Case series of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy during extracorporeal life support.

Therapeutic hypothermia initiated within 6 hours of birth is currently the standard of care for the management of neonates with hypoxic-ischemic encephalopathy. Neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy are also at risk for severe respiratory failure and need for extracorporeal life support. The risks and benefits of therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support are still not well defined. We report our experience of a case series of six neonates who underwent therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support. We also report long-term neurodevelopmental follow-up from 6 to 24 months and add to the current body of evidence regarding feasibility, clinical experience, and short-term complications.

Impact of in utero drug exposure on neonates requiring ECMO: A retrospective cohort study.

The incidence of in utero drug exposure (IUDE) and neonatal extracorporeal membrane oxygenation (ECMO) utilization have both increased over the past decade. However, there are no studies to date that examine the impact that IUDE has on neonates requiring ECMO. In this retrospective cohort study, we compared the clinic course and outcomes of neonates who were placed on ECMO with IUDE vs. neonates without IUDE. Analysis included data extracted from medical records from all neonatal ECMO runs between January 2014 and January 2021 at the University of Kentucky Children's Hospital. A total of 56 neonatal patients were placed on ECMO during this time period and there were a total of 57 ECMO runs. Nearly one-third of neonates (16) had documented IUDE. There were no differences in gestational age, length of ECMO run, survival to discharge, or number of major complications while on ECMO in the neonates with IUDE compared to those without. In contrast, greater use of sedative and analgesic adjuvant medications during ECMO was required for IUDE-ECMO cases (p < 0.01). Trending results indicated that post-ECMO feeding complications and total hospitalization length were also greater in the IUDE-ECMO group. These findings illustrate the complex influence of prenatal drug exposures on neonatal patient care and warrant the development of clinical care strategies optimized for this unique patient group.

Pulmonary function outcomes in bronchopulmonary dysplasia through childhood and into adulthood: implications for primary care.

Bronchopulmonary dysplasia (BPD) results from prematurity and surfactant deficiency with contributing factors from barotrauma, volutrauma, and oxygen toxicity from supportive mechanical ventilation care and infection. These factors result in chronic inflammation with recurring cycles of lung damage and repair that impair alveolarisation and vascularisation in developing infant lungs. With advancement in the understanding of its pathophysiology and resulting therapy, BPD has evolved into a different disorder which has been coined the 'new' BPD. As these patients age, primary care physicians need to understand the impact on pulmonary function. This discussion reviews the pulmonary function outcomes resulting from BPD through later childhood and young adulthood.

Pathogenesis of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) refers to a heterogeneous group of lung disorders in infants that is commonly associated with prematurity and surfactant deficiency. BPD results from the complex interplay between impairments in the premature lung such as surfactant deficiency, perinatal insults such as infection, and damage resulting from supportive care of the infant due to barotrauma or volutrauma from mechanical ventilation and oxygen toxicity from supplemental oxygen administration. These factors result in chronic inflammation in the infant lung with recurring cycles of lung damage and repair that may impair alveolarization and vascularization in the developing lungs. As our insight in how to treat BPD improves along with the ability to do so with developing technology and therapies, the underlying pathogenesis will also change. The term 'new' BPD is now commonly used, to describe the changes seen in the post-surfactant era. This discussion reviews the pathogenesis of BPD according to the current medical literature.

Frequent ventricular premature beats in children with a structurally normal heart: a cause for reversible left ventricular dysfunction?

Ventricular premature beats (VPBs) in a structurally normal heart generally are a benign condition. Rarely, however, reversible cardiomyopathy may develop. This study aimed to evaluate the incidence of cardiomyopathy among pediatric patients in a cohort with frequent VPBs and to examine the characteristics of the ventricular ectopic beats as well as therapeutic options. This study reviewed the charts of all pediatric patients between the ages of 1 day and 18 years seen at the University of Kentucky with the diagnosis of VPBs between 2003 and 2007. Frequent VPBs were defined as an ectopy burden of 5% or more in 24 h. Electrocardiograms, Holter monitors, and echocardiograms were reviewed. The review identified 28 patients (17 boys, age 13.3 ± 5.9 years, and 11 girls, age 13 ± 5.2 years) with frequent VPBs. The echocardiograms of four patients (2 boys, 14%) showed cardiomyopathy. Cardiac function normalized in all four patients, with spontaneous resolution of the VPBs (2 patients) or with antiarrhythmic therapy (2 patients). During a follow-up period of 2.7 ± 2.3 years, 32% of the patients without cardiomyopathy showed a marked spontaneous improvement in arrhythmia burden. Most of the patients showed VPBs with a left bundle branch block (LBBB) and inferior axis morphology. The most commonly associated symptoms were chest pain (17.8%) and dizziness and syncope (21.4%). Generally, VPBs in structurally normal hearts are considered benign. Rarely, a reversible cardiomyopathy can develop, requiring therapeutic intervention.

Epistaxis due to Wegener's granulomatosis in a pediatric patient.

Epistaxis is a common problem in children that typically is not severe and seldom requires hospitalization. The nose is a highly vascular structure with a large surface area; subsequently, it is highly predisposed to bleeding. Childhood vasculitides are very rare and are commonly diagnosed by characteristic lesions on imaging studies along with syndrome recognition by clinicians. We present a case of recurrent epistaxis that persisted over 3 months due to Wegener's granulomatosis in an adolescent that was misdiagnosed as a benign hemorrhage from Kiesselbach's plexus.

Varicose bronchiectasis and bronchopulmonary dysplasia.

As a result of improved therapies and technology, including the use of surfactant replacement, the features of bronchopulmonary dysplasia (BPD) have changed, and a "new BPD" is emerging that is substantially different from the classical form of the disease. As the pathogenesis of BPD is evolving, so are other features of the disorder, including radiologic features. We describe varicose bronchiectasis with a bulbous appearance in a 6-year-old child with a complicated course including BPD during the neonatal period.

Variability of ASA physical status class assignment among pediatric sedation practitioners.

Our goal was to determine the consistency of the Society of Anesthesiologists Physical Status (ASA-PS) Classification Scale with respect to different training, experience, and activity levels. A questionnaire comprised of 10 pediatric sedation scenarios was distributed via electronic mailing lists. Data were collected on training, experience, annual sedations performed, and ASA-PS score assigned. 100 questionnaires (38 anesthesiologists, 8 advanced nurses, 14 hospitalists, 22 intensivists, 15 registered nurses (RN), 3 others) were returned. Ratings for four scenarios varied significantly with respect to practitioner (p < .05). In one of the scenarios, pediatric hospitalists were more likely to rank a higher ASA-PS score, whereas registered nurses were more likely to rate patient scenarios at a lower ASA-PS (OR = 11.78, 95% CI = (2.10, 66.07), p-value = .0051). Number of annual sedations and practicing years were different among practitioner groups (p-values = .0019 and < .0001 respectively). In three scenarios, practitioners rated a lower ASA-PS score for each additional year in practice. The ASA-PS scores for two scenarios were marginally lower if the practitioner performed greater than 1000 sedations each year (p < .1). Our results indicate that the type of training and experience affect a practitioner's view of the severity of a patient's condition.

Novel animal model for teaching chest tube placement.

BACKGROUND: The number of procedures available to pediatric residency trainees is few in number and patient size leaves little margin for error. Artificial simulation labs have not been developed for neonatal chest tubes. Use of live animal models is coming under increased scrutiny and is expensive. METHODS: We conducted a simulation skills lab for neonatal chest tube placement using a fryer chicken model. Thirty incoming pediatric interns were prospectively queried on comfort levels of inserting chest tubes prior to and following the simulation lab. RESULTS: On a 5-point Likert scale, comfort levels increased from a median of 1 to 3. All interns reported feeling more comfortable with chest tube placement and all reported having better understanding of the process of chest tube placement following the procedure lab. CONCLUSION: The fryer chicken model is an advantageous, effective model of teaching chest tube placement.

Hollow Fiber Oxygenator Composition Has a Significant Impact on Failure Rates in Neonates on Extracorporeal Membrane Oxygenation: A Retrospective Analysis.

In extracorporeal life support (ECLS), there are two main types of oxygenators in clinical use for neonates: polymethylpentene (PMP) hollow fiber and polypropylene (PP) hollow fiber. A retrospective study was performed on neonates ( n = 44) who had undergone ECLS for noncardiac indications from 2009 to 2015. Between the two groups (PMP n = 21, PP n = 23), the PP oxygenators failed 91% of the time, whereas the PMP oxygenators failed 43% of the time ( p < 0.05). Analysis suggests PMP oxygenators are less prone to failure than PP oxygenators, and they require fewer number of oxygenator changes during a neonatal ECLS.

Azithromycin in the extremely low birth weight infant for the prevention of bronchopulmonary dysplasia: a pilot study.

BACKGROUND: Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (< or = 1000 grams) population. METHODS: Infants < or = 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA. RESULTS: A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and birth weight were similar between groups. Mortality, incidence of BPD, days of IMV, and other morbidities were not significantly different between groups. Post-natal steroid use was significantly less in the treatment group [31% (6/19)] vs. placebo group [62% (10/16)] (p = 0.05). Duration of mechanical ventilation was significantly less in treatment survivors, with a median of 13 days (1-47 days) vs. 35 days (1-112 days)(p = 0.02). CONCLUSION: Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants. Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects, before any recommendations regarding routine clinical use can be made.

Azithromycin protects against hyperoxic lung injury in neonatal rats.

Bronchopulmonary dysplasia (BPD) is a pulmonary disorder that causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis, and mucosal necrosis, which leads to emphysematous coalescence of alveoli. We tested the hypothesis that azithromycin, a macrolide antibiotic, would decrease the severity of lung injury in an animal model of BPD. Sixty-three rat pups were randomly divided equally into control, hyperoxia, and hyperoxia plus azithromycin groups. The hyperoxia groups were exposed to > 95% oxygen from days of life 4 to 14. On day 14, the animals were processed for lung histology and tissue analysis. Lung morphology was assessed by mean linear intercept, a measure of alveolar size, with larger values corresponding to lungs that are more emphysematous. The degree of lung inflammation was assessed by quantifying interleukin-6 (IL-6) from lung homogenate. Fifty pups survived to day 14 (control = 21, hyperoxia = 11, hyperoxia + azithromycin = 18). Mortality was increased in the hyperoxia group versus the control group (p < .0001). Treatment with azithromycin improved survival in animals subjected to hyperoxia (p < .05). Azithromycin significantly decreased lung damage as determined by the mean linear intercept in the hyperoxia groups (p < .001). Finally, azithromycin-treated pups had lower levels of IL-6 in lung homogenate from the hyperoxia groups (p < .05). Azithromycin treatment resulted in improved survival, less emphysematous change, and decreased IL-6 levels in an animal model of BPD.

Neonatal research and the validity of informed consent obtained in the perinatal period.

BACKGROUND: Consent for participation in clinical research is considered valid if it is informed, understood, and voluntary. In the case of minors, parents give permission for their child to participate in research studies after being presented with all information needed to make an informed decision. Although informed consent is a vital component of clinical research, there is little information evaluating its validity in neonatal intensive-care populations. The objective of this project was to determine the validity of informed consent obtained from parents of infants enrolled in the multicenter randomized research study, neurologic outcomes and pre-emptive analgesia in the neonate (NEOPAIN). DESIGN/METHODS: Parents of infants who survived to discharge and had signed consent for their newborn to participate in the NEOPAIN study at the University of Kentucky were asked 20 open-ended questions to determine their level of understanding about the NEOPAIN study. The NEOPAIN consent form, which had been approved by the University of Kentucky Medical Institutional Review Board (IRB), was used to formulate these questions. Questions addressed the timing of consent, parental understanding of the purpose, benefits, and risks of the study, the voluntary nature of the project, and their willingness to enroll in future studies if the opportunity presented. Answers were scored on a Likert scale, with 1 for no understanding and 5 for complete understanding. RESULTS: Five of 64 parents (7.8%) had no recollection of the NEOPAIN study or of signing consent. Of those who remembered the study, only 67.8% understood the purpose of the study, with a higher proportion of the mothers than fathers knowing the purpose of the study (73.3% vs 57.1%), (p=0.029). Of those who understood the purpose of the study 95% were able to verbalize the benefits, but only 5% understood any potential risks. No parents reported feeling pressured or coerced to sign consent for the project and all parents reported they would enroll their child in additional studies if asked. CONCLUSIONS: Valid consent in the antenatal/perinatal population is difficult, if not impossible, to obtain. To maximize validity of consent in the antenatal/perinatal population every effort should be made to include mothers in the consent process. Additional attention during the consent process should be given to possible risks of the study.

Elevated high-sensitivity C-reactive protein in preterm infants with pulmonary colonization with Ureaplasma.

BACKGROUND: A link between pulmonary Ureaplasma spp. colonization in premature infants and bronchopulmonary dysplasia (BPD) exists and could possibly contribute to systemic inflammation. METHODS: A prospective cohort study was performed from July 2006 to July 2007 where very low birth weight (VLBW) premature infants were screened at birth. Serum and tracheal aspirate samples were collected during the first 28 days of life that represented the early high-sensitivity C-reactive protein (hs-CRP) group, and follow-up samples obtained between 28-42 days of life were the late hs-CRP group. An Enzyme-linked immunosorbent assay (ELISA) for hs-CRP was performed on serum samples while tracheal aspirates underwent polymerase chain reaction (PCR) analysis for Ureaplasma spp. RESULTS: A total of 65 patients were screened. 30 patients completed full analysis, 15 died before early and late hs-CRP samples could be obtained, and 20 had incomplete data due to early discharge or transfer. There was no significant difference between all early and late hs-CRP group levels (mg/L), median [interquartile range] 1.019 [0.242, 5.844] vs. 0.773 [0.143, 8.954] (P=0.3958); however, there was a significant difference when comparing Ureaplasma spp. positivity vs. negativity between both groups, median 2.223 [0.398, 7.099] vs. 0.675 [0.219, 4.038] (P=0.0131) for the early group and median 2.335 [0.359, 14.91] vs. 0.2155 [0.122, 2.296] (P=0.03) for the late group, respectively. CONCLUSIONS: VLBW premature infants colonized with Ureaplasma spp. have an elevated hs-CRP, suggestive of a chronic low-grade systemic inflammatory response.

Ambulatory venovenous extracorporeal respiratory support as a bridge for cystic fibrosis patients to emergent lung transplantation.

Venovenous extracorporeal membrane oxygenation (VV ECMO) is a therapeutic option to bridge patients with advanced lung disease to lung transplantation. The use of VV ECMO avoids the use of mechanical ventilation while allowing patients to participate in physical therapy and to eat normally while receiving respiratory support. We describe the successful use of ambulatory single-venous VV ECMO as a bridge to bilateral lung transplantation in 4 patients with end-stage lung disease due to cystic fibrosis who developed acute hypercapnic respiratory failure. The use of ambulatory single-venous VV ECMO was safe and effective in this small cohort of CF patients. Based on our experiences, our belief is that a key step in the treatment course was early application of VV ECMO soon after development of acute respiratory failure requiring mechanical ventilation.

Improved survival in venovenous vs venoarterial extracorporeal membrane oxygenation for pediatric noncardiac sepsis patients: a study of the Extracorporeal Life Support Organization registry.

BACKGROUND/PURPOSE: There are few studies comparing venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO) in pediatric noncardiac sepsis patients. METHODS: Following approval, we reviewed the Extracorporeal Life Support Organization registry data from 1990 to 2008 for patients 0 to 18 years with a diagnosis of sepsis and without diagnosis of congenital heart disease. Survival to discharge was compared between VA and VV ECMO using χ(2) analysis and multivariable logistic regression. RESULTS: Four thousand three hundred thirty-two ECMO runs were reviewed, 3256 VA (75%) and 1076 VV (25%). A majority of VA modality was noted in each decade studied. Overall survival was 68% and was higher in VV (79%) than in VA ECMO (64%, P < .001). Survival decreased with increasing age (73% in newborns ≤ 1 month, 40% in children 1 month to 12 years, and 32% in adolescents >12 years, P < .001). VA ECMO had increased mortality risk after adjustment for age, use of vasoactive agents, and advanced respiratory support (odds ratio, 2.06; 95% confidence interval, 1.74-2.44; P < .001). CONCLUSIONS: These data demonstrate improved survival in VV vs. VA ECMO in select pediatric septic patients without congenital heart disease. When technically feasible, physicians should consider VV ECMO as first therapeutic choice in this patient population.

Use of azithromycin for the prevention of bronchopulmonary dysplasia in preterm infants: a randomized, double-blind, placebo controlled trial.

OBJECTIVE: Since preventive therapies for bronchopulmonary dysplasia (BPD) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD. METHODS: Infants less than 1,250 g birth weight were randomized to azithromycin or placebo within 12 hr of beginning mechanical ventilation and within 72 hr of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for a maximum of 6 weeks. Aspirates were collected during the study to assay for Ureaplasma. The primary endpoints were incidence of BPD or mortality. (Clinical Trials Identifier: NCT00319956.) RESULTS: A total of 220 infants were enrolled (n=111 azithromycin, and 109 placebo). Mortality was 18% for the azithromycin group versus 22% for the placebo group (P = 0.45). Incidence of BPD was 76% for the azithromycin group versus 84% for the placebo group (P=0.2). The multiple logistic regression analysis demonstrated an odds ratio of 0.46 decrease in the chance of developing BPD or death for the azithromycin group, but was not statistically significant. The incidence of BPD in the Ureaplasma subgroup was 73% in the azithromycin group versus 94% in the placebo group (P=0.03). Analysis of patients in the Ureaplasma subgroup only, using the exact logistic model demonstrated a decrease in BPD or death in the azithromycin group with an estimated odds ratio of 0.026 (0.001-0.618, 95% confidence interval). CONCLUSIONS: Routine use of azithromycin therapy for the prevention of BPD cannot be recommended. The early treatment of Ureaplasma colonized/infected patients might be beneficial, but a larger multi-centered trial is required to assess this more definitively.

Inhaled morphine for palliation of dyspnea in end-stage cystic fibrosis.

PURPOSE: The successful use of inhaled morphine to relieve dyspnea in a patient with end-stage cystic fibrosis (CF) lung disease is described. SUMMARY: A 48-year-old man with CF was hospitalized for a pulmonary exacerbation caused by infection with Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). His medical history included long-standing depression, chronic pain, spinal stenosis, benign prostatic hypertrophy, iron-deficiency anemia, and colectomy. Over the two previous years, his chronic pain had progressively worsened, and he had developed narcotic dependency. The etiology of his pain was unclear. During this time, his pulmonary status had slowly deteriorated due to chronic infection with P. aeruginosa and MRSA. As his lung function had deteriorated, he and his family had declined consideration for lung transplantation and requested no heroic interventions when death was imminent. His medications at time of admission included supplemental oxygen, dornase alfa, ipratropium bromide, and albuterol. The opioids used by the patient at the time of admission included oral methadone, oral oxycodone, transdermal fentanyl, and oral morphine sulfate. Upon admission with this pulmonary exacerbation, the patient was started on antibiotics. His pain was eventually controlled with i.v. methadone and ketamine, but his dyspnea continued. Inhaled morphine sulfate 2 mg in 5 mL of 0.9% sodium chloride injection was started and administered every four hours. Clinically significant improvements in the patient's dyspnea, measured using a modified Borg score, were observed with subsequent doses. His dyspnea remained well controlled until his death two days later. CONCLUSION: Inhaled morphine was effective in relieving dyspnea in a patient with end-stage CF lung disease.