Background Opioid-related deaths are a leading cause of accidental death, with most occurring in patients receiving chronic pain therapy. Respiratory arrest is the usual cause of death, but mechanisms increasing that risk with increased length of treatment remain unclear. Repeated administration produces tolerance to opioid analgesia, prompting increased dosing, but depression of ventilation may not gain tolerance to the same degree. This study addresses differences in the degree to which chronic morphine (1) produces tolerance to ventilatory depression versus analgesia and (2) alters the magnitude and time course of ventilatory depression. Methods Juvenile rats received subcutaneous morphine for 3 days (n = 116) or vehicle control (n = 119) and were then tested on day 4 following one of a range of morphine doses for (a) analgesia by paw withdraw from heat or (b) respiratory parameters by plethysmography–respirometry. Results Rats receiving chronic morphine showed significant tolerance to morphine sedation and analgesia (five times increased ED50). When sedation was achieved for all animals in a dose group (lowest effective doses: opioid-tolerant, 15 mg/kg; opioid-naive, 3 mg/kg), the opioid-tolerant showed similar magnitudes of depressed ventilation (−41.4 ± 7.0%, mean ± SD) and hypercapnic response (−80.9 ± 15.7%) as found for morphine-naive (−35.5 ± 16.9% and −67.7 ± 15.1%, respectively). Ventilation recovered due to tidal volume without recovery of respiratory rate or hypercapnic sensitivity and more slowly in morphine-tolerant. Conclusions In rats, gaining tolerance to morphine analgesia does not reduce ventilatory depression effects when sedated and may inhibit recovery of ventilation.

Background Occupational stress in resident physicians has profound implications for wellness, professionalism, and patient care. This observational pilot trial measured psychological and physiological stress biomarkers before, during, and after the start of anesthesia residency. Methods Eighteen physician interns scheduled to begin anesthesia residency were recruited for evaluation at three time points: baseline (collected remotely before residency in June 2013); first month visit 1 (July); and follow-up visit 2 (residency month 3–5, Sept–Nov). Validated scales were used to measure stress, anxiety, resilience, and wellness at all 3 time points. During visits 1 and 2, we measured resting heart rate variability, responses to laboratory mental stress (hemodynamic, catecholamine, cortisol, and interleukin-6) and chronic stress indices (C-reactive protein, 24 h ambulatory heart rate and blood pressure, 24 h urinary cortisol and catecholamines, overnight heart rate variability). Results Thirteen interns agreed to participate (72% enrollment). There were seven men and six women, ages 27–33 years. The mean ± SD of all study variables are reported. Conclusion The novelty of our report is the prospective design in a defined cohort of residents newly exposed to the similar occupational stress of the operating environment. Because of the paucity of literature specific to the measures and stress conditions in this investigation, no data were available to generate a priori definition of primary outcomes and a data analytic plan. These findings will allow power analysis for future design of trials examining occupational stress and stress-reducing interventions. Given the importance of physician burnout in our country, the impact of chronic stress on resident wellness requires further study.

The major cycling “Grand Tours” have shown an attenuation of performance over the last decade. This has been interpreted as circumstantial evidence that newer anti-doping strategies have reduced the use of performance-enhancing drugs. To examine this idea under more controlled conditions, speed trends for world class 5000 m, 10000 m, and marathon performances by men from 1980 to 2013 were analyzed. We obtained comprehensive records from the International Association of Athletics Federations, Association of Road Racing Statisticians, and the Track and Field All-time Performances database webpages. The top 40 performances for each event and year were selected for regression analysis. For the three distances, we noted cumulative performance improvements in the 1990s thru the mid-2000s. After the peak speed years of the mid 2000 s, there has been limited improvement in the 5000 m and 10,000 m and world records set during that time remain in place today, marking the longest period of time between new records since the early 1940s. By contrast marathon speed continues to increase and the world record has been lowered four times since 2007, including in 2013. While the speed trends for 5000 m and 10000 m track results parallel those seen in elite cycling, the marathon trends do not. We discuss a number of explanations other than improved anti-doping strategies that might account for these divergent findings.

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