Billie L. Short

Neurodevelopmental status at age five years of neonates treated with extracorporeal membrane oxygenation

OBJECTIVE To determine the neurodevelopmental status at age 5 years among children who received extracorporeal membrane oxygenation (ECMO) in the newborn period as a treatment for severe cardiorespiratory failure. METHODS We conducted a prospective cohort study of 103 five-year-old ECMO-treated children born between June 1984 and July 1988, and treated at our institution. Thirty-seven healthy control children were recruited locally. The assessment protocol included a complete neuropsychologic assessment, psychosocial assessment with parent questionnaires, a standard neurologic evaluation, assessment of gross motor and fine motor function, a medical history, and physical examination. RESULTS Major disability was present in 17 of the ECMO cohort. Eleven ECMO-treated children (11%) were mentally retarded, one of whom was profoundly impaired. Two additional children had severe learning disabilities. Cerebral palsy was diagnosed in 5 (5%) ECMO-treated children, but all cases were mild in nature and the patients were walking unaided. One child has paraplegia. The mean Full Scale, Verbal, and Performance IQs of the EMCO-treated children were within the normal range, but as a group were significantly lower than in control children (96 vs 115, p < 0.001). Children treated with ECMO had increased risk relative to the control children for academic difficulties at school age (49% VS 22%, P < 0.01) and a higher rate of behavioral problems reported by parents (42% vs 16%, p = 0.01). CONCLUSIONS The rate of major disability was comparable to that in other high-risk populations. The high rate of behavioral problems and increased risk of subsequent school failure among nonretarded ECMO-treated children supports the need for close follow-up of these children after hospital discharge.

Criteria for extracorporeal membrane oxygenation in a population of infants with persistent pulmonary hypertension of the newborn

Extracorporeal membrane oxygenation (ECMO) has been available since 1975 as a therapy of last resort to provide adequate oxygenation for term infants with acute lung disorders that do not respond to maximal medical therapy. Virtually all term infants with serious lung disease have persistent pulmonary hypertension of the newborn (PPHN) characterized by significant right-to-left shunting of blood and severe diffusion defects manifested as increased alveolar-arterial oxygen gradients (AaDO2). Criteria for initiation of ECMO therapy have been developed in several institutions but at the present time there are no universal criteria applicable to all infants with PPHN. We have attempted to establish entry criteria that may be used for different populations of infants with PPHN. Based on a retrospective review of 30 infants with PPHN in our institution, we have defined standards of maximal medical therapy. An alveolar-arterial oxygen difference (AaDO2) of greater than or equal to 610 for 8 hours has been shown to be associated with 79% mortality in this population. This AaDO2/time interval is established as a major criterion for institution of extracorporeal membrane oxygenation.

Doppler Echocardiographic Evaluation of Cardiac Performance in Infants on Prolonged Extracorporeal Membrane Oxygenation

Cardiac performance was evaluated by Doppler echocardiography in 19 infants with persistent pulmonary hypertension before, during and after prolonged extracorporeal membrane oxygenation (ECMO). Systemic arterial pressure was normal before ECMO (67 +/- 12 mm Hg), increased during ECMO (78 +/- 13 mm Hg) and decreased to baseline after ECMO (p less than or equal to 0.01). Heart rate was normal before ECMO and did not change during or after ECMO. The left ventricular shortening fraction was normal before ECMO (37 +/- 11%), decreased after beginning ECMO (25 +/- 11%) and returned to baseline 72 hours after beginning ECMO (p less than or equal to 0.01). Pulmonary arterial and aortic blood flow velocities were normal before ECMO, decreased 30 to 50% during ECMO and increased to baseline 72 hours after beginning ECMO (p less than or equal to 0.01). Stroke volume had an identical trend (p less than or equal to 0.01). Left ventricular velocity of circumferential shortening--an index of contractility--decreased after beginning ECMO (p less than or equal to 0.05). Left ventricular systolic wall stress--an index of systemic afterload--increased after beginning ECMO (p less than or equal to 0.01). A patent ductus arteriosus was present in 13 of 19 infants before ECMO, 16 of 19 infants during ECMO and in none of 19 infants after ECMO. Pulmonary arterial systolic pressure was high before ECMO (72 +/- 25 mm Hg), began to decrease after 48 hours on ECMO (59 +/- 24 mm Hg) and was normal after ECMO (38 +/- 18 mm Hg), p less than or equal to 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2-ethylhexyl)phthalate.

OBJECTIVES To determine the exposure to, and evaluate the potential toxicity from, the plasticizer, di(2-ethylhexyl)phthalate (DEHP) during extracorporeal membrane oxygenation (ECMO) therapy. DESIGN Protocol 1 consisted of a prospective comparison of three ECMO circuit designs in vitro. Protocol 2 consisted of a prospective, comparative clinical study evaluating DEHP plasma concentrations in ECMO vs. non-ECMO patients with respiratory failure. SETTING Neonatal intensive care unit at The Childrens National Medical Center, Washington, DC. PATIENTS In protocol 2, 28 consecutive term infants were referred for ECMO therapy. Eighteen infants required ECMO; ten control patients received conventional ventilation and improved without ECMO. INTERVENTIONS In protocol 1, three ECMO circuit designs were primed in vitro with normal saline, albumin, and human blood, which was maintained at 37 degrees C and recirculated at 400 mL/min for 48 hrs. Plasma samples were obtained at time 0, 1 hr, and every 6 hrs. In protocol 2, ventilatory and cardiovascular management of the patients in the study was conducted by the attending physician. Patients were placed on ECMO when they met the institutional criteria for ECMO therapy. Daily plasma concentrations for DEHP were collected until 3 days after decannulation from bypass in the ECMO group. Control patients were sampled daily until extubation. Evidence of cardiac, liver, or lung toxicity was evaluated by Chest Radiographic Scores, liver function studies, and echocardiograms obtained on day 1, day 3, and the day of decannulation in the ECMO group, or at the time of extubation in the control group. Sedation, blood product transfusions as indicated, antibiotics, and hyperalimentation were administered to all patients. MEASUREMENTS AND MAIN RESULTS All DEHP plasma concentrations were measured by gas chromatography. In protocol 1, three circuits were studied: circuit A (small surface area); circuit B (larger surface area); and circuit C (surface area of A but with heparin-bonded tubing in the circuit). DEHP leached from circuit A at 0.32 +/- 0.12 microgram/ mL/hr, compared with 0.57 +/- 0.14 microgram/mL/hr from circuit B (p < .05). This amount of DEHP extrapolates in the ECMO patient to a potential exposure of 20 to 70 times that exposure from other medical devices or procedures, such as transfusions, dialysis, or short-term cardiopulmonary bypass. Circuit C showed almost no leaching from the circuit; DEHP concentrations decreased at a rate of 0.2 +/- 0.04 microgram/mL/ hr. In protocol 2, DEHP was undetected in the control patients. DEHP concentrations in ECMO patients were greater in the early course of ECMO. However, most patients cleared this compound from the plasma before decannulation. In contrast to the in vitro results in protocol 1, the average highest concentration at any time on bypass was 8.3 +/- 5.7 micrograms/mL or 2 mg/kg. CONCLUSIONS DEHP leaches from ECMO circuits, with potential exposure concentrations related to the surface area of the tubing in the ECMO circuit. Heparin bonding of the tubing eliminates this risk. Although significant concentrations of DEHP leach from the nonheparin-bonded circuits over time, our in vivo studies showed that the DEHP plasma concentrations were less than the previously reported values and do not correlate with any observable short-term toxicity. This compound may be either efficiently metabolized by the newborn, or redistributed into various tissues. Although signs of toxicity were not found in this study, long-term complications from chronic exposure to DEHP have not been determined.

Follow-up study of adolescents exposed to di(2-ethylhexyl) phthalate (DEHP) as neonates on extracorporeal membrane oxygenation (ECMO) support.

Di(2-ethylhexyl) phthalate (DEHP) is used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Animal data show that adverse effects of DEHP exposure may include reduced fertility, reduced sperm production in males, and ovarian dysfunction in females. Known treatments that involve high DEHP exposures are blood exchange transfusions, extracorporeal membrane oxygenation (ECMO), and cardiovascular surgery. Although potential exposure to DEHP in ECMO patients is significant, the exposure has not been associated with short-term toxicity. To evaluate long-term toxicity, we undertook a study of neonatal ECMO survivors to assess their onset of puberty and sexual maturity. We evaluated 13 male and 6 female subjects at 14–16 years of age who had undergone ECMO as neonates. All subjects had a complete physical examination including measurements for height, weight, head circumference, and pubertal assessment by Tanner staging. The testicular volume and the phallic length were measured in male participants. Laboratory tests included thyroid, liver, and renal function as well as measurements of luteinizing hormone, follicle-stimulating hormone, testosterone for males, and estradiol for females. Except for one patient with Marfan syndrome, the rest had normal growth percentile for age and sex. All had normal values for thyroid, liver, and renal functions. Sexual hormones were appropriate for the stage of pubertal maturity. Our results indicate that adolescents exposed to significant quantities of DEHP as neonates showed no significant adverse effects on their physical growth and pubertal maturity. Thyroid, liver, renal, and male and female gonadal functions tested were within normal range for age and sex distribution.

Clinical and economic impact of methicillin-resistant Staphylococcus aureus colonization or infection on neonates in intensive care units.

OBJECTIVE The rising incidence and mortality of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in children has become a great concern. This study aimed to determine the clinical and economic impact of MRSA colonization or infection on infants and to measure excess mortality, length of stay, and hospital charges attributable to MRSA. DESIGN This is a retrospective cohort study. SETTING AND PATIENTS The study included infants admitted to a level III-IV neonatal intensive care unit from September 1, 2004, through March 31, 2008. METHODS A time-dependent proportional hazard model was used to analyze the association between MRSA colonization or infection and mortality. The relationships between MRSA colonization or infection and length of stay and between MRSA colonization or infection and hospital charges were assessed using a matched cohort study design. RESULTS Of 2,280 infants, 191 (8.4%) had MRSA colonization or infection. Of 132 MRSA isolates with antibiotic susceptibility results, 106 were resistant to clindamycin and/or trimethoprim-sulfamethoxazole, thus representing a noncommunity phenotype. The mortality rate was 17.8% for patients with MRSA colonization or infection and 11.5% for control subjects. Neither MRSA colonization (hazard ratio [HR], 0.9 [95% confidence interval {CI}, 0.5-1.5]; P > .05 ) nor infection (HR, 1.2 [95% CI, 0.7-1.9]; P > .05 ) was associated with increased mortality risk. Infection caused by MRSA strains that were resistant to clindamycin and/or trimethoprim-sulfamethoxazole increased the mortality risk by 40% (HR, 1.4 [95% CI, 0.9-2.2]; P > .05 ), compared with the mortality risk of control subjects, but the increase was not statistically significant. MRSA infection independently increased length of stay by 40 days (95% CI, 34.2-45.6; P < .001) and was associated with an extra charge of

Impairment of Cerebral Autoregulation during Extracorporeal Membrane Oxygenation in Newborn Lambs

164,301 (95% CI,

Surfactant protein A concentrations in tracheal aspirate fluid from infants requiring extracorporeal membrane oxygenation

158,712-

Impaired cerebral autoregulation in the newborn lamb during recovery from severe, prolonged hypoxia, combined with carotid artery and jugular vein ligation

169,889; P < .001). CONCLUSIONS MRSA colonization or infection in infants is associated with significant morbidity and financial burden but is not independently associated with increased mortality.

Control of vancomycin-resistant enterococci in the neonatal intensive care unit.

ABSTRACT: This study was designed to evaluate the effect of normothermic partial bypass, or venoarterial extracorporeal membrane oxygenation (ECMO), on cerebral autoregulation. Fourteen newborn lambs, 1–7 d of age, were randomized into two groups: control (ligation of right carotid artery and jugular vein without ECMO; n = 7) and ECMO (ligation with placement on routine venoarterial ECMO at 120–150 mL/kg/min; n = 7). After 1 h of ECMO or stabilization in controls, cerebral autoregulation was evaluated by lowering cerebral perfusion pressure (CPP) by increasing intracranial pressure through infusion of artificial cerebrospinal fluid into the lateral ventricle. Four ranges of CPP were evaluated: 1) baseline, 2) 55–40, 3) 39–25, and 4) < 25 mm Hg. In ECMO animals, cerebral blood flow (CBF) decreased from baseline (39 ± 7 mL/100 g/min) to 23 ± 7 and 12 ± 2 at CPP of 39–25 and < 25 mm Hg. In the control group, CBF was unchanged from baseline (48 ± 11 mL/100 g/min) until CPP was < 25 mm Hg, at which time it decreased to 27 ± 16 mL/100 g/min. Cerebral oxygen consumption decreased from baseline (4.2 ± 1.1 mL/100 g/min) to 4.0 ± 0.7 and 3.2 ± 1.3 mL/100 g/min at CPP of 39–25 and < 25 mm Hg, respectively, in the ECMO group. In the control group, cerebral oxygen consumption was unchanged from baseline (4.2 ± 1.1 mL/100 g/min) until CPP was reduced to < 25 mm Hg (3.2 ± 1.3 mL/100 g/min). When CBF autoregulation was altered, i. e. when total CBF decreased, right-left hemispheric CBF differences were noted in both groups. These findings show that venoarterial ECMO, at flow rates of 120–150 mL/kg/min, alters cerebral autoregulation in healthy newborn lambs and that, if CBF is decreased by an increase in intracranial pressure, carotid artery ligation can result in lower CBF on the ipsilateral side.