Jeffrey R. Kaiser, MD, MA
Physiological Disturbances Associated with Neonatal Intraventricular
Hemorrhage: Annually, nearly 5,000 extremely low birth weight (ELBW,
birth weight ≤1000 g) infants in the US develop severe intraventricular
hemorrhage (IVH, grades III and IV); this devastating complication of
prematurity is associated with long-term adverse neurodevelopmental
sequelae, such as cognitive, behavioral, and learning disabilities, as
well as cerebral palsy. Unfortunately, identifying the ELBW infants who
are at highest risk for developing IVH and who could benefit most from
specific interventions has been difficult and based on retrospective
studies. Our overall goal is to prospectively evaluate and understand
disturbed physiological phenomena associated with IVH in order to
predict those infants most at risk and to develop best care clinical
practices that may subsequently limit severe brain injury in ELBW
infants. While the etiology of IVH is multifactorial, disturbances of
cerebral blood flow (CBF) and cerebral autoregulation play important
roles; both are influenced by alterations of gas exchange and systemic
hemodynamics associated with routine intensive care procedures. Extremes
of CO2 may have deleterious effects on infants' CBF because the arterial
CO2 tension (PaCO2) is a potent mediator of cerebral vascular tone and
influences cerebral blood supply. Hypotension or hypertension may cause
cerebral hypo- or hyperperfusion, respectively, leading to IVH in
infants with impaired cerebral autoregulation by an ischemia/reperfusion
mechanism. Because disturbances of PaCO2, blood pressure (BP), and heart
rhythm are common in ELBW infants undergoing intensive care, our central
hypothesis is that alterations and extremes of these physiological
factors that influence CBF and cerebral autoregulation in ELBW infants
may initiate IVH and serve as important predictors of ELBW infants most
at risk of IVH, thereby allowing identification of a high-risk subgroup
of infants who may benefit most from intervention.
Doppler ultrasound is a widely used non-invasive
method to study neonatal cerebral hemodynamics; it was first
used in newborns in 1979. Determining cerebral blood flow (CBF)
velocity by ultrasound is based upon the Doppler principle
where a change in the frequency of a sound wave is caused by
the relative motion between an observer and a sound source. The
procedure is non-invasive, safe, easily performed at the
bedside without disturbing the infant, provides real-time
information, and is ideal for making serial measurements
from stable or sick infants. Additional
advantages of using Doppler ultrasound to measure CBF
velocity (an indirect measure of CBF) are that no
radioactive materials or chemicals (such as xenon or nitrous
oxide) are used, manipulations are not required (as with
venous plethysmography), and the technique does not require
alterations of oxygen concentration (as with near infrared
spectroscopy). Dynamic monitoring is another important
benefit of this technique because it allows continuous and
instantaneous measurements of CBF velocity. Thus, this
method offers a non-invasive approach to investigate how
disturbances of CBF velocity in VLBW infants may be linked
with brain injury.
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cerebral and systemic hemodynamics and gas exchange in very low birth
weight infants. J Pediatr 2004; 144: 809-814.
Kronsberg SS, Barton BA, Kaiser JR, Anand KJS. Morphine,
hypotension, and adverse outcomes in premature neonates: Who's to blame?
Secondary results from the NEOPAIN trial. Pediatrics 2005; 115:
Gauss CH, Williams DK.
Effects of hypercapnia on cerebral autoregulation in ventilated very low
birth weight infants. Pediatr Res 58 (5):931-935, 2005.
Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD,
Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ, on
behalf of the CoolCap Study Group. Selective head cooling with
mild systemic hypothermia after neonatal encephalopathy: multicenter
randomised trial. The Lancet, 2005; 365: 663-670.
Gauss CH, Pont MK, Williams DK. Hypercapnia during the first three days
of life is associated with severe intraventricular hemorrhage in very
low birth weight infants. J Perinatol, 2006; 26:279-285.
May-Wewers J, Kaiser JR, Moore EK, Blackall DP. Severe
neonatal hemolysis due to a maternal antibody to the low-frequency Rh
Antigen Cw. Am J Perinatol, 2006; 23: 1-5
Chalak LF, Kaiser JR, Arrington RW. Resolution of
pulmonary interstitial emphysema following selective left main stem
intubation in a premature newborn: an old procedure revisited.
Pediatric Anesthesia, 2007; 17: 183-186.
Neurologic Sequelae following Mechanical Ventilation. In Hot Topics
in Neonatal Neurology, Michael Schimmel (ed), Nova Scientific