Therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury (interventional procedures consultation)

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

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 in a baby's brain during labour and/or delivery. It can lead to death or permanent brain damage. Therapeutic hypothermia (deliberate lowering of the body temperature) aims to cool the brain soon after birth and for several days afterwards to prevent brain damage. It is done by cooling either the baby's head with a purpose-made cap, or the whole body with a purpose-made blanket or mattress. The baby's temperature is measured throughout to ensure that the right amount of cooling is used. After cooling, the baby's temperature is gradually returned to normal.

The National Institute for Health and Clinical Excellence is examining 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. The Institute'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 preliminary recommendations
the identification of factual inaccuracies
additional relevant evidence.

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

The process that the Institute 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The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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 Institute's website (www.nice.org.uk/ipprocessmanual).

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 how it might be improved.

Closing date for comments: 28 July 2008
Target date for publication of guidance: October 2008

Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation.

1	Provisional recommendations
1.1	Despite randomised controlled trial (RCT) evidence showing a reduction in mortality, there is uncertainty about efficacy of therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury, specifically regarding the avoidance of disability and long-term effects. The procedure itself raises no major safety concerns, but uncertainties about patient selection and the various steps in the care process (such as inter-hospital transfer) may introduce potential safety issues. Therefore clinicians wishing to use this procedure should do so only with special arrangements for clinical governance, consent and audit or research. Trials of therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury are in progress. Further evidence from RCTs is likely to become available within the next 2 years, and the Institute will review this guidance upon publication of further evidence.
1.2	Clinicians wishing to undertake therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that parents understand the uncertainty about the procedure's role in reducing the risk of severe disability or death. Parents should be provided with clear written information. In addition, the use of the Institute's information for patients (‘Understanding NICE guidance') is recommended (available from www.nice.org.uk/IPGXXXpublicinfo). *[[details to be completed at publication]]* Audit and review clinical outcomes of all patients having therapeutic hypothermia with intracorporeal temperature monitoring for hypoxic perinatal brain injury (see section 3.1).
1.3	Patient selection should involve a full neurological assessment.


2	The procedure
*2.1*	*Indications* *and current treatments*
2.1.1	Hypoxic perinatal brain injury is caused by a fall in oxygen delivery to the brain around the time of birth. Possible outcomes include stillbirth, neonatal death, neonatal multi-organ failure and the development of hypoxic-ischaemic encephalopathy, which can result in various levels of permanent disability.
2.1.2	Signs of hypoxic perinatal brain injury include fetal distress and acidosis; affected neonates often require artificial ventilation from birth. Diagnosis involves a combination of history, clinical examination and, if available, paired umbilical arterial and venous blood gas analysis. Amplitude-integrated electroencephalography may also be used. The usual treatment is supportive care.

*2.2*	*Outline of the procedure*
2.2.1	Therapeutic hypothermia cools the brain to several degrees below its normal temperature, usually to a temperature of between 33°C and 35°C, with the aim of preventing further neuronal loss in the days following the hypoxic injury. Hypothermia is induced by cooling either the head with a purpose-made cap, or the whole body with a purpose-made blanket or mattress. Treatment is started as soon as possible following diagnosis and continues for a few days. The infant is then slowly warmed to normal body temperature.

Sections 2.3 and 2.4 describe efficacy and safety outcomes which were available in the published literature and which the Committee considered as part of the evidence about this procedure. For more details, refer to the Sources of evidence.
*2.3*	*Efficacy*
2.3.1	A meta-analysis of eight RCTs including 638 infants reported a lower risk of death in infants treated with therapeutic hypothermia (head or whole body cooling) compared with those treated with standard care (relative risk [RR] 0.74, 95% confidence interval [CI] 0.58 to 0.94); and lower risk of major neurodevelopmental disability in the 336 survivors of four RCTS that reported this outcome at 12-18 month follow-up (RR 0.68, 95% CI 0.51 to 0.92).
2.3.2	An RCT (included in the meta-analysis) of 234 infants reported death in 13% (15/116) and 16% (19/118) of therapeutic hypothermia-treated (head cooled) versus control infants, respectively, during the 76-hour cooling period (and in the equivalent time period for controls).
2.3.3	An RCT (included in the meta-analysis) of 208 infants reported death in 13% (13/102) and 10% (11/106) of therapeutic hypothermia treated (whole body cooled) versus control infants, respectively, during the 72-hour cooling period.
2.3.4	The Specialist Advisers considered key efficacy outcomes to include decreased mortality, absence of motor and cognitive neurodevelopmental disability at 18–24 months, educational performance at 6–7 years, and changes on MRI before discharge.

*2.4*	*Safety*
2.4.1	The meta-analysis reported an increased risk of sinus bradycardia (RR 5.96, 95% CI 2.15 to 6.49), 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 infants treated with therapeutic hypothermia compared with infants treated with standard care.
2.4.2	The RCTs of 234 and 208 infants reported higher incidences of minor cardiac arrhythmia, hypotension and hypocalcaemia in the infants treated with therapeutic hypothermia.
2.4.3	One case report described sclerema at the point of contact with a whole body cooling mattress and another described subcutaneous fat necrosis at the point of contact with the ice pack. Both skin changes resolved.
2.4.4	The Specialist Advisers stated that theoretical or anecdotal adverse events include hypotension, overcooling, pulmonary hypertension, infection, cardiac arrhythmia, bleeding, thrombosis, pneumonia, biochemical disturbance, tissue necrosis and acidosis. The Advisers stated that training in performing the procedure is important.

*2.5*	*Other comments*
2.5.1	The Committee noted that the efficacy of the procedure may vary depending on the stage and degree of the pre-existing hypoxic brain damage and other factors. Uncertainties about these factors can make both patient selection and interpretation of the published evidence difficult.

3	*Further information*
3.1	This guidance requires that clinicians undertaking the procedure make special arrangements for audit. The Institute has identified relevant audit criteria and is developing an audit tool (which is for use at local discretion), which will be available when the guidance is published.

Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
June 2008

Appendix:	Sources of evidence

The evidence considered by the Interventional Procedures Advisory Committee is described in the overview, available at: www.nice.org.uk/ip552overview.

This page was last updated: 24 May 2010