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.

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.



Publication History

Received: 16 December 2019

Accepted: 28 August 2020

Article published online:
14 October 2020

© 2020. Thieme. All rights reserved.

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  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 13 Gunn AJ, Gunn TR. The ‘pharmacology’ of neuronal rescue with cerebral hypothermia. Early Hum Dev 1998; 53 (01) 19-35
  • 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
  • 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
  • 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
  • 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
  • 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
  • 19 Eicher DJ, Wagner CL, Katikaneni LP. et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005; 32 (01) 11-17
  • 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
  • 21 Kornhauser M, Schneiderman R. How plans can improve outcomes and cut costs for preterm infant care. Manag Care 2010; 19 (01) 28-30
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 28 Chaudhary R, Farrer K, Broster S, McRitchie L, Austin T. Active versus passive cooling during neonatal transport. Pediatrics 2013; 132 (05) 841-846
  • 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
  • 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
  • 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
  • 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