FIG 15.2 Relationship between mean arterial pressure and left ventricular output or superior vena cava flow in 46 neonates assessed at three time points following surgical ligation of the ductus arteriosus The dashed lines represent lower acceptable limits according to gestational norms LVO, Left ventricle outflow; MBP, mean blood pressure; SVC, Superior vena cava (From Teixeira LS et al Pediatr Res 2006;59:239.) Does Hypotension Lead to Brain Injury? The rationale for treating hypotension is based on two important considerations First, the cerebral circulation becomes pressure-passive below a critical level for blood pressure (Fig 15.3).51,52 The autoregulatory mechanism is thought to fail below a mean arterial pressure of 30 mm Hg.53 There is also evidence suggesting that neonates with hypotension have impaired cerebral oxygenation, as determined by near-infrared spectroscopy, and are at increased risk of intracranial hemorrhage or periventricular leukomalacia.54 Other investigators have shown no relationship between blood pressure and cerebral blood flow.55 Second, associations have been shown between adverse neurologic consequences and systemic hypotension.56–59 There is a significant body of evidence, nonetheless, which challenges these assumptions For example, there are data suggesting that the association of hypotension to injury to the white matter and adverse neurodevelopmental outcome is not one of cause and effect, but an epiphenomenon Studies with superior designs and larger numbers have failed to demonstrate any positive association between blood pressure and adverse neurologic outcomes.60–69 When corrected for associated risk factors, such as intrauterine growth retardation, postnatal use of steroids, and chronic lung disease, the association between hypotension and abnormal neurodevelopmental outcomes was lost.70 The discrepancy between individual studies may reflect the fact that the association is much more complex than any direct effect of blood pressure on cerebral blood flow (Fig 15.4) There may be concurrent changes in cardiac output and regional differences in flow of blood independent of blood pressure that are influencing cerebral perfusion, but these studies have not been performed FIG 15.3 Schematic drawing of the relationship between cerebral blood flow and mean arterial pressure The flat portion of the curve reflects the autoregulatory plateau Below the lower part of the plateau cerebral blood flow falls proportionate to mean arterial pressure CrCP, Continuous retrograde cerebral perfusion (From Greisen G Autoregulation of cerebral blood flow in newborn babies Early Hum Dev 2005;81[5]:423–428.) FIG 15.4 Complex relationship among disease state, blood pressure, systemic blood flow, and therapeutic intervention in neonates at risk of brain injury How Should We Monitor the Preterm Circulation? Failure of the neonatal transition may lead to myocardial dysfunction, low cardiac output, and hypotension, which may compromise perfusion of the end organs with consequent damage The vulnerability of the cerebral circulation in the first 72 hours of life increases the likelihood of injury to the brain more than any other organ It is essential that the systemic flow be monitored adequately at all stages Tachycardia and capillary refill time are poorly validated and nonspecific measures of systemic flow In isolation, capillary refill time is inaccurate, highly subjective, and a poor overall predictor of the adequacy of perfusion.71 The measurement of cardiac output at the bedside is a useful adjunct to the clinical assessment, and there are normative data for both right and left ventricular outputs.72,73 The normal range for cardiac output in normal premature infants is between 170 and 320 mL/kg per minute These measurements should be interpreted in context in the early neonatal period due to the effects of transductal shunting Left ventricular output reflects flow to the central nervous system because the cerebral circulation is preductal, and its