Cerebrovascular Effects of Rapid Volume Expansion in Preterm Fetal Sheep

Abstract

Preterm human infants are often treated with volume expansion during their initial stabilization. There are limited data regarding the cerebral vascular effects of this therapeutic approach. The effects of blood volume expansion on cerebral vascular reactivity and oxygen metabolism in very immature animals have not been determined. We examined the effects of volume expansion, with and without hypoxia, on cerebral blood flow and metabolism in unanesthetized, chronically catheterized, preterm fetal sheep. Rapid volume expansion with i.v. dextran increased circulating blood volume. Arterial blood pressure did not increase, nor did cerebral blood flow. However, volume expansion resulted in lower arterial Hb concentration and, consequently, oxygen content without a compensatory increase in cerebral blood flow. Cerebral oxygen delivery fell significantly. Induction of severe hypoxia after volume expansion resulted in an increase in cerebral blood flow, as expected, but the increase in flow was not enough to maintain cerebral oxygen delivery. Rapid volume expansion in normovolemic preterm fetal sheep is associated with decreased cerebral oxygen delivery, and this is further compromised when oxygen content is decreased. Very preterm infants are often treated with boluses of normal saline during their initial stabilization (1-3). The clinical indications are usually low blood pressure and/or poor perfusion, often without other signs of, or risk factors for, hypovolemia. There are limited data regarding the cerebral vascular effects of this therapeutic approach. In piglets, volume expansion after hypotension and asphyxia results in increased CBF (4). In adult dogs, CBF decreases when volume expansion is given with closed-chest cardiopulmonary resuscitation (5). Developmental or species differences in systemic responses, including baroreceptor activation and left ventricular responses, may account for these conflicting results (6).Hypoxic cerebral vasodilatation occurs in the late-term fetal (7, 8), neonatal (9), and adult sheep (9). In preterm fetal sheep, this response is blunted, and severe hypoxia results in a limitation in cerebral OD when compared with the near-term fetus (10). Cerebral oxygen consumption is maintained, in part, by an increase in fractional oxygen extraction (10). Volume expansion in the face of hypoxemia could further impair cerebral OD by limiting oxygen carrying capacity, particularly in very preterm fetuses.We hypothesized that acute volume expansion in normovolemic developing animals could result in abnormalities in CBF regulation, possibly associated with changes in cerebral venous pressure. We further hypothesized that these changes in cerebral venous pressure could limit hypoxic cerebral vasodilatation. We chose to study the preterm fetal sheep because Brace et al. (11) had previously demonstrated that i.v. dextran infusion could significantly expand fetal blood volume and that this effect could be maintained for several hours. However, Brace and colleagues did not examine the effects of vo...

Dopamine does not limit fetal cerebrovascular responses to hypoxia

“…Baseline measurement of blood gases, pH, heart rate, arterial blood pressure, hematocrit, hemoglobin, and CBF are presented in Table 1. These measures are similar to those previously published for fetal sheep at this gestation (8,17).…”

“…A catheter (Tygon tubing) was sewn to a fetal hoof to measure amniotic fluid pressure. The fetal weight was estimated by visual inspection (8,17). Vascular catheters were prefilled with heparinized saline (10 units/ml).…”

Prospective Evaluation of Postnatal Steroid Administration: A 1-Year Experience From the California Perinatal Quality Care Collaborative

“…58,59 There was also a recent suggestion that volume administration to preterm hypoxic animals may impair cerebral oxygen delivery. 60 These observations may be encouraging the use of alternate pharmacological approaches for the hypotensive VLBW infant. For the EDG units surveyed in this study, Ͼ15% of VLBW infants received hydrocortisone for hypotension confirming the high incidence of hypotension in this population.…”

Part 11: Neonatal Resuscitation

“…Many with pallor and tachycardia responded to volume expansion without having received chest compressions. In the absence of a history of blood loss there is limited evidence of benefit from administration of volume during resuscitation unresponsive to chest compressions/epinephrine (LOE 4 111 ) and some suggestion of potential harm from animal studies (LOE 5 112,113 ).…”