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OBJECTIVES: Dim light melatonin onset, or the rise in melatonin levels representing the beginning of the biological night, is the gold standard indicator of circadian phase. Considerably less is known about dim light melatonin offset, or the decrease in melatonin to low daytime levels representing the end of the biological night. In the context of insufficient sleep, morning circadian misalignment, or energy intake after waketime but before dim light melatonin offset, is linked to impaired insulin sensitivity, suggesting the need to characterize dim light melatonin offset and identify risk for morning circadian misalignment. METHODS: We examined the distributions of dim light melatonin offset clock hour and the phase relationship between dim light melatonin offset and waketime, and associations between dim light melatonin offset, phase relationship, and chronotype in healthy adults (N = 62) who completed baseline protocols measuring components of the circadian melatonin rhythm and chronotype. RESULTS: 74.4% demonstrated dim light melatonin offset after waketime, indicating most healthy adults wake up before the end of biological night. Later chronotype (morningness-eveningness, mid-sleep on free days corrected, and average mid-sleep) was associated with later dim light melatonin offset clock hour. Later chronotype was also associated with a larger, positive phase relationship between dim light melatonin offset and waketime, except for morningness-eveningness. CONCLUSIONS: These findings suggest morning circadian misalignment risk among healthy adults, which would not be detected if only dim light melatonin onset were assessed. Chronotype measured by sleep timing may better predict this risk in healthy adults keeping a consistent sleep schedule than morningness-eveningness preferences. Additional research is needed to develop circadian biomarkers to predict dim light melatonin offset and evaluate appropriate dim light melatonin offset timing to promote health.
RESUMO
Objective: Donation after circulatory death (DCD) procurement and transplantation after thoracoabdominal normothermic regional perfusion (TA-NRP) remains a novel technique to improve cardiac and hepatic allograft preservation but may be complicated by lung allograft pulmonary edema. We present a single-center series on early implementation of a lung-protective protocol with strategies to mitigate posttransplant pulmonary edema in DCD lung allografts after TA-NRP procurement. Methods: Data from all lung transplantations performed using a TA-NRP procurement strategy from October 2022 to April 2023 are presented. Donor management consisted of key factors to reduce lung allograft pulmonary edema: aggressive predonation and early posttransplant diuresis, complete venous drainage at TA-NRP initiation, and early pulmonary artery venting upon initiation of systemic perfusion. Donor and recipient characteristics, procurement characteristics such as TA-NRP intervals, and 30-day postoperative outcomes were assessed. Results: During the study period, 8 lung transplants were performed utilizing TA-NRP procurement from DCD donors. Donor ages ranged from 16 to 39 years and extubation time to declaration of death ranged from 10 to 90 minutes. Time from declaration to TA-NRP initiation was 7 to 17 minutes with TA-NRP perfusion times of 49 to 111 minutes. Median left and right allograft warm ischemia times were 55.5 minutes (interquartile range, 46.5-67.5 minutes) and 41.0 minutes (interquartile range, 39.0-53.0 minutes, respectively, with 2 recipients supported with cardiopulmonary bypass or venoarterial extracorporeal membrane oxygenation during implantation. No postoperative extracorporeal membrane oxygenation was required. There were no pulmonary-related deaths; however, 1 patient died from complications of severe necrotizing pancreatitis with a normal functioning allograft. All patients were extubated within 24 hours. Index intensive care unit length of stay ranged from 3 to 11 days with a hospital length of stay of 13 to 37 days. Conclusions: Despite concern regarding quality of DCD lung allografts recovered using the TA-NRP technique, we report initial success using this procurement method. Implementation of strategies to mitigate pulmonary edema can result in acceptable outcomes following lung transplantation. Demonstration of short- and long-term safety and efficacy of this technique will become increasingly important as the use of TA-NRP for thoracic and abdominal allografts in DCD donors expands.
