Download PDF
Am J Perinatol 2022; 39(06): 633-639
DOI: 10.1055/s-0040-1718372
Original Article

Therapeutic Hypothermia in Transport Permits Earlier Treatment Regardless of Transfer Distance

Rachel L. Leon
1   Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, Indiana
2   Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
,
Katherine E. Krause
3   Departments of Pediatrics and Internal Medicine, Indiana University School of Medicine, Indianapolis, Indiana
,
Rebecca S. Sides
1   Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, Indiana
,
Mary Beth Koch
4   Riley Hospital for Children at IU Health, Indianapolis, Indiana
,
Michael S. Trautman
5   Indiana University Health Lifeline Transport Services, Indianapolis, Indiana
,
Ulrike Mietzsch
1   Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, Indiana
6   Department of Pediatrics, Division of Neonatology, University of Washington School of Medicine, Seattle, Washington
› Author Affiliations Funding This project was funded by the Riley Children's Foundation.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective Therapeutic hypothermia (TH) is currently the only effective therapy available to improve outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) and has maximal effect when initiated within 6 hours of birth. Neonates affected by HIE are commonly born outside of cooling centers and transport is a barrier to timely initiation. In this study, we sought to determine if the initiation of servo-controlled TH in transport allowed neonates to reach target temperature earlier, without a significant delay in the transfer process, for both local and long-distance transport.

Study Design In this single-center cohort study of neonates referred to a level IV neonatal intensive care unit for TH, we determined the chronologic age at which target temperature was reached for those cooled in transport. Short-term outcome measures were assessed, including survival, incidence of electrographic seizures, discharge feeding method, and length of hospitalization.

Results In a study population of 85 neonates, those receiving TH during transport (n = 23), achieved target temperature (33–34°C) 77 minutes sooner (230 ± 71 vs. 307 ± 79 minutes of life (MOL); p < 0.001). Locally transported neonates (<15 miles) achieved target temperature 69 minutes earlier (215 ± 48 vs. 284 ± 74 MOL; p < 0.01). TH during long-distance transports allowed neonates to reach target temperature 81 minutes sooner (213 ± 85 vs. 294 ± 79 MOL; p < 0.01). Infants who were cooled in transport discharged 4 days earlier (13.7 ± 8 vs. 17.8 ± 13 days; p = 0.18) and showed a significantly higher rate of oral feeding at discharge (95 vs. 71%; p = 0.03).

Conclusion For those starting TH in transport, time to target temperature was decreased. In our cohort, cooling in transport was associated with improved short-term outcomes, although additional studies are needed to correlate these findings with long-term outcomes.

Key Points

  • Therapeutic hypothermia started during transport allows shorter time to target temperature.

  • Transfer was minimally delayed by starting cooling in transport.

  • Cooling in transport was associated with increased rate of oral feeding at hospital discharge.

Keywords

hypoxic-ischemic encephalopathy - neonatal transport - therapeutic hypothermia - birth asphyxia - active cooling - transport cooling - birth depression


Publication History

Received: 16 December 2019

Accepted: 28 August 2020

Article published online:
14 October 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86 (06) 329-338
    CrossrefPubMedSearch in Google Scholar
  • 2 Liu L, Johnson HL, Cousens S. et al; Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 379 (9832): 2151-2161
    CrossrefPubMedSearch in Google Scholar
  • 3 Sabir H, Scull-Brown E, Liu X, Thoresen M. Immediate hypothermia is not neuroprotective after severe hypoxia-ischemia and is deleterious when delayed by 12 hours in neonatal rats. Stroke 2012; 43 (12) 3364-3370
    CrossrefPubMedSearch in Google Scholar
  • 4 Gunn AJ, Gunn TR, Gunning MI, Williams CE, Gluckman PD. Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep. Pediatrics 1998; 102 (05) 1098-1106
    CrossrefPubMedSearch in Google Scholar
  • 5 Thoresen M, Tooley J, Liu X. et al. Time is brain: starting therapeutic hypothermia within three hours after birth improves motor outcome in asphyxiated newborns. Neonatology 2013; 104 (03) 228-233
    CrossrefPubMedSearch in Google Scholar
  • 6 Gunn AJ, Bennet L, Gunning MI, Gluckman PD, Gunn TR. Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep. Pediatr Res 1999; 46 (03) 274-280
    CrossrefPubMedSearch in Google Scholar
  • 7 Gunn AJ, Gunn TR, de Haan HH, Williams CE, Gluckman PD. Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. J Clin Invest 1997; 99 (02) 248-256
    CrossrefPubMedSearch in Google Scholar
  • 8 Thoresen M, Penrice J, Lorek A. et al. Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet. Pediatr Res 1995; 37 (05) 667-670
    CrossrefPubMedSearch in Google Scholar
  • 9 Wagner BP, Nedelcu J, Martin E. Delayed postischemic hypothermia improves long-term behavioral outcome after cerebral hypoxia-ischemia in neonatal rats. Pediatr Res 2002; 51 (03) 354-360
    CrossrefPubMedSearch in Google Scholar
  • 10 Shankaran S, Laptook AR, Ehrenkranz RA. et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
    CrossrefPubMedSearch in Google Scholar
  • 11 Coimbra C, Wieloch T. Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia. Acta Neuropathol 1994; 87 (04) 325-331
    CrossrefPubMedSearch in Google Scholar
  • 12 Thoresen M, Bågenholm R, Løberg EM, Apricena F, Kjellmer I. Posthypoxic cooling of neonatal rats provides protection against brain injury. Arch Dis Child Fetal Neonatal Ed 1996; 74 (01) F3-F9
    CrossrefPubMedSearch in Google Scholar
  • 13 Gunn AJ, Gunn TR. The ‘pharmacology’ of neuronal rescue with cerebral hypothermia. Early Hum Dev 1998; 53 (01) 19-35
    CrossrefPubMedSearch in Google Scholar
  • 14 Karlsson M, Tooley JR, Satas S. et al. Delayed hypothermia as selective head cooling or whole body cooling does not protect brain or body in newborn pig subjected to hypoxia-ischemia. Pediatr Res 2008; 64 (01) 74-78
    CrossrefPubMedSearch in Google Scholar
  • 15 Azzopardi D, Brocklehurst P, Edwards D. et al; TOBY Study Group. The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr 2008; 8: 17
    CrossrefPubMedSearch in Google Scholar
  • 16 Gluckman PD, Wyatt JS, Azzopardi D. et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365 (9460): 663-670
    CrossrefPubMedSearch in Google Scholar
  • 17 Azzopardi DV, Strohm B, Edwards AD. et al; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009; 361 (14) 1349-1358
    CrossrefPubMedSearch in Google Scholar
  • 18 Zhou WH, Cheng GQ, Shao XM. et al; China Study Group. Selective head cooling with mild systemic hypothermia after neonatal hypoxic-ischemic encephalopathy: a multicenter randomized controlled trial in China. J Pediatr 2010; 157 (03) 367-372 , 372.e1–372.e3
    CrossrefPubMedSearch in Google Scholar
  • 19 Eicher DJ, Wagner CL, Katikaneni LP. et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005; 32 (01) 11-17
    CrossrefPubMedSearch in Google Scholar
  • 20 Natarajan G, Pappas A, Shankaran S. et al. Effect of inborn vs. outborn delivery on neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy: secondary analyses of the NICHD whole-body cooling trial. Pediatr Res 2012; 72 (04) 414-419
    CrossrefPubMedSearch in Google Scholar
  • 21 Kornhauser M, Schneiderman R. How plans can improve outcomes and cut costs for preterm infant care. Manag Care 2010; 19 (01) 28-30
    PubMedSearch in Google Scholar
  • 22 Fairchild K, Sokora D, Scott J, Zanelli S. Therapeutic hypothermia on neonatal transport: 4-year experience in a single NICU. J Perinatol 2010; 30 (05) 324-329
    CrossrefPubMedSearch in Google Scholar
  • 23 Goel N, Mohinuddin SM, Ratnavel N, Kempley S, Sinha A. Comparison of passive and servo-controlled active cooling for infants with hypoxic-ischemic encephalopathy during neonatal transfers. Am J Perinatol 2017; 34 (01) 19-25
    PubMedSearch in Google Scholar
  • 24 Buchiboyina A, Ma E, Yip A. et al. Servo controlled versus manual cooling methods in neonates with hypoxic ischemic encephalopathy. Early Hum Dev 2017; 112: 35-41
    CrossrefPubMedSearch in Google Scholar
  • 25 Akula VP, Joe P, Thusu K. et al. A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy. J Pediatr 2015; 166 (04) 856-61.e1 , 2
    CrossrefPubMedSearch in Google Scholar
  • 26 Hallberg B, Olson L, Bartocci M, Edqvist I, Blennow M. Passive induction of hypothermia during transport of asphyxiated infants: a risk of excessive cooling. Acta Paediatr 2009; 98 (06) 942-946
    CrossrefPubMedSearch in Google Scholar
  • 27 Akula VP, Gould JB, Davis AS, Hackel A, Oehlert J, Van Meurs KP. Therapeutic hypothermia during neonatal transport: data from the California Perinatal Quality Care Collaborative (CPQCC) and California Perinatal Transport System (CPeTS) for 2010. J Perinatol 2013; 33 (03) 194-197
    CrossrefPubMedSearch in Google Scholar
  • 28 Chaudhary R, Farrer K, Broster S, McRitchie L, Austin T. Active versus passive cooling during neonatal transport. Pediatrics 2013; 132 (05) 841-846
    CrossrefPubMedSearch in Google Scholar
  • 29 Sellam A, Lode N, Ayachi A, Jourdain G, Dauger S, Jones P. Passive hypothermia (≥35 - <36°C) during transport of newborns with hypoxic-ischaemic encephalopathy. PLoS One 2017; 12 (03) e0170100
    CrossrefPubMedSearch in Google Scholar
  • 30 O'Reilly D, Labrecque M, O'Melia M, Bacic J, Hansen A, Soul JS. Passive cooling during transport of asphyxiated term newborns. J Perinatol 2013; 33 (06) 435-440
    CrossrefPubMedSearch in Google Scholar
  • 31 Szakmar E, Kovacs K, Meder U. et al. Feasibility and safety of controlled active hypothermia treatment during transport in neonates with hypoxic-ischemic encephalopathy. Pediatr Crit Care Med 2017; 18 (12) 1159-1165
    CrossrefPubMedSearch in Google Scholar
  • 32 Higgins RD, Raju T, Edwards AD. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Hypothermia Workshop Speakers and Moderators. Hypothermia and other treatment options for neonatal encephalopathy: an executive summary of the Eunice Kennedy Shriver NICHD workshop. J Pediatr 2011; 159 (05) 851-858.e1
    CrossrefPubMedSearch in Google Scholar