Intrathecal Dexamethasone Research Articles

P.103 Intrathecal dexamethasone for arterial hypotension management during spinal anaesthesia for elective caesarean section

P.103 Intrathecal dexamethasone for arterial hypotension management during spinal anaesthesia for elective caesarean section

Comparison Between Analgesic Effect of Dexamethasone and Dexmedetomidine as an Adjuvant to Bupivacaine for Spinal Anaesthesia for Elective Caesarean Sections

Background Caesarean sections are usually performed under spinal anaesthesia. It provides effective postoperative pain control over a limited period of time. As a result, various intrathecal additives have been used. Recently, dexamethasone and dexmedetomidine have been used as adjuncts for different types of regional anaesthesia without increasing the risk of neurological complications. Objectives: We compared the analgesic effects of intrathecal dexamethasone and dexmedetomidine in elective caesarean sections. Design: A single-blind randomized trial. Setting: Benha University Hospital, between February 2021 and July 2021. Patients: We randomly enrolled 633 pregnant women in this study. Only 580 patients met all the inclusion and exclusion criteria. The inclusion criteria were age of 18 to 40 years old, an ASA class ІІ - III, gestational age > 37 weeks, BMI less than 30 kg/m2 who were electively scheduled for. The exclusion criteria included patient refusal, age < 18 or > 40 years, known allergy to medications used in the study, BMI more than 30 kg/m2, coagulopathies or anticoagulant use, cerebrovascular insufficiency, neuromuscular diseases and diabetic neuropathy. Intervention: The dexmedetomidine group (A) received 10 μg of dexmedetomidine with 12.5 mg hyperbaric bupivacaine 0.5%intrathecally(n=290). The dexamethasone group (B) received 4 mg of dexamethasone with 12.5 mg hyperbaric bupivacaine 0.5%intrathecally(n=290). Main outcome: The time to initial analgesic rescue (pethidine 0.5 mg/kg) and the duration of motor blockage were assessed. Results: The time to the first rescue analgesia and motor blockade were significantly higher in the dexmedetomidine group. (418 min vs 190 min), P<0.001, (324 min vs 144 min), P <0.001 respectively. Conclusion: According to this study, both drugs could be safely added to bupivacaine intrathecally. Dexmedetomidine provides significantly longer postoperative analgesia and motor blockade times than dexamethasone. Further dose-response studies are needed to determine the optimum dosage of dexamethasone and dexmedetomidine and the safety of the intrathecal route.

Icans Prophylaxis with Simvastatin and Intrathecal Dexamethasone in Adults Receiving Axicabtagene Ciloleucel (Axi‐Cel) Treatment

BackgroundAxi-cel is approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma since 2017 and has demonstrated efficacy and durability but with significant side effects, namely cytokine release syndrome (CRS) and neurotoxicity (ICANS). In patients receiving axi-cel for aggressive lymphomas, any grade ICANS occurs at a rate of 50% and grade 3/4 occurs about 35% of the time. The mechanism underlying ICANS remains unclear. The current working hypothesis is that endothelial injury caused by the disease and lymphodepleting chemotherapy leads to breakdown of the blood-brain-barrier. Following activation of axi-cel, cytokines are trafficked into the central nervous system leading to local production of cytokines and the clinical syndrome observed. ICANS is treated with systemic steroids with good CNS penetration. Statins have been shown to stabilize the endothelium and have anti-inflammatory effects. We are currently evaluating the safety and feasibility of administering simvastatin to stabilize the endothelium in addition to dexamethasone delivered intrathecally to prevent the occurrence and decrease the severity of neurotoxicity.Methods:This is a feasibility study combining simvastatin 40 mg orally, daily, starting at least 5 days prior to apheresis in addition to dexamethasone delivered intrathecally on days -1, +6, +13 in relation to axi-cel. A schema of the trial is presented in figure 1. This is registered on Clinicaltrials.gov number (NCT04514029).Results:We have accrued 6/20 planned patients with r/r DLBCL who received axi-cel per institutional guidelines. One passed away prior to apheresis due to disease progression and was non-evaluable. Table 1 shows the patient characteristics. With a median follow up of 123 days (50-245), all patients achieved a complete response and remained alive. Table 2 summarizes the feasibility, safety, and dose-density received out of prescribed. None of the 5 patients had grade 3 or 4 ICANS and only 1 patient had grade 1 neurotoxicity (Table 3). A cytokine analysis and markers of endothelial and neuronal activation is underway.Discussion:In a preliminary analysis, simvastatin and intrathecal dexamethasone appears to be feasible to administer, safe and efficacious in a population of patients receiving axi-cel for relapsed and refractory DLBCL. There appears to be a signal in abrogating neurotoxicity without any effect on the efficacy of axi-cel. This will allow for a safer delivery of axi-cel and improve access to this treatment. This study is ongoing. [Display omitted] DisclosuresBachanova: FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Weisdorf: Fate Therapeutics: Research Funding; Incyte: Research Funding. Miller: Wugen: Membership on an entity's Board of Directors or advisory committees; GT Biopharma: Consultancy, Patents & Royalties, Research Funding; Vycellix: Consultancy; ONK Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics, Inc: Consultancy, Patents & Royalties, Research Funding. Janakiram: FATE, Nektar Therapeutics: Research Funding; Bristol Meyer Squibb, Kyowa Kirin, ADCT Therapeutics: Honoraria. OffLabel Disclosure:Simvastatin is an HMG-CoA reductase inhibitor approved for hyperlipidemia and cardiovascular health.

CLINICAL COMPARATIVE STUDY BETWEEN INTRATHECAL DEXMEDETOMIDINE AND DEXAMETHASONE ON PROLONGING THE DURATION OF INTRATHECAL BLOCKADE IN LOWER LIMB ORTHOPEDIC SURGERY

Background: Spinal anesthesia is safer than general anesthesia during lower limb operations; many studies have been concerned about prolonging the duration of spinal anesthesia by adding different adjuvants. Objective: To compare the efficacy of intrathecal dexmedetomidine versus intrathecal dexamethasone in prolonging duration of spinal anesthesia, and postoperative analgesia, safety and hemodynamic stability. Patients and methods: Our study was carried out on 60 patients of American Society of Anesthesiologists (ASA) physical status I or II, scheduled for orthopedic operation under spinal anesthesiadivided into A, B and C from March 2020 to November 2020. They were divided into 3 equal groups: Group A received 2ml bupivacaine (0.5%) and 10μg dexmedetomidine in 1ml normal saline intrathecal, Group B received 2ml bupivacaine (0.5%) and 4 mg dexamethasone in 1 ml normal saline intrathecal and Group Creceived 2ml bupivacaine (o.5%) and 1ml normal saline Intrathecal. The study was carried out at Al-Azhar University Hospitals (Al- Hussein and Sayed Galal Hospitals). Results: The present study showed statistically significant difference (P-value <0.001) between the three groups according to time of motor and sensory regression. The regression time of block (both sensory and motor) were prolonged in A (sensory 359.50±20.32, motor 319.00±21.06) and B (sensory 199.75±18.22, motor 170.00±20.00) when compared to the C group (sensory 149.55±10.83, motor 141.00±22.09). However, the duration was longest in A group among the three groups. According to amount of analgesic consumption postoperatively, there was significant decrease in amount in A group in comparison to B and C groups. The amount is insignificantly decreased in B group in comparison to C group. Regarding safety and hemodynamic stability there was no statistically significant difference between the three groups. Conclusion: Dexmedetomidine had prolonging the duration of spinal anesthesia more than dexamethasone and control group with statistically significant difference between the three groups and provided prolonged postoperative analgesia compared to dexamethasone and control group.

Prospective Randomized Control Trial Comparing Effect of Dexamethasone Versus Fentanyl as Adjuvants to Intrathecal Bupivacaine for Orthopedic Surgery.

IntroductionSpinal anesthesia is the most consistent block for lower limb orthopedic surgeries. We conducted this randomized prospective study to evaluate comparative efficacy of intrathecal dexamethasone with fentanyl and normal saline as adjuvants to hyperbaric bupivacaine in spinal anesthesia administered to patients scheduled for lower limb orthopedic surgery.Materials and methods105 patients scheduled for lower limb orthopedic surgeries under spinal anesthesia were included in this clinical trial. After randomization, patients received an intrathecal injection of hyperbaric bupivacaine (12.5 mg) with 4 mg of dexamethasone in group I, hyperbaric bupivacaine (12.5 mg) with 25 ug fentanyl with 0.5 ml of normal saline in group II and hyperbaric bupivacaine (12.5 mg) with normal saline (1 ml) in group III, so as to make volume of drug equal in all three groups. The observer evaluated the sensory and motor blocks and other parameters like time to self-void, stay in post-anesthesia care unit (PACU) and complications. ResultsThe total duration of sensory blockade was found to be 311.43, 197.86 and 115.29 minutes and motor blockade of 223.43, 163.86 and 83.0 minutes in groups I, II and III respectively. The PACU stay was 233.14, 173.86 and 93.00 minutes in groups I, II and III, respectively. The average time to self-void was 400.00, 315.29 and 203.00 in three groups, respectively.ConclusionIntrathecal dexamethasone seemed to be an effective adjuvant to spinal bupivacaine as it prolongs the duration of analgesia, stable hemodynamic profile with minimal side effects. Further studies are required to evaluate the optimum dose and long-term safety of intrathecal dexamethasone.

Intrathecal dexamethasone therapy for febrile infection-related epilepsy syndrome.

ObjectiveIncreasing reports suggest a role for immunological mechanisms in febrile infection‐related epilepsy syndrome (FIRES). The objective of this study was to elucidate the efficacy and safety of intrathecal dexamethasone therapy (IT‐DEX).MethodsWe assessed six pediatric patients with FIRES who were administered add‐on IT‐DEX in the acute (n = 5) and chronic (n = 1) phases. We evaluated clinical courses and prognosis. We measured cytokines/chemokines in cerebrospinal fluid (CSF) from FIRES patients at several points, including pre‐ and post‐IT‐DEX, and compared them with control patients with chronic epilepsy (n = 12, for cytokines/chemokines) or with noninflammatory neurological disease (NIND, n = 13, for neopterin).ResultsAnesthesia was weaned after a median of 5.5 days from IT‐DEX initiation (n = 6). There was a positive correlation between the duration from the disease onset to the introduction of IT‐DEX and the length of ICU stay and the duration of mechanical ventilation. No patient experienced severe adverse events. Seizure spreading and background activities on electroencephalography were improved after IT‐DEX in all patients. The levels of CXCL10, CXCL9, IFN‐γ, and neopterin at pre‐IT‐DEX were significantly elevated compared to levels in epilepsy controls, and CXCL10 and neopterin were significantly decreased post‐IT‐DEX, but were still higher compared to patients with chronic epilepsy. IL‐6, IL‐8, and IL‐1β were significantly elevated before IT‐DEX compared to epilepsy controls, though there was no significant decrease post‐treatment.InterpretationIT‐DEX represents a therapeutic option for patients with FIRES that could shorten the duration of the critical stage of the disease. The effect of IT‐DEX on FIRES might include cytokine‐independent mechanisms.

Anesthesiologic management of pregnant women with SARS-COV-2 infection undergoing cesarean delivery

Background: Pregnant women are usually more susceptible to infection due to typical physiological and mechanical changes, such as increased heart rate, stroke volume and pulmonary residual capacity. The aim of this study was to evaluate an innovative anesthesiologic opioid-free management protocol in symptomatic pregnant women, with COVID-19 and with oxygen therapy, undergoing cesarean delivery with spinal anesthesia. Methods: With the patient in the sitting position, spinal anesthesia was performed at the L1–L2 level. Vertebral level has been identified starting from the sacrum, we counted the laminae in the caudal-to-cephalad direction, which was then marked with a surgical pen. The technique was performed in asepsis, in the subarachnoid space after vision of clear Cephalo-Spinal Fluid (CSF) in the spinal needle 27 Gauge, without letting out the CSF, bupivacaine 0.5% 10 mg, dexmedetomidine 10 μg and dexamethasone 4 mg was injected. Results: During the study period, 40 pregnant women with one or more symptoms and supplemental oxygen (FiO2 35–40%) who underwent cesarean delivery were included in the study. All pregnant women had pain visual analog scale (VAS) ≤3, and no pregnant women required rescue dose. Adverse effects, such as nausea, vomiting, shivering, or pruritus were not recorded in any case. After a mean of 2.5 hours from the spinal anesthesia, all the included women had a complete motility of the lower limbs and were able to mobilize independently within 12 hours after delivery. Mean time to first flatus was about 8 hours after delivery. Conclusions: Pregnant women in COVID-19 can safely receive intrathecal dexamethasone and dexmedetomidine during planned cesarean delivery.

THE EFFICACY OF INTRATHECAL DEXAMETHASONE TO PREVENT EARLY COMPLICATIONS OF SPINAL ANAESTHESIA FOR ELECTIVE CAESAREAN SECTION

Spinal anaesthesia is commonly used for elective caesarean section. But it has some disadvantages and complications in intra- and postoperative period. The aim of this study was to explore the efficacy of intrathecal or intravenous dexamethasone to prevent some early complications of spinal anaesthesia such as arterial hypotonia, nausea, vomiting, bradycardia, shivering etc. Material and methods: there were examined 154 healthy, not obese women, ASA I–II, 18–36 years old, 36–40 weeks of gestation, undergoing elective caesarean section under spinal anaesthesia. All patients were divided into three equal groups for randomized, prospective, double-blinded, placebo-controlled clinical trial. The women of each group received intrathecal hyperbaric bupivacaine 0.5 % 10 mg. Group B (n=51) additionally received intrathecal 1 ml of normal saline=placebo; Group BD (n=52) additionally received 4 mg (1 ml) intrathecal dexamethasone, and Group D (n=51) received 8 mg intravenous dexamethasone directly after spinal puncture. The patients were evaluated for blood pressure, heart rate, nausea, vomiting, shivering or other complications during intra- or postoperative period (24 h). The complications that required medicines correction were recorded and cured. Results: the addition of intrathecal dexamethasone in Group BD vs Group B significantly decreased frequency and manifestations of arterial hypotonia and nausea (Pearson's χ2 =0.486 and χ2=0.479, p&lt;0.05) in intra- and postoperative period after the spinal anaesthesia in elective caesarean section. Intrathecal dexamethasone in Group BD vs Group B significantly reduced shivering (Pearson's χ2=0.316, p&lt;0.05) in intra- and postoperative period, and significantly didn`t impact on vomiting and bradycardia. Conclusions: the addition of 4 mg intrathecal dexamethasone as an adjuvant for spinal anaesthesia can significantly decrease frequency and manifestations of arterial hypotonia and nausea, reduce shivering during perioperative period. The addition of 8 mg intravenous dexamethasone has not the same quality.

Disseminated Cryptococcosis revealed by transverse myelitis in Immunocompetent patient: a case report and review of the literature

BackgroundTransverse myelitis (TM) is due to inflammatory spinal cord injury with bilateral neurologic involvement, which is sensory, motor, or autonomic in nature. It may be associated with autoimmune disease, vaccination, intoxication and infections. The most common infection cause of TM is Coxsackie virus and Mycoplasma pneumoniae. The cryptococcosis is rare. We present the case of disseminated cryptococcosis revealed by transverse myelitis in an immunocompetent 55-year-old male patient. The literature review is also stated.Case presentationThe 55-year-old man suffered from gradual numbness, weakness in both lower limbs and finally paralyzed in the bed. The thoracic spine Computed tomography (CT) was normal, but multiple nodules in the lung were accidentally discovered. Thoracic Magnetic Resonance Imaging (MRI) showed diffused thoracic spinal cord thickening and extensively intramedullary T2 hyper intensity areas. Gadolinium contrast enhanced T1WI showed an intramedullary circle-enhanced nodule at 9th thoracic level. Diagnosis was made by histological examination of the bilateral lung biopsy. The patient was treated successfully with systemic amphotericin B liposome and fluconazole and intrathecal dexamethasone and amphotericin B liposome.ConclusionsThis is a patient with disseminated cryptococcosis involving the lung, spinal cord and adrenal glands, which is rare in the absence of immunodeficiency.

Addition of intrathecal dexamethasone to bupivacaine for spinal anesthesia in cesarean section

Background: Post-caesarean section pain is an important issue in obstetrics. Several studies have shown the importance of adequate postoperative analgesia on mobilization, rehabilitation and decreasing the length of hospital stay. Large amounts of opioid analgesic drugs are often required in the management of intense post-operative pain. However, this option is associated with many side effects.Objective: The aim of the study was to assess the efficacy of adding dexamethasone to bupivacaine for spinal anesthesia in prolonging the duration and anesthetic effect in women undergoing cesarean section.Patients and Methods: Populations of the study were comprised of 100 pregnant full term female planed for cesarean section. All patients had cesarean section under spinal anesthesia. Pain was assessed using 10 cm visual analogue scale (VAS) after 0, 15, 30 min and 2, 4, 6 hours post-operatively and until the mother asked for an analgesic. The duration of sensory block as well as postoperative analgesia were calculated.The study population had been randomized into 2 groups: The 1st group C (n=50 women) included 50 women receiving intrathecal dexamethasone added to bupivacaine. The 2nd group B (n=50 women) included 50 women receiving placebo which was added to intrathecal bupivacaine.Results: This study has shown that the addition of intrathecal dexamethasone to bupivacaine significantly improved the duration of sensory block in spinal anesthesia as the duration of sensory block in the study group was 122 + 7.9 minutes while in the control group it was 91.8 + 10.8 minutes and p 6 and the first analgesic dose prescription in the case group was significantly longer than that in the control group (P<0.001) as the pain free period in the study group was 434.3 + 43.8 minutes while in the control group it was 215.3 + 40.3minutes. Also, the motor block duration in the study group was significantly prolonged when compared with control group (p<0.01).There was no difference in onset time between the two groups and the addition of dexamethasone cause no complications.Conclusion: This study has shown that the addition of intrathecal dexamethasone to bupivacaine significantly improved the duration of sensory block in spinal anesthesia without any changes in onset time and complications, and has increased the pain free period statistically.Recommendations: Further studies are needed to evaluate the optimal dose of dexamethasone to be used in spinal anesthesia.

DEXAMETHASONE - INTRATHECAL MINIMISER OF SIMPLE HAEMATHOLOGIC STRESS BIOMARKERS IN HIP FRACTURE.

SUMMARYProximal femoral fractures are the most common cause of emergency admission to hospital with high postoperative morbidity. The hypothesis was that a single shot of intrathecal dexamethasone and levobupivacaine in anaesthesia for surgical correction of proximal femoral fracture in elderly patients reduces surgical stress with better quality hospitalisation. The study included sixty elderly patients with proximal femoral fracture, ASA status 2 and 3, randomised into two groups. The study group of thirty patients received 8 mg of dexamethasone and 12,5 mg of levobupivacaine 0,5% intrathecally, DLSA group, and the parallel group of thirty patients received 12,5 mg of levobupivacaine 0,5% intrathecally, LSA group. Plasma cortisol and glucose concentrations were assessed before and after anaesthesia, pain intensity was evaluated using Visual Analogue Scale score and hospitalisation was analysed. Results showed decreased cortisol concentrations, longer analgesia duration and shorter hospitalisation in the DLSA group. Glucose concentrations did not differ significantly between the patients in either group. Enlightening the study results collected, single shot of intrathecal administration of dexamethasone in spinal anaesthesia for surgical treatment of proximal femoral fractures reduces the stress response by decreasing plasma cortisol concentrations prolonging analgesia with better rehabilitation possibilities, hence shortening hospitalisation which explains this pattern of anaesthesia.

Metronomic regimen as an effective treatment for aggressive T-LGL leukemia with central nervous system infiltration: clinical experience and review of literature.

A 71-year-old man was diagnosed with T-Large granular lymphocytic (LGL) leukemia, which usually represents a relatively indolent clinical course. While the clinical manifestation of this patient we report herein was aggressive with lasting fever, splenomegaly and hemophagocytic lymphohistiocytosis (HLH). T-cell immunophenotype was CD3+CD4-CD8-CD5-CD7-TCRαβ+. After comprehensive evaluation, an adjusted chemotherapy regimen CEOP (cyclophosphamide, vincristine, etoposide, prednisone) with etoposide, a potential effective regimen for HLH was administrated to the patient. Although he received intensive regimen, the patient showed drug resistance and disease progression with central nervous system (CNS) involvement during treatment and showed only transiently response to intrathecal methotrexate, cytarabine and dexamethasone. Therefore, considering the refractory elderly patient with fragile physical condition, metronomic regimen T-PEPC (oral administration of thalidomide, prednisone, cyclophosphamide, etoposide and methylhydrazine) was recommended, which refers to the frequent even daily administration of cytotoxic drugs at comparatively low doses with minimal or prolonged drug-free breaks. The patient responded well to this treatment and remained symptom-free for 8-month follow-up. To our knowledge, this is the first case of reporting this unique immunophenotype of dual CD4-/CD8- with aggressive clinical course and CNS involvement that successfully treated with metronomic regimen, suggesting that low dose metronomic regimen could be a better option for elderly patient with aggressive T-LGL leukemia.

Intrathecal dexamethasone and methotrexate treatment of neoplastic meningitis from solid tumors

Aim: Neoplastic meningitis (NM) from solid tumors is an advanced malignancy with poor prognosis. Intrathecal chemotherapy is a reliable treatment, and we have obtained some experiences in the treatment of NM with intrathecal dexamethasone and methotrexate (IT DXM and MTX). Methods: Retrospective study of 23 patients with NM from lung cancer ( n = 11), breast cancer ( n = 3), gastric cancer ( n = 1), malignant melanoma ( n = 1), unknown cancer ( n = 7) was conducted. Among these patients, eight received IT DXM and MTX treatment, and 15 patients were placed into a palliative care group. Overall survival (OS) was compared, and the patients' characteristics, symptoms, and some laboratory examinations were analyzed to find the risk factors affecting OS. Results: OS of IT DXM and MTX group was significantly longer than that of the palliative care group ( P = 0.01). The median survival (MS) of palliative care group was 7.53 weeks (5.50-9.57; n = 15), and of the IT DXM and MTX group, 28.63 weeks (12.50-44.75; n = 8); IT DXM and MTX prolonged the OS of NM patients (regression coefficient = −2.923), with odds ratio (OR) being 0.054 (0.09-0.323). Spinal nerves damage decreased the OS (regression coefficient = 1.595), with OR being 4.928 (1.382-17.579). Conclusion: IT DXM and MTX have prolonged the patients' MS, which could be used as a fundamental treatment of NM. Time of induction treatment should be flexible and individualized, and induction treatment could restart when central nervous system relapse. Patients with spinal nerves damage are apt to live shorter.

Comparing the effect of adding dexmedetomidine versus dexamethasone on prolonging the duration of intrathecal bupivacaine in lower abdominal operations

Objective The aim of this study was to evaluate the efficacy of adding dexmedetomidine compared with dexamethasone to bupivacaine to prolong the duration of spinal anesthesia and analgesia in lower abdominal operations. Patients and methods This randomized double-blind study included 60 ASA I or II patients, aged between 25 and 55 years old, scheduled for lower abdominal operations. They were administered 0.5% intrathecal bupivacaine injection and randomly divided into one of three groups: control group (GC), in which patients were administered additional 1 ml of saline; GDX group, in which patients were administered 4 mg dexamethasone; and GDM group, in which patients were administered 10 μg dexmedetomidine. The patients were monitored for heart rate, mean arterial pressure, oxygen saturation, onset and duration of sensory and motor block, intraoperative and postoperative sedation and pain, and adverse events. Results Compared with GC, GDM had significantly faster onset of sensory block (P = 0.006), longer duration of sensory block (P Conclusion Intrathecal dexmedetomidine and dexamethasone are safe and effective adjuncts to intrathecal bupivacaine anesthesia in lower abdominal surgery. Dexmedetomidine showed to provide more rapid onset and longer duration of sensory block, longer duration of motor block, and longer postoperative analgesia.

Effect of coadministration of dexamethasone with intrathecal morphine on postoperative outcomes after cesarean delivery

Objective To investigate the effect of intrathecal dexamethasone administered with intrathecal morphine at cesarean delivery on postoperative adverse effects and patient satisfaction. Methods A triple-blind, randomized, placebo-controlled trial conducted between February 2008 and December 2009 of 120 pregnant women scheduled to undergo cesarean delivery. The patients were randomized into 2 groups: group 1 received 0.2 mg of intrathecal morphine plus 8 mg of intrathecal dexamethasone, while group 2 received 0.2 mg of intrathecal morphine plus 0.9% saline solution (placebo). The occurrence of postoperative nausea and vomiting (PONV), postoperative itching, number of vomiting attacks, and need for antiemetics were recorded in both groups. Overall patient satisfaction was also recorded. Results PONV was 3 times less likely to occur in the dexamethasone group than in the placebo group. When vomiting did occur, the number of attacks was lower in the dexamethasone group (23 vs 87 attacks; OR 0.26, 95% CI, 0.18–0.39). Administration of antiemetics was markedly lower in the dexamethasone group (18 vs 49 shots; OR 0.10, 95% CI, 0.04–0.23) and less postoperative itching was experienced (OR 0.39; 95% CI, 0.19–0.81). The dexamethasone group reported significantly higher mean overall satisfaction scores (77 ± 17 vs 51 ± 22; mean difference 26.00; 95% CI, 18.97–33.03). Conclusion Intrathecal administration of dexamethasone with morphine significantly decreased PONV and improved overall patient satisfaction after cesarean delivery.

Analgesia effects of intrathecally coadministered dexamethasone and Alt inhibitors on chronic dorsal root ganglion compression-induced pain in mouse

Objective To investigate the analgesic effects of intrathecal dexamethasone injection on pain induced by chronic compression of dorsal root ganglion in mouse.Methods Using rat model of radicular pain induced by chronic compression of dorsal root ganglion ( CCD), 40 male SD rats successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into 5 groups:Sham-operation group ( Sham group, n = 8 ), Control group ( CCD group, n = 8), Dexamethasone group ( D group, n = 8), Akt inhibitor V group (A group, n = 8 ) and Dexamethasone plus Akt inhibitor Ⅳ group (DA group, n = 8 ).Rats in D group, A group or DA group were intrathecally treated with dexamethasone (100μg/kg) ,Akt inhibitor Ⅳ (0.6μg/10μl) or dexamethasone ( 100 μg/kg) plus Akt inhibitor Ⅳ (0.6 μg/10 μl) on Day 3,13 after CCD respectively, while rats in C and Sham group received Vehicle (10% DMSO).Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested on 3 d before and 3 d,4 d,7 d,10 d,13 d,14 d and 15 d after operation.Results Compared with Sham group,both PWMT (P＜0.01) and PWTL (P＜0.01) were significantly decreased after CCD surgery on the ipsilateral side.After dexamethasone and Akt inhibitor were respectively intrathecally injected at 3 postoperative day,PWMT (7.33 ± 1.03 ) g, (5.67 ± 1.03 ) g, (2.67 ± 1.03 ) g (P ＜0.01 ) ,PWTL( 16.47 ±0.46)s, ( 14.48 ±0.84) s, ( 10.82 ±2.21 ) s(P＜0.01 ) ,then decreased gradually,and intrathecally injected again at 13 postoperative day, PWMT ( 7.33 ± 1.03 ) g, ( 5.67 ± 1.03 ) g, (2.33 ± 0.81 ) g (P ＜0.01 ), PWTL( 16.44 ±0.90) s, ( 14.01 ±0.82)s, ( 10.22 ± 1.28)s (P＜0.01).Coadministration dexamethasone and Akt inhibitor exhibit significant synergies, postoperative 4 d PWMT( 10.83 ± 2.04)g, (2.67 ± 1.03 )g (P ＜0.01),PWTL(19.11 ±2.01)s,(10.82 ±2.21)s (P＜0.01);14 d PWMT (7 ±0.82)g,(2.33 ±0.81)g (P ＜ 0.01 ), PWTL( 17.16 ± 1.14)s, ( 10.22 ± 1.28 ) s (P ＜ 0.01 ).Conclusion Intrathecal high-dose dexamethas one or PKB / Akt inhibitors can effectively improve pain behavior response induced by chronic compression of dorsal root ganglia,combination of these two drugs could generate significant synergies, and the effection is more obvious, more durable. Key words: Glucocorticoid ; PKB/Akt ; Neuropathic pain ;

Acute painful lumbosacral paresthesia after intrathecal rituximab

Acute painful lumbosacral paresthesia after intrathecal rituximab

Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in orthopedic surgery

Objectives:Spinal anesthesia has the advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anesthetic. Intrathecal local anesthetics have limited duration. Different additives have been used to prolong spinal anesthesia. The effect of corticosteroids in prolonging the analgesic effects of local anesthetics in peripheral nerves is well documented. The purpose of this investigation was to determine whether the addition of dexamethasone to intrathecal bupivacaine would prolong the duration of sensory analgesia or not.Methods:We conducted a randomized, prospective, double-blind, case-control, clinical trial. A total of 50 patients were scheduled for orthopedic surgery under spinal anesthesia. The patients were randomly allocated to receive 15 mg hyperbaric bupivacaine 0.5% with 2 cc normal saline (control group) or 15 mg hyperbaric bupivacaine 0.5% plus 8 mg dexamethasone (case group) intrathecally. The patients were evaluated for quality, quantity, and duration of block; blood pressure, heart rate, nausea, and vomiting or other complications.Results:There were no signification differences in demographic data, sensory level, and onset time of the sensory block between two groups. Sensory block duration in the case group was 119±10.69 minutes and in the control group was 89.44±8.37 minutes which was significantly higher in the case group (P<0.001). The duration of analgesia was 401.92±72.44 minutes in the case group; whereas it was 202±43.67 minutes in the control group (P<0.001). The frequency of complications was not different between two groups.Conclusion:This study has shown that the addition of intrathecal dexamethasone to bupivacaine significantly improved the duration of sensory block in spinal anesthesia without any changes in onset time and complications.

Liposomal cytarabine is effective and tolerable in the treatment of central nervous system relapse of acute lymphoblastic leukemia and very aggressive lymphoma

Treatment of central nervous system relapse in adult acute lymphoblastic leukemia is a challenge and outcome is poor. Liposomal cytarabine has a prolonged half-life and, given intrathecally, has produced high response rates in patients with central nervous system relapse of non-Hodgkin's lymphoma. The aim of this study was to evaluate the efficacy and tolerability of liposomal cytarabine in central nervous system relapse of acute lymphoblastic leukemia or Burkitt's lymphoma/leukemia. Liposomal cytarabine (50 mg) was given intrathecally together with systemic or intrathecal dexamethasone once every 2 weeks in a phase II European trial. The primary end-point, cytological response in the cerebrospinal fluid after one or two cycles, was evaluated at the time of next treatment. Nineteen heavily pretreated patients (median age, 53 years; range 24-76 years) were evaluable: 14 with acute lymphoblastic leukemia and 5 with Burkitt's lymphoma/leukemia). Complete cytological remission as best response after two cycles of liposomal cytarabine was confirmed in 74% of the patients: 86% of those with acute lymphoblastic leukemia and 40% of those with Burkitt's lymphoma/leukemia). Nine of the 14 patients who achieved complete remission relapsed after a median of 7 months. The median overall survival was 11 months. Adverse events were observed in 89% of the patients (57% of cycles). Grade III-IV events with potential correlation to liposomal cytarabine occurred in 32% of the patients. The most frequent adverse event was headache. One patient developed severe neurological complications with loss of vision and a conus syndrome. Overall, liposomal cytarabine showed excellent antileukemic activity. Toxicity was acceptable but appeared to increase with the number of cycles. Future evaluation in prophylaxis is of interest.

Role of glucocorticoid receptor in induction of neuronal apoptosis in spinal dorsal horn in chronic morphine tolerant rats

Objective To investigate the role of glucocorticoid receptor (GR) in the induction of neuronal apoptosis in spinal dorsal horn in chronic morphine tolerant rats. Methods Twenty healthy male SD rats weighing 300-350 g in which intrathecal (IT) catheter was successfully implanted without complication were randomized into 4 groups ( n = 5 each): group Ⅰ control ( group C);group Ⅱ morphine ( group M );group Ⅲ morphine +RU38486 (GR antagonist) (group MR) and group Ⅳ morphine + dexamethasone (GR agonist) (group MD).Normal saline 10 μl, morphine 10 μg, morphine 10 μg + RU38486 2 μg and morphine 10μg + dexamethasone 4 μg were injected IT twice a day at 8:00 and 20:00 for6 consecutive days in group C, M, MR and MD respectively. Tail flick latency (TFL) to a thermal nociceptive stimulus was measured every day at 30 min after IT administration in the morning (8:00). Hyperalgesia was considered to be a sign of morphine tolerance. The animals were killed at 7 days after IT drug administration. The L3-5 segment of the spinal cord was isolated for determination of neuronal apoptosis in spinal dorsal horn by TUNEL staining. Apoptotic index was calculated ( the number of apoptotic neurons/the total number of neurons × 100% ). Results TFL was significantly prolonged at day 1 and 3 of IT morphine 10 μg twice a day and returned to baseline at day 5 and 7 indicating morphine tolerance. RU38486 inhibited while dexamethasone enhanced morphine tolerance. IT morphine significantly increased the number of apoptotic neurons in spinal dorsal horn. Morphine-induced neuronal apoptosis was decreased by IT RU38486 and increased by IT dexamethasone. Conclusion Glucocorticoid receptors may be involved in morphine tolerance by inducing neuronal apoptosis in spinal dorsal horn. Key words: Glucocorticoids; Morphine; Drug tolerance; Spinal cord; Apoptosis