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.

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)

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.

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 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

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.

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.

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.

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.

Evaluation of adjunctive analgesia with intrathecal fentanyl along with hyperbaric bupivacaine in spinal anesthesia for elective cesarean section

Background: Cesarean section (CS) is one of the most common surgical procedures in female patients. Authors aimed to evaluate the postoperative analgesic efficacy of adding intrathecal fentanyl to bupivacaine, and its effect on the onset and duration of spinal anesthesia along with its effect on mother and neonate.Methods: Study was performed on 60 cesarean section parturients divided into two groups. Group F received 2 ml of 0.5% hyperbaric bupivacaine (10 mg) plus 0.4 ml fentanyl (20 µg), and Group B received 2 ml of 0.5% hyperbaric bupivacaine (10 mg) plus 0.4 ml of normal saline. The parameters taken into consideration were pain scores, analgesic requirement, hemodynamic stability and side effects.Results: It was found that duration of sensory block was prolonged in fentanyl group (111 minutes vs 86 minutes, p<0.001). Duration of effective analgesia (174.36 minutes vs 127.81; p value <0.001) were also found to be prolonged in Group F with requirement of fewer postoperative analgesics (1.02 vs 2.76, p=0.03). There was not much difference in the occurrence of side effects in both the groups.Conclusions: Addition of fentanyl to intrathecal bupivacaine for cesarean section increases the duration of postoperative analgesia without increasing maternal or neonatal side effects.

Comparison of Analgesic Effect of Fentanyl and Fentanyl with Midazolam as an Adjuvant to Intrathecal Bupivacaine in Lower Limb Surgeries

Introduction: Coadministration of drugs with synergistic effects considered one of the methods to increase the effectivenessof analgesia. The aim of this study is to evaluate the efficacy of midazolam to potentiate the analgesic effect of fentanyl as anadjuvant to bupivacaine.Materials and Methods: This is a hospital based prospective, randomized, double-blind interventional control study conductedat SMS medical college and hospitals, Jaipur. A total of 90 patients were enrolled in the study. They were allocated into threegroups, 30 in each. A total of 3.7 ml study drugs injected in each group. Intraoperative monitoring of hemodynamic parameters,duration of surgery, onset of sensory and motor block, duration of analgesia, sensory and motor block, and incidence of adverseeffects was done and compared.Results: There was no significant difference in mean pulse rate, systolic blood pressure, diastolic blood pressure, and meanarterial pressure (P > 0.05). The mean duration of surgery in Group A, B, and C was 101.3 ± 13.08, 92.93 ± 15.28, and 95.93± 16.03 min, respectively (P > 0.05). The mean onset time of sensory block in Group A was 7.29 ± 1.23, in B 4.92 ± 0.60, andin C 4.79 ± 0.91 min (P < 0.05). The mean onset time of motor block in Group A was 8.75 ± 0.55, in B 7.79 ± 0.42, and in C7.57 ± 0.29 min. In Group A, mean time of sensory block was 194.4 ± 6.80, in B 236.60 ± 12.79, and in C 254.30 ± 7.32 min. InGroup A, mean duration of motor block was 180.2 ± 5.22, in B 188.7 ± 4.04 and in C 199.6±6.69 min. In Group A, mean durationof analgesia was 215.7 ± 14.6, in B 445.8 ± 18.92, and in C 522.3 ± 16.33 min. The incidence of adverse effects was insignificant.Conclusion: We conclude that midazolam potentiates the effect of fentanyl in terms of prolonged duration of analgesia andprolonged motor and sensory block when used as an adjuvant of bupivacaine without any significant hemodynamic compromise.

A Comparison of Intrathecal Dexmedetomidine and Fentanyl as Adjuvant to Spinal Bupivacaine in Lower Abdominal and Lower Limb Surgeries- A Double Blind Randomised Study.

Spinal anaesthesia is a popular regional anaesthetic technique. Hyperbaric bupivacaine is the most common intrathecally used local anaesthetic. Use of intrathecal adjuncts with local anaesthetic helps to prolong the duration of analgesia and decreases the local anaesthetic dosage. We compared dexmedetomidine and fentanyl as adjuncts to intrathecal hyperbaric bupivacaine.METHODSA randomised double blind control study was conducted on 120 patients posted for elective lower abdominal and lower limb surgery under spinal anaesthesia in a tertiary care hospital. Group A received 2.5 mL of 0.5% hyperbaric bupivacaine with 0.5 mL of 0.9% saline into the sub-arachnoid space. Group B received 2.5 mL of 0.5% hyperbaric bupivacaine with 0.5 mL of dexmedetomidine (5 µg) into sub-arachnoid space. Group C received 2.5 mL of 0.5% hyperbaric bupivacaine with 0.5 mL of fentanyl (25 µg).RESULTSThere was a statistically significant drop in HR as early as 25 minutes in the dexmedetomidine group compared to saline group (p=0.033); and at 30 minutes in fentanyl group compared to saline group (p=0.015). Significant drop in SBP was seen at 30 minutes after the centrineuraxial blockade in the dexmedetomidine group compared to saline group (p=0.012) and remained so till 180 minutes after the blockade.CONCLUSIONSThe combination of 0.5% hyperbaric bupivacaine with dexmedetomidine (5 µg) is better compared to 0.5% hyperbaric bupivacaine with fentanyl (25 µg) or 0.5% hyperbaric bupivacaine alone in providing analgesia, as the combination offers a convenient, simple, inexpensive, effective and safe means of good post-operative analgesia for lower abdominal & lower limb surgery.

A Clinical Comparative Study of Dexmedetomidine with Fentanyl as an Adjuvant to Intrathecal Hyperbaric Bupivacaine for Vaginal Hysterectomy.

Currently only few local anaesthetics are used for intrathecal administration, like bupivacaine, lignocaine, ropivacaine and tetracaine. Opioid analogues have been used as additive in spinal anaesthesia to improve the onset of action, to prolong the duration of block and to improve the quality of intraoperative and postoperative analgesia. Fentanyl is a partial agonist on μ-opioid receptors and Dexmedetomidine is a α2-agonist. Intrathecal dexmedetomidine when combined with spinal bupivacaine prolongs the sensory block by depressing the release of C-fibers transmitters and by hyperpolarization of post-synaptic dorsal horn neurons.1 We compared the effects of adding Dexmedetomidine and Fentanyl as an adjuvant to intrathecal hyperbaric bupivacaine for vaginal hysterectomy.METHODSA total of 100 patients of age 35 to 65 yrs. of body mass index (BMI) within normal range (18.5 to 24.9 Kg/m2) posted for vaginal hysterectomy were divided into two equal groups (Group 1 and 2) in a prospective, randomized, double-blind fashion. In Group 1 (n=50), (2.5 ml) Hyperbaric Bupivacaine + (0.5 ml) Dexmedetomidine (5 mcg) and in Group 2 (n=50) (2.5 ml) Hyperbaric Bupivacaine + (0.5 ml) Fentanyl (25 mcg) were used. Total volume injected intrathecally was 3.0 ml. We observed the effect on onset of sensory and motor blockade, maximum level of sensory and motor blockade, haemodynamic effects during intraoperative period (for 120 min), effect on overall duration and quality of analgesia during postoperative period using VAS score and any side effects.RESULTSWe observed that mean time to achieve sensory block and motor block/ Bromage-3 was shorter in dexmedetomidine group. There was no statistically significant difference for the onset of sensory and motor block in dexmedetomidine and fentanyl group (p value > 0.05). The sensory and motor block were more prolonged in dexmedetomidine group than fentanyl group showing significant difference among the two groups (p value<0.001). Overall duration of analgesia was significantly longer in dexmedetomidine group than fentanyl group showing significant difference among the two groups (p value <0.001).CONCLUSIONSIn our opinion adding Dexmedetomidine 5 mcg to Bupivacaine 12.5 mg not only provides rapid onset, profound analgesia with good relaxation for surgery but also prolongs the duration of sensory and motor blockade. The overall effect and duration are superior to addition of 25 mcg of Fentanyl.

A Comparative Study of Intrathecal 0.5% Hyperbaric Bupivacaine & Intrathecal 0.75% Isobaric Ropivacaine in Lower Abdominal Surgeries

Ropivacaine, a long acting amide local anaesthetic, has reduced potential for neurotoxicity and cardiotoxicity and is considered to block sensory nerves to a greater degree than motor nerves. In today’s world, faster recovery along with minimal side effects and early ambulation after surgeries under spinal anaesthesia are very important. So, this prospective randomized study was aimed at evaluating and comparing the efficacy and safety of intrathecally injected isobaric ropivacaine and intrathecally injected hyperbaric bupivacaine in patients posted for lower abdominal surgeries under spinal anaesthesia.METHODS90 patients belonging to ASA physical status I & II scheduled for lower abdomen surgeries were randomly selected for the study and were divided into two groups of 45 each. Group B received 3 ml of 0.5% hyperbaric (15 mg) bupivacaine intrathecally. Group R received 3 ml of 0.75% isobaric (22.5 mg) ropivacaine intrathecally. Onset and extent of sensory block, onset and duration of motor block, maximum height of sensory block, duration of analgesia, hemodynamic parameters and adverse effects if any were studied. SPSS 20.0 and GraphPad Prism 6.0 were used for the analysis of the data.RESULTSThe mean time for onset of sensory block was significantly faster in group B as compared to group R (8.28±2.2 min v/s 7.98±2.2 min). There was no significant difference between the groups regarding the time for two segment regression. Mean time of onset of motor block was significantly faster in group B. The mean duration of motor blockade was 146.89±14.11 min in group R and 208.91±14.62 min in group B. The mean duration of analgesia was comparable in both the groups. Hemodynamic parameters and side effects were comparable in both the groups.CONCLUSIONS0.75% isobaric ropivacaine provided similar duration of analgesia with a shorter duration of motor block as compared to hyperbaric 0.5% bupivacaine and it also provided adequate level of sensory block for the surgery with minimal intraoperative and postoperative side effects and stable haemodynamics throughout the surgery.

Comparative study of intrathecal fentanyl, tramadol, clonidine mixed with bupivacaine for peri and post operative pain relief in lower limb and lower abdominal surgery

Background: Pain relief is of paramount importance in patients undergoing surgery during perioperative and post-operative period. After effective pain relief a smoother post-operative period and early discharge from the hospital is anticipated. Intrathecal and epidural narcotics have been widely used to relieve pain and provide post-operative analgesia. Here three drugs tramadol, fentanyl, and clonidine used as adjuvant with bupivacaine in intrathecal injection for post-operative pain relief and comparative study had been done.Methods: After the study protocol was approved by the Ethical clearance committee of the DMCH, Laheriasarai, Bihar. Study design was prospective, randomized and double-blind techniques. A group of 80 patients undergoing lower abdominal and lower limb surgery were included in the study. Every patient was fully explained about the anaesthesia and surgical procedure before inclusion in the study. The patients were in the (25-65) years age group and belonged to the American Society of Anaesthesiologist (ASA) physical status class I-II and scheduled for lower abdominal and lower limbs surgery were randomly allocated to four groups with equal number: group B [Bupivacaine (35)% 3 cc + 0.4 cc normal saline], group BT [Bupivacaine (5)% 3 cc + 25 mg tramadol], BC [Bupivacaine (0.5)% 3 c.c + 30 μg clonidine], BF [Bupivacaine (0.5)% 3 c.c + 20 μg fentanyl]. All additive drugs used intrathecally were preservative free. All intrathecal punctures were performed in the lateral (Right or Left) position with a (25G) Quinke needle, using the midline approach at the L3-L4 intervertebral space.Results: The study revealed that administration of additives in group BC and group BF did prolong analgesia. In group B, duration of analgesia and mean duration of rescue analgesic requirement was (3.57±0.45) hrs. For group BC it was (9.47±0.85) hrs, for group BF (7.6±1.14) hrs, for group BT (3.72±0.42) hrs.Conclusions:Addition of adjuvants (Fentanyl, Clonidine) to intrathecal bupivacaine for perioperative pain relief does prolong postoperative analgesia and improves the intraoperative quality of analgesia than bupivacaine alone.Background: Pain relief is of paramount importance in patients undergoing surgery during perioperative and post-operative period. After effective pain relief a smoother post-operative period and early discharge from the hospital is anticipated. Intrathecal and epidural narcotics have been widely used to relieve pain and provide post-operative analgesia. Here three drugs tramadol, fentanyl, and clonidine used as adjuvant with bupivacaine in intrathecal injection for post-operative pain relief and comparative study had been done.Methods: After the study protocol was approved by the Ethical clearance committee of the DMCH, Laheriasarai, Bihar. Study design was prospective, randomized and double-blind techniques. A group of 80 patients undergoing lower abdominal and lower limb surgery were included in the study. Every patient was fully explained about the anaesthesia and surgical procedure before inclusion in the study. The patients were in the (25-65) years age group and belonged to the American Society of Anaesthesiologist (ASA) physical status class I-II and scheduled for lower abdominal and lower limbs surgery were randomly allocated to four groups with equal number: group B [Bupivacaine (35)% 3 cc + 0.4 cc normal saline], group BT [Bupivacaine (5)% 3 cc + 25 mg tramadol], BC [Bupivacaine (0.5)% 3 c.c + 30 μg clonidine], BF [Bupivacaine (0.5)% 3 c.c + 20 μg fentanyl]. All additive drugs used intrathecally were preservative free. All intrathecal punctures were performed in the lateral (Right or Left) position with a (25G) Quinke needle, using the midline approach at the L3-L4 intervertebral space.Results: The study revealed that administration of additives in group BC and group BF did prolong analgesia. In group B, duration of analgesia and mean duration of rescue analgesic requirement was (3.57±0.45) hrs. For group BC it was (9.47±0.85) hrs, for group BF (7.6±1.14) hrs, for group BT (3.72±0.42) hrs.Conclusions: Addition of adjuvants (Fentanyl, Clonidine) to intrathecal bupivacaine for perioperative pain relief does prolong postoperative analgesia and improves the intraoperative quality of analgesia than bupivacaine alone.

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.

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

OBJETIVES: 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% 0.45-14.54, p = 0.28), nausea without vomiting (OR 1.82, CI 95% 0.82-4.01, p = 0.13), urinary retention (OR 2.02, CI 95% 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 artroplastia 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 artroplastia 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, IC95% 0,45-14,54, p = 0,28), náuseas y vómitos (OR 1,82, CI95% 0,82-4,01, p = 0,13), retención urinaria (OR 2,02, CI95% 0,88-4,61, p = 0,09) y prurito (OR 3,55, CI95% 1,61-7,82, p < 0,01). CONCLUSIONES: 80 mcg ITM, en anestesia espinal para artroplastia cadera, proporciona analgesia postoperatoria comparable a 100 mcg pero con menor incidencia de efectos adversos relacionados a opioides.