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ECMO CENTRE HANDBOOK
Great Ormond Street
June 2006
ISRCTN72635512
Contents Page Numbers 1. Introduction 1 Overview of the study design 1 Organisation 3 2. Contacts for the study 4 Documentation 5 3. Recruiting babies to the study 6 Which babies can be recruited to NEST 6 Consent 6 Randomisation 7 Randomisation in error 9 Recording and reporting CFM data 9 4. Study Interventions 11 ECMO management 11 Rewarming 11 Heparin 12 General Care 12 5. Data Collection 13 6. Brain Imaging for NEST 14
Cranial US examinations 14 Magnetic Resonance (MR) Brain Imaging 17
7. Transfers 21 Transfer of a baby recruited to NEST from your unit 21 Instructions for transfer of the baby 21 8. Serious Adverse Event Reporting 23 9. Contact with parents 24 10. Definitions of terms in Data Collection Forms 25 NEST Flow Chart 26
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1. INTRODUCTION
Existing evidence indicates that once mature neonates with severe cardio- respiratory failure become eligible for ECMO their chances of intact survival are doubled if they actually receive ECMO. However, significant numbers survive with disability. NEST is a mult-centre prospective randomised trial designed to test whether, in neonates requiring ECMO, cooling to 34°C for the first 48 to 72 hours of their ECMO course leads to improved later health status. Control infants will receive ECMO at 37°C throughout their course, which is current normal practice around the world. Health status of both groups will be determined formally at 2 years of age. 1.1 Overview of the study design Eligibility: Babies are eligible for inclusion in NEST if:
• they are referred for ECMO (based on the decision of the clinician responsible for the child’s overall care)
• they meet the standard criteria for the use of ECMO • they are less than 29 days of age.
Exclusion criteria for the NEST Study:
• All neonates referred with diaphragmatic hernia. • All neonates receiving ECMO for post operative cardiac support.
Recruitment and randomisation:
Babies are recruited only after informed consent has been obtained from the parent(s) (see Section 3.2).
Randomisation to “cooling” or to normothermic ECMO (standard care) is via a web based system (see Section 3.3). Interventions and clinical management: The normothermic group receive ECMO at 37°C ± 0.2°C. The cooled group are managed at 34°C ± 0.2°C for up to 72 hours from the start of their ECMO run. The minimum duration of cooling is 48 hours even in those babies who are already to come off ECMO before 48 hours. Rewarming (to 37°C) occurs at a rate of no more than 0.5°C per hour. All other aspects of ECMO management are identical in both groups.
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Primary outcome: The primary outcome of the study is the MDI of the Bayley scales of the surviving children in each arm of the study at the age of 2 years (24 - 27 months).
Note: Where the MDI cannot be assessed because of severe disability or death, a score of either 40 or 0 will be recorded respectively.
Secondary outcomes:
• death • a global neurological score (optimality score) • Parent Report of Children’s Abilities, PARCA • PDI of the Bayley scales • Visiospatial function • Child behaviour rating • Cerebral Palsy • Measures of growth – height, weight and head circumference
Sample size Study size estimates have been made based on potential differences in the MDI of the Bayley scores at two years.
The table below gives a range of calculations based on variations in the mean scores and standard deviations of these scores.
Assumed mean scores of the two arms
Assumed SD of Bayley MDI scores
Total sample size required for 90% power
Number needed to be recruited assuming 80% survival to 2 years
85 & 95 15 94 118
85 & 95 10 42 53
90 & 95 10 168 210 The first of these options (requiring the recruitment of 118 infants) offers a realistic recruitment target whilst also giving 90% power to detect a significant difference between the two arms (at the 5% level). The choice of 85 and 95 as the two Bayley scores on which to derive the trial size is based on: a) what might be considered a clinically significant outcome and b) existing knowledge of ECMO survivors.
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Analysis The primary analysis will be an intention-to-treat analysis, comparing the outcome of all babies allocated to “ECMO with cooling” with all those allocated to “ECMO” alone. 1.2 Organisation
• Project management group - A core team of individuals will liaise regularly regarding the general progress and management of the study. This will normally occur by teleconference every 6 weeks.
• Trial Steering Committee - The Trial Steering Committee will provide overall supervision of the study on behalf of the British Heart Foundation (the funder of the study). Meetings will occur annually.
• Data Monitoring Committee - This committee will be independent of the study organisers and will meet annually.
• Sponsor - The study is sponsored by The University Hospitals of Leicester NHS Trust.
For more details of the background to the study and the study design, please refer to the protocol in the NEST Documents Box.
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2. CONTACTS FOR THE STUDY The Chief Investigator and Clinical lead in Leicester is:
Professor David Field Consultant Paediatrician Leicester Royal Infirmary Infirmary Square Leicester LE1 5WW Tel: 0116 254 1414 direct line, 0116 287 1471 hospital, 0116 258 7707 secretary Email: [email protected]
The study is co-ordinated by:
Denise Jennings NEST Co-ordinating Centre National Perinatal Epidemiology Unit University of Oxford, Old Road Campus Headington Oxford OX3 7LF Tel: 01865 289737 Fax: 01865 289740 Email: [email protected]
In each of the four ECMO centres, there is a lead clinician and a designated ECMO specialist responsible for the study. Dr Aparna Hoskote(PI) Consultant Cardiac Intensivist Level 7, Nurses Home Great Ormond Street Children's Hospital Great Ormond Street Bloomsbury London WC1N 3JH [email protected] 020 7405 9200 x5492
Ms Liz Smith (ECMO Specialist) ECMO Coordinator ECMO Office, Room 6060, Level 6, Nurses Home Great Ormond Street Children's Hospital Great Ormond Street Bloomsbury London WC1N 3JH [email protected] 020 7813 8180 020 7813 8400
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2.1 Documentation All of the documentation for NEST is stored in a NEST Documents Box. This is kept in, or close to, the ECMO unit. The local co-ordinators will also have a reference folder with copies of all relevant NEST documents. The documents in the NEST Documents Box are:
1. Baby Pack (Blue=Male, Pink=Female)
2. Flow Chart 3. Study Protocol 4. Summary Protocol
5. ECMO Centre Handbook 6. Transfer Hospital Handbook
7. Study Information Leaflet (Male and Female) 8. Further Information Leaflet (Male and Female) 9. Consent Form
10. Study Entry Form 11. Daily Progress Form 12. ECMO Unit Discharge Form 13. Transfer Hospital Discharge Form
14. Going Home Pack (Male and Female) 15. Transfer Pack (Male and Female) 16. Bereavement Leaflet 17. Going Home Leaflet (Male and Female)
18. Serious Adverse Event (SAE)/Suspected Unexpected Serious Adverse
Reaction (SUSAR) Form 19. Hospital notes label 20. Change of address card 21. FREEPOST envelope
22. Local contact information 23. Re-order Documents Form
All the NEST documents can also be accessed at www.npeu.ox.ac.uk/nest
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3. RECRUITING BABIES TO THE STUDY 3.1 Which babies can be recruited to NEST? Babies recruited to the study must meet the existing standard criteria for ECMO eligibility. These include:
• at least 35 weeks gestation;
• at least 2000g weight;
• no uncontrolled bleeding disorder;
• no known congenital or acquired CNS disorder;
• no more than 7 consecutive days of high pressure ventilation prior to referral for ECMO;
• the underlying condition is potentially reversible;
• evidence of severe cardio-respiratory failure such as an oxygenation
index of 40 or more;
• less than 29 days of age.
Exclusion criteria:
• All neonates referred with diaphragmatic hernia;
• All neonates receiving ECMO for post operative cardiac support. (Among the babies with diaphragmatic hernia referred for ECMO a number have severe pulmonary hypoplasia incompatible with survival. These infants cannot be reliably detected prior to ECMO and there is no rationale for believing that cooling will help these infants. Babies receiving ECMO following cardiac surgery, in general, are not comparable in terms of risk of serious adverse neurodevelopmental outcome).
All other infants will be eligible unless aspects of their medical condition prevent or render the use of ECMO inappropriate. 3.2 Consent Neonates will be recruited only after informed consent has been obtained from the parent(s). There will be major logistic problems in achieving this since cooling will commence at the start of the ECMO run and in many cases there will be an urgent need to establish ECMO. In order to optimise recruitment:
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• ECMO centres involved in the NEST study will discuss the study with the parents of all children likely to need ECMO. These discussions will be supported by 2 separate parents’ leaflets describing a) ECMO (this will be the ECMO centres’ existing information for parents) b) the NEST Information Leaflet.
• Where neonates are “retrieved” for ECMO from other centres there will be
a period (of up to 2 days) during which a transfer for ECMO is being considered. In these circumstances the ECMO centre will have the opportunity to fax ahead detailed information about both ECMO and the NEST study and also brief the local clinical team prior to any retrieval. Should the referral for ECMO subsequently go ahead, and parents agree to their child joining the study, formal consent can be obtained by the routine retrieval team without undue haste. On other occasions such referrals and transfers for ECMO take place at very short notice. On these occasions the team should include sufficient personnel to allow time to be spent with the parents both to explain the study and obtain informed consent. In order for this to happen funds are available to make sessional payments to “an extra team member” (i.e. an ECMO specialist, or doctor or senior nurse involved with the ECMO programme) in order that such staff are available to take part in these transfers and fulfil this role.
The actual consent procedures will involve a two stage process. At the time of initial recruitment and randomisation parents will receive an initial information leaflet about the study, NEST Information Leaflet, (as well as the leaflet explaining ECMO produced by the ECMO centre retrieving and caring for the baby) and at that time parents will be asked to give written consent. Where parents do not have a good grasp of English, unless a good interpreter is immediately available, recruitment should not proceed. Where a child is recruited, a follow up conversation (using the second information leaflet about the study NEST Further Information Leaflet) should take place during the stay in the ECMO centre. No “re-consenting” is required but the conversation and the parent’s agreement to continue cooperating with the study should be documented in the medical records. 3.3 Randomisation When a baby’s eligibility has been confirmed and the parent(s) have signed a consent form, the baby can be randomised into the study. All the documents required can be found in the Baby Pack (Blue=Male, Pink=Female) in the front of the NEST Documents Box. Please follow these steps: a) Complete the first page of the NEST Study Entry Form. b) Type this address into your internet address bar. https://rct.npeu.ox.ac.uk/nest
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Each authorised person will have received a password in order to recruit a baby in this way. Fill in the entry form details on screen as requested and you will then receive the study number and allocation (you will be able to print this page). There is a help section on the site, but if you have any problems you can always use one of the options below to contact us and randomise the baby via the bleep system.
i. By telephone: Telephone 07623 947508, hold to speak to an operator and then leave the following message: “Please phone <YOUR NAME>, at <YOUR HOSPITAL>, on <YOUR FULL TELEPHONE NUMBER>** about NEST”. This option is available 24 hours a day, seven days a week and you should receive a return call within a few minutes. **Please remember to give the national dialling code.
DO NOT give the number of the busiest telephone on the unit; another call might block the line when we are trying to call you back!
ii. Via the internet: This will be faster than option iii (email) Log on to the Paging Website at www.npeu.ox.ac.uk/pager Enter your email address in the box as requested. Enter the following message in the <Message> box: “Please phone <YOUR NAME>, at <YOUR HOSPITAL>, on <YOUR FULL TELEPHONE NUMBER>** about NEST” Click on “Send pager message”. This activates the pager (as in option i) and we will ring you back. iii. By sending an Email: Send an email to [email protected] You will receive an email acknowledgement that the message has been accepted. Do remember that this method depends on the speed with which your Internet Service Provider delivers your message. The total message size is limited to 175 characters. Again, this activates the pager (as in option i) and we will ring you back. Whichever method of contact you use you should receive a reply within 15 minutes of the message acknowledgement. If you do not get a response then we suggest that you try again and wait for another 15 minutes. If there is still no reply then telephone the following number: 07885 720537 (you might occasionally be diverted to voice mail but we will respond as soon as we get your message).
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c) Record the baby’s study number and allocation on the Study Entry Form. d) Write the baby’s study number on a NEST Hospital notes label and attach it to the front of the baby’s notes. e) Commence the allocated treatment. f) Once the baby is stabilised, complete the remainder of the Study Entry Form. g) Start recording the requested information about the baby on the Daily Progress Form (use Day 1 to Day 4 in order). h) Send the completed Study Entry Form to the NEST Study Co-ordinating Centre using the FREEPOST envelope provided. 3.4 Randomisation in error If it is felt that a baby has been randomised to NEST inappropriately, the clinical team caring for the baby must decide whether or not to continue with the allocated intervention. Regardless of what decision is made, the baby will remain part of NEST and data should be collected when the baby is discharged. If you have any difficulties there are three ways to contact the co-ordinating centre (see 3.3b i, ii and iii). You will be called back as soon as we receive your message (24 hour cover). 3.5 Recording and reporting Cerebral Function Monitoring (CFM) data The EEG/aEEG (CFM) is being recorded in infants enrolled into NEST because it is an objective record of the occurrence and severity of encephalopathy which may be present at randomisation and may influence subsequent neurological outcome. When to record the CFM:
• Start the CFM recording as soon as possible on admission to the ECMO centre, preferably prior to starting ECMO and preferably before giving large intravenous doses of sedatives.
• Record for a minimum of 1 hour following randomisation but if possible continue the CFM recording throughout the duration of ECMO. The CFM may be helpful in identifying cerebral complications. The first indication may be the onset of seizures which may be difficult to recognise clinically.
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Providing the NEST co-ordinating centre with the CFM trace:
• Send a copy of the CFM trace recorded from before enrolment until 1 hour after randomisation. This can be printed off the CFM, photocopied and posted to the NEST co-ordinator. Indicate clearly on the record the time of starting the recording and mark any procedures done to the baby.
• If long term recording is done download the record according to the instructions of the specific CFM monitor being used, and send the record on CD if possible to the NEST co-ordinator. Details on how to send the record can be discussed with the co-ordinator.
Interpretation: For the purposes of the NEST Study, the CFM record will be reported by Denis Azzopardi who will be unaware of the treatment allocation. Information on the interpretation of the aEEG can be found on the following web site: www.azzopardi.freeserve.co.uk/CFM/interpretation_of_cfm.htm
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4. STUDY INTERVENTION 4.1 ECMO management Temperature adjustment will begin immediately upon initiation of the extra-corporeal circulation. For the cooled group the water heater of the ECMO circuit will be set at 34°C. For the normothermic group it will be set at 37°C. The baby’s temperature will be measured either by a nasopharyngeal, rectal or urinary electronic temperature probe. The water heater will be adjusted to maintain the core temperature at the allocated temperature. Once the period of temperature adjustment has passed, babies allocated to cooling will be rewarmed by increasing the target temperature by no more than 0.5°C every hour. Cerebral function monitoring (using the aEEG) will be used from the onset of ECMO for all babies in the study to both aid clinical management and provide additional information when assessing the outcome data. All clinical decisions will be made by the local ECMO team but adherence to the allocated temperature should be maintained unless there are strong and documented reasons for breaching the protocol. 4.2 Rewarming cooled babies Babies who are ready to stop ECMO earlier than 48 hours i. ECMO should be continued to ensure that the minimum 48 hours of
cooling has been completed and to allow rewarming by a maximum of 0.5°C per hour.
ii. The baby should not be taken off ECMO until the core temperature is 37°C.
iii. Continue to provide all the data requested and enter it in the Daily Progress Form up to 96 hours from cannulation.
Babies who are ready to stop ECMO between 48 and 72 hours When the decision is made to stop ECMO after at least 48 hours of cooling has been completed: i. ECMO must be continued to allow rewarming by a maximum of 0.5°C per
hour. ii. The baby should not be taken off ECMO until the core temperature is
37°C. iii. Continue to provide all the data requested and enter it in the Daily
Progress Form up to 96 hours from cannulation. Babies who need to remain on ECMO longer than 72 hours When 72 hours of cooling has been completed, as calculated from the time of cannulation: i. Commence rewarming by a maximum of 0.5°C per hour.
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ii. The baby should not be taken off ECMO until the core temperature is at
least 36°C. iii. Continue to provide all the data requested and enter it in the Daily
Progress Form up to 96 hours from cannulation. 4.3 Heparin For the cooled and normothermic group, heparin management will continue according to institutional protocols, however, it is important to note that the pilot study was done using the Hemochron System (ITC, NJ, USA) and P214 tubes. The hemochron machine itself measures the ACT at 37°C. In addition none of the babies in the pilot study received amicar, which should therefore not be administered during the study. If an anti-fibrinolytic drug is indicated it is recommended that aprotinin is used with a loading dose of 1ml/kg followed by an infusion of 1ml/kg/hr. Two babies in the pilot study received aprotinin. 4.4 General care All other aspects of ECMO and general care will follow institutional protocols. This will include choice of veno-arterial and veno-venous ECMO (minimisation will ensure an even distribution of VA and VV patients in the two arms of the study). All of the UK ECMO centres have agreed not to provide speculative neuro-protective cooling outside the context of the NEST study.
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5. DATA COLLECTION The NEST Study Entry Form should be completed when the baby is randomised and sent to the NEST Co-ordinating Centre as soon as possible. The NEST Daily Progress Form should be completed for Day 1 to Day 4 for ALL babies recruited to the study and sent to the NEST Co-ordinating Centre as soon as possible. The NEST ECMO Unit Discharge Form should be completed as soon as possible after the baby leaves the ECMO unit, i.e. when he or she is discharged home, dies or is transferred to another hospital (see Section 8). When completing this form, include only data relating to the baby’s stay in your unit. If the baby is transferred to another hospital, complete the identifiers on the Transfer Hospital Discharge Form and send this with a Transfer Pack with the baby to the transfer hospital. Once all the items on the NEST ECMO Unit Discharge Form have been completed, please keep a photocopy of the form for the babies’ hospital notes and send the original form to the NEST Co-ordinating centre in a FREEPOST envelope provided in the NEST Documents Box.
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6. BRAIN IMAGING FOR THE NEST STUDY 6.1 Cranial Ultrasound Examinations i. Check for normal anatomy or evidence of longstanding damage/atrophy /calcification (see page 17). ii. Please take at least 6 coronal and 7 sagittal/parasagittal views (see list on page 18). iii. Classification of haemorrhage and major parenchymal abnormality Haemorrhage (from Volpe JJ 1995)
• Grade I Germinal matrix haemorrhage (GMH) with no, or minimal intraventricular haemorrhage (IVH)
• Grade II GMH + IVH (10-50% on parasagittal view)
• Grade III GMH + IVH (> 50% + acute dilatation) Parenchymal abnormality (note side and site)
• Parenchymal haemorrhage adjacent to the ventricle (grade IV)
(venous infarction / haemorrhagic parenchymal infarction) • separate focal haematoma in the cerebral hemisphere
• focal echogenicity in the parenchyma ? infarction
• haemorrhage in the posterior fossa
Please make a copy of the scans on to CD if possible. If this is not possible please make two paper copies. Send these to: Denise Jennings NEST Co-ordinating Centre National Perinatal Epidemiology Unit University of Oxford Old Road Campus Headington Oxford OX3 7LF
For any queries contact: Dr Frances Cowan Dept of Paediatrics 5th floor Ham House Hammersmith Hospital Du Cane Rd London W12 OHS Tel: 0208 383 8515 (secretary) Tel: 0208 383 1000 bleep 9850 Fax: 0208 383 2473 Email: [email protected]
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Check list of items to look for on any cranial US examination Anatomy
• Gyri – coronal and sagittal views – do not forget extreme parasagittal views for the Sylvian fissure
• Corpus callosum - mid-sagittal view - check for completeness • Cerebellum – mid-sagittal for vermis (height about 25 mm at term) and 4th
ventricle; coronal view just behind thalami for maximal cerebellar width – transverse width (mm) should be on average 50 mm in the term infant and always greater than the gestational age in weeks.
• Cavum septum pellucidum – coronal view small triangular shape – not large and rectangular
• Lateral ventricular shape – smooth walled and minimal dilatation • 3rd ventricle – barely visible except more anteriorly
Non-anatomical abnormality
• Parenchymal cysts or abnormal echogenicity on first scan suggestive of an antenatal insult.
• Cysts in region of caudothalamic notch (sub-ependymal or germinolytic
cysts) – more common in viral and metabolic disease and chromosomal abnormality
• Calcification, lenticulostriate vasculopathy (LSV) – more common in viral
and metabolic disease and chromosomal abnormality
• GMH/IVH – see page 16
• Parenchymal abnormality - note its timing and evolution e.g. generalised swelling +/- loss of grey-white matter differentiation
haemorrhage
focal unilateral echogenicity (infarction)
bilateral basal ganglia /thalamic echogenicity
bilateral white matter echogenicity
abnormally bright or thickened cortex
Evidence of atrophy Increased extracerebral space, widened interhemispheric fissure, large cisterna magna, increasing dilatation of the lateral ventricles without ballooning or IVH or without increase in head circumference, later dilation of the 3rd ventricle.
Table 1
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Table 2
Ultrasound scanning views – via anterior fontanelle
• Coronal
• Mid coronal through the Foramen of Monro, T shape of Sylvian fissures and temporal horn
• Anterior Coronal
through the anterior horns anterior to anterior horns through the frontal lobes
• Posterior Coronal through the posterior basal ganglia through the thalami and cerebellar hemispheres
through the posterior horns of the lateral ventricles and occipital lobes
posterior to ventricles parieto-temporal white matter
• Sagittal mid-line to show the corpus callosum, the 3rd and 4th ventricles, the vermis of cerebellum and the midline gyri
• Parasagittal - both sides
through the caudo-thalamic notch to look for cysts through the basal ganglia/thalami and cerebellar hemispheres through the white matter through the Sylvian fissure
Supplementary acoustic windows Axial views though the temporal windows or mastoid windows and posterior views though posterior fontanelle can be tried if better views of the brainstem, posterior fossa, cerebellum or posterior white matter are needed.
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6.2 Magnetic Resonance (MR) Brain Imaging i. Optimal time for scanning Ideally this should be done in the first month after birth (or from the time of ECMO if that is not in the first week after birth), before any tissue atrophy related to peri-ECMO insults has begun. Another reason for early scanning is that round 2-3 post-natal months the T1 and the T2 properties of the brain tissues begin to change making interpretation of tissue signal characteristics more difficult. It would be very useful to know if early MR imaging post ECMO is predictive of outcome, so imaging as many infants as possible in the first month would be very instructive. We know that after hypothermia for perinatal hypoxic-ischaemic insults MR imaging shows detectable changes in MR images¹. Experience from non-cooled term infants shows that patterns of injury seen on neonatal MR scans correlate well with outcome. However, if it is not possible to scan neonatally then do an MR scan as soon as possible in the post-neonatal period. ii. Magnet hardware Use whatever magnet you have available to you but try and use as small a coil as possible to gain maximum signal to noise. An adult knee coil is great. A sense head coil made for adults will also suffice. iii. Scan preparation Most neonates and young infants can be imaged using oral sedation with chloral hydrate². All infants should:
• be assessed pre-MR for fitness for sedation • have pre-sedation /anaesthetic measure of weight, heart rate, respiratory
rate, temperature and oxygen saturation documented • have all metal removed from them and not be wearing clothes with metal
poppers • be monitored (oxygen saturation and ECG) using MR compatible
monitoring during the scan • have continued oxygen saturation monitoring until awake and able to feed.
Immobilisation during the scan is very important. It usually helps to swaddle the baby and to use foam padding or a pillow from which air can be evacuated to fit snugly around the head. It is usual to position the infants supine but they can be in a lateral position if they find this more comfortable. Scans are noisy and ear protection is helpful and essential if using EPI sequences. A silicon-based dental putty (President putty, Coltene/Whaledent, 750 Corporate Drive, Mahwah, New Jersey, USA) and mini-muffs (Natus
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MiniMuffs, Natus Medical Inc, San Carlos, CA, USA) to keep it in place can be used, achieving an attenuation of approximately 30 decibels. Care needs to be taken that infants do not become too hot or cold. This is usually not a problem for term infants. iv. Sequences Sequences need to be adapted for the immature brain. This will usually mean altering the parameters on the preset adult sequences. Suggested parameters are given in the table below for imaging at 1.5 Tesla. Please see below about individual sequences. Do not use an adult protocol. MR parameters routine clinical examination for a neonate at 1.5 T (taken from reference 3)
Sequence TE (ms)
TR (ms)
TI (ms)
Slice thickness (mm)
nsa Matrix FOV (mm)
Other
T1 weighted conventional spin echo
15 500 – 4 2 192×256 220–240
T2 weighted fast spin echo
208 4000 – 4 2 192×256 220–240
T1 weighted volume acquisition
4.5 30 – 1.6 1 192×256 220–240
Inversion recovery 30 3500 1000 4–5 2 192×256 220–240
Diffusion weighted imaging
~6000 ~90
4 1 112×112 240 b value, 750
• T1 weighted sequence acquired in the transverse plane (a). This is ideal for assessing the basal ganglia and thalami and provides the best views of the posterior limb of the internal capsule. Assessment of the PLIC is very helpful for the prediction of motor outcome4.
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Normal MR appearances of the term neonatal brain. (a) Inversion recovery sequence. Myelin is seen as high signal intensity within the posterior limb of the internal capsule; (b) T2-weighted sequence. Myelin in the posterior limb of the internal capsule is seen as a smaller region of low signal intensity.
• T2 weighted sequence acquired in the transverse plane. This is better than T1 weighted imaging for identifying early ischaemic change and provides excellent grey/white matter contrast in the very immature brain (b).
• T1 weighted sequence acquired in the sagittal plane. A volume acquisition is ideal as it provides thin slices and can be reformatted into any plane. It can be used for absolute quantification of brain structures.
• Diffusion weighted imaging which is ideal for early (<1 week) identification of ischaemic tissue.
• A venogram to exclude the presence of sinus thrombosis and differentiate this from subdural haemorrhage.
In addition the following may be required:
• Intravenous contrast, gadolinium dimeglumine gadopentetate at a dose of 0.2 ml/kg, in suspected infection.
• Angiography to look at both cerebral and neck vessels, which may be implicated in focal stroke.
Please make a copy of the MR scan on disc or if this is not possible make a hard copy. Send these to:
Denise Jennings NEST Co-ordinating Centre National Perinatal Epidemiology Unit University of Oxford Old Road Campus Headington Oxford OX3 7LF
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v. Contacts and advice We are happy for you to contact us for any scanning related advice:
Prof Mary Rutherford or Dr Serena Counsell Robert Steiner MR imaging dept, Hammersmith Hospital, London Tel: 0208 383 3298 Email: [email protected] or [email protected] Dr Frances Cowan Dept of Paediatrics 5th floor Ham House Hammersmith Hospital Du Cane Rd, London W12 OHS Tel: 0208 383 8515 Fax: 0208 383 2473 Email: [email protected]
vi. References for Section 6.2
1. Rutherford MA, Azzopardi D, Whitelaw A, Cowan FM, Renowden S, Edwards AD, Thoresen M. Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischaemic encephalopathy. Pediatrics 2005; 116:1001-6
2. Cowan FM. Sedation for Magnetic Resonance Scanning of Infants and Young Children in Principles and Practice of Sedation. Eds Whitwam JG & McCloy RF. Publishers Blackwell Healthcare, London 1998 15.3 pp 206-213
3. Rutherford M, Ward P, Allsop J, Malamatentiou C, Counsell S. Magnetic resonance imaging in neonatal encephalopathy. Early Human Dev 2005;81(1):13-25
4. Rutherford MA, Pennock J, Counsell S, Mercuri M, Cowan FM, Dubowitz
LMS, Edwards AD. Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischaemic encephalopathy. Pediatrics 1998:102;323-328
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7. TRANSFERS 7.1 Transfer of a baby recruited to NEST from your unit Many babies are transferred between hospitals, and it is important that data collection is continued for the whole of the baby’s stay in hospital. Each hospital with a baby taking part in NEST should complete the appropriate discharge form when the baby leaves that hospital, whether it is discharged home, transferred or dies. Each completed discharge form will include details of the baby’s stay in that hospital only. Babies that are transferred will therefore have one ECMO Unit Discharge Form and one or more Transfer Hospital Discharge Forms, each one recording the details of the baby’s stay in one hospital. To help the receiving hospitals each ECMO centre has been provided with Transfer Hospital Discharge Forms and Transfer Packs, which contain all of the necessary documentation for completing the data collection for a baby who is transferred to a different hospital. The transfer pack contains:
• A list of contents • Summary Protocol • NEST Handbook for Transfer Hospitals • NEST Parent Information Leaflet • Hospital notes label • A copy of the Serious Adverse Event/Suspected Unexpected Serious
Adverse Reaction Form, in case of serious adverse events in the receiving hospital
• FREEPOST envelope, for return of the Transfer Hospital Discharge Form • A Going Home Pack, to be given to the parents if the baby is discharged
home from the receiving hospital • NEST Bereavement Leaflet to be given to the parents if the baby dies
whilst in the receiving hospital 7.2 Instructions for transfer of the baby If a baby who has been recruited to NEST is to be transferred to another hospital then please follow the instructions below and liaise closely with the hospital the baby is being transferred to. i. On the day the baby is transferred from your unit complete a NEST ECMO
Unit Discharge Form for the time that the baby has been in your unit. Take a photocopy and keep this with the baby’s notes. Return the original form to the NEST Co-ordinating Centre in a FREEPOST envelope.
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ii. To allow the receiving hospital to identify the NEST baby, please complete the following information on the Transfer Hospital Discharge Form:
(a) Baby’s name (b) Baby’s date of birth. (c) Baby’s NEST study number (d) ECMO Centre Name (e) Baby’s case notes number in the ECMO Centre (f) Transfer Hospital Name
iii. Send the Transfer Hospital Discharge Form with a Transfer Pack with the
baby to the hospital the baby is being transferred to.
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8. SERIOUS ADVERSE EVENT/ SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTION REPORTING If a serious adverse event or a suspected unexpected serious adverse reaction occurs, it should be reported to the NEST Co-ordinating Centre using one of the Serious Adverse Event / Suspected Unexpected Serious Adverse Reaction Forms in the NEST Documentation Box. Definition of SAE and SUSAR SAE (Serious Adverse Event): A serious adverse event is one which is not anticipated, not known to be related to the condition being studied or the intervention being used. In the context of this study SAE’s will include:
• death • major haemorrhage • arrhythmias requiring treatment • serious problem with the ECMO circuit
SUSAR (Suspected Unexpected Serious Adverse Reaction): An adverse reaction, the nature or severity of which is not consistent with the expected outcomes of the treatment being offered. Action required by clinician(s) in the event of an SAE or SUSAR
• Complete a copy of the Serious Adverse Event / Suspected Unexpected Serious Adverse Reaction form (within 48 hours)
• Fax it immediately to the NEST Co-ordinating Centre in Oxford (Fax:
01865 289740)
The Study Co-ordinator will then:
• Immediately notify the Chief Investigator of receipt of SAE / SUSAR
• Inform the study DMC and TSC - the chairmen for the DMC and TSC will be notified in writing.
• Inform the Trent MREC in writing. • Inform the R&D Office of the hospital reporting the adverse event.
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9. CONTACT WITH PARENTS The NEST Co-ordinating Centre will maintain contact with families after discharge from hospital in order to facilitate arrangements for later follow up. We will be sending newsletters at regular intervals to parents whose babies have participated in NEST. A newsletter will be sent to all parents regardless of the outcome for their baby. On each occasion, parents will be asked if they wish to continue receiving the newsletter. We will send copies of the newsletters to the Local Co-ordinators of all participating centres in case parents seek further information from the centre where their baby was recruited as a consequence of the newsletter’s contents.
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10. DEFINITIONS OF TERMS IN DATA COLLECTION FORMS Study Entry Form EDD Expected date of delivery. Use the best estimate (dates or ultrasound) based on a 40 week gestation.
Is this baby eligible for ECMO? In order to be eligible for ECMO the baby must meet the following criteria:
at least 35 weeks gestation; at least 2000g weight; no uncontrolled bleeding disorder; no congenital or acquired CNS disorder no more than 7 consecutive days of high pressure ventilation prior to referral for ECMO; the underlying condition is potentially reversible; evidence of severe cardio-respiratory failure; less than 29 days of age.
Complications around the time of delivery. Please record what diagnosis were made in the mother’s notes. For example, only record ‘Abruption’ if a diagnosis of abruption was made by the obstetrician and recorded in the mother’s notes. Bleeding at the time of birth may not always indicate abruption. Duration of ventilation. During episode leading up to referral. Daily Progress Form Blood-derived clotting factors. Include cryoprecipitate, fresh frozen plasma and platelet transfusions as well as specific clotting factors such as Factor VIII.
Volume of colloid. Include total volume of whole blood, packed cells and other colloid infusions given in this 24 hour period but exclude blood derived clotting factors.
Clinical seizures. Do not record seizures seen on an aEEG unless they are accompanied by clinical seizures. ECMO Unit Discharge Form Respiratory support. Include part of any day as 1 day. Transfer Hospital Discharge Form. Respiratory support. Include part of any day as 1 day.
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NEST Flow Chart
