Hubert O. Ballard

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.

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.

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

Since preventive therapies for bronchopulmonary dysplasia (BPD) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD.

Azithromycin in the extremely low birth weight infant for the prevention of Bronchopulmonary Dysplasia: a pilot study

BackgroundAzithromycin 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 (≤ 1000 grams) population.MethodsInfants ≤ 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.ResultsA 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).ConclusionOur 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.

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.

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.

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.

Acyclovir Use in Sick Infants

Background: Infantile herpes simplex virus encephalitis (HSVE) infection remains a significant cause of morbidity and mortality. Diagnosis is often difficult in this population, where a specific pattern of clinical and laboratory signs are lacking. This often results in unnecessary treatment of infants with empiric acyclovir. This study evaluates the use of empiric acyclovir at the Kentucky Childrens Hospital and attempts to correlate any laboratory or clinical findings that may be highly suggestive of HSVE. Methods: Medical records of infants younger than 1 year admitted and treated with acyclovir were evaluated for any consistent pattern of clinical findings suggestive of HSVE. Specifically, serum and cerebrospinal fluid (CSF) white blood cell counts, red blood cell counts, cerebrospinal glucose and protein, and clinical neurological findings upon admission were evaluated. Results: Two hundred eighteen infants were identified and included in the study. Three infants were identified with polymerase chain reaction-positive HSVE. Only CSF leukocytosis was consistent among HSVE-positive infants. All infants with HSVE exhibited generalized neurological findings. Neither hemorrhagic CSF nor focal neurological findings were indicative of HSVE infection. Discussion: Herpes simplex virus encephalitis has a very low prevalence within this population. Clinically significant neurological findings as well as specific risk factors must be present to consider treatment with empiric acyclovir. Apnea and focal seizures are not specific risk factors for herpetic meningitis in infants. Lack of a CSF leukocytosis is a strong negative predictor for HSVE, and hemorrhagic fluid is not specific for HSVE.

Current approaches to pediatric heart catheterizations

Sedation for pediatric cardiac catheterization is a common requirement in many institutions. As the field of cardiac catheterization has evolved, the provision of sedation for these procedures has been varied. Increasingly the demand is for dedicated personnel focused on monitoring and delivery of sedation while in the catheterization suite. This article describes the considerations one must use when undertaking these cases.

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 Wegeners granulomatosis in an adolescent that was misdiagnosed as a benign hemorrhage from Kiesselbachs plexus.