Recent discussions
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Виктория Антонова
We thank ILCOR and the ALS Task Force for inviting comment on the draft consensus on science and treatment recommendations on the use of vasopressors for cardiac arrest. As authors of the PARAMEDIC2 study[1] we wish to share the following insights. The Core Outcome Set for Cardiac Arrest (COSCA)[2] highlights the difficulty of identifying the optimal time for measuring neurological outcomes after cardiac arrest. Assessment at hospital discharge has the advantage of ease of data collection but does not allow sufficient time for any functional recovery to occur over the months ahead. Follow-up at 3 to 12 months may provide a more stable assessment of long term outcomes, but is limited by loss to follow-up. This increases the risk of attrition bias as those with worse outcomes are more likely to be lost to follow-up.[3, 4] In PARAMEDIC2, loss to follow-up amongst survivors at hospital discharge was 5 (4%) in the placebo group and 8 (6%) in the adrenaline group. By 3 months this had increased to 20 (23%) in the placebo and 29 (24%) in the adrenaline group. Sensitivity analyses exploring the different possible reasons for loss to follow-up are contained in the electronic supplemental material presented with the main paper. Our assessment of the PARAMEDIC2 data on longer term outcomes is that adrenaline increases survival with both good and poor neurological outcomes. The overall effect is small (0.8% absolute difference in survival). Resource use is high – extrapolating PARAMEDIC2 data across the UK National Health Service, the use of adrenaline in out of hospital cardiac arrest contributes to 3555 additional hospital admissions each year (1643 ITU admissions, for 5143 ICU days) for 68 additional survivors with a favourable neurological outcome and 135 with an unfavourable neurological outcome at hospital discharge. We suggest the cost to health care systems should be highlighted in the undesirable effects section of the evidence to decision framework. The balance of survival, survival with a favourable neurological outcome and survival with an unfavourable neurological outcome will mean different things to different people and will likely vary between communities. We suggest it should be noted in the evidence to decision tables that societal values and preferences may vary and should inform the treatment recommendations in different settings. Furthermore, our lack of knowledge about patient and public preferences for outcomes should be specifically identified as a knowledge gap. The presence of resuscitation time bias[5] limits the interpretation of observational studies which seek to evaluate the influence of time to treatment. Our preliminary analyses of time to treatment in PARAMEDIC2, support the recommendation, that if adrenaline is going to be given, it is better given as soon as possible. We did not find evidence of an interaction favouring early administration by shockable or non-shockable rhythms, but note the difficulty in interpretation of the shockable rhythm data (as some patients will convert to a non-shockable rhythm after the first attempt at defibrillation). In the PARAMEDIC2 trial, treatment protocols recommended deferring adrenaline until after the third attempt at defibrillation for patients with shockable rhythms.[6, 7] The findings for the ILCOR review and consensus on science is broadly similar to our Cochrane review of vasopressors for cardiac arrest.[8] Small differences are noted which appear to relate to whether a random effects or fixed effects Mantel-Haenszel meta-analysis was performed. These differences do not materially affect interpretation. Data on adjusted analyses are presented in both the PARAMEDIC2[1] and PACA[9] trial publications should the Task Force wish to use these in the meta-analysis as has been performed in other ILCOR consensus on science reviews. Finally, we believe the PARAMEDIC2 trial highlights the importance of the community response to cardiac arrest (early access (NNT 11), early bystander CPR (NNT 15), early defibrillation(NNT 5). PARAMEDIC2 and this ILCOR review draws attention to the gap in our knowledge around treatments that can enhance neurological recovery after cardiac arrest. It highlights the urgent need for further research to ensure both successful cardio and cerebral recovery. PARAMEDIC2 investigators https://warwick.ac.uk/paramedic2/ Clinical Trial Registration: ISRCTN73485024 This project was funded by the NIHR HTA Programme (ref 12/127/126). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. References 1. Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med 2018;379(8):711-21. doi: 10.1056/NEJMoa1806842 [published Online First: 2018/07/19] 2. Haywood K, Whitehead L, Nadkarni VM, et al. COSCA (Core Outcome Set for Cardiac Arrest) in Adults: An Advisory Statement From the International Liaison Committee on Resuscitation. Resuscitation 2018;127:147-63. doi: 10.1016/j.resuscitation.2018.03.022 [published Online First: 2018/05/01] 3. Nichol G, Guffey D, Stiell IG, et al. Post-discharge outcomes after resuscitation from out-of-hospital cardiac arrest: A ROC PRIMED substudy. Resuscitation 2015;93:74-81. doi: 10.1016/j.resuscitation.2015.05.011 4. Ji C, Lall R, Quinn T, et al. Post-admission outcomes of participants in the PARAMEDIC trial: A cluster randomised trial of mechanical or manual chest compressions. Resuscitation 2017;118:82-88. doi: 10.1016/j.resuscitation.2017.06.026 [published Online First: 2017/07/10] 5. Andersen LW, Grossestreuer AV, Donnino MW. "Resuscitation time bias"-A unique challenge for observational cardiac arrest research. Resuscitation 2018;125:79-82. doi: 10.1016/j.resuscitation.2018.02.006 [published Online First: 2018/02/10] 6. Soar J, Nolan JP, Bottiger BW, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support. Resuscitation 2015;95:100-47. doi: 10.1016/j.resuscitation.2015.07.016 7. Soar J, Deakin C, Lockey A, et al. Adult advanced life support. 2015. https://www.resus.org.uk/resuscitation-guidelines/adult-advanced-life-support/. 8. Finn J, Jacobs I, Williams TA, et al. Adrenaline and vasopressin for cardiac arrest. Cochrane Database Syst Rev 2019;1:CD003179. doi: 10.1002/14651858.CD003179.pub2 [published Online First: 2019/01/18] 9. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Resuscitation 2011;82(9):1138-43. doi: S0300-9572(11)00405-9 [pii] 10.1016/j.resuscitation.2011.06.029 [published Online First: 2011/07/13] -
Виктория Антонова
I am not convinced that epinephrine should be routinely administered. There are cost implications to the use of the drug itself. There are huge costs (fiscal and suffering, for healthcare systems/ relatives/ patients) implications to caring for people with poor neurological outcome even to hospital discharge, and beyond. I doubt that this cost is worthwhile given the few who may survive with good neuro-outcome. I am not sure that the suffering faced by those who do badly can be traded for the good outcome for others. -
Виктория Антонова
In remote areas where the first responder with health care training is likely to be a nurse, and sometimes no-one else with adequate training, a supraglottic airway is feasible and makes CPR simpler. Endotracheal tube is usually outside their scope of practice, and juggling a bag valve mask with chest compressions wastes time. -
Виктория Антонова
The primary source for the recommendation to keep things the same is a brand new study - PARAMEDIC2. This showed no statistically significant improvement in the only outcome that matter - survival without severe brain damage. A larger study might show that there is a real improvement - or it may put the epi hypothesis out of its misery. I will eventually have a cardiac arrest. If I am resuscitated, whom will ILCOR send to change my diaper, and attend to the other things I can no longer attend to? We need evidence of a significant benefit in order to justify distracting everyone from interventions that actually do improve survival without severe brain damage. . -
Виктория Антонова
I am not a researcher. I am a retired paediatrician and the mother of a CPR survivor. I have just published a book about my son's incredible journey and I would like to share it with you. I hope this testimony can contribute positively to the field of cardiopulmonary resuscitation. I will try to give you the link; but in case I don't succeed, please take note that the book is available at Amazon under the title “Why was I resuscitated?” , by Anne Beaudoin. Here is the link: https://www.amazon.ca/dp/298169684X/ref=cm_sw_em_r_mt_dp_U_YUIOCb2WPVNF3 -
Виктория Антонова
I find Rory Spiegel's arguments against the use of epinephrine in cardiac arrest very persuasive. A minimal number of extra survivors at a very high price in terms of the neurologically impaired ones, who will suffer themselves, cause suffering to their relatives and consume a lot of expensive health care resources in the long term. ROSC is only the first step in successful resuscitation. The goal is a neurologically or "nearly neurological " intact survivor. Remember Peter Safar's writings on "Cardiopulmonary - Cerebral Resuscitation". I would respectfully ask the committee to review the evidence again and reconsider their recommendations,which will have an impact over the next 5 years.If epinephrine was a new drug - would it be recommended. -
Виктория Антонова
If we wish to promote bystander CPR to be done by members of the general public, then the supraglottic airway, bag valve mask, will be more easier for them, as training is more easy, with the skills more easier to retain. Moreover, success in using these skills shall be better, and this will help to uplift their willingness to help in emergencies. -
Виктория Антонова
The ILCOR treatment recommendations concerning vasopressors in cardiac arrest call for the administration of epinephrine during cardiopulmonary resuscitation This is designated as a strong recommendation with low to moderate certainty of evidence. The authors justify this recommendation stating, “the findings that epinephrine compared with placebo substantially improves ROSC, and also improves hospital admission and survival. The task force made a strong recommendation given that the intervention may reduce mortality in a life-threatening situation and adverse events are not prohibitive.” In their literature review, the authors discuss Perkins et al (1), the major RCT examining the use of bolus-dose epinephrine in cardiac arrest. They note Perkins et al demonstrated a statistically significant difference in 30-day survival (3.2% vs 2.4% unadjusted odds ratio for survival 1.39; 95% confidence interval 1.06 to 1.82; P=.02), when the use of bolus dose epinephrine was compared to placebo. Perkins et al also reported an increase in the number of patients who were transported to the hospital (50.8% vs 30.7%) and survived to ICU admission (14.1% vs 6.8%). Despite a small increase in overall survival, there was no difference in the rate of neurologically intact survival in patients randomized to receive epinephrine versus placebo. When writing the ILCOR recommendations, the authors state they balanced the potential benefits and harms associated with the use of bolus-dose epinephrine in cardiac arrest. Despite this assertion, Perkins et al demonstrates a clear signal of harm not discussed by the authors. In this case we are asked to weigh a 0.8% increase in survival to hospital discharge with the harms associated with its use. The harms come in the form of a significant increase in the risk of survival with neurologic devastation. Although more patients who received epinephrine were transported to the hospital (50.8% vs 30.7%) and survived to ICU admission (14.1% vs 6.8%), 31% of the survivors in the epinephrine group had a modified Rankin Scale score of 4 or 5 (unable to walk or bedridden), compared with 17% in the placebo group. These results suggest the use of bolus-dose epinephrine does not result in a larger number of neurologically intact survivors. Rather it shifts a small number of patients from death to a state of neurological devastation. This is not a small price. Imagine the increase in societal resources required to care for the large increase in the number of patients transported to the hospital alive, the moderate increase in the number of patients that survive to ICU admission, and the few neurologically devastated patients requiring long-term care. All with no increase in clinically meaningful neurologically intact survival. Sources Cited: Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N. July 2018. doi:10.1056/nejmoa1806842 -
Виктория Антонова
I completely agree that in the out of hospital patient population bag mask ventilation is superior per the EB findings. This in no way indicates that the same would be true in a controlled setting in hospital, per this research "There were no RCTs of airway management for in-hospital cardiac arrest." Future RCTs comparing endotracheal intubation, LMA insertion and video laryngoscopy use for endotracheal intubation with time and success rates would be beneficial. -
Виктория Антонова
LMA is a user-friendly device with a high success rate. If there is any difficulty in securing the airway with LMA (which is a possibility), an oropharyngeal airway of appropriate size might be adequate for ventilation until skilled help is available for an advanced airway. Aspiration can happen with any device.