Impact of red blood cell transfusion on regional cerebral oxygen saturation during pediatric ECMO.

BACKGROUND: Low cerebral regional tissue oxygenation (crSO2) is associated with unfavorable neurological outcomes in children requiring extracorporeal membrane oxygenation (ECMO) support. Red blood cell (RBC) transfusion can improve brain oxygenation and crSO2 has been proposed as a noninvasive monitoring tool that could aid in RBC transfusion decision-making. However, how crSO2 responds to RBC transfusion is largely unknown. STUDY DESIGN AND METHODS: This was a retrospective, observational cohort study of all patients <21 years supported on ECMO at a single institution from 2011 to 2018. Transfusion events were grouped by pre-transfusion hemoglobin concentration (<10, 10- < 12, and ≥ 12 g/dL). Post- versus pre-transfusion crSO2 changes were analyzed using linear mixed-effects models. RESULTS: The final cohort included 830 transfusion events in 111 patients. Hemoglobin increased significantly post- versus pre-RBC transfusion (estimated mean increase of 0.47 g/dL [95% CI, 0.35-0.58], p < .001), as did crSO2 (estimated mean increase of 1.82 percentage points [95% CI, 1.23-2.40], p < .001). Larger improvements in crSO2 were associated with lower pre-transfusion crSO2 values (p < .001). There was no difference in mean change in crSO2 across the three hemoglobin groups in unadjusted analysis (p = .5) or after adjusting for age, diagnostic category, and pre-transfusion rSO2 (p = .15). Pre-transfusion crSO2 was <50% for 112 of 830 (13.5%) transfusion events, with only 30 (26.8%) crSO2 measurements noted to increase ≥50% post-transfusion. DISCUSSION: Among neonatal and pediatric patients on ECMO support, there was a statistically significant increase in crSO2 following RBC transfusion, although clinical significance needs to be investigated further. The effect was strongest among patients with lower crSO2 pre-transfusion.

Cardioprotective mechanisms of mitochondria-targeted S-nitrosating agent and adenosine triphosphate-sensitive potassium channel opener are mutually exclusive.

Background: Myocytes exposed to stress exhibit significant swelling and reduced contractility. These consequences are ameliorated by adenosine triphosphate-sensitive potassium (KATP) channel opener diazoxide (DZX) via an unknown mechanism. KATP channel openers also provide cardioprotection in multiple animal models. Nitric oxide donors are similarly cardioprotective, and their combination with KATP activation may provide synergistic benefit. We hypothesized that mitochondria-targeted S-nitrosating agent (MitoSNO) would provide synergistic cardioprotection with DZX. Methods: Myocyte volume and contractility were compared following Tyrode's physiologic solution (20 minutes) and stress (hyperkalemic cardioplegia [CPG] ± DZX; n = 5-20 each; 20 minutes) with or without MitoSNO (n = 5-11 each) at the end of stress, followed by Tyrode's solution (20 minutes). Isolated mouse hearts received CPG ± DZX (n = 8-10 each) before global ischemia (90 minutes) with or without MitoSNO (n = 8 each) at the end of ischemia, followed by reperfusion (30 minutes). Left ventricular (LV) pressures were compared using a linear mixed model to assess the impact of treatment on the outcome, adjusting for baseline and balloon volume. Results: Stress (CPG) was associated with reduced myocyte contractility that was prevented by DZX and MitoSNO individually; however, their combination was associated with loss of cardioprotection. Similarly, DZX and MitoSNO improved LV function after prolonged ischemia compared with CPG alone, and cardioprotection was lost with their combination. Conclusions: MitoSNO and DZX provide cardioprotection that is lost with their combination, suggesting mutually exclusive mechanisms of action. The lack of a synergistic beneficial effect informs the current knowledge of the cardioprotective mechanisms of DZX and will aid planning of future clinical trials.