Xenon ventilation during therapeutic hypothermia in neonatal encephalopathy: a feasibility study.
OBJECTIVE
Therapeutic hypothermia has become standard of care in newborns with moderate and severe neonatal encephalopathy; however, additional interventions are needed. In experimental models, breathing xenon gas during cooling offers long-term additive neuroprotection. This is the first xenon feasibility study in cooled infants. Xenon is expensive, requiring a closed-circuit delivery system.


METHODS
Cooled newborns with neonatal encephalopathy were eligible for this single-arm, dose-escalation study if clinically stable, under 18 hours of age and requiring less than 35% oxygen. Xenon duration increased stepwise from 3 to 18 hours in 14 subjects; 1 received 25% xenon and 13 received 50%. Respiratory, cardiovascular, neurologic (ie, amplitude-integrated EEG, seizures), and inflammatory (C-reactive protein) effects were examined. The effects of starting or stopping xenon rapidly or slowly were studied. Three matched control subjects per xenon treated subject were selected from our cooling database. Follow-up was at 18 months using mental developmental and physical developmental indexes of the Bayley Scales of Infant Development II.


RESULTS
No adverse respiratory or cardiovascular effects, including post-extubation stridor, were seen. Xenon increased sedation and suppressed seizures and background electroencephalographic activity. Seizures sometimes occurred during rapid weaning of xenon but not during slow weaning. C-reactive protein levels were similar between groups. Hourly xenon consumption was 0.52 L. Three died, and 7 of 11 survivors had mental and physical developmental index scores ≥70 at follow-up.


CONCLUSIONS
Breathing 50% xenon for up to 18 hours with 72 hours of cooling was feasible, with no adverse effects seen with 18 months' follow-up.
College of Medicine, Swansea University, Swansea, United Kingdom;
John
J
Dingley
Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and.
James
J
Tooley
Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and.
Xun
X
Liu
Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and.
Emma
E
Scull-Brown
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Maja
M
Elstad
Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and.
Ela
E
Chakkarapani
Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and.
Hemmen
H
Sabir
Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; and Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway Marianne.Thoresen@bris.ac.uk.
Marianne
M
Thoresen
D000764:Anesthesia, Closed-Circuit / Q000295:instrumentation*; D001238:Asphyxia Neonatorum / Q000175:diagnosis / Q000628:therapy*; D001925:Brain Damage, Chronic / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis / Q000628:therapy*; D007223:Infant; D007231:Infant, Newborn; D009460:Neurologic Examination; D062606:Tertiary Care Centers; D014978:Xenon / Q000627:therapeutic use*
D014978:Xenon
hypothermia; hypoxic-ischemic encephalopathy; neonatal encephalopathy; newborn; quality of life; sedation; ventilation; xenon