Interventional procedure consultation document

Drainage, irrigation and fibrinolytic therapy (DRIFT) for post-haemorrhagic hydrocephalus in preterm infants

Treating bleeding-related progressive enlargement of the head in babies born prematurely by drainage, irrigation and breaking down blood clots

Bleeding in the brain is a serious complication in babies born prematurely. It can result in obstruction of the flow of fluid (called cerebrospinal fluid [CSF]) within the cavities of the brain leading to progressive enlargement of the head (hydrocephalus). Death or permanent brain damage may follow. There are very few treatments for this condition.

This procedure aims to remove the blockage and reduce its harmful effects by draining excess CSF from the brain, washing out the blood, and breaking down blood clots using drugs (fibrinolytics).

The National Institute for Health and Clinical Excellence (NICE) is examining drainage, irrigation and fibrinolytic therapy for post-haemorrhagic hydrocephalus in preterm infants 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 drainage, irrigation and fibrinolytic therapy for post-haemorrhagic hydrocephalus in preterm infants.

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• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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).

Through its guidance NICE is committed to promoting race and disability equality, 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 interventional procedures guidance. In particular, we aim to encourage people and organisations from groups who might not normally comment on our guidance to do so.

In order to help us promote equality through our guidance, we should be grateful if you would consider the following question:

Are there any issues that require special attention in light of NICE’s duties to have due regard to the need to eliminate unlawful discrimination and promote equality and foster good relations between people with a characteristic protected by the equalities legislation and others?

Please note that 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: 26 July

Target date for publication of guidance: October 2011

 

1   Provisional recommendations

1.1   Current evidence on the efficacy and safety of drainage, irrigation and fibrinolytic therapy (DRIFT) for post-haemorrhagic hydrocephalus in preterm infants is inadequate in quantity and quality. Therefore this procedure should only be used in the context of research. Research should aim to establish the risk of secondary haemorrhage and its consequences, and the need for shunt insertion. Outcomes should include death and disability in the long-term: these should be reported separately.

2   The procedure

2.1   Indications and current treatments

2.1.1   Intraventricular haemorrhage is a serious complication occurring within a few days of birth in a small proportion of preterm infants. It is more common and severe in infants born before 30 weeks of gestation and can be fatal. Among surviving infants, more than half will develop post-haemorrhagic hydrocephalus associated with varying degrees of neuro-developmental disability.

2.1.2   Management of post-haemorrhagic hydrocephalus in preterm infants typically involves repeated CSF drainage followed by subsequent insertion of a ventriculo-peritoneal (V-P) shunt. No particular treatment has been shown to improve neurological outcomes.

2.2   Outline of the procedure

2.2.1   The aim of DRIFT is to reduce the risk of death, the risk of neuro-developmental disability, and the need for shunt insertion.

2.2.2   The procedure is performed with the infant under general anaesthesia. Two catheters are inserted into the lateral ventricles from right frontal to left occipital or vice versa. A fibrinolytic agent is given intraventricularly with the aim of lysing thrombi in the ventricles. After 8 hours, ventricular irrigation is commenced, by infusing artificial CSF through the frontal catheter (typically at a flow rate of 20 ml/h) and draining it through the occipital catheter to a closed drainage system. Outflow is adjusted so that intracranial pressure readings remain less than 7 mm Hg. Irrigation continues until the colour of the drained fluid becomes normal (‘cola to white wine’), typically within 3 days.

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/guidance/IP/855/overview

2.3   Efficacy

2.3.1   A randomised controlled trial (RCT) of 70 infants treated by DRIFT (n = 34) or standard treatment (n = 36) reported that DRIFT did not reduce mortality at follow-up to 6 months of age or discharge from hospital (whichever was longer) compared with standard treatment (relative risk [RR] 0.42, 95% confidence interval [CI] 0.09 to 2.04). A second publication from the same RCT, including an additional 7 infants, reported mortality rates of 8% (3/39) and 13% (5/38) respectively at 2-year follow-up (timing of death and significance not stated).

2.3.2   The RCT of 70 infants treated by DRIFT or standard treatment reported that DRIFT did not reduce the use of shunt surgery compared with standard treatment at follow-up to 6 months of age or discharge (RR 0.98, 95% CI 0.54 to 1.78). The subsequent publication from the same RCT reported that permanent shunting was required in 41% (16/39) of infants treated by DRIFT and 40% (15/38) treated by standard treatment within 2 years (timing not stated).

2.3.3   A case series of 24 infants reported that 26% (6/23) of the surviving infants required ventriculo-peritoneal shunt surgery (follow-up interval not stated).

2.3.4   The second publication from the RCT (77 infants) reported on crude and adjusted (for sex, birth weight, and intraventricular haemorrhage [IVH] grade) odds of mental and psychomotor infant development status scores using Bayley Scales of Infant Development II (BSIDII; range: 0–100). Infants treated by DRIFT had significantly lower odds of mental development index score < 55 (representing severe cognitive disability at a mean follow-up of 25 months (crude odds ratio [OR] 0.31, 95% CI 0.11 to 0.86, p = 0.024, adjusted OR 0.17, 95% CI 0.05 to 0.57). Infants treated by DRIFT had lower odds of psychomotor development index score < 55 (representing severe psychomotor disability) at a mean follow-up of 25 months (crude OR 0.54, 95% CI 0.20 to 1.40, p = 0.22, adjusted OR 0.21, 95% CI 0.05 to 0.85, p = 0.028).

2.3.5   The case series of 24 infants reported that 58% (11/19) of infants who were evaluated at 12 months post-term developed disability, including 21% (4/19) with multiple disabilities (assessment of cognitive disability based on the Ruth Griffiths Scales of Infant Development, scores not reported).

2.3.6   The Specialist Advisers listed key efficacy outcomes as reduction in the need for a ventriculo-peritoneal shunt and improved cognitive and motor development in the long term.

2.4   Safety

2.4.1   The RCT of 70 infants treated by DRIFT or standard treatment reported secondary intraventricular haemorrhage (IVH) (diagnosed by ultrasound appearance of echodensities combined with a fall in haemoglobin of 2 g/dl in 2 days) in 35% (12/34) and 8% (3/36) of infants respectively (p = 0.014). Secondary IVH was asymptomatic in all but 1 infant who developed acute thrombocytopenia.

2.4.2   The case series of 24 infants reported clinically significant secondary IVH in 2 infants. One was successfully treated with intravenous tranexamic acid and the other stabilised without treatment (timing not stated).

2.4.3   The RCT of 70 infants treated by DRIFT or standard treatment reported mean numbers of blood transfusions required in the first 7 days after randomisation of 1.7 (range: 0–4) and 0.8 (range: 0–2) respectively (p < 0.001). In the DRIFT group, the mean number of transfusions given was 2.2 (range: 1–4) in those with secondary IVH and 1.4 (range: 0–4) in those without secondary IVH (p = 0.012).

2.4.4   The Specialist Advisers listed anecdotal adverse events as further intraventricular bleeds and secondary bleeds after administration of the thrombolytic agent. They considered theoretical adverse events to include infection, meningitis, displacement or blockage of catheters, trauma to the brain.

2.5   Other comments

2.5.1   The Committee noted that there is a lack of effective treatments for post-haemorrhagic hydrocephalus in preterm infants who may suffer severe disability as a result. The Committee acknowledged that there is a reasonable conceptual basis for DRIFT, but considered the current evidence on its potential efficacy to be insufficient.

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

June 2011

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