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Plasma Leak From the Circulation Contributes to Poor Outcomes for Preterm Infants: A Working Hypothesis
Yvonne A Eiby1, Barbara E Lingwood1,2, Ian M R Wright1,3,4
1Faculty of Medicine, Perinatal Research Centre, Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.
Insights
Hypovolemia in preterm infants, caused by plasma loss, leads to poor brain oxygenation and cardiovascular instability. New strategies targeting plasma loss mechanisms are needed to improve outcomes for these vulnerable infants.
Area of Science:
- Neonatal physiology
- Perinatal medicine
- Pediatric neurology
Background:
- Preterm infants face significant risks of brain injury, death, and disability.
- Impaired cardiovascular function and cerebral oxygenation contribute to adverse outcomes.
- Current therapies have not improved outcomes for preterm infants with brain injury.
Purpose of the Study:
- To re-examine evidence linking hypovolemia to cardiovascular instability and poor cerebral oxygenation in preterm infants.
- To identify mechanisms driving plasma loss in the preterm circulation.
- To propose a framework for testing a novel hypothesis regarding hypovolemia and preterm infant brain injury.
Main Methods:
- Review and synthesis of existing evidence on hypovolemia in preterm infants.
- Analysis of factors contributing to plasma loss, including capillary permeability and pressure gradients.
- Examination of the role of impaired lymphatic return, inflammation, and current treatments.
Main Results:
- Hypovolemia in preterm infants is driven by plasma loss from the circulation.
- High capillary permeability, altered pressure gradients, and reduced lymphatic return increase plasma loss.
- Early hypovolemia is evident in preterm infants, exacerbated by inflammation and certain treatments.
Conclusions:
- Hypovolemia is a significant factor in preterm infant cardiovascular instability and poor cerebral oxygenation.
- Understanding plasma loss mechanisms offers potential for novel therapeutic strategies.
- New treatments targeting cardiovascular support and cerebral oxygenation are needed to improve outcomes.
Abstract:
Preterm infants are at high risk of death and disability resulting from brain injury. Impaired cardiovascular function leading to poor cerebral oxygenation is a significant contributor to these adverse outcomes, but current therapeutic approaches have failed to improve outcome. We have re-examined existing evidence regarding hypovolemia and have concluded that in the preterm infant loss of plasma from the circulation results in hypovolemia; and that this is a significant driver of cardiovascular instability and thus poor cerebral oxygenation. High capillary permeability, altered hydrostatic and oncotic pressure gradients, and reduced lymphatic return all combine to increase net loss of plasma from the circulation at the capillary. Evidence is presented that early hypovolemia occurs in preterm infants, and that capillary permeability and pressure gradients all change in a way that promotes rapid plasma loss at the capillary. Impaired lymph flow, inflammation and some current treatment strategies may further exacerbate this plasma loss. A framework for testing this hypothesis is presented. Understanding these mechanisms opens the way to novel treatment strategies to support cardiovascular function and cerebral oxygenation, to replace current therapies, which have been shown not to change outcomes.
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