Whole body physiology model to simulate respiratory depression of fentanyl and associated naloxone reversal.

BACKGROUND: Opioid use in the United States and abroad is an endemic part of society with yearly increases in overdose rates and deaths. In response, the use of the safe and effective reversal agent, naloxone, is being fielded and used by emergency medical technicians at a greater rate. There is evidence that repeated dosing of a naloxone nasal spray is becoming more common. Despite this we lack repeated dosing guidelines as a function of the amount of opiate the patient has taken. METHODS: To measure repeat dosing guidelines, we construct a whole-body model of the pharmacokinetics and dynamics of an opiate, fentanyl on respiratory depression. We then construct a model of nasal deposition and administration of naloxone to investigate repeat dosing requirements for large overdose scenarios. We run a single patient through multiple goal directed resuscitation protocols and measure total naloxone administered. RESULTS: Here we show that naloxone is highly effective at reversing the respiratory symptoms of the patient and recommend dosing requirements as a function of the fentanyl amount administered. We show that for increasing doses of fentanyl, naloxone requirements also increase. The rescue dose displays a nonlinear response to the initial opioid dose. This nonlinear response is largely logistic with three distinct phases: onset, rapid acceleration, and a plateau period for doses above 1.2 mg. CONCLUSIONS: This paper investigates the total naloxone dose needed to properly reverse respiratory depression associated with fentanyl overdose. We show that the current guidelines for a rescue dose may be much lower than required.

Opioids such as fentanyl are a type of drug that reduce pain. However, the overdose of opioids causes severe breathing issues that can lead to death. Overdose of opioids is an increasing problem across the globe, particularly among people with opioid use disorder. To prevent death, first responders can administer a drug called naloxone that rapidly reverses the effects of opioids. However, the optimum amount of naloxone to administer is unclear. We use a mathematical model to investigate the effect of administering different amounts of naloxone during fentanyl overdose. Our findings suggest that the amount of naloxone to administer that is currently usually administered may be insufficient. Further research should enable naloxone usage guidelines to be optimized, which could improve survival following opioid overdose.

Current Diagnosis and Management of Necrotizing Soft Tissue Infections: What You Need to Know.

LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Defining the Culture of Surgery.

BACKGROUND: Surgical culture is often referenced but not well defined. Recent research and changing policies in graduate medical education have influenced the training paradigm and expectations of surgical trainees. It is unclear how these changes impact surgeons' understanding of surgical culture today and how those views impact surgical training. We sought to understand surgical culture and its impact on training from the perspective of a diverse group of surgeons with varied amounts of experience. STUDY DESIGN: A series of semi-structured, qualitative interviews were conducted with 21 surgeons and trainees in a single academic institution. Interviews were transcribed, coded, and analyzed using directed content analysis. RESULTS: We identified 7 major themes that impact surgical culture. Cohorts were separated by those who had been promoted to at least associate professor (late-career surgeons) and assistant professors, fellows, residents, and students (early-career surgeons). Both cohorts similarly emphasized patient-centered care, hierarchy, high standards, and meaningful work. Late- and early-career surgeons highlighted themes differently: late-career surgeons' perceptions were informed by experience and focused on challenges, complications, humility, and work ethic, while perceptions of early-career surgeons were more individually focused and referenced being goal-oriented and self-sacrificing, and focus on education and work-life balance. CONCLUSIONS: Late- and early-career surgeons both emphasize that patient-centered care is core to surgical culture. Early-career surgeons expressed more themes related to personal well-being, while late-career surgeons emphasized themes related to professional accomplishment. Differences in the perceived culture can lead to strained interactions between generations of surgeons and trainees, and a better understanding of these differences would lead to improved communication and interactions between these groups, as well as better management of expectations for surgeons in their training and career.