Techniques for therapeutic hypothermia during transport and in hospital for perinatal asphyxial encephalopathy

https://doi.org/10.1016/j.siny.2010.03.006Get rights and content

Summary

Over the past 10 years, several randomised clinical trials of therapeutic hypothermia for perinatal asphyxial encephalopathy have demonstrated both safety and efficacy of therapeutic hypothermia in improving neurological outcome. Today cooling is increasingly used in tertiary level units throughout the developed world. Therapeutic hypothermia (cooling to a rectal or core temperature of 33–34 °C for 72 h) is easier to achieve in newborn infants than in adults. There is a natural tendency for the core temperature of infants who suffered birth asphyxia to fall and remain lower than non-asphyxiated infants for up to 16 h after birth. A variety of high- and low-tech surface cooling methods have been used in neonates – newer systems are servo-controlled and provide very stable temperature control. It is well accepted that to be most effective, cooling needs to be initiated as soon as possible after birth and, thus, needs to be commenced prior to the transfer of infants to cooling centres. We describe our experience of passive cooling before and during the transfer of infants with encephalopathy to cooling centres in a major city in the UK.

Introduction

Within the last decade, therapeutic hypothermia for infants with perinatal asphyxial encephalopathy has been studied in preclinical models1, 2, 3 and several major randomised clinical trials in the developed world.4, 5, 6, 7 Despite the clinical heterogeneity of perinatal asphyxia and the use of different cooling methods, there are consistent findings that hypothermia reduces the extent of neurological damage and improves survival without disability.8 Therapeutic hypothermia is now widely offered to moderately or severely asphyxiated infants in countries and centres which participated in the trials.9 Anecdotally, other countries are also adopting cooling therapy. At present, however, the safety and efficacy of therapeutic hypothermia in low-resource and transitional-care countries has not been proven.10, 11, 12 ‘Low-tech’, simple methods of cooling are now being developed that could allow therapeutic hypothermia to be provided in an economical and sustainable fashion in future trials of cooling in such settings.13

The extent of neuroprotection by hypothermia depends on the time of initiation of cooling and its duration – prolonged cooling within the ‘therapeutic window’ (defined in the current neonatal trials as within 6 h of birth) is essential for long-term, robust protection.14, 15 Although the precise brain temperature that provides optimal neuroprotection following perinatal asphyxia is unknown,15, 16 there is increasing evidence from the adult literature that the depth of cooling, within the mild hypothermia range (32–35 °C; see below), may be a less important factor. As reviewed by Sarkar and Barks in this issue (‘Systemic complications and hypothermia’), at least potentially, there may be greater risk of systemic complications when cooling is moderate or deep (<30 °C) which might counteract the potential benefit of cooling. This is an area of active research in preclinical models of perinatal asphyxia. The effect of temperature stability on outcome is also unknown; however, rapid swings in temperature will impact on many enzyme and physiological functions and therefore at present it is recommended that it should be avoided if possible.

This review outlines some of the unique factors that need consideration when cooling infants, such as the recent transition from fetal to extrauterine life, the effect of body size, the occurrence of natural hypothermia, and the site of temperature measurement. Different cooling methods are reviewed and recent experience in the UK, Europe and USA of cooling during transport to cooling centres is described.

Section snippets

Mechanisms of heat loss in the newborn

Mammals are homeotherms – organisms capable of maintaining body temperature within a narrow range, usually above that of the surroundings despite large variations in environmental temperature. In the human, a highly effective thermoregulatory system controls core body temperature to near 37 °C (this is set slightly higher in some mammals such as the piglet and sheep).17, 18

The temperature of the fetus is 0.3–0.5 °C higher than that of the mother; heat is transferred via the placenta and the

‘Natural’ hypothermia in infants with perinatal asphyxial encephalopathy

The phenomenon of exaggerated cooling in term babies after birth with perinatal asphyxia was first described more than 50 years ago.29 The authors compared babies with ‘asphyxia’ (defined as a failure to establish respiration within 3 min of birth) with non-asphyxiated babies. The rectal temperature of the asphyxiated infants was ∼34.5 °C within 2 h of birth compared with control babies who were ∼2 °C warmer (Figure 1a). We have recently observed the same phenomenon of ‘natural’ hypothermia in

Temperature measurement

The human body can be divided into two thermal compartments: a ‘core’ compartment consisting of the trunk and head and a ‘peripheral’ compartment consisting of the skin and extremities. In mammals, the core body temperature is maintained within a narrow range to facilitate optimal functioning of physiological processes. Core temperature measurements are typically slightly higher than oral measurements, and oral measurements are higher than skin temperature. The commonly accepted adult average

Cooling methods and phases of cooling

An ideal cooling device should induce cooling rapidly to the desired core temperature, maintain the core temperature tightly within the target range for the desired duration (usually 72 h) and should allow rewarming in a slow and controlled manner at a set rate (at present, usually 0.2–0.5 °C/h).44 The device should be easy to use, require minimal nursing input, should not interfere with access to the baby and should not cause undesirable side-effects such as shivering. When evaluating the

Sedation during cooling

In awake patients shivering can result in 40–100% increase in oxygen consumption and is an undesirable situation in post-hypoxic brain injury. In post-surgical adult patients, shivering is associated with increased morbidity.63 Shivering is not commonly seen in infants (see discussion above on brown adipose tissue). Studies of cooling using ice, frozen gel packs and fans have reported apparently higher incidences of shivering59, 60, 61 than more recent studies using active conductive cooling.

Cooling during transport

In order to initiate therapeutic hypothermia as early as possible after birth, and hence maximise the neuroprotective effect in encephalopathic infants, initiation of therapeutic hypothermia at the referring centre and during transport to the cooling centre remains an attractive proposition.66, 67, 68, 69 Cooling of neonates on transport presents a particular challenge over and above that of cooling at the receiving centre. The babies transferred are often sick, and require significant

Conflict of interest statement

None declared.

Funding sources

This work was undertaken at UCH/UCL who received a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centers Funding Scheme.

References (70)

  • F. Colbourne et al.

    Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil

    Brain Res

    (1994)
  • E. Bona et al.

    Protective effects of moderate hypothermia after neonatal hypoxia–ischemia: short- and long-term outcome

    Pediatr Res

    (1998)
  • M. Thoresen et al.

    Mild hypothermia after severe transient hypoxia–ischemia ameliorates delayed cerebral energy failure in the newborn piglet

    Pediatr Res

    (1995)
  • S. Shankaran 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)
  • D. Azzopardi et al.

    Moderate hypothermia to treat perinatal asphyxial encephalopathy

    N Engl J Med

    (2009)
  • A. Edwards et al.

    Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data

    BMJ

    (2010)
  • A. Kapetanakis et al.

    Therapeutic hypothermia for neonatal encephalopathy: a UK survey of opinion, practice and neuro-investigation at the end of 2007

    Acta Paediatr

    (2009)
  • Thayyil S, Bhutta Z, Ramji S, Costello A, Robertson N. Global applications of therapeutic hypothermia to treat...
  • R. Higgins et al.

    Hypothermia and perinatal asphyxia: executive summary of the National Institute of Child Health and Human Development workshop

    J Pediatr

    (2006)
  • S. Iwata et al.

    Therapeutic hypothermia can be induced and maintained using either commercial water bottles or a "phase changing material" mattress in a newborn piglet model

    Arch Dis Child

    (2009)
  • A. Gunn et al.

    Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep

    Pediatrics

    (1998)
  • F. Colbourne et al.

    Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection

    J Neurosci

    (1995)
  • L. Mount

    Nutrition and thermoregulation in the newborn pig

    Proc Nutr Soc

    (1969)
  • S. Recabarren et al.

    Circadian variation of rectal temperature in newborn sheep

    J Dev Physiol

    (1987)
  • H. Asakura

    Fetal and neonatal thermoregulation

    J Nippon Med Sch

    (2004)
  • K.J. Adamsons et al.

    Influence of temperature on blood pH of the human adult and newborn

    J Physiol

    (1969)
  • V. Kumar et al.

    Neonatal hypothermia in low resource settings: a review

    J Perinatol

    (2009)
  • N. Rutter

    Temperature control and disorders

  • P. Lyden et al.

    Therapeutic hypothermia for acute stroke

    Int J Stroke

    (2006)
  • A. van Zanten et al.

    Blowing hot or cold? Skin counter warming to prevent shivering during therapeutic hypothermia

    Crit Care Med

    (2009)
  • M. Dawkins et al.

    Non-shivering thermogenesis and brown adipose tissue in the human new-born infant

    Nature

    (1965)
  • M. Hardman et al.

    Fat metabolism and heat production in young rabbits

    J Physiol

    (1969)
  • L. Clarke et al.

    Influence of route of delivery and ambient temperature on thermoregulation in newborn lambs

    Am J Physiol Regulatory Integrative Comp Physiol

    (1997)
  • E. Burnard et al.

    Rectal temperature in the newborn after birth asphyxia

    BMJ

    (1958)
  • A. Morimoto et al.

    Stimulation of ventromedial hypothalamus induces cold defense responses in conscious rabbits

    Am J Physiol

    (1986)
  • Cited by (34)

    • Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy

      2017, Pediatrics and Neonatology
      Citation Excerpt :

      It is more complex and expensive than WBC devices and requires manual adjustments of radiant warmers. The aim of SHC is to cool the head by surface cooling and to maintain the core body temperature around 34–35°C.13 Fully servo-controlled devices are suggested for WBC because they offer better temperature stability compared with manual or semiautomated devices.

    • Cool and transfer - The way forward

      2015, Journal of Neonatal Nursing
      Citation Excerpt :

      However, this may not be in the infant's best interests as there could be a delay in reaching the target rectal temperature if the infant requires transfer to a level 3 unit before treatment is commenced. Further, as with any time-critical intervention, it places logistical pressure on neonatal transport teams to stabilise and prepare infants safely for a quick transfer to a tertiary centre (Robertson et al., 2010). Initiation of passive cooling measures at the referring hospital does offer a degree of cooling for some infants.

    • Cooling in a low-resource environment: Lost in translation

      2015, Seminars in Fetal and Neonatal Medicine
    View all citing articles on Scopus
    View full text