Jeffrey R. Kaiser

Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants.

Objective:To examine whether hypercapnia in very low birth weight (VLBW) infants during the first 3 days of life is associated with severe intraventricular hemorrhage (IVH).Study design:Retrospective cohort study of inborn VLBW infants between January 1999 and May 2004 with arterial access during the first 3 days of life. A multiple logistic regression analysis was used where IVH was dichotomized ((grades 0/1/2)=non-severe; (grades 3/4)=severe). Measures of hypercapnia were entered into the model to ascertain their association with severe IVH.Results:In total, 574 VLBW infants met entry criteria. Worst IVH grade was 0 in 400; 1: 54; 2: 42; 3: 47; and 4: 31 infants. The logistic regression model consisted of the following predictors of severe IVH: gestational age, gender, 1 min Apgar score (dichotomized into two groups: >3 vs ⩽3), multifetal gestation, vasopressor use, and maximum PaCO2.Conclusion:In addition to traditional risk factors, it appears maximum PaCO2 is a dose-dependent predictor of severe IVH during the permissive hypercapnia era.

The effects of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants.

Permissive hypercapnia, a strategy allowing high Paco2, is widely used by neonatologists to minimize lung damage in ventilated very low birth weight (VLBW) infants. While hypercapnia increases cerebral blood flow (CBF), its effects on cerebral autoregulation of VLBW infants are unknown. Monitoring of mean CBF velocity (mCBFv), Paco2, and mean arterial blood pressure (MABP) from 43 ventilated VLBW infants during the first week of life was performed during and after 117 tracheal suctioning procedures. Autoregulation status was determined during tracheal suctioning because it perturbs cerebral and systemic hemodynamics. The slope of the relationship between mCBFv and MABP was estimated when Paco2 was fixed at 30, 35, 40, 45, 50, 55, and 60 mm Hg. A slope near or equal to 0 suggests intact autoregulation, i.e. CBF is not influenced by MABP. Increasing values >0 indicate progressively impaired autoregulation. Infants weighed 905 ± 259 g and were 26.9 ± 2.3 wk gestation. The autoregulatory slope increased as Paco2 increased from 30 to 60 mm Hg. While the slopes for Paco2 values of 30 to 40 mm Hg were not statistically different from 0, slopes for Paco2 ≥45 mm Hg indicated a progressive loss of cerebral autoregulation. The autoregulatory slope increases with increasing Paco2, suggesting the cerebral circulation becomes progressively pressure passive with hypercapnia. These data raise concerns regarding the use of permissive hypercapnia in ventilated VLBW infants during the first week of life, as impaired autoregulation during this period may be associated with increased vulnerability to brain injury.

A population-based study of congenital diaphragmatic hernia: Impact of associated anomalies and preoperative blood gases on survival

BACKGROUND/PURPOSE Although neonatal care has improved over the past 20 years, mortality rate with congenital diaphragmatic hernia (CDH) remains 50% to 60%, possibly reflecting differences in management or selection biases. The authors determined the incidence, outcome, effect of coexisting anomalies, and prognostic indicators for neonates with CDH in a single inborn population older than 13 years. METHODS Forty-three neonates with CDH, those symptomatic within the first 6 hours of life, were identified using a validated neonatal database and diagnosis coding data from medical records among 180,643 live inborn neonates delivered at Parkland Memorial Hospital between 1983 and 1995. Charts were reviewed for prenatal history, demographic variables, presence of coexisting malformations, preoperative arterial blood gases, surgical findings, and outcome. Survival to hospital discharge was the primary outcome variable. RESULTS The incidence of CDH was 1 in 4,200 live births; overall survival rate was 51%. Thirty-two (74%) neonates underwent surgical repair, often at less than 8 hours of life; postoperative mortality rate was 31%. Eighteen (42%) had coexisting major anomalies or chromosomal abnormalities. Eighty percent of neonates with isolated CDH survived, whereas 89% with CDH and associated defects died. Nonsurvivors had lower birth weights and Apgar scores, were more acidotic, and had more severe respiratory compromise. When best preoperative pH was > or = 7.25 or PaCO2 < or = 50 mm Hg, 80% of neonates survived. CONCLUSION In this inborn population-based review of neonatal CDH between 1983 and 1995, the best predictors of survival were the presence or absence of other anomalies and the best preoperative PaCO2 and pH.

Tracheal suctioning is associated with prolonged disturbances of cerebral hemodynamics in very low birth weight infants.

Objectives:Examining the effects of tracheal suctioning on cerebral hemodynamics of normotensive ventilated very low birth weight (VLBW) infants with normal cranial ultrasounds; determining the factor(s) influencing changes in mean cerebral blood flow velocity (CBFv) after suctioning.Methods:Seventy-three VLBW infants had continuous monitoring of mean arterial blood pressure (MABP), PaCO2, PaO2 and mean CBFv before, during, and after 202 suctioning sessions during the first week of life. Peak (or nadir) and relative changes of the four variables for 45 min after suctioning were calculated. Multiple linear regression was used to determine the factor(s) influencing changes in mean CBFv after suctioning.Result:Birth weight was 928±244 g; gestational age was 27.0±2.0 weeks. Mean CBFv increased to 31.0±26.4% after suctioning and remained elevated for 25 min. PaCO2 was highly associated with mean CBFv (P<0.001), whereas MABP and PaO2 were not.Conclusion:We observed prolonged increases of mean CBFv following suctioning in ventilated VLBW infants that were previously unrecognized. This is concerning since disturbances of CBF may be associated with subsequent brain injury.

Hospital survival of very-low-birth-weight neonates from 1977 to 2000.

OBJECTIVE: To determine patterns of survival for very low birth weight (VLBW, birth weight 501 to 1500 g) neonates over 23 years.STUDY DESIGN: Data for 4873 VLBW neonates born from 1977 to 2000 were divided into five epochs. The primary outcome was survival to hospital discharge. Birth weight-specific survival rates were estimated by race and gender for each epoch. Presence of comorbidities and congenital anomalies, delivery mode, and provision of artificial ventilation were investigated to determine whether they could explain observed survival patterns.RESULTS: From 1977 to 1995, survival increased from 50.2% to 81.0% as the proportion of VLBW neonates receiving artificial ventilation rose from 59.0% to 80.9%. Survival was unchanged between 1990 to 1995 and 1996 to 2000. Black females maintained a survival advantage over the entire study period. Survival improved for neonates with congenital anomalies over time, but had little impact on race/gender survival patterns. Survival patterns also could not be explained by comorbidity status, delivery mode, or access to artificial ventilation.CONCLUSION: The survival advantage of VLBW black females persists and remains unexplained.

Should antibiotics be discontinued at 48 hours for negative late-onset sepsis evaluations in the neonatal intensive care unit?

OBJECTIVE: To establish the appropriate length of antibiotic therapy for negative late-onset sepsis evaluations in the neonatal intensive care unit (NICU), based on time to detection of positive bacterial cultures.STUDY DESIGN: Culture results from late-onset sepsis evaluations between January 1, 1994 and June 30, 1998 from outborn neonates at the Arkansas Childrens Hospital NICU were retrospectively reviewed. The time period from specimen collection to notification of NICU personnel was calculated for positive cultures.RESULTS: There were 2783 blood, 724 urine, and 294 cerebrospinal fluid cultures obtained, of which 10.2%, 6.6%, and 5.4%, respectively, were positive for bacterial isolates. Of positive cultures, 98% had a time to detection ≤48 hours. Of cultures that became positive >48 hours, 7 of 8 grew coagulase-negative staphylococci; 4 were contaminants.CONCLUSION: Discontinuing antibiotic therapy for neonates with possible late-onset sepsis and negative cultures at 48 hours is appropriate and is now standard care in our NICU.

Maternal race, demography, and health care disparities impact risk for intraventricular hemorrhage in preterm neonates.

OBJECTIVE To determine whether risk factors associated with grade 2-4 intraventricular hemorrhage (IVH) differs between infants of African ancestry and white infants. STUDY DESIGN Inborn, appropriate for gestational age infants with birth weight 500-1250 g and exposure to at least 1 dose of antenatal steroids were enrolled in 24 neonatal intensive care units. Cases had grade 2-4 IVH and controls matched for site, race, and birth weight range had 2 normal ultrasounds read centrally. Multivariate logistic regression modeling identified factors associated with IVH across African ancestry and white race. RESULTS Subjects included 579 African ancestry or white race infants with grade 2-4 IVH and 532 controls. Mothers of African ancestry children were less educated, and white case mothers were more likely to have more than 1 prenatal visit and multiple gestation (P ≤ .01 for all). Increasing gestational age (P = .01), preeclampsia (P < .001), complete antenatal steroid exposure (P = .02), cesarean delivery (P < .001), and white race (P = .01) were associated with decreased risk for IVH. Chorioamnionitis (P = .01), 5-minute Apgar score <3 (P < .004), surfactant use (P < .001), and high-frequency ventilation (P < .001) were associated with increased risk for IVH. Among African ancestry infants, having more than 1 prenatal visit was associated with decreased risk (P = .02). Among white infants, multiple gestation was associated with increased risk (P < .001), and higher maternal education was associated with decreased risk (P < .05). CONCLUSION The risk for IVH differs between infants of African ancestry and white infants, possibly attributable to both race and health care disparities.

Differential development of umbilical and systemic arteries. I. ANG II receptor subtype expression

In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1 mediates vasoconstriction in adult tissues. Thus differences in reactivity could reflect differences in subtype expression. Using competitive radioligand binding assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral arteries. Steady-state responses to intravenous ANG II (0.229-1.72 μg/min) were studied in 16 fetuses with umbilical and/or femoral artery flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade. ANG II dose dependently ( P < 0.001) increased umbilical resistance more than arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular resistance also increased dose dependently ( P = 0.02), but responses were less than umbilical ( P = 0.0001) and paralleled increases in MAP; blood flow was unaffected. Cumulative local doses of L-158,809 (125 μg) inhibited all responses ( P< 0.001); however, 1,000 μg of the AT2 antagonist had no effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas PRA doubled ( P = 0.001) after systemic infusion of only 50 μg of the AT1 antagonist and remained elevated. Differences in umbilical and femoral vascular responses to ANG II are in large part due to differences in AT subtype expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is mediated by AT1 receptors, and it is substantially more sensitive to receptor blockade than the vasculature.In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1 mediates vasoconstriction in adult tissues. Thus differences in reactivity could reflect differences in subtype expression. Using competitive radioligand binding assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral arteries. Steady-state responses to intravenous ANG II (0.229-1.72 micrograms/min) were studied in 16 fetuses with umbilical and/or femoral artery flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade. ANG II dose dependently (P < 0.001) increased umbilical resistance more than arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular resistance also increased dose dependently (P = 0.02), but responses were less than umbilical (P = 0.0001) and paralleled increases in MAP; blood flow was unaffected. Cumulative local doses of L-158,809 (125 micrograms) inhibited all responses (P < 0.001); however, 1,000 micrograms of the AT2 antagonist had no effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas PRA doubled (P = 0.001) after systemic infusion of only 50 micrograms of the AT1 antagonist and remained elevated. Differences in umbilical and femoral vascular responses to ANG II are in large part due to differences in AT subtype expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is mediated by AT1 receptors, and it is substantially more sensitive to receptor blockade than the vasculature.

Low-voltage aEEG as predictor of intracranial hemorrhage in preterm infants

The objectives of this prospective cohort study were to identify amplitude-integrated electroencephalography (aEEG) background patterns predictive of severe intracranial hemorrhage. Thirty ventilated preterm newborns weighing <1,000 g were assessed by an aEEG cerebral function monitor and ultrasound measurement of cerebral blood flow velocity at time of surfactant administration and tracheal suctioning simultaneously during first 48 hours of life. Birth weight was 624 ± 200 g (mean ± S.D.) and gestational age was 25 ± 2 weeks. Background electrical activity was predominantly discontinuous in 72% of infants. A sharp increase in electrical activity/burst density was observed during surfactant administration and tracheal suctioning in most infants, with a 33.5% increase in mean cerebral blood flow velocity. Burst suppression with low voltage was identified in 57% infants with severe intracranial hemorrhage, whereas no infant without hemorrhage exhibited this pattern (P = 0.014). We conclude that aEEG low-voltage burst suppression might have useful clinical applications with 100% positive predictive value for severe intracranial hemorrhage.

The ontogeny of cerebrovascular pressure autoregulation in premature infants

Objective:To quantify cerebrovascular autoregulation as a function of gestational age (GA) and across the phases of the cardiac cycle.Study design:The present study is a hypothesis-generating re-analysis of previously published data. Premature infants (n=179) with a GA range of 23 to 33 weeks were monitored with umbilical artery catheters and transcranial Doppler insonation of the middle cerebral artery for 1-h sessions over the first week of life. Autoregulation was quantified by three methods, as a moving correlation coefficient between: (1) systolic arterial blood pressure (ABP) and systolic cerebral blood flow (CBF) velocity (Sx); (2) mean ABP and mean CBF velocity (Mx); and (3) diastolic ABP and diastolic CBF velocity (Dx). Comparisons of individual and cohort cerebrovascular pressure autoregulation were made across GA for each aspect of the cardiac cycle.Results:Systolic, mean and diastolic ABP increased with GA (r=0.3, 0.4 and 0.4; P<0.0001). Systolic CBF velocity was pressure-passive in infants with the lowest GA, and Sx decreased with advancing GA (r=−0.3; P<0.001), indicating increased capacity for cerebral autoregulation during systole during development. By contrast, Dx was elevated, indicating dysautoregulation, in all subjects and showed minimal change with advancing GA (r=−0.06; P=0.05). Multivariate analysis confirmed that both GA (P<0.001) and ‘effective cerebral perfusion pressure’ (ABP minus critical closing pressure (CrCP); P<0.01) were associated with Sx.Conclusion:Premature infants have low and usually pressure-passive diastolic CBF velocity. By contrast, the regulation of systolic CBF velocity by pressure autoregulation developed in this cohort between 23 and 33 weeks GA. Elevated effective cerebral perfusion pressure derived from the CrCP was associated with dysautoregulation.