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Background: Cardiac bypass surgery patients have early postoperative interventions that elicit breakthrough pain. We evaluated the use of intranasal fentanyl for breakthrough pain management in these patients. Methods: Multimodal analgesia (paracetamol 1 g three times a day, oxycodone 2–3 mg boluses with a patient-controlled intravenous pump) was used in 16 patients (age 49–70 years, weight 59–129 kg) after cardiac bypass surgery. Intranasal fentanyl 100 µg or 200 µg was used to manage breakthrough pain on the first and third postoperative mornings in a randomised order. Blood samples were collected for up to 3 h after fentanyl administration, pain was assessed with a numeric rating scale of 0–10. Plasma fentanyl concentration was assayed using liquid chromatography-mass spectrometry. Body composition was measured with a bioelectrical impedance device. Results: Bioavailability of intranasal fentanyl was high (77%), absorption half-time short (< 2 min) and an analgesic plasma concentration ≥ 0.5 ng/mL was achieved in 31 of 32 administrations. Fentanyl exposure correlated inversely with skeletal muscle mass and total body water. Fentanyl analgesia was effective both on the first postoperative morning with chest pleural tube removal and during physiotherapy on the third postoperative morning. The median time of subsequent oxycodone administration was 1.1 h after intranasal fentanyl 100 µg and 2.1 h after intranasal fentanyl 200 µg, despite similar oxycodone concentrations (median 13.8, range 5.2–35 ng/mL) in both fentanyl dose groups. Conclusions: Intranasal fentanyl 100 µg provided rapid-onset analgesia within 10 min and is an appropriate starting dose for incidental breakthrough pain in the first 3 postoperative days after cardiac bypass surgery. Clinical Trial Registration: EudraCT Number: 2018-001280-22. [ABSTRACT FROM AUTHOR]

The purpose of the study was to examine in vivo placental transfer of metformin, its association with neonatal outcome in metformin-treated gestational diabetes (GDM) patients, and influence of metformin exposure on maternal glycemic control and weight gain. Two hundred and seventeen GDM patients were randomized to metformin or insulin in Turku University Hospital, Finland. Metformin concentrations were determined by mass spectrometry in maternal serum at 36 gestational weeks (gw) and at birth, and in umbilical cord blood. Main outcome measures were birth weight, gw at birth, umbilical artery pH and neonatal hypoglycemia, maternal weight gain, HbA1c and fructosamine concentration. Median umbilical cord/maternal serum metformin concentration ratio was 0.73. There were no differences in birth weight measured in grams or SD units ( p = 0.49), or gw at birth ( p always ≥0.49) between insulin- and metformin-treated patients stratified by trough metformin concentration tertiles measured at 36 gw. Rate of neonatal hypoglycemia ( p = 0.92) and umbilical artery pH value ( p = 0.78) was similar in insulin- and metformin-treated patients stratified by cord metformin concentration tertiles. Maternal glycemic control was similar in metformin concentration tertiles at 36 gw. Maternal weight gain was 223 g greater per week ( p = 0.038) in the lowest metformin tertile compared to other tertiles combined. Maternal and fetal exposure to metformin is similar. Maternal or fetal metformin concentrations do not predict maternal glycemic control or neonatal outcome, but low maternal exposure may lead to greater maternal weight gain. [ABSTRACT FROM AUTHOR]