Danielle R. Rios

Usefulness of Routine Head Ultrasound Scans Before Surgery for Congenital Heart Disease

OBJECTIVE: The purpose of this study was to assess the utility of preoperative head ultrasound scan (HUS) in a cohort of newborns also undergoing preoperative MRI as part of a prospective research study of brain injury in infants having surgery for congenital heart disease (CHD). METHODS: A total of 167 infants diagnosed with CHD were included in this 3-center study. None of the patients had clinical signs or symptoms of preoperative brain injury, and all patients received both HUS and brain MRI before undergoing surgical intervention. HUS and MRI results were reported by experienced neuroradiologists who were blinded to any specific clinical details of the study participants. The findings of the individual imaging modes were compared to evaluate for the presence of brain injury. RESULTS: Preoperative brain injury was present on HUS in 5 infants (3%) and on MRI in 44 infants (26%) (P < .001). Four of the HUS showed intraventricular hemorrhage not seen on MRI, suggesting false-positive results, and the fifth showed periventricular leukomalacia. The predominant MRI abnormality was white matter injury (n = 32). Other findings included infarct (n = 16) and hemorrhage (n = 5). CONCLUSIONS: Preoperative brain injury on MRI was present in 26% of infants with CHD, but only 3% had any evidence of brain injury on HUS. Among positive HUS, 80% were false-positive results. Our findings suggest that routine HUS is not indicated in asymptomatic term or near-term neonates undergoing surgery for CHD, and MRI may be a preferable tool when the assessment of these infants is warranted.

Development and validation of a highly sensitive LC–MS/MS assay for the quantification of arginine vasopressin in human plasma and urine: Application in preterm neonates and child

Arginine vasopressin is an endogenous neuropeptide secreted in response to situations such as hyperosmolality, hypotension and hypovolemia. The purpose of this study was to develop a reliable assay using small volumes of plasma and urine samples to quantify vasopressin levels in preterm infants. Weak cation solid-phase extraction was used to extract vasopressin from 200μl human plasma and urine samples. Separation was achieved on a Waters Acquity UPLC BEH C18 column by gradient elution at 0.55ml/min, with a mobile phase composed of methanol and 0.02% aqueous acetic acid solution. Analysis was performed under a hybrid triple quadrupole linear ion trap mass spectrometer, operated in multiple reaction monitoring mode using positive ionization. The linear response range was 1.0-40pg/ml for vasopressin, with the lower limit of quantification (LLOQ) of 1.0pg/ml in human plasma and urine. Recoveries at concentrations of 3, 10 and 32pg/ml were all greater than 70%, and matrix effects were within 15%. The method was validated with intra-day and inter-day precision of less than 8% for human plasma and urine. The intra-day and inter-day accuracy for human plasma were 91.9-100.6% and 92.3-104.8%, respectively. The intra-day and inter-day accuracy for human urine were 89.2-95.9% and 89.3-91.3%, respectively. The validated method was successfully applied to analyze two preterm neonate plasma samples and one child urine sample. In conclusion, the developed and validated method was sensitive and reliable, and was successfully used to quantify endogenous vasopressin levels in neonate plasma and child urine.

Quantitative determination of dopamine in human plasma by a highly sensitive LC–MS/MS assay: Application in preterm neonates

The determination of dopamine facilitates better understanding of the complex brain disorders in the central nervous system and the regulation of endocrine system, cardiovascular functions and renal functions in the periphery. The purpose of this study was to develop a highly sensitive and reliable assay for the quantification of dopamine in human neonate plasma. Dopamine was extracted from human plasma by strong cation exchange (SCX) solid phase extraction (SPE), and subsequently derivatized with propionic anhydride. The derivatized analyte was separated by a Waters Acquity UPLC BEH C18 column using gradient elution at 0.4 ml/min with mobile phases A (0.2% formic acid in water [v/v]) and B (MeOH-ACN [v/v, 30:70]). Analysis was performed under positive electrospray ionization tandem mass spectrometer (ESI-MS/MS) in the multiple reaction monitoring (MRM) mode. The stable and relatively non-polar nature of the derivatized analyte enables reliable quantification of dopamine in the range of 10-1000 pg/ml using 200 μl of plasma sample. The method was validated with intra-day and inter-day precision less than 7%, and the intra-day and inter-day accuracy of 91.9-101.9% and 92.3-102.6%, respectively. The validated assay was applied to quantify dopamine levels in two preterm neonate plasma samples. In conclusion, a sensitive and selective LC-MS/MS method has been developed and validated, and successfully used for the determination of plasma dopamine levels in preterm neonates.

Use of Vasopressin in Neonatal Intensive Care Unit Patients With Hypotension

OBJECTIVE To evaluate the safety and efficacy of vasopressin for the treatment of hypotension in patients admitted to neonatal intensive care units (NICUs). METHODS Vasopressin use in 69 infants admitted to our NICU between 2011 and 2014 was examined. Data evaluated included demographics; serum creatinine, sodium, and lactate concentrations; urine output; and systolic, diastolic, and mean blood pressures (BPs). Parameters prior to vasopressin use were compared to those at maximum dose. RESULTS Vasopressin use was associated with increased urine output (p < 0.05), and increased systolic (p < 0.0005), diastolic (p < 0.01), and mean (p < 0.001) BP. There were no differences in sodium or lactate concentrations before vs during infusion; vasopressin use was not associated with hyponatremia (sodium < 130 mEq/L) at the maximum dose. CONCLUSIONS Vasopressin for the treatment of neonatal hypotension appears safe and was efficacious in raising BP. These data suggest that vasopressin could be considered a viable option in the treatment regimen in hypotensive infants in the NICU.

Effect of Exogenous Antithrombin Administration on Anti-Xa Levels in Infants Treated With Enoxaparin

OBJECTIVES Determine the effect of exogenous antithrombin III administration on low molecular weight heparin anti-Xa levels in the context of enoxaparin dosing in infants. METHODS A retrospective chart review of infants receiving concomitant antithrombin III and enoxaparin. The primary objective of this study was to determine the median change in anti-Xa level with antithrombin III supplementation. Secondary objectives were to analyze the median change in antithrombin III levels after administration of exogenous antithrombin III, the dosing of antithrombin III, and the dose of enoxaparin throughout therapy. For a safety analysis, any bleeding events were recorded. RESULTS The study included 17 patients who received a total of 33 doses of antithrombin III. The median change in anti-Xa levels in infants receiving exogenous antithrombin III was 0.2 units/mL (p < 0.001). The median dose of antithrombin III was 50 units/kg and was administered when patients were receiving a median enoxaparin dose of 1.71 mg/kg. The median increase in antithrombin III levels was 16.5% (p < 0.001). CONCLUSIONS These results demonstrated that administration of exogenous antithrombin III to infants who were being treated with enoxaparin results in a significant increase in anti-Xa levels. At this time, there is insufficient evidence to recommend routine administration of antithrombin III to infants on enoxaparin. However, antithrombin III supplementation could be considered a potential option for patients who are unable to adequately achieve therapeutic anti-Xa levels with enoxaparin alone.

Circulatory insufficiency and hypotension related to the ductus arteriosus in neonates

The biological role of the ductus arteriosus (DA) in neonates varies from an innocent bystander role during normal postnatal transition, to a supportive role when there is compromise to either systemic or pulmonary blood flow, to a pathological state in the presence of hemodynamically significant systemic to pulmonary shunts, as occurs in low birth weight infants. Among a wide array of clinical manifestations arising due to the ductal entity, systemic circulatory insufficiency and hypotension are of significant concern as they are particularly challenging to manage. An understanding of the physiologic interplay between the DA and the circulatory system is the key to developing appropriate targeted therapeutic strategies. In this review, we discuss the relationship of systemic hypotension to the DA, emphasizing the importance of critical thinking and a precise individual approach to intensive care support. We particularly focus on the variable states of hypotension arising directly due to a hemodynamically significant DA or seen in the period following successful surgical ligation. In addition, we explore the mechanistic contributions of the ductus to circulatory insufficiency that may manifest during the transitional period, states of maladapted transition (such as acute pulmonary hypertension of the newborn), and congenital heart disease (both ductal dependent and non-ductal dependent lesions). Understanding the dynamic modulator role of the ductus according to the ambient physiology enables a more precise approach to management. We review the pathophysiology, clinical manifestations, diagnosis, monitoring, and therapeutic intervention for the spectrum of DA-related circulatory compromise.