natural course of lumbar disc herniation is favorable regardless of treatment. More than 70% of routine cases improve within 6 weeks. However, it does not take a full 6 weeks to decide whether to perform surgery or not. The evidence for transforaminal epidural steroid injections for short-term pain control is grade A. There is grade B evidence for nonoperative treatment with the goal of mid- to long-term pain control. However, we cannot say that those outcomes are better than the natural course of the disease itself. In cases of radicular weakness, the degree of weakness is correlated with the final outcomes, but it is not evident whether the duration of weakness is correlated with surgical outcomes. Early surgery is usually necessary due to intolerable pain, rather than stable motor weakness. The social cost of herniated discs arises from the loss of patients’ productivity, rather than from direct medical expenses. The natural course of spinal stenosis involves provoked pain and the need for palliative care. Unlike disc herniation, rapid deterioration and marked improvement do not occur. The symptoms of mild to moderate lumbar stenosis are unchanged in 70% of cases, improve in 15%, and worsen in 15%. No study has compared nonoperative treatment with the natural course of the disease. There is no evidence for nonoperative treatment of severe stenosis. Epidural spinal injections are effective for controlling short-term pain. Spontaneous recovery of radicular weakness does not occur, and urgent surgery is necessary in such cases. There is no evidence regarding the natural course and nonoperative treatment of degenerative spondylolisthesis. The working group consensus recommends that it should follow the pattern of nonoperative treatment of spinal stenosis when radicular stenosis symptoms are predominant. Overall, 40%–66% of cases of adult bilateral isthmic spondylolysis progress to symptomatic spondylolisthesis. No studies have investigated nonoperative treatment except physical exercise.CONCLUSIONS: Although short-term symptom amelioration can be achieved by nonoperative treatment, the fundamental progression of the disease is not affected. For conditions excluded from most studies, such as prior spine surgery, cauda equina syndrome, progressive neurological deficit, and uncontrollable severe pain associated with instability, deformity, or vertebral fractures, there were not enough studies to reach informed conclusions. Our review found no evidence regarding nonoperative treatment for such conditions. Furthermore, the treatment methods for each disease are not clearly distinguished from each other, and the techniques used for disc herniation have been applied to other diseases without any evidence.

Inhibition of MicroRNA-15a/16 Expression Alleviates Neuropathic Pain Development through Upregulation of G Protein-Coupled Receptor Kinase 2

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

Safety and Biodistribution of Human Bone Marrow-Derived Mesenchymal Stromal Cells Injected Intrathecally in Non-Obese Diabetic Severe Combined Immunodefi ciency Mice: Preclinical Study

BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 × 10⁵ cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human β2M and β-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.

Sequential intrathecal injection of fentanyl and hyperbaric bupivacaine at different rates: does it make a difference? A randomized controlled trial / 대한마취과학회지

BACKGROUND: Previous studies have shown that sequential intrathecal injection of fentanyl and hyperbaric bupivacaine for cesarean section (CS) anesthesia provides a superior anesthetic effect than use of bupivacaine alone, and prolongs postoperative analgesia. Herein, we investigated whether rapid intrathecal injection of fentanyl followed by slow injection of hyperbaric bupivacaine affects the duration of postoperative analgesia, the effectiveness of anesthesia, and hemodynamic status. METHODS: Fifty-six parturients with American Society of Anesthesiologists physical status I or II, aged 18–40 years, and scheduled to undergo elective CS were randomly assigned to 2 groups of 28 patients each. The normal sequential group received sequential intrathecal injections of fentanyl and hyperbaric bupivacaine at the same rate, each with a 5 ml syringe. The rapid sequential group received a rapid intrathecal injection of fentanyl with an insulin syringe, followed by a slow injection of hyperbaric bupivacaine with a 5 ml syringe. The onset of sensory block, the timing of the first rescue analgesia, the doses of rescue analgesics, the degree of postoperative pain, the onset and duration of motor block, the incidence and duration of hypotension, and spinal anesthesia-related complications were recorded. RESULTS: While both approaches had comparable spinal anesthesia-related complications, incidence and duration of hypotension, and doses of ephedrine, the rapid sequential group exhibited a more rapid onset of sensory block, a higher sensory level, and more prolonged postoperative analgesia. CONCLUSIONS: Rapid sequential injection of fentanyl and hyperbaric bupivacaine produced superior anesthesia and more prolonged postoperative analgesia than sequential injections of both at the same rate.

Wnt3a signaling pathway plays a role in neuropathic pain through epigenetic modification of JMJD6 / 中南大学学报(医学版)

To explore whether Wnt3a exerts a role in neuropathic pain through Jumonji C domain 6 (JMJD6)-associated epigenetic modification. 
 Methods: SD rats were divided into 4 groups: A sham group, a chronic constriction injury (CCI) group, a CCI+negative lentiviral expression vector (LV-NC) group and a CCI+lentiviral overexpression vector (LV-JMJD6) group. The sciatic nerve CCI model of SD rat and JMJD6 lentiviral expression vector were constructed. On the third day after CCI, the intrathecal catheter was prepared, and 20 μL of normal saline and lentivirus-containing reagent (virus titer 1×108 TU/mL) were administered. The rats' paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were monitored, and Western blotting was used to detect the expression of Wnt3a and NR2B protein in the spinal cord. Co-immunoprecipitation was applied to detect the interaction between JMJD6 and Wnt3a.
 Results: Compared with the sham group, the PWMT of the rats in each group after CCI was significantly decreased and the PWTL was significantly shortened (P<0.05). Compared with the CCI group and the CCI+LV-NC group, PWMT in the CCI+LV-JMJD6 group was increased significantly on the 10th day and the 14th day after CCI, and the PWTL was significantly prolonged on the 14th day after CCI (P<0.05). On the 14th day after CCI, the expression levels of Wnt3a and NR2B in the CCI group and the CCI+LV-NC group were significantly higher than those in the sham group. After intrathecal injection of lentiviral vector, Wnt3a and NR2B protein expression levels in the CCI+LV-JMJD6 group were lower compared with the CCI+LV-NC group (P<0.05). The results of co-immunoprecipitation showed no direct interaction between Wnt3a and JMJD6.
 Conclusion: Wnt3a is involved in mediating neuropathic pain, and its effect may be related to the epigenetic modification of JMJD6, which is likely regulated through indirect interaction.