NeoNotes Journal Club
Andrew B. Kairalla MD, Editor


6-040 |
Additional Comments | Previous Article | Next Article | Search | List of Articles | Submit Comments | Index | FSN Home Page


Whole-Body Hypothermia for HIE

Shankaran S, Laptook AR, Ehrenkranz RA, et al.  Whole-Body Hypothermia for Neonates with Hypoxic–Ischemic Encephalopathy.  New Engl J Med (Oct 23, 2005); 353:1574-1584.  [FULL TEXT

Background. Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain.

Methods.  We conducted a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability.

Results.   Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20).

Conclusions.  Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic–ischemic encephalopathy.


Comments:  This is a large randomized-controlled trial that demonstrates both the safety and efficacy of whole body hypothermia to improve outcomes in babies with moderate or severe HIE.  Unlike the previous paper, this study did not require an abnormal aEEG as part of its selection criteria.  Instead, patients were selected based on physiologic criteria (pH < 7, or base deficit > 16) and evidence of moderate or severe HIE on neurologic exam.  The results are conclusive and impressive.  Is it time to invest in some cooling blankets so we can offer this therapy to our next baby with moderate or severe HIE?  I think so, and I invite those with a different opinion to visit our web site (www.neonotes.com) and join the discussion.  ABK. 


Additional Comments:

Date: 09 Dec 2005
Time: 11:36:09

I just attended the 2005 Hot Topics meeting where hypothermia for HIE was discussed. The consensus was that there need to be more clinical trials. First to decide which patients for whom it will be most effective, second when it should be started to be most effective and third whether brain cooling is more effective than whole body cooling. Until these questions are answered it was felt that this is not presently the standard of care and consent should be obtained from them family to use it.

UserName: Howard Harris, MD
Institution: Methodist Hospital of Indiana
telephone: 317-962-8175
email: hharris@clarian.org


Date: 09 Dec 2005
Time: 20:10:00

I agree that it is still appropriate to obtain informed consent from parents before using this new therapy.  As you said, we do still have some unanswered questions, and it will likely be years before we can answer all of them (if ever).  On the other hand, I feel that the present study confirms both the safety and efficacy of whole body hypothermia in the patient population described.  It should no longer be necessary to be participating in a randomized, controlled trial to offer this treatment to eligible patients as described in this study.  From an ethical standpoint, I would have trouble not offering this treatment to a family whose baby is likely to benefit from it. 

Andy Kairalla MD
Editor


Date: 12 Jan 2006
Time: 07:06:51

I agree that, to date, risks of hypothermia have been minimal, but I am not sold on the benefits. Clearly, animal models show a therapeutic advantage to hypothermia. However, in the NICHD Study, look carefully at the control group. Many of these babies had elevations in esophogeal temerature (while surface temperature was being monitored and acted upon). This may have led to the control infants having a worse outcome than if the core temperature were better monitored and acted upon to prevent hyperthermia. Animal and adult stroke work clearly show that hyperthermia after brain injury can be devestating. I would be interested in seeing a sub-analysis of the data with those control infants with hyperthermia removed from the analysis.

UserName: David J. Burchfield, MD
Institution: University of Florida
telephone: 352-392-4195
email: burchdj@peds.ufl.edu


Date: 23 Jan 2006
Time: 03:17:19

We are a small hospital well we have not even proven the hypotherm in cases of encefalopatia HIE..por which we did not count experience to think.

UserName: Monica sanchez
Institution: Imss servicio de neonatologia
telephone: 612 1039913
email: mcsaynes@hotmail.com


You may add your own comments to the discussion of this topic by selecting : Submit Comments.

Return to top

Hit Counter