Intrathecal pain treatment for severe pain in patients with terminal cancer: A retrospective analysis of treatment-related complications and side effects.

OBJECTIVES: Two-thirds of patients with advanced cancer experience pain. Some of these patients have severe pain refractory to oral and parenteral medication, for whom intrathecal pain treatment could be an option. While intrathecal therapy is presently used with good results in clinical practice, the current evidence is limited. Hence, increased knowledge of intrathecal pain treatment is needed. This retrospective study aimed to assess complications and side effects related to intrathecal pain treatment in patients with terminal cancer. METHODS: A retrospective study on all patients who received intrathecal treatment with morphine and bupivacaine through externalized catheters for cancer-related pain at a single university hospital during a 5-year period. RESULTS: Treatment-related complications were reported in 24 out of 53 patients. The most common complications were catheter dislocation (13%), catheter occlusion (9%), falls due to bupivacaine-related numbness or weakness (9%), and reversible respiratory depression (8%). There were five serious complications, i.e., meningitis or neurological impairment, of which four were reversible. Side effects related to intrathecal drugs, or the implantation procedure were observed in 35 patients. The most common were bupivacaine-related numbness or weakness (57%) and reversible post-dural puncture headache (19%). Systemic opioid doses decreased during the first 3 weeks of intrathecal treatment, from a median daily dose of 681 to 319 oral morphine milligram equivalents. The median treatment duration time was 62 days. CONCLUSIONS: Complications related to intrathecal treatment are common, but mostly minor and reversible. Side effects are predominantly related to unwanted pharmacological effects from intrathecal drugs. Intrathecal treatment enables the reduction of systemic opioid doses, which indicates a good treatment effect on pain. Hence, intrathecal therapy can be considered a safe pain-relieving treatment in patients with severe refractory cancer-related pain. Future research is warranted on patient acceptability and satisfaction of intrathecal pain treatment.

Intrathecal administration of MCRT produced potent antinociception in chronic inflammatory pain models via µ-δ heterodimer with limited side effects.

An important goal in the opioid field is to discover effective analgesic drugs with minimal side effects. MCRT demonstrated potent antinociceptive effects with limited side effects, making it a promising candidate. However, its pharmacological properties and how it minimizes side effects remain unknown. Various mouse pain and opioid side effect models were used to evaluate the antinociceptive properties and safety at the spinal level. The targets of MCRT were identified through cAMP measurement, isolated tissue assays, and pharmacological experiments. Immunofluorescence was employed to visualize protein expression. MCRT displayed distinct antinociceptive effects between acute and chronic inflammatory pain models due to its multifunctional properties at the µ opioid receptor (MOR), µ-δ heterodimer (MDOR), and neuropeptide FF receptor 2 (NPFFR2). Activation of NPFFR2 reduced MOR-mediated antinociception, leading to bell-shaped response curves in acute pain models. However, activation of MDOR produced more effective antinociception in chronic inflammatory pain models. MCRT showed limited tolerance and opioid-induced hyperalgesia in both acute and chronic pain models and did not develop cross-tolerance to morphine. Additionally, MCRT did not exhibit addictive properties, gastrointestinal inhibition, and effects on motor coordination. Mechanistically, peripheral chronic inflammation or repeated administration of morphine and MCRT induced an increase in MDOR in the spinal cord. Chronic administration of MCRT had no apparent effect on microglial activation in the spinal cord. These findings suggest that MCRT is a versatile compound that provides potent antinociception with minimal opioid-related side effects. MDOR could be a promising target for managing chronic inflammatory pain and addressing the opioid crisis.

Safety and effectiveness of dual channels vancomycin administration in the treatment of intracranial infection after severe brain injury surgery.

To observe the clinical efficacy and safety of vancomycin intravenous drip combined with vancomycin intrathecal injection in the treatment of intracranial infection after severe brain injury surgery. From January 2020 to June 2022, 80 patients with intracranial infection after severe brain injury surgery were selected and randomly divided into 2 subgroups; there were 40 patients in each subgroup. All patients were treated with vancomycin. The control subgroup was medicated with intravenous drip, and the observation subgroup was treated through 2 channels (intravenous drip + intrathecal injection), with a course of 7 days. The clinical efficacy, intracranial pressure, infection control time, routine indexes of cerebrospinal fluid (white blood cell count [WBC], glucose content [Glu], and total protein content [Pro]) and the incidence of adverse reactions were contrasted between the 2 subgroups. Versus the control subgroup, the total effective rate in the observation subgroup was notably higher (95.00% vs 77.50%). After treatment, aiming at the intracranial pressure and infection control time, versus the control subgroup (146.20 ±â€…22.37) mmH2O and (9.86 ±â€…1.62) days, the observation subgroup were (125.43 ±â€…18.5) mmH2O and (7.35 ±â€…1.57) days respectively, which were notably lower. After treatment, versus the control subgroup, the concentrations of WBC and Pro in cerebrospinal fluid in the observation subgroup were lower, and the content of Glu was higher. There was no statistical distinction in the incidence of adverse reactions between the 2 subgroups (17.50% vs 10.00%). Two-channel administration of vancomycin can improve the clinical efficacy of internal infection after severe craniocerebral injury, reduce intracranial pressure, and cerebrospinal fluid WBC and Pro levels, and has high safety.

Intrathecal Dexmedetomidine as an Adjuvant to Low Dose Hyperbaric 0.5% Bupivacaine on Haemodynamic Parameters in Patients Undergoing Transurethral Resection of Prostate.

OBJECTIVE: To determine the role of dexmedetomidine in potentiating the local anaesthetic efficacy of a low dose of bupivacaine when used as an adjuvant. STUDY DESIGN: A prospective, double-blind, randomised study. Place and Duration of the Study: Department of Anaesthesia, Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from July 2021 to February 2022. METHODOLOGY: One hundred and eight patients of ASA physical class I-III undergoing transurethral resection of the prostate (TURP) under sub-arachnoid block (SAB) were enroled and distributed into two equal groups. Group BUPIPURE (BP) was given 7.5 mg of pure 0.5% hyperbaric bupivacain whereas group BUPIDEX (BD) was given 6 mg of 0.5% hyperbaric bupivacain with 3 µg dexmedetomidine intrathecally. The effects in Both groups were compared using chi-square and unpaired t-tests. A significance level of p <0.05 was used to evaluate the statistical significance. RESULTS: Both groups demonstrated a steady decrease in mean heart rate (mean HR 98.9-62.7 per minute as compared to 79.1-59.4 per minute in groups BP and BD, respectively), however, no patient reached to HR <50/min. Group BP had a higher HR variability than group BD. The two groups' median peak sensory levels were similar. However, a statistically significant difference was revealed in the time taken for 2-segment regression (87.5 ± 11.3 min vs. 115.5 ± 6.2 min p <0.001 in BP and BD), as well as the time to reach T10 sensory level (13.56 ± 2.5 min vs. 10.9 ± 3.0 min p <0.001). CONCLUSION: In patients having TURP, intrathecal dexmedetomidine combined with low-dose bupivacaine results in a quicker start, extended sensory and motor block, and a decreased need for rescue analgesics. KEY WORDS: Adjuvants, Dexmedetomidine, Spinal anaesthesia, Transurethral Resection of Prostate.

SPIDOL study protocol for the assessment of intrathecal ziconotide antalgic efficacy for severe refractory neuropathic pain due to spinal cord lesions.

RATIONALE: Central neuropathic pain resulting from spinal cord injury is notoriously debilitating and difficult to treat with few currently available treatments. A novel molecule with intrathecal administration: Ziconotide has been approved for treatment of refractory neuropathic pain in general. It acts as a presynaptic calcium channel blocker. A pilot study has shown its potential in SCI neuropathic pain patients. OBJECTIVE: The aim of this study is to determine the long-term (6 months) efficacy of chronic intrathecal ziconotide for the treatment of neuropathic SCI pain. STUDY DESIGN: Multicenter, Randomized, Comparative, Placebo controlled, Double blind clinical trial, with a crossover of random alternated periods of 6 months (placebo or ITZ) for a total of 15 months including a total of 44 patients. STUDY POPULATION: • Patients with SCI of various etiologies exhibiting neuropathic pain refractory to non-invasive treatments. • > 18 years. INTERVENTION: Intrathecal administration of ziconotide via an implanted pump. STUDY OUTCOMES: Primary study outcome Difference in pain intensity for all patients between effective treatment and placebo periods. Secondary study outcomes 1. Continuous evaluation of pain intensity. 2. Percentage of patients with at least 30% of pain reduction. 3. Satisfaction level of the patient pain relief. 4. Declarations of serious adverse events. 5. Duration and intensity of spontaneous and provoked pain. 6. Quality of life. 7. Patient global impression of change. 8. Quantification of daily dosages of analgesic drug intake. 9. Long term memory and neurocognitive effects. 10. Assessment of the patient's physical and emotional distress. NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT, AND GROUP RELATEDNESS: Participation in this study is in accordance with current treatment protocols for SCI neuropathic pain in France therefore it proposes a treatment that would currently be considered regular practice even though no RCT evidence is yet available. The study gives patients the advantage of directly testing versus placebo a treatment that otherwise entails significant constraints. A Data Safety Monitoring board (DSMB) will be created for continuous safety analysis. Furthermore, patients will be followed in specialized pain centers offering the possibility of continuing their treatment after the study period.

Ultrasound as a reliable guide for lumbar intrathecal injection in rats: A pilot study.

Lumbar intrathecal administration provides an ideal route for drug delivery into the central nervous system, especially when dorsal root ganglions are the main target for the therapy in rat model of chronic pain. Two main methods of lumbar intrathecal administrations are chronic catheter implantation and the acute needle puncture. Chronic catheter implantation involves surgical manipulation to insert micro indwelling catheter into the intrathecal space. However, this method is invasive, produces inflammatory reactions, and generates more surgical stress. Acute needle puncture is less invasive and cheaper however is technically challenging to perform. We performed an ultrasound-guided lumbar intrathecal injection in six male Sprague Dawley rat cadavers, on average weighing 250-300 grams. Fresh rat cadavers were positioned in a sternal recumbent position, vertebrae were palpated and scanned using a linear probe ultrasound. A 25G needle insertion was advanced with real-time ultrasound guidance, and placement was confirmed prior to dye injection (Methylene blue, Sigma Aldrich). Cadavers were then dissected, and the vertebrae were visually inspected for dye staining. All three cadavers that underwent intrathecal injection with sagittal and axial plane ultrasound guidance showed positive dye staining within the intrathecal space, confirming successful acute intrathecal administration. There was one successful intrathecal injection under sagittal plane-only ultrasound guidance. Ultrasound is a useful, operator-dependent tool to guide acute needle puncture intrathecal administration.

Repeated intrathecal injections of peripheral nerve-derived stem cell spheroids improve outcomes in a rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. METHODS: We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. RESULTS: PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. CONCLUSION: Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Intrathecal Morphine Enhances Postoperative Analgesia and Recovery in Robotic-Assisted Laparoscopic Partial Nephrectomy: A Retrospective Study of 272 Patients.

BACKGROUND Robot-assisted laparoscopic partial nephrectomy (RAPN) has been increasingly used for treating renal tumors due to its advantages over other approaches. However, RAPN can induce acute incisional, peritoneal, visceral, and referred pain. Therefore, acute pain control in robotic surgery is a concern. This retrospective study aimed to evaluate the efficacy of intrathecal morphine (ITM) for postoperative analgesia and recovery after RAPN. MATERIAL AND METHODS We retrospectively investigated consecutive patients who underwent RAPN at our institute between 2020 and 2021. Among the 272 patients who met the inclusion criteria, 135 patients were administered 200 µg of ITM preoperatively (ITM group), while 137 patients were not (control group). Postoperative pain assessments using the numeric rating scale (NRS), opioid requirements, and recovery profiles during the first postoperative 24 h were compared between the 2 groups. RESULTS As the primary endpoint, the incidence of moderate-to-severe pain (24-h average NRS pain score ≥4) was significantly lower in the ITM group than in the control group (36.3% vs 61.3%, P<0.001). Pain scores and cumulative opioid requirements were also significantly lower in the ITM group for all assessments (P<0.001). Moreover, the ITM group had a higher score on the Quality of Recovery-15 questionnaire on the first postoperative day (129 vs 120, P=0.003) despite an increased rate of postoperative nausea/vomiting (27.4% vs 13.1%, P=0.003). CONCLUSIONS Our findings indicate that ITM provided superior pain control during the early period following RAPN, with reduced postoperative opioid requirements. Moreover, ITM improved patient satisfaction with recovery.

Intrathecal ziconotide for the treatment of chronic pain: a collection of clinical experiences and literature review.

OBJECTIVE: Despite the wide use of ziconotide in the USA for treating refractory cancer- and noncancer-related pain, this agent is little used in Europe, even if licensed by the European Medicines Agency (EMA). The reason could be attributed to the high, fixed starting dose required for ziconotide, as stated in the EMA Summary of Product Characteristics (SmPC). This dosage recommendation is based on the results of pivotal clinical studies of ziconotide, which utilized aggressive titration schedules. Thus, a reappraisal of the available evidence, as well as a reflection on real-life clinical experiences, might be useful to identify practice adjustments to improve the clinical application of ziconotide in the European scenario. In line with this need, this paper reports some clinical experiences of patients with chronic pain treated with ziconotide intrathecal (IT) therapy in Italy, particularly focusing on long-term treatment to further characterize and improve the use of this agent in real practice. Moreover, a literature review of the available data on the effectiveness and safety of IT ziconotide is provided. CASE SERIES: Collected clinical experiences suggested that the use of IT ziconotide represents a valuable option, particularly in cases where other treatments have been ineffective or poorly tolerated. Ziconotide was shown to not cause severe side effects in the long-term treatment, leading to a constant pain relief effect at stable doses, without adverse events that caused therapy interruption. The overall constant ziconotide dosages also suggest the absence of a tolerance effect. In parallel, the evidence in the literature aligns with real-world evidence and further supports the use of IT ziconotide as an important option for the management of chronic pain. CONCLUSIONS: IT ziconotide represents a valuable addition to the armamentarium of pain management strategies, offering hope for improved quality of life for patients suffering from chronic, treatment-resistant pain. Continued research and clinical experience will further elucidate its optimal use and role in comprehensive pain care.

Safety and potential effects of intrathecal injection of allogeneic human umbilical cord mesenchymal stem cell-derived exosomes in complete subacute spinal cord injury: a first-in-human, single-arm, open-label, phase I clinical trial.

OBJECTIVE: Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI. METHODS: This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire. RESULTS: Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline. CONCLUSIONS: This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .

Is intrathecal bupivacaine plus dexmedetomidine superior to bupivacaine in spinal anesthesia for a cesarean section? A systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate whether the administration of intrathecal dexmedetomidine as a bupivacaine adjuvant for caesarean section can prolong the duration of analgesia compared with bupivacaine alone. Secondary outcomes included postoperative pain, the time interval to the first analgesic request, the level of sedation, the incidence of adverse effects, and the fetal outcomes. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted. The study compared the intrathecal administration of bupivacaine plus dexmedetomidine (group BD) to the intrathecal administration of bupivacaine alone (group B) for cesarean sections. RESULTS: Fourteen publications were included. Among patients who underwent spinal anesthesia for a cesarean section, 514 patients received intrathecal bupivacaine alone, and 533 patients received intrathecal bupivacaine plus dexmedetomidine. The onset of sensory and motor block was essentially the same in both groups; the time for sensory and motor block regression was significantly longer in the BD group. Postoperative Visual Analogue Scale (VAS) values were similar in group BD when compared to group B. Postoperative VAS scores remained consistently low in Group BD compared to Group B, starting from 1 hour after surgery. The level of sedation measured at the end of the cesarean section in both groups was almost similar. No difference in terms of safety, adverse events, and neonatal outcomes was found between the two groups. CONCLUSIONS: Use of intrathecal dexmedetomidine for spinal anesthesia in cesarean section significantly prolongs sensory and motor block compared to using bupivacaine alone as an adjuvant. It also improves analgesia after 1 hour with no difference in the incidence of maternal and neonatal adverse effects compared to bupivacaine alone. The optimal dose of dexmedetomidine to use remains to be ingested.

IT-DEX and B cell depletion in a child with anti-GAD 65 autoimmune encephalitis presenting as NORSE: A case report.

New-onset refractory status epilepticus (NORSE) is a devastating clinical condition that often leads to severe disability. Intrathecal dexamethasone (IT-DEX) has been reported to improve refractory status epilepticus. We present an 11-year-old female with anti-GAD 65 encephalitis presenting as NORSE who had minimal response to standard anti-seizure medications and first-line immunotherapies. The patient received 6 doses of IT-DEX in conjunction with rituximab which correlated with subsequent decreased neuroinflammation, reduced seizure burden and aided in weaning anesthetic infusions. Our case with literature review suggests IT-DEX may be utilized as an early intervention in those with refractory status epilepticus from various etiologies.

Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression.

BACKGROUND: Intrathecal morphine provides effective analgesia for a range of operations. However, widespread implementation into clinical practice is hampered by concerns for potential side-effects. We undertook a systematic review, meta-analysis, and meta-regression with the primary objective of determining whether a threshold dose for non-pulmonary complications could be defined and whether an association could be established between dose and complication rates when intrathecal morphine is administered for perioperative or obstetric analgesia. METHODS: We systematically searched the literature for randomised controlled trials comparing intrathecal morphine vs control in patients undergoing any type of surgery under general or spinal anaesthesia, or women in labour. Primary outcomes were rates of postoperative nausea and vomiting, pruritus, and urinary retention within the first 24 postoperative hours, analysed according to doses (1-100 µg; 101-200 µg; 201-500 µg; >500 µg), type of surgery, and anaesthetic strategy. Trials were excluded if doses were not specified. RESULTS: Our analysis included 168 trials with 9917 patients. The rates of postoperative nausea and vomiting, pruritus, and urinary retention were significantly increased in the intrathecal morphine group, with an odds ratio (95% confidence interval) of 1.52 (1.29-1.79), P<0.0001; 6.11 (5.25-7.10), P<0.0001; and 1.73 (1.17-2.56), P=0.005, respectively. Meta-regression could not establish an association between dose and rates of non-pulmonary complications. There was no subgroup difference according to surgery for any outcome. The quality of evidence was low (Grading of Recommendations Assessment, Development, and Evaluation [GRADE] system). CONCLUSIONS: Intrathecal morphine significantly increased postoperative nausea and vomiting, pruritus, and urinary retention after surgery or labour in a dose-independent manner. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023387838).

Fentanyl induces analgesic effect through miR-381-3p/TRPM7 when combined with bupivacaine in subarachnoid injection.

Fentanyl combined with bupivacaine in subarachnoid anesthesia exerts a strong synergistic analgesic effect, extending the duration of analgesia. However, the mechanism of enhanced analgesic effect of fentanyl remains elusive. The present study investigated the potential mechanism of the analgesic effect of fentanyl when combined with bupivacaine. The subarachnoid injection (SI) rat model was employed, and SI of fentanyl or/and bupivacaine was used to investigate their analgesic effect. Dorsal root ganglion (DRG)' RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to evaluate the downstream mechanisms of MicroRNAs (miRNAs). Further validation tests included RT-PCR, Western blot, and immunofluorescence. A single SI of fentanyl or bupivacaine decreased the positive responses to stimulation when used alone or in combination. RNA-seq results revealed that miR-381-3p played a role in the fentanyl-driven promotion of analgesia. Bioinformatics analysis and dual-luciferase reporter identified TRPM7 as a direct downstream target gene of miR-381-3p. In vitro, overexpression of miR-381-3p could further block fentanyl-induced expression of TRPM7, p-ERK1/2, CGRP, and SP. In addition, antagomir-381-3p reversed the inhibitory effect of fentanyl on the expression of TRPM7, p-ERK1/2, CGRP, and SP, in vivo; however, TRPM7 siRNA rescued the effect of antagomir-381-3p. In conclusion, fentanyl inhibits p-ERK by targeting TRPM7 via miR-381-3p, lowering the production of CGRP and SP, and ultimately inducing analgesic effects.

Intrathecal dexamethasone as an adjuvant for spinal anesthesia: a systematic review.

INTRODUCTION: Spinal anesthesia is a common anesthetic technique for lower limb and abdominal surgery. Despite its efficacy, its use is limited because of its duration and potential severe side effects, especially in high-risk patients undergoing major surgery. Adjuvants such as dexamethasone offer the potential to prolong the anesthetic effect and reduce the need for local anesthetics while reducing the incidence of serious adverse events. The purpose of this systematic review is to evaluate the efficacy of dexamethasone as an intrathecal adjuvant in prolonging anesthetic duration, delaying pain onset, and minimizing adverse events (PROSPERO registration: CRD42022350218). EVIDENCE ACQUISITION: We included randomized controlled trials conducted in adult patients undergoing spinal anesthesia for lower limb or abdominal surgery and comparing the performance of dexamethasone with alternative spinal treatments. A comprehensive systematic search was conducted on PubMed/MEDLINE, Scopus, CINAHL, EMBASE, CENTRAL, and Cochrane Library from February to June 2023 without language restriction. Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB2). EVIDENCE SYNTHESIS: Ten studies, nine of which were at high risk of bias, were included (N.=685 patients). Overall, intrathecal dexamethasone was associated with a longer duration of sensory block, improvement in the duration or extent of postoperative analgesia, and significant shortening of block onset. The role of dexamethasone in prolonging motor block was not clear. The incidence of adverse events was low. Intrathecal dexamethasone has been shown to be a potentially valuable adjuvant to prolong the duration of sensory block and improve postoperative analgesia without increasing adverse events. CONCLUSIONS: Given the wide heterogeneity of methodological approaches, further investigation is needed. Considering the limitations of the included studies and awaiting more conclusive evidence, the prudent use of dexamethasone could be recommended in those specific situations where general anesthesia or higher local anesthetics should be avoided.

Evaluating the effect of injection protocols on intrathecal solute dispersion in non-human primates: an in vitro study using a cynomolgus cerebrospinal fluid system.

BACKGROUND: Achieving effective drug delivery to the central nervous system (CNS) remains a challenge for treating neurological disorders. Intrathecal (IT) delivery, which involves direct injection into the cerebrospinal fluid (CSF), presents a promising strategy. Large animal studies are important to assess the safety and efficacy of most drugs and treatments and translate the data to humans. An understanding of the influence of IT injection parameters on solute distribution within the CNS is essential to optimize preclinical research, which would potentially help design human clinical studies. METHODS: A three-dimensional (3D) in vitro model of a cynomolgus monkey, based on MRI data, was developed to evaluate the impact of lumbar injection parameters on intrathecal solute dispersion. The parameters evaluated were (a) injection location, (b) bolus volume, (c) flush volume, (d) bolus rate, and (e) flush rate. To simulate the CSF flow within the subarachnoid space (SAS), an idealized CSF flow waveform with both cardiac and respiratory-induced components was input into the model. A solution of fluorescein drug surrogate tracer was administered in the lumbar region of the 3D in vitro model filled with deionized water. After injection of the tracer, the CSF system wide-solute dispersion was imaged using high-resolution cameras every thirty seconds for a duration of three hours. To ensure repeatability each injection protocol was repeated three times. For each protocol, the average spatial-temporal distribution over three hours post-injection, the area under the curve (AUC), and the percent injected dose (%ID) to extra-axial CSF (eaCSF) at three hours were determined. RESULTS: The changes to the lumbar injection parameters led to variations in solute distribution along the neuro-axis. Specifically, injection location showed the most impact, enhancing the delivery to the eaCSF up to + 10.5%ID (p = 0.0282) at three hours post-injection. Adding a post-injection flush of 1.5 ml at 1 ml/min increased the solute delivery to the eaCSF by + 6.5%ID (p = 0.0218), while the larger bolus volume resulted in a + 2.3%ID (p = 0.1910) increase. The bolus and flush rates analyzed had minimal, statistically non-significant effects. CONCLUSION: These results predict the effects of lumbar injection parameters on solute distribution in the intrathecal space in NHPs. Specifically, the choice of injection location, flush, and bolus volume significantly improved solute delivery to eaCSF. The in vitro NHP CSF model and results offer a system to help predict and optimize IT delivery protocols for pre-clinical NHP studies.

Clinical observation of the treatment of refractory cancer pain with cancer pain information platform and IDDS under home analgesia mode: A retrospective study.

To evaluate the effectiveness and safety of a cancer pain information platform combined with semi-implantable intrathecal drug delivery systems among the patients with refractory cancer pain under a "home analgesia" model. This was a retrospective study. A total of 49 patients underwent semi-implantable intrathecal drug delivery systems with patient-controlled analgesia in conjunction with the establishment of a cancer pain information platform. Numeric rating scales (NRS), Bruggrmann comfort scale (BCS), high-quality sleep duration, and opioid-related adverse effects were recorded at various time points and analyzed: the day on admission (T0), the day of discharge (T1), 30 days post-discharge (T2), 60 days post-discharge (T3), 90 days post-discharge (T4), 120 days post-discharge (T5), 150 days post-discharge (T6), 180 days post-discharge (T7), and the day before death (T8). Compared with T0, NRS significantly decreased and BCS significantly increased at T1 to T8 time points (P < .05). However, NRS and BCS did not show differences at T1 to T8 time points (P > .05). The duration of high-quality sleep was significantly extended, and the incidence of opioid-related adverse effects was significantly reduced. Postoperative complications included 1 case of cerebrospinal fluid leakage, 3 cases of infection at the butterfly needle insertion site, 6 cases of hospital readmission for equipment malfunction, and no cases of respiratory depression. Eleven patients continued standardized antitreatment after IDDS surgery. The mean survival time for all patients was 135.51 ±â€…102.69 days, and the survival rate at T7 was 30.61%. The cancer pain information platform combined with semi-implantable IDDS is beneficial for the pain management of refractory cancer patients under the "home analgesia" model, improving their quality of life.

Intrathecal baclofen therapy for spasticity in a person with spinal cord injury and end-stage renal disease dependent on hemodialysis: a case report.

INTRODUCTION: Spasticity is one of the most common secondary complications following a spinal cord injury (SCI), which can significantly debilitate a patient irrespective of the severity of the injury. Intrathecal baclofen therapy can effectively reduce global spasticity in bilateral lower extremities at lower doses and allows precise dose titration to manage spasticity optimally. In complex patients with spasticity and multiple medical comorbidities, multidisciplinary teamwork is required to assess ITB safety and deliver timely intervention to prevent secondary complications of spasticity and improve quality of life. CASE PRESENTATION: A 61-year-old African American male with multiple comorbidities, including end-stage renal disease (ESRD) requiring dialysis sustained non-traumatic SCI due to epidural abscess resulting in paraplegia and severe debilitating spasticity. Spasticity gradually worsened and interfered with his ability to achieve independence with functional activities appropriate for his neurological level of injury. A multidisciplinary team approach in this complex case resulted in a successful ITB trial and subsequent ITB implantation, resulting in reduced spasticity and improved quality of life. To our knowledge, this is the first case report of the administration of intrathecal baclofen pump therapy in a person with SCI and end-stage renal disease (ESRD) dependent on hemodialysis. DISCUSSION: ITB therapy can be safely delivered in a person with SCI and multiple medical comorbidities, including ESRD, dependent on hemodialysis to manage spasticity. However, a careful evaluation and discussion among the multidisciplinary team managing the patient's morbidities and patient is required to assess the risks and benefits of ITB therapy to allow the patient to make an informed decision.