Therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury - Interventional Procedures Consultation Document

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Interventional procedure consultation document

Therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury

Hypoxic perinatal brain injury is caused by lack of oxygen to a baby’s brain during labour and/or delivery. It can lead to death or permanent brain damage. Therapeutic hypothermia aims to cool the brain (soon after birth and for several days) to prevent permanent brain damage. Hypothermia may be induced by whole body cooling (using a mattress or blanket filled with cooled fluid or air) or by head cooling (using a cap filled with cooled fluid or air). Throughout the procedure, the baby’s temperature is measured using a thermometer inside the body (either the rectum or the gullet) to help ensure that cooling is adequate but not excessive. After cooling, the baby’s body temperature is gradually returned to normal.

The National Institute for Health and Clinical Excellence (NICE) is examining macular translocation for therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

  • comments on the provisional recommendations
  • the identification of factual inaccuracies
  • additional relevant evidence, with bibliographic references where possible.

Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

  • The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
  • The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).

NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved. NICE reserves the right to summarise and edit comments received during consultations, or not to publish them at all, where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

Closing date for comments: 24 February 2010

Target date for publication of guidance: May 2010

 

1       Provisional recommendations

1.1  Current evidence on the safety and efficacy of therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury is adequate to support the use of this procedure in carefully selected neonates provided that normal arrangements are in place for clinical governance, consent and audit.

1.2  This procedure should only be carried out in units experienced in the care of severely ill neonates, by staff who have been specifically trained in the use of therapeutic hypothermia.

1.3  NICE encourages clinicians to enter details about all neonates undergoing this procedure into the UK TOBY cooling register (www.npeu.ox.ac.uk/tobyregister). The register provides a suggested management algorithm. Submitting data to the register will contribute to the evidence on long-term follow-up and may lead to improvements in the management algorithm.

2       The procedure

2.1    Indications and current treatments

2.1.1  Hypoxic perinatal brain injury is caused by a decrease in the amount of oxygen supplied to an infant’s brain close to the time of birth. Surviving infants may develop hypoxic-ischaemic encephalopathy and other organ damage, which can lead to severe, lifelong disability or death.

2.1.2  Hypoxic perinatal brain injury is characterised by fetal distress and may be associated with acidosis. Diagnosis includes clinical examination, paired umbilical arterial and venous blood gas analysis and amplitude-integrated electroencephalography.

2.1.3  Hypoxic perinatal brain injury is usually treated with supportive care only, since no specific pharmacological agents or interventions have been shown to prevent the neuronal damage that perinatal hypoxia causes.

2.2    Outline of the procedure

2.2.1  In therapeutic hypothermia the infant is cooled to between 33°C and 35°C, with the aim of preventing further neuronal loss in the days following the hypoxic injury.

2.2.2  Hypothermia is induced by cooling the whole body with a blanket or mattress (or sometimes by cooling the head only with a purpose made cap). Intracorporeal temperature is continuously monitored using a rectal or nasopharyngeal thermometer as a proxy for brain temperature.

2.2.3  Treatment is started as soon as possible after diagnosis, usually within 6 hours of birth, and continued for approximately 72 hours. The infant is then slowly warmed to normal body temperature.

Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/IP552overview.

 

2.3    Efficacy

2.3.1  A systematic review of 8 randomised controlled trials (RCTs) (total of 638 infants) reported a lower risk of death in cooled infants (whole body or head) in the first 18 months of life than infants treated by standard care (relative risk [RR] 0.74; 95% confidence interval [CI] 0.58 to 0.94).

2.3.2  An RCT of 325 infants treated by whole body cooling or standard care reported survival without neurologic abnormality in 44% (71/163) and 28% (45/162) of infants respectively at 18-month follow-up (RR 1.57; 95% CI 1.16 to 2.12). Among the surviving infants, there was a lower rate of cerebral palsy in those treated by cooling (28% [33/120] vs 41% [48/117], RR 0.67; 95% CI 0.47 to 0.96).

2.3.3  An RCT of 234 infants treated by head cooling or standard care reported death or severe neurodevelopmental disability at 18-month follow-up in 55% (59/108) and 66% (73/110) of infants respectively (odds ratio 0.61; 95% CI 0.34 to 1.09).

2.3.4  The Specialist Advisers listed key efficacy outcomes as improvement in survival without neurological impairment, reduction in severe disability, improvement in Motor and Psychomotor Development Index scores and reduction in cerebral palsy.

2.4    Safety

2.4.1  The systematic review of 638 infants reported a higher risk of thrombocytopenia (RR 1.55; 95% CI 1.14 to 2.11) and hypotension requiring inotropic treatment (RR 1.17; 95% CI 1.00 to 1.38) in cooled infants compared with infants treated by standard care.

2.4.2  An RCT of 208 infants reported a higher incidence of hypocalcaemia in cooled infants than in those treated by standard care (27% (28/102) and 19% (20/106) respectively; p values not reported.

2.4.3  In the RCT of 234 infants, 1 cooled infant (who died of other causes) had skin breakdown and local haemorrhage under the cooling cap. A case report described fat necrosis in an infant treated by whole body cooling using ice packs applied to the skin: at 9 months, asymptomatic firm nodules with no calcification were present. In another case report, an infant treated by whole body cooling using a water-filled mattress developed sclerema on the area of his back in contact with the cooling mattress at 3-week follow-up; this resolved without scarring after 3 months.

2.4.4  The Specialist Advisers considered theoretical or anecdotal adverse events to include blood hyperviscosity syndrome, increased infections and seizures during rewarming if it is carried out too quickly.

2.5    Other comments

2.5.1  The Committee noted the uncertainties and difficulties in selecting neonates for this procedure. Specifically, they noted the lack of evidence for using the procedure in neonates with less severe hypoxic brain injury, and the difficulties in deciding not to use the procedure for neonates whose degree of brain injury or comorbidities are too severe to expect survival without severe neurological deficit.

 

Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
January 2010

Personal data will not be posted on the NICE website. In accordance with the Data Protection Act names will be anonymised, other than in circumstances where explicit permission has been given.

 It is the responsibility of consultees to accurately cite academic work in order that they can be validated.

This page was last updated: 24 May 2010

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Copyright 2014 National Institute for Health and Care Excellence. All rights reserved.

Accessibility | Cymraeg | Freedom of information | Vision Impaired | Contact Us | Glossary | Data protection | Copyright | Disclaimer | Terms and conditions

Copyright 2014 National Institute for Health and Care Excellence. All rights reserved.