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PURPOSE OF REVIEW: Spinal cord stimulation (SCS) is an increasingly utilized therapy for the treatment of neuropathic pain conditions. Though minimally invasive and reversable, there are several important device-related complications that physicians should be aware of before offering this therapy to patients. The aim of this review is to synthesize recent studies in device-related SCS complications pertaining to cylindrical lead implantation and to discuss etiologies, symptoms and presentations, diagnostic evaluation, clinical implications, and treatment options. RECENT FINDINGS: Device-related complications are more common than biologic complications. Device-related complications covered in this review include lead migration, lead fracture, lead disconnection, generator failure, loss of charge, generator flipping, hardware related pain, and paresthesia intolerance. The use of SCS continues to be an effective option for neuropathic pain conditions. Consideration of complications prior to moving forward with SCS trials and implantation is a vital part of patient management and device selection. Knowledge of these complications can provide physicians and other healthcare professionals the ability to maximize patient outcomes.
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PURPOSE OF REVIEW: It is essential to have validated and reliable pain measurement tools that cover a wide range of areas and are tailored to individual patients to ensure effective pain management. The main objective of this review is to provide comprehensive information on commonly used pain scales and questionnaires, including their usefulness, intended purpose, applicability to different patient populations, and associated advantages and disadvantages. RECENT FINDINGS: Acute pain questionnaires typically focus on measuring the severity of pain and the extent of relief achieved through interventions. Chronic pain questionnaires evaluate additional aspects such as pain-related functional limitations, psychological distress, and psychological well-being. The selection of an appropriate pain scale depends on the specific assessment objectives. Additionally, each pain scale has its strengths and limitations. Understanding the differences among these pain scales is essential for selecting the most appropriate tool tailored to individual patient needs in different settings. CONCLUSION: Medical professionals encounter challenges in accurately assessing pain. Physicians must be familiar with the different pain scales and their applicability to specific patient population.
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Dor Aguda , Dor Crônica , Humanos , Medição da Dor , Dor Crônica/diagnóstico , Dor Crônica/terapia , Dor Crônica/psicologia , Inquéritos e Questionários , Manejo da Dor , Avaliação da DeficiênciaRESUMO
BACKGROUND: Thalamic pain syndrome (TPS) is an enigmatic and rare condition. Thalamic pain syndrome is under the umbrella of central pain syndrome, which is classically associated with multiple sclerosis, spinal cord injury, postamputation, epilepsy, stroke, tumor, and Parkinson's disease. The mainstay treatment of TPS is polypharmacy. There is uncertainty about the intermediate options to manage medication-resistant TPS before resorting to invasive, and often expensive, intracranial therapies. Stellate ganglion block (SGB) has shown promise in reducing TPS symptoms of the upper extremity and face following a thalamic ischemic event. AIMS: Discuss the effect and potential utility of SGB on ipsilateral headache, facial, and upper extremity neuropathic pain due to thalamic malignancies. MATERIALS AND METHODS: A review of two patient records that underwent SGB for treatment of TPS of oncologic origin. RESULTS: We present two cases of the successful use of SGB for the treatment of oncologic-related TPS for patients who had failed other conservative pharmacologic measures. DISCUSSION: Chronic pain is a complex experience that often simultaneously involves psychosocial, neuropathic, and nociceptive constituents. Among advanced cancer patients, factors such as an individual's spirituality, psychological stressors, and views on their mortality add layers of intricacy in addressing their pain. While TPS has been characterized in both stroke populations and oncologic populations, the treatment of SGB for pain relief in TPS has been limited to the stroke population. Repeated SGB worked to alleviate the ipsilateral headache, facial, and upper extremity pain in these two patients. The benefits of utilization of SGB, with the possibility of pain relief, within the thalamic malignancy population cannot be understated. CONCLUSION: In summary, ultrasound-guided SGB may be considered in patients with TPS due to thalamic cancer, before pursuing more invasive intracranial surgeries to treat pain.
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Bloqueio Nervoso Autônomo , Dor Crônica , Neoplasias , Acidente Vascular Cerebral , Humanos , Gânglio Estrelado , CefaleiaRESUMO
PURPOSE OF REVIEW: The aim of this review is to educate healthcare professionals regarding buprenorphine for the use of opioid use disorder (OUD) as well as for chronic pain management. This review provides physicians and practitioners with updated information regarding the distinct characteristics and intricacies of prescribing buprenorphine. RECENT FINDINGS: Buprenorphine is approved by the US Food and Drug Administration (FDA) for acute pain, chronic pain, opioid use disorder (OUD), and opioid dependence. When compared to most other opioids, buprenorphine offers superior patient tolerability, an excellent half-life, and minimal respiratory depression. Buprenorphine does have notable side effects as well as pharmacokinetic properties that require special attention, especially if patients require future surgical interventions. Many physicians are not trained to initiate or manage patients on buprenorphine. However, buprenorphine offers a potentially safer alternative for medication management for patients who require chronic opioid therapy for pain or have OUD. This review provides updated information on buprenorphine for both chronic pain and OUD.
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Dor Aguda , Buprenorfina , Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Humanos , Buprenorfina/uso terapêutico , Dor Crônica/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor Aguda/tratamento farmacológico , Tratamento de Substituição de OpiáceosRESUMO
OBJECTIVES: Patients with spinal lesions or vertebral compression fractures from multiple myeloma often present with back pain that restricts their ability to lie flat and prevents them from undergoing cancer treatment. Temporary, percutaneous peripheral nerve stimulation (PNS) has been described for cancer pain secondary to oncologic surgery or neuropathy/radiculopathy from tumor invasion. The purpose of this case series is to show the use of PNS as an analgesic bridge therapy to treat myeloma-related back pain and allow patients to complete their course of radiation. MATERIALS AND METHODS: Temporary, percutaneous PNS was placed under fluoroscopic guidance for four patients with unremitting low back pain secondary to myelomatous spinal lesions. Before PNS, the patients had pain refractory to medical management and were unable to tolerate radiation mapping and treatment owing to low back pain while supine. Patients were followed with routine clinic visits to monitor pain and progression through cancer therapy. PNS was removed after approximately 60 days or after completion of radiation. RESULTS: This case series presents four successful cases of PNS to treat low back pain from myelomatous spinal lesions and associated vertebral compression fractures. PNS targeted the medial branch nerves to treat both nociceptive and neuropathic low back pain. All four patients successfully completed radiation therapy with PNS in place. CONCLUSIONS: PNS can effectively treat low back pain secondary to myeloma-related spinal lesions as a bridge therapy to radiation. The use of PNS is a promising option for back pain from other primary or metastatic tumors. Further research is needed into the use of PNS for cancer-related back pain.
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Fraturas por Compressão , Dor Lombar , Mieloma Múltiplo , Doenças do Sistema Nervoso Periférico , Fraturas da Coluna Vertebral , Humanos , Dor Lombar/etiologia , Dor Lombar/terapia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Terapia Ponte , Resultado do Tratamento , Fraturas da Coluna Vertebral/terapia , Fraturas da Coluna Vertebral/cirurgia , Dor nas Costas/etiologia , Dor nas Costas/terapia , Nervos PeriféricosRESUMO
PURPOSE OF REVIEW: Chronic lower back pain is a crippling condition for the individual and a significant burden on society. It is notoriously challenging to manage despite access to invasive interventions. Understanding hypnosis as a powerful therapeutic adjunct to this condition allows holistic treatment of patients in distress. RECENT FINDINGS: In addition to classic etiologies of chronic lower back pain, hypnosis has proven to be beneficial in chronic back pain caused by pregnancy, diabetic and HIV neuropathy. Combination of hypnosis with other mind-body techniques such as olfactory stimulation, music therapy and patient education offers further promise to this treatment modality. Our review provides a run-through of the fundamental mechanisms of hypnosis in moderating chronic back pain, its quantifiable benefits, its novel areas of use and its potentials in the future based on the most recent and relevant peer-reviewed literature in order to guide clinicians to better deploy this valuable resource.
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Dor Crônica , Hipnose , Dor Lombar , Dor nas Costas , Dor Crônica/terapia , Feminino , Humanos , Dor Lombar/terapia , Manejo da Dor , GravidezRESUMO
OBJECTIVES: Spinal cord stimulation (SCS) involves electrical stimulation of the dorsal spinal cord to disrupt the transmission of ascending pain signals. SCS has been used successfully to manage a variety of chronic pain conditions, but its efficacy in the treatment of pain syndromes in patients with cancer has not been established because most studies have involved a limited number of patients. The purpose of this study was to assess the efficacy of SCS in a large group of patients with cancer. MATERIALS AND METHODS: A retrospective review was performed for all patients who had SCS trials and implants placed at Memorial Sloan Kettering Cancer Center between 2003 and 2021. Patients were divided into groups based on whether their pain could be directly attributed to cancer or its treatment (cancer dependent, n = 51) and those who had incidental pain unrelated to cancer (cancer independent, n = 22). The cancer-dependent group was further subdivided into those whose pain was directly related to primary tumor invasion or metastasis (cancer related, n = 26) and those whose pain was a result of cancer treatment such as chemotherapy or surgery (treatment related, n = 25). The primary outcomes were changes in pain scores and daily oral morphine equivalents (OMEs) before intervention to one year after implant. Secondary measures included the SCS trial success rate, change in pain scores immediately after the SCS trial, and change in pain scores immediately after the SCS implant. RESULTS: Most patients in the cancer-dependent pain group (59%) and the cancer-independent pain group (68%) had successful SCS trials and subsequently went on to have SCS implants placed. The patients with cancer-dependent pain as a whole had median reduction of 1.5 points (or 23%) on a 10-point pain score immediately after implant (p = 0.001), with the effect diminishing to a median reduction of 1 point (or 15%) by one year after implant (p = 0.027). The cancer-dependent pain groups did not have a significant reduction in daily OMEs, following implantation (p = 0.30), but the cancer-independent group did have a significant reduction (p = 0.01). CONCLUSIONS: SCS can be considered as a treatment modality for patients with cancer whose pain is not adequately controlled with medical therapy or by less invasive interventions.
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Dor do Câncer , Dor Crônica , Neoplasias , Estimulação da Medula Espinal , Dor do Câncer/etiologia , Dor do Câncer/terapia , Dor Crônica/complicações , Dor Crônica/terapia , Humanos , Neoplasias/complicações , Neoplasias/terapia , Manejo da Dor/efeitos adversos , Estudos Retrospectivos , Medula Espinal , Estimulação da Medula Espinal/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to determine whether the implementation of a structured exercise stretching routine targeted at resolving myofascial pain is effective in improving outcomes of "legacy pain" patients. DESIGN: Retrospective cohort study. SETTING: Private community-based interventional pain management practice. SUBJECTS: "Legacy pain" patients, defined as patients on opioid therapy for >1 year. METHODS: Subjects were initiated on a structured home exercise stretching routine targeted at resolving myofascial pain consisting of 14 lumbar, four thoracic, and seven cervical stretches as appropriate. Daily morphine milligram equivalent, functional status (Oswestry Disability Index), and pain level (Numeric Rating Scale) were compared pre- and post-treatment at one year. RESULTS: After 1 year, exercise techniques reduced daily morphine milligram equivalent intake on average from 76.3 to 21.0 mg (p < 0.001) with 84.4% of patients decreasing their total opioid dose (p < 0.001) and 34.4% of patients being completely weaned off of opioids (p < 0.001). Numeric Rating Scale of pain and Oswestry Disability Indices were unchanged with treatment, 7.0-6.7 (p = 0.122) and 30.4-29.3 (p = 0.181), respectively. CONCLUSIONS: The addition of a structured stretching exercise program focusing on the resolution of the myofascial pain in the treatment of "legacy pain" patients was shown to significantly reduce and often discontinue opioid use without adversely affecting pain score or functionality.
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Analgésicos Opioides , Síndromes da Dor Miofascial , Analgésicos Opioides/uso terapêutico , Terapia por Exercício , Humanos , Morfina/uso terapêutico , Síndromes da Dor Miofascial/terapia , Dor/tratamento farmacológico , Estudos RetrospectivosRESUMO
OBJECTIVE: Breast cancer is the most common female malignancy worldwide. Breast surgery and adjuvant oncological therapies are often required to increase survival. Treatment-related pain may persist and evolve into postmastectomy pain syndrome (PMPS) in a significant subset of breast cancer survivors. In this retrospective investigation, we will present our experience in applying an interventional algorithmic approach to treat PMPS. DESIGN: A retrospective study. SETTING: An academic cancer hospital. SUBJECTS: Adult females with PMPS diagnosis. METHODS: We reviewed 169 records with the diagnosis of PMPS from 2015 to 2019 within our health system. Pre- and post-injection pain scores, relief duration, and medication usage changes were collected. The decision to perform each procedure was based on the anatomic location of the painful area with the corresponding peripheral sensory innervation. Decision-making flow diagrams were created to present our experience in managing PMPS beyond peripheral nerve blocks. RESULTS: Ultrasound-guided peripheral nerve block results (n=350) were analyzed. The mean baseline pain score was 7, compared with the post-treatment mean score of 3 (95% confidence interval: 3.58 to 3.98, P = 0.0001). Among the responders, the mean pain relief duration was 45 days, with a median of 84 days. Opioid medication consumption was reduced by 11% (t = 0.72, P = 0.47). CONCLUSIONS: Ultrasound-guided nerve blocks of this area could be performed safely and effectively after breast surgeries. We also present our proposed algorithm to provide a stepwise application for selecting the appropriate therapies in the management of more complex PMPS.
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Neoplasias da Mama , Adulto , Algoritmos , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos , Ultrassonografia de IntervençãoRESUMO
OBJECTIVE: The sympathetic nervous system has a recognized role in transmission of pain, and the lumbar sympathetic blockade is intended to provide analgesia. We share our experiences of lumbar sympathetic blockade in the treatment of cancer-related pain. METHODS: We performed a retrospective analysis of patients with cancer-related pain in the back, abdomen, pelvis, or legs treated at Memorial Sloan Kettering Cancer Center between 2000 and 2018 undergoing lumbar sympathetic blockade at L2 or L3. Blocks were accomplished by injection of local anesthetic or local anesthetic with steroid under fluoroscopy. We measured numerical rating scale scores, percent relief, and relief time. The primary end point was defined as "effective" or "ineffective" pain relief. Effective pain relief was defined as ≥30% relief for at least one day. RESULTS: We identified 124 data points of lumbar sympathetic blockade at L2 or L3, of which 57 were with complete data and used for analysis. Peri-injection, 42 data points had active disease whereas 15 were in remission. Lumbar sympathetic blockade was 67% effective in the back pain cohort, 82% effective in the abdominopelvic pain cohort, and 75% effective in the leg pain cohort. Seventeen data points went on to neurolysis, two to neuromodulation, and eight to intrathecal pump implantation. CONCLUSIONS: Lumbar sympathetic blockade is effective for back, abdominopelvic, and leg pain related to cancer and its treatments. Future research should be aimed at refining its role within multimodal pain management.
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Bloqueio Nervoso Autônomo/métodos , Dor do Câncer/terapia , Manejo da Dor/métodos , Feminino , Humanos , Vértebras Lombares , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: Intrathecal drug delivery systems (IDDS) are an important method of pain control for patients with refractory oncologic pain. Local anesthetics such as bupivacaine have been infused either alone or with opioids. While effective, bupivacaine can cause adverse effects such as numbness, weakness, and urinary retention. This study looks to establish a safe and efficacious fixed bupivacaine dosing algorithm in intrathecal pumps for cancer patients. MATERIALS AND METHODS: A bupivacaine dosing algorithm was developed using data from 120 previous patients who underwent IDDS placement at Memorial Sloan Kettering Cancer Center. The outcomes were then evaluated for 43 subsequent patients who were treated with bupivacaine IDDS according to our aforementioned algorithm. RESULTS: Our data show that in patients treated with our bupivacaine guideline, visual analog pain scale scores decreased by 59% and oral morphine equivalence decreased by 70% from the period between IDDS implantation until discharge from the MSKCC hospital. However, 16.3% of our patients had bupivacaine-related side effects. CONCLUSIONS: For oncological patients, our data and experience support the initiation of intrathecal bupivacaine at the following doses: 5 mg/day for catheter tips in the cervical spine, 8 mg/day for catheter tips at T1-4, and 10 mg/day for catheter tips at T5-8. Given the higher likelihood of adverse effects in catheters at T9-12 and the lumbar spine, we start at 8 mg/day with close follow-up of the patient. Initiating these doses allow our patients to safely reach adequate analgesia faster, with a shorter hospitalization and quicker return to anti-cancer therapy.
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Bupivacaína , Dor do Câncer/tratamento farmacológico , Injeções Espinhais , Dor Intratável , Algoritmos , Anestésicos Locais , Bupivacaína/administração & dosagem , Humanos , Morfina/uso terapêutico , Dor Intratável/tratamento farmacológicoRESUMO
Postmastectomy pain syndrome is common after surgical treatment for breast cancer and may be challenging to manage. Currently, there are a wide variety of approaches to treat this type of pain, including medications, physical therapy, and interventional procedures. However, because of the complexity of innervation of the breast, the serratus plane block may better target the web of nerves innervating the anterior chest wall including the breast. We present a case series of 8 patients who were successfully treated with serratus plane block for pain after treatment for breast cancer. We feel that this particular application for the serratus plane block deserves further investigation, as it is relatively easy to perform and has good clinical utility for this type of pain.
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Mastectomia/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/cirurgia , Ultrassonografia de Intervenção/métodos , Neoplasias da Mama/cirurgia , Feminino , Humanos , Medição da Dor , SíndromeAssuntos
Infecções por Coronavirus/terapia , Respiração com Pressão Positiva Intermitente/métodos , Pneumonia Viral/terapia , Respiração Artificial/métodos , Volume de Ventilação Pulmonar , Ventiladores Mecânicos , COVID-19 , Infecções por Coronavirus/complicações , Humanos , Pandemias , Segurança do Paciente , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapiaRESUMO
Chronic knee pain, affecting over 25% of adults in the United States, has surged by 65% over the past two decades leading to rising functional deficits, mobility problems, and a diminished quality of life. While conservative management with pharmacologic and minimally invasive injections are pursued early in the disease process, total knee arthroplasty for refractory osteoarthritis of the knee is often considered. This procedure usually improves pain and functionality within the first three months. However, a significant portion of patients often suffer from postoperative pain that can become chronic and debilitating. We detail the case of a patient with a previous TKA as well as a non-operable patella fracture who obtained significant relief with PNS despite prior conservative and minimally invasive management.
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Cervical radicular pain is commonly treated with cervical epidural steroid injections. The transforaminal approach allows for direct treatment of the steroid at a particular nerve root or level. Still, it carries a significant risk of morbidity and mortality with thromboembolism or injury to cervical vasculature. The interlaminar approach is commonly utilized as it avoids vascular structures. However, the epidural space becomes narrower at higher levels, limiting the ability to perform this approach at higher cervical levels. Cervical epidural catheters can be used and advanced to target higher cervical pathology through the interlaminar approach. We present clinical images demonstrating the utility of a cervical catheter for treating higher cervical levels.
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BACKGROUND: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine. OBJECTIVES/STUDY DESIGN: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists. METHODS: In this study, all 114 pain program directors listed on the Accreditation Council for Graduate Medical Education (ACGME) website, or their administrative assistants were directly contacted via email. All email addresses were obtained from the ACGME website. The survey opened in September 2021, with reminder emails sent before the closing of the survey in December 2021. A final reminder email was sent 4 weeks prior to the closing of the survey. RESULTS: Of all the respondents, 79 (89.77%) were currently practicing pain medicine, and 9 (10.23%) were no longer practicing pain medicine. LIMITATIONS: Our study has a major limitation as we are unable to determine the response rate and are limited in the data points gathered. CONCLUSION: We hope this study will allow for pain medicine fellowship program directors to improve recruitment and retention of pain fellows in the field while addressing the pros and cons of future career aspirations with anesthesiology residents prior to fellowship selection. A larger, more thorough study with an exact response rate can compare the various outcomes based upon different types of settings, such as private practice, partnership, and academia, as well as geographical locations.
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Anestesiologistas , Bolsas de Estudo , Humanos , Educação de Pós-Graduação em Medicina , Inquéritos e Questionários , DorRESUMO
CONTEXT: Opioids have become a mainstay treatment for severe cancer pain. Although opioid prescribing has decreased, opioid mortality continues to rise. Utilizing urine drug tests (UDT) can help monitor medication adherence and identify use of unprescribed or illicit substances. OBJECTIVES: To identify the prevalence of abnormal UDT among oncologic pain patients, associated demographic and clinical factors, and the most common abnormal substances. METHODS: A retrospective chart review of 2472 patients with a cancer diagnosis and documented UDT in a single center was conducted from January 1, 2018 to February 15, 2020. Multivariable analyses were conducted for 10 baseline patient factors on each of the two primary outcomes-illicit drugs excluding tetrahydrocannabinol and amphetamines and detected-not-prescribed. RESULTS: Of the 2472 patients, 840 patients (34%) had abnormal results. For illicit drugs, the significant factors (incidence rate ratio [95% CI]) were age (45-54 vs. ≥ 65 years: 7.27 [2.27-23.23]), race (black vs. white: 2.99 [1.39-6.42]), smoking status (current vs. former: 2.63 [1.41-4.90]); never vs. former: 0.27 (0.10-0.76), and benzodiazepine use (use vs. no use: 2.06 [1.03-4.12]). For detected-not-prescribed, the significant factors (incidence rate ratio [95% CI]) were race (black vs. white: 1.37 [1.01-1.85]), smoking status (current vs. former: 1.27 [1.00-1.62]); never vs. former: 0.82 (0.67-1.00), log-transformed morphine milligram equivalence (1.04 [1.01-1.07]), and benzodiazepine use (use vs. no use: 1.64 [1.35-1.98]). CONCLUSIONS: This study demonstrates that oncologic pain patients are not a risk-free population for abnormal UDT, thus recommends a UDT with initial opioid prescriptions and annually thereafter, with more frequent tests for patients suspected to be at higher risk for misuse.
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Dor do Câncer , Neoplasias , Preparações Farmacêuticas , Analgésicos Opioides/uso terapêutico , Dor do Câncer/diagnóstico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/epidemiologia , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Padrões de Prática Médica , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Objective: The article that follows is purposed at demonstrating how IT opioid plus bupivacaine achieves sustained acceptable pain relief while simultaneously rapidly reducing oral morphine equivalents (OME). Background: Cancer patients represent a population with significant morbidity, pain, and limited life expectancy. It is, therefore, vital to achieve satisfactory analgesia quickly and safely. To date, there is limited data in the literature that discusses efficacy of combined intrathecal (IT) medication therapy in reducing systemic opioids in the oncological population. Methods: This was a retrospective analysis that reviewed cancer pain patients from day of IT pump implantation through the six-month postoperative time point. A cohort of 50 oncological patients who had intrathecal drug delivery systems (IDDSs) implanted at Memorial Sloan Kettering Cancer Center between 2017 and 2019 were studied. Median OMEs were the primary modality of analysis for this review. Mean visual analogue scale scores were secondarily reviewed. Results: Median OMEs decreased from 503 preoperative to 105 at six months postoperative time point. Median time to discharge was 6.5 days. Unfortunately, due to malignant mortality, 27 patients did not make it to the 6-month postoperative time point. Discussion: IDDSs with opioid plus bupivacaine represent a safe and efficient route toward expeditious pain relief and decreased OMEs in the cancer pain population.