scholarly journals Ziconotide Adverse Events in Patients with Cancer Pain: A Multicenter Observational Study of a Slow Titration, Multidrug Protocol

2012 ◽  
Vol 5;15 (5;9) ◽  
pp. 395-403
Author(s):  
Denis Dupoiron
Keyword(s):  
Adverse Events ◽  
Cancer Pain ◽  
Initial Dosage ◽  
Oral Morphine ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Serious Adverse Events ◽  
Patients With Cancer ◽  
Intractable Cancer Pain ◽  
Intrathecal Analgesia

Background: Ziconotide is a new analgesic agent administered intrathecally. It is challenging to use and can induce several and sometimes serious adverse events. A low initial dosage followed by slow titration may reduce serious adverse events. Objective: To determine whether a low starting dosage of ziconotide, followed by slow titration, decreases the incidence of major adverse events associated with ziconotide when used for intractable cancer pain. Study Design: Observational cohort study. Setting: Three French cancer centers. Methods: Patients with incurable cancer causing chronic pain rated above 6/10 on a numerical scale while receiving high-dose opioid therapy (more than 200 mg/d of oral morphine equivalent) and/or exhibiting severe opioid-related adverse events received intrathecal infusions of ziconotide combined with morphine, ropivacaine, and clonidine. Results: Seventy-seven patients were included. Adverse events were recorded in 57% of them; moderate adverse events occurred in 51%. Adverse events required treatment discontinuation in 7 (9%) including 5 (6%) for whom a causal role for ziconotide was highly likely; among them 4 (5%) were serious. All patients experienced a significant and lasting decrease in pain intensity (by 48%) in response to intrathecal analgesic therapy that included ziconotide. Limitations: Limitations include the nonrandomized, observational nature of the study. Determining the relative contributions of each drug to adverse events was difficult, and some of the adverse events manifested as clinical symptoms of a subjective nature. Conclusions: The rates of minor and moderate adverse events were consistent with previous reports. However, the rate of serious adverse events was substantially lower. Our study confirms the efficacy of intrathecal analgesia with ziconotide for relieving refractory cancer pain. These results indicate that multimodal intrathecal analgesia in patients with cancer pain should include ziconotide from the outset in order to provide time for subsequent slow titration. Key words: Ziconotide, adverse events, intrathecal therapy, cancer pain, morphine, ropivacaine, clonidine.

Factors Predicting Requirement of High-dose Transdermal Fentanyl in Opioid Switching From Oral Morphine or Oxycodone in Patients With Cancer Pain

2011 ◽  
Vol 27 (8) ◽  
pp. 664-667 ◽  
Author(s):  
Yuko Kanbayashi ◽  
Toyoshi Hosokawa ◽  
Kousuke Okamoto ◽  
Sawako Fujimoto ◽  
Hideyuki Konishi ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Oral Morphine ◽  
High Dose ◽  
Transdermal Fentanyl ◽  
Patients With Cancer ◽  
Opioid Switching

scholarly journals Open-Label Clinical Trials of Oral Pulse Dexamethasone for Adults with Idiopathic Nephrotic Syndrome

2019 ◽  
Vol 49 (5) ◽  
pp. 377-385 ◽  
Author(s):  
Monique E. Cho ◽  
Mary H. Branton ◽  
David A. Smith ◽  
Linda Bartlett ◽  
Lilian Howard ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Adverse Events ◽  
Idiopathic Nephrotic Syndrome ◽  
High Dose ◽  
Open Label ◽  
Serious Adverse Events ◽  
Oral Dexamethasone ◽  
Dose Oral ◽  
Pulse Dexamethasone ◽  
Daily Prednisone

Background: In adults with primary focal segmental glomerulosclerosis (FSGS), daily prednisone may induce complete remissions (CR) and partial remissions (PR), but relapses are frequent and adverse events are common. Methods: We carried out 2 open-label, uncontrolled trials to explore the efficacy and tolerability of pulse oral dexamethasone as an alternative to daily prednisone. We enrolled adult patients with proteinuria > 3.5 g/day despite the use of renin-angiotensin-aldosterone blockade. In the first trial, we enrolled 14 subjects with FSGS and administered 4 dexamethasone doses (25 mg/m2) daily for 4 days, repeated every 28 days over 32 weeks. The second trial involved a more intensive regimen. Eight subjects received 4 dexamethasone doses of 50 mg/m2 every 4 weeks for 12 weeks, followed by 4 doses of 25 mg/m2 every 4 weeks for 36 weeks; subjects were randomized to 2 doses every 2 weeks or 4 doses every 4 weeks. Results: In the first trial, we enrolled 13 subjects with FSGS and 1 with minimal change disease and found a combined CR and PR rate of 36%. In the second trial, we enrolled 8 subjects. The combined CR and PR rate was 29%. Analysis combining both trials showed a combined CR and PR rate of 33%. Adverse events were observed in 32% of subjects, with mood symptoms being most common. There were no serious adverse events related to the study. Conclusion: We conclude that high dose oral dexamethasone is well tolerated by adults with idiopathic nephrotic syndrome and may have some efficacy.

scholarly journals The Effect of Early Treatment with Intravenous Magnesium Sulfate on the Incidence of Cardiac Comorbidities in Hospitalized Stroke Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Kameron Bechler ◽  
Kristina Shkirkova ◽  
Jeffrey L. Saver ◽  
Sidney Starkman ◽  
Scott Hamilton ◽  
...  
Keyword(s):  
Adverse Events ◽  
Acute Stroke ◽  
Magnesium Sulfate ◽  
Serum Magnesium ◽  
High Dose ◽  
Stroke Patients ◽  
Serious Adverse Events ◽  
Intravenous Magnesium ◽  
Prophylactic Measures ◽  
Cardiac Adverse Events

Background. Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. Methods. This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. Results. Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R=1.04, 95% CI 1.03-1.06, p<0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. Conclusion. Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.

Intrathecal Liposomal Cytarabine (Depocyt) Is Safe and Effective for Prevention of Meningeal Disease in Patients with Acute Lymphoblastic Leukemia and High-Grade Lymphoma Treated with the HyperCVAD Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4594-4594 ◽  
Author(s):  
Brian McClune ◽  
Francis Buadi ◽  
Naveed Aslam ◽  
Donna Przepiorka
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adverse Events ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Liposomal Cytarabine ◽  
High Grade ◽  
Platelet Recovery ◽  
Significant Difference ◽  
Meningeal Disease

Patients with acute lymphoblastic leukemia (ALL) and high-grade lymphoma have a 10–20% risk of meningeal disease during induction and in remission when given standard-dose chemotherapy. This risk has been reduced to about 1% using intrathecal prophylaxis with cytarabine and methotrexate in addition to the systemic regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyperCVAD) alternating with high-dose methotrexate-cytarabine (MA). The discomfort and potential adverse events with frequent lumbar punctures may impair patient compliance. Liposomal cytarabine (Depocyt) is an intrathecal preparation of cytarabine with a prolonged half-life. Use of Depocyt could potentially reduce the number of lumbar punctures needed for routine neuroprophylaxis. We reviewed the tolerability and activity of Depocyt for neuroprophylaxis in 15 patients treated with the hyperCVAD regimen. The cohort included 12 males and 3 females of median age 48 years (range, 23–72 years) with precursor B-cell ALL (8), T-cell ALL (3), Burkitt lymphoma and HIV (2), Ph-positive ALL (1), and lymphoblastic lymphoma (1). The patients received a total of 65 cycles of systemic chemotherapy, 36 with hyperCVAD and 29 with MA. Depocyt was given IT or IO in 33 cycles, methotrexate IT in 5, and no intrathecal therapy in 27. When treated with Depocyt, patients also received dexamethasone pre- and postmedication.. The planned dose of Depocyt was 50 mg for all patients, but after one serious adverse event, the dose was reduced to 25 mg when administered by Omaya. Depocyt was instilled on a median of day 8 of the cycle (range, −4 to 13). To date, a meningeal relapse has not occurred in any of the patients. Although minor neurological events (transient headache or neckache) were not uncommon, there were two serious adverse events. One patient developed a severe but transient headache during the fourth cycle and was readmitted for pain control. A second patient received Depocyt four days prior to MA. Shortly after completing chemotherapy, this patient developed hyponatremia and somnolence. The neurological status normalized after several days with supportive care alone. Since leakage of Depocyt into the peripheral blood might cause myelosuppression, hematologic recovery was also assessed. There was a significant difference in time to ANC>500 (p=0.02) and platelets >20,000 (p=0.005) between hyperCVAD and MA cycles, so hematologic recovery was assessed separately for these regimens, as shown in the Table. Median Day of Hematopoietic Recovery Cycle Outcome All Cycles Depocyt No IT PX MTX IT “1” indicates the platelet count did not fall below 20,000 during that cycle. HyperCVAD ANC>500 15 15 14 16.5 Plts>20,000 1 1 1 1 MA ANC>500 16 16 16 15 Plts>20,000 13 13 14 15 There were no significant differences in time to neutrophil or platelet recovery between neuroprophylaxis regimens. Three patients received cranial or craniospinal radiation to compete neuroprophylaxis prior to allogeneic stem cell transplantation without notable neurotoxicity after transplantation. We conclude that it is safe to use a single dose of Depocyt (50 mg IT or 25 mg IO) following completion of administration of chemotherapy (around Days 6 – 8) during each cycle of the hyperCVAD regimen. This approach should be studied in a randomized trial to further assess its efficacy in comparison to more frequent instillations of methotrexate/cytarabine.

Balloon Kyphoplasty Improves Both Roland-Morris Disability Scores and Bone Pain among Cancer Patients with Vertebral Compression Fractures: Interim Analysis of Results from a Phase IV Random Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3695-3695
Author(s):  
James R. Berenson ◽  
John B Tillman ◽  
Mohamad A. Hussein ◽  
Robert Pflugmacher ◽  
Peter Jarzem ◽  
...  
Keyword(s):  
Back Pain ◽  
Adverse Events ◽  
Cancer Patients ◽  
Interim Analysis ◽  
Balloon Kyphoplasty ◽  
The United States ◽  
Vertebral Compression Fractures ◽  
Serious Adverse Events ◽  
Compression Fractures ◽  
Patients With Cancer

Abstract Destructive vertebral lesions are a common source of morbidity among patients with cancer. Balloon kyphoplasty is a minimally invasive surgical procedure performed for patients with painful vertebral compression fractures (VCFs) with the goal of reducing pain and disability and improving quality of life. We report the results of the first randomized trial among cancer patients with VCFs to assess the efficacy and safety of this procedure. Twenty-one sites in Europe, the United States, Canada and Australia enrolled 134 patients after consent and ethical review board approval. Adult patients diagnosed with a variety of cancers and ≤ 3 painful VCFs (VAS ≥ 4) were randomly assigned to immediate kyphoplasty (N=70) or nonsurgical supportive care (N=64). Patients with primary bone tumors, osteoblastic tumors or solitary plasmacytoma at the fracture site were excluded as well as patients with spinal cord compression. The primary objective was to determine the change in the Roland-Morris Disability questionnaire, a 0- (no disability) to 24-point (maximum disability) instrument validated for assessing back-specific physical functioning, at one month. Back pain was also assessed using a validated 0- (no pain) to 10-point (worst pain imaginable) numerical rating scale. Data from a preplanned interim analysis of this ongoing study are now reported. For pain and function, patients with complete data that has been evaluated through one month are included whereas all enrolled patients were analyzed for safety. Mean patient age was 64 years (range 37 to 88), 58% were female, and tumor types included multiple myeloma (36%), cancers of the breast (20%), lung (8%), prostate (6%) and other sites (30%). At study enrollment, 23% of patients were on daily corticosteroids and 48% had received bisphosphonates within 12 months of study entry. Prior to randomization, single VCFs were identified by the local investigators in 43% of patients; an equal proportion (29%) of patients had 2 or 3 fractures. Among the kyphoplasty and nonsurgical cohorts, 59 and 56 subjects, respectively were evaluable for the efficacy analysis. At baseline, average Roland-Morris scores were similar between the groups; 17.7 and 18.3 points for kyphoplasty and non-surgical-treated patients, respectively. However, at one month, there were marked differences between the two groups with a mean improvement for patients randomized to kyphoplasty of −8.3 points (95% CI −6.2 to −10.5) whereas those receiving non-surgical care showed no significant change (−0.1 points, 95% CI 0.9 to −1.0; p<0.0001 for difference). Mean baseline pain scores were also not different between the two groups (7.2 and 7.3 points for the kyphoplasty and nonsurgical groups, respectively). At one week, kyphoplasty-treated patients showed significant improvement in their back pain (−3.6 points, 95%CI, −2.8 to −4.4) whereas those patients treated non-surgically had no change in their pain (−0.3 points, 95%CI, 0.1 to −0.8; p<0.0001 for difference). Similar results for pain were obtained at one month; kyphoplasty resulted in a −4.1 point change (95%CI, −3.2 to −4.9) and those patients treated non-surgically had no change in their pain (−0.5 points; 95%CI, 0.04 to −1.0; p<0.0001 for difference). There was no significant difference in the number of patients with serious adverse events between the kyphoplasty (16) and nonsurgical (10) groups at one month. None of the serious adverse events in the kyphoplasty group were related to the devices used, including bone cement extravasation; one serious adverse event in the form of an intra-operative non-Q-wave myocardial infarction resolved and was attributed to anesthesia. This randomized study shows, at a pre-planned interim analysis time point, that patients with cancer-related VCFs treated with immediate balloon kyphoplasty show a marked reduction in back disability and pain at one month compared to non-surgical treatment. Pain reduction was also statistically significantly improved within one week postoperatively. Importantly, minimally clinically important differences for the Roland-Morris and pain scales used in this trial have been determined from previous studies and are estimated to be approximately 2.5 and 2.0 points, respectively. Thus, these improvements in disability and pain with balloon kyphoplasty were both statistically and clinically significant and achieved without an increase in adverse events.

scholarly journals Cingulotomy for medically refractory cancer pain

2013 ◽  
Vol 35 (3) ◽  
pp. E1 ◽  
Author(s):  
Ashwin Viswanathan ◽  
Viraat Harsh ◽  
Erlick A. C. Pereira ◽  
Tipu Z. Aziz
Keyword(s):  
Cancer Pain ◽  
Treatment Option ◽  
Early Postoperative Period ◽  
Cochrane Library ◽  
Cognitive Changes ◽  
Serious Adverse Events ◽  
Patients With Cancer ◽  
Pain Syndromes ◽  
Stereotactic Technique ◽  
The Cochrane Library

Object Cingulotomy has been reported in the literature as a potential treatment option for refractory cancer-related pain. However, the optimal candidates for this intervention and the outcomes are not well characterized. The goal of this study was to review the available literature on cingulotomy, specifically for cancer-related pain. Methods A search of PubMed, PubMed Central, the Cochrane Library, and MEDLINE was performed to identify all articles discussing cingulotomy for cancer pain. The text strings “cingul*” and “pain” were separated by the Boolean AND operator, and used to perform the query on PubMed. Only studies in which a stereotactic technique was used, as opposed to an open technique, and specifically detailing outcomes for cancer pain were included. For centers with multiple publications, care was taken not to double-count individual patients. Results The literature review revealed only 8 unique studies describing outcomes of stereotactic cingulotomy for cancer pain. Between 32% and 83% of patients had meaningful pain relief. The location of the lesion was variable, ranging between 1 cm and 4 cm posterior to the tip of the anterior horn. Although serious adverse events are rare, a decline in focused attention can been seen in the early postoperative period, along with apathy and decreased activity. Conclusions For patients with cancer pain with diffuse pain syndromes, head and neck malignancies, and significant emotional distress, cingulotomy may be a safe treatment option with minimal cognitive changes.

scholarly journals Intrathecal Analgesia Via a Percutaneous Port For the Management of Movement-Evoked Breakthrough Cancer Pain of Refractory Lower Extremity Cancer Pain: A Retrospective Review and Commentary

2021 ◽  
Author(s):  
Liang Zhou ◽  
Zhenggang Guo
Keyword(s):  
Lower Extremity ◽  
Cancer Pain ◽  
Pain Intensity ◽  
Breakthrough Pain ◽  
Infusion Therapy ◽  
The Mean ◽  
Intractable Cancer Pain ◽  
Time To Onset ◽  
Morphine Equivalent ◽  
Intrathecal Analgesia

Abstract Background and Objectives: Intrathecal analgesia (ITA) is a trusty treatment option for refractory and intractable cancer pain. However, there is still no general consensus on the analgesic effect of movement-evoked breakthrough pain (MEBTP) in the ITA setting. This study examined the effect of patient-controlled intrathecal analgesia (PCIA) on analgesic efficacy, emphasizing movement evoked breakthrough pain (MEBTP) in patients with refractory lower extremity cancer pain. Methods: A retrospective chart review included all patients with refractory lower extremity cancer pain who received Intrathecal morphine infusion therapy via percutaneous port (IMITPP) at our hospital between January 2017 and December 2020. Data on the numerical pain rating scales (NRS) scores, opioid doses, and complications were collected from medical records prior to IMITPP and at a one-month postimplant visit.Results: A total of 16 patients were included in the study group. Mean SRPI (spontaneous resting pain intensity) decreased from 8.75 pre- IMITPP to 3.75 post- IMITPP, (P < 0.001); mean MEPI (movement-evoked breakthrough pain intensity) fell from 8.83 pre- IMITPP to 4.25 post- IMITPP (P < 0.001); mean daily morphine equivalent dosing decreased from 360 mg/d to 48mg/d (P< 0.001); mean daily morphine equivalent dosing for MEBTP decreased from 87 mg/d to 6 mg/d (P< 0.001). Both total and breakthrough dosing of conventional opioid medications significantly decreased following the initiation of ITT with PCIA. The mean perceived time to onset with conventional movement evoked breakthrough medications was 38 minutes, and the mean perceived time to onset with PCIA was 8 minutes (P < 0.001). Conclusions: IMITPP was associated with improved pain control in patients with refractory lower extremity cancer pain. Compared with conventional MEBTP medication, appropriate PCIA provided superior analgesia and a much faster onset of action.

scholarly journals Pharmacokinetics, safety, and tolerability of a THC:CBD oil formulation in patients with chronic non-cancer pain on long term high dose opioid analgesia.

2021 ◽  
Author(s):  
Yvonne Bonomo ◽  
Amanda Norman ◽  
Lisa Collins ◽  
Helen O'Neill ◽  
Peter Galettis ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Oral Morphine ◽  
Individual Variability ◽  
Secondary Outcome ◽  
Opioid Analgesia ◽  
High Dose ◽  
Clinical Effects ◽  
Open Label ◽  
Blood Concentrations ◽  
Sleep Parameters

Aim This Phase I open label study examined pharmacokinetics, safety, and tolerability of escalating doses of a combination cannabinoid medication (1:1 ratio THC:CBD) in patients with chronic non-cancer pain (CNCP) on high dose opioid analgesia. Methods Nine people with CNCP and oral morphine equivalent daily dose of ≥60mg were recruited. Blood concentrations of THC, 11-hydroxytetrahydrocannabinol (OH-THC), 11-nor-9-carboxy-tetrahydrocannabinol (COOH-THC) and CBD were assayed weekly. Concentrations were measured after a single dose of 2.5mg THC/2.5mg CBD up to 12.5mg THC/12.5mg CBD on Day 29. Follow-up was on Day 36 after 7 day washout. Secondary outcome data encompassed pain, mood, and sleep parameters. Results The parent THC, CBD, OH-THC, COOH-THC were detected at most time points. In general, the concentration of all analytes increased until 2 hours post-administration, decreasing to approximately pre-dose concentrations by 8 hrs. There was considerable inter- and intra-individual variability. The study medication was well tolerated. Eight participants reported at least one Adverse Event (AE), with a total of 62 AEs; most common were euphoric mood, headache, and agitation, none classified as severe. There was no significant change to pain severity self-ratings, nor use of pain medications. Improvements in pain interference scores, mood, and some sleep parameters were observed. Conclusion The THC:CBD formulation was tolerated well in a CNCP patient group. Between-participant variability supports personalized dosing and “start low-go slow” titration. Improvements in pain, mood, and sleep parameters suggest that on relatively low dosages clinical effects are apparent. To validate and quantify findings a comparison placebo group study is needed.

scholarly journals Intracerebroventricular Pain Treatment with Analgesic Mixtures including Ziconotide for Intractable Pain

2016 ◽  
Vol 6;19 (6;7) ◽  
pp. E905-E915
Author(s):  
Hélène Staquet
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Cancer Pain ◽  
Rating Scale ◽  
Pain Treatment ◽  
Third Ventricle ◽  
High Dose ◽  
Intractable Pain ◽  
Intracerebroventricular Infusion ◽  
Intractable Cancer Pain

Intracerebroventricular (ICV) administration of opioids for control of intractable cancer pain has been used since 1982. We present here our experience of intracerebroventricular administration of pain treatments including ziconotide associated with morphine and ropivacaine for patients resistant to a conventional approach, with nociceptive, neuropathic, or mixed pain. These clinical cases were conducted with patients suffering from refractory pain, more than 6/10 on a numerical pain rating scale (NPRS) while on high-dose medical treatment and/ or intolerance with significant side effects from oral medication. The baseline study visit included a physical examination and an assessment of pain intensity on a NPRS. Under general anesthesia, a neuronavigation device was used to place the catheter on the floor of the third ventricle, supported by an endoscope. Then, drugs were injected in the cerebroventricular system, through a pump (external or subcutaneous). The primary objective was to measure pain evaluation with ICV treatment after a complete withdrawal of other medications. Four patients were enrolled: 3 with intractable cancer pain and one with central neuropathic pain. The median NPRS at baseline was 9.5 [8.5; 19]. The mean NPRS after one month was 3.5 [3; 4.5]. Ziconotide was initiated at 0.48 µg/dy and up to a median of 1.2 µg/dy [1.0; 1.56]. The median dose of morphine and ropivacaine used initially was respectively 0.36 mg/dy [0.24; 0.66] up to 0.6 mg/dy [0.45; 4.63] and 1.2 mg/dy [0; 2.4] up to 2.23 mg/dy [1.2; 3.35]. Minor side effects were initially observed but transiently. One psychiatric agitation required discontinuation of ziconotide infusion. For intractable pain, using ziconotide by intracerebroventricular infusion seems safe and efficient, specifically for chronic neoplastic pain of cervicocephalic, thoracic, or diffuse origin and also for pain arising from a central neuropathic mechanism. Key words: Intracerebroventricular infusion, ziconotide, intractable pain, nociceptive and neuropathic pain

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