BACKGROUND: Painful diabetic neuropathy (PDN) is one of the major complications of diabetes mellitus. It is often debilitating and refractory to pharmaceutical therapies. Our goal was to systematically review and evaluate the strength of evidence of interventional management options for PDN and make evidence-based recommendations for clinical practice. METHODS: We searched PubMed, Scopus, Google Scholar, and Cochrane Llibrary and systematically reviewed all types of clinical studies on interventional management modalities for PDN. RESULTS: We identified and analyzed 10 relevant randomized clinical trials (RCTs), 8 systematic reviews/meta-analyses, and 5 observational studies of interventional modalities for PDN using pain as primary outcome. We assessed the risk of bias in grading of evidence and found that there is moderate to strong evidence to support the use of dorsal column spinal cord stimulation (SCS) in treating PDN in the lower extremities (evidence level: 1B+), while studies investigating its efficacy in the upper extremities are lacking. Evidence exists that acupuncture and injection of botulinum toxin-A provide relief in pain or muscle cramps due to PDN with minimal side effects (2B+/1B+). Similar level of evidence supports surgical decompression of lower limb peripheral nerves in patients with intractable PDN and superimposed nerve compression (2B±/1B+). Evidence for sympathetic blocks or neurolysis and dorsal root ganglion (DRG) stimulation is limited to case series (2C+). CONCLUSIONS: Moderate to strong evidence exists to support the use of SCS in managing lower extremity pain in patients who have failed conventional medical management for PDN. Acupuncture or injection of botulinum toxin-A can be considered as an adjunctive therapy for PDN. Surgical decompression of peripheral nerves may be considered in patients with PDN superimposed with nerve compression. High-quality studies are warranted to further evaluate the safety, efficacy, and cost-effectiveness of interventional therapies for PDN. (Anesth Analg 2022;134:1215-28) KEY POINTS• Question: What options are available to manage patients with painful diabetic neuropathy (PDN) beyond pharmaceutical therapies? • Findings: Emerging evidence indicates that interventional therapies such as spinal cord stimulation (SCS), acupuncture, botulinum toxin A injection, and surgical decompression of lower limb peripheral nerves can provide clinically meaningful pain relief in patients with refractory PDN. • Meaning: When PDN is refractory to pharmaceutical therapies, clinician should explore interventional management options.

Introduction: Two protocols were developed to guide the use of subdissociative dose ketamine (SDDK) for analgesia and dissociative sedation ketamine for severe agitation/excited delirium in the emergency department (ED). We sought to evaluate the safety of these protocols implemented in 18 EDs within a large health system. Methods: We conducted a retrospective chart review to evaluate all adult patients who received intravenous (IV) SDDK for analgesia and intramuscular (IM) dissociative sedation ketamine for severe agitation/excited delirium in 12 hospital-based and six freestanding EDs over a one-year period from the protocol implementation. We developed a standardized data collection form and used it to record patient information regarding ketamine use, concomitant medication use, and any comorbidities that could have impacted the incidence of adverse events. Results: Approximately 570,000 ED visits occurred during the study period. SDDK was used in 210 ED encounters, while dissociative sedation ketamine for severe agitation/excited delirium was used in 37 ED encounters. SDDK was used in 83% (15/18) of sites while dissociative sedation ketamine was used in 50% (9/18) of sites. Endotracheal intubation, non-rebreather mask, and nasal cannula ≥ four liters per minute were identified in one, five, and three patients, respectively. Neuropsychiatric adverse events were identified in 4% (9/210) of patients who received SDDK. Conclusion: Patients experienced limited neuropsychiatric adverse events from SDDK. Additionally, dissociative sedation ketamine for severe agitation/excited delirium led to less endotracheal intubation than reported in the prehospital literature. The favorable safety profile of ketamine use in the ED may prompt further increases in usage.

Objective Growth hormone (GH) and GH-related signaling molecules play an important role in nociception and development of chronic pain. This review aims to examine the potential molecular mechanisms through which GH-related signaling modulates sensory hypersensitivity in rodents, the clinical pharmacology of GH, and the clinical evidence of GH treatment for several common pain syndromes. Methods A search was conducted using the PUBMED/MEDLINE database, Scopus, and the Cochrane library for all reports published in English on GH in pain management from inception through May 2018. A critical review was performed on the mechanisms of GH-related signaling and the pharmacology of GH. The levels of clinical evidence and implications for recommendations of all of the included studies were graded. Results The search yielded 379 articles, of which 201 articles were deemed irrelevant by reading the titles. There were 53 reports deemed relevant after reading abstracts. All of these 53 articles were retrieved for the analysis and discussion. Conclusions Dysfunction of the GH/insulin-like growth factor 1 (IGF-1)/ghrelin axis was linked to hyperalgesia and several common clinical pain syndromes. Low levels of GH and IGF-1 were linked to pain hypersensitivity, whereas ghrelin appeared to provide analgesic effects. Pretreatment of GH reversed mechanical and thermal hypersensitivity in an animal model of inflammatory pain. Clinical trials support GH treatment in a subgroup of patients with fibromyalgia syndrome (level of evidence: 1B+) or chronic lower back pain syndrome (level of evidence: 2C+).

Background: Opioid use is classified as an epidemic by many due to the impact of these medications on society. Federal and state laws for prescribing and dispensing opioids have changed rapidly in a short period of time to hopefully balance proper pain control with their use. Pharmacy directors must be informed of these rapid changes to effectively work as part of any opioid stewardship team. Objective: The objective of this study was to provide foundational leadership guidance to pharmacy directors on current opioid legislation, literature, and best practices to assist in improving opioid use. Methods: A review of the literature from 2003 to the present was conducted along with collating important up to date resources and other publications that provide foundational information to help support a comprehensive management of opioid use. A summary of these data has been collated into an easy to use table and summarized throughout this article. Conclusion: The information provided in this article helps to properly inform pharmacy leaders to the resources available to improve the prescribing, dispensing, and monitoring of opioids and alternatives.

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