Keeping tabs: Reducing postoperative opioid prescriptions for patients after breast surgical procedures.

BACKGROUND: As the opioid crisis continues, it is critical that health care providers ensure they are not overprescribing opioid medications. At our institution (Walter Reed National Military Medical Center, Bethesda, MD), postoperative patients after breast surgeries are discharged with variable amounts of opioid medications. However, many patients report minimal opioid use. The objectives of this study were to characterize postoperative opioid usage and prescribing practices for patients undergoing various breast surgeries and to recommend the number of opioid pills for discharge for each procedure. METHODS: This was a prospective, single-institution study of all patients undergoing breast surgery from October 2018 to 2019. All patients were enrolled in our institution's enhanced recovery after surgery protocol. Patients were given questionnaires at their 2-week postoperative clinic appointment that evaluated perioperative pain and use of pain medications. The electronic medical record was reviewed to obtain additional information. Appropriate parametric and nonparametric tests were used for analysis. RESULTS: A total of 190 breast surgery patients completed the survey. We observed no significant differences in pain scores except between re-excision and mastectomy. Of these patients, 99% were prescribed opioids; however, only 53% of patients used them. Of those patients who were prescribed opioids, on average, all were prescribed more pills than were used. CONCLUSION: Our study demonstrates that it is possible to discharge all breast surgery patients with fewer than 10 opioid pills, except for special circumstances. This is the first study to provide a set of specific recommended discharge medications. Utilization of an enhanced recovery after surgery protocol with standardized discharge opioids can be used successfully to reduce the number of opioids prescribed to patients.

Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice.

Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway.