15th May: Should We Cool Children Following Out-Of-Hospital Cardiac Arrest?

 

-nativeNEJM2

 

Where can I find this paper?

http://www.ncbi.nlm.nih.gov/pubmed/25913022

What is this paper about (what is the research question)?

Does therapeutic hypothermia increase the proportion of patients surviving at one year with good functional status following paediatric out-of-hospital cardiac arrest?

Summary of the Paper

Design: single-blinded, multicentre randomised controlled trial

Objective: to determine whether therapeutic hypothermia after out-of-hospital cardiac arrest confers a benefit in children

Primary outcome measure: survival at 12 months with good neurological function (defined as age-corrected standard score of 70 or more on the Vineland Adaptive Behaviour Scales (VABS-II)

Intervention: subjects were randomly assigned in 1:1 (permuted blocks stratified by age) to therapeutic hypothermia (target temperature 33°C) for 48h then normothermia (target temperature 36.8°C) for 72h, or normothermia for 120h. Active cooling was undertaken in either case to achieve the target temperature.

Participants: 295 patients randomised between September 2009 – December 2012. 155 were randomised to hypothermia, 140 to normothermia.

  • Inclusions: patients aged 48hrs-18 years presenting following out-of-hospital cardiac arrest to one of 38 sites in the US and Canada, having required chest compressions for at least two minutes and with an ongoing requirement for mechanical ventilation after return of spontaneous circulation (ROSC)
  • Exclusions: inability to undergo randomisation within 6h, score of 5-6 on the motor component of the Glasgow Coma Scale, decision to withhold aggressive treatment, major trauma as cause of arrest, patients with pre-existing VABS-II score <70

Results: 

Survivors at 12 months with VABS-II score >70

Hypothermia 27/138 (20%)

Normothermia 15/122 (12%)

Risk difference 7.3 (95% confidence interval -1.5 to 16.1)

Relative likelihood 1.54 (95% confidence interval 0.86 to 2.76, P=0.14)

Authors’  conclusions

In comatose children who survive out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit with respect to survival with good functional outcome at one year.

On the study design

The study was utilised multicentre collaboration to recruit a sample with 85% power to detect a 15-20% difference in the primary outcome between treatment groups. This was a pragmatic design; although the subjects and those providing care to the patients could not be blinded to the intervention, reasonable steps were taken to ensure that the investigators recording the primary outcome were a) independent from those delivering care and b) blinded to the arm of the study to which subjects had been randomised.

Unlike other studies, the normothermia in this case was also an active decision; the patients’ temperature was actively controlled according to the group to which they were randomised.

The authors tells us that other than the temperature targeted, care between the groups was identical although they later state that “all other aspects of care were determined by the clinical teams.” This does leave us to wonder what if and how knowledge of the treatment arm and expectation of its efficacy (or otherwise) might have influenced those treating clinicians.

What were the results and what does this mean?

There was no statistical difference in survival with a good neurological outcome at 12 months between the two groups. In the secondary outcomes, there was no difference in absolute survival between the groups, nor in the reduction in neurological performance score, however there was increased incidence of hypokalaemia and thrombocytopenia in the hypothermia group and increased requirement for renal replacement therapy in the normothermia group.

Results were analysed using intention to treat analysis, which includes subjects in the final analysis of the arm to which they were randomised irrespective of whether they dropped out of the study or received an alternative treatment in the end. This is a conservative approach which can help to ameliorate the effects of unpleasant side effects of treatments; there’s a nice explanation of intention to treat here. It helps give us a realistic expectation of the results we might see in clinical practice.

What can we take from this paper into clinical practice?

In this study the null hypothesis was no difference between the groups, this study doesn’t prove that hypothermia is harmful or not beneficial; there is simply insufficient evidence to reject the null hypothesis of no difference, based on this study. We should continue to follow local protocols in terms of cooling but this paper does give clinicians a little additional confidence in deviating from protocols if indicated.

More questions to ask

  • Is there evidence for cooling patients following in-hospital cardiac arrest?
  • Would a larger sample size demonstrate a benefit and is this feasible?

See Also:

This post at St Emlyns: JC: Getting Chilly Quickly 4. Doing It For The Kids

This post at Academic Life in Emergency Medicine:

This post at Resus.Me: Post Arrest Hypothermia in Children Did Not Improve Outcome

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Reducing PED Reattendance Rates

Title 060914

http://www.ncbi.nlm.nih.gov/pubmed/25162691

What is this paper about (what is the research question)?

Can we reduce the number of reattendances to the paediatric emergency department by telephoning within 24h of discharge?

Summary of the Paper

Design: Single-centre, prospective randomised controlled trial

Objective:  to examine whether a follow-up telephone call by a non-health care provider from the ED within 24h of discharge can reduce the rate of returning to the ED within 72h

Outcomes:  rate of return visits within 72h of discharge. It is unclear how this was determined but subjects were contacted by telephone at 96h after discharge in both intervention and control groups.

Intervention: follow-up phone call within 12-24h of discharge undertaken by a “research assistant” (medical student)

Comparison:  standard care (i.e. no follow up phone call)

Participants: convenience sample of parents of patients presenting to a single centre between 1st July 2009 and 30th August 2009.

  • Inclusions: parents of patients for whom the responsible clinician thought ED discharge was likely
  • Exclusions: families without a telephone, those who left without being seen, those leaving against medical advice

Results: 371 subjects were recruited of whom 171 were in the study group and received a follow-up phone call and 200 were in the control group. Demographics were broadly similar between the two groups.

24/171 in the study group reattended within 72h (14%)

14/200 in the control group reattended within 72h (7%)

There was a statistically significant difference between reattendance rates with a greater proportion of reattendances in the intervention group (p<0.03).

Authors’  conclusions

 Emergency Departments practicing follow-up calls without response to medical questions should consider a forecasted increase in return rates

On the study design

This is a single centre pseudo-randomised controlled trial – the authors tell us that it was pseudo-randomised because there were research staff available to recruit at different hours of the day. It’s not clear exactly how this statement refers to randomisation but if the time of day patients presented to the ED predicted whether they entered the intervention or control group then there’s potentially a major confounder in the first premise of the paper.

Inclusion and exclusion criteria seem reasonable but the demographics of the subjects throws up some interesting issues; the mean age of the presenting child was 5.7years with a mean parental age of 38.3 years. I can’t help but wonder whether a similar study in my own department would reveal a rather different (substantially younger) parental population and there are sociological implications to this.

There is no sample size calculation so although there were reasonable numbers in each group we don’t know whether the study was fundamentally underpowered and unable to detect a statistical difference between groups. Whether this statistical difference represents a clinically relevant outcome measure is also in question (and addressed below).

What were the results and what does this mean?

On the surface it seems that telephone follow-up within 12-24 hours of ED discharge increases rather than decreases reattendance rates, but the picture is rather more complicated.

Firstly, there is an intrinsic uncertainty surrounding the value of follow-up calls by non-healthcare professionals. Of particular note, the telephone interviews were undertaken by medical students. It seems that conversations were one-way; parents were asked whether they had any questions but there was no opportunity for them to be answered. It seems possible that introducing the concept that there might be unanswered questions could actualise occult parental anxiety, prompting them to seek clarification from a healthcare professional.

Secondly, it’s not even clear how reattendance data was obtained. Was this self-reported by parents at the 96h phone call? It seems so – in which case it could almost certainly have been collected more reliably using ED computerised records.

Thirdly, all manner of data about these reattending subjects is omitted. Were they actually unwell and then admitted to the hospital? Were all reattenders in both groups discharged from  ED again? Without this information it is difficult to ascertain whether reattendance was inappropriate.

What can we take from this paper into clinical practice?

Follow-up phone calls by non-healthcare professionals do not seem to reduce reattendances. However it’s unlikely that this model would ever be rolled out and there are plenty of other questions we still need answers to.

More questions to ask

  • Are these effects the same in an adequately powered study where outcomes are divided into admission or discharge at reattendance (arguably more clinical relevant)?
  • Would attendances be reduced if phone calls were made by healthcare professionals and provided an opportunity to obtain advice and have questions answered?

 

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