Top resus papers for TBS. St Emlyn’s

This week I am in Zermatt, Switzerland for ‘The Big Sick’ conference. This is something I have been looking forward to years, but major heart surgery (valves not pipes) and COVID scuppered my plans to join the team to discuss the latest and greatest science in resuscitation. Even more than that I am really excited to be meeting up with ATACC colleagues to discuss how we innovate in education.

Watch my talk live and the rest of the conference for free here The conference starts this morning at 0730 UK time

My contribution is to kick off the conference with a review of the key literature from the last 12 months that will hopefully frame some of the discussions over the next few days. As usual it’s my personal view of what’s been interesting and not a formalised review, but I hope that you find it interesting.

Theme 1: Airway

Paper 1.

As a PHEM/EM doctor I am always very, very cautious about anaesthetising shocked, bleeding patients unless I can see the whites of the eyes of the surgeon/IR doc who is going to turn the tap off. That often means a quite scary journey to the OR, but I’ve seen too many people crash on induction to not know that caution is wise, but what’s the evidence.

In this observational study from the US researchers hypothesized that intubation in the ED, as opposed to the operating room (OR), for patients requiring urgent hemorrhage control surgery is associated with adverse outcomes at both patient and hospital levels​. It is an observational study and so it’s a description of practice rather than an intervention. The authors looked primarily at death, but also at time in ED, blood product use and complications. They also looked at institutional factors such as the proprortion of patients intubated in the ED vs. OR and controlled this data for patient type and severity of illness (to hopefully account for differences in patient mix – though this is never perfect).

Amongst 9667 patients in 253 trauma centres, they found that there was a 20% increase in mortality if intubation was performed in the ED. There were also worse outcomes for time in ED , transfusion and complications. After adjusting for patient factors the difference remained with an increased risk of death (aOR 1.85 CI 1.54-2.23).

They also found that intubation rates differed widely between departments, in a way that could not be accounted for by patient mix. This suggests that culture, decision making, judgement and practice variation may be impacting patient outcomes.

Dunton Z, Seamon MJ, Subramanian M, Jopling J, Manukyan M, Kent A, Sakran JV, Stevens K, Haut E, Byrne JP. Emergency department versus operating room intubation of patients undergoing immediate hemorrhage control surgery. J Trauma Acute Care Surg. 2023 Jul 1;95(1):69-77. doi: 10.1097/TA.0000000000003907. Epub 2023 Feb 28. PMID: 36850033.

Paper 2.

We reviewed this paper last year and you can read the full appraisal here.

This was a randomised controlled trial of ED intubation comparing the use of video vs. direct laryngoscopy.

The authors found a significant improvement in first pass success with the VL as compared to the DL.

Successful first-attempt intubation in the VL group was 85.1% (600 of the 705 patients) vs 70.8% (504 of the 712 patients) in the DL group. Giving a p value of < 0.001 and a 95% confidence interval of 9.9-18.7.

Additionally, the difference diminished greatly with more experience. The VL appears to be a great learning tool, and that’s what I’ve found too. When teaching laryngoscopy/intubation the ability to see the screen and guide is absolutely fantastic (something Scott Weingart articulates really well on the EMCRIT podcast). I converted over to VL first after reading this paper, having been a DL first clinician for years (I am old school). In our HEMS service where I am often the intubator it also allows my critical care paramedic to see what I’m doing and to anticipate any issues and to support adjustments etc. I still use DL in kids as they are rarely tricky in HEMS practice, but I may well change that soon too.

Prekker et al: Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults August 3, 2023 N Engl J Med 2023; 389:418-429 DOI: 10.1056/NEJMoa2301601

Paper 3.

This paper has led to some animated debate amongst my anaesthetic colleagues. When I did anaesthetics i was taught that you can use a mac 4 as a mac 3 but not the other way around. So if yo uare chasing a high first pass success rate then stick with the 4. The counterargument is that if the patient is smaller then a size 3 blade gives better mechanical advantage and control.

This observational study looked at 979 intubations for critical care patients in

They found that the Cormack-Lehane view was substantially better when a Mac 3 blade was used, and that the first pass success was also improved.

  • Grade 1 view 55% vs. 37.6%
  • Grade 2 view 26.1% vs. 35.9%
  • Grade 3 view 15.8% vs. 18.5%
  • Grade 4 view 3.2% vs. 8%
  • First pass success 82.8% for mac 3 vs. 73.2% for mac 4

We have to be cautious as this is observational data and it may be that there were some significant differences between those patients who had a mac 3 selected, or it may be that clinicians who use mac 3s more often are better at laryngoscopy/intubation.

That said, the data supports the biomechanics argument and the one size fits all argument may need a revisit.

Landefeld KR, Koike S, Ran R, Semler MW, Barnes C, Stempek SB, Janz DR, Rice TW, Russell DW, Self WH, Vonderhaar D, West JR, Casey JD, Khan A. Effect of Laryngoscope Blade Size on First Pass Success of Tracheal Intubation in Critically Ill Adults. Crit Care Explor. 2023 Mar 6;5(3):e0855. doi: 10.1097/CCE.0000000000000855. PMID: 36895888; PMCID: PMC9990830.

Paper 4

We moved to paediatric bags for resuscitation a few years ago. The argument was that the standard adult sized BVM was too large and thus likely to lead to hyperventilation, respiratory alkalosis and thus worse outcomes for our patients. This does make sense to a degree, although we must remember that many of our patients have a significant metabolic acidosis and so a bit of respiratory compensation may not be a bad thing.

Our local decision and that of other services was not entirelty evidence based as there was a paucity of large well conducted RCTS to inform the decision.

Seattle made the change in 2017 and have been tracking their data from their well developed data collection systems. What did they find over a 6 year analysis from 2015-2021?

The authors analysed their database to look at rates of ROSC, ventilation rate and ETCO2 up to the end of EMS care.

Amongst 1994 patients, of whom 1331 were treated with a small bag, the raqte of ROSC was lower (33% vs, 40%). After adjusting for patient mix the difference remained with an aOR of 0.74 (CI 0.61 – 0.91).

We must remember that association is not causation, but this data once again asks us to consider the whole metabolic impact of cardiac arrest on our patients, It’s also a reminder that changes to practice may have unintended consequences, and that good data monitoring and review is an important tool to guide practice. My thoughts here are that if we are trying to achieve a change to ventilatory strategy then we probably need to think more about teaching/learning than just changing the tools (and expecting it to improve outcomes).

Snyder BD, Van Dyke MR, Walker RG, Latimer AJ, Grabman BC, Maynard C, Rea TD, Johnson NJ, Sayre MR, Counts CR. Association of small adult ventilation bags with return of spontaneous circulation in out of hospital cardiac arrest. Resuscitation. 2023 Dec;193:109991. doi: 10.1016/j.resuscitation.2023.109991. Epub 2023 Oct 5. PMID: 37805062.

Papers 5-7

Just some one liner honourable mentions here to tell us that.

  • Many patients who are comatose from poisoning can be safely managed without intubation. Win ratio of 1.85 (95% CI, 1.33 to 2.58) and fewer complications.
    • Freund Y et al. Effect of Noninvasive Airway Management of Comatose Patients With Acute Poisoning: A Randomized Clinical Trial. JAMA. 2023 Dec 19;330(23):2267-2274. doi: 10.1001/jama.2023.24391. PMID: 38019968; PMCID: PMC10687712.
  • A large RCT of ROSC patients showed that there was no difference between normocapnia and mild hypercapnia. 1700 patients. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P=0.76
    • Eastwood G et al, TAME Study Investigators. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest. N Engl J Med. 2023 Jul 6;389(1):45-57. doi: 10.1056/NEJMoa2214552. Epub 2023 Jun 15. PMID: 37318140.
  • Lots of bad things happen around the time of intubation in the critically ill (but you knew that already). 30% major adverse event rate (hypoxia, hypotension/cardiovascular collapse, or cardiac arrest) in this study of 34,357 intubations outside the OR.
    • Downing J, et al. Prevalence of peri-intubation major adverse events among critically ill patients: A systematic review and meta analysis. Am J Emerg Med. 2023 Sep;71:200-216. doi: 10.1016/j.ajem.2023.06.046. Epub 2023 Jun 28. PMID: 37437438.

Theme 2. Haemorrhage

Paper 8

We covered the UK REBOA trial back in 2023. As you will remember this was an RCT of REBOA vs. usual care for patients presenting with exsanguinating lower body hemorrhage. It was an ED based study.

The study aimed to assess the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA), combined with standard care, in reducing mortality among trauma patients with exsanguinating hemorrhage compared to standard care alone

The authors stopped the trial early after signals of potential harm in the intervention arm of the study. Mortality was 54% in the reboa arm vs 42% in the standard care arm, with concomitant delays in the ED.

Although some have called this paper the death of REBOA it’s clearly more complex than that. Running this trial in the ED meant that the intervention was delivered about 90 mins post injury, and so this may not be the population who might benefit the most. In addition the procedure was rarely conducted in most centres in the trial meaning that experience and skills were arguably not mature enough to test the system. Those using REBOA prehospitally in mature systems are still advocating for it, but with careful case selection and rigorous review. In the UK, and in the emergency departnent setting it remaines a questionable intervention.

Jansen JO et al. Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial. JAMA. 2023 Nov 21;330(19):1862-1871. doi: 10.1001/jama.2023.20850. PMID: 37824132; PMCID: PMC10570916.

Paper 9.

The long awaited CRYOSTAT-2 trial achieved publication in 2023. You will remember that this is an open label multicentre, international RCT of 3 pools of cryo vs standard care for patients receiving a major haemorrhage protocol in hospital.

Amongst the 1604 participants the principle outcome measure (28 day mortality) the trial showed no difference 25.3% for cryo vs. 26.1% for usual care. However, there were interesting differences between penetrating and blunt trauma patients in prespecified secondary analyses. Contrary to my expectations it was blunt trauma patients who appeared to have better outcomes with cryo as opposed to penetrating patients where they were worse. Quite what this means in practice is unclear, but a general consensus seems to be that we should not blindly give cryo to bleeding patients, but prioritise a fibrinogen level and act on that.

Davenport R et al. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA. 2023 Nov 21;330(19):1882-1891. doi: 10.1001/jama.2023.21019. PMID: 37824155; PMCID: PMC10570921.

Paper 10.

If you want to start a fight with a cross-atlantic group of resuscitationists then just mention TXA for trauma patients. I can’t think of a more controversial issue in resuscitation, which is odd as there is a lot of data out there. The PATCH trial sought to look at TXA in a high performing trauma system. They recruited 1310 patients across the antipodes. Their outcome measure was an interesting one (funcrional outcome at 6 months) which showed no statistical difference. However, TXA was associated with increased survival at 24h and 28 days (but not 6 months). The mortality data is consistent with other RCTs of TXA and probably believable. The longer term data is interesting and needs more work, but for now, this is another trial that shows that TXA increases survival.

PATCH-Trauma Investigators and the ANZICS Clinical Trials Group; Prehospital Tranexamic Acid for Severe Trauma. N Engl J Med. 2023 Jul 13;389(2):127-136. doi: 10.1056/NEJMoa2215457. Epub 2023 Jun 14. PMID: 37314244.

Papers 11-15

Honourable mentions for

  • TOP-ART. An RCT of Artesunate in 90 UK trauma patients. No difference found in outcomes, but more VTE in the treatment group.
    • Shepherd JM et al Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial. Intensive Care Med. 2023 Aug;49(8):922-933. doi: 10.1007/s00134-023-07135-3. Epub 2023 Jul 20. PMID: 37470832; PMCID: PMC10425486.
  • PROCOAG – An RCT of 327 MHP patients given 4 factor Prothrombin Complex Concentrate. No difference in outcomes.
    • Bouzat P et al. Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial. JAMA. 2023 Apr 25;329(16):1367-1375. doi: 10.1001/jama.2023.4080. PMID: 36942533; PMCID: PMC10031505.
  • A retrospective cohort study of US data showing an association between whole blood use and improved outcomes. 2785 patients. Whole blood use was associated with improved survival at 24 hours, demonstrating a 37% lower risk of mortality (hazard ratio, 0.63; 95% CI, 0.41-0.96; P = .03)
    • Torres CM, Kent A, Scantling D, Joseph B, Haut ER, Sakran JV. Association of Whole Blood With Survival Among Patients Presenting With Severe Hemorrhage in US and Canadian Adult Civilian Trauma Centers. JAMA Surg. 2023 May 1;158(5):532-540. doi: 10.1001/jamasurg.2022.6978. Erratum in: JAMA Surg. 2023 Apr 5;: PMID: 36652255; PMCID: PMC9857728.
  • A qualitative study that examined decision making for using prehospital blood. The themes were the use of recognition promed decision making and uncertainty in effect and outcome.
    • Marsden MER, Kellett S, Bagga R, Wohlgemut JM, Lyon RL, Perkins ZB, Gillies K, Tai NR. Understanding pre-hospital blood transfusion decision-making for injured patients: an interview study. Emerg Med J. 2023 Nov;40(11):777-784. doi: 10.1136/emermed-2023-213086. Epub 2023 Sep 13. PMID: 37704359; PMCID: PMC10646861.
  • A review of the sensitivity of prehospital clinicians in detecting major haemorrhage amongst 947 patients. With a sensitivity of 70% there is work to do, especially as if missed the mortality rate increased 3-fold. Specificity was good though at 94%
    • Wohlgemut JM, Pisirir E, Stoner RS, Kyrimi E, Christian M, Hurst T, Marsh W, Perkins ZB, Tai NRM. Identification of major hemorrhage in trauma patients in the prehospital setting: diagnostic accuracy and impact on outcome. Trauma Surg Acute Care Open. 2024 Jan 12;9(1):e001214. doi: 10.1136/tsaco-2023-001214. PMID: 38274019; PMCID: PMC10806521.

The story for bleeding in 2023 is that it remains complex and difficult. Several trials have suggest that blindly giving additional products to support coagulation does not work. You might be thinking that we need more bespoke approaches, but you may also remember the iTACTIC trial that did just that, and also showed no difference in early outcomes.

We still need more well designed trials as observational data is rarely definitive.

Theme 3. Cardiac

Paper 16.

Defibrillation remains a core part of cardiac arrest management, but can we do it better? this year we saw the results of the DOSE VF trial, an RCT that trialled alternative defibrillation strategies for patients in refractory VF (defined as still in VF after three shocks). I’ve been using alternative pad positions and rarely dual sequence defibrillation for several years, but this is the first decent sized RCT (405 patients).

There were three arms to the trial. Carry on with AP pad positions, change to AP, or use dual sequence defibrillation where two defibrillators are used 1 second apart to give two shocks.

The results were really quite dramatic with significant improvements with DSD over the other strategies, though just changing to AP also looks better as describef in the abstract ‘Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71].’

This paper is already having an impact and I’ve used DSD several times this year with anecdotal success. When working on HEMS/BASICS I’m often turning up after three shocks have already been given so I’m moving alternative defibrillation options up in my options to add value to the arrest management.

Cheskes S, Verbeek PR, Drennan IR, McLeod SL, Turner L, Pinto R, Feldman M, Davis M, Vaillancourt C, Morrison LJ, Dorian P, Scales DC. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med. 2022 Nov 24;387(21):1947-1956. doi: 10.1056/NEJMoa2207304. Epub 2022 Nov 6. PMID: 36342151.

Papers 17-19

Honourable mentions to the following….

  • A nice but small RCT of high (bolus + 100mcg/min) vs. low dose (20-40mcg/min) intravenous nitrates for crashing pulmonary oedema patients. Bottom line – give high dose as at 6 hours resolution differed from 65% to 11%. Although a small trial, this fits with my long standing practice of giving as much nitrates as the patient (and I) can tolerate.
    • Siddiqua N, Mathew R, Sahu AK, Jamshed N, Bhaskararayuni J, Aggarwal P, Kumar A, Khan MA. High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial. Emerg Med J. 2024 Jan 22;41(2):96-102. doi: 10.1136/emermed-2023-213285. PMID: 38050078.
  • On the theme of nitrates I was always told to avoid them in Right Ventricular infarction, but this large meta-analysis found no evidence to support this. It seems like the original concern came from a single small paper, and has now become dogma. Definately something to review and reconsider.
    • Wilkinson-Stokes M, Betson J, Sawyer S. Adverse events from nitrate administration during right ventricular myocardial infarction: a systematic review and meta-analysis. Emerg Med J. 2023 Feb;40(2):108-113. doi: 10.1136/emermed-2021-212294. Epub 2022 Sep 30. PMID: 36180168.
  • There remains international interest in cardiac arrest centres and it’s something we are instituting in Virchester. For patients with ST elevation I think there is some consensus to getting them to a hospital capable of PCI is a good idea, but what of the non-ST elevation patients? In this RCT of patients in London the authors found no survival advantage for transferring non-ST elevation ROSC patients to a specialist cardiac centre. This is interesting, and perhaps unexpected, but there are variety of causes of cardiac arrest, and some of the centres in London were standalone cardiac centres. So before we dismiss cardiac centres we must look at geographical issues too (as it might still make sense in your health locality).
    • Patterson T, Perkins GD, Perkins A, Clayton T, Evans R, Dodd M, Robertson S, Wilson K, Mellett-Smith A, Fothergill RT, McCrone P, Dalby M, MacCarthy P, Firoozi S, Malik I, Rakhit R, Jain A, Nolan JP, Redwood SR; ARREST trial collaborators. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. Lancet. 2023 Oct 14;402(10410):1329-1337. doi: 10.1016/S0140-6736(23)01351-X. Epub 2023 Aug 27. PMID: 37647928.

Theme 4

Paper 20.

Just for fun we will finish with the Syringe Hickey that I learned about on the EMCRIT podcast. We all have to mark the skin for procedures at some point or other and that can be tricky. I tend to use a sharpie, but it’s not perfect. In this study the authors used a 10ml syringe to create a ‘hickey’ (aka Lovebite).

This not only marked the skin well, but was resistant to all cleaning methods and was also visible across a range of Fitzpatrick skin types.

Unlike everything else I’ve talked about this is cheap, quick and fast. I love it.

Issa EC, Ware PJ, Bitange P, Cooper GJ, Galea T, Bengiamin DI, Young TP. The “Syringe Hickey”: An Alternative Skin Marking Method for Lumbar Puncture. J Emerg Med. 2023 Mar;64(3):400-404. doi: 10.1016/j.jemermed.2023.01.013. PMID: 37019501.

Final thoughts.

I love putting these talks together, although they take hours and hours to get right. If I had to look for an overarching theme it would be that resuscitation remains complex and nuanced. Clinical judgement and expertise is really important, and yet it’s also flawed.

You may also note that I’ve not mentioned ECMO as we are still ECNO and the current data is somewhat inconsistent.

What of the future of resuscitation research? I hope that we see more high quality trials looking for marginal gains in our current strategies, I hope that we see more studies on how humans (or AI) fit into protocols, more on decision support and uncertainty etc. Finally, I hope that we look at the equity of resuscitation opportunity for patients both geographically and chronologically as there is no doubt that the patient would want the same care at midday in London/Paris/Sydney that they might get in the outer reaches of Virchester at 2am on a Tuesday.

The bottom line. There is much to be done, and it’s going to be fascinating to see where we end up.

Cite this article as: Simon Carley, "Top resus papers for TBS. St Emlyn’s," in St.Emlyn's, February 7, 2024,

Thanks so much for following. Viva la #FOAMed

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