Methylene blue for intractable pain from oral mucositis related to cancer treatment: a randomized phase 2 clinical trial.

BACKGROUND: Oral mucositis (OM) in patients receiving cancer therapy is thus far not well managed with standard approaches. We aimed to assess the safety and effectiveness of methylene blue (MB) oral rinse for OM pain in patients receiving cancer therapy. METHODS: In this randomized, single-blind phase 2 clinical trial, patients were randomized to one of four arms: MB 0.025%+conventional therapy (CTx) (n = 15), MB 0.05%+CTx (n = 14), MB 0.1%+CTx (n = 15), or CTx alone (n = 16). Intervention groups received MB oral rinse every 6 h for 2 days with outcomes measured at days 1-2; safety was evaluated up to 30 days. The primary outcome measured change in the pain numeric rating scale (0-10) from baseline to day 2. Secondary outcome measured change in oral function burden scores from baseline to day 2, World Health Organization OM grades, morphine equivalent daily doses, and adverse events. The trial was registered with ClinicalTrials.gov ID: NCT03469284. RESULTS: Sixty patients (mean age 43, range 22-62 years) completed the study. Compared with those who received CTx alone, those who received MB had a significant reduction of pain scores at day 2 of treatment (mean ± SD); 0.025%: 5.2 ± 2.9, 0.05%: 4.5 ± 2.9, 0.1%: 5.15 ± 2.6) and reduction of oral function burden scores (0.025%: 2.5 ± 1.55, 0.05%: 2.8 ± 1.7, 0.1%: 2.9 ± 1.60). No serious adverse events were noted, but eight patients reported burning sensation of the oral cavity with the first dose, and this caused one patient to discontinue therapy. CONCLUSIONS: MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03469284.

Methylene Blue for the Treatment of Intractable Pain From Oral Mucositis Related to Cancer Treatment: An Uncontrolled Cohort.

BACKGROUND: Oral mucositis is a complication of cancer therapy, causing severe pain that affects oral functioning, nutrition, and quality of life, as well as therapy nonadherence or dose-limiting toxicity. Anecdotal experience has suggested that methylene blue (MB) oral rinse may be an effective and safe treatment of this oral pain. METHODS: To evaluate the efficacy and safety of MB oral rinse for the treatment of oral pain due to mucositis in patients with cancer, we retrospectively evaluated patients who experienced refractory pain despite conventional therapy. RESULTS: We identified 281 patients who received MB oral rinse. Most were receiving treatment for leukemia (n=85; 30.3%) and head and neck squamous cell carcinoma (n=84; 29.9%). The most common treatments were radiation therapy alone (n=108; 38.4%) and chemoradiation (n=86; 30.6%). Median duration of symptoms was 14 days. Mean (SD) numeric rating scale pain scores were 7.7 (1.83; median, 8) before MB oral rinse and 2.51 (2.76; median, 2) after MB oral rinse (P<.0001). Most patients achieved pain control within the first 3 doses. The effectiveness of MB oral rinse was independent of patient age, sex, cancer type, cancer stage, MB dilution, and pain duration or baseline pain scores. The lowest response to treatment was reported in individuals with esophageal mucositis. Few patients experienced adverse effects of MB oral rinse (n=13; 4.6%); 10 had a transient burning sensation, 2 had transient blue discoloration of the teeth and mouth, and 1 had increased pain. CONCLUSIONS: MB oral rinse is an effective and safe treatment for refractory pain from oral mucositis related to cancer treatment.

High-flow oxygen and pro-serotonin agents for non-interventional treatment of post-dural-puncture headache.

OBJECTIVE: Post dural puncture headache (PDPH) is a common complication in patients following diagnostic or therapeutic lumbar puncture, procedures requiring epidural access, and spinal surgery. Epidural blood patch (EBP), the gold standard for the treatment of this pathology requires training not provided to emergency physicians. In addition, the presence of concomitant pathology and abnormal laboratory values are contraindications to perform EBP. In presence of these limitations, we sought for a non-interventional management of PDPH utilizing high-flow oxygen and pro-serotonin agents. We reviewed the mechanism of action of this therapy METHODS: To illustrate our proposal, we report a series of twelve consecutive patients with PDPH treated with high-flow oxygen therapy at 12 L/min via a non-rebreathing mask and intravenous metoclopramide. RESULTS: All patients were treated with this conservative therapy, no adverse reactions were observed. After the intervention, the headache resolved without further indications for PDPH. CONCLUSION: Our series suggests that combining high-flow oxygen and pro-serotonin agents such metoclopramide in the ED might be a feasible option as effective as the invasive methods used in treating PDPH. This therapy appears to be efficient and to minimize risk, cost and side effects. It presents an easily accessible alternative that should be considered when PDPH is not a viable option.

Normal Saline Trigger Point Injections vs Conventional Active Drug Mix for Myofascial Pain Syndromes.

BACKGROUND: Myofascial pain syndrome (MPS) originates in the muscle and fascia. MPS presents with referred pain specific for each muscle and a trigger point that reproduces the symptoms. Trigger-point-injection (TPI) is an effective approach to treating MPS. Some TPI agents, however, are associated with systemic and local side effects. OBJECTIVE: The aim of this study was to evaluate the effectiveness of TPI with a conventional active drug mixture (CADM) vs. that with normal saline solution (NS) alone in patients with MPS presenting to the emergency department (ED). METHODS: Adults with MPS diagnosed in the ED, participants were randomly assigned to receive TPI with NS or with CADM. Pain intensity was scored using a 0-10 numeric rating scale prior to and after TPI, before discharge and 2 weeks after TPI. RESULTS: Among 48 patients analyzed, 23 received TPI with NS. The mean pain scores were as follows: immediately before TPI, 7.59 (NS) and 7.44 (CADM); immediately after TPI, 2.22 (NS) and 1.76 (CADM); prior to discharge, 1.52 (NS) and 1.76 (CADM). At 2-week follow up, the mean pain scores were 4.29 (NS) and 4.14 (CADM). Pain was significantly reduced after TPI in both groups. At 2 weeks, the mean pain scores were similar between the groups. No adverse events were reported. CONCLUSION: In cases of MPS in the ED, pain can be controlled with TPI independent of the injectate. TPI with NS may be preferred over CADM because of its lower cost and more favorable side effect profile.

Methylene Blue for the Treatment of Intractable Pain Associated with Oral Mucositis.

Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develops intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative. Current recommendations to treat mucositis and its related pain include basic oral care, bland oral rinses, topical anesthetics, and systemic analgesics. We believe that chemical neurolysis of the affected areas with methylene blue used as an oral rinse is a noninvasive, efficient, safe, and cost-effective alternative that can provide prolonged analgesia in patients with intractable pain of oral mucositis. The benefits of this therapy are reflected in its improvement of patients' quality of life by enabling oral feeding and controlling pain. We report a series of 5 consecutive patients with intractable oral mucositis-related pain despite conventional treatment with systemic opiates. All 5 patients responded well to the use of 0.05% methylene blue as mouth rinse, demonstrating sustained analgesia over 3 weeks. The treatment was tolerated well, and overall patient satisfaction was very high. We also observed that methylene blue rinse significantly reduced the total opioid requirement, as demonstrated by reductions in the patients' morphine equivalent daily dose scores after its use. Our case series suggests that 0.5% methylene blue oral rinse therapy is an effective and inexpensive modality that can be used safely to palliate intractable oral pain in patients with mucositis associated with cancer treatment. To our knowledge, this is the first report using this therapy to treat pain from oral mucositis.

Magnetic fields and intrathecal pump malfunction.

Medical technology has impacted the overall life expectancy. Many conditions traditionally considered fatal are now curable. Surviving chronic diseases and aging of the population have increased the number of people with chronic pain. Many devices are also available to manage severe refractory pain. As such, implantable drug-delivery system (IDDS) is a small battery-powered, programmable pump implanted under the subcutaneous tissue of the abdomen and connected to a small catheter tunneled into the spine. Implantable drug-delivery system is used for the administration of morphine, ziconotide, baclofen, or their mixtures into the cerebrospinal fluid. Like many medical devices, IDDS has technical glitch which limits its performance under certain conditions. Implantable drug-delivery system is susceptible to magnetic field such as a magnetic resonance imaging (MRI) which can temporarily stall the rotor of the pump motor and suspend drug delivery. We encountered a patient from out of town seen at emergency department with increased pain and symptoms of opiates withdrawal after intermittent IDDS malfunction. He denied any exposure to magnetic fields or MRI. However, the pump interrogation showed multiple motor stall events in the event log. After a detailed inquiry, the most likely cause of pump malfunction appears to be frequent placement of a laptop computer on his abdomen close to the pump. The magnets in the laptop speakers may have caused the rotor of the pump motor to stall during the computer use, and frequent stall has caused symptoms of withdrawal. No other mechanical failures were found. The patient was discharged home after the symptoms resolved, and the pump was reprogrammed.

Myofascial Pain Syndromes in the Emergency Department: What Are We Missing?

BACKGROUND: Myofascial pain syndrome (MPS), pain originating in the myofascial tissue, is a widely recognized pathology characterized by the presence of referred pain (often distant from its origin and specific to each muscle) that can resemble other pathologies and by the presence of a trigger point, a localized hyperirritable band able to reproduce the pain and its associated symptoms. Patients with acute or chronic MPS are commonly seen in the emergency department (ED), usually complaining of pain of undetermined origin. Traditionally, the emergency physician (EP) is not trained to diagnose and treat MPS, and many patients with MPS have received less than optimal management of this condition in the ED. Many types of treatments are known to be effective against MPS. Among these, trigger point injection (TPI) is considered a practical and rapid approach that can be carried out in the ED by EPs. OBJECTIVE: This article reviews the current diagnostic methods, treatment options, and procedures for MPS patients seen in the ED to enable EPs to diagnose and successfully treat this condition. DISCUSSION: This article discusses the clinical characteristics, etiology, diagnosis, and treatment of MPS in the ED, including a description of performing TPI. CONCLUSIONS: MPS can mimic other clinical conditions commonly seen in the ED. MPS can be diagnosed on the basis of clinical findings; in many cases, no imaging or laboratory testing is needed. Therefore, MPS diagnosis and treatment can be successfully accomplished in the ED by EPs.

Chest pain a manifestation of migraine.

BACKGROUND: Chest pain is an alarming symptom; it justifies many visits to the emergency department (ED). The etiology is often unknown. Chest wall pain in the presence of migraine headache, although not a common occurrence, is intriguing when it resolves with antimigraine treatment. OBJECTIVES: To characterize the manifestations and outcomes and investigate the relationship between chest wall pain and headache as a manifestation of migraine exacerbation. METHODS: Among patients visiting our ED, we identified those individuals whose pain originated in the chest wall in the setting of migraine exacerbation. Patients with clinical indications for specific treatments were dispositioned accordingly. Control of symptoms including chest pain and headache with antimigraine agents was considered the primary outcome. A prospective follow-up via telephone interview and medical records review was performed. RESULTS: We collected a convenience sample of 33 patients. All manifested migraine headache with an earlier onset than the chest pain, and all had taken medications prior to visiting the ED. Twelve patients reported a higher visual analog scale score for the headache than for the chest pain. Still, chest pain was the main complaint. The chest pain originated at the chest wall. Ten patients received sublingual nitroglycerin or opiates, or both; no pain relief was reported. However, all symptoms resolved with metoclopramide. On follow-up, 6 patients reported recurrence of chest pain with subsequent migraines. CONCLUSIONS: Chest pain can be a complication of migraine. The treatment should be focused on migraine control. Migraine should be included in the differential diagnosis of chest pain.

Diagnostic and therapeutic value of intracellular biomarker testing in chronic pain.

Aim: Micronutrient and metabolic compound supplementation as a method of treating chronic pain is not well understood. Case: A 58 year-old woman presented with refractory painful neuropathy. She did not respond to conservative treatment and was seeking spinal cord stimulator implantation. She underwent a biomarker panel that revealed low intracellular levels of multiple compounds. As she supplemented her deficiencies, her symptoms fully resolved, and the implant was no longer indicated. Discussion: Micronutrient and metabolic compound testing could potentially expand non-invasive treatment options for patients with refractory chronic pain. Caution should be exercised given limited regulatory oversight in the supplement industry and actively ongoing nutritional research. Conclusion: Biomarker testing panels may be a useful adjunct in the management of refractory neuropathic pain.

Methylene Blue, a Unique Topical Analgesic: A Case Report.

Background: Rectal prolapse is a circumferential, full-thickness protrusion of the rectum through the anus, which, if not properly managed, may become incarcerated and pose a risk of strangulation. This pathology is rarely a medical emergency unless a complication is encountered. Such complications include infection, necrosis, perforation, incarceration, and uncontrolled pain. Case Presentation: We report a case of an elderly patient with pain associated with chronic rectal prolapse. Surgical intervention had been ruled out, and there had been no pain relief after using systemic analgesics. Case Management: Based on increasing reports of analgesic properties, topical methylene blue (MB) 0.1% was applied externally at the prolapsed organ, obtaining pain relief. Case Outcome: The patient experienced immediate and long-lasting pain relief; MB applications were continued every 12 hours as needed. After this therapy, the patient was no longer in need of systemic analgesics. No side effects were reported. Conclusion: Topical MB may be an effective analgesic for the management of pain associated with chronic rectal prolapse. This treatment might be extrapolated to other clinical scenarios of tegumentary pain. Similar use has been shown to be safe and effective in other pathologies, including pain in oral mucositis associated with cancer therapy.

Longus colli tendonitis, clinical consequences of a misdiagnosis.

Numerous pathologies diagnosed in the emergency department (ED) are treated with invasive procedures involving anesthetic and surgical risks. Retropharyngeal abscess is a serious condition requiring emergent treatment, often in need of trans-oral incision and drainage under general anesthesia. A misdiagnosis, especially after surgical treatment, might generate undesirable consequences, more so if the final diagnosis is a non-surgical pathology such as longus colli (LC) tendonitis. To discuss the etiology, differential diagnosis and treatment of LC tendonitis, a clinical condition still misdiagnosed despite advanced imaging techniques. A middle-aged man presented to a satellite ED with sore throat, neck pain and stiffness. A computed tomography (CT) scan of the neck with intravenous contrast was read as retropharyngeal abscess. He was transferred to our ED after acceptance by ear-nose-throat (ENT) surgery. He was scheduled for open incision and drainage under general anesthesia. A detailed evaluation by our ED staff revealed a nontoxic patient with no compromise of the airway. His physical exam was unrevealing and a second review of the CT demonstrated typical radiological signs for LC tendonitis. After a discussion with ENT the patient was discharged home on anti-inflammatory medications and oral steroids. He recovered well and no further intervention was needed. Longus colli tendonitis is a rare condition that mimics emergent surgical conditions. Emergency physicians are qualified to make a clinical and radiological diagnosis. While CT scan can provide a diagnosis, the primary evaluation tool is an adequate medical interview and physical exam.

Methylene Blue for the Treatment of Radiation-Induced Oral Mucositis during Head and Neck Cancer Treatment: An Uncontrolled Cohort.

Pain from radiation-therapy-induced oral mucositis during head-neck cancer treatment is aggravated by concurrent chemotherapy and commonly fails traditional treatments. To explore safe and sustainable alternatives, we investigated methylene blue oral rinse to reduce radiation-therapy-related oral mucositis pain. For this, we conducted a retrospective observational cohort study in a tertiary-care academic care cancer center including 85 patients with refractory oral mucositis pain during radiation therapy for head-neck cancer. Changes in pain (scale 0-10), oral function burden (scale 0-6) and requirement for percutaneous endoscopic gastrostomy tube placement were measured. Among 58 patients, 60% received radiation therapy alone and 40% received concurrent chemotherapy-radiation therapy. Methylene blue oral rinse (MBOR) significantly decreased oral mucositis pain for at least 6.2 h (median + SD 8 ± 1.68 before vs. 2 ± 2.20 after; p < 0.0001) and oral function burden (3.5 ± 1.33 before vs. 0 ± 0.86 after; p < 0.0001). Eleven patients (19%) had percutaneous endoscopic gastrostomy tubes placed before using methylene blue oral rinse; subsequently, four (36%) resumed oral alimentation after methylene blue oral rinse. Two patients (3%) required percutaneous endoscopic gastrostomy tubes despite methylene blue oral rinse. Minimal adverse events were reported (n = 9, 15%). Our study showed that methylene blue oral rinse was an effective and safe topical treatment for opioid-refractory oral pain from oral mucositis associated with radiation therapy for head-neck cancer.

Temporal characterization of acute pain and toxicity kinetics during radiation therapy for head and neck cancer. A retrospective study.

Objectives: Pain during Radiation Therapy (RT) for oral cavity/oropharyngeal cancer (OC/OPC) is a clinical challenge due to its multifactorial etiology and variable management. The objective of this study was to define complex pain profiles through temporal characterization of pain descriptors, physiologic state, and RT-induced toxicities for pain trajectories understanding. Materials and methods: Using an electronic health record registry, 351 OC/OPC patients treated with RT from 2013 to 2021 were included. Weekly numeric scale pain scores, pain descriptors, vital signs, physician-reported toxicities, and analgesics were analyzed using linear mixed effect models and Spearman's correlation. Area under the pain curve (AUCpain) was calculated to measure pain burden over time. Results: Median pain scores increased from 0 during the weekly visit (WSV)-1 to 5 during WSV-7. By WSV-7, 60% and 74% of patients reported mouth and throat pain, respectively, with a median pain score of 5. Soreness and burning pain peaked during WSV-6/7 (51%). Median AUCpain was 16% (IQR (9.3-23)), and AUCpain significantly varied based on gender, tumor site, surgery, drug use history, and pre-RT pain. A temporal increase in mucositis and dermatitis, declining mean bodyweight (-7.1%; P < 0.001) and mean arterial pressure (MAP) 6.8 mmHg; P < 0.001 were detected. Pulse rate was positively associated while weight and MAP were negatively associated with pain over time (P < 0.001). Conclusion: This study provides insight on in-depth characterization and associations between dynamic pain, physiologic, and toxicity kinetics. Our findings support further needs of optimized pain control through temporal data-driven clinical decision support systems for acute pain management.

Penetrating atherosclerotic ulcerative disease of the aorta: do emergency physicians need to worry?

BACKGROUND: In recent years, different aortic pathologies have been grouped together and described in terms of a spectrum of disease referred to as Acute Aortic Syndrome (AAS). Overlapping of these conditions has traditionally introduced discrepancy to the understanding of the pathophysiology and definitive care. Penetrating atherosclerotic ulcer (PAU), an ulceration of an atherosclerotic plaque, has been increasingly recognized as the individual cause of the acute aortic pathology. OBJECTIVE: The natural evolution and complications of PAU are described, as well as the current diagnostic strategies, definitive management options, and initial care in the emergency department. DISCUSSION: The natural history of PAU is variable but is generally considered to be an AAS with a high incidence of complications. The clinical differentiation of symptomatic PAU from other causes of AAS is very challenging. Computed tomography imaging has provided additional accuracy with the use of the retrospective electrocardiographic gating technique. Despite traditional surgical therapies for aortic pathology, later studies have demonstrated the success of non-operative management, such as endoluminal grafting. CONCLUSION: The relative rarity of this disease, the difficulties in its detection, and the lack of precise guidelines about its management may result in diagnostic delays. Asymptomatic patients with well-controlled blood pressure are safely managed as outpatients in close consultation with vascular surgery.

Non-Invasive Pelvic Floor Rehabilitation in Cancer Population: An Incomplete Cohort.

BACKGROUND: Pelvic floor dysfunction and its associated symptoms are a common clinical challenge in the cancer population. Despite the noninvasive nature of pelvic floor rehabilitation (PFR) for this condition and the promising clinical results observed with its use, PFR appears to be an underused therapy. OBJECTIVES: The purpose of this study was to quantify the association between physical therapy of the pelvic floor and its effect on pain relief and the associated symptoms in cancer patients with pelvic floor dysfunction. STUDY DESIGN: Retrospective cohort study. METHODS: With the use of an electronic database in our pain medicine department, we retrospectively quantified the pain relief and symptom improvement in patients diagnosed as having chronic pelvic floor dysfunction who had undergone PFR. RESULTS: Of the 68 patients available for analysis, 49 met the inclusion criteria. Baseline characteristics of included patients were generally similar. The duration of pelvic pain before PFR was 53.7 months (mean) (SD, 182.5 months; median, 12 months). Of the 49 study patients, 23 (47%) had bladder dysfunction, 24 (49%) had dyspareunia, 2 (4%) had erectile dysfunction, and one (2%) had rectal dysfunction. Most symptoms associated with pelvic floor dysfunction resolved after PFR. LIMITATIONS: Single-center, small data, retrospective study. CONCLUSIONS: PFR is an effective tool for treating the pain associated with pelvic floor dysfunction and its related symptoms. This conservative approach can contribute to lowering the use of opiate analgesics.

Sacroiliitis in cancer patients: a review of current literature.

The sacroiliac (SI) joint can be directly jeopardized by malignancy and indirectly by ergonomic changes of pelvic obliquity that introduces uneven weight distribution. Cancer treatment can exacerbate preexisting arthritis and cause diffuse arthropathies, but these are unlikely to be isolated to the SI joint. The cancer population is exposed to unique stressors that might facilitate development of SI joint pain that includes cancer itself and therapy-related complications. Like the general population, cancer patients are subject to aging and BMI and musculoskeletal structural changes that affect symmetric body functioning and posturing. No frank association between sacroiliitis and cancer has been identified. Therefore, we believe there is a need to characterize any relationship between cancer and SI joint dysfunction and pain.

Lack of association between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and pain improvement in patients with oral cancer.

BACKGROUND: There is a growing body of literature implicating angiotensin II in the modulation of tumour-associated inflammation and pain. However, the impact of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) on pain and inflammation has not yet been studied in oral cancers. The objective is to investigate the role of ACEi and ARB pharmacotherapy on preoperative pain and inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), in patients with oral cancer. METHODS: We performed a retrospective study on patients who underwent oral cancer surgery. The Wilcoxon rank-sum test or Kruskal-Wallis analysis was used to evaluate differences in demographic, tumour-related and preoperative characteristics and amongst patients using ARBs, ACEis and no treatment. Multivariable analysis was fitted to estimate the effects of important covariates on severe preoperative pain. RESULTS: A total of 162 patients with oral malignancies were included in the study. After adjusting for significant covariates, patients with perineural invasion were found to have higher levels of pain (p = 0.0278). Similarly, patients taking ARBs were found to have lower levels of perineural invasion (p = 0.035). The analysis did not demonstrate a significant difference in pain levels when comparing ARBs or ACEis to the no treatment group (p = 0.250). Furthermore, the use of ARB or ACEi did not significantly alter preoperative NLR (p = 0.701) or MLR (p = 0.869). CONCLUSIONS: When compared to no treatment, ARBs and ACEis are not associated with significant analgesic effect or decreased inflammatory scores (NLR, PLR and MLR).