Estimated reading time: 7 minutes
Research in cardiac arrest management has improved a lot in recent years. We are now seeing large randomised controlled trials looking at specific therapies in the management of these critically unwell patients. Studies such as AIRWAYS2 and PARAMEDIC2 have been covered on the blog previously and we are always on the look out for more ideas.
There are many complexities in cardiac arrest research. RCTs often require quite significant numbers to show any difference in outcome and there are also challenges in obtaining consent (though these have mostly been addressed in the UK). Another more philosophical question is whether trials should focus on individual interventions or whether it would be more appropriate in looking at packages of care. One such problem arises around the use of head up CPR in cardiac arrest patients. Should we look at this in isolation or is more appropriate to look at it as part of a package of related interventions? A recent systematic review identified a number of trials of HU-CPR suggesting a benefit, but the majority were animal based and those in humans were not of a high quality.
HU-CPR in conjunction with active compression:decompression CPR (as delivered by a mechanical CPR (mCPR) device such as a LUCAS), and an impedance threshold device (ITD) has been shown in animal models to decrease intracranial pressure and improve cerebral perfusion pressure, cerebral blood flow and neurologically favorable survival in animal models. The combination of HU-SPR with compression/decompression CPR an an impedance threshold device is referred to as ACE-CPR, and it is generally regarded that HU-CPR is most likely to be effective if combined with mCPR and and ITF So in theory we would hope that such benefits would translate to improved outcomes in humans. Ideally we would want to see a clinical trial that randomised such an intervention to patients in cardiac arrest with routine care as a comparison. However, we don’t have such a trial at this time. Is there anything we can do in the meantime to assess whether or not to adopt this theoretically advantageous approach to cardiac arrest management. One approach is to consider observational data, but as we will discuss there are limitations with such an approach.
This month we do have an observational paper to review that addresses the question, but does it give us an answer. Have a read of the abstract below, and then please have a read of the full paper too.
What kind of paper is this?
This is an interesting design. The authors have taken data from a number of studies that used or did not use ACE-CPR and then used the outcomes from the patients in those trials to perform a comparison. So this is an observational trial where the authors have tried to match ACE-CPR patients with those that did not receive this intervention and then compared outcomes. The data on the patients was not obtained prospectively for this trial, but was rather obtained from other studies.
Tell me about the patients.
Patients in the ACE-CPR group were obtained from a registry of patients entered from EMS schemes that voluntarily submit data to a registry (the national Device Assisted Controlled Sequential Elevation CPR Registry). Patient in the comparison group were obtained from three large NIH trials (PRIMED, ROC-ALPS and ResQtrial). The key fact here is that the patients in the two groups were not in the same trial, nor the same system, nor the same time points. It is therefore likely that the patient groups are quite different.
To try and mitigate this the authors have matched on a 1:4 basis such that one ACE-CPR patient to 4 patients with similar characteristics in the C-CPR group. The groups were also adjusted using propensity matching which is a way of adjusting the likely outcome (in this case survival) based on the factors that we know are likely to influence outcome (e.g. age, sex, whether arrest witnessed etc.). It’s a way of trying to match patients from different cohorts according to their underlying characteristics. The issue with propensity scoring in this setting is that the cohorts are different and thus it is likely that there are other differences that may not have been taken into account by propensity scoring. It’s one of the reasons why we prefer an RCT design when testing interventions such as this.
What about the intervention?
Arguably the most interesting aspect to this study is that they are looking at a combination of interventions that have been around for a long time, but which have not been well studied in combination. There is a pathophysiological argument that the combination of mCPR, ITD and head up position may be synergistic in their effects. In the past we have looked at mCPR on the blog and found little benefit (though it remains widely used for practical and health and safety reasons), but past trials have not used it in combination which in animal models appears to show a potential advantage. The device used in the trial slowly elevates the head position whist the mCPR and ITD are used in combination. The idea is that this improves venous drainage from the brain, improves venous return to the heart and may improve cerebral circulation as a result.
What did they find?
The headline figure from the authors is that ACE-CPR was associated with a higher probability of survival when started between 7 and 18 minutes (ACE-CPR (OR 4.8, 95 % CI, 1.33–17.29) to up to 18 min (OR 1.88, 95 % CI 1.03–3.44) versus matched C-CPR patients). The odds of survival appear to be better if ACE-CPR is started earlier. I’m not a big fan of odds ratios as a way of sharing information and so I’ve gone into the data and estimated that if applied within 20 mins then 202/1354 (14.9%) patients on ACE-CPR survived as compared to 372/5652 (6.6%) on C-CPR.
This is quite a significant difference and really interesting. However, due to the nature of the study we can only consider this to be hypothesis generating. There were small numbers of patients within the 7 minute window which may account for that finding. Similar time based factors were seen in the results for ROSC and favourable neurological outcome. The effect was seen in both shockable and non-shockable rhythms.
UPDATE – as Swami points out in the comments below if we look at the authors original primary outcome there is no difference, and it’s only when they looked at secondary outcomes based on time splits that a difference was found. This is even more reason to consider this paper as hypothesis generating only.
Should we adopt this therapy?
This is an interesting paper and consistent with some work we are planning in Virchester. However, this sort of study is at risk of significant bias. The different cohorts and statistical manipulation to try and develop comparable cohorts is a reasonable approach, but also very risky when trying to draw firm conclusions. What we really need is a well conducted RCT in the same patient population, systems and time points to tell us whether this interesting combination of therapies offers a benefit over standard ALS care.
It’s also worth noting that there are challenges ahead if this is to be done. Practically, getting this combination of devices to the patient’s side in the time scales indicated in this paper may be a challenge if they are limited to specialist services, and may be more likely achieved in urban settings (simply because of geography).
This is an interesting hypothesis generating paper that reminds us that the cardiac arrest story is far from over and that there are many more trials and innovations out there that are yet to be tested and explored.
From a critical appraisal perspective it’s important that we look carefully at research design to determine how reliable study results are likely to be and how that might influence future papers and research.
- The role of head-up cardiopulmonary resuscitation in sudden cardiac arrest: a systematic review and meta-analysis https://pubmed.ncbi.nlm.nih.gov/35928751/
- Head and thorax elevation during cardiopulmonary resuscitation using circulatory adjuncts is associated with improved survival. https://pubmed.ncbi.nlm.nih.gov/35933057/
- JC: PARAMEDIC trial m-CPR at St.Emlyn’s https://www.stemlynsblog.org/jc-paramedic-trial-m-cpr-st-emlyns/