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19 - Combining hypothermia with other therapies for neonatal neuroprotection

from Section 3 - The future

Published online by Cambridge University Press:  05 March 2013

By
Faye S. Silverstein  and
John D. Barks
Edited by
A. David Edwards ,
Denis V. Azzopardi  and
Alistair J. Gunn
A. David Edwards
Affiliation:
Institute of Reproductive and Developmental Biology, Imperial College, London
Denis V. Azzopardi
Affiliation:
Institute of Reproductive and Developmental Biology, Imperial College, London
Alistair J. Gunn
Affiliation:
School of Medical Sciences, University of Auckland
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Summary

Introduction

There is compelling evidence that therapeutic hypothermia confers significant benefit in term neonates with post-asphyxial encephalopathy. Yet, over 40% of treated infants have poor neurodevelopmental outcomes and there is an urgent need to identify treatments that effectively supplement the beneficial effects of hypothermia. This chapter focuses on discussion of clinically available therapeutic agents that could be administered in conjunction with hypothermia and that have the potential to augment the neuroprotective efficacy of cooling. Target populations for combination therapies include both infants who have poor outcomes with current treatments and also infants who are ultimately classified as having “good” outcomes, but who could have the potential for better long-term neurobehavioural function.

There is an inevitable delay period before therapeutic hypothermia can be started. Since time to onset of cooling is a major determinant of neuroprotective efficacy experimentally, agents that extended the duration of the therapeutic window for initiation of hypothermia would be desirable. Supplemental therapies could conceivably be administered prenatally, intra-partum, in conjunction with resuscitation, during post-resuscitation stabilization, or during transport to a neonatal intensive care unit. For any treatment administered more broadly to “at risk” neonates, before a diagnosis of encephalopathy, safety would be a critical pre-requisite and adequate documentation of safety in this population would inevitably be very challenging. For agents administered to symptomatic neonates, concurrently with onset of cooling, it would be essential to analyze drug/hypothermia interactions and take into account the impact of acute kidney or liver injury on drug pharmacokinetics. As more is understood both about endogenous mechanisms of brain repair and the mechanisms that underlie the beneficial effects of hypothermia, it may also become feasible to target therapies specifically to replicate or strengthen these mechanisms to enhance recovery after the end of hypothermia.

Type
Chapter
Information
Neonatal Neural Rescue
A Clinical Guide
 , pp. 208 - 218
Publisher: Cambridge University Press
Print publication year: 2013

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