Current contextOpioid overdoses have quadrupled in the past 15 years, and in 2015 there were over 33,000 opioidrelated deaths in the United States. 1 Opioid overdose induces respiratory depression that can lead to hypoxia, hypercarbia and death. In an attempt to expedite treatment and improve outcomes following overdose, naloxone is increasingly being utilized in a pre-hospital setting by both emergency personnel and prescribed to laypersons for out-of-hospital administration. 2 Efficacy of reversal following naloxone administration by laypersons is high, having been reported at 75-100%, 3 and in general take-home naloxone programs are considered effective for reducing opioid-overdose mortality. 4 Naloxone overall is a safe medication, and is not known to cause harm when administered in typical doses to opioid-naïve patients. [5][6][7][8] There is concern about the precipitation of opioid-withdrawal syndrome following its administration in the setting of prior opioid exposure. Despite the long-standing use of naloxone to reverse the symptoms of opioid overdose or toxicity, appropriate dosing remains controversial, with varying doses recommended over time and by medical specialty. 9 In a hospital setting, this medication is typically administered initially in a low dose, which is then titrated to optimize reversal of opioid-induced respiratory depression while attempting to minimize the risk of withdrawal. 10 In a non-medical setting, the ideal of gradually titrating naloxone to effect is not practical, thus a single standardized initial dose for out-of-hospital naloxone rescue has been sought. This review will evaluate the literature to address the question of optimal naloxone dosing to reverse opioidinduced respiratory depression while minimizing patient risk. HistoryNaloxone was developed in the early 1960s as a novel opioid antagonist with fewer side effects than its predecessors. 11 Naloxone hydrochloride is a competitive mu-opioid receptor antagonist historically used only by trained clinical professionals for the reversal of opioid overdose in an emergency or inpatient setting. It is approved for administration by a variety of routes, including intravenous (IV), intramuscular (IM), subcutaneous (SQ) and intranasal (IN), but is also administered via inhalation following nebulization or endotracheal tube in intubated patients. [12][13][14] Formulations for many other routes of administration are currently under development, including sublingual and buccal. 15 Naloxone is not typically administered orally due Naloxone dosage for opioid reversal: current evidence and clinical implications Rachael Rzasa Lynn and JL Galinkin Abstract: Opioid-related mortality is a growing problem in the United States, and in 2015 there were over 33,000 opioid-related deaths. To combat this mortality trend, naloxone is increasingly being utilized in a pre-hospital setting by emergency personnel and prescribed to laypersons for out-of-hospital administration. With increased utilization of naloxone there has been a subsequent reduc...

Systemic effects associated with obesity decrease morphine metabolism and excretion. A previous study from our laboratory demonstrated that obesity and leptin deficiency decrease the sensitivity of central respiratory control centers to carbon dioxide. Obesity and leptin deficiency substantially decreased morphine metabolism and clearance, and replacing leptin attenuated the PK changes associated with leptin deficiency, suggesting leptin has a direct role in morphine metabolism.

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Background: More patients with cardiac implantable electrical devices (CIEDs) are presenting to spine and pain practices for radiofrequency ablation (RFA) procedures for chronic pain. Although the potential for electromagnetic interference (EMI) affecting CIED function is known with RFA procedures, available guidelines do not specifically address CIED management for percutaneous RFA for zygapophyseal (z-joint) joint pain, and thus physician practice may vary. Objectives: To better understand current practices of physicians who perform RFA for chronic z-joint pain with respect to management of CIEDs. Perioperative CIED management guidelines are also reviewed to specifically address risk mitigation strategies for potential EMI created by ambulatory percutaneous spine RFA procedures. Study Design: Web-based provider survey and narrative review. Setting: Multispecialty pain clinic, academic medical center. Methods: A web-based survey was created using Research Electronic Data Capture (REDCap). A survey link was provided via e-mail to active members of the Spine Intervention Society (SIS), American Society of Regional Anesthesia and Pain Medicine, as well as distributed freely to community Pain Physicians and any receptive academic departments of PM&R or Anesthesiology. The narrative review summarizes pertinent case series, review articles, a SIS recommendation statement, and multi-specialty peri-operative guidelines as they relate specifically to spine RFA procedures. Results: A total of 197 clinicians participated in the survey from diverse clinical backgrounds, including anesthesiology, physical medicine and rehabilitation, radiology, neurosurgery, and neurology, with 81% reporting fellowship training. Survey responses indicate wide variability in provider management of CIEDs before, during, and after RFA for z-joint pain. Respondents indicated they would like more specific guidelines to aid in management and decision-making around CIEDs and spine RFA procedures. Literature review yielded several practice guidelines related to perioperative management of CIEDs, but no specific guideline for percutaneous spine RFA procedures. However, combining the risk mitigation strategies provided in these guidelines, with interventional pain physician clinical experience allows for reasonable management recommendations to aid in decision-making. Limitations: Although this manuscript can serve as a review of CIEDs and aid in management decisions in patients with CIEDs, it is not a clinical practice guideline. Conclusions: Practice patterns vary regarding CIED management in ambulatory spine RFA procedures. CIED presence is not a contraindication for spine RFA but does increase the complexity of a spine RFA procedure and necessitates some added precautions. Key words: Radiofrequency ablation, neurotomy, cardiac implantable electrical device, zygapophyseal joint, spondylosis, neck pain, low back pain, chronic pain

Breakthrough pain (BTP) is experienced by approximately 65% of children and adults with chronic pain. Undiagnosed or untreated BTP produces negative emotional, physical, and economic consequences. BTP episodes have a rapid onset and short duration. Short acting oral opioids are the cornerstone of BTP management. Oral medications available to treat BTP episodes like immediaterelease morphine or oxycodone have a delayed onset of action so that there is a mismatch between the episode of BTP and the effect of the oral opioids. Novel fentanyl delivery systems for BTP offer pharmacokinetic properties that match the time profile of BTP. Among the transmucosal routes, intranasal fentanyl has gained popularity due to its high bioavailability, rapid onset of action, high potency, short duration, and ease of administration. Its efficacy and safety have been demonstrated in adults who are opioid tolerant. Although children with chronic cancer pain also experience BTP, there is paucity of data on the use of intranasal fentanyl for BTP in this age group.