Rashmi Sahay

Oxidative Stress Causes Vascular Dysfunction in the Placenta

Increased production of superoxide and nitric oxide may produce oxidative stress in the placenta by formation of the prooxidant peroxynitrite, which itself causes vascular dysfunction. Nitrotyrosine residues, which are a marker of peroxynitrite formation and action, are found in placental vessels of preeclamptic and diabetic pregnancies, indicating oxidative stress. Treatment of the placental vasculature with authentic peroxynitrite in vitro attenuates responses both to vasoconstrictors such as the thromboxane mimetic U46619 and to vasodilators, including glyceryl trinitrate and prostacyclin, indicating it has caused vascular dysfunction. Further, the responses of the fetal-placental vasculature of diabetic and preeclamptic placentae to these same vasoconstrictor and vasodilator agents are significantly attenuated when compared to responses in normal control placentae. Together these data suggest there may be a cause and effect relationship between formation and action of peroxynitrite and vascular dysfunction in the placenta of both preeclamptic and diabetic pregnancies. The presence of such attenuated vascular responses indicates that perhaps the placenta may not be able to adequately respond to demands for altered blood flow in situations where this is necessary in preeclamptic or diabetic pregnancies, thus leading to further fetal compromise.

The Incidence of Acute Kidney Injury and Its Effect on Neonatal and Pediatric Extracorporeal Membrane Oxygenation Outcomes: A Multicenter Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Study Group

Objective: In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation; to describe the prevalence and timing of acute kidney injury utilizing a consensus acute kidney injury definition and investigate the association of acute kidney injury with outcomes (length of extracorporeal membrane oxygenation and mortality). Design: Multicenter retrospective observational cohort study. Setting: Six pediatric extracorporeal membrane oxygenation centers. Patients: Pediatric patients (age, < 18 yr) on extracorporeal membrane oxygenation at six centers during a period of January 1, 2007, to December 31, 2011. Interventions: None. Measurements and Main Results: Complete data were analyzed for 832 patients on extracorporeal membrane oxygenation. Sixty percent of patients had acute kidney injury utilizing the serum creatinine Kidney Disease Improving Global Outcomes criteria (AKISCr) and 74% had acute kidney injury using the full Kidney Disease Improving Global Outcomes criteria including renal support therapy (AKISCr + RST). Of those who developed acute kidney injury, it was present at extracorporeal membrane oxygenation initiation in a majority of cases (52% AKISCr and 65% AKISCr + RST) and present by 48 hours of extracorporeal membrane oxygenation support in 86% (AKISCr) and 93% (AKISCr + RST). When adjusted for patient age, center of support, mode of support, patient complications and preextracorporeal membrane oxygenation pH, the presence of acute kidney injury by either criteria was associated with a significantly longer duration of extracorporeal membrane oxygenation support (AKISCr, 152 vs 110 hr; AKISCr + RST, 153 vs 99 hr) and increased adjusted odds of mortality at hospital discharge (AKISCr: odds ratio, 1.77; 1.22–2.55 and AKISCr + RST: odds ratio, 2.50; 1.61–3.90). With the addition of renal support therapy to the model, acute kidney injury was associated with a longer duration of extracorporeal membrane oxygenation support (AKISCr, 149 vs 121 hr) and increased risk of mortality at hospital discharge (AKISCr: odds ratio, 1.52; 1.04–2.21). Conclusion: Acute kidney injury is present in 60–74% of neonatal-pediatric patients supported on extracorporeal membrane oxygenation and is present by 48 hours of extracorporeal membrane oxygenation support in 86–93% of cases. Acute kidney injury has a significant association with increased duration of extracorporeal membrane oxygenation support and increased adjusted odds of mortality at hospital discharge.Objective In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation (ECMO); to describe the incidence and timing of acute kidney injury (AKI) utilizing a consensus AKI definition and investigate the association of AKI with outcomes (length of ECMO and mortality).

The Impact of Fluid Overload on Outcomes in Children Treated with Extracorporeal Membrane Oxygenation: A Multicenter Retrospective Cohort Study

Objective: To characterize the epidemiology of fluid overload and its association with mortality and duration of extracorporeal membrane oxygenation in children treated with extracorporeal membrane oxygenation. Design: Retrospective cohort study. Setting: Six tertiary children’s hospital ICUs. Patients: Seven hundred fifty-six children younger than 18 years old treated with extracorporeal membrane oxygenation for greater than or equal to 24 hours from January 1, 2007, to December 31, 2011. Interventions: None. Measurements and Main Results: Overall survival to extracorporeal membrane oxygenation decannulation and hospital discharge was 74.9% (n = 566) and 57.7% (n = 436), respectively. Median fluid overload at extracorporeal membrane oxygenation initiation was 8.8% (interquartile range, 0.3–19.2), and it differed between hospital survivors and non survival, though not between extracorporeal membrane oxygenation survivors and non survivors. Median peak fluid overload on extracorporeal membrane oxygenation was 30.9% (interquartile range, 15.4–54.8). During extracorporeal membrane oxygenation, 84.8% had a peak fluid overload greater than or equal to 10%; 67.2% of patients had a peak fluid overload of greater than or equal to 20% and 29% of patients had a peak fluid overload of greater than or equal to 50%. The median peak fluid overload was lower in patients who survived on extracorporeal membrane oxygenation (27.2% vs 44.4%; p < 0.0001) and survived to hospital discharge (24.8% vs 43.3%; p < 0.0001). After adjusting for acute kidney injury, pH at extracorporeal membrane oxygenation initiation, nonrenal complications, extracorporeal membrane oxygenation mode, support type, center and patient age, the degree of fluid overload at extracorporeal membrane oxygenation initiation (p = 0.05), and the peak fluid overload on extracorporeal membrane oxygenation (p < 0.0001) predicted duration of extracorporeal membrane oxygenation in survivors. Multivariable analysis showed that peak fluid overload on extracorporeal membrane oxygenation (adjusted odds ratio, 1.09; 95% CI, 1.04–1.15) predicted mortality on extracorporeal membrane oxygenation; fluid overload at extracorporeal membrane oxygenation initiation (adjusted odds ratio, 1.13; 95% CI, 1.05–1.22) and peak fluid overload (adjusted odds ratio, 1.18; 95% CI, 1.12–1.24) both predicted hospital morality. Conclusions: Fluid overload occurs commonly and is independently associated with adverse outcomes including increased mortality and increased duration of extracorporeal membrane oxygenation in a broad pediatric extracorporeal membrane oxygenation population. These results suggest that fluid overload is a potential target for intervention to improve outcomes in children on extracorporeal membrane oxygenation.