Maria Gillam-Krakauer

Evidence-Based Use of Indomethacin and Ibuprofen in the Neonatal Intensive Care Unit

Indomethacin and ibuprofen are potent inhibitors of prostaglandin synthesis. Neonates have been exposed to these compounds for more than 3 decades. Indomethacin is commonly used to prevent intraventricular hemorrhage (IVH), and both drugs are prescribed for the treatment or prevention of patent ductus arteriosus (PDA). This review examines the basis for indomethacin and ibuprofen use in the neonatal intensive care population. Despite the call for restrained use of each drug, the most immature infants are likely to need pharmacologic approaches to reduce high-grade IVH, avoid the need for PDA ligation, and preserve the opportunity for an optimal outcome.

Correlation of abdominal rSO2 with superior mesenteric artery velocities in preterm infants.

Objective:Near-infrared spectroscopy (NIRS) is used to monitor brain and kidney perfusion in at-risk premature and term neonates. Although NIRS holds potential for bedside monitoring of intestinal perfusion, there is insufficient evidence showing correlation with mesenteric blood flow. To determine if an association exists between abdominal regional oxygen saturation (A-rSO2) and mesenteric blood flow, we compared changes in A-rSO2 to changes in blood flow velocity in the superior mesenteric artery (SMA) before and after feedings in very-low birthweight infants.Study Design:A-rSO2 was continuously monitored midline below the umbilicus for 3 days in 18 stable 25 to 31 week bolus-fed infants (median BW 1203 g, median age 5 days). We compared change in SMA velocity from immediately before to 10 min and 60 to 120 min after feeding with change in A-rSO2 over the same time. Spearman’s rank correlation was used to ascertain if a significant association existed.Result:Change in A-rSO2 was significantly associated with change in systolic, diastolic, and mean SMA velocity from fasting to 60 to 120 min after feeding (P=0.016, 0.021, 0.010) and from 10 min after a feed to 60 to 120 min after feeding (P=0.009, 0.035, 0.032).Conclusion:In very preterm infants, A-rSO2 reflects blood flow in the SMA and can provide non-invasive continuous monitoring of intestinal perfusion. Further studies are indicated to determine the sensitivity of NIRS to detect early intestinal pathology in this population.

Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation

Objective:We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation.Study Design:A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was >15 μg kg–1min–1. Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension).Result:Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration.Conclusion:We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.

Neonatal hypoxia and seizures.

1. Maria Gillam-Krakauer, MD* 2. Brian S. Carter, MD† 1. *Assistant Professor of Pediatrics, Division of Neonatology, Vanderbilt University Medical Center, Nashville, TN. 2. †Professor of Pediatrics, Section of Neonatology, Childrens Mercy Hospital, Kansas City, MO. * Abbreviations: AED: : antiepileptic drug AMPA: : α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid ATP: : adenosine triphosphate CSF: : cerebrospinal fluid HIE: : hypoxic-ischemic encephalopathy MOCO: : molybdenum cofactor NMDA: : N -methyl-d-aspartic acid With 1 to 3 in 1,000 term neonates experiencing seizures, pediatricians need to know how to determine the seizure cause and manage appropriately, using brain imaging and treatments such as therapeutic hypothermia, xenon, and other pharmacologic therapies, in order to minimize long-term sequelae and leverage the infant brains tremendous capacity for repair in the first 2 years after birth. After completing this article, readers should be able to: 1. Understand the pathophysiology of neonatal seizures. 2. Know the many disorders associated with seizures in the newborn. 3. Be aware of the characteristics of different neonatal seizure syndromes. 4. Know how to evaluate a newborn who is having seizures. 5. Be aware of the treatments for neonatal seizures. 6. Understand the characteristics and management of hypoxic-ischemic encephalopathy. Seizures occur during the newborn period at an incidence of ∼1 to 3 per 1,000 infants born at term. (1)(2)(3) Numerous systemic and neurologic conditions can manifest as seizures. Cerebral hypoxia-ischemia, defined as partial lack of oxygen resulting in reduction of blood flow to the brain, is the most frequent cause of seizures in the newborn period. It is important to determine the cause of neonatal seizures and institute the appropriate therapy to minimize the long-term sequelae of both the underlying condition and the seizure. Seizures are paroxysmal alterations in neurologic function caused by excessive synchronous depolarization of neurons within the central nervous system. Regardless of the underlying pathology manifesting as a seizure, all seizures are due to a shift in cell energy. This shift can result from failure of the adenosine triphosphate (ATP)–dependent sodium-potassium (Na+-K+) pump, an imbalance of inhibitory and excitatory neurotransmitters, and both excessive …

Superior mesenteric artery blood flow velocities following medical treatment of a patent ductus arteriosus

We examined superior mesenteric artery blood flow velocity in response to feeding in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during previous treatment for patent ductus arteriosus. Blood flow velocity increased earlier in the fed infants, but was similar in the 2 groups at 30 minutes after feeding.

Use of Near-Infrared Spectroscopy in the Management of Patients in Neonatal Intensive Care Units - An Example of Implementation of a New Technology

Near-infrared spectroscopy (NIRS) is a spectroscopic technique which uses the NIR region of the electromagnetic spectrum to gain information about natural samples through their absorption of NIR light. This method is used in several branches of science. In medicine, it was first used in adult patients, who were placed on by-pass during cardiac surgery to follow cerebral oxygenation, cerebral rSO2 (rSO2-c,) and thereby perfusion and metabolism of the brain. Its many other possibilities soon became apparent. Although the brain remains the main organ of interest in patients of all ages, other tissues are being studied as well. Aside from cardiac surgery clinicians in specialties such as sports medicine, plastic surgery (to assess flap viability), and neonatology apply NIRS in clinical settings. (Feng et al., 2001)

Cerebral regional oxygen saturation trends in infants with hypoxic-ischemic encephalopathy

BACKGROUND Neurological outcomes in neonatal hypoxic-ischemic encephalopathy (HIE) continue to be sub-optimal despite therapeutic hypothermia (TH). Cerebral near-infrared spectroscopy provides real-time regional oxygen saturation (CrSO2) that may be a marker of adverse MRI findings and neurodevelopmental outcomes. AIM The aim of this study was to examine the value of CrSO2 monitoring in infants with HIE undergoing TH. STUDY DESIGN AND SUBJECTS In this prospective study, CrSO2 was continuously recorded in 21 infants with HIE admitted for TH. OUTCOME MEASURES Brain MRI signal abnormalities at 2weeks were scored in individual brain region and classified as none/mild, moderate and severe. 13 infants completed Bayley Scales of Infant Development (BSID) testing at 18-24months. RESULTS Between 24 and 36h of life, there was a significant increase in odds of having moderate-severe brain MRI abnormalities with higher absolute CrSO2 values. Per 10% increase in absolute CrSO2, the odds ratio for moderate-severe brain MRI abnormalities was greatest at 30h (OR 3.78; confidence intervals (CI): 1.23-11.6, p=0.011). CrSO2 increased more rapidly in infants with greater injury seen on MRI (0.20/h for MRI scores 0/1, by 0.48/h for MRI score 2, and by 0.68/h for MRI score 3, p=0.05). At 30h, absolute CrSO2 correlated significantly with abnormal MRI findings in basal ganglia (92% vs. 78%, p=0.001), white matter (88% vs. 76%, p=0.01), posterior limb of internal capsule (92% vs. 78%, p=0.001), and brain stem (94% vs. 80%, p=0.03) but not with cortical injury (86% vs. 80%, p=0.17). Higher CrSO2 beyond 24h correlated with greater odds of worse BSID scores. CONCLUSIONS Increasing CrSO2 is associated with moderate-severe brain injury as assessed by MRI. Higher absolute CrSO2 values during TH correlates with subcortical injury on MRI and poor neurodevelopmental outcomes in infants with HIE undergoing TH. CrSO2 can inform providers seeking early identification of patients at risk of worse injury who may benefit from further intervention.