A comparative study of intrathecal isobaric ropivacaine and hyperbaric bupivacaine for elective lower segment caesarean section

Background: The study was to compare intrathecal isobaric ropivacaine and hyperbaric bupivacaine in terms of onset of sensory block, maximum height of sensory block, total sensory duration, onset of motor block, degree of motor block and duration of motor block, quality of anesthesia. Methods: The 100 cases of ASA II undergoing elective lower segment caesarean section were taken for the study and divided into two groups. Group B patients received 2 ml of hyperbaric bupivacaine intrathecally. Group R patients received 2ml of isobaric ropivacaine intrathecally. Patients were evaluated for onset and duration of sensory block, onset and duration of motor block, maximum height of sensory block, quality of anaesthesia, time to request for analgesia, hemodynamic parameters and side effects if any were studied. Results: There were no significant differences between the two groups in mean time to onset of sensory block. Maximum sensory height attained in group B ranged between T4 and T6, where as in group R, it ranged between T2 and T6 which was clinically and statistically highly significant (p<0.001). Total duration of sensory block in group B and in group R, which is not significant (p=0.068). Mean time onset of motor block was 4min in group B and 8 min in group R, (p<0.001). Duration of motor block was 155.20±14.95 min in group B and 94.10±8.31 min group R, which is clinically and statistically significant (p<0.001). Conclusions: Ropivacaine 15 mg (2 ml of 0.75% isobaric ropivacaine) provides comparable quality of sensory block but has slower onset and significantly shorter duration of motor block compared to bupivacaine.

A comparative study between intrathecal fentanyl and intrathecal buprenorphine as adjuvants to 0.5% hyperbaric bupivacaine in females undergoing lower segment caesarean section under spinal anesthesia: a randomized and double blinded study

Background: Double blinded study involving intrathecal hyperbaric bupivacaine (1.5 ml) with adjuvants as Fentanyl and Buprenorphine Methods: Sixty-six females posted for lower segment caesarean section under spinal anesthesia were randomized into two groups-A and B. Group A received 1.5 ml of hyperbaric Bupivacaine and 0.5 ml (75 µg) of Buprenorphine. Group B received 1.5 ml of hyperbaric Bupivacaine and 0.5 ml (25µg) of Fentanyl. Sensory blockade, motor blockade and duration of analgesia were evaluated. Randomization was done using randomization.com program with GraphPad Quick Cals. Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS) statistics version 28 software. Results: There is no statistical difference in the demographic profiles of both groups. Duration of analgesia(minutes) in group A=255.37±34.63 and in group B=175.43±23.58 with p<0.001. Conclusions: A significant drop in mean arterial pressure in both groups from preoperative values throughout surgery, (p<0.05) with the exception of MAP at 50 minutes in B (p=0.139). A significant increase in heart rate at 2 and 4 minutes in group A when compared with baseline HR (p<0.05). In group B, a significant increase only at 2 minutes post spinal anesthesia, p=0.002. Forty-three patients had hypotension (28 vs. 15), p=0.008. Nausea is higher in Group A than B (26 vs. 4). The difference in sensory level of blockade is statistically insignificant, p=0.62. The difference in time of onset of motor blockade of Bromage score 1 was statistically insignificant, p=0.093. Duration of analgesia (minutes) in group A=255.37±34.63 and in group B=175.43±23.58 with p<0.001.

Technical guideline for intra-prepontine cisternal drug delivery via spinal puncture through subarachnoid catheterization / 中南大学学报(医学版)

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

Meta-analysis of efficacy and safety of intravenous combined with intrathecal/intraventricular injection of polymyxin against intracranial infection with multidrug-resistant bacteria / 临床神经病学杂志

Objective Evaluation of the efficacy and safety of intravenous(IV)combined with intrathecal/intraventricular injection(ITH/IVT)of polymyxin against intracranial infection with multidrug-resistant bacteria.Methods The databases,including Wanfang,VIP,Chinese Biomedical Literature,Pubmed,Embase,ScienceDirect,and Cochrane Library were searched,case-control studies on IV+ITH/IVT polymyxin against intracranial infection with multidrug-resistant bacteria by January 2023 were screen.RevMan 5.4 software was used for meta-analysis.Results A total of 9 retrospective studies were included.The fatality rate in IV+ITH/IVT polymyxin group was significantly lower than that in IV group(OR =0.19,95%CI:0.11-0.35,P＜0.01).There was no significant difference in ICU hospitalization days(OR =-2.32,95%CI:-23.59-18.89,P =0.83)and adverse reaction rate(OR =0.93,95%CI:0.26-3.38,P =0.91)between IV+ITH/IVT group and IV group.Conclusion IV+ITH/IVT polymyxin in treating the intracranial infection with multidrug-resistant bacteria can significantly reduce fatality rate,and does not significantly increase adverse reactions.

Application of the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice: a retrospective analysis apart from the clinical trial at two centers in Brazil

ABSTRACT Introduction: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. Methods: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. Results: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. Conclusion: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy.

CURRENT ADVANCEMENTS AND COMPLICATIONS IN INTRATHECAL DRUG DELIVERY SYSTEM

Intrathecal drug delivery systems (IDDS) have emerged as a valuable treatment option for patients with chronic pain who have failed to achieve adequate relief with conventional therapies. These systems provide targeted delivery of medications directly to the cerebrospinal fluid, resulting in improved pain control and reduced systemic side effects. However, the use of IDDS is not without potential complications and considerations that must be addressed to ensure optimal patient outcomes. This comprehensive review examines the various complications associated with IDDS and the considerations that healthcare providers and patients need to be aware of. Surgical complications, such as infection, bleeding, spinal fluid leaks, and nerve damage, are discussed, along with strategies to minimize these risks. Device malfunctions, including pump failure, catheter issues, and electronic problems, are explored, highlighting the importance of regular monitoring and maintenance. Medication-related side effects, such as nausea, sedation, and respiratory depression, are addressed, emphasizing the need for close monitoring and appropriate dosage adjustments. Long-term considerations, including tolerance to medication, physical dependence, and withdrawal symptoms, are also examined, emphasizing the significance of gradual tapering and proper discontinuation protocols. The review underscores the importance of regular follow-up appointments to assess the system's functionality, medication dosages, and patient response to treatment. By proactively managing and addressing complications, healthcare providers can optimize pain relief and minimize adverse effects, ensuring the long-term effectiveness and safety of IDDS.

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.

Intrathecal administration of Maresin 1 attenuates bone cancer pain by inhibiting the glial cells acti-vation and neuroinflammation in the spinal cord / 临床麻醉学杂志

Objective To investigate the effects of intrathecal administration of Maresin 1 on pain behavior and glial cells activation in spinal dorsal horn of mice with bone cancer pain(BCP).Methods Experiment Ⅰ,twenty-eight clean male C57BL/6 mice,aged 4-6 weeks,weighing 18-22 g,were ran-domly divided into two groups:sham 1 group(group S1)and BCP 1 group(group B1),14 mice in each group.BCP model was established in group B1 by injecting PBS 20 μl containing 2 × 105 lewis lung carcino-ma cells into the intramedullary space.Group S,received PBS 20 μl without tumor cells.Six mice in each group were randomly selected to determine the mechanical withdrawal threshold(MWT)and thermal with-drawal latency(TWL)1 day before implantation,3,7,14,21 days after implantation.Four mice were randomly sacrificed on days 7,14 and 21 in group S,and group B1.The expressions of spinal glial fibrillary acidic protein(GFAP)and ionized calcium-binding adapter molecule 1(Iba1)were detected by Western blot.Experiment Ⅱ,thirty-six clean male C57BL/6 mice were randomly divided into three groups:sham 2 group(group S2),BCP 2 group(group B2),and Maresin 1 group(group M),12 mice in each group.BCP models were established in groups B2 and M while group S2 received PBS 20 μl without tumor cells.Maresin 1 50 ng/5 μl were intrathecally injected from days 14 to 16 after tumor cells implantation.Six mice in each group were randomly selected to determine the MWT and TWL on days 14 to 18 after implantation.Mice were sacrificed on day 18 after pain behavior tests.The expressions of spinal GFAP and Iba1 were de-tected by Western blot and immunofluorescence staining.The levels of spinal IL-1 β,IL-6,and TNF-α were detected by ELISA.Results Experiment Ⅰ:compared with group S1,the MWT and TWL were significantly lower on days 7,10,14,and 21 after implantation in group B,(P＜0.05),the expressions of spinal GFAP and Iba1 were upregulated on days 7,14,and 21 after implantation in group B1(P＜0.05).Experiment Ⅱ:compared with group S2,the levels of spinal GFAP,Iba1,IL-1β,IL-6,and TNF-α were increased on day 18 after implantation in group B2(P＜0.05).Compared with group B2,the MWT and TWL were significantly higher on days 15-18 after implantation while levels of spinal GFAP,Iba1,IL-1β,IL-6,and TNF-α on day 18 were decreased in group M(P＜0.05).Conclusion Intrathecal administra-tion of Maresin 1 attenuates BCP maybe by inhibiting the glial cells activation and neuroinflammation in the spinal cord.

Intrathecal delivery of nusinersen using the Ommaya reservoir in a spinal muscular atrophy type 2 patient: a case report / 中华神经科杂志

Ommaya reservoir implantation is generally used in the treatment of hydrocephalus and intraventricular drug administration. Ommaya reservoir implantation in the subarachnoid space of the spinal cord for the intrathecal drug administration has not been carried out in China, and only several reports can be retrieved from PubMed. About 60%-90% of untreated patients with spinal muscular atrophy type 2 (SMA2) who survive to adulthood often have complex scoliosis and joint deformities. Nusinersen is an effective drug for the treatment of SMA2. And the route of administration is intrathecal injection, which is difficult for patients with severe scoliosis. This article summarizes the process of Ommaya reservoir implantation and postoperative drug administration in a patient with complex scoliosis type SMA2, which provides a new method for clinical treatment of this disease.

Evidencia de respuesta inmune intratecal poliespecífica en pacientes pediátricos con procesos neuroinflamatorios / Evidence of polyspecific intrathecal immune response in pediatric patients with neuroinflammatory processes

Introducción: La síntesis intratecal de anticuerpos contra algunos virus neurotrópicos como sarampión, rubéola y virus varicela zoster en pacientes con esclerosis múltiple, con una frecuencia muy superior a la esperada, llevó a la introducción de la reacción sarampión-rubéola-varicela. La presencia de anticuerpos específicos detectados en el líquido cefalorraquídeo contra dos o más de estos virus apoyó el diagnóstico no solo de la esclerosis múltiple, sino de otras enfermedades autoinmunes que involucran al sistema nervioso central. Objetivo: Identificar la presencia de respuesta inmune intratecal poliespecífica en pacientes pediátricos con proceso neuroinflamatorio independiente del agente biológico involucrado. Presentación de caso: Se estudiaron ocho niños a los cuales, mediante inmunodifusión radial simple y por ensayo inmunoenzimático, se les cuantificaron las concentraciones de inmunoglobulina G y albúmina en suero, y líquido cefalorraquídeo, lo que permitió determinar la síntesis intratecal de inmunoglobulinas. Por métodos inmunoenzimáticos se cuantificaron las concentraciones de IgG específica contra los virus estudiados en suero y líquido cefalorraquídeo, con lo cual se determinó el índice de anticuerpo específico. La reacción sarampión-rubéola-varicela fue positiva en cinco pacientes y los valores medios de este índice se encontraron por encima de 1,5 para citomegalovirus y virus herpes simple. Conclusiones: Se identificaron repuestas neuroinmune antiviral poliespecífica en pacientes pediátricos con proceso neuroinflamatorio(AU)

Introduction: The intrathecal synthesis of antibodies against some neurotropic viruses such as measles, rubella and varicella zoster virus in patients with multiple sclerosis, with a frequency much higher than expected, led to the introduction of the measles-rubella-varicella reaction. The presence of specific antibodies detected in cerebrospinal fluid against two or more of these viruses supported the diagnosis not only of multiple sclerosis, but also of other autoimmune diseases involving the central nervous system. Objective: To identify the presence of polyspecific intrathecal immune response in pediatric patients with neuroinflammatory process independent of the biological agent involved. Case presentation: Eight children were studied and their serum and cerebrospinal fluid immunoglobulin G and albumin concentrations were quantified by simple radial immunodiffusion and enzyme-linked immunosorbent assay to determine intrathecal immunoglobulin synthesis. The concentrations of specific IgG against the viruses studied in serum and cerebrospinal fluid were quantified by enzyme-linked immunosorbent assay methods, thus determining the specific antibody index. The measles-rubella-varicella reaction was positive in five patients and the mean values of this index were found to be above 1.5 for cytomegalovirus and herpes simplex virus. Conclusions: Polyspecific antiviral neuroimmune antiviral responses were identified in pediatric patients with neuroinflammatory process(AU)

Comparison of onset of action of Intrathecal Clonidine vs Intrathecal Fentanyl as an adjuvant with hyperbaric Bupivacaine and Bupivacaine alone under spinal anesthesia for lower limb orthopedic surgeries

Background: Adjuvants are added to a local anesthetic solution to prolong the duration of analgesia. There is a paucity of studies comparing the onset of action of adjuvants like Clonidine and Fentanyl. In this study, the time of onset of action of intrathecal clonidine and intrathecal fentanyl as adjuvants to bupivacaine and bupivacaine alone were compared in the subarachnoid block for lower limb orthopedic surgeries. Materials and Methods: 90 adult patients posted for orthopedic surgery of the lower limb were divided into three equal groups of 30 each. Group A being the control group was given hyperbaric Bupivacaine(3ml) +0.5ml of Normal saline, Group B was given Intrathecal hyperbaric Bupivacaine (3 ml) +30 ?g Clonidine and Group C was given Intrathecal hyperbaric Bupivacaine (3 ml) + Fentanyl 25 ?g. The primary objective was to compare the time of onset of block and duration of analgesia. The secondary outcomes were the duration of sensory and motor block, duration of analgesia, hemodynamic parameters, and side effects. Results: The time of onset of the sensory blockade was 4.83 ± 0.64, 1.72 ± 1.47, and 3.4 ± 1.43 mins in groups A, B, and C respectively. The time of onset of the motor blockade as estimated by the time to reach level 2 on the Bromage scale, was 6.07 ± 0.55, 2.38 ± 1.32, and 5.06 ± 1.28 mins in groups A, B, and C respectively. The duration of postoperative analgesia was prolonged in the Clonidine group compared to the Fentanyl group. Conclusion: The study reveals that the time of onset of action of sensory and motor block was faster and the duration of analgesia was prolonged with adjuvants like Clonidine when compared to Fentanyl when added to Bupivacaine.

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.

Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

A Case Report of Intrathecal Baclofen Therapy with Infusion Pump Implantation into the Antero-medial Thigh / The Japanese Journal of Rehabilitation Medicine

Intrathecal baclofen (ITB) therapy is used to treat patients with spasticity. The pump that delivers baclofen to the intrathecal space of the thoracolumbar spine is generally implanted under the skin or fascia of the anterolateral abdomen. Here we present a case in which the pump was implanted in an alternative site, under the skin of the anteromedial thigh. The patient was a 61-year-old man who was 148 cm tall. He had spastic paraplegia (ASIA Impairment Scale grade B) caused by severe scoliosis related to dystrophic neurofibromatosis. No safety space for pump implantation existed in his abdomen because of a stoma, scars, and adhesions that resulted from surgeries for ileus and abdominal aortic aneurysms. The catheter ran from the lumbar spine to the anteromedial thigh via the point between the iliac crest and the great trochanter. The catheter and pump caused no trouble over 1 year of follow-up. This case demonstrates that the thigh can be an alternative site for ITB pump implantation in some patients with abdominal wall problems. This surgical modification may not be indicated for some patients with ambulators or frequent hip motion, who are at risk of catheter problems or pump migration.

A Case Report of Intrathecal Baclofen Therapy with Infusion Pump Implantation into the Antero-medial Thigh / The Japanese Journal of Rehabilitation Medicine

Intrathecal baclofen (ITB) therapy is used to treat patients with spasticity. The pump that delivers baclofen to the intrathecal space of the thoracolumbar spine is generally implanted under the skin or fascia of the anterolateral abdomen. Here we present a case in which the pump was implanted in an alternative site, under the skin of the anteromedial thigh. The patient was a 61-year-old man who was 148 cm tall. He had spastic paraplegia (ASIA Impairment Scale grade B) caused by severe scoliosis related to dystrophic neurofibromatosis. No safety space for pump implantation existed in his abdomen because of a stoma, scars, and adhesions that resulted from surgeries for ileus and abdominal aortic aneurysms. The catheter ran from the lumbar spine to the anteromedial thigh via the point between the iliac crest and the great trochanter. The catheter and pump caused no trouble over 1 year of follow-up. This case demonstrates that the thigh can be an alternative site for ITB pump implantation in some patients with abdominal wall problems. This surgical modification may not be indicated for some patients with ambulators or frequent hip motion, who are at risk of catheter problems or pump migration.

Clinical characteristics, management, and outcome of gestational trophoblastic neoplasia patients with brain metastasis: A 10-year experience at the Philippine General Hospital / Philippine Journal of Obstetrics and Gynecology

Objective@#This study aimed to determine the clinical characteristics, management, and outcome of gestational trophoblastic neoplasia (GTN) patients with brain metastasis.@*Materials and Methods@#This was a 10‑year descriptive study that included all patients with brain metastasis from GTN. Patients’ sociodemographic and clinicopathological profiles were described. Using Kaplan–Meier survival curve, the survival time was determined@*Results@#From January 1, 2010, to December 31, 2019, there were 33 GTN patients with brain metastasis. Four were excluded from the study due to incomplete records. Twenty‑nine patients were included in the study. Nineteen (65.51%) patients presented with neurologic symptoms upon diagnosis and one (3.44%) during treatment. All received etoposide, methotrexate, actinomycin, oncovin (EMACO) as first‑line treatment. Five (17.24%) patients were given induction chemotherapy with low‑dose etoposide–cisplatin. Seventeen (58.62%) patients underwent whole‑brain radiation and two (6.89%) were given intrathecal methotrexate. Thirteen patients (44.82%) achieved biochemical remission with EMACO chemotherapy. Four patients (13.79%) had resistance to EMACO and were given Etoposide Cisplatin Etoposide Methotrexate Actinomycin (EP EMA). Four patients (13.79%) underwent an adjunctive hysterectomy. Four patients (13.79%) died during treatment. One patient (3.44%) was unable to continue her chemotherapy because she got pregnant before her first consolidation course. There were eight early deaths (<4 weeks of admission) and hence were excluded in the analysis. Three patients who went into biochemical remission relapsed on the 1st, 2nd, and 3rd months after their last consolidation course, respectively. The median follow‑up time was 27 months. After excluding early deaths, the survival rate between 3 and 7 years after treatment is at 61.9%. The mean survival time was 5.43 years. Six surviving patients were contacted. Five (17.24%) of them had resumed their everyday life, and one is currently undergoing chemotherapy.@*Conclusion@#The study was able to document brain metastasis from GTN to be 14.28% (29/203) among metastatic high‑risk admissions. The biochemical remission rate from first‑line treatment was of 61.90% (13/21) and resistance rate was 19.04% (4/21). Lost to follow up after achieving biochemical remission was a challenge encountered

Morfina intratecal en analgesia poscesárea / Intratecal morphine in cesarian section

The Cesarean section is the most frequently performed surgical intervention in most countries, in Chile there are approximately 80,000 cases per year. In the postoperative period, effective analgesia is essential since patients define the absence of intra- and post-cesarean pain as priorities. On the other hand, entities such as cronical pain and postpartum depression have been associated with persistent postoperative pain and difficulty in mother-child interaction. Intrathecal morphine (ITM) was first described in obstetric analgesia in the 1980s and has since become widely used for post-cesarean section analgesia due to its prolonged analgesic action. In this review we will focus on the most relevant aspects that may lead to the incorporation of MIT in the Analgesia protocols for Cesarean section in our country.

La Operación Cesárea es la intervención quirúrgica más frecuentemente realizada en la mayoría de los países, en Chile son aproximadamente 80.000 casos por año. En su posoperatorio la analgesia eficaz es fundamental, dado que las pacientes definen la ausencia de dolor intra y poscesárea como prioritarios. Por otra parte, entidades como dolor cónico y depresión posparto han sido asociados con dolor posoperatorio persistente y dificultad en la interacción madre-hijo. La morfina intratecal (MIT) se describió por primera vez en analgesia obstétrica en la década de 1980 y desde entonces se ha vuelto ampliamente utilizada para la analgesia poscesárea debido a su prolongada acción analgésica. En esta revisión nos centraremos en los aspectos más relevantes que puedan conducir a la incorporación de MIT en los protocolos de Analgesia para Cesárea en nuestro país.

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.

Diagnostic Value of Locally Produced Tumor Markers and Blood Brain Barrier Integrity in Lung Cancer Patients with Leptomeningeal Metastasis / 中国肺癌杂志

BACKGROUND@#Tumor markers (TM) in cerebrospinal fluid (CSF) are useful for diagnosing leptomeningeal metastasis (LM). It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier (BBB). To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM. Therefore, the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM.@*METHODS@#Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases (NMNDs) admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included. We compared the integrity of BBB and intrathecal TM synthesis between two groups, analyzed the correlation of CSF TM between the detection and intrathecal synthesis, and evaluated serial CSF cytology, the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient.@*RESULTS@#Ninety-four percent LM patients showed the dysfunction of BBB, and all LM patients showed at least one intrathecal synthesized TM in CSF. In one patient, the CSF cytology was negative for the first time, but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture. In LM group, no correlation was observed between the detection and intrathecal synthesized TM in CSF. In the control group, only 3.5% (2/57) NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis, both the differences of which were statistically significant (P<0.05). Finally, evaluating the CSF cytology, integrity of BBB and intrathecal TM synthesis can be used to assess the intracranial treatment effect. Moreover, intrathecal TM synthesis changes earlier than cytology.@*CONCLUSIONS@#The evaluation of intrathecal TM synthesis and integrity of BBB are novel clinical diagnostic tools. In addition, serial measurement of intrathecal synthesized TM may play an important role in monitoring efficacy of lung cancer patients with LM, which is worthy of further promotion and clinical application.

Standardization of an experimental model of intradural injection after spinal cord injury in rats

OBJECTIVES: The intrathecal route has not yet been thoroughly standardized and evaluated in an experimental model of spinal cord injury (SCI) in Wistar rats. The objective of this study was to standardize and evaluate the effect of intradural injection in this animal model. METHOD: The animals were divided into 6 groups: 1) laminectomy and intradural catheter; 2) laminectomy, intradural catheter and infusion; 3) only SCI; 4) SCI and intradural catheter; 5) SCI, intradural catheter and infusion; and 6) control (laminectomy only). Motor evaluations were performed using the Basso, Beattie and Bresnahan (BBB) scale and the horizontal ladder test; motor evoked potentials were measured for functional evaluation, and histological evaluation was performed as well. All experimental data underwent statistical analysis. RESULTS: Regarding motor evoked potentials, the groups with experimental SCI had worse results than those without, but neither dural puncture nor the injection of intrathecal solution aggravated the effects of isolated SCI. Regarding histology, adverse tissue effects were observed in animals with SCI. On average, the BBB scores had the same statistical behaviour as the horizontal ladder results, and at every evaluated timepoint, the groups without SCI presented scored significantly better than those with SCI (p<0.05). The difference in performance on motor tests between rats with and without experimental SCI persisted from the first to the last test. CONCLUSIONS: The present work standardizes the model of intradural injection in experimental SCI in rats. Intrathecal puncture and injection did not independently cause significant functional or histological changes.